Possible Serious Bacterial Infection Research Articles

Effect of community-based newborn care implementation strategies on access to and effective coverage of possible serious bacterial infection (PSBI) treatment for sick young infants during COVID-19 pandemic.

In Ethiopia, neonatal mortality is persistently high. The country has been implementing community-based treatment of possible serious bacterial infection (PSBI) in young infants when referral to a hospital is not feasible since 2012. However, access to and quality of PSBI services remained low and were worsened by COVID-19. From November 2020 to June 2022, we conducted implementation research to mitigate the impact of COVID-19 and improve PSBI management implementation uptake and delivery in two woredas in Ethiopia. In April-May 2021, guided by implementation research frameworks, we conducted formative research to understand the PSBI management implementation challenges, including those due to the COVID-19 pandemic. Through a participatory process engaging stakeholders, we designed adaptive implementation strategies to bridge identified gaps using mechanism mapping to achieve implementation outcomes. Strategies included training and coaching, supportive supervision and mentorship, technical support units, improved supply of essential commodities, and community awareness creation about PSBI and COVID-19. We conducted cross-sectional household surveys in the two woredas before (April 2021) and after the implementation of strategies (June 2022) to measure changes in targeted outcomes. We interviewed 4,262 and 4,082 women who gave live birth 2-14 months before data collection and identified 374 and 264 PSBI cases in April 2021 and June 2022, respectively. The prevalence of PSBI significantly decreased (p-value = 0.018) from 8.7% in April 2021 to 6.4% while the mothers' care-seeking behavior from medical care for their sick newborns increased significantly from 56% to 91% (p-value <0.01). Effective coverage of severely ill young infants that took appropriate antibiotics significantly improved from 33% [95% CI: 25.5-40.7] to 62% [95% CI: 51.0-71.6]. Despite improvements in the uptake of PSBI treatment, persisting challenges at the facility and systems levels impeded optimal PSBI service delivery and uptake, including perceived low quality of service, lack of community trust, and shortage of supplies. The participatory design and implementation of adaptive COVID-19 strategies effectively improved the uptake and delivery of PSBI treatment. Support systems were critical for frontline health workers to deliver PSBI services and create a resilient community health system to provide quality PSBI care during the pandemic. Additional strategies are needed to address persistent gaps, including improvement in client-provider interactions, supply of essential drugs, and increased social mobilization strategies targeting families and communities to further increase uptake.

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

BackgroundEthiopia 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.MethodsFrom 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.ResultsStrategies 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.ConclusionPragmatic 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.

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.

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. 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. 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). 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. Australian New Zealand Clinical Trials Registry: ACTRN12610000286044.

Factors influencing community-facility linkage forcase management ofpossible serious bacterial infections among young infants inKenya.

Despite evidence showing the feasibility and acceptability of implementing the World Health Organization's guidelines on managing possible serious bacterial infection (PSBI) in Kenya, the initial implementation revealed sub-optimal community-facility referrals and follow-up of PSBI cases. This study explores facilitators and barriers of community-facility linkages in implementing PSBI guidelines in Busia and Migori counties, Kenya. We used an exploratory qualitative study design drawing on endline evaluation data from the 'COVID-19: Mitigating Neonatal Mortality' project collected between June and July 2022. Data include case narratives with caregivers of sick young infants (0-59 days old) (18), focus group discussions with community health volunteers (CHVs) (6), and in-depth interviews with facility-based providers (18). Data were analysed using an inductive thematic analysis framework. Between August 2021 and July 2022, CHVs assessed 10 187 newborns, with 1176 (12%) identified with PSBI danger signs and referred to the nearest facility, of which 820 (70%) accepted referral. Analysis revealed several factors facilitating community-facility linkage for PSBI treatment, including CHVs' relationship with community members and facilities, availability of a CHV desk and tools, use of mobile app, training and supportive supervision. However, challenges such as health system-related factors (inadequate providers, stockout of essential commodities and supplies, and lack of transport/ambulance) and individual-related factors (caregivers' refusal to take referrals) hindered community-facility linkage. Addressing common barriers and fostering positive relationships between community health workers and facilities can enhance acceptance and access to PSBI services at the community level. Combining community health workers' efforts with a mobile digital strategy can improve the efficiency of the identification, referral and tracking of PSBI cases in the community and facilitate linkage with primary healthcare facilities.

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).

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. 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. 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. 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.

How long should young infants less than two months of age with moderate-mortality-risk signs of possible serious bacterial infection be hospitalised for? Study protocol for a randomised controlled trial from low- and middle-income countries.

Hospitalisation and a seven-day injectable antibiotics course are recommended by the World Health Organization (WHO) to treat suspected clinical neonatal sepsis / possible serious bacterial infection (PSBI). Some infants presenting with PSBI signs associated with a moderate risk of mortality may only need a two-day hospitalisation followed by outpatient care treatment with oral antibiotics to complete seven days of antibiotics. A multi-centre, individually randomised, open-label trial will be conducted in seven sites in six countries: Bangladesh, Ethiopia, India (two sites), Nigeria, Pakistan and Tanzania. A common protocol will be used with the same study design, including the participants, intervention, comparison, outcomes, quality control, and analysis procedures. 0-59 days old infants presenting with moderate-mortality risk signs (low body temperature (<35.5°C), movement only when stimulated, stopped feeding well) or two or more signs of clinical severe infection (CSI) will be assessed and pre-enrolled. After 48 hours of hospital stay, clinically stable infants with a negative C-reactive protein test will be randomised either to hospital discharge on oral amoxicillin (intervention) or continued hospitalisation (control) arm. The intervention arm will receive oral amoxicillin for five days, whereas the control arm will receive injection gentamicin plus injection ampicillin for five more days plus supportive therapy if needed. We plan to enrol 5250 eligible young infants, 2625 infants in each of the two study arms. An experienced, well-trained independent outcome assessor will visit all enrolled cases on days 4, 8 and 15 after the initiation of treatment to assess the study outcomes in both intervention and control arms. The primary outcome of poor clinical outcome defined as death between randomisation and day 15 of initiation of treatment, deterioration during the 7-day treatment period, or persistence of the presenting sign of CSI at the end of the 7-day treatment period will be compared to assess if an early discharge and outpatient treatment leads to superior or at least non-inferior clinical outcome than continued inpatient treatment. The harmonisation of activities, including methods and processes, will be carried out diligently. Central training will be conducted by the WHO coordinating team, a central data coordination centre to collate all data, standardisation exercises for all clinical signs and internal and external monitoring. All the selected sites have extensive research experience. Through regular online and physical meetings, data-based monitoring, and physical site visits by WHO monitors, quality assurance and harmonisation will be ensured. This trial has been approved by the WHO and local site institutional ethics committees. If the results show that young infants with moderate-mortality risk PSBI signs can be safely and effectively treated on an outpatient basis after a shorter hospital stay, it will reduce the burden on the hospitals, potentially reduce nosocomial hospital infections and increase access to treatment for families with poor access to health facilities. It may also reduce the health system costs (human and materials) and allow the overburdened hospitals to pay more attention to critically ill young infants. In addition, this evidence will contribute to making a case for reviewing the WHO PSBI guideline. International Standard Randomised Controlled Trial Number, ISRCTN16872570.

Care-seeking behaviours of mothers and associated factors for possible serious bacterial infection in young infants during COVID-19 pandemic in Ethiopia: mixed-methods formative research

ObjectivesImplementation research was employed to examine rates and contextual factors associated with mothers’ care-seeking for their sick neonates and identify challenges for community-based possible serious bacterial infection (PSBI) services access...

Measuring implementation outcomes in the context of scaling up possible serious bacterial infection guidelines: Implications for measurement and programs.

Reducing the burden of neonatal sepsis requires timely identification and initiation of suitable antibiotic treatment in primary health care (PHC) settings. Countries are encouraged to adopt simplified antibiotic regimens at the PHC level for treating sick young infants (SYI) with signs of possible serious bacterial infection (PSBI). As countries implement PSBI guidelines, more lessons on effective implementation strategies and outcome measurements are needed. We document pragmatic approaches used to design, measure and report implementation strategies and outcomes while adopting PSBI guidelines in Kenya. We designed implementation research using longitudinal mixed methods embedded in a continuous regular systematic learning and adoption of evidence in the PHC context. We synthesized formative data to co-create with stakeholders, implementation strategies to incorporate PSBI guidelines into routine service delivery for SYIs. This was followed by quarterly monitoring for learning and feedback on the effect of implementation strategies, documented lessons learned and tracked implementation outcomes. We collected endline data to measure the overall effect on service level outcomes. Our findings show that characterizing implementation strategies and linking them with implementation outcomes, helps illustrate the pathway between the implementation process and outcomes. Although we have demonstrated that it is feasible to implement PSBI in PHC, effective investment in continuous capacity strengthening of providers through blended approaches, efficient use of available human resources, and improving the efficiency of service areas for managing SYIs optimizes timely identification and management of SYI. Sustained provision of commodities for management of SYI facilitates increased uptake of services. Strengthening facility-community linkages supports adherence to scheduled visits. Enhancing the caregiver's preparedness during postnatal contacts in the community or facility will facilitate the effective completion of treatment. Careful design, and definition of terms related to the measurement of implementation outcomes and strategies enable ease of interpretation of findings. Using the taxonomy of implementation outcomes help frame the measurement process and provides empirical evidence in a structured way to demonstrate causal relationships between implementation strategies and outcomes. Using this approach, we have illustrated that the implementation of simplified antibiotic regimens for treating SYIs with PSBI in PHC settings is feasible in Kenya.

Strengthening community-facility linkage in implementing the World Health Organization (WHO) case management guideline for Possible Serious Bacterial Infection (PSBI) among sick young infants in western, Kenya

Strengthening community-facility linkage in implementing the World Health Organization (WHO) case management guideline for Possible Serious Bacterial Infection (PSBI) among sick young infants in western, Kenya

Institutionalizing the Management of Sick Young Infants: Kenya's Experience in Revising National Guidelines on Integrated Management of Newborn and Childhood Illnesses.

In 2015, the World Health Organization (WHO) developed guidelines for the management of sick young infants (SYIs) with possible serious bacterial infection (PSBI) where referral is not feasible. The Ponya Mtoto project was designed as an implementation research project to demonstrate how to adopt the WHO PSBI guidelines in the Kenyan context. Between October 2017 and June 2021, Ponya Mtoto was implemented in 4 Kenyan counties with higher infant and newborn mortality rates than the national mean. A total of 48 health facilities stratified by level of services were selected as study sites. The following activities were done to institutionalize the management of SYIs with PSBI where referral is not feasible in Kenya's health system: (1) participating in a cocreation workshop and development of a theory of change; (2) revising the national integrated management of newborn and childhood illnesses guidelines to incorporate the management of PSBI where referral is not feasible; (3) improving availability of essential commodities; (4) strengthening provider confidence in the management of SYIs; (5) strengthening awareness about PSBI services for SYIs at the community level; and (6) harmonizing the national integrated management of newborn and childhood illnesses guidelines to address discrepancies in the content on the management of PSBI. In addition, the project focused on strengthening quality of care for SYIs and using implementation research to track progress in achieving project targets and outcomes. Using an implementation research approach to introduce new WHO guidelines on PSBI where referral is not feasible into Kenya's health care service was critical to fostering engagement of a diverse range of stakeholders, monitoring provider skills and confidence-building, strengthening provision of key commodities for managing SYIs with PSBI, and sustaining community-facility linkages.

Using the Implementation Research Logic Model to design and implement community-based management of possible serious bacterial infection during COVID-19 pandemic in Ethiopia

BackgroundCommunity-based treatment of possible serious bacterial infection (PSBI) in young infants, when referral to a hospital is not possible, can result in high treatment coverage and low case fatality. However, in Ethiopia, the coverage of PSBI treatment remains low, worsened by COVID-19. To understand the challenges of delivery of PSBI treatment and design and test adaptative strategies to mitigate the impact of COVID-19 on neonatal mortality, we did implementation research (IR) employing Implementation Research Logic Model (IRLM). In this paper, we describe IRLM application experiences in designing, implementing, and evaluating strategies to improve community-based treatment of PSBI during the COVID-19 pandemic in Ethiopia.MethodsThis IR was conducted between November 2020-April 2022 at Dembecha and Lume woredas of Amhara and Oromia regions, respectively. We employed narrative reviews, formative assessment and facilitated stakeholder engagement to develop the PSBI treatment IRLM to identify barriers, understand the conceptual linkages among determinants, choose implementation strategies, elicit mechanisms, and link to implementation outcomes. In addition, we used the IRLM to structure the capture of emerging implementation challenges and resulting strategy adaptations throughout implementation.ResultsThis IR identified COVID-19 and multiple pre-existing contextual factors. We designed and implemented implementation strategies to address these challenges. These adaptive strategies were implemented with sufficient strength to maintain the delivery of PSBI services and improve mothers’ care-seeking behavior for their sick young infants.The IRLM offers us a clear process and path to prioritize implementation challenges, choose strategies informed by mechanisms of action, and where the adaptive implementation of community-based management of PSBI would lead to high-implementation fidelity and change in mother behavior to seek care for their sick young infants. The IRLM was also an effective tool for stakeholder engagement, easily explained and used to structure discussion and decision-making during co-design meetings.ConclusionsThe use of the IRLM helps us to specify the conceptual links between the implementation challenges, strategies, mechanisms of action, and outcomes to explore the complex community-based management of PSBI during complex contexts to improve high-fidelity implementation and integration of PSBI treatment in the primary healthcare delivery systems through active engagement of stakeholders.

Barriers to optimal care and strategies to promote safe and optimal management of sick young infants during the COVID-19 pandemic: A multi-country formative research study.

BackgroundEssential health and nutrition services for pregnant women, newborns, and children, particularly in low- and middle-income countries (LMICs), are disrupted by the COVID-19 pandemic. This formative research was conducted at five LMICs to understand the pandemic’s impact on barriers to and mitigation for strategies of care-seeking and managing possible serious bacterial infection (PSBI) in young infants.MethodsWe used a convergent parallel mixed-method design to explore the possible factors influencing PSBI management, barriers, and facilitators at three levels: 1) national and local policy, 2) the health systems, public and private facilities, and 3) community and caregivers. We ascertained trends in service provision and utilisation across pre-lockdown, lockdown, and post-lockdown periods by examining facility records and community health worker registers.ResultsThe pandemic aggravated pre-existing challenges in the identification of young infants with PSBI; care-seeking, referral, and treatment due to several factors at the policy level (limited staff and resource reallocation), health facility level (staff quarantine, sub-optimal treatment in facilities, limited duration of service availability, lack of clear guidelines on the management of sick young infants, and inadequate supplies of protective kits and essential medicines) and at the community level (travel restrictions, lack of transportation, and fear of contracting the infection in hospitals). Care-seeking shifted to faith healers, traditional and informal private sources, or home remedies. However, caregivers were willing to admit their sick young infants to the hospital if advised by doctors. A review of facility records showed low attendance (<50%) of sick young infants in the OPD/emergencies during lockdowns in Bangladesh, India (both sites) and Pakistan, but it gradually increased as lockdowns eased. Stakeholders suggested aspirational and pragmatic mitigation strategies.ConclusionsWe obtained useful insights on health system preparedness during catastrophes and strategies to strengthen services and improve utilisation regarding PSBI management. The current pandemic provides an opportunity for implementing various mitigation strategies at the policy, health system, and community levels to improve preparedness.

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

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. 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. 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. 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.

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.

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. 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. 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. 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. Trial is registered on Australian New Zealand Clinical Trials registry (ANZCTR) ACTRN12617001373369.

Effectiveness of a short-structured training programme on knowledge of healthcare providers and programme managers involved in maternal and child health programmes in Odisha, India: a quality improvement study

ObjectiveTo evaluate the effectiveness of training programme on knowledge related to new interventions proposed under India Newborn Action Plan (INAP) and Integrated Action Plan against Pneumonia and Diarrhoea (IAPPD).DesignQuality improvement...

Lessons from implementation research on community management of Possible Serious Bacterial Infection (PSBI) in young infants (0-59 days), when the referral is not feasible in Palwal district of Haryana, India.

Neonatal sepsis is a major cause of death in India, which needs hospital management but many families cannot access hospitals. The World Health Organization and the Government of India developed a guideline to manage possible serious bacterial infection (PSBI) when a referral is not feasible. We implemented this guideline to achieve high coverage of treatment of PSBI with low mortality. The implementation research study was conducted in over 50 villages of Palwal district, Haryana during August 2017-March 2019 and covered a population of 199143. Policy dialogue with central, state and district health authorities was held before initiation of the study. A baseline assessment of the barriers in the implementation of the PSBI intervention was conducted. The intervention was implemented in the program setting. The research team collected data throughout and also co-participated in the implementation of the intervention for the first six months to identify bottlenecks in the health system and at the community level. RE-AIM framework was utilized to document implementation strategies of PSBI management guideline. Implementation strategies by the district technical support unit (TSU) included: (i) empower mothers and families through social mobilization to improve care-seeking of sick young infants 0-59 days of age, (ii) build capacity through training and build confidence through technical support of health staff at primary health centers (PHC), community health centers (CHC) and sub-centers to manage young infants with PSBI signs and (iii) improve performance of accredited social health activists (ASHAs). A total of 370 young infants with signs of PSBI were identified and managed in 5270 live births. Treatment coverage was 70% assuming that 10% of live births would have PSBI within the first two months of life. Mothers identified 87.6% (324/370) of PSBI cases. PHCs and CHCs became functional and managed 150 (40%) sick young infants with PSBI. Twenty four young infants (7-59days) who had only fast breathing were treated with oral amoxicillin without a referral. Referral to a hospital was refused by 126 (84%); 119 had clinical severe infection (CSI), one 0-6 days old had fast breathing and six had critical illness (CI). Of 119 CSI cases managed on outpatient injection gentamicin and oral amoxicillin, 116 (96.7%) recovered, 55 (45.8%) received all seven gentamicin injections and only one died. All 7-59 day old infants with fast breathing recovered, 23 on outpatient oral amoxicillin treatment; and 19 (79%) received all doses. Of 65 infants managed at either district or tertiary hospital, two (3.1%) died, rest recovered. Private providers managed 155 (41.9%) PSBI cases, all except one recovered, but sub-classification and treatment were unknown. Sub-centers could not be activated to manage PSBI. The study demonstrated resolution of implementation bottlenecks with existing resources, activated PHCs and CHCs to manage CSI and fast breathers (7-59 day old) on an outpatient basis with low mortality when a referral was not feasible. TSU was instrumental in these achievements. We established the effectiveness of oral amoxicillin alone in 7-59 days old fast breathers and recommend a review of the current national policy.

Evaluating the efficacy of a multistrain probiotic supplementation for prevention of neonatal sepsis in 0\u20132-month-old low birth weight infants in India\u2014the \u201cProSPoNS\u201d Study protocol for a phase III, multicentric, randomized, double-blind, placebo-controlled trial

BackgroundProgress has been made in the reduction of under-five mortality in India; however, neonatal mortality is reducing at a slower rate. Efforts are required to bring down neonatal mortality in order to attain the Sustainable Development Goal-3. Prevention of sepsis among the high-risk, vulnerable low birth weight neonates by a newer intervention with probiotic supplementation is promising.MethodsA phase III, multicenter, randomized, double-blind, placebo-controlled study is being conducted at six sites in India. A total of 6144 healthy low birth weight (LBW) infants fulfilling the eligibility criteria would be enrolled within the first week of life, after obtaining written informed consent from the parents of the infant. Randomization in 1:1 ratio, stratified by site, sex, and birth weight, would be done through an interactive web response system (IWRS) using a standard web browser and email service. Vivomixx®, a probiotic containing a mix of 8 strains of bacteria, in a suspension form standardized to deliver 10 billion CFU/ml, or an organoleptically similar placebo would be fed to enrolled infants in a 1-ml/day dose for 30 days. The follow-up of enrolled infants for 60 days would take place as per a pre-specified schedule for recording morbidities and outcome assessments at the six participating sites. Screening for morbidities would be conducted by trained field workers in the community, and sick infants would be referred to designated clinics/hospitals. A physician would examine the referred infants presenting with complaints and clinical signs, and blood samples would be collected from sick infants for diagnosis of neonatal sepsis by performing sepsis screen and blood culture. Appropriate treatment would be provided as per hospital protocol. The study would be implemented as per the MRC guideline for the management of Global Health Trials in accordance with ICH-GCP and Indian Regulatory guidelines. A contract research organization would be engaged for comprehensive monitoring and quality assurance. The final analysis would be conducted in a blinded manner as per the statistical analysis plan (SAP) to estimate the primary outcomes of sepsis, possible serious bacterial infection (PSBI), and secondary outcomes. The codes will be broken after DMC permission. The protocol has been reviewed by the Research Ethics Committee of the Liverpool School of Tropical Medicine (REC-LSTM), from Research Ethics Committees of the six subject recruitment participating sites.DiscussionThis adequately powered and well-designed trial would conclusively answer the question whether probiotics can prevent neonatal sepsis in the high-risk group of low birth weight infants as indicated by a pilot study in 1340 LBW infants, evidence from systematic reviews of hospital-based studies, and a primary study on healthy newborns in Orissa. Results of the study would be generalizable to India and other low–middle-income countries.Trial registrationClinical Trial Registry of India (CTRI) CTRI/2019/05/019197. Registered on 16 May 2019

#70: Comparing Prospectively Identified Etiologic Agents of Neonatal Sepsis in Southwest Ethiopia with WHO Empiric Antibiotic Guidelines

Abstract Background Neonatal sepsis accounts for one third of global neonatal mortality. To improve access to treatment for neonatal sepsis, in 2015 the World Health Organization (WHO) released guidance for outpatient treatment (when referral is not possible or refused) of Possible Serious Bacterial Infection (PSBI).1 However, studies from low and middle-income countries suggest that bacteria causing neonatal infection differ from high-income countries, with higher rates of Staphylococcus aureus, Escherichia coli, and Klebsiella species and high rates of antimicrobial resistance. For this reason, local surveillance is vital to develop local antibiograms and tailor appropriate prescribing. Methods This is an analysis of the first 6 months of a prospective study of young infants admitted to Jimma University Hospital with PSBI. Young infants admitted to Jimma University Hospital with PSBI (defined by WHO danger signs: poor feeding, seizures, fever, lethargy, hypothermia, tachypnea, and increased work of breathing) are being recruited over a 12-month period. Blood cultures are obtained on admission, incubated in the BACTEC system and positive cultures evaluated for antibiotic susceptibility by Kirby-Bauer Disc diffusion. Primary outcomes are culture positivity, organism identification, and rates of antimicrobial resistance. Secondary outcomes include mortality rates and duration of hospital stay. The data included in this analysis were collected from March 21, 2019, through September 20, 2019. Data collection is ongoing. Results In total, 196 infants have been enrolled with a culture positivity rate of 58%. At this time, most frequently identified organisms are Klebsiella spp. (43.4%) and Staphylococcus aureus (12.2%). Gram-negative rods represent 67.8% of the isolates and gram-positive cocci 32.2%. Less than half the isolates (44.4%) were susceptible to either first-line antibiotic (ampicillin and gentamicin). Only 17.4% of the gram-positive cocci were sensitive to oxacillin. In-hospital mortality rates for those with positive cultures approached 15% (compared with 5% for culture negative). The average hospital stay for infants with positive cultures was 13.9 days compared with 10.1 for those with negative cultures. Conclusion Klebsiella spp. are responsible for a plurality of neonatal sepsis admissions at Jimma University Hospital. The organisms responsible for neonatal sepsis in southwest Ethiopia are highly resistant to the WHO recommended first-line antibiotics. It is possible that adoption of the WHO guidelines may be inappropriate in this population, which could be better served by tailoring empiric antibiotics to the identified organisms. Reference 1. World Health Organization. Guideline: Managing possible serious bacterial infection in young infants when a referral is not feasible. (2015) Geneva, CH.

Costs and cost-effectiveness of management of possible serious bacterial infections in young infants in outpatient settings when referral to a hospital was not possible: Results from randomized trials in Africa.

Serious bacterial neonatal infections are a major cause of global neonatal mortality. While hospitalized treatment is recommended, families cannot access inpatient treatment in low resource settings. Two parallel randomized control trials were conducted at five sites in three countries (Democratic Republic of Congo, Kenya, and Nigeria) to compare the effectiveness of treatment with experimental regimens requiring fewer injections with a reference regimen A (injection gentamicin plus injection procaine penicillin both once daily for 7 days) on the outpatient basis provided to young infants (0-59 days) with signs of possible serious bacterial infection (PSBI) when the referral was not feasible. Costs were estimated to quantify the financial implications of scaleup, and cost-effectiveness of these regimens. Direct economic costs (including personnel, drugs and consumable costs) were estimated for identification, prenatal and postnatal visits, assessment, classification, treatment and follow-up. Data on time spent by providers on each activity was collected from 83% of providers. Indirect marginal financial costs were estimated for non-consumables/capital, training, transport, communication, administration and supervision by considering only a share of the total research and health system costs considered important for the program. Total economic costs (direct plus indirect) per young infant treated were estimated based on 39% of young infants enrolled in the trial during 2012 and the number of days each treated during one year. The incremental cost-effectiveness ratio was calculated using treatment failure after one week as the outcome indicator. Experimental regimens were compared to the reference regimen and pairwise comparisons were also made. The average costs of treating a young infant with clinical severe infection (a sub-category of PSBI) in 2012 was lowest with regimen D (injection gentamicin once daily for 2 days plus oral amoxicillin twice daily for 7 days) at US$ 20.9 (95% CI US$ 16.4-25.3) or US$ 32.5 (2018 prices). While all experimental regimens B (injection gentamicin once daily plus oral amoxicillin twice daily, both for 7 days), regimen C (once daily of injection gentamicin injection plus injection procaine penicillin for 2 days, thereafter oral amoxicillin twice daily for 5 days) and regimen D were found to be more cost-effective as compared with the reference regimen A; pairwise comparison showed regimen D was more cost-effective than B or C. For fast breathing, the average cost of treatment with regimen E (oral amoxicillin twice daily for 7 days) at US$ 18.3 (95% CI US$ 13.4-23.3) or US$ 29.0 (2018 prices) was more cost-effective than regimen A. Indirect costs were 32% of the total treatment costs. Scaling up of outpatient treatment for PSBI when the referral is not feasible with fewer injections and oral antibiotics is cost-effective for young infants and can lead to increased access to treatment resulting in potential reductions in neonatal mortality. The trial was registered with Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.

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.

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. 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. 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. 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. 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.