Access to care in Afghanistan after august 2021: a cross-sectional study exploring Afghans' perspectives in 10 provinces.

BACKGROUND: The Taliban takeover in August 2021 ended a decades-long conflict in Afghanistan. Yet, along with improved security, there have been collateral changes, such as the exacerbation of the economic crisis and brain drain. Although these changes have altered the lives of Afghans in many ways, it is unclear whether they have affected access to care. This study aimed to analyse Afghans' access to care and how this access has changed after August 2021. METHODS: The study relied on the collaboration with the non-governmental organisation EMERGENCY, running a network of three hospitals and 41 First Aid Posts in 10 Afghan provinces. A 67-item questionnaire about access to care changes after August 2021 was developed and disseminated at EMERGENCY facilities. Ordinal logistic regression was used to evaluate whether access to care changes were associated with participants' characteristics. RESULTS: In total, 1807 valid responses were returned. Most respondents (54.34%) reported improved security when visiting healthcare facilities, while the ability to reach facilities has remained stable for the majority of them (50.28%). Care is less affordable for the majority of respondents (45.82%). Female respondents, those who are unmarried and not engaged, and patients in the Panjshir province were less likely to perceive improvements in access to care. CONCLUSIONS: Findings outline which dimensions of access to care need resource allocation. The inability to pay for care is the most relevant barrier to access care after August 2021 and must therefore be prioritised. Women and people from the Panjshir province may require ad hoc interventions to improve their access to care.

Uncovering the causes and socio-demographic constructs of stillbirths and neonatal deaths in an urban slum of Karachi.

INTRODUCTION: Neonatal deaths and stillbirths are significant public health concerns in Pakistan, with an estimated stillbirth rate of 43 per 1,000 births and a neonatal mortality rate of 46 deaths per 1,000 live births. Limited access to obstetric care, poor health seeking behaviors and lack of quality healthcare are the leading root causes for stillbirths and neonatal deaths. Rehri Goth, a coastal slum in Karachi, faces even greater challenges due to extreme poverty, and inadequate infrastructure. This study aims to investigate the causes and pathways leading to stillbirths and neonatal deaths in Rehri Goth to develop effective maternal and child health interventions. METHODS: A mixed-method cohort study was nested with the implementation of large maternal, neonatal and child health program, captured all stillbirths and neonatal death during the period of May 2014 till June 2018. The Verbal and Social Autopsy (VASA) tool (WHO 2016) was used to collect primary data from all death events to determine the causes as well as the pathways. Interviews were conducted both retrospectively and prospectively with mothers and caregivers. Two trained physicians reviewed the VASA form and the medical records (if available) and coded the cause of death blinded to each other. Descriptive analysis was used to categorize stillbirth and neonatal mortality data into high- and low-mortality clusters, followed by chi-square tests to explore associations between categories, and concluded with a qualitative analysis. RESULTS: Out of 421 events captured, complete VASA interviews were conducted for 317 cases. The leading causes of antepartum stillbirths were pregnancy-induced hypertension (22.4%) and maternal infections (13.4%), while obstructed labor was the primary cause of intrapartum stillbirths (38.3%). Neonatal deaths were primarily caused by perinatal asphyxia (36.1%) and preterm birth complications (27.8%). The qualitative analysis on a subset of 40 death events showed that health system (62.5%) and community factors (37.5%) contributing to adverse outcomes, such as delayed referrals, poor triage systems, suboptimal quality of care, and delayed care-seeking behaviors. CONCLUSION: The study provides an opportunity to understand the causes of stillbirths and neonatal deaths in one of the impoverished slums of Karachi. The data segregation by clusters as well as triangulation with qualitative analysis highlight the needs of evidence-based strategies for maternal and child health interventions in disadvantaged communities.

Impact of Ebola and COVID-19 on maternal, neonatal, and child health care among populations affected by conflicts: a scoping review exploring demand and supply-side barriers and solutions.

INTRODUCTION: Armed conflicts have a severe impact on the health of women and children. Global health emergencies such as pandemics and disease outbreaks further exacerbate the challenges faced by vulnerable populations in accessing maternal, neonatal, and child healthcare (MNCH). There is a lack of evidence that summarizes the challenges faced by conflict-affected pregnant women, mothers, and children in accessing MNCH services during global health emergencies, mainly the Ebola and COVID-19 pandemics. This scoping review aimed to analyze studies evaluating and addressing barriers to accessing comprehensive MNCH services during Ebola and COVID-19 emergencies in populations affected by conflict. METHODS: The search was conducted on PubMed, Scopus, and Web of Science databases using terms related to Ebola and COVID-19, conflicts, and MNCH. Original studies published between 1990 and 2022 were retrieved. Articles addressing the challenges in accessing MNCH-related services during pandemics in conflict-affected settings were included. Thematic analysis was performed to categorize the findings and identify barriers and solutions. RESULTS: Twenty-nine studies met the inclusion criteria. Challenges were identified in various MNCH domains, including antenatal care, intrapartum care, postnatal care, vaccination, family planning, and the management of childhood illnesses. Ebola-related supply-side challenges mainly concerned accessibility issues, health workforce constraints, and the adoption of stringent protocols. COVID-19 has resulted in barriers related to access to care, challenges pertaining to the health workforce, and new service adoption. On the demand-side, Ebola- and COVID-19-related risks and apprehensions were the leading barriers in accessing MNCH care. Community constraints on utilizing services during Ebola were caused by a lack of trust and awareness. Demand-side challenges of COVID-19 included fear of disease, language barriers, and communication difficulties. Strategies such as partnerships, strengthening of health systems, service innovation, and community-based initiatives have been employed to overcome these barriers. CONCLUSION: Global health emergencies amplify the barriers to accessing MNCH services faced by conflict-affected populations. Cultural, linguistic, and supply-side factors are key challenges affecting various MNCH domains. Community-sensitive initiatives enhancing primary health care (PHC), mobile clinics, or outreach programs, and the integration of MNCH into PHC delivery should be implemented. Efforts should prioritize the well-being and empowerment of vulnerable populations. Addressing these barriers is crucial for achieving universal health coverage and the Sustainable Development Goals.

Causes of maternal deaths in Sierra Leone from 2016 to 2019: analysis of districts' maternal death surveillance and response data.

INTRODUCTION: Sierra Leone is among the top countries with the highest maternal mortality rates. Although progress has been made in reducing maternal mortality, challenges remain, including limited access to skilled care and regional disparities in accessing quality care. This paper presents the first comprehensive analysis of the burden of different causes of maternal deaths reported in the Maternal Death Surveillance and Response (MDSR) system at the district level from 2016 to 2019. METHODS: The MDSR data are accessed from the Ministry of Health and Sanitation, and the secondary data analysis was done to determine the causes of maternal death in Sierra Leone. The proportions of each leading cause of maternal deaths were estimated by districts. A subgroup analysis of the selected causes of death was also performed. RESULTS: Overall, obstetric haemorrhage was the leading cause of maternal death (39.4%), followed by hypertensive disorders (15.8%) and pregnancy-related infections (10.1%). Within obstetric haemorrhage, postpartum haemorrhage was the leading cause in each district. The burden of death due to obstetric haemorrhage slightly increased over the study period, while hypertensive disorders showed a slightly decreasing trend. Disparities were found among districts for all causes of maternal death, but no clear geographical pattern emerged. Non-obstetric complications were reported in 11.5% of cases. CONCLUSION: The MDSR database provides an opportunity for shared learning and can be used to improve the quality of maternal health services. To improve the accuracy and availability of data, under-reporting must be addressed, and frontline community staff must be trained to accurately capture and report death events.

Client-centered counseling and facilitation in improving modern contraceptive uptake in urban slum of Karachi Pakistan.

BACKGROUND: Population growth in Pakistan necessitates the implementation of comprehensive family planning (FP) initiatives. The adoption of modern contraceptives, especially long-acting reversible contraceptives (LARC), and permanent family planning methods in the country is challenging and has yet to reach an optimal level. These challenges are deeply rooted in the lack of informed decision-making, as well as demographic and maternal obstetric history. Interventions tailored according to women's needs can address the challenges faced by FP programs. This paper presents the findings of the implementation of a client-centered counseling and facilitation approach in an urban slum in Karachi, Pakistan. Such an approach has the potential to inform women and help them make better decisions regarding their health. METHODS: In Rehri Goth, a slum located in Karachi, client-centered counseling along with facilitation at the facility was implemented to encourage the adoption of any modern contraceptive methods, with a specific emphasis on promoting the use of LARCs and permanent methods (where needed) among married women of reproductive age (MWRA). This approach was integrated into the existing Maternal, Neonatal, and Child Health (MNCH) services established in 2014. During the routine delivery of services, data were collected on various aspects including demographic characteristics, obstetric history, motivation to adopt LARCs, and reasons for refusal. RESULTS: A total of N = 3079 eligible MWRA received client-centered counseling, and 60.3% accepted modern contraceptive methods after counseling. Furthermore, 32.5% of these MWRA adopted LARCs or permanent methods. Factors explaining reluctance to adopt any method by MWRA despite specialized counselling were: age >25 years (AOR:1.28, 95% CI:1.08-1.51), no formal education (AOR:1.58, 95% CI:1.36-1.89), having no decision making role at household (AOR:1.60, 95% CI:1.36-1.89), the desire of female or male progeny (AOR:1.86, 95% CI:1.59-2.25) and age of youngest alive ≥3 years (AOR:1.50, 95% CI:1.22-1.84). Factors explaining adoption of short-term methods instead of LARCs or permanent method were: being resident in high under-five mortality clusters (AOR:1.56, 95% CI:1.14-2.14), maternal age > 25 years (AOR:1.88, 95% CI: 1.47-2.40), no decision-making role (AOR:11.19, 95% CI:8.74-14.34), no history of abortions (AOR:2.59, 95% CI:1.79-3.75), no female child (AOR:1.85, 95% CI:1.30-2.65) and ≤ 2 children (AOR:1.74, 95% CI:1.08-2.81). CONCLUSION: Considering the obstacles mothers face when it comes to accessing extended contraception, public health officials can devise effective strategies that empower MWRA to make well-informed and empowered choices regarding their families and reproductive health.

Barriers to childhood vaccination in urban slums of Pakistan.

Background: The urban slums of Pakistan continue to record low childhood vaccination coverage. It is therefore vital to understand the demand-side barriers to childhood vaccination in the slums to determine the required demand-generation interventions. Aims: To document the demand-side barriers related to childhood vaccination in urban slums of Pakistan and recommend appropriate demand-generation interventions. Methods: We investigated the demand-side barriers to childhood vaccination in 4 urban slums of Karachi, Pakistan, and disseminated the findings to the Expanded Program on Immunization and their partners. Using the findings, we made recommendations for collaborations with the various partners and for the design of demand-generation interventions to address the barriers. We then expanded the scope of the original research through a mapping exercise that gathered information on the vaccination-related research and interventions of the partners and used the information gathered to create a portfolio of activities. We present the demand-side barriers from the original research and the portfolio of demand-generation interventions. Results: The original research showed that 412 (49.0%) children aged 12-23 months, from 840 households, were fully vaccinated. Reasons given for not receiving the recommended vaccinations were mainly related to the fear of side effects, social and religious influences, lack of awareness, and misconceptions about vaccine administration. The mapping of activities revealed 47 initiatives that aimed to generate demand for childhood vaccination in the urban slums of Pakistan. Conclusion: Several stakeholders involved in childhood vaccination in the urban slums of Pakistan act independently, operating programmes that are disconnected. There is a need for better coordination and integration of the childhood vaccination interventions by these partners to achieve the goal of universal vaccination coverage.

Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses - finding and creating similarities in variables and data collection.

BACKGROUND: Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. METHODS: We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. DISCUSSION: We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.

Gutka consumption and dietary partialities explaining anemia in women of a coastal slum of Karachi, Pakistan: A mixed-method study.

BACKGROUND: Limited literature is available on the dietary pattern and its consequences on health of women living in coastal slums of Karachi, Pakistan. MATERIAL AND METHODS: The study employed a mixed-method approach where concurrent quantitative and qualitative assessments were carried out. An analytical cross-sectional survey was conducted to collect information on demographic, household, obstetrics characteristics, and dietary pattern of married women of reproductive age (MWRA). Blood samples were collected to identify the hemoglobin level to determine anemia. For the qualitative component, focus group discussions were carried out with women and in-depth interviews with shopkeepers to understand the availability of food items at household level and in local markets respectively. In addition, observational visits were carried out at different points in time to the local market to document the availability of iron-rich foods for the community. RESULTS: The overall prevalence of anemia in sample population was 68.0%. Women with no formal education (AOR: 2.93 95% CI: 1.90-4.52), who consumed gutka (AOR: 2.84 95% CI: 1.81-4.46), did not eat red meat (AOR: 1.68 95% CI: 1.06-2.65), and only had seafood (AOR: 4.56 95% CI: 1.38-15.02) were more likely to be anemic as compared to their counterparts. Qualitative data revealed that any kind of meat and fruits were beyond the reach of community people due to non-affordable cost. A high percentage of women used a locally produced recreational substance known as gutka which gives them a feeling of wellbeing and suppresses hunger. CONCLUSION: In our study population, lack of access to diversity of food items, illiteracy, and use of gutka are the statistically significant factors which are associated with anemia in married women of this coastal slum area. The lack of demand for diversity in food is related to poverty and preference of spending money on gutka.

Infectious aetiologies of neonatal illness in south Asia classified using WHO definitions: a primary analysis of the ANISA study.

BACKGROUND: Globally, neonatal mortality accounts for almost half of all deaths in children younger than 5 years. Aetiological agents of neonatal infection are difficult to identify because the clinical signs are non-specific. Using data from the Aetiology of Neonatal Infections in south Asia (ANISA) cohort, we aimed to describe the spectrum of infectious aetiologies of acute neonatal illness categorised post-hoc using the 2015 WHO case definitions of critical illness, clinical severe infection, and fast breathing only. METHODS: Eligible infants were aged 0-59 days with possible serious bacterial infection and healthy infants enrolled in the ANISA study in Bangladesh, India, and Pakistan. We applied a partial latent class Bayesian model to estimate the prevalence of 27 pathogens detectable on PCR, pathogens detected by blood culture only, and illness not attributed to any infectious aetiology. Infants with at least one clinical specimen available were included in the analysis. We assessed the prevalence of these aetiologies according to WHO's case definitions of critically ill, clinical severe infection, and infants with late onset, isolated fast breathing. For the clinical severe definition, we compared the prevalence of signs by bacterial versus viral aetiology. FINDINGS: There were 934 infants (992 episodes) in the critically ill category, 3769 (4000 episodes) in the clinical severe infection category, and 738 (771 episodes) in the late-onset isolated fast breathing category. We estimated the proportion of illness attributable to bacterial infection was 32·7% in infants in the critically ill group, 15·6% in the clinical severe infection group, and 8·8% among infants with late-onset isolated fast breathing group. An infectious aetiology was not identified in 58-82% of infants in these categories. Among 4000 episodes of clinical severe infection, those with bacterial versus viral attribution had higher proportions of hypothermia, movement only when stimulated, convulsions, and poor feeding. INTERPRETATION: Our modelled results generally support the revised WHO case definitions, although a revision of the most severe case definition could be considered. Clinical criteria do not clearly differentiate between young infants with and without infectious aetiologies. Our results highlight the need for improved point-of-care diagnostics, and further study into neonatal deaths and episodes with no identified aetiology, to ensure antibiotic stewardship and targeted interventions. FUNDING: The Bill and Melinda Gates Foundation.

Newborn weight change and predictors of underweight in the neonatal period in Guinea-Bissau, Nepal, Pakistan and Uganda.

In low- and middle-income countries (LMIC), growth impairment is common; however, the trajectory of growth over the course of the first month has not been well characterised. To describe newborn growth trajectory and predictors of growth impairment, we assessed growth frequently over the first 30 days among infants born ≥2000 g in Guinea-Bissau, Nepal, Pakistan and Uganda. In this cohort of 741 infants, the mean birth weight was 3036 ± 424 g. For 721 (98%) infants, weight loss occurred for a median of 2 days (interquartile range, 1-4) following birth until weight nadir was reached 5.9 ± 4.3% below birth weight. At 30 days of age, the mean weight was 3934 ± 592 g. The prevalence of being underweight at 30 days ranged from 5% in Uganda to 31% in Pakistan. Of those underweight at 30 days of age, 56 (59%) had not been low birth weight (LBW), and 48 (50%) had reached weight nadir subsequent to 4 days of age. Male sex (relative risk [RR] 2.73 [1.58, 3.57]), LBW (RR 6.41 [4.67, 8.81]), maternal primiparity (1.74 [1.20, 2.51]) and reaching weight nadir subsequent to 4 days of age (RR 5.03 [3.46, 7.31]) were highly predictive of being underweight at 30 days of age. In this LMIC cohort, country of birth, male sex, LBW and maternal primiparity increased the risk of impaired growth, as did the modifiable factor of delayed initiation of growth. Interventions tailored to infants with modifiable risk factors could reduce the burden of growth impairment in LMIC.

Nutritional support and prophylaxis of azithromycin for pregnant women to improve birth outcomes in peri-urban slums of Karachi, Pakistan-a protocol of multi-arm assessor-blinded randomized controlled trial (Mumta PW trial).

BACKGROUND: Maternal undernutrition is critical in the etiology of poor perinatal outcomes and accounts for 20% of small-for-gestational-age (SGA) births. High levels of food insecurity, antenatal undernourishment, and childhood undernutrition necessitate the supplementation of fortified balanced energy protein (BEP) during pregnancy in low-income settings especially with scarce literature available in this subject. Hence, this paper extensively covers the protocol of such a trial conducted in an urban slum of Karachi, Pakistan. METHODS: The trial is community-based, open-labelled, four-arm, and randomized controlled that will include parallel group assignments with a 1:1:1:1 allocation ratio in low-income squatter settlements in urban Karachi, Pakistan. All pregnant women (PW), if identified between > 8 and < 19 weeks of gestation based on ultrasound, will be offered routine antenatal care (ANC) counseling and voluntary participation in the trial after written informed consent. A total number of 1836 PW will be enrolled with informed consent and randomly allocated to one of the four arms receiving: (1) ANC counseling only (control group), (2) ANC counseling plus BEP supplement (intervention arm 1), (3) ANC counseling plus BEP supplement plus 2 doses azithromycin (intervention arm 2), or (4) ANC counseling plus BEP supplement plus daily single dose of nicotinamide and choline (intervention arm 3). TRIAL REGISTRATION: ClinicalTrials.gov NCT04012177 . Registered on July 9, 2019.

The Politics of Covid-19 Vaccine Distribution and Recognition.

With COVAX touted as the only platform that is built on equity and fairness, there is growing discontent and concern that the platform is falling short of its goals as COVID ravages across multiple countries. There are two serious issues that we address here. Firstly, COVID distribution principles and mechanisms need to be rethought in terms of a shift from private to global interests with a focus on prioritizing deliveries. Secondly, with multiple vaccines present, it is vital that countries recognize all of them, once proven safe and effective, to prevent any form of vaccine apartheid and discrimination.

Unveiling and addressing implementation barriers to routine immunization in the peri-urban slums of Karachi, Pakistan: a mixed-methods study.

BACKGROUND: Great disparities in immunization coverage exist in Pakistan between urban and rural areas. However, coverage estimates for large peri-urban slums in Sindh are largely unknown and implementation challenges remain unexplored. This study explores key supply- and demand-side immunization barriers in peri-urban slums, as well as strategies to address them. It also assesses immunization coverage in the target slums. METHODS: Conducted in four peri-urban slums in Karachi, this mixed-methods study consists of a baseline cross-sectional coverage survey of a representative sample of 840 caregivers of children aged 12-23 months, and 155 in-depth interviews (IDIs) through purposive sampling of respondents (caregivers, community influencers and immunization staff). After identifying the barriers, a further six IDIs were then conducted with immunization policy-makers and policy influencers to determine strategies to address these barriers, resulting in the development of an original validated implementation framework for immunization in peri-urban slums. A thematic analysis approach was applied to qualitative data. RESULTS: The survey revealed 49% of children were fully vaccinated, 43% were partially vaccinated and 8% were unvaccinated. Demand-side immunization barriers included household barriers, lack of knowledge and awareness, misconceptions and fears regarding vaccines and social and religious barriers. Supply-side barriers included underperformance of staff, inefficient utilization of funds, unreliable immunization and household data and interference of polio campaigns with immunization. The implementation framework's policy recommendations to address these barriers include: (1) improved human resource management; (2) staff training on counselling; (3) re-allocation of funds towards incentives, outreach, salaries and infrastructure; (4) a digital platform integrating birth registry and vaccination tracking systems for monitoring and reporting by frontline staff; (5) use of digital platform for immunization targets and generating dose reminders; and (6) mutual sharing of resources and data between the immunization, Lady Health Worker and polio programmes for improved coverage. CONCLUSIONS: The implementation framework is underpinned by the study of uncharted immunization barriers in complex peri-urban slums, and can be used by implementers in Pakistan and other developing countries to improve immunization programmes in limited-resource settings, with possible application at a larger scale. In particular, a digital platform integrating vaccination tracking and birth registry data can be expanded for nationwide use.

Nutritional support for lactating women with or without azithromycin for infants compared to breastfeeding counseling alone in improving the 6-month growth outcomes among infants of peri-urban slums in Karachi, Pakistan-the protocol for a multiarm assessor-blinded randomized controlled trial (Mumta LW trial).

BACKGROUND: Globally, 45% of under-five deaths are either directly or indirectly attributable to malnutrition, and most of these deaths are in low- and middle-income countries (LMICs). Children are particularly vulnerable in the first 6 months of life. An estimated 4.7 million infants under the age of 6 months are moderately wasted, whereas 3.8 million are severely wasted. Although the children of malnourished women have an increased risk of stunting and wasting, there is little information on this issue. METHODS: This is a community-based, open-label, multiarm randomized controlled trial that will include parallel group assignments with a 1:1:1 allocation ratio in low-income squatter settlements in urban Karachi, Pakistan. The women in the control group (control arm) will receive standard counseling only, whereas the lactating women in the first intervention group (intervention arm 1) will receive two sachets of balanced energy protein (BEP) supplementation per day from enrollment until the infant reaches 6 months of age. The lactating women in the second intervention group (intervention arm 2) will receive the same BEP supplementation as those in intervention arm 1 while their babies will also receive a single stat dose (20 mg/kg orally) of azithromycin at 42 days. The primary outcome will be the relative length velocity from 0 to 6 months by intervention arm. The primary analysis will be intention-to-treat analysis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03564652 . Registered on 21 June 2018.

Randomized Trial of Amoxicillin for Pneumonia in Pakistan.

BACKGROUND: The World Health Organization (WHO) recommends oral amoxicillin for patients who have pneumonia with tachypnea, yet trial data indicate that not using amoxicillin to treat this condition may be noninferior to using amoxicillin. METHODS: We conducted a double-blind, randomized, placebo-controlled noninferiority trial involving children at primary health care centers in low-income communities in Karachi, Pakistan. Children who were 2 to 59 months of age and who met WHO criteria for nonsevere pneumonia with tachypnea were randomly assigned to a 3-day course of a suspension of amoxicillin (the active control) of 50 mg per milliliter or matched volume of placebo (the test regimen), according to WHO weight bands (500 mg every 12 hours for a weight of 4 to <10 kg, 1000 mg every 12 hours for a weight of 10 to <14 kg, or 1500 mg every 12 hours for a weight of 14 to <20 kg). The primary outcome was treatment failure during the 3-day course of amoxicillin or placebo. The prespecified noninferiority margin was 1.75 percentage points. RESULTS: From November 9, 2014, through November 30, 2017, a total of 4002 children underwent randomization (1999 in the placebo group and 2003 in the amoxicillin group). In the per-protocol analysis, the incidence of treatment failure was 4.9% among placebo recipients (95 of 1927 children) and 2.6% among amoxicillin recipients (51 of 1929 children) (between-group difference, 2.3 percentage points; 95% confidence interval [CI], 0.9 to 3.7). Results were similar in the intention-to-treat analysis. The presence of fever and wheeze predicted treatment failure. The number needed to treat to prevent one treatment failure was 44 (95% CI, 31 to 80). One patient (<0.1%) in each group died. Relapse occurred in 40 children (2.2%) in the placebo group and in 58 children (3.1%) in the amoxicillin group. CONCLUSIONS: Among children younger than 5 years of age with nonsevere pneumonia, the frequency of treatment failure was higher in the placebo group than in the amoxicillin group, a difference that did not meet the noninferiority margin for placebo. (Funded by the Joint Global Health Trials Scheme [of the Department for International Development, Medical Research Council, and Wellcome] and others; RETAPP ClinicalTrials.gov number, NCT02372461.).

Causes and incidence of community-acquired serious infections among young children in south Asia (ANISA): an observational cohort study.

BACKGROUND: More than 500 000 neonatal deaths per year result from possible serious bacterial infections (pSBIs), but the causes are largely unknown. We investigated the incidence of community-acquired infections caused by specific organisms among neonates in south Asia. METHODS: From 2011 to 2014, we identified babies through population-based pregnancy surveillance at five sites in Bangladesh, India, and Pakistan. Babies were visited at home by community health workers up to ten times from age 0 to 59 days. Illness meeting the WHO definition of pSBI and randomly selected healthy babies were referred to study physicians. The primary objective was to estimate proportions of specific infectious causes by blood culture and Custom TaqMan Array Cards molecular assay (Thermo Fisher, Bartlesville, OK, USA) of blood and respiratory samples. FINDINGS: 6022 pSBI episodes were identified among 63 114 babies (95·4 per 1000 livebirths). Causes were attributed in 28% of episodes (16% bacterial and 12% viral). Mean incidence of bacterial infections was 13·2 (95% credible interval [CrI] 11·2-15·6) per 1000 livebirths and of viral infections was 10·1 (9·4-11·6) per 1000 livebirths. The leading pathogen was respiratory syncytial virus (5·4, 95% CrI 4·8-6·3 episodes per 1000 livebirths), followed by Ureaplasma spp (2·4, 1·6-3·2 episodes per 1000 livebirths). Among babies who died, causes were attributed to 46% of pSBI episodes, among which 92% were bacterial. 85 (83%) of 102 blood culture isolates were susceptible to penicillin, ampicillin, gentamicin, or a combination of these drugs. INTERPRETATION: Non-attribution of a cause in a high proportion of patients suggests that a substantial proportion of pSBI episodes might not have been due to infection. The predominance of bacterial causes among babies who died, however, indicates that appropriate prevention measures and management could substantially affect neonatal mortality. Susceptibility of bacterial isolates to first-line antibiotics emphasises the need for prudent and limited use of newer-generation antibiotics. Furthermore, the predominance of atypical bacteria we found and high incidence of respiratory syncytial virus indicated that changes in management strategies for treatment and prevention are needed. Given the burden of disease, prevention of respiratory syncytial virus would have a notable effect on the overall health system and achievement of Sustainable Development Goal. FUNDING: Bill & Melinda Gates Foundation.