Human Parainfluenza Virus (HPIV) Detection in Hospitalized Children with Acute Respiratory Tract Infection in the Western Cape, South Africa during 2014–2022 Reveals a Shift in Dominance of HPIV 3 and 4 Infections

The epidemiology of human parainfluenza viruses (HPIV), particularly its role as a cause of acute respiratory infection (ARI) in infants, has not been formally studied in South Africa. We evaluated HPIV prevalence in diagnostic samples from hospitalized children from public sector hospitals in the Western Cape between 2014 and 2022. HPIV infection was detected in 2–10% of patients, with the majority of infections detected in children less than 1 year of age. Prior to 2020, HPIV 4 (40%) and HPIV 3 (34%) were the most prevalent types, with seasonal peaks in late winter/spring for HPIV 3 and autumn/winter for HPIV 4. HPIV 4A and 4B co-circulated during the seasonal activity between 2014 and 2017. Pandemic restrictions in 2020 had a profound effect on HPIV circulation and the rebound was dominated by waves of HPIV 3, accounting for 66% of detections and a sustained decline in the circulation of HPIV 1, 2 and 4. An immunity gap could account for the surge in HPIV 3 infections, but the decline in prior HPIV 4 dominance is unexplained and requires further study

False-negative HIV-1 polymerase chain reaction in a 15-month-old boy with HIV-1 subtype C infection

Polymerase chain reaction (PCR) testing is the gold standard for determining the HIV status in children <18 months of age. However, when clinicalmanifestations are not consistent with laboratory results, additional investigation is required. We report a 15-month-old HIV-exposed boy referredto our hospital after he had been admitted several times for infectious diseases. A rapid antibody test on the child was positive, while routinediagnostic HIV PCRs using the Roche COBAS Ampliprep/COBAS TaqMan HIV Qual Test were negative at 6 weeks, 6 months, 7 months and15 months. In addition, the same PCR test performed on the HIV-infected mother was also negative. Alternative PCR and viral load assays usingdifferent primer sets detected HIV RNA or proviral DNA in both child and mother. Gag sequences from the child and his mother classified bothinfections as HIV-1 subtype C, with very rare mutations that may have resulted in PCR assay primer/probe mismatch. Consequently, the child wascommenced on antiretroviral therapy and made a remarkable recovery. These findings indicate that more reliable PCR assays capable of detectinga wide range of HIV subtypes are desirable to circumvent the clinical problems created by false-negative PCR results

A retrospective study assessing the clinical outcomes and costs of acute hepatitis A in Cape Town, South Africa

Background While some evidence has been demonstrated the cost-effectiveness of routine hepatitis A vaccination in middle-income countries, the evidence is still limited in other settings including in South Africa. Given this, the evidence base around the cost of care for hepatitis A needs to be developed towards considerations of introducing hepatitis A vaccines in the national immunisation schedule and guidelines. Objectives To describe the severity, clinical outcomes, and cost of hepatitis A cases presenting to two tertiary healthcare centers in Cape Town, South Africa. Methods We conducted a retrospective folder review of patients presenting with hepatitis A at two tertiary level hospitals providing care for urban communities of metropolitan Cape Town, South Africa. Patients included in this folder review tested positive for hepatitis A immunoglobulin M between 1 January 2008 and 1 March 2018. Results In total, 239 folders of hepatitis A paediatric patients < 15 years old and 212 folders of hepatitis A adult patients $$\ge$$ ≥ 15 years old were included in the study. Before presenting for tertiary level care, more than half of patients presented for an initial consultation at either a community clinic or general physician. The mean length of hospital stay was 7.45 days for adult patients and 3.11 days for paediatric patients. Three adult patients in the study population died as a result of hepatitis A infection and 29 developed complicated hepatitis A. One paediatric patient in the study population died as a result of hepatitis A infection and 27 developed complicated hepatitis A, including 4 paediatric patients diagnosed with acute liver failure. The total cost per hepatitis A hospitalisation was $1935.41 for adult patients and$563.06 for paediatric patients, with overhead costs dictated by the length of stay being the largest cost driver. Conclusion More than 1 in every 10 hepatitis A cases (13.3%) included in this study developed complicated hepatitis A or resulted in death. Given the severity of clinical outcomes and high costs associated with hepatitis A hospitalisation, it is important to consider the introduction of hepatitis A immunisation in the public sector in South Africa to potentially avert future morbidity, mortality, and healthcare spending

Hepatitis E virus: Western Cape, South Africa

AIM To conduct a prospective assessment of anti-hepatitis E virus (HEV) IgG seroprevalence in the Western Cape Province of South Africa in conjunction with evaluating risk factors for exposure. METHODS Consenting participants attending clinics and wards of Groote Schuur, Red Cross Children's Hospital and their affiliated teaching hospitals in Cape Town, South Africa, were sampled. Healthy adults attending blood donor clinics were also recruited. Patients with known liver disease were excluded and all major ethnic/race groups were included to broadly represent local demographics. Relevant demographic data was captured at the time of sampling using an interviewer-administered confidential questionnaire. Human immunodeficiency virus (HIV) status was self-disclosed. HEV IgG testing was performed using the Wantai assay. RESULTS HEV is endemic in the region with a seroprevalence of 27.9% (n = 324/1161) 95%CI: 25.3%-30.5% (21.9% when age-adjusted) with no significant differences between ethnic groups or HIV status. Seroprevalence in children is low but rapidly increases in early adulthood. With univariate analysis, age ? 30 years old, pork and bacon/ham consumption suggested risk. In the multivariate analysis, the highest risk factor for HEV IgG seropositivity (OR = 7.679, 95%CI: 5.38-10.96, p < 0.001) was being 30 years or older followed by pork consumption (OR = 2.052, 95%CI: 1.39-3.03, p < 0.001). A recent clinical case demonstrates that HEV genotype 3 may be currently circulating in the Western Cape. CONCLUSION Hepatitis E seroprevalence was considerably higher than previously thought suggesting that hepatitis E warrants consideration in any patient pre

Molecular epidemiology of mother-to-child transmission of HIV-1 in children at Tygerberg Hospital

Thesis (MMed (Medical Microbiology))--University of Stellenbosch, 2006.One of the major routes of transmission of human immunodeficiency virus (HIV) in the developing world is vertical transmission from mother to infant – pre-, intra-, or post-partum. In the Western Cape, HIV-1 subtype C is the predominant subtype in the heterosexual population, and this trend was expected to be seen amongst cases of mother-to-child transmission of HIV. The aim of this study was to perform genetic characterisation and phylogenetic analysis of the HIV-1 genome in positive serum/plasma samples obtained from children (age 0 to 18 months) from 2000-2002, and temporally related specimens from their mothers. We obtained 27 suitable pairs of samples taken within 6 months of delivery. From this pool, we obtained 21 infant DNA sequences and 17 maternal sequences, resulting in 16 mother-infant pairs. All patient sequences were identified as HIV-1 subtype C, and, as expected, mother and infant viral sequences clustered together. In some cases where a mother was suspected to have two dominant quasispecies based on the electropherogram, only one sequence was detectable in the infant. Single or multiple amino acid deletions were consistent between mothers and infants, and some pairs showed the same amino acid deletions seen in other pairs

Molecular characterization of an outbreak of enterovirus-associated meningitis in Mossel Bay, South Africa, December 2015–January 2016

Abstract Background Human enteroviruses (HEVs) are common causal agents of aseptic meningitis in young children. Laboratory and syndromic surveillance during December 2015 and January 2016 noted an unusually high number of paediatric aseptic meningitis cases at a hospital in Mossel Bay, Western Cape Province, South Africa. HEV was detected in clinical samples, prompting an outbreak investigation. Methods Epidemiological investigations were conducted to ascertain possible linkage between cases. Amplification, sequencing and phylogenetic analysis of the 5’UTR and VP1 regions was undertaken to determine the HEV serotype associated with the outbreak as well as other cases of aseptic meningitis in the area in the preceding 6 weeks. Results Over the 2-month period, 63 CSF samples were available for testing. A total of 43 outbreak cases (68.3%) were observed, and the 26 (60.5%) that could be typed were coxsackie virus A9 (CVA9). Children attending three crèche facilities were epidemiologically linked, accounting for 60.5% (26/43) of the CVA9 cases. The majority of patients were under 10 years of age (55/63, 87.3%) and there was a male predominance (66%). Nucleotide sequence analysis of the 5’UTR and VP1 regions identified 2 lineages of CVA9 co-circulating during the outbreak, although the VP1 capsid protein sequence was identical as all nucleotide differences were synonymous. There was a unique isoleucine at position 64 and all outbreak viruses had a valine to threonine change in the hypervariable BC loop of VP1. Other HEV types circulating in the preceding period were echovirus 30 (n = 4), echovirus 5 (n = 3) and 1 each of echovirus 6, echovirus 9 and echovirus 15. Conclusion CVA9 was identified as the pathogen responsible for the large outbreak of aseptic meningitis, with 2 distinct co-circulating lineages

High positive HIV serology results can still be false positive

The consequences of falsely reactive HIV test results can be significant, for patients and healthcare providers. This case describes a diagnostic investigation of a patient with pronounced discordant HIV serological results, to determine HIV status. The fourth generation serological screening assay (Roche COBAS Elecsys HIV combiPT) had high positive results but confirmatory testing was negative (Abbott HIV Ag/Ab Combo). Five separate samples over 13 days were tested using multiple fourth generation HIV immunoassays and molecular tests for HIV-1 and HIV-2. Potential causes of falsely reactive serological results were investigated. Samples were sent to the manufacturer for analysis.The screening assay was positive on all samples with a very high signal to cut-off ratio (S/CO) of greater than 400. However, multiple serological and molecular assays did not detect HIV-1 or HIV-2 specific antibodies, antigen or nucleic acid. A recombinant immunochromatographic assay had faint reactivity to gp41 peptide and the manufacturer investigation reported cross-reactivity to one of the screening assay’s synthetic peptides. Possible causes of the false positive result include cross reactivity to other antigens, including prior schistosomiasis infection, or the patient’s previously excised ameloblastoma (a rare germ cell tumor of the jaw). This is a rare case of false high positive results on fourth-generation HIV serology testing due to high level non-specific reactivity to an isolated synthetic peptide component of the assay. It highlights the need for confirmatory testing even in settings with HIV high prevalence and awareness that false-positive serological results may have a high S/CO

Contamination with HIV antibody may be responsible for false positive results in specimens tested on automated platforms running HIV 4th generation assays in a region of high HIV prevalence

<div><p>Introduction</p><p>In South Africa where the prevalence of HIV infection is very high, 4^th generation HIV antibody/p24 antigen combo immunoassays are the tests of choice for laboratory based screening. Testing is usually performed in clinical pathology laboratories on automated analysers. To investigate the cause of false positive results on 4^th generation HIV testing platforms in public sector laboratories, the performance of two automated platforms was compared in a clinical pathology setting, firstly on routine diagnostic specimens and secondly on known sero-negative samples.</p><p>Methods</p><p>Firstly, 1181 routine diagnostic specimens were sequentially tested on Siemens and Roche automated 4^th generation platforms. HIV viral load, western blot and follow up testing were used to determine the true status of inconclusive specimens. Subsequently, known HIV seronegative samples from a single donor were repeatedly tested on both platforms and an analyser was tested for surface contamination with HIV positive serum to identify how suspected specimen contamination could be occurring.</p><p>Results</p><p>Serial testing of diagnostic specimens yielded 163 weakly positive or discordant results. Only 3 of 163 were conclusively shown to indicate true HIV infection. Specimen contamination with HIV antibody was suspected, based on the following evidence: the proportion of positive specimens increased on repeated passage through the analysers; viral loads were low or undetectable and western blots negative or indeterminate on problem specimens; screen negative, 2^nd test positive specimens tested positive when reanalysed on the screening assay; follow up specimens (where available) were negative. Similarly, an increasing number of known negative specimens became (repeatedly) sero-positive on serial passage through one of the analysers. Internal and external analyser surfaces were contaminated with HIV serum, evidence that sample splashes occur during testing.</p><p>Conclusions</p><p>Due to the extreme sensitivity of these assays, contamination with minute amounts of HIV antibody can cause a negative sample to test positive. Better contamination control measures are needed on analysers used in clinical pathology environments, especially in regions where HIV sero-prevalence is high.</p></div

Determining sero-positivity at first and second testing episodes.

<p>The number of negative results decreased and the number of positive results increased on second testing on the Roche analyser at UN laboratory.</p