HIV Viral Load Estimation Using Hematocrit Corrected Dried Blood Spot Results on a BioMerieux NucliSENS® Platform.

While reporting human immunodeficiency virus (HIV) viral load (VL) using dried blood spot (DBS) in the BioMerieux NucliSENS platform, application of the hematocrit correction factor has been suggested. In this cross-sectional study from the National Microbiology Reference Laboratory of Zimbabwe, we assessed whether hematocrit correction (individual and/or mean) in DBS results improved the correlation with plasma VL and prediction of VL non-suppression (≥1000 copies per ml in plasma). Of 517 specimens during August-December 2018, 65(12.6%) had non-suppressed plasma VL results. The hematocrit correction factor ranged from 1.3 to 2.0 with a mean of 1.6, standard deviation (SD: 1.5, 1.7). The intraclass correlation (ICC) for mean (0.859, 95% CI: 0.834, 0.880) and individual (0.809, 95% CI: 0.777, 0.837) hematocrit corrected DBS results were not significantly different. The uncorrected DBS results had a significantly lower ICC (0.640, 95% CI: 0.586, 0.688) when compared to corrected DBS results. There were no significant differences in validity, predictive values, and areas under the receiver operating characteristics curves for all three DBS results when predicting VL non-suppression. To conclude, hematocrit correction of DBS VL results improved agreement with the plasma results but did not improve prediction of VL non-suppression. The results were not significantly different for individual and mean corrected results

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa.

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants

Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial.

BACKGROUND: Child stunting reduces survival and impairs neurodevelopment. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in in Zimbabwe. METHODS: We did a cluster-randomised, community-based, 2 × 2 factorial trial in two rural districts in Zimbabwe. Clusters were defined as the catchment area of between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Women were eligible for inclusion if they permanently lived in clusters and were confirmed pregnant. Clusters were randomly assigned (1:1:1:1) to standard of care (52 clusters), IYCF (20 g of a small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counselling; 53 clusters), WASH (construction of a ventilated improved pit latrine, provision of two handwashing stations, liquid soap, chlorine, and play space plus hygiene counselling; 53 clusters), or IYCF plus WASH (53 clusters). A constrained randomisation technique was used to achieve balance across the groups for 14 variables related to geography, demography, water access, and community-level sanitation coverage. Masking of participants and fieldworkers was not possible. The primary outcomes were infant length-for-age Z score and haemoglobin concentrations at 18 months of age among children born to mothers who were HIV negative during pregnancy. These outcomes were analysed in the intention-to-treat population. We estimated the effects of the interventions by comparing the two IYCF groups with the two non-IYCF groups and the two WASH groups with the two non-WASH groups, except for outcomes that had an important statistical interaction between the interventions. This trial is registered with ClinicalTrials.gov, number NCT01824940. FINDINGS: Between Nov 22, 2012, and March 27, 2015, 5280 pregnant women were enrolled from 211 clusters. 3686 children born to HIV-negative mothers were assessed at age 18 months (884 in the standard of care group from 52 clusters, 893 in the IYCF group from 53 clusters, 918 in the WASH group from 53 clusters, and 991 in the IYCF plus WASH group from 51 clusters). In the IYCF intervention groups, the mean length-for-age Z score was 0·16 (95% CI 0·08-0·23) higher and the mean haemoglobin concentration was 2·03 g/L (1·28-2·79) higher than those in the non-IYCF intervention groups. The IYCF intervention reduced the number of stunted children from 620 (35%) of 1792 to 514 (27%) of 1879, and the number of children with anaemia from 245 (13·9%) of 1759 to 193 (10·5%) of 1845. The WASH intervention had no effect on either primary outcome. Neither intervention reduced the prevalence of diarrhoea at 12 or 18 months. No trial-related serious adverse events, and only three trial-related adverse events, were reported. INTERPRETATION: Household-level elementary WASH interventions implemented in rural areas in low-income countries are unlikely to reduce stunting or anaemia and might not reduce diarrhoea. Implementation of these WASH interventions in combination with IYCF interventions is unlikely to reduce stunting or anaemia more than implementation of IYCF alone. FUNDING: Bill & Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Development Cooperation, UNICEF, and US National Institutes of Health.The SHINE trial is funded by the Bill & Melinda Gates Foundation (OPP1021542 and OPP113707); UK Department for International Development; Wellcome Trust, UK (093768/Z/10/Z, 108065/Z/15/Z and 203905/Z/16/Z); Swiss Agency for Development and Cooperation; US National Institutes of Health (2R01HD060338-06); and UNICEF (PCA-2017-0002)

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

Characteristics of mothers and infants by CMV status.

<p>*All values are mean (standard deviation), unless shown otherwise.</p><p>For variables with missing data, the number of participants with available data is shown in square brackets.</p><p>CMV: Cytomegalovirus; SD: standard deviation; MUAC: mid-upper arm circumference; WAZ: weight-for-age Z score; HAZ: height-for-age Z-score; HCZ: head circumference-for-age Z-score. P value is for comparison between three groups.</p><p>Characteristics of mothers and infants by CMV status.</p

Survival in HIV-infected infants by postnatal CMV status.

<p>Survival among infants with postnatal CMV infection (negative CMV PCR at birth, positive CMV PCR at 6 weeks of age) or without CMV co-infection (negative CMV PCR at 6 weeks of age), from time of viral testing (6 weeks of age) through 6 months of age. Adjusted hazard ratio from Cox proportional hazards model is shown, adjusting for maternal education, CD4 count and death, and infant gender, low birth weight and 6-week HIV viral load.</p

Characteristics of mothers and infants by EBV status.

<p>*All values are mean (standard deviation), unless shown otherwise.</p><p>For variables with missing data, the number of participants with available data is shown in square brackets.</p><p>EBV: Epstein Barr virus; SD: standard deviation; MUAC: mid-upper arm circumference; WAZ: weight-for-age Z score; HAZ: height-for-age Z-score; HCZ: head circumference-for-age Z-score. P value is for comparison between three groups.</p><p>Characteristics of mothers and infants by EBV status.</p

EBV viral loads and impact of EBV co-infection on survival in HIV-infected infants.

<p>A: Infants with congenital EBV had viral loads measured at birth (within 96 hours of delivery) and at 6 weeks of age. Viral loads were measured following viral nucleic acid extraction from 100 uL plasma by real-time PCR, using the EBV Artus LC kit (Qiagen) on a LightCycler 2.0 (Roche) machine, with limit of detection of 5.78 copies/uL (equivalent to 2890 copies/mL; shown as dotted line labeled LOD) and limit of quantification of 10 copies/uL (equivalent to 5000 copies/mL; shown as dotted line labeled LOQ). Infants with low positive results (above LOD but below LOQ) are shown arbitrarily as having a result halfway between the LOD and LOQ. B: Survival among infants with postnatal EBV infection (negative EBV PCR at birth, positive EBV PCR at 6 weeks of age) or without EBV co-infection (negative EBV PCR at 6 weeks of age), from time of viral testing (6 weeks of age) through 6 months of age. Adjusted hazard ratio from Cox proportional hazards model is shown, adjusting for maternal education, CD4 count and death, and infant gender, low birth weight and 6-week HIV viral load.</p

CMV viral loads in HIV-infected infants.

<p>A: CMV viral loads at birth (within 96 hours of delivery) and at 6 weeks of age in 27 infants with congenital CMV. Viral loads were measured following viral nucleic acid extraction from 100 uL plasma by real-time PCR, using the CMV Artus LC kit (Qiagen) on a LightCycler 2.0 (Roche) machine, with limit of detection of 0.65 copies/uL (equivalent to 325 copies/mL; shown as dotted line labeled LOD) and limit of quantification of 10 copies/uL (equivalent to 5000 copies/mL; shown as dotted line labeled LOQ). Infants with low positive results (above LOD but below LOQ) are shown arbitrarily as having a result halfway between the LOD and LOQ. B: Comparison of CMV viral loads at 6 weeks of age in 27 infants with congenital CMV and 108 infants with postnatal CMV. Infants with viral loads between LOD and LOQ are excluded because viral load could not be quantified, but numbers in each group with low-positive viral loads are shown.</p