Shorter regimens improved treatment outcomes of multidrug-resistant tuberculosis patients in Tanzania in 2018 cohort.

OBJECTIVE: In 2018, shorter treatment regimens (STR) for people with drug-resistant tuberculosis (DR-TB) were introduced in Tanzania and included kanamycin, high-dose moxifloxacin, prothionamide, high-dose isoniazid, clofazimine, ethambutol and pyrazinamide. We describe treatment outcomes of people diagnosed with DR-TB in a cohort initiating treatment in 2018 in Tanzania. METHODS: This was a retrospective cohort study conducted at the National Centre of Excellence and decentralised DR-TB treatment sites for the 2018 cohort followed from January 2018 to August 2020. We reviewed data from the National Tuberculosis and Leprosy Program DR-TB database to assess clinical and demographic information. The association between different DR-TB regimens and treatment outcome was assessed using logistic regression analysis. Treatment outcomes were described as treatment complete, cure, death, failure or lost to follow-up. A successful treatment outcome was assigned when the patient achieved treatment completion or cure. RESULTS: A total of 449 people were diagnosed with DR-TB of whom 382 had final treatment outcomes: 268 (70%) cured; 36 (9%) treatment completed; 16 (4%) lost to follow-up; 62 (16%) died. There was no treatment failure. The treatment success rate was 79% (304 patients). The 2018 DR-TB treatment cohort was initiated on the following regimens: 140 (46%) received STR, 90 (30%) received the standard longer regimen (SLR), 74 (24%) received a new drug regimen. Normal nutritional status at baseline [adjusted odds ratio (aOR) = 6.57, 95% CI (3.33-12.94), p < 0.001] and the STR [aOR = 2.67, 95% CI (1.38-5.18), p = 0.004] were independently associated with successful DR-TB treatment outcome. CONCLUSION: The majority of DR-TB patients on STR in Tanzania achieved a better treatment outcome than on SLR. The acceptance and implementation of STR at decentralised sites promises greater treatment success. Assessing and improving nutritional status at baseline and introducing new shorter DR-TB treatment regimens may strengthen favourable treatment outcomes.

Multiple pathogens contribute to human immunodeficiency virus-related sepsis in addition to Mycobacterium tuberculosis: A prospective cohort in Tanzania.

Background: Mortality from tuberculosis (TB) sepsis is common among patients living with human immunodeficiency virus (PLHIV). We aimed to detect M. tuberculosis (MTB) and additional sepsis etiologies, and mortality determinants in PLHIV. Methods: This prospective cohort study consented and followed-up PLHIV for 28 days in northern Tanzania. From May through December 2021, patients provided urine and sputum for TB testing in lateral-flow lipoarabinomannan (LF-LAM) and Xpert® MTB/RIF. Bacterial blood culture, cryptococcal antigen, malaria rapid diagnostic, C-reactive-protein (CRP), and international normalized ratio (INR) tests were also performed. Sepsis severity was clinically measured by Karnofsky and modified early warning signs (MEWS) scores. Anti-TB, broad-spectrum antibiotics, and antimalarial and antifungal agents were prescribed in accordance with Tanzania treatment guideline. An independent t-test and Chi-square or Fisher's exact tests compared means and proportions, respectively. P < 0.05 was statistically significant. Results: Among 98 patients, 59 (60.2%) were female. Their mean (standard deviation) age was 44 (12.9) years. TB detection increased from 24 (24.5%) by Xpert® MTB/RIF to 36 (36.7%) when LF-LAM was added. In total, 23 (23.5%) patients had other than TB etiologies of sepsis, including Staphylococcus aureus, Streptococcus pneumoniae, Cryptococcus spp., and Plasmodium spp. Twenty-four (94.4%) of 36 patients with TB had higher CRP (≥10 mg/l) compared to 25 (40.3%) non-TB patients (P < 0.001). Nine (9.2%) patients died and almost all had INR ≥1.8 (n = 8), Karnofsky score <50% (n = 9), MEWS score >6 (n = 8), and malnutrition (n = 9). Conclusions: MTB and other microbes contributed to sepsis in PLHIV. Adding non-TB tests informed clinical decisions. Mortality was predicted by conventional sepsis and severity scoring, malnutrition, and elevated INR.

Whole-genome sequencing of SARS-CoV-2 isolates from symptomatic and asymptomatic individuals in Tanzania.

Background: Coronavirus Disease-2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) accounts for considerable morbidity and mortality globally. Paucity of SARS-CoV-2 genetic data from Tanzania challenges in-country tracking of the pandemic. We sequenced SARS-CoV-2 isolated in the country to determine circulating strains, mutations and phylogenies and finally enrich international genetic databases especially with sequences from Africa. Methods: This cross-sectional study utilized nasopharyngeal swabs of symptomatic and asymptomatic adults with positive polymerase chain reaction tests for COVID-19 from January to May 2021. Viral genomic libraries were prepared using ARTIC nCoV-2019 sequencing protocol version three. Whole-genome sequencing (WGS) was performed using Oxford Nanopore Technologies MinION device. In silico genomic data analysis was done on ARTIC pipeline version 1.2.1 using ARTIC nCoV-2019 bioinformatics protocol version 1.1.0. Results: Twenty-nine (42%) out of 69 samples qualified for sequencing based on gel electrophoretic band intensity of multiplex PCR amplicons. Out of 29 isolates, 26 were variants of concern [Beta (n = 22); and Delta (n = 4)]. Other variants included Eta (n = 2) and B.1.530 (n = 1). We found combination of mutations (S: D80A, S: D215G, S: K417N, ORF3a: Q57H, E: P71L) in all Beta variants and absent in other lineages. The B.1.530 lineage carried mutations with very low cumulative global prevalence, these were nsp13:M233I, nsp14:S434G, ORF3a:A99S, S: T22I and S: N164H. The B.1.530 lineage clustered phylogenetically with isolates first reported in south-east Kenya, suggesting regional evolution of SARS-CoV-2. Conclusion: We provide evidence of existence of Beta, Delta, Eta variants and a locally evolving lineage (B.1.530) from samples collected in early 2021 in Tanzania. This work provides a model for ongoing WGS surveillance that will be required to inform on emerging and circulating SARS-CoV-2 diversity in Tanzania and East Africa.

Project extension for community healthcare outcomes improves care and treatment for multidrug-resistant tuberculosis patients in Tanzania.

Background: Project Extension for Community Healthcare Outcomes (Project ECHO) is a telementoring, case based virtual community of practice training and education model connecting experts to primary care clinicians (PCCs). Project ECHO has good evidence for favorable treatment outcomes on wide range of diseases. Since 2017, Tanzania hosts multidrug resistant tuberculosis (MDR TB) ECHO with hub at Kibong'oto Infectious Diseases Hospital. However, little is known on outcomes of MDR TB ECHO. This study aimed to describe the outcomes of MDR TB ECHO in managing MDR TB patients in Tanzania. Methods: Review of case studies was conducted at MDR TB ECHO hub in Tanzania. Up to June 2020, a total of 134 sessions and 60 patient cases were presented in MDR TB ECHO. This article describes outcomes of MDR TB ECHO in managing three selected complicated MDR TB patient cases presented. Case 1: Child with MDR TB, neck abscess, and anemia secondary to chronic illness. Case 2: Adult with MDR TB and end stage renal disease co morbidity. Case 3: Adult failing standard MDR TB treatment. Results: Anemia resolved in Case 1; surgical dressing was done to neck abscess and neck healed. Case 2 was initiated with end stage renal disease management; uremic encephalopathy and lower limb edema resolved. Case 3 was initiated with individualized MDR TB treatment. All three patients attained smear and culture conversion and continue with MDR TB treatment. Conclusions: To our knowledge, this is the first report on effectiveness of project ECHO in supporting PCCs in bringing favorable treatment outcomes to MDR TB patients. We advocate adaptation and scale up of ECHO model as an effective approach for strengthening management of MDR TB and other infectious diseases.

Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania.

Emergence of HIV drug resistance poses a serious risk of inactivity to all currently approved antiretroviral drugs. Profiles of HIV drug resistance mutations (HIVDRM) and virological failure (VF) are not extensively studied in Tanzania. This study aimed to determine HIVDRM and predictors of VF in HIV-infected individuals failing first-line HIV drugs in Moshi, Northern Tanzania. A case-control study was conducted at Kilimanjaro Christian Medical Centre, Mawenzi, Pasua and Majengo health facilities with HIV-care and treatment clinics from October, 2017 to August, 2018. Cases and controls were HIV-infected individuals with VF and viral suppression (VS) respectively. HIV-1 reverse transcriptase and protease genes were amplified and sequenced. Stanford University's HIV drug resistance database and REGA subtyping tool 3.0 determined HIVDRM and HIV-1 subtypes respectively. Odds ratios (OR) with 95% confidence interval (95% CI) investigated predictors of VF. P-value < 5% was considered statistically significant. A total of 124 participants were recruited, of whom 63 (50.8%) had VF, 61 (49.2%) had VS and 82 (66.1%) were females. Median [IQR] age and duration on ART were 45 [35-52] years and 72 [48-104] months respectively. Twenty-five out of 26 selected samples from cases were successfully sequenced. Twenty-four samples (96%) had at least one major mutation conferring resistance to HIV drugs, with non-nucleoside analogue reverse transcriptase inhibitor (NNRTI)-resistance associated mutations as the majority (92%). Frequent NNRTI-resistance associated mutations were K103N (n = 11), V106M (n = 5) and G190A (n = 5). Prevalent nucleoside analogue reverse transcriptase inhibitors-resistance associated mutations were M184V (n = 17), K70R (n = 7) and D67N (n = 6). Dual-class resistance was observed in 16 (64%) samples. Thirteen samples (52%) had at least one thymidine analogue-resistance associated mutation (TAM). Three samples (12%) had T69D mutation with at least 1 TAM. Two samples (8%) had at least one mutation associated with protease inhibitor resistance. Age [aOR = 0.94, 95% CI (0.90-0.97), p < 0.001] and occupation [aOR = 0.35, 95% CI (0.12-1.04), p = 0.059] associated with VF. In conclusion, HIV drug resistance is common among people failing antiretroviral therapy. Resistance testing will help to guide switching of HIV drugs.