A retrospective review on the histopathological pattern of childhood malignant solid tumors in Ethiopia.

In low- and middle-income countries (LMICs), malignancies remain underreported due to lack of quality data. This study outlines the histopathological pattern of pediatric solid malignancies in children aged 0-15 years at the largest referral hospital in Ethiopia. A total of 432 solid malignancies were evaluated. The most common malignancies were lymphoma (21.8%), retinoblastoma (19.4%), and Wilms tumor (13.9%). Burkitt lymphoma accounted for 2.1%, despite being the most reported pediatric malignancy in sub-Saharan Africa in published literature. Definitive diagnosis could not be made in 7% of cases, related to the lack of confirmatory testing. The study highlights the need for improvement in diagnostic capabilities in LMICs.

Evaluation of distance learning IMCI training program: the case of Tanzania.

BACKGROUND: The standard 11-days IMCI (Integrated Management of Childhood Illness) training course (standard IMCI) has faced barriers such as high cost to scale up. Distance learning IMCI training program was developed as an alternative to the standard IMCI course. This article presents the evaluation results of the implementation of distance learning IMCI training program in Tanzania. METHODS: From December 2012 to end of June 2015, a total of 4806 health care providers (HCP) were trained on distance learning IMCI from 1427 health facilities {HF) in 68 districts in Tanzania. Clinical assessments were done at the end of each course and on follow up visits of health facilities 4 to 6 weeks after training. The results of those assessments are used to compare performance of health care providers trained in distance learning IMCI with those trained in the standard IMCI course. Statistical analysis is done by comparing proportions of those with appropriate performances using four WHO priority performance indicators as well as cost of conducting the courses. In addition, the perspectives of health care providers, IMCI course facilitators, policy makers and partners were gathered using either focussed group discussions or structured questionnaires. RESULTS: Distance learning IMCI allowed clusters of training courses to take place in parallel, allowing rapid expansion of IMCI coverage. Health care providers trained in distance learning IMCI performed equally well as those trained in the standard IMCI course in assessing Main Symptoms, treating sick children and counselling caretakers appropriately. They performed better in assessing Danger Signs. Distance learning IMCI gave a 70% reduction in cost of conducting the training courses. CONCLUSION: Distance learning IMCI is an alternative to scaling up IMCI as it provides an effective option with significant cost reduction in conducting training courses.

A Prospective Study of Causes of Illness and Death in Preterm Infants in Ethiopia: The SIP Study Protocol.

BACKGROUND: With nearly 15 million annual preterm births globally, preterm birth is the most common cause of neonatal death. Forty to 60 % of neonatal deaths are directly or indirectly associated with preterm mortality. As countries aim to meet the Sustainable Development Goals to reduce neonatal mortality, significant reductions in preterm mortality are needed. This study aims to identify the common causes of preterm illness and their contribution to preterm mortality in low-resource settings. This article will describe the methods used to undertake the study. METHODS: This is a prospective, multi-centre, descriptive clinical study. Socio-demographic, obstetric, and maternal factors, and clinical and laboratory findings will be documented. The major causes of preterm mortality will be identified using clinical, laboratory, imaging, and autopsy methods and use the national Ethiopian guidelines on management of preterm infants including required investigations to reach final diagnoses. The study will document the clinical and management protocols followed in these settings. The approach consists of clinical examinations and monitoring, laboratory investigations, and determination of primary and contributory causes of mortality through both clinical means and by post-mortem examinations. An independent panel of experts will validate the primary and contributory causes of mortality. To obtain the estimated sample size of 5000 preterm births, the study will be undertaken in five hospitals in three regions of Ethiopia, which are geographically distributed across the country. All preterm infants who are either born or transferred to these hospitals will be eligible for the study. Three methods (last menstrual period, physical examination using the New Ballard Score, and ultrasound) will be used to determine gestational age. All clinical procedures will be conducted per hospital protocol and informed consent will be taken from parents or caretakers prior to their participation in the study as well as for autopsy if the infant dies. DISCUSSION: This study will determine the major causes of death and illness among hospitalized preterm infants in a low-resource setting. The result will inform policy makers and implementers of areas that can be prioritized in order to contribute to a significant reduction in neonatal mortality.

Incidence of Opportunistic Infections and the Impact of Antiretroviral Therapy Among HIV-Infected Adults in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis.

BACKGROUND: To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral therapy (ART) on incidence of key opportunistic infections (OIs) in human immunodeficiency virus (HIV)-infected adults in low- and middle-income countries (LMICs). METHODS: Eligible studies describing the cumulative incidence of OIs and proportion on ART from 1990 to November 2013 were identified using multiple databases. Summary incident risks for the ART-naive period, and during and after the first year of ART, were calculated using random-effects meta-analyses. Summary estimates from ART subgroups were compared using meta-regression. The number of OI cases and associated costs averted if ART was initiated at a CD4 count ≥200 cells/µL were estimated using Joint United Nations Programme on HIV/AIDS (UNAIDS) country estimates and global average OI treatment cost per case. RESULTS: We identified 7965 citations, and included 126 studies describing 491 608 HIV-infected persons. In ART-naive patients, summary risk was highest (>5%) for oral candidiasis, tuberculosis, herpes zoster, and bacterial pneumonia. The reduction in incidence was greatest for all OIs during the first 12 months of ART (range, 57%-91%) except for tuberculosis, and was largest for oral candidiasis, Pneumocystis pneumonia, and toxoplasmosis. Earlier ART was estimated to have averted 857 828 cases in 2013 (95% confidence interval [CI], 828 032-874 853), with cost savings of $46.7 million (95% CI, $43.8-$49.4 million). CONCLUSIONS: There was a major reduction in risk for most OIs with ART use in LMICs, with the greatest effect seen in the first year of treatment. ART has resulted in substantial cost savings from OIs averted.

Incidence and Prevalence of Opportunistic and Other Infections and the Impact of Antiretroviral Therapy Among HIV-infected Children in Low- and Middle-income Countries: A Systematic Review and Meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to evaluate the incidence and prevalence of 14 opportunistic infections (OIs) and other infections as well as the impact of antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected children (aged <18 years) in low- and middle-income countries (LMICs), to understand regional burden of disease, and inform delivery of HIV services. METHODS: Eligible studies described the incidence of OIs and other infections in ART-naive and -exposed children from January 1990 to November 2013, using Medline, Global Health, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Knowledge, and Literatura Latino Americana em Ciências da Saúde databases. Summary incident risk (IR) and prevalent risk for each OI in ART-naive and ART-exposed children were calculated, and unadjusted odds ratios calculated for impact of ART. The number of OI cases and associated costs averted were estimated using the AIDS impact model. RESULTS: We identified 4542 citations, and 88 studies were included, comprising 55 679 HIV-infected children. Bacterial pneumonia and tuberculosis were the most common incident and prevalent infections in both ART-naive and ART-exposed children. There was a significant reduction in IR with ART for the majority of OIs. There was a smaller impact on bacterial sepsis and pneumonia, and an increase observed for varicella zoster. ART initiation based on 2010 World Health Organization guidelines criteria for ART initiation in children was estimated to potentially avert >161 000 OIs (2013 UNAIDS data) with estimated cost savings of at least US$17 million per year. CONCLUSIONS: There is a decrease in the risk of most OIs with ART use in HIV-infected children in LMICs, and estimated large potential cost savings in OIs averted with ART use, although there are greater uncertainties in pediatric data compared with that of adults.

Childhood diarrhoeal deaths in seven low- and middle-income countries.

OBJECTIVE: To investigate the clinical characteristics of children who died from diarrhoea in low- and middle-income countries, such as the duration of diarrhoea, comorbid conditions, care-seeking behaviour and oral rehydration therapy use. METHODS: The study included verbal autopsy data on children who died from diarrhoea between 2000 and 2012 at seven sites in Bangladesh, Ethiopia, Ghana, India, Pakistan, Uganda and the United Republic of Tanzania, respectively. Data came from demographic surveillance sites, randomized trials and an extended Demographic and Health Survey. The type of diarrhoea was classified as acute watery, acute bloody or persistent and risk factors were identified. Deaths in children aged 1 to 11 months and 1 to 4 years were analysed separately. FINDINGS: The proportion of childhood deaths due to diarrhoea varied considerably across the seven sites from less than 3% to 30%. Among children aged 1-4 years, acute watery diarrhoea accounted for 31-69% of diarrhoeal deaths, acute bloody diarrhoea for 12-28%, and persistent diarrhoea for 12-56%. Among infants aged 1-11 months, persistent diarrhoea accounted for over 30% of diarrhoeal deaths in Ethiopia, India, Pakistan, Uganda and the United Republic of Tanzania. At most sites, more than 40% of children who died from persistent diarrhoea were malnourished. CONCLUSION: Persistent diarrhoea remains an important cause of diarrhoeal death in young children in low- and middle-income countries. Research is needed on the public health burden of persistent diarrhoea and current treatment practices to understand why children are still dying from the condition.

Optimisation of antiretroviral therapy in HIV-infected children under 3 years of age.

BACKGROUND: In the absence of antiretroviral therapy (ART), over 50% of HIV-infected infants progress to AIDS and death by 2 years of age. However, there are challenges to initiation of ART in early life, including the possibility of drug resistance in the context of prevention of mother-to-child transmission (PMTCT) programs, a paucity of drug choices , uncertain dosing for some medications and long-term toxicities. Key management decisions include when to start ART, what regimen to start, and whether and when to substitute drugs or interrupt therapy. This review, an update of a previous review, aims to summarize the currently available evidence on this topic and inform the ART management in HIV-infected children less than 3 years of age. OBJECTIVES: To evaluate 1) when to start ART in young children (less than 3 years); 2) what ART to start with, comparing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI)-based regimens; and 3) whether alternative strategies should be used to optimize antiretroviral treatment in this population: induction (initiation with 4 drugs rather than 3 drugs) followed by maintenance ART, interruption of ART and substitution of PI with NNRTI drugs once virological suppression is achieved on a PI-based regimen. SEARCH METHODS: Search methodsWe searched for published studies in the Cochrane HIV/AIDS Review Group Trials Register, The Cochrane Library, Pubmed, EMBASE and CENTRAL. We screened abstracts from relevant conference proceedings and searched for unpublished and ongoing trials in clinical trial registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform). SELECTION CRITERIA: We identified RCTs that recruited perinatally HIV-infected children under 3 years of age without restriction of setting. We rejected trials that did not include children less than 3 years of age, did not provide stratified outcomes for those less than 3 years or did not evaluate either timing of ART initiation, choice of drug regimen or treatment switch/interruption strategy. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied study selection criteria, assessed study quality and extracted data. Effects were assessed using the hazard ratio (HR) for time-to-event outcomes, relative risk for dichotomous outcomes and weighted mean difference for continuous outcomes. MAIN RESULTS: A search of the databases identified a total of 735 unique, previously unreviewed studies, of which 731 were excluded to leave 4 new studies to incorporate into the review. Four additional studies were identified in conference proceedings, for a total of 8 studies addressing when to start treatment (n=2), what to start (n=3), whether to substitute lopinavir/ritonavir (LPV/r) with nevirapine (NVP) (n=1), whether to use an induction-maintenance ART strategy (n=1) and whether to interrupt treatment (n=1).Treatment initiation in asymptomatic infants with good immunological status was associated with a 75% reduction (HR=0.25; 95%CI 0.12-0.51; p=0.0002) in mortality or disease progression in the one trial with sufficient power to address this question. In a smaller pilot trial, median CD4 cell count was not significantly different between early and deferred treatment groups 12 months after ART.Regardless of previous exposure to nevirapine for PMTCT, the hazard for treatment failure at 24 weeks was 1.79 (95%CI 1.33, 2.41) times higher in children starting ART with a NVP-based regimen compared to those starting with a LPV/r-based regimen (p=0.0001) with no clear difference in the effect observed for children younger or older than 1 year. The hazard for virological failure at 24 weeks was overall 1.84 (95%CI 1.29, 2.63) times higher for children starting ART with a NVP-based regimen compared to those starting with a LPV/r-based regimen (p=0.0008) with a larger difference in time to virological failure (or death) between the NVP and LPV/r-based regimens when ART was initiated in the first year of life.Infants starting a LPV/r regimen and achieving sustained virological suppression who then substituted LPV/r with NVP after median 9 months on LPV/r were less likely to develop virological failure (defined as at least one VL greater than 50 copies/mL) compared with infants who started and stayed on LPV/r (HR=0.62, 95%CI 0.41, 0.92, p=0.02). However the hazard for confirmed failure at a higher viral load (>1000 copies/mL) was greater among children who switched to NVP compared to those who remained on LPV/r (HR=10.19, 95% CI 2.36, 43.94, p=0.002).Children undergoing an induction-maintenance ART approach with a 4-drug NNRTI-based regimen for 36 weeks, followed by 3-drug ART, had significantly greater CD4 rise than children receiving a standard 3-drug NNRTI-based ART at 36 weeks (mean difference 1.70 [95%CI 0.61, 2.79] p=0.002) and significantly better viral load response at 24 weeks (OR 1.99 [95%CI 1.09, 3.62] p=0.02). However, the immunological and virological benefits were short-term.The one trial of treatment interruption that compared children initiating continuous ART from infancy with children interrupting ART was terminated early because the duration of treatment interruption was less than 3 months in most infants. Children interrupting treatment had similar growth and occurrence of serious adverse events as those in the continuous arm. AUTHORS' CONCLUSIONS: ART initiation in asymptomatic children under 1 year of age reduces morbidity and mortality, but it remains unclear whether there are clinical benefits to starting ART in asymptomatic children diagnosed with HIV infection between 1-3 years.The available evidence shows that a LPV/r-based first-line regimen is more efficacious than a NVP-based regimen, regardless of PMTCT exposure status. New formulations of LPV/r are urgently required to enable new WHO recommendations to be implemented. An alternative approach to long-term LPV/r is substituting LPV/r with NVP once virological suppression is achieved. This strategy looked promising in the one trial undertaken, but may be difficult to implement in the absence of routine viral load testing.A 4-drug induction-maintenance approach showed short-term virological and immunological benefits during the induction phase but, in the absence of sustained benefits, is not recommended as a routine treatment strategy. Treatment interruption following early ART initiation in infancy was challenging for children who were severely immunocompromised in the context of poor clinical immunological condition at ART initiation due to the short duration of interruption, and is therefore not practical in ART treatment programmes where close monitoring is not feasible.

Prevalence and causes of ocular disorders and visual impairment among preterm children in Ethiopia.

OBJECTIVE: The aim of this study was to determine the prevalence, causes of ocular disorders and visual impairment among preterm children previously admitted to neonatal intensive care units in Addis Ababa, Ethiopia. METHODS AND ANALYSIS: A prospective screening survey was conducted from February to June 2019 at the paediatric eye clinic of Menelik II Hospital. Children who were preterm at birth and who attended the eye clinic were included in the study. Data on demographic and neonatal characteristics, neonatal and maternal comorbidities and ocular disorders were collected. OR and univariate analysis were used to identify predictors of ocular diseases and visual impairment. RESULTS: There were 222 children included in the study with a mean age at presentation of 2.62 years (range 2.08-6.38 years), mean gestational age 34.11 weeks (range 30-36) weeks and mean birth weight 1941.72 g (range 953-3500 g). Nearly two-thirds had ocular disorders with refractive error (51.8%), strabismus (11.3%) and a history of retinopathy of prematurity (ROP) (7.2%) being more common. One-fourth of the children had visual impairment, and the prevalence of amblyopia was 40.1%. Uncorrected refractive errors, strabismus and ROP were causes for visual impairment. CONCLUSION: Visual impairment and amblyopia are common in Ethiopia. There is a need to develop a screening protocol for ocular disorders for preterm children to enhance early detection and prevention of childhood visual impairment.

Challenges and opportunities in neonatal sepsis management: insights from a survey among clinicians in 25 Sub-Saharan African countries.

BACKGROUND: Neonatal sepsis (NS) is a global health issue, particularly in Sub-Saharan Africa, where it accounts for a substantial portion of neonatal morbimortality. This multicountry survey aimed to elucidate current practices, challenges and case definitions in managing NS among clinicians in Sub-Saharan Africa. METHODS: The survey targeted physicians and medical practitioners working in neonatal care who participated in a Self-Administered Web Questionnaire. The main objective was to understand NS and infection case definitions and management from the clinician's point of view and to identify challenges and opportunities in sepsis management. Participants were queried on demographics, definitions and diagnostic criteria, treatment approaches, and infection prevention and control (IPC) measures. A total of 136 participants from 93 healthcare structures responded, providing valuable insights into NS management practices. RESULTS: From May to July 2022 across 21 Sub-Saharan African countries, 136 neonatal clinicians with an average from 93 structures with on average 10-year experience took the survey. NS ranked highest among prevalent neonatal conditions. Diagnostic case definitions between sepsis and infection were attributed to clinical signs, anamnesis, C reactive protein, white blood cll count and blood cultures with no statistically significant differences. Early-onset sepsis was defined within 72 hours by 48%, while late-onset varied. Antibiotics were likely on admission (86.4%) and during the stay (82.2%). Treatment abandonment was reported unlikely. The preferred antibiotic regimen for early-onset sepsis was intravenous amoxicillin (or ampicillin), gentamycin and cefotaxime. Blood culture availability and IPC protocols were reported as limited, particularly concerning patient environment, pharmacy protocols and clean-dirty circuits. CONCLUSIONS: This NS survey emphasises clinicians' challenges due to limited access to diagnostic tools and raises concerns about antimicrobial overexposure. IPC also seem limited, according to participants. Addressing these challenges can enhance diagnostic practices, antibiotic stewardship and infection control in the region.

When to start antiretroviral therapy in children aged 2-5 years: a collaborative causal modelling analysis of cohort studies from southern Africa.

BACKGROUND: There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2-5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2-5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4 percentage (CD4%) <25%. METHODS AND FINDINGS: ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm(3) (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1-6.5) (no ART) to 2.1% (95% CI: 1.3%-3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%-3.5%) and 2.2% (95% CI: 1.4%-3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data. CONCLUSIONS: The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm(3) or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors' Summary.

Optimal time for initiating antiretroviral therapy (ART) in HIV-infected, treatment-naive children aged 2 to 5 years old.

BACKGROUND: The use of combination antiretroviral therapy (cART) comprising three antiretroviral medications from at least two classes of drugs is the current standard treatment for HIV infection in adults and children. Current World Health Organization (WHO) guidelines for antiretroviral therapy recommend early treatment regardless of immunologic thresholds or the clinical condition for all infants (less than one years of age) and children under the age of two years. For children aged two to five years current WHO guidelines recommend (based on low quality evidence) that clinical and immunological thresholds be used to identify those who need to start cART (advanced clinical stage or CD4 counts ≤ 750 cells/mm(3) or per cent CD4 ≤ 25%). This Cochrane review will inform the current available evidence regarding the optimal time for treatment initiation in children aged two to five years with the goal of informing the revision of WHO 2013 recommendations on when to initiate cART in children. OBJECTIVES: To assess the evidence for the optimal time to initiate cART in treatment-naive, HIV-infected children aged 2 to 5 years. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the AEGIS conference database, specific relevant conferences, www.clinicaltrials.gov, the World Health Organization International Clinical Trials Registry platform and reference lists of articles. The date of the most recent search was 30 September 2012. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared immediate with deferred initiation of cART, and prospective cohort studies which followed children from enrolment to start of cART and on cART. DATA COLLECTION AND ANALYSIS: Two review authors considered studies for inclusion in the review, assessed the risk of bias, and extracted data on the primary outcome of death from all causes and several secondary outcomes, including incidence of CDC category C and B clinical events and per cent CD4 cells (CD4%) at study end. For RCTs we calculated relative risks (RR) or mean differences with 95% confidence intervals (95% CI). For cohort data, we extracted relative risks with 95% CI from adjusted analyses. We combined results from RCTs using a random effects model and examined statistical heterogeneity. MAIN RESULTS: Two RCTs in HIV-positive children aged 1 to 12 years were identified. One trial was the pilot study for the larger second trial and both compared initiation of cART regardless of clinical-immunological conditions with deferred initiation until per cent CD4 dropped to <15%. The two trials were conducted in Thailand, and Thailand and Cambodia, respectively. Unpublished analyses of the 122 children enrolled at ages 2 to 5 years were included in this review. There was one death in the immediate cART group and no deaths in the deferred group (RR 2.9; 95% CI 0.12 to 68.9). In the subgroup analysis of children aged 24 to 59 months, there was one CDC C event in each group (RR 0.96; 95% CI 0.06 to 14.87) and 8 and 11 CDC B events in the immediate and deferred groups respectively (RR 0.95; 95% CI 0.24 to 3.73). In this subgroup, the mean difference in CD4 per cent at study end was 5.9% (95% CI 2.7 to 9.1). One cohort study from South Africa, which compared the effect of delaying cART for up to 60 days in 573 HIV-positive children starting tuberculosis treatment (median age 3.5 years), was also included. The adjusted hazard ratios for the effect on mortality of delaying ART for more than 60 days was 1.32 (95% CI 0.55 to 3.16). AUTHORS' CONCLUSIONS: This systematic review shows that there is insufficient evidence from clinical trials in support of either early or CD4-guided initiation of ART in HIV-infected children aged 2 to 5 years. Programmatic issues such as the retention in care of children in ART programmes in resource-limited settings will need to be considered when formulating WHO 2013 recommendations.  

A prospective observational study of nurses performing minimally invasive tissue sampling of brain, liver, and lung tissues among deceased neonates and stillbirths in Ethiopia.

Background: With a neonatal mortality rate of 33 per 1,000 live births in 2019, Ethiopia is striving to attain the Sustainable Development Goal target of 12 deaths per 1,000 live births by 2030. A better understanding of the major causes of neonatal mortality is needed to effectively design and implement interventions to achieve this goal. Minimally Invasive Tissue Sampling (MITS), an alternative to conventional autopsy, requires fewer resources and through task-shifting of sample collection from pathologists to nurses, has the potential to support the expansion of pathology-based post-mortem examination and improve mortality data. This paper evaluates the accuracy and adequacy of MITS performed by nurses at a tertiary and general hospital and in the home of the deceased. Methods: Nurses in a tertiary and general hospital in Ethiopia were trained in MITS sample collection on neonatal deaths and stillbirths using standardized protocols. MITS sample collection was performed by both pathologists and nurses in the tertiary hospital and by nurses in the general hospital and home-setting. Agreement in the performance of MITS between pathologists and nurses was calculated for samples collected at the tertiary hospital. Samples collected by nurses in the general hospital and home-setting were evaluated for technical adequacy using preestablished criteria. Results: One hundred thirty-nine MITS were done: 125 in hospitals and 14 inside homes. There was a perfect or almost perfect agreement between the pathologists and the nurses in the tertiary hospital using Gwet's agreement interpretation criteria. The adequacy of MITS samples collected by nurses in the general hospital was more than 72% when compared to the preset criteria. The adequacy of the MITS sampling yield ranged from 87% to 91% on liveborn neonatal deaths and 76% for the liver, right and left lungs and 55% for brain tissues in stillbirths. Conclusions: This study demonstrated that task-shifting MITS sample collection to nurses can be achieved with comparable accuracy and adequacy as pathologists. Our study showed that with standardized training and supportive supervision MITS sample collection can be conducted by nurses in a tertiary, general hospital and, at the home of the deceased. Future studies should validate and expand on this work by evaluating task-shifting of MITS sample collection to nurses within community settings and with larger sample sizes.

2.5 Million Annual Deaths-Are Neonates in Low- and Middle-Income Countries Too Small to Be Seen? A Bottom-Up Overview on Neonatal Morbi-Mortality.

(1) Background: Every year, 2.5 million neonates die, mostly in low- and middle-income countries (LMIC), in total disregard of their fundamental human rights. Many of these deaths are preventable. For decades, the leading causes of neonatal mortality (prematurity, perinatal hypoxia, and infection) have been known, so why does neonatal mortality fail to diminish effectively? A bottom-up understanding of neonatal morbi-mortality and neonatal rights is essential to achieve adequate progress, and so is increased visibility. (2) Methods: We performed an overview on the leading causes of neonatal morbi-mortality and analyzed the key interventions to reduce it with a bottom-up approach: from the clinician in the field to the policy maker. (3) Results and Conclusions: Overall, more than half of neonatal deaths in LMIC are avoidable through established and well-known cost-effective interventions, good quality antenatal and intrapartum care, neonatal resuscitation, thermal care, nasal CPAP, infection control and prevention, and antibiotic stewardship. Implementing these requires education and training, particularly at the bottom of the healthcare pyramid, and advocacy at the highest levels of government for health policies supporting better newborn care. Moreover, to plan and follow interventions, better-quality data are paramount. For healthcare developments and improvement, neonates must be acknowledged as humans entitled to rights and freedoms, as stipulated by international law. Most importantly, they deserve more respectful care.

Global challenges with scale-up of the integrated management of childhood illness strategy: results of a multi-country survey.

BACKGROUND: The Integrated Management of Childhood Illness Strategy (IMCI), developed by WHO/UNICEF, aims to contribute to reducing childhood morbidity and mortality (MDG4) in resource-limited settings. Since 1996 more than 100 countries have adopted IMCI. IMCI case management training (ICMT) is one of three IMCI components and training is usually residential over 11 consecutive days. Follow-up after ICMT is an essential part of training. We describe the barriers to rapid acceleration of ICMT and review country perspectives on how to address these barriers. METHODS: A multi-country exploratory cross-sectional questionnaire survey of in-service ICMT approaches, using quantitative and qualitative methods, was conducted in 2006-7: 27 countries were purposively selected from all six WHO regions. Data for this paper are from three questionnaires (QA, QB and QC), distributed to selected national focal IMCI persons/programme officers, course directors/facilitators and IMCI trainees respectively. QC only gathered data on experiences with IMCI follow-up. RESULTS: 33 QA, 163 QB and 272 QC were received. The commonest challenges to ICMT scale-up relate to funding (high cost and long duration of the residential ICMT), poor literacy of health workers, differing opinions about the role of IMCI in improving child health, lack of political support, frequent changes in staff or rules at Ministries of Health and lack of skilled facilitators. Countries addressed these challenges in several ways including increased advocacy, developing strategic linkages with other priorities, intensifying pre-service training, re-distribution of funds and shortening course duration. The commonest challenges to follow-up after ICMT were lack of funding (93.1% of respondents), inadequate funds for travelling or planning (75.9% and 44.8% respectively), lack of gas for travelling (41.4%), inadequately trained or few supervisors (41.4%) and inadequate job aids for follow-up (27.6%). Countries addressed these by piggy backing IMCI follow-up with routine supervisory visits. CONCLUSIONS: Financial challenges to ICMT scale-up and follow-up after training are common. As IMCI is accepted globally as one of the key strategies to meet MDG4 several steps need to be taken to facilitate rapid acceleration of ICMT, including reviewing core competencies followed by competency-driven shortened training duration or 'on the job' training, 'distance learning' or training using mobile phones. Linkages with other 'better-funded' programmes e.g. HIV or malaria need to be improved. Routine Primary Health Care (PHC) supervision needs to include follow-up after ICMT.

Antenatal Steroid Utilization in Ethiopia.

Background. Administration of antenatal corticosteroids to pregnant mothers is one of the most effective interventions to decrease preterm neonatal mortality. In this study we assessed antenatal steroid utilization by the mother and its effect on preterm babies. Method. Two years prospective, multicenter, observational study was conducted in selected hospitals of Ethiopia. Significance of the study outcomes was tested by chi-square and binary logistic regression. Result. Out of 4919 participants, 1575 preterm babies whose gestational ages were below 35 weeks were included in the study. Use of antenatal dexamethasone was 37.5% among study participants. The risk of early onset neonatal sepsis 235 (40.4%) was higher in preterm babies whose mother took antenatal dexamethasone (P-value .002) than those who did not. Conclusion. Antenatal dexamethasone use in our study was comparable with other low and middle-income countries. Risk of early onset neonatal sepsis was higher among infants whose mother took antenatal dexamethasone.

Factors Associated with the Death of Preterm Babies Admitted to Neonatal Intensive Care Units in Ethiopia: A Prospective, Cross-sectional, and Observational Study.

Aim. To determine the risk factors for death among preterm neonates. Methods and materials. The data set used was derived from a prospective, multi-center, observational clinical study conducted in 5 tertiary hospitals in Ethiopia from July, 2016 to May, 2018. Subjects were infants admitted into neonatal intensive care unit. Results. Risk factors were determined using statistical model developed for this study. The mean gestational age was 32.87 (SD ± 2.42) weeks with a range of 20 to 36 weeks. There were 2667 (70.69%) survivors and 1106 (29.31%) deaths. The significant risk factors for preterm death were low gestational age, low birth weight, being female, feeding problem, no antenatal care visits and vaginal delivery among mothers with higher educational level. Conclusions. The study identified several risk factors for death among preterm neonates. Most of the risk factors are preventable. Thus, it is important to address neonatal and maternal factors identified in this study through appropriate ANC and optimum infant medical care and feeding practices to decrease the high rate of preterm death.

Disparity in Birth Size of Ethiopian Preterm Infants in Comparison to International INTERGROWTH-21st Data.

Background. Patterns of fetal growth are largely influenced by environmental, nutritional, and socioeconomic factors more than differences in populations. The aim of this study was to assess anthropometric measurements of Ethiopian preterm infants at birth and compare the results with the international INTERGROWTH-21st data. Patients and methods. We analyzed anthropometric data on live-born singleton preterm infants enrolled in a hospital-based multicenter study of illness in preterm infants (SIP). Eligible newborns with gestational age of 28-36 weeks were included. Gestational age (GA) and sex-specific mean and standard deviations (SD), 10th, 50th, 90th, centile values for birth weight, length and head circumference (HC) were calculated and compared with INTERGROWTH-21st data. Result. A total of 2763 preterm infants were included in the study, 54% were male. The prevalence of small for GA (SGA) (<10th percentile) and large for GA (LGA) (>90th percentile) were 10.8% and 9.9%, respectively. In all 3 parameters, the mean values of boys were higher than of girls. Birth weight centiles were comparable to international averages at lower GA, then after GA of 32 weeks the 10th, 50th, and 90th centile values were 100-500 g less than the international averages. The head circumference centiles were mostly comparable, and the 90th centile values were greater than the international averages across the GA and in both sexes. Conclusion. The infants' birth weights were smaller at higher GA, which may indicate maternal undernutrition in the third trimester of pregnancy. Strengthening antenatal nutrition counseling and providing nutrition supplementation might improve the birth weight.

Incidence and associated factors of extrauterine growth restriction (EUGR) in preterm infants, a cross-sectional study in selected NICUs in Ethiopia.

BACKGROUND: Preterm infants have high risk of developing growth restriction and long-term complications. Enteral feeding is often delayed in neonatal intensive care units (NICUs) for the fear of feeding intolerance and the associated necrotising enterocolitis, and recent advances in nutritional support are unavailable in low-income countries. OBJECTIVE: The aim of this study was to assess the incidence and associated factors of extrauterine growth restriction (EUGR) among preterm infants in selected NICUs in Ethiopia. METHOD: This was a cross-sectional study involving a subgroup analysis of preterm infants admitted to hospitals, from a multicentre descriptive study of cause of illness and death in preterm infants in Ethiopia, conducted from 2016 to 2018. EUGR was defined as weight at discharge Z-scores <-1.29 for corrected age. Clinical profiles of the infants were analysed for associated factors. SPSS V.23 software was used for analysis with a significance level of 5% and 95% CI. RESULT: From 436 preterm infants included in the analysis, 223 (51%) were male, 224 (51.4%) very low birth weight (VLBW) and 185 (42.4%) small for gestational age (SGA). The mean (SD) of weight for corrected age Z-score at the time of discharge was -2.5 (1.1). The incidence of EUGR was 86.2%. Infants who were SGA, VLBW and longer hospital stay over 21 days had increased risk of growth restriction (p-value<0.01). SGA infants had a 15-fold higher risk of developing EUGR at the time of discharge from hospital than those who were appropriate or large for gestational age (OR (95% CI)=15.2 (4.6 to 50.1). CONCLUSION: The majority of the infants had EUGR at the time of discharge from the hospital, which indicates suboptimal nutrition. Revision of national guidelines for preterm infants feeding and improvement in clinical practice is highly required.

Comparison of neonatal outcomes of small for gestational age and appropriate for gestational age preterm infants born at 28-36 weeks of gestation: a multicentre study in Ethiopia.

PURPOSE: The aim of this study was to assess morbidity and mortality pattern of small for gestational age (SGA) preterm infants in comparison to appropriate for gestational age (AGA) preterm infants of similar gestational age. METHOD: We compared neonatal outcomes of 1336, 1:1 matched, singleton SGA and AGA preterm infants based on their gestational age using data from the study 'Causes of Illness and Death of Preterm Infants in Ethiopia (SIP)'. Data were analysed using SPSS V.23. ORs and 95% CIs and χ2 tests were done, p value of <0.05 was considered statistically significant. RESULT: The majority of the infants (1194, 89%) were moderate to late preterm (32-36 weeks of gestation), 763 (57%) were females. Male preterm infants had higher risk of being SGA than female infants (p<0.001). SGA infants had increased risk of hypoglycaemic (OR and 95% CI 1.6 (1.2 to 2.0), necrotising enterocolitis (NEC) 2.3 (1.2 to 4.1), polycythaemia 3.0 (1.6 to 5.4), late-onset neonatal sepsis (LOS) 3.6 (1.1 to 10.9)) and prolonged hospitalisation 2.9 (2.0 to 4.2). The rates of respiratory distress syndrome (RDS), apnoea and mortality were similar in the SGA and AGA groups. CONCLUSION: Neonatal complications such as hypoglycaemic, NEC, LOS, polycythaemia and prolonged hospitalisation are more common in SGA infants, while rates of RDS and mortality are similar in SGA and AGA groups. Early recognition of SGA status, high index of suspicion and screening for complications associated and timely intervention to prevent complications need due consideration.

Hyperbilirubinemia in Preterm Infants Admitted to Neonatal Intensive Care Units in Ethiopia.

Background. Hyperbilirubinemia is prevalent and protracted in preterm infants. This study assessed the pattern of hyperbilirubinemia in preterm infants in Ethiopia. Methods. This study was part of multi-centered prospective, cross-sectional, observational study that determined causes of death among preterm infants. Jaundice was first identified based on clinical visual assessment. Venous blood was then sent for total and direct serum bilirubin level measurements. For this study, a total serum bilirubin level ≥5 mg/dL was taken as the cutoff point to diagnose hyperbilirubinemia. Based on the bilirubin level and clinical findings, the final diagnoses of hyperbilirubinemia and associated complications were made by the physician. Result. A total of 4919 preterm infants were enrolled into the overall study, and 3852 were admitted to one of the study's newborn intensive care units. Of these, 1779 (46.2%) infants were diagnosed with hyperbilirubinemia. Ten of these (0.6%) developed acute bilirubin encephalopathy. The prevalence of hyperbilirubinemia was 66.7% among the infants who were less than 28 weeks of gestation who survived. Rh incompatibility (P = .002), ABO incompatibility (P = .0001), and sepsis (P = .0001) were significantly associated with hyperbilirubinemia. Perinatal asphyxia (P-value = 0.0001) was negatively associated with hyperbilirubinemia. Conclusion. The prevalence of hyperbilirubinemia in preterm babies admitted to neonatal care units in Ethiopia was high. The major risk factors associated with hyperbilirubinemia in preterm babies in this study were found to be ABO incompatibility, sepsis, and Rh isoimmunization.