Summary 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. Funding USAID , WHO , Save the Children-US , and Bill & Melinda Gates Foundation.
BACKGROUND:The impact of SARS-CoV-2 on neonates remains largely unknown in low- and middle-income countries (LMICs). We provide an epidemiologic and clinical report of SARS-CoV-2 infections in ...neonates hospitalized in Bangladesh.
METHODS:Outborn neonates admitted to Dhaka Shishu Hospital, a tertiary-care referral hospital, between 29 March and 1 July were screened for SARS-CoV-2. We reviewed clinical data, including chest radiograph and laboratory reports, and conducted SARS-CoV-2 genome sequencing. Patients were followed-up for 27–75 days. A subset of caregivers was also tested.
RESULTS:Of 83 neonates tested, 26 were positive (median age 8 days). Most neonates were admitted with diagnosis unrelated to SARS-CoV-211 presented with serious non-communicable diseases, 7 with early-onset sepsis, 5 with late-onset sepsis and 2 with pneumonia. In 3 of 5 chest radiograph, infiltrates and ground-glass or patchy opacities were noted. Two neonates developed metabolic acidosis, one developed disseminated intravascular coagulation. Most SARS-CoV-2 positive neonates were referred to government-designated COVID-19 hospitals, leading to gaps in treatment. Twenty-three neonates could be followed-up12 were healthy, 8 died and 3 were still seeking medical care. Of 9 caregivers tested, 8 were positive.
CONCLUSIONS:SARS-CoV-2 may have serious adverse effects on children born in LMICs. The virus likely contributed directly to two deaths, but the remaining 6 neonates who died had serious comorbidities. Positive SARS-CoV-2 test results led to gaps in immediate clinical care for other morbidities, which likely contributed to adverse outcomes. This case series emphasizes the need to understand COVID-19 in neonates in LMICs and its indirect impacts.
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.
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).
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).
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.
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.
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.
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.
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.
Published online March 3, 2005 http://image.thelancet.com/extras/04art11050web.pdf
Background Topical treatment with sunflower seed oil (SSO) or AquaphorR 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, AquaphorR, 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 AquaphorR 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 Keywords: Emollient, Neurodevelopment, Preterm, Follow-up, Newborn, Neonatal
Pneumonia is the leading infectious cause of morbidity and mortality in young children in Bangladesh. We present the epidemiology of pneumonia in Bangladeshi children <5 years before 10-valent ...pneumococcal conjugate vaccine introduction and investigate factors associated with disease severity and mortality.
Children aged 2-59 months admitted to three Bangladeshi hospitals with pneumonia (i.e., cough or difficulty breathing and age-specific tachypnea without danger signs) or severe pneumonia (i.e., cough or difficulty breathing and ≥1 danger signs) were included. Demographic, clinical, laboratory, and vaccine history data were collected. We assessed associations between characteristics and pneumonia severity and mortality using multivariable logistic regression.
Among 3639 Bangladeshi children with pneumonia, 61% had severe disease, and 2% died. Factors independently associated with severe pneumonia included ages 2-5 months (adjusted odds ratio aOR 1.60 95% CI: 1.26-2.01) and 6-11 months (aOR 1.31 1.10-1.56) relative to 12-59 months, low weight for age (aOR 1.22 1.04-1.42), unsafe drinking water source (aOR 2.00 1.50-2.69), higher paternal education (aOR 1.34 1.15-1.57), higher maternal education (aOR 0.74 0.64-0.87), and being fully vaccinated for age with pentavalent vaccination (aOR 0.64 0.51-0.82). Increased risk of pneumonia mortality was associated with age <12 months, low weight for age, unsafe drinking water source, lower paternal education, disease severity, and having ≥1 co-morbid condition.
Modifiable factors for severe pneumonia and mortality included low weight for age and access to safe drinking water. Improving vaccination status could decrease disease severity.
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.
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.
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.
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 ≥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.
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