Helena Rabie’s research while affiliated with Stellenbosch University and other places

BACKGROUND This study assessed growth trajectories in children presenting with presumptive pulmonary TB (PTB). METHODS This sub-study of the Umoya TB diagnostic study was conducted in South Africa from November 2017 until November 2021. Children (0–13 years) with presumptive PTB were recruited from and followed up for 12 months. Anthropometric measurements of children with TB, symptomatic controls (TB excluded), and healthy controls were taken at baseline and follow-up (2, 8, 16, 24 and 52 weeks). Changes in weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ) and body mass index for age (BAZ) over time were assessed using multivariable mixed-effect linear regression adjusted for confounders. RESULTS Of the 372 children included in the analyses (median age: 2 years, IQR 1–4), 153 children had TB, 168 were symptomatic and 51 were healthy controls. Median WAZ was similar between groups; however, more children with TB were underweight than symptomatic and healthy controls. WAZ increased over time for children with TB. Median HAZ of children with TB (–1.34, IQR –2.17 to –0.21) was lower compared to symptomatic (–1.06, IQR –1.90 to –0.10) and healthy controls (–0.74, IQR –1.26 to –0.03; P = 0.0037). There was no significant change over time for HAZ. CONCLUSION To improve the long-term outcomes of TB and other illnesses, the overall nutrition of children needs to be improved.

Background Data on tuberculosis (TB) incidence and risk factors among children living with HIV (CLHIV) in the universal ART era are limited. Methods We analysed routinely-collected data on TB diagnoses for CLHIV age ≤5 years, born 2018-2022, in the Westen Cape, South Africa. We examined factors associated with TB diagnosis, with death and loss to follow-up as competing events. Results Among 2,219 CLHIV, 30% were diagnosed with HIV at birth. Median follow-up from birth was 38 months (IQR 24-50); 90% started antiretroviral therapy (ART). TB was diagnosed in 28% of CLHIV (n=626/2219); 62% were first diagnosed before/within 3 months of ART start (‘TB before ART’) and 38% >3 months after ART start (‘TB after ART’). Of those with ‘TB before ART’ (n=390), median age at HIV diagnosis was 13 months (IQR:6-22); median time between HIV and TB diagnoses was 5 days (IQR:0-31). ‘TB before ART’ was associated with older age at HIV diagnosis and advanced/severe immunodeficiency. Of those with ‘TB after ART’ (n=258), median age at HIV diagnosis was 2 months (IQR 0-8) and median time from ART start to TB diagnosis was 12 months (IQR:7-21). ‘TB after ART’ was associated with increased viral load and advanced/severe immunosuppression (time-updated). Overall, 5% (n=112/2219) of CLHIV died, 36% of whom were diagnosed with TB (median time from TB diagnosis to death: 58 days; IQR:17-191). Conclusions Young CLHIV in this setting have high TB-associated morbidity and mortality. Efforts to improve early HIV and TB diagnosis, viral suppression and TB preventive therapy are needed.

INTRODUCTION Children with underlying comorbidities and infants are most severely affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including in low- and middle-income countries with a high prevalence of HIV and TB. We describe the clinical presentation of SARS-CoV-2 infection in children during the Omicron wave, in Cape Town, South Africa. METHODS We analysed routine care data from a prospective cohort of children aged 0–13 years, with a positive SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) or SARS-CoV-2 antigen test, admitted to Tygerberg Hospital between 1 November 2021 until 1 March 2022. Risk factors for severity of disease were assessed. RESULTS Ninety-five children tested positive for SARS-CoV-2, of whom 87 (91.6%) were symptomatic. Clinical data were available for 86 children. The median age was 11 months (IQR 3.0–60.0), 37 (43.0%) were females, 21 (24.7%) were HIV-exposed and 7 (8.1%) were living with HIV (CLHIV). In total, 44 (51.2%) children had at least one underlying comorbidity. TB co-infection was seen in 11 children, 6 children were newly diagnosed and 5 children were already on TB treatment at the time of admission. CONCLUSION There was no evidence of more severe disease in children living with HIV or TB.

Empyema necessitans is a rare complication of pneumonia in which pus formed in the pleural cavity extends into the surrounding tissue. In children it is mostly caused by Mycobacterium tuberculosis, but other bacterial organisms are implicated occasionally. Early diagnosis through appropriate imaging, cultures and molecular diagnostic tests of samples taken from the lesion is recommended. Outcome is good provided appropriate medical and surgical treatment are provided.

BACKGROUND These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents. METHODS Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document. RESULTS Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent. CONCLUSION These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

Importance: Little is known about COVID-19 outcomes among children and adolescents in sub-Saharan Africa, where preexisting comorbidities are prevalent. / Objective: To assess the clinical outcomes and factors associated with outcomes among children and adolescents hospitalized with COVID-19 in 6 countries in sub-Saharan Africa. / Design, Setting, and Participants: This cohort study was a retrospective record review of data from 25 hospitals in the Democratic Republic of the Congo, Ghana, Kenya, Nigeria, South Africa, and Uganda from March 1 to December 31, 2020, and included 469 hospitalized patients aged 0 to 19 years with SARS-CoV-2 infection. / Exposures: Age, sex, preexisting comorbidities, and region of residence. / Main Outcomes and Measures: An ordinal primary outcome scale was used comprising 5 categories: (1) hospitalization without oxygen supplementation, (2) hospitalization with oxygen supplementation, (3) ICU admission, (4) invasive mechanical ventilation, and (5) death. The secondary outcome was length of hospital stay. / Results: Among 469 hospitalized children and adolescents, the median age was 5.9 years (IQR, 1.6-11.1 years); 245 patients (52.4%) were male, and 115 (24.5%) had comorbidities. A total of 39 patients (8.3%) were from central Africa, 172 (36.7%) from eastern Africa, 208 (44.3%) from southern Africa, and 50 (10.7%) from western Africa. Eighteen patients had suspected (n = 6) or confirmed (n = 12) multisystem inflammatory syndrome in children. Thirty-nine patients (8.3%) died, including 22 of 69 patients (31.9%) who required intensive care unit admission and 4 of 18 patients (22.2%) with suspected or confirmed multisystem inflammatory syndrome in children. Among 468 patients, 418 (89.3%) were discharged, and 16 (3.4%) remained hospitalized. The likelihood of outcomes with higher vs lower severity among children younger than 1 year expressed as adjusted odds ratio (aOR) was 4.89 (95% CI, 1.44-16.61) times higher than that of adolescents aged 15 to 19 years. The presence of hypertension (aOR, 5.91; 95% CI, 1.89-18.50), chronic lung disease (aOR, 2.97; 95% CI, 1.65-5.37), or a hematological disorder (aOR, 3.10; 95% CI, 1.04-9.24) was associated with severe outcomes. Age younger than 1 year (adjusted subdistribution hazard ratio [asHR], 0.48; 95% CI, 0.27-0.87), the presence of 1 comorbidity (asHR, 0.54; 95% CI, 0.40-0.72), and the presence of 2 or more comorbidities (asHR, 0.26; 95% CI, 0.18-0.38) were associated with reduced rates of hospital discharge. / Conclusions and Relevance: In this cohort study of children and adolescents hospitalized with COVID-19 in sub-Saharan Africa, high rates of morbidity and mortality were observed among infants and patients with noncommunicable disease comorbidities, suggesting that COVID-19 vaccination and therapeutic interventions are needed for young populations in this region.

Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children and adolescents; and these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of coronavirus disease 2019 (COVID-19) among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and coinfections such as human immunodeficiency virus (HIV), tuberculosis, malaria, sickle cell disease, and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policy-making for COVID-19 while concurrently addressing other major diseases affecting children in African countries.