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BACKGROUND: We conducted the first national TB prevalence survey to provide accurate estimates of bacteriologically confirmed pulmonary TB disease among adults aged ≥15 years in 2014.METHODS: A TB symptoms screen and chest X-ray (CXR) were used to identify presumptive TB cases who submitted two sputum samples for smear microscopy, liquid and solid culture. Bacteriological confirmation included acid-fast bacilli smear positivity confirmed using Xpert® MTB/RIF and/or culture. Prevalence estimates were calculated using random effects logistic regression with multiple imputations and inverse probability weighting.RESULTS: Of 43,478 eligible participants, 33,736 (78%) were screened; of these 5,820 (17%) presumptive cases were identified. There were 107 (1.9%) bacteriologically confirmed TB cases, of which 23 (21%) were smear-positive. The adjusted prevalences of smear-positive and bacteriologically confirmed TB disease were respectively 82/100,000 population (95% CI 47-118/100,000) and 344/100,000 (95% CI 268-420/100,000), with an overall all-ages, all-forms TB prevalence of 275/100,000 population (95% CI 217-334/100,000). TB prevalence was higher in males, and age groups 35-44 and ≥65 years. CXR identified 93/107 (87%) cases vs. 39/107 (36%) using the symptom screen.CONCLUSION: Zimbabwe TB disease prevalence has decreased relative to prior estimates, possibly due to increased antiretroviral therapy coverage and successful national TB control strategies. Continued investments in TB diagnostics for improved case detection are required.

Background: As a result of shared social and structural risk factors, people in households affected by tuberculosis may have an increased risk of chronic conditions; at the same time, tuberculosis screening may be an opportunity for interventions. We sought to describe the prevalence of HIV, nutritional disorders, and noncommunicable diseases (NCDs) among members of tuberculosis-affected households in 3 African countries., Methods and Findings: A part of a multicountry cohort study, we screened for tuberculosis, HIV, nutritional disorders (underweight, anaemia, overweight/obesity), and NCDs (diabetes, hypertension, and chronic lung disease) among members of tuberculosis-affected households aged ≥10 years in Mozambique, Tanzania, and Zimbabwe. We describe the prevalence of these conditions, their co-occurence within individuals (multimorbidity) and household-level clustering. Of 2,109 household contacts recruited, 93% (n = 1,958, from 786 households) had complete data and were included in the analysis. Sixty-two percent were female, median age was 27 years, and 0.7% (n = 14) were diagnosed with co-prevalent tuberculosis. Six percent of household members (n = 120) had previous tuberculosis, 15% (n = 294) were living with HIV, 10% (n = 194) had chronic lung disease, and 18% (n = 347) were anaemic. Nine percent of adults (n = 127) had diabetes by HbA1c criteria, 32% (n = 439) had hypertension. By body mass index criteria, 18% household members (n = 341) were underweight while 29% (n = 549) were overweight or obese. Almost half the household members (n = 658) had at least 1 modifiable tuberculosis risk factor. Sixty-one percent of adults (n = 822) had at least 1 chronic condition, 1 in 4 had multimorbidity. While most people with HIV knew their status and were on treatment, people with NCDs were usually undiagnosed and untreated. Limitations of this study include use of point-of-care HbA1c for definition of diabetes and definition of hypertension based on single-day measurements., Conclusions: Households affected by tuberculosis also face multiple other health challenges. Integrated approaches to tuberculosis screening may represent an opportunity for identification and treatment, including prioritisation of individuals at highest risk for tuberculosis to receive preventive therapy., Competing Interests: EDCTP Grant funding for this research to NH’s institution. DZIF Grant funding for this research to NH’s institution. Funding by Beckman Coulter to NH’s institution., (Copyright: © 2024 Calderwood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Tuberculous meningitis (TBM) mortality is high and current diagnostics perform suboptimally. We evaluated the diagnostic performance of a DNA-based assay (GeneXpert Ultra) against a new same-day immunodiagnostic assay that detects unstimulated interferon-gamma (IRISA-TB)., Methods: In a stage 1 evaluation, IRISA-TB was evaluated in biobanked samples from Zambia (n = 82; tuberculosis [TB] and non-TBM), and specificity in a South African biobank (n = 291; non-TBM only). Given encouraging results, a stage 2 evaluation was performed in suspected TBM patients from Zimbabwe and Malawi (n = 668). Patients were classified as having definite, probable or possible TBM, or non-TBM based on their microbiological results, cerebrospinal fluid (CSF) chemistry, and whether they received treatment., Results: In the stage 1 evaluation, sensitivity and specificity of IRISA-TB were 75% and 87% in the Zambian samples, and specificity was 100% in the South African samples. In the stage 2 validation, IRISA-TB sensitivity (95% confidence interval [CI]) was significantly higher than Xpert Ultra (76.2% [55.0%-89.4%] vs 25% [8.9%-53.3%]; P = .0048) when trace readouts were considered negative. Specificity (95% CI) was similar for both assays (91.4% [88.8%-93.4%] vs 86.9% [83.4%-89.8%]). When the Xpert Ultra polymerase chain reaction product was verified by sequencing, the positive predictive value of trace readouts in CSF was 27.8%. Sensitivity of IRISA-TB was higher in human immunodeficiency virus (HIV)-infected versus uninfected participants (85.8% vs 66.7%)., Conclusions: As a same-day rule-in test, IRISA-TB had significantly better sensitivity than Xpert Ultra in a TB/HIV-endemic setting. An immunodiagnostic approach to TBM is promising, and further studies are warranted., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: In Zimbabwe, children, adolescents and young adults living with HIV (CALWH) who are on public health antiretroviral therapy (ART) have inadequate viral load (VL) suppression. We assessed whether a clinic-based VL monitoring could decrease 12-month virologic failure rates among these CALWH., Methods: The study was registered on ClinicalTrials.gov: NCT03986099. CALWH in care at Chidamoyo Christian Hospital (CCH) and 8 rural outreach sites (ROS) on long-term community-based ART were randomized (1:1) to 6 monthly VL monitoring by COBAS®Ampliprep®/Taqman48® HIV-1 at the provincial referral laboratory (PRL) as per standard of care (SOC) or by the clinic-based SAMBA II assay, Diagnostics for the Real World, at CCH. VL suppression, turn-around-time (TAT) for VL results, drug switching and drug resistance in second-line failure were assessed at 12 months., Results: Of 390 CALWH enrolled 347 (89%) completed 12 months follow-up. Median (IQR) age and ART duration were 14.1 (9.7-18.2) and 6.4 (3.7-7.9) years, respectively. Over half (57%) of the participants were female. At enrolment, 78 (20%) had VL ≥1,000 copies/ml and VL suppression of 80% was unchanged after 12 months, with no significant difference between the SOC (81%) and the clinic-based (80%) arms (p = 0.528). Median (IQR) months to confirmatory VL result at CCH vs PRL was 4.0 (2.1-4.4) vs 4.5 (3.5-6.3) respectively; p = 0.027 at 12 months. Drug switching was documented among 26/347 (7%) participants with no difference between the median (IQR) time to switch in SOC vs clinic-based arms (5.1 (3.9-10.0) months vs 4.4 (2.5-8.4) respectively; p = 0.569). Out of 24 confirmed second-line failures, only 4/19 (21%) had protease inhibitor resistance., Conclusion: In rural Zimbabwe, the clinic-based SAMBA II assay was able to provide confirmatory VL results faster than the SOC VL assay at the PRL. However, this rapid TAT did not allow for a more efficient drug switch among these CALWH., Competing Interests: At the time of the study, DI and MB were paid employees of Gilead Sciences Inc. There are no patents, products in development or marketed products to declare. This does not alter our adherence to policies on sharing data and materials., (Copyright: © 2023 Kouamou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) as a safe and more effective single daily dose regimen is rolling out in Africa for people living with HIV. Although access to viral load (VL) testing is improving, patients may still be transitioned to TLD with virological failure and potential drug resistance. We reviewed annual VL test results of 390 children and adolescents who had enrolled in a community-based antiretroviral therapy program in rural Zimbabwe between 2018 and 2019. VL testing was done by the near point of care simplified amplification-based assays (Diagnostics for the Real World, Sunnyvale, CA, USA) at Chidamoyo Christian Hospital and rate of virological suppression (VS) on TLD (VL <1,000 copies/mL) was assessed. Overall, 184 children and adolescents on TLD were enrolled in this study. The median [interquartile range (IQR)] age was 15 (11-19) years, above half of the participants were female (57%). Before switching to TLD, rate of VS was 76% (139/184). After a median (IQR) duration of 6.9 (5.5-9.1) months on TLD, VS was observed in 95% (174/184) of the participants. Of the 10 participants with VL ≥1,000 copies/mL on TLD, 90% (9/10) were failing on their previous regimens, 6 of 9 (67%) having been on boosted protease inhibitor-based regimens. A high rate (95%) of VS was observed among children and adolescents on TLD in rural Zimbabwe. TLD may address the problems of virological failure and emergence of resistance in Africa. However, longer follow-up might be needed to ascertain sustained VS in this vulnerable population. Randomized Control Trial NCT03986099.

Introduction: The WHO End-TB Strategy calls for the development of novel diagnostics to detect tuberculosis (TB) earlier and more accurately. Better diagnostics, together with tools to predict disease progression, are critical for achieving WHO End-TB targets. The E arly R isk A ssessment in TB Contacts by new diagno S tic t E sts (ERASE-TB) study aims to evaluate novel diagnostics and testing algorithms for early TB diagnosis and accurate prediction of disease progression among household contacts (HHCs) exposed to confirmed index cases in Mozambique, Tanzania and Zimbabwe., Methods and Analysis: A total of 2100 HHCs (aged ≥10 years) of adults with microbiologically-confirmed pulmonary TB will be recruited and followed up at 6-month intervals for 18-24 months. At each time point, a WHO symptom screen and digital chest radiograph (dCXR) will be performed, and blood and urine samples will be collected. Individuals screening positive (WHO symptom screen or dCXR) will be requested to provide sputum for Xpert MTB/Rif Ultra. At baseline, HHCs will also be screened for HIV, diabetes (HbA1c), chronic lung disease (spirometry), hypertension and anaemia. Study outcomes will be coprevalent TB (diagnosed at enrolment), incident TB (diagnosed during follow-up) or no TB at completion of follow-up. Novel diagnostics will be validated using fresh and biobanked samples with a nested case-control design. Cases are defined as HHCs diagnosed with TB (for early diagnosis) or with incident TB (for prediction of progression) and will be matched by age, sex and country to HHCs who remain healthy (controls). Statistical analyses will include assessment of diagnostic accuracy by constructing receiver operating curves and calculation of sensitivity and specificity., Ethics and Dissemination: ERASE-TB has been approved by regulatory and ethical committees in each African country and by each partner organisation. Consent, with additional assent for participants <18 years, is voluntary. Attestation by impartial witnesses is sought in case of illiteracy. Confidentiality of participants is being maintained throughout. Study findings will be presented at scientific conferences and published in peer-reviewed international journals., Trial Registration Number: NCT04781257.Cite Now., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Maintaining virologic suppression of children and adolescents on ART in rural communities in sub-Saharan Africa is challenging. We explored switching drug regimens to protease inhibitor (PI) based treatment and reducing nevirapine and zidovudine use in a differentiated community service delivery model in rural Zimbabwe., Methods: From 2016 through 2018, we followed 306 children and adolescents on ART in Hurungwe, Zimbabwe at Chidamoyo Christian Hospital, which provides compact ART regimens at 8 dispersed rural community outreach sites. Viral load testing was performed (2016) by Roche and at follow-up (2018) by a point of care viral load assay. Virologic failure was defined as viral load ≥1,000 copies/ml. A logistic regression model which included demographics, treatment regimens and caregiver's characteristics was used to assess risks for virologic failure and loss to follow-up (LTFU)., Results: At baseline in 2016, 296 of 306 children and adolescents (97%) were on first-line ART, and only 10 were receiving a PI-based regimen. The median age was 12 years (IQR 8-15) and 55% were female. Two hundred and nine (68%) had viral load suppression (<1,000 copies/ml) and 97(32%) were unsuppressed (viral load ≥1000). At follow-up in 2018, 42/306 (14%) were either transferred 23 (7%) or LTFU 17 (6%) and 2 had died. In 2018, of the 264 retained in care, 107/264 (41%), had been switched to second-line, ritonavir-boosted PI with abacavir as a new nucleotide analog reverse transcriptase inhibitor (NRTI). Overall viral load suppression increased from 68% in 2016 to 81% in 2018 (P<0.001)., Conclusion: Viral load testing, and switching to second-line, ritonavir-boosted PI with abacavir significantly increased virologic suppression among HIV-infected children and adolescents in rural Zimbabwe., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: DI and MB are paid employees of Gilead Sciences Inc. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: The Manicaland cohort was established to provide robust scientific data on HIV prevalence and incidence, patterns of sexual risk behaviour and the demographic impact of HIV in a sub-Saharan African population subject to a generalised HIV epidemic. The aims were later broadened to include provision of data on the coverage and effectiveness of national HIV control programmes including antiretroviral therapy (ART)., Participants: General population open cohort located in 12 sites in Manicaland, east Zimbabwe, representing 4 major socioeconomic strata (small towns, agricultural estates, roadside settlements and subsistence farming areas). 9,109 of 11,453 (79.5%) eligible adults (men 17-54 years; women 15-44 years) were recruited in a phased household census between July 1998 and January 2000. Five rounds of follow-up of the prospective household census and the open cohort were conducted at 2-year or 3-year intervals between July 2001 and November 2013. Follow-up rates among surviving residents ranged between 77.0% (over 3 years) and 96.4% (2 years)., Findings to Date: HIV prevalence was 25.1% at baseline and had a substantial demographic impact with 10-fold higher mortality in HIV-infected adults than in uninfected adults and a reduction in the growth rate in the worst affected areas (towns) from 2.9% to 1.0%pa. HIV infection rates have been highest in young adults with earlier commencement of sexual activity and in those with older sexual partners and larger numbers of lifetime partners. HIV prevalence has since fallen to 15.8% and HIV incidence has also declined from 2.1% (1998-2003) to 0.63% (2009-2013) largely due to reduced sexual risk behaviour. HIV-associated mortality fell substantially after 2009 with increased availability of ART., Future Plans: We plan to extend the cohort to measure the effects on the epidemic of current and future HIV prevention and treatment programmes. Proposals for access to these data and for collaboration are welcome., Competing Interests: Competing interests: SG has shares in AstraZeneca and GSK., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: HIV genotyping is often unavailable in low and middle-income countries due to infrastructure requirements and cost. We compared genotype resistance testing in patients with virologic failure, by amplification of HIV pol gene, followed by "in-house" sequencing and commercial sequencing., Methods: Remnant plasma samples from adults and children failing second-line ART were amplified and sequenced using in-house and commercial di-deoxysequencing, and analyzed in Harare, Zimbabwe and at Stanford, U.S.A, respectively. HIV drug resistance mutations were determined using the Stanford HIV drug resistance database., Results: Twenty-six of 28 samples were amplified and 25 were successfully genotyped. Comparison of average percent nucleotide and amino acid identities between 23 pairs sequenced in both laboratories were 99.51 (±0.56) and 99.11 (±0.95), respectively. All pairs clustered together in phylogenetic analysis. Sequencing analysis identified 6/23 pairs with mutation discordances resulting in differences in phenotype, but these did not impact future regimens., Conclusions: The results demonstrate our ability to produce good quality drug resistance data in-house. Despite discordant mutations in some sequence pairs, the phenotypic predictions were not clinically significant., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Periodic etiological surveillance of sexually transmitted infection (STI) syndromes is required to validate treatment algorithms used to control STIs. However, such surveys have not been performed in Zimbabwe over the past decade., Methods: A cross-sectional study design was used to determine the prevalence of the key STI etiological agents causing male urethral discharge (MUD). Urethral swab specimens were collected for molecular analysis and Neisseria gonorrhoeae isolation from consenting men 18 years and older who presented with MUD to the 12 clinics in Harare, Zimbabwe, between November 2010 and May 2011. A validated in-house multiplex polymerase chain reaction assay was used to detect the presence of N. gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma genitalium. Gonococci were cultured on selective media, and antimicrobial susceptibilities were determined locally for ciprofloxacin, kanamycin, ceftriaxone, and cefixime using Etest strips, and minimum inhibitory concentrations were reported using defined breakpoints., Results: Among 130 participants, N. gonorrhoeae was the most frequent pathogen detected (106; 82.8%), followed by C. trachomatis (15; 11.7%), M. genitalium (6; 4.7%), and T. vaginalis (2; 1.6%). Four (6.1%) of the 66 gonococci isolated were resistant to fluoroquinolones, whereas all viable isolates were susceptible to kanamycin, cefixime, and ceftriaxone., Conclusions: Gonorrhea is the most important cause of MUD in men in Harare, and our study highlights the emergence of fluoroquinolone-resistant N. gonorrhoeae. Further STI surveys are required in other regions of Zimbabwe to obtain a nationally representative picture of gonococcal burden and antimicrobial resistance among MUD patients.

Introduction: This study was designed to compare the detection of malaria parasites in peripheral blood smears using the Cyscope malaria rapid fluorescent microscopic technique and light microscopy of Giemsa-stained smears., Methodology: A total of 295 blood smears were collected from patients of all age groups presenting with clinical signs and symptoms of malaria to 10 City Health Clinics in Harare. For each patient two blood films were prepared. Microscopic examination was done independently in two laboratories, with one performing the Giemsa stain and the other the Cyscope method. After the tests were completed, the results were then matched and recorded without any alterations., Results: An equal number of men and women were malaria positive and their ages ranged from five to 66 years. Concordance in the detection of parasites (positive or negative) was 98.6% (291/295). In all four cases of discordance, malaria parasites were detected using the Cyscope but not with conventional microscopy. The Cyscope gave a 100% sensitivity and a specificity of 98.6%., Conclusion: The Cyscope may be a valuable addition to diagnostics of malaria in resource-limited settings such as Zimbabwe.

The concentration of human immunodeficiency virus type 1 (HIV-1) is generally lower in breast milk than in blood. Mastitis, or inflammation of the breast, is associated with increased levels of milk HIV-1 and risk of mother-to-child transmission through breastfeeding. We hypothesized that mastitis facilitates the passage of HIV-1 from blood into milk or stimulates virus production within the breast. HIV-1 env sequences were generated from single amplicons obtained from breast milk and blood samples in a cross-sectional study. Viral compartmentalization was evaluated using several statistical methods, including the Slatkin and Maddison (SM) test. Mastitis was defined as an elevated milk sodium (Na(+)) concentration. The association between milk Na(+) and the pairwise genetic distance between milk and blood viral sequences was modeled using linear regression. HIV-1 was compartmentalized within milk by SM testing in 6/17 (35%) specimens obtained from 9 women, but all phylogenetic clades included viral sequences from milk and blood samples. Monotypic sequences were more prevalent in milk samples than in blood samples (22% versus 13%; P = 0.012), which accounted for half of the compartmentalization observed. Mastitis was not associated with compartmentalization by SM testing (P = 0.621), but Na(+) was correlated with greater genetic distance between milk and blood HIV-1 populations (P = 0.041). In conclusion, local production of HIV-1 within the breast is suggested by compartmentalization of virus and a higher prevalence of monotypic viruses in milk specimens. However, phylogenetic trees demonstrate extensive mixing of viruses between milk and blood specimens. HIV-1 replication in breast milk appears to increase with inflammation, contributing to higher milk viral loads during mastitis.

Background: Breast milk HIV-1 load is associated with clinical and subclinical mastitis, and both milk viral load and mastitis are associated with increased mother-to-child-transmission of HIV-1 through breastfeeding. Bacterial infections may cause clinical mastitis, but whether other copathogens common in HIV-1 infection are associated with subclinical mastitis or HIV-1 shedding is unknown., Design: A cross-sectional study of HIV-1-infected breastfeeding women in Zimbabwe was performed to examine the relationship between a wide range of breast coinfections, mastitis, and HIV-1 shedding., Methods: Breast milk was cultured for bacteria and fungi and tested by PCR for mycobacteria, mycoplasmas, human herpesvirus (HHV)-6, HHV-7, HHV-8, cytomegalovirus, Epstein-Barr virus, and HIV-1 RNA and DNA. Symptoms of clinical mastitis were documented and subclinical mastitis was identified by breast milk sodium concentration (Na) and leukocyte counts., Results: Coinfections of milk were not associated with clinical or subclinical mastitis in the 217 women studied. Detection of HIV-1 RNA, but not DNA, in breast milk was associated with cytomegalovirus concentration (odds ratio = 1.8, P = 0.002) and detection of Epstein-Barr virus (odds ratio = 3.8, P = 0.0003) but not other coinfections in multivariate analysis., Conclusion: Coinfection of breast milk with bacteria, fungi, or herpes viruses was not associated with mastitis. The associations between shedding of cytomegalovirus and Epstein-Barr virus with HIV-1 in milk suggest a local interaction between herpes virus infection and HIV-1 independent of mastitis. Cytomegalovirus and Epstein-Barr virus infections may impact HIV-1 shedding in breast milk and the risk of MTCT.

Setting: Gweru Provincial Hospital, Zimbabwe., Objectives: To evaluate the accuracy of the diagnosis of pulmonary tuberculosis (PTB) in routine circumstances., Design: Prospective cohort study of routinely diagnosed PTB patients between September 2000 and September 2001., Results: Of 300 patients started on treatment, 161 (53.7%) were positive on direct microscopy. Of the 139 sputum-negative patients, 51 (36.7%) were positive after concentration of specimens, an additional 30 (21.6%) were positive on culture only and 58 (19.3% of the total) were negative for all laboratory investigations. There was no difference in sex, human immunodeficiency virus (HIV) serostatus or treatment outcome between the culture-positive and culture-negative presumed PTB patients. Sputum-negative patients had an increased risk of dying during treatment (RR 2.39, P = 0.015)., Conclusions: The laboratory findings reveal that PTB could be confirmed in more than 80% of patients put on treatment in this setting. The treatment outcomes of the remainder did not differ from those in patients with microbiologically confirmed PTB. In a high HIV-prevalent area, clinicians rightly consider the results of the sputum microscopy test as only one element in the decision making process to put a patient on TB treatment.

Setting: In countries with high human immunodeficiency virus prevalence, laboratory diagnosis of pulmonary tuberculosis with the standard Ziehl-Neelsen (ZN) technique is characterised by low sensitivity., Objective: To compare test characteristics of direct microscopy, the concentration method and the Mycobacteria Growth Indicator Tube (MGIT)., Design: Three hundred specimens from patients diagnosed with pulmonary tuberculosis were tested for the presence of mycobacteria. Specimens were stained with ZN, decontaminated by adding 4% NaOH, concentrated by centrifuging and processed in MGIT broth. The gold standard was defined as a positive MGIT culture or a positive acid-fast bacilli smear of material obtained from a negative culture after 42 days., Results: A total of 44 (14.7%) specimens were contaminated. Of 256 valid specimens, 234 (91.4%) were positive according to the gold standard definition. Decontamination and concentration of the sample increased the sensitivity of direct microscopy from 67.5% to 87.1%. Specificity remained unchanged (95.5%). The overall median time to detection of MGIT culture-positive specimens was 5 days, ranging from 4 (direct smear-positive specimens) to 12 days (concentration smear-negative specimens)., Conclusion: The concentration method substantially increases the sensitivity of direct microscopy without much extra input. The MGIT culture technique has considerable advantages, but its relatively high contamination rate and its high cost make it a less recommendable option for widespread use in routine district laboratories.