Theunis Avenant

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.

Increased risk and mortality of invasive pneumococcal disease in HIV-exposed-uninfected infants <1 year of age 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.

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.

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.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. Pediatr Blood Cancer

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.

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.

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.

Risk factors for pertussis among hospitalized children in a high HIV prevalence setting, South Africa

BACKGROUND In low- and middle-income countries, including South Africa, the epidemiology of pertussis in relation to immunization, nutritional, and HIV status is poorly described. This article reports on risk factors in South African children hospitalized with pertussis. METHODS A prospective, hospital-based, sentinel surveillance programme for pertussis was conducted in Gauteng Province, South Africa. Hospitalized children (≤10 years) meeting the surveillance criteria for clinically suspected pertussis were screened and enrolled. Nasopharyngeal specimens were collected for real-time multiplex PCR and culture of Bordetella species. RESULTS Bordetella pertussis was detected in 6.2% (61/992) of children. Pertussis was significantly more prevalent in infants younger than 3 months (9.8%; 38/392) and in young children between the ages of 5 and 9 years (12%; 4/34) (p=0.0013). Of the 61 confirmed pertussis cases, 17 were too young for vaccination. Of the remaining 44 infants, vaccination DTP1 was administered in 73% (32/44) of pertussis-confirmed patients who were eligible, DTP2 in 50% (16/32), DTP3 in 54% (14/26), and DTP4 in 56% (5/9) of vaccine-eligible cases at 18 months of age. B. pertussis infection was less likely in children immunized at least once (5%, 32/692) than in unvaccinated children (10%, 24/230) (p=0.0001). HIV exposure and infection status were determined in 978 (99%) patients: 69% (678/978) were HIV-unexposed and uninfected and 31% (300/978) were HIV-exposed. Of these HIV-exposed patients, 218 (22%) were proven HIV-exposed and uninfected and 82 patients were HIV-infected (8.4%, 82/978). HIV prevalence was similar in pertussis-positive (6%, 5/82) and pertussis-negative (6%, 55/896) children (p=0.90). B. pertussis infection was unrelated to poor nutritional status. CONCLUSIONS In South Africa, B. pertussis poses a greater risk to infants who are too young for the first vaccine dose, those who are not vaccinated in a timely manner, and those who do not receive all three primary doses. HIV infection and HIV exposure were not associated with pertussis infection.