Antibiotic resistance is a global threat, with a disproportionate burden of mortality in low- and middle-income countries. It is increasing in both the public and private healthcare sectors within South Africa, especially in Gram-negative organisms, and is associated with increased use of World Health Organization watch and reserve antibiotics. There is a need for improved access to new antibiotics to treat infections caused by drug-resistant organisms in order to limit side-effects and improve patient outcomes of currently available antibiotics. We propose the responsible introduction of these new antibiotics with both administrative and clinical oversight in order to preserve the longevity of these precious antibiotics.

A previously healthy 10-year-old girl, living in a sheep-farming community in South Africa with exposure to dogs, presented to her local hospital with generalised tonic-clonic seizures. The initial clinical assessment and laboratory work-up were unremarkable. When she presented with further seizures 6 months later, attempts to arrange neuroimaging and specialist assessment were unsuccessful owing to restrictions on routine healthcare services during the SARS-CoV-2 nationwide lockdown. Subsequently, 11 months after her first presentation, she developed focal neurological signs suggestive of raised intracranial pressure. A brain computed tomography scan revealed a left-sided cerebral cyst and imminent tonsillar herniation. An emergency burr-hole procedure was performed to relieve the raised intracranial pressure, followed by definitive neurosurgical excision of cysts. Hydatid protoscolices and hooklets were seen on microscopy of cyst fluid, and treatment with albendazole and praziquantel was initiated. While her infection was treated successfully, long-term sequelae including permanent blindness and hemiparesis could potentially have been prevented with early neuroimaging and surgical intervention.

BACKGROUND: There is an increasing need for third-line treatment regimens in HIV-infected children with antiretroviral treatment (ART) failure. Data are limited on darunavir/ritonavir (DRV/r)-, raltegravir (RAL)- and etravirine (ETR)-containing regimens in treatment-experienced children from resource-constrained settings receiving these drugs as part of routine care. OBJECTIVE: To describe the characteristics and early outcomes of treatment-experienced children (<20 years of age) in the Western Cape Province of South Africa treated with DRV/r-, RAL- or ETR-containing regimens. METHODS: This was a retrospective review of treatment-experienced children receiving a DRV/r-, RAL- or ETR-containing regimen as recommended by a paediatric expert review committee, based on HIV drug resistance testing. RESULTS: Thirty-five children of median age 8.8 years (interquartile range (IQR) 5.5 - 11) who had received ART for a median of 6.9 years (IQR 5 - 9.9) and started a DRV/r-, RAL- or ETR-containing regimen were included. Before starting such a regimen, the median CD4+ lymphocyte count and HIV-1 RNA level were 405.5 cells/uL (IQR 251.5 - 541) and 28 314 copies/mL (IQR 5 595.5 - 120 186.5) (log 4.5 (IQR 3.7 - 5)), respectively, in 24 subjects with available results. After a median of 2 years (IQR 1.3 - 4) on treatment, 29/30 (96.7%) and 23/30 (76.7%) subjects with available results had HIV-1 RNA levels of <400 and <50 copies/mL, respectively. CONCLUSIONS: This study found DRV/r-, RAL- and ETR-containing regimens to be effective in a group of treatment-experienced children and adolescents with multidrug-resistant HIV. Although the treatment regimens in this study were individualised based on HIV genotyping results, further research evaluating the safety and efficacy of standardised third-line treatment regimens in children of all ages is needed.

Concern and general awareness about the impacts of climate change in all sectors of the social-ecological-economic system is growing as a result of improved climate science products and information, as well as increased media coverage of the apparent manifestations of the phenomenon in our society. However, scales of climate variability and change, in space and time, are often confused and so attribution of impacts on various sectors, including the health sector, can be misunderstood and misrepresented. In this review, we assess the mechanistic links between climate and infectious diseases in particular, and consider how this relationship varies, and may vary according to different time scales, especially for aetiologically climate-linked diseases. While climate varies in the medium (inter-annual) time frame, this variability itself may be oscillating and/or trending on cyclical and long-term (climate change) scales because of regional and global scale climate phenomena such as the El-Nino southern oscillation coupled with global-warming drivers of climate change. As several studies have shown, quantifying and modelling these linkages and associations at appropriate time and space scales is both necessary and increasingly feasible with improved climate science products and better epidemiological data. The application of this approach is considered for South Africa, and the need for a more concerted effort in this regard is supported.

INTRODUCTION: Between 2009 and 2010, South Africa experienced a major measles outbreak, with more than 18 000 confirmed cases reported to the National Institute of Communicable Diseases. METHODS: We studied measles admissions during the outbreak to Red Cross War Memorial Children's Hospital, Cape Town, between 1 November 2009 and 31 July 2010. Factors associated with mortality were retrospectively identified from notification records and hospital admissions data. Multivariate logistic regression was used to investigate potential risk factors for death. RESULTS: In total, 1 861 children were diagnosed with measles; 552 (30%) were admitted to hospital. The most common reason for admission was pneumonia (379 (68%)) and/or diarrhoea (262 (48%)). The median age at admission was 7.36 months (interquartile range (IQR) 5.0 - 10.7). The median duration of admission was 4 days (IQR 2 - 6); total hospital admission time was 3 746 days (10.3 child-years). HIV status was known in 404 (73%) children: 39/400 (14%) were HIV-infected. Eighteen children died (3% of all admissions); 15 (83%) of them were less than 1 year old. In the regression model, HIV-infection (adjusted odds ratio (aOR) 7.55, 95% confidence interval (CI) 2.27 - 25.12) and female sex (aOR 3.86, 95% CI 1.26 - 11.84) were associated with higher odds of death. CONCLUSIONS: There was a large paediatric admission burden during the 2009 - 2010 measles outbreak in Cape Town; young children were predominantly affected. HIV-infected children had a significantly higher case fatality.

A case of a child with chronic granulomatous disease (CGD) presenting with recurrent mycobacterial infections and invasive Aspergillus fumigatus disease is described. Genetic analysis confirmed X-linked CGD with a novel mutation in exon 10 of the CYBB gene - the first South African report of genetically confirmed CGD.

OBJECTIVE: To determine the population-based incidence of disseminated bacille Calmette-Guérin (BCG) disease in HIV-infected infants (aged < 1 year) in a setting with a high burden of tuberculosis and HIV infection coupled with a well-functioning programme for the prevention of HIV infection in infants. METHODS: The numerator, or number of new cases of disseminated BCG disease, was derived from multicentre surveillance data collected prospectively on infants with a confirmed HIV infection during 2004-2006. The denominator, or total number of HIV-infected infants who were BCG-vaccinated, was derived from population-based estimates of the number of live infants and from reported maternal HIV infection prevalence, vertical HIV transmission rates and BCG vaccination rates. FINDINGS: The estimated incidences of disseminated BCG disease per 100 000 BCG-vaccinated, HIV-infected infants were as follows: 778 (95% confidence interval, CI: 361-1319) in 2004 (vertical HIV transmission rate: 10.4%); 1300 (95% CI: 587-2290) in 2005 (transmission rate: 6.1%); and 1013 (95% CI: 377-1895) in 2006 (transmission rate: 5.4%). The pooled incidence over the study period was 992 (95% CI: 567-1495) per 100 000. CONCLUSION: Multicentre surveillance data showed that the risk of disseminated BCG disease in HIV-infected infants is considerably higher than previously estimated, although likely to be under-estimated. There is an urgent need for data on the risk-benefit ratio of BCG vaccination in HIV-infected infants to inform decision-making in settings where HIV infection and tuberculosis burdens are high. Safe and effective tuberculosis prevention strategies are needed for HIV-infected infants.

OBJETIVO: Determinar la incidencia poblacional de la infección diseminada por el bacilo de Calmette-Guérin (BCG) en lactantes (niños < 1 años) en un entorno de alta carga de tuberculosis e infección por VIH y de aplicación satisfactoria de un programa de prevención de la infección por VIH en los lactantes. MÉTODOS: El numerador, o número de nuevos casos de infección diseminada por BCG, se calculó a partir de datos de vigilancia multicéntricos reunidos prospectivamente sobre lactantes con infección confirmada por VIH durante 2004-2006. El denominador, o número total de lactantes infectados por el VIH y vacunados con la BCG, se calculó a partir de estimaciones poblacionales del número de lactantes vivos y de la prevalencia de infección materna por VIH, de las tasas de transmisión vertical del VIH y de las tasas de vacunación con BCG. RESULTADOS: Las incidencias estimadas de infección diseminada por BCG por 100 000 lactantes infectados por el VIH y vacunados con BCG fueron las siguientes: 778 (intervalo de confianza del 95%, IC95%: 361-1319) en 2004 (transmisión vertical del VIH: 10,4%); 1300 (IC95%: 587-2290) en 2005 (tasa de transmisión: 6,1%); y 1013 (IC95%: 377-1895) en 2006 (tasa de transmisión: 5,4%). La incidencia combinada a lo largo del periodo estudiado fue de 992 (IC95%: 567-1495) por 100 000. CONCLUSIÓN: Los datos de la vigilancia multicéntrica revelaron que el riesgo de infección diseminada por BCG en los lactantes infectados por el VIH era considerablemente superior al estimado anteriormente. Urge disponer de datos sobre la relación riesgo-beneficio de la vacunación con BCG en los lactantes infectados por el VIH a fin de fundamentar la adopción de decisiones en los entornos con alta carga de infección por VIH y de tuberculosis. Es preciso formular estrategias seguras y eficaces de prevención de la tuberculosis para los lactantes infectados por el VIH.

OBJECTIF: Déterminer l'incidence en population de l'infection disséminée par le bacille de Calmette-Guérin (BCG) chez les nourrissons infectés par le VIH (âge < 1 an) dans une situation caractérisée par une forte charge de tuberculose et d'infections à VIH, mais aussi par un bon fonctionnement du programme de prévention de l'infection par le VIH chez les nourrissons. MÉTHODES: Le numérateur, ou nombre de nouveaux cas d'infection disséminée par le BCG, a été déterminé à partir des données de surveillance multicentrique, collectées prospectivement au sujet des nourrissons présentant une infection à VIH confirmée au cours de la période 2004-2006. Le dénominateur, ou nombre total de nourrissons infectés par le VIH et vaccinés par le BCG, a été obtenu à partir d'estimations en population du nombre de nourrissons vivants et à partir de la prévalence rapportée des infections à VIH maternelles, des taux de transmission verticale du VIH et des taux de vaccination par le BCG. RÉSULTATS: L'incidence de l'infection disséminée par le BCG pour 100 000 nourrissons vaccinés par le BCG a été estimée à : 778 cas (intervalle de confiance à 95 %, IC : 361-1319) en 2004 (taux de transmission verticale du VIH : 10,4 %) ; 1300 cas (IC à 95 % : 587-2290) en 2005 (taux de transmission : 6,1 %) ; et 1013 cas (IC à 95 % : 377-1895) en 2006 (taux de transmission : 5,4 %). L'incidence globale sur l'ensemble de la période étudiée était de 992 (IC à 95 % : 567-1495) pour 100 000. CONCLUSION: Les données de surveillance multicentrique ont montré que le risque d'infection disséminée par le BCG chez les nourrissons infectés par le VIH était considérablement plus élevé qu'on ne l'avait estimé auparavant, bien que probablement encore sous-estimé. On a besoin d'urgence de données sur le rapport risque/bénéfice de la vaccination par le BCG chez les nourrissons infectés par le VIH pour étayer la prise de décisions dans des contextes où les charges d'infection à VIH et de tuberculose sont importantes. Des stratégies sûres et efficaces de prévention de la tuberculose sont nécessaires pour les nourrissons infectés par le VIH.