Optimizing integration of community-based management of possible serious bacterial infection (PSBI) in young infants into primary healthcare systems in Ethiopia and Kenya: successes and challenges.

BACKGROUND: Ethiopia and Kenya have adopted the community-based integrated community case management (iCCM) of common childhood illnesses and newborn care strategy to improve access to treatment of infections in newborns and young infants since 2012 and 2018, respectively. However, the iCCM strategy implementation has not been fully integrated into the health system in both countries. This paper describes the extent of integration of iCCM program at the district/county health system level, related barriers to optimal integration and implementation of strategies. METHODS: From November 2020 to August 2021, Ethiopia and Kenya implemented the community-based treatment of possible serious bacterial infection (PSBI) when referral to a higher facility is not possible using embedded implementation research (eIR) to mitigate the impact of COVID-19 on the delivery of this life-saving intervention. Both projects conducted mixed methods research from April-May 2021 to identify barriers and facilitators and inform strategies and summative evaluations from June-July 2022 to monitor the effectiveness of implementation outcomes including integration of strategies. RESULTS: Strategies identified as needed for successful implementation and sustainability of the management of PSBI integrated at the primary care level included continued coaching and support systems for frontline health workers, technical oversight from the district/county health system, and ensuring adequate supply of commodities. As a result, support and technical oversight capacity and collaborative learning were strengthened between primary care facilities and community health workers, resulting in improved bidirectional linkages. Improvement of PSBI treatment was seen with over 85% and 81% of estimated sick young infants identified and treated in Ethiopia and Kenya, respectively. However, perceived low quality of service, lack of community trust, and shortage of supplies remained barriers impeding optimal PSBI services access and delivery. CONCLUSION: Pragmatic eIR identified shared and unique contextual challenges between and across the two countries which informed the design and implementation of strategies to optimize the integration of PSBI management into the health system during the COVID-19 pandemic. The eIR participatory design also strengthened ownership to operationalize the implementation of identified strategies needed to improve the health system's capacity for PSBI treatment.

Implementation research to increase treatment coverage of possible serious bacterial infections in young infants when a referral is not feasible: lessons learnt.

BACKGROUND: The objective was to achieve high coverage of possible serious bacterial infections (PSBI) treatment using the World Health Organization (WHO) guideline for managing it on an outpatient basis when referral to a hospital is not feasible. METHODS: We implemented this guideline in the programme settings at 10 Basic Health Units (BHU) in two rural districts of Sindh in Pakistan using implementation research. A Technical Support Unit supported the programme to operationalize guidelines, built capacity of health workers through training, monitored their clinical skills, mentored them and assured quality. The community-based health workers visited households to identify sick infants and referred them to the nearest BHU for further management. The research team collected data. RESULTS: Of 17 600 identified livebirths, 1860 young infants with any sign of PSBI sought care at BHUs and 1113 (59.8%) were brought by families. We achieved treatment coverage of 95%, assuming an estimated 10% incidence of PSBI in the first 2 months of life and that 10% of young infants came from outside the study catchment area. All 923 infants (49%; 923/1860) 7-59 days old with only fast breathing (pneumonia) treated with outpatient oral amoxicillin were cured. Hospital referral was refused by 83.4% (781/937) families who accepted outpatient treatment; 92.2% (720/781) were cured and 0.8% (6/781) died. Twelve (7.6%; 12/156) died among those treated in a hospital. CONCLUSION: It is feasible to achieve high coverage by implementing WHO PSBI management guidelines in a programmatic setting when a referral is not feasible.

Prospective cohort study of referred Malawian children and their survival by hypoxaemia and hypoglycaemia status.

Objective: To investigate survival in children referred from primary care in Malawi, with a focus on hypoglycaemia and hypoxaemia progression. Methods: The study involved a prospective cohort of children aged 12 years or under referred from primary health-care facilities in Mchinji district, Malawi in 2019 and 2020. Peripheral blood oxygen saturation (SpO2) and blood glucose were measured at recruitment and on arrival at a subsequent health-care facility (i.e. four hospitals and 14 primary health-care facilities). Children were followed up 2 weeks after discharge or their last clinical visit. The primary study outcome was the case fatality ratio at 2 weeks. Associations between SpO2 and blood glucose levels and death were evaluated using Cox proportional hazards models and the treatment effect of hospitalization was assessed using propensity score matching. Findings: Of 826 children recruited, 784 (94.9%) completed follow-up. At presentation, hypoxaemia was moderate (SpO2: 90-93%) in 13.1% (108/826) and severe (SpO2: < 90%) in 8.6% (71/826) and hypoglycaemia was moderate (blood glucose: 2.5-4.0 mmol/L) in 9.0% (74/826) and severe (blood glucose: < 2.5 mmol/L) in 2.3% (19/826). The case fatality ratio was 3.7% (29/784) overall but 26.3% (5/19) in severely hypoglycaemic children and 12.7% (9/71) in severely hypoxaemic children. Neither moderate hypoglycaemia nor moderate hypoxaemia was associated with mortality. Conclusion: Presumptive pre-referral glucose treatment and better management of hypoglycaemia could reduce the high case fatality ratio observed in children with severe hypoglycaemia. The morbidity and mortality burden of severe hypoxaemia was high; ways of improving hypoxaemia identification and management are needed.

Qualitative exploration of facilitating factors and barriers to use of antenatal care services by pregnant women in urban and rural settings in Pakistan.

BACKGROUND: World Health Organisation recommends that pregnant women with no complications should visit a healthcare provider at least four times to receive sufficient antenatal care services. In Pakistan only 37% of women reported to have had four or more antenatal care visits during their last pregnancy. This study aimed to explore facilitators and barriers to use of antenatal care services in rural and urban communities of two selected districts in Pakistan. METHODS: Qualitative explorative study using in-depth interviews with currently pregnant women, lady health workers and doctors providing antenatal care services, and focus group discussion with women who had a child aged 5 years or younger, was conducted in a rural community in the district Swabi and in a tertiary care hospital in urban Islamabad in Pakistan. The audio-recorded interviews and discussions were transcribed verbatim in Urdu (the language spoken by the respondents). A list of topical codes for all topics related to the research questions was developed. Subsequently the text pertaining to each topical code was discussed and summarised in a document that presented the findings for each topic using quotes and tables. RESULTS: We conducted in-depth interviews with six lady health workers, four doctors, and ten currently pregnant women, and facilitated ten focus group discussions with women who had a child aged 5 years or younger. Currently pregnant women, and women who had a child aged 5 years or younger, were not aware of the recommended minimum number of antenatal care visits to be made during pregnancy. Facilitating factors to visit a particular health care facility were: availability of qualified healthcare providers (private facility); trust in healthcare providers; recommendation from a family member, friend or lady health worker (in rural areas); availability of good quality services including medical equipment and laboratory facilities; low cost (public facility); and easy access to the health facility (private facility). Common barriers to visiting a health facility for antenatal care services were: financial limitations; perceived absence of any major health problems during pregnancy; difficulties in reaching the health facility; restriction from husband or mother-in-law; busy performing household chores; no previous experience of antenatal care visits; and perceived unavailability of healthcare providers and/or services. CONCLUSIONS: The current study identified several policy-relevant facilitating factors and barriers to visiting a health facility for antenatal care services as reported by urban and rural women, and healthcare providers. There is a need to formulate and implement intervention packages based on these findings to increase the coverage of the recommended four antenatal care visits in Pakistan.

Association of haematological and radiological Findings with clinical outcome in hospitalized Children 2-36 months old with severe lower Respiratory tract infection.

BACKGROUND: Despite reduction in child mortality during last decade, lower respiratory tract infection (LRTI) remained number one killer of under-five. The current study aimed to assess the association of haematological and radiological findings with clinical outcome in hospitalized children 2-36 months old with severe LRTI. METHODS: In the current cross sectional study, 581 children 2-36 months old with severe LRTI were enrolled and followed at the Children Hospital, Islamabad, between 2011 and 2014. At the time of enrolment, complete history of present illness, anthropometric measurements, blood sample and chest radiograph were obtained. The primary outcome was either early clinical response (within 72 hours) or delayed clinical response (>72 hours). Multivariable logistic regression was performed to examine the association between haematological and radiological findings with clinical outcome, adjusted for potential confounding factors. RESULTS: Of 581 enrolled children, 292 (50.3%) children had early, and 289 (49.7%) had delayed clinical response. The multivariable logistic regression showed that leucocytosis (OR 1.79, 95% CI 1.15-2.79), neutrophilia (OR 1.91, 95% CI 1.29-2.84), radiological interstitial pneumonia (OR 2.49, 95%CI 1.70-3.64), and lobar consolidation (OR 6.00, 95%CI 2.41-14.96) were significantly associated with delayed clinical response, after adjusted for potential confounding factors. CONCLUSIONS: Delayed clinical response was significantly associated with abnormal haematological and radiological findings at the time of admission in children 2-36 months old with severe LRTI. Haematological and radiological findings at the time of presentation are useful for predicting delayed clinical response in children 2-36 months old with severe LRTI.

Antenatal Iron-Folic Acid Supplementation Reduces Neonatal and Under-5 Mortality in Nepal.

BACKGROUND: Antenatal iron-folic acid (IFA) supplementation improves maternal anemia and poor pregnancy outcomes. Antenatal use of IFA supplements also has an effect on child survival. OBJECTIVE: The current study investigated the effect of antenatal IFA supplements on the risk of childhood mortality in Nepal over a 15-y period from 1996 to 2011. METHODS: Survival information of 12,891 singleton most recent live-born infants from pooled 2001, 2006, and 2011 Nepal Demographic and Health Surveys was used. Primary outcomes were mortality indicators in children <5 y of age and the main exposure variable was use of IFA supplements. Data were analyzed by using STATA 13.1 (StataCorp) and were adjusted for the cluster sampling design. Analyses used multivariate Cox proportional hazards regression adjusted for potential confounders. RESULTS: Antenatal use of IFA supplements significantly reduced the risk of early neonatal deaths by 45% [adjusted HR (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 IFA at 1-4 mo of pregnancy and used 150-240 supplements, neonatal and under-5 mortality were significantly reduced by 55% (aHR: 0.45; 95% CI: 0.24, 0.85) and 57% (aHR: 0.43; 95% CI: 0.23, 0.78), respectively. Population attributable risk estimates found 15% of under-5 deaths were attributed to nonuse of IFA, and 29,000 under-5 deaths could be prevented in the next 5 y with universal IFA coverage. CONCLUSIONS: Antenatal IFA supplementation significantly reduces the risk of neonatal and under-5 deaths in Nepal. The greatest effect on child survival was found in women who started IFA early in pregnancy and took 150-240 supplements. Universal IFA coverage could improve neonatal and child survival.

Factors associated with non-use of antenatal iron and folic acid supplements among Pakistani women: a cross sectional household survey.

BACKGROUND: World Health Organization recommends a standard daily oral dose of iron and folic acid (IFA) supplements throughout pregnancy to begin as early as possible. The aim of the present study was to determine the prevalence of use of antenatal IFA supplements, and the socio-demographic factors associated with the non-use of antenatal IFA supplements from 14 selected districts in Pakistan. METHODS: Data was derived from a cross sectional household survey conducted in 14 project districts across Pakistan. Trained female field workers conducted interviews with married women of reproductive age from December 2011 to March 2012. Women with the most recent 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 associated with the non-use of antenatal IFA supplements. RESULTS: Of 6,266 women interviewed, 2,400 (38.3%, 95% CI, 36.6%, 40.1%) reported taking IFA supplements during their last pregnancy. Among IFA users, the most common source of supplements was doctors (49.4%) followed by community health workers (40.3%). The mean (±SE) number of supplements used was 76.9 (±51.6), and the mean (±SE) month of pregnancy at initiation of supplementation was 5.3 (±1.7) months. Socio-demographic factors significantly associated with the non-use of antenatal IFA supplements were living in Dera Ghazi Khan district (AdjOR: 1.72), maternal age 45 years and above (AdjOR: 1.97), no maternal education (AdjOR: 2.36), no paternal education (AdjOR: 1.58), belonging to the lowest household wealth index quartile (AdjOR: 1.47), and no use of antenatal care (ANC) services (AdjOR: 13.39). CONCLUSIONS: The coverage of antenatal IFA supplements is very 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 use of ANC services were all significantly associated with non-use of these supplements. These findings highlight the urgent need to develop interventions targeting all pregnant women by improving ANC coverage to increase the use of antenatal IFA supplements in Pakistan.

Perceptions of antenatal iron-folic acid supplements in urban and rural Pakistan: a qualitative study.

BACKGROUND: In Pakistan, 51% of women are anaemic in pregnancy yet only 44% of women use antenatal iron-folic acid (IFA) supplements. Little information exits on the perception and barriers to the use of IFA supplements during pregnancy in Pakistan. The aim of the study was 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: We conducted 10 focus group discussions with mothers, 10 in-depth interviews with currently pregnant women, 6 in-depth interviews with Lady Health Workers and 4 in-depth interviews with doctors providing antenatal care services. The study was conducted in two districts of Pakistan--district Swabi and Islamabad for rural and urban samples, respectively. Data was collected between August and November 2012. RESULTS: The majority of women were aware of the perceived benefits of antenatal IFA supplements. However, the rural women had more limited information about the benefits of IFA supplements than the urban women. 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. CONCLUSION: 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.

Determinants of neonatal mortality in Pakistan: secondary analysis of Pakistan Demographic and Health Survey 2006-07.

BACKGROUND: Globally 7.6 million children died in 2010 before reaching their fifth birthday and 40% of these deaths occur in the neonatal period. Pakistan has the third highest rate of neonatal mortality globally. To implement evidence-based interventions for the reduction of neonatal mortality, it is important to investigate factors associated with neonatal mortality. The aim of the current study was to identify determinants of neonatal mortality in Pakistan. METHODS: Data was derived from the Pakistan Demographic and Health Survey 2006-07. All singleton live births between 2002 and 2006 were selected for the current analyses. Data was analysed by using STATA 13 and adjusted for the cluster sampling design. Multivariate Cox proportional hazard models were performed using step-wise backward elimination procedures to identify the determinants of neonatal mortality. RESULTS: A total of 5,702 singleton live births in the last five years preceding the survey were selected. Multivariate analyses showed that living in Punjab province (Adj HR = 2.10, p = 0.015), belonging to the poorest household wealth index quintile (Adj HR = 1.95, p = 0.035), male infants (Adj HR = 1.57, p = 0.014), first rank baby (Adj HR = 1.59, p = 0.049), smaller than average birth size (Adj HR = 1.61, p = 0.023) and mothers with delivery complications (Adj HR = 1.93, p = 0.001) had significantly higher hazards of neonatal death in Pakistan. CONCLUSIONS: To reduce neonatal mortality, there is a need to implement interventions focusing on antenatal care, effective referral system and retraining of healthcare providers to manage delivery complications and smaller than average birth size babies in resource poor communities of Pakistan.

Incidence of possible serious bacterial infection in young infants in the three high-burden countries of the Democratic Republic of the Congo, Kenya, and Nigeria: A secondary analysis of a large, multi-country, multi-centre clinical trial.

Background: Neonatal infections are a major public health concern worldwide, particularly in low- and middle-income countries, where most of the infection-related deaths in under-five children occur. Sub-Saharan Africa has the highest mortality rates, but there is a lack of data on the incidence of sepsis from this region, hindering efforts to improve child survival. We aimed to determine the incidence of possible serious bacterial infection (PSBI) in young infants in three high-burden countries in Africa. Methods: This is a secondary analysis of data from the African Neonatal Sepsis (AFRINEST) trial, conducted in the Democratic Republic of the Congo (DRC), Kenya, and Nigeria between 15 March 2012 and 15 July 2013. We recorded baseline characteristics, the incidence of PSBI (as defined by the World Health Organization), and the incidence of local infections among infants from 0-59 days after birth. We report descriptive statistics. Results: The incidence of PSBI among 0-59-day-old infants across all three countries was 11.2% (95% confidence interval (CI) = 11.0-11.4). The DRC had the highest incidence of PSBI (19.0%; 95% CI = 18.2-19.8). Likewise, PSBI rates were higher in low birth weight infants (24.5%; 95% CI = 23.1-26.0) and infants born to mothers aged <20 years (14.1%; 95% CI = 13.4-14.8). The incidence of PSBI was higher among infants delivered at home (11.7%; 95% CI = 11.4-12.0). Conclusions: The high burden of PSBI among young infants in DRC, Kenya, and Nigeria demonstrates the importance of addressing PSBI in improving child survival in sub-Saharan Africa to reach the Sustainable Development Goals (SDGs). These data can support government authorities, policymakers, programme implementers, non-governmental organisations, and international partners in reducing preventable under-five deaths. Registration: Australian New Zealand Clinical Trials Registry: ACTRN12610000286044.

Determinants of suboptimal breast-feeding practices in Pakistan.

OBJECTIVE: Exclusive breast-feeding is estimated to reduce infant mortality in low-income countries by up to 13 %. The aim of the present study was to determine the risk factors associated with suboptimal breast-feeding practices in Pakistan. DESIGN: A cross-sectional study using data extracted from the multistage cluster sample survey of the Pakistan Demographic and Health Survey 2006-2007. SETTING: A nationally representative sample of households. SUBJECTS: Last-born alive children aged 0-23 months (total weighted sample size 3103). RESULTS: The prevalences of timely initiation of breast-feeding, bottle-feeding in children aged 0-23 months, exclusive breast-feeding and predominant breast-feeding in infants aged 0-5 months were 27·3 %, 32·1 %, 37·1 % and 18·7 %, respectively. Multivariate analysis indicated that working mothers (OR = 1·48, 95 % CI 1·16, 1·87; P = 0·001) and mothers who delivered by Caesarean section (OR = 1·95, 95 % CI 1·30, 2·90; P = 0·001) had significantly higher odds for no timely initiation of breast-feeding. Mothers from North West Frontier Province were significantly less likely (OR = 0·37, 95 % CI 0·23, 0·59; P < 0·001) not to breast-feed their babies exclusively. Mothers delivered by traditional birth attendants had significantly higher odds to predominantly breast-feed their babies (OR = 1·96, 95 % CI 1·18, 3·24; P = 0·009). The odds of being bottle-fed was significantly higher in infants whose mothers had four or more antenatal clinic visits (OR = 1·93, 95 % CI 1·46, 2·55; P < 0·001) and belonged to the richest wealth quintile (OR = 2·41, 95 % CI 1·62, 3·58; P < 0·001). CONCLUSIONS: The majority of Pakistani mothers have suboptimal breast-feeding practices. To gain the full benefits of breast-feeding for child health and nutrition, there is an urgent need to develop interventions to improve the rates of exclusive breast-feeding.

Cost of treating sick young infants (0-59 days) with Possible Serious Bacterial Infection in resource-constrained outpatient primary care facilities: An insight from implementation research in two districts of Haryana and Uttar Pradesh (India).

Background: Information on the average and incremental costs of implementing alternative strategies for treating young infants 0-59 days old in primary health facilities with signs of possible serious bacterial infection (PSBI) when a referral is not feasible is limited but valuable for policymakers. Methods: Direct activity costs were calculated for outpatient treatment of PSBI and pneumonia in two districts of India: Palwal, Haryana and Lucknow, Uttar Pradesh. These included costs of staff time and consumables for initial assessment, classification, and referrals; recommended treatment of fast breathing (oral amoxicillin for seven days) and PSBI (injection gentamicin and oral amoxicillin for seven days); and daily assessments. Indirect operational costs included staff training; staff time cost for general management, supervision, and coordination; referral transport; and communication. Results: The average cost per young infant treated for recommended and acceptable treatment for PSBI was 16 US dollars (US$) (95% CI = US$15.4-16.3) in 2018-19 and US$18.5 in 2022 (adjusted for inflation) when all direct and indirect operational costs were considered. The average cost of recommended treatment for pneumonia was US$10.1 (95% CI = US$9.7-10.6) or US$11.7 in 2022, per treated young infant. The incremental cost 2018-2019 for supplies, medicines, and operations (excluding staff time costs) per infant treated for PSBI was US$6.1 and US$4.3 and for pneumonia was US$3.5 and US$2.2 in Palwal and Lucknow, respectively. Operation and administrative costs were 25% in Palwal and 12% in Lucknow of the total PSBI treatment costs. The average cost per live birth for treating PSBI in each population was US$5 in Palwal and US$3 in Lucknow. Higher operation costs for social mobilisation activities in Palwal led to the empowerment of families and timely care-seeking. Conclusions: Costs of treatment of PSBI with the recommended regimen in an outpatient setting, when a referral is not feasible, are under US$20 per treated child and must be budgeted to reduce deaths from neonatal sepsis. The investment must be made in activities that lead to successful identification, prompt care seeking, timely initiation of treatment and follow-up.

Simplified antibiotic regimens for young infants with possible serious bacterial infection when the referral is not feasible in the Democratic Republic of the Congo.

INTRODUCTION: Neonates with serious bacterial infections should be treated with injectable antibiotics after hospitalization, which may not be feasible in many low resource settings. In 2015, the World Health Organization (WHO) launched a guideline for the management of young infants (0-59 days old) with possible serious bacterial infection (PSBI) when referral for hospital treatment is not feasible. We evaluated the feasibility of the WHO guideline implementation in the Democratic Republic of the Congo (DRC) to achieve high coverage of PSBI treatment. METHODS: From April 2016 to March 2017, in a longitudinal, descriptive, mixed methods implementation research study, we implemented WHO PSBI guideline for sick young infants (0-59 dyas of age) in the public health programme setting in five health areas of North and South Ubangi Provinces with an overall population of about 60,000. We conducted policy dialogue with national and sub-national level government planners, decision-makers, academics and other stakeholders. We established a Technical Support Unit to provide implementation support. We built the capacity of health workers and managers and ensured the availability of necessary medicines and commodities. We followed infants with PSBI signs up to 14 days. The research team systematically collected data on adherence to treatment and outcomes. RESULTS: We identified 3050 live births and 285 (9.3%) young infants with signs of PSBI in the study area, of whom 256 were treated. Published data have reported 10% PSBI incidence rate in young infants. Therefore, the estimated coverage of treatment was 83.9% (256/305). Another 426 from outside the study catchment area were also identified with PSBI signs by the nurses of a health centre within the study area. Thus, a total of 711 young infants with PSBI were identified, 285 (40%) 7-59 days old infants had fast breathing (pneumonia), 141 (20%) 0-6 days old had fast breathing (severe pneumonia), 233 (33%) had signs of clinical severe infection (CSI), and 52 (7%) had signs of critical illness. Referral to a hospital was advised to 426 (60%) infants with CSI, critical illness or severe pneumonia. The referral was refused by 282 families who accepted simplified antibiotic treatment on an outpatient basis at the health centres. Treatment failure among those who received outpatient treatment occurred in 10/128 (8%) with severe pneumonia, 25/147 (17%) with CSI, including one death, and 2/7 (29%) young infants with a critical illness. Among 285 infants with pneumonia, 257 (90%) received oral amoxicillin treatment, and 8 (3%) failed treatment. Adherence to outpatient treatment was 98% to 100% for various PSBI sub-categories. Among 144 infants treated in a hospital, 8% (1/13) with severe pneumonia, 23% (20/86) with CSI and 40% (18/45) with critical illness died. CONCLUSION: Implementation of the WHO PSBI guideline when a referral was not possible was feasible in our context with high coverage. Without financial and technical input to strengthen the health system at all levels, including the community and the referral level, it may not be possible to achieve and sustain the same high treatment coverage.

A multi-country implementation research initiative to jump-start scale-up of outpatient management of possible serious bacterial infections (PSBI) when a referral is not feasible: Summary findings and implications for programs.

INTRODUCTION: Research on simplified antibiotic regimens for outpatient treatment of 'Possible Serious Bacterial Infection' (PSBI) and the subsequent World Health Organization (WHO) guidelines provide an opportunity to increase treatment coverage. This multi-country implementation research initiative aimed to learn how to implement the WHO guideline in diverse contexts. These experiences have been individually published; this overview paper provides a summary of results and lessons learned across sites. METHODS SUMMARY: A common mixed qualitative and quantitative methods protocol for implementation research was used in eleven sites in the Democratic Republic of Congo (Equateur province), Ethiopia (Tigray and Oromia regions), India (Haryana, Himachal Pradesh, Maharashtra, and Uttar Pradesh states), Malawi (Central Region), Nigeria (Kaduna and Oyo states), and Pakistan (Sindh province). Key steps in implementation research were: i) policy dialogue with the national government and key stakeholders, ii) the establishment of a 'Technical Support Unit' with the research team and district level managers, and iii) development of an implementation strategy and its refinement using an iterative process of implementation, programme learning and evaluation. RESULTS SUMMARY: All sites successfully developed and evaluated an implementation strategy to increase coverage of PSBI treatment. During the study period, a total of 6677 young infants from the study catchment area were identified and treated at health facilities in the study area as inpatients or outpatients among 88179 live births identified. The estimated coverage of PSBI treatment was 75.7% (95% CI 74.8% to 78.6%), assuming a 10% incidence of PSBI among all live births. The treatment coverage was variable, ranging from 53.3% in Lucknow, India to 97.3% in Ibadan, Nigeria. The coverage of inpatient treatment ranged from 1.9% in Zaria, Nigeria, to 33.9% in Tigray, Ethiopia. The outpatient treatment coverage ranged from 30.6% in Pune, India, to 93.6% in Zaria, Nigeria. Overall, the case fatality rate (CFR) was 14.6% (95% CI 11.5% to 18.2%) for 0-59-day old infants with critical illness, 1.9% (95% CI 1.5% to 2.4%) for 0-59-day old infants with clinical severe infection and 0.1% for fast breathing in 7-59 days old. Among infants treated as outpatients, CFR was 13.7% (95% CI 8.7% to 20.2%) for 0-59-day old infants with critical illness, 0.9% (95% CI 0.6% to 1.2%) for 0-59-day old infants with clinical severe infection, and 0.1% for infants 7-59 days old with fast breathing. CONCLUSION: Important lessons on how to conduct each step of implementation research, and the challenges and facilitators for implementation of PSBI management guideline in routine health systems are summarised and discussed. These lessons will be used to introduce and scale-up implementation in relevant Low- and middle-income countries.

Comparison of oral amoxicillin with placebo for the treatment of world health organization-defined nonsevere pneumonia in children aged 2-59 months: a multicenter, double-blind, randomized, placebo-controlled trial in pakistan.

BACKGROUND: world Health Organization (WHO) acute respiratory illness case management guidelines classify children with fast breathing as having pneumonia and recommend treatment with an antibiotic. There is concern that many of these children may not have pneumonia and are receiving antibiotics unnecessarily. This could increase antibiotic resistance in the community. The aim was to compare the clinical outcome at 72 h in children with WHO-defined nonsevere pneumonia when treated with amoxicillin, compared with placebo. METHODS: we performed a double-blind, randomized, equivalence trial in 4 tertiary hospitals in Pakistan. Nine hundred children aged 2-59 months with WHO defined nonsevere pneumonia were randomized to receive either 3 days of oral amoxicillin (45mg/kg/day) or placebo; 873 children completed the study. All children were followed up on days 3, 5, and 14. The primary outcome was therapy failure defined a priori at 72 h. RESULTS: in per-protocol analysis at day 3, 31 (7.2%) of the 431 children in the amoxicillin arm and 37 (8.3%) of the 442 in placebo group had therapy failure. This difference was not statistically significant (odds ratio [OR], .85; 95%CI, .50-1.43; P = .60). The multivariate analysis identified history of difficult breathing (OR, 2.86; 95% CI, 1.29-7.23; P = .027) and temperature >37.5°C 100°F at presentation (OR, 1.99; 95% CI, 1.37-2.90; P = .0001) as risk factors for treatment failure by day 5. CONCLUSION: clinical outcome in children aged 2-59 months with WHO-defined nonsevere pneumonia is not different when treated with an antibiotic or placebo. Similar trials are needed in countries with a high burden of pneumonia to rationalize the use of antibiotics in these communities.

Management of possible serious bacterial infection in young infants where referral is not possible in the context of existing health system structure in Ibadan, South-west Nigeria.

INTRODUCTION: Neonatal infections contribute substantially to infant mortality in Nigeria and globally. Management requires hospitalization, which is not accessible to many in low resource settings. World Health Organization developed a guideline to manage possible serious bacterial infection (PSBI) in young infants up to two months of age when a referral is not feasible. We evaluated the feasibility of implementing this guideline to achieve high coverage of treatment. METHODS: This implementation research was conducted in out-patient settings of eight primary health care centres (PHC) in Lagelu Local Government Area (LGA) of Ibadan, Oyo State, Nigeria. We conducted policy dialogue with the Federal and State officials to adopt the WHO guideline within the existing programme setting and held orientation and sensitization meetings with communities. We established a Technical Support Unit (TSU), built the capacity of health care providers, supervised and mentored them, monitored the quality of services and collected data for management and outcomes of sick young infants with PSBI signs. The Primary Health Care Directorate of the state ministry and the local government led the implementation and provided technical support. The enablers and barriers to implementation were documented. RESULTS: From 1 April 2016 to 31 July 2017 we identified 5278 live births and of these, 1214 had a sign of PSBI. Assuming 30% of births were missed due to temporary migration to maternal homes for delivery care and approximately 45% cases came from outside the catchment area due to free availability of medicines, the treatment coverage was 97.3% (668 cases/6861 expected births) with an expected 10% PSBI prevalence within the first 2 months of life. Of 1214 infants with PSBI, 392 (32%) infants 7-59 days had only fast breathing (pneumonia), 338 (27.8%) infants 0-6 days had only fast breathing (severe pneumonia), 462 (38%) presented with signs of clinical severe infection (CSI) and 22 (1.8%) with signs of critical illness. All but two, 7-59 days old infants with pneumonia were treated with oral amoxicillin without a referral; 80% (312/390) adhered to full treatment; 97.7% (381/390) were cured, and no deaths were reported. Referral to the hospital was not accepted by 87.7% (721/822) families of infants presenting with signs of PSBI needing hospitalization (critical illness 5/22; clinical severe infection; 399/462 and severe pneumonia 317/338). They were treated on an outpatient basis with two days of injectable gentamicin and seven days of oral amoxicillin. Among these 81% (584/721) completed treatment; 97% (700/721) were cured, and three deaths were reported (two with critical illness and one with clinical severe infection). We identified health system gaps including lack of staff motivation and work strikes, medicines stockouts, sub-optimal home visits that affected implementation. CONCLUSIONS: When a referral is not feasible, outpatient treatment for young infants with signs of PSBI is possible within existing programme structures in Nigeria with high coverage and low case fatality. To scale up this intervention successfully, government commitment is needed to strengthen the health system, motivate and train health workers, provide necessary commodities, establish technical support for implementation and strengthen linkages with communities. REGISTRATION: Trial is registered on Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001373369.

Innovative approach for potential scale-up to jump-start simplified management of sick young infants with possible serious bacterial infection when a referral is not feasible: Findings from implementation research.

BACKGROUND: Neonatal bacterial infections are a common cause of death, which can be managed well with inpatient treatment. Unfortunately, many families in low resource settings do not accept referral to a hospital. The World Health Organization (WHO) developed a guideline for management of young infants up to 2 months of age with possible serious bacterial infection (PSBI) when referral is not feasible. Government of Ethiopia with WHO evaluated the feasibility of implementing this guideline to increase coverage of treatment. OBJECTIVE: The objective of this study was to implement a simplified antibiotic regimen (2 days gentamicin injection and 7 days oral amoxicillin) for management of sick young infants with PSBI in a programme setting when referral was not feasible to identify at least 80% of PSBI cases, achieve an overall adequate treatment coverage of at least 80% and document the challenges and opportunities for implementation at the community level in two districts in Tigray, Ethiopia. METHODS: Using implementation research, we applied the PSBI guideline in a programme setting from January 2016 to August 2017 in Raya Alamata and Raya Azebo Woredas (districts) in Southern Tigray, Ethiopia with a population of 260884. Policy dialogue was held with decision-makers, programme implementers and stakeholders at federal, regional and district levels, and a Technical Support Unit (TSU) was established. Health Extension Workers (HEWs) working at the health posts and supervisors working at the health centres were trained in WHO guideline to manage sick young infants when referral was not feasible. Communities were sensitized towards appropriate home care. RESULTS: We identified 854 young infants with any sign of PSBI in the study population of 7857 live births. The expected live births during the study period were 9821. Assuming 10% of neonates will have any sign of PSBI within the first 2 months of life (n = 982), the coverage of appropriate treatment of PSBI cases in our study area was 87% (854/982). Of the 854 sick young infants, 333 (39%) were taken directly to a hospital and 521 (61%) were identified by HEW at health posts. Of the 521 young infants, 27 (5.2%) had signs of critical illness, 181 (34.7%) had signs of clinical severe infection, whereas 313 (60.1%) young infants 7-59 days of age had only fast breathing pneumonia. All young infants with critical illness accepted referral to a hospital, while 117/181 (64.6%) infants with clinical severe infection accepted referral. Families of 64 (35.3%) infants with clinical severe infection refused referral and were treated at the health post with injectable gentamicin for 2 days plus oral amoxicillin for 7 days. All 64 completed recommended gentamicin doses and 63/64 (98%) completed recommended amoxicillin doses. Of 313 young infants, 7-59 days with pneumonia who were treated by the HEWs without referral with oral amoxicillin for 7 days, 310 (99%) received all 14 doses. No deaths were reported among those treated on an outpatient basis at health posts. But 35/477 (7%) deaths occurred among young infants treated at hospital. CONCLUSIONS: When referral is not feasible, young infants with PSBI can be managed appropriately at health posts by HEWs in the existing health system in Ethiopia with high coverage, low treatment failure and a low case fatality rate. Moreover, fast breathing pneumonia in infants 7-59 days of age can be successfully treated at the health post without referral. Relatively higher mortality in sick young infants at the referral level health facilities warrants further investigation.

Implementation research on management of sick young infants with possible serious bacterial infection when referral is not possible in Jimma Zone, Ethiopia: Challenges and solutions.

INTRODUCTION: Of 2.5 million newborn deaths each year, serious neonatal infections are a leading cause of neonatal death for which inpatient treatment is recommended. However, manysick newborns in sub-Saharan Africa and south Asia do not have access to inpatientcare. A World Health Organization (WHO) guideline recommends simplified antibiotic treatment atan outpatient level for young infants up to two months of age with possible serious bacterial infection (PSBI), when referral is not feasible.We implemented this guidelinein Ethiopia to increase coverage of treatment and to learn about potential facilitating factors and barriers for implementation. METHODS: We conducted implementation research in two districts (Tiro Afata and Gera) in Jimma Zone, Ethiopia, to learn about the feasibility of implementing the WHO PSBI guideline within a programme setting using the existing health care structure. We conducted orientation meetings and policy dialogue with key stakeholders and trained health extension workers and health centre staff to identify and manage sick young infants with PSBI signs at a primary health care unit. We established a Technical Support Unit (TSU) to facilitate programme learning, built health workers' capacity and provided support for quality control, monitoring and data collection.We sensitized the community to appropriate care-seeking and supported the health care system in implementation. The research team collected data using structured case recording forms. RESULTS: From September 2016 to August 2017, 6185 live births and 601 sick young infants 0-59 days of age with signs of PSBI were identified. Assuming that 25% of births were missed (total births 7731) and 10% of births had an episode of PSBI in the first two months of life, the coverage of appropriate treatment for PSBI was 77.7% (601/773). Of 601 infants with PSBI, fast breathing only (pneumonia) was recorded in 432 (71.9%) infants 7-59 days of age; signs of clinical severe infection (CSI) in 155 (25.8%) and critical illnessin 14 (2.3%). Of the 432 pneumonia cases who received oral amoxicillin treatment without referral, 419 (97.0%) were successfully treated without any deaths. Of 169 sick young infants with either CSI or critical illness, only 110 were referred to a hospital; 83 did not accept referral advice and received outpatient injectable gentamicin plus oral amoxicillin treatment either at a health post or health centre. Additionally, 59 infants who should have been referred, but were not received injectable gentamicin plus oral amoxicillin outpatient treatment. Of infants with CSI, 129 (82.2%) were successfully treated as outpatients, while two died (1.3%). Of 14 infants with critical illness, the caregivers of five accepted referral to a hospital, and nine were treated with simplified antibiotics on an outpatient basis. Two of 14 (14.3%) infants with critical illness died within 14 days of initial presentation. CONCLUSION: In settings where referral to a hospital is not feasible, young infants with PSBI can be treated on an outpatient basis at either a health post or health centre, which can contribute to saving many lives. Scaling-up will require health system strengthening including community mobilization. REGISTRATION: Trial is registered on Australian New Zealand Clinical Trials registry (ANZCTR) ACTRN12617001373369.

Clinical signs of possible serious infection and associated mortality among young infants presenting at first-level health facilities.

BACKGROUND: The World Health Organization recommends inpatient hospital treatment of young infants up to two months old with any sign of possible serious infection. However, each sign may have a different risk of death. The current study aims to calculate the case fatality ratio for infants with individual or combined signs of possible serious infection, stratified by inpatient or outpatient treatment. METHODS: We analysed data from the African Neonatal Sepsis Trial conducted in five sites in the Democratic Republic of the Congo, Kenya and Nigeria. Trained study nurses classified sick infants as pneumonia (fast breathing in 7-59 days old), severe pneumonia (fast breathing in 0-6 days old), clinical severe infection [severe chest indrawing, high (> = 38°C) or low body temperature (<35.5°C), stopped feeding well, or movement only when stimulated] or critical illness (convulsions, not able to feed at all, or no movement at all), and referred them to a hospital for inpatient treatment. Infants whose caregivers refused referral received outpatient treatment. The case fatality ratio by day 15 was calculated for individual and combined clinical signs and stratified by place of treatment. An infant with signs of clinical severe infection or severe pneumonia was recategorised as having low- (case fatality ratio ≤2%) or moderate- (case fatality ratio >2%) mortality risk. RESULTS: Of 7129 young infants with a possible serious infection, fast breathing (in 7-59 days old) was the most prevalent sign (26%), followed by high body temperature (20%) and severe chest indrawing (19%). Infants with pneumonia had the lowest case fatality ratio (0.2%), followed by severe pneumonia (2.0%), clinical severe infection (2.3%) and critical illness (16.9%). Infants with clinical severe infection had a wide range of case fatality ratios for individual signs (from 0.8% to 11.0%). Infants with pneumonia had similar case fatality ratio for outpatient and inpatient treatment (0.2% vs. 0.3%, p = 0.74). Infants with clinical severe infection or severe pneumonia had a lower case fatality ratio among those who received outpatient treatment compared to inpatient treatment (1.9% vs. 6.5%, p<0.0001). We recategorised infants into low-mortality risk signs (case fatality ratio ≤2%) of clinical severe infection (high body temperature, or severe chest indrawing) or severe pneumonia and moderate-mortality risk signs (case fatality ratio >2%) (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection). We found that both categories had four times lower case fatality ratio when treated as outpatient than inpatient treatment, i.e., 1.0% vs. 4.0% (p<0.0001) and 5.3% vs. 22.4% (p<0.0001), respectively. In contrast, infants with signs of critical illness had nearly two times higher case fatality ratio when treated as outpatient versus inpatient treatment (21.7% vs. 12.1%, p = 0.097). CONCLUSIONS: The mortality risk differs with clinical signs. Young infants with a possible serious infection can be grouped into those with low-mortality risk signs (high body temperature, or severe chest indrawing or severe pneumonia); moderate-mortality risk signs (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection), or high-mortality risk signs (signs of critical illness). New treatment strategies that consider differential mortality risks for the place of treatment and duration of inpatient treatment could be developed and evaluated based on these findings. CLINICAL TRIAL REGISTRATION: This trial was registered with the Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.

Prevalence of clinical signs of possible serious bacterial infection and mortality associated with them from population-based surveillance of young infants from birth to 2 months of age.

BACKGROUND: Community-based data on the prevalence of clinical signs of possible serious bacterial infection (PSBI) and the mortality associated with them are scarce. The aim was to examine the prevalence for each sign of infection and mortality associated with infants in the first two months of life, using community surveillance through community health workers (CHW). METHODS: We used population-based surveillance data of infants up to two months of age from the African Neonatal Sepsis Trial (AFRINEST). In this study, CHWs visited infants up to 10 times during the first two months of life at five sites in three sub-Saharan African countries. CHW assessed the infant for signs of infection (local or systemic) and referred infants who presented with any sign of infection to a health facility. We used a longitudinal analysis to calculate the risk of death associated with the presence of a sign of infection at the time of the visit until the subsequent visit. RESULTS: During the first two months of their life, CHWs visited 84,759 live-born infants at least twice. In 11,089 infants (13.1%), one or more signs of infection were identified, of which 237 (2.1%) died. A sign of infection was detected at 2.1% of total visits. In 52% of visits, infants had one or more sign of systemic infection, while 25% had fast breathing in 7-59 days period and 23% had a local infection. All signs of infection, including multiple signs, were more frequently seen in the first week of life. The risk of mortality was very low (0.2%) for local infections and fast breathing in 7-59 days old, it was low for fast breathing 0-6 days old (0.6%), high body temperature (0.7%) and severe chest indrawing (1.0%), moderate for low body temperature (4.9%) and stopped feeding well/not able to feed at all (5.0%) and high for movement only when stimulated or no movement at all (10%) and multiple signs of systemic infection (15.5%). The risk of death associated with most clinical signs was higher (1.5 to 9 times) in the first week of life than at later age, except for low body temperature (4 times lower) as well as high body temperature (2 times lower). CONCLUSION: Signs of infections are common in the first two months of life. The mortality risk differs with clinical signs and can be grouped as very low (local infections, fast breathing 7-59 days), low (fever, severe chest indrawing and fast breathing 0-6 days), moderate (low body temperature and stopped feeding well/not able to feed at all) and high (for movements only on stimulation or no movements at all and multiple signs of infection). New treatment strategies that consider differential mortality risk could be developed and evaluated based on these findings. CLINICAL TRIAL REGISTRATION: The trial was registered with Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.