Samir K. Saha

Effect of community-based newborn-care intervention package implemented through two service-delivery strategies in Sylhet district, Bangladesh: a cluster-randomised controlled trial

BACKGROUND Neonatal mortality accounts for a high proportion of deaths in children under the age of 5 years in Bangladesh. Therefore the project for advancing the health of newborns and mothers (Projahnmo) implemented a community-based intervention package through government and non-government organisation infrastructures to reduce neonatal mortality. METHODS In Sylhet district, 24 clusters (with a population of about 20 000 each) were randomly assigned in equal numbers to one of two intervention arms or to the comparison arm. Because of the study design, masking was not feasible. All married women of reproductive age (15-49 years) were eligible to participate. In the home-care arm, female community health workers (one per 4000 population) identified pregnant women, made two antenatal home visits to promote birth and newborn-care preparedness, made postnatal home visits to assess newborns on the first, third, and seventh days of birth, and referred or treated sick neonates. In the community-care arm, birth and newborn-care preparedness and careseeking from qualified providers were promoted solely through group sessions held by female and male community mobilisers. The primary outcome was reduction in neonatal mortality. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number 00198705. FINDINGS The number of clusters per arm was eight. The number of participants was 36059, 40159, and 37598 in the home-care, community-care, and comparison arms, respectively, with 14 769, 16 325, and 15 350 livebirths, respectively. In the last 6 months of the 30-month intervention, neonatal mortality rates were 29.2 per 1000, 45.2 per 1000, and 43.5 per 1000 in the home-care, community-care, and comparison arms, respectively. Neonatal mortality was reduced in the home-care arm by 34% (adjusted relative risk 0.66; 95% CI 0.47-0.93) during the last 6 months versus that in the comparison arm. No mortality reduction was noted in the community-care arm (0.95; 0.69-1.31). INTERPRETATION A home-care strategy to promote an integrated package of preventive and curative newborn care is effective in reducing neonatal mortality in communities with a weak health system, low health-care use, and high neonatal mortality.

Pneumococcal vaccination in developing countries

WHO estimates that about 1·6 million people, including up to 1 million children under 5 years old, die every year of pneumococcal pneumonia, meningitis, and sepsis.1 In populations with high child-mortality rates, pneumonia is the leading infectious cause of mortality and accounts for about 20–25% of all child deaths.2 In these populations, Streptococcus pneumoniae is identified consistently as the leading cause of bacterial pneumonia, and pneumococcal bacteraemia is an important cause of child mortality. 3, 4 and 5 HIV infection increases risk for pneumococcal disease 20–40-fold, and antibiotic resistance makes treatment difficult and expensive. 6 Thus pneumococcal disease is a major global-health issue.

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.

Typhoid fever in Bangladesh: implications for vaccination policy.

OBJECTIVE To describe the age-specific distribution of typhoid fever including the degree of Salmonella typhi bacteremia among patients evaluated at a large private diagnostic center in Bangladesh, a highly endemic area. METHODS We conducted a prospective-, passive- and laboratory-based study to identify patients with S. typhi bacteremia. Subjects (n = 4,650) from whom blood cultures were obtained during 16-month period were enrolled from private clinics and hospitals throughout Dhaka. Isolation and quantification of S. typhi from blood cultures were performed by the lysis direct plating/ centrifugation method. RESULTS Bacterial pathogens were recovered from blood of 538 of 4,650 patients (11.6%) evaluated. S. typhi was the single most common pathogen recovered, comprising nearly three-fourths of isolates (72.7%; 391 of 538). Isolation rate of S. typhi was highest in monsoon and summer seasons and lowest in winter months. The majority (54.5%; 213 of 391) of S. typhi isolates were from children who were younger than 5 years, and 27% (105 of 391) were from children in the first 2 years of life. The isolation rate was highest (17.4%, 68 of 486) in the second year of life. The number of bacteria in blood on the basis of colony-forming units per ml of blood by age group was inversely related to age. CONCLUSIONS Detection of S. typhi bacteremia in young children in Dhaka, Bangladesh, was considerably higher than previously appreciated, with a peak detection rate in children < or =2 years of age, indicating the need to reassess the age-specific burden of typhoid fever in the community on a regional basis. Contrary to current recommendations this study suggests that development of new vaccines should target infants and young children.

Effect of Skin Barrier Therapy on Neonatal Mortality Rates in Preterm Infants in Bangladesh: A Randomized, Controlled, Clinical Trial

OBJECTIVE. Skin barrier therapy during the neonatal period, when the skin barrier is most highly compromised and the risk of death is greatest, has been shown to have a number of potential benefits, including reduced risk of nosocomial sepsis. Topical application of emollients that augment skin barrier function was evaluated as a strategy for improving survival rates among hospitalized preterm infants in Bangladesh. METHODS. A prospective, randomized, controlled, clinical trial was conducted in the special care nursery at Dhaka Shishu (Children) Hospital, the largest tertiary care childrens hospital in Bangladesh. Preterm infants (gestational age: ≤33 weeks; N = 497) received daily topical applications of sunflower seed oil or Aquaphor ointment. Neonatal mortality rates were compared in an intent-to-treat analysis with a control group that did not receive emollient therapy. RESULTS. Treatment with sunflower seed oil resulted in a statistically significant 26% reduction in mortality rates, compared with infants not receiving topical emollient therapy. Aquaphor therapy also significantly reduced mortality rates, by 32%. CONCLUSIONS. Topical therapy with skin barrier-enhancing emollients improved survival rates among preterm hospitalized infants in Bangladesh. This study provides strong evidence for the implementation of topical therapy for high-risk preterm neonates in developing countries.

Effectiveness of Haemophilus influenzae type B conjugate vaccine on prevention of pneumonia and meningitis in Bangladeshi children : A case-control study

Background: Few Asian countries have introduced Haemophilus influenzae type b (Hib) conjugate vaccine because of its cost and uncertainty regarding disease burden. Methods: To estimate the effectiveness of Hib conjugate vaccine in preventing pneumonia and meningitis in children age <2 years, an incident case–control study was conducted in a birth cohort of about 68,000 infants in Dhaka city, Bangladesh. DPT vaccine was systematically replaced by a combined Hib-DPT vaccine in selected immunization centers of the study area. Four matched community- and 2 hospital-controls were randomly selected for each confirmed case of pneumonia and meningitis from the study area. Results: About 35% of the infants received each of the 3 doses of Hib-DPT vaccine. There were 2679 children who had a chest roentgenogram. For 475 children, a radiologist and a pediatrician independently identified substantial alveolar consolidation. Following at least 2 doses of Hib vaccine, the preventable fractions [95% confidence intervals (CI)] using community and hospital controls were 17% (−10% to 38%) and 35% (13% to 52%) respectively. Of these 475 cases, 2 radiologists with the World Health Organization concurred with the findings for 343 patients, yielding preventable fractions of 34% (6% to 53%) and 44% (20% to 61%). Fifteen confirmed Hib meningitis cases were identified; the preventable fractions (95% CI) using community and hospital controls, respectively, were 89% (28% to 100%) and 93% (53% to 100%). Conclusions: The study documented that significant fractions of pneumonia and meningitis in Bangladeshi children age <2 years can be prevented by the Hib conjugate vaccine.

Evaluation of a Cluster-Randomized Controlled Trial of a Package of Community-Based Maternal and Newborn Interventions in Mirzapur, Bangladesh

Background To evaluate a delivery strategy for newborn interventions in rural Bangladesh. Methods A cluster-randomized controlled trial was conducted in Mirzapur, Bangladesh. Twelve unions were randomized to intervention or comparison arm. All women of reproductive age were eligible to participate. In the intervention arm, community health workers identified pregnant women; made two antenatal home visits to promote birth and newborn care preparedness; made four postnatal home visits to negotiate preventive care practices and to assess newborns for illness; and referred sick neonates to a hospital and facilitated compliance. Primary outcome measures were antenatal and immediate newborn care behaviours, knowledge of danger signs, care seeking for neonatal complications, and neonatal mortality. Findings A total of 4616 and 5241 live births were recorded from 9987 and 11153 participants in the intervention and comparison arm, respectively. High coverage of antenatal (91% visited twice) and postnatal (69% visited on days 0 or 1) home visitations was achieved. Indicators of care practices and knowledge of maternal and neonatal danger signs improved. Adjusted mortality hazard ratio in the intervention arm, compared to the comparison arm, was 1.02 (95% CI: 0.80–1.30) at baseline and 0.87 (95% CI: 0.68–1.12) at endline. Primary causes of death were birth asphyxia (49%) and prematurity (26%). No adverse events associated with interventions were reported. Conclusion Lack of evidence for mortality impact despite high program coverage and quality assurance of implementation, and improvements in targeted newborn care practices suggests the intervention did not adequately address risk factors for mortality. The level and cause-structure of neonatal mortality in the local population must be considered in developing interventions. Programs must ensure skilled care during childbirth, including management of birth asphyxia and prematurity, and curative postnatal care during the first two days of life, in addition to essential newborn care and infection prevention and management. Trial Registration Clinicaltrials.gov NCT00198627

Chloramphenicol versus ampicillin plus gentamicin for community acquired very severe pneumonia among children aged 2-59 months in low resource settings: multicentre randomised controlled trial (SPEAR study)

Objective To evaluate whether five days’ treatment with injectable ampicillin plus gentamicin compared with chloramphenicol reduces treatment failure in children aged 2-59 months with community acquired very severe pneumonia in low resource settings. Design Open label randomised controlled trial. Setting Inpatient wards within tertiary care hospitals in Bangladesh, Ecuador, India, Mexico, Pakistan, Yemen, and Zambia. Participants Children aged 2-59 months with WHO defined very severe pneumonia. Intervention Chloramphenicol versus a combination of ampicillin plus gentamicin. Main outcome measures Primary outcome measure was treatment failure at five days. Secondary outcomes were treatment failure defined similarly among all participants evaluated at 48 hours and at 10 and 21 days. Results More children failed treatment with chloramphenicol at day 5 (16% v 11%; relative risk 1.43, 95% confidence interval 1.03 to 1.97) and also by days 10 and 21. Overall, 112 bacterial isolates were obtained from blood and lung aspirates in 110 children (11.5%), with the most common organisms being Staphylococcus aureus (n=47) and Streptococcus pneumoniae (n=22). In subgroup analysis, bacteraemia with any organism increased the risk of treatment failure at 21 days in the chloramphenicol group (2.09, 1.41 to 3.10) but not in the ampicillin plus gentamicin group (1.12, 0.59 to 2.13). Similarly, isolation of S pneumoniae increased the risk of treatment failure at day 21 (4.06, 2.73 to 6.03) and death (5.80, 2.62 to 12.85) in the chloramphenicol group but not in the ampicillin plus gentamicin group. No difference was found in treatment failure for children with S aureus bacteraemia in the two groups, but the power to detect a difference in this subgroup analysis was low. Independent predictors of treatment failure by multivariate analysis were hypoxaemia (oxygen saturation <90%), receiving chloramphenicol, being female, and poor immunisation status. Conclusion Injectable ampicillin plus gentamicin is superior to injectable chloramphenicol for the treatment of community acquired very severe pneumonia in children aged 2-59 months in low resource settings. Trial registration Current Controlled Trials ISRCTN39543942.

Population-Based Incidence and Etiology of Community-Acquired Neonatal Bacteremia in Mirzapur, Bangladesh: An Observational Study

BACKGROUND To devise treatment strategies for neonatal infections, the population-level incidence and antibiotic susceptibility of pathogens must be defined. METHODS Surveillance for suspected neonatal sepsis was conducted in Mirzapur, Bangladesh, from February 2004 through November 2006. Community health workers assessed neonates on postnatal days 0, 2, 5, and 8 and referred sick neonates to a hospital, where blood was collected for culture from neonates with suspected sepsis. We estimated the incidence and pattern of community-acquired neonatal bacteremia and determined the antibiotic susceptibility profile of pathogens. RESULTS The incidence rate of community-acquired neonatal bacteremia was 3.0 per 1000 person-neonatal periods. Among the 30 pathogens identified, the most common was Staphylococcus aureus (n = 10); half of all isolates were gram positive. Nine were resistant to ampicillin and gentamicin or to ceftiaxone, and 13 were resistant to cotrimoxazole. CONCLUSION S. aureus was the most common pathogen to cause community-acquired neonatal bacteremia. Nearly 40% of infections were identified on days 0-3, emphasizing the need to address maternal and environmental sources of infection. The combination of parenteral procaine benzyl penicillin and an aminoglycoside is recommended for the first-line treatment of serious community-acquired neonatal infections in rural Bangladesh, which has a moderate level of neonatal mortality. Additional population-based data are needed to further guide national and global strategies.

Identification of Serotype in Culture Negative Pneumococcal Meningitis Using Sequential Multiplex PCR: Implication for Surveillance and Vaccine Design

Background PCR-based serotyping of Streptococcus pneumoniae has been proposed as a simpler approach than conventional methods, but has not been applied to strains in Asia where serotypes are diverse and different from other part of the world. Furthermore, PCR has not been used to determine serotype distribution in culture-negative meningitis cases. Methodology Thirty six serotype-specific primers, 7 newly designed and 29 previously published, were arranged in 7 multiplex PCR sets, each in new hierarchies designed for overall serotype distribution in Bangladesh, and specifically for meningitis and non-meningitis isolates. Culture-negative CSF specimens were then tested directly for serotype-specific sequences using the meningitis-specific set of primers. PCR-based serotyping of 367 strains of 56 known serotypes showed 100% concordance with quellung reaction test. The first 7 multiplex reactions revealed the serotype of 40% of all, and 31% and 48% non-meningitis and meningitis isolates, respectively. By redesigning the multiplex scheme specifically for non-meningitis or meningitis, the quellung reaction of 43% and 48% of respective isolates could be identified. Direct examination of 127 culture-negative CSF specimens, using the meningitis-specific set of primers, yielded serotype for 51 additional cases. Conclusions This PCR approach, could improve ascertainment of pneumococcal serotype distributions, especially for meningitis in settings with high prior use of antibiotics.