Drug-resistant tuberculosis is a global cause of concern.

The number of patients with drug-resistant tuberculosis (DR-TB) is increasing worldwide. This review summarises the global epidemiology of DR-TB and current treatment challenges. Luckily, novel regimens comprising bedaquiline, pretomanid, linezolid, and moxifloxacin have seemingly mitigated the global threat posed by DR-TB. However, emerging resistance against bedaquiline and pretomanid, among other factors, persists as ongoing concerns in the global fight against DR-TB. While the new regimens are groundbreaking, the sustained development of novel drugs targeting the most resistant forms of tuberculosis is of utmost importance for future efforts against DR-TB.

The association between common mental disorders and tuberculosis: a case-control study from Guinea-Bissau.

OBJECTIVE: The aim of the study was to explore the association between tuberculosis (TB) and common mental disorders (CMD), in an area with high prevalence of TB. METHODS: We performed a case-control study of TB patients and unmatched healthy controls, from a demographic surveillance site in Guinea-Bissau. Screening for CMD was performed once for controls and at inclusion and follow-up for TB patients. Kessler 10 (K-10) and a brief version of Hopkins Symptom Checklist 25 (SCL-8d) were used as screening instruments. RESULTS: 571 controls were interviewed and 416 interviews were performed for 215 TB cases. Estimated CMD prevalence at the time of diagnosis of TB was 33.6 % (SCL-8d) and 46.2 % (K-10), compared with 6.8 % (SCL-8d) and 6.7 % (K-10) among controls; adjusted OR 7.18 (95 % CI 4.07 to 12.67) and 14.52 (95 % CI 8.15 to 25.84), respectively. No significant difference in CMD prevalence rates was observed between TB patients, after 6 months of treatment, and controls. CONCLUSION: Psychological distress and common mental disorders were more prevalent among TB patients at the time of diagnosis compared with the background population, but after completion of TB treatment no increased prevalence of psychological distress was found.

Severe Ureaplasma urealyticum infection in a patient with ocrelizumab-induced hypogammaglobulinaemia.

Infections caused by Ureaplasma urealyticum in immune-competent people are typically simple and uncomplicated. However, in cases of immunosuppression, severe disseminated infections can occur.This case report describes the case of a severe, disseminated infection caused by U. urealyticum in a young female with unacknowledged humoral immunosuppression due to treatment with ocrelizumab for multiple sclerosis.The patient was admitted due to a recurrent episode of a tubo-ovarian abscess. Throughout the following 2 months of hospitalisation, treatment with several types of antibiotics and the placement of various drains led to no improvement. As extensive investigations indicated hypogammaglobulinaemia, U. urealyticum was suspected, and tests came back positive. Treatment with doxycycline and moxifloxacin led to a full recovery.This demonstrates how humoral immunosuppression is a risk factor for severe disseminated infections and how these may be avoided through monitoring of immunoglobulin levels in patients treated with ocrelizumab.

Life expectancy among patients with pulmonary tuberculosis is less than one-third of life expectancy in the background population in Guinea-Bissau-an observational study.

BACKGROUND: Few studies have assessed life expectancy of patients with tuberculosis (TB) against a comparable background population, particularly in low-income, high-incidence settings. This study aimed to estimate the life expectancy (LE) of patients with TB in the West African country of Guinea-Bissau and compare it with the LE of the background population. METHODS: This study used data from the Bandim TB cohort from 2004-20 as well as census data from the capital of Guinea-Bissau. LE was estimated using a bootstrapped Kaplan-Meier survival analysis for patients with TB and the background population, stratifying by age of entry and various patient subgroups. The analysis was further stratified by diagnosis period and length of schooling (an indicator of socioeconomic status), to assess their influence on LE. A sensitivity analysis was performed assuming death at loss to follow-up. RESULTS: The analysis included 2278 patients and a background population of 169 760 individuals. Overall median LE among 30-year-old patients with TB was 10.7 years (95% CI: 8.7-12.6), compared with 35.8 (95% CI: 35.1-36.5) in the background population. LE was shorter in HIV-infected patients and those who had unsuccessful treatment outcome; however, even among those who were both uninfected with HIV and experienced successful treatment outcome, LE was 20% shorter than in the background population. Longer schooling appeared to decrease mortality. CONCLUSIONS: TB substantially shortens LE. This effect is present even in patients who are uninfected with HIV and who have successful treatment outcome.

BCG is protective against death in male but not female patients with pulmonary tuberculosis in Guinea-Bissau.

BACKGROUND: Growing evidence supports the existence of a sex difference in immunity to tuberculosis (TB). This is most often to the detriment of males. This study aimed to assess the association between scar size from bacillus Calmette-Guérin (BCG) and mortality risk stratified by sex. METHODS: Kaplan-Meier survivor functions and Cox proportional hazard models were used to assess mortality risk by sex and scar size. Groups were further compared by clinical and epidemiological characteristics. RESULTS: Between 2003 and 2019, 2944 eligible patients were identified, of whom 1003 were included in the final analysis. Males with BCG scars, particularly large scars, were less likely to die within 1 y of diagnosis than males with no scar (adjusted hazard ratio 0.36 [95% confidence interval 0.15 to 0.88]). In contrast, females with small scars trended towards higher mortality than females with no scars or females with large scars. CONCLUSIONS: BCG protects against death in male but not female patients with TB. More research is needed to determine the mechanisms underpinning these sex differences and whether they are generalizable beyond this setting.

Incidence of pulmonary tuberculosis in suburban Bissau, Guinea-Bissau between 2004 and 2020: a prospective cohort study.

OBJECTIVES: Previous studies have found declining incidence of tuberculosis (TB) in Bissau, Guinea-Bissau. This study aimed to report incidence rates of TB for the period 2004-2020, stratifying by sex, smear-status, and HIV-status, as well as describe developments in TB case fatality rate and diagnostic delay. DESIGN AND METHODS: Data from the Bandim Health Project HDSS and the TB registry from Jan 1st, 2004 to Dec 31st, 2020 were used. Incidence rates were calculated for each year and for smear-positive, smear-negative, HIV-positive, HIV-negative, and unknown HIV-status. Incidence rate ratio and test for trend were done using a one-step Newton approximation to the log-linear Poisson regression coefficient. RESULTS: Overall TB incidence declined only slightly over the period from 294 per 100,000 in 2004 to 273 in 2020. TB/HIV coinfection declined from 108 in 2004 to 14 in 2020, as did incidence among females and smear-negative cases. CONCLUSIONS: Incidence of PTB in Bissau, Guinea-Bissau is declining slowly, if at all. TB incidence among females, smear-negative TB, TB case fatality rate, and TB/HIV coinfection and diagnostic delay are declining.

Tobacco smoking impact on tuberculosis treatment outcome: an observational study from West Africa.

OBJECTIVE: Both tuberculosis (TB) and tobacco smoking are preventable health hazards. Few studies have examined the relationship between TB and tobacco smoking in an African setting, where the two health burdens collide heavily. This study aimed to describe the severity of TB disease and treatment outcomes among smokers with TB compared with nonsmokers with TB in Guinea-Bissau. METHODS: We conducted a prospective follow-up study between 2003-2017 in Guinea-Bissau, enrolling adult patients with TB classified as nonsmokers or smokers. Disease severity was assessed using the Bandim TBscore. Multivariate logistic and Cox proportional hazard regressions were used to analyse treatment outcomes. RESULTS: Of 1780 included patients, 385 were smokers who had smoked for a median 10 years (interquartile range [IQR] 5-20). No difference in disease severity at the time of diagnosis was observed. Smokers were not significantly more prone to a nonsuccessful treatment outcome, although a trend was seen (adjusted odds ratio [OR] 1.24, 95% confidence interval [CI] 0.91-1.70), and smokers tended to be more often lost to follow-up, but this also was not a significant finding (adjusted hazard ratio [HR] 2.09, 95% CI 0.89-4.94). CONCLUSION: In a TB high-endemic setting with few tobacco smokers, smoking was not associated with disease severity or worse outcome, possibly because of socioeconomic confounders.

Assessing gender differences among presumed and diagnosed patients with pulmonary TB: observations from Guinea-Bissau.

BACKGROUND: Globally, more males than females are diagnosed with pulmonary TB (PTB); however, the cause of this gender disparity remains unknown. We aimed to assess gender differences in an observational cohort of patients with presumed PTB (prePTB) at the Bandim Health Project, Guinea-Bissau. METHODS: Adult patients with signs and symptoms suggestive of PTB seeking medical care were invited to participate and were referred to comprehensive diagnostic work-up. RESULTS: We included 2020 patients with prePTB; 54.6% were female. Females were younger than males and more often infected with HIV. More male patients with prePTB were diagnosed with PTB and the proportion of smear-positive cases was greater among males. There was no gender difference in loss to follow-up during the diagnostic process. Of 219 patients with PTB, 205 started treatment, with no difference between genders regarding pretreatment loss to follow-up or treatment outcome. CONCLUSIONS: More women sought help for symptoms indicative of PTB, yet more men were diagnosed. Women did not have more clinically severe disease at presentation, did not drop out of diagnostic procedures more frequently and did not experience a worse outcome than men. This suggests that the gender gap in PTB is unlikely to be due solely to differences in care-seeking behaviour or diagnostic procedures in our setting.

Increasing smear positive tuberculosis detection using a clinical score - A stepped wedge multicenter trial from Africa.

BACKGROUND: The Bandim TBscore is a clinical score that predicts treatment outcome in Tuberculosis (TB) patients and proved useful as an indicator of which healthcare-seeking adults to refer for sputum smear microcopy. We aimed to test in a randomized trial if the TBscore could be used to enhance the detection of smear positive (SP) TB. METHODS: We carried out a stepped wedge cluster-randomized trial at six health centers in Bissau, Guinea-Bissau, and Gondar, Ethiopia. The primary outcome was diagnostic yield for SP TB. Secondary outcomes were successful treatment and effect on overall 12 months mortality. The study was registered at the Pan African Clinical Trials Registry (PACTR201611001838365). RESULTS: We included 3571 adults. Overall, there was no effect of the intervention on SP PTB detected (OR 1.39 (95%CI 0.75 - 2.56). Analysis stratified by country, showed that the TBscore increased case detection in Gondar (OR 4.05 (95%CI 1.67 - 9.85)) but no effect was found in Bissau (OR 0.47 (95%CI 0.22 - 1.05)) where take-up was much lower. Overall mortality decreased during the intervention (HR 0.31 (95%CI 0.13-0.72)). CONCLUSION: Using the TBscore for triage before smear microscopy may improve case detection and decrease mortality if there is sufficient laboratory capacity to increase sputum smears.

Active case-finding of tuberculosis in general populations and at-risk groups: a systematic review and meta-analysis.

BACKGROUND: The World Health Organization (WHO) recommends active case-finding (ACF) of tuberculosis (TB) in certain high-risk groups; however, more evidence is needed to elucidate the scope of ACF beyond the current recommendations. In this study we aimed to systematically review yields (the prevalence of active TB) of studies on ACF in general populations and at-risk groups. METHODS: A literature search in PubMed, Embase and the Cochrane Central Library (CENTRAL) was performed for studies concluded after 31 December 1999 and published before 1 September 2020. Screening yields were estimated and yield/prevalence ratios (ratio between yield of study and WHO estimated prevalence of TB) were calculated to assess which groups might especially benefit from ACF. Finally, risk of bias was assessed and heterogeneity was investigated using meta-regression and sensitivity analyses. RESULTS: We included 197 studies, with a total of 12 372 530 screened and 53 158 cases found. Yields were high among drug users, close contacts, the poor and marginalised, people living with HIV, and prison inmates across incidence strata, and estimated yield/prevalence ratios in screenings of general populations tended to be >1 with an overall ratio of 1.4 and ranging between 1.0 and 1.5. Sensitivity analyses suggested that inclusion of studies at high risk of bias contributed to underestimation of yields. CONCLUSION: Despite many studies using insensitive screening methods, these results suggest that more at-risk groups should be considered for inclusion in future screening recommendations and that screening of general populations may outperform current case-finding practices, providing evidence for extending ACF beyond the current recommendations.

Diabetes in urban Guinea-Bissau; patient characteristics, mortality and prevalence of undiagnosed dysglycemia.

BACKGROUND: The burden of diabetes mellitus in Sub-Saharan Africa is growing rapidly, and yet the prevalence and patient characteristics are still largely unknown. OBJECTIVES: We analyzed clinical and demographic characteristics of Type 2 diabetes (T2DM) patients attending a diabetes clinic in Guinea-Bissau from February 2008 to April 2014, and estimated the prevalence and risk factors of unknown-impaired fasting plasma glucose (FPG) and diabetes, as well as excess mortality associated with T2DM. METHODS: We characterized T2DM patients attending the national diabetes clinic in Bissau. Diabetes was diagnosed based on FPG. We matched T2DM patients 1:1 with non-diabetes community controls on age and sex to determine relevant risk factors for T2DM using logistic regression. Furthermore, we matched patients 1:6 with community controls to assess long-term survival (until February 2019) in a Cox regression using calendar time as the underlying timescale. Verbal autopsies determined the cause of death among T2DM patients and controls. RESULTS: The mean age among T2DM was 50.6 (SD 11.1), and the mean FPG at first consultation was high (13.2 mmol/L (SD 5.1)). Ethnicity, family history of diabetes, hypertension, and anthropometrics differed among T2DM patients, community controls with impaired FPG, and healthy controls. Family history of diabetes (OR = 5.65, 95% CI: 3.10-10.3) and elevated waist circumference (2.33, 1.26-4.29) were significant risk factors for T2DM. 20.4% (59/289) of community controls had abnormal FPG. T2DM patients had an excess mortality hazard ratio of 3.53 (95%CI: 1.92-6.52). Deaths caused by bacterial infections, including foot ulcers, were more common among T2DM patients, compared with community controls (54% (7/13) vs. 19% (5/27) (P = 0.02)). CONCLUSION: Several risk factors including were associated with T2DM in Guinea-Bissau. We found a high prevalence of elevated FPG among randomly selected community controls. In combination with higher mortality among T2DM patients, an urgent need for better treatment options and increased awareness.

Neonatal BCG vaccination and child survival in TB-exposed and TB-unexposed children: a prospective cohort study.

OBJECTIVES: To assess the association between neonatal BCG vaccination and mortality between 28 days and 3 years of age among tuberculosis (TB)-exposed and TB-unexposed children. DESIGN: Prospective cohort study. SETTING: Bandim Health Project runs an urban Health and Demographic Surveillance site in Guinea-Bissau with registration of mortality, vaccination status and TB cases. PARTICIPANTS: Children entered the analysis when their vaccination card was inspected after 28 days of age and remained under surveillance to 3 years of age. Children residing in the same house as a TB case were classified as TB-exposed from 3 months prior to case registration to the end of follow-up. METHODS: Using Cox-proportional hazards models with age as underlying time scale, we compared mortality of children with and without neonatal BCG between October 2003 and September 2017. MAIN OUTCOME MEASURE: HR for neonatal BCG compared with no neonatal BCG by TB-exposure status. RESULTS: Among the 39 421 children who entered the analyses, 3022 (8%) had observation time as TB-exposed. In total, 84% of children received neonatal BCG. Children with neonatal BCG had lower mortality both in TB-exposed (adjusted HR: 0.57 (0.26 to 1.27)) and in TB-unexposed children (HR: 0.57 (95% CI 0.47 to 0.69)) than children without neonatal BCG. Children exposed to TB had higher mortality than TB-unexposed children if they had not received neonatal BCG. CONCLUSION: Neonatal BCG vaccination was associated with lower mortality among both TB-exposed and TB-unexposed children, consistent with neonatal BCG vaccination having beneficial non-specific effects. Interventions to increase timely BCG vaccination are urgently warranted.

A clinical score has utility in tuberculosis case-finding among patients with HIV: A feasibility study from Bissau.

BACKGROUND: Clinical scores are promising case-finding tools for tuberculosis (TB) among HIV-infected patients. The Bandim TBscore has been shown to increase the diagnostic yield among patients with presumed TB in general, but has not previously been tested among newly diagnosed HIV patients at high risk of TB. METHODS: HIV-infected patients were included in this cross-sectional study. A pre-post-intervention study design was used to assess the outcome of a change in practice, i.e. the application of a clinical score (TBscore) consisting of 13 signs and symptoms to assess the need for further TB diagnostics. Patients with a TBscore ≥2 were evaluated using smear microscopy and Xpert MTB/RIF. A TB diagnosis was made based on microbiology or clinical evaluation. The sensitivity and specificity of the TBscore were compared with those of World Health Organization symptoms. RESULTS: The TB prevalence among newly enrolled HIV-infected patients during the study period was 13.4% (22/164). Using the TBscore and a diagnostic algorithm, it was possible to increase the proportion of patients started on TB treatment from 2.7% (10/367) the year before the study to 10.4% (17/164) during the study period. Five patients diagnosed with TB were not started on TB treatment as they were lost to follow-up or died. With a cut-off value of 2, the TBscore had a sensitivity, specificity, positive predictive value, and negative predictive value of 95.5% (21/22), 36.9% (41/111), 23.1% (22/118), and 97.6% (41/42), respectively. CONCLUSION: The TBscore is useful for standardized TB screening among HIV-infected individuals and may be a valuable tool to prioritize patients at high risk of TB.

Utility of a clinical scoring system in prioritizing TB investigations - a systematic review.

Introduction: Tuberculosis (TB) is among the 10 most common causes of death worldwide and it is the leading cause of mortality in people with human immunodeficiency virus (HIV). Clinical scoring systems have the potential to improve case finding and to prioritize patients for TB testing. Areas covered: This systematic review investigated the utility of prediction models to improve pulmonary tuberculosis (pTB) case finding. Studies were searched through PubMed until 15th of August 2018 and 20 studies were eligible according to the inclusion criteria. Data on study population, outcome measurements, predictors, and performance were extracted. Many studies showed promising results but lacked external validation. Furthermore, head-to-head studies are needed to compare the different prediction models. Sensitivities of the prediction models ranged from 26% to 96% and specificities from 18% to 92%, negative likelihood ratios (LR-) from 0.22 to 0.8 and positive likelihood ratios(LR+) 1.07 to 7.32. Composite scores including paraclinical measures added to sensitivity. Expert opinion: TB case finding is of utmost importance to advance the quest for global TB elimination, and simple measures to identify high-risk populations or persons to undergo further diagnostic evaluation are highly needed. A number of clinical scores are available and could be implemented in practice to improve case finding.

Dietary intake in undernourished adults living in Guinea-Bissau; a cross-sectional study.

BACKGROUND: Data on dietary intake in Guinea-Bissau is limited. The main purpose of this study was to compare mean daily energy intake (EI) with mean daily energy expenditure (EE) for a moderately active lifestyle in health-seeking individuals with a body mass index < 20.0 kg/m2. Furthermore, dietary composition was evaluated by estimates of macronutrient energy distribution, individual dietary diversity scores, and the identification of frequently consumed food items, stratified by sex. METHODS: A cross-sectional dietary survey was conducted at the suburban health- and demographic surveillance site in Guinea-Bissau, West Africa, from May 2014-February 2015. Each participant answered one interviewer-administered 24-h dietary recall at baseline, from which dietary intake was assessed. Differences in dietary intake between men and women were analysed using the X 2 test or Fisher's Exact test for categorical outcomes, and the Student's t-test for continuous variables. RESULTS: Forty-three men and forty-eight women were included. Mean EI for men was 6326 kJ/d (sd 2104) and for women 6822 kJ/d (sd 2210). Mean EE for a moderately active lifestyle with a physical activity level of 1.75 was 10,479 kJ/d (sd 658) for men and 8729 kJ/d (sd 731) for women. Both men and women had a significantly lower mean EI compared with mean EE (p-values both < 0.001). Dietary diversity was low with a score of 3.5 (sd 1.0) for men and 4.0 (sd 1.3) for women, p-value 0.046. Macronutrient energy was distributed as 66% (sd 11) carbohydrate, 15% (sd 5) protein, and 19% (sd 9) fat, with no significant difference in distribution between men and women. Consumption of starchy and sugary carbohydrates accounted for two thirds of mean EI. Cereals were the main source of protein, in place of animal protein. CONCLUSIONS: Both men and women in this study had low mean EI compared with mean EE for a moderately active lifestyle. Dietary intake was characterized by a seemingly low dietary diversity and imbalanced macronutrient energy distribution, comprising insufficient fat intake and excess carbohydrate intake. Cereals were the main source of protein. TRIAL REGISTRATION: PACTR2009110001673419. Registered 22 Oct 2009.

[Treatment of HIV, tuberculosis and malaria in Guinea-Bissau].

For 40 years, Bandim Health Project in Guinea-Bissau has been working on mapping epidemics, uncovering the impact of health interventions and trying to improve the health of the population in one of the world's poorest countries. The primary focus has been on child mortality and vaccine effects, but considerable effort has also been made in many other fields. This review describes the work with the three major infectious diseases: HIV, tuberculosis and malaria, and the most important findings are reviewed for each disease.

Influence of Referral Pathway on Ebola Virus Disease Case-Fatality Rate and Effect of Survival Selection Bias.

Case-fatality rates in Ebola treatment centers (ETCs) varied widely during the Ebola virus disease (EVD) outbreak in West Africa. We assessed the influence of referral pathway on ETC case-fatality rates with a retrospective cohort of 126 patients treated at the Mathaska ETC in Port Loko, Sierra Leone. The patients consisted of persons who had confirmed EVD when transferred to the ETC or who had been diagnosed onsite. The case-fatality rate for transferred patients was 46% versus 67% for patients diagnosed onsite (p = 0.02). The difference was mediated by Ebola viral load at diagnosis, suggesting a survival selection bias. Comparisons of case-fatality rates across ETCs and clinical management strategies should account for potential survival selection bias.

Tuberculosis and hypertension-a systematic review of the literature.

BACKGROUND: Tuberculosis (TB) remains a major health problem in low- and middle-income countries, and in many of these countries, the burden of non-communicable diseases such as hypertension is rising. Knowledge about how these diseases influence each other is limited. METHODS: A systematic review of the literature was performed to evaluate the evidence for an association between hypertension and TB. RESULTS: Three retrospective cohort studies, three case-control studies, eight cross-sectional studies, 12 case series, and 20 case reports exploring the association between hypertension and TB were included in the review. One cohort study found a significantly higher prevalence of hypertension among TB patients compared to controls. Cross-sectional studies reported a prevalence of hypertension in TB patients ranging from 0.7% to 38.3%. No studies were designed to assess whether hypertension is a risk factor for developing active TB. CONCLUSIONS: Overall, no evidence was found to support an association between TB and hypertension; however, the results of this review must be interpreted with caution due to the lack of properly designed studies.