Changes in Prevalence and Seasonality of Pathogens Identified in Acute Respiratory Tract Infections in Hospitalised Individuals in Rural and Urban Settings in South Africa; 2018-2022.

Severe acute respiratory tract infections (SARIs) has been well described in South Africa with seasonal patterns described for influenza and respiratory syncytial virus (RSV), while others occur year-round (rhinovirus and adenovirus). This prospective syndromic hospital-based surveillance study describes the prevalence and impact of public interventions on the seasonality of other respiratory pathogens during the coronavirus disease-19 (COVID-19) pandemic. This occurred from August 2018 to April 2022, with 2595 patients who met the SARS case definition and 442 controls, from three sentinel urban and rural hospital sites in South Africa. Naso/oro-pharyngeal (NP/OP) swabs were tested using the FastTrack Diagnostics® Respiratory pathogens 33 (RUO) kit. Descriptive statistics, odds ratios, and univariate/multivariate analyses were used. Rhinovirus (14.80%, 228/1540) and Streptococcus pneumoniae (28.50%, 439/1540) were most frequently detected in NP/OP swabs and in children <1 years old (35%, 648/1876). Among others, pathogens associated with SARI cases causing disease were influenza A&B, HRV, RSV, hCoV 229e, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae. Pre-COVID-19, seasonal trends of these pathogens correlated with previous years, with RSV and influenza A seasons only resuming after the national lockdown (2021). It is evident that stringent lockdown conditions have severe impacts on the prevalence of respiratory tract infections.

West Nile Virus, an Underdiagnosed Cause of Acute Fever of Unknown Origin and Neurological Disease among Hospitalized Patients in South Africa.

West Nile virus (WNV), a mosquito-borne flavivirus, is endemic to South Africa. However, its contribution to acute febrile and neurological disease in hospitalized patients in South Africa is unknown. This study examined two patient cohorts for WNV using molecular testing and IgM serology with confirmation of serological results by viral neutralization tests (VNT) to address this knowledge gap. Univariate analysis was performed using collected demographic and clinical information to identify risk factors. In the first cohort, 219 cerebrospinal fluid (CSF) specimens from patients with acute neurological disease in Gauteng hospitals collected in January to June 2017 were tested for WNV. The study identified WNV in 8/219 (3.65%, 95.00% CI (1.59-7.07)) patients with unsolved neurological infections. The second cohort, from 2019 to 2021, included 441 patients enrolled between January and June with acute febrile or neurological disease from urban and rural sites in Gauteng and Mpumalanga provinces. West Nile virus was diagnosed in 40/441 (9.07%, 95.00% CI (6.73-12.12)) of patients, of which 29/40 (72.50%, 95.00% CI (56.11-85.40)) had neurological signs, including headaches, encephalitis, meningitis, and acute flaccid paralysis (AFP). Notably, most of the cases were identified in children although adolescents and senior adults had a significantly higher risk of testing WNV positive. This suggests a previously underestimated disease burden and that WNV might be underrecognized as a cause of febrile and neurological diseases in hospitalized patients in South Africa, especially in children. This emphasizes the importance of further research and awareness regarding arboviruses of public health concern.

Epidemiology and aetiology of moderate to severe diarrhoea in hospitalised patients ≥5 years old living with HIV in South Africa, 2018-2021: A case-control analysis.

Diarrhoea is a recognised complication of HIV-infection, yet there are limited local aetiological data in this high-risk group. These data are important for informing public health interventions and updating diagnostic and treatment guidelines. This study aimed to determine the pathogenic causes of diarrhoeal admissions in people living with HIV (PLHIV) compared to hospital controls between July 2018 and November 2021. Admitted diarrhoeal cases (n = 243) and non-diarrhoeal hospital controls (n = 101) ≥5 years of age were enrolled at Kalafong, Mapulaneng and Matikwana hospitals. Stool specimens/rectal swabs were collected and pathogen screening was performed on multiple platforms. Differences in pathogen detections between cases and controls, stratified by HIV status, were investigated. The majority (n = 164, 67.5%) of enrolled diarrhoeal cases with known HIV status were HIV-infected. Pathogens could be detected in 66.3% (n = 228) of specimens, with significantly higher detection in cases compared to controls (72.8% versus 50.5%, p<0.001). Amongst PLHIV, prevalence of Cystoisospora spp. was significantly higher in cases than controls (17.7% versus 0.0%, p = 0.028), while Schistosoma was detected more often in controls than cases (17.4% versus 2.4%, p = 0.009). Amongst the HIV-uninfected participants, prevalence of Shigella spp., Salmonella spp. and Helicobacter pylori was significantly higher in cases compared to controls (36.7% versus 12.0%, p = 0.002; 11.4% versus 0.0%, p = 0.012; 10.1% versus 0.0%, p = 0.023). Diarrhoeal aetiology differed by HIV status, with Shigella spp. (36.7%) and Salmonella spp. (11.4%) having the highest prevalence amongst HIV-uninfected cases and Shigella spp. (18.3%), Cystoisospora (17.7%), and Cryptosporidium spp. (15.9%) having the highest prevalence in cases amongst PLHIV. These differences should be considered for the development of diagnostic and treatment guidelines.

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.

Healthcare without borders: A cross-sectional study of immigrant and nonimmigrant children admitted to a large public sector hospital in the Gauteng Province of South Africa.

BACKGROUND: Human migration is a worldwide phenomenon that receives considerable attention from the media and healthcare authorities alike. A significant proportion of children seen at public sector health facilities in South Africa (SA) are immigrants, and gaps have previously been noted in their healthcare provision. The objective of the study was to describe the characteristics and differences between the immigrant and SA children admitted to Kalafong Provincial Tertiary Hospital (KPTH), a large public sector hospital in the urban Gauteng Province of SA. METHODS AND FINDINGS: A cross-sectional study was conducted over a 4-month period during 2016 to 2017. Information was obtained through a structured questionnaire and health record review. The enrolled study participants included 508 children divided into 2 groups, namely 271 general paediatric patients and 237 neonates. Twenty-five percent of children in the neonatal group and 22.5% in the general paediatric group were immigrants. The parents/caregivers of the immigrant group had a lower educational level (p < 0.0001 neonatal and paediatric), lower income (neonatal p < 0.001; paediatric p = 0.024), difficulty communicating in English (p < 0.001 neonatal and paediatric), and were more likely residing in informal settlements (neonatal p = 0.001; paediatric p = 0.007) compared to the SA group. In the neonatal group, there was no difference in the number of antenatal care (ANC) visits, type of delivery, gestational age, and birth weight. In the general paediatric group, there was no difference in immunisation and vitamin A supplementation coverage, but when comparing growth, the immigrant group had more malnutrition compared to the SA group (p = 0.029 for wasting). There was no difference in the prevalence of maternal human immunodeficiency virus (HIV) infection, with equally good prevention of mother-to-child transmission (PMTCT) coverage. There was also no difference in reported difficulties by immigrants in terms of access to healthcare (neonatal p = 0.379; paediatric p = 0.246), although a large proportion (10%) of the neonates of immigrant mothers were born outside a medical facility. CONCLUSIONS: Although there were health-related differences between immigrant and SA children accessing in-hospital care, these were fewer than expected. Differences were found in parental educational level and socioeconomic factors, but these did not significantly affect ANC attendance, delivery outcomes, immunisation coverage, HIV prevalence, or PMTCT coverage. The immigrant population should be viewed as a high-risk group, with potential problems including suboptimal child growth. Health workers should advocate for all children in the community they are serving and promote tolerance, respect, and equal healthcare access.

Virus Etiology, Diversity and Clinical Characteristics in South African Children Hospitalised with Gastroenteritis.

BACKGROUND: Viral gastroenteritis remains a major cause of hospitalisation in young children. This study aimed to determine the distribution and diversity of enteric viruses in children ≤5 years, hospitalised with gastroenteritis at Kalafong Provincial Tertiary Hospital, Pretoria, South Africa, between July 2016 and December 2017. METHODS: Stool specimens (n = 205) were screened for norovirus GI and GII, rotavirus, sapovirus, astrovirus and adenovirus by multiplex RT-PCR. HIV exposure and FUT2 secretor status were evaluated. Secretor status was determined by FUT2 genotyping. RESULTS: At least one gastroenteritis virus was detected in 47% (96/205) of children. Rotavirus predominated (46/205), followed by norovirus (32/205), adenovirus (15/205), sapovirus (9/205) and astrovirus (3/205). Norovirus genotypes GI.3, GII.2, GII.3, GII.4, GII.7, GII.12, GII.21, and rotavirus strains G1P[8], G2P[4], G2P[6], G3P[4], G3P[8], G8P[4], G8P[6], G9P[6], G9P[8] and sapovirus genotypes GI.1, GI.2, GII.1, GII.4, GII.8 were detected; norovirus GII.4[P31] and rotavirus G3P[4] predominated. Asymptomatic norovirus infection (GI.3, GI.7, GII.4, GII.6, GII.13) was detected in 22% of 46 six-week follow up stools. HIV exposure (30%) was not associated with more frequent or severe viral gastroenteritis hospitalisations compared to unexposed children. Rotavirus preferentially infected secretor children (p = 0.143) and norovirus infected 78% secretors and 22% non-secretors. CONCLUSION: Rotavirus was still the leading cause of gastroenteritis hospitalisations, but norovirus caused more severe symptoms.

Epidemiologic Shift in Candidemia Driven by Candida auris, South Africa, 2016-20171.

Candida auris is an invasive healthcare-associated fungal pathogen. Cases of candidemia, defined as illness in patients with Candida cultured from blood, were detected through national laboratory-based surveillance in South Africa during 2016-2017. We identified viable isolates by using mass spectrometry and sequencing. Among 6,669 cases (5,876 with species identification) from 269 hospitals, 794 (14%) were caused by C. auris. The incidence risk for all candidemia at 133 hospitals was 83.8 (95% CI 81.2-86.4) cases/100,000 admissions. Prior systemic antifungal drug therapy was associated with a 40% increased adjusted odds of C. auris fungemia compared with bloodstream infection caused by other Candida species (adjusted odds ratio 1.4 [95% CI 0.8-2.3]). The crude in-hospital case-fatality ratio did not differ between Candida species and was 45% for C. auris candidemia, compared with 43% for non-C. auris candidemia. C. auris has caused a major epidemiologic shift in candidemia in South Africa.

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.

An Early Infant HIV Risk Score for Targeted HIV Testing at Birth.

BACKGROUND: Early HIV testing is needed for treatment success in young infants, but universal testing is expensive. In this study, we examined the feasibility of early infant HIV risk scores for targeted polymerase chain reaction (PCR) testing and early HIV diagnosis. METHODS: A cross-sectional cohort of newborns exposed to HIV was enrolled and PCR tested within 72 hours. We quantified associations between HIV infection and clinical and laboratory maternal-infant parameters by logistic regression models and determined sensitivity and specificity for derived risk scores. RESULTS: From August 2014 to December 2016, 1759 participants were enrolled. Mothers without antenatal care (5.7% [97 of 1688]) were more likely to deliver newborns who are PCR-positive (P = .0005). A total of 1 in 5 mothers (217 of 990; 21.9%) had HIV viral load (VL) >1000 copies per µL. A total of 432 of 1655 (26.1%) infants were preterm. Low birth weight was documented in 398 of 1598 (24.55%) and 13 of 31 (40.63%) newborns who are PCR-negative and -positive, respectively (P = .0329). A total of 204 of 1689 (12.08%) were growth restricted or small for gestational age, and 6 of 37 (16.22%) were PCR-positive. Symptomatic newborns frequently tested positive (P = .0042). The HIV PCR positivity rate was 2.2% (37 of 1703). Two-risk (combined 3-drug antiretroviral therapy [cART] duration, VL), 3-risk (cART duration, VL, symptomatic newborn), and 4-risk (cART duration, VL, symptomatic, small for gestational age newborn) models for HIV acquisition had predictive probability of 0.28, 0.498, and 0.57, respectively; this could guide targeted birth testing. However, using the 3- and 4-risk scores (probability 0.02 and 0.04), 20% and 24% will be missed compared with universal testing. CONCLUSIONS: Targeted newborn testing requires access to maternal VL. Even if risk models include parameters such as maternal cART history, birth weight, weeks' gestation, and symptoms, 1 in 5 newborns who are infected will not be targeted. At present, we support universal PCR testing at birth within the South African prevention of mother-to-child transmission of HIV context.

Federation of Infectious Diseases Societies of Southern Africa guideline: Recommendations for the detection, management and prevention of healthcare-associated Candida auris colonisation and disease in South Africa.

Candida auris has been detected at almost 100 South African hospitals, causing large outbreaks in some facilities, and this pathogen now accounts for approximately 1 in 10 cases of candidaemia. The objective of this guideline is to provide updated, evidence-informed recommendations outlining a best-practice approach to prevent, diagnose and manage C. auris disease in public- and private-sector healthcare settings in South Africa. The 18 practical recommendations cover five focus areas: laboratory identification and antifungal susceptibility testing, surveillance and outbreak response, infection prevention and control, clinical management and antifungal stewardship.

Federation of infectious diseases societies of southern Africa guideline: Recommendations for the detection, management and prevention of healthcare-associated candida auris colonisation and disease in South Africa

Candida auris has been detected at almost 100 South African hospitals, causing large outbreaksinsome facilities, and this pathogen now accounts for approximately 1 in 10 cases of candidaemia. The objective of this guideline is to provide updated, evidence-informed recommendations outlining a best-practice approach to prevent, diagnose and manage C.auris disease in public- and private-sector healthcare settings in South Africa. The 18 practical recommendations cover five focus areas: laboratory identification and antifungal susceptibility testing, surveillance and outbreak response, infection prevention and control, clinical management and antifungal stewardship

Completeness of the Road-to-Health Booklet and Road-to-Health Card: Results of cross-sectional surveillance at a provincial tertiary hospital.

BACKGROUND: Accurate record-keeping is important for continuity and quality of care. Completing a child's Road-to-Health Booklet (RTHB), or the older, less detailed, Road-to-Health Card/Chart (RTHC), immediate interpretation thereof and appropriate action facilitates comprehensive care, which could contribute to a decline in child morbidity and mortality. OBJECTIVE: This study aimed to assess the extent to which healthcare personnel working in catchment clinics of Kalafong Provincial Tertiary Hospital (KPTH), Tshwane district, South Africa, complete HIV-related, sociodemographic, neonatal, growth and immunisation information in the RTHC and/or RTHB. METHODS: A cross-sectional, quantitative record review was conducted. Data were extracted from 318 RTHCs and/or RTHBs of children attending KPTH for paediatric care. Data extraction focused on six main areas, namely documentation of HIV-related, neonatal, sociodemographic, anthropometric, immunisation and vitamin A-related information. During data analysis, age-appropriate completeness scores were generated for each area and completeness of documentation in the RTHB and RTHC was assessed. RESULTS: Data demonstrate significantly less unrecorded HIV-related information (maternal HIV status, timing of maternal HIV testing, timing of maternal antiretroviral therapy [ART] initiation, current maternal ART use and infant feeding decisions) in RTHBs compared with RTHCs (p < 001). Despite this, 24% of all RTHBs had no record of maternal HIV status and 67% of RTHBs from documented HIV-exposed infants had no record of maternal ART duration. Neonatal information completeness was similar between RTHBs and RTHCs, but socio-demographic completeness was significantly better in RTHBs compared with RTHCs (p = 0.006). Growth (especially weight), immunisation and vitamin A completeness was > 80% and similar between RTHBs and RTHCs. Length-for-age, weight-for-length and head circumference were plotted in < 5% of RTHBs and none of the RTHCs. CONCLUSION: Although completeness of key HIV-related information was better in RTHBs compared with RTHCs, RTHB completeness was suboptimal. Healthcare personnel need reminders to utilise the RTHB optimally to improve continuity and quality of child healthcare.

Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa.

OBJECTIVE: Limited data are available from the developing world on antiretroviral drug resistance in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in the context of a high tuberculosis burden. We describe the proportion of children with drug resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as associated factors. METHODS: Data from children initiated on protease inhibitor-based antiretroviral therapy with subsequent virological failure referred for genotypic drug resistance testing between 2008 and 2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined and associations with these mutations identified through logistic regression analysis. RESULTS: The study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;-2.4]), high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47) and frequent tuberculosis co-infection (66%) at antiretroviral therapy initiation. Major protease inhibitor mutations were found in 49% of children and associated with low weight-for-age and height-for-age (p = 0.039; p = 0.05); longer duration of protease inhibitor regimens and virological failure (p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor (p = 0.038). On multivariate analysis, cumulative months on protease inhibitor regimens and use of ritonavir as single protease inhibitor remained significant (p = 0.008; p = 0.033). CONCLUSION: Major protease inhibitor resistance mutations were common in this study of HIV-1-infected children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing strategy proving to be important associated factors. There is an urgent need for safe, effective, and practicable HIV/tuberculosis co-treatment in young children and the optimal timing of treatment, optimal dosing of antiretroviral therapy, and alternative tuberculosis treatment strategies should be urgently addressed.

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.

Increased risk for and mortality from invasive pneumococcal disease in HIV-exposed but uninfected infants aged <1 year in South Africa, 2009-2013.

BACKGROUND: High antenatal human immunodeficiency virus (HIV) seroprevalence rates (∼ 30%) with low perinatal HIV transmission rates (2.5%), due to HIV prevention of mother-to-child transmission program improvements in South Africa, has resulted in increasing numbers of HIV-exposed but uninfected (HEU) children. We aimed to describe the epidemiology of invasive pneumococcal disease (IPD) in HEU infants. METHODS: We conducted a cross-sectional study of infants aged <1 year with IPD enrolled in a national, laboratory-based surveillance program for incidence estimations. Incidence was reported for 2 time points, 2009 and 2013. At enhanced sites we collected additional data including HIV status and in-hospital outcome. RESULTS: We identified 2099 IPD cases in infants from 2009 to 2013 from all sites. In infants from enhanced sites (n = 1015), 92% had known HIV exposure status and 86% had known outcomes. IPD incidence was highest in HIV-infected infants, ranging from 272 to 654 per 100,000 population between time points (2013 and 2009), followed by HEU (33-88 per 100,000) and HIV-unexposed and uninfected (HUU) infants (18-28 per 100,000). The case-fatality rate in HEU infants (29% [74/253]) was intermediate between HUU (25% [94/377]) and HIV-infected infants (34% [81/242]). When restricted to infants <6 months of age, HEU infants (37% [59/175]) were at significantly higher risk of dying than HUU infants (32% [51/228]; adjusted relative risk ratio, 1.76 [95% confidence interval, 1.09-2.85]). DISCUSSION: HEU infants are at increased risk of IPD and mortality from IPD compared with HUU children, especially as young infants. HEU infants, whose numbers will likely continue to increase, should be prioritized for interventions such as pneumococcal vaccination along with HIV-infected infants and children.

Molecular characterisation of enteroviruses and clinical findings from a cluster of paediatric viral meningitis cases in Tshwane, South Africa 2010-2011.

BACKGROUND: Human enteroviruses (HEVs) are the most common viral pathogen associated with paediatric aseptic meningitis. From October 2010 to February 2011 a cluster of HEV-associated meningitis cases was identified in paediatric patients who had presented at two large tertiary hospitals in Pretoria in the Tshwane Metropolitan Area, Gauteng, South Africa (SA). OBJECTIVES: The aim of this study was to review the clinical features and to characterise the HEV strains associated with this cluster of meningitis cases. STUDY DESIGN: In this retrospective study HEVs, detected by real time reverse transcription-polymerase chain reaction in acute phase cerebrospinal fluid specimens from 30 patients with aseptic meningitis, were characterised and the clinical presentations of these patients were described. RESULTS: Fever (83%), headache (70%) and vomiting (67%) were the most prominent symptoms with signs of meningeal irritation recorded in 67% of the patients. There was a neutrophil predominance in the cerebrospinal fluid of 57% of the patients with pleocytosis. Based on partial nucleotide sequence analysis of the HEV viral protein 1 gene, echovirus (E) serotype 4 (E-4) was identified in 80% (24/30) of specimens with E-9 (3/30) and coxsackie virus B5 (1/30) detected less frequently. CONCLUSION: In this cluster of aseptic meningitis cases E-4 was the predominant strain with E-9, and to a lesser extent other HEVs, identified less frequently.

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.

Emerging norovirus GII.4 2008 variant detected in hospitalised paediatric patients in South Africa.

BACKGROUND: Noroviruses (NoVs) are important enteric pathogens that cause gastroenteritis worldwide. The first documented NoV outbreaks in South Africa (SA) were described in 1993. The current NoV prevalence and circulating genotypes are unknown. SA lacks NoV outbreak reporting systems and therefore the number and impact of NoV infections is underestimated. OBJECTIVES: This study aimed to determine the prevalence and genetic diversity of NoV infections in hospitalised paediatric patients with gastroenteritis in SA during 2008. STUDY DESIGN: Stool specimens referred for virological analysis from hospitalised children ≤13 years, with gastroenteritis, were screened for rotavirus, human adenovirus and human astrovirus by enzyme immunoassay and for NoV genogroup I (GI), II (GII) and sapovirus by real-time RT-PCR. NoV strains were genotyped, and variants identified, based on sequence and phylogenetic analyses of the 5' end or the full length of the capsid gene, respectively. RESULTS: Rotavirus was the most prevalent virus detected in 24.2% (61/252) of specimens, followed by NoV in 14.3% (35/245) and adenovirus, astrovirus and sapovirus in 9.6%, 6.7% and 4% of specimens, respectively. NoVs were only detected in children ≤2 years. The GII NoVs (89%) predominated and eight types were identified with GII.4 (43%) detected most frequently. The emerging 2008 GII.4 variant represented 80% of the GII.4 strains. CONCLUSIONS: A diverse range of NoV genotypes were identified in hospitalised children with gastroenteritis. The 2008 GII.4 variant was the most frequently detected strain in the study. This is the first report of NoV GII.4 viruses in SA.

Neonatal near miss: a measure of the quality of obstetric care.

Thirty-seven percent of under-five deaths occur in the neonatal period. Identifying and correcting factors that contribute to neonatal and maternal care are of the utmost importance. Evaluation of severe acute maternal morbidity, also known as "near miss", is used to improve obstetric practice. Neonatal near miss in conjunction with neonatal mortality can be used in a similar fashion to identify deficiencies in care. No accepted definition of neonatal near miss currently exists. None of the neonatal morbidity scoring systems is applicable or appropriate for this purpose. Organ system based criteria are objective and allow for identifying severe morbidities and identifying primary causes. This system can be of use in a variety of settings to identify health system problems and to institute remedial action where necessary.