Derivation and Internal Validation of a Novel Risk Assessment Tool to Identify Infants and Young Children at Risk for Post-Discharge Mortality in Dar es Salaam, Tanzania and Monrovia, Liberia.

OBJECTIVE: To derive and validate internally a novel risk assessment tool to identify young children at risk for all-cause mortality ≤60 days of discharge from hospitals in sub-Saharan Africa. STUDY DESIGN: We performed a prospective observational cohort study of children aged 1-59 months discharged from Muhimbili National Hospital in Dar es Salaam, Tanzania and John F. Kennedy Medical Center in Monrovia, Liberia (2019 to 2022). Caregivers received telephone calls up to 60 days after discharge to ascertain participant vital status. We collected socioeconomic, demographic, clinical, and anthropometric data during hospitalization. Candidate variables with P<0.20 in bivariate analyses were included in a multivariable logistic regression model with best subset selection to identify risk factors for the outcome. We internally validated our tool using bootstrapping with 500 repetitions. RESULTS: There were 1,933 young children enrolled in the study. The median (interquartile range) age was 11 (4, 23) months and 58.7% were male. In total, 67 (3.5%) died during follow-up. Ten variables contributed to our tool (total possible score 82). Cancer (adjusted odds ratio [aOR] 10.6, 95% CI 2.58, 34.6), pedal edema (aOR 6.94, 95% CI 1.69, 22.6), and leaving against medical advice (aOR 6.46, 95% CI 2.46, 15.3) were most predictive of post-discharge mortality. Our risk assessment tool demonstrated good discriminatory value (optimism corrected area under the receiver operating characteristic curve 0.77), high precision, and sufficient calibration. CONCLUSIONS: After validation, this tool may be used to identify young children at risk for post-discharge mortality to direct resources for follow-up of high-risk children.

Enteric viral pathogens and child growth among under-five children: findings from South Asia and sub-Saharan Africa.

Enteric viral pathogens are associated with a significant burden of childhood morbidity and mortality. We investigated the relationship between viral pathogens and child growth among under-5 children. We analyzed data from 5572/22,567 children enrolled in the Global Enteric Multicenter Study across seven study sites (2007-2011). Multiple linear regression was used to examine the association between the viral pathogens and changes of length/height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length/height (WHZ) z-scores, stratified by diarrheal symptoms and adjusted for potential covariates. Rotavirus (18.51%) and norovirus (7.33%) were the most prevalent enteric viral pathogens among symptomatic and asymptomatic under-5 children, respectively. Infection with individual enteric viral pathogens hurts child growth in asymptomatic children. However, the relationship with HAZ was less clear and statistically non-significant. On the other hand, the combined viral pathogens demonstrated a strong negative influence on child growth [WAZ: ß coef.: - 0.10 (95%, CI - 0.15, - 0.05); P < 0.001 and WHZ: ß: - 0.12 (95% CI - 0.17, - 0.07); P < 0.001] among asymptomatic children. Infection with any viral pathogen was associated with growth shortfalls [HAZ: ß: - 0.05 (95% CI - 0.09, 0.00); P = 0.03 and WAZ: ß: - 0.11 (95% CI - 0.16, - 0.07); P < 0.001 and WHZ: ß: - 0.13 (95% CI - 0.18, - 0.09); P < 0.001], though the relationship with HAZ was less evident and became statistically non-significant in older children. Notably, among symptomatic children with moderate-to-severe diarrhea, individual enteric viral pathogens, as well as the combined effects of these pathogens [WHZ: ß: 0.07; (95% CI 0.01, 0.14); P = 0.03] and the presence of any virus [HAZ: ß: 0.09 (95% CI 0.05, 0.13) & WAZ: ß: 0.08 (95% CI 0.03, 0.12); P < 0.001], exhibited positive effects on child growth. While previous studies hypothesized that several viral pathogens had a conflicting controversial role in child growth, we find clear indications that enteric viral pathogens are associated with growth shortfalls, specifically among asymptomatic children. These findings highlight the need for preventive strategies targeting children with enteric viral pathogens, which could address the consequences of growth faltering.

Morbidity and unplanned healthcare encounters after hospital discharge among young children in Dar es Salaam, Tanzania and Monrovia, Liberia.

BACKGROUND: Researchers and healthcare providers have paid little attention to morbidity and unplanned healthcare encounters for children following hospital discharge in low- and middle-income countries. Our objective was to compare symptoms and unplanned healthcare encounters among children aged <5 years who survived with those who died within 60 days of hospital discharge through follow-up phone calls. METHODS: We conducted a secondary analysis of a prospective observational cohort of children aged <5 years discharged from neonatal and paediatric wards of two national referral hospitals in Dar es Salaam, Tanzania and Monrovia, Liberia. Caregivers of enrolled participants received phone calls 7, 14, 30, 45, and 60 days after hospital discharge to record symptoms, unplanned healthcare encounters, and vital status. We used logistic regression to determine the association between reported symptoms and unplanned healthcare encounters with 60-day post-discharge mortality. RESULTS: A total of 4243 participants were enrolled and had 60-day vital status available; 138 (3.3%) died. For every additional symptom ever reported following discharge, there was a 35% greater likelihood of post-discharge mortality (adjusted odds ratio [aOR] 1.35, 95% confidence interval [CI] 1.10 to 1.66; p=0.004). The greatest survival difference was noted for children who had difficulty breathing (2.1% among those who survived vs 36.0% among those who died, p<0.001). Caregivers who took their child home from the hospital against medical advice during the initial hospitalisation had over eight times greater odds of post-discharge mortality (aOR 8.06, 95% CI 3.87 to 16.3; p<0.001) and those who were readmitted to a hospital had 3.42 greater odds (95% CI 1.55 to 8.47; p=0.004) of post-discharge mortality than those who did not seek care when adjusting for site, sociodemographic factors, and clinical variables. CONCLUSION: Surveillance for symptoms and repeated admissions following hospital discharge by healthcare providers is crucial to identify children at risk for post-discharge mortality.

Widening geographic range of Rift Valley fever disease clusters associated with climate change in East Africa.

BACKGROUND: Recent epidemiology of Rift Valley fever (RVF) disease in Africa suggests growing frequency and expanding geographic range of small disease clusters in regions that previously had not reported the disease. We investigated factors associated with the phenomenon by characterising recent RVF disease events in East Africa. METHODS: Data on 100 disease events (2008-2022) from Kenya, Uganda and Tanzania were obtained from public databases and institutions, and modelled against possible geoecological risk factors of occurrence including altitude, soil type, rainfall/precipitation, temperature, normalised difference vegetation index (NDVI), livestock production system, land-use change and long-term climatic variations. Decadal climatic variations between 1980 and 2022 were evaluated for association with the changing disease pattern. RESULTS: Of 100 events, 91% were small RVF clusters with a median of one human (IQR, 1-3) and three livestock cases (IQR, 2-7). These clusters exhibited minimal human mortality (IQR, 0-1), and occurred primarily in highlands (67%), with 35% reported in areas that had never reported RVF disease. Multivariate regression analysis of geoecological variables showed a positive correlation between occurrence and increasing temperature and rainfall. A 1°C increase in temperature and a 1-unit increase in NDVI, one months prior were associated with increased RVF incidence rate ratios of 1.20 (95% CI 1.1, 1.2) and 1.93 (95% CI 1.01, 3.71), respectively. Long-term climatic trends showed a significant decadal increase in annual mean temperature (0.12-0.3°C/decade, p<0.05), associated with decreasing rainfall in arid and semi-arid lowlands but increasing rainfall trends in highlands (p<0.05). These hotter and wetter highlands showed increasing frequency of RVF clusters, accounting for 76% and 43% in Uganda and Kenya, respectively. CONCLUSION: These findings demonstrate the changing epidemiology of RVF disease. The widening geographic range of disease is associated with climatic variations, with the likely impact of wider dispersal of virus to new areas of endemicity and future epidemics.

Widening geographic range of Rift Valley fever disease clusters associated with climate change in East Africa.

Background: Recent epidemiology of Rift Valley fever (RVF) disease in Africa suggests growing frequency and expanding geographic range of small disease clusters in regions that previously had not reported the disease. We investigated factors associated with the phenomenon by characterizing recent RVF disease events in East Africa. Methods: Data on 100 disease events (2008 - 2022) from Kenya, Uganda, and Tanzania were obtained from public databases and institutions, and modeled against possible geo-ecological risk factors of occurrence including altitude, soil type, rainfall/precipitation, temperature, normalized difference vegetation index (NDVI), livestock production system, land-use change, and long-term climatic variations. Decadal climatic variations between 1980-2022 were evaluated for association with the changing disease pattern. Results: Of 100 events, 91% were small RVF clusters with a median of one human (IQR, 1-3) and 3 livestock cases (IQR, 2-7). These clusters exhibited minimal human mortality (IQR 0-1), and occurred primarily in highlands (67%), with 35% reported in areas that had never reported RVF disease. Multivariate regression analysis of geo-ecological variables showed a positive correlation between occurrence and increasing temperature and rainfall. A 1oC increase in temperature and 1-unit increase in NDVI, 1-3 months prior were associated with increased RVF incidence rate ratios (IRR) of 1.20 (95% CI 1.1,1.2) and 9.88 (95% CI 0.85, 119.52), respectively. Long-term climatic trends showed significant decadal increase in annual mean temperature (0.12 to 0.3oC/decade, P<0.05), associated with decreasing rainfall in arid and semi-arid lowlands but increasing rainfall trends in highlands (P<0.05). These hotter and wetter highlands showed increasing frequency of RVF clusters, accounting for 76% and 43% in Uganda and Kenya, respectively. Conclusion: These findings demonstrate the changing epidemiology of RVF disease. The widening geographic range of disease is associated with climatic variations, with the likely impact of wider dispersal of virus to new areas of endemicity and future epidemics. Key questions: What is already known on this topic?: Rift Valley fever is recognized for its association with heavy rainfall, flooding, and El Niño rains in the East African region. A growing body of recent studies has highlighted a shifting landscape of the disease, marked by an expanding geographic range and an increasing number of small RVF clusters.What this study adds: This study challenges previous beliefs about RVF, revealing that it predominantly occurs in small clusters rather than large outbreaks, and its association with El Niño is not as pronounced as previously thought. Over 65% of these clusters are concentrated in the highlands of Kenya and Uganda, with 35% occurring in previously unaffected regions, accompanied by an increase in temperature and total rainfall between 1980 and 2022, along with a rise in the annual number of rainy days. Notably, the observed rainfall increases are particularly significant during the short-rains season (October-December), aligning with a secondary peak in RVF incidence. In contrast, the lowlands of East Africa, where typical RVF epidemics occur, display smaller and more varied trends in annual rainfall.How this study might affect research, practice, or policy: The worldwide consequence of the expanding RVF cluster is the broader dispersion of the virus, leading to the establishment of new regions with virus endemicity. This escalation heightens the risk of more extensive extreme-weather-associated RVF epidemics in the future. Global public health institutions must persist in developing preparedness and response strategies for such scenarios. This involves the creation and approval of human RVF vaccines and therapeutics, coupled with a rapid distribution plan through regional banks.

Clinical severity of enteric viruses detected using a quantitative molecular assay compared to conventional assays in the Global Enteric Multicenter Study.

BACKGROUND: Quantitative molecular assays are increasingly used for detection of enteric viruses. METHODS: We compared the clinical severity using modified Vesikari score (mVS) of enteric viruses detected by conventional assays (enzyme immunoassays [EIA] for rotavirus and adenovirus 40/41 and conventional polymerase chain reaction for astrovirus, sapovirus, and norovirus) and a quantitative molecular assay (TaqMan Array Card [TAC]) among children aged 0-59 months in the Global Enteric Multicenter Study. For rotavirus and adenovirus 40/41, we compared severity between EIA-positive and TAC-positive cases assigned etiologies using different cycle threshold (CT) cutoffs. RESULTS: Using conventional assays, the median (interquartile range) mVS was 10 (8, 11) for rotavirus, 9 (7, 11) for adenovirus 40/41, 8 (6, 10) for astrovirus, sapovirus, and norovirus GII, and 7 (6, 9) for norovirus GI. Compared to rotavirus EIA-positive cases, the median mVS was 2 and 3 points lower for EIA-negative/TAC-positive cases with CT<32.6 and 32.6≤CT<35, respectively (p-value<.0001). Adenovirus 40/41 EIA-positive and EIA-negative/TAC-positive cases were similar, regardless of CT cutoff. CONCLUSIONS: Quantitative molecular assays compared to conventional assays, such as EIA, may influence severity of identified cases, especially for rotavirus. Cutoffs to assign etiology for quantitative assays should be considered in the design and interpretation of enteric virus studies.

Identifying delays in healthcare seeking and provision: The Three Delays-in-Healthcare and mortality among infants and children aged 1-59 months.

Delays in illness recognition, healthcare seeking, and in the provision of appropriate clinical care are common in resource-limited settings. Our objective was to determine the frequency of delays in the "Three Delays-in-Healthcare", and factors associated with delays, among deceased infants and children in seven countries with high childhood mortality. We conducted a retrospective, descriptive study using data from verbal autopsies and medical records for infants and children aged 1-59 months who died between December 2016 and February 2022 in six sites in sub-Saharan Africa and one in South Asia (Bangladesh) and were enrolled in Child Health and Mortality Prevention Surveillance (CHAMPS). Delays in 1) illness recognition in the home/decision to seek care, 2) transportation to healthcare facilities, and 3) the receipt of clinical care in healthcare facilities were categorized according to the "Three Delays-in-Healthcare". Comparisons in factors associated with delays were made using Chi-square testing. Information was available for 1,326 deaths among infants and under 5 children. The majority had at least one identified delay (n = 854, 64%). Waiting >72 hours after illness recognition to seek health care (n = 422, 32%) was the most common delay. Challenges in obtaining transportation occurred infrequently when seeking care (n = 51, 4%). In healthcare facilities, prescribed medications were sometimes unavailable (n = 102, 8%). Deceased children aged 12-59 months experienced more delay than infants aged 1-11 months (68% vs. 61%, P = 0.018). Delays in seeking clinical care were common among deceased infants and children. Additional study to assess the frequency of delays in seeking clinical care and its provision among children who survive is warranted.

Identifying neonates at risk for post-discharge mortality in Dar es Salaam, Tanzania, and Monrovia, Liberia: Derivation and internal validation of a novel risk assessment tool.

INTRODUCTION: The immediate period after hospital discharge carries a large burden of childhood mortality in sub-Saharan Africa. Our objective was to derive and internally validate a risk assessment tool to identify neonates discharged from the neonatal ward at risk for 60-day post-discharge mortality. METHODS: We conducted a prospective observational cohort study of neonates discharged from Muhimbili National Hospital in Dar es Salaam, Tanzania, and John F Kennedy Medical Centre in Monrovia, Liberia. Research staff called caregivers to ascertain vital status up to 60 days after discharge. We conducted multivariable logistic regression analyses with best subset selection to identify socioeconomic, demographic, clinical, and anthropometric factors associated with post-discharge mortality. We used adjusted log coefficients to assign points to each variable and internally validated our tool with bootstrap validation with 500 repetitions. RESULTS: There were 2344 neonates discharged and 2310 (98.5%) had post-discharge outcomes available. The median (IQR) age at discharge was 8 (4, 15) days; 1238 (53.6%) were male. In total, 71 (3.1%) died during follow-up (26.8% within 7 days of discharge). Leaving against medical advice (adjusted OR [aOR] 5.62, 95% CI 2.40 to 12.10) and diagnosis of meconium aspiration (aOR 6.98, 95% CI 1.69 to 21.70) conferred the greatest risk for post-discharge mortality. The risk assessment tool included nine variables (total possible score=63) and had an optimism corrected area under the receiver operating characteristic curve of 0.77 (95% CI 0.75 to 0.80). A score of ≥6 was most optimal (sensitivity 68.3% [95% CI 64.8% to 71.5%], specificity 72.1% [95% CI 71.5% to 72.7%]). CONCLUSIONS: A small number of factors predicted all-cause, 60-day mortality after discharge from neonatal wards in Tanzania and Liberia. After external validation, this risk assessment tool may facilitate clinical decision making for eligibility for discharge and the direction of resources to follow-up high risk neonates.

Post-mortem investigation of deaths due to pneumonia in children aged 1-59 months in sub-Saharan Africa and South Asia from 2016 to 2022: an observational study.

BACKGROUND: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network programme undertakes post-mortem minimally invasive tissue sampling (MITS), together with collection of ante-mortem clinical information, to investigate causes of childhood deaths across multiple countries. We aimed to evaluate the overall contribution of pneumonia in the causal pathway to death and the causative pathogens of fatal pneumonia in children aged 1-59 months enrolled in the CHAMPS Network. METHODS: In this observational study we analysed deaths occurring between Dec 16, 2016, and Dec 31, 2022, in the CHAMPS Network across six countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and one in South Asia (Bangladesh). A standardised approach of MITS was undertaken on decedents within 24-72 h of death. Diagnostic tests included blood culture, multi-organism targeted nucleic acid amplifications tests (NAATs) of blood and lung tissue, and histopathology examination of various organ tissue samples. An interdisciplinary expert panel at each site reviewed case data to attribute the cause of death and pathogenesis thereof on the basis of WHO-recommended reporting standards. FINDINGS: Pneumonia was attributed in the causal pathway of death in 455 (40·6%) of 1120 decedents, with a median age at death of 9 (IQR 4-19) months. Causative pathogens were identified in 377 (82·9%) of 455 pneumonia deaths, and multiple pathogens were implicated in 218 (57·8%) of 377 deaths. 306 (67·3%) of 455 deaths occurred in the community or within 72 h of hospital admission (presumed to be community-acquired pneumonia), with the leading bacterial pathogens being Streptococcus pneumoniae (108 [35·3%]), Klebsiella pneumoniae (78 [25·5%]), and non-typeable Haemophilus influenzae (37 [12·1%]). 149 (32·7%) deaths occurred 72 h or more after hospital admission (presumed to be hospital-acquired pneumonia), with the most common pathogens being K pneumoniae (64 [43·0%]), Acinetobacter baumannii (19 [12·8%]), S pneumoniae (15 [10·1%]), and Pseudomonas aeruginosa (15 [10·1%]). Overall, viruses were implicated in 145 (31·9%) of 455 pneumonia-related deaths, including 54 (11·9%) of 455 attributed to cytomegalovirus and 29 (6·4%) of 455 attributed to respiratory syncytial virus. INTERPRETATION: Pneumonia contributed to 40·6% of all childhood deaths in this analysis. The use of post-mortem MITS enabled biological ascertainment of the cause of death in the majority (82·9%) of childhood deaths attributed to pneumonia, with more than one pathogen being commonly implicated in the same case. The prominent role of K pneumoniae, non-typable H influenzae, and S pneumoniae highlight the need to review empirical management guidelines for management of very severe pneumonia in low-income and middle-income settings, and the need for research into new or improved vaccines against these pathogens. FUNDING: Bill & Melinda Gates Foundation.

Child deaths caused by Klebsiella pneumoniae in sub-Saharan Africa and south Asia: a secondary analysis of Child Health and Mortality Prevention Surveillance (CHAMPS) data.

BACKGROUND: Klebsiella pneumoniae is an important cause of nosocomial and community-acquired pneumonia and sepsis in children, and antibiotic-resistant K pneumoniae is a growing public health threat. We aimed to characterise child mortality associated with this pathogen in seven high-mortality settings. METHODS: We analysed Child Health and Mortality Prevention Surveillance (CHAMPS) data on the causes of deaths in children younger than 5 years and stillbirths in sites located in seven countries across sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and south Asia (Bangladesh) from Dec 9, 2016, to Dec 31, 2021. CHAMPS sites conduct active surveillance for deaths in catchment populations and following reporting of an eligible death or stillbirth seek consent for minimally invasive tissue sampling followed by extensive aetiological testing (microbiological, molecular, and pathological); cases are reviewed by expert panels to assign immediate, intermediate, and underlying causes of death. We reported on susceptibility to antibiotics for which at least 30 isolates had been tested, and excluded data on antibiotics for which susceptibility testing is not recommended for Klebsiella spp due to lack of clinical activity (eg, penicillin and ampicillin). FINDINGS: Among 2352 child deaths with cause of death assigned, 497 (21%, 95% CI 20-23) had K pneumoniae in the causal chain of death; 100 (20%, 17-24) had K pneumoniae as the underlying cause. The frequency of K pneumoniae in the causal chain was highest in children aged 1-11 months (30%, 95% CI 26-34; 144 of 485 deaths) and 12-23 months (28%, 22-34; 63 of 225 deaths); frequency by site ranged from 6% (95% CI 3-11; 11 of 184 deaths) in Bangladesh to 52% (44-61; 71 of 136 deaths) in Ethiopia. K pneumoniae was in the causal chain for 450 (22%, 95% CI 20-24) of 2023 deaths that occurred in health facilities and 47 (14%, 11-19) of 329 deaths in the community. The most common clinical syndromes among deaths with K pneumoniae in the causal chain were sepsis (44%, 95% CI 40-49; 221 of 2352 deaths), sepsis in conjunction with pneumonia (19%, 16-23; 94 of 2352 deaths), and pneumonia (16%, 13-20; 80 of 2352 deaths). Among K pneumoniae isolates tested, 121 (84%) of 144 were resistant to ceftriaxone and 80 (75%) of 106 to gentamicin. INTERPRETATION: K pneumoniae substantially contributed to deaths in the first 2 years of life across multiple high-mortality settings, and resistance to antibiotics used for sepsis treatment was common. Improved strategies are needed to rapidly identify and appropriately treat children who might be infected with this pathogen. These data suggest a potential impact of developing and using effective K pneumoniae vaccines in reducing neonatal, infant, and child deaths globally. FUNDING: Bill & Melinda Gates Foundation.

Strain features of pneumococcal isolates in the pre- and post-PCV10 era in Pakistan.

Pakistan is amongst the four countries with the highest number of pneumococcal deaths. While the PCV10 vaccine was introduced in Pakistan in October 2012, data regarding the impact of the vaccine on the population dynamics of Streptococcus pneumoniae in Pakistan remain obscure. Using whole genome sequencing of 190 isolates (nasopharyngeal carriage=75, disease=113, unknown sites=2) collected between 2002 and 2020, this study presents characteristics of pneumococcal strains in Pakistan in the pre- and post-vaccine era. The isolates were characterized on the basis of serotype distribution, genetic lineages (or Global Pneumococcal Sequence Cluster, GPSC) and antibiotic resistance. A high level of diversity in serotype and genetic lineages of pneumococci was observed in Pakistan. Among 190 isolates, we identified 54 serotypes, 67 GPSCs and 116 sequence types (STs) including 23 new STs. The most prevalent GPSCs and their associated serotypes in nasopharyngeal carriage were GPSC54 (expressing serotype 9V), GPSC5 (15A and 7B, and serogroup 24), GPSC25 (15B/15C), GPSC67 (18C) and GPSC376 (6A and 6D). Similarly, among 113 disease-causing isolates, the most prevalent GPSC/serotype combinations were GPSC2 (serotype 1), GPSC10 (serotypes 14, 10A, 19A and 19F), GPSC43 (serotypes 13, 11A, 23B, 35A and 9V), GPSC67 (serotypes 18A and 18C) and GPSC642 (serotype 11A). Of the 190 isolates, the highest levels of resistance were observed against penicillin (58.9 %, n=122), erythromycin (29.5 %, n=56), clindamycin (13.2 %, n=25), co-trimoxazole (94.2 %, n=179) and tetracycline/doxycycline (53.2 %, n=101). A higher proportion of disease-causing isolates were multidrug resistant as compared to carriage isolates (54 % vs 25 %). Our data suggest limited coverage of PCV10 in nasopharyngeal (21.6 %, 16/74) as well as disease-causing (38.1 %, 16/42) isolates among children ≤5 years old; however, higher valent vaccine PCV13 would increase the coverage rates to 33.8 % in nasopharyngeal and 54.8 % in disease-causing isolates, whereas PCV24/25 would offer the highest coverage rates. Owing to the diversity of serotypes observed during the post-vaccine period, the suggested inclusion of serotype in future vaccine formulations will require investigations with larger data sets with an extended temporal window. This article contains data hosted by Microreact.

Corrigendum: LetsTalkShots: personalized vaccine risk communication.

[This corrects the article DOI: 10.3389/fpubh.2023.1195751.].

Symptomatic and asymptomatic enteric protozoan parasitic infection and their association with subsequent growth parameters in under five children in South Asia and sub-Saharan Africa.

BACKGROUND: Entamoeba histolytica, Giardia, and Cryptosporidium are common intestinal protozoan parasites that contribute to a high burden of childhood morbidity and mortality. Our study quantified the association between intestinal protozoan parasites and child anthropometric outcomes among children under-5. METHODS: We analyzed data from 7,800 children enrolled in the Global Enteric Multicenter Study (GEMS) across seven study sites that were positive for intestinal protozoan parasites between December 2007 and March 2011. Parasites were assessed using stool immunoassays (ELISA). We applied multiple linear regression to test the association between any or concurrent parasite and child anthropometric outcomes: length/height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length/height (WHZ) z-score after 60 days of enrollment. Models were stratified by diarrheal symptoms, driven by the study design, and adjusted for potential covariates. FINDINGS: During the follow-up at day 60 after enrollment, child anthropometric outcomes, among the asymptomatic children showed, negative associations between Giardia with HAZ [ß: -0.13; 95% CI: -0.17, -0.09; p<0.001] and WAZ [ß -0.07; 95% CI: -0.11, -0.04; p<0.001], but not WHZ [ß: -0.02; 95% CI:-0.06, 0.02; p = 0.36]; Cryptosporidium with WAZ [ß: -0.15; 95% CI: -0.22, -0.09; p<0.001] and WHZ [ß: -0.18; 95%CI: -0.25, -0.12; p<0.001], but not with HAZ [ß: -0.03; 95% CI: -0.09, 0.04; p = 0.40]. For symptomatic children, no associations were found between Giardia and anthropometry; negative associations were found between Cryptosporidium with HAZ [ß: -0.17; 95% CI: -0.23, -0.11; p<0.001], WAZ [ß: -0.25; 95% CI: -0.31, -0.19; p<0.001] and WHZ [ß: -0.23; 95% CI: -0.30, -0.17; p<0.001]. Among the asymptomatic 24-59 months children, Giardia had a negative association with HAZ [ß: -0.09; 95% CI: -0.15, -0.04; p = 0.001]. No significant associations were found between E. histolytica with child growth. CONCLUSIONS: While some studies have found that Giardia is not associated with (or protective against) acute diarrhea, our findings suggest that it is associated with growth shortfall. This observation underscores the need for preventive strategies targeting enteric protozoan parasites among young children, to reduce the burden of childhood malnutrition.

Evaluation of online videos to engage viewers and support decision-making for COVID-19 vaccination: how narratives and race/ethnicity enhance viewer experiences.

Background: Vaccine hesitancy has hampered the control of COVID-19 and other vaccine-preventable diseases. Methods: We conducted a national internet-based, quasi-experimental study to evaluate COVID-19 vaccine informational videos. Participants received an informational animated video paired with the randomized assignment of (1) a credible source (differing race/ethnicity) and (2) sequencing of a personal narrative before or after the video addressing their primary vaccine concern. We examined viewing time and asked video evaluation questions to those who viewed the full video. Results: Among 14,235 participants, 2,422 (17.0%) viewed the full video. Those who viewed a personal story first (concern video second) were 10 times more likely to view the full video (p < 0.01). Respondent-provider race/ethnicity congruence was associated with increased odds of viewing the full video (aOR: 1.89, p < 0.01). Most viewers rated the informational video(s) to be helpful, easy to understand, trustworthy, and likely to impact others' vaccine decisions, with differences by demographics and also vaccine intentions and concerns. Conclusion: Using peer-delivered, personal narrative, and/or racially congruent credible sources to introduce and deliver vaccine safety information may improve the openness of vaccine message recipients to messages and engagement.

Molecular characterization of Streptococcus pneumoniae causing disease among children in Nigeria during the introduction of PCV10 (GSK).

Streptococcus pneumoniae (pneumococcus) is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated ~49 000 child deaths caused by pneumococcal infections each year. Ten-valent pneumococcal conjugate vaccine (GSK; PCV10) was introduced in December 2014 in a phased approach. However, few studies have characterized the disease-causing pneumococci from Nigeria. This study assessed the prevalence of serotypes, antibiotic susceptibility and genomic lineages using whole genome sequencing and identified lineages that could potentially escape PCV10 (GSK). We also investigated the potential differences in pneumococcal lineage features between children with and without sickle cell disease. A collection of 192 disease-causing pneumococcal isolates was obtained from Kano (n=189) and Abuja (n=3) states, Nigeria, between 1 January 2014 and 31 May 2018. The majority (99 %, 190/192) of specimens were recovered from children aged 5 years or under. Among them, 37 children had confirmed or traits of sickle cell disease. Our findings identified 25 serotypes expressed by 43 Global Pneumococcal Sequence Clusters (GPSCs) and 85 sequence types (STs). The most common serotypes were 14 (18 %, n=35), 6B (16 %, n=31), 1 (9 %, n=17), 5 (9 %, n=17) and 6A (9 %, n=17); all except serotype 6A are included in PCV10 (GSK). PCV10 (SII; PNEUMOSIL) and PCV13 formulations include serotypes 6A and 19A which would increase the overall coverage from 67 % by PCV10 (GSK) to 78 and 82 %, respectively. The pneumococcal lineages were a mix of globally spreading and unique local lineages. Following the use of PCV10 (GSK), GPSC5 expressing serotype 6A, GPSC10 (19A), GPSC26 (12F and 46) and GPSC627 (9L) are non-vaccine type lineages that could persist and potentially expand under vaccine-selective pressure. Approximately half (52 %, 99/192) of the pneumococcal isolates were resistant to the first-line antibiotic penicillin and 44 % (85/192) were multidrug-resistant. Erythromycin resistance was very low (2 %, 3/192). There was no significant difference in clinical manifestation, serotype prevalence or antibiotic resistance between children with and without traits of or confirmed sickle cell disease. In summary, our findings show that a high percentage of the pneumococcal disease were caused by the serotypes that are covered by currently available vaccines. Given the low prevalence of resistance, macrolide antibiotics, such as erythromycin, should be considered as an option to treat pneumococcal disease in Nigeria. However, appropriate use of macrolide antibiotics should be vigilantly monitored to prevent the potential increase in macrolide resistance.

Provider adherence to clinical care recommendations for infants and children who died in seven low- and middle-income countries in the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

Background: Most childhood deaths globally are considered preventable through high-quality clinical care, which includes adherence to clinical care recommendations. Our objective was to describe adherence to World Health Organization recommendations for the management of leading causes of death among children. Methods: We conducted a retrospective, descriptive study examining clinical data for children aged 1-59 months who were hospitalized and died in a Child Health and Mortality Prevention Surveillance (CHAMPS) catchment, December 2016-June 2021. Catchment areas included: Baliakandi and Faridpur, Bangladesh; Kersa, Haramaya, and Harar, Ethiopia; Kisumu and Siaya, Kenya; Bamako, Mali; Manhiça and Quelimane, Mozambique; Makeni, Sierra Leone; Soweto, South Africa. We reviewed medical records of those who died from lower respiratory tract infections, sepsis, malnutrition, malaria, and diarrheal diseases to determine the proportion who received recommended treatments and compared adherence by hospitalization duration. Findings: CHAMPS enrolled 460 hospitalized children who died from the leading causes (median age 12 months, 53.0% male). Median hospital admission was 31 h. There were 51.0% (n = 127/249) of children who died from lower respiratory tract infections received supplemental oxygen. Administration of intravenous fluids for sepsis (15.9%, n = 36/226) and supplemental feeds for malnutrition (14.0%, n = 18/129) were uncommon. There were 51.4% (n = 55/107) of those who died from malaria received antimalarials. Of the 80 children who died from diarrheal diseases, 76.2% received intravenous fluids. Those admitted for ≥24 h more commonly received antibiotics for lower respiratory tract infections and sepsis, supplemental feeds for malnutrition, and intravenous fluids for sepsis than those admitted <24 h. Interpretation: Provision of recommended clinical care for leading causes of death among young children was suboptimal. Further studies are needed to understand the reasons for deficits in clinical care recommendation adherence. Funding: Bill & Melinda Gates Foundation.

LetsTalkShots: personalized vaccine risk communication.

Introduction: Vaccine hesitancy is a global health threat undermining control of many vaccine-preventable diseases. Patient-level education has largely been ineffective in reducing vaccine concerns and increasing vaccine uptake. We built and evaluated a personalized vaccine risk communication website called LetsTalkShots in English, Spanish and French (Canadian) for vaccines across the lifespan. LetsTalkShots tailors lived experiences, credible sources and informational animations to disseminate the right message from the right messenger to the right person, applying a broad range of behavioral theories. Methods: We used mixed-methods research to test our animation and some aspects of credible sources and personal narratives. We conducted 67 discussion groups (n = 325 persons), stratified by race/ethnicity (African American, Hispanic, and White people) and population (e.g., parents, pregnant women, adolescents, younger adults, and older adults). Using a large Ipsos survey among English-speaking respondents (n = 2,272), we tested animations aligned with vaccine concerns and specific to population (e.g., parents of children, parents of adolescents, younger adults, older adults). Results: Discussion groups provided robust feedback specific to each animation as well as areas for improvements across animations. Most respondents indicated that the information presented was interesting (85.5%), clear (96.0%), helpful (87.0%), and trustworthy (82.2%). Discussion: Tailored vaccine risk communication can assist decision makers as they consider vaccination for themselves, their families, and their communities. LetsTalkShots presents a model for personalized communication in other areas of medicine and public health.

Mortality patterns over a 10-year period in Kibera, an urban informal settlement in Nairobi, Kenya, 2009-2018.

BACKGROUND: Reliable mortality data are important for evaluating the impact of health interventions. However, data on mortality patterns among populations living in urban informal settlements are limited. OBJECTIVES: To examine the mortality patterns and trends in an urban informal settlement in Kibera, Nairobi, Kenya. METHODS: Using data from a population-based surveillance platform we estimated overall and cause-specific mortality rates for all age groups using person-year-observation (pyo) denominators and using Poisson regression tested for trends in mortality rates over time. We compared associated mortality rates across groups using incidence rate ratios (IRR). Assignment of probable cause(s) of death was done using the InterVA-4 model. RESULTS: We registered 1134 deaths from 2009 to 2018, yielding a crude mortality rate of 4.4 (95% Confidence Interval [CI]4.2-4.7) per 1,000 pyo. Males had higher overall mortality rates than females (incidence rate ratio [IRR], 1.44; 95% CI, 1.28-1.62). The highest mortality rate was observed among children aged < 12 months (41.5 per 1,000 pyo; 95% CI 36.6-46.9). All-cause mortality rates among children < 12 months were higher than that of children aged 1-4 years (IRR, 8.5; 95% CI, 6.95-10.35). The overall mortality rate significantly declined over the period, from 6.7 per 1,000 pyo (95% CI, 5.7-7.8) in 2009 to 2.7 (95% CI, 2.0-3.4) per 1,000 pyo in 2018. The most common cause of death was acute respiratory infections (ARI)/pneumonia (18.1%). Among children < 5 years, the ARI/pneumonia deaths rate declined significantly over the study period (5.06 per 1,000 pyo in 2009 to 0.61 per 1,000 pyo in 2018; p = 0.004). Similarly, death due to pulmonary tuberculosis among persons 5 years and above significantly declined (0.98 per 1,000 pyo in 2009 to 0.25 per 1,000 pyo in 2018; p = 0.006). CONCLUSIONS: Overall and some cause-specific mortality rates declined over time, representing important public health successes among this population.

Causes of Death Among Infants and Children in the Child Health and Mortality Prevention Surveillance (CHAMPS) Network.

Importance: The number of deaths of children younger than 5 years has been steadily decreasing worldwide, from more than 17 million annual deaths in the 1970s to an estimated 5.3 million in 2019 (with 2.8 million deaths occurring in those aged 1-59 months [53% of all deaths in children aged <5 years]). More detailed characterization of childhood deaths could inform interventions to improve child survival. Objective: To describe causes of postneonatal child deaths across 7 mortality surveillance sentinel sites in Africa and Asia. Design, Setting, and Participants: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network conducts childhood mortality surveillance in sub-Saharan Africa and South Asia using innovative postmortem minimally invasive tissue sampling (MITS). In this cross-sectional study, MITS was conducted in deceased children aged 1 to 59 months at 7 sites in sub-Saharan Africa and South Asia from December 3, 2016, to December 3, 2020. Data analysis was conducted between October and November 2021. Main Outcomes and Measures: The expert panel attributed underlying, intermediate, and immediate conditions in the chain of events leading to death, based on histopathologic analysis, microbiological diagnostics, clinical data, and verbal autopsies. Results: In this study, MITS was performed in 632 deceased children (mean [SD] age at death, 1.3 [0.3] years; 342 [54.1%] male). The 6 most common underlying causes of death were malnutrition (104 [16.5%]), HIV (75 [11.9%]), malaria (71 [11.2%]), congenital birth defects (64 [10.1%]), lower respiratory tract infections (LRTIs; 53 [8.4%]), and diarrheal diseases (46 [7.2%]). When considering immediate causes only, sepsis (191 [36.7%]) and LRTI (129 [24.8%]) were the 2 dominant causes. An infection was present in the causal chain in 549 of 632 deaths (86.9%); pathogens most frequently contributing to infectious deaths included Klebsiella pneumoniae (155 of 549 infectious deaths [28.2%]; 127 [81.9%] considered nosocomial), Plasmodium falciparum (122 of 549 [22.2%]), and Streptococcus pneumoniae (109 of 549 [19.9%]). Other organisms, such as cytomegalovirus (57 [10.4%]) and Acinetobacter baumannii (39 [7.1%]; 35 of 39 [89.7%] considered nosocomial), also played important roles. For the top underlying causes of death, the median number of conditions in the chain of events leading to death was 3 for malnutrition, 3 for HIV, 1 for malaria, 3 for congenital birth defects, and 1 for LRTI. Expert panels considered 494 of 632 deaths (78.2%) preventable and 26 of 632 deaths (4.1%) preventable under certain conditions. Conclusions and Relevance: In this cross-sectional study investigating causes of child mortality in the CHAMPS Network, results indicate that, in these high-mortality settings, infectious diseases continue to cause most deaths in infants and children, often in conjunction with malnutrition. These results also highlight opportunities for action to prevent deaths and reveal common interaction of various causes in the path toward death.

Predictive value of clinician impression for readmission and postdischarge mortality among neonates and young children in Dar es Salaam, Tanzania and Monrovia, Liberia.

BACKGROUND: There are no validated clinical decision aids to identify neonates and young children at risk of hospital readmission or postdischarge mortality in sub-Saharan Africa, leaving the decision to discharge a child to a clinician's impression. Our objective was to determine the precision of clinician impression to identify neonates and young children at risk for readmission and postdischarge mortality. METHODS: We conducted a survey study nested in a prospective observational cohort of neonates and children aged 1-59 months followed 60 days after hospital discharge from Muhimbili National Hospital in Dar es Salaam, Tanzania or John F. Kennedy Medical Center in Monrovia, Liberia. Clinicians who discharged each enrolled patient were surveyed to determine their perceived probability of the patient's risk of 60-day hospital readmission or postdischarge mortality. We calculated the area under the precision-recall curve (AUPRC) to determine the precision of clinician impression for both outcomes. RESULTS: Of 4247 discharged patients, 3896 (91.7%) had available clinician surveys and 3847 (98.7%) had 60-day outcomes available: 187 (4.8%) were readmitted and 120 (3.1%) died within 60 days of hospital discharge. Clinician impression had poor precision in identifying neonates and young children at risk of hospital readmission (AUPRC: 0.06, 95% CI: 0.04 to 0.08) and postdischarge mortality (AUPRC: 0.05, 95% CI: 0.03 to 0.08). Patients for whom clinicians attributed inability to pay for future medical treatment as the reason for risk for unplanned hospital readmission had 4.76 times the odds hospital readmission (95% CI: 1.31 to 17.25, p=0.02). CONCLUSIONS: Given the poor precision of clinician impression alone to identify neonates and young children at risk of hospital readmission and postdischarge mortality, validated clinical decision aids are needed to aid in the identification of young children at risk for these outcomes.