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Common causes of EID sample rejection in Zimbabwe and how to mitigate them.

ABSTRACT: Early infant diagnosis (EID) of HIV provides an opportunity for early HIV detection and access to appropriate Antiretroviral treatment (ART). Dried Blood Spot (DBS) samples are used for EID of exposed infants, born to HIV-positive mothers. However, DBS rejection rates in Zimbabwe have been exceeding the target of less than 2% per month set by the National Microbiology Reference Laboratory (NMRL), in Harare. The aim of this study was to determine the DBS sample rejection rate, the reasons for rejection and the possible associations between rejection and level of health facility where the samples were collected. This is an analytical cross-sectional study using routine DBS sample data from the NMRL in Harare, Zimbabwe, between January and December 2017.A total of 34 950 DBS samples were received at the NMRL. Of these, 1291(4%) were rejected. Reasons for rejection were insufficient specimen volume (72%), missing request form (11%), missing sample (6%), cross-contamination (6%), mismatch of information (4%) and clotted sample (1%). Samples collected from clinics/rural health facilities were five times more likely to be rejected compared to those from a central hospital. Rejection rates were above the set target of <2%. The reasons for rejection were 'pre-analytical' errors including labelling errors, missing or inconsistent data, and insufficient blood collected. Samples collected at primary healthcare facilities had higher rejection rates.

SUBMITTER: Chiku C

PROVIDER: S-EPMC6687112 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Common causes of EID sample rejection in Zimbabwe and how to mitigate them.

Chiku Charles C Zolfo Maria M Senkoro Mbazi M Mabhala Mzwandile M Tweya Hannock H Musasa Patience P Shukusho Fungai D FD Mazarura Exervia E Mushavi Angela A Mangwanya Douglas D

PloS one 20190808 8

Early infant diagnosis (EID) of HIV provides an opportunity for early HIV detection and access to appropriate Antiretroviral treatment (ART). Dried Blood Spot (DBS) samples are used for EID of exposed infants, born to HIV-positive mothers. However, DBS rejection rates in Zimbabwe have been exceeding the target of less than 2% per month set by the National Microbiology Reference Laboratory (NMRL), in Harare. The aim of this study was to determine the DBS sample rejection rate, the reasons for rej ...[more]

PMID: 31393883

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Project description:BackgroundThere are an estimated half-million children living with HIV in sub-Saharan Africa. The predominant source of infection is presumed to be perinatal mother-to-child transmission, but general population data about paediatric HIV are sparse. We characterise the epidemiology of HIV in children in sub-Saharan Africa by describing the prevalence, possible source of infection, and effects of paediatric HIV in a southern African population.MethodsFrom 2009 to 2011, we conducted a household-based survey of 3389 children (aged 2-14 years) in Manicaland, eastern Zimbabwe (response rate: 73.5%). Data about socio-demographic correlates of HIV, risk factors for infection, and effects on child health were analysed using multi-variable logistic regression. To assess the plausibility of mother-to-child transmission, child HIV infection was linked to maternal survival and HIV status using data from a 12-year adult HIV cohort.ResultsHIV prevalence was (2.2%, 95% CI: 1.6-2.8%) and did not differ significantly by sex, socio-economic status, location, religion, or child age. Infected children were more likely to be underweight (19.6% versus 10.0%, p = 0.03) or stunted (39.1% versus 30.6%, p = 0.04) but did not report poorer physical or psychological ill-health. Where maternal data were available, reported mothers of 61/62 HIV-positive children were deceased or HIV-positive. Risk factors for other sources of infection were not associated with child HIV infection, including blood transfusion, vaccinations, caring for a sick relative, and sexual abuse. The observed flat age-pattern of HIV prevalence was consistent with UNAIDS estimates which assumes perinatal mother-to-child transmission, although modelled prevalence was higher than observed prevalence. Only 19/73 HIV-positive children (26.0%) were diagnosed, but, of these, 17 were on antiretroviral therapy.ConclusionsChildhood HIV infection likely arises predominantly from mother-to-child transmission and is associated with poorer physical development. Overall antiretroviral therapy uptake was low, with the primary barrier to treatment appearing to be lack of diagnosis.

Project description:Limited sample sizes can lead to spurious modeling findings in biomedical research. The objective of this work is to present a new method to generate synthetic populations (SPs) from limited samples using matched case-control data (n = 180 pairs), considered as two separate limited samples. SPs were generated with multivariate kernel density estimations (KDEs) with unconstrained bandwidth matrices. We included four continuous variables and one categorical variable for each individual. Bandwidth matrices were determined with Differential Evolution (DE) optimization by covariance comparisons. Four synthetic samples (n = 180) were derived from their respective SPs. Similarity between observed samples with synthetic samples was compared assuming their empirical probability density functions (EPDFs) were similar. EPDFs were compared with the maximum mean discrepancy (MMD) test statistic based on the Kernel Two-Sample Test. To evaluate similarity within a modeling context, EPDFs derived from the Principal Component Analysis (PCA) scores and residuals were summarized with the distance to the model in X-space (DModX) as additional comparisons. Four SPs were generated from each sample. The probability of selecting a replicate when randomly constructing synthetic samples (n = 180) was infinitesimally small. MMD tests indicated that the observed sample EPDFs were similar to the respective synthetic EPDFs. For the samples, PCA scores and residuals did not deviate significantly when compared with their respective synthetic samples. The feasibility of this approach was demonstrated by producing synthetic data at the individual level, statistically similar to the observed samples. The methodology coupled KDE with DE optimization and deployed novel similarity metrics derived from PCA. This approach could be used to generate larger-sized synthetic samples. To develop this approach into a research tool for data exploration purposes, additional evaluation with increased dimensionality is required. Moreover, given a fully specified population, the degree to which individuals can be discarded while synthesizing the respective population accurately will be investigated. When these objectives are addressed, comparisons with other techniques such as bootstrapping will be required for a complete evaluation.

Project description:Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for non-transplant indications, could regulate specific CRM genes and reduce the number of graft infiltrating cells during acute rejection. We treated mice with HLA-mismatched murine cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatina on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning and rational drug design. The eight transplant data sets used for discovery include GSE4315, GSE2596, GSE4470, GSE9377, GSE1563, GSE9493, GSE13440, GSE6095. The two additional independent cohorts of 151 transplant biopsies are GSE25902 and GSE1563. Not all samples from all studies were used. Only the samples marked as either AR or STA in each data set were used for analysis. The 101 samples in this study were used as case-control experiment between acute rejection (AR) and stable (STA) in renal transplant. The samples in this series are one of the three independent validation cohorts. The other two cohorts are described in GSE21374 and GSE36059

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Common causes of EID sample rejection in Zimbabwe and how to mitigate them.

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Common causes of EID sample rejection in Zimbabwe and how to mitigate them.

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