Diagnostic accuracy of the Xpert® MTB/XDR assay for detection of Isoniazid and second-line antituberculosis drugs resistance at central TB reference laboratory in Tanzania.

INTRODUCTION: Early diagnosis of tuberculosis (TB) and universal access to drug-susceptibility testing (DST) are critical elements of the WHO End TB Strategy. Current rapid tests (e.g., Xpert® MTB/RIF and Ultra-assays) can detect rifampicin resistance-conferring mutations, but cannot detect resistance to Isoniazid and second-line anti-TB agents. Although Line Probe Assay is capable of detecting resistance to second-line anti-TB agents, it requires sophisticated laboratory infrastructure and advanced skills which are often not readily available in settings replete with TB. A rapid test capable of detecting Isoniazid and second-line anti-TB drug resistance is highly needed. METHODS: We conducted a diagnostic accuracy study to evaluate a new automated Xpert MTB/XDR 10-colour assay for rapid detection of Isoniazid and second-line drugs, including ethionamide, fluoroquinolones, and injectable drugs (Amikacin, Kanamycin, and Capreomycin). Positive Xpert MTB/RIF respiratory specimens were prospectively collected through routine diagnosis and surveillance of drug resistance at the Central TB Reference Laboratory in Tanzania. Specimens were tested by both Xpert XDR assay and LPA against culture-based phenotypic DST as the reference standard. FINDINGS: We analysed specimens from 151 TB patients with a mean age (SD) of 36.2 (12.7) years. The majority (n = 109, 72.2%) were males. The sensitivity for Xpert MTB/XDR was 93.5% (95% CI, 87.4-96.7); for Isoniazid, 96.6 (95% CI, 92.1-98.6); for Fluoroquinolone, 98.7% (95% Cl 94.8-99.7); for Amikacin, 96.6%; and (95% CI 92.1-98.6) for Ethionamide. Ethionamide had the lowest specificity of 50% and the highest was 100% for Fluoroquinolone. The diagnostic performance was generally comparable to that of LPA with slight variations between the two assays. The non-determinate rate (i.e., invalid M. tuberculosis complex detection) of Xpert MTB/XDR was 2·96%. CONCLUSION: The Xpert MTB/XDR demonstrated high sensitivity and specificity for detecting resistance to Isoniazid, Fluoroquinolones, and injectable agents. This assay can be used in clinical settings to facilitate rapid diagnosis of mono-isoniazid and extensively drug-resistant TB.

Implementation of evidence-based multiple focus integrated intensified TB screening to end TB (EXIT-TB) package in East Africa: a qualitative study.

INTRODUCTION: Tuberculosis (TB) remains a major cause of morbidity and mortality, especially in sub-Saharan Africa. We qualitatively evaluated the implementation of an Evidence-Based Multiple Focus Integrated Intensified TB Screening package (EXIT-TB) in the East African region, aimed at increasing TB case detection and number of patients receiving care. OBJECTIVE: We present the accounts of participants from Tanzania, Kenya, Uganda, and Ethiopia regarding the implementation of EXIT-TB, and suggestions for scaling up. METHODS: A qualitative descriptive design was used to gather insights from purposefully selected healthcare workers, community health workers, and other stakeholders. A total of 27, 13, 14, and 19 in-depth interviews were conducted in Tanzania, Kenya, Uganda, and Ethiopia respectively. Data were transcribed and translated simultaneously and then thematically analysed. RESULTS: The EXIT-TB project was described to contribute to increased TB case detection, improved detection of Multidrug-resistant TB patients, reduced delays and waiting time for diagnosis, raised the index of TB suspicion, and improved decision-making among HCWs. The attributes of TB case detection were: (i) free X-ray screening services; (ii) integrating TB case-finding activities in other clinics such as Reproductive and Child Health clinics (RCH), and diabetic clinics; (iii), engagement of CHWs, policymakers, and ministry level program managers; (iv) enhanced community awareness and linkage of clients; (v) cooperation between HCWs and CHWs, (vi) improved screening infrastructure, (vii) the adoption of the new simplified screening criteria and (viii) training of implementers. The supply-side challenges encountered ranged from disorganized care, limited space, the COVID-19 pandemic, inadequate human resources, inadequate knowledge and expertise, stock out of supplies, delayed maintenance of equipment, to absence of X-ray and GeneXpert machines in some facilities. The demand side challenges ranged from delayed care seeking, inadequate awareness, negative beliefs, fears towards screening, to financial challenges. Suggestions for scaling up ranged from improving service delivery, access to diagnostic equipment and supplies, and infrastructure, to addressing client fears and stigma. CONCLUSION: The EXIT-TB package appears to have contributed towards increasing TB case detection and reducing delays in TB treatment in the study settings. Addressing the challenges identified is needed to maximize the impact of the EXIT-TB intervention.

Implementation of WHO guidelines on management of advanced HIV disease and its impact among TB co-infected patients in Tanzania: a retrospective follow-up study.

BACKGROUND: The commonest causes of mortality in people living with HIV (PLHIV) are preventable and the majority can be attributed to undiagnosed tuberculosis (TB). National HIV/AIDS control programs are encouraged to implement the WHO package of interventions to improve survival among PLHIV. We assessed the implementation of the WHO TB-related package of care for Advanced HIV Disease (AHD) and its impact on treatment outcomes among HIV/TB patients in Tanzania. METHODS: A retrospective cohort study was employed among HIV/AIDS patients on antiretroviral therapy from 21 public health facilities in three regions (Dar es Salaam, Coastal, and Morogoro) of Tanzania. Patients enrolled in care between January 2013- June 2017 (before the introduction of the WHO guidelines) and July 2017-Sept 2018 (during the implementation of the guidelines) were recruited. Data abstraction was done from patient hospital files using a structured questionnaire uploaded on a tablet. RESULTS: Data from 2624 patients records were collected. Overall, 50% of patients with HIV had AHD with 7.8% of these co-infected with TB. Among AHD participants, 58.3% were female, 80.7% were from urban areas and 40.0% visited care and treatment centres as self-referrals. Implementation of the WHO AHD package of care was very low, ranging from 0% for Urine LF-LAM test done among patients with symptoms and signs of TB to 39.7% AHD concurrent with TB patients whose ART initiation was deferred for 2 weeks. Overall, the Proportion of AHD patients diagnosed with TB was 4.8%, Of which sputum Xpert as the first test for TB diagnosis was 4.4%. Five patients (0.6%) were documented to have received IPT at enrolment. Tailored counselling to ensure optimal adherence to ART for viral suppression was given to 12.1%. AHD patients co-infected with TB were retained in care more before the introduction of WHO AHD guideline (82.1%) compared to the period after the introduction of the guideline (53.9%) (p = 0.008). Clinical failure at 6 months among AHD patients was 10.6% before the guideline and 11.4% after the guideline. Immunological failure was observed in 1 patient (9.1%) before the guideline and 1 patient (7.1%) after the guideline. After the introduction of the guideline, mortality was 5.9% and no mortality was observed before the guideline. All the differences were not statistically significant. CONCLUSIONS: Implementation of the TB related WHO packages of care for AHD is very low. Except for TB diagnosis, other parameters did not improve with the introduction of the guidelines. More research is recommended to ascertain the effectiveness of guidelines as well as an understanding of the mechanisms involved.

Advancing disease genomics beyond COVID-19 and reducing health disparities: what does the future hold for Africa?

The COVID-19 pandemic has ushered in high-throughput sequencing technology as an essential public health tool. Scaling up and operationalizing genomics in Africa is crucial as enhanced capacity for genome sequencing could address key health problems relevant to African populations. High-quality genomics research can be leveraged to improve diagnosis, understand the aetiology of unexplained illnesses, improve surveillance of infectious diseases and inform efficient control and therapeutic methods of known, rare and emerging infectious diseases. Achieving these within Africa requires strong commitment from stakeholders. A roadmap is needed to guide training of scientists, infrastructural development, research funding, international collaboration as well as promote public-private partnerships. Although the COVID-19 pandemic has significantly boosted genomics capacity in Africa, the continent still lags other regions. Here, we highlighted key initiatives in genomics research and efforts to address health challenges facing the diverse and fast-growing populations on the continent. We explore the scalability of genomic tools and techniques to tackle a broader range of infectious diseases in Africa, a continent that desperately requires a boost from genomic science.

Emergomycosis in Africa: Time to Pay Attention to This Emerging Deadly Fungal Infection.

Emergomycosis is an emerging deadly infectious disease caused primarily by a little-known airborne pathogen Emergomyces africanus, which can cause clinical management challenge especially in patients with advanced HIV disease. This minireview describes Es. africanus as the main cause of emergomycosis in Africa as well as considers contributing factors to the difficulties encountered in managing this infection. Emergomycosis is common in HIV-positive persons with low CD4 lymphocyte count and has an estimated fatality of 50%. The infection exhibits airborne transmission with pulmonary and extrapulmonary manifestations leading to skin lesions. However, the pathogenesis of Es. africanus is still poorly understood. The management of the infection is complicated due to lack of defined diagnostic and therapeutic guidelines. Limited expertise, poor research funding, and lack of awareness and national surveillance are thought to impact the recognition and prioritisation of the infection. These factors may ultimately assign emergomycosis a 'neglected infection status' even as it is suspected to be prevalent in more African countries than previously recognised. Increased awareness and integrated and targeted strategies such as mobilising manpower in clinical mycology are of paramount importance in managing emergomycosis in Africa and beyond.

Clinical characteristics and outcomes of confirmed COVID-19 patients in the early months of the pandemic in Tanzania: a multicenter cohort study.

Background: A prospective cohort study of the clinical presentations and management outcomes of laboratory-confirmed COVID-19 patients in the early months of the pandemic was performed at two hospitals in Dar es Salaam, Tanzania. Methods: Between April 1 and May 31, 2020, laboratory-confirmed COVID-19 patients seen at two tertiary facilities were consecutively enrolled in the study and followed up for 21 days. Results: 121 COVID-19 patients were enrolled; 112 (92.6%) were admitted while nine (7.4%) were seen as outpatients. The median (IQR) age of patients was 41 (30-54) years; 72 (59.5%) were male. The median (IQR) reported days from hospital admission to recovery and to death were 10 (6-18) and 5.5 (3-9), respectively. Forty-four (36.4%) patients had at least one underlying condition. Of the 112 admissions, 17 (15.2%) went to ICU, of whom 14 (82.3%) died. At the end of follow-up, 93 (76.9%) recovered, 18 (14.9%) died, seven (5.8%) remained asymptomatic, and one (0.8%) remained ill. Conclusion: Three-quarters of all COVID-19 patients were less than 60 years, reflecting Africa's young population . High ICU admissions and mortality were observed.

Tuberculosis Prevalence and Predictors Among Health Care-Seeking People Screened for Cough of Any Duration in Ethiopia: A Multicenter Cross-Sectional Study.

Background: Tuberculosis (TB) remains a major cause of morbidity and mortality in sub-Saharan Africa. This high burden is mainly attributed to low case detection and delayed diagnosis. We aimed to determine the prevalence and predictors of TB among health care-seeking people screened for cough of any duration in Ethiopia. Methods: In this multicenter cross-sectional study, we screened 195,713 (81.2%) for cough of any duration. We recruited a sample of 1,853 presumptive TB (PTB) cases and assigned them into three groups: group I with cough ≥2 weeks, group II with cough of <2 weeks, and group III pregnant women, patients on antiretroviral therapy, and patients with diabetes. The first two groups underwent chest radiograph (CXR) followed by sputum Xpert MTB/RIF assay or smear microscopy. The third group was exempted from CXR but underwent sputum Xpert MTB/RIF assay or smear microscopy. TB prevalence was calculated across the groups and TB predictors were analyzed using modified Poisson regression to compute adjusted prevalence ratio (aPR) with a 95% confidence interval (CI). Results: The overall prevalence of PTB was 16.7% (309/1853). Of the positive cases, 81.2% (251/309) were in group I (cough ≥2 weeks), 14.2% (44/309) in group II (cough of <2), and 4.5% (14/309) in group III (CXR exempted). PTB predictors were age group of 25-34 [aPR = 2.0 (95% CI 1.3-2.8)], history of weight loss [aPR = 1.2 (95% CI 1.1-1.3)], and TB suggestive CXRs [aPR = 41.1 (95% CI 23.2-72.8)]. Conclusion: The prevalence of confirmed PTB among routine outpatients was high, and this included those with a low duration of cough who can serve as a source of infection. Screening all patients at outpatient departments who passively report any cough irrespective of duration is important to increase TB case finding and reduce TB transmission and mortality.

Antibiotic Susceptibility Patterns of Bacterial Isolates from Routine Clinical Specimens from Referral Hospitals in Tanzania: A Prospective Hospital-Based Observational Study.

INTRODUCTION: Antimicrobial resistance is one of the biggest threats of modern public health. Although sub-Saharan Africa is highly burdened with infectious diseases, current data on antimicrobial resistance are sparse. METHODS: A prospective study was conducted between October 2018 and September 2019 to assess the antibiotic susceptibility patterns of clinical bacterial isolates obtained from four referral hospitals in Tanzania. We used standard media and Kirby-Bauer disc diffusion methods as per Clinical and Laboratory Standards Institute (CLSI) standards. RESULTS: We processed a total of 2620 specimens of which 388 (14.8%) were culture-positive from patients with a median (IQR) age of 28 (12-44) years. Of the positive cultures, 52.3% (203) were from females. Most collected specimens were ear pus 28.6% (111), urine 24.0% (93), wound pus 20.6% (80), stool 14.9% (58), and blood 8.3% (32). Predominant isolates were S. aureus 28.4% (110), E. coli 15.2% (59), P. aeruginosa 10.6% (41), P. mirabilis 7.0% (27), V. cholerae 01 Ogawa 6.2% (24), Klebsiella spp. 5.2% (20) and Streptococcus spp. 4.6% (18). Generally, the isolates exhibited a high level of resistance to commonly used antibiotics such as Ampicillin, Amoxicillin-Clavulanic acid, Erythromycin, Gentamicin, Tetracycline, Trimethoprim, third-generation Cephalosporins (Ceftriaxone and Ceftazidime), and reserved drugs (Clindamycin and Meropenem). S. aureus isolates were resistant to most of the antibiotics tested; 66.7% were classified as MRSA infections. CONCLUSION: Antibiotic resistance to commonly prescribed antibiotics was alarmingly high. Our findings emphasize the need for comprehensive national control programs to combat antibiotic resistance.

Gaps related to screening and diagnosis of tuberculosis in care cascade in selected health facilities in East Africa countries: A retrospective study.

INTRODUCTION: East Africa countries (Tanzania, Kenya, and Uganda) are among tuberculosis high burdened countries globally. As we race to accelerate progress towards a world free of tuberculosis by 2035, gaps related to screening and diagnosis in the cascade care need to be addressed. METHODS: We conducted a three-year (2015-2017) retrospective study using routine program data in 21 health facilities from East Africa. Data abstraction were done at tuberculosis clinics, outpatient departments (OPD), human immunodeficiency virus (HIV) and diabetic clinics, and then complemented with structured interviews with healthcare providers to identify possible gaps related to integration, screening, and diagnosis of tuberculosis. Data were analyzed using STATA™ Version 14.1. RESULTS: We extracted information from 49,454 presumptive TB patients who were registered in the 21 facilities between January 2015 and December 2017. A total of 9,565 tuberculosis cases were notified; 46.5% (4,450) were bacteriologically confirmed and 31.5% (3,013) were HIV-infected. Prevalence of tuberculosis among presumptive pulmonary tuberculosis cases was 17.4%. The outcomes observed were as follows: 79.8% (7,646) cured or completed treatment, 6.6% (634) died, 13.3% (1,270) lost to follow-up or undocumented and 0.4% (34) treatment failure. In all countries, tuberculosis screening was largely integrated at OPD and HIV clinics. High patient load, weak laboratory specimen referral system, shortage of trained personnel, and frequent interruption of laboratory supplies were the major cited challenges in screening and diagnosis of tuberculosis. CONCLUSION: Screening and diagnostic activities were frequently affected by scarcity of human and financial resources. Tuberculosis screening was mainly integrated at OPD and HIV clinics, with less emphasis on the other health facility clinics. Closing gaps related to TB case finding and diagnosis in developing countries requires sustainable investment for both human and financial resources and strengthen the integration of TB activities within the health system.

Evaluation of stool GeneXpert MTB/RIF for the diagnosis of pulmonary tuberculosis among presumptive patients in Tanzania.

BACKGROUND: Diagnosis of pulmonary tuberculosis remains grim, especially in resource-limited settings. Low quality of sputum, particularly among seriously ill, HIV/AIDS, and pediatric patients might result in missing the diagnosis. This study evaluated the performance of GeneXpert MTB/RIF for the detection of pulmonary tuberculosis on stool specimens as an alternative to respiratory specimens. METHODS: A cross-sectional study design was used to evaluate the performance of GeneXpert MTB/RIF to detect TB in stool specimens from presumptive TB patients. Sputum culture on Lowenstein-Jensen media was used as the gold standard. Recruitment of patients into the study was conducted in 12 selected health facilities in Tanzania. Two sputa and a stool specimen were collected from each study participant. Both sputa and stool samples were tested at their respective study sites of collection using GeneXpert, and their respective portions shipped to the Central Tuberculosis Reference Laboratory for testing by stool GeneXpert and sputum culture in the LJ media. Statistical analysis was performed using STATA software version 14.1. RESULTS: A total of 590 presumptive tuberculosis patients were enrolled in this study. Their median age was 35 years (IQR = 21-47 years). More than half (57.5%, n = 339) of the study participants, were males. Children aged below 15 years constituted 17.6% (n = 104) of the study participants. A total of 75 tuberculosis cases were detected by sputum culture. The sensitivity and specificity of Stool GeneXpert conducted at CTRL was 84% (95% CI: 81.0-87.0%), and 93.4% (CI: 98.5-99.9%) respectively. The overall sensitivity and specificity of stool GeneXpert at the peripheral laboratories was 63.0% (95% CI: 47.8-76.1) and 76.7% (95% CI: 72.1-81.4), respectively. CONCLUSION: Findings from this study suggest that stool is a potential alternative to respiratory specimen for use in routine diagnosis of tuberculosis, especially when obtaining a respiratory specimen is challenging.