Hospitalization of Pediatric Enteric Fever Cases, Dhaka, Bangladesh, 2017-2019: Incidence and Risk Factors.

BACKGROUND: Enteric fever causes substantial morbidity and mortality in low- and middle-income countries. Here, we analyzed Surveillance for Enteric Fever in Asia Project (SEAP) data to estimate the burden of enteric fever hospitalization among children aged <15 years and identify risk factors for hospitalization in Bangladesh. METHODS: SEAP used hospital surveillance paired with a community-based health-care utilization assessment. In SEAP hospital surveillance, blood was obtained for culture from children aged <15 years with ≥3 days of fever. In the hospital catchment area, a health-care utilization survey (HCUS) was conducted to estimate the proportion of febrile children hospitalized at the study hospitals. We analyzed hospital surveillance and HCUS data to estimate the health care-adjusted incidence of enteric fever hospitalization, and conducted univariable and multivariable logistic regressions. RESULTS: From July 2017 through June 2019, 2243 laboratory-confirmed enteric fever cases were detected in 2 study hospitals; 673 (30%) were hospitalized. The health care-adjusted incidence of enteric fever hospitalization among children <15 years old was 303/100 000 children/year (95% confidence interval [CI], 293-313). Salmonella Typhi contributed most to the enteric fever hospitalization incidence (277/100 000 children/year; 95% CI, 267-287). The incidence was highest among children aged 2 to <5 years (552/100 000 children/year; 95% CI, 522-583), followed by those aged <2 years (316/100 000 children/year; 95% CI, 288-344). Factors independently associated with enteric fever hospitalization included fever duration, diarrhea, vomiting, abdominal pain, and leukocytopenia. CONCLUSIONS: We estimated a high burden of hospitalization due to enteric fever among children aged <5 years in Bangladesh. The introduction of a typhoid conjugate vaccine would protect children from typhoid and avert typhoid hospitalizations.

Measuring coverage in MNCH: a prospective validation study in Pakistan and Bangladesh on measuring correct treatment of childhood pneumonia.

BACKGROUND: Antibiotic treatment for pneumonia as measured by Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) is a key indicator for tracking progress in achieving Millennium Development Goal 4. Concerns about the validity of this indicator led us to perform an evaluation in urban and rural settings in Pakistan and Bangladesh. METHODS AND FINDINGS: Caregivers of 950 children under 5 y with pneumonia and 980 with "no pneumonia" were identified in urban and rural settings and allocated for DHS/MICS questions 2 or 4 wk later. Study physicians assigned a diagnosis of pneumonia as reference standard; the predictive ability of DHS/MICS questions and additional measurement tools to identify pneumonia versus non-pneumonia cases was evaluated. Results at both sites showed suboptimal discriminative power, with no difference between 2- or 4-wk recall. Individual patterns of sensitivity and specificity varied substantially across study sites (sensitivity 66.9% and 45.5%, and specificity 68.8% and 69.5%, for DHS in Pakistan and Bangladesh, respectively). Prescribed antibiotics for pneumonia were correctly recalled by about two-thirds of caregivers using DHS questions, increasing to 72% and 82% in Pakistan and Bangladesh, respectively, using a drug chart and detailed enquiry. CONCLUSIONS: Monitoring antibiotic treatment of pneumonia is essential for national and global programs. Current (DHS/MICS questions) and proposed new (video and pneumonia score) methods of identifying pneumonia based on maternal recall discriminate poorly between pneumonia and children with cough. Furthermore, these methods have a low yield to identify children who have true pneumonia. Reported antibiotic treatment rates among these children are therefore not a valid proxy indicator of pneumonia treatment rates. These results have important implications for program monitoring and suggest that data in its current format from DHS/MICS surveys should not be used for the purpose of monitoring antibiotic treatment rates in children with pneumonia at the present time.

Follow-up of cases of Haemophilus influenzae type b meningitis to determine its long-term sequelae.

OBJECTIVE: To measure physical and neurologic impact of Haemophilus influenzae type b (Hib) meningitis on surviving children through short- and long-term follow-up. STUDY DESIGN: Cases of Hib meningitis, diagnosed at a tertiary level pediatric hospital, were subjected to short- and long-term follow-up and compared with age, sex, and area of residence matched healthy controls. Follow-up assessments included thorough physical and neurodevelopmental assessments using a standardized protocol by a multidisciplinary team. RESULTS: Assessments of short-term follow-up cohort (n = 64) revealed hearing, vision, mental, and psychomotor deficits in 7.8%, 3%, 20%, and 25% of the cases, respectively. Deficits were 10%, 1.4%, 21%, and 25% in long-term follow-up cohort (n = 71), in that order. Mental and psychomotor deficits were found in 2% of the controls, none of whom had vision or hearing deficits. CONCLUSIONS: In addition to risk of death, Hib meningitis in children causes severe disabilities in survivors. These data facilitated a comprehensive understanding of the burden of Hib meningitis, specifically in developing countries where disabled children remain incapacitated because of lack of resources and facilities. The evidence generated from this study is expected to provide a compelling argument in favor of introduction and continuation of Hib conjugate vaccine in the national immunization program for children.

Impact of emollient therapy for preterm infants in the neonatal period on child neurodevelopment in Bangladesh: an observational cohort study.

BACKGROUND: Topical treatment with sunflower seed oil (SSO) or Aquaphor® reduced sepsis and neonatal mortality in hospitalized preterm infants <33 weeks' gestational age in Bangladesh. We sought to determine whether the emollient treatments improved neurodevelopmental outcomes during early childhood. METHODS: 497 infants were randomized to receive SSO, Aquaphor®, or neither through the neonatal period or hospital discharge. 159 infant survivors were enrolled in the longitudinal follow-up study using a validated Rapid Neurodevelopmental Assessment tool and the Bayley Scales of Infant Development II (BSID II) administered at three-monthly intervals for the first year and thereafter at six-monthly intervals. Lowess smoothing was used to display neurodevelopmental status across multiple domains by age and treatment group, and Generalized Estimating Equations (GEE) were used to compare treatment groups across age points. RESULTS: 123 children completed at least one follow-up visit. Lowess graphs suggest that lower proportions of children who received massage with either SSO or Aquaphor® had neurodevelopmental delays than control infants in a composite outcome of disabilities. In GEE analysis, infants receiving SSO showed a significant protective effect on the development of fine motor skills [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.86-0.98, p=0.006]. The Psychomotor Development Index (PDI) in the BSID II showed significantly lower disability rates in the Aquaphor group (23.6%) compared to the control (55.2%) (OR 0.21, 95% CI 0.06-0.72, p=0.004). CONCLUSIONS: Emollient massage of very preterm, hospitalized newborn infants improved some child neurodevelopmental outcomes over the first 2 years of follow-up. Findings warrant further confirmatory research. TRIAL REGISTRATION: ClinicalTrials.gov (98-04-21-03-2) under weblink https://clinicaltrials.gov/ct2/show/NCT00162747.

Cost-effectiveness of skin-barrier-enhancing emollients among preterm infants in Bangladesh.

OBJECTIVE: To evaluate the cost-effectiveness of topical emollients, sunflower seed oil (SSO) and synthetic Aquaphor, versus no treatment, in preventing mortality among hospitalized preterm infants (< 33 weeks gestation) at a tertiary hospital in Bangladesh. METHODS: Evidence from a randomized controlled efficacy trial was evaluated using standard Monte Carlo simulation. Programme costs were obtained from a retrospective review of activities. Patient costs were collected from patient records. Health outcomes were calculated as deaths averted and discounted years of life lost (YLLs) averted. Results were deemed cost-effective if they fell below a ceiling ratio based on the per capita gross national income of Bangladesh (United States dollars, US$ 470). FINDINGS: Aquaphor and SSO were both highly cost-effective relative to control, reducing neonatal mortality by 26% and 32%, respectively. SSO cost US$ 61 per death averted and US$ 2.15 per YLL averted (I$ 6.39, international dollars, per YLL averted). Aquaphor cost US$ 162 per death averted and US$ 5.74 per YLL averted (I$ 17.09 per YLL averted). Results were robust to sensitivity analysis. Aquaphor was cost-effective relative to SSO with 77% certainty: it cost an incremental US$ 26 more per patient treated, but averted 1.25 YLLs (US$ 20.74 per YLL averted). CONCLUSION: Topical therapy with SSO or Aquaphor was highly cost-effective in reducing deaths from infection among the preterm neonates studied. The choice of emollient should be made taking into account budgetary limitations and ease of supply. Further research is warranted on additional locally available emollients, use of emollients in community-based settings and generalizability to other geographic regions.

Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network.

OBJECTIVE: To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR). DESIGN: A web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns. SETTING: 39 NNUs from 12 countries. PATIENTS: Any neonate admitted to one of the participating NNUs. INTERVENTIONS: This was an observational cohort study. RESULTS: The number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List 'Access' antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%. CONCLUSION: AMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally.

Validation of community health workers' assessment of neonatal illness in rural Bangladesh.

OBJECTIVE: To estimate the validity (sensitivity, specificity, and positive and negative predictive values) of a clinical algorithm as used by community health workers (CHWs) to detect and classify neonatal illness during routine household visits in rural Bangladesh. METHODS: CHWs evaluated breastfeeding and symptoms and signs of illness in 395 neonates selected randomly from neonatal illness surveillance during household visits on postnatal days 0, 2, 5 and 8. Neonates classified with very severe disease (VSD) were referred to a community-based hospital. Within 12 hours of CHW assessments, physicians independently evaluated all neonates seen in a given day by one CHW, randomly chosen from among 36 project CHWs. Physicians recorded symptoms and signs of illness, classified the illness, and determined whether the newborn needed referral-level care at the hospital. Physicians' identification and classification were used as the gold standard in determining the validity of CHWs' identification of symptoms and signs of illness and its classification. FINDINGS: CHWs' classification of VSD showed a sensitivity of 73%, a specificity of 98%, a positive predictive value of 57% and a negative predictive value of 99%. A maternal report of any feeding problem as ascertained by physician questioning was significantly associated (P < 0.001) with 'not sucking at all' and 'not attached at all' or 'not well attached' as determined clinically by CHWs during feeding assessment. CONCLUSION: CHWs identified with high validity the neonates with severe illness needing referral-level care. Home-based illness recognition and management, including referral of neonates with severe illness by CHWs, is a promising strategy for improving neonatal health and survival in low-resource developing country settings.

Retinopathy of prematurity in Bangladeshi neonates.

BACKGROUND: Retinopathy of prematurity (ROP) is a potentially blinding eye disorder that primarily affects premature infants. Increased survival of extremely low birth weight infants following advances in antenatal and neonatal care has resulted in a population of infants at high risk of developing ROP. Long term morbidity of ROP has a spectrum ranging from myopia to blindness. Screening programs and early intervention can provide enormous economic and social benefits. MATERIALS AND METHODS: Preterm infants of gestational age <33 weeks admitted to the Special Care Nursery of Dhaka Shishu Hospital for a trial of topical emollient therapy during December 1998-July 2003 were followed-up after hospital discharge, including detailed ophthalmologic examination. Detailed history regarding risks during pregnancy, delivery and hospital stay was documented. ROP cases were managed according to the stage of the disease at diagnosis. RESULTS: Five out of the 114 (4.4%) children seen in follow-up were diagnosed with ROP. Low gestational age, low birth weight, administration of oxygen, apneic spells, sepsis and blood transfusions were common factors among cases who developed ROP. CONCLUSION: As survival of preterm infants in low resource settings increases, ROP will become increasingly important as a potential cause of blindness, emphasizing the critical need for ophthalmologic examination in premature infants, with immediate initiation of treatment when ROP is diagnosed.

Acceptability of massage with skin barrier-enhancing emollients in young neonates in Bangladesh.

Oil massage of newborns has been practised for generations in the Indian sub-continent; however, oils may vary from potentially beneficial, e.g. sunflower seed oil, to potentially toxic, e.g. mustard oil. The study was carried out to gain insights into oil-massage practices and acceptability of skin barrier-enhancing emollients in young, preterm Bangladeshi neonates. Preterm infants of <33 weeks gestational age were randomized to high-linoleate sunflower seed oil, Aquaphor Original Emollient Ointment, or the comparison group (usual care). A survey was administered at admission to assess routine skin-care practices prior to admission and at discharge to assess acceptability of emollient therapy during hospitalization. Oil massage was given to 83 (21%) of 405 babies before hospital admission, 86% (71/83) of whom were delivered at home. Application of oil, most commonly mustard oil (88%, 73/83), was started within one hour of birth in 51 cases (61%) and was applied all over the body (89%, 74/83) one to six (mean 2.2) times before admission. Of infants who received emollient therapy in the hospital, 42% (n=32) of mothers reported that the emollient applied in the hospital was better than that available at home, and only 29% would use the same oil (i.e. mustard oil) in the future as used previously at home. No problems resulted from use of emollient in the hospital. Topical therapy with sunflower seed oil or Aquaphor was perceived by many families to be superior to mustard oil. If caregivers and health professionals can be motivated to use inexpensive, available emollients, such as sunflower seed oil that are beneficial, emollient therapy could have substantial public-health benefit.

Effect of topical treatment with skin barrier-enhancing emollients on nosocomial infections in preterm infants in Bangladesh: a randomised controlled trial.

BACKGROUND: Infections and complications of prematurity are main causes of neonatal mortality. Very low birthweight premature infants have compromised skin barrier function, and are at especially high risk for serious infections and mortality. Our aim was to ascertain whether topical application of emollients to enhance skin barrier function would prevent nosocomial infections in this population. METHODS: We randomly assigned infants born before week 33 of gestation after admission to Dhaka Shishu Hospital, Bangladesh, to daily massage with sunflower seed oil (n=159) or Aquaphor (petrolatum, mineral oil, mineral wax, lanolin alcohol; n=157). We then compared incidence of nosocomial infections among infants in these two groups with an untreated control group (n=181) by an intention-to-treat analysis. FINDINGS: 20 patients in the control group, and 22 in each of the treatment groups left the hospital early, but were included in the final analysis. Overall, infants treated with sunflower seed oil were 41% less likely to develop nosocomial infections than controls (adjusted incidence rate ratio [IRR] 0.59, 95% CI 0.37-0.96, p=0.032). Aquaphor did not significantly reduce the risk of infection (0.60, 0.35-1.03, p=0.065). No adverse events were seen. INTERPRETATION: Our findings confirm that skin application of sunflower seed oil provides protection against nosocomial infections in preterm very low birthweight infants. The low cost, availability, simplicity, and effect of treatment make it an important intervention for very low birthweight infants admitted to hospital in developing countries.

Ciprofloxacin treatment in preterm neonates in Bangladesh: lack of effects on growth and development.

BACKGROUND: Quinolone-induced arthropathic toxicity in weight-bearing joints observed in juvenile animals during preclinical testing has largely restricted the routine use of ciprofloxacin in the pediatric age group. As histopathologic, radiologic and magnetic resonance imaging monitoring evidence has gathered supporting the safety of fluoroquinolones in children, many pediatricians have started to prescribe quinolones to some patients on a compassionate basis. OBJECTIVE: The objective of this study was to ascertain the safety of ciprofloxacin in preterm neonates <33 weeks gestational age treated at Dhaka Shishu (Children) Hospital in Bangladesh. METHODS: Long-term follow up was done to monitor the growth and development of preterm infants who were administered intravenous ciprofloxacin in the neonatal period. Ciprofloxacin was used only as a life-saving therapy in cases of sepsis produced by bacterial agents resistant to other antibiotics. Another group of preterm neonates with septicemia who were not exposed to ciprofloxacin, but effectively treated with other antibiotics and followed up, were matched with cases for gender, gestational age and birth weight and included as a comparison group. Forty-eight patients in the ciprofloxacin group and 66 patients in the comparison group were followed up for a mean of 24.7 +/- 18.5 months and 21.6 +/- 18.8 months, respectively. RESULTS: No osteoarticular problems or joint deformities were observed in the ciprofloxacin group during treatment or follow up. No differences in growth and development between the groups were found. CONCLUSIONS: Ciprofloxacin is a safe therapeutic option for newborns with sepsis produced by multiply resistant organisms.

Trends in use of referral hospital services for care of sick newborns in a community-based intervention in Tangail District, Bangladesh.

The Projahnmo-II Project in Mirzapur upazila (sub-district), Tangail district, Bangladesh, is promoting care-seeking for sick newborns through health education of families, identification and referral of sick newborns in the community by community health workers (CHWs), and strengthening of neonatal care in Kumudini Hospital, Mirzapur. Data were drawn from records maintained by the CHWs, referral hospital registers, a baseline household survey of recently-delivered women conducted from March to June 2003, and two interim household surveys in January and September 2005. Increases were observed in self-referral of sick newborns for care, compliance after referral by the CHWs, and care-seeking from qualified providers and from the Kumudini Hospital, and decreases were observed in care-seeking from unqualified providers in the intervention arm. An active surveillance for illness by the CHWs in the home, education of families by them on recognition of danger signs and counselling to seek immediate care for serious illness, and improved linkages between the community and the hospital can produce substantial increases in care-seeking for sick newborns.

Centralized Data Management in a Multicountry, Multisite Population-based Study.

BACKGROUND: A centralized data management system was developed for data collection and processing for the Aetiology of Neonatal Infection in South Asia (ANISA) study. ANISA is a longitudinal cohort study involving neonatal infection surveillance and etiology detection in multiple sites in South Asia. The primary goal of designing such a system was to collect and store data from different sites in a standardized way to pool the data for analysis. METHODS: We designed the data management system centrally and implemented it to enable data entry at individual sites. This system uses validation rules and audit that reduce errors. The study sites employ a dual data entry method to minimize keystroke errors. They upload collected data weekly to a central server via internet to create a pooled central database. Any inconsistent data identified in the central database are flagged and corrected after discussion with the relevant site. The ANISA Data Coordination Centre in Dhaka provides technical support for operations, maintenance and updating the data management system centrally. Password-protected login identifications and audit trails are maintained for the management system to ensure the integrity and safety of stored data. CONCLUSION: Centralized management of the ANISA database helps to use common data capture forms (DCFs), adapted to site-specific contextual requirements. DCFs and data entry interfaces allow on-site data entry. This reduces the workload as DCFs do not need to be shipped to a single location for entry. It also improves data quality as all collected data from ANISA goes through the same quality check and cleaning process.

Classification of Blood Culture Isolates Into Contaminants and Pathogens on the Basis of Clinical and Laboratory Data.

The multisite community-based study, Aetiology of Neonatal Infection in South Asia (ANISA), uses blood culture as the gold standard for identifying the etiology of neonatal infection. Considering the importance of this age-old diagnostic tool and the risk of contamination, ANISA has employed rigorous measures to prevent contamination at all stages of blood collection, processing and culture. Because contamination may still occur, an independent expert group evaluates the routinely collected clinical and laboratory data to determine whether a blood culture isolate is a contaminant or a true pathogen. This article describes the methodology used by ANISA to determine whether a blood culture isolate is likely to be a true pathogen or a contaminant in neonatal sepsis.

Safety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial.

BACKGROUND: Severe infections remain one of the main causes of neonatal deaths worldwide. Possible severe infection is diagnosed in young infants (aged 0-59 days) according to the presence of one or more clinical signs. The recommended treatment is hospital admission with 7-10 days of injectable antibiotic therapy. In low-income and middle-income countries, barriers to hospital care lead to delayed, inadequate, or no treatment for many young infants. We aimed to identify effective alternative antibiotic regimens to expand treatment options for situations where hospital admission is not possible. METHODS: We did this randomised, open-label, equivalence trial in four urban hospitals and one rural field site in Bangladesh to determine whether two alternative antibiotic regimens with reduced numbers of injectable antibiotics combined with oral antibiotics had similar efficacy and safety to the standard regimen, which was also used as outpatient treatment. We randomly assigned infants who showed at least one clinical sign of severe, but not critical, infection (except fast breathing alone), whose parents refused hospital admission, to one of the three treatment regimens. We stratified randomisation by study site and age (<7 days or 7-59 days) using computer-generated randomisation sequences. The standard treatment was intramuscular procaine benzylpenicillin and gentamicin once per day for 7 days (group A). The alternative regimens were intramuscular gentamicin once per day and oral amoxicillin twice per day for 7 days (group B) or intramuscular procaine benzylpenicillin and gentamicin once per day for 2 days, then oral amoxicillin twice per day for 5 days (group C). The primary outcome was treatment failure within 7 days after enrolment. Assessors of treatment failure were masked to treatment allocation. Primary analysis was per protocol. We used a prespecified similarity margin of 5% to assess equivalence between regimens. This study is registered with ClinicalTrials.gov, number NCT00844337. FINDINGS: Between July 1, 2009, and June 30, 2013, we recruited 2490 young infants into the trial. We assigned 830 infants to group A, 831 infants to group B, and 829 infants to group C. 2367 (95%) infants fulfilled per-protocol criteria. 78 (10%) of 795 per-protocol infants had treatment failure in group A compared with 65 (8%) of 782 infants in group B (risk difference -1.5%, 95% CI -4.3 to 1.3) and 64 (8%) of 790 infants in group C (-1.7%, -4.5 to 1.1). In group A, 14 (2%) infants died before day 15, compared with 12 (2%) infants in group B and 12 (2%) infants in group C. Non-fatal relapse rates were similar in all three groups (12 [2%] infants in group A vs 13 [2%] infants in group B and 10 [1%] infants in group C). INTERPRETATION: Our results suggest that the two alternative antibiotic regimens for outpatient treatment of clinical signs of severe infection in young infants whose parents refused hospital admission are as efficacious as the standard regimen. This finding could increase treatment options in resource-poor settings when referral care is not available or acceptable.

Clinical and bacteriological profile of neonatal septicemia in a tertiary level pediatric hospital in Bangladesh.

The present article is a descriptive analysis of clinical and bacteriological profile of neonatal septicemia in a tertiary care hospital in Bangladesh. Eighty six neonates with suspected sepsis were enrolled, out of which 30 were culture positive. Clinical presentation was non-specific. Majority (70%) of the cultures isolated gram negative bacilli, most commonly E.coli and Klebsiella. These isolates were most often sensitive to gentamicin, ciprofloxacin, and third generation cephalosporins. Twelve out of 30 culture positive cases died.

Mechanism for prevention of infection in preterm neonates by topical emollients: a randomized, controlled clinical trial.

BACKGROUND: Topical applications of emollients such as sunflower seed oil and Aquaphor have been shown to reduce the incidence of bloodstream infections and mortality of preterm infants in resource-poor settings. The causal mechanism for prevention of infection through cutaneous portals of entry is not well understood. METHODS: We examined the relationship between skin condition score as a measure of skin barrier integrity and risk for bloodstream infection, and the effect of emollients on that relationship. Data for this study come from a randomized controlled trial of the impact of topical emollient therapy on nosocomial infections in 491 preterm infants <33 weeks gestational age at Dhaka Shishu Hospital, Bangladesh. Latent growth trajectory model with random-coefficient and multivariable logistic regression were utilized. RESULTS: Rate of deterioration of skin condition was significantly lower (P < 0.05) in both emollient arms compared with the untreated control group. Adjusted odds ratio of skin score for infection was 1.32 (95% confidence interval: 1.06-1.65). Emollients reduced the incidence of infection only when the skin had no signs of deterioration [Aquaphor incidence rate ratio: 0.43 (95% confidence interval: 0.19-0.97) and sunflower seed oil incidence rate ratio: 0.46 (95% confidence interval: 0.21-0.99)]. CONCLUSION: Skin condition deteriorated progressively after birth and compromised skin condition increased the risk of infection. Emollients preserved skin integrity and thus prevented infection in preterm neonates. To optimize benefits of emollients for the prevention of bloodstream infection, use of emollients should begin immediately after birth when the skin is still intact.

Safety and efficacy of simplified antibiotic regimens for outpatient treatment of serious infection in neonates and young infants 0-59 days of age in Bangladesh: design of a randomized controlled trial.

BACKGROUND: Because access to care is limited in settings with high mortality, exclusive reliance on the current recommendation of 7-10 days of parenteral antibiotic treatment is a barrier to provision of adequate treatment of newborn infections. METHODS: We are conducting a trial to determine if simplified antibiotic regimens with fewer injections are as efficacious as the standard course of parenteral antibiotics for empiric treatment of young infants with clinical signs suggestive of severe infection in 4 urban hospitals and in a rural surveillance site in Bangladesh. The reference regimen of intramuscular procaine-benzyl penicillin and gentamicin given once daily for 7 days is being compared with (1) intramuscular gentamicin once daily and oral amoxicillin twice daily for 7 days and (2) intramuscular penicillin and gentamicin once daily for 2 days followed by oral amoxicillin twice daily for additional 5 days. All regimens are provided in the infant's home. The primary outcome is treatment failure (death or lack of clinical improvement) within 7 days of enrolment. The sample size is 750 evaluable infants enrolled per treatment group, and results will be reported at the end of 2013. DISCUSSION: The trial builds upon previous studies of community case management of clinical severe infections in young infants conducted by our research team in Bangladesh. The approach although effective was not widely accepted in part because of feasibility concerns about the large number of injections. The proposed research that includes fewer doses of parenteral antibiotics if shown efficacious will address this concern.

Validation of a clinical algorithm to identify neonates with severe illness during routine household visits in rural Bangladesh.

BACKGROUND: To validate a clinical algorithm for community health workers (CHWs) during routine household surveillance for neonatal illness in rural Bangladesh. METHODS: Surveillance was conducted in the intervention arm of a trial of newborn interventions. CHWs assessed 7587 neonates on postnatal days 0, 2, 5 and 8 and identified neonates with very severe disease (VSD) using an 11-sign algorithm. A nested prospective study was conducted to validate the algorithm (n=395). Physicians evaluated neonates to determine whether newborns with VSD needed referral. The authors calculated algorithm sensitivity and specificity in identifying (1) neonates needing referral and (2) mortality during the first 10 days of life. RESULTS: The 11-sign algorithm had sensitivity of 50.0% (95% CI 24.7% to 75.3%) and specificity of 98.4% (96.6% to 99.4%) for identifying neonates needing referral-level care. A simplified 6-sign algorithm had sensitivity of 81.3% (54.4% to 96.0%) and specificity of 96.0% (93.6% to 97.8%) for identifying referral need and sensitivity of 58.0% (45.5% to 69.8%) and specificity of 93.2% (92.5% to 93.7%) for screening mortality. Compared to our 6-sign algorithm, the Young Infant Study 7-sign (YIS7) algorithm with minor modifications had similar sensitivity and specificity. CONCLUSION: Community-based surveillance for neonatal illness by CHWs using a simple 6-sign clinical algorithm is a promising strategy to effectively identify neonates at risk of mortality and needing referral to hospital. The YIS7 algorithm was also validated with high sensitivity and specificity at community level, and is recommended for routine household surveillance for newborn illness. ClinicalTrials.gov no. NCT00198627.

Household surveillance of severe neonatal illness by community health workers in Mirzapur, Bangladesh: coverage and compliance with referral.

BACKGROUND: Effective and scalable community-based strategies are needed for identification and management of serious neonatal illness. METHODS: As part of a community-based, cluster-randomized controlled trial of the impact of a package of maternal-neonatal health care, community health workers (CHWs) were trained to conduct household surveillance and to identify and refer sick newborns according to a clinical algorithm. Assessments of newborns by CHWs at home were linked to hospital-based assessments by physicians, and factors impacting referral, referral compliance and outcome were evaluated. RESULTS: Seventy-three per cent (7310/10,006) of live-born neonates enrolled in the study were assessed by CHWs at least once; 54% were assessed within 2 days of birth, but only 15% were attended at delivery. Among assessments for which referral was recommended, compliance was verified in 54% (495/919). Referrals recommended to young neonates 0-6 days old were 30% less likely to be complied with compared to older neonates. Compliance was positively associated with having very severe disease and selected clinical signs, including respiratory rate > or = 70/minute; weak, abnormal or absent cry; lethargic or less than normal movement; and feeding problem. Among 239 neonates who died, only 38% were assessed by a CHW before death. CONCLUSIONS: Despite rigorous programmatic effort, reaching neonates within the first 2 days after birth remained a challenge, and parental compliance with referral recommendation was limited, particularly among young neonates. To optimize potential impact, community postnatal surveillance must be coupled with skilled attendance at delivery, and/or a worker skilled in recognition of neonatal illness must be placed in close proximity to the community to allow for rapid case management to avert early deaths.