Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 98 Records) |
Query Trace: Gurley ES[original query] |
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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. |
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. |
Prevalence and incidence of tuberculosis infection among healthcare workers in chest diseases hospitals, Bangladesh: Putting infection control into context
Islam MS , Gurley ES , Banu S , Hossain K , Heffelfinger JD , Amin Chowdhury KI , Ahmed S , Afreen S , Islam MT , Rahman SMM , Rahman A , Pearson ML , Chai SJ . PLoS One 2023 18 (9) e0291484 BACKGROUND: Healthcare workers (HCWs) are at increased risk of tuberculosis infection (TBI). We estimated the prevalence and incidence of TBI and risk factors among HCWs in Bangladeshi hospitals to target TB infection prevention and control (IPC) interventions. METHODS: During 2013-2016, we conducted a longitudinal study among HCWs in four chest disease hospitals. At baseline, we administered a questionnaire on sociodemographic and occupational factors for TB, tuberculin skin tests (TST) in all hospitals, and QuantiFERON ®-TB Gold in-Tube (QFT-GIT) tests in one hospital. We assessed factors associated with baseline TST positivity (induration ≥10mm), TST conversion (induration increase ≥10mm from baseline), baseline QFT-GIT positivity (interferon-gamma ≥0.35 IU/mL), and QFT-GIT conversion (interferon-gamma <0.35 IU/mL to ≥0.35 IU/mL). We included factors with a biologically plausible relationship with TBI identified in prior studies or having an association (p = <0.20) in the bivariate analyses with TST positivity or QFT-GIT positivity in multivariable generalized linear models. The Kaplan-Meier was used to estimate the cumulative TBI incidence rate per 100 person-years. RESULTS: Of the 758 HCWs invited, 732 (97%) consented to participate and 731 completed the one-step TST, 40% had a positive TST result, and 48% had a positive QFT-GIT result. In multivariable models, HCWs years of service 11-20 years had 2.1 (95% CI: 1.5-3.0) times higher odds of being TST-positive and 1.6 (95% CI 1.1-2.5) times higher odds of QFT-GIT-positivity at baseline compared with those working ≤10 years. HCWs working 11-20 years in pulmonary TB ward had 2.0 (95% CI: 1.4-2.9) times higher odds of TST positivity, and those >20 years had 2.5 (95% CI: 1.3-4.9) times higher odds of QFT-GIT-positivity at baseline compared with those working <10 years. TBI incidence was 4.8/100 person-years by TST and 4.2/100 person-years by QFT-GIT. Females had 8.5 (95% CI: 1.5-49.5) times higher odds of TST conversion than males. CONCLUSIONS: Prevalent TST and QFT-GIT positivity was associated with an increased number of years working as a healthcare worker and in pulmonary TB wards. The incidence of TBI among HCWs suggests ongoing TB exposure in these facilities and an urgent need for improved TB IPC in chest disease hospitals in Bangladesh. |
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 <24ā 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 <24ā 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. |
Hepatitis E as a cause of adult hospitalization in Bangladesh: Results from an acute jaundice surveillance study in six tertiary hospitals, 2014-2017 (preprint)
Paul RC , Nazneen A , Banik KC , Sumon SA , Paul KK , Akram A , Uzzaman MS , Iqbal T , Tejada-Strop A , Kamili S , Luby SP , Gidding HF , Hayen A , Gurley ES . bioRxiv 2019 688721 In the absence of reliable data on the burden of hepatitis E virus (HEV) in high endemic countries, we established a hospital-based acute jaundice surveillance program in six tertiary hospitals in Bangladesh to estimate the burden of HEV infection among hospitalized acute jaundice patients aged ≥14 years, identify seasonal and geographic patterns in the prevalence of hepatitis E, and examine factors associated with death.We collected blood specimens from enrolled acute jaundice patients, defined as new onset of either yellow eyes or skin during the past three months of hospital admission, and tested for immunoglobulin M (IgM) antibodies against HEV, HBV and HAV. The enrolled patients were followed up three months after hospital discharge to assess their survival status; pregnant women were followed up three months after their delivery to assess pregnancy outcomes.From December’2014 to September’2017, 1925 patients with acute jaundice were enrolled; 661 (34%) had acute hepatitis E, 48 (8%) had hepatitis A, and 293 (15%) had acute hepatitis B infection. Case fatality among hepatitis E patients was 5% (28/589). Most of the hepatitis E cases were males (74%; 486/661), but case fatality was higher among females—12% (8/68) among pregnant and 8% (7/91) among non-pregnant women. Half of the patients who died with acute hepatitis E had co-infection with HAV or HBV. Of the 62 HEV infected mothers who were alive until the delivery, 9 (15%) had miscarriage/stillbirth, and of those children who were born alive, 19% (10/53) died, all within one week of birth.This study confirms that hepatitis E is the leading cause of acute jaundice, leads to hospitalizations in all regions in Bangladesh, occurs throughout the year, and is associated with considerable morbidity and mortality. Effective control measures should be taken to reduce the risk of HEV infections including improvements in water quality, sanitation and hygiene practices and the introduction of HEV vaccine to high-risk groups.Author summary In the absence of reliable surveillance data on the burden of hepatitis E in endemic countries, we conducted a hospital-based acute jaundice surveillance study over a two and a half year period in six tertiary hospitals in Bangladesh. The study confirms that HEV infections occur throughout the year, and is a major (34%) cause of acute jaundice in tertiary hospitals in Bangladesh. Three-quarters of the acute hepatitis E cases were male, and HEV infection was higher among patients residing in urban areas than patients in rural areas (41% vs 32%). The overall case fatality rate of acute HEV infections in hospitals was 5%, but was higher among pregnant women (12%). Hepatitis E patients who died were more likely to have co-infection with HAV or HBV than the HEV infected patients who did not die. Fifteen percent of HEV infected mothers had miscarriage/stillbirth. Of the children who were born alive, 19% died, all within one week of birth. Considering the high burden of hepatitis E among hospitalized acute jaundice patients, Bangladesh could take control measures to reduce this risk including improvements in water quality, sanitation and hygiene practices and the introduction of hepatitis E vaccine in high-risk areas. |
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. |
Quail rearing practices and potential for avian influenza virus transmission, Bangladesh
Hasan SMM , Sturm-Ramirez K , Kamal AM , Islam MA , Rahman M , Kile JC , Kennedy ED , Gurley ES , Islam MS . Ecohealth 2023 20 (2) 167-177 In 2015, human influenza surveillance identified a human infection with A/H9N2 in Dhaka, Bangladesh with evidence of exposure to a sick quail. We conducted in-depth interviews with household quail caregivers, pet bird retail shop owners, and mobile vendors, key informant interviews with pet bird wholesale shop owners, one group discussion with pet bird retail shop workers and unstructured observations in households, pet bird wholesale and retail markets, and mobile bird vendor's travelling areas to explore quail rearing and selling practices among households, mobile vendors, and retail pet bird and wholesale bird markets in Dhaka. Every day, quail were supplied from 23 districts to two wholesale markets, and then sold to households and restaurants directly, or through bird shops and mobile vendors. All respondents (67) reported keeping quail with other birds in cages, feeding quail, cleaning feeding pots, removing quail faeces, slaughtering sick quail, and discarding dead quail. Children played with quail and assisted in slaughtering of quail. Most respondents (94%) reported rinsing hands with water only after slaughtering and disposing of wastes and dead quail. No personal protective equipment was used during any activities. Frequent unprotected contact with quail and their by-products potentially increased the risk of cross-species avian influenza virus transmission. Avian influenza surveillance in retail pet bird and wholesale bird markets, mobile vendors, and households may identify cases promptly and reduce the risk of virus transmission. |
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 10ā000 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 10ā000 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. |
Human exposure to bats, rodents and monkeys in Bangladesh
Shanta IS , Luby SP , Hossain K , Heffelfinger JD , Kilpatrick AM , Haider N , Rahman T , Chakma S , Ahmed SSU , Sharker Y , Pulliam JRC , Kennedy ED , Gurley ES . Ecohealth 2023 1-12 Bats, rodents and monkeys are reservoirs for emerging zoonotic infections. We sought to describe the frequency of human exposure to these animals and the seasonal and geographic variation of these exposures in Bangladesh. During 2013-2016, we conducted a cross-sectional survey in a nationally representative sample of 10,002 households from 1001 randomly selected communities. We interviewed household members about exposures to bats, rodents and monkeys, including a key human-bat interface-raw date palm sap consumption. Respondents reported observing rodents (90%), bats (52%) and monkeys (2%) in or around their households, although fewer reported direct contact. The presence of monkeys around the household was reported more often in Sylhet division (7%) compared to other divisions. Households in Khulna (17%) and Rajshahi (13%) were more likely to report drinking date palm sap than in other divisions (1.5-5.6%). Date palm sap was mostly consumed during winter with higher frequencies in January (16%) and February (12%) than in other months (0-5.6%). There was a decreasing trend in drinking sap over the three years. Overall, we observed substantial geographic and seasonal patterns in human exposure to animals that could be sources of zoonotic disease. These findings could facilitate targeting emerging zoonoses surveillance, research and prevention efforts to areas and seasons with the highest levels of exposure. |
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. |
Nipah virus exposure in domestic and peridomestic animals living in human outbreak sites, Bangladesh, 2013-2015
Islam A , Cannon DL , Rahman MZ , Khan SU , Epstein JH , Daszak P , Luby SP , Montgomery JM , Klena JD , Gurley ES . Emerg Infect Dis 2023 29 (2) 393-396 Spillovers of Nipah virus (NiV) from Pteropus bats to humans occurs frequently in Bangladesh, but the risk for spillover into other animals is poorly understood. We detected NiV antibodies in cattle, dogs, and cats from 6 sites where spillover human NiV infection cases occurred during 2013-2015. |
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. |
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. |
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). |
Postmortem investigations and identification of multiple causes of child deaths: An analysis of findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) network
Breiman RF , Blau DM , Mutevedzi P , Akelo V , Mandomando I , Ogbuanu IU , Sow SO , Madrid L , El Arifeen S , Garel M , Thwala NB , Onyango D , Sitoe A , Bassey IA , Keita AM , Alemu A , Alam M , Mahtab S , Gethi D , Varo R , Ojulong J , Samura S , Mehta A , Ibrahim AM , Rahman A , Vitorino P , Baillie VL , Agaya J , Tapia MD , Assefa N , Chowdhury AI , Scott JAG , Gurley ES , Kotloff KL , Jambai A , Bassat Q , Tippett-Barr BA , Madhi SA , Whitney CG . PLoS Med 2021 18 (9) e1003814 BACKGROUND: The current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death. METHODS AND FINDINGS: We examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child <5 years deaths for which results from Determination of Cause of Death (DeCoDe) panels were complete. DeCoDe panelists included all conditions in the causal chain according to the ICD-10 guidelines and assessed if prevention or effective management of the condition would have prevented the death. We analyzed the distribution of all conditions listed as causal, including underlying, antecedent, and immediate causes of death. Among 1,232 deaths with an underlying condition determined, we found a range of 0 to 6 (mean 1.5, IQR 0 to 2) additional conditions in the causal chain leading to death. While pathology provides very helpful clues, we cannot always be certain that conditions identified led to death or occurred in an agonal stage of death. For neonates, preterm birth complications (most commonly respiratory distress syndrome) were the most common underlying condition (n = 282, 38%); among those with preterm birth complications, 256 (91%) had additional conditions in causal chains, including 184 (65%) with a different preterm birth complication, 128 (45%) with neonatal sepsis, 69 (24%) with lower respiratory infection (LRI), 60 (21%) with meningitis, and 25 (9%) with perinatal asphyxia/hypoxia. Of the 278 infant deaths, 212 (79%) had ≥1 additional cause of death (CoD) beyond the underlying cause. The 2 most common underlying conditions in infants were malnutrition and congenital birth defects; LRI and sepsis were the most common additional conditions in causal chains, each accounting for approximately half of deaths with either underlying condition. Of the 241 child deaths, 178 (75%) had ≥1 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had ≥1 other condition in the causal chain, most commonly sepsis, followed by LRI, malaria, and diarrheal disease. Including all positions in the causal chain for neonatal deaths resulted in 19-fold and 11-fold increases in attributable roles for meningitis and LRI, respectively. For infant deaths, the proportion caused by meningitis and sepsis increased by 16-fold and 11-fold, respectively; for child deaths, sepsis and LRI are increased 12-fold and 10-fold, respectively. While comprehensive CoD determinations were done for a substantial number of deaths, there is potential for bias regarding which deaths in surveillance areas underwent minimally invasive tissue sampling (MITS), potentially reducing representativeness of findings. CONCLUSIONS: Including conditions that appear anywhere in the causal chain, rather than considering underlying condition alone, markedly changed the proportion of deaths attributed to various diagnoses, especially LRI, sepsis, and meningitis. While CHAMPS methods cannot determine when 2 conditions cause death independently or may be synergistic, our findings suggest that considering the chain of events leading to death can better guide research and prevention priorities aimed at reducing child deaths. |
Coding-Complete Sequence of a SARS-CoV-2 B.1.1.25 Lineage Obtained from an 8-Day-Old Deceased Neonate.
Alam M , Jahan MI , Jahan S , Blau DM , Rahman A , Rahman MZ , Hossain MZ , Gurley ES , Arifeen SE , Rahman M . Microbiol Resour Announc 2021 10 (35) e0075621 We report the complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain, hCoV-19/Bangladesh/icddrb-CHAMPS-BDAA02205/2021, obtained from a nasopharyngeal swab from a deceased neonate from Faridpur, Bangladesh. The strain belongs to lineage B.1.1.25 but contains some notable mutations similar to the B.1.1.7 lineage. |
Deaths attributed to respiratory syncytial virus in young children in high-mortality rate settings: Report from Child Health and Mortality Prevention Surveillance (CHAMPS)
Blau DM , Baillie VL , Els T , Mahtab S , Mutevedzi P , Keita AM , Kotloff KL , Mehta A , Sow SO , Tapia MD , Tippett Barr BA , Oluoch BO , Onyango C , Revathi G , Verani JR , Abayneh M , Assefa N , Madrid L , Oundo JO , Scott JAG , Bassat Q , Mandomando I , Sitoe A , Valente M , Varo R , Bassey IA , Cain CJ , Jambai A , Ogbuanu I , Ojulong J , Alam M , El Arifeen S , Gurley ES , Rahman A , Rahman M , Waller JL , Dewey B , Breiman RF , Whitney CG , Madhi SA . Clin Infect Dis 2021 73 S218-s228 BACKGROUND: Lower respiratory tract infections are a leading cause of death in young children, but few studies have collected the specimens needed to define the role of specific causes. The Child Health and Mortality Prevention Surveillance (CHAMPS) platform aims to investigate causes of death in children aged <5 years in high-mortality rate settings, using postmortem minimally invasive tissue sampling and other advanced diagnostic techniques. We examined findings for deaths identified in CHAMPS sites in 7 countries in sub-Saharan Africa and south Asia to evaluate the role of respiratory syncytial virus (RSV). METHODS: We included deaths that occurred between December 2016 and December 2019. Panels determined causes of deaths by reviewing all available data including pathological results from minimally invasive tissue sampling, polymerase chain reaction screening for multiple infectious pathogens in lung tissue, nasopharyngeal swab, blood, and cerebrospinal fluid samples, clinical information from medical records, and verbal autopsies. RESULTS: We evaluated 1213 deaths, including 695 in neonates (aged <28 days), 283 in infants (28 days to <12 months), and 235 in children (12-59 months). RSV was detected in postmortem specimens in 67 of 1213 deaths (5.5%); in 24 deaths (2.0% of total), RSV was determined to be a cause of death, and it contributed to 5 other deaths. Younger infants (28 days to <6 months of age) accounted for half of all deaths attributed to RSV; 6.5% of all deaths in younger infants were attributed to RSV. RSV was the underlying and only cause in 4 deaths; the remainder (nā =ā 20) had a median of 2 (range, 1-5) other conditions in the causal chain. Birth defects (nā =ā 8) and infections with other pathogens (nā =ā 17) were common comorbid conditions. CONCLUSIONS: RSV is an important cause of child deaths, particularly in young infants. These findings add to the substantial body of literature calling for better treatment and prevention options for RSV in high-mortality rate settings. |
Global respiratory syncytial virus-related infant community deaths
Mazur NI , Löwensteyn YN , Willemsen JE , Gill CJ , Forman L , Mwananyanda LM , Blau DM , Breiman RF , Madhi SA , Mahtab S , Gurley ES , El Arifeen S , Assefa N , Scott JAG , Onyango D , Tippet Barr BA , Kotloff KL , Sow SO , Mandomando I , Ogbuanu I , Jambai A , Bassat Q , Caballero MT , Polack FP , Omer S , Kazi AM , Simões EAF , Satav A , Bont LJ . Clin Infect Dis 2021 73 S229-s237 BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. METHODS: The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. RESULTS: We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8-3.3) was lower than in-hospital (2.4 months; IQR: 1.5-4.0; Pā <ā .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, Pā <ā 0.0001). CONCLUSIONS: We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines. |
Inference of Nipah virus evolution, 1999-2015.
Whitmer SLM , Lo MK , Sazzad HMS , Zufan S , Gurley ES , Sultana S , Amman B , Ladner JT , Rahman MZ , Doan S , Satter SM , Flora MS , Montgomery JM , Nichol ST , Spiropoulou CF , Klena JD . Virus Evol 2021 7 (1) veaa062 Despite near-annual human outbreaks of Nipah virus (NiV) disease in Bangladesh, typically due to individual spillover events from the local bat population, only twenty whole-genome NiV sequences exist from humans and ten from bats. NiV whole-genome sequences from annual outbreaks have been challenging to generate, primarily due to the low viral load in human throat swab and serum specimens. Here, we used targeted enrichment with custom NiV-specific probes and generated thirty-five additional unique full-length genomic sequences directly from human specimens and viral isolates. We inferred the temporal and geographic evolutionary history of NiV in Bangladesh and expanded a tool to visualize NiV spatio-temporal spread from a Bayesian continuous diffusion analysis. We observed that strains from Bangladesh segregated into two distinct clades that have intermingled geographically in Bangladesh over time and space. As these clades expanded geographically and temporally, we did not observe evidence for significant branch and site-specific selection, except for a single site in the Henipavirus L polymerase. However, the Bangladesh 1 and 2 clades are differentiated by mutations initially occurring in the polymerase, with additional mutations accumulating in the N, G, F, P, and L genes on external branches. Modeling the historic geographical and temporal spread demonstrates that while widespread, NiV does not exhibit significant genetic variation in Bangladesh. Thus, future public health measures should address whether NiV within in the bat population also exhibits comparable genetic variation, if zoonotic transmission results in a genetic bottleneck and if surveillance techniques are detecting only a subset of NiV. Copyright © 2020 Published by Oxford University Press 2020. This work is written by a US Government employee and is in the public domain in the US. |
Rumor surveillance in support of minimally invasive tissue sampling for diagnosing the cause of child death in low-income countries: A qualitative study
Islam MS , Al-Masud A , Maixenchs M , Cossa S , Guilaze R , Diarra K , Fofana I , Hussain F , Blevins J , Kone A , Arifeen SE , Mandomando I , Bassat Q , Sage EO , Gurley ES , Munguambe K . PLoS One 2021 16 (1) e0244552 In low-and middle-income countries, determining the cause of death of any given individual is impaired by poor access to healthcare systems, resource-poor diagnostic facilities, and limited acceptance of complete diagnostic autopsies. Minimally invasive tissue sampling (MITS), an innovative post-mortem procedure based on obtaining tissue specimens using fine needle biopsies suitable for laboratory analysis, is an acceptable proxy of the complete diagnostic autopsy, and thus could reduce the uncertainty of cause of death. This study describes rumor surveillance activities developed and implemented in Bangladesh, Mali, and Mozambique to identify, track and understand rumors about the MITS procedure. Our surveillance activities included observations and interviews with stakeholders to understand how rumors are developed and spread and to anticipate rumors in the program areas. We also engaged young volunteers, local stakeholders, community leaders, and study staff to report rumors being spread in the community after MITS launch. Through community meetings, we also managed and responded to rumors. When a rumor was reported, the field team purposively conducted interviews and group discussions to track, verify and understand the rumor. From July 2016 through April 2018, the surveillance identified several rumors including suspicions of organs being harvested or transplanted; MITS having been performed on a living child, and concerns related to disrespecting the body and mistrust related to the study purpose. These rumors, concerns, and cues of mistrust were passed by word of mouth. We managed the rumors by modifying the consent protocol and giving additional information and support to the bereaved family and to the community members. Rumor surveillance was critical for anticipating and readily identifying rumors and managing them. Setting up rumor surveillance by engaging community residents, stakeholders, and volunteers could be an essential part of any public health program where there is a need to identify and react in real-time to public concern. |
Hospital-based Surveillance for Pediatric Norovirus Gastroenteritis in Bangladesh, 2012-2016.
Satter SM , Abdullah Z , Cardemil CV , Flora MS , Gurley ES , Rahman M , Talha M , Islam MD , Hossain ME , Balachandran N , Lopman B , Rahman M , Vinjé J , Hall AJ , Parashar UD . Pediatr Infect Dis J 2020 40 (3) 215-219 BACKGROUND: Globally, noroviruses are recognized as an important cause of acute gastroenteritis (AGE), but data from low and middle-income countries are limited. AIMS: To examine the epidemiology and strain diversity of norovirus infections among children hospitalized for AGE in Bangladesh. METHODS: We implemented active surveillance of children <5 years of age hospitalized with AGE at 8 geographically dispersed tertiary care hospitals in Bangladesh from July 2012 to June 2016. We tested random samples of AGE cases stratified by site and age group for norovirus by real-time RT-PCR. Noro-positive specimens were genotyped. Coinfection with rotavirus was assessed based on prior EIA testing. RESULTS: We enrolled 5622 total AGE cases, of which 1008 were tested for norovirus. Total of 137 (14%) AGE cases tested positive for norovirus (range, 11%-17% by site). Most (94%) norovirus-associated hospitalizations were among children less than 2 years of age. Norovirus was detected year-round, with higher detection from March to June (20%-38%) and November to January (9%-18%). Genogroup II (GII) noroviruses were detected in 96% of cases, and the most frequent genotypes were GII.4 Sydney [P4 New Orleans] (33%), GII.3 [P16] (20%), and GII.4 Sydney [P16] (11%). The proportion of norovirus-positive specimens was significantly greater among rotavirus-negative AGE patients compared with rotavirus-positive AGE patients (27% vs. 5%, P < 0.001). As measured by the Vesikari severity score, a similar proportion of norovirus and rotavirus positive AGE patients were considered severe (68% vs. 70%, P = 0.86). CONCLUSIONS: Norovirus is an important cause of AGE hospitalization in Bangladeshi children with most infections caused by GII viruses. |
Genetic Diversity of Nipah virus in Bangladesh.
Rahman MZ , Islam MM , Hossain ME , Rahman MM , Islam A , Siddika A , Hossain MSS , Sultana S , Islam A , Rahman M , Rahman M , Klena JD , Flora MS , Daszak P , Epstein JH , Luby SP , Gurley ES . Int J Infect Dis 2020 102 144-151 BACKGROUND: Nipah virus (NiV) infection, often fatal in humans, is primarily transmitted in Bangladesh through consumption of date palm sap contaminated by Pteropus bats. Person to person transmission is also common and increases the concern of large outbreaks. This study aimed to characterize the molecular epidemiology, phylogenetic relationship, and evolution of the nucleocapsid gene (N gene) of NiV. METHODS: We conducted molecular detection, genetic characterization and Bayesian time-scale evolution analyses of NiV using pooled Pteropid bat roost urine samples from an outbreak area in 2012 and archived RNA samples from NiV case-patients identified during 2012-2018 in Bangladesh. RESULTS: NiV-RNA was detected in 19% (38/456) of bat roost urine samples and among them; nine N gene sequences were recovered. We also retrieved sequences from 53% (21 out of 39) of archived RNA samples from patients. Phylogenetic analysis revealed that all Bangladeshi strains belonged to NiV-BD genotype and had an evolutionary rate of 4.64 × 10(-4) substitutions/site/year. The analyses suggested that the strains of NiV-BD genotype diverged around1995 and formed two sub-lineages. CONCLUSION: This analysis provides further evidence that the NiV strains of the Malaysian and Bangladesh genotypes departed recently and continues to evolve. More extensive surveillance of NiV in bats and human will be helpful to explore strain diversity and virulence potential to infect humans via direct or person-to-person virus transmission. |
Human exposures to by-products from animals suspected to have died of anthrax in Bangladesh: An exploratory study
Islam MS , Hasan SM , Salzer JS , Kadzik M , Haque F , Haider N , Hossain MB , Islam MA , Rahman M , Kennedy E , Gurley ES . Transbound Emerg Dis 2020 68 (4) 2514-2520 Anthrax is a zoonotic disease caused by the bacterium Bacillus anthracis that is considered endemic in Bangladesh, where cases among animals and people have been reported almost annually since 2009. Contaminated by-products from animals are suspected to play a role in transmission to people, but minimal information is known on the supply-chain of these potentially contaminated products. Between April 2013 and May 2016, we conducted a qualitative study in 17 villages located in 5 districts in Bangladesh, which had experienced suspected anthrax outbreaks. The study explored how by-products from suspected animal cases were collected, discarded, processed, distributed, and used by people. We conducted open-ended interviews, group discussions, and unstructured observations of people's exposure to animal by-products. The practice of slaughtering acutely ill domestic ruminants before they died was common. Respondents reported that moribund animals were typically butchered, and the waste products were discarded in nearby rivers, ditches, bamboo bushes, or on privately owned land. Regardless of health status before death, very few carcasses were buried, and none were incinerated or burned. The hides were reportedly used to make wallets, belts, shoes, balls, and clothing. Discarded bones were often ground into granular and powder forms to produce bone meal and fertilizer. Therefore, given anthrax is endemic in the study region, livestock with acute onset of fatal disease or found dead with no known cause of death may be an anthrax case and subsequently pose a health risk to those involved in the collection and processing of the carcass, as well as the end-user of these products. Improved bio-security practices and safe carcass disposal measures could reduce the risk of human exposure, but resource and other constraints make implementation a challenge. Therefore, targeting at-risk animal populations for vaccination may be the most effective strategy to reduce anthrax outbreaks, protect the supply chain, and reduce the risk of exposure to B. anthracis. |
Association of biosecurity and hygiene practices with environmental contamination with influenza A viruses in live bird markets, Bangladesh
Chowdhury S , Azziz-Baumgartner E , Kile JC , Hoque MA , Rahman MZ , Hossain ME , Ghosh PK , Ahmed SSU , Kennedy ED , Sturm-Ramirez K , Gurley ES . Emerg Infect Dis 2020 26 (9) 2087-2096 In Bangladesh, live bird market environments are frequently contaminated with avian influenza viruses. Shop-level biosecurity practices might increase risk for environmental contamination. We sought to determine which shop-level biosecurity practices were associated with environmental contamination. We surveyed 800 poultry shops to describe biosecurity practices and collect environmental samples. Samples from 205 (26%) shops were positive for influenza A viral RNA, 108 (14%) for H9, and 60 (8%) for H5. Shops that slaughtered poultry, kept poultry overnight, remained open without rest days, had uneven muddy floors, held poultry on the floor, and housed sick and healthy poultry together were more frequently positive for influenza A viruses. Reported monthly cleaning seemed protective, but disinfection practices were not otherwise associated with influenza A virus detection. Slaughtering, keeping poultry overnight, weekly rest days, infrastructure, and disinfection practices could be targets for interventions to reduce environmental contamination. |
Hospital-based surveillance for Japanese encephalitis in Bangladesh, 2007-2016: Implications for introduction of immunization
Paul KK , Sazzad HMS , Rahman M , Sultana S , Hossain MJ , Ledermann JP , Burns P , Friedman MS , Flora MS , Fischer M , Hills S , Luby SP , Gurley ES . Int J Infect Dis 2020 99 69-74 BACKGROUND: Japanese encephalitis (JE) virus is recognized as a major cause of encephalitis in Bangladesh. The World Health Organization (WHO) recommends human immunization as the most effective means to control JE. Several WHO-prequalified vaccines are available to prevent JE but no vaccination program has been implemented in Bangladesh. METHODS: We conducted hospital-based surveillance for acute meningitis-encephalitis syndrome (AMES) to describe JE epidemiology and help inform policy decisions about possible immunization strategies for Bangladesh. RESULTS: During 2007-2016, a total of 6,543 AMES patients were identified at four tertiary hospitals. Of the 6,525 patients tested, 548 (8%) were classified as JE cases. These 548 patients resided in 36 (56%) out of 64 districts of Bangladesh, with the highest proportion of JE cases among AMES patients (12% and 7%) presenting at two hospitals in the northwestern part of the country. The median age of JE cases was 30 years, and 193 (35%) were aged ≤15 years. The majority of JE cases (80%) were identified from July through November. CONCLUSIONS: Surveillance results suggest that JE continues to be an important cause of meningo-encephalitis in Bangladesh. Immunization strategies including JE vaccine introduction into the routine childhood immunization program or mass vaccination in certain age groups or geographic areas need to be examined, taking into consideration the cost-effectiveness ratio of the approach and potential for decreasing disease burden. |
Initial findings from a novel population-based child mortality surveillance approach: a descriptive study
Taylor AW , Blau DM , Bassat Q , Onyango D , Kotloff KL , Arifeen SE , Mandomando I , Chawana R , Baillie VL , Akelo V , Tapia MD , Salzberg NT , Keita AM , Morris T , Nair S , Assefa N , Seale AC , Scott JAG , Kaiser R , Jambai A , Barr BAT , Gurley ES , Ordi J , Zaki SR , Sow SO , Islam F , Rahman A , Dowell SF , Koplan JP , Raghunathan PL , Madhi SA , Breiman RF . Lancet Glob Health 2020 8 (7) e909-e919 BACKGROUND: Sub-Saharan Africa and south Asia contributed 81% of 5.9 million under-5 deaths and 77% of 2.6 million stillbirths worldwide in 2015. Vital registration and verbal autopsy data are mainstays for the estimation of leading causes of death, but both are non-specific and focus on a single underlying cause. We aimed to provide granular data on the contributory causes of death in stillborn fetuses and in deceased neonates and children younger than 5 years, to inform child mortality prevention efforts. METHODS: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network was established at sites in seven countries (Baliakandi, Bangladesh; Harar and Kersa, Ethiopia; Siaya and Kisumu, Kenya; Bamako, Mali; Manhica, Mozambique; Bombali, Sierra Leone; and Soweto, South Africa) to collect standardised, population-based, longitudinal data on under-5 mortality and stillbirths in sub-Saharan Africa and south Asia, to improve the accuracy of determining causes of death. Here, we analysed data obtained in the first 2 years after the implementation of CHAMPS at the first five operational sites, during which surveillance and post-mortem diagnostics, including minimally invasive tissue sampling (MITS), were used. Data were abstracted from all available clinical records of deceased children, and relevant maternal health records were also extracted for stillbirths and neonatal deaths, to incorporate reported pregnancy or delivery complications. Expert panels followed standardised procedures to characterise causal chains leading to death, including underlying, intermediate (comorbid or antecedent causes), and immediate causes of death for stillbirths, neonatal deaths, and child (age 1-59 months) deaths. FINDINGS: Between Dec 10, 2016, and Dec 31, 2018, MITS procedures were implemented at five sites in Mozambique, South Africa, Kenya, Mali, and Bangladesh. We screened 2385 death notifications for inclusion eligibility, following which 1295 families were approached for consent; consent was provided for MITS by 963 (74%) of 1295 eligible cases approached. At least one cause of death was identified in 912 (98%) of 933 cases (180 stillbirths, 449 neonatal deaths, and 304 child deaths); two or more conditions were identified in the causal chain for 585 (63%) of 933 cases. The most common underlying causes of stillbirth were perinatal asphyxia or hypoxia (130 [72%] of 180 stillbirths) and congenital infection or sepsis (27 [15%]). The most common underlying causes of neonatal death were preterm birth complications (187 [42%] of 449 neonatal deaths), perinatal asphyxia or hypoxia (98 [22%]), and neonatal sepsis (50 [11%]). The most common underlying causes of child deaths were congenital birth defects (39 [13%] of 304 deaths), lower respiratory infection (37 [12%]), and HIV (35 [12%]). In 503 (54%) of 933 cases, at least one contributory pathogen was identified. Cytomegalovirus, Escherichia coli, group B Streptococcus, and other infections contributed to 30 (17%) of 180 stillbirths. Among neonatal deaths with underlying prematurity, 60% were precipitated by other infectious causes. Of the 275 child deaths with infectious causes, the most common contributory pathogens were Klebsiella pneumoniae (86 [31%]), Streptococcus pneumoniae (54 [20%]), HIV (40 [15%]), and cytomegalovirus (34 [12%]), and multiple infections were common. Lower respiratory tract infection contributed to 174 (57%) of 304 child deaths. INTERPRETATION: Cause of death determination using MITS enabled detailed characterisation of contributing conditions. Global estimates of child mortality aetiologies, which are currently based on a single syndromic cause for each death, will be strengthened by findings from CHAMPS. This approach adds specificity and provides a more complete overview of the chain of events leading to death, highlighting multiple potential interventions to prevent under-5 mortality and stillbirths. FUNDING: Bill & Melinda Gates Foundation. |
Twenty years of Nipah virus research: Where do we go from here
Gurley ES , Spiropoulou CF , de Wit E . J Infect Dis 2020 221 S359-s362 Twenty years ago, the world had only just discovered Nipah virus, a new zoonotic paramyxovirus closely related to Hendra virus. A concurrent disease outbreak in pigs and humans in Malaysia led to the discovery of this virus in 1999 [1]. Through the intermediate host involved in this outbreak—domestic pigs—the outbreak spread to Singapore, resulting in a total of 276 reported cases with 106 deaths; the outbreak ended with the culling of more than 1 000 000 pigs [1, 2]. |
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