Retrospective review of maternal HIV viral load electronic gatekeeping codes in South Africa.

Background: Maternal electronic gatekeeping (eGK) codes for HIV viral load (VL) testing of pregnant and breastfeeding women were developed to permit increased frequency of maternal HIV VL testing without automated gatekeeping cancellation, and to enable virological surveillance. Objectives: This study describes the national uptake of maternal eGK codes and VL suppression (VLS) rates disaggregated by age during antenatal, delivery and postnatal periods in South Africa during 2022. Method: HIV VL tests associated with C#PMTCT (used for antenatal and postnatal testing) and C#DELIVERY (used at delivery) eGK codes between 01 January and 31 December 2022, were extracted from the National Institute for Communicable Diseases Data Warehouse. Uptake of eGK codes was calculated using indicators from the District Health Information System as denominators while HIV VLS rates (< 1000 copies/mL) were calculated as monthly and annual percentages. Results: Overall, national maternal eGK code uptake was 41.8%, 24.5% and 0.12% for the antenatal, delivery and postnatal periods, respectively. The monthly antenatal eGK uptake increased from 27.5% to 58.5% while delivery uptake increased from 17.3% to 30.0%. The overall annual maternal HIV VLS rate was 86.7% antenatally and 87.2% during delivery. The monthly average HIV VLS for adolescent girls and young women (AGYW) was 76.1% antenatally and 79.6% during delivery. Conclusion: Although overall national uptake of maternal HIV VL eGK codes was low, antenatal and delivery uptake improved over time, thereby facilitating use of eGK codes for programmatic monitoring of maternal VLS rates for the first time. Quality of care among pregnant AGYW requires urgent attention.

Eliminating Vertical Transmission of HIV in South Africa: Establishing a Baseline for the Global Alliance to End AIDS in Children.

To gain a detailed overview of vertical transmission in South Africa, we describe insights from the triangulation of data sources used to monitor the national HIV program. HIV PCR results from the National Health Laboratory Service (NHLS) were analysed from the National Institute of Communicable Diseases (NICD) data warehouse to describe HIV testing coverage and positivity among children <2 years old from 2017-2021. NICD data were compared and triangulated with the District Health Information System (DHIS) and the Thembisa 4.6 model. For 2021, Thembisa estimates a third of children living with HIV go undiagnosed, with NICD and DHIS data indicating low HIV testing coverage at 6 months (49%) and 18 months (33%) of age, respectively. As immunisation coverage is reported at 84% and 66% at these time points, better integration of HIV testing services within the Expanded Programme for Immunization is likely to yield improved case findings. Thembisa projects a gradual decrease in vertical transmission to 450 cases per 100,000 live births by 2030. Unless major advances and strengthening of maternal and child health services, including HIV prevention, diagnosis, and care, can be achieved, the goal to end AIDS in children by 2030 in South Africa is unlikely to be realised.

Healing Our Own: A Randomized Trial to Assess Benefits of Peer Support.

OBJECTIVES: This study aimed to develop and evaluate a structured peer support program to address the needs of providers involved in obstetric adverse outcomes. METHODS: In this pilot randomized controlled trial, participants were providers who experienced an obstetric-related adverse outcome. Providers were randomly assigned to routine support (no further follow-up) or enhanced support (follow-up with a trained peer supporter). Participants completed surveys at baseline, 3 months, and 6 months. The primary outcome was the use of resources and the perception of their helpfulness. Secondary outcomes were the effect on the recovery stages and the duration of use of peer support. RESULTS: Fifty participants were enrolled and randomly assigned 1:1 to each group; 42 completed the program (enhanced, 23; routine, 19). The 2 groups were not significantly different with respect to event type, demographics, or baseline stage; in both groups, most participants started at the stage 6 thriving path. Most participants required less than 3 months of support: 65.2% did not need follow-up after the first contact, and 91.3% did not need follow-up after the second contact. Participants who transitioned from an early stage of recovery (stages 1-3) to the stage 6 thriving path reported that they most often sought support from peers (P = 0.02) and departmental leadership (P = 0.07). Those in the enhanced support group were significantly more likely to consider departmental leadership as one of the most helpful resources (P = 0.02). CONCLUSIONS: For supporting health care providers involved in adverse outcomes, structured peer support is a practicable intervention that can be initiated with limited resources.

Achieving maternal viral load suppression for elimination of mother-to-child transmission of HIV in South Africa.

OBJECTIVE: To describe changes in maternal viral control over time in South African women living with HIV (WLHIV) using surveillance data from the National Health Laboratory Service's Corporate Data Warehouse (NHLS CDW). DESIGN: A retrospective cohort analysis of maternal viral load during pregnancy and up to 15 months postpartum was performed amongst WLHIV (15-49 years) within the public-health sector between 2016 and 2017. METHODS: HIV and pregnancy-related test data were used to create a synthetic cohort of pregnant WLHIV from the NHLS CDW. Syphilis-screening, in association with ward type and/or postpregnancy cervical screening and/or birth HIV test and/or positive ß-hCG, was used as a proxy for pregnancy. The syphilis-screening date marked the first antenatal care visit (fANC). Fractional polynomial models described viral load evolution from fANC up to 15 months postdelivery. Piecewise linear regression models determined factors associated with viral load decline. FINDINGS: Among 178 319 pregnant WLHIV, 345 174 viral load tests were performed [median = 2 (IQR: 2-3) per woman]. At fANC, 85 545 (48%) women were antiretroviral therapy (ART) experienced; 88 877 (49.8%) were not and 3897 (2.2%) unknown. Proportions of viraemia (viral load ≥50 copies/ml) were 39 756 (53.6%) at first viral load performed during pregnancy, 14 780 (36.9%) at delivery and 24 328 (33.5%) postpartum. Maternal age at least 25 years, CD4+ cell count at least 500 cells/µl and viral load less than 50 copies/ml at baseline predicted sustained viral load suppression during follow-up. CONCLUSION: Despite high-ART coverage among pregnant women in South Africa, only 63% of WLHIV achieved viral load less than 50 copies/ml at delivery. Maternal viral load monitoring requires prioritization for maternal health and eMTCT.

Point-of-care HIV maternal viral load and early infant diagnosis testing around time of delivery at tertiary obstetric units in South Africa: a prospective study of coverage, results return and turn-around times.

INTRODUCTION: Maternal viral load monitoring (mVL) and early infant diagnosis (EID) are necessary to achieve elimination of mother-to-child transmission of HIV. Point-of-care testing can achieve better outcomes compared to centralized laboratory testing (CLT). We describe the first implementation of point-of-care (POC) mVL and EID testing around delivery at four high volume tertiary obstetric units (TOUs) in Gauteng, South Africa. METHODS: Prospective study of pregnant women living with HIV (WLHIV) and their infants. During the period 1 June 2018 to 31 March 2019, routine staff collected blood specimens from women and their infants around delivery. Specimen collection occurred throughout the week while dedicated POC operators, conducted testing during working hours on weekdays. Descriptive statistics and multivariable Poisson regression with robust error variance were used to describe outcomes and associated factors. Outcomes determined were (i) coverage of mVL and EID testing defined as a proportion of live births to WLHIV admitted at each facility (ii) results returned prior to discharge (iii) turn-around time (TAT) and iv) performance of POC testing compared to CLT. RESULTS: In total, 8147 live births to pregnant WLHIV were recorded in the implementation period. Of these, 2912 mVL and 5074 EID specimens were included in the analysis, with 131 (4.5%) mVL and 715 (14.1%) EID specimens having initial invalid/error results. Overall coverage of POC mVL and EID testing was 35.6% (range 20.9% to 60.1%) and 61.9% (range 47.0% to 88.0%) respectively. Proportions of POC tested mothers and infants with results returned prior to discharge were 74.3% (range 39.0% to 95.7%) and 73.0% (range 50.0 to 97.9%). Return of results was independently associated with TOU, after-hours specimen collection, having an initial invalid or error result and period of implementation. Overall TAT for specimens collected from mother-infant pairs where both had POC testing, during weekdays was longer for EID compared to mVL testing (median 3.3 hours vs. 2.9 hours, p-value sign test <0.001). POC results were comparable to those from laboratory testing. CONCLUSION: Accurate and timely POC mVL and EID testing around delivery was implemented with variable success across TOUs. Further scale up would need to address health system factors at facility level and high analytical error rates.

Characterizing Viral Load Burden Among HIV-Infected Women Around the Time of Delivery: Findings From Four Tertiary Obstetric Units in Gauteng, South Africa.

BACKGROUND: Elimination of mother-to-child transmission of HIV requires sustained viral load suppression during pregnancy and breastfeeding among women living with HIV (WLHIV). Antenatal antiretroviral therapy coverage is reported at >95% in South Africa, but viral load suppression rates are unknown. We describe maternal VL burden around time of delivery at 4 tertiary obstetric units (TOUs) in Gauteng Province. METHODS: Between June 2018 and March 2019, routine point-of-care (PoC) maternal HIV VL and early infant diagnosis (EID) testing were implemented at 3 TOUs in Johannesburg and 1 in Tshwane district. WLHIV and HIV-exposed neonates were eligible for HIV VL (Xpert HIV-1 VL) and EID (Xpert HIV-1 EID or m-PIMA HIV1/2 detection) testing around time of delivery, respectively. Proportions of viremic women and intrauterine (IU)-infected neonates were calculated among valid PoC results. RESULTS: Among 8147 live births to WLHIV, 2769 (34.0%) women and 4333 (53.2%) neonates had valid PoC results. Median VL at delivery was <40 copies/mL (interquartile range: 0-398). The proportion of women with a VL < 50, 50 to <1000, and ≥1000 copies/mL was 63.6%, 13.9% and 22.4%, respectively. There were 65/4333 (1.5%) IU-infected neonates. Among 1449 mother-neonate pairs with both VL and EID results, IU transmission by VL threshold was 3/946 (0.3%), 6/187 (3.2%), and 25/316 (7.9%) for VL < 50, 50 to <1000, and ≥1000 copies/mL, respectively (P < 0.001). CONCLUSIONS: Despite high antiretroviral therapy coverage, >1/3 of WLHIV had a VL ≥50 copies/mL at delivery. Among mother-neonate pairs, maternal VL ≥50 copies/mL accounted for 31/34 (91%) IU infections. Improvement in the quality of HIV care among WLHIV is essential if South Africa is to achieve elimination of mother-to-child transmission.

Non-nucleoside reverse transcriptase inhibitor levels among HIV-exposed uninfected infants at the time of HIV PCR testing - findings from a tertiary healthcare facility in Pretoria, South Africa.

INTRODUCTION: To date, very little programmatic data has been published regarding serial antiretroviral (ARV) levels in infants exposed to maternal treatment and/or infant prophylaxis during the first months of life. Such data provide the opportunity to describe the proportion of infants exposed to virologically suppressive levels of ARVs and to gauge adherence to the prevention of mother-to-child transmission of HIV (PMTCT) programme. METHODS: From August 2014 to January 2016, HIV-exposed infants born at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa were enrolled as part of an observational cohort study. Plasma samples from HIV-exposed uninfected infants were obtained at birth, 6-weeks, 10-weeks and 14-weeks of age and quantitative efavirenz (EFV) and nevirapine (NVP) drug level testing performed using liquid chromatography-mass spectrometry, irrespective of maternal ARV regimen. Descriptive analysis of EFV and NVP levels in relation to self-reported maternal and infant ARV exposure was performed. EFV levels >500 ng/mL and NVP levels >100 ng/mL were reported based on studies suggesting that trough levels above these thresholds are associated with virological suppression and PMTCT respectively. RESULTS: Among 66 infants exposed to maternal EFVin utero, 29 (44%) had virologically suppressive plasma EFV levels at birth, with a median level of 1665 ng/mL (IQR: 1094 to 3673). Among infants who were exclusively breastfed at 6-, 10- and 14 weeks, 13/48 (27%), 5/25 (25%) and 0/21 (0%) had virologically suppressive EFV levels. Among 64 infants whose mothers reported administering daily infant NVP at time of their 6-week HIV PCR test, only 45 (70%) had NVP levels above the minimum prophylactic trough level. CONCLUSIONS: During the first 10-weeks after delivery, a quarter of breastfed infants born to women on an EFV-containing treatment regimen maintained virologically suppressive EFV plasma levels. This finding highlights the importance of both careful monitoring of ARV side effects and repeat HIV PCR after the first few months of life among HIV-exposed uninfected infants. As 30% of infants had inadequate NVP plasma levels at 6-weeks of age, adherence counselling to caregivers regarding infant prophylaxis needs to be enhanced to further reduce mother-to-child transmission of HIV.

Field Evaluation of Performance of Alere and Cepheid Qualitative HIV Assays for Pediatric Point-of-Care Testing in an Academic Hospital in Soweto, South Africa.

Point-of-care (POC) technologies for HIV diagnosis in infants have the potential to overcome logistical challenges that delay treatment initiation and prevent improvements in morbidity and mortality. This study aimed to evaluate the performance of two POC technologies against the current standard-of-care (SOC) laboratory-based assay in South Africa, when operated by nurses in a hospital environment. Children <18 months of age who were treatment naive (excluding prophylaxis) and in whom an HIV PCR test was indicated were eligible for the study. To increase the rate of enrollment of HIV PCR-positive children, HIV-exposed neonates at high risk of mother-to-child transmission and children requiring confirmatory HIV testing were preferentially enrolled. The two POC technologies demonstrated excellent concordance, with 315 (97.8%) results consistent with the SOC result. The POC technologies yielded 102 positive and 220 negative tests each. The SOC assay had 101 positive, 214 negative, 4 indeterminate, 1 invalid, and 2 specimen-rejected results. To include the indeterminate results in sensitivity/specificity calculations, a sensitivity analysis was performed, which yielded a simulated sensitivity of 0.9904 (interquartile range [IQR], 0.9808 to 0.9904) and a specificity of 0.9954 (IQR, 0.9954 to 1.0). This study confirmed that both POC technologies can be successfully used outside the laboratory environment to yield precise sensitivity/specificity values for pediatric, including neonatal, HIV testing.

Validating Obstetric Emergency Checklists using Simulation: A Randomized Controlled Trial.

Background The World Health Organization's Surgical Safety Checklist has demonstrated significant reduction in surgical morbidity. The American Congress of Obstetricians and Gynecologists District II Safe Motherhood Initiative (SMI) safety bundles include eclampsia and postpartum hemorrhage (PPH) checklists. Objective To determine whether use of the SMI checklists during simulated obstetric emergencies improved completion of critical actions and to elicit feedback to facilitate checklist revision. Study Design During this randomized controlled trial, teams were assigned to use a checklist during one of two emergencies: eclampsia and PPH. Raters scored teams on critical step completion. Feedback was elicited through structured debriefing. Results In total, 30 teams completed 60 scenarios. For eclampsia, trends toward higher completion were noted for blood pressure and airway management. For PPH, trends toward higher completion rates were noted for PPH stage assessment and fundal massage. Feedback resulted in substantial checklist revision. Participants were enthusiastic about using checklists in a clinical emergency. Conclusion Despite trends toward higher rates of completion of critical tasks, teams using checklists did not approach 100% task completion. Teams were interested in the application of checklists and provided feedback necessary to substantially revise the checklists. Intensive implementation planning and training in use of the revised checklists will result in improved patient outcomes.

Sapovirus prevalence in children less than five years of age hospitalised for diarrhoeal disease in South Africa, 2009-2013.

BACKGROUND: Although sapovirus (SaV) has been detected in 2.2-12.7% of gastroenteritis cases globally, there are limited data on SaV epidemiology. OBJECTIVES: Describe the epidemiology, clinical characteristics and factors associated with SaV gastroenteritis in hospitalised children <5 years of age in South Africa. STUDY DESIGN: Between 2009 and 2013 during prospective diarrhoeal surveillance, stool specimens were collected from four sites and screened for SaVs and associated enteric pathogens using ELISA, microscopy, conventional and real-time PCR. Epidemiological and clinical data were compared in patients with or without SaV. Odds ratios were assessed by bivariate and stepwise multivariable logistic regression analysis. RESULTS: Sapoviruses were detected in 7.7% (238/3103) of children admitted to hospital and 11.4% (9/79) of deaths. Sapovirus was detected more commonly in children 19-24 months compared to<6months (aOR=2.3; p=0.018) and in males (aOR=2.0; p=0.001). Additional factors associated with SaV detection included residing with≥7 inhabitants compared to ≤3 (aOR=2.2; p=0.011) and concomitant norovirus infections (aOR=3.0; p=0.003). HIV-infected children with SaV were more likely to have bloody stools (aOR=16.8; p<0.001), low birth weight (<2.5kg; aOR=5.8; p=0.007) and live in environments without flush toilets (aOR=8.1; p=0.003) compared to HIV-uninfected children. CONCLUSIONS: Sapoviruses, which are perceived to cause mild diarrhoea, were detected in hospitalised children and diarrhoeal deaths in South Africa. Determinants increasing the odds of SaV included overcrowding and concomitant infections while HIV-infected children with SaV displayed bloody stools, low birth weight and reduced access to proper sanitation. Mitigation strategies against SaV infections include improved sanitation.

Diverse sapovirus genotypes identified in children hospitalised with gastroenteritis in selected regions of South Africa.

BACKGROUND: Sapoviruses (SaVs) are recognised as causative agents of gastroenteritis worldwide. However, data on the genetic diversity of this virus in Africa are lacking, particularly in the form of current long-term studies. OBJECTIVE: To determine the genetic diversity of SaVs in children hospitalised with gastroenteritis in South Africa (SA). STUDY DESIGN: From April 2009 to December 2013, SaVs were characterised from stool specimens from children hospitalised with gastroenteritis in four provinces of SA. RESULTS: Fourteen different SaV genotypes were identified from the 221 strains that were characterised. Genogroup (G) IV predominated overall and was detected in 24% (53/221) of specimens. The other identified genotypes included six belonging to GI (GI.1-GI.3, GI.5, GI.6, and GI.7) and seven belonging to GII (GII.1-GII.7). CONCLUSION: This study has provided the first comprehensive data on the genetic diversity of SaVs in a clinical setting in SA, contributing to the global knowledge of this virus.

Quantification and molecular characterisation of human sapoviruses in water sources impacted by highly polluted discharged wastewater in South Africa.

Sapoviruses (SaVs) were detected and quantified in 8/10 water samples collected from wastewater treatment works (WWTWs) and water sources impacted by these WWTWs in Limpopo Province, South Africa. The median SaV concentration was 2.45 × 106 copies/L and SaV genotypes I.2 and IV were characterised. This study provides new data on the high concentrations of clinically relevant SaVs in rivers and dams impacted by poor-performing WWTWs.

Novel norovirus recombinants detected in South Africa.

BACKGROUND: Noroviruses (NoV) are the leading cause of viral gastroenteritis worldwide. Recombination frequently occurs within and between NoV genotypes and recombinants have been implicated in sporadic cases, outbreaks and pandemics of NoV. There is a lack of data on NoV recombinants in Africa and therefore their presence and diversity was investigated in South Africa (SA). RESULTS: Between 2010 and 2013, eleven types of NoV recombinants were identified in SA. Amplification of the polymerase/capsid region spanning the ORF1/2 junction and phylogenetic analysis confirmed each of the recombinant types. SimPlot and maximum x2 analysis indicated that all recombinants had a breakpoint in the region of the ORF1/2 junction (P < 0.05). The majority (9/11) were intergenotype recombinants, but two intragenotype GII.4 recombinants were characterised. Three combinations represent novel recombinants namely GII.P not assigned (NA)/GII.3, GII.P4 New Orleans 2009/GII.4 NA and GII.P16/GII.17. Several widely reported recombinants were identified and included GII.P21/GII.2, GII.P21/GII.3, GII.Pe/GII.4 Sydney 2012, and GII.Pg/GII.12. Other recombinants that were identified were GII.Pg/GII.1, GII.Pe/GII.4 Osaka 2007, GII.P4 New Orleans 2009/GII.4 Sydney 2012, GII.P7/GII.6. To date these recombinant types all have a reportedly restricted geographic distribution. This is the first report of the GII.P4 New Orleans 2009/GII.4 Sydney 2012 recombinant in Africa. CONCLUSIONS: Over the past four years, remarkably diverse NoV recombinants have been circulating in SA. Pandemic strains such as the GII.Pe/GII.4 Sydney 2012 recombinant co-circulated with novel and emerging recombinant strains. Combined polymerase- and capsid-based NoV genotyping is essential to determine the true diversity and global prevalence of these viruses.

Human caliciviruses detected in HIV-seropositive children in Kenya.

The human caliciviruses (HuCVs) are important causes of gastroenteritis worldwide. Norovirus (NoV) and sapovirus (SaV) have been detected in HIV-seropositive children but the genetic diversity of HuCVs circulating in these individuals is largely unknown. In this study the prevalence and genotype diversity of HuCVs circulating in Kenyan HIV-positive children, with or without diarrhea, from the year 1999 to 2000 was investigated. The overall prevalence of HuCVs was 19% with NoV predominating at 17% (18/105) and SaV present in 5.7% (6/105) of specimens. Human CVs were detected in both symptomatic (24%) and asymptomatic (16%) children. Co-infections with other enteric viruses were detected in 21.6% of children with diarrhea but only in 4.4% of children without diarrhea. Remarkable genetic diversity was observed with 12 genotypes (7 NoV, 5 SaV) being identified in 20 HuCV-infected children. NoV genogroup II (GII) strains predominated with GII.2 and GII.4 each representing 27% of the NoV-positive strains. The GII.4 strain was most closely related to the nonepidemic GII.4 Kaiso 2003 variant. Other NoV genotypes detected were GI.3, GII.6, GII.12, GII.14, and GII.17. Five different SaV genotypes (GI.2, GI.6, GII.1, GII.2, and GII.4) were characterized from six specimens. Diarrheal symptoms were not associated with any specific HuCV genotype. Overall the HuCV genotype distribution detected in this study reflects those in other studies worldwide. The strains detected are closely related to genotypes that have circulated on several continents since the year 2000.

Application of a competitive internal amplification control for the detection of sapoviruses in wastewater.

In this study, a competitive internal amplification control (IAC) was constructed for application in the real-time reverse transcription-polymerase chain reaction detection of sapoviruses (SaVs). A SaV RNA standard was also created for quantification of the virus. The IAC was included in the screening of environmental samples for SaVs. From August 2010 to December 2011, 51 wastewater samples were collected from five provinces in South Africa. SaVs were found in 72.5 % (37/51) of samples, including four samples where detection was initially inhibited. SaV concentrations ranged from 4.24 × 10(3) to 1.31 × 10(6) copies/ml. The IAC successfully identified samples which contained inhibitors and inclusion of an IAC is necessary to ensure the prevalence of SaVs is accurately determined. SaVs are present at high concentrations in wastewater in several provinces of South Africa. This widespread occurrence indicates that SaV circulation in the South African population may be underestimated.

Ungulate and topographic control of arbuscular mycorrhizal fungal spore community composition in a temperate grassland.

Large herbivores and topo-edaphic gradients are well-documented, major determinants of grassland plant production and species composition. In contrast, there is limited information about how these factors together may influence the composition of the arbuscular mycorrhizal fungus (AMF) communities associated with plants. AMF are a common component of grassland ecosystems where they can influence plant productivity, diversity, and soil stability. In this study, AMF community composition was analyzed in paired plots located inside and outside 40-44-year-old ungulate exclosures at six grassland sites in Yellowstone National Park (YNP), USA, that varied in soil moisture and the availability of soil nitrogen (N) and phosphorus (P). AMF spore abundance, species richness, and the relative abundance of AMF species were determined from soil samples collected (1) randomly (n = 5 samples) within each of the 12 plots and (2) from beneath the dominant grass (n = 5 samples per plot) at each site. Randomly collected soil samples explored the effects of ungulates and topographic position on AMF composition at the plant community level, subsuming potential effects of ungulates on plant species composition. Dominant plant samples examined how grazers, in particular, influenced AMF communities, while controlling for host-plant identity. Grazing decreased AMF spore abundance across the landscape (examined by random sampling) but increased the AMF species richness associated with dominant plants. Grazing influenced the AMF species composition at the plant community level and at the host-plant level by shifting the relative abundances of individual AMF species. Individual AMF species responded differently to grazing and N and P availability. Our results demonstrate how soil moisture and N and P availability across the landscape interact with grazing to influence AMF species composition.