Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 101 Records) |
Query Trace: Blau D [original query] |
---|
High HIV diversity, recombination, and superinfection revealed in a large outbreak among persons who inject drugs in Kentucky and Ohio, USA
Switzer WM , Shankar A , Jia H , Knyazev S , Ambrosio F , Kelly R , Zheng H , Campbell EM , Cintron R , Pan Y , Saduvala N , Panneer N , Richman R , Singh MB , Thoroughman DA , Blau EF , Khalil GM , Lyss S , Heneine W . Virus Evol 2024 10 (1) veae015 We investigated transmission dynamics of a large human immunodeficiency virus (HIV) outbreak among persons who inject drugs (PWID) in KY and OH during 2017-20 by using detailed phylogenetic, network, recombination, and cluster dating analyses. Using polymerase (pol) sequences from 193 people associated with the investigation, we document high HIV-1 diversity, including Subtype B (44.6 per cent); numerous circulating recombinant forms (CRFs) including CRF02_AG (2.5 per cent) and CRF02_AG-like (21.8 per cent); and many unique recombinant forms composed of CRFs with major subtypes and sub-subtypes [CRF02_AG/B (24.3 per cent), B/CRF02_AG/B (0.5 per cent), and A6/D/B (6.4 per cent)]. Cluster analysis of sequences using a 1.5 per cent genetic distance identified thirteen clusters, including a seventy-five-member cluster composed of CRF02_AG-like and CRF02_AG/B, an eighteen-member CRF02_AG/B cluster, Subtype B clusters of sizes ranging from two to twenty-three, and a nine-member A6/D and A6/D/B cluster. Recombination and phylogenetic analyses identified CRF02_AG/B variants with ten unique breakpoints likely originating from Subtype B and CRF02_AG-like viruses in the largest clusters. The addition of contact tracing results from OH to the genetic networks identified linkage between persons with Subtype B, CRF02_AG, and CRF02_AG/B sequences in the clusters supporting de novo recombinant generation. Superinfection prevalence was 13.3 per cent (8/60) in persons with multiple specimens and included infection with B and CRF02_AG; B and CRF02_AG/B; or B and A6/D/B. In addition to the presence of multiple, distinct molecular clusters associated with this outbreak, cluster dating inferred transmission associated with the largest molecular cluster occurred as early as 2006, with high transmission rates during 2017-8 in certain other molecular clusters. This outbreak among PWID in KY and OH was likely driven by rapid transmission of multiple HIV-1 variants including de novo viral recombinants from circulating viruses within the community. Our findings documenting the high HIV-1 transmission rate and clustering through partner services and molecular clusters emphasize the importance of leveraging multiple different data sources and analyses, including those from disease intervention specialist investigations, to better understand outbreak dynamics and interrupt HIV spread. |
Experience on postmortem minimally invasive tissue sampling to ascertain the cause of death determination in South African children: A case for implementing as standard of care
Du Toit J , Storath K , Dunn I , Makekeng P , Moosa M , Mothibi K , Umuneza N , Rees CA , Blau D , Lala S , Adam Y , Velaphi S , Hale M , Swart P , Wadula J , Mothibi L , Wise A , Baba V , Jaglal P , Mahtab S , Madhi S , Dangor Z . S Afr Med J 2024 114 (2) e1538 Determining the death burden for prioritising public health interventions necessitates detailed data on the causal pathways to death. Postmortem minimally invasive tissue sampling (MITS), incorporating histology, molecular and microbial culture diagnostics, enhances cause-of-death attribution, particularly for infectious deaths. MITS proves a valid alternative to full diagnostic autopsies, especially in low- and middle-income countries. In Soweto, South Africa (SA), the Child Health and Mortality Prevention Surveillance (CHAMPS) programme has delineated over 1 000 child and stillbirth deaths since 2017. This SA CHAMPS site supports advocating for the use of postmortem MITS as routine practice, for more granular insights into under-5 mortality causes. This knowledge is crucial for SA's pursuit of Sustainable Development Goal 3.2, targeting reduced neonatal and under-5 mortality rates. This commentary explores the public health advantages and ethicolegal considerations surrounding implementing MITS as standard of care for stillbirths, neonatal and paediatric deaths in SA. Furthermore, based on the data from CHAMPS, we present three pragmatic algorithmic approaches to the wide array of testing options for cost-effectiveness and scalability of postmortem MITS in South African state facilities. |
Autoimmune hepatitis: Brighton Collaboration case definition and guidelines for data collection, analysis, and presentation of immunisation safety data
Kochhar S , Assis DN , Mack C , Izurieta HS , Muratori L , Munoz A , Nordenberg D , Gidudu JF , Blau EF , Vierling JM . Vaccine 2024 This report introduces a Brighton Collaboration (BC) case definition for autoimmune hepatitis (AIH), which has been classified as a priority adverse event of special interest (AESI), as there were possible cases seen following COVID-19 vaccination. The case definition was developed by a group of subject matter and BC process experts to facilitate safety data comparability across pre- and post-licensure clinical trials, as well as pharmacovigilance activities in multiple settings with diverse resources and healthcare access. The usual BC case definition development process was followed in an expedited manner, and took two months to complete, including finalising the manuscript for publication, instead of the usual 1 year development time. It includes a systematic review of the literature and an expert consensus to define levels of diagnostic certainty for AIH, and provides specific guidelines for data collection and analysis. Histology, serological and biochemical tests and exclusion of alternate diagnosis were considered necessary to define the levels of certainty (definitive, probable and possible). AEFI reports of suspected AIH were independently classified by the WG members to test its useability and these classifications were used to finalise the case definition. The document underwent peer review by external AIH experts and a Reference Group of vaccine safety stakeholders in high-, low- and middle-income countries to ensure case definition useability, applicability, and scientific integrity. The expedited process can be replicated for development of other standardised case definitions for priority AESIs for endemics and epidemics. While applicable to cases reported following immunisation, the case definition is independent of lapsed time following vaccination and, as such, can also be used to determine background incidence for vaccinated and unvaccinated control groups in studies of causal association. While use of this case definition is also appropriate for the study of safety of other products including drugs, it is not meant to guide clinical case management. |
Identifying delays in healthcare seeking and provision: The Three Delays-in-Healthcare and mortality among infants and children aged 1-59 months
Garcia Gomez E , Igunza KA , Madewell ZJ , Akelo V , Onyango D , El Arifeen S , Gurley ES , Hossain MZ , Chowdhury MAI , Islam KM , Assefa N , Scott JAG , Madrid L , Tilahun Y , Orlien S , Kotloff KL , Tapia MD , Keita AM , Mehta A , Magaço A , Torres-Fernandez D , Nhacolo A , Bassat Q , Mandomando I , Ogbuanu I , Cain CJ , Luke R , Kamara SIB , Legesse H , Madhi S , Dangor Z , Mahtab S , Wise A , Adam Y , Whitney CG , Mutevedzi PC , Blau DM , Breiman RF , Tippett Barr BA , Rees CA . PLOS Glob Public Health 2024 4 (2) e0002494 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. |
Phenylketonuria Scientific Review Conference: state of the science and future research needs.
Camp KM , Parisi MA , Acosta PB , Berry GT , Bilder DA , Blau N , Bodamer OA , Brosco JP , Brown CS , Burlina AB , Burton BK , Chang CS , Coates PM , Cunningham AC , Dobrowolski SF , Ferguson JH , Franklin TD , Frazier DM , Grange DK , Greene CL , Groft SC , Harding CO , Howell RR , Huntington KL , Hyatt-Knorr HD , Jevaji IP , Levy HL , Lichter-Konecki U , Lindegren ML , Lloyd-Puryear MA , Matalon K , MacDonald A , McPheeters ML , Mitchell JJ , Mofidi S , Moseley KD , Mueller CM , Mulberg AE , Nerurkar LS , Ogata BN , Pariser AR , Prasad S , Pridjian G , Rasmussen SA , Reddy UM , Rohr FJ , Singh RH , Sirrs SM , Stremer SE , Tagle DA , Thompson SM , Urv TK , Utz JR , van Spronsen F , Vockley J , Waisbren SE , Weglicki LS , White DA , Whitley CB , Wilfond BS , Yannicelli S , Young JM . Mol Genet Metab 2014 112 (2) 87-122 New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism. |
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
Mahtab S , Blau DM , Madewell ZJ , Ogbuanu I , Ojulong J , Lako S , Legesse H , Bangura JS , Bassat Q , Mandomando I , Xerinda E , Fernandes F , Varo R , Sow SO , Kotloff KL , Tapia MD , Keita AM , Sidibe D , Onyango D , Akelo V , Gethi D , Verani JR , Revathi G , Scott JAG , Assefa N , Madrid L , Bizuayehu H , Tirfe TT , El Arifeen S , Gurley ES , Islam KM , Alam M , Zahid Hossain M , Dangor Z , Baillie VL , Hale M , Mutevedzi P , Breiman RF , Whitney CG , Madhi SA . Lancet Child Adolesc Health 2024 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. |
Burden of child mortality from malaria in high endemic areas: results from the CHAMPS Network using minimally invasive tissue sampling
Ogbuanu IU , Otieno K , Varo R , Sow SO , Ojulong J , Duduyemi B , Kowuor D , Cain CJ , Rogena EA , Onyango D , Akelo V , Tippett Barr BA , terKuile F , Kotloff KL , Tapia MD , Keita AM , Juma J , Assefa N , Assegid N , Acham Y , Madrid L , Scott JAG , Arifeen SE , Gurley ES , Mahtab S , Dangor Z , Wadula J , Dutoit J , Madhi SA , Mandomando I , Torres-Fernandez D , Kincardett M , Mabunda R , Mutevedzi P , Madewell ZJ , Blau DM , Whitney CG , Samuels AM , Bassat Q . J Infect 2024 BACKGROUND: Malaria is a leading cause of childhood mortality worldwide. However, accurate estimates of malaria prevalence and causality among patients who die at the country level are lacking due to the limited specificity of diagnostic tools used to attribute etiologies. Accurate estimates are crucial for prioritizing interventions and resources aimed at reducing malaria-related mortality. METHODS: Seven Child Health and Mortality Prevention Surveillance (CHAMPS) Network sites collected comprehensive data on stillbirths and children <5 years, using minimally invasive tissue sampling (MITS). A DeCoDe (Determination of Cause of Death) panel employed standardized protocols for assigning underlying, intermediate, and immediate causes of death, integrating sociodemographic, clinical, laboratory (including extensive microbiology, histopathology, and malaria testing), and verbal autopsy data. Analyses were conducted to ascertain the strength of evidence for cause of death (CoD), describe factors associated with malaria-related deaths, estimate malaria-specific mortality, and assess the proportion of preventable deaths. FINDINGS: Between December 3, 2016, and December 31, 2022, 2673 deaths underwent MITS and had a CoD attributed from four CHAMPS sites with at least 1 malaria-attributed death. No malaria-attributable deaths were documented among 891 stillbirths or 924 neonatal deaths, therefore this analysis concentrates on the remaining 858 deaths among children aged 1-59 months. Malaria was in the causal chain for 42.9% (126/294) of deaths from Sierra Leone, 31.4% (96/306) in Kenya, 18.2% (36/198) in Mozambique, 6.7% (4/60) in Mali, and 0.3% (1/292) in South Africa. Compared to non-malaria related deaths, malaria-related deaths skewed towards older infants and children (p<0.001), with 71.0% among ages 12-59 months. Malaria was the sole infecting pathogen in 184 (70.2%) of malaria-attributed deaths, whereas bacterial and viral co-infections were identified in the causal pathway in 24·0% and 12.2% of cases, respectively. Malnutrition was found at a similar level in the causal pathway of both malaria (26.7%) and non-malaria (30.7%, p=0.256) deaths. Less than two-thirds (164/262; 62.6%) of malaria deaths had received antimalarials prior to death. Nearly all (98·9%) malaria-related deaths were deemed preventable. INTERPRETATION: Malaria remains a significant cause of childhood mortality in the CHAMPS malaria-endemic sites. The high bacterial co-infection prevalence among malaria deaths underscores the potential benefits of antibiotics for severe malaria patients. Compared to non-malaria deaths, many of malaria-attributed deaths are preventable through accessible malaria control measures. FUNDING: This work was supported by the Bill & Melinda Gates Foundation [OPP1126780]. |
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
Verani JR , Blau DM , Gurley ES , Akelo V , Assefa N , Baillie V , Bassat Q , Berhane M , Bunn J , Cossa ACA , El Arifeen S , Gunturu R , Hale M , Igunza A , Keita AM , Kenneh S , Kotloff KL , Kowuor D , Mabunda R , Madewell ZJ , Madhi S , Madrid L , Mahtab S , Miguel J , Murila FV , Ogbuanu IU , Ojulong J , Onyango D , Oundo JO , Scott JAG , Sow S , Tapia M , Traore CB , Velaphi S , Whitney CG , Mandomando I , Breiman RF . Lancet Microbe 2024 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. |
Progress in immunization safety monitoring - Worldwide, 2020-2022
Blau EF , Balakrishnan MR , Sköld H , Santhana Gopala Krishnan RS , Lundquist P , Pal S , Gidudu JF . MMWR Morb Mortal Wkly Rep 2023 72 (49) 1321-1326 Effective surveillance of adverse events following immunization (AEFIs) primarily relies on the collaboration of two partners: national regulatory authorities (NRAs) and national expanded programs on immunization (EPIs). In December 2020, the World Health Organization (WHO) Global Advisory Committee for Vaccine Safety recommended a new case-based indicator of national capacity to monitor immunization safety: at least one serious AEFI reported per 1 million total population per year. To achieve this indicator, WHO-affiliated countries and territories (WHO countries) rely upon data generated from functional AEFI surveillance systems. This report describes 2020-2022 global, regional, and national progress in use of the newly introduced immunization safety monitoring indicator and progress on joint AEFI reporting from national EPIs and NRAs. Among WHO countries, 51 (24%) of 214 implemented the new indicator in 2020, 111 (52%) of 214 implemented it in 2021, and 92 (43%) of 215 in 2022. In 2020, 41 (19%) WHO countries reported AEFI data jointly from EPIs and NRAs; this increased to 55 (26%) in 2021 and 57 (27%) in 2022. These findings, resulting in part from the intensified support for COVID-19 vaccination, demonstrate that national AEFI surveillance systems increasingly support the timely use and sharing of case-based immunization safety data, but work is still needed to strengthen global vaccine safety monitoring. |
Prevalence and missed cases of respiratory distress syndrome disease amongst neonatal deaths enrolled in the Kenya Child Health and Mortality Prevention Surveillance Network (CHAMPS) Program Between 2017 and 2021
Owuor HO , Akelo V , Murila F , Onyango D , Kuria M , Rogena E , Revathi G , Mitei P , Sava S , Were J , Igunza A , Khagayi S , Zielinski-Gutierrez E , Hawi S , Gethi D , Verani JR , Onyango C , Blau DM , Tippett Barr BA . Glob Pediatr Health 2023 10 2333794x231212819 Objectives. To describe RDS in neonatal deaths at the CHAMPS-Kenya site between 2017 and 2021. Methods. We included 165 neonatal deaths whose their Causes of death (COD) were determined by a panel of experts using data from post-mortem conducted through minimally invasive tissue specimen testing, clinical records, and verbal autopsy. Results. Twenty-six percent (43/165) of neonatal deaths were attributable to RDS. Most cases occurred in low birthweight and preterm neonates. From these cases, less than half of the hospitalizations were diagnosed with RDS before death, and essential diagnostic tests were not performed in most cases. Most cases received suboptimal levels of supplemental oxygen, and critical interventions like surfactant replacement therapy and mechanical ventilation were not adequately utilized when available. Conclusion. The study highlights the urgent need for improved diagnosis and management of RDS, emphasizing the importance of increasing clinical suspicion and enhancing training in its clinical management to reduce mortality rates. |
The Human Phenotype Ontology in 2024: phenotypes around the world
Gargano MA , Matentzoglu N , Coleman B , Addo-Lartey EB , Anagnostopoulos AV , Anderton J , Avillach P , Bagley AM , Bakštein E , Balhoff JP , Baynam G , Bello SM , Berk M , Bertram H , Bishop S , Blau H , Bodenstein DF , Botas P , Boztug K , Čady J , Callahan TJ , Cameron R , Carbon SJ , Castellanos F , Caufield JH , Chan LE , Chute CG , Cruz-Rojo J , Dahan-Oliel N , Davids JR , de Dieuleveult M , de Souza V , de Vries BBA , de Vries E , DePaulo JR , Derfalvi B , Dhombres F , Diaz-Byrd C , Dingemans AJM , Donadille B , Duyzend M , Elfeky R , Essaid S , Fabrizzi C , Fico G , Firth HV , Freudenberg-Hua Y , Fullerton JM , Gabriel DL , Gilmour K , Giordano J , Goes FS , Moses RG , Green I , Griese M , Groza T , Gu W , Guthrie J , Gyori B , Hamosh A , Hanauer M , Hanušová K , He YO , Hegde H , Helbig I , Holasová K , Hoyt CT , Huang S , Hurwitz E , Jacobsen JOB , Jiang X , Joseph L , Keramatian K , King B , Knoflach K , Koolen DA , Kraus ML , Kroll C , Kusters M , Ladewig MS , Lagorce D , Lai MC , Lapunzina P , Laraway B , Lewis-Smith D , Li X , Lucano C , Majd M , Marazita ML , Martinez-Glez V , McHenry TH , McInnis MG , McMurry JA , Mihulová M , Millett CE , Mitchell PB , Moslerová V , Narutomi K , Nematollahi S , Nevado J , Nierenberg AA , Čajbiková NN , Nurnberger JI Jr , Ogishima S , Olson D , Ortiz A , Pachajoa H , Perez de Nanclares G , Peters A , Putman T , Rapp CK , Rath A , Reese J , Rekerle L , Roberts AM , Roy S , Sanders SJ , Schuetz C , Schulte EC , Schulze TG , Schwarz M , Scott K , Seelow D , Seitz B , Shen Y , Similuk MN , Simon ES , Singh B , Smedley D , Smith CL , Smolinsky JT , Sperry S , Stafford E , Stefancsik R , Steinhaus R , Strawbridge R , Sundaramurthi JC , Talapova P , Tenorio Castano JA , Tesner P , Thomas RH , Thurm A , Turnovec M , van Gijn ME , Vasilevsky NA , Vlčková M , Walden A , Wang K , Wapner R , Ware JS , Wiafe AA , Wiafe SA , Wiggins LD , Williams AE , Wu C , Wyrwoll MJ , Xiong H , Yalin N , Yamamoto Y , Yatham LN , Yocum AK , Young AH , Yüksel Z , Zandi PP , Zankl A , Zarante I , Zvolský M , Toro S , Carmody LC , Harris NL , Munoz-Torres MC , Danis D , Mungall CJ , Köhler S , Haendel MA , Robinson PN . Nucleic Acids Res 2023 52 D1333-D1346 The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs. |
Hepatic vitamin A concentrations and association with infectious causes of child death
Gupta PM , Madewell ZJ , Gannon BM , Grahn M , Akelo V , Onyango D , Mahtab S , Madhi SA , Giri J , Blau DM , Ramakrishnan U , Stein AD , Whitney CG , Young MF , Tanumihardjo SA , Suchdev PS . J Pediatr 2023 265 113816 OBJECTIVES: To assess postmortem vitamin A (VA) concentrations in children under 5 years of age and evaluate the association between vitamin A deficiency (VAD) and infectious causes of death (CoD). STUDY DESIGN: In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72 hours of death were analyzed from 405 stillbirths and children under 5 years in Kenya and South Africa. Total liver vitamin A (VA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1 μmol/g, >0.1 to <0.7 μmol/g, ≥0.7 to <1.0 μmol/g, and ≥1.0 μmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. Causes of death (CoD) were determined by expert panel review. RESULTS: Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight, underweight, or stunting (p<0.05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95%CI 0.9, 3.8, p=0.073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95%CI 1.3, 10.3, p=0.013). CONCLUSIONS: Definitive post-mortem assessment of VA status identified both VAD and VA excess among children under 5 years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation to targeted strategies in certain countries. |
An approach to determining the most common causes of stillbirth in low and middle-income countries: A commentary
Goldenberg RL , Ordi J , Blau DM , Rakislova N , Kulkarni V , Ghanchi NK , Saleem S , Goudar SS , Goco N , Paganelli C , McClure EM . Gates Open Res 2023 7 102 Stillbirth, one of the most common adverse pregnancy outcomes, is especially prevalent in low and middle-income countries (LMICs). Understanding the causes of stillbirth is crucial to developing effective interventions. In this commentary, investigators working across several LMICs discuss the most useful investigations to determine causes of stillbirths in LMICs. Useful data were defined as 1) feasible to obtain accurately and 2) informative to determine or help eliminate a cause of death. Recently, new tools for LMIC settings to determine cause of death in stillbirths, including minimally invasive tissue sampling (MITS) - a method using needle biopsies to obtain internal organ tissue from deceased fetuses for histology and pathogen identification in those tissues have become available. While placental histology has been available for some time, the development of the Amsterdam Criteria in 2016 has provided a useful framework to categorize placental lesions. The authors recommend focusing on the clinical history, the placental evaluation, the external examination of the fetus, and, when available, fetal tissue obtained by MITS, especially of the lung (focused on histology and microbiology) and brain/cerebral spinal fluid (CSF) and fetal blood (focused on microbiological analysis). The authors recognize that this approach may not identify some causes of stillbirth, including some genetic abnormalities and internal organ anomalies, but believe it will identify the most common causes of stillbirth, and most of the preventable causes. |
Impact of anthropometry training and feasibility of 3D imaging on anthropometry data quality among children under five years in a postmortem setting
Gupta PM , Sivalogan K , Oliech R , Alexander E , Klein J , Addo OY , Gethi D , Akelo V , Blau DM , Suchdev PS . PLoS One 2023 18 (9) e0292046 BACKGROUND: The Child Health and Mortality Prevention Surveillance Network (CHAMPS) identifies causes of under-5 mortality in high mortality countries. OBJECTIVE: To address challenges in postmortem nutritional assessment, we evaluated the impact of anthropometry training and the feasibility of 3D imaging on data quality within the CHAMPS Kenya site. DESIGN: Staff were trained using World Health Organization (WHO)-recommended manual anthropometry equipment and novel 3D imaging methods to collect postmortem measurements. Following training, 76 deceased children were measured in duplicate and were compared to measurements of 75 pre-training deceased children. Outcomes included measures of data quality (standard deviations of anthropometric indices and digit preference scores (DPS)), precision (absolute and relative technical errors of measurement, TEMs or rTEMs), and accuracy (Bland-Altman plots). WHO growth standards were used to produce anthropometric indices. Post-training surveys and in-depth interviews collected qualitative feedback on measurer experience with performing manual anthropometry and ease of using 3D imaging software. RESULTS: Manual anthropometry data quality improved after training, as indicated by DPS. Standard deviations of anthropometric indices exceeded limits for high data quality when using the WHO growth standards. Reliability of measurements post-training was high as indicated by rTEMs below 1.5%. 3D imaging was highly correlated with manual measurements; however, on average 3D scans overestimated length and head circumference by 1.61 cm and 2.27 cm, respectively. Site staff preferred manual anthropometry to 3D imaging, as the imaging technology required adequate lighting and additional considerations when performing the measurements. CONCLUSIONS: Manual anthropometry was feasible and reliable postmortem in the presence of rigor mortis. 3D imaging may be an accurate alternative to manual anthropometry, but technology adjustments are needed to ensure accuracy and usability. |
Seasonal trends in emergency department visits for mental and behavioral health conditions among children and adolescents aged 5-17 years - United States, January 2018-June 2023
Radhakrishnan L , Carey K , Pell D , Ising A , Brathwaite D , Waller A , Gay J , Watson-Smith H , Person M , Zamore K , Brumsted T , Price C , Clark PM , Haas GA , Gracy L , Johnston S , Chen Y , Muñoz K , Henry M , Willis B , Nevels D , Asaolu I , Lee S , Wilkins NJ , Bacon S , Sheppard M , Kite-Powell A , Blau G , King M , Whittaker M , Leeb RT . MMWR Morb Mortal Wkly Rep 2023 72 (38) 1032-1040 Mental and behavioral health conditions among school-aged children, including substance use disorders and overall emotional well-being, are a public health concern in the United States. Timely data on seasonal patterns in child and adolescent conditions can guide optimal timing of prevention and intervention strategies. CDC examined emergency department (ED) visit data from the National Syndromic Surveillance Program for 25 distinct conditions during January 2018-June 2023 among U.S. children and adolescents aged 5-17 years, stratified by age group. Each year, during 2018-2023, among persons aged 10-14 and 15-17 years, the number and proportion of weekly ED visits for eight conditions increased in the fall school semester and remained elevated throughout the spring semester; ED visits were up to twice as high during school semesters compared with the summer period. Among children aged 5-9 years, the number and proportion of visits increased for five mental and behavioral health conditions. Seasonal increases in ED visits for some conditions among school-aged children warrant enhanced awareness about mental distress symptoms and the challenges and stressors in the school environment. Systemic changes that prioritize protective factors (e.g., physical activity; nutrition; sleep; social, community, or faith-based support; and inclusive school and community environments) and incorporate preparedness for increases in conditions during back-to-school planning might improve child and adolescent mental health. |
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
Rees CA , Igunza KA , Madewell ZJ , Akelo V , Onyango D , El Arifeen S , Gurley ES , Hossain MZ , Rahman A , Alam M , Scott JAG , Assefa N , Madrid L , Belachew A , Leulseged H , Kotloff KL , Sow SO , Tapia MD , Keita AM , Sidibe D , Sitoe A , Varo R , Ajanovic S , Bassat Q , Mandomando I , Tippett Barr BA , Ogbuanu I , Cain CJ , Bassey IA , Luke R , Gassama K , Madhi S , Dangor Z , Mahtab S , Velaphi S , du Toit J , Mutevedzi PC , Blau DM , Breiman RF , Whitney CG . EClinicalMedicine 2023 63 102198 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. |
Stillbirths and neonatal deaths caused by group B streptococcus in Africa and South Asia identified through Child Health and Mortality Prevention Surveillance (CHAMPS)
Mahtab S , Madewell ZJ , Madhi SA , Wise A , Swart PJ , Velaphi S , Mandomando I , Bramugy J , Mabunda R , Xerinda E , Scott AG , Assefa N , Madrid L , Bweihun M , Temesgen F , Onyango D , Akelo V , Oliech R , Otieno P , Verani JR , Arifeen SE , Gurley ES , Alam M , Rahman A , Hossain MZ , Sow S , Kotloff K , Tapia M , Keita AM , Sanogo D , Ogbuanu I , Ojulong J , Lako S , Ita O , Kaluma E , Wilson T , Mutevedzi P , Barr BAT , Whitney CG , Blau DM , Bassat Q . Open Forum Infect Dis 2023 10 (9) ofad356 BACKGROUND: Invasive Group B Streptococcus (GBS) is a common cause of early-onset neonatal sepsis and is also associated with stillbirth. This study aimed to determine the proportion of stillborn infants and infants who died between 0 and 90 days attributable to GBS using postmortem minimally invasive tissue sampling (MITS) in 7 low- and middle-income countries (LMICs) participating in Child Health and Mortality Prevention Surveillance (CHAMPS). METHODS: Deaths that occurred between December 2016 and December 2021 were investigated with MITS, including culture for bacteria of blood and cerebrospinal fluid (CSF), multipathogen polymerase chain reaction on blood, CSF, and lung tissue and histopathology of lung, liver, and brain. Data collection included clinical record review and verbal autopsy. Expert panels reviewed all information and assigned causes of death. RESULTS: We evaluated 2966 deaths, including stillborn infants (n = 1322), infants who died during first day of life (0 to <24 hours, n = 597), early neonatal deaths (END) (1 day to <7 days; END; n = 593), and deaths from 7 to 90 days (n = 454). Group B Streptococcus was determined to be in the causal pathway of death for 2.7% of infants (79 of 2, 966; range, 0.3% in Sierra Leone to 7.2% in South Africa), including 2.3% (31 of 1322) of stillbirths, 4.7% (28 of 597) 0 to <24 hours, 1.9% (11 of 593) END, and 2.0% (9 of 454) of deaths from 7 to 90 days of age. Among deaths attributed to GBS with birth weight data available, 61.9% (39 of 63) of decedents weighed <2500 grams at birth. Group B Streptococcus sepsis was the postmortem diagnosis for 100% (31 of 31) of stillbirths. For deaths <90 days, postmortem diagnoses included GBS sepsis (83.3%, 40 of 48), GBS meningitis (4.2%, 2 of 48), and GBS pneumonia (2.1%, 1 of 48). CONCLUSIONS: Our study reveals significant heterogeneity in the contribution of invasive GBS disease to infant mortality across different countries, emphasizing the need for tailored prevention strategies. Moreover, our findings highlight the substantial impact of GBS on stillbirths, shedding light on a previously underestimated aspect in LMICs. |
Causes of death among infants and children in the Child Health and Mortality Prevention Surveillance (CHAMPS) Network
Bassat Q , Blau DM , Ogbuanu IU , Samura S , Kaluma E , Bassey IA , Sow S , Keita AM , Tapia MD , Mehta A , Kotloff KL , Rahman A , Islam KM , Alam M , El Arifeen S , Gurley ES , Baillie V , Mutevedzi P , Mahtab S , Thwala BN , Tippett Barr BA , Onyango D , Akelo V , Rogena E , Onyango P , Omore R , Mandomando I , Ajanovic S , Varo R , Sitoe A , Duran-Frigola M , Assefa N , Scott JAG , Madrid L , Tesfaye T , Dessie Y , Madewell ZJ , Breiman RF , Whitney CG , Madhi SA . JAMA Netw Open 2023 6 (7) e2322494 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. |
Causes of stillbirth and death among children younger than 5 years in eastern Hararghe, Ethiopia: a population-based post-mortem study
Madrid L , Alemu A , Seale AC , Oundo J , Tesfaye T , Marami D , Yigzaw H , Ibrahim A , Degefa K , Dufera T , Teklemariam Z , Gure T , Leulseged H , Wittmann S , Abayneh M , Fentaw S , Temesgen F , Yeshi MM , Dubale M , Girma Z , Ackley C , Damisse B , Breines M , Orlien SMS , Blau DM , Breiman RF , Abate E , Dessie Y , Assefa N , Scott JAG . Lancet Glob Health 2023 11 (7) e1032-e1040 BACKGROUND: Child mortality is high in Ethiopia, but reliable data on the causes of death are scarce. We aimed to gather data for the contributory causes of stillbirth and child deaths in eastern Ethiopia. METHODS: In this population-based post-mortem study, we established a death-notification system in health facilities and in the community in Kersa (rural), Haramaya (rural) and Harar (urban) in eastern Ethiopia, at a new site of the Child Health and Mortality Prevention Surveillance (CHAMPS) network. We collected ante-mortem data, did verbal autopsies, and collected post-mortem samples via minimally invasive tissue sampling from stillbirths (weighing at least 1000 g or with an estimated gestational age of at least 28 weeks) and children who died younger than 5 years. Children-or their mothers, in the case of stillbirths and deaths in children younger than 6 months-had to have lived in the catchment area for the past 6 months to be included. Molecular, microbiological, and histopathological analyses were done in collected samples. Cause of death was established by an expert panel on the basis of these data and classified as underlying, comorbid, or immediate separately for stillbirths, neonatal deaths (deaths aged 0-27 days), and child deaths (aged 28 days to <5 years). FINDINGS: Between Feb 4, 2019, and Feb 3, 2021, 312 deaths were eligible for inclusion, and the families gave consent in 195 (63%) cases. Cause of death was established in 193 (99%) cases. Among 114 stillbirths, the underlying cause of death was perinatal asphyxia or hypoxia in 60 (53%) and birth defects in 24 (21%). Among 59 neonatal deaths, the most common underlying cause was perinatal asphyxia or hypoxia (17 [29%]) and the most common immediate cause of death was neonatal sepsis, which occurred in 27 (60%). Among 20 deaths in children aged 28 days to 59 months, malnutrition was the leading underlying cause (15 [75%]) and infections were common immediate and comorbid causes. Pathogens were identified in 19 (95%) child deaths, most commonly Klebsiella pneumoniae and Streptococcus pneumoniae. INTERPRETATION: Perinatal asphyxia or hypoxia, infections, and birth defects accounted for most stillbirths and child deaths. Most deaths could have been prevented with feasible interventions, such as improved maternity services, folate supplementation, and improved vaccine uptake. FUNDING: Bill & Melinda Gates Foundation. |
Neural tube defects as a cause of death among stillbirths, infants, and children younger than 5 years in sub-Saharan Africa and southeast Asia: an analysis of the CHAMPS network
Madrid L , Vyas KJ , Kancherla V , Leulseged H , Suchdev PS , Bassat Q , Sow SO , El Arifeen S , Madhi SA , Onyango D , Ogbuanu I , Scott JAG , Blau D , Mandomando I , Keita AM , Gurley ES , Mahtab S , Akelo V , Sannoh S , Tilahun Y , Varo R , Onwuchekwa U , Rahman A , Adam Y , Omore R , Lako S , Xerinda E , Islam KM , Wise A , Tippet-Barr BA , Kaluma E , Ajanovic S , Kotloff KL , Hossain MZ , Mutevedzi P , Tapia MD , Rogena E , Moses F , Whitney CG , Assefa N . Lancet Glob Health 2023 11 (7) e1041-e1052 BACKGROUND: Neural tube defects are common birth defects resulting in severe morbidity and mortality; they can largely be prevented with periconceptional maternal intake of folic acid. Understanding the occurrence of neural tube defects and their contribution to mortality in settings where their burden is highest could inform prevention and health-care policy. We aimed to estimate the mortality attributed to neural tube defects in seven countries in sub-Saharan Africa and southeast Asia. METHODS: This analysis used data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network and health and demographic surveillance systems from South Africa, Mozambique, Bangladesh, Kenya, Mali, Ethiopia, and Sierra Leone. All stillbirths and infants and children younger than 5 years who died, who were enrolled in CHAMPS, whose families consented to post-mortem minimally invasive tissue sampling (MITS) between Jan 1, 2017, and Dec 31, 2021, and who were assigned a cause of death by a determination of cause of death panel as of May 24, 2022, were included in this analysis, regardless the cause of death. MITS and advanced diagnostic methods were used to describe the frequency and characteristics of neural tube defects among eligible deaths, identify risk factors, and estimate the mortality fraction and mortality rate (per 10 000 births) by CHAMPS site. FINDINGS: Causes of death were determined for 3232 stillbirths, infants, and children younger than 5 years, of whom 69 (2%) died with a neural tube defect. Most deaths with a neural tube defect were stillbirths (51 [74%]); 46 (67%) were neural tube defects incompatible with life (ie, anencephaly, craniorachischisis, or iniencephaly) and 22 (32%) were spina bifida. Deaths with a neural tube defect were more common in Ethiopia (adjusted odds ratio 8·09 [95% CI 2·84-23·02]), among female individuals (4·40 [2·44-7·93]), and among those whose mothers had no antenatal care (2·48 [1·12-5·51]). Ethiopia had the highest adjusted mortality fraction of deaths with neural tube defects (7·5% [6·7-8·4]) and the highest adjusted mortality rate attributed to neural tube defects (104·0 per 10 000 births [92·9-116·4]), 4-23 times greater than in any other site. INTERPRETATION: CHAMPS identified neural tube defects, a largely preventable condition, as a common cause of death among stillbirths and neonatal deaths, especially in Ethiopia. Implementing interventions such as mandatory folic acid fortification could reduce mortality due to neural tube defects. FUNDING: Bill & Melinda Gates Foundation. |
Correcting for verbal autopsy misclassification bias in cause-specific mortality estimates
Fiksel J , Gilbert B , Wilson E , Kalter H , Kante A , Akum A , Blau D , Bassat Q , Macicame I , Samo Gudo E , Black R , Zeger S , Amouzou A , Datta A . Am J Trop Med Hyg 2023 108 66-77 Verbal autopsies (VAs) are extensively used to determine cause of death (COD) in many low- and middle-income countries. However, COD determination from VA can be inaccurate. Computer coded verbal autopsy (CCVA) algorithms used for this task are imperfect and misclassify COD for a large proportion of deaths. If not accounted for, this misclassification leads to biased estimates of cause-specific mortality fractions (CSMFs), a critical piece in health-policy making. Recent work has demonstrated that the knowledge of the CCVA misclassification rates can be used to calibrate raw VA-based CSMF estimates to account for the misclassification bias. In this manuscript, we review the current practices and issues with raw COD predictions from CCVA algorithms and provide a complete primer on how to use the VA calibration approach with the calibratedVA software to correct for verbal autopsy misclassification bias in cause-specific mortality estimates. We use calibratedVA to obtain CSMFs for child (1-59 months) and neonatal deaths using VA data from the Countrywide Mortality Surveillance for Action project in Mozambique. |
Multi-cause calibration of verbal autopsy-based cause-specific mortality estimates of children and neonates in Mozambique
Gilbert B , Fiksel J , Wilson E , Kalter H , Kante A , Akum A , Blau D , Bassat Q , Macicame I , Samo Gudo E , Black R , Zeger S , Amouzou A , Datta A . Am J Trop Med Hyg 2023 108 78-89 The Countrywide Mortality Surveillance for Action platform is collecting verbal autopsy (VA) records from a nationally representative sample in Mozambique. These records are used to estimate the national and subnational cause-specific mortality fractions (CSMFs) for children (1-59 months) and neonates (1-28 days). Cross-tabulation of VA-based cause-of-death (COD) determination against that from the minimally invasive tissue sampling (MITS) from the Child Health and Mortality Prevention project revealed important misclassification errors for all the VA algorithms, which if not accounted for will lead to bias in the estimates of CSMF from VA. A recently proposed Bayesian VA-calibration method is used that accounts for this misclassification bias and produces calibrated estimates of CSMF. Both the VA-COD and the MITS-COD can be multi-cause (i.e., suggest more than one probable COD for some of the records). To fully use this probabilistic COD data, we use the multi-cause VA calibration. Two different computer-coded VA algorithms are considered-InSilicoVA and EAVA-and the final CSMF estimates are obtained using an ensemble calibration that uses data from both the algorithms. The calibrated estimates consistently offer a better fit to the data and reveal important changes in the CSMF for both children and neonates in Mozambique after accounting for VA misclassification bias. |
Causes of death identified in neonates enrolled through Child Health and Mortality Prevention Surveillance (CHAMPS), December 2016 -December 2021
Mahtab S , Madhi SA , Baillie VL , Els T , Thwala BN , Onyango D , Tippet-Barr BA , Akelo V , Igunza KA , Omore R , Arifeen SE , Gurley ES , Alam M , Chowdhury AI , Rahman A , Bassat Q , Mandomando I , Ajanovic S , Sitoe A , Varo R , Sow SO , Kotloff KL , Badji H , Tapia MD , Traore CB , Ogbuanu IU , Bunn J , Luke R , Sannoh S , Swarray-Deen A , Assefa N , Scott JAG , Madrid L , Marami D , Fentaw S , Diaz MH , Martines RB , Breiman RF , Madewell ZJ , Blau DM , Whitney CG . PLOS Glob Public Health 2023 3 (3) e0001612 Each year, 2.4 million children die within their first month of life. Child Health and Mortality Prevention Surveillance (CHAMPS) established in 7 countries aims to generate accurate data on why such deaths occur and inform prevention strategies. Neonatal deaths that occurred between December 2016 and December 2021 were investigated with MITS within 24-72 hours of death. Testing included blood, cerebrospinal fluid and lung cultures, multi-pathogen PCR on blood, CSF, nasopharyngeal swabs and lung tissue, and histopathology examination of lung, liver and brain. Data collection included clinical record review and family interview using standardized verbal autopsy. The full set of data was reviewed by local experts using a standardized process (Determination of Cause of Death) to identify all relevant conditions leading to death (causal chain), per WHO recommendations. For analysis we stratified neonatal death into 24-hours of birth, early (1-<7 days) and late (7-<28 days) neonatal deaths. We analyzed 1458 deaths, 41% occurring within 24-hours, 41% early and 18% late neonatal deaths. Leading underlying causes of death were complications of intrapartum events (31%), complications of prematurity (28%), infections (17%), respiratory disorders (11%), and congenital malformations (8%). In addition to the underlying cause, 62% of deaths had additional conditions and 14% had ≥3 other conditions in the causal chain. The most common causes considering the whole causal chain were infection (40%), prematurity (32%) and respiratory distress syndrome (28%). Common maternal conditions linked to neonatal death were maternal hypertension (10%), labour and delivery complications (8%), multiple gestation (7%), placental complications (6%) obstructed labour and chorioamnionitis (5%, each). CHAMPS' findings showing the full causal chain of events that lead to death, in addition to maternal factors, highlights the complexities involved in each death along with the multiple opportunities for prevention. Highlighting improvements to prenatal and obstetric care and infection prevention are urgently needed in high-mortality settings. |
CDC's COVID-19 international vaccine implementation and evaluation program and lessons from earlier vaccine introductions
Soeters HM , Doshi RH , Fleming M , Adegoke OJ , Ajene U , Aksnes BN , Bennett S , Blau EF , Carlton JG , Clements S , Conklin L , Dahlke M , Duca LM , Feldstein LR , Gidudu JF , Grant G , Hercules M , Igboh LS , Ishizumi A , Jacenko S , Kerr Y , Konne NM , Kulkarni S , Kumar A , Lafond KE , Lam E , Longley AT , McCarron M , Namageyo-Funa A , Ortiz N , Patel JC , Perry RT , Prybylski D , Reddi P , Salman O , Sciarratta CN , Shragai T , Siddula A , Sikare E , Tchoualeu DD , Traicoff D , Tuttle A , Victory KR , Wallace A , Ward K , Wong MKA , Zhou W , Schluter WW , Fitter DL , Mounts A , Bresee JS , Hyde TB . Emerg Infect Dis 2022 28 (13) S208-s216 The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions. |
Population-based linked longitudinal surveillance of pregnant people and their infants: A critical resource for emerging, re-emerging, and persistent threats
Tong VT , Woodworth KR , Blau E , Shinde N , Akosa A , Gilboa SM , Meaney-Delman D . J Womens Health (Larchmt) 2022 32 (1) 1-9 Public health emergencies, from Zika to COVID-19, have underscored the importance of addressing the needs of pregnant people and their infants. Recent events have underlined the critical role of mother-infant-linked longitudinal surveillance to characterize and assess the impacts of emerging, re-emerging, and persistent threats, including infectious diseases, on these populations. In partnership with state, local, and territorial health departments, CDC's National Center on Birth Defects and Developmental Disabilities activated the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET) to capture information about pregnant people with laboratory-confirmed infection with SARS-CoV-2 (the virus that causes COVID-19) and their infants. SET-NET data were critical in recognizing the severe risks of COVID-19 during pregnancy, which ultimately informed clinical decisions and public health policy, specifically vaccine prioritization at the local, state, and national levels. This commentary describes the activation of SET-NET to monitor COVID-19 in pregnancy and highlights the experiences of health departments. We provide examples of how SET-NET findings informed COVID-19 prevention efforts and public health policy. Lastly, we identify opportunities to improve and advance surveillance efforts to protect the health of pregnant people and their infants in the United States from current and future threats. |
Prioritizing health care strategies to reduce childhood mortality
Madewell ZJ , Whitney CG , Velaphi S , Mutevedzi P , Mahtab S , Madhi SA , Fritz A , Swaray-Deen A , Sesay T , Ogbuanu IU , Mannah MT , Xerinda EG , Sitoe A , Mandomando I , Bassat Q , Ajanovic S , Tapia MD , Sow SO , Mehta A , Kotloff KL , Keita AM , Tippett Barr BA , Onyango D , Oele E , Igunza KA , Agaya J , Akelo V , Scott JAG , Madrid L , Kelil YE , Dufera T , Assefa N , Gurley ES , El Arifeen S , Spotts Whitney EA , Seib K , Rees CA , Blau DM . JAMA Netw Open 2022 5 (10) e2237689 IMPORTANCE: Although child mortality trends have decreased worldwide, deaths among children younger than 5 years of age remain high and disproportionately circumscribed to sub-Saharan Africa and Southern Asia. Tailored and innovative approaches are needed to increase access, coverage, and quality of child health care services to reduce mortality, but an understanding of health system deficiencies that may have the greatest impact on mortality among children younger than 5 years is lacking. OBJECTIVE: To investigate which health care and public health improvements could have prevented the most stillbirths and deaths in children younger than 5 years using data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used longitudinal, population-based, and mortality surveillance data collected by CHAMPS to understand preventable causes of death. Overall, 3390 eligible deaths across all 7 CHAMPS sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) between December 9, 2016, and December 31, 2021 (1190 stillbirths, 1340 neonatal deaths, 860 infant and child deaths), were included. Deaths were investigated using minimally invasive tissue sampling (MITS), a postmortem approach using biopsy needles for sampling key organs and fluids. MAIN OUTCOMES AND MEASURES: For each death, an expert multidisciplinary panel reviewed case data to determine the plausible pathway and causes of death. If the death was deemed preventable, the panel identified which of 10 predetermined health system gaps could have prevented the death. The health system improvements that could have prevented the most deaths were evaluated for each age group: stillbirths, neonatal deaths (aged <28 days), and infant and child deaths (aged 1 month to <5 years). RESULTS: Of 3390 deaths, 1505 (44.4%) were female and 1880 (55.5%) were male; sex was not recorded for 5 deaths. Of all deaths, 3045 (89.8%) occurred in a healthcare facility and 344 (11.9%) in the community. Overall, 2607 (76.9%) were deemed potentially preventable: 883 of 1190 stillbirths (74.2%), 1010 of 1340 neonatal deaths (75.4%), and 714 of 860 infant and child deaths (83.0%). Recommended measures to prevent deaths were improvements in antenatal and obstetric care (recommended for 588 of 1190 stillbirths [49.4%], 496 of 1340 neonatal deaths [37.0%]), clinical management and quality of care (stillbirths, 280 [23.5%]; neonates, 498 [37.2%]; infants and children, 393 of 860 [45.7%]), health-seeking behavior (infants and children, 237 [27.6%]), and health education (infants and children, 262 [30.5%]). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, interventions prioritizing antenatal, intrapartum, and postnatal care could have prevented the most deaths among children younger than 5 years because 75% of deaths among children younger than 5 were stillbirths and neonatal deaths. Measures to reduce mortality in this population should prioritize improving existing systems, such as better access to antenatal care, implementation of standardized clinical protocols, and public education campaigns. |
Mixed-methods analysis of select issues reported in the 2016 World Health Organization verbal autopsy questionnaire
Nichols E , Pettrone K , Vickers B , Gebrehiwet H , Surek-Clark C , Leitao J , Amouzou A , Blau DM , Bradshaw D , Abdelilah EM , Groenewald P , Munkombwe B , Mwango C , Notzon FS , Biko Odhiambo S , Scanlon P . PLoS One 2022 17 (10) e0274304 BACKGROUND: Use of a standardized verbal autopsy (VA) questionnaire, such as the World Health Organization (WHO) instrument, can improve the consistency and reliability of the data it collects. Systematically revising a questionnaire, however, requires evidence about the performance of its questions. The purpose of this investigation was to use a mixed methods approach to evaluate the performance of questions related to 14 previously reported issues in the 2016 version of the WHO questionnaire, where there were concerns of potential confusion, redundancy, or inability of the respondent to answer the question. The results from this mixed methods analysis are discussed across common themes that may have contributed to the underperformance of questions and have been compiled to inform decisions around the revision of the current VA instrument. METHODS: Quantitative analysis of 19,150 VAs for neonates, children, and adults from five project teams implementing VAs predominately in Sub-Saharan Africa included frequency distributions and cross-tabulations to evaluate response patterns among related questions. The association of respondent characteristics and response patterns was evaluated using prevalence ratios. Qualitative analysis included results from cognitive interviewing, an approach that provides a detailed understanding of the meanings and processes that respondents use to answer interview questions. Cognitive interviews were conducted among 149 participants in Morocco and Zambia. Findings from the qualitative and quantitative analyses were triangulated to identify common themes. RESULTS: Four broad themes contributing to the underperformance or redundancy within the instrument were identified: question sequence, overlap within the question series, questions outside the frame of reference of the respondent, and questions needing clarification. The series of questions associated with one of the 14 identified issues (the series of questions on injuries) related to question sequence; seven (tobacco use, sores, breast swelling, abdominal problem, vomiting, vaccination, and baby size) demonstrated similar response patterns among questions within each series capturing overlapping information. Respondent characteristics, including relationship to the deceased and whether or not the respondent lived with the deceased, were associated with differing frequencies of non-substantive responses in three question series (female health related issues, tobacco use, and baby size). An inconsistent understanding of related constructs was observed between questions related to sores/ulcers, birth weight/baby size, and diagnosis of dementia/presence of mental confusion. An incorrect association of the intended construct with that which was interpreted by the respondent was observed in the medical diagnosis question series. CONCLUSIONS: In this mixed methods analysis, we identified series of questions which could be shortened through elimination of redundancy, series of questions requiring clarification due to unclear constructs, and the impact of respondent characteristics on the quality of responses. These changes can lead to a better understanding of the question constructs by the respondents, increase the acceptance of the tool, and improve the overall accuracy of the VA instrument. |
Insights on the differentiation of stillbirths and early neonatal deaths: A study from the Child Health and Mortality Prevention Surveillance (CHAMPS) network
Quincer E , Philipsborn R , Morof D , Salzberg NT , Vitorino P , Ajanovic S , Onyango D , Ogbuanu I , Assefa N , Sow SO , Mutevedzi P , El Arifeen S , Tippet Barr BA , Scott JAG , Mandomando I , Kotloff KL , Jambai A , Akelo V , Cain CJ , Chowdhury AI , Gure T , Igunza KA , Islam F , Keita AM , Madrid L , Mahtab S , Mehta A , Mitei PK , Ntuli C , Ojulong J , Rahman A , Samura S , Sidibe D , Thwala BN , Varo R , Madhi SA , Bassat Q , Gurley ES , Blau DM , Whitney CG . PLoS One 2022 17 (7) e0271662 INTRODUCTION: The high burden of stillbirths and neonatal deaths is driving global initiatives to improve birth outcomes. Discerning stillbirths from neonatal deaths can be difficult in some settings, yet this distinction is critical for understanding causes of perinatal deaths and improving resuscitation practices for live born babies. METHODS: We evaluated data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network to compare the accuracy of determining stillbirths versus neonatal deaths from different data sources and to evaluate evidence of resuscitation at delivery in accordance with World Health Organization (WHO) guidelines. CHAMPS works to identify causes of stillbirth and death in children <5 years of age in Bangladesh and 6 countries in sub-Saharan Africa. Using CHAMPS data, we compared the final classification of a case as a stillbirth or neonatal death as certified by the CHAMPS Determining Cause of Death (DeCoDe) panel to both the initial report of the case by the family member or healthcare worker at CHAMPS enrollment and the birth outcome as stillbirth or livebirth documented in the maternal health record. RESULTS: Of 1967 deaths ultimately classified as stillbirth, only 28 (1.4%) were initially reported as livebirths. Of 845 cases classified as very early neonatal death, 33 (4%) were initially reported as stillbirth. Of 367 cases with post-mortem examination showing delivery weight >1000g and no maceration, the maternal clinical record documented that resuscitation was not performed in 161 cases (44%), performed in 14 (3%), and unknown or data missing for 192 (52%). CONCLUSION: This analysis found that CHAMPS cases assigned as stillbirth or neonatal death after DeCoDe expert panel review were generally consistent with the initial report of the case as a stillbirth or neonatal death. Our findings suggest that more frequent use of resuscitation at delivery and improvements in documentation around events at birth could help improve perinatal outcomes. |
Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis
Li Y , Wang X , Blau DM , Caballero MT , Feikin DR , Gill CJ , Madhi SA , Omer SB , Simões EAF , Campbell H , Pariente AB , Bardach D , Bassat Q , Casalegno JS , Chakhunashvili G , Crawford N , Danilenko D , Do LAH , Echavarria M , Gentile A , Gordon A , Heikkinen T , Huang QS , Jullien S , Krishnan A , Lopez EL , Markić J , Mira-Iglesias A , Moore HC , Moyes J , Mwananyanda L , Nokes DJ , Noordeen F , Obodai E , Palani N , Romero C , Salimi V , Satav A , Seo E , Shchomak Z , Singleton R , Stolyarov K , Stoszek SK , von Gottberg A , Wurzel D , Yoshida LM , Yung CF , Zar HJ , Nair H . Lancet 2022 399 (10340) 2047-2064 BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU). |
Prioritising health-care strategies to reduce childhood mortality, insights from Child Health and Mortality Prevention Surveillance (CHAMPS): a longitudinal study
Madewell ZJ , Whitney CG , Assefa N , Bassat Q , Arifeen SE , Gurley ES , Jambai A , Kotloff KL , Madhi SA , Mandomando I , Ogbuanu IU , Onyango D , Scott JAG , Sow SO , Barr BAT , Blau DM . Lancet Glob Health 2022 10 Suppl 1 S8 BACKGROUND: Globally, mortality in children younger than 5 years has been decreasing over the past few decades, but high under-5 mortality persists across regions of sub-Saharan Africa and southern Asia. Interventions-such as improved quality of clinical and antenatal care, better access to emergency obstetrical procedures, better triage and risk stratification, better immunisation coverage, or infection control measures-could substantially reduce deaths, but it is unclear which strategies could save the most lives. We aimed to use data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network to examine which health-care and public health improvements could have prevented the most deaths. METHODS: We used standardised, population-based, mortality surveillance data collected by CHAMPS from seven sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) to understand preventable causes of death in children younger than 5 years. Deaths were investigated with minimally invasive tissue sampling, a post-mortem approach using biopsy needles for sampling key organs and body fluids. For each death, an expert panel reviewed case data to determine whether the death was preventable and (if preventable) provided recommendations as to how the death could have been avoided. We evaluated which health system improvements could have prevented the most deaths among those who underwent minimally invasive tissue sampling for each age group: stillbirths, neonatal deaths (aged <28 days), and infant or child deaths (aged 1 month to <5 years). FINDINGS: We included 1982 eligible deaths (with minimally invasive tissue sampling performed) that occurred between Dec 9, 2016, and Feb 29, 2020, including 556 stillbirths, 828 neonatal deaths, and 598 child deaths. Of these 1982 deaths across all seven CHAMPS sites, 393 (71%) stillbirths, 583 (70%) neonatal deaths, and 487 (81%) child deaths were deemed preventable. The most recommended measures to prevent deaths were improvements in antenatal or obstetric care (recommended for 44% of stillbirths and 31% of neonatal deaths), clinical management and quality of care (stillbirths 26%, neonates 32%, children 46%), health-seeking behaviour (children 24%), and health education (children 22%). Given that 70% of under-5 deaths are stillbirths and neonatal deaths, an intervention that focuses on these age groups (eg, improved antenatal care) could prevent the most under-5 deaths. INTERPRETATION: These data indicate areas in which greater focus on improving existing systems could prevent the most deaths. Investments in interventions such as better access to antenatal care, improvements in clinical practice, and public education campaigns could substantially reduce child mortality. FUNDING: Bill & Melinda Gates Foundation (OPP1126780). |
- Page last reviewed:Feb 1, 2024
- Page last updated:Apr 29, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure