Postmortem investigations and identification of multiple causes of child deaths: An analysis of findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) network.
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SUBMITTER: Breiman RF
PROVIDER: S-EPMC8516282 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
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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 Robert F RF Blau Dianna M DM Mutevedzi Portia P Akelo Victor V Mandomando Inacio I Ogbuanu Ikechukwu U IU Sow Samba O SO Madrid Lola L El Arifeen Shams S Garel Mischka M Thwala Nana Bukiwe NB Onyango Dickens D Sitoe Antonio A Bassey Ima-Abasi IA Keita Adama Mamby AM Alemu Addisu A Alam Muntasir M Mahtab Sana S Gethi Dickson D Varo Rosauro R Ojulong Julius J Samura Solomon S Mehta Ashka A Ibrahim Alexander M AM Rahman Afruna A Vitorino Pio P Baillie Vicky L VL Agaya Janet J Tapia Milagritos D MD Assefa Nega N Chowdhury Atique Iqbal AI Scott J Anthony G JAG Gurley Emily S ES Kotloff Karen L KL Jambai Amara A Bassat Quique Q Tippett-Barr Beth A BA Madhi Shabir A SA Whitney Cynthia G CG
PLoS medicine 20210930 9
<h4>Background</h4>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 ...[more]
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Project description:ImportanceThe 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.ObjectiveTo describe causes of postneonatal child deaths across 7 mortality surveillance sentinel sites in Africa and Asia.Design, setting, and participantsThe 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 measuresThe 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.ResultsIn 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 relevanceIn 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.
| S-EPMC10372710 | biostudies-literature
Project description:BackgroundLower 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).MethodsWe 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.ResultsWe 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 (n = 20) had a median of 2 (range, 1-5) other conditions in the causal chain. Birth defects (n = 8) and infections with other pathogens (n = 17) were common comorbid conditions.ConclusionsRSV 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.
| S-EPMC8411256 | biostudies-literature
Project description: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.
| S-EPMC10027211 | biostudies-literature
Project description:BackgroundKlebsiella 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.MethodsWe 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).FindingsAmong 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.InterpretationK 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.FundingBill & Melinda Gates Foundation.
| S-EPMC10849973 | biostudies-literature
Project description:Abstract 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.
| S-EPMC10478157 | biostudies-literature
Project description:Despite reductions over the past 2 decades, childhood mortality remains high in low- and middle-income countries in sub-Saharan Africa and South Asia. In these settings, children often die at home, without contact with the health system, and are neither accounted for, nor attributed with a cause of death. In addition, when cause of death determinations occur, they often use nonspecific methods. Consequently, findings from models currently utilized to build national and global estimates of causes of death are associated with substantial uncertainty. Higher-quality data would enable stakeholders to effectively target interventions for the leading causes of childhood mortality, a critical component to achieving the Sustainable Development Goals by eliminating preventable perinatal and childhood deaths. The Child Health and Mortality Prevention Surveillance (CHAMPS) Network tracks the causes of under-5 mortality and stillbirths at sites in sub-Saharan Africa and South Asia through comprehensive mortality surveillance, utilizing minimally invasive tissue sampling (MITS), postmortem laboratory and pathology testing, verbal autopsy, and clinical and demographic data. CHAMPS sites have established facility- and community-based mortality notification systems, which aim to report potentially eligible deaths, defined as under-5 deaths and stillbirths within a defined catchment area, within 24-36 hours so that MITS can be conducted quickly after death. Where MITS has been conducted, a final cause of death is determined by an expert review panel. Data on cause of death will be provided to local, national, and global stakeholders to inform strategies to reduce perinatal and childhood mortality in sub-Saharan Africa and South Asia.
| S-EPMC6785672 | biostudies-literature
Project description:ObjectiveTo directly measure the fatal impact of coronavirus disease 2019 (covid-19) in an urban African population.DesignProspective systematic postmortem surveillance study.SettingZambia's largest tertiary care referral hospital.ParticipantsDeceased people of all ages at the University Teaching Hospital morgue in Lusaka, Zambia, enrolled within 48 hours of death.Main outcome measurePostmortem nasopharyngeal swabs were tested via reverse transcriptase quantitative polymerase chain reaction (PCR) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Deaths were stratified by covis-19 status, location, age, sex, and underlying risk factors.Results372 participants were enrolled between June and September 2020; PCR results were available for 364 (97.8%). SARS-CoV-2 was detected in 58/364 (15.9%) according to the recommended cycle threshold value of <40 and in 70/364 (19.2%) when expanded to any level of PCR detection. The median age at death among people with a positive test for SARS-CoV-2 was 48 (interquartile range 36-72) years, and 69% (n=48) were male. Most deaths in people with covid-19 (51/70; 73%) occurred in the community; none had been tested for SARS-CoV-2 before death. Among the 19/70 people who died in hospital, six were tested before death. Among the 52/70 people with data on symptoms, 44/52 had typical symptoms of covid-19 (cough, fever, shortness of breath), of whom only five were tested before death. Covid-19 was identified in seven children, only one of whom had been tested before death. The proportion of deaths with covid-19 increased with age, but 76% (n=53) of people who died were aged under 60 years. The five most common comorbidities among people who died with covid-19 were tuberculosis (22; 31%), hypertension (19; 27%), HIV/AIDS (16; 23%), alcohol misuse (12; 17%), and diabetes (9; 13%).ConclusionsContrary to expectations, deaths with covid-19 were common in Lusaka. Most occurred in the community, where testing capacity is lacking. However, few people who died at facilities were tested, despite presenting with typical symptoms of covid-19. Therefore, cases of covid-19 were under-reported because testing was rarely done not because covid-19 was rare. If these data are generalizable, the impact of covid-19 in Africa has been vastly underestimated.
| S-EPMC7887952 | biostudies-literature
Project description:BackgroundMost 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.MethodsWe 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.FindingsCHAMPS 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.InterpretationProvision 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.FundingBill & Melinda Gates Foundation.
| S-EPMC10484959 | biostudies-literature
Project description:BackgroundVerbal autopsy is the main method used in countries with weak civil registration systems for estimating community causes of neonatal and 1-59-month-old deaths. However, validation studies of verbal autopsy methods are limited and assessment has been dependent on hospital-based studies, with uncertain implications for its validity in community settings. If the distribution of community deaths by cause was similar to that of facility deaths, or could be adjusted according to related demographic factors, then the causes of facility deaths could be used to estimate population causes.MethodsCauses of neonatal and 1-59-month-old deaths from verbal/social autopsy (VASA) surveys in four African countries were estimated using expert algorithms (EAVA) and physician coding (PCVA). Differences between facility and community deaths in individual causes and cause distributions were examined using chi-square and cause-specific mortality fractions (CSMF) accuracy, respectively. Multinomial logistic regression and random forest models including factors from the VASA studies that are commonly available in Demographic and Health Surveys were built to predict population causes from facility deaths.ResultsLevels of facility and community deaths in the four countries differed for one to four of 10 EAVA or PCVA neonatal causes and zero to three of 12 child causes. CSMF accuracy for facility compared to community deaths in the four countries ranged from 0.74 to 0.87 for neonates and 0.85 to 0.95 for 1-59-month-olds. Crude CSMF accuracy in the prediction models averaged 0.86 to 0.88 for neonates and 0.93 for 1-59-month-olds. Adjusted random forest prediction models increased average CSMF accuracy for neonates to, at most, 0.90, based on small increases in all countries.ConclusionsThere were few differences in facility and community causes of neonatal and 1-59-month-old deaths in the four countries, and it was possible to project the population CSMF from facility deaths with accuracy greater than the validity of verbal autopsy diagnoses. Confirmation of these findings in additional settings would warrant research into how medical causes of deaths in a representative sample of health facilities can be utilized to estimate the population causes of child death.
| S-EPMC7291588 | biostudies-literature
Project description: Not available
| S-EPMC7303945 | biostudies-literature