Prevalence of Extensively Drug Resistant Tuberculosis among Archived Multidrug Resistant Tuberculosis Isolates in Zimbabwe

We conducted a cross-sectional study of second line drug resistance patterns and genetic diversity of MDR-TB isolates archived at the BRTI-TB Laboratory, Harare, between January 2007 and December 2011. DSTs were performed for second line antituberculosis drugs. XDR-TB strains were defined as MDR-TB strains with resistance to either kanamycin and ofloxacin or capreomycin and ofloxacin. Strain types were identified by spoligotyping. No resistance to any second line drugs was shown in 73% of the isolates, with 23% resistant to one or two drugs but not meeting the definition of XDR-TB. A total of 26 shared types were identified, and 18 (69%) matched preexisting shared types in the current published spoligotype databases. Of the 11 out of 18 clustered SITs, 4 predominant (>6 isolates per shared type) were identified. The most and least abundant types were SIT 1468 (LAM 11-ZWE) with 12 (18%) isolates and SIT 53 (T1) with 6 (9%) isolates, respectively. XDR-TB strains are rare in Zimbabwe, but the high proportion of "pre-XDR-TB" strains and treatment failure cases is of concern. The genetic diversity of the MDR-TB strains showed no significant association between SITs and drug resistance

Uptake of Workplace HIV Counselling and Testing: A Cluster-Randomised Trial in Zimbabwe

BACKGROUND: HIV counselling and testing is a key component of both HIV care and HIV prevention, but uptake is currently low. We investigated the impact of rapid HIV testing at the workplace on uptake of voluntary counselling and testing (VCT). METHODS AND FINDINGS: The study was a cluster-randomised trial of two VCT strategies, with business occupational health clinics as the unit of randomisation. VCT was directly offered to all employees, followed by 2 y of open access to VCT and basic HIV care. Businesses were randomised to either on-site rapid HIV testing at their occupational clinic (11 businesses) or to vouchers for off-site VCT at a chain of free-standing centres also using rapid tests (11 businesses). Baseline anonymised HIV serology was requested from all employees. HIV prevalence was 19.8% and 18.4%, respectively, at businesses randomised to on-site and off-site VCT. In total, 1,957 of 3,950 employees at clinics randomised to on-site testing had VCT (mean uptake by site 51.1%) compared to 586 of 3,532 employees taking vouchers at clinics randomised to off-site testing (mean uptake by site 19.2%). The risk ratio for on-site VCT compared to voucher uptake was 2.8 (95% confidence interval 1.8 to 3.8) after adjustment for potential confounders. Only 125 employees (mean uptake by site 4.3%) reported using their voucher, so that the true adjusted risk ratio for on-site compared to off-site VCT may have been as high as 12.5 (95% confidence interval 8.2 to 16.8). CONCLUSIONS: High-impact VCT strategies are urgently needed to maximise HIV prevention and access to care in Africa. VCT at the workplace offers the potential for high uptake when offered on-site and linked to basic HIV care. Convenience and accessibility appear to have critical roles in the acceptability of community-based VCT

Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial.

BACKGROUND: Child stunting reduces survival and impairs neurodevelopment. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in in Zimbabwe. METHODS: We did a cluster-randomised, community-based, 2 × 2 factorial trial in two rural districts in Zimbabwe. Clusters were defined as the catchment area of between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Women were eligible for inclusion if they permanently lived in clusters and were confirmed pregnant. Clusters were randomly assigned (1:1:1:1) to standard of care (52 clusters), IYCF (20 g of a small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counselling; 53 clusters), WASH (construction of a ventilated improved pit latrine, provision of two handwashing stations, liquid soap, chlorine, and play space plus hygiene counselling; 53 clusters), or IYCF plus WASH (53 clusters). A constrained randomisation technique was used to achieve balance across the groups for 14 variables related to geography, demography, water access, and community-level sanitation coverage. Masking of participants and fieldworkers was not possible. The primary outcomes were infant length-for-age Z score and haemoglobin concentrations at 18 months of age among children born to mothers who were HIV negative during pregnancy. These outcomes were analysed in the intention-to-treat population. We estimated the effects of the interventions by comparing the two IYCF groups with the two non-IYCF groups and the two WASH groups with the two non-WASH groups, except for outcomes that had an important statistical interaction between the interventions. This trial is registered with ClinicalTrials.gov, number NCT01824940. FINDINGS: Between Nov 22, 2012, and March 27, 2015, 5280 pregnant women were enrolled from 211 clusters. 3686 children born to HIV-negative mothers were assessed at age 18 months (884 in the standard of care group from 52 clusters, 893 in the IYCF group from 53 clusters, 918 in the WASH group from 53 clusters, and 991 in the IYCF plus WASH group from 51 clusters). In the IYCF intervention groups, the mean length-for-age Z score was 0·16 (95% CI 0·08-0·23) higher and the mean haemoglobin concentration was 2·03 g/L (1·28-2·79) higher than those in the non-IYCF intervention groups. The IYCF intervention reduced the number of stunted children from 620 (35%) of 1792 to 514 (27%) of 1879, and the number of children with anaemia from 245 (13·9%) of 1759 to 193 (10·5%) of 1845. The WASH intervention had no effect on either primary outcome. Neither intervention reduced the prevalence of diarrhoea at 12 or 18 months. No trial-related serious adverse events, and only three trial-related adverse events, were reported. INTERPRETATION: Household-level elementary WASH interventions implemented in rural areas in low-income countries are unlikely to reduce stunting or anaemia and might not reduce diarrhoea. Implementation of these WASH interventions in combination with IYCF interventions is unlikely to reduce stunting or anaemia more than implementation of IYCF alone. FUNDING: Bill & Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Development Cooperation, UNICEF, and US National Institutes of Health.The SHINE trial is funded by the Bill & Melinda Gates Foundation (OPP1021542 and OPP113707); UK Department for International Development; Wellcome Trust, UK (093768/Z/10/Z, 108065/Z/15/Z and 203905/Z/16/Z); Swiss Agency for Development and Cooperation; US National Institutes of Health (2R01HD060338-06); and UNICEF (PCA-2017-0002)

Xpert<SUP>®</SUP> MTB/RIF detection of rifampin resistance and time to treatment initiation in Harare, Zimbabwe

BACKGROUND: Patients at elevated risk of drug-resistant tuberculosis are prioritized for testing with Xpert MTB/RIF® (“Xpert”), though clinical utility in this population is understudied. DESIGN: From November 2011 to June 2014, consecutive outpatients with history of prior tuberculosis in high-density suburbs of Harare, Zimbabwe were tested with Xpert, solid and liquid culture, and the microscopically-observed drug susceptibility assay. Diagnostic accuracy for rifampin-resistance and time to second-line regimens were ascertained. The rpoB gene was sequenced in cases of culture-confirmed rifampin resistance and genotypic sensitivity. RESULTS: Among 352 retreatment patients, 71 (20%) had rifampin-resistant, 98 (28%) rifampin-susceptible, 64 (18%) culture-negative/Xpert-positive, and 119 (34%) culture-negative/Xpert-negative TB. Xpert was 86% (95% CI 75-93%) sensitive and 98% (95% CI 92-100%) specific for rifampin-resistant TB. The positive predictive value of Xpert-determined rifampin resistance for MDR-TB was 82% (95% CI 70-91%). Fifty-nine of 71 (83%) participants initiated SLDs, with a median time to regimen initiation of 18 days (IQR, 10-44 days). CONCLUSION: The diagnostic accuracy of Xpert for rifampin-resistance is high, though predictive value for MDR-TB is lower than anticipated. Xpert allows for faster SLD initiation under programmatic conditions, relative to culture-based drug susceptibility testing

Comparison of the Microscopic-observation Drug-Susceptibility (MODS) Assay with Reference Standard Culture for Detection of <i>M. tuberculosis</i>.

*<p>Among persons with known HIV status (<i>n</i> = 59/98 (60%)).</p

Characteristics of the Study Population.

<p>Values are percentages unless otherwise stated. All categories are mutually exclusive. The denominator for each characteristic excludes missing or unknown values unless otherwise stated.</p><p>Definition of abbreviations: MODS, microscopic-observation drug-susceptibility assay.</p>*<p>Among persons with known HIV status (<i>n</i> = 59/99 (60%)).</p>†<p>Available for <i>n</i> = 27/59 (46%) HIV-infected persons.</p>‡<p>Retreatment categories were defined according to World Health Organization criteria; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055872#pone.0055872-World1" target="_blank">[1]</a> smear- or culture-positivity at the fifth month or later was defined as treatment failure, stratified according to Category I or Category II treatment at the time failure occurred.</p>§<p>Hardy Diagnostics, Santa Maria, CA USA.</p

Drug-Susceptibility Test Results from the MODS Assay.

*<p>Analysis limited to samples with positive microscopic-observation drug-susceptibility and reference standard culture.</p>†<p>Among directly inoculated patient specimens.</p

Study Flow Diagram.

<p><i>Definition of abbreviation</i>: MDR TB = multidrug resistant tuberculosis; MODS = microscopic-observation drug-susceptibility. ^†Six additional previously cultured isolates of known MDR status were included for analysis of drug susceptibility testing only and are not included here.</p

Kaplan-Meier Curves of Time to <i>M. tuberculosis</i> Detection.

<p>Time to positivity for <i>Mycobacterium tuberculosis</i> detection for microscopic-observation drug-susceptibility (MODS) and reference standard culture (manual mycobacterial growth indicator tube (MGIT)). Median time to positivity was significantly shorter for MODS than for manual MGIT (MODS 7 days [IQR 7–15 days] vs. MGIT 12 days [IQR 6–16 days]; p<0.001).</p