How paediatric HIV services weathered the COVID-19 storm in Tshwane District, South Africa.

Background: The coronavirus disease 2019 (COVID-19) pandemic disrupted paediatric HIV services across South Africa. Shortly before COVID-19, updated national HIV guidelines were released. Objectives: This study describes COVID-19's impact on paediatric HIV services in Tshwane District, South Africa. Method: A retrospective review of National Institute for Communicable Diseases and District Health Information System data for Tshwane District from April 2019 to March 2022. Data included: Early Infant Diagnosis (EID), HIV viral load (VL) and CD4 monitoring and HIV management among children (< 15 years) living with HIV (CLHIV). Pre-pandemic (2019/2020) and pandemic periods (2020/2021, 2021/2022) were compared. Results: Year-on-year, HIV testing improved at 10 weeks, 6 months, and 18 months, whereas birth testing decreased. HIV EID case rates were 485 (2019/2020), 410 (2020/2021) and 454 (2021/2022). HIV EID test positivity was 0.77% - 1.2%. Antiretroviral treatment initiation declined from 2019/2020 to 2020/2021, but improved in 2021/2022.Initial HIV VL and CD4 testing declined, with HIV VL testing increasing in 2021/2022, and CD4 testing further declining. HIV VL suppression rate among CLHIV ranged from 69% to 73%. Conclusion: Initially, COVID-19 resulted in reduced paediatric HIV services as children disengaged from care. Indicators eventually recovered to proximate pre-pandemic levels; however, compensatory increases did not occur. Thus, some children may not have returned to care.

Attrition Rates in HIV Viral Load Monitoring and Factors Associated With Overdue Testing Among Children Within South Africa's Antiretroviral Treatment Program: Retrospective Descriptive Analysis.

BACKGROUND: Numerous studies in South Africa have reported low HIV viral load (VL) suppression and high attrition rates within the pediatric HIV treatment program. OBJECTIVE: Using routine laboratory data, we evaluated HIV VL monitoring, including mobility and overdue VL (OVL) testing, within 5 priority districts in South Africa. METHODS: We performed a retrospective descriptive analysis of National Health Laboratory Service (NHLS) data for children and adolescents aged 1-15 years having undergone HIV VL testing between May 1, 2019, and April 30, 2020, from 152 facilities within the City of Johannesburg, City of Tshwane, eThekwini, uMgungundlovu, and Zululand. HIV VL test-level data were deduplicated to patient-level data using the NHLS CDW (Corporate Data Warehouse) probabilistic record-linking algorithm and then further manually deduplicated. An OVL was defined as no subsequent VL determined within 18 months of the last test. Variables associated with the last VL test, including age, sex, VL findings, district type, and facility type, are described. A multivariate logistic regression analysis was performed to identify variables associated with an OVL test. RESULTS: Among 21,338 children and adolescents aged 1-15 years who had an HIV VL test, 72.70% (n=15,512) had a follow-up VL test within 18 months. Furthermore, 13.33% (n=2194) of them were followed up at a different facility, of whom 3.79% (n=624) were in a different district and 1.71% (n=281) were in a different province. Among patients with a VL of ≥1000 RNA copies/mL of plasma, the median time to subsequent testing was 6 (IQR 4-10) months. The younger the age of the patient, the greater the proportion with an OVL, ranging from a peak of 52% among 1-year-olds to a trough of 21% among 14-year-olds. On multivariate analysis, 2 consecutive HIV VL findings of ≥1000 RNA copies/mL of plasma were associated with an increased adjusted odds ratio (AOR) of having an OVL (AOR 2.07, 95% CI 1.71-2.51). Conversely, patients examined at a hospital (AOR 0.86, 95% CI 0.77-0.96), those with ≥2 previous tests (AOR 0.78, 95% CI 0.70-0.86), those examined in a rural district (AOR 0.63, 95% CI 0.54-0.73), and older age groups of 5-9 years (AOR 0.56, 95% CI 0.47-0.65) and 10-14 years (AOR 0.51, 95% CI 0.44-0.59) compared to 1-4 years were associated with a significantly decreased odds of having an OVL test. CONCLUSIONS: Considerable attrition occurs within South Africa's pediatric HIV treatment program, with over one-fourth of children having an OVL test 18 months subsequent to their previous test. In particular, younger children and those with virological failure were found to be at increased risk of having an OVL test. Improved HIV VL monitoring is essential for improving outcomes within South Africa's pediatric antiretroviral treatment program.

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.

Hepatitis A virus seroprevalence among children and adolescents in a high-burden HIV setting in urban South Africa.

Hepatitis A virus (HAV) infection is one of the most important global causes of viral hepatitis. Recent reviews suggested that HAV endemicity in South Africa could shift from high to intermediate. A hospital-based HAV seroprevalence study was conducted between February 2018 and December 2019 in Pretoria, South Africa. Systematic sampling was performed on children and adolescents (1-15 years) who attended outpatient services. Participants with a known HIV status and valid HAV serology results were included. Of the 1220 participants, the median age was 7 years (IQR: 4-11), with 648 (53.11%) males and 572 (46.89%) females. Of 628 (51.48%) HIV-infected participants, most (329, 71.83%) were both immunologically and virologically controlled or had low-level viremia (74, 16.16%). Almost three-quarters (894, 73.28%) were living in formal dwellings, and just over half (688, 56.39%) had access to clean water sources inside the house. Increasing age was associated with testing HAV IgG-positive (OR 1.25; 95% CI 1.20-1.30, p < 0.001), with 19.8% of participants one year of age compared with 86.7% of participants 15 years of age. This study suggests that South Africa has an intermediate HAV seroprevalence, with rates < 90% by 10 years of age (68.6%). Increased age and informal dwellings are statistically associated with HAV seropositivity, while HIV status does not significantly influence HAV seropositivity.

Evaluating patient data quality in South Africa's National Health Laboratory Service Data Warehouse, 2017-2020: implications for monitoring child health programmes.

BACKGROUND: South Africa's National Health Laboratory Service (NHLS), the only clinical laboratory service in the country's public health sector, is an important resource for monitoring public health programmes. OBJECTIVES: We describe NHLS data quality, particularly patient demographics among infants, and the effect this has on linking multiple test results to a single patient. METHODS: Retrospective descriptive analysis of NHLS data from 1st January 2017-1st September 2020 was performed. A validated probabilistic record-linking algorithm linked multiple results to individual patients in lieu of a unique patient identifier. Paediatric HIV PCR data was used to illustrate the effect on monitoring and evaluating a public health programme. Descriptive statistics including medians, proportions and inter quartile ranges are reported, with Chi-square univariate tests for independence used to determine association between variables. RESULTS: During the period analysed, 485 300 007 tests, 98 217 642 encounters and 35 771 846 patients met criteria for analysis. Overall, 15.80% (n = 15 515 380) of all encounters had a registered national identity (ID) number, 2.11% (n = 2 069 785) were registered without a given name, 63.15% (n = 62 020 107) were registered to women and 32.89% (n = 32 304 329) of all folder numbers were listed as either the patient's date of birth or unknown. For infants tested at < 7 days of age (n = 2 565 329), 0.099% (n = 2 534) had an associated ID number and 48.87% (n = 1 253 620) were registered without a given name. Encounters with a given name were linked to a subsequent encounter 40.78% (n = 14 180 409 of 34 775 617) of the time, significantly more often than the 21.85% (n = 217 660 of 996 229) of encounters registered with a baby-derivative name (p-value < 0.001). CONCLUSION: Unavailability and poor capturing of patient demographics, especially among infants and children, affects the ability to accurately monitor routine health programmes. A unique national patient identifier, other than the national ID number, is urgently required and must be available at birth if South Africa is to accurately monitor programmes such as the Prevention of Mother-to-Child Transmission of HIV.

Indeterminate HIV PCR results within South Africa's early infant diagnosis programme, 2010-2019.

OBJECTIVES: We describe the extent of, and variables associated with, indeterminate HIV-PCR results and final HIV status within South Africa's early infant diagnosis (EID) programme between 2010 and 2019. METHODS: Retrospective analysis of routine paediatric HIV-PCR laboratory data from South Africa's National Health Laboratory Service Data Warehouse between 2010 and 2019. Final HIV status was determined by linking patient results (including HIV-PCR, HIV viral load, HIV serology and CD4 counts) using a probabilistic matching algorithm. Multivariate logistic regression was performed to determine variables associated with final HIV status among patients with an indeterminate HIV-PCR result. RESULTS: Among 4 429 742 specimens registered for HIV-PCR testing from 3 816 166 patients, 113 209 (2.97%) tested positive and 22 899 (0.6%) tested indeterminate. As a proportion of HIV-detected results, 15.7% (23 896/151 832) of total and 31.5% (4900/15 566), 18.8% (11 400/60 794) and 10.1% (7596/75 472) among patients aged <7 days, 7 days-3 months and ≥3 months, respectively, were reported as indeterminate. Overall, 39.7% of patients with an indeterminate result had a linked HIV test to determine HIV status, of which 53.6% were positive with a median time to repeat testing of 30 days (interquartile range 15-69). Among patients who tested indeterminate, variables associated with a significantly higher odds of having a positive HIV status included testing indeterminate at birth (adjusted odds ratio (AOR) 0.63 (0.48-0.83) and 0.52 (0.39-0.69) for testing indeterminate at 7 days-3 months and ≥3 months respectively compared with birth), within a hospital (AOR 2.45 (1.99-3.03)), and in districts with an intra-uterine transmission rate ≥1.1% (AOR 3.14 (1.84-5.35)) (p < 0.001). DISCUSSION: Indeterminate HIV-PCR results represent a considerable burden of missed diagnostic opportunities, diagnostic dilemmas and delays in making a definite diagnosis among HIV-infected infants within South Africa's EID programme. Alternative EID verification practices are urgently needed.

Minding the gap-Providing quality transplant care for South African children with acute liver failure.

Pediatric ALF is rare but life-threatening and may require urgent transplantation. In low and middle-income countries, access to transplantation is limited, deceased organ donation rates are low, and data on outcomes scarce. The Wits Donald Gordon Medical Centre, in Johannesburg, is one of only two centers in South Africa that perform pediatric liver transplant. We describe the etiology, clinical presentation, and outcomes of children undergoing liver transplant for ALF at our center over the past 14 years. We performed a retrospective chart review of all children undergoing liver transplantation for ALF from November 2005 to September 2019. Recipient data included demographics, clinical and biochemical characteristics pretransplant, post-operative complications, and survival. We conducted descriptive data analysis and used the Kaplan-Meier method for survival analysis. We performed 182 primary pediatric liver transplants. Of these, 27 (15%) were for ALF, mostly from acute hepatitis A infection (11/27;41%). Just over half of the grafts were from living donors (15/27;56%), and five grafts (5/27;19%) were ABO-incompatible. The most frequent post-transplant complications were biliary leaks (9/27;33%). There were two cases of hepatic artery thrombosis (2/27;7%), one of whom required re-transplantation. Unadjusted patient and graft survival at one and 3 years were the same, at 81% (95% CI 61%-92%) and 78% (95% CI 57%-89%), respectively. At WDGMC, our outcomes for children who undergo liver transplantation for ALF are excellent. We found workable solutions that effectively addressed our pervasive organ shortages without compromising patient outcomes.

The geographic distribution of priority population groups for the elimination of mother-to-child transmission of HIV in South Africa.

BACKGROUND: Women of reproductive age living with HIV (WRLHIV), HIV-positive pregnant women, adolescent girls and young women (AGYW) are key populations for eliminating mother-to-child of HIV (eMTCT) in South Africa. We describe the geographical distribution of WRLHIV, their pregnant counterparts and AGYW for risk-adjusted allocation of eMTCT interventions. METHODS: For the year 2018, we triangulated data from the Thembisa Model with five routine HIV-related and demographic data sources to determine the distribution of WRLHIV (15-49 years) and AGYW (15-24 years) nationally and by province. Data analysed included total population estimates, number of live-births, live-births to HIV-positive women, age-specific HIV prevalence rates, intrauterine (IU)-transmission rates and IU-case rates/100 000 live-births. IU-transmission rates and IU-case rates were calculated from de-duplicated routine HIV test-data for neonates (aged <7days). Data de-duplication was achieved by a patient-linking algorithm that uses probabilistic matching of demographics (name, surname, date of birth), supplemented by manual matching to account for spelling errors. RESULTS: There were 58 million people in South Africa in 2018. Females (all ages) constituted 51% of the population. Women of reproductive age constituted 27% and AGYW constituted 8% of the total population. WRLHIV, AGYW living with HIV and HIV-positive pregnant women accounted for 7%, 0.8% and 0.4% of the total population respectively. Gauteng was the most populous province followed by KwaZulu-Natal, with Western Cape and Eastern Cape in third and fourth positions. The distribution of WRLHIV and AGYW followed a similar trend. However, Mpumalanga and Limpopo provinces had higher proportions of WRLHIV and AGYW living with HIV ahead of Western Cape. KwaZulu-Natal had the highest number of live-births to HIV-positive women. The national IU-transmission rate of <1% translated into 241 cases/100 000. While provincial IU-case rates were fairly similar at 179-325, districts IU-case rates varied, ranging from 87-415 cases/100 000 live-births. CONCLUSION: Findings suggest that the need for eMTCT interventions is greatest in Gauteng, KwaZulu-Natal, Western Cape and Eastern Cape. Limpopo and Mpumalanga provinces may require more HIV prevention and family planning services because of high fertility rates, high number of WRLHIV and AGYW living with HIV. eMTCT will require robust viral load monitoring among WRLHIV, pregnant and breastfeeding women. The national laboratory database can provide this service near-real time.

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.

Evolving complexities of infant HIV diagnosis within Prevention of Mother-to-Child Transmission programs.

Early diagnosis of HIV infection among infants and children is critical as prompt initiation of antiretroviral therapy prevents morbidity and death. Yet despite advances in the accuracy and availability of infant HIV diagnostic testing, there are increasing challenges with making an early definitive diagnosis. These challenges relate primarily to advances in prevention of mother-to-child transmission (PMTCT) of HIV. Although PMTCT programs have proven to be highly effective in reducing infant HIV infection, infants who are HIV-infected may achieve virological suppression and loss of detectability of HIV nucleic acid prior to diagnosis because of antiretroviral drug exposure. Hence, false-negative and indeterminate HIV polymerase chain reaction (PCR) results can occur, especially among high-risk infants given multi-drug prophylactic regimens. However, the infant HIV diagnostic landscape is also complicated by the inevitable decline in the positive predictive value of early infant diagnosis (EID) assays. As PMTCT programs successfully reduce the mother-to-child transmission rate, the proportion of false-positive EID results will increase. Consequently, false-negative and false-positive HIV PCR results are increasingly likely despite highly accurate diagnostic assays. The problem is compounded by the seemingly intractable prevalence of maternal HIV within some settings, resulting in a considerable absolute burden of HIV-infected infants despite a low mother-to-child transmission rate.

Hepatitis A virus seroprevalence in South Africa - Estimates using routine laboratory data, 2005-2015.

INTRODUCTION: South Africa is considered highly endemic for hepatitis A virus (HAV) although few seroprevalence studies have been conducted over the past two decades. The World Health Organization recommends integrating HAV vaccination into national childhood immunization schedules where there is transition from high to intermediate endemicity. As a means of gauging age-specific rates of infection, we report HAV seroprevalence rates among specimens tested for HAV serology within South Africa's public health sector from 2005-2015. MATERIALS AND METHODS: Hepatitis A serology results (Anti-HAV IgM, IgG and total antibody) from 2005-2015 were extracted from South Africa's National Health Laboratory Service's Corporate Data Warehouse (NHLS CDW), the central data repository of all laboratory test-sets within the public health sector. Results were extracted according to test-set, result, date of testing, health facility, name, surname, age, and sex. Anti-HAV IgG results were merged with total antibody results to reflect anti-HAV seroprevalence. Testing volume, positivity rates and age-specific anti-HAV seroprevalence rates by year and geographic distribution are described. RESULTS AND DISCUSSION: A total of 501 083 HAV IgM results were retrieved, of which 16 423 (3.3%) were positive, 484 259 (96.6%) negative and 401 (0.1%) equivocal; and 34 710 HAV total antibody/IgG tests of which 30 675 (88.4%) were positive, 4 020 (11.6%) negative and 15 equivocal. Whereas IgM positivity was highest among the 1-4 year age group (33.5%) and lowest among patients >45 years (<0.5%), total antibody positivity ranged from its lowest level of 52.7% in the 1-4 year age group increasing to levels of >90% only after 25 years of age. CONCLUSION: Anti-HAV total antibody testing within the South African public health sector demonstrates seroprevalence rates reach levels >90% only in adulthood, suggesting South Africa could be in transition from high to intermediate endemicity. Prospective studies with geographically representative sampling are required to confirm these findings and evaluate provincial and urban/rural heterogeneity.

Early infant diagnosis HIV-1 PCR cycle-threshold predicts infant viral load at birth.

BACKGROUND: HIV-1 viral load (VL) has been found to be an independent predictor for disease progression among untreated HIV-infected children. However, qualitative polymerase chain reaction (PCR) assays are routinely used for early infant diagnosis (EID). OBJECTIVES: To predict HIV-1 VL at birth using qualitative EID real-time PCR cycle-threshold (Ct) values. STUDY DESIGN: This study was a secondary analysis of results from a cohort of intrauterine HIV-1 infected neonates. Neonates were enrolled at Rahima Moosa Mother & Child Hospital in Johannesburg, South Africa between June 2014 and November 2017. Laboratory EID HIV-1 PCR testing was performed at birth using COBAS AmpliPrep/COBAS TaqMan HIV-1 Qualitative Test v2.0 (EID CAP/CTM). Some infants had simultaneous EID point-of-care (POC) testing using Xpert HIV-1 Qualitative assay (EID Xpert). Neonates with a confirmed HIV-1 detected EID result and plasma HIV-1 RNA VL test were included in this analysis. Bland-Altman analysis was used to determine extent of agreement between Ct values of both EID assays. Multivariable linear regression models adjusting for time between EID and VL testing were used to describe the association between EID Ct values and VL and to predict VL at given EID Ct values. RESULTS: Among 107 HIV-1 infected neonates included in the study, 59 had POC EID testing. Median VL was 28 400 copies per millilitre (cps/ml) (IQR: 1 918-218 358) - two neonates had VL < 100 cps/ml prior to antiretroviral therapy initiation. There was good correlation between Ct values of both EID assays (Spearman correlation coefficient 0.9, 95% CI: 0.8-1.0). The limits of agreement between EID CAP/CTM and Xpert Ct values were 4-11 cycles. For every one cycle increase in Ct value there was 0.3 log10 RNA decrease (95% CI: -0.3 to -0.2) for both EID assays. An EID CAP/CTM Ct value ≤ 23 and an EID Xpert Ct value ≤ 31 predicted a VL of > 5.0 log10 cps/ml in 82.2% (95% CI: 73.9-88.3) and 84.7% (95% CI: 73.7-91.8) of cases, respectively. CONCLUSION: EID Ct values at birth predict VL and accurately identify infants with VL > 5.0 log10 cps/ml.

Living donor liver transplant from an HIV-positive mother to her HIV-negative child: opening up new therapeutic options.

OBJECTIVE: Transplant a liver from an HIV-positive mother to her HIV-negative child to save the child's life. DESIGN: A unique case of living donor liver transplantation from an HIV-positive mother to her HIV-negative child in South Africa. Two aspects of this case are ground-breaking. First, it involves living donation by someone who is HIV-positive and second it involves controlled transplant of an organ from an HIV-positive donor into an HIV-negative recipient, with the potential to prevent infection in the recipient. METHODS: Standard surgical procedure for living donor liver transplantation at our centre was followed. HIV-prophylaxis was administered preoperatively. Extensive, ultrasensitive HIV testing, over and above standard diagnostic assays, was undertaken to investigate recipient serostatus and is ongoing. RESULTS: Both mother and child are well, over 1 year posttransplantation. HIV seroconversion in our recipient was detected with serological testing at day 43 posttransplant. However, a decline in HIV antibody titres approaching undetectable levels is now being observed. No plasma, or cell-associated HIV-1 DNA has been detected in the recipient at any time-point since transplant. CONCLUSION: This case potentially opens up a new living liver donor pool which might have clinical relevance in countries where there is a high burden of HIV and a limited number of deceased donor organs or limited access to transplantation. However, our recipient's HIV status is equivocal at present and additional investigation regarding seroconversion events in this unique profile is ongoing.

Differentiating clearly positive from indeterminate results: A review of irreproducible HIV-1 PCR positive samples from South Africa's Early Infant Diagnosis Program, 2010-2015.

We describe the extent of and variables associated with irreproducible HIV-1 PCR positive results within South Africa's Early Infant Diagnosis (EID) program from 2010 to 2015 and propose criteria for differentiating indeterminate from clearly positive results using the COBAS® AmpliPrep/COBAS® TaqMan HIV-1 Qualitative Test version 2.0 (CAP/CTM Qual v2.0). Fourteen percent of specimens with an instrument-positive result that were repeat-tested yielded a negative result for which cycle threshold (Ct) proved to be the only predictive variable. A Ct <33.0 was found to be the most accurate threshold value for differentiating clearly positive from irreproducible cases, correctly predicting 96.8% of results. Among 70 patients with an irreproducible positive result linked to a follow up HIV-1 PCR test, 67 (95.7%) were negative and 3 (4.3%) were instrument-positive. Criteria differentiating clearly positive from indeterminate results need to be retained within EID services and infants with indeterminate results closely monitored and final HIV status determined.

Introduction of Routine HIV Birth Testing in the South African National Consolidated Guidelines.

BACKGROUND: South Africa represents the first high-burden setting to introduce routine virologic testing at birth within its early infant diagnosis program, implemented in June 2015. National HIV birth testing coverage, intrauterine transmission rates and case rates for the first year since introduction of universal birth testing are reported. METHODS: HIV polymerase chain reaction (PCR) test data from June 2015 to May 2016 were extracted from the National Health Laboratory Service's central data repository by year, month, age, result and geographic location. Birth testing was defined as all HIV PCR tests performed at <7 days of life; coverage as the proportion of all HIV-exposed neonates born who were tested at birth; estimated intrauterine transmission rate as the percentage of HIV PCR positive tests in HIV-exposed neonates tested and case rates as the number of HIV PCR positive tests per 100,000 total live births. RESULTS: Between June 2015 and May 2016, the South African national monthly birth testing coverage increased from 39% (8636 tests) to 93% (20,479 tests). During this period, the number of positive tests at birth increased from 114 to 234 per month, equating to a national intrauterine transmission rate of 1.1% and a birth case rate of 247 per 100,000 live births. CONCLUSIONS: Universal birth testing for all HIV-exposed neonates is rapidly being achieved in South Africa, facilitating earlier detection of intrauterine infected neonates. However, the successful linkage into care of HIV-infected neonates and their treatment outcomes remain to be assessed.

Missed diagnostic opportunities within South Africa's early infant diagnosis program, 2010-2015.

BACKGROUND: Samples submitted for HIV PCR testing that fail to yield a positive or negative result represent missed diagnostic opportunities. We describe HIV PCR test rejections and indeterminate results, and the associated delay in diagnosis, within South Africa's early infant diagnosis (EID) program from 2010 to 2015. METHODS: HIV PCR test data from January 2010 to December 2015 were extracted from the National Health Laboratory Service Corporate Data Warehouse, a central data repository of all registered test-sets within the public health sector in South Africa, by laboratory number, result, date, facility, and testing laboratory. Samples that failed to yield either a positive or negative result were categorized according to the rejection code on the laboratory information system, and descriptive analysis performed using Microsoft Excel. Delay in diagnosis was calculated for patients who had a missed diagnostic opportunity registered between January 2013 and December 2015 by means of a patient linking-algorithm employing demographic details. RESULTS: Between 2010 and 2015, 2 178 582 samples were registered for HIV PCR testing of which 6.2% (n = 134 339) failed to yield either a positive or negative result, decreasing proportionally from 7.0% (n = 20 556) in 2010 to 4.4% (n = 21 388) in 2015 (p<0.001). Amongst 76 972 coded missed diagnostic opportunities, 49 585 (64.4%) were a result of pre-analytical error and 27 387 (35.6%) analytical error. Amongst 49 694 patients searched for follow-up results, 16 895 (34.0%) had at least one subsequent HIV PCR test registered after a median of 29 days (IQR: 13-57), of which 8.4% tested positive compared with 3.6% of all samples submitted for the same period. CONCLUSIONS: Routine laboratory data provides the opportunity for near real-time surveillance and quality improvement within the EID program. Delay in diagnosis and wastage of resources associated with missed diagnostic opportunities must be addressed and infants actively followed-up as South Africa works towards elimination of mother-to-child transmission.

Nosocomial outbreak of hepatitis B virus infection in a pediatric hematology and oncology unit in South Africa: Epidemiological investigation and measures to prevent further transmission.

BACKGROUND: Hospital-acquired hepatitis B virus (HBV) infection has been well described and continues to occur worldwide. Recent nosocomial outbreaks have been linked to unsafe injection practices, use of multi-dose vials, and poor staff compliance with standard precautions. This report describes a nosocomial outbreak that occurred in a pediatric hematology and oncology unit of a large academic hospital, the epidemiological investigation of the outbreak, and preventive measures implemented to limit further in-hospital transmission. METHODS: Outbreak investigation including contact tracing and HBV screening were initially carried out on all patients seen by the unit during the same period as the first three cases. Routine screening for the entire patient population of the unit was initiated in February 2013 when it was realized that numerous patients may have been exposed. RESULTS: Forty-nine cases of HBV infection were confirmed in 408 patients tested between July 2011 and October 2013. Phylogenetic analysis of the HBV preC/C gene nucleotide sequences revealed that all tested outbreak strains clustered together. Most (67%) patients were HBeAg positive. The cause of transmission could not be established. Preventive measures targeted three proposed routes. HBV screening and vaccination protocols were started in the unit. CONCLUSIONS: The high number of HBeAg positive patients, together with suspected lapses in infection prevention and control measures, are believed to have played a major role in the transmission. Measures implemented to prevent further in-hospital transmission were successful. On-going HBV screening and vaccination programs in pediatric hematology and oncology units should become standard of care.

Recommendations for the medical evaluation of children prior to adoption in South Africa.

The current legislative framework in South Africa (SA) supports adoption as the preferred form of care for children with inadequate or no parental or family support. There are an estimated 3.8 million orphans in SA, with approximately 1.5 - 2 million children considered adoptable. As a means of improving services, newly drafted adoption guidelines from the National Department of Social Development will in future require both non-profit and private sector adoption agencies to obtain a medical report on a child prior to placement. However, no local guidelines specify what an appropriate medical examination entails or how it should be reported. For the purposes of proposing and developing such guidelines, an open forum was convened at the Institute of Pathology, University of Pretoria, in March 2013. These 'Recommendations for the medical evaluation of children prior to adoption in South Africa' emanate from this meeting.

Loss of detectability and indeterminate results: Challenges facing HIV infant diagnosis in South Africa's expanding ART programme.

BACKGROUND: Early infant diagnosis with rapid access to treatment has been found to reduce HIV-associated infant mortality and morbidity considerably. In line with international standards, current South African guidelines advocate routine HIV-1 polymerase chain reaction (PCR) testing at 6 weeks of age for all HIV-exposed infants and 'fast-track' entry into the HIV treatment programme for those who test positive. Importantly, testing occurs within the context of increasing efforts at prevention of mother-to-child transmission (PMTCT) by means of maternal and infant antiretroviral therapy (ART). In addition, infants already initiated on combination ART (cART) may be retested with PCR assays for 'confirmatory' purposes, including assessment prior to adoption. The potential for cART to compromise the sensitivity of HIV-1 PCR assays has been described, although there are limited and conflicting data regarding the effect of PMTCT regimens on HIV-1 PCR diagnostic sensitivity. METHODS: We describe a case series of three infants with different ART exposures in whom HIV diagnosis, confirmation or the result of retesting for adoption purposes were uncertain. RESULTS: These cases demonstrate that ART can be associated with a loss of detectability of HIV, leading to 'false-negative' HIV-1 PCR results in infants on cART. Furthermore, current PMTCT practices may lead to repeatedly indeterminate results with a subsequent delay in initiation of cART. CONCLUSION: The sensitivity of HIV-1 PCR assays needs to be re-evaluated within the context of different ART exposures, and diagnostic algorithms should be reviewed accordingly.

Community care workers, poor referral networks and consumption of personal resources in rural South Africa.

Although home-based care (HBC) programs are widely implemented throughout Africa, their success depends on the existence of an enabling environment, including a referral system and supply of essential commodities. The objective of this study was to explore the current state of client referral patterns and practices by community care workers (CCWs), in an evolving environment of one rural South African sub-district. Using a participant triangulation approach, in-depth qualitative interviews were conducted with 17 CCWs, 32 HBC clients and 32 primary caregivers (PCGs). An open-ended interview guide was used for data collection. Participants were selected from comprehensive lists of CCWs and their clients, using a diversified criterion-based sampling method. Three independent researchers coded three sets of data - CCWs, Clients and PCGs, for referral patterns and practices of CCWs. Referrals from clinics and hospitals to HBC occurred infrequently, as only eight (25%) of the 32 clients interviewed were formally referred. Community care workers showed high levels of commitment and personal investment in supporting their clients to use the formal health care system. They went to the extent of using their own personal resources. Seven CCWs used their own money to ensure client access to clinics, and eight gave their own food to ensure treatment adherence. Community care workers are essential in linking clients to clinics and hospitals and to promote the appropriate use of medical services, although this effort frequently necessitated consumption of their own personal resources. Therefore, risk protection strategies are urgently needed so as to ensure sustainability of the current work performed by HBC organizations and the CCW volunteers.