Search

Objectives: The aim of this study was to produce Geo Spatial Distribution of Frequencies of MTB/RIF Detected Specimens based on Requesting Health Facilities in Manicaland Zimbabwe for 2017 and 2018, so as to give insight to TB program managers. Focusing elimination interventions on hot pockets of Tuberculosis (TB) strengthens rationale use of resources in resource limited countries like Zimbabwe. Early detection and early treatment is backbone of breaking TB transmission. Drug resistant tuberculosis (DRTB) control interventions like Programmatic Management of Drug Resistant TB or mentoring on Short, all Oral Regimen for Rifampicin resistant Tuberculosis (ShORRT) will be driven by science. Materials and Methods: The retrospective study was carried out in Manicaland, Zimbabwe. Manicaland one of the 10 provinces in Zimbabwe, has 7 districts with 308 health facilities. During this retrospective cross sectional study 2221 MTB detected results of 2017 and 2018, downloaded from 14 of the 15 Genexpert sites in Manicaland were employed to generate hotspot maps. Fifteenth Genexpert site lost its electronic records when Genexpert CPU crushed. Geographical Positioning System (GPS) of the health facilities were recorded.The study used MTB detected frequencies at a facility in relation to surrounding facilities in Manicaland, then ran optimised hotspot analysis function in Arc Map 10.5 to implement the Gi* statistic. Results: Overall provincial MTB detected positivity was 2221/36055 (6.2%). Overall provincial Rifampicin Resistant (RR) positivity was. 111.2221(5.0%). Geo-spatial map of Manicaland showed 10 facilities that are RR hotspots with 7/10 (70%) of the facilities in Buhera district. Chipinge district had facilities that were MTB detected high hotspots.For the whole of Manicaland, Buhera district had100% MTB detected low hotspots facilities. Ninety percent hotspots were clustered around 2 of the 15 Genexpert Sites in Manicaland, namely Murambinda Mission Hospital and Chipinge District Hospital. Conclusion: Study identified health facilities with high frequencies of RR areas. For the identified health facilities with high frequencies of RR specimens, NTP may focus DRTB control interventions like PMDT, or mentoring on ShORRT. For the health facilities with high frequencies of MTB detected NTP can focus trainings in TB Case Management. Instead of uniformly spreading the limited resources to all 325 facilities, efforts streamlined to manageable number of 20 facilities in commensurate with identified gap(e.g. objective selection of cadres for training, data driven supportive supervision & targeted awareness campaigns). [ABSTRACT FROM AUTHOR]

An oligonucleotide ligation assay (OLA) designed to detect Human Immunodeficiency Virus type-1 (HIV)-drug-resistance to the nevirapine (NVP) selected mutations K103N, Y181C, V106M and G190A was used to evaluate 200 archived dried blood spots (DBS) from infected infants participating in the Zimbabwean Early Infant Diagnosis (EID) Program. Consensus sequencing of specimens with indeterminate OLA results was performed to identify genetic sequence polymorphisms that appeared to compromise performance of the OLA. When consistent patterns of polymorphisms were observed the probes were redesigned, and DBS specimens with indeterminate OLA results were retested with the new Zimbabwe-specific (ZW) probes. OLA results obtained in Zimbabwe were compared to repeat testing in a US reference laboratory. 188/200 (94%) DBS yielded polymerase chain reaction (PCR) amplification of HIV pol . ZW probes reduced indeterminate OLA results from 5.2% to 2.8% of codons evaluated ( p = 0.02), with 98.2% concordance between results obtained in the Zimbabwean and US laboratories. Optimization of OLA probes to accommodate polymorphisms in regional HIV variants improved OLA performance, and comparison to the USA results showed successful implementation of the OLA in Zimbabwe for detection of NVP resistance mutations in DBS specimens. [ABSTRACT FROM AUTHOR]

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: 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.

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.

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.

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.

Understanding the epidemiology and clinical course of tuberculosis is hampered by the absence of a perfect test for latent tuberculosis infection. The tuberculin skin test (TST) is widely used but suffers poor specificity in those receiving the bacille Calmette-Guérin vaccine and poor sensitivity in individuals with human immunodeficiency virus (HIV) infections. TST responses for a target population in Harare, Zimbabwe (HIV prevalence, 21%), recruited in 2005-2006, were interpreted by using a separate calibration population in Harare, for which interferon-gamma release assays (enzyme-linked immunosorbent spot (ELISpot)) results were also known. Statistical fitting of the responses in the calibration population allowed computation of the probability that an individual in the target population with a given TST and HIV result would have tested ELISpot positive. From this, estimates of the prevalence of tuberculosis infection, and optimal TST cutpoints to minimize misdiagnosis, were computed for different assumptions about ELISpot performance. Different assumptions about the sensitivity and specificity of ELISpot gave a 40%-57% prevalence of tuberculosis infection in the target population (including HIV-infected individuals) and optimal TST cutpoints typically in the 10 mm-20 mm range. However, the optimal cutpoint for HIV-infected individuals was consistently 0 mm. This calibration method may provide a valuable tool for interpreting TST results in other populations.

Background: Accurate diagnosis of latent tuberculosis infection (LTBI) in recently exposed HIV-infected tuberculosis (TB) contacts is a public health priority because of the high risk of progression to active TB but is hampered by the high background prevalence of LTBI in high-burden populations and poor sensitivity of tuberculin skin testing (TST) in HIV co-infection., Methods: The prevalence of LTBI in 222 recent household contacts of TB cases and 176 household contacts of community controls without TB in Harare, Zimbabwe were compared using TST and interferon gamma enzyme-linked immunospot (ELISpot) responses to ESAT-6 (early secretory antigenic target-6) and CFP-10 (culture filtrate protein-10). TST and ELISpot results were correlated with markers of recent TB exposure and the impact of HIV co-infection was assessed., Results: In this high-incidence population, the proportion of ELISpot-positive contacts was not significantly different from community controls. However, ELISpot, unlike TST, revealed a higher prevalence of LTBI in recent contacts of sputum smear-positive cases than in contacts of controls. ELISpot results correlated significantly with positive sputum smear and culture status of the index case (adjusted OR 2.40, CI 1.12 to 5.14), even in the subgroup of HIV-infected contacts (adjusted OR 5.36, CI 1.11 to 25.93). and were independent of contacts' HIV status. TST results were also associated with positive smear and culture status of the index case (adjusted OR 4.41, CI 1.82 to 10.67) but were negatively associated with contacts' HIV status (adjusted OR 0.25, CI 0.10 to 0.60)., Conclusions: Contact investigations in high-burden populations should focus on contacts of sputum smear-positive cases in whom recent infection can be detected by ELISpot, even in the presence of HIV co-infection.

Background: Cough lasting for > or = 3 weeks (i.e., chronic cough) indicates that a patient has suspected tuberculosis (TB). At the primary health care level, the spectrum of disease that causes chronic cough has not been previously investigated in a setting with a high prevalence of human immunodeficiency virus (HIV) infection., Methods: A total of 544 adults with chronic cough were recruited systematically from 2 primary health care clinics, and they were evaluated using preset first- and second-line investigations and diagnostic case definitions., Results: The overall prevalence of HIV infection among the study cohort was 83%. TB was the most common diagnosis, with 207 HIV-positive patients (46%) and 27 HIV-negative patients (30%) having confirmed or probable TB. Of these, 145 HIV-positive patients with TB (70%) and 20 HIV-negative patients with TB (74%) had smear-positive cases of TB. Only 17 HIV-positive and 2 HIV-negative patients had smear-negative but culture-positive cases of TB. Lower respiratory tract infections (n = 178; HIV prevalence, 79%) and pneumonia (n = 87; HIV prevalence, 89%) were the next most common diagnoses. Asthma (n = 26; HIV prevalence, 46%), posttuberculous disease and other fibrotic lung disease (n = 34; HIV prevalence, 88%), and cardiac disease (n = 15; HIV prevalence, 93%) were more common than were Pneumocystis jiroveci pneumonia and cryptococcosis (n = 8 and n = 5, respectively; HIV prevalence, 100%), and we found no cases of nocardiosis or histoplasmosis., Conclusions: TB was diagnosed for 43% of patients who presented with chronic cough to primary health care clinics in Harare, with 71% having smear-positive disease. The findings of TB culture added relatively little to the findings of fluorescent microscopy of concentrated sputum specimens. The prevalence of HIV infection was high across a range of diagnoses, suggesting that an HIV test should be recommended in the initial investigation of chronic cough.

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.