Facilitators and barriers in implementation of active TB drug safety monitoring and management (aDSM) in programmatic management of drug resistance TB in Dar es Salaam region.

BACKGROUND: World Health Organization (WHO) recommends that active TB Dug Safety Monitoring and Management (aDSM) be adopted in countries' programmatic management of DR-TB services. In Tanzania, the National TB Leprosy Programme (NTLP), under the ministry of health, adopted the aDSM component in 2018. The study evaluated the facilitators and barriers of aDSM implementation in Dar es Salaam. MATERIALS AND METHODS: This was a process evaluation study that adapted the descriptive cross-sectional approach, conducted in Dar es Salaam region. A total of 19 respondents, including clinicians, DOT (Direct Observed Therapy) nurses and key NTLP personnel, were interviewed using interview guides. Qualitative content analysis based on Graneheim & Lundman was used to guide the analysis. RESULTS: For aDSM to be implemented in a health facility, tools like forms for recoding and reporting, access to a functional laboratory for carrying out the required monitoring tests are a necessity. Moreover, the NTLP monitors the implementation through received aDSM reports and DR-TB supportive supervisions. However, it was found that in many health facilities, aDSM was partially being implemented due to various barriers: inadequate trained staff for aDSM implementation, administrative burden in reporting and delaying in AE management. CONCLUSION: aDSM is inadequately being implemented due to the many setbacks faced by HCWs. aDSM-specific supportive supervisions and trainings to HCWs; incorporating the current manual aDSM reporting flow into the already existing electronic (Tanzania Medicine and Medical Drugs Authority) TMDA database seems useful.

Ultrasononography in Managing Extrapulmonary Tuberculosis: A Randomized, Controlled, Parallel, Superiority, Open-Label Trial.

BACKGROUND: Patients with suspected extrapulmonary tuberculosis are often treated empirically. We hypothesized that extended focused assessment with sonography for human immunodeficiency virus (HIV) and tuberculosis (eFASH), in combination with other tests, would increase the proportion of correctly managed patients with suspected extrapulmonary tuberculosis. METHODS: This trial in adults with suspected extrapulmonary tuberculosis was performed in a rural and an urban hospital in Tanzania. Participants were randomized 1:1 to intervention or routine care, stratified by site and HIV status. All participants underwent clinical evaluation, chest radiography, and testing with sputum Xpert MTB/RIF and urine Xpert MTB/RIF Ultra assays. The intervention was a management algorithm based on results of eFASH plus microbiology, adenosine deaminase (ADA), and chest radiography. The primary outcome was the proportion of correctly managed patients. The presence of positive microbiological or ADA results defined definite tuberculosis. An independent end-point review committee determined diagnoses of probable or no tuberculosis. We evaluated outcomes using logistic regression models, adjusted for randomization stratification factors. RESULTS: From September 2018 to October 2020, a total of 1036 patients were screened and 701 were randomized (350 to the intervention and 351 to the control group). Of participants in the intervention group, 251 (72%) had a positive eFASH outcome. In 258 (74%) of the intervention and 227 (65%) of the control participants antituberculosis was initiated treatment at baseline. More intervention participants had definite tuberculosis (n = 124 [35%]), compared with controls (n = 85 [24%]). There was no difference between groups for the primary outcome (intervention group, 266 of 286 [93%]; control group, 245 of 266 [92%]; odds ratio, 1.14 [95% confidence interval: .60-2.16]; P = .68). There were no procedure-associated adverse events. CONCLUSIONS: eFASH did not change the proportion of correctly managed patients but increased the proportion of those with definite tuberculosis. CLINICAL TRIALS REGISTRATION: Pan African Registry: PACTR201712002829221.

Symptoms and functional limitations related to respiratory health and carbon monoxide poisoning in Tanzania: a cross sectional study.

BACKGROUND: The burden of chronic respiratory symptoms and respiratory functional limitations is underestimated in Africa. Few data are available on carbon monoxide (CO) poisoning in sub-Saharan Africa and existing data is derived from CO in ambient air, but not from biomarkers in the blood. METHODS: Data from the Tanzanian Lung Health study, a cross-sectional study on lung health among outpatients and visitors to an urban as well as a rural hospital in Tanzania, was analyzed to describe respiratory symptoms and functional limitations. Saturation of peripheral blood with carbon monoxide (SpCO) was measured transcutaneously and non-invasively in participants using a modified pulse oxymeter indicative of CO poisoning. Univariate and multivariate analysis was performed. RESULTS: Nine hundred and ninety-seven participants were included in the analysis, the median age of participants was 46 years (49% male). 38% of participants reported some degree of chronic shortness of breath and 26% felt limited in their daily activities or at work by this symptom. The median SpCO was 7% (IQR 4-13, range 2-31%) among all participants without active smoking status (N = 808). Participants cooking with gas or electricity had the lowest SpCO (median 5%), followed by participants cooking with charcoal (median 7%). Cooking with wood, particularly using a stove, resulted in highest SpCO (median 11.5%). Participants from households where cooking takes place in a separate room had the lowest SpCO as compared to cooking outside or cooking in a shared room inside (6% vs. 9% vs.10.5%, p < 0.01). Sex or the activity of cooking itself was not associated with a difference in SpCO. Multivariate analysis confirmed cooking in a separate room (as compared to cooking outside) and living in a rural vs. urban setting as protective factors against high SpCO. CONCLUSION: The findings demonstrate a high burden of chronic respiratory symptoms which also cause socioeconomic impact. High levels of SpCO indicate a relevant burden of carbon monoxide poisoning in the local population. The level of CO in the blood is more dependent on shared exposure to sources of CO with the type of housing and type of cooking fuel as most relevant factors, and less on person-individual risk factors or activities.

The Sputum Microbiome in Pulmonary Tuberculosis and Its Association With Disease Manifestations: A Cross-Sectional Study.

Each day, approximately 27,000 people become ill with tuberculosis (TB), and 4,000 die from this disease. Pulmonary TB is the main clinical form of TB, and affects the lungs with a considerably heterogeneous manifestation among patients. Immunomodulation by an interplay of host-, environment-, and pathogen-associated factors partially explains such heterogeneity. Microbial communities residing in the host's airways have immunomodulatory effects, but it is unclear if the inter-individual variability of these microbial communities is associated with the heterogeneity of pulmonary TB. Here, we investigated this possibility by characterizing the microbial composition in the sputum of 334 TB patients from Tanzania, and by assessing its association with three aspects of disease manifestations: sputum mycobacterial load, severe clinical findings, and chest x-ray (CXR) findings. Compositional data analysis of taxonomic profiles based on 16S-rRNA gene amplicon sequencing and on whole metagenome shotgun sequencing, and graph-based inference of microbial associations revealed that the airway microbiome of TB patients was shaped by inverse relationships between Streptococcus and two anaerobes: Selenomonas and Fusobacterium. Specifically, the strength of these microbial associations was negatively correlated with Faith's phylogenetic diversity (PD) and with the accumulation of transient genera. Furthermore, low body mass index (BMI) determined the association between abnormal CXRs and community diversity and composition. These associations were mediated by increased abundance of Selenomonas and Fusobacterium, relative to the abundance of Streptococcus, in underweight patients with lung parenchymal infiltrates and in comparison to those with normal chest x-rays. And last, the detection of herpesviruses and anelloviruses in sputum microbial assemblage was linked to co-infection with HIV. Given the anaerobic metabolism of Selenomonas and Fusobacterium, and the hypoxic environment of lung infiltrates, our results suggest that in underweight TB patients, lung tissue remodeling toward anaerobic conditions favors the growth of Selenomonas and Fusobacterium at the expense of Streptococcus. These new insights into the interplay among particular members of the airway microbiome, BMI, and lung parenchymal lesions in TB patients, add a new dimension to the long-known association between low BMI and pulmonary TB. Our results also drive attention to the airways virome in the context of HIV-TB coinfection.

Mortality and associated factors among adult patients on tuberculosis treatment in Tanzania: A retrospective cohort study.

INTRODUCTION: Tuberculosis (TB) is the global leading cause of death from an infectious agent. Tanzania is among the 30 high TB burden countries with a mortality rate of 47 per 100,000 population and a case fatality of 4%. This study assessed mortality rate, survival probabilities, and factors associated with death among adult TB patients on TB treatment in Tanzania. METHODS: A retrospective cohort study was conducted utilizing case-based national TB program data of adult (≥15 years) TB cases enrolled on TB treatment from January 2017 to December 2017. We determined survival probabilities using the Kaplan-Meier estimator and a Cox proportional hazard model was used to identify independent risk factors of TB mortality. Hazard ratios and their respective 95% confidence intervals were reported. RESULTS: Of 53,753 adult TB patients, 1927 (3.6%) died during TB treatment and the crude mortality rate was 6.31 per 1000 person-months. Male accounted for 33,297 (61.9%) of the study population and the median (interquartile range [IQR]) age was 40 (30-53) years. More than half 1027 (56.7%) of deaths occurred in first two months of treatment. Overall survival probabilities were 96%, and 92% at 6th and 12th month respectively. The independent risk factors for TB mortality among TB patients included: advanced age ≥ 45 years (adjusted hazard ratio (aHR) = 1.74, 95% confidence interval (CI) = 1.45-2.08); receiving service at the hospital level (aHR = 1.22, 95% CI = 1.09-1.36); TB/HIV co-infection (aHR = 2.51, 95% CI = 2.26-2.79); facility-based direct observed therapy (DOT) option (aHR = 2.23, 95% CI = 1.95-2.72); having bacteriological unconfirmed TB results (aHR = 1.58, 95% CI = 1.42-1.76); and other referral type (aHR = 1.44, 95% CI = 1.16-1.78). CONCLUSION: Advanced age, TB/HIV co-infection, bacteriological unconfirmed TB results, other referral types, receiving service at facility-based DOT option and obtaining service at the hospital level were significant contributors to TB death in Tanzania. Appropriate targeted intervention to improve TB referral systems, improve diagnostic capacity in the primary health facilities, minimize delay and misdiagnosis of TB patients might reduce TB mortality.

Ultrasound in managing extrapulmonary tuberculosis: a randomized controlled two-center study.

BACKGROUND: Patients with clinically suspected tuberculosis are often treated empirically, as diagnosis - especially of extrapulmonary tuberculosis - remains challenging. This leads to an overtreatment of tuberculosis and to underdiagnosis of possible differential diagnoses. METHODS: This open-label, parallel-group, superiority randomized controlled trial is done in a rural and an urban center in Tanzania. HIV-positive and -negative adults (≥18 years) with clinically suspected extrapulmonary tuberculosis are randomized in a 1:1 ratio to an intervention- or control group, stratified by center and HIV status. The intervention consists of a management algorithm including extended focused assessment of sonography for HIV and tuberculosis (eFASH) in combination with chest X-ray and microbiological tests. Treatment with anti-tuberculosis drugs is started, if eFASH is positive, chest X-ray suggests tuberculosis, or a microbiological result is positive for tuberculosis. Patients in the control group are managed according national guidelines. Treatment is started if microbiology is positive or empirically according to the treating physician. The primary outcome is the proportion of correctly managed patients at 6 months (i.e patients who were treated with anti-tuberculosis treatment and had definite or probable tuberculosis, and patients who were not treated with anti-tuberculosis treatment and did not have tuberculosis). Secondary outcomes are the proportion of symptom-free patients at two and 6 months, and time to death. The sample size is 650 patients. DISCUSSION: This study will determine, whether ultrasound in combination with other tests can increase the proportion of correctly managed patients with clinically suspected extrapulmonary tuberculosis, thus reducing overtreatment with anti-tuberculosis drugs. TRIAL REGISTRATION: PACTR, Registration number: PACTR201712002829221, registered December 1st 2017.

Explaining patient delay in healthcare seeking and loss to diagnostic follow-up among patients with presumptive tuberculosis in Tanzania: a mixed-methods study.

BACKGROUND: Delay in healthcare seeking and loss to diagnostic follow-up (LDFU) contribute to substantial increase in tuberculosis (TB) morbidity and mortality. We examined factors, including perceived causes and prior help seeking, contributing to delay and LDFU during referral to a TB clinic among patients with presumptive TB initially seeking help at the pharmacies in Dar es Salaam Tanzania. METHODS: In a TB clinic, a semi-structured interview based on the explanatory model interview catalogue (EMIC) framework for cultural epidemiology was administered to presumptive TB patients enrolled at pharmacies during an intervention study. We assessed delay in seeking care at any medical care provider for a period of ≥3 weeks after the onset of symptoms, LDFU during referral (not reaching the TB clinic), and LDFU for three required TB clinic visits among the presumptive and confirmed TB patients. Logistic regression models were used to assess factors associated with delay and LDFU. RESULTS: Among 136 interviewed patients, 86 (63.2%) were LDFU from pharmacies and TB clinic while 50 (36.8%) were non-LDFU. Out of 136 patients 88 (64.7%) delayed seeking care, of whom 59 (67%) were females. Among the 86 (63.2%) patients in LDFU group, 62 (72.1%) delayed seeking care, while among the 50 (36.8%) non-LDFU, 26 (52.0%) had also delayed seeking care. Prior consultation with a traditional healer (aOR 2.84, 95% CI 1.08-7.40), perceived causes as ingestion (water and food) (aOR 0.38 CI 0.16-0.89), and substance use (smoking and alcohol) (aOR 1.45 CI 0.98-2.14) were all associated with patient delay. Female gender was associated with LDFU (aOR 3.80, 95% CI 1.62-8.87) but not with delay. Other conditions as prior illness and heredity were also associated with LDFU but not delay (aOR 1.48 CI 1.01-2.17). CONCLUSION: Delay and LDFU after referral from the pharmacies were substantial. Notable effects of diagnosis and female gender indicate a need for more attention to women's health to promote timely and sustained TB treatment. Public awareness to counter misconceptions about the causes of TB is needed.

Pathways and associated costs of care in patients with confirmed and presumptive tuberculosis in Tanzania: A cross-sectional study.

OBJECTIVE: To assess pathways and associated costs of seeking care from the onset of symptoms to diagnosis in patients with confirmed and presumptive tuberculosis (TB). DESIGN: Cross-sectional study. SETTING: District hospital in Dar es Salaam, Tanzania. PARTICIPANTS: Bacteriologically confirmed TB and presumptive TB patients. PRIMARY AND SECONDARY OUTCOME MEASURES: We calculated distance in metres and visualised pathways to healthcare up to five visits for the current episode of sickness. Costs were described by medians and IQRs, with comparisons by gender and poverty status. RESULTS: Of 100 confirmed and 100 presumptive TB patients, 44% of confirmed patients sought care first at pharmacies after the onset of symptoms, and 42% of presumptive patients did so at hospitals. The median visits made by confirmed patients was 2 (range 1-5) and 2 (range 1-3) by presumptive patients. Patients spent a median of 31% of their monthly household income on health expenditures for all visits. The median total direct costs were higher in confirmed compared with presumptive patients (USD 27.4 [IQR 18.7-48.4] vs USD 19.8 [IQR 13.8-34.0], p=0.02), as were the indirect costs (USD 66.9 [IQR 35.5-150.0] vs USD 46.8 [IQR 20.1-115.3], p<0.001). The indirect costs were higher in men compared with women (USD 64.6 [IQR 31.8-159.1] vs USD 55.6 [IQR 25.1-141.1], p<0.001). The median total distance from patients' household to healthcare facilities for patients with confirmed and presumptive TB was 2338 m (IQR 1373-4122) and 2009 m (IQR 986-2976) respectively. CONCLUSIONS: Patients with confirmed TB have complex pathways and higher costs of care compared with patients with presumptive TB, but the costs of the latter are also substantial. Improving access to healthcare and ensuring integration of different healthcare providers including private, public health practitioners and patients themselves could help in reducing the complex pathways during healthcare seeking and optimal healthcare utilisation.

Immunologic-based Diagnosis of Latent Tuberculosis Among Children Younger Than 5 Years of Age Exposed and Unexposed to Tuberculosis in Tanzania.

BACKGROUND: Childhood tuberculosis (TB) is acquired after exposure to an infectious TB case, often within the household. We prospectively screened children 6-59 months of age, exposed and unexposed to an infectious TB case within the same household, for latent tuberculosis infection (LTBI), in Dar es Salaam, Tanzania. METHODS: We collected medical data and clinical specimens (to evaluate for helminths, TB and HIV coinfections) and performed physical examinations at enrollment and at 3-month and 6-month follow-up surveys. LTBI was assessed using QuantiFERON-TB Gold (QFT) at enrollment and at 3 months. RESULTS: In total, 301 children had complete data records (186 with TB exposure and 115 without known TB exposure). The median age of children was 26 months (range: 6-58); 52% were females, and 4 were HIV positive. Eight children (3%) developed TB during the 6-month follow-up. We found equal proportions of children with LTBI among those with and without exposure: 20% (38/186) versus 20% (23/115) QFT-positive, and 2% (4/186) versus 4% (5/115) indeterminate QFT. QFT conversion rate was 7% (22 children) and reversion 8% (25 children). Of the TB-exposed children, 72% initiated isoniazid preventive therapy, but 61% of parents/caregivers of children with unknown TB exposure and positive QFT refused isoniazid preventive therapy. CONCLUSIONS: In this high burden TB setting, TB exposure from sources other than the household was equally important as household exposure. Nearly one third of eligible children did not receive isoniazid preventive therapy. Evaluation for LTBI in children remains an important strategy for controlling TB but should not be limited to children with documented TB exposure.

Boosting effect of IL-7 in interferon gamma release assays to diagnose Mycobacterium tuberculosis infection.

BACKGROUND: A quarter of the world's population is estimated to be infected with Myobacterium tuberculosis (Mtb). Infection is detected by immune response to M. tuberculosis antigens using either tuberculin skin test (TST) and interferon gamma release (IGRA's), tests which have low sensitivity in immunocompromised. IL-7 is an important cytokine for T-cell function with potential to augment cytokine release in in-vitro assays. This study aimed to determine whether the addition of IL-7 in interferon-gamma release assays (IGRAs) improves its diagnostic performance of Mtb infection. METHODS: 44 cases with confirmed TB and 45 household contacts without TB were recruited and 1ml of blood was stimulated in two separate IGRA's tube set: one set of standard Quantiferon TB gold tubes mitogen, TB antigen and TB Nil; one set of customized Quantiferon TB gold tubes with added IL-7. Following IFN-γ and IP-10 release was determined using ELISA. RESULTS: We found that the addition of IL-7 led to significantly higher release of IFN-γ in individuals with active TB from 4.2IU/ml (IQR 1.4-6.9IU/ml) to 5.1IU/ml (IQR 1.5-8.1IU/ml, p = 0.0057), and we found an indication of a lower release of both IFN-γ and IP-10 in participants with negative tests. CONCLUSIONS: In TB cases addition of IL-7 in IGRA tubes augments IFN-γ but not IP-10 release, and seems to lower the response in controls. Whether IL-7 boosted IGRA holds potential over standard IGRA needs to be confirmed in larger studies in high and low TB incidence countries.

Causative agents and antimicrobial resistance patterns of human skin and soft tissue infections in Bagamoyo, Tanzania.

Few epidemiological studies have been carried out to assess the aetiology and antimicrobial susceptibility patterns of pathogens giving rise to skin and soft tissue infections (SSTIs) in sub-Saharan Africa. In the present study from six healthcare facilities in Bagamoyo, Tanzania, wound swabs from outpatients with SSTIs were analysed by a suite of methods, including microbiological culture techniques, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry and resistance testing. Among 185 patients with SSTIs, 179 (96.8%) swabs showed microbiological growth. In total, 327 organisms were found, of which 285 were of potential aetiological relevance. Staphylococcus aureus was the predominant pathogen (prevalence: 71.4%), followed by the Gram-negative bacteria Enterobacter cloacae complex (14.6%), Klebsiella pneumoniae (12.4%) and Pseudomonas aeruginosa (11.8%). While one out of three isolates of S. aureus showed resistance to macrolides, tetracyclines, cotrimoxazole and clindamycin, only a single methicillin-resistant S. aureus (MRSA) strain was found. In Gram-negative bacteria, resistance to ampicillin and cotrimoxazole was common, while extended-spectrum beta-lactamases were rarely detected (<1%). We conclude that S. aureus was the most frequently detected pathogen in community-acquired SSTIs in Bagamoyo, Tanzania. Resistance to commonly prescribed oral antibiotics was considerable, but multi-resistant strains were rarely encountered. Monitoring of antibiotic susceptibility patterns in SSTIs is important to provide specific data for tailoring treatment recommendations.

Anemia in tuberculosis cases and household controls from Tanzania: Contribution of disease, coinfections, and the role of hepcidin.

BACKGROUND: Tuberculosis (TB) induces a systemic inflammatory state affecting iron homeostasis. Patients with TB often have additional comorbidities such as anemia which can result in poorer treat outcomes. We studied the contribution of anemia and the role of the iron regulatory hormone hepcidin among TB patients and household contacts. METHODS: We analyzed serum samples from 102 TB cases and 98 controls without TB, matched by age/sex, for hepcidin, iron, and inflammation parameters. Five controls developed TB within 12 months. We used linear regression to assess associations. RESULTS: Anemia of chronic disease (ACD) was more frequent among cases than controls (59.8% vs. 26.1%), but iron-deficiency anemia more frequent in controls (10% vs. 1%). The median hepcidin level was higher in cases than controls (63.7 vs. 14.2 ng/mL), but coinfections with HIV, helminths, and respiratory pathogens did not show cumulative effects. Hepcidin was associated with more severe TB symptom scoring (coefficient 0.8, 95% confidence interval [CI] 0.5-1.2) and higher mycobacterial load (0.7, 95% CI 0.4-1.0). Hepcidin was higher in TB cases and controls who developed TB compared to controls without TB (p<0.001), even when restricting to HIV-negative study participants. CONCLUSIONS: ACD was the predominate etiology in TB patients suggesting limited benefit from iron supplementation. Increased hepcidin levels long before active disease, indicating altered iron metabolism, may be a marker for developing disease among TB-exposed individuals. Clinical management of anemia and nutrition interventions in TB patients need to be considered to improve the clinical course and outcomes.

Distinct clinical characteristics and helminth co-infections in adult tuberculosis patients from urban compared to rural Tanzania.

BACKGROUND: Differences in rural and urban settings could account for distinct characteristics in the epidemiology of tuberculosis (TB). We comparatively studied epidemiological features of TB and helminth co-infections in adult patients from rural and urban settings of Tanzania. METHODS: Adult patients (≥ 18 years) with microbiologically confirmed pulmonary TB were consecutively enrolled into two cohorts in Dar es Salaam, with ~ 4.4 million inhabitants (urban), and Ifakara in the sparsely populated Kilombero District with ~ 400 000 inhabitants (rural). Clinical data were obtained at recruitment. Stool and urine samples were subjected to diagnose helminthiases using Kato-Katz, Baermann, urine filtration, and circulating cathodic antigen tests. Differences between groups were assessed by χ2, Fisher's exact, and Wilcoxon rank sum tests. Logistic regression models were used to determine associations. RESULTS: Between August 2015 and February 2017, 668 patients were enrolled, 460 (68.9%) at the urban and 208 (31.1%) at the rural site. Median patient age was 35 years (interquartile range [IQR]: 27-41.5 years), and 454 (68%) were males. Patients from the rural setting were older (median age 37 years vs. 34 years, P = 0.003), had a lower median body mass index (17.5 kg/m2 vs. 18.5 kg/m2, P <  0.001), a higher proportion of recurrent TB cases (9% vs. 1%, P <  0.001), and in HIV/TB co-infected patients a lower median CD4 cell counts (147 cells/µl vs. 249 cells/µl, P = 0.02) compared to those from urban Tanzania. There was no significant difference in frequencies of HIV infection, diabetes mellitus, and haemoglobin concentration levels between the two settings. The overall prevalence of helminth co-infections was 22.9% (95% confidence interval [CI]: 20.4-27.0%). The significantly higher prevalence of helminth infections at the urban site (25.7% vs. 17.3%, P = 0.018) was predominantly driven by Strongyloides stercoralis (17.0% vs. 4.8%, P <  0.001) and Schistosoma mansoni infection (4.1% vs. 16.4%, P <  0.001). Recurrent TB was associated with living in a rural setting (adjusted odds ratio [aOR]: 3.97, 95% CI: 1.16-13.67) and increasing age (aOR: 1.06, 95% CI: 1.02-1.10). CONCLUSIONS: Clinical characteristics and helminth co-infections pattern differ in TB patients in urban and rural Tanzania. The differences underline the need for setting-specific, tailored public health interventions to improve clinical management of TB and comorbidities.

Chronic airflow obstruction in Tanzania - a cross-sectional study.

BACKGROUND: Chronic obstructive pulmonary disease is a global problem and available data from sub-Saharan Africa is very limited. METHODS: A cross-sectional facility-based pilot study among patients and visitors to an urban and a rural primary healthcare facility was conducted in coastal Tanzania. The primary outcome was the prevalence of chronic airflow obstruction. RESULTS: The final analysis included 598 participants with valid post-bronchodilator spirometry. Applying ATS/ERS spirometric criteria, chronic airflow obstruction was found in n = 24 (4%, CI95 2.7-5.9) participants and in n = 30 (5%, CI95 3.5-7.1) applying GOLD spirometric criteria. To analyse risk factors for chronic airflow obstruction including those not meeting ATS/ERS or GOLD criteria, FEF25-75 and FEV1% predicted was analysed in participants without evidence of pulmonary restriction among those exposed or not exposed to risk factors (n = 552). FEV1% predicted, but in particular FEF25-75 decreased with increasing symptom severity of shortness of breath as well as limitations in daily activities of participants. Cooking in general and cooking with biomass fuels vs. gas or electricity was associated with significantly lower FEF25-75, but not with lower FEV1% predicted. Participants having refrained from taking a job because of shortness of breath exhibited lower FEF25-75 (p < 0.01). A history of prior active TB was the most relevant risk factor associated with a decrease in FEF25-75 as well as FEV1% predicted. CONCLUSION: This study demonstrated a relevant prevalence of chronic airflow obstruction in primary healthcare attendants and healthy visitors of a Tanzanian hospital. Using the baseline data provided, larger and population-based studies are needed to validate these findings. TB may have more impact on development of chronic airway obstruction than smoking in Africa. Due to the influence of age on the GOLD definition of chronic airflow obstruction, studies should report results using both ATS/ERS and GOLD definitions and include age-stratified analysis. Analysis of FEV1 and in particular FEF25-75 may yield additional information on risk factors and earlier stages of chronic airflow obstruction.

Interventions to increase tuberculosis case detection at primary healthcare or community-level services.

BACKGROUND: Pulmonary tuberculosis is usually diagnosed when symptomatic individuals seek care at healthcare facilities, and healthcare workers have a minimal role in promoting the health-seeking behaviour. However, some policy specialists believe the healthcare system could be more active in tuberculosis diagnosis to increase tuberculosis case detection. OBJECTIVES: To evaluate the effectiveness of different strategies to increase tuberculosis case detection through improving access (geographical, financial, educational) to tuberculosis diagnosis at primary healthcare or community-level services. SEARCH METHODS: We searched the following databases for relevant studies up to 19 December 2016: the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library, Issue 12, 2016; MEDLINE; Embase; Science Citation Index Expanded, Social Sciences Citation Index; BIOSIS Previews; and Scopus. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and the metaRegister of Controlled Trials (mRCT) for ongoing trials. SELECTION CRITERIA: Randomized and non-randomized controlled studies comparing any intervention that aims to improve access to a tuberculosis diagnosis, with no intervention or an alternative intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and risk of bias, and extracted data. We compared interventions using risk ratios (RR) and 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included nine cluster-randomized trials, one individual randomized trial, and seven non-randomized controlled studies. Nine studies were conducted in sub-Saharan Africa (Ethiopia, Nigeria, South Africa, Zambia, and Zimbabwe), six in Asia (Bangladesh, Cambodia, India, Nepal, and Pakistan), and two in South America (Brazil and Colombia); which are all high tuberculosis prevalence areas.Tuberculosis outreach screening, using house-to-house visits, sometimes combined with printed information about going to clinic, may increase tuberculosis case detection (RR 1.24, 95% CI 0.86 to 1.79; 4 trials, 6,458,591 participants in 297 clusters, low-certainty evidence); and probably increases case detection in areas with tuberculosis prevalence of 5% or more (RR 1.52, 95% CI 1.10 to 2.09; 3 trials, 155,918 participants, moderate-certainty evidence; prespecified stratified analysis). These interventions may lower the early default (prior to starting treatment) or default during treatment (RR 0.67, 95% CI 0.47 to 0.96; 3 trials, 849 participants, low-certainty evidence). However, this intervention may have may have little or no effect on treatment success (RR 1.07, 95% CI 1.00 to 1.15; 3 trials, 849 participants, low-certainty evidence), and we do not know if there is an effect on treatment failure or mortality. One study investigated long-term prevalence in the community, but with no clear effect due to imprecision and differences in care between the two groups (RR 1.14, 95% CI 0.65 to 2.00; 1 trial, 556,836 participants, very low-certainty evidence).Four studies examined health promotion activities to encourage people to attend for screening, including mass media strategies and more locally organized activities. There was some increase, but this could have been related to temporal trends, with no corresponding increase in case notifications, and no evidence of an effect on long-term tuberculosis prevalence. Two studies examined the effects of two to six nurse practitioner educational sessions in tuberculosis diagnosis, with no clear effect on tuberculosis cases detected. One trial compared mobile clinics every five days with house-to-house screening every six months, and showed an increase in tuberculosis cases.There was also insufficient evidence to determine if sustained improvements in case detection impact on long-term tuberculosis prevalence; this was evaluated in one study, which indicated little or no effect after four years of either contact tracing, extensive health promotion activities, or both (RR 1.31, 95% CI 0.75 to 2.30; 1 study, 405,788 participants in 12 clusters, very low-certainty evidence). AUTHORS' CONCLUSIONS: The available evidence demonstrates that when used in appropriate settings, active case-finding approaches may result in increase in tuberculosis case detection in the short term. The effect of active case finding on treatment outcome needs to be further evaluated in sufficiently powered studies.

Schistosoma, other helminth infections, and associated risk factors in preschool-aged children in urban Tanzania.

BACKGROUND: Despite the high prevalence of helminth infections among preschool-aged children, control programs in sub-Saharan countries primarily focus on school-aged populations. We assessed the prevalence of helminth infections and determined risk factors for infection among preschool-aged children in the urban setting of Dar es Salaam, Tanzania. METHODOLOGY: Starting in October 2015, we conducted a 12-month prospective study among tuberculosis (TB)-exposed children under the age of 5 years and unexposed controls from neighboring households. At the time of recruitment, we collected medical histories, assessed development and cognitive functions, and performed medical examinations. We performed full blood cell counts and screened for HIV and malaria. Point-of-care circulating cathodic antigen (POC-CCA), urine filtration, Kato-Katz, FLOTAC, and Baermann tests were employed to detect helminth infections in urine and stool. Helminth infections were stratified for Schistosoma and other helminths to identify risk factors, using logistic regression. PRINCIPAL FINDINGS: We included 310 children with a median age of 26 months (inter quartile range 17-42 months) in the study. Among these, 189 were TB-exposed and 121 TB-unexposed. Two thirds of the children were anemic (hemoglobin level <11 g/dl) and the HIV prevalence was 1.3%. Schistosoma spp. was the predominant helminth species (15.8%; 95% confidence interval [CI] 12.1-20.3%). Other helminth infections were less frequent (9.0%, 95% CI 6.3-12.8%). Poor hygiene, use of household water sources, and TB-exposure were not associated with helminth infection. Development and cognitive scores did not significantly differ in helminth-infected and uninfected peers, but hemoglobin levels were significantly lower in helminth-infected children (10.1 g/dl vs. 10.4 g/dl, p = 0.027). CONCLUSIONS/SIGNIFICANCE: In Dar es Salaam, a city with more than 4 million inhabitants, the prevalence of Schistosoma spp. infection among preschool-aged children was unexpectedly high. Setting-specific interventions that target preschool-aged children and urban settlements should be considered to reduce the transmission of Schistosoma and other helminth infections and to improve children's health.

Preservation of sputum samples with cetylpyridinium chloride (CPC) for tuberculosis cultures and Xpert MTB/RIF in a low-income country.

BACKGROUND: Culture contamination with environmental bacteria is a major challenge in tuberculosis (TB) laboratories in hot and humid climate zones. We studied the effect of cetylpyridinium chloride (CPC) preservation on culture results and performance of Xpert MTB/RIF. METHODS: Consecutive sputum samples from microscopy smear-positive TB patients were collected. Two-hundred samples were equally split in two aliquots, one aliquot was treated with CPC and stored at ambient temperature for 7 days. The second aliquot was immediately processed. Samples were decontaminated for 20, 15 or 10 min, and subsequently cultured on Löwenstein-Jensen medium. Furthermore, 50 samples were stored for 7, 14 and 21 days, and 100 CPC-pretreated samples tested by Xpert MTB/RIF. RESULTS: CPC pretreated samples showed a higher culture yield compared to non-treated sputum samples across all decontamination times: 94% vs. 73% at 10 min (p = 0.01), 94% vs. 64% at 15 min (p = 0.004), and 90% vs. 52% at 20 min (p < 0.001). The quantitative culture grading was consistently higher in CPC treated compared to non-CPC treated samples. The proportion of contaminated cultures was lower in CPC pretreated samples across all decontamination times (range 2-6%) compared to non-CPC treated samples (15-16%). For storage times of CPC treated samples of 7, 14, and 21 days, 84, 86, and 84% of the respective cultures were positive. Of 91 CPC treated samples with a positive culture, 90 were also Xpert MTB/RIF positive. CONCLUSIONS: CPC increases culture yield, decreases the proportion of contamination, and does not alter the performance of Xpert MTB/RIF.

Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania.

Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-γ and dual IFN-γ/TNF-α and associated with TB-induced systemic inflammation and elevated serum levels of type I IFNs. Of note, the proportion of patients with Mtb-specific CD8 T cells was significantly reduced in Mtb/helminth co-infected patients from TZ. It is likely that the underlying helminth infection and possibly genetic and other unknown environmental factors may have caused the induction of mixed Th1/Th2 Mtb-specific CD4 T cell responses in patients from TZ. Taken together, these results indicate that the generation of Mtb-specific CD4 and CD8 T cell responses may be substantially influenced by environmental factors in vivo. These observations may have major impact in the identification of immune biomarkers of disease status and correlates of protection.

Tuberculosis transmission in public locations in Tanzania: A novel approach to studying airborne disease transmission.

OBJECTIVES: For tuberculosis (TB) transmission to occur, an uninfected individual must inhale the previously infected breath. Our objective was to identify potential TB transmission hotspots in metropolitan city of Dar es Salaam, Tanzania and to model the annual risk of TB transmission in different locations of public importance. METHODS: We collected indoor carbon dioxide (CO2) data from markets, prisons, night clubs, public transportation, religious and social halls, and from schools. Study volunteers recorded social contacts at each of the locations. We then estimated the annual risks of TB transmission using a modified Wells-Riley equation for different locations. RESULTS: The annual risks of TB transmission were highest among prison inmates (41.6%) and drivers (20.3%) in public transport. Lower transmission risks were found in central markets (4.8% for traders, but 0.5% for their customers), passengers on public transport (2.4%), public schools (4.0%), nightclubs (1.7%), religious (0.13%), and social halls (0.12%). CONCLUSION: For the first time in a country representative of sub-Saharan Africa, we modelled the risk of TB transmission in important public locations by using a novel approach of studying airborne transmission. This approach can guide identification of TB transmission hotspots and targeted interventions to reach WHO's ambitious End TB targets.

High sero-prevalence of hepatitis B virus and human immunodeficiency virus infections among pregnant women attending antenatal clinic at Temeke municipal health facilities, Dar es Salaam, Tanzania: a cross sectional study.

BACKGROUND: Hepatitis B virus (HBV) and Human immunodeficiency virus (HIV) infection in pregnancy is associated with direct effect of pregnancy and potential viral transmission from mother to newborn. In Tanzania very little in known on prevalence of HBV infection and their associated factors among pregnant women in lower health facilities. The main objective of the study was to determine the prevalence of HBsAg, HIV and HBV-HIV co-infection among pregnant women attending antenatal clinics in Dar es Salaam. METHODS: This cross sectional study was conducted in three Temeke municipal health-care facilities between May 2014 and June 2014. A total of 249 pregnant women attending antenatal clinic (ANC) were consecutively enrolled in the study. A data collection tool was used to extract socio-demographic characteristics from ANC card. Commercial ARCHITECT® ci4100™ was used to assess HBsAg status and liver function (Alanine amino-transferase (ALAT). HIV status was determined by anti-HIV antibody test. RESULTS: Of 249 pregnant women enrolled the median age was 25 years (IQR 22-30) and most of them were married (72.4%). The overall prevalence of HBsAg and HIV were 8.03% (95% CI: 5.0-12.1%) and 17.2% (95% CI: 12.8-22.5%), respectively. HBV/HIV co-infection rate was 2.8% (95% CI; 1.3-5.4%). HBsAg positive rate was significantly high in women who were HIV positive (p < 0.05). Being employed /student were less associated with HBV infection (aOR 0.35, 95% CI 0.13-0.95). Only 3 (15%) of pregnant women with HBsAg positive had abnormal ALAT. CONCLUSIONS: High prevalence of HBV and HIV infections among pregnant women were reported in this setting thus calls for the national expansion of the integration of prevention of mother-to-child transmission (PMTCT) services for HBV infection.