Factors Affecting Improved Community Health Fund Members in Mbarali District: A Case of Mbarali District Council in Mbeya Region (Tanzania).

The study on Improved Community Health Fund (iCHF) is aimed at looking into the factors affecting low number of iCHF enrolment. This study was guided by three specific objectives. The objectives were: To examine the socio-cultural practices that affect enrolment; To assess the perception of both beneficiaries and non-beneficiaries on affordable health care services and to determine how the national health policy of 2007 affects affecting enrolment Improved Community Health Fund in Mbarali District council. Data collection, presentation, and interpretation were done using both qualitative and quantitative approaches, as well as focus group discussions and in-depth interviews. Purposive sampling was used for in-depth interviews, and basic random sampling was used for social survey and focus group participants. The sample size for social survey respondents was calculated using Yamane's formula and distributed using Wilinkison and Bhandarkar's formula, while respondents for in-depth interviews were purposefully chosen. For qualitative and quantitative data analysis, content analysis and SPSS Version 20 were used, respectively. The study's key findings showed that people's willingness to enrol in iCHF is influenced by their awareness, cultural aspects of life, and policy implementation. Although the group is hesitant to enter iCHF, there is an urgent need for affordable healthcare that is provided by prepayment plans rather than out-of-pocket payments. Enrolment in iCHF is often subject to other factors such as a lack of knowledge about iCHF, insufficient resources in government facilities, the proliferation of alternative healing solutions, and people's perceptions of the prepayment scheme. Keywords: Enrolment, Community Health Fund and Tanzanian Health Insurance Pla

Epidemiology of co-infections in tuberculosis patients in Tanzania : HIV, helminth infection and respiratory pathogens

Background: Tuberculosis (TB) caused by Mycobacterium tuberculosis complex is a global public health concern, causing significant morbidity and mortality. The resource limited settings are the worst hit, especially where there is also high burden of co-infections which increase the risk of developing TB and negatively affect TB treatment outcomes. HIV, helminth and respiratory pathogens are prevalent in Tanzania, a country that is in among the top 30 high burden countries as categorized by World Health Organization (WHO). There is epidemiological evidence of increased risk of developing TB with HIV, and little evidence on the association of TB and helminth infection and respiratory pathogens. It is therefore important to understand the epidemiology of TB and co-infections, so that we can design interventions that will address the burden of TB and relevant co-infections. The objectives: The main objective of this PhD thesis was to determine the burden and the association of HIV, helminth and respiratory pathogens (viruses and bacteria) co-infections and TB at Temeke district, Dar es Salaam, Tanzania. The specific objectives were: i) to determine the treatment outcome of TB and HIV co-infected patients routinely diagnosed at Temeke district treated under home- and facility-based direct observed therapy (DOT), ii) to determine the prevalence of helminth infection and respiratory pathogens among smear positive TB cases and household contact controls without TB, iii) to investigate the risk factors for helminth infection and respiratory pathogens among smear-positive TB cases and household contact controls without TB, and iv) to determine the clinical effects of helminth infection and respiratory pathogens on clinical phenotypes and clinical outcomes among smear-positive TB patients. Methods: This PhD is nested within a large TB cohort in Dar es Salaam region (TB-DAR): a prospective collection of clinical data and biological specimens to study the epidemiology of tuberculosis, including molecular epidemiology and the evaluation of new diagnostics and biomarkers). There are two distinctive methodological parts as described below: Objective 1: We obtained anonymized electronic data from the TB district register of all adult TB patients (aged ≥15 years) who were notified between 2010 and 2013 in a single geographical area of two TB sub-districts (Wailes I and Wailes II) in the Temeke district, Dar es Salaam, Tanzania. Objective 2-4: We consecutively enrolled ≥18 years TB patients and household contact controls between November 2013 until October 2015 to reach the required sample size. Any individual living in the same household as the index TB patients enrolled in the study is referred to as a household contact control. Controls at recruitment were free of symptoms and signs suggestive of TB, healthy on physical examination, and had a negative Xpert MTB/RIF result (Cepheid; California, USA). We collected sputum, nasopharyngeal swabs, stool and urine samples from TB patients and household controls at recruitment. Löwenstein-Jensen mycobacterial culture was used to confirm TB. Kato-katz and Bearman methods for detection of soil transmitted helminths infections from stool. Urine filtration and Circulating Cathodic Antigen (CCA) assay for detection of Schistosomiasis. Nasopharyngeal swabs samples were analyzed using Allplex™ Respiratory full panel assay and PCR Anyplex™II RV16 for detection of respiratory bacterial and viral pathogens respectively. Principle findings: In a study to determine the treatment outcome of TB and HIV co-infected patients routinely diagnosed at Temeke district treated under home- and facility-based DOT: data of 4,835 adult TB patients were analyzed, with a median age of 35 years, 2,943 (60.9%) were men and TB/HIV co-infection prevalence of 39.9%. A total of 3,593 (74.3%) patients were treated under home-based DOT. Patients on home-based DOT were more likely to die compared to patients on facility-based DOT (RR 2.04, 95% Confidence Interval [95% CI]: 1.52-2.73), and more likely to complete TB treatment (RR 1.14, 95% CI: 1.06-1.23), but less likely to have a successful treatment outcome (RR 0.94, 95% CI: 0.92-0.97). Home-based DOT was preferred by women (adjusted Odds Ratio [aOR] 1.55, 95% CI: 1.34-1.80, p<0.001), older people (aOR 1.01 for each year increase, 95% CI: 1.00-1.02, p=0.001) and patients with extra-pulmonary TB (aOR 1.45, 95% CI: 1.16-1.81, p=0.001), but less frequently by patients on a retreatment regimen (aOR 0.12, 95% CI: 0.08-0.19, p<0.001). In a study to assess the association of TB and helminth infection: a total of 597 TB patients and 375 household contact controls were included. The median age was 33 years and 60.2% (585/972) were men. The prevalence of any helminth infection among TB patients was 31.8% (190/597) and 25.9% (97/375) among controls. Strongyloides stercoralis was the predominant helminth species (16.6%, 161), followed by hookworm (9.0%, 87) and Schistosoma mansoni (5.7%, 55). An infection with any helminth was not associated with TB (aOR 1.26, 95% CI: 0.88-1.80, p=0.22), but S. mansoni infection was (aOR 2.15, 95% CI: 1.03-4.45, p=0.040). Moreover, S. mansoni infection was associated with lower sputum bacterial load (aOR 2.63, 95% CI: 1.38-5.26, p=0.004) and tended to have fewer lung cavitations (aOR 0.41, 95% CI: 0.12-1.16, p=0.088). When assessing the interaction between TB and respiratory pathogens: we analyzed 794 study participants, of which 489 (61.6%) were TB patients and 305 (38.4%) were household contact controls. The median age of the study participants was 33 years; 61% (484/794) were men, and 21% (168/ 794) were HIV-positive. TB patients had a higher prevalence of HIV (28.6%; 140/489) than controls (9.2%; 28/305). Overall prevalence of respiratory viral pathogens was 20.4% (160/794; 95%CI 17.7-23.3%) and of bacterial pathogens 38.2% (303/794; 95%CI 34.9-41.6%). TB patients and controls did not differ in the prevalence of respiratory viruses (Odds Ratio [OR] 1.00, 95%CI 0.71-1.44), but respiratory bacteria were less frequently detected in TB patients (OR 0.70, 95%CI 0.53-0.94). TB patients with both respiratory viruses and respiratory bacteria were likely to have more severe disease (adjusted OR [aOR] 1.6, 95%CI 1.1-2.4; p=0.011). TB patients with respiratory viruses tended to have more frequent lung cavitations (aOR 1.6, 95%CI 0.93-2.7; p=0.089). Conclusion: TB patients under home-based DOT had more risk factors for death such as older age, HIV infection and sputum smear-negative TB, and had higher TB mortality compared to patients under facility-based DOT. Assessment of TB mortality risk factors and offering additional clinical care could be beneficial in reducing TB mortality. Further operational research is warranted to monitor implementation of DOT and discern other risk factors for deaths. S. mansoni infection was an independent risk factor for active TB and altered the clinical presentation in TB patients. S. mansoni infection may play a role in TB pathogenesis in humans. Bidirectional screening of TB and helminth including treatment for both diseases should be considered in a clinical management of patients. Respiratory viruses are common for both TB patients and household controls. TB patients may present with more severe TB disease, particularly when they are co- infected with both bacteria and viruses

Xpert® MTB/RIF assay testing on stool for the diagnosis of paediatric pulmonary TB in Tanzania.

SETTING: Six health facilities in Dar es Salaam, Tanzania. OBJECTIVE: To evaluate the use of stool specimens in the diagnostic workup of paediatric TB using the Xpert® MTB/RIF assay. DESIGN: Between December 2018 and May 2019, we performed a cross-sectional diagnostic study of children aged between 1 month and 14 years with presumptive TB. A single stool specimen was tested using Xpert. The result was compared with the reference microbiological standard for respiratory or gastric specimens tested using Xpert and/or solid culture. The sensitivity, specificity and predictive values of stool Xpert assay were assessed. RESULTS: A total of 225 children with a median age of 2.17 years (IQR 1.16-5.19) were enrolled; 165/225 (73.3%) were aged <5 years. Of 225 children, 8 (3.6%) were diagnosed with TB as they were culture- or Xpert-positive on sputum/gastric aspirate. The stool Xpert assay showed a sensitivity of 62.5% (95% CI 25-92) and specificity of 100% (95% CI 98-100) against the reference standard. CONCLUSION: Use of the Xpert assay on stool specimens had a moderate sensitivity and high specificity in the diagnosis of pulmonary TB in children. Our data adds to the body of evidence for the use of Xpert assay on stool as a non-respiratory specimen to complement conventional methods used to diagnose the disease

Diagnostic Delay and Associated Factors among Patients with Pulmonary Tuberculosis in Dar es Salaam, Tanzania.

Tanzania is among the 30 countries with the highest tuberculosis (TB) burdens. Because TB has a long infectious period, early diagnosis is not only important for reducing transmission, but also for improving treatment outcomes. We assessed diagnostic delay and associated factors among infectious TB patients. We interviewed new smear-positive adult pulmonary TB patients enrolled in an ongoing TB cohort study in Dar es Salaam, Tanzania, between November 2013 and June 2015. TB patients were interviewed to collect information on socio-demographics, socio-economic status, health-seeking behaviour, and residential geocodes. We categorized diagnostic delay into ≤ 3 or > 3 weeks. We used logistic regression models to identify risk factors for diagnostic delay, presented as crude (OR) and adjusted Odds Ratios (aOR). We also assessed association between geographical distance (incremental increase of 500 meters between household and the nearest pharmacy) with binary outcomes. We analysed 513 patients with a median age of 34 years (interquartile range 27-41); 353 (69%) were men. Overall, 444 (87%) reported seeking care from health care providers prior to TB diagnosis, of whom 211 (48%) sought care > 2 times. Only six (1%) visited traditional healers before TB diagnosis. Diagnostic delay was positively associated with absence of chest pain (aOR = 7.97, 95% confidence intervals [CI]: 3.15-20.19; P < 0.001), and presence of hemoptysis (aOR = 25.37, 95% CI: 11.15-57.74; P < 0.001) and negatively associated with use of medication prior to TB diagnosis (aOR = 0.31, 95% CI: 0.14-0.71; P = 0.01). Age, sex, HIV status, education level, household income, and visiting health care facilities (HCFs) were not associated with diagnostic delay. Patients living far from pharmacies were less likely to visit a HCF (incremental increase of distance versus visit to any facility: OR = 0.51, 95% CI: 0.28-0.96; P = 0.037). TB diagnostic delay was common in Dar es Salaam, and was more likely among patients without prior use of medication and presenting with hemoptysis. Geographical distance to HCFs may have an impact on health-seeking behaviour. Increasing community awareness of TB signs and symptoms could further reduce diagnostic delays and interrupt TB transmission

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

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.; 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.; 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 &lt; 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.; CPC increases culture yield, decreases the proportion of contamination, and does not alter the performance of Xpert MTB/RIF

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

Prevalence and clinical relevance of helminth co-infections among tuberculosis patients in urban Tanzania

Helminth infections can negatively affect the immunologic host control, which may increase the risk of progression from latent Mycobacterium tuberculosis infection to tuberculosis (TB) disease and alter the clinical presentation of TB. We assessed the prevalence and determined the clinical relevance of helminth co-infection among TB patients and household contact controls in urban Tanzania.; Between November 2013 and October 2015, we enrolled adult (≥18 years) sputum smear-positive TB patients and household contact controls without TB during an ongoing TB cohort study in Dar es Salaam, Tanzania. We used Baermann, FLOTAC, Kato-Katz, point-of-care circulating cathodic antigen, and urine filtration to diagnose helminth infections. Multivariable logistic regression models with and without random effects for households were used to assess for associations between helminth infection and TB.; A total of 597 TB patients and 375 household contact controls were included. The median age was 33 years and 60.2% (585/972) were men. The prevalence of any helminth infection among TB patients was 31.8% (190/597) and 25.9% (97/375) among controls. Strongyloides stercoralis was the predominant helminth species (16.6%, 161), followed by hookworm (9.0%, 87) and Schistosoma mansoni (5.7%, 55). An infection with any helminth was not associated with TB (adjusted odds ratio (aOR) 1.26, 95% confidence interval (CI): 0.88-1.80, p = 0.22), but S. mansoni infection was (aOR 2.15, 95% CI: 1.03-4.45, p = 0.040). Moreover, S. mansoni infection was associated with lower sputum bacterial load (aOR 2.63, 95% CI: 1.38-5.26, p = 0.004) and tended to have fewer lung cavitations (aOR 0.41, 95% CI: 0.12-1.16, p = 0.088).; S. mansoni infection was an independent risk factor for active TB and altered the clinical presentation in TB patients. These findings suggest a role for schistosomiasis in modulating the pathogenesis of human TB. Treatment of helminths should be considered in clinical management of TB and TB control programs

Evaluation of Xpert® MTB/RIF and ustar easyNAT™ TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania : a prospective descriptive study

Fine needle aspiration biopsy has become a standard approach for diagnosis of peripheral tuberculous lymphadenitis. The aim of this study was to compare the performance of Xpert MTB/RIF and Ustar EasyNAT TB IAD nucleic acid amplification assays, against acid-fast bacilli microscopy, cytology and mycobacterial culture for the diagnosis of TB lymphadenitis in children from a TB-endemic setting in Tanzania.; Children of 8 weeks to 16 years of age, suspected of having TB lymphadenitis, were recruited at a district hospital in Tanzania. Fine needle aspirates of lymph nodes were analysed using acid-fast bacilli microscopy, liquid TB culture, cytology, Xpert MTB/RIF and EasyNAT. Latent class analysis and comparison against a composite reference standard comprising "culture and/or cytology" was done, to assess the performance of Xpert MTB/RIF and EasyNAT for the diagnosis of TB lymphadenitis.; Seventy-nine children were recruited; 4 were excluded from analysis. Against a composite reference standard of culture and/or cytology, Xpert MTB/RIF and EasyNAT had a sensitivity and specificity of 58 % and 93 %; and 19 % and 100 % respectively. Relative to latent class definitions, cytology had a sensitivity of 100 % and specificity of 94.7 %.; Combining clinical assessment, cytology and Xpert MTB/RIF may allow for a rapid and accurate diagnosis of childhood TB lymphadenitis. Larger diagnostic evaluation studies are recommended to validate these findings and on Xpert MTB/RIF to assess its use as a solitary initial test for TB lymphadenitis in children

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

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

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.; 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.; 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.; PACTR, Registration number: PACTR201712002829221, registered December 1st 2017