What's new in childhood tuberculosis.

PURPOSE OF REVIEW: The current review identifies recent advances in the prevention, diagnosis, and treatment of childhood tuberculosis (TB) with a focus on the WHO's updated TB management guidelines released in 2022. RECENT FINDINGS: The COVID-19 pandemic negatively affected global TB control due to the diversion of healthcare resources and decreased patient care-seeking behaviour. Despite this, key advances in childhood TB management have continued. The WHO now recommends shorter rifamycin-based regimens for TB preventive treatment as well as shorter regimens for the treatment of both drug-susceptible and drug-resistant TB. The Xpert Ultra assay is now recommended as the initial diagnostic test for TB in children with presumed TB and can also be used on stool samples. Point-of-care urinary lipoarabinomannan assays are promising as 'rule-in' tests for children with presumed TB living with HIV. Treatment decision algorithms can be used to diagnose TB in symptomatic children in settings with and without access to chest X-rays; bacteriological confirmation should always be attempted. SUMMARY: Recent guideline updates are a key milestone in the management of childhood TB, and the paediatric TB community should now prioritize their efficient implementation in high TB burden countries while generating evidence to close current evidence gaps.

Clinical Experience With Severe Acute Respiratory Syndrome Coronavirus 2-Related Illness in Children: Hospital Experience in Cape Town, South Africa.

BACKGROUND: Children seem relatively protected from serious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease, but little is known about children living in settings with high tuberculosis and human immunodeficiency virus (HIV) burden. This study reflects clinical data on South African children with SARS-CoV-2. METHODS: We collected clinical data of children aged <13 years with laboratory-confirmed SARS-CoV-2 presenting to Tygerberg Hospital, Cape Town, between 17 April and 24 July 2020. RESULTS: One hundred fifty-nine children (median age, 48.0 months [interquartile range {IQR}, 12.0-106.0 months]) were included. Hospitalized children (n = 62), with a median age of 13.5 months (IQR, 1.8-43.5 months) were younger than children not admitted (n = 97; median age, 81.0 months [IQR, 34.5-120.5 months]; P < .01.). Thirty-three of 159 (20.8%) children had preexisting medical conditions. Fifty-one of 62 (82.3%) hospitalized children were symptomatic; lower respiratory tract infection was diagnosed in 21 of 51 (41.2%) children, and in 11 of 16 (68.8%) children <3 months of age. Respiratory support was required in 25 of 51 (49.0%) children; 13 of these (52.0%) were <3 months of age. One child was HIV infected and 11 of 51 (21.2%) were HIV exposed but uninfected, and 7 of 51 (13.7%) children had a recent or new diagnosis of tuberculosis. CONCLUSIONS: Children <1 year of age hospitalized with SARS-CoV-2 in Cape Town frequently required respiratory support. Access to oxygen may be limited in some low- and middle-income countries, which could potentially drive morbidity and mortality. HIV infection was uncommon but a relationship between HIV exposure, tuberculosis, and SARS-CoV-2 should be explored.

HIV-associated tuberculosis in infants, children, and adolescents younger than 15 years: an update on the epidemiology, diagnosis, prevention, and treatment.

PURPOSE OF REVIEW: HIV-associated tuberculosis (TB) remains a major driver of morbidity and mortality in children and adolescents younger than 15 years (CLWH). The purpose of this review is to highlight recent findings in the areas of prevention, diagnosis, and treatment of HIV-associated TB in CLWH and to highlight knowledge and implementation gaps. RECENT FINDINGS: We found that despite access to antiretroviral therapy (ART), high rates of HIV-associated TB are still reported, and with an unacceptably high mortality. There are no advances in screening for TB, but shorter courses of rifapentine-based TB preventive therapy are becoming available. The use of algorithms in TB diagnosis can potentially simplify the therapeutic decision making. There are more data supporting the use of dolutegravir (DTG) with rifampicin and a need to study unadjusted DTG especially in the youngest children. Short course therapy for nonsevere pulmonary TB is currently implemented and programmatic outcome should be studied in CLWH. Low uptake of ART and poor suppression remains an important driver of HIV-associated TB. SUMMARY: Although screening and diagnosis remains challenging, there are several advances in the prevention and treatment of HIV-associated TB. Effective implementation of these strategies is needed to advance the outcomes of CLWH.

Short-term outcomes of South African children with multisystem inflammatory syndrome in children: a prospective cohort study.

BACKGROUND: Despite the life-threatening presentation of multisystem inflammatory syndrome in children (MIS-C), the overall prognosis is favourable in centres with access to appropriate supportive care. In this study, we investigate the short-term outcomes in children with MIS-C in Cape Town, South Africa. METHODS: This prospective observational cohort study included children <13 years who fulfilled the WHO case definition of MIS-C and were admitted to Tygerberg Hospital in Cape Town, South Africa between 1 June 2020 and 31 October 2021. Clinical features were recorded at baseline and at follow-up at the 6-week cardiology and 3-month rheumatology-immunology clinics, respectively. FINDINGS: Fifty-three children with a median age of 7.4 years (IQR 4.2-9.9) were included. There was a slight male predominance (30/53; 56.6%) and the majority was of mixed ancestry (28/53; 52.83%) or black African ancestry (24/53; 45.3%). Fourteen children (14/53; 26.4%) had comorbid disease. The median length of hospital stay was 8 days (IQR 6-10). All children had an echocardiogram performed at baseline of which 39 were abnormal (39/53; 73.6%). All children were discharged alive. The median days from discharge to cardiology follow-up was 39 days (IQR 33.5-41.5) and for rheumatology-immunology clinic was 70.5 days (IQR 59.5-85.0). Eleven children (11/41; 26.8%) had a persistently abnormal echocardiogram at cardiology follow-up. Systemic inflammation and organ dysfunction resolved in most. INTERPRETATION: Although the short-term outcomes of MIS-C in our cohort were generally good, the cardiac morbidity needs further characterisation and follow-up.

Clinical Presentation and Outcome of Acute Respiratory Illnesses in South African Children During the COVID-19 Pandemic.

BACKGROUND: Data from low- and middle-income countries (LMICs) show higher morbidity and mortality in children with acute respiratory illness (ARI) from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, whether SARS-CoV-2 infection is distinct from other causes of ARI in this regard is unclear. We describe clinical characteristics and outcomes of South African children with SARS-CoV-2 and non-SARS-CoV-2 ARIs. METHODS: We performed a cross-sectional study including 0-13 years old children admitted to Tygerberg Hospital between May and December 2020 with an ARI. Routine clinical data were collected by the attending clinicians. All children underwent SARS-CoV-2 polymerase chain reaction testing. For severity of disease, the need for respiratory support and duration of support was considered. Multivariable logistic regression models were built to determine the factors associated with SARS-CoV-2 infection and severity. RESULTS: Data for 176 children were available, 38 (22%) children were SARS-CoV-2 polymerase chain reaction positive and 138 (78%) were negative. SARS-CoV-2 positive children were more likely to be female (OR: 2.68, 95% CI: 1.18-6.07), had lower weight-for-age Z score (OR: 0.76, 95% CI: 0.63-0.93), presented more frequently with fever (OR: 3.56, 95% CI: 1.54-8.24) and less often with cough (OR: 0.27, 95% CI: 0.11-0.66). SARS-CoV-2 infection was associated with significantly longer duration of oxygen treatment (median 8 vs. 3 days; OR: 1.1, 95% CI: 1.01-1.20). Overall, 66% of children had viral coinfection, with no significant difference between the groups. In total, 18% of SARS-CoV-2 positive children were readmitted within 3 months for a respiratory reason, compared with 15% SARS-CoV-2 negative children ( P = 0.64). CONCLUSIONS: Our data show that ARIs from SARS-CoV-2 cannot be easily differentiated, but were associated with a higher morbidity compared with ARIs from other causes. Overall outcomes were good. The long-term implications of severe SARS-CoV-2 pneumonia in young children in low- and middle-income countries require further study.

The Impact of SARS-CoV-2 Variants on the Clinical Phenotype and Severity of Multisystem Inflammatory Syndrome in Children in South Africa.

The effects of SARS-CoV-2 variants on disease phenotype and severity of multisystem inflammatory syndrome in children (MIS-C) are unknown. We compared the clinical phenotype of MIS-C in 129 South African children across four distinct (Ancestral type, Beta, Delta, and Omicron) variant-driven waves and found that MIS-C remains a severe disease with a stable clinical presentation, regardless of variant.

SARS-CoV-2 in children and their accompanying caregivers: Implications for testing strategies in resource limited hospitals.

Background: Identification of SARS-CoV-2 infected individuals is imperative to prevent hospital transmission, but symptom-based screening may fail to identify asymptomatic/mildly symptomatic infectious children and their caregivers. Methods: A COVID-19 period prevalence study was conducted between 13 and 26 August 2020 at Tygerberg Hospital, testing all children and their accompanying asymptomatic caregivers after initial symptom screening. One nasopharyngeal swab was submitted for SARS-CoV-2 using real-time reverse-transcription polymerase chain reaction (rRT-PCR). An additional Respiratory Viral 16-multiplex rRT-PCR test was simultaneously done in children presenting with symptoms compatible with possible SARS-CoV-2 infection. Results: SARS-Co-V 2 RT-PCR tests from 196 children and 116 caregivers were included in the analysis. The SARS-CoV-2 period prevalence in children was 5.6% (11/196) versus 15.5% (18/116) in asymptomatic caregivers (p<0.01). Presenting symptoms did not correlate with SARS-CoV-2 test positivity; children without typical symptoms of SARS-CoV-2 were more likely to be positive than those with typical symptoms (10.2% [10/99] vs 1% [1/97]; p<0.01). Children with typical symptoms (97/196; 49.5%) mainly presented with acute respiratory (68/97; 70.1%), fever (17/97; 17.5%), or gastro-intestinal complaints (12/97; 12.4%); Human Rhinovirus (23/81; 28.4%) and Respiratory Syncytial Virus (18/81; 22.2%) were frequently identified in this group. Children-caregiver pairs' SARS-CoV-2 tests were discordant in 83.3%; 15/18 infected caregivers' children tested negative. Symptom-based COVID-19 screening alone would have missed 90% of the positive children and 100% of asymptomatic but positive caregivers. Conclusion: Given the poor correlation between SARS-CoV-2 symptoms and RT-PCR test positivity, universal testing of children and their accompanying caregivers should be considered for emergency and inpatient paediatric admissions during high COVID-19 community transmission periods. Universal PPE and optimising ventilation is likely the most effective way to control transmission of respiratory viral infections, including SARS-CoV-2, where universal testing is not feasible. In these settings, repeated point prevalence studies may be useful to inform local testing and cohorting strategies.

Infants 21-90 days presenting with a possible serious bacterial infection - are evaluation algorithms from high income countries applicable in the South African public health sector?

BACKGROUND: Young infants with a possible serious bacterial infection (SBI) are a very common presentation to emergency centres (ECs). It is often difficult to distinguish clinically between self-limiting viral infections and an SBI. Available evaluation algorithms to assist clinicians are mostly from high-income countries. Data to inform clinical practice in low- and middle-income countries are lacking. OBJECTIVES: To determine the period prevalence of SBI and invasive bacterial infection (IBI) and describe current practice in the assessment and management of young infants aged 21-90 days presenting with a possible SBI to a Paediatric Emergency centre (PEC) in Cape Town, South Africa. METHODS: A retrospective cross-sectional review of infants 21-90 days old presenting to the Tygerberg Hospital PED between 1 January 2016 and 31 May 2016. RESULTS: A total of 248 infants 21-90 days were included in the study. Sixty-two patients (25%, 95% CI 20-30) had an SBI and 13 (5.2%, 95% CI 3-8) had an IBI. One hundred and sixty-five infants had a possible SBI based on WHO IMCI criteria. The sensitivity of the WHO IMCI criteria in detecting SBI was 82.3% (95% CI 70.5-90.8) and the specificity 38.7% (95% CI 31.7-46.1). More than half (51.2%) of the infants received antibiotics within the 48 h prior to presentation, of which 33.5% included intramuscular injection of Ceftriaxone. Only 20 (8.0%) patients in this age group were discharged home after initial evaluation. A significant relationship was noted between fever and the risk of SBI (p-value 0.010) and IBI (p-value 0.009). There also appeared to be a significant relationship between nutritional status and IBI (p-value 0.013). CONCLUSION: Period prevalence of SBI and IBI was higher compared to that published in the literature. Validated evaluation algorithms to stratify risk of SBI are needed to assist clinicians in diagnosing and managing infants appropriately in low- and middle-income settings.

Transient acetylcholine receptor-related myasthenia gravis, post multisystem inflammatory syndrome in children (MIS-C) temporally associated with COVID-19 infection.

We report on a unique case of a 7-year-old girl with new onset ocular myasthenia gravis shortly after recovery from multisystem inflammatory syndrome in children (MIS-C) temporally associated with SARS-CoV-2 infection. The diagnosis of myasthenia gravis was based on suggestive symptoms of fatigable bilateral orbital ptosis, diplopia, positive ocular cold compression test and serum acetylcholine receptor antibody positivity, as well as a favourable treatment response to pyridostigmine. The addition of corticosteroids and methotrexate resulted in complete resolution of the ocular signs.