Neurological Symptoms and Cause of Death Among Young Children in Low- and Middle-Income Countries.

Importance: The emergence of acute neurological symptoms in children necessitates immediate intervention. Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources. Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies. Objective: To characterize the association of premortem neurological symptoms and their management with postmortem-confirmed cause of death among children aged younger than 5 years in LMICs and to identify current gaps and improve strategies to enhance child survival. Design, Setting, and Participants: This cross-sectional study was conducted between December 3, 2016, and July 22, 2022, at the 7 participating sites in the Child Health and Mortality Prevention Surveillance (CHAMPS) network (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa). Minimally invasive tissue sampling was performed at the CHAMPS sites with specimens from deceased children aged younger than 5 years. This study included deceased children who underwent a premortem neurological evaluation and had a postmortem-confirmed cause of death. Data analysis was performed between July 22, 2022, and January 15, 2023. Main Outcomes and Measures: Descriptive analysis was performed using neurological evaluations from premortem clinical records and from postmortem determination of cause of death (based on histopathology, microbiological testing, clinical records, and verbal autopsies). Results: Of the 2127 deaths of children codified during the study period, 1330 (62.5%) had neurological evaluations recorded and were included in this analysis. The 1330 children had a median age of 11 (IQR, 2-324) days; 745 (56.0%) were male and 727 (54.7%) presented with neurological symptoms during illness before death. The most common postmortem-confirmed neurological diagnoses related to death were hypoxic events (308 [23.2%]), meningoencephalitis (135 [10.2%]), and cerebral malaria (68 [5.1%]). There were 12 neonates with overlapping hypoxic events and meningoencephalitis, but there were no patients with overlapping meningoencephalitis and cerebral malaria. Neurological symptoms were similar among diagnoses, and no combination of symptoms was accurate in differentiating them without complementary tools. However, only 25 children (18.5%) with meningitis had a lumbar puncture performed before death. Nearly 90% of deaths (442 of 511 [86.5%]) with neurological diagnoses in the chain of events leading to death were considered preventable. Conclusions and Relevance: In this cross-sectional study of children aged younger than 5 years, neurological symptoms were frequent before death. However, clinical phenotypes were insufficient to differentiate the most common underlying neurological diagnoses. The low rate of lumbar punctures performed was especially worrying, suggesting a challenge in quality of care of children presenting with neurological symptoms. Improved diagnostic management of neurological emergencies is necessary to ultimately reduce mortality in this vulnerable population.

Heparin-Binding Protein Stratifies Mortality Risk Among Ugandan Children Hospitalized With Respiratory Distress.

Background: Current prognostic tools do not reliably and objectively identify children with pneumonia at risk of a severe or life-threatening episode. Heparin-binding protein (HBP) is a host immune protein that is released in response to infection. We hypothesized that measuring HBP concentrations at hospital admission could help risk-stratify children with pneumonia and identify those at higher risk of an adverse prognosis. Methods: We evaluated the prognostic accuracy of HBP for predicting in-hospital mortality among children with respiratory distress, and whether HBP could improve the accuracy of validated composite clinical severity scores. Results: Of 778 Ugandan children under 5 years of age and presenting with clinically defined pneumonia, 60 (7.7%) died during hospital admission. HBP concentrations at presentation were significantly higher in children with fatal outcomes (median, 76 ng/mL [interquartile range {IQR}, 41-150]) compared to children who survived (median, 31 ng/mL [IQR, 18-57]) (P < .001). Children with HBP >41 ng/mL on admission had an elevated risk of death (hazard ratio, 5.3 [95% confidence interval {CI}, 2.9-9.5]; P < .0001). In receiver operating characteristic (ROC) curve analysis, HBP concentrations distinguished between fatal and nonfatal outcomes (area under the ROC curve, 0.75 [95% CI, .66-.84]) and significantly improved the prediction provided by the Respiratory Index of Severity in Children, a composite clinical severity score (P = .0026). Conclusions: Measuring HBP at presentation could help identify children at risk of severe and fatal pneumonia. Adding HBP to clinical scores could improve the recognition and triage of children with pneumonia at risk of death.

Detection of Enteric Viruses in Children under Five Years of Age before and after Rotavirus Vaccine Introduction in Manhiça District, Southern Mozambique, 2008-2019.

Enteric viruses are the leading cause of diarrhoea in children <5 years. Despite existing studies describing rotavirus diarrhoea in Mozambique, data on other enteric viruses remains scarce, especially after rotavirus vaccine introduction. We explored the prevalence of norovirus GI and GII, adenovirus 40/41, astrovirus, and sapovirus in children <5 years with moderate-to-severe (MSD), less severe (LSD) diarrhoea and community healthy controls, before (2008-2012) and after (2016-2019) rotavirus vaccine introduction in Manhiça District, Mozambique. The viruses were detected using ELISA and conventional reverse transcription PCR from stool samples. Overall, all of the viruses except norovirus GI were significantly more detected after rotavirus vaccine introduction compared to the period before vaccine introduction: norovirus GII in MSD (13/195, 6.7% vs. 24/886, 2.7%, respectively; p = 0.006) and LSD (25/268, 9.3% vs. 9/430, 2.1%, p < 0.001); adenovirus 40/41 in MSD (7.2% vs. 1.8%, p < 0.001); astrovirus in LSD (7.5% vs. 2.6%, p = 0.002); and sapovirus in MSD (7.1% vs. 1.4%, p = 0.047) and controls (21/475, 4.4% vs. 51/2380, 2.1%, p = 0.004). Norovirus GII, adenovirus 40/41, astrovirus, and sapovirus detection increased in MSD and LSD cases after rotavirus vaccine introduction, supporting the need for continued molecular surveillance for the implementation of appropriate control and prevention measures.

Clinicopathological discrepancies in the diagnoses of childhood causes of death in the CHAMPS network: An analysis of antemortem diagnostic inaccuracies.

INTRODUCTION: Determining aetiology of severe illness can be difficult, especially in settings with limited diagnostic resources, yet critical for providing life-saving care. Our objective was to describe the accuracy of antemortem clinical diagnoses in young children in high-mortality settings, compared with results of specific postmortem diagnoses obtained from Child Health and Mortality Prevention Surveillance (CHAMPS). METHODS: We analysed data collected during 2016-2022 from seven sites in Africa and South Asia. We compared antemortem clinical diagnoses from clinical records to a reference standard of postmortem diagnoses determined by expert panels at each site who reviewed the results of histopathological and microbiological testing of tissue, blood, and cerebrospinal fluid. We calculated test characteristics and 95% CIs of antemortem clinical diagnostic accuracy for the 10 most common causes of death. We classified diagnostic discrepancies as major and minor, per Goldman criteria later modified by Battle. RESULTS: CHAMPS enrolled 1454 deceased young children aged 1-59 months during the study period; 881 had available clinical records and were analysed. The median age at death was 11 months (IQR 4-21 months) and 47.3% (n=417) were female. We identified a clinicopathological discrepancy in 39.5% (n=348) of deaths; 82.3% of diagnostic errors were major. The sensitivity of clinician antemortem diagnosis ranged from 26% (95% CI 14.6% to 40.3%) for non-infectious respiratory diseases (eg, aspiration pneumonia, interstitial lung disease, etc) to 82.2% (95% CI 72.7% to 89.5%) for diarrhoeal diseases. Antemortem clinical diagnostic specificity ranged from 75.2% (95% CI 72.1% to 78.2%) for diarrhoeal diseases to 99.0% (95% CI 98.1% to 99.6%) for HIV. CONCLUSIONS: Antemortem clinical diagnostic errors were common for young children who died in areas with high childhood mortality rates. To further reduce childhood mortality in resource-limited settings, there is an urgent need to improve antemortem diagnostic capability through advances in the availability of diagnostic testing and clinical skills.

Coronavirus awareness and household hardship survey data for the CHAMPS HDSS network: Data collected between April 2021 and February 2022 in the Manhiça HDSS, Mozambique.

Data collection was implemented through an initiative by the Child Health and Mortality Prevention Surveillance (CHAMPS) Network to assess whether lockdowns and other social distancing policies during COVID-19 had implications for household economic status, maternal and child health, and healthcare accessibility for pregnant women and children. The data were collected from April 2021 until February 2022 from a population living in a rural community of Mozambique. This rural community is located within a Health and Demographic Surveillance System (HDSS) that operates in the Manhiça district of Maputo province. The survey instrument used for data collection was specifically designed to examine household awareness, knowledge, and prevalence of COVID-19; it was also designed to document hardships experienced by households during the pandemic period such as food insecurity, job losses and/or business closures of household members, and access to healthcare. The data are generalizable to a contiguous community in Manhiça, Mozambique of approximately 200,000 inhabitants.

Coronavirus awareness and household hardship survey data for the CHAMPS HDSS network: Data collected between April 2021 and February 2022 in the Manhiça HDSS, Mozambique

Data collection was implemented through an initiative by the Child Health and Mortality Prevention Surveillance (CHAMPS) Network to assess whether lockdowns and other social distancing policies during COVID-19 had implications for household economic status, maternal and child health, and healthcare accessibility for pregnant women and children. The data were collected from April 2021 until February 2022 from a population living in a rural community of Mozambique. This rural community is located within a Health and Demographic Surveillance System (HDSS) that operates in the Manhiça district of Maputo province. The survey instrument used for data collection was specifically designed to examine household awareness, knowledge, and prevalence of COVID-19; it was also designed to document hardships experienced by households during the pandemic period such as food insecurity, job losses and/or business closures of household members, and access to healthcare. The data are generalizable to a contiguous community in Manhiça, Mozambique of approximately 200,000 inhabitants.

Perceptions and compliance with COVID-19 preventive measures in Southern and Central regions of Mozambique: A quantitative in-person household survey in the districts of Manhiça and Quelimane

The COVID-19 pandemic has prompted countries to swiftly implement rigorous preventive measures on a population-wide scale worldwide. However, in low-income countries like Mozambique this was difficult, coupled with a generalised lack of knowledge on how the population understood and complied with these measures. This study assessed community perceptions and implementation of anti-COVID-19 measures recommended by Mozambican authorities in Manhiça and Quelimane districts, including confinement, social distancing, frequent handwashing, mask wearing, and quarantine as the key practices to evaluate. We conducted a cross-sectional quantitative survey in October 2020 and February 2021, interviewing heads of households, face-to-face. The data collected included self-evaluation of compliance and existence of handwashing facilities and face-masks in the households, aided by observations. We present descriptive statistics on perceptions and compliance at individual and household levels. Out of the 770 participants, nearly all (98.7%) were aware of Coronavirus disease, including the term COVID-19 (89.2%). Knowledge varied between districts, with Manhiça participants showing higher levels of sufficient ability to define the disease. The symptoms most mentioned were dry cough (17.8%), fever (15.7%), flu-like symptoms (14.2%), breathing difficulties (13.6%), and headache (13.1%). Participants recognized various transmission modes, including touching infected objects and inhaling infected air. Preventive measures like handwashing with soap or sanitizing hands with alcohol, wearing masks, and social distancing were acknowledged, but the understanding varied. Compliance with these measures was generally low, with fewer than half of respondents reporting adherence to them. Only 30.4% of households had handwashing facilities (of which only 41.0% had water), and masks were often limited to one per person aged 6 years or more. Community members in Manhica and Quelimane were aware of COVID-19 but had limited understanding of what the preventive measures meant, and had lower levels of compliance. Understanding and addressing the factors affecting the proper implementation of these measures is crucial for improving community adherence in preventing infectious diseases with epidemic potential.The COVID-19 pandemic has prompted countries to swiftly implement rigorous preventive measures on a population-wide scale worldwide. However, in low-income countries like Mozambique this was difficult, coupled with a generalised lack of knowledge on how the population understood and complied with these measures. This study assessed community perceptions and implementation of anti-COVID-19 measures recommended by Mozambican authorities in Manhiça and Quelimane districts, including confinement, social distancing, frequent handwashing, mask wearing, and quarantine as the key practices to evaluate. We conducted a cross-sectional quantitative survey in October 2020 and February 2021, interviewing heads of households, face-to-face. The data collected included self-evaluation of compliance and existence of handwashing facilities and face-masks in the households, aided by observations. We present descriptive statistics on perceptions and compliance at individual and household levels. Out of the 770 participants, nearly all (98.7%) were aware of Coronavirus disease, including the term COVID-19 (89.2%). Knowledge varied between districts, with Manhiça participants showing higher levels of sufficient ability to define the disease. The symptoms most mentioned were dry cough (17.8%), fever (15.7%), flu-like symptoms (14.2%), breathing difficulties (13.6%), and headache (13.1%). Participants recognized various transmission modes, including touching infected objects and inhaling infected air. Preventive measures like handwashing with soap or sanitizing hands with alcohol, wearing masks, and social distancing were acknowledged, but the understanding varied. Compliance with these measures was generally low, with fewer than half of respondents reporting adherence to them. Only 30.4% of households had handwashing facilities (of which only 41.0% had water), and masks were often limited to one per person aged 6 years or more. Community members in Manhica and Quelimane were aware of COVID-19 but had limited understanding of what the preventive measures meant, and had lower levels of compliance. Understanding and addressing the factors affecting the proper implementation of these measures is crucial for improving community adherence in preventing infectious diseases with epidemic potential.

Perceptions and compliance with COVID-19 preventive measures in Southern and Central regions of Mozambique: A quantitative in-person household survey in the districts of Manhiça and Quelimane.

The COVID-19 pandemic has prompted countries to swiftly implement rigorous preventive measures on a population-wide scale worldwide. However, in low-income countries like Mozambique this was difficult, coupled with a generalised lack of knowledge on how the population understood and complied with these measures. This study assessed community perceptions and implementation of anti-COVID-19 measures recommended by Mozambican authorities in Manhiça and Quelimane districts, including confinement, social distancing, frequent handwashing, mask wearing, and quarantine as the key practices to evaluate. We conducted a cross-sectional quantitative survey in October 2020 and February 2021, interviewing heads of households, face-to-face. The data collected included self-evaluation of compliance and existence of handwashing facilities and face-masks in the households, aided by observations. We present descriptive statistics on perceptions and compliance at individual and household levels. Out of the 770 participants, nearly all (98.7%) were aware of Coronavirus disease, including the term COVID-19 (89.2%). Knowledge varied between districts, with Manhiça participants showing higher levels of sufficient ability to define the disease. The symptoms most mentioned were dry cough (17.8%), fever (15.7%), flu-like symptoms (14.2%), breathing difficulties (13.6%), and headache (13.1%). Participants recognized various transmission modes, including touching infected objects and inhaling infected air. Preventive measures like handwashing with soap or sanitizing hands with alcohol, wearing masks, and social distancing were acknowledged, but the understanding varied. Compliance with these measures was generally low, with fewer than half of respondents reporting adherence to them. Only 30.4% of households had handwashing facilities (of which only 41.0% had water), and masks were often limited to one per person aged 6 years or more. Community members in Manhica and Quelimane were aware of COVID-19 but had limited understanding of what the preventive measures meant, and had lower levels of compliance. Understanding and addressing the factors affecting the proper implementation of these measures is crucial for improving community adherence in preventing infectious diseases with epidemic potential.

Dataset of acute respiratory infections: Epidemiological and etiological data from a cohort of 801 Moroccan children.

Acute respiratory infections remain a leading cause of death among young children in low- and middle-income countries. The etiological diagnosis of these infections is challenging due to the similarity in clinical presentations and overlapping symptoms caused by various pathogens. This database provides comprehensive epidemiological, clinical, paraclinical, and biological data on 801 Moroccan children admitted to the Children's Hospital of Rabat for the management of Clinical Severe Pneumonia. Identification of the pathogens responsible of respiratory infections was carried out using blood samples for hemoculture, standard bacterial culture and multiplex RT-PCR using the TrueScience RespiFinder Pathogen Identification Panel (Applied Biosystems).

Long-term healthcare utilisation, costs and quality of life after invasive group B Streptococcus disease: a cohort study in five low-income and middle-income countries.

INTRODUCTION: There are no published data on the long-term impact of invasive group B Streptococcus disease (iGBS) on economic costs or health-related quality of life (HRQoL) in low-income and middle-income countries. We assessed the impact of iGBS on healthcare utilisation, costs and HRQoL in Argentina, India, Kenya, Mozambique and South Africa. METHODS: Inpatient and outpatient visits, out-of-pocket (OOP) healthcare payments in the 12 months before study enrolment, and health-state utility of children and caregivers (using the EuroQol 5-Dimensions-3-Level) were collected from iGBS survivors and an unexposed cohort matched on site, age at recruitment and sex. We used logistic or Poisson regression for analysing healthcare utilisation and zero-inflated gamma regression models for family and health system costs. For HRQoL, we used a zero-inflated beta model of disutility pooled data. RESULTS: 161 iGBS-exposed and 439 unexposed children and young adults (age 1-20) were included in the analysis. Compared with unexposed participants, iGBS was associated with increased odds of any healthcare utilisation in India (adjusted OR 11.2, 95% CI 2.9 to 43.1) and Mozambique (6.8, 95% CI 2.2 to 21.1) and more frequent healthcare visits (adjusted incidence rate ratio (IRR) for India 1.7 (95% CI 1.4 to 2.2) and for Mozambique 6.0 (95% CI 3.2 to 11.2)). iGBS was also associated with more frequent days in inpatient care in India (adjusted IRR 4.0 (95% CI 2.3 to 6.8) and Kenya 6.4 (95% CI 2.9 to 14.3)). OOP payments were higher in the iGBS cohort in India (adjusted mean: Int$682.22 (95% CI Int$364.28 to Int$1000.16) vs Int$133.95 (95% CI Int$72.83 to Int$195.06)) and Argentina (Int$244.86 (95% CI Int$47.38 to Int$442.33) vs Int$52.38 (95% CI Int$-1.39 to Int$106.1)). For all remaining sites, differences were in the same direction but not statistically significant for almost all outcomes. Health-state disutility was higher in iGBS survivors (0.08, 0.04-0.13 vs 0.06, 0.02-0.10). CONCLUSION: The iGBS health and economic burden may persist for years after acute disease. Larger studies are needed for more robust estimates to inform the cost-effectiveness of iGBS prevention.

Innovative strategies for the surveillance, prevention, and management of pediatric infections applied to low-income settings.

INTRODUCTION: Infectious diseases still cause a significant burden of morbidity and mortality among children in low- and middle-income countries (LMICs). There are ample opportunities for innovation in surveillance, prevention, and management, with the ultimate goal of improving survival. AREAS COVERED: This review discusses the current status in the use and development of innovative strategies for pediatric infectious diseases in LMICs by focusing on surveillance, diagnosis, prevention, and management. Topics covered are: Minimally Invasive Tissue Sampling as a technique to accurately ascertain the cause of death; Genetic Surveillance to trace the pathogen genomic diversity and emergence of resistance; Artificial Intelligence as a multidisciplinary tool; Portable noninvasive imaging methods; and Prognostic Biomarkers to triage and risk stratify pediatric patients. EXPERT OPINION: To overcome the specific hurdles in child health for LMICs, some innovative strategies appear at the forefront of research. If the development of these next-generation tools remains focused on accessibility, sustainability and capacity building, reshaping epidemiological surveillance, diagnosis, and treatment in LMICs, can become a reality and result in a significant public health impact. Their integration with existing healthcare infrastructures may revolutionize disease detection and surveillance, and improve child health and survival.

Net benefit of smaller human populations to environmental integrity and individual health and wellbeing.

Introduction: The global human population is still growing such that our collective enterprise is driving environmental catastrophe. Despite a decline in average population growth rate, we are still experiencing the highest annual increase of global human population size in the history of our species-averaging an additional 84 million people per year since 1990. No review to date has accumulated the available evidence describing the associations between increasing population and environmental decline, nor solutions for mitigating the problems arising. Methods: We summarize the available evidence of the relationships between human population size and growth and environmental integrity, human prosperity and wellbeing, and climate change. We used PubMed, Google Scholar, and Web of Science to identify all relevant peer-reviewed and gray-literature sources examining the consequences of human population size and growth on the biosphere. We reviewed papers describing and quantifying the risks associated with population growth, especially relating to climate change. Results: These risks are global in scale, such as greenhouse-gas emissions, climate disruption, pollution, loss of biodiversity, and spread of disease-all potentially catastrophic for human standards of living, health, and general wellbeing. The trends increasing the risks of global population growth are country development, demographics, maternal education, access to family planning, and child and maternal health. Conclusion: Support for nations still going through a demographic transition is required to ensure progress occurs within planetary boundaries and promotes equity and human rights. Ensuring the wellbeing for all under this aim itself will lower population growth and further promote environmental sustainability.

Diagnosis of human leptospirosis: systematic review and meta-analysis of the diagnostic accuracy of the Leptospira microscopic agglutination test, PCR targeting Lfb1, and IgM ELISA to Leptospira fainei serovar Hurstbridge.

BACKGROUND: Leptospirosis is an underdiagnosed infectious disease with non-specific clinical presentation that requires laboratory confirmation for diagnosis. The serologic reference standard remains the microscopic agglutination test (MAT) on paired serum samples. However, reported estimates of MAT's sensitivity vary. We evaluated the accuracy of four index tests, MAT on paired samples as well as alternative standards for leptospirosis diagnosis: MAT on single acute-phase samples, polymerase chain reaction (PCR) with the target gene Lfb1, and ELISA IgM with Leptospira fainei serovar Hurstbridge as an antigen. METHODS: We performed a systematic review of studies reporting results of leptospirosis diagnostic tests. We searched eight electronic databases and selected studies that tested human blood samples and compared index tests with blood culture and/or PCR and/or MAT (comparator tests). For MAT selection criteria we defined a threshold for single acute-phase samples according to a national classification of leptospirosis endemicity. We used a Bayesian random-effect meta-analysis to estimate the sensitivity and specificity of MAT in single acute-phase and paired samples separately, and assessed risk of bias using the Quality Assessment of Studies of Diagnostic Accuracy Approach- 2 (QUADAS-2) tool. RESULTS: For the MAT accuracy evaluation, 15 studies were included, 11 with single acute-phase serum, and 12 with paired sera. Two included studies used PCR targeting the Lfb1 gene, and one included study used IgM ELISA with Leptospira fainei serovar Hurstbridge as antigen. For MAT in single acute-phase samples, the pooled sensitivity and specificity were 14% (95% credible interval [CrI] 3-38%) and 86% (95% CrI 59-96%), respectively, and the predicted sensitivity and specificity were 14% (95% CrI 0-90%) and 86% (95% CrI 9-100%). Among paired MAT samples, the pooled sensitivity and specificity were 68% (95% CrI 32-92%) and 75% (95% CrI 45-93%) respectively, and the predicted sensitivity and specificity were 69% (95% CrI 2-100%) and 75% (2-100%). CONCLUSIONS: Based on our analysis, the accuracy of MAT in paired samples was not high, but it remains the reference standard until a more accurate diagnostic test is developed. Future studies that include larger numbers of participants with paired samples will improve the certainty of accuracy estimates.