Nicolette M. du Plessis

Coronavirus disease 2019 (COVID-19) following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection caused a 41-month global public health emergency (January 2020–May 2023). Although the pandemic has subsided, there is ongoing concern about emerging viral variants [1]. Furthermore, knowledge gaps persist regarding paediatric COVID-19 clinical presentation, treatment and outcomes in high HIV prevalence settings, with […]

We hypothesized that HIV-dolutegravir resistance is more frequent when coadministered with nucleos(t)ides with shorter intracellular half-lives. Multivariable analysis of 183 viremic (≥200 c/mL) participants from 4 cohorts (N = 660 participants) found dolutegravir resistance in 21 (11.5%). Dolutegravir resistance was greater with dolutegravir + lamivudine + zidovudine/(1 on stavudine) (odds ratio [OR] = 19.4, 95% confidence interval [CI]: 5.1–74.3) or dolutegravir + lamivudine +abacavir (OR = 5.4, 95% CI: 1.1–25.8), compared with dolutegravir + lamivudine + tenofovir.

Background: Increasing multidrug-resistant bacterial infections are a global health challenge. Colistin, a polymyxin antimicrobial, has activity against some resistant strains, and despite its adverse effects, it presents a last-line option to treat resistant Gram-negative pathogens. However, paediatric colistin prescribing guidelines are lacking. Objectives: To determine paediatric colistin prescribing practices and challenges in South Africa (SA) to aid the development of a paediatric colistin guideline. Method: We conducted an anonymous online survey of registered medical practitioners in SA who prescribed colistin to patients aged ≤ 14 years in the past 12 months. Results: Of 196 participants, 71.9% (n = 141/196) completed the survey. Eighty-six respondents (n = 86/146; 58.9%) reported prescribing loading doses (LD), with the median LD and maintenance doses of 150 000 IU/kg/dose (interquartile range (IQR), 75 000–150 000) and 50 000 IU/kg/dose (IQR, 40 000–50 000), respectively. Empiric colistin use was reported by 47.2% (n = 69/146), of whom 46.3% (n = 32/69) continued empiric colistin for ≥ 72 h. Using the Likert scale, respondents highly perceived that therapeutic drug monitoring should be readily available (mean = 3.97). The perception that prescribing colistin should be advised by a microbiologist or infectious disease specialist had a mean score of 2.97, indicating moderate agreement. Conclusion: This survey demonstrated varied paediatric colistin prescribing practices. Recently, a new evidence-based paediatric guideline for colistin use in SA has been published. A follow-up survey will be conducted to assess the impact of the guideline on paediatric colistin prescribing practices in SA. Contribution: This study highlighted paediatric colistin dosing practices in the absence of a paediatric colistin guideline in South Africa.

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 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.

Background: Birth HIV point-of-care (POC) tests curtail analytical testing issues and expedite diagnosis, potentially allowing for earlier mother-infant pair engagement and improved outcomes. Many children are lost post antiretroviral therapy (ART) initiation within the first 6 months of follow-up. Objectives: We compared 6-month retention in care, HIV viral load (VL) suppression and mortality among infants diagnosed with HIV at birth, using laboratory-based versus POC HIV PCR testing. Method: From 2018 to 2019, infants exposed to HIV underwent birth HIV PCR POC testing at Kalafong Provincial Tertiary Hospital in Tshwane District. Their outcomes were compared to a historical control born between 2014 and 2016, who exclusively underwent laboratory-based HIV PCR testing. Both groups received comparable HIV care following national guidelines. Results: Fifty-seven infants were studied (POC: 27; Control: 30). The POC turnaround time was significantly shorter (POC: 15.5 h [IQR: 4.3–24.7], Control: 68.3 h [IQR 46.0–93.9]; p = < 0.0001). Both populations had the same elapsed time from HIV diagnosis to ART initiation (median: 13 days, POC: IQR 8–21 days; Control: IQR 9–36 days). Six infants were never initiated (POC: 2 [7%]; Control: 4 [13%]). At 6 months, overall care retention was 72% (41/57), higher among the Control group (Control 23/30, 77%; POC: 18/27, 67%). HIV viral suppression at 6 months was higher among the POC group (POC: 14/18, 78%; Control: 9/19, 47%, p = 0.09). No deaths were reported. Conclusion: Poor care retention at 6 months post ART initiation is concerning. Initial mother-infant visits should be effectively utilised to assess and manage potential risk factors for loss of follow-up. Contribution: This study highlights the ongoing need to find workable solutions to improve retention in care, thereby ensuring the benefits of expedited HIV diagnosis and ART initiation.

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.

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%,pCystoisosporaspp. was significantly higher in cases than controls (17.7% versus 0.0%,p= 0.028), whileSchistosomawas detected more often in controls than cases (17.4% versus 2.4%,p= 0.009). Amongst the HIV-uninfected participants, prevalence ofShigellaspp.,Salmonellaspp. andHelicobacter pyloriwas 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, withShigellaspp. (36.7%) andSalmonellaspp. (11.4%) having the highest prevalence amongst HIV-uninfected cases andShigellaspp. (18.3%),Cystoisospora(17.7%), andCryptosporidiumspp. (15.9%) having the highest prevalence in cases amongst PLHIV. These differences should be considered for the development of diagnostic and treatment guidelines.

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 for diarrhoeal admissions in HIV-infected patients 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 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 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 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 amongst HIV-infected cases. These differences should be considered for the development of diagnostic and treatment guidelines.

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.

Background 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 be shifting from high to intermediate. Methods A hospital-based HAV-seroprevalence study was conducted between February 2018 to December 2019, in Pretoria, South Africa. Systematic sampling was done of children and adolescents (1–15 years) who attended outpatient services. Participants with a known HIV-status and valid HAV-serology results were included. Results Of 1220 participants, the median age was 7-years (IQR: 4–11) with 648 (53.11%) male and 572 (46.89%) female. Of 628 (51.48%) HIV-infected participants, most (329, 71.83%) were both immunologically and virologically controlled or with 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 IgG-positive (OR 1.24; 95% CI 1.21–1.28), with 19.8% of participants one year of age compared with 86.7% of participants 15-years of age. Conclusions 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, whilst HIV-status does not significantly influence HAV-seropositivity.