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.
To describe causes of postneonatal child deaths across 7 mortality surveillance sentinel sites in Africa and Asia.
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.
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.
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.
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.
SARS-CoV-2 infection in pregnant women has been associated with severe illness in the women and higher rates of premature delivery. There is, however, paucity of data on the impact of the timing of ...SARS-CoV-2 infection and on symptomatic or asymptomatic infections on birth outcomes. Data from low-middle income settings is also lacking.
We conducted a longitudinal study from April 2020 to March 2021, in South Africa, where symptomatic or asymptomatic pregnant women were investigated for SARS-CoV-2 infection during the antepartum period. We aimed to evaluate if there was an association between antepartum SARS-CoV-2 infection on birth outcomes. SARS-CoV-2 infection was investigated by nucleic acid amplification test (NAAT), histological examination was performed in a sub-set of placentas.
Overall, 793 women were tested for SARS-CoV-2 antenatally, including 275 (35%) who were symptomatic. SARS-CoV-2 infection was identified in 138 (17%) women, of whom 119 had symptoms (COVID-19 group) and 19 were asymptomatic. The 493 women who were asymptomatic and had a negative SARS-CoV-2 NAAT were used as the referent comparator group for outcomes evaluation. Women with COVID-19 compared with the referent group were 1.66-times (95% confidence interval (CI) = 1.02-2.71) more likely to have a low-birthweight newborn (30% vs 21%) and 3.25-times more likely to deliver a very low-birthweight newborn (5% vs 2%). Similar results for low-birthweight were obtained comparing women with SARS-CoV-2 confirmed infection (30%) with those who had a negative NAAT result (22%) independent of symptoms presentation. The placentas from women with antenatal SARS-CoV-2 infection had higher percentage of chorangiosis (odds ratio (OR) = 3.40, 95% CI = 1.18-.84), while maternal vascular malperfusion was more frequently identified in women who tested negative for SARS-CoV-2 (aOR = 0.28, 95% CI = 0.09-0.89).
Our study demonstrates that in a setting with high HIV infection prevalence and other comorbidities antenatal SARS-CoV-2 infection was associated with low-birthweight delivery.
Access to emergency contraception (EC) has little restriction in South Africa. EC is a contraceptive method that can be used by women up to 7 days after unprotected intercourse. It can be used in the ...following situations: when no contraceptive has been used; for condom accidents; after intrauterine contraceptive device expulsion; when a contraceptive method has been incorrectly used, or contraceptive pills missed; if there has been a > 3-hour delay in taking the progestogen-only pill, a > 2-week delay for intramuscular depot medroxyprogesterone acetate or a > 1-week delay for intramuscular norethisterone enanthate; or after delayed placement or early removal or dislodgement of a contraceptive transdermal patch or vaginal ring.
Objectives
To assess whether women with HIV who had low‐grade squamous intraepithelial lesions (LSIL) on cytology had cervical disease.
Methods
The present retrospective cross‐sectional study ...included data from women with LSIL who attended a tertiary hospital in South Africa between April 1, 2003, and December 31, 2013. Patient information was extracted from a colposcopy database.
Results
The study included 652 patients. The median age was 36 years (interquartile range IQR 31–42 years; range 18–66 years) and the median parity was three (IQR 2–5; range 0–10). In all, 266 (40.8%) women had a histology result of HPV or cervical intraepithelial neoplasia 1 (CIN1); 386 (59.2%) had a histology result of CIN2 or higher. The median cluster of differentiation 4 (CD4) count was 275.00 cells/mm3 (IQR 173.50–434.00 cells/mm3; range 2–1211 cells/mm3). A total of 312 (47.9%) women were using antiretroviral therapy. Use of antiretroviral therapy (unadjusted odds ratio 0.57; P=0.001) and a CD4 count of at least 200 cells/mm3 (unadjusted odds ratio 0.81; P=0.002) were associated with a histology result of HPV or CIN1.
Conclusion
Most of the women with a cytology report of LSIL had CIN2 or higher, suggesting that the practice of referral for colposcopy should continue.
Most women with low‐grade squamous intraepithelial lesions on cytologic examination had cervical intraepithelial neoplasia 2, which suggested that referral for colposcopy should continue.
Background. A systematic review concluded that a caesarean section (CS) performed for medical indications will save lives; however, it is associated with short- and long-term complications. The CS ...rate at Chris Hani Baragwanath Academic Hospital (CHBAH) was 39.78% in 2015. Objectives. To evaluate the indications for CSs at CHBAH. Methods. This was a cross-sectional study conducted on the data collected in the week of 23 June to 29 June 2015. Each file was evaluated for the correctness of the decision by at least two researchers. Each reviewer could state that he/she absolutely agreed, partially agreed, did not agree or could not make an assessment. Results. The mean (standard deviation (SD)) age of the women was 27.01 (6.35) (range 15 - 44) years. The median (interquartile range (IQR)) parity was 1 (0 - 2) (range 0 - 4). No co-morbidities were found in 13.6% (n=20) of the reviewed cases. Complications were found to have occurred in 17% (n=25) of women who gave birth over the week reviewed. The median (IQR) gestational age at delivery was 38.14 (36.39 - 40.14) (range 28.0 - 42.4) weeks. The median (IQR) Apgar (5 minutes) was 10 (9 - 10) (range 0 - 10). The median (IQR) birth weight was 3 040 (2 530 - 3 440) (range 825 - 4 575) g. The most common indications were fetal distress (n=73; 49.66%) and dystocia (n=42; 28.57%). There was absolute agreement between the two reviewers in the following: retained second twin, antepartum haemorrhage (APH) of unknown origin, placenta previa, severe intrauterine growth restriction, multiple pregnancy, abnormal presentation, eclampsia and two previous CSs. When the indication was fetal distress, dystocia, second-stage CS, or one previous CS, the absolute agreement was between 73.85% and 90.24%. Conclusion. There were few absolute disagreements with the indication cited. Methods used to diagnose fetal distress and dystocia must be evaluated.
Licensure of a Group B streptococcus (GBS) polysaccharide-protein conjugate vaccine for protecting infants against invasive GBS disease (IGbsD) will likely need to be based on demonstrating vaccine ...safety in pregnant women, and benchmarking immunogenicity against a serological threshold associated with risk reduction of IGbsD. We investigated the association between naturally-derived GBS serotype-Ia and III IgG and risk reduction of IGbsD in infants' ≤90 days of age.
In a matched case-control study (ClinicalTrials.gov NCT02215226), IGbsD cases were identified from a cohort of 38,233 mother-newborn dyads. Mothers colonized vaginally with serotype-Ia or III at birth, and their healthy infants were eligible as matched controls. GBS serotype-specific anti-capsular IgG was measured on maternal and cord blood/infant sera by multiplex Luminex assay; and the IgG threshold associated with 90% risk reduction of IGbsD derived by estimating absolute disease risk.
In infants born ≥34 weeks gestational age, cord-blood IgG geometric mean concentrations (GMC) were lower in cases than controls for serotype-Ia (0.05 vs. 0.50µg/ml; p=0.004) and III (0.20 vs. 0.38µg/ml; p=0.078). Cord-blood IgG concentration ≥1.04 and ≥1.53µg/ml were associated with 90% risk reduction of serotype-Ia and III IGbsD, respectively. The maternal sera IgG threshold associated with 90% risk reduction was ≥2.31 and ≥3.41µg/ml for serotype-Ia and III, respectively.
The threshold associated with a reduced risk for serotype-Ia and III IGbsD identified on infant sera supports the case for licensure of a GBS polysaccharide-protein conjugate vaccine based on immunogenicity evaluation benchmarked against the defined thresholds.
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.
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.
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.
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.
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.
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.
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.
Bill & Melinda Gates Foundation.
PDF
