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

Performance evaluation of the Pima™ point-of-care CD4 analyser using capillary blood sampling in field tests in South Africa

<p>Abstract</p> <p>Background</p> <p>Point-of-care CD4 testing can provide immediate CD4 reporting at HIV-testing sites. This study evaluated performance of capillary blood sampling using the point-of-care Pima™ CD4 device in representative primary health care clinics doing HIV testing.</p> <p>Methods</p> <p>Prior to testing, prescribed capillary-sampling and instrument training was undertaken by suppliers across all sites. Matching venous EDTA samples were drawn throughout for comparison to laboratory predicate methodology (PLG/CD4). In Phase I, Pima™ cartridges were pipette-filled with EDTA venous blood in the laboratory (N = 100). In Phase II (N = 77), Pima™ CD4 with capillary sampling was performed by a single operator in a hospital-based antenatal clinic. During subsequent field testing, Pima™ CD4 with capillary sampling was performed in primary health care clinics on HIV-positive patients by multiple attending nursing personnel in a rural clinic (Phase-IIIA, N = 96) and an inner-city clinic (Phase-IIIB, N = 139).</p> <p>Results</p> <p>Pima™ CD4 compared favourably to predicate/CD4 when cartridges were pipette-filled with venous blood (bias -17.3 ± STDev = 36.7 cells/mm³; precision-to-predicate %CV < 6%). Decreased precision of Pima™ CD4 to predicate/CD4 (varying from 17.6 to 28.8%SIM CV; mean bias = 37.9 ± STDev = 179.5 cells/mm³) was noted during field testing in the hospital antenatal clinic. In the rural clinic field-studies, unacceptable precision-to-predicate and positive bias was noted (mean 28.4%SIM CV; mean bias = +105.7 ± STDev = 225.4 cells/mm³). With additional proactive manufacturer support, reliable performance was noted in the subsequent inner-city clinic field study where acceptable precision-to-predicate (11%SIM CV) and less bias of Pima™ to predicate was shown (BA bias ~11 ± STDev = 69 cells/mm³).</p> <p>Conclusions</p> <p>Variable precision of Pima™ to predicate CD4 across study sites was attributable to variable capillary sampling. Poor precision was noted in the outlying primary health care clinic where the system is most likely to be used. Stringent attention to capillary blood collection technique is therefore imperative if technologies like Pima™ are used with capillary sampling at the POC. Pima™ CD4 analysis with venous blood was shown to be reproducible, but testing at the point of care exposes operators to biohazard risk related to uncapping vacutainer samples and pipetting of blood, and is best placed in smaller laboratories using established principles of Good Clinical Laboratory Practice. The development of capillary sampling quality control methods that assure reliable CD4 counts at the point of care are awaited.</p

How to Estimate the Cost of Point-of-Care CD4 Testing in Program Settings: An Example Using the Alere Pima™ Analyzer in South Africa

Integrating POC CD4 testing technologies into HIV counseling and testing (HCT) programs may improve post-HIV testing linkage to care and treatment. As evaluations of these technologies in program settings continue, estimates of the costs of POC CD4 tests to the service provider will be needed and estimates have begun to be reported. Without a consistent and transparent methodology, estimates of the cost per CD4 test using POC technologies are likely to be difficult to compare and may lead to erroneous conclusions about costs and cost-effectiveness. This paper provides a step-by-step approach for estimating the cost per CD4 test from a provider's perspective. As an example, the approach is applied to one specific POC technology, the Pima™ Analyzer. The costing approach is illustrated with data from a mobile HCT program in Gauteng Province of South Africa. For this program, the cost per test in 2010 was estimated at $23.76 (material costs =$8.70; labor cost per test = $7.33; and equipment, insurance, and daily quality control =$7.72). Labor and equipment costs can vary widely depending on how the program operates and the number of CD4 tests completed over time. Additional costs not included in the above analysis, for on-going training, supervision, and quality control, are likely to increase further the cost per test. The main contribution of this paper is to outline a methodology for estimating the costs of incorporating POC CD4 testing technologies into an HCT program. The details of the program setting matter significantly for the cost estimate, so that such details should be clearly documented to improve the consistency, transparency, and comparability of cost estimates

The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods

Background: Commencing lifelong antiretroviral therapy (ART) immediately following HIV diagnosis (Option B+), has greatly improved maternal-infant health. Thus, large and increasing numbers of HIV-infected women are on ART during pregnancy, a situation concurrently increasing numbers of HIV-exposed-uninfected (HEU) infants. Compared to their HIV-unexposed-uninfected (HUU) counterparts, HEU infants show higher rates of adverse birth outcomes, mortality, infectious/non-communicable diseases including impaired growth and neurocognitive development. There is an urgent need to understand the impact of HIV and early life ART exposures, immune-metabolic dysregulation, comorbidities and environmental confounders on adverse paediatric outcomes. Methods: Six hundred (600) HIV-infected and 600 HIV-uninfected pregnant women ≥20 weeks of gestation will be enrolled from four primary health centres in high density residential areas of Harare. Participants will be followed up as mother-infant-pairs at delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72 and 96 after birth. Clinical, socio-economic, nutritional and environmental data will be assessed for adverse birth outcomes, impaired growth, immune/neurodevelopment, vertical transmission of HIV, hepatitis-B/C viruses, cytomegalovirus and syphilis. Maternal urine, stool, plasma, cord blood, amniotic fluid, placenta and milk including infant plasma, dried blood spot and stool will be collected at enrolment and follow-up visits. The composite primary endpoint is stillbirth and infant mortality within the first two years of life in HEU versus HUU infants. Maternal mortality in HIV-infected versus -uninfected women is another primary outcome. Secondary endpoints include a range of maternal and infant outcomes. Sub-studies will address maternal stress and malnutrition, maternal-infant latent tuberculosis, Helicobacter pylori infections, immune-metabolomic dysregulation including gut, breast milk and amniotic fluid dysbiosis. Discussion: The University of Zimbabwe-College of Health-Sciences-Birth-Cohort study will provide a comprehensive assessment of risk factors and biomarkers for HEU infants’ adverse outcomes. This will ultimately help developing strategies to mitigate effects of maternal HIV, early-life ART exposures and comorbidities on infants’ mortality and morbidity. Trial registration: ClinicalTrial.gov Identifier: NCT04087239. Registered 12 September 2019

Impact of Schistosome Infection on Plasmodium falciparum Malariometric Indices and Immune Correlates in School Age Children in Burma Valley, Zimbabwe

A group of children aged 6–17 years was recruited and followed up for 12 months to study the impact of schistosome infection on malaria parasite prevalence, density, distribution and anemia. Levels of cytokines, malaria specific antibodies in plasma and parasite growth inhibition capacities were assessed. Baseline results suggested an increased prevalence of malaria parasites in children co-infected with schistosomiasis (31%) compared to children infected with malaria only (25%) (p = 0.064). Moreover, children co-infected with schistosomes and malaria had higher sexual stage geometric mean malaria parasite density (189 gametocytes/µl) than children infected with malaria only (73/µl gametocytes) (p = 0.043). In addition, a larger percentage of co-infected children (57%) had gametocytes as observed by microscopy compared to the malaria only infected children (36%) (p = 0.06). There was no difference between the two groups in terms of the prevalence of anemia, which was approximately 64% in both groups (p = 0.9). Plasma from malaria-infected children exhibited higher malaria antibody activity compared to the controls (p = 0.001) but was not different between malaria and schistosome plus malaria infected groups (p = 0.44) and malaria parasite growth inhibition activity at baseline was higher in the malaria-only infected group of children than in the co-infected group though not reaching statistical significance (p = 0.5). Higher prevalence and higher mean gametocyte density in the peripheral blood may have implications in malaria transmission dynamics during co-infection with helminths

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Comparative Analysis of Genexpert MTB/Rif version 4 and Genexpert MTB/Rif Ultra on Frozen Sputum

Objectives: The aim of this study was to carry out a comparative analysis using Genexpert MTB/Rif Ultra (Ultra) on clinical samples of frozen sputum previously analyzed on Genexpert MTB/Rif version 4 (Xpert)and Mycobacterium Growth Indicator Tube (MGIT) culture.Design: The study employed both retrospective and prospective cross sectional design.Setting: Mutare Provincial Hospital Manicaland, Zimbabwe.Subjects: One hundred and nine de-identified frozen sputum.Interventions: Ultra test.Main Outcome Measures: Ultra results.Results: There was 96/109 (88%) concordance and 10/109 (9.2%) discordance between Xpert and Ultra. Sputum frozen for 7 years then analyzed on Ultra performed better than 7 years previously when it was analyzed as raw sputum on Xpert using MGIT as gold standard (95.6% and 93.2% respectively).The results were comparable and statistically significant, kappa analysis between Xpert and frozen sputum Ultra was not statistically significant showing a slight level of agreement of 0.147 (p value =0.079), 95% CI (-0.1078, 0.4018).Conclusion: Results of Ultra on frozen sputum correlate reasonably well. The study findings show that TB positive frozen sputum from presumptive DRTB, run on Ultra after 7 years freezing can perform better than previously run Xpert results compared to MGIT as gold standard. In light of the research findings, potential implication are that to save on cost, comparison of performance of newly diagnosed tests can be done using frozen sputum, pre run on panel of TB tests

Impact of solar radiation in disinfecting drinking water contaminated with Giardia duodenalis and Entamoeba histolytica/dispar at a point-of-use water treatment.

Solar disinfection system using PET containers painted black on one side can be used to disinfect water against Giardia duodenalis and Entamoeba histolytica/dispar using natural sunlight

Changes in the humoral immune responses after chemotherapy in single and co-infected individuals with Schisosoma haematobuim and Plasmodium falciparum

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