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Title: phd thesis. computer-aided assessment of tuberculosis with radiological imaging: from rule-based methods to deep learning.

Abstract: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb.) that produces pulmonary damage due to its airborne nature. This fact facilitates the disease fast-spreading, which, according to the World Health Organization (WHO), in 2021 caused 1.2 million deaths and 9.9 million new cases. Fortunately, X-Ray Computed Tomography (CT) images enable capturing specific manifestations of TB that are undetectable using regular diagnostic tests. However, this procedure is unfeasible to process the thousands of volume images belonging to the different TB animal models and humans required for a suitable (pre-)clinical trial. To achieve suitable results, automatization of different image analysis processes is a must to quantify TB. Thus, in this thesis, we introduce a set of novel methods based on the state of the art Artificial Intelligence (AI) and Computer Vision (CV). Initially, we present an algorithm to assess Pathological Lung Segmentation (PLS). Next, a Gaussian Mixture Model ruled by an Expectation-Maximization (EM) algorithm is employed to automatically. Chapter 3 introduces a model to automate the identification of TB lesions and the characterization of disease progression. Chapter 4 extends the classification of TB lesions. Namely, we introduce a computational model to infer TB manifestations present in each lung lobe of CT scans by employing the associated radiologist reports as ground truth. In Chapter 5, we present a DL model capable of extracting disentangled information from images of different animal models, as well as information of the mechanisms that generate the CT volumes. To sum up, the thesis presents a collection of valuable tools to automate the quantification of pathological lungs. Chapter 6 elaborates on these conclusions.

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• Open access
• Published: 10 September 2022

Living with tuberculosis: a qualitative study of patients’ experiences with disease and treatment

• Juliet Addo 1 ,
• Dave Pearce 2 ,
• Marilyn Metcalf 3 ,
• Courtney Lundquist 1 ,
• Gillian Thomas 4 ,
• David Barros-Aguirre 5 ,
• Gavin C. K. W. Koh 6 &
• Mike Strange 1  

BMC Public Health volume  22 , Article number:  1717 ( 2022 ) Cite this article

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Although tuberculosis (TB) is a curable disease, treatment is complex and prolonged, requiring considerable commitment from patients. This study aimed to understand the common perspectives of TB patients across Brazil, Russia, India, China, and South Africa throughout their disease journey, including the emotional, psychological, and practical challenges that patients and their families face.

This qualitative market research study was conducted between July 2020 and February 2021. Eight TB patients from each country ( n  = 40) completed health questionnaires, video/telephone interviews, and diaries regarding their experiences of TB. Additionally, 52 household members were interviewed. Patients at different stages of their TB treatment journey, from a range of socioeconomic groups, with or without TB risk factors were sought. Anonymized data underwent triangulation and thematic analysis by iterative coding of statements.

The sample included 23 men and 17 women aged 13–60 years old, with risk factors for TB reported by 23/40 patients. Although patients were from different countries and cultural backgrounds, experiencing diverse health system contexts, five themes emerged as common across the sample. 1) Economic hardship from loss of income and medical/travel expenses. 2) Widespread stigma, delaying presentation and deeply affecting patients’ emotional wellbeing. 3) TB and HIV co-infection was particularly challenging, but increased TB awareness and accelerated diagnosis. 4) Disruption to family life strained relationships and increased patients’ feelings of isolation and loneliness. 5) The COVID-19 pandemic made it easier for TB patients to keep their condition private, but disrupted access to services.

Conclusions

Despite disparate cultural, socio-economic, and systemic contexts across countries, TB patients experience common challenges. A robust examination of the needs of individual patients and their families is required to improve the patient experience, encourage adherence, and promote cure, given the limitations of current treatment.

Peer Review reports

Tuberculosis (TB) is a communicable infectious disease affecting around one quarter of the world’s population [ 1 ]. The ‘BRICS’ countries of Brazil​, Russia, India, China, and South Africa account for 47% of the total number of TB cases annually [ 1 , 2 , 3 ].

Caused by the bacillus Mycobacterium tuberculosis , around 5–10% of those infected will develop active disease. In 2019, 10 million new active cases and 1.4 million deaths were reported [ 1 ]. In 2020, the coronavirus disease 2019 (COVID-19) pandemic severely impacted the reporting of new cases and impeded diagnosis and treatment [ 3 ]. Treatment for multidrug-resistant TB (MDR-TB) also declined by 15% (from 177,100 in 2019 to 150,359 in 2020), with only about a third of patients who needed this treatment obtaining access [ 3 ].

Ambitious targets to end the TB epidemic by 2035 were established in 2015 by the WHO’s End TB Strategy [ 4 ], aligned with the United Nations Sustainable Development Goals [ 5 ]. In 2018, a United Nations General Assembly High-Level Meeting on Tuberculosis resulted in a Political Declaration on Tuberculosis, committing to end TB globally by 2030 [ 6 ]. Achieving these goals requires more equitable deployment of existing measures, and the development of new tools for TB prevention, diagnosis and treatment [ 7 ]. Progress towards ending TB also demands that interventions are aligned to patients’ experiences and address the challenges that they face [ 8 , 9 ].

TB typically involves the lungs (pulmonary TB) and is acquired via inhalation of droplet nuclei in the air following exposure usually over several hours. Close contact and the infectiousness of the source patient are key risk factors for the infection of tuberculin-negative persons [ 10 ]. Current treatment of drug-susceptible TB requires combination therapy consisting of an intensive phase of 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol, followed by a continuation phase of 4 months of isoniazid and rifampin [ 11 ]. Directly observed therapy (DOT) is recommended to ensure adherence to the complex regimen and to deter the emergence and spread of MDR-TB. Treatment is successful in around 85% of patients following 6 months’ therapy [ 1 ]. Also, individuals can become non-infectious within two weeks of treatment initiation, restraining disease transmission [ 1 ]. Thus, prompt initiation of therapy is important for both the patient and their close contacts. However, the management of TB is complicated by the increasing prevalence of MDR-TB, which requires prolonged and complex therapy, and is more likely to be associated with poor outcomes [ 12 ]. Even after successful treatment, patients may have ongoing lung disease and a decreased life expectancy [ 13 , 14 , 15 ].

The drugs used to treat tuberculosis are well understood clinically, and susceptibility testing will indicate which treatment regimen is appropriate [ 11 , 12 ]. However, treatment effectiveness depends on patient adherence to a demanding and lengthy treatment regimen with associated side effects. In this context, a patient-focused approach which considers the individual’s specific circumstances is needed to ensure sufficient adherence and good outcomes from therapy. Interest in this field has been building steadily and is most suited to a qualitative investigational approach which allows deep exploration of motivations, reactions, goals, aspirations, and circumstances. However, studies more often consider the challenges faced by healthcare workers caring for TB patients [ 16 ], or the implementation of new management tools [ 17 , 18 ].

Previous studies have examined how patients manage their illness and the impact that TB has on their daily lives, their families, and the wider community [ 19 , 20 ], as well as the stigma associated with poverty and HIV and the effects of discrimination [ 21 ]. However, defining studies on the experiences of TB patients and their families are not available for all the BRICS countries, and comparison between studies with different methodologies and objectives is problematic. It is, therefore, unclear to what extent the experiences of TB patients are shared across countries.

We report the findings of a qualitative evaluation of TB patients’ experiences across the five BRICS countries. The study aimed to identify commonalities across the different country contexts, by examining the perspectives of TB patients throughout their full disease journey, including the emotional, psychosocial and practical challenges that patients and their families face. A greater understanding of these factors could inform care more focused on patients’ needs, with the aim of improving outcomes and directing the development of new tools to end TB.

Study design

This qualitative market research study was designed collaboratively by GSK and Adelphi Research and conducted between July 2020 and February 2021 across the five BRICS countries (Brazil, Russia, India, China, and South Africa). The study was non-interventional and without clinical endpoints. The aim was to achieve a better understanding of the TB market across the BRICS countries by identifying common challenges faced by TB patients and their families in their daily lives throughout their treatment journey.

The study conformed to ethical principles laid down in the Declaration of Helsinki, all national data protection laws and industry guidelines. Participants’ data was protected by compliance with General Data Protection Regulation [ 22 ]. All participating patients and household members provided written voluntary informed consent, and parents provided written consent for children under the age of consent. Consent was also provided for anonymized publication of the findings. For consent forms see supplementary materials, Additional file 1.

To investigate the experiences, meanings, and perspectives of TB patients, qualitative methodology was employed to identify themes within and across countries from in-depth interviews and self-recorded videos, supported by a self-completed health questionnaire.

Participants with experiences relevant to the study objectives were actively recruited from BRICS countries because they account for more TB cases than any other country in their respective WHO regions, and because of the different additional challenges confronting these countries such as the burden of TB-HIV co-infection in South Africa, the diversity of private sector care in India, and the burden of MDR-TB in India, China and Russia [ 1 , 2 , 23 ]. Remote data collection both preserved the privacy of participants and ensured the safety of moderators given the infectious nature of TB and the timing of the study during the COVID-19 pandemic.

Recruitment

Participants were recruited through independent healthcare fieldwork agencies in the different countries via referral from healthcare professionals and social or community workers, as well as using market research databases, posters and adverts in TB clinics, patient groups, and word of mouth referrals. Participants had the opportunity to discuss the study with recruiters before completing a screening guide to confirm patient eligibility (Additional file 2). Recruited participants received an honorarium at fair market value for their participation.

Recruitment continued until TB patients from 40 households, that is 8 per country, plus 1–5 members of their households had been sampled. The minimum target sample size was 80 participants. Previous studies have indicated that for this type of qualitative research as few as 6 interviews per setting are required to identify major themes [ 24 , 25 ], with saturation occurring within 12 interviews [ 26 ].

Participants

Eligible participants had a confirmed diagnosis of TB and were receiving treatment or had completed treatment within the previous 12 months. Close family and other household members were included where appropriate for support and additional information, except for China where the social stigma prevented discussion with individuals other than the patient. Participants were recruited from a range of socio-economic backgrounds, assessed based on income, education levels, and living standard. At least three participants from each country were to be female. The study sought to include a range of specific patient types, for example, persons living with HIV (PLWH), those with diabetes, smokers, those with a history of excessive alcohol consumption, and those with MDR-TB/relapsed TB. At least two patients per country were to be living in households which included a child diagnosed with TB or receiving preventive treatment. No participant was excluded because of lack of access to technology as the necessary equipment was loaned to participants where needed.

Data collection

The interview moderators, fluent in the local languages, were taken through a training process in each setting, detailing study objectives, inclusion criteria, and study methodology, followed by subsequent monitoring of the process and active feedback to ensure quality control. Data quality was assured by consistent and thorough briefing of the field workers, including regular follow up to ensure study procedures were followed. The discussion guide and videoing instructions were carefully designed to contain clear respondent instructions at each question.

Patients first completed a 5-min health questionnaire based on their physical health over the previous four weeks. Interviews with TB patients and household members were conducted remotely by a trained moderator in the form of either a 60-min video-streamed interview or a 60-min telephone interview. The questionnaire and interview guides are provided in the supplementary materials (Additional file 3). Participants also completed a 45-min follow up video task to create four short videos on a mobile phone in their own time to capture their personal experience, such as their living environment, changes in their living arrangements as a result of TB, the biggest challenges since the diagnosis, perception of the changes in their life from others around them, and their hopes and expectations for the future.

The interviews were transcribed verbatim from the original languages, that is: Brazil, Portuguese; Russia, Russian; India, Hindi and English; China, Mandarin; South Africa, English, Sesotho, isiZulu, Tswana, or Afrikaans with switching between languages as necessary. Following translation into English, the information was analysed manually using a thematic and comparative analysis approach to identify key themes both within countries and across all participants’ responses [ 27 , 28 ]. Analysts had no access to patient medical records and all patient identifying information was anonymized.

Interviews were coded thematically by three analysts, aiming to reach consensus through regular team meetings where the emerging findings were discussed. Additionally, non-verbal communication (including visual evidence of living conditions) present in the videos from the streamed interviews and the video tasks were shared with the full team at regular intervals and discussed/analysed using the thematic framework developed from the transcripts. Triangulation across the different data sources was done using cross-checking to assess convergence, complementarity and divergence at the individual participant level, between patients and their families, and at the country level between informants from the same country. The analysis was therefore grouped initially by country and then analysed for cross-cutting themes across all respondents. Quality control was achieved by continuous review by two senior analysts, one of whom was not involved in the initial analysis, plus a final check through all the analyses.

The sample consisted of 40 TB patients (8 from each country) plus 52 household members. Each patient was assigned an identifier to illustrate their country and number. Of the TB patients, 23 were men and 17 women, ranging between 13 and 60 years old. Fourteen were receiving first-line treatment, 10 second-line treatment, 2 patients had received multiple treatment lines, 11 had completed treatment, and 3 patients (all from Russia) were on a treatment break (Table 1 , Fig.  1 ). Risk factors for TB were reported in 23/40 patients, with some patients having multiple risk factors (Table 1 , Fig.  1 ). Most patients were of medium socio-economic status for their country (26/40), and no patients with high socio-economic status were recruited (Table 1 ). Except for India and South Africa, it was not possible to recruit at least two households with a child diagnosed with TB or receiving preventive treatment (Table 1 ).

Summary of patient characteristics. Note that patients may have had more than one risk factor/co-morbidity

Patient health status

The self-reported health questionnaire indicated that most respondents (25/40) found that the physical impact of TB limited their activity. A higher proportion of patients who were currently receiving treatment (69.6% [16/23]) reported a physical impact of TB compared with those that had completed treatment (57.1% [8/14]) or who were on a treatment break (33.3% [1/3]). Most patients whose physical activity was impacted by TB reported that this affected them all or most of the time (88.0% [22/25]) (Fig.  2 A). Most patients (38/40) reported that their daily living was impacted in at least two ways (Fig.  2 B). Seven patients, five of whom were receiving treatment and two who had completed first-line treatment, stated that they were impacted by all six areas assessed (Fig.  2 B). Looking at specific impacts, the most reported were that TB stopped patients doing things that they liked to do (35/40), and economic hardship (28/40) (Fig.  2 C). Overall, it was clear that TB had significantly impaired the health status of patients and had a negative impact on daily living.

Results of a self-reported health questionnaire. A The effect of TB on limiting daily activity due to patients’ physical health; B ) the impact of TB on daily living; and C ) the number of impacts on daily living experienced by patients

Patient journey

Pre-diagnosis.

The most common initial symptoms reported by patients were a long-lasting cough increasing in severity over time, fever, weight loss, and tiredness. Some patients experienced more severe symptoms such as haemoptysis, and pleural effusion. However, symptoms were often non-specific, and unless they were aware of a source of infection or had known risk factors (e.g. HIV), most patients did not consider TB as a potential cause. Notably, patients in South Africa were more likely to suspect TB because of a higher awareness in the community and the link with HIV. In India, recent typhoid infection was suspected as the cause of symptoms in some cases.

Patients tended to hope that the symptoms would resolve on their own using over-the-counter products and traditional medicine. Patients with addiction to alcohol did not always perceive the severity of their symptoms and were less willing to engage with healthcare providers. However, avoidance of healthcare providers was common across all settings, because of concerns for the associated costs.

“The symptoms were there for the last 2 ½ months but I did not know. He was coughing a lot, so I asked him to go to the doctor. He did not listen to me. He feared talking to the doctor.” Relative of TB patient, India (IN19). “One day, I started to have fever in the afternoon. After work, I went to receive infusion in a small local clinic. I remember my body temperature was 39.5 to 39.6 degrees Celsius. The doctor said my condition was very serious, so he prescribed 5 bottles of infusion to me, and I received all of them. But my fever persisted after such a lengthy infusion.” China (CN09).

The pathway for TB cases depended on symptom severity at presentation but navigating the healthcare system was tortuous for some patients. Patients first sought help using a familiar and accessible route (Fig.  3 ).

The TB patient pathway. *There were no deaths during the study

Across all countries, the TB diagnosis came as a shock to most patients – their initial thought was ‘Will I die?’. PLWH were less surprised as they were aware of the association with TB. Some patients in South Africa believed they had been vaccinated against TB as children and were therefore protected. Many patients questioned how they had caught TB and worried about the negative misconceptions associated with the disease, particularly in Russia and Brazil. Patients feared that they would be ostracized and shunned by their families and communities. Young people with TB feared for their future, for example their careers, education, and prospects of marriage. Further concerns expressed by patients included the potential disruption to their life, job security and providing for their dependents, especially in India. Overall, there was uncertainty among patients as to whether they could cope; some expressed the fear of unintentional disclosure of their TB diagnosis to others. Notably, across all countries, families were often fearful of the potential costs, with a lack of clarity regarding which elements of treatment would be covered by insurance (where available) or were refundable from the public health system.

“[I thought] it is some kind of prison disease, which occurs more and more often in people who have served a sentence somewhere. That is, more disadvantaged groups of the population. I always thought about it in this way until I met it myself.” Russia (RU10).

Following diagnosis, healthcare providers were quick to reassure patients that TB is treatable but that it will take time and that they must try not to infect others. In South Africa some patients reported being warned of drug resistance. However, beyond this, TB-focused education was limited, and patients often conducted their own research via the Internet and word of mouth, though patient-friendly resources were described as inadequate in some settings.

“[The nurse] said if you don’t take your meds, they send you to [a TB hospital] and then you will receive extreme treatment. They inject you with needles and stuff. That is if you don’t use this meds at home, they will send you there and stay for six months.” South Africa (SA05).

Treatment side effects, pill burden, lifestyle restrictions and the long-term commitment required were very challenging for patients (Fig.  4 ). Patients generally did not know the names of their medications, but described having to take many pills of different types several times a day. Patients reported intolerable side effects, including nausea and vomiting, and patients with MDR-TB faced painful daily injections. In Russia, and to a lesser extent in China, patients were admitted to hospital to increase adherence. In Russia, patients recounted being admitted to sanatoriums for the treatment of TB.

“I take many anti-TB pills every day, covering 4–5 classes, about 20 tablets in total. Sometimes, it’s difficult for me to take medication, as I was quite reluctant to take it initially, but I had no choice, but to take it as a treatment.” China (CN11).

Factors identified by patients as affecting adherence to TB therapy

Monitoring and adherence

Across countries and socioeconomic bands, patients perceived minimal therapy monitoring by healthcare providers, with little evidence of DOT. It is possible that this was because of interruption to normal healthcare services because of the COVID-19 pandemic (see below). Most patients visited healthcare settings frequently to pick up their medications. Less frequently, their weight was measured during clinic visits, sputum tests were conducted, and some patients were informed when they were no longer infectious and could return to work/education. Family played a key role in monitoring during treatment, encouraging patients to continue with their treatment, sharing regular reminders, and helping to pick up medication from health centres. Motivation to comply was prompted by the desire to get back to normal family life and work, the fear of death, potential drug resistance, and hospitalization. Although patients would briefly lapse without serious consequences, they were usually encouraged to continue treatment by family and healthcare providers.

“Sometimes [redacted] forgets to take the medication, and I argue with him because if one of us forgets the treatment and the other one doesn’t then it won’t work, if we don’t take it together, it won’t work.” Brazil (BR04).

Once treatment was initiated, health improvements were quickly apparent to most patients, with resolution of fever and abatement in cough. Although this increased patients’ optimism and secured a return to some of their previous activities, it could also lead patients to believe that they had recovered, undermining adherence to therapy. Adherence was also jeopardized where there were high barriers to accessing treatment, a poor understanding of drug resistance, and when patients were alcohol dependent (Fig.  4 ). Patients who did adhere to treatment were often well supported by family and well informed of the consequences of non-adherence. Conversely, those who did not adhere to treatment were often unaware of the consequences.

“By December I was already feeling like I’m already cured, I nearly decided not to continue with the treatment.” South Africa (SA01). “Actually, they didn’t tell me about the details then. It was very important to emphasize it to me, but the physician didn’t do it. If he did, it would draw my attention and it won’t lead to drug resistance, as I often missed the dose I was supposed to take.” China (CN06). “I live in a little town which is quite far from the city. I can either go by bus which takes at least an hour and a half, or I can get to the nearest bullet train, but there aren’t many trains available and they are expensive.” China (CN08).

Completion of treatment

Eleven patients had completed treatment, 4 from South Africa, 4 from India, 2 from Brazil, and 1 from China. All had recovered, 10 following first-line treatment and 1 following second-line treatment (India). Some respondents said that their time in isolation was a time of reflection where their lives had been ‘put on pause’ making them ‘appreciate the little things in life’ they had really missed. A few patients said that their experience with TB has driven them to want to increase awareness, and remove stigma around the disease e.g., patients in Brazil and China set up informal support networks with fellow patients, particularly where patients met during hospital stays. Most patients expressed relief that they were cured, and that treatment was over, and were generally hopeful for their future.

"My TB is cured, and I want to start again with my studies. I was preparing for a railway job but I had to give that up because of TB. Now I will start my studies again and apply for a government job." India (IN04). "Thanks to this [TB] I got rid of bad habits, I do not drink alcohol now and smoke less… And I found a job, and I earn some money at the moment, during the first period my brother supported me fully, thanks to him, and my mother helped what she could.” Russia (RU05). "After these three months since I have recovered, this is what it has brought me, the willingness to fight, to battle, also to take even more care of my health, not just mine but also of people around me, and take this story, my testament, my lived experience with TB… So it’s a goal in my life, to spread information among all those who are close to me." Relative of TB patient (BR01).

Access to services

Before TB was diagnosed, in some cases patients consulted healthcare providers in the private sector, for example, the local family doctor, traditional medicine providers, or pharmacies. Following diagnosis, more affluent patients claimed on insurance or paid for private sector treatment due to poor perceptions of the public sector, and some sought support in the private sector for a ‘second opinion’ or for problems which they felt were not being addressed in the public sector. However, the majority of patients (36/40) obtained their TB care through the public sector; three patients used the private sector with one accessing both public and private sector healthcare. Treatment was provided for free through the national programs, with relatively good access in most settings, though travel distance and wait times were a barrier to access. There were reports of drug stock outs and out of pocket expenses for additional diagnostic tests or prescriptions, including having to pay for MDR-TB treatment in some settings (China). A minority of patients reported being turned away from the public sector for not having the correct paperwork or not being able to book an appointment. The public sector had a poor reputation for long queues and poor service and most patients aspired to be able to afford private treatment where services were described as being better.

“In public [sector healthcare] those nurses don’t care, I remember when I accompanied him, I was told I was not allowed to get inside, so he went in on his own. You go in pick up whatever you need and get out because those people don’t have time for anything.” Relative of TB patient, South Africa (SA01). “In the Government hospital, the doctors do not listen to us. They come when they wish and give medicines. As it is, the doctors do not listen to poor people. I had to buy some medicines from outside.” Relative of TB patient, India (IN17). “Obtaining the medication – because the drugs can only be obtained in the hospital, you can’t buy them in retail pharmacies. If I run out of my medication, I wouldn’t be able to buy it from the retail pharmacy, I would have to go the hospital, which is inconvenient.” China (CN08).

The use of sanatoriums in Russia was unique. Following diagnosis, patients were sent to a dedicated facility or a TB unit within a hospital where they remained for at least 3–4 months, though confinement could last for up to a year. They were only allowed to leave with permission, for example, at weekends or holidays. Although patients generally accepted that it was for the ‘greater good’ it was frightening at first because some other patients on the ward had very severe disease. However, some patients expressed surprise that other patients were ‘normal’, because they believed the disease to be often associated with homelessness and prisons.

“They told me I had a resistant form of TB and that the treatment is very, very long lasting. At first, they said I would have to be hospitalized three to four months and that then I would be able to go home but when I got to the hospital, the ‘girls’ told me that three to four months is optimistic… In short, eight months. Eight in the hospital and a year after the hospital. That was a shock.” Russia (RU12). “In my room there were all young women and all were so great. All of them were socially adapted: an accountant, a paediatrician student. So, let’s say it was good company.” Russia (RU01).

Thematic analysis

Five major themes were identified as common across all the countries studied (Fig.  5 ).

Thematic areas identified as common across five countries describing the challenges faced by TB patients

Economic hardship

Loss of earnings has the greatest economic impact for TB patients. Most patients stopped work because they felt too unwell to continue or were embarrassed by the symptoms, such as the persistent cough and severe weight loss. Some patients also felt the need to stay away from work to limit transmission to others or were ‘asked to leave’ by their employers as they were not covered by contracts. Many had no entitlement to sick pay. In some cases, patients were concerned that their financial situation could get worse as their diagnosis may mean prospective employers may be reluctant to take them on.

“The main problem is money. There is no problem greater than financial problems.” India (IN01). “I had to keep away from work because there was a lot of dust involved.” Brazil (BR15). “I cannot officially get a job, and I cannot unofficially either. But, what? Am I going to work as a loader? I cannot. This has seriously affected my finances… And who would hire if information comes out that there was TB? You will not get a job. I received a disability [payment].” Russia (RU05).

Even in regions where TB treatment was publicly funded, associated costs such as tests, hospitalization, prescriptions, travel, special food/supplements to manage weight loss, and medications to manage adverse effects were often borne by patients. The financial impact of TB meant that most patients had to rely on family or sometimes charities for support or take out loans. Time off for appointments still impacted earnings even after patients had returned to work.

“I also buy medications at my own expense [for gastric side effects] i.e. for TB, everything is free of charge due to the medical insurance policy, everything is fine, but if there is something secondary or something else not related to the diagnosis, then that is at your own expense.” Russia (RU07). “We are not educated people. I just wanted my child to recover. We are poor people; we could not work during lockdown. We had to borrow money from many people and requested help from doctors too. I thought my child would recover, but he did not. We were very stressed out.” Relative of TB patient, India (IN21). “To avoid delaying treatment, the doctor told me to take these four drugs upon diagnosis, and urged me to buy them elsewhere, as they were unavailable in the hospital. My wife found they were unavailable in many pharmacies either. Finally, she found them in several pharmacies, from where we bought them in early stage.” China (CN09).

Stigma associated with TB

Across all countries stigma was associated with TB, though it manifested in different ways. In China, TB was often kept a secret, even from family, whereas in South Africa, there was greater openness. In Brazil, though patients were open with family, there was reluctance to acknowledge their diagnosis with their community as TB is associated with wider social issues such as poverty, incarceration and ‘immoral lifestyles’. In India, TB patients felt discriminated against for other reasons, such as poverty, as well as TB. Stigma in Russia was related to the personal circumstances of the patient.

Young patients faced bullying at school/college and being dropped by friendship groups. Adults were ostracized by friends and relatives afraid of contracting TB, and relationships with friends and family suffered, leading to loneliness and depression. Respondents described instances when they were not invited to family events even after they had completed treatment and were cured. In some cases, TB appeared to ‘run in families’ meaning the stigma was intergenerational. Importantly, a family with TB was often considered a ‘low status’ family and this was compounded by the financial difficulties that accompany TB.

“A lot of my friends kept away from me because of this, because that’s what people know, that it’s contagious, but they don’t understand that the person on the other side is suffering as well, and we don’t only suffer a little bit, at least myself, it’s a very painful process, very painful, very complicated.” Relative of TB patient, Brazil (BR01). “The community was no longer as close to us because we are staying with a person that has TB – people at the queue at shops would turn around and come back when we have left.” Relative of TB patient, South Africa (SA14). “When a person has TB he becomes very annoyed as he has to go through a lot of things, plus there also comes a phase were people start avoiding you, they feel that if we come in contact with this person even we might acquire it.” India (IN01). “A person who has TB is not somebody who is well-regarded.” Brazil (BR04).

HIV co-infection played a major role in the TB experience, particularly in South Africa. Awareness of TB was higher among PLWH given their greater risk and regular contact with healthcare services. Also, the path to diagnosis was shorter given their engagement with HIV services with rapid referral reflecting the associated co-infection risks. In many cases, the HIV and TB clinics were co-located improving patient access. However, PLWH were highly aware of the stigma that TB carries with fear around the community reaction during the early stages of their journey.

"Now I’m scared I’m HIV positive, I have TB and now there’s Corona [COVID-19], what’s going to happen when I have all three of them?" South Africa (SA18). “So people were really scared, I think they are now more afraid of TB than HIV. I told my neighbour that I was diagnosed with TB and luckily she doesn’t talk much but still I was aware of their behaviour when they came by to do my laundry they would wait outside to hand it over to them and when they are done they would leave it by the door." South Africa (SA10).

Disruption to family life

A diagnosis of TB affects everyone in the household and the wider family. Cleaning and disinfecting routines have to be established and maintained, and there was a general awareness that separate cutlery must be used, living spaces needed good ventilation, and clothes and bedding should be washed more frequently. Sleeping arrangements to isolate TB patients were particularly problematic in India and South Africa where large families live together, and parental co-sleeping with children was no longer possible where this was practiced. In some cases, children were looked after in the homes of extended family members, away from parents with TB. Married patients feared abandonment or divorce and respondents felt ‘lucky’ that their partners had stayed with them despite their TB status. The reduced family contact, demands of treatment and financial hardship often strained family relationships.

“Life at home isn’t the same because I had to begin separating my cutlery and a glass – my clothes had to be washed separately, we have to clean down the house and open the windows to let the air circulate.” Brazil (BR15). “I’m worried I may infect my parents. So I’ve had to reduce my interactions with them, the time spent with them, the number of occasions I’m with them. And as they get older, they become confused and they don’t understand why I stay away.” China (CN08). “Our house always used to be full at weekends, friends would come around to watch films, sometimes we would make lunch, get pizza and sit and watch films, and then suddenly the house was empty.” Relative of TB patient, Brazil (BR01).

Mixed effects of COVID-19

Some TB patients observed that the COVID-19 pandemic normalized the idea of infection prevention, with mask wearing becoming common. Also, TB patients were able to hide their diagnosis more easily with social distancing measures. There was also less fear that they could infect the wider community. However, access to healthcare and medication was compromised with restrictions to movement and hospitals not accepting admissions for other conditions. Patients were fearful of ‘catching’ COVID-19 given their impaired respiratory health and existing co-morbidities, such as HIV and diabetes. Some respondents who were coming to the end of their isolation and anticipating greater freedoms and a return to a more normal life then faced COVID-19 restrictions.

“During the pandemic I was unable to go to the hospital for my regular follow-ups and prescription renewal, and so because of that my condition worsened, and I eventually ended up infecting my family.” CN08.

Assuming that efficacious treatment is provided, TB is curable. However, outcomes are often sub-optimal. This study aimed to explore common themes in the experiences of TB patients and their families in the five BRICS countries from diagnosis to completion of treatment. Using consistent methodology, economic hardship, stigma, TB-HIV co-infection, disruption to family life, and the mixed effects of COVID-19 were identified as themes encompassing the challenges facing TB patients across the five BRICS countries (Fig.  5 ). These factors, therefore, appear to be independent of the country setting. Further research should investigate the degree to which these factors and are potentially mutable by targeting systemic changes in healthcare and social provision and providing attention to patients’ individual needs.

Economic hardship was reported across all countries. TB is associated with economic vulnerability but can also drive families into poverty through loss of income, the costs of transportation and food supplements, and associated medical expenses [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Programs providing social protection to TB patients have been linked to improved outcomes and the increased uptake of preventive therapy but must be easily accessible [ 29 , 37 , 38 ]. Improvement of TB services can also reduce the number of families facing financial hardship [ 39 ]. Even though most healthcare systems in our study provided TB drugs free of charge, to be effective, treatment should encompass the wider economic impacts that patients experience. Despite various approaches, patients from all of the countries surveyed found themselves struggling financially and a more holistic approach to patient support is needed.

Stigma attached to TB is culturally distinct, but stems from a lack of awareness of TB and the persistence of stereotypes [ 40 , 41 ]. For example, in Russia, an association with prisons and poverty has persisted, despite TB affecting all sectors of society [ 42 ]. Stigma was most acutely felt in China, and a recent study described psychological distress in nearly two-thirds of TB patients, associated with a high experienced stigma [ 43 ]. In our study, some patients did not even disclose their diagnosis to close family. In newly diagnosed Chinese TB patients, non-disclosure of their TB status magnified patient-perceived stigma and was associated with depression – a risk factor for non-adherence [ 44 , 45 ]. Social support and doctor–patient communication appeared key factors for reducing TB-related stigma in China [ 46 ]. Also, educational approaches to raise awareness of TB diagnosis and treatment among the public are needed, particularly focused on those with low educational levels and more rural communities [ 40 , 47 , 48 ].

The association between TB and HIV is well documented. However, the impact on patients is less well understood. In this study, PLWH were more aware of TB and were more likely to seek care early and be diagnosed quickly. This is in contrast to a study in Thailand where PLWH had low TB awareness and attributed their early symptoms to AIDS, resulting in delayed TB diagnosis [ 49 ]. This emphasizes the importance of raising TB awareness in PLWH. In South Africa, TB and HIV services are often co-located and integrated [ 50 ]. However, a detailed analysis in South Africa of the challenges faced by PLWH who had MDR-TB highlighted similar issues to those described here for all TB patients, such as fear, stigma, dissociation from family and social networks, poor provider support, drug adverse events, and financial insecurity [ 51 ]. Also, patients tended to prioritize adherence to anti-retroviral therapy versus TB therapy because it was less challenging in terms of pill burden and adverse effects [ 52 ]. Until less demanding treatment regimens are available, targeted support to address the challenges of adherence in patients co-infected with TB-HIV is necessary.

The respondents in this study described a severely disrupted home life following a TB diagnosis. Patients were isolated and often infirm, and the economic and care responsibilities for family members were considerable. Families also suffered socially, being isolated or shunned by friends and the wider family. In many cases, it was family members who ensured adherence to medication, and social and family support for patients has been previously shown as a key factor in therapy adherence [ 41 , 53 , 54 ]. Despite this, the impact of the TB diagnosis on the family and how family members can best be supported has been rarely investigated [ 47 ], and we identify this as an important area for further research.

The COVID-19 epidemic has disrupted healthcare access globally [ 55 ]. In our study, TB patients reported drug shortages and restrictions to services during the period. TB patients also expressed concern regarding the consequences of contracting COVID-19. Similarly, a recent study in Brazil reported that TB patients were fearful of attending medical appointments [ 56 ]. TB patients do appear to be at greater risk of death or poor outcome with COVID-19 [ 57 ], and should therefore socially isolate or ‘shield’ [ 58 ]. TB patients did feel less stigmatized as social distancing and infection control measures were deployed for COVID-19. However, the interruption of treatment, with the risk of therapy failure, selection of MDR-TB, and increased transmissibility is a major threat to TB patients and their close contacts [ 59 ].

This study has several limitations. Although participants were identified through a variety of channels and a range of socioeconomic groups were sampled, this was not a randomized sample and we acknowledge that both marginalized and privileged groups may not engage in this kind of research. Also, there were no data on whether susceptibility testing was conducted following the TB diagnosis, so the appropriateness of therapy could not be assessed. Neither did we examine the differences between patients’ experiences of drug-susceptible versus MDR-TB; patients were not consistently aware of the difference and most patients were receiving or had recently completed first-line therapy. The patient pathway was not integrated into the thematic analysis but analysed separately in terms of the systemic challenges that patients face. This was because the complexity of the pathway did not map onto the themes in a meaningful way. For example, patients experienced economic hardship, stigma, and disruption to family life at most stages in the patient pathway, whereas TB-HIV co-infection had an important effect on the speed of diagnosis. Thus, patient pathway was examined systematically and separately to the thematic analysis which focused on the emotional, socio-economic and practical impacts of TB on patients’ daily lives. The analysis methods sought to remain impartial with repeated reviews by multiple analysts to reach consensus. However, the analysts were all based in the UK and we recognize that the cultural subtleties of some of the patients’ experiences may not have been fully appreciated.

In our study, TB patients’ perceptions and needs were expressed in their own words, from within their home environment, in confidence, to interviewers who were not involved in their healthcare. Most had struggled to adjust to their diagnosis, had poor access to information, lacked support from healthcare workers, were under significant financial pressure, and were highly conscious of stigma and the burden TB placed on their families.

Our findings highlight that much work still needs to be done before the goal of ending TB can be achieved. Structural changes require simplification of the TB patient pathway, reliable access to services, and the alleviation of financial pressures. Health education for patients, their families, healthcare providers and the public to increase awareness of TB symptoms and diagnosis, to encourage adherence, and to reduce stigma around the disease is needed. Importantly, TB patients do better with strong family and social networks to sustain them, and a greater understanding of how these can be better supported at the level of the individual patient throughout the TB treatment journey requires further investigation.

Despite the different cultural, political, and healthcare settings across the BRICS countries, TB patients faced very similar challenges. This commonality would not necessarily have been expected. It suggests that these factors are not only a product of the healthcare provision in the countries or the social, economic, and cultural pressures that patients face, but reflect an overarching insufficiency in the treatment of TB. The efficient delivery of comprehensive individualized care and support would certainly mitigate the negative impacts of TB on patients. However, these issues will likely not be fully resolved until treatment options are available that rapidly cure TB and prevent onward transmission.

Availability of data and materials

All relevant data are included in this publication. Recorded interviews will not be made available in order to maintain patient confidentiality. However, anonymised transcripts are available on reasonable request to the authors for ten years following study completion. For data requests please contact the corresponding author at [email protected].

Abbreviations

Coronavirus disease of 2019 (severe acute respiratory syndrome coronavirus 2)

Human immunodeficiency virus

Multidrug-resistant tuberculosis

People living with HIV

• Tuberculosis

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Acknowledgements

Naomi Richardson of Magenta Communications Ltd. in collaboration with Juliet Addo developed the first draft of this article from a research report, provided editorial and graphic services and was funded by GSK. Elizabeth Kehler, Francesca Trewartha and Thea Westwater Smith of Adelphi were co-authors of the original report and co-analysts. Carly Davies, Vera Gielen and Myriam Drysdale from GSK reviewed and provided comments on the screening and interview guides.

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J.A. made substantial contributions to the conception and design of the work, interpretation of the data and drafting of the manuscript. C.L., M.M., M.S., D.B-A., G.C.K.W.K. and D.P. made substantial contributions to the conception and design of the work and interpretation of the data and critically revised the manuscript for intellectual content. G.T. made significant contributions to the design of the work, the acquisition of data, analysis and interpretation of data for the work and critically revised the manuscript for intellectual content. All authors read and approved the final manuscript.

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Addo, J., Pearce, D., Metcalf, M. et al. Living with tuberculosis: a qualitative study of patients’ experiences with disease and treatment. BMC Public Health 22 , 1717 (2022). https://doi.org/10.1186/s12889-022-14115-7

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Knowledge, attitudes and practices on tuberculosis infection prevention and associated factors among rural and urban adults in northeast Tanzania: A cross-sectional study

Roles Conceptualization, Data curation, Formal analysis, Methodology, Supervision, Writing – original draft, Writing – review & editing

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Affiliation Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

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Affiliation Behavioral Sciences Department, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

• Method Kazaura, 
• Switbert Rwechungura Kamazima

• Published: December 8, 2021
• https://doi.org/10.1371/journal.pgph.0000104
• Reader Comments

Almost 10 million of the global population was infected with tuberculosis (TB) in 2017. Tanzania is among countries with high incidence of TB. Although control measures of TB are multi factorial, it is important to understand the individual’s knowledge, attitudes and practices (KAP) in order to control TB infection. We conducted a cross-sectional study in northeast Tanzania; recruited and interviewed 1519 adults from two districts, one rural and another urban. We scored each participant using several questions for each construct of KAP. A study participant scoring at least 60% of the possible maximum scores was considered as having a good knowledge, positive attitude or good practices. And herein, a participant having positive TB attitude would mean they acknowledge TB exist, recognizes its impact on health and would seek or advise TB-infected individuals to seek the correct remedies. We applied multiple linear regression analysis to assess independent individual-level factors related to TB on KAP scores in the rural and urban populations. Overall, less than half (44%) of the study participants had good overall knowledge about TB infection and significantly more urban than rural adult population had good overall knowledge ( p <0.001). Almost one in ten, (11%) of all study participants had positive attitudes towards TB infection. More urban study participants, (16%) had positive attitudes than their rural counterparts, 6%). Almost nine in ten (89%) of all study participants had good practices towards TB prevention and control; significantly more adults in urban, (97%) than the rural populations (56%) ( p <0.01). Predictors of KAP scores were individual’s education and main source of income. Adults in rural and urban northeast Tanzania have poor knowledge, attitudes and practices for TB infection and prevention. Strategies focusing on health education are important for control of TB, especially among rural communities.

Citation: Kazaura M, Kamazima SR (2021) Knowledge, attitudes and practices on tuberculosis infection prevention and associated factors among rural and urban adults in northeast Tanzania: A cross-sectional study. PLOS Glob Public Health 1(12): e0000104. https://doi.org/10.1371/journal.pgph.0000104

Editor: Sanghyuk Shin, University of California Irvine, UNITED STATES

Received: June 21, 2021; Accepted: November 15, 2021; Published: December 8, 2021

Copyright: © 2021 Kazaura, Kamazima. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The relevant data file for this study is within the manuscript.

Funding: The author received no specific funding for this work.

Competing interests: The authors declare that they have no conflicts of interest associated with this article.

Abbreviations: CI, Confidence interval; HIV&AIDS, Human immunodeficiency virus infection and Acquired Immunodeficiency Syndrome; KAP, Knowledge, attitudes and practices; SE, Standard error; TB, Tuberculosis; WHO, World Health Organization

Introduction

Human tuberculosis (TB) is a chronic infectious disease mainly caused by a family of organisms known as Mycobacterium tuberculosis . Although TB can either be latent or active, 90% of the active TB cases arise from the latent, commonly referred to as reactivation tuberculosis [ 1 , 2 ]. In 2018, it was estimated that the global incidence of TB was more than 10 million people and almost one-fifth of the cases died [ 3 ]. In view of the fact that HIV-infected people are more likely to develop TB [ 3 , 4 ], there are more TB cases in less developed countries where the burden of HIV&AIDS is high [ 5 , 6 ]. Major countries with more TB cases and deaths include Indonesia, China, Philippines, Pakistan, Nigeria and South Africa [ 7 ].

Tanzania is among sub-Saharan countries with high burden of TB [ 8 ]. In 2018, the notification rate for new and relapsed TB cases in northeast Tanzania, was about 129 per 100,000 population [ 9 ]. In 2011, the World Health Organization (WHO) estimated the prevalence of TB infection in Tanzania to be 0.2% with a more recent estimate of 295 per 100,000 adult populations [ 10 – 12 ]. A higher burden is also seen in children, whereby in 2016 almost 14% of children under the age of 15 years from Central and Eastern Tanzania were detected as having TB infection [ 13 ]. Data from some sub-Sahara African countries suggest higher burden of TB in urban than from the rural settings [ 14 ].

There is higher regional variability of TB prevalence across the 26 administrative regions of mainland Tanzania [ 15 , 16 ]. However, the TB cases notification rate rose from 2.69 per 100,000 population in 2017 to 2.81 in 2019 [ 16 ]. In order to control and reduce the burden of TB at the community or individual-level, various measures have been suggested [ 17 , 18 ]. At an individual level, some studies suggest sex, age, education, marital status, main sources of income and exposure to mass media are associated with knowledge, attitudes and practices (KAP) towards TB prevention and control [ 19 – 25 ]. In addition, adults living in urban areas have been associated with higher overall better knowledge of TB as compared to their counterparts in rural areas [ 26 , 27 ].

Understanding these KAP factors at the community and individual levels is very important especially when planning the implementation and even evaluation of programs aimed at preventing and controlling TB infection [ 28 ]. Nevertheless, to the best of our search, there are limited current data in Tanzania that focus on KAP towards tuberculosis. The available data are old, not specific to the study population or beyond examining KAP towards prevention and control of TB infection. Therefore in this study, we assessed KAP about TB infection prevention and control among adults in rural and urban areas of northeast Tanzania and determined their associated individual-level factors that are essential for appropriate design of control measures against TB infection in Tanzania.

Materials and methods

Study design and settings.

We conducted a cross-sectional analytical study design in Tanga region, northeast Tanzania. We purposefully selected Tanga because it is one of the regions with higher TB case notification rates than the national average of 1.38 per 100,000 population [ 16 ]. In 2019, the estimated region’s population was about 2.4 million [ 29 ]. The region has eight administrative districts; with an average population density of about 77 persons per square kilometre. Whereas the main activities of the population in rural areas are agriculture followed by livestock keeping, in urban centres there are large and small businesses.

Study population

The study population included adults who usually reside ( de jure population ) in the selected households in Tanga city and Korogwe rural districts.

Sample size estimation

Sampling procedure

Since we aimed at comparing KAP among adults in urban and in rural settings, the sampling strategy was organized based on this structure. Although there are several towns in the region, most of them have a mixture of rural and urban (semi-urban) characteristics. There is only one city in the region, the Tanga city. Therefore, we purposefully selected Tanga City to represent the urban population. We used a four-stage sampling strategy to get the required study participants in this stratum. In the first stage, we randomly selected eight out of 24 wards in Tanga City. In the second, we randomly selected one street from each of the selected eight wards. The third stage involved a systematic selection of 100 households from each street, whereas the in the fourth stage we used a ballot box to randomly select one adult (at least 18 years old) for an interview.

In selecting adults to represent the rural population, we used a five-stage cluster sampling strategy. First, from a list of the available seven well-defined rural districts (Handeni, Kilindi, Korogwe, Lushoto, Mkinga, Muheza and Pangani), we randomly selected Korogwe rural district. Second, we randomly selected six wards out of the 20 wards in the district. The third stage involved, from each selected ward, we randomly selected one village. Fourth, in each village we systematically selected 130 households. Finally, in each selected household, we used a ballot box to randomly select only one adult for inclusion in the study.

Data collection tools

We used an interview form to collect data on knowledge, attitudes and practices about TB infection control. The tool was designed based on expertise in the field and benchmarking with previous similar studies [ 21 , 32 , 33 ]. The interview form included structured questions organized into four main themes: (a) the background (social and demographic) information, (b) knowledge about TB infection, (c) practices about TB control and (d) attitudes towards TB infection. The tool was first prepared in English and translated to Kiswahili, a medium language of communication to almost everybody in Tanzania. However, in case of an adult proficient in English language, there were few surveys earmarked for this purpose.

The tool was pre-tested among adults in 10 households in one street and 10 others in one village. The village and the street were beside those earmarked for the main study. Based on the results from the pre-tests, we revised the tool to make sure the language is understandable and all options of possible answers for each item in the tool have been captured. Furthermore, through pre-testing we were able to assess the ability and skills of research assistants in collecting data. All research assistants had medical or social background and were well-trained to execute the task of data collection.

Study variables and measures

Dependent variables..

The main dependent variables were three: knowledge about TB infection, attitudes towards TB and practices about TB infection control.

Knowledge about TB infection.

We asked nine questions about knowledge of TB symptoms; for example “what TB symptoms do you know?” There were eight questions on TB transmission; for example “How can an individual contract TB?” All questions were structured, pre-coded and mainly with the expected “yes”, “no” and “I don’t know” answers.

Attitudes towards TB infection.

Participants self-reported their individual feelings about TB infection by answering nine questions, each on a Likert-scale with the expected opinions ranging from “Very strongly agree” to “Very strongly disagree”. These questions were towards both the disease and to the people with TB. Examples of these questions include, “People with TB should be avoided” and “People with TB should be feared”.

Practices about TB infection control.

We asked study participants about what they were actually doing or they would do to protect themselves from contracting TB infection. Questions were about the general prevention practices and about health-seeking behaviour. For example, “How frequently do you do the following about TB: (a) boiling milk before use, (b) opening widows in your bed/living room”. Options were: (1) Always, (2) Most of the time, (3) Sometimes and (4) Not at all.

Independent variables.

Independent variables were individual-level background characteristics: sex, age, education, marital status and the main source of income of the study participants.

Data processing and analysis

Collected data were entered into statistical software (Statistical Package for Social Sciences; version 24) for processing and analysis. Responses on knowledge about TB infection were all aligned in a positive direction making sure that the correct answer is scored 1 and the wrong answer scored 0. Responses from questions for each component of knowledge (symptoms and transmission) were summed up to create a separate composite quantitative variable having possible score ranging positively from 0 to 9 and from 0 to 8 respectively. Later on, the overall knowledge score was created by a combination of knowledge on symptoms and of transmission scores, potentially ranging from 0 to 17. Similarly, responses about attitude towards TB infection were arranged from 1 = low score that implied low attitudes to 5 = high score implying positive attitude. In this study, a person having positive attitudes towards people with TB would mean an individual acknowledges TB exist, recognizes its impact on health and would seek or advise TB-infected individuals to seek the correct remedies.

During data processing, in case of questions with opposite direction, we reversed the coding. For each respondent we created a composite variable about attitudes with possible scores ranging from 9 to 45. Scores for practices ranged between 0 and 8. For each construct, we categorized a study participant with a score below 60% of the possible maximum score having a poor knowledge, negative attitudes or bad practices. The 60% mark was based on a modified Bloom’s cut-off and has been recently used in other studies of similar settings [ 34 , 35 ].

We calculated the means with standard deviations for quantitative variables and ran frequencies for categorical variables to get proportions. We applied Chi-squared test (χ 2 ) to assess the association between a pair of categorical variables. In the multivariable analyses, we used multiple linear regression analysis to model overall scores of knowledge, attitudes and practices with the independent individual-level variables. Linear regression analysis was considered the best procedure in order to maintain the original measurements. Otherwise, the binary logistic regression analyses would have over-estimated the measures of association because all outcomes were not rare. In addition, the same procedure has been used previously in a KAP study in South Africa [ 25 ]. We calculated 95% confidence intervals (CI) as a measure of strength for the association. During the bivariate and multivariable analyses, the level of significance was set at 5%. Furthermore, we applied robust estimation of the standard errors and confidence intervals using bootstrapping method because of using cluster sampling rather than the simple random sampling technique.

Ethics statement

The protocol of this research was reviewed and approved by the Muhimbili University of Health and Allied Sciences (MUHAS) Institutional Review Board. The Regional Administrative Secretary and the District Administrative Secretaries for Tanga City and Korogwe districts granted permission to conduct the survey in the study areas. While all literate study participants provided written informed consent, illiterate individuals provided the verbal. Thereafter, to document their consent, the literature and illiterate study participants signed or provided a thump-print respectively on their consent forms. Throughout the study, we adhered to anonymity, privacy, confidentiality and collected only information related to the study. Filled-in interview forms were stored in a safe locker with key only accessible by the principal investigator. Data in electronic form were password-protected and were only accessed by the authorized persons.

Description of the study participants

We recruited 761 (95.7% recruitment rate) and 758 (95.3% recruitment rate) from the urban (Tanga city) and rural areas (Korogwe rural district) respectively. In Table 1 , we present the distribution of the study participants by the study area and by background characteristics. The majority, 999 (65.8%), were females who also dominated in each of the two study areas. The median age of all study participants was 32.0 (Inter-quartile range = 19.0) years and did not differ by residence status (rural or urban). Regardless of residence, the majority 645 (84.8%) and 412 (54.3%) of the study participants from urban and rural areas respectively, reported their highest education level was primary school. This level was reported in urban areas, 645 (84.8%), and rural areas, 412 (54.4%). Almost half, 726 (47.8%) of all study participants reported business being their main source of income. The majority, 349 (46.0%) of study participants from rural areas reported peasantry and livestock keeping being their main sources of income.

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https://doi.org/10.1371/journal.pgph.0000104.t001

Awareness of tuberculosis (TB)

In total, 1444 (95.1%) of the study participants reported being aware of TB. The proportions of study participants reporting aware of TB did not differ by the study area, 717 (94.2%) [95%CI = 92.3, 95.7] and 727 (95.9%) [95%CI = 94.2, 97.2] for urban and rural areas respectively.

Overall knowledge about TB infection

The average score for the overall knowledge among all study participants was 7.2 (standard deviation (SD) = 2.9). Of the 1359 study participants who responded to all items in this construct, 601 (44.2%) had good overall knowledge. While 460 (64.2%) study participants from urban areas had good overall knowledge, less than a quarter, 141 (22.0%) from rural settings had good overall knowledge about TB infection (χ 2 = 244.5, p < 0.001) ( Table 2 ).

https://doi.org/10.1371/journal.pgph.0000104.t002

Knowledge about TB symptoms

The average score on knowledge about TB symptoms among all study participants was 2.7 (SD = 2.3) and it was significantly higher among study participants from urban than rural settings, 3.2 (SD = 2.6) and 2.2 (SD = 1.6) respectively ( p <0.001). In total, 1211 (83.9%) had good knowledge about TB symptoms. Knowledge of TB symptoms was dependent on residence such that 660 (92.0%) as compared to 551 (75.8%) of the study participants from urban and rural areas respectively had good knowledge on TB symptoms (χ 2 = 70.5, p < 0.001) ( Table 2 ).

Knowledge about TB transmission

The average score for knowledge about TB transmission among all study participants was 4.5 (SD = 1.5). Of the 1358 study participants who respondent to all items, 952 (70.1%) had good knowledge about TB transmission. While 678 (94.7%) of the study participants residing in urban areas had good knowledge about TB transmission, only 274 (42.7%) from rural areas had such knowledge (χ 2 = 436.9, p < 0.001) ( Table 2 ).

Attitudes about TB infection

When assessing the strength of consistency of the nine items we used to measure attitudes on a Likert-scale, Cronbach’s alpha (α) was 0.742; indicating a good reliability. The overall average attitudes score about TB infection was 19.1 (SD = 6.2). The average score was significantly ( p <0.001) higher, 22.7 (SD = 4.0) among adults in urban areas as compared to their counterparts, 15.6 (6.0). In general, of the 1444 study participants, 158 (10.9%) had positive attitudes towards TB infection. There were significantly more study participants from urban areas, 113 (15.8%) with positive attitudes towards TB infection as compared to adults dwelling in the rural settings, 45 (6.2%), (χ 2 = 33.9, p < 0.001) ( Table 2 ).

Practices about TB infection control

Among 882 study participants who respondent to this construct, 785 (89.0%) had good practices in controlling TB infection. Their average score on this construct was 5.0 (SD = 1.2). Some of the unexpected practices reported controlling TB infection included, avoiding hand shake 734 (83.2%), having good diet 799 (90.6%) and avoiding sharing utensils 576 (65.3%). The average score about practices in controlling TB infection was higher, 5.1 (SD = 0.9) among adults in urban as compared to 4.0 (SD = 1.7) for those in rural areas ( p <0.001). Significantly more adults, 692 (96.5%) from urban areas as compared to 93 (56.4%) of the rural adult population had good practices about TB infection control (χ 2 = 220.9, p <0.001) ( Table 2 ).

Factors associated with overall knowledge scores about TB infection control

In a multiple linear regression analysis for the overall knowledge scores about TB infection on individual-level factors, regardless of place of residence (whether rural or urban), adults with secondary education were significant positively associated with higher overall knowledge scores about TB infection. Adjusting for residence, they had almost 2 scores of overall knowledge higher (beta-coefficient (β) = 1.9, 95%CI = 1.0, 2.8; p = 0.001) than adults reporting never been to school or with informal education ( Table 3 ).

https://doi.org/10.1371/journal.pgph.0000104.t003

Factors associated with attitudes TB infection.

Contrary to the overall knowledge scores, attitudes towards TB infection control was negatively associated with the education status of the adults. Irrespective of place of residence, adults with secondary had 5.2 significantly less scores of having negative attitudes as compared to those never been to school or with informal education (β = -5.2, 95%CI = -7.2, -3.4; p = 0.001). Likewise, adults with higher than secondary education had 4.3 less scores of having negative attitudes as compared to those never been to school or with informal education (β = -4.3, 95%CI = -6.8, -1.9; p = 0.001) ( Table 4 ).

https://doi.org/10.1371/journal.pgph.0000104.t004

While peasants and livestock keepers were negatively associated with positive attitudes towards TB infection control, adults working for salaries were positively associated with positive attitudes towards TB infection control. Peasant and livestock keepers had 2.6 less of having negative attitudes as compared to unemployed adults (β = -2.6, 95%CI = -3.5, -1.7; p = 0.001). Salaried adults were positively associated with attitudes towards TB infection control such that they had 2.1 higher scores of attitudes as compared to unemployed adults (β = 2.1, 95%CI = 0.2, 3.9; p = 0.017).

Factors associated with practices towards TB control.

In Table 5 , we present multiple linear regression analysis outcomes of scores of practices towards TB prevention and control on selected individual-level variables. Education was negatively associated with scores of practices towards TB control. An adult with primary education had 0.6 less scores of practices towards TB preventive control measures as compared to adults who have never been to school or those with informal education, (β = -0.6, 95%CI = -1.0, -0.3; p = 0.001). Similarly, controlling for residence, adults with secondary education had 1.4 less scores of practices towards TB control as compared to those never been in school or having informal education (β = -1.4, 95%CI = -1.9, -1.0; p = 0.001).

https://doi.org/10.1371/journal.pgph.0000104.t005

In addition, peasants and respondents engaging in livestock keeping were significant negatively associated with scores of practices towards TB infection control (β = -0.4, 95%CI = -0.7, -0.1; p = 0.010) ( Table 5 ).

In this study, we assessed knowledge, attitudes and practices towards prevention and control measures against TB infection among rural and urban adult populations in northeast Tanzania. Although the majority (95%) of adults from the study area are aware of TB, less than half (44%) has good overall knowledge about TB infection. In this study, the proportion of the study participants with good overall knowledge is almost the same as that of Nigeria but lower than in the Gambian study [ 26 , 27 ]. The variation in the proportions of population with good knowledge about TB infection between urban and rural in not a new phenomenon. For example, a study in Lesotho [ 20 ], Ethiopia [ 22 ] and Nigeria [ 26 ] have also reported differences of TB knowledge between urban and rural communities. One possible explanation for the underlying source of variability in the good overall knowledge between rural and urban could be the education status that favors most of the population in urban area [ 36 ].

Despite a larger proportion of adults having good knowledge on symptoms, transmission and good practices about TB infection, it is surprising that as few as only 11% have positive attitudes towards the TB infection. This level is in contrast with recent figures from Nigeria, Gambia and Ethiopia [ 26 , 27 , 37 ]. In 2019, a study in Nigeria reported a link between education among men and their families and TB knowledge scores [ 38 ]. Furthermore, Balogun, et al., report the association between knowledge and attitudes in Nigeria [ 24 ]. Nevertheless, negative attitudes will always imply poor health seeking behaviours and adherence to medications.

It is of critical importance to underscore the knowledge gap especially of TB transmission in rural areas in this study. It is underscored that inadequate knowledge about TB symptoms and transmission is among the threats to employ good prevention practices [ 24 , 27 , 31 , 39 ]. Therefore, one of the implications from this study is that, with poor knowledge and negative attitudes towards TB it is likely the community will have poor efforts in prevention practices against TB infection and possibly end up with limited health care seeking behaviors [ 40 , 41 ].

In this study, there is a negative association between practice and attitudes towards TB infection control and adults working as peasants or livestock keepers. Although the negative attitudes about TB has also been reported in Ethiopia more among livestock keepers than the sedentary communities [ 38 ], the mechanism through which both negative attitudes and practice evolve are unclear. However, in the same study in Ethiopia, they mention the observed high overall perceived stigma could be contributing to a negative attitudes [ 38 ].

It is imperative to note that more than 70% of the population in Tanzania resides in rural areas [ 42 ]. Having a substantial variability between rural and urban communities with respect to knowledge, attitudes and practices towards prevention and control of TB infection favoring the urban population, suggests for strategies to find ways of imparting TB knowledge on symptoms and transmission specifically to the rural population as long as this phenomenon is consistent even in other areas.

There are variations of KAP definitions in different health-related behaviours between and within countries. Therefore, even after benchmarking our tool against other similar studies at national and international levels and the further validation in terms of its face and content, the differences we are observing in this study could be a result of the variability in KAP definition.

Our study has several potential limitations. One, although we maximally trained our research assistants, who had also medical background, we cannot rule out the possibility of social desirability bias. Two, due to the literacy level among our study participants especially in rural areas, we decided to use a face-to-face interview schedule. In spite of its merits, one of the disadvantages of this survey method is the possibility of having the interviewer effects leading to the interviewer bias. The extensive training of the research assistants could have reduced this bias.

Conclusions

In conclusion, TB awareness among adults in rural and urban areas of northeast Tanzania is very high. Adults have inadequate overall knowledge and extremely negative attitudes towards TB. The most disadvantaged adults are those residing in rural than their counterparts in urban settings. Factors that were strongly associated with scores on knowledge, attitudes and practices included education (primary, secondary and above secondary) and the main source of income (peasantry/livestock keeping and salaried). Findings from this study suggest the need to have community-health campaigns especially among rural communities. In order to improve community members’ knowledge, attitudes and practices towards the prevention and control of TB in Tanzania, we recommend focused community-based campaigns to educate the rural and urban communities on several aspects of TB. Furthermore, a comprehensive health education strategy is needed to patients and their supporters visiting the health facilities and outreach stations. We recommend for further research to examine possible sources of the negative association between education status and scores of attitude and practices on TB infection control.

Supporting information

S1 file. tb questionnaire english..

Questionnaire in English version.

https://doi.org/10.1371/journal.pgph.0000104.s001

S2 File. TB Questionnaire Kiswahili.

Questionnaire in Kiswahili version.

https://doi.org/10.1371/journal.pgph.0000104.s002

S3 File. TB Tanzania data.

Data file in SPSS data format.

https://doi.org/10.1371/journal.pgph.0000104.s003

Acknowledgments

We thank Prof. Anna Tengia-Kessy for constructive comments and support during development of the manuscript.

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• Open access
• Published: 27 May 2021

Knowledge, attitudes and practices regarding tuberculosis amongst healthcare workers in Moyen-Ogooué Province, Gabon

• Anja Vigenschow 1 , 2 ,
• Jean Ronald Edoa 1 ,
• Bayode Romeo Adegbite 1 , 3 ,
• Pacome Achimi Agbo 1 ,
• Ayola A. Adegnika 1 , 2 ,
• Abraham Alabi 1 ,
• Marguerite Massinga-Loembe 1 , 2 &
• Martin P. Grobusch 1 , 2 , 3  

BMC Infectious Diseases volume  21 , Article number:  486 ( 2021 ) Cite this article

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Metrics details

In countries with a high tuberculosis incidence such as Gabon, healthcare workers are at enhanced risk to become infected with tuberculosis due to their occupational exposure. In addition, transmission can occur between patients and visitors, if a tuberculosis infection is not suspected in time. Knowledge about tuberculosis and correct infection control measures are therefore highly relevant in healthcare settings.

We conducted an interviewer-administered knowledge, attitude and practice survey amongst healthcare workers in 20 healthcare facilities at all levels in the Moyen-Ogooué province, Gabon. Correctly answered knowledge questions were scored and then categorised into four knowledge levels. Additionally, factors associated with high knowledge levels were identified. Fisher’s Exact test was used to identify factors associated with high knowledge levels.

A total of 103 questionnaires were completed by various healthcare personnel. The most-frequently scored category was ‘intermediate knowledge’, which was scored by 40.8% (42/103), followed by ‘good knowledge’ with 28.2% (29/103) and ‘poor knowledge’ with 21.4% (22/103) of participating healthcare workers, respectively. ‘Excellent knowledge’ was achieved by 9.7% (10/103) of the interviewees. Apart from the profession, education level, type of employing healthcare facility, as well as former training on tuberculosis were significantly associated with high knowledge scores.

Attitudes were generally positive towards tuberculosis infection control efforts. Of note, healthcare workers reported that infection control measures were not consistently practiced; 72.8% (75/103) of the participants were scared of becoming infected with tuberculosis, and 98.1% saw a need for improvement of local tuberculosis control.

Conclusions

The survey results lead to the assumption that healthcare workers in the Moyen-Ogooué province are at high risk to become infected with tuberculosis. There is an urgent need for improvement of tuberculosis infection control training for local healthcare personnel, particularly for less trained staff such as assistant nurses. Furthermore, the lack of adequate infection control measures reported by staff could possibly be correlated with a lack of adequate facility structures and protective equipment and requires further investigation.

Peer Review reports

Healthcare workers (HCWs) play a fundamental role in the global fight against tuberculosis (TB). However, HCWs have a high risk of becoming infected with TB themselves, as they are often exposed to TB patients [ 1 , 2 , 3 ]. A recent meta-analysis found an approximately three-times higher incidence of active TB amongst HCWs as compared to the general population [ 4 ]. Occupational TB prevention and infection control (TBIC) measures in healthcare facilities are therefore of paramount importance.

In low-and-middle-income country (LMIC) settings such as Gabon, TBIC often poses challenges. The World Health Organization (WHO) recommends managerial, administrative and environmental controls that are feasible in all settings [ 5 ]. Those recommendations comprise, amongst others, the implementation of an infection control plan, triaging of presumed TB cases, regular TB screening amongst HCWs and optimising natural ventilation in the facility. In addition, the availability and correct use of particular respirators are an important personal protective measure.

In Gabon, TB is a significant public health problem and ranks amongst the main causes of death. In 2019, the prevalence of HIV was estimated at 2.35% (2348 cases per 100.000 population) [ 6 ]. The estimated incidence of TB was 521 cases per 100.000 population, with 22/100.000 population cases of multi-drug resistant (MDR-) and rifampicin-resistant (RR-) TB. The mortality rate was 147/100.000 population and therefore the third-highest in the world [ 7 ]. Thus, Gabon ranks amongst the countries with the highest TB incidence in the world. Regarding the high TB incidence and the absence of national TBIC guidelines at the time of the study, we assume that HCWs in Gabon are at high risk to become infected with TB, and thus to develop active disease. The situation is aggravated by a considerable HIV prevalence as well as a high proportion of MDR-TB [ 8 , 9 , 10 ]. At the time of the study, there was no systematic TB training program implemented for HCWs in Gabon.

For effective infection control and TB management, essential knowledge about TB is crucial. We therefore conducted a knowledge, attitude and practice (KAP) survey amongst HCWs in 20 healthcare facilities in Moyen-Ogooué province, Gabon, in order to assess HCWs awareness of the disease and to gain insight into currently practiced infection control measures.

Study population

Participants were included at 20 individual healthcare facilities at different levels of the healthcare pyramid in Moyen-Ogooué province. These included the two hospitals of Lambaréné (one public and one private), the province’s capital, an ambulatory HIV clinic and 17 rural dispensaries. Despite being chosen conveniently, the sites provide a fair representation of all primary and intermediate healthcare services of Moyen-Ogooué province. In the two hospitals, participants were recruited at departments that were considered as high-risk areas of TB transmission, including the outpatient, radiology and emergency departments as well as the internal medicine and paediatric wards. Each department as well as the HIV clinic was visited on two to three days, and all employees present during this period were asked to participate. Due to their small number of staff, dispensaries were visited on a single day only.

Survey questionnaire

We conducted the KAP survey based on an interviewer-administered questionnaire, which was specifically designed for the study. Questions were partly based on a TB KAP survey manual [ 11 ]. The questionnaire was validated in a pilot study with 10 HCWs from the local research center, and adjusted accordingly. The survey comprised 11 socio-demographic variables, 16 knowledge questions including six questions with multiple possible correct answers, nine attitude questions and 10 practice questions. The questionnaire is provided as Supplement 1 .

Study procedures

Interviews were held between November 2016 and March 2017. Open questions were read out to the interviewees, and, if necessary, non-leading explanations were given. All interviews were held by the same investigator during working hours in the respective facility. Answers given to the open questions were then documented in terms of pre-defined categories. Each correct answer given to a knowledge question was scored 1. The maximum score achievable was 27. Knowledge levels were categorised as ‘excellent’ (> 80% correct answers), ‘good’ (> 60–80%), ‘intermediate’ (> 40–60%) and ‘poor’ (< 40%). Attitudes and practices were collected as qualitative data only.

Statistical analysis

Knowledge levels amongst different healthcare workers were compared using cross-tabulation. Given the small numbers, Fisher’s exact test, was used to assess the correlation of influencing factors with knowledge levels. Statistical analysis was performed with IBM SPSS (Version 24). The p -value of 5% was considered statistically significant.

Ethical considerations

All methods were performed in accordance with the relevant guidelines and regulations. Survey participation was voluntary, and written informed consent was obtained from all participants prior to the interviews. The questionnaires were completely anonymous and did not contain any personal identifying information. Authorisation was obtained from the regional health director of Moyen-Ogooué province as well as the institutional ethics committee of CERMEL (reference number: CEI-CERMEL 008/2016).

Study population characteristics

Out of the 103 questionnaires, 68 (66.0%) were completed at the two hospitals, followed by 25 (24.3%) at the dispensaries and 10 (0.7%) at the regional HIV clinic. Interviewees represented a cross-section of the various relevant health professions involved (Table  1 ). Work experience of the interviewees across professions ranged from one month to 38 years (mean 11.5 years; SD = 7.6).

Knowledge levels

Table 1 displays knowledge levels of different groups of HCWs. The category ‘intermediate knowledge’ comprises 42 HCWs and therewith the largest number of respondents (40.8%). This was followed by ‘good knowledge’ with 29 (28.2%) HCWs. The knowledge category ‘poor’ was scored by 22 (21.4%) respondents. Ten HCWs (9.7%) achieved ‘excellent’ knowledge scores in the questionnaire.

The mean knowledge score was 10 (SD = 3.7) for auxiliary nurses, 14.2 (SD = 1) for assistant nurses, 17.7 (SD = 2.8) for nurses, 22.4 (SD = 1.4) for physicians, and 12.5 (SD = 2.7) for other HCWs.

Factors associated with knowledge levels

Since not all subgroups included physicians, who had overall good or excellent knowledge, Fisher’s exact test was only conducted on the other 93 HCWs.

As presented in Table  2 ; age, gender, work experience, and family TB cases did not have any significant influence on knowledge about TB. Statistically significant associations with higher knowledge levels were found regarding the level of education ( p  = 0.001), type of healthcare facility ( p  = 0.018), and former TB training ( p  = 0.001).

Answers given by HCWs to questions about their attitude towards TB are presented in Table  3 . While 84 HCWs (81.6%) affirmed that they could get TB themselves, 15 HCWs (14.6%) claimed that they could not be infected. The explanations provided for this assumption were: (1) BCG vaccination ( n  = 7; 46.7%); (2) lack of exposure due to sufficient precautions ( n  = 4; 26.7%).

The majority ( n  = 75, 72.8%) was scared of getting TB and named the following reasons (multiple answers were possible): (1) severity of active TB infection ( n  = 35, 46.7%); (2) risk of infecting a family member ( n  = 21, 28.0%); and (3) long duration and/or adverse effects of TB treatment ( n  = 20; 26.7%).

Fear of death, social isolation and irreversible damage to the lung were further reasons given by the respondents.

Almost all HCWs ( n  = 97; 94.2%) said that they would keep seeing a friend who was diagnosed with TB; however, 91 (88.3%) would not continue to use the same cutlery, plates and glasses if someone in their family was infected with TB. TB was considered as a stigmatising disease by 65 HCWs (63.1%).

Except for two HCWs, all respondents said that they wished to learn more about TB; and 100 (97.1%) would approve to be screened regularly for TB. Most HCWs ( n  = 98; 95.1%) considered TB as a major public health problem in Gabon; and 101 (98.1%) saw a need for improvement in regional TB control. The following three measures were the most-frequently suggested ideas to improve general TB control (multiple answers possible): (1) conduction of awareness-raising campaigns ( n  = 70; 68,0%); (2) intensifying case finding ( n  = 16; 15.5%); and (3) vaccination programs ( n  = 10; 9.7%).

Table  4 presents various TB infection control measures and the number of HCWs who reported to practice them. The majority ( n  = 82; 79.6%) would suspect TB infection in a patient presenting with a chronic cough, and 50 (48.5%) would separate them from other patients. About half of the interviewed HCWs ( n  = 56; 54.4%) reported to wear a face mask when being with a coughing patient, whereas 73 (70.9%) would wear one when TB infection was confirmed. Ensuring cough hygiene by providing a mask to coughing patients was named by 55 (53.4%).

In order to increase the natural ventilation as an environmental TB control measure, 69 (67%) of the respondents would open windows and doors and only 16 (15.5%) would make use of a fan. Triage by prioritising coughing patients was reported to be practiced by 32 (31.1%) HCWs.

Patient education in terms of providing information about TB to newly diagnosed TB patients was practiced by 63 (61.2%) of the HCWs, and 77 (74.8%) would give cough hygiene instructions to patients with a cough.

This study provides insight into the knowledge levels about TB of all kinds of HCWs in the Moyen-Ogooué province and can help to elaborate future training programs. In their study from South Africa, Naidoo et al. showed that training programs for HCWs can increase their knowledge levels significantly [ 12 ].

Not surprisingly, well-trained HCWs with a university degree or state’s diploma had good and excellent knowledge about TB. However, they represent the smallest portion of personnel working in regional healthcare facilities. Almost two-thirds of the respondents were auxiliary or assistant nurses, who had significantly lower knowledge levels. In conclusion, as knowledge about TB is evolving, TB training updates should be made available to all levels of HCWs; however, the emphasis of the training efforts should be on focused need-tailored TB training for HCWs with lower professional degrees and thus facilitate improvements for the broad majority of their staff.

Factors associated with good knowledge

The study identified factors associated with good knowledge levels in order to determine which group of HCWs needs to be focused on. The professional level, and accordingly, the highest level of education, were both significantly associated with good knowledge about TB. In addition, HCWs who had received former TB training, irrespective of the extent of training, had significantly higher knowledge levels than their colleagues. Work experience, however, was not statistically associated with good knowledge about TB. These findings empathise the importance of regular training.

HCWs in hospitals had generally better knowledge levels than in dispensaries, which can lead to the assumption that primary healthcare services, particularly in rural areas, are often neglected in training programs.

These findings are comparable to the factors identified in a KAP survey conducted amongst healthcare workers in Mozambique, which also showed an association of knowledge scores with the level of education and profession, while gender and age did not have any significant influence [ 13 ].

The fact that the majority of the participants would not share the same cutlery, plates and glasses with a TB infected family member implies that there are common knowledge gaps about the ways of TB transmission. This can possibly promote stigmatisation and social exclusion of TB-infected individuals. The idea that TB can be transmitted by eating from the same plate was also found in other surveys [ 14 , 15 ].

Almost two-thirds of the HCWs considered TB as a stigmatising disease. A study with TB patients in Lambaréné from 2013 found similar perceptions, as the majority of the patients had experienced stigma themselves [ 16 ]. Nevertheless, almost all HCWs would agree to get themselves tested for TB regularly. In addition, most respondents stated that they would like to learn more about TB. Studies from other countries have shown a similar positive attitude of HCWs towards TBIC [ 17 ].

Most respondents saw a need for improvement of regional TB control and perceived it as a major public health threat. The high awareness amongst HCWs of TB being a serious health issue in their region is an optimal pre-condition for new TBIC policies implementation as well as training programs. The fact that 72.8% of HCWs were scared of becoming infected with TB emphasises even more the urgent need for action.

Good practice

The reasons why certain TBIC measures were practiced or not were not implied in the survey. The absence of resources such as appropriate respirators or fans was not taken into account in the questionnaire.

About half of the respondents said that they would wear a mask when dealing with a coughing patient. However, since appropriate respirators were unavailable in most facilities, HCWs were referring to surgical masks, which are most appropriate when worn by the patient. A study from Uganda has shown that only a third of the HCWs knew that a surgical mask would not adequately protect them from getting TB from a patient [ 18 ]. Therefore, training programs should not only explain in what situation the use of a mask is adequate, but also which kind of mask would be the most appropriate for the patient and the attending HCW, respectively. Almost the same number of HCWs reported to provide coughing patients with a surgical mask. Due to the general lack of resources, particularly in primary healthcare facilities such as dispensaries, this is not surprising. On the other hand, it could also be attributed to the fear of stigmatising patients. As mentioned above, this could not be concluded from the survey and requires further investigation.

Nosocomial transmission is less likely if the time a TB patient spends in the facility is reduced to a minimum, which is one of the key recommendations of the so-called FAST strategy, an administrative approach to TBIC that is also feasible in LMIC settings [ 19 ]. The survey findings indicate that most HCWs were not aware of the importance of this measure, as less than a third of them reported to prioritise coughing patients in the admission process. Once implemented into the patient management routine, this TBIC measure can prevent transmission within the facility, particularly in waiting areas.

Only a minority reported to turn on a fan in order to direct the airflow away from them when receiving a TB patient, as it is recommended by WHO [ 20 ]. However, fans were unavailable in most facilities. Despite the economical advantage and high effectiveness of natural ventilation compared to mechanical ventilation [ 21 ], only about two-thirds of the interviewees reported to open doors and windows when dealing with an infectious TB patient. This possibly indicates a general lack of awareness towards environmental measures.

Strengths and limitations

Several KAP surveys relating to TB control have been conducted all over the world. However, this was the first survey conducted amongst HCWs in Gabon. Although the sample size is relatively small, the study population represents the full range of healthcare workers in the Moyen-Ogooué province. Another strength of the study was that the survey was carried out as personal interviews and thus had a maximum response rate. The interviews were all carried out by the same interviewer, ensuring that questions were asked in the same way, leading to comparable responses. Most surveys assessing knowledge levels about TB were designed as self-administered multiple-choice questions, allowing to guess the correct answer. Due to the open question format, the survey allowed insight into the actual awareness level of HCWs about TB.

General conclusions

There is no data available regarding the actual TB incidence amongst HCWs in Gabon. However, the survey findings suggest that due to a lack of general knowledge about TBIC, they are not adequately protected. However, HCWs seemed to be generally motivated for training and open for screening procedures amongst themselves, even though many perceived TB as a stigmatising disease.

Way forward

Standardized TBIC training of HCWs should be implemented on a national level with focus on assistant nurses, as they represent the primary healthcare level in Gabon. Another crucial step is the implementation of administrative measures in the daily routine work. In order to improve practices, resources for effective TBIC need to be available in all facilities, particularly personal protective equipment such as N-95 respirators for HCWs and a sufficient supply of surgical masks for TB patients. Although stigma did not seem to be problematic amongst HCWs themselves, awareness campaigns should also be conducted amongst the general population, as misbeliefs about TB increase stigma, thus hampering TB control efforts in the country.

Availability of data and materials

The datasets used and analysed in the framework of this study can be requested from the corresponding author.

Abbreviations

Centre de Recherches Médicales de Lambaréné

• Healthcare workers

Human immunodeficiency virus

Knowledge, attitudes and practices

Low-and-middle-income country

Multi-drug resistant tuberculosis

• Tuberculosis

Tuberculosis infection control

World Health Organization

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Acknowledgements

We are indebted to all health care workers who contributed to this study.

This work was funded by Deutsches Zentrum fuer Infektiologie (DZIF) as part of its support for routine data collection and description of the epidemiology of tuberculosis in Lambaréné.

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AV, MML and MPG conceived the study and developed the protocol. All authors contributed to data interpretation. AV drafted the paper, and AAA, JRE, AA, BRA and PAA contributed to its final version, and approved submission of the manuscript. The data of this manuscript formed part of AV’s German (Dr. med.) doctoral thesis. The authors read and approved the final manuscript.

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Vigenschow, A., Edoa, J.R., Adegbite, B.R. et al. Knowledge, attitudes and practices regarding tuberculosis amongst healthcare workers in Moyen-Ogooué Province, Gabon. BMC Infect Dis 21 , 486 (2021). https://doi.org/10.1186/s12879-021-06225-1

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WHO says we can 'write the final chapter in the story of TB.' How close are we?

A doctor checks chest x-rays of a tuberculosis patient at a clinic in Mumbai, India, that treats those with drug-resistant strains of the disease. The World Health Organization has called for the eradication of this ancient and deadly infectious disease. Punit Paranjpe/AFP via Getty Images hide caption

A doctor checks chest x-rays of a tuberculosis patient at a clinic in Mumbai, India, that treats those with drug-resistant strains of the disease. The World Health Organization has called for the eradication of this ancient and deadly infectious disease.

The head of the World Health Organization is eager to wipe out one of the oldest and deadliest diseases.

Last week Tedros Adhanom Ghebreyesus declared: "We have an opportunity that no generation in the history of humanity has had: the opportunity to write the final chapter in the story of TB."

It's a story that began thousands of years ago. One history of TB notes: "Fragments of the spinal column from Egyptian mummies from 2400 BCE show definite signs of tuberculosis."

But as events of 2023 illustrate, there are a few chapters still to be written before Tedros's dream could come true.

Encouraging news about a familiar drug

A promising way to prevent the spread of drug-resistant tuberculosis was announced at the Union World Conference on Lung Health on Thursday in Paris.

Two clinical trials, conducted in South Africa and Vietnam, looked at levofloxacin, one of the antibiotics most commonly used to treat people who've developed drug-resistant TB. Now there's strong evidence that taking the drug can reduce the risk of developing drug-resistant strains of the bacterial disease by about 60%. Researchers say the treatment was safe and effective in both children and adults living in environments with high exposure to multi-drug resistant strains, like the two countries where the trials took place.

"Yes, you can actually prevent drug-resistant TB," says Dr. Anneke Hesseling , a TB researcher and pediatrician at Stellenbosch University who was the overall principal investigator for one of the trials. "So that is very compelling. It's like giving an effective vaccine to kids.

Hesseling hopes the new data will inform global TB guidelines going forward.

Pandemic setbacks ...

But the challenges of conquering TB remain daunting — and the pandemic is partly to blame.

As the World Health Organization puts it: "The COVID-19 pandemic has reversed years of progress made in the flight to end tuberculosis."

The focus on SARS-CoV-2 disrupted the ability of health systems to diagnose and treat people with TB – and has meant fewer resources "for essential TB services" as well as for the development of future treatments.

In a new report, WHO painted a bleak picture of the disease's toll.

Globally an estimated 10.6 million people fell ill with TB in 2022, up from 10.3 million in 2021. Before the pandemic, TB had been on the downswing.

And even though COVID dislodged TB from the notorious title of "deadliest infectious disease" based on annual death counts –TB did remain a major killer, with 1.3 million TB-related deaths in 2022.

What's more, it looks as if in 2023, with COVID deaths waning, TB could regain its top berth, says Dr. Anand Date , chief, global TB at the Centers for Disease Control and Prevention.

... and challenges that lie ahead

Other findings illustrate what a challenge it will be to fulfill Tedros's prediction:

• The U.N.'s has been to reduce TB-related deaths by 75% in the ten years from 2015 to 2025 is far from being realized. From 2015 to 2022, TB-related deaths fell only 19%.
• Of the 30 million people with TB who are targeted for preventive treatment, only 52% received such care.
• Fund-raising is lagging. In 2018, WHO set a goal of $13 billion in annual global funding for essential TB services in low- and middle-income countries during the United Nations General Assembly first-ever high-level meeting on tuberculosis. The current assessment: Less than half of that amount is available on a yearly basis.

This spring, an expert panel convened this spring by the Gates Foundation (which is a funder of NPR and this blog), discussed what needs to be done to better vanquish TB. Among the concerns is the way the disease is diagnosed.

The most common diagnostic method is 130 years old – and not highly effective. Health workers use a microscope to check sputum samples for the telltale rod-shaped bacteria that indicate TB. (Sputum is the mix of saliva and mucus coughed up from the respiratory tract.)

The microscope method is in wide use because it's the least expensive way to diagnosis TB, says Dr. Madukar Pai , head of epidemiology, biostatistics and occupational health at McGill University. Newer molecular lab tests are more sensitive to picking up an infection and can also test for drug resistance in sputum samples, he says. In a 2023 commentary in Nature Microbiology, Pai notes that "although the World Health Organization recommends molecular diagnostics as the preferred frontline testing option, only 38% of all notified cases in 2021 were tested with a WHO-recommended rapid molecular diagnostic at initial diagnosis.

As for vaccines – the only one available is effective only in infants and small children and offers roughly a 70% rate of protection..

But it's not given to older kids and adults. And if they do contract TB, access to the best drugs is spotty.

Even though there's a six-month regimen of oral drugs effective for most forms of TB, many countries can't afford to provide this type of care, says Dr. Date. The less expensive alternative is a yearlong course of 20 daily pills plus several shots. Side effects can include psychosis, extreme vomiting and loss of hearing. Patients often stop the arduous longer treatment courses, says Carole Mitnick , a professor of global health and social medicine at Harvard Medical School, "leaving them at risk for developing harder to treat [drug] resistant TB and for exposing others to the infection."

A patent expiration is welcomed by advocates

At least one drug may soon be more affordable for lower income countries.

This year the patent was due to expire on one of the more effective drugs in the six-month regimen: bedaquiline. That would mean a less expensive generic version could be manufactured.

In September, after a summer of pressure from advocacy groups and their allies, Johnson & Johnson announced that it wouldn't enforce secondary patents it took out on the drug, based on a small modification. Those patents would have meant no generic versions in the immediate future.

The news was welcomed as a boon for wider availability of the drug. According to Doctors Without Borders, "bedaquiline is the backbone of almost all treatment combinations newly recommended by the World Health Organization (WHO) for drug resistant TB" and is the most expensive in the 6-month oral regiment, "accounting for $272 out of the total $570 price. J&J currently prices the drug at $1.50 a day for an adult. That should fall to 50 cents per day and should free up more funds in lower- and middle-income countries to treat TB with the regimen," says Christophe Perrin, a pharmacist with MSF.

Another key weapon in the fight against TB will also be more affordable moving forward. The GeneXpert, a rapid laboratory diagnostic test made by Cepheid, tests a patient's sputum and can both detect TB and determine if it is resistant to certain drugs for TB. With such results, health providers avoid wasting time on drugs that won't work, Pai says. Advocacy groups were successful this year in getting Cepheid to drop its price this summer.

But it's still not an ideal test. Pai says the ultimate best test will be a home test like the ones developed for COVID-19 which could deliver comparable results to the Cepheid product.

And then ... there's $$

Developing a home test would of course take money.

And advocates are well aware of the funding shortfalls.

Mel Spigelman, president of the TB Alliance, a nonprofit working on treatments, says "the greatest barrier" to progress is "lack of funding and investment" –needed for research and development of diagnostics, drugs, health infrastructure – and vaccines.

The CDC's Date says increased funds could speed up testing of about 15 to 20 vaccines now in the pipeline, including one, M72, which is 50% effective in ongoing clinical trials. Emilio Emini, CEO of the Bill & Melinda Gates Medical Research Institute, which will conduct a late-stage clinical trial for M72 starting early next year, says, "one quarter of the global population is latently infected with TB and each year 10 million of these people develop active tuberculosis resulting in 1.5 million deaths. Given the numbers, a vaccine with even 50% efficacy can have substantial public health impact."

Ari Daniel of NPR also contributed to this story.

Fran Kritz is a health policy reporter based in Washington, D.C., and a regular contributor to NPR. She also reports for the Washington Post and Verywell Health . Find her on Twitter: @fkritz

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Thesis and dissertations examining tuberculosis in Brazil between 2013 and 2019: an overview

Ana júlia reis.

1 Universidade Federal do Rio Grande, Faculdade de Medicina, Núcleo de Pesquisa em Microbiologia Médica, Rio Grande, RS, Brasil.

Juliana Lemos Dal Pizzol

Rúbia gattelli.

2 Universidade Federal do Rio Grande, Biblioteca Setorial da Área Acadêmica da Saúde, Rio Grande, RS, Brasil.

Andrea von Groll

Daniela fernandes ramos, ivy bastos ramis, afrânio kritski.

3 Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Programa Acadêmico de Tuberculose, Rio de Janeiro, RJ, Brasil.

José Roberto Lapa e Silva

Pedro eduardo almeida da silva.

Authors' contribution: AJR, JLDP, RG, IBR, PEAS: Paper conception and planning, as well as the evidence interpretation; AJR, JLDP, RG, AvG, DFR, IBR, AK, JRLS, PEAS: Writing and/or reviewing the preliminary and definitive versions; AJR, JLDP, RG, AvG, DFR, IBR, AK, JRLS, PEAS: Final version approval.

Background:

Tuberculosis (TB) remains a serious public health problem, with approximately 10 million new cases reported annually. Knowledge about the quantitative evolution of theses and dissertations (T&Ds) examining human TB in Brazil can contribute to generating strategic planning for training professionals in this field and disease control. Therefore, this study highlights the role of T&Ds on TB in national scientific disclosures.

An integrative review related to TB was performed, including T&Ds produced in Brazil and completed between 2013 and 2019.

A total of 559,457 T&Ds were produced, of which 1,342 were associated with TB, accounting for 0.24% of the total number of T&Ds in Brazil. This was evidenced by a predominance of themes such as attention/health care, epidemiology, and TB treatment, and 80.2% of the T&Ds on TB were related to the large areas of health and biological sciences. Only 19.7% of T&Ds were associated with groups of patients considered at risk for TB, and 50.9% were produced in southeastern Brazil. The 1,342 T&Ds on TB were developed in 416 postgraduate programs linked to 121 higher education institutions (HEIs). We highlight that 72.7% of T&Ds on TB were produced in federal HEIs, 27.4% in state HEIs, and 8.5% in private HEIs.

Conclusions:

Strategic themes, such as TB control, require public policies that aim to increase the number of doctors and masters with expertise in TB, with geographic uniformity, and in line with the priorities for disease control.

INTRODUCTION

Tuberculosis (TB) remains a serious public health problem and is responsible for approximately 10 million new cases and 1.5 million deaths annually. Moreover, it is one of the main causes of death caused by a single infectious agent. Brazil is a priority country for this public health problem 1 , with approximately 90,000 new cases per year and a TB/human immunodeficiency virus (HIV) coinfection proportion of 11% 2 .

At the World Health Assembly in 2014, the World Health Organization approved the End Tuberculosis Strategy. Their main objectives were to reduce 90% of TB cases and 95% of TB deaths by 2035. In addition, the strategy aims to eliminate or minimize the economic impact on families affected by TB 3 . In the following year, the United Nations launched the Sustainable Development Goals, which included a 90% reduction in deaths caused by TB by 2030 4 , 5 .

Brazil's National Tuberculosis Control Program has used several strategies to control the disease, most of which are consistent with scientific evidence and guidelines recommended by the World Health Organization. This effort has resulted in improvements in epidemiological indicators, such as a reduction in the incidence and mortality of TB 6 , 7 . However, there are still many challenges, such as TB in prisons, TB/HIV coinfection, drug-resistant TB, other comorbidities (e.g., diabetes mellitus, mental health disorder, alcohol, illicit drugs, and tobacco use), a high proportion of treatment abandonment, low adherence to directly observed treatment, low contact evaluation, latent TB diagnosis and treatment, low coverage of rapid molecular diagnosis, and a low proportion of patients and family members who receive social protection 6 , 8 .

The success of actions that support global and national TB control and elimination strategies depends on qualified professionals generating, evaluating, and correctly using scientific knowledge. In Brazil, doctors and masters (D&M) are formed within the National Postgraduate System, whose Postgraduate Programs (PGPs) are accredited and periodically evaluated using the Coordination of Higher-level Personnel Improvement (CAPES) evaluation system 9 .

Knowledge about the quantitative evolution of theses and dissertations (T&Ds) produced in the area of human TB, as well as information about the spatiotemporal, thematic, and institutional distribution and its relationship with the TB burden in different populations and regions of Brazil, can contribute to generating strategic planning for the training of professionals in this theme. In addition, this study highlights the essential role of T&Ds in national scientific disclosures.

An integrative review was performed, including T&Ds related to TB, completed between January 1, 2013 and December 31, 2019, and made available in the CAPES database. This study was carried out based on the principles of scientometrics, which consist of “Quantitative assessment and analysis of intercomparisons of activity, productivity, and scientific progress 10 . ”

T&Ds identification and classification were performed independently by two researchers using the T&Ds catalog made available using the CAPES (Ministry of Education, Federal Government, Brazil) in Portuguese at https://dadosabertos.capes.gov.br/dataset.

The search for T&Ds was performed using the following Portuguese terms: Mycobacterium tuberculosis, Mycobacteria , antituberculostatics, isoniazid, and rifampicin. In addition, authorized descriptors in Portuguese, synonyms/alternative terms, related terms, and generic terms were used (DeCS/MeSH Health Sciences Descriptors - https://decs.bvsalud.org/) ( Supplementary Material Table 1S ). T&Ds that had any of these terms in the title, abstract, or keywords I were selected.

After the initial screening, the selected T&Ds were individually analyzed by two researchers, and those that mentioned any of the terms used in the search ( Supplementary Material Table 1S ) but whose work content was not associated with TB were excluded. The data were analyzed considering each thesis and dissertation equivalent to a doctorate and master's degree (professional and academic), respectively. In addition, the following variables were evaluated: T&Ds theme, the total number of T&Ds on TB produced in Brazil, period of time for D&M academic formation, CAPES assessment area, CAPES large knowledge areas, CAPES knowledge areas, subareas, risk groups for TB included in T&Ds, and T&Ds geographic and institutional distribution.

According to the CAPES, the assessment areas are grouped into a large knowledge area, which in turn are grouped into knowledge areas and subareas (first level: large knowledge area: gathering of different knowledge areas, due to the affinity of their objects, cognitive methods, instrumental resources, and reflecting specific sociopolitical contexts; second level: knowledge area: set of interrelated knowledge, collectively constructed, gathered according to the nature of the investigation object, and for the purposes of teaching, research, and practical applications; and third level: subarea: segmentation of the knowledge area established according to the object of study and recognized and widely used methodological procedures) 11 .

T&Ds were classified into the following themes: attention/health care, biochemistry, diagnosis, drugs, epidemiology, genetics, immunology, resistance, and treatment. The classification was performed by searching for keyword II in Portuguese associated with different themes ( Supplementary Material List 1S ). For T&Ds related to more than one theme, the main theme and its associated themes were independently defined by two researchers.

Data were tabulated in Microsoft Excel and analyzed using International Business Machine (IBM) Statistical Package for the Social Sciences (SPSS) software version 20.0 (International Business Machines Corporation - IBM - Armonk - New York - USA). The absolute and relative frequencies were determined.

Between 2013 and 2019, considering all PGPs and knowledge areas, 559,457 T&Ds were produced in Brazil, of which 2,665 were initially selected as being associated with TB using the terms described in the Supplementary Material Table 1S . After an individual analysis, 1,342 T&Ds were selected for their association with TB, accounting for 0.24% of the total number of T&Ds produced in Brazil, of which 31.8% (427/1,342) were theses and 68.2% (915/1,342) were dissertations.

The total number of completed T&Ds in Brazil increased by 38.7% between 2013 and 2019, while the number of T&Ds on TB was proportionally reduced annually, beginning in 2014. When comparing 2013 and 2019, there was a 24.5% reduction in academic dissertations associated with TB, whereas the number of theses increased by 26%. Despite this, the number of theses concluded showed a 9% reduction between 2018 (the year with the greatest production) and 2019 ( Table 1 ).

* Total production and percentage of each production type per year in Brazil. ** Total productions and percentage of each type of production per year, associated with TB.

Between 2013 and 2019, there was a 77% increase in the number of professional dissertations. In 2016, professional master’s degrees represented 20.7% (41/198) of the T&Ds on TB produced in Brazil ( Table 1 ). Of these, 48.8% (20/41) were carried out in Rio de Janeiro, with 85% (17/20) linked to the PGP of Family Health and Epidemiology in public health, coordinated by the Fundação Oswaldo Cruz (Fiocruz); 29.3% (12/41) were carried out in the state of Pernambuco, with 66.7% (8/12) linked to the PGP of public health of the Fiocruz.

When evaluating the necessary time to complete the postgraduate course, only approximately half of the T&Ds - doctorate 52.5% (224/427), academic master's degree 52.5% (404/770), and professional master's degree 48.3% (70/145) - were completed within 48 (doctorate) and 24 (master’s) months, the periods expected for presenting T&Ds in Brazil.

Regarding the large knowledge areas, among the 1,342 T&Ds produced during the study period, 67.9% and 12.3% were related to health sciences and biological sciences, respectively. The remaining T&Ds (19.8%) were multidisciplinary (8.4%), exact and earth sciences (6.8%), engineering (1.3%), applied social sciences (1.0%), human sciences (1.1%), agricultural sciences (1.0%), and linguistics, letters, and arts (0.3%).

When the knowledge areas were evaluated, 67.4% of the T&Ds associated with TB were concentrated in medicine (27.8%), public health (16.7%), and nursing (13.5%) ( Table 2 ).

*administration (0.1% - 02/1,342); agronomy (0.4% - 06/1,342); botany (0.1% - 01/1,342); computer science (0.2% - 03/1,342); information science (0.1% - 02/1,342); food science and technology (0.1% - 01/1,342); political science (0.1% - 01/1,342); communication (0.1% - 01/1,342); ecology (0.1% - 01/1,342); economy (0.4% - 05/1,342); education (0.1% - 01/1,342); biomedical engineering (0.1% - 01/1,342); materials and metallurgical engineering (0.1% - 02/1,342); production engineering (0.1% - 02/1,342); mechanical engineering (0.1% - 01/1,342); nuclear engineering (0.1% - 01/1,342); chemical engineering (0.1% - 01/1,342); physics (0.3% - 04/1,342); geography (0.4% - 05/1,342); history (0.4% - 06/1,342); language (0.2% - 03/1,342); linguistics (0.1% - 01/1,342); mathematics (0.1% - 01/1,342); materials (0.4% - 05/1,342); veterinary medicine (0.4% - 05/1,342); morphology (0.1% - 01/1,342); nutrition (0.1% - 01/1,342); odontology (0.4% - 06/1,342); urban and regional planning (0.1% - 02/1,342); social service (0.1% - 01/1,342); sociology (0.1% - 02/1,342); zootechnics (0.1% - 01/1,342). **public and business administration, accounting science and tourism (0.1% - 02/1,342); astronomy/physics (0.3% - 04/1,342); biodiversity (0.1% - 02/1,342); computer science (0.2% - 03/1,342); food science (0.1% - 01/1,342); political science and international relations (0.1% - 01/1,342); agrarian sciences I (0,4% - 06/1342); biological sciences II (0.1% - 01/1,342); communication and information (0.2% - 03/1,342); economy (0.4% - 05/1,342); education (0.1% - 01/1,342); engineering II (0.3% - 04/1,342); engineering III (0.2% - 03/1,342); engineering IV (0.1% - 01/1,342,); geography (0.4% - 05/1,342); history (0.4% - 06/1,342); language/linguistics (0.1% - 01/1,342); linguistics and literature (0.2% - 03/1,342); mathematics/probability and statistics (0.1% - 01/1,342); materials (0.4% - 05/1,342); veterinary medicine (0.4% - 05/1,342); nutrition (0.1% - 01/1,342); odontology (0.4% - 06/1,342); urban and regional planning/demography (0.1% - 02/1,342); social service (0.1% - 01/1,342); sociology (0.1% - 02/1,342); zootechnics/fishing resources (0.1% - 01/1,342).

Almost all T&Ds within the knowledge area of medicine were related to the assessment areas of Medicine I and II. In the Medicine II assessment area, 209 T&Ds were concluded, with 38.8% on the infectious and parasitic diseases or tropical and infectious disease subareas. In the Medicine I assessment area, 162 T&Ds were concluded, with 53.7% distributed among the subareas of pulmonology, infectious diseases, and pneumological sciences. In addition to the subareas mentioned above, 26 other subareas were observed in the assessment area of Medicine I and 38 in Medicine II.

Thematic classification

T&Ds on TB were developed within a wide range of themes. Although 50.3% (675/1,342) of T&Ds could be classified as a single theme, 49.7% (667/1,342) were related to more than one theme, which was named “associated themes” in this study. With a predominance of themes, such as attention/health care, epidemiology, and treatment ( Supplementary Material Table 2S ), the association frequency between the main and associated themes was evaluated ( Figure 1 ).

T&Ds on TB were also classified according to the type of study, with 50.1% related to basic research (drugs, genetics, immunology, resistance, and biochemistry), 33.9% to translational research (attention/healthcare), 30.5% to epidemiological research, 26.7% to TB treatment, and 19.4% to TB diagnosis.

T&Ds associated with groups of patients at risk for tuberculosis development

Only 19.7% (264/1,342) of T&Ds cases were associated with groups of patients considered at risk for TB development ( Table 3 ), with 5.7% (15/264) associated with more than one risk group.

Source: National Congress, Federal Government. BRASIL, 1990: According to the Child and Teenagers Statute, were considered children those aged up to 12 years and teenagers those aged up to 18 years. Source: National Congress, Federal Government. BRASIL, 2003: According to the Elderly Statute, all patients aged > 60 years were considered. & Source: SINAN, 2021. Calculation based on the average per year of all TB cases in Brazil between 2013 and 2019 (89,104): # 12 children and teenagers (< 1 year, 1-4, 5-9, 10-14, and 15-19 years); * 13 and older adults (60-64, 65-69, 70-79, and ≥ 80 years).

T&Ds geographical and institutional distribution

The 1,342 T&Ds on TB were produced in 416 PGPs and linked to 121 higher education institutions (HEIs) ( Figure 2 ): 48.8% were federal, 19.8% were state, and 31.4% were private HEIs. Although approximately 1/3 (31.4%) of the HEIs were private, only 8.5% of the T&Ds on TB were produced in this type of institution, while 72.7% were in federal HEIs, and 27.4% were in state HEIs.

Overall, 50.9% of T&Ds on TB are produced in southeast Brazil. The state of Rio de Janeiro was responsible for 23% of T&Ds on TB produced in Brazil between 2013 and 2019, and 17.6% of T&Ds were produced in southern Brazil. Rio Grande do Sul produced 10% and 55.9% of T&Ds on TB in the country and southern Brazil, respectively. Finally, 16.8% and 8.2% of T&Ds were produced in the northeast and northern Brazil, respectively ( Supplementary Material Table S3 ).

Between 2013 and 2019, 0.24% of T&Ds produced in Brazil were associated with TB. According to a previous study, Brazil ranked sixth among countries that published the most on TB between 2007 and 2016, representing 3.8% of global publications associated with this theme 15 .

The total number of T&Ds in Brazil increased by 38.7% between 2013 and 2019, while the number of T&Ds on TB was proportionally reduced annually beginning in 2014, showing a reduction in the generation of D&M. This reduced formation of human capital in this area could put Brazilian TB control efforts at risk, harming the promotion, assistance, management, research, development, and innovation related to TB.

It is important to emphasize that the number of professional master's degree dissertations showed significant growth during the study period, which may be related to the fact that this is the newest modality of stricto sensu postgraduate study in recent years. For example, in 2016, the number of professional master's degrees represented 20.7% of the T&Ds on TB produced in Brazil, with a 77% increase when comparing 2013 and 2019.

In general, professional and academic master's degrees differ primarily in the formation of professionals who meet specific needs and have immediate applicability of the generated knowledge (professional) from those who will follow an academic career with a doctorate as their next goal (academic).

Regarding scholarships offered by the CAPES, there was an 11% increase in master's scholarships between 2011 and 2017 and a 23% increase in doctorate scholarships between 2010 and 2014 16 . Although there is a dissociation between the number of T&Ds on TB and the increase in scholarship offerings, the ratio between academic dissertations and theses decreased from 2.3 to 1.5 between 2013 and 2019, while the ratio between academic and professional dissertations decreased from 8.8 to 4.1 during the same period. These results indicate a policy to encourage the development of doctors and professional masters in relation to academic masters.

Although the CAPES recommended (before the coronavirus disease 2019 [COVID-19] pandemic) a maximum time for the training of masters and doctors of 24 and 48 months, respectively, only approximately half of the T&Ds on TB were completed within this time. Even though there is not necessarily a direct relationship between the deadline to complete the postgraduate course and the quality of T&Ds or the formation process, the time to complete a doctorate could be reduced through the implementation of strategies such as reducing the time for a master's degree to 1 year, as was recently proposed to the CAPES 17 .

As mentioned above, TB remains a serious public health problem in Brazil, with a high number of cases, a high proportion of TB/HIV coinfection, underreporting of cases (10-20% of undetected and/or untreated cases), high proportions of treatment abandonment, and a high incidence in vulnerable populations 1 , 6 , 18 . In this demanding scenario of needs and questions, T&Ds on TB were developed within a wide range of themes. There was a greater association between different themes, indicating an important multi-disciplinarity in the formation of D&M in the area of TB. This combination of themes boosts the formation of D&M with diverse skills and a broader view of problems.

Furthermore, according to previous studies 19 , 20 , T&Ds on TB were classified according to the type of study, with 50.1% related to basic research, 33.9% to translational research, 30.5% to epidemiological research, 26.7% to TB treatment, and 19.4% to TB diagnosis. A study evaluating publications on TB from BRICS countries (Brazil, Russia, India, China, and South Africa) indicated that 29.6% of publications were associated with epidemiological research, 33.8% with basic research, 13.1% with operational research, 10.1% with TB diagnosis, and 6.6% with TB treatment 15 .

When the groups of patients considered at risk for TB development were evaluated, we observed that only 19.7% of the T&Ds on TB were associated with these groups of patients, with 5.7% being associated with more than one risk group. Among the priority groups for TB control are people with positive serology for HIV (HIV+), prisoners, children/teenagers, indigenous individuals, health professionals, patients with diabetes mellitus, older adults, homeless populations, alcohol, drugs, and tobacco users 2 , 18 , only 8.2%, 2.9%, 2.5%, 1.6%, 1.5%, 1.3%, 0.8%, and 0.8% of T&Ds on TB were associated with these groups of patients, respectively. This dissonance between the main risk groups for TB development and the production of scientific knowledge, as well as the formation of professionals related to these essential issues, shows a precarious balance between academic needs and solutions, limiting the transfer of scientific benefits to the society. A significant number of TB cases in Brazil are among HIV+ patients, prisoners, children/teenagers, elderly people, and patients with diabetes mellitus 6 ; however, only 16% of the T&Ds on TB were associated with these groups of patients.

Brazil is a continental country with profound inter- and intra-regional social, economic, educational, and public health asymmetries. This diversity of scenarios is also observed in relation to the T&Ds produced within the TB theme. Most T&Ds were concentrated in southeastern and southern Brazil and were produced in PGPs from public HEIs, particularly federal HEIs. The necessary impetus for the formation of D&M in regions such as northern and northeastern Brazil can be facilitated by public policies using connections established by the Brazilian Tuberculosis Research Network (REDE-TB) 21 .

In southeast Brazil, where 45.2% of TB cases occur, with a prevalence of 45.9 cases per 100,000 inhabitants, which is higher than that of the overall prevalence in Brazil (41.9 cases per 100,000 inhabitants), 50.9% of T&Ds on TB were produced. The state of Rio de Janeiro, with a TB prevalence of 79.5 cases per 100,000 inhabitants, was responsible for 23% of T&Ds on TB produced between 2013 and 2019. In southern Brazil, where 12.7% of TB cases occurred, with a TB prevalence of 37.4 cases per 100,000 inhabitants, 17.6% of T&Ds on TB were produced. Interestingly, 26% of T&Ds produced in southern Brazil were associated with private HEIs. The state of Rio Grande do Sul has approximately 50% of the HEIs and PGPs in southern Brazil and produces 10% and 55.9% of T&Ds on TB in the country and southern region, respectively 2 , 14 .

Northeast Brazil, which was home to 26.3% of TB cases in Brazil between 2013 and 2019, produced 16.8% of T&Ds on TB. Despite having 10.9% of TB cases with a prevalence of 51.6 cases per 100,000 inhabitants, Northern Brazil produced only 8.2% of the T&Ds on TB. Finally, we highlight the state of Amazonas, which has the highest TB prevalence in Brazil, with 81.2 cases per 100,000 inhabitants, and produces only 3.1% of the T&Ds on TB. In both regions, northeast and northern Brazil, unlike in southeast and southern Brazil, there is a dissonance between the TB burden and the number of D&M formed in the TB theme, which is likely related to the lowest number of PGPs in these regions 2 , 14 .

D&M can act in government institutions and civil society, both public and private, as a protagonist in the promotion, production, evaluation, and implementation of scientific knowledge. Scientific knowledge generation, which is necessary to overcome the challenges faced by society, depends on investments in infrastructure, the provision of money for research, and the formation of human capital. Furthermore, strategic themes, such as disease control, including TB, should be prioritized. Therefore, it is necessary to create public policies that can integrate PGPs, public health agencies, and entities representing civil society, among others, aiming for an expansion in the number of D&M with expertise in TB as well as a greater geographic uniformity in D&M formation, in line with the priorities for TB control.

Despite this, we highlight that a limitation of this study is related to the number and themes of T&Ds associated with TB may not reflect the quality of the research and product generation in Brazil, as this is evaluated through article impact factors and patent registration.

Finally, the development, evaluation, and implementation of new diagnostic platforms, more effective vaccines, new antimicrobials, evaluation of new therapies, and management strategies are essential and constitute the pillar of research and innovation in the End Tuberculosis Strategy. Despite this, the formation of D&M in knowledge areas with a technological profile that can meet the technological demands of the Brazilian Unified Health System has decreased, not exceeding 1/5 of the titled D&M. This scenario puts efforts for TB control at risk and jeopardizes technological sovereignty promotion, foreign exchange savings, and the universalization of academic knowledge benefits 22 .

SUPPLEMENTARY MATERIAL. 

LIST S1: KEYWORDS USED TO CLASSIFY THESES AND DISSERTATIONS IN THEMES.

ATTENTION/HEALTH CARE: healthcare access; assistance; attention to the person with tuberculosis; attitudes and practices; basic health care; basic health indicators; basic health unit/units; brief intervention; capacity building; collective health; committee methods; communicators; community councils; community health agent; comprehensive health care; contacts; control measures; control program; cost/costs; cost-effectiveness; disease control; educational material/materials; educational technology; interventions effectiveness; family health; fight against tuberculosis; healthcare promotion; healthcare; health communication; health conditions analysis; health education; health evaluation; health policies; health service/services; health surveillance; health teaching; health training; health unic system; health unit/units; home contact; home visit; income; inequalities/inequality; infection control; information source; information system/systems; integrated management; knowledge about tuberculosis; knowledge evaluation; living condition/conditions; management; meanings and experiences; medical education; nurses' actions/appointment; nursing practice; health professionals' performance; permanent education; pharmaceutical attention; post-discharge management; prevention and control; primary health care; public health; public health policies; service qualification; life quality; information quality; reference center/laboratory/unit; referral hospital/service; referral outpatient clinic; respiratory symptomatic; route; sanitary service; social condition/conditions; social determinants; social development; social indicators; social inequity; social mobilization; social protection; social representations; social security; social support; stigma; trajectories/trajectory; tuberculosis control; tuberculosis indicators; undernotification; vulnerability.

BIOCHEMISTRY: acetyltransferase/acetyltransferases; ATP: biochemicals; biochemistry; cathepsin; enzymatic; enzyme/enzymes; glycation; leptina; lipid mediators; metalloproteinase/metalloproteinases; oxidative stress; phospholipase; protease; proteolysis; reductase/reductases; shikimate; transferase; transpeptidase/transpeptidase.

DIAGNOSIS: accuracy; bacilloscopy/BAAR; biomarker/biomarkers; clinical decision; clinical laboratory; detection; diagnosis; diagnoses/diagnosis; GeneXPERT/XPERT; signs and symptoms identification; IGRA; immunodiagnostic; molecular rapid test; mpt64; multiplex/multiplex PCR; mycobacteria identification; point-of-care; quantiferon/quantiferon-TB; radiography; screening exam; tomographic features; tuberculin proof; tuberculin test/skin test; X-ray.

EPIDEMIOLOGY: age/age and sex effects; associated determinants/factors; association measures; case analysis; case-control; clinical and laboratory profile; clinical-epidemiological; determinant factors; epidemiological; epidemiology; genotyping; geoepidemiological; geographic aspects; health geography; hospitalization time; incidence; lethality; MIRU/MIRU-VNTR; molecular characterization; morbidity; mortality; notification; notified; pharmacoepidemiological; prevalence; probabilistic correlation; related factors; risk factor/factors; score; spatial analysis/distribution; spatio-temporal; sociodemographic; socioeconomic; spoligotyping; survival; systematic review; temporal analysis.

GENETICS: alleles; beijing; chemogenomics; epigenetic/epigenetics; gene/genes; gene expression; gene transcription; genetic/genetics; genome; genotype/genotypes; hemeproteins; lineage/lineages; metabolomics; microRNA; mutation/mutations; polymorphism/polymorphisms; protein/proteins; protein subunit; proteomics; transcriptional regulation; transcriptional repressor; sequencing; sub-lineage.

IMMUNOLOGY: antibodies; antigen/antigens; apolipoprotein; BCG; CD cells; cytokine/cytokines; dendritic cells; epitopes; granuloma; HLA; humoral response; IFN; immune; immunodiagnostic; immunological; immunomodulation; immunomodulator/immunomodulators; immunomodulatory; immunopathogenesis; immunopathology; inflammatory markers; inflammasome/inflammasomes; interleukin/IL; interferon; lymphocyte/lymphocytes; lysosome; macrophage; monocytes; neutrophils; T-cells; toll-like; tumor necrosis factor/TNF; vaccine/vaccines.

DRUGS: activity evaluation; anti- Mycobacterium tuberculosis activity/activities; antimicrobial action/activity/potential; antimycobacterial activity/potential; antituberculosis activity; biocomposites; biological activity/activities; biological evaluation; biological prospecting; bioprospecting; biosynthesis; chemical and biological study; computational modeling; computational simulation; cytotoxicity; cytotoxicity; cytotoxicological evaluation; drug development; drug planning; extract/extracts; formulation/formulation development; inhibitor development; medicine innovation; microparticles; nanocarriers; nanocomposite/nanocomposites; nanofibers; nanomaterials; nanoparticle/nanoparticles; nanoreservoir; new derivatives; new drugs/molecules; obtaining and characterization; pharmaceutical excipient; pharmaceutical innovations; pharmacokinetic studies; pharmacophore; pharmacophoric; phytochemical study; physical stability; physicochemical characterization; potential action; potential activity; randomized clinical trial; rational drug design; molecule reuse; secondary metabolites; solubility; drug structural characterization; structure activity; synthesis; synthetic and antimicrobial potential; tuberculostatic activity.

RESISTANCE: antibiofilm; biofilm/biofilm; drug resistant; efflux; MDR-TB: minimal inhibitory concentration; modulatory effect: monoresistant; multidrug resistant/resistance; multi-resistant; resistance to drugs; sensitivity test/tests.

TREATMENT: abandonment; acetylation; adverse reactions; anti-tuberculosis drugs; anti-tuberculosis therapy; anti-tuberculosis regimens; bacteriological conversion; blood concentrations; case outcomes; chemoprevention; chemoprophylaxis; clinical/clinical and therapeutic evolution; combined therapy; cure; directly observed therapy; drug exposure; drug interaction/interactions; drug therapy; fixed combined dose; hepatotoxicity; isoniazid; quadruple scheme; plasmatic concentrations; post-treatment; medicines rational use; retreatment; rifampicin; serum concentrations; therapeutic adherence; therapeutic effect; therapeutic intervention; therapeutic itinerary/itineraries; therapeutic outcomes; therapeutic scheme; treaties; treatment; tuberculosis therapy.

Supplementary Material Table 1S:

Supplementary material table 2s:.

* Based on total T&D. ** T&D not classified in any of the themes.

Supplementary Material Table 3S:

I = Keywords of T&D; II = Keywords used to classify T&D by theme.

Journal of Materials Chemistry B

Surface plasmon resonance biosensor chip integrated with mos2-moo3 hybrid microflowers for rapid cfp-10 tuberculosis detection.

This study reports on the modification of the surface plasmon resonance (SPR) chip with molybdenum disulfide-molybdenum trioxide (MoS2-MoO3) microflowers to detect the tuberculosis (TB) markers of CFP-10. The MoS2-MoO3 were prepared by hydrothermal methods with variations of pH and amount of trisodium citrate (Na3Ct), which were projected to influence the shape and size of microflower particles. The analysis shows that the optimum MoS2-MoO3 hybrid microflowers were obtained at neutral pH with 0.5 g Na3Ct. The modified SPR biosensor performs a ten times higher response than the bare Au. Moreover, increasing MoS2-MoO3 thickness results in higher detection response, sensitivity, and smaller limit of detection (LOD). Using the optimized material composition, the Au/MoS2-MoO3-integrated SPR sensor can demonstrate sensitivity and LOD of 1.005 and 3.45 ng/mL, respectively. This biosensor also has good selectivity and reproducibility based on cross-sensitivity characterization to other analytes and repeated measurements on six chips. Therefore, this proposed SPR biosensor possesses high potential to be further developed and applied as a detection technology for CFP-10 in monitoring and diagnosing TB.

Supplementary files

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C. Wulandari, N. L. W. Septiani, G. Gumilar, A. Nuruddin, N. Nugraha, M. Iqbal, H. S. Wasisto and B. Yuliarto, J. Mater. Chem. B , 2023, Accepted Manuscript , DOI: 10.1039/D3TB01327H

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The N.Y.C. Neighborhood Where Families Are Filling Up Empty Offices

Five financial district buildings are being turned into housing, including the country’s largest such conversion. Will it work elsewhere in Manhattan?

By Matthew Haag

For all the talk about converting New York City’s languishing office buildings into housing, just one neighborhood has done it on a large scale: the financial district.

In the past few years, luxury apartments have been carved out of a 1907 office tower at 84 William Street and an Art Deco skyscraper at 1 Wall Street that was once the Bank of New York’s headquarters. Five other office buildings are being gutted and turned into residences, including a project that is the largest such conversion in the United States.

But the high-rise conversions are just part of a wave of modifications in the area that started decades ago with the transformation of low-rise buildings and continues today with enormous glass and steel towers.

The financial district name has become something of a misnomer as the neighborhood, once derided as a desert after the bankers commute home, becomes a vibrant residential enclave at Manhattan’s southernmost tip.

There are now 66,000 residents, up from 13,700 in 1990, in the area roughly bounded by Chambers Street and the Brooklyn Bridge to the north and the West Side Highway on the west. There is even a new Whole Foods.

The financial district’s shift offers a road map for, and glimmer of hope about, what could happen in neighborhoods from Lower to Midtown Manhattan that are saddled with a glut of empty offices as companies continue to slash space in the pandemic’s wake. Real estate analysts predict that a large swath of buildings — notably decades-old offices with outdated layouts — will remain unattractive to most companies and will need to find other uses.

Mayor Eric Adams and Governor Kathy Hochul have championed residential conversions as a solution to both the office surplus and another major problem, the city’s housing shortage. But few buildings are making the change. Such modifications can be expensive and impractical given the difficulty of creating light-filled residences from dark, deep interiors.

The transformation of the financial district grew out of two setbacks — the exodus of banks and insurance companies from Lower Manhattan to Midtown, and the Sept. 11 attack — that have led to suited 9-to-5 workers being steadily replaced by parents pushing strollers.

The area’s compact lots created a preponderance of slender buildings with high ceilings and large windows, making conversions easier.

Since the pandemic began, nearly 1,500 residences in new buildings and conversions have been added in the neighborhood. Thousands more are expected in the coming years, including in what is considered the country’s largest conversion: 1,300 apartments in an office tower vacated by JPMorgan Chase in early 2021.

Cory Levy, 26, said he had long been fascinated by the financial district’s charm, like its short streets that are a reminder of when the Dutch settled the area as New Amsterdam, before Manhattan was laid out on a grid.

Yet, friends warned him not to move there.

“They said it was a ghost town,” Mr. Levy said.

He decided to have a look after work, visiting a rooftop bar, restaurants and coffee shops.

“It’s not the East Village,” he said, “but it is residential, and if you like to go out and do stuff late at night, there are places to eat and drink.”

He loved the area and signed a lease on an apartment with his girlfriend in April, a one-bedroom unit in a 57-story former office tower that was converted in 2008.

Mr. Levy said the area had major advantages over other neighborhoods. About half of the city’s subway lines stop nearby, as well as multiple ferries and the PATH Train to New Jersey. There are drawbacks, he acknowledged: Sunlight can be hard to find on the narrow corridors.

The financial district’s makeover began in the mid-1990s when the office market faced similar challenges. As vacancies climbed, state lawmakers approved tax incentives for developers who converted languishing office towers into residences. A building boom followed.

Nearly 13,000 units had been created by the time the incentives expired in 2006, according to an analysis by the Citizens Budget Commission . Before 1990, the area had about 7,400 total residences, according to the Downtown Alliance, a nonprofit organization that manages the local business improvement district.

The conversion of offices continued even after the incentives expired, but at a slower pace. Joey Chilelli, a managing director at Vanbarton Group, a real estate company, predicted that the latest blow to the office market would most likely cause more conversions in the financial district, sometimes called FiDi.

The neighborhood has the highest office vacancy rate in Manhattan, according to the real estate firm Colliers . Nearly 27 percent of office space is for lease, the group said, up from 11 percent before the pandemic.

Vanbarton Group is redeveloping the latest conversion in the neighborhood, creating 588 apartments at 160 Water Street . The company bought the property in 2014 and had planned to keep it as offices until the pandemic arrived. Apartment leasing starts this winter.

“A lot of buildings down there are ripe for conversion,” Mr. Chilelli said. “There will be this continued march forward as people discover that FiDi is actually a great place to live.”

Over the years, some of the city’s earliest skyscrapers, including 15 Park Row, have become housing. But so have many modern office buildings that struggled to keep business tenants in the 1980s and ’90s, including 90 William Street, near the Federal Reserve Bank of New York.

Ruth Cheng was one of the first tenants to move into 90 William Street in 2008, buying a condominium with her husband after they visited a sample unit. They raised two children there until they had a third and needed more space.

“We didn't even really look elsewhere,” said Ms. Cheng, 49, adding that her children’s schools were in the neighborhood. “We wanted to stay in FiDi.” The family now lives in a new building two blocks away.

During the family’s 15 years in the area, multiple schools have opened, as have new restaurants and shops, including at the nearby South Street Seaport. One of the neighborhood’s newest shops is Best Sicily Bottega, an Italian cafe and grocery store on Beaver Street.

The store’s founders, Silvia Lombardo and Nicolas Calia, met via Instagram during the pandemic and discovered that they both lived in the financial district and had grown up 10 minutes from each other in Sicily. When they met, Ms. Lombardo owned an online store that sold Italian goods but she wanted to showcase them in a brick-and-mortar shop along with food like olive oil cakes and meatballs that were made from her family’s recipes.

With their shared love for Sicily and food, they opened the shop in May across the street from Ms. Lombardo’s apartment. They said they had not considered opening anywhere else and had decided to stay open after work hours to serve local residents takeout dinners, like pasta on Fridays.

“We really believe that something is changing here,” Ms. Lombardo said.

Matthew Haag covers the intersection of real estate and politics in the New York region. He previously was a general assignment and breaking news reporter at The Times and worked as an education reporter at The Dallas Morning News. More about Matthew Haag

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