TB prevalence in Zimbabwe: a national cross-sectional survey, 2014.

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.

The impact of changing the diagnostic algorithm for TB in Manicaland, Zimbabwe.

SETTING: Governmental health facilities performing TB diagnostics in Manicaland, Zimbabwe. OBJECTIVE: To investigate the effect of making Xpert® MTB/RIF the primary TB diagnostic for all patients presenting with presumptive TB on 1) the number of samples investigated for TB, 2) the proportion testing TB-positive, and 3) the proportion of unsuccessful results over time. DESIGN: This retrospective study used data from GeneX-pert downloads, laboratory registers and quality assurance reports between 1 January 2017 and 31 December 2018. RESULTS: The total number of Xpert tests performed in Manicaland increased from 3,967 in the first quarter of 2017 to 7,011 in the last quarter of 2018. Mycobacterium tuberculosis DNA was detected in 4.9-8.6% of the samples investigated using Xpert, with a higher yield in 2017 than in 2018. The overall proportion of unsuccessful Xpert assays due to "no results", errors and invalid results was 6.3%, and highly variable across sites. CONCLUSION: Roll out of more sensitive TB diagnostics does not necessarily result in an increase of microbiologically confirmed TB diagnosis. While the number of samples tested using Xpert increased, the proportion of TB-positive tests decreased. GeneXpert soft- and hardware infrastructure needs to be strengthened to reduce the rate of unsuccessful assays and therefore, costs and staff time.

LIEU: Centres de soins gouvernementaux réalisant des tests diagnostiques de la TB au Manicaland, Zimbabwe. OBJECTIF: Analyser l'effet de l'utilisation du test Xpert® MTB/RIF en tant que test diagnostique principal de la TB chez tous les patients suspects de TB sur 1) le nombre d'échantillons analysés pour TB, 2) la proportion d'échantillons testés positifs à la TB et 3) la proportion de résultats infructueux au fil du temps. MÉTHODE: Cette étude rétrospective a utilisé les données extraites du système GeneXpert, des registres de laboratoire et des rapports d'assurance qualité entre le 1er janvier 2017 et le 31 décembre 2018. RÉSULTATS: Le nombre total de tests Xpert réalisés au Manicaland a augmenté, de 3 967 au premier trimestre 2017 à 7 011 au dernier trimestre 2018. L'ADN de Mycobacterium tuberculosis a été détecté dans 4,9­8,6% des échantillons analysés par test Xpert, avec un rendement plus élevé en 2017 qu'en 2018. La proportion globale de tests Xpert infructueux en raison d'une « absence de résultat ¼, d'erreurs ou de résultats non valides était de 6,3%, avec une forte variation en fonction des sites. CONCLUSION: Le déploiement de tests diagnostiques de la TB plus sensibles n'entraîne pas nécessairement une hausse des diagnostics de TB confirmés microbiologiquement. Alors que le nombre d'échantillons testés par test Xpert a augmenté, la proportion de tests positifs pour la TB a diminué. L'infrastructure du matériel et du logiciel GeneXpert doit être renforcée pour réduire le taux de tests infructueux, et donc les coûts et le temps consacré par le personnel à la réalisation de ces tests.

Optimization of the oligonucleotide ligation assay for the detection of nevirapine resistance mutations in Zimbabwean Human Immunodeficiency Virus type-1 subtype C.

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.

Accuracy of routine diagnosis of pulmonary tuberculosis in an area of high HIV prevalence.

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.

A comparison of direct microscopy, the concentration method and the Mycobacteria Growth Indicator Tube for the examination of sputum for acid-fast bacilli.

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.