The burden of poisoning in children hospitalised at a tertiary-level hospital in South Africa.

Introduction: Globally, childhood poisoning, accounts for a significant proportion of emergency department admissions. There is a paucity of data from low- and middle-income countries on poisoning in children. Objective: To describe the incidence, case fatality rate, and types of poisoning in children admitted to a tertiary-level hospital in Johannesburg, South Africa. Methods: This was a retrospective descriptive study of children hospitalised with poisoning from January 2016 to December 2021 at Chris Hani Baragwanath Academic Hospital. Children were identified from a discharge summary database using ICD-10 codes that describe poisoning. Trends in incidence of poison exposure were reported. Results: Of the 60,901 admissions during the study period, 2,652 (4.4%) children were diagnosed with poisoning. Most (71.3%) children were less than 5 years of age and 55% were male. The incidence of poisoning per 100,000 was highest at 108.4 (95% CI: 104.3-112.6) in 2019 and decreased to 77.3 (95% CI: 73.9-80.7) in 2020 and 59.6 (95% CI: 56.3-62.5) in 2021. Main causes of poisoning were organic solvents (37.6%), medications (32.9%), and pesticides (17.5%). The overall case fatality rate was 2.1%. In a multivariate analysis, poisoning secondary to pesticides (aOR: 13.9; 95% CI: 4.52-60.8; p < 0.001), and unspecified agents (aOR: 12.7; 95% CI: 3.27-62.8; p < 0.001) were associated with an increased odds of death. Conclusion: We report a high prevalence of poisoning in children hospitalised in this tertiary-level hospital in South Africa. Public health measures to reduce the burden of organic solvents, medications and pesticide poisoning are urgently warranted.

All-cause and pathogen-specific lower respiratory tract infection hospital admissions in children younger than 5 years during the COVID-19 pandemic (2020-22) compared with the pre-pandemic period (2015-19) in South Africa: an observational study.

BACKGROUND: Non-pharmaceutical interventions affected the circulation of and illness due to endemic respiratory pathogens during the COVID-19 pandemic. We investigated the incidence of admissions to hospital for overall and specific pathogen-associated lower respiratory tract infection (LRTI) during the COVID-19 pandemic compared with incidence in the pre-pandemic period. METHODS: In this observational study, we analysed surveillance data for children younger than 5 years from two public hospitals in Soweto, South Africa, for all-cause LRTI, respiratory syncytial virus (RSV), influenza, human metapneumovirus, and Bordetella pertussis from Jan 1, 2015 to Dec 31, 2022. Data were obtained from an electronic database that includes information for all admissions to the general paediatric wards at the two hospitals, automatically identified by a computer program. We excluded children admitted to hospital with incidental SARS-CoV-2 infection or COVID-19 without LRTI diagnosis. Incidence during COVID-19 pandemic years (2020, 2021, and 2022) were compared with pre-pandemic rates (2015-19). FINDINGS: Overall, there were 42 068 all-cause hospital admissions, including 18 303 all-cause LRTI hospital admissions, from Jan 1, 2015, to Dec 31, 2022, 17 822 (42·4%) of whom were female, 23 893 (57·0%) were male, and 353 (0·8%) had missing data. All-cause LRTI incidence risk ratio (IRR) was 30% lower in 2020 (IRR 0·70, 95% CI 0·67-0·74) and 13% lower in 2021 (0·87, 0·83-0·91), but 16% higher in 2022 (1·16, 1·11-1·21) compared with the pre-pandemic period. Furthermore, compared with the pre-pandemic period, incidence of RSV-associated LRTI (0·52, 0·45-0·58), influenza-associated LRTI (0·05, 0·02-0·11), and pulmonary tuberculosis (0·52, 0·41-0·65) were lower in 2020, with similar trends observed for human-metapneumovirus-associated LRTI, pertussis, and invasive pneumococcal disease (IPD). Compared with the pre-pandemic period, by 2022, RSV-associated LRTI incidence was similar (1·04, 0·95-1·14) and influenza-associated LRTI showed a non-significant increase (1·14, 0·92-1·39), whereas incidence remained lower for tuberculosis (0·79, 0·65-0·94) and IPD (0·51, 0·24-0·99). In 2022, the incidence of COVID-19-associated LRTI hospital admission (65 per 100 000 children younger than 5 years) was lower than pre-pandemic RSV-associated LRTI (0·23, 0·19-0·27) but higher than pre-pandemic influenza-associated LRTI (1·19, 0·97-1·45), although the difference was not significant. All-cause LRTI death in 2022 (57 per 100 000 children younger than 5 years) was 28% higher than in the pre-pandemic period (1·28, 1·03-1·58). INTERPRETATION: The higher incidence of all-cause LRTI admissions to hospital in 2022 compared with the pre-pandemic period is partly due to ongoing COVID-19 admission to hospital, and could worsen if other endemic respiratory pathogens revert to pre-pandemic incidence. Interventions, including the introduction of vaccines for people who are pregnant that aim to prevent RSV and possibly COVID-19 in young children, are warranted. FUNDING: The Bill & Melinda Gates Foundation.

The association between early-onset sepsis and neonatal encephalopathy.

OBJECTIVE: We evaluated the association between early-onset sepsis and neonatal encephalopathy in a low-middle-income setting. METHODS: We undertook a retrospective study in newborns with gestational age ≥35 weeks and/or birth weight ≥2500 grams, diagnosed with neonatal encephalopathy. Early-onset sepsis was defined as culture-confirmed sepsis or probable sepsis. RESULTS: Of 10,182 hospitalised newborns, 1027 (10.1%) were diagnosed with neonatal encephalopathy, of whom 52 (5.1%) had culture-confirmed and 129 (12.5%) probable sepsis. The case fatality rate for culture-confirmed sepsis associated neonatal encephalopathy was threefold higher compared to neonatal encephalopathy without sepsis (30.8% vs. 10.5%, p < 0.001). Predictors of mortality for culture-confirmed sepsis associated neonatal encephalopathy included severe neonatal encephalopathy (aOR 6.51, 95%CI: 1.03-41.44) and seizures (aOR 10.64, 95%CI: 1.05-107.39). CONCLUSION: In this setting, 5% of neonatal encephalopathy cases was associated with culture-confirmed sepsis and a high case fatality rate.

Potential of Minimally Invasive Tissue Sampling for Attributing Specific Causes of Childhood Deaths in South Africa: A Pilot, Epidemiological Study.

BACKGROUND: Current estimates for causes of childhood deaths are mainly premised on modeling of vital registration and limited verbal autopsy data and generally only characterize the underlying cause of death (CoD). We investigated the potential of minimally invasive tissue sampling (MITS) for ascertaining the underlying and immediate CoD in children 1 month to 14 years of age. METHODS: MITS included postmortem tissue biopsies of brain, liver, and lung for histopathology examination; microbial culture of blood, cerebrospinal fluid (CSF), liver, and lung samples; and molecular microbial testing on blood, CSF, lung, and rectal swabs. Each case was individually adjudicated for underlying, antecedent, and immediate CoD by an international multidisciplinary team of medical experts and coded using the International Classification of Diseases, Tenth Revision (ICD-10). RESULTS: An underlying CoD was determined for 99% of 127 cases, leading causes being congenital malformations (18.9%), complications of prematurity (14.2%), human immunodeficiency virus/AIDS (12.6%), diarrheal disease (8.7%), acute respiratory infections (7.9%), injuries (7.9%), and malignancies (7.1%). The main immediate CoD was pneumonia, sepsis, and diarrhea in 33.9%, 19.7%, and 10.2% of cases, respectively. Infection-related deaths were either an underlying or immediate CoD in 78.0% of cases. Community-acquired pneumonia deaths (n = 32) were attributed to respiratory syncytial virus (21.9%), Pneumocystis jirovecii (18.8%), cytomegalovirus (15.6%), Klebsiella pneumoniae (15.6%), and Streptococcus pneumoniae (12.5%). Seventy-one percent of 24 sepsis deaths were hospital-acquired, mainly due to Acinetobacter baumannii (47.1%) and K. pneumoniae (35.3%). Sixty-two percent of cases were malnourished. CONCLUSIONS: MITS, coupled with antemortem clinical information, provides detailed insight into causes of childhood deaths that could be informative for prioritization of strategies aimed at reducing under-5 mortality.

An Observational Pilot Study Evaluating the Utility of Minimally Invasive Tissue Sampling to Determine the Cause of Stillbirths in South African Women.

BACKGROUND: Despite approximately 2.6 million stillbirths occurring annually, there is a paucity of systematic biological investigation and consequently knowledge on the causes of these deaths in low- and middle-income countries (LMICs). We investigated the utility of minimally invasive tissue sampling (MITS), placental examination, and clinical history, in attributing the causes of stillbirth in a South African LMIC setting. METHODS: This prospective, observational pilot study undertook sampling of brain, lung, and liver tissue using core biopsy needles, blood and cerebrospinal fluid collection, and placental examination. Testing included microbial culture and/or molecular testing and tissue histological examination. The cause of death was determined for each case by an international panel of medical specialists and categorized using the World Health Organization's International Classification of Diseases, Tenth Revision application to perinatal deaths. RESULTS: A cause of stillbirth was identifiable for 117 of 129 (90.7%) stillbirths, including an underlying maternal cause in 63.4% (n = 83) and an immediate fetal cause in 79.1% (n = 102) of cases. The leading underlying causes of stillbirth were maternal hypertensive disorders (16.3%), placental separation and hemorrhage (14.0%), and chorioamnionitis (10.9%). The leading immediate causes of fetal death were antepartum hypoxia (35.7%) and fetal infection (37.2%), including due to Escherichia coli (16.3%), Enterococcus species (3.9%), and group B Streptococcus (3.1%). CONCLUSIONS: In this pilot, proof-of-concept study, focused investigation of stillbirth provided granular detail on the causes thereof in an LMIC setting, including provisionally highlighting the largely underrecognized role of fetal sepsis as a dominant cause.

Unraveling Specific Causes of Neonatal Mortality Using Minimally Invasive Tissue Sampling: An Observational Study.

BACKGROUND: Postmortem minimally invasive tissue sampling (MITS) is a potential alternative to the gold standard complete diagnostic autopsy for identifying specific causes of childhood deaths. We investigated the utility of MITS, interpreted with available clinical data, for attributing underlying and immediate causes of neonatal deaths. METHODS: This prospective, observational pilot study enrolled neonatal deaths at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. The MITS included needle core-biopsy sampling for histopathology of brain, lung, and liver tissue. Microbiological culture and/or molecular tests were performed on lung, liver, blood, cerebrospinal fluid, and stool samples. The "underlying" and "immediate" causes of death (CoD) were determined for each case by an international panel of 12-15 medical specialists. RESULTS: We enrolled 153 neonatal deaths, 106 aged 3-28 days. Leading underlying CoD included "complications of prematurity" (52.9%), "complications of intrapartum events" (15.0%), "congenital malformations" (13.1%), and "infection related" (9.8%). Overall, infections were the immediate or underlying CoD in 57.5% (n = 88) of all neonatal deaths, including the immediate CoD in 70.4% (58/81) of neonates with "complications of prematurity" as the underlying cause. Overall, 74.4% of 90 infection-related deaths were hospital acquired, mainly due to multidrug-resistant Acinetobacter baumannii (52.2%), Klebsiella pneumoniae (22.4%), and Staphylococcus aureus (20.9%). Streptococcus agalactiae was the most common pathogen (5/15 [33.3%]) among deaths with "infections" as the underlying cause. CONCLUSIONS: MITS has potential to address the knowledge gap on specific causes of neonatal mortality. In our setting, this included the hitherto underrecognized dominant role of hospital-acquired multidrug-resistant bacterial infections as the leading immediate cause of neonatal deaths.

The Burden of Acute Diarrheal Disease in Young Hospitalized Urban South African Children Five Years After Rotavirus Vaccine Introduction: A Retrospective Descriptive Study.

BACKGROUND: Diarrheal disease is a leading cause of childhood morbidity and mortality worldwide. Multiple interventions, including rotavirus vaccination to infants since 2009, have reduced the incidence of diarrheal disease in South African children. Our study aimed to determine the burden of diarrheal disease 5 years after rotavirus vaccine introduction at a tertiary-level hospital. METHODS: A retrospective review of a discharge summary database of children less than 5 years of age hospitalized with acute diarrheal illness from 2015 to 2016 at the Chris Hani Baragwanath Academic Hospital. RESULTS: Diarrheal disease accounted for 14.8% of hospital admissions. The incidence (per 100,000 population) was 675.8 (95% CI: 638.8-714.3) in 2015 and 612.2 (95% CI: 577.0-648.9) in 2016. The case fatality ratio was 2.9% over the study period. The median age at diagnosis was 12 months (interquartile range: 6.2-21.4) and 50.4% of cases occurred during infancy. One third of cases were underweight and/or stunted. In a multivariable analysis using logistic regression, the adjusted odds ratio (aOR) for death was higher in children with an associated acute lower respiratory tract infection (aOR: 3.7, 95% CI: 1.2-11.5; P = 0.021), HIV infection (aOR: 9.1, 95% CI: 2.6-31.6; P = 0.001), and an age of less than 6 months (aOR: 6.9, 95% CI: 2.1-22.9; P = 0.002). CONCLUSIONS: Sustained reductions in diarrheal disease incidence were observed 5 years post rotavirus vaccine implementation. In children hospitalized with an acute diarrheal illness, an increased risk of mortality occurs in young infants, children that are HIV infected, and those with an associated acute lower respiratory tract infection.

Pneumococcal conjugate vaccines and hospitalization of children for pneumonia: a time-series analysis, South Africa, 2006-2014.

OBJECTIVE: To assess the impact of immunization with pneumococcal conjugate vaccines on all-cause pneumonia hospitalizations among children in Soweto, South Africa. METHODS: We used data collected at the Chris Hani Baragwanath Hospital in Soweto between 2006 and 2014 - i.e. before and after April 2009, when a pneumococcal conjugate vaccine was first included in South Africa's routine immunization programme. Using a Bayesian generalized seasonal autoregressive moving-average model and the data collected in 2006-2008, we estimated the numbers of children that would have been hospitalized for pneumonia between 2010 and 2014 if no pneumococcal conjugate vaccines had been used. These estimates were then compared with the corresponding numbers of hospitalizations observed. FINDINGS: Between 2006 and 2014, 26 778 children younger than five years - including 3388 known to be infected with human immunodeficiency virus (HIV) - were admitted to the study hospital for pneumonia. We estimated that, for the children known to be infected with HIV and for the other children, pneumococcal conjugate vaccines reduced the numbers of hospitalizations for pneumonia in 2014 by 33% (50% credible interval, CrI: 6 to 52) and 39% (50% CrI: 24 to 50), respectively. In the study hospital in 2012-2014, as a result of immunizations with these vaccines, there were an estimated 3100 fewer pneumonia hospitalizations of children younger than five years. CONCLUSION: In our study hospital, following the introduction of pneumococcal conjugate vaccines into the national immunization programme, there were significant reductions in pneumonia hospitalizations among children.

Pneumococcal conjugate vaccines and hospitalization of children for pneumonia: a time-series analysis, South Africa, 2006­2014

Objective To assess the impact of immunization with pneumococcal conjugate vaccines on all-cause pneumonia hospitalizations among children in Soweto, South Africa. Methods We used data collected at the Chris Hani Baragwanath Hospital in Soweto between 2006 and 2014 ­ i.e. before and after April 2009, when a pneumococcal conjugate vaccine was first included in South Africa's routine immunization programme. Using a Bayesian generalized seasonal autoregressive moving-average model and the data collected in 2006­2008, we estimated the numbers of children that would have been hospitalized for pneumonia between 2010 and 2014 if no pneumococcal conjugate vaccines had been used. These estimates were then compared with the corresponding numbers of hospitalizations observed. Findings Between 2006 and 2014, 26 778 children younger than five years ­ including 3388 known to be infected with human immunodeficiency virus (HIV) ­ were admitted to the study hospital for pneumonia. We estimated that, for the children known to be infected with HIV and for the other children, pneumococcal conjugate vaccines reduced the numbers of hospitalizations for pneumonia in 2014 by 33% (50% credible interval, CrI: 6 to 52) and 39% (50% CrI: 24 to 50), respectively. In the study hospital in 2012­2014, as a result of immunizations with these vaccines, there were an estimated 3100 fewer pneumonia hospitalizations of children younger than five years. Conclusion. In our study hospital, following the introduction of pneumococcal conjugate vaccines into the national immunization programme, there were significant reductions in pneumonia hospitalizations among children

Temporal Association of Rotavirus Vaccine Introduction and Reduction in All-Cause Childhood Diarrheal Hospitalizations in South Africa.

BACKGROUND: The public health impact of rotavirus vaccination in African settings with a high human immunodeficiency virus (HIV) infection prevalence is yet to be established. We evaluated trends in all-cause diarrheal hospitalizations in Soweto, Johannesburg, before and after the introduction of rotavirus vaccine into South Africa's national immunization program in August 2009. METHODS: Hospitalizations in children <5 years of age with a diagnosis of diarrhea, defined byInternational Classification of Diseases, Tenth Revisioncodes A00-A05, A06.0-A06.3, A06.9, A07.0-A07.2, A07.9, and A08-A09, were identified at the Chris Hani Baragwanath Academic Hospital from 1 January 2006 to 31 December 2014. The median annual prevaccine (2006-2008) hospitalization incidence was compared to that of the vaccine era (2010-2014), and stratified by age group and HIV infection status. RESULTS: Incidence reductions (per 1000 population) were greatest in children aged <12 months: 54.4 in the prevaccine era vs 30.0, 23.6, 20.0, 18.8, and 18.9 in the postvaccine years 2010-2014, respectively (a 44.9%-65.4% reduction). Lower incidence reductions (39.8%-49.4%) were observed among children aged 12-24 months from the second year post-vaccine introduction onward. Reductions were observed in both HIV-infected and HIV-uninfected children. There was a change in the seasonal pattern of diarrheal hospitalizations post-vaccine introduction, with flattening of the autumn-winter peaks seen in the prevaccine years. CONCLUSIONS: An accelerated and sustained decline in all-cause diarrheal hospitalizations, temporally associated with rotavirus vaccine introduction, was observed in children <2 years of age. However, the impact of other interventions such as improved sanitation and changes in HIV management cannot be discounted.

Temporal association in hospitalizations for tuberculosis, invasive pneumococcal disease and influenza virus illness in South African children.

INTRODUCTION: The seasonal variability in hospitalization for tuberculosis may in part relate to super-imposed bacterial or predisposing respiratory viral infections. We aimed to study the temporal association between hospitalization for culture-confirmed pulmonary tuberculosis (PTB), invasive pneumococcal disease (IPD) and influenza virus epidemics in South African children. METHODS: We undertook a retrospective analysis which examined seasonal trends, from 2005 to 2008, for hospitalization for culture-confirmed PTB and IPD among children in relation to the influenza epidemics in Soweto, South Africa. Original time-series of the influenza virus epidemics and hospitalization rates for PTB and IPD were decomposed into three components: a trend cycle component, a seasonal component and an irregular component using the X-11 seasonal adjustment method. To compare the seasonality amongst the three series, the trend and irregular components were removed and only seasonal components examined. RESULTS: Across the study period, the influenza virus epidemics peaked during May to July (winter) months, which was closely followed by an increase in the incidence of hospitalization for IPD (August to October) and PTB (August to November). DISCUSSION: Within- and between-year temporal changes associated with childhood TB hospitalization may in part be driven by factors which influence temporal changes in pneumococcal disease, including potential variability in the severity of influenza virus epidemics in temperate climates. The dynamics of the interplay between the host and these infectious agents appears to be complex and multifactorial.

Impact of the antiretroviral treatment program on the burden of hospitalization for culture-confirmed tuberculosis in South African children: a time-series analysis.

BACKGROUND: The HIV epidemic increased the burden of tuberculosis (TB) in sub-Saharan Africa. We evaluated the impact that scaling-up of the public-funded antiretroviral treatment (ART) program had on incidence of hospitalization for culture-confirmed and overall-TB in HIV-infected and HIV-uninfected children from 2005 to 2009. METHODS: The study was undertaken in Soweto, South Africa, where ART coverage of HIV-infected children increased from 43% in 2005 to 84% by 2009. Trends in incidence of hospitalization for clinically diagnosed and culture-confirmed TB in children 3 months to <15 years of age, identified through laboratory and electronic databases, were analyzed by comparing crude incidence and regression analysis. RESULTS: The incidence (per 100,000) of culture-confirmed TB declined by 63.1% from 2005 (69.8) compared with 2009 (25.8; P < 0.0001). This included a 70.6% reduction between 2005 and 2009 among HIV-infected children (incidence: 1566.3 versus 460.7, respectively; P < 0.0001) and 41.3% decrease in HIV-uninfected children (18.7 versus 11.0, respectively; P = 0.0003). The month-by-month rate of decline of culture-confirmed TB was 2.3% in HIV-infected and 1.1% in HIV-uninfected children over the study period. The residual burden of TB remained 42-fold greater in HIV-infected children, 78% of whom were severely immune compromised, compared with HIV-uninfected children by 2009. CONCLUSION: Increase in ART coverage was associated with significant decline in TB hospitalizations in HIV-infected children. This reduction may also in part have been due to reduced Mycobacterium tuberculosis transmission resulting from increased ART access among HIV-infected adults, which may have contributed to the reduction of culture-confirmed TB in HIV-uninfected children.