Improving possible serious bacterial infection (PSBI) management in young infants when referral is not feasible: lessons from embedded implementation research in Ethiopia and Kenya.

BACKGROUND: Sepsis is a leading cause of neonatal mortality, despite the availability of effective treatment of possible serious bacterial illness (PSBI), including when referral to a hospital is not feasible. Gaps in access and delivery worsened during COVID-19. We conducted embedded implementation research in Ethiopia and Kenya aimed at mitigating the impact of COVID-19 and addressing various implementation challenges to improve PSBI management. METHODS: The implementation research projects were implemented at the subnational level in Ethiopia and Kenya between November 2020-June 2022 (Ethiopia) and December 2020-August 2022 (Kenya). Guided by the implementation research frameworks, both projects conducted mixed formative quantitative and exploratory research from April to May 2021, followed by summative evaluations conducted between June and July 2022. Frameworks encompassed Consolidated Framework for Implementation Research (CFIR), Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM), as well as health systems framework that incorporates cascades of care and World Health Organization Health Systems Building Blocks. Results were synthesized across the projects through document review and sharing cross-project measures and strategies through a project community of practice. RESULTS: Despite differences in settings across the projects, cross-cutting facilitators included community health worker program and support, and existence of guidelines for PSBI management at primary care levels. Barriers included community attitudes towards seeking care for sick newborns, COVID-19 risks and fear, and lack of health care worker competence. Country-specific contextual barriers included supply chain issues, civil conflict (Ethiopia), and labor strikes (Kenya). Strategies chosen to mitigate barriers and support implementation and sustainability in both settings included leveraging community health workers to address resistance to care-seeking, health workers' training, COVID-19 infection prevention measures, stakeholder engagement, and advocacy to integrate PSBI management into existing programs, policies, and training. Other strategies addressing emerging project-specific barriers, included improving follow-up through a community health desk and PSBI mobile app (Kenya) and supply chain strengthening (Ethiopia). Both projects improved PSBI management coverage, increased adoption and uptake, and informed national policy changes supporting potential for sustainability. CONCLUSIONS: Pragmatic embedded implementation research effectively supports the identification of barriers and mapping to strategies designed to increase effective coverage of PSBI management when referral is not feasible during the COVID-19 pandemic. Despite differences in context, cross-cutting strategies identified could inform broader scale-up in the region, including during future health system shocks.

Antibiotic resistance trends for common bacterial aetiologies of childhood diarrhoea in low- and middle-income countries: A systematic review.

Background: Diarrhoea is the second most common cause of death among children under the age of five worldwide. The World Health Organization (WHO) recommends treating diarrhoea with oral rehydration therapy, intravenous fluids for severe dehydration, and zinc supplements. Antibiotics are only recommended to treat acute, invasive diarrhoea. Rising antibiotic resistance has led to a decrease in the effectiveness of treatments for diarrhoea. Methods: A systematic literature review in PubMed, Web of Science, and EMBASE was conducted to identify articles relevant to antibiotic-resistant childhood diarrhoea. Articles in English published between 1990 to 2020 that described antibiotic resistance patterns of common pathogens causing childhood diarrhoea in low- and middle-income countries were included. The studies were limited to papers that categorized children as 0-5 years or 0-10 years old. The proportion of isolates with resistance to major classes of antibiotics stratified by major WHO global regions and time was determined. Results: Quantitative data were extracted from 44 articles that met screening criteria; most focused on children under five years. Escherichia coli isolates had relatively high resistance rates to ampicillin and tetracycline in the African (AFR), American (AMR), and Eastern Mediterranean Regions (EMR). There was moderate to high resistance to ampicillin and third generation cephalosporins among Salmonella spp in the AFR, EMR, and the Western Pacific Region (WPR). Resistance rates for ampicillin, co-trimoxazole, and chloramphenicol for Shigella in the AFR started at an alarmingly high rate ( ~ 90%) in 2006 and fluctuated over time. There were limited antibiotic resistance data for Aeromonas, Yersinia, and V. cholerae. The 161 isolates of Campylobacter analysed showed initially low rates of fluoroquinolone resistance with high rates of resistance in recent years, especially in the Southeast Asian Region. Conclusions: Resistance to inexpensive antibiotics for treatment of invasive diarrhoea in children under ten years is widespread (although data on 6- to 10-year-old children are limited), and resistance rates to fluoroquinolones and later-generation cephalosporins are increasing. A strong regional surveillance system is needed to carefully monitor trends in antibiotic resistance, future studies should include school-aged children, and interventions are needed to reduce inappropriate use of antibiotics for the treatment of community-acquired, non-invasive diarrhoea. Registration: This systematic review was registered in Prospero (registration number CRD42020204004) in August 2020.

Importance of breastfeeding and complementary feeding for management and prevention of childhood diarrhoea in low- and middle-income countries.

Background: Early and exclusive breastfeeding have been shown to protect young infants from all-cause and diarrhoea-related mortality. Ideally breastfeeding should be initiated within the first hour of birth. Despite efforts to increase rates of early and exclusive breastfeeding in low- and middle-income countries (LMICs), challenges with uptake remain. This analysis reviews trends in early and exclusive breastfeeding, and the impact of infant feeding interventions in reducing childhood diarrhoea. Methods: We conducted a detailed review of articles written in English between 1990 and 2020 on the impact and efficacy of breastfeeding and complementary feeding on diarrhoea in children aged 0-2 years in LMICs. Using data from 86 countries and all WHO global regions collected from the mid-1980s through 2018 obtained from publicly available Demographic Health Surveys, we assessed trends in five-year intervals of timing of breastfeeding initiation, exclusive breastfeeding, median and mean duration of exclusive breastfeeding, and complementary feeding. Results: The literature search identified ten articles that described variable rates of early initiation of breastfeeding from 20% in Pakistan to 76% in Egypt. An analysis of 288 DHS studies found that the proportion of women who reported initiating breastfeeding within an hour of birth increased from 32% in the early 1990s to 55% between 2016 and 2020. Exclusive breastfeeding increased from 20% in the late 1980s to 48% between 2016 and 2020 and the mean duration of exclusive breastfeeding of 2-to-4-month-old infants doubled. Early initiation of breastfeeding and exclusive breastfeeding was associated with reductions in diarrhoea prevalence in the South East Asian, Western Pacific, Eastern Mediterranean, and African regions. Eight studies evaluating the effectiveness of different maternal education interventions, health care worker training, and media campaigns demonstrated improvements in exclusive breastfeeding, and most resulted in reductions in the incidence or duration of diarrhoea. Conclusions: During the last two decades, early and exclusive breastfeeding have increased. Nevertheless, the uptake of this basic, low-cost intervention remains suboptimal across all global regions. Given the potential benefits the in reduction of diarrhoea and diarrhoea-associated mortality, interventions for improving the uptake of early and exclusive breastfeeding in different sociological contexts need to be designed, implemented, and evaluated.

Measuring coverage and quality of supportive care for inpatient neonatal infections: EN-BIRTH multi-country validation study.

Background: An estimated 7 million episodes of severe newborn infections occur annually worldwide, with half a million newborn deaths, most occurring in low- and middle-income countries. Whilst injectable antibiotics are necessary to treat the infection, supportive care is also crucial in ending preventable mortality and morbidity. This study uses multi-country data to assess gaps in coverage, quality, and documentation of supportive care, considering implications for measurement. Methods: The EN-BIRTH study was conducted in five hospitals in Bangladesh, Nepal, and Tanzania (July 2017-July 2018). Newborns with an admission diagnosis of clinically-defined infection (sepsis, meningitis, and/or pneumonia) were included. Researchers extracted data from inpatient case notes and interviews with women (usually the mothers) as the primary family caretakers after discharge. The interviews were conducted using a structured survey questionnaire. We used descriptive statistics to report coverage of newborn supportive care components such as oxygen use, phototherapy, and appropriate feeding, and we assessed the validity of measurement through survey-reports using a random-effects model to generate pooled estimates. In this study, key supportive care components were assessment and correction of hypoxaemia, hyperbilirubinemia, and hypoglycaemia. Results: Among 1015 neonates who met the inclusion criteria, 89% had an admission clinical diagnosis of sepsis. Major gaps in documentation and care practices related to supportive care varied substantially across the participating hospitals. The pooled sensitivity was low for the survey-reported oxygen use (47%; 95% confidence interval (CI) = 30%-64%) and moderate for phototherapy (60%; 95% CI = 44%-75%). The pooled specificity was high for both the survey-reported oxygen use (85%; 95% CI = 80%-89%) and phototherapy (91%; 95% CI = 82%-97%). Conclusions: The women's reports during the exit survey consistently underestimated the coverage of supportive care components for managing infection. We have observed high variability in the inpatient documents across facilities. A standardised ward register for inpatient small and sick newborn care may capture selected supportive care data. However, tracking the detailed care will require standardised individual-level data sets linked to newborn case notes. We recommend investments in assessing the implementation aspects of a standardised inpatient register in resource-poor settings.

Community-based amoxicillin treatment for fast breathing pneumonia in young infants 7-59 days old: a cluster randomised trial in rural Bangladesh, Ethiopia, India and Malawi.

INTRODUCTION: Young infants 7-59 days old with fast breathing pneumonia presented to a primary level health facility receive a 7-day course of amoxicillin as per the WHO guideline. However, community-level health workers (CLHW) are not allowed to treat these infants. This trial evaluated the community level treatment of non-hypoxaemic young infants with fast breathing pneumonia by CLHWs. METHODS: This cluster-randomised, open-label, non-inferiority trial was conducted in rural areas of Bangladesh, Ethiopia, India and Malawi. We randomly allocated clusters (first-level health facility) 1:1, stratified by the population size, to an intervention group (enhanced community case management) or control group (standard community case management). Infants aged 7-59 days with a respiratory rate of ≥60 breaths/min and oxygen saturation (SpO2) ≥90% were enrolled. In the intervention clusters, these infants were treated with a 7-day course of oral amoxicillin (according to WHO weight bands) and were regularly followed up by CLHWs. In the control clusters, CLHWs continued the standard management (assess and refer after pre-referral antibiotic dose) and followed up according to the national programme guideline. The primary outcome of treatment failure was assessed in both groups by independent outcome assessors on days 6 and 14 after enrolment. Secondary outcomes (accuracy and impact of pulse oximetry) were also assessed. RESULTS: Between September 2016 and December 2018, we enrolled 2334 infants (1168 in intervention and 1166 in control clusters) from 208 clusters (104 intervention and 104 control). Of 2334, 22 infants with fast breathing were excluded from analysis, leaving 2312 (1155 in intervention clusters and 1157 in control clusters) for intention-to-treat analysis. The proportion of treatment failure was 5.4% (63/1155) in intervention and 6.3% (73/1157) in the control clusters, including two deaths (0.2%) in each group. The adjusted risk difference for treatment failure between the two groups was -1.0% (95% CI -3.0% to 1.1%). The secondary outcome showed that CLHWs in the intervention clusters performed all recommended steps of pulse oximetry assessment in 94% (1050/1115) of enrolled patients. CONCLUSIONS: The 7-day amoxicillin treatment for 7-59 days old non-hypoxaemic infants with fast breathing pneumonia by CLHWs was non-inferior to the currently recommended referral strategy. TRIAL REGISTRATION NUMBERS: CTRI/2017/02/007761 and ACTRN12617000857303.

An analysis of clinical predictive values for radiographic pneumonia in children.

INTRODUCTION: Healthcare providers in resource-limited settings rely on the presence of tachypnoea and chest indrawing to establish a diagnosis of pneumonia in children. We aimed to determine the test characteristics of commonly assessed signs and symptoms for the radiographic diagnosis of pneumonia in children 0-59 months of age. METHODS: We conducted an analysis using patient-level pooled data from 41 shared datasets of paediatric pneumonia. We included hospital-based studies in which >80% of children had chest radiography performed. Primary endpoint pneumonia (presence of dense opacity occupying a portion or entire lobe of the lung or presence of pleural effusion on chest radiograph) was used as the reference criterion radiographic standard. We assessed the sensitivity, specificity, and likelihood ratios for clinical findings, and combinations of findings, for the diagnosis of primary endpoint pneumonia among children 0-59 months of age. RESULTS: Ten studies met inclusion criteria comprising 15 029 children; 24.9% (n=3743) had radiographic pneumonia. The presence of age-based tachypnoea demonstrated a sensitivity of 0.92 and a specificity of 0.22 while lower chest indrawing revealed a sensitivity of 0.74 and specificity of 0.15 for the diagnosis of radiographic pneumonia. The sensitivity and specificity for oxygen saturation <90% was 0.40 and 0.67, respectively, and was 0.17 and 0.88 for oxygen saturation <85%. Specificity was improved when individual clinical factors such as tachypnoea, fever and hypoxaemia were combined, however, the sensitivity was lower. CONCLUSIONS: No single sign or symptom was strongly associated with radiographic primary end point pneumonia in children. Performance characteristics were improved by combining individual signs and symptoms.

Iron/folic acid supplementation during pregnancy prevents neonatal and under-five mortality in Pakistan: propensity score matched sample from two Pakistan Demographic and Health Surveys.

BACKGROUND: Several epidemiological studies from low- and middle-income countries have reported a protective effect of maternal antenatal iron/folic acid (IFA) on childhood mortality. OBJECTIVE: The current study aimed to evaluate the effect of maternal antenatal IFA supplementation on childhood mortality in Pakistan. DESIGN: A propensity score-matched sample of 8,512 infants live-born within the 5 years prior to interview was selected from the pooled data of two Pakistan Demographic and Health Surveys (2006/07 and 2012/13). The primary outcomes were childhood mortality indicators and the main exposure variable was maternal antenatal IFA supplementation. Post-matched analyses used Cox proportional hazards regression and adjusted for 16 potential confounders. RESULTS: Maternal antenatal IFA supplementation significantly reduced the adjusted risk of death on day 0 by 33% [adjusted hazard ratio (aHR)=0.67, 95% confidence interval (95% CI) 0.48-0.94], during the neonatal period by 29% (aHR=0.71, 95% CI 0.57-0.88), and for under-fives by 27% (aHR=0.73, 95% CI 0.60-0.89). When IFA was initiated in the first 4 months of pregnancy, the adjusted risk of neonatal and under-five deaths was significantly reduced by 35 and 33%, respectively. Twenty percent of under-five deaths were attributable to non-initiation of IFA in the first 4 months of pregnancy. With universal initiation of IFA in the first 4 months of pregnancy, 80,300 under-five deaths could be prevented annually in Pakistan. CONCLUSIONS: Maternal antenatal IFA supplementation significantly reduced neonatal and under-five deaths in Pakistan. Earlier initiation of supplements in pregnancy was associated with a greater prevention of neonatal and under-five deaths.

Relationship of Antenatal Iron-folic Acid (IFA) Supplementation and Birth Size: Evidence from Nepal.

Objectives: To determine the effect of antenatal IFA supplementation on maternal perceived birth size in Nepal using pooled data from 3 Nepal Demographic and Health Survey (DHS) 2001, 2006 and 2011. Methods: We used survival information from 13,111 most recent live-born infants. Primary outcome was maternal perceived birth size and the main exposure variable was the antenatal IFA supplementation. Birth weight was reported in 19% of live births. Perceived birth size was considered as surrogate for birth weight. Data was analysed by using STATA 13 and adjusted for the cluster sampling design. Analyses used multivariate logistic regression adjusted for 18 potential confounders. Results: Maternal use of IFA supplementation during pregnancy significantly reduced the risk of less than average birth size by 15% (aOR: 0.85 p=0.01) compared to no IFA use after adjustment for other confounders. The protective effect of IFA supplementation on less than average birth size remained there whether other antenatal services used or not (aOR: 0.81, p=0.001) compared to no IFA supplementation and no antenatal services. A slightly greater magnitude of protective effect was observed when mother used ≥90 supplements in their pregnancy (aOR: 0.84, p=0.03) than those mothers who never used any IFA supplements after adjustment for other confounding factors. Conclusions: Maternal use of IFA supplements during pregnancy significantly reduces the risk of less than average birth size in Nepal. The magnitude of protective effect on the risk of having less than average birth size was greater in infants whose mothers used ≥90 supplements in their pregnancy.

Antenatal Iron-folic Acid Supplementation Reduces Risk of Low Birth Weight in Pakistan.

Objectives: To examine the effect of iron-folic acid (IFA) supplementation on perceived birth size and birth weight using Pakistan Demographic and Health Survey (PDHS) 2006-07. Methods: Information from 5,692 most recent live-born infants within 5 years prior to survey was used. The primary outcomes were maternal perception of birth size and birth weight and the main exposure was any use of antenatal IFA supplements. Birth weight was reported for only 10% of live births in PDHS 2006-07. Data was analysed by using STATA 13 and adjusted for the cluster sampling design. Analyses used multivariate logistic regression adjusted for 14 potential confounders. Results: The risk of having less than average birth size babies was significantly reduced by 18% (aOR: 0.82, 95% CI 0.71, 0.96) for mothers who used any IFA supplements compared to no IFA use. A similar (18%), but non-significant reduction in the risk of low birth weight babies was found with maternal use of IFA supplements. Mothers who started IFA in the first trimester of pregnancy, significantly reduced the risk of having less than average birth size babies by 19%. Population attributable risk estimates showed 11% of ‘less than average birth size’ were attributed to non-use of antenatal IFA supplementation and universal coverage of IFA supplementation could prevent 112,000 newborns to have ‘less than average birth size’ each year in Pakistan. Conclusions: Antenatal IFA supplementation significantly reduces the risk of less than average birth size and low birth weight babies in Pakistan. Universal coverage of supplementation improves birth size.

Enhanced Iron-folic Acid (IFA) Supplementation Program Reduces Risk of Under 5 Mortality in Nepal.

Objectives: To investigate the impact of a decade-long program to improve coverage of antenatal IFA supplementation on child survival in Nepal over a 15 year period from 1996 to 2011. Methods: We used pooled data of 3 Nepal Demographic and Health Survey (DHS) 2001, 2006 and 2011 with survival information from 13,106 most recent live-born infants. Primary outcomes were mortality indicators in children <5 years and the main exposure variable was the implementation of an improved IFA supplementation program. The improved program was implemented in 70 out of 75 districts in a phased manner at district level starting in 2003-04 and continuing till 2011. Data was analysed by using STATA 13 and adjusted for the cluster sampling design. Analyses used multivariate Cox proportional hazards regression adjusted for 22 potential confounders. Results: After the phased implementation of the program to improve coverage of IFA supplementation, the risk of mortality on day 0 (first day of life) and early neonatal mortality (0-7 days) significantly reduced by 56% and 55% respectively compared to before the implementation of program after the adjustment of other confounders. The protective effect of implementation of improved IFA supplementation program was also observed in infant (aHR: 0.53, p=0.011) and under five mortality (aHR: 0.64, p=0.046) compared to before the program started. Conclusions: An enhanced IFA supplementation program significantly reduces the deaths on first day of life and in early neonatal period in Nepal. The protective effect of the program was also seen in infants and in children <5 years of age.

Perceptions of Antenatal Iron-folic Acid Supplements in Urban and Rural Pakistan: A Qualitative Study.

Objectives: To understand women and healthcare providers’ perceptions, and to investigate the cultural and behavioural factors influencing the use of antenatal IFA supplements in rural and urban settings of Pakistan. Methods: Focus group discussions and in-depth interviews with mothers, currently pregnant women, community health workers and doctors were conducted in rural and urban areas of two districts of Pakistan. Data was collected between August and November 2012. Results: The majority of women were aware of the perceived benefits of antenatal IFA supplements. The facilitating factors for the women’s use of supplements were: they had knowledge of benefits; they had trust in the healthcare providers; the supplements were available; they had the financial capacity to buy them; they felt better after taking these supplements; and they received support from family members. The barriers to the women’s use of supplements were: they forgot to take them; the non-availability of supplements; their limited financial capacity to buy them; the lack of antenatal care services; family members not allowing use of the supplements; not knowing about the benefits or no education; fear or experience of side effects; considering them as contraceptives; and felt better thus stopped. Conclusions: The coverage of antenatal IFA supplementation can be improved by reducing the barriers related to the use of antenatal IFA supplementation in Pakistan. Interventions focused on providing adequate awareness, good quality counselling, reminder messages, availability of free supplements throughout pregnancy and reducing the side effects should be developed and implemented.

Factors Associated with Non-use of Antenatal Iron and Folic Acid Supplements among Pakistani Women: A Cross Sectional Household Survey.

Objectives: To determine the prevalence of use of antenatal iron-folic acid (IFA) supplements, and to identify socio-demographic risk factors for non-use of antenatal IFA supplements. Methods: A cross sectional household cluster sample survey was conducted in 14 districts in Pakistan. Trained female fieldworkers conducted interviews with married women of reproductive age from December 2011 to March 2012. Women with live births in the preceding five years of the survey were selected for this study. Data was analysed by using STATA 13 and adjusted for the cluster sampling design. Multivariate logistic regression models were constructed to identify the independent factors for non-use of antenatal IFA supplements. Results: Out of 6,266, 2,400 (38.3%, 95% CI: 36.6%, 40.1%) women took antenatal IFA supplements during their last pregnancy. Common sources of supplements were doctors (49.4%) and community health workers (40.3%). The mean (±SD) month of pregnancy at initiation of supplementation was 5.3 (±1.7) months. Living in Dera Ghazi Khan district (Adj OR=1.72), maternal age ≥45 years (Adj OR=2.01), no maternal education (Adj OR=2.33), no paternal education (Adj OR=1.58), belonging to the lowest household wealth index quartile (Adj OR=1.47), and no antenatal care services used (Adj OR=13.44) were risk factors for non-use of antenatal IFA supplements. Conclusions: The coverage of antenatal IFA supplements is low in the surveyed districts of Pakistan, and the lack of parental education, older aged women, belonging to poorest households, residence in Dera Ghazi Khan district and no antenatal care services used were risk factors for non-use of IFA supplements.

Antenatal Iron-folic Acid (IFA) Supplementation Reduces Mortality in Children Less than 5 years of Age in Nepal.

Objectives: To examine the effect of antenatal iron-folic acid (IFA) supplements on the risk of childhood mortality in Nepal using pooled data from 3 Nepal Demographic and Health Survey (DHS) 2001, 2006 and 2011. Methods: Survival information was used from 13,009 singleton most recent live-born infants. Primary outcomes were mortality indicators in children <5 years and the main exposure variable was any use of IFA supplements. Data was analysed by using STATA 13 and adjusted for the cluster sampling design. Analyses used multivariate Cox proportional hazards regression adjusted for 24 potential confounders based on Mosley and Chen framework for childhood survival in developing countries. Results: Any use of IFA supplements significantly reduced risk of early neonatal deaths by 45% (aHR: 0.55, 95% CI: 0.38, 0.79), and total neonatal deaths by 42% (aHR: 0.58, 95% CI: 0.39, 0.85). Similarly, the risk of infant and under-5 mortality was significantly reduced by 32% and 48%, respectively. For mothers who started ≤4 months of pregnancy and used ≥150 supplements under- 5 mortality was significantly reduced by 57% (aHR: 0.43, 95% CI: 0.23, 0.78). Population attributable risk estimates found 15% of under-5 deaths were attributed to non-use of IFA, and 29,000 under-5 deaths could be prevented in the next 5 years with universal IFA coverage. Conclusions: Antenatal IFA supplementation significantly reduces the risk of neonatal and under- 5 deaths in Nepal. The greatest impact on child survival was found in women who started early in pregnancy and took ≥150 supplements. Universal IFA coverage could improve childhood survival.