Diagnostic accuracy of a three-gene Mycobacterium tuberculosis host response cartridge using fingerstick blood for childhood tuberculosis: a multicentre prospective study in low-income and middle-income countries.

BACKGROUND: Childhood tuberculosis remains a major cause of morbidity and mortality in part due to missed diagnosis. Diagnostic methods with enhanced sensitivity using easy-to-obtain specimens are needed. We aimed to assess the diagnostic accuracy of the Cepheid Mycobacterium tuberculosis Host Response prototype cartridge (MTB-HR), a candidate test measuring a three-gene transcriptomic signature from fingerstick blood, in children with presumptive tuberculosis disease. METHODS: RaPaed-TB was a prospective diagnostic accuracy study conducted at four sites in African countries (Malawi, Mozambique, South Africa, and Tanzania) and one site in India. Children younger than 15 years with presumptive pulmonary or extrapulmonary tuberculosis were enrolled between Jan 21, 2019, and June 30, 2021. MTB-HR was performed at baseline and at 1 month in all children and was repeated at 3 months and 6 months in children on tuberculosis treatment. Accuracy was compared with tuberculosis status based on standardised microbiological, radiological, and clinical data. FINDINGS: 5313 potentially eligible children were screened, of whom 975 were eligible. 784 children had MTB-HR test results, of whom 639 had a diagnostic classification and were included in the analysis. MTB-HR differentiated children with culture-confirmed tuberculosis from those with unlikely tuberculosis with a sensitivity of 59·8% (95% CI 50·8-68·4). Using any microbiological confirmation (culture, Xpert MTB/RIF Ultra, or both), sensitivity was 41·6% (34·7-48·7), and using a composite clinical reference standard, sensitivity was 29·6% (25·4-34·2). Specificity for all three reference standards was 90·3% (95% CI 85·5-94·0). Performance was similar in different age groups and by malnutrition status. Among children living with HIV, accuracy against the strict reference standard tended to be lower (sensitivity 50·0%, 15·7-84·3) compared with those without HIV (61·0%, 51·6-69·9), although the difference did not reach statistical significance. Combining baseline MTB-HR result with one Ultra result identified 71·2% of children with microbiologically confirmed tuberculosis. INTERPRETATION: MTB-HR showed promising diagnostic accuracy for culture-confirmed tuberculosis in this large, geographically diverse, paediatric cohort and hard-to-diagnose subgroups. FUNDING: European and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung; German Center for Infection Research (DZIF).

Burden and associated phenotypic characteristics of tuberculosis infection in adult Africans with diabetes: a systematic review.

Diabetes mellitus (DM) increases the risk of developing tuberculosis infection (TBI). However, the evidence on the burden and phenotypic characteristics of TBI in African patients with DM is limited. This study aimed to determine the prevalence and characterisation of TBI in native African patients living with DM. We searched PubMed, EMBASE, and African Journals Online for original studies reporting information on the prevalence and characteristics of TBI in adult Africans with DM. A forest plot was used to describe the pooled prevalence estimate of TBI and the corresponding 95% confidence intervals (CI). Six studies conducted in four African countries involving 721 participants with DM were included in this systematic review. The pooled prevalence estimate of TBI was 40% (95% CI 20-60%, I2 = 98.52%, p < 0.001). Age ≥ 40 years and glycated haemoglobin levels independently predicted TBI positivity in patients with DM in three studies. Africans with DM have a high prevalence of TBI, especially those who are older or with poorly controlled diabetes. This justifies the need for studies to explore how to screen and manage TBI to avert the progression to active TB disease.

Qualification of the differential leukocyte count and immunophenotyping in cryopreserved ex vivo whole blood assay.

We developed a flow cytometry-based assay, termed Differential Leukocyte Counting and Immunophenotyping in Cryopreserved Ex vivo whole blood (DLC-ICE), that allows quantification of absolute counts and frequencies of leukocyte subsets and measures expression of activation, phenotypic and functional markers. We evaluated the performance of the DLC-ICE assay by determining inter-operator variability for processing fresh whole blood (WB) from healthy donors collected at multiple clinical sites. In addition, we assessed inter-operator variability for staining of fixed cells and robustness across different anticoagulants. Accuracy was evaluated by comparing DLC-ICE measurements to real-time cell enumeration using an accredited hematology analyzer. Finally, we developed and tested the performance of a 27-colour immunophenotyping panel on cryopreserved fixed WB and compared results to matched fresh WB. Overall, we observed <20% variability in absolute counts and frequencies of granulocytes, monocytes and lymphocytes (T, B and NK cells) when fresh WB was collected in different anti-coagulant tubes, processed or stained by independent operators. Absolute cell counts measured across operators and anti-coagulants using the DLC-ICE method exhibited excellent correlation with the reference method, complete blood count (CBC) with differential, measured using a hematology analyzer (r2 > 0.9 for majority of measurements). A comparison of leukocyte immunophenotyping on fresh WB versus DLC-ICE processed blood yielded equivalent and linear results over a wide dynamic range (r2 = 0.94 over 10-104 cells/µL). These results demonstrate low variability across trained operators, high robustness, linearity and accuracy, supporting utility of the DLC-ICE assay for large cohort studies involving multiple clinical research sites.

Performance of Tuberculosis Molecular Bacterial Load Assay Compared to Alere TB-LAM in Urine of Pulmonary Tuberculosis Patients with HIV Co-Infections.

Alternative tools are needed to improve the detection of M. tuberculosis (M. tb) in HIV co-infections. We evaluated the utility of Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) compared to lipoarabinomannan (LAM) to detect M. tb in urine. Sputum Xpert MTB/RIF-positive patients were consented to provide urine at baseline, weeks 2, 8, 16, and 24 of treatment for TB-MBLA, culture, and LAM. Results were compared with sputum cultures and microscopy. Initial M. tb. H37Rv spiking experiments were performed to validate the tests. A total of 63 urine samples from 47 patients were analyzed. The median age (IQR) was 38 (30-41) years; 25 (53.2%) were male, 3 (6.5%) had urine for all visits, 45 (95.7%) were HIV positive, of whom 18 (40%) had CD4 cell counts below 200 cells/µL, and 33 (73.3%) were on ART at enrollment. Overall urine LAM positivity was 14.3% compared to 4.8% with TB-MBLA. Culture and microscopy of their sputum counterparts were positive in 20.6% and 12.7% of patients, respectively. Of the three patients with urine and sputum at baseline, one (33.33%) had urine TB-MBLA and LAM positive compared to 100% with sputum MGIT culture positive. Spearman's rank correction coefficient (r) between TB-MBLA and MGIT was -0.85 and 0.89 with a solid culture, p > 0.05. TB-MBLA has the promising potential to improve M. tb detection in urine of HIV-co-infected patients and complement current TB diagnostics.

Rapid and Accurate Diagnosis of Pediatric Tuberculosis Disease: A Diagnostic Accuracy Study for Pediatric Tuberculosis.

INTRODUCTION: An estimated 1.2 million children develop tuberculosis (TB) every year with 240,000 dying because of missed diagnosis. Existing tools suffer from lack of accuracy and are often unavailable. Here, we describe the scientific and clinical methodology applied in RaPaed-TB, a diagnostic accuracy study. METHODS: This prospective diagnostic accuracy study evaluating several candidate tests for TB was set out to recruit 1000 children <15 years with presumptive TB in 5 countries (Malawi, Mozambique, South Africa, Tanzania, India). Assessments at baseline included documentation of TB signs and symptoms, TB history, radiography, tuberculin skin test, HIV testing and spirometry. Respiratory samples for reference standard testing (culture, Xpert Ultra) included sputum (induced/spontaneous) or gastric aspirate, and nasopharyngeal aspirate (if <5 years). For novel tests, blood, urine and stool were collected. All participants were followed up at months 1 and 3, and month 6 if on TB treatment or unwell. The primary endpoint followed NIH-consensus statements on categorization of TB disease status for each participant. The study was approved by the sponsor's and all relevant local ethics committees. DISCUSSION: As a diagnostic accuracy study for a disease with an imperfect reference standard, Rapid and Accurate Diagnosis of Pediatric Tuberculosis Disease (RaPaed-TB) was designed following a rigorous and complex methodology. This allows for the determination of diagnostic accuracy of novel assays and combination of testing strategies for optimal care for children, including high-risk groups (ie, very young, malnourished, children living with HIV). Being one of the largest of its kind, RaPaed-TB will inform the development of improved diagnostic approaches to increase case detection in pediatric TB.

Indicators of optimal diabetes care and burden of diabetes complications in Africa: a systematic review and meta-analysis.

OBJECTIVE: Contemporary data on the attainment of optimal diabetes treatment goals and the burden of diabetes complications in adult populations with type 2 diabetes in Africa are lacking. We aimed to document the current status of attainment of three key indicators of optimal diabetes care and the prevalence of five diabetes complications in adult African populations with type 2 diabetes. METHODS: We systematically searched Embase, PubMed and the Cochrane library for published studies from January 2000 to December 2020. Included studies reported any information on the proportion of attainment of optimal glycated haemoglobin (HbA1c), blood pressure (BP) and low-density lipoprotein cholesterol (LDLC) goals and/or prevalence of five diabetes complications (diabetic peripheral neuropathy, retinopathy, nephropathy, foot ulcers and peripheral arterial disease). Random effect model meta-analysis was performed to determine the pooled proportion of attainment of the three treatment goals and the prevalence of five diabetes complications. RESULTS: In total, 109 studies with a total of 63 890 participants (53.3% being females) were included in the meta-analysis. Most of the studies were conducted in Eastern African countries (n=44, 40.4%). The pooled proportion of attainment of an optimal HbA1c, BP and LDLC goal was 27% (95% CI 24 to 30, I2=94.7%), 38% (95% CI 30 to 46, I2=98.7%) and 42% (95% CI 32 to 52, I2=97.4%), respectively. The pooled prevalence of diabetic peripheral neuropathy, retinopathy, diabetic nephropathy, peripheral arterial disease and foot ulcers was 38% (95% CI 31 to 45, I2=98.2%), 32% (95% CI 28 to 36, I2=98%), 31% (95% CI 22 to 41, I2=99.3%), 19% (95% CI 12 to 25, I2=98.1%) and 11% (95% CI 9 to 14, I2=97.4%), respectively. CONCLUSION: Attainment of optimal diabetes treatment goals, especially HbA1c, in adult patients with type 2 diabetes in Africa remains a challenge. Diabetes complications, especially diabetic peripheral neuropathy and retinopathy, are highly prevalent in adult populations with type 2 diabetes in Africa.

Systematic assessment of clinical and bacteriological markers for tuberculosis reveals discordance and inaccuracy of symptom-based diagnosis for treatment response monitoring.

Background: Clinical symptoms are the benchmark of tuberculosis (TB) diagnosis and monitoring of treatment response but are not clear how they relate to TB bacteriology, particularly the novel tuberculosis-molecular bacterial load assay (TB-MBLA). Methods: Presumptive cases were bacteriologically confirmed for TB and assessed for symptoms and bacteriological resolution using smear microscopy (SM), culture, and TB-MBLA over 6-month treatment course. Kaplan-Meier and Kappa statistics were used to test the relationship between symptoms and bacteriological positivity. Results: A cohort of 46 bacteriologically confirmed TB cases were analyzed for treatment response over a 6-month treatment course. Pre-treatment symptoms and bacteriological positivity concurred in over 70% of the cases. This agreement was lost in over 50% of cases whose chest pain, night sweat, and loss of appetite had resolved by week 2 of treatment. Cough resolved at a 3.2% rate weekly and was 0.3% slower than the combined bacteriological (average of MGIT and TB-MBLA positivity) resolution rate, 3.5% per week. A decrease in TB-MBLA positivity reflected a fall in bacillary load, 5.7 ± 1.3- at baseline to 0.30 ± 1.0- log10 eCFU/ml at month 6, and closer to cough resolution than other bacteriological measures, accounting for the only one bacteriologically positive case out of seven still coughing at month 6. Low baseline bacillary load patients were more likely to be bacteriologically negative, HR 5.6, p = 0.003 and HR 3.2, p = 0.014 by months 2 and 6 of treatment, respectively. Conclusion: The probability of clinical symptoms reflecting bacteriological positivity weakens as the patient progresses on anti-TB therapy, making the symptom-based diagnosis a less reliable marker of treatment response.

Rifapentine and isoniazid for prevention of tuberculosis in people with diabetes (PROTID): protocol for a randomised controlled trial.

BACKGROUND: Diabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP). METHODS: The 'Prevention of tuberculosis in diabetes mellitus' (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM. DISCUSSION: PROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control. TRIAL REGISTRATION: ClinicalTrials.gov NCT04600167 . Registered on 23 October 2020.

Health-related quality of life and psychological distress among adults in Tanzania: a cross-sectional study.

BACKGROUND: Little data is available on health-related quality of life (HRQoL) and mental health of the general population in Tanzania. We aimed to describe HRQoL and level of psychological distress among adults in Mbeya and Songwe Regions of Tanzania. METHODS: We conducted a cross-sectional study between April and October 2019 in Mbeya and Songwe Regions. Data were collected using the Medical Outcomes Short Form-36 (SF-36) questionnaire and the Page Kessler Psychological Distress Scale (K10). We described demographic characteristics of participants and used log-binomial regression to identify participant characteristics associated with psychological distress (K10 score ≥ 20). RESULTS: A total of 393 adults were enrolled. The participants had a median age of 29 years (IQR 23-40) and 54.2% were male. Participants reported a physical component summary score (PCS) with a mean of 54.7 (SD7.1) and a mental component summary score (MCS) with a mean of 55.5 (SD5.1). Older participants (≥ 40 year) and those that were divorced/widowed reported lower physical functioning, energy/vitality and emotional well-being compared to their counterparts (p < 0.05). In terms of psychological distress, majority of participants (78.4%; 305/389) reported that they were likely to be well (K10 score < 20), while 13.4% (52/389) reported to have mild (K10 score 20-24), 5.7% (22/389) moderate (K10 score 25-29), and 2.6% (10/389) severe (K10 score ≥ 30) psychological distress. CONCLUSIONS: Physical function and mental well-being in this adult population from Tanzania were lower than that reported in other similar research in Tanzania and other African countries. This study provides valuable references for other research initiatives and clinical services in this region.

Treatment outcomes of multi-drug resistant tuberculosis patients with or without human immunodeficiency virus co-infection in Africa and Asia: Systematic review and meta-analysis.

Background: Treatment outcomes of multidrug resistant tuberculosis (MDRTB) is a challenge, especially in resource limited settings. The aim of this study was to compare whether Human Immune Virus (HIV) has influence on the treatment outcomes of MDRTB among patients in Africa and Asia. Methods: Studies were searched from PubMed, Google scholar, African Journals online, EBSCOhost and CENTRAL from year 2000 until January 2021. The participants in the studies were reported of using MDRTB treatment regimen and also included those with HIV. Studies published before 2000 were excluded. Quality of the review was assessed by AMSTEL 2 criteria. The Mantel- Haenszel random effects method was used for the analysis, with risk ratio (RR) as an effect estimate, with 95% confidence interval and using Stata 14 software. Results: Nine studies were included in the meta-analysis. Treatment success was low in HIV negative participants (RR 0.62, 95% CI 0.58-0.67). However, death was higher in the HIV co-infected participants. (RR 1.35, 95% CI 1.25-1.45). There was no significant difference in treatment failure among patients with or without HIV. (RR 1.08, 95% CI 0.97-1.20). Consistently, no significant difference was found in lost to follow up (LTF) between the two groups (RR 1.07, 95% CI 0.93-1.20). Conclusion: Treatment success was lower for the MDRTB and HIV co-infections. No significant difference has been found on other outcomes like failure and lost to follow up between patients with HIV co-infected and HIV negative group. The study limitations are that we had only 2 studies representing Asia, and this could have affected the outcome of results. There is need for interventions to improve treatment success in the HIV co-infected group. Other: The protocol was registered in International prospective register of systematic reviews (PROSPERO), ID: CRD42021247883. There was no funding for the review.

HIV testing and linkage to care-A case of a mobile diagnostic and counseling service in Mbeya, Tanzania; A quantitative study.

HIV-care programmes are faced with significant challenges in getting newly diagnosed People Living with Human Immunodeficiency Virus (PLHIV) linked to care despite massive investment in HIV prevention, treatment and care. This study assessed the performance of mobile HIV Testing and Counseling service (mHTC) in provision of HIV-testing and linkage to care of newly diagnosed PLHIV from Key and Vulnerable Populations (KVPs). A retrospective review of the records of 25,248 clients was extracted from the mHTC database from October-2016 to September-2018. Of 25,248 clients, 51.71% were in 25-45 years age group, 55.4% were males, 60.5% were married and 62.1% had primary level of education. The median age of clients was 31 (IQR: 23-42) years. Out of the clients tested, 800 (3.17%) were diagnosed HIV-positive. Positivity was high among females 450 (4%), age group 25-45 years 538 (4.12%), divorced 202 (7.41%) and clients with primary level of education 504 (3.21%). An association between HIV status and sex, age group, relationship status and level of education was observed (P<0001). Out of the 800 HIV-positive clients, 418 (52.30%) were successfully linked to care. Among the positive clients, 5/6 (83.33%) children below 15 years old, 238/450 (52.89%) females and 39/64 (60.94%) widows were successfully linked to care. In the multivariable log binomial regression model age of the clients was associated with successful linkage to care. The mHTC was able to reach KVP clients; overall linkage for both sexes was 52.30% below the recommended UNAIDS 90-90-90 target. Raising the need to address the challenges associated with linkage and specific care for KVPs as a subset of the general population. The mHTC has shown that it is feasible to improve the reach of KVP clients; however, further research is required to examine the quality of this service at the community level.

Proceedings from the CIHLMU occupational safety and health symposium 2019 "Protecting workers' health: global challenges and opportunities in work-related respiratory diseases".

The international CIHLMU Occupational Safety and Health Symposium 2019 was held on 16th March, 2019 at the Ludwig-Maximilians-Universität Munich, Germany. About 60 participants from around the world representing occupational health and safety professionals, students, instructors from several institutions in Germany and abroad, attended the symposium.The main objective of the symposium was to create awareness on global challenges and opportunities in work-related respiratory diseases. One keynote lecture and six presentations were made. While the keynote lecture addressed issues on occupational diseases in the twenty-first century, the six presentations were centered on: Prevention and control of work-related respiratory diseases, considerations; Occupational health and safety in Mining: Respiratory diseases; The prevention of TB among health workers is our collective responsibility; Compensation and prevention of occupational diseases and discussion on how artificial intelligence can support them: Overview of international approaches; Work-related Asthma: Evidence from high-income countries; and The role of imaging in the diagnosis of work- related respiratory diseases. A panel discussion was conducted following the presentations on the importance and challenges of data acquisition which is needed to have a realistic picture of the occupational safety and health status of workers at different levels. The current summary is an attempt to share the proceedings of the symposium.

Adrenal Insufficiency: A Forgotten Diagnosis in HIV/AIDS Patients in Developing Countries.

Adrenal insufficiency (AI) is one of the most common endocrine disease in patients with HIV/AIDS, leading to high morbidity and mortality in HIV patients who become critically ill. Various etiologies are associated with the condition, including cytomegalovirus (CMV), Mycobacterium tuberculosis, lymphoma, Kaposi's sarcoma, and drugs such as rifampin, among others. HIV patients with advanced disease develop relative cortisol deficiency largely due to the reduction of cortisol reserve, which predisposes patients to adrenal crisis in periods of stress or critical illness. The prevalence of AI in HIV/AIDS patients during HAART era is higher in developing than developed countries, probably due to limited access to both diagnosis and adequate treatments which increases the risk of opportunistic infections. The clinical features of functional adrenal insufficiency in HIV/AIDS patients can be masked by various infectious, noninfectious, and iatrogenic causes, which reduce clinical recognition of the condition. Development of simple screening algorithms may help clinicians reach the diagnosis when approaching these patients. In many low-income countries, most HIV patients are diagnosed with advanced disease; thus, further research is necessary to elucidate the prevalence of adrenal insufficiency in HIV/AIDS patients and the condition's impact on mortality in this population.

Molecular Bacterial Load Assay Concurs with Culture on NaOH-Induced Loss of Mycobacterium tuberculosis Viability.

Effective methods to detect viable Mycobacterium tuberculosis, the main causative agent of tuberculosis (TB), are urgently needed. To date, cultivation of M. tuberculosis is the gold standard, which depends on initial sample processing with N-acetyl-l-cysteine-sodium hydroxide (NALC-NaOH), chemicals that compromise M. tuberculosis viability and, consequently, the performance of downstream tests. We applied culture and the novel molecular bacterial load assay (MBLA) to measure the loss of M. tuberculosis viability following NALC-NaOH treatment of M. tuberculosis H37Rv pure culture and clinical sputum samples from pulmonary TB patients. Compared to the bacterial loads of untreated controls, NALC-NaOH treatment of M. tuberculosis reduced the MBLA-detectable bacillary load (estimated number of CFU [eCFU] per milliliter) by 0.66 ± 0.21 log10 at 23°C (P = 0.018) and 0.72 ± 0.08 log10 at 30°C (P = 0.013). Likewise, NALC-NaOH treatment reduced the viable count on solid culture by 0.84 ± 0.02 log10 CFU/ml at 23°C (P < 0.001) and 0.85 ± 0.01 log10 CFU/ml at 30°C (P < 0.001), respectively. The reduction in the viable count was reflected by a corresponding increase in the time to positivity of the mycobacterial growth indicator tube (MGIT) liquid culture: 1.2 days at 23°C (P < 0.001) and 1.1 days at 30°C (P < 0.001). This NaOH-induced M. tuberculosis viability loss was replicated in clinical sputum samples, with the bacterial load dropping by 0.65 ± 0.17 log10 from 5.36 ± 0.24 log10 eCFU/ml to 4.71 ± 0.16 log10 eCFU/ml for untreated and treated sputa, respectively. Applying the model of Bowness et al. (R. Bowness, M. J. Boeree, R. Aarnoutse, R. Dawson, et al., J Antimicrob Chemother 70:448-455, 2015, https://doi.org/10.1093/jac/dku415) revealed that the treated MGIT time to culture positivity of 142 ± 7.02 h was equivalent to 4.86 ± 0.28 log10 CFU, consistent with the MBLA-measured bacterial load. Our study confirms the contribution of NALC-NaOH treatment to the loss of viable bacterial counts. Tests that obviate the need for decontamination may offer an alternative option for the accurate detection of viable M. tuberculosis and treatment response monitoring.

Accuracy and Operational Characteristics of Xpert Human Immunodeficiency Virus Point-of-Care Testing at Birth and Until Week 6 in Human Immunodeficiency Virus-exposed Neonates in Tanzania.

Background: Point-of-care (PoC) systems for early infant diagnosis (EID) may improve timely infant human immunodeficiency virus (HIV) management. Experiences within African public health settings are limited. Methods: We evaluated the accuracy and operational feasibility of the Xpert HIV-1 Qual for PoC-EID testing, using fresh blood and dried blood spots (DBS) samples at obstetric health facilities in Tanzania at birth and at postpartum weeks 1, 2, 3, and 6 in HIV-exposed infants. Test results were confirmed using TaqMan DBS HIV-deoxyribonucleic acid and/or plasma HIV-ribonucleic acid (RNA) testing. Results: At week 6, 15 (2.5%) out of 614 infants were diagnosed with HIV; 10 (66.7%) of them at birth (median HIV-RNA 4570 copies/mL). At birth, the Xpert-PoC and Xpert-DBS were 100% sensitive (95% confidence intervals: PoC, 69.2-100%; DBS, 66.4-100%) and 100% specific (PoC, 92.1-100%; DBS, 88.4-100%). By week 3, 5 infants with intra/postpartum HIV-infection (median HIV-RNA 1 160 000 copies/mL) were all correctly diagnosed by Xpert. In 2 cases, Xpert-PoC testing correctly identified HIV-infection when DBS tests (Xpert and TaqMan) were negative, suggesting a greater sensitivity. In 2 infants with confirmed HIV at birth, all tests were negative at week 6, possibly because of viral suppression under nevirapine prophylaxis. Problems were reported in 183/2736 (6.7%) of Xpert-PoC tests, mostly related to power cuts (57.9%). Conclusions: We demonstrated excellent Xpert HIV-1 Qual performance and good operational feasibility for PoC-EID testing at obstetric health facilities. Week 6 sensitivity issues were possibly related to nevirapine prophylaxis, supporting additional birth PoC-EID testing to avoid underdiagnosis. Clinical Trials Registration: NCT02545296.

Xpert MTB/RIF Ultra assay for the diagnosis of pulmonary tuberculosis in children: a multicentre comparative accuracy study.

OBJECTIVES: We evaluated the diagnostic performance of the novel next-generation Xpert MTB/RIF Ultra (Xpert Ultra) in comparison to Xpert MTB/RIF (Xpert) assay for the detection of paediatric pulmonary tuberculosis in high burden settings. METHODS: From May 2011 to September 2012, children with suspected pulmonary tuberculosis were enrolled at two Tanzanian sites and sputum samples were examined using sputum smear, Xpert and culture. Xpert Ultra was tested between January and June 2017 using sputum pellets, which had been stored at -80°C. The diagnostic accuracy of Ultra versus Xpert was determined using well-defined case definitions as reference standard. RESULTS: In total, 215 children were included. The median age was 5.4 years, the HIV prevalence was 52% and 13% had culture-confirmed pulmonary tuberculosis. When only the first available sample of each patient was analysed, the sensitivity of Xpert Ultra was 64.3 % (95% CI: 44.1 to 81.4) while that of Xpert was 53.6% (95%CI: 33.9 to 72.5). The specificity of Xpert Ultra based on analysis of all available samples was 98.1% (95%CI: 93.4 to 99.7), that of Xpert was 100%. CONCLUSIONS: Xpert Ultra was found to have a higher sensitivity, but slightly reduced specificity compared to Xpert in detecting pulmonary tuberculosis in children.

Tuberculosis Contact Screening and Isoniazid Preventive Therapy Among Children Under 5 in the Mbeya and Songwe Regions, Tanzania.

INTRODUCTION: The World Health Organization (WHO) recommends contact screening and initiation of isoniazid preventive therapy (IPT) for children under 5 years of age exposed to a sputum smear-positive (SS+) tuberculosis (TB) source case. We conducted this study in order to assess implementation of these recommendations in southwestern Tanzania. METHODS: We conducted this cross-sectional study from June to August 2015 in 12 selected health facilities in the Mbeya and Songwe regions of Tanzania. Adult SS+ pulmonary TB patients living in the same household as children under 5 were enrolled. Structured questionnaires were used to obtain sociodemographic information and details about screening and intervention activity related to contact children under 5. Data were analysed using Stata version 11.0. RESULTS: We enrolled 257 index cases, who collectively had 433 contact children under 5. The median age of the index cases was 34 years (interquartile range 28 to 41) and 52.9% were male. Out of 433 contacts, 31 (7.2%) were screened for TB, of whom 7 (22.6%) were treated for presumptive TB. Among those screened, 24 were not diagnosed with TB, of whom only 8 (33.3%) received IPT. CONCLUSION: Low uptake of TB contact screening and IPT administration among eligible children under 5 was observed in this study. Health-care workers should be sensitized to screening of household contacts of adults with SS+ TB and initiate IPT in those who are eligible.

Prevalence and Risk Factors Associated With Chronic Kidney Disease Among Patients Presenting at a Haemodialysis Unit in Dodoma, Tanzania.

BACKGROUND: Chronic kidney disease (CKD) is a major public health problem worldwide, due to its epidemic proportions and the associated cardiovascular morbidity and mortality. However, data on the burden of CKD among patients attending hospitals in Tanzania are still limited. The aim of this study was to determine the prevalence and risk factors associated with CKD among patients presenting at the University of Dodoma (UDOM) haemodialysis unit in Tanzania. METHODS: In this retrospective study, we reviewed data of 1,395 patients who presented at the UDOM haemodialysis unit from January 2013 to June 2015. Data were descriptively and inferentially analysed using Stata version 11.0. RESULTS: From January 2013 to June 2015, a total of 1,395 patients presented at the UDOM haemodialysis unit with history of kidney disease. Of these patients, 1244 (89.2%) enrolled into this study, 651 (52.3%) of them were female. Almost two-thirds (n=792, 63.7%) of the patients were found to have CKD, 59.1% with an estimated glomerular filtration rate of <60 mL/min/1.73 m2. Among those who had CKD, 347 (43.8%) had hypertension, 241 (30.4%) had diabetic mellitus, 79 (10.0%) had chronic glomerulonephritis, 70 (8.8%) had hypertension and diabetes mellitus, 38 (4.8%) had HIV/AIDS, and 17 (2.1%) had hepatitis B. The median serum creatinine level was 222 lmol/L (interquartile range [IQR] 126 to 317), urea level was 14.5 mmol/L (IQR 5 to 24), hemoglobin was 11.0 g/dL (IQR 6.2 to 15.7), and body mass index was 27.1 kg/m2 (IQR 17.3 to 36.8). Obesity, diabetes mellitus, and systolic hypertension were associated with developing CKD (P<.001). A total of 116 patients received haemodialysis during the study period. CONCLUSION: CKD was common among patients presenting in our hospital and is associated with high cardiovascular risk. To that end, patients should be thoroughly evaluated to identify and correct causes of their kidney disease, and efforts should be put in place for early detection and screening as well as advocacy on risk factors for CKD development in Tanzania.

Challenges and outcomes of haemodialysis among patients presenting with kidney diseases in Dodoma, Tanzania.

BACKGROUND: Kidney Diseases contribute a significant proportion to the global burden of non-communicable diseases. Haemodialysis services as the main modality of renal replacement therapy in most resource limited countries is only available in few cities and at higher costs. The aim of this study was to determine the challenges and outcomes of patients who were on haemodialysis at the University of Dodoma (UDOM) haemodialysis unit in Tanzania. METHODS: In this retrospective study; we reviewed haemodialysis registers and charts of 116 patients dialyzed from January 2013 to June 2015 at The UDOM haemodialysis unit. Data were descriptively and inferentially analysed using Stata version 11 software. RESULTS: Of the 116 patients, 52 (44.9%) were male, and 38(32.8%) were married. Their median age was 45 years. Thirty-two (27.6%) had acute kidney injury, of them 26 (81.3%) patients had recovery of renal function after haemodialysis. Indications for hemodialysis were anuria (18), intoxications (14), electrolyte imbalance (9), uraemia (7) infections (6) and fluid overload (4). Eighty-four (72.4%) patients had End Stage Renal Diseases (ESRD), of which 37 (44.1%) absconded/lost to follow up, 15 (17.9%) died, 22 (26.2%) were referred to Muhimbili National Hospital (MNH), 12 for possible kidney transplant abroad after haemodialysis, and 10 (11.9%) were still attending our unit for haemodialysis. Residing outside Dodoma was predictive for poor outcomes while on haemodialysis (OR 5.2, 95% CI 3.2-8.6, p < 0.001). In addition the odds ratio for poor outcomes was 7.3 times for a patient ESRD (OR7.34, 95% CI 3.26-18.17, p < 0.001). Patients who had no National Health Insurance Fund (NHIF) coverage (OR 6.6, 95% CI 5.4-12.7, p < 0.001) also had higher odds of poor outcomes after starting haemodialysis. CONCLUSION: Unavailability and high costs related to utilization of haemodialysis services among patients needing dialysis are the challenges for better outcomes. Therefore, haemodialysis and renal transplants services should be made easily available in regional referral hospitals at reasonable costs. In addition, members of the public should be educated on joining health insurance schemes and on making healthy life style choices for preventing chronic kidney disease and its progression.