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1.  Animal Husbandry Practices in Rural Bangladesh: Potential Risk Factors for Antimicrobial Drug Resistance and Emerging Diseases 
Antimicrobial drug administration to household livestock may put humans and animals at risk for acquisition of antimicrobial drug–resistant pathogens. To describe animal husbandry practices, including animal healthcare-seeking and antimicrobial drug use in rural Bangladesh, we conducted semi-structured in-depth interviews with key informants, including female household members (n = 79), village doctors (n = 10), and pharmaceutical representatives, veterinarians, and government officials (n = 27), and performed observations at animal health clinics (n = 3). Prevalent animal husbandry practices that may put persons at risk for acquisition of pathogens included shared housing and water for animals and humans, antimicrobial drug use for humans and animals, and crowding. Household members reported seeking human and animal healthcare from unlicensed village doctors rather than formal-sector healthcare providers and cited cost and convenience as reasons. Five times more per household was spent on animal than on human healthcare. Strengthening animal and human disease surveillance systems should be continued. Interventions are recommended to provide vulnerable populations with a means of protecting their livelihood and health.
doi:10.4269/ajtmh.12-0713
PMCID: PMC3820344  PMID: 24062478
2.  Determinants and pattern of care seeking for preterm newborns in a rural Bangladeshi cohort 
Background
Despite the increased burden of preterm birth and its complications, the dearth of care seeking data for preterm newborns remains a significant knowledge gap. Among preterm babies in rural Bangladesh, we examined: 1) determinants and patterns of care seeking, and 2) risk analysis for care-seeking from qualified and unqualified providers.
Method
Trained community health workers collected data prospectively from 27,460 mother-liveborn baby pairs, including 6,090 preterm babies, between June 2007 and September 2009. Statistical analyses included binomial and multinomial logistic regressions.
Results
Only one-fifth (19.7%) of preterm newborns were taken to seek either preventive or curative health care. Among care-seeker preterm newborns, preferred providers included homeopathic practitioners (50.0%), and less than a third (30.9%) sought care from qualified providers. Care-seeking from either unqualified or qualified providers was significantly lower for female preterm babies, compared to male babies [Relative Risk Ratio (RRR) for unqualified care: 0.68; 95% Confidence Interval (CI): 0.58, 0.80; RRR for qualified care: 0.52; 95% CI: 0.41, 0.66]. Among preterm babies, care-seeking was significantly higher among caregivers who recognized symptoms of illness [RR: 2.14; 95% CI: 1.93, 2.38] or signs of local infection (RR: 2.53; 95% CI: 2.23, 2.87), had a history of child death [RR: 1.21; 95% CI: 1.07, 1.37], any antenatal care (ANC) visit [RR: 1.41; 95% CI: 1.25, 1.59]. Birth preparedness (RRR: 1.24; 95% CI: 1.09, 1.68) and any ANC visit (RRR: 1.73; 95% CI: 1.50, 2.49) were also associated with increased likelihood of care seeking for preterm babies from qualified providers.
Conclusion
To improve care seeking practices for preterm babies and referral of sick newborns to qualified providers/facilities, we recommend: 1) involving community-preferred health care providers in community-based health education and awareness raising programs; 2) integrating postnatal care seeking messages into antenatal counselling; and 3) further research on care seeking practices for preterm babies.
Electronic supplementary material
The online version of this article (doi:10.1186/1472-6963-14-417) contains supplementary material, which is available to authorized users.
doi:10.1186/1472-6963-14-417
PMCID: PMC4261985  PMID: 25242278
3.  The effect of umbilical cord cleansing with chlorhexidine on omphalitis and neonatal mortality in community settings in developing countries: a meta-analysis 
BMC Public Health  2013;13(Suppl 3):S15.
Background
There is an increased risk of serious neonatal infection arising through exposure of the umbilical cord to invasive pathogen in home and facility births where hygienic practices are difficult to achieve. The World Health Organization currently recommends ‘dry cord care’ because of insufficient data in favor of or against topical application of an antiseptic. The primary objective of this meta-analysis is to evaluate the effects of application of chlorhexidine (CHX) to the umbilical cord to children born in low income countries on cord infection (omphalitis) and neonatal mortality. Standardized guidelines of Child Health Epidemiology Reference Group (CHERG) were followed to generate estimates of effectiveness of topical chlorhexidine application to umbilical cord for prevention of sepsis specific mortality, for inclusion in the Lives Saved Tool (LiST).
Methods
Systematic review and meta-analysis. Data sources included Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, CINHAL and WHO international clinical trials registry. Only randomized trials were included. Studies of children in hospital settings were excluded. The comparison group received no application to the umbilical cord (dry cord care), no intervention, or a non-CHX intervention. Primary outcomes were omphalitis and all-cause neonatal mortality.
Results
There were three cluster-randomised community trials (total participants 54,624) conducted in Nepal, Bangladesh and Pakistan that assessed impact of CHX application to the newborn umbilical cord for prevention of cord infection and mortality. Application of any CHX to the umbilical cord of the newborn led to a 23% reduction in all-cause neonatal mortality in the intervention group compared to control [RR 0.77, 95 % CI 0.63, 0.94; random effects model, I2=50 %]. The reduction in omphalitis ranged from 27 % to 56 % compared to control group depending on severity of infection. Based on CHERG rules, effect size for all-cause mortality was used for inclusion to LiST model as a proxy for sepsis specific mortality.
Conclusions
Application of CHX to newborn umbilical cord can significantly reduce incidence of umbilical cord infection and all-cause mortality among home births in community settings. This inexpensive and simple intervention can save a significant number of newborn lives in developing countries.
doi:10.1186/1471-2458-13-S3-S15
PMCID: PMC3847355  PMID: 24564621
4.  Measuring Coverage in MNCH: A Prospective Validation Study in Pakistan and Bangladesh on Measuring Correct Treatment of Childhood Pneumonia 
PLoS Medicine  2013;10(5):e1001422.
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.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Pneumonia is a major cause of death in children younger than five years across the globe, with approximately 1.2 million children younger than five years dying from pneumonia every year. Pneumonia can be caused by bacteria, fungi, or viruses. It is possible to effectively treat bacterial pneumonia with appropriate antibiotics; however, only about 30% of children receive the antibiotic treatment they need. The Millennium Development Goals (MDGs) are eight international development goals that were established in 2000. The fourth goal (MDG 4) aims to reduce child mortality, specifically, to reduce the under-five mortality rate by two-thirds, between 1990 and 2015. Given that approximately 18% of all deaths in children under five are caused by pneumonia, providing universal coverage with effective treatments for pneumonia is an important part of MDG 4.
To ensure that MDG 4 targets are met, it is important to measure progress in providing effective treatments. For pneumonia, one of the key indicators for measuring progress is the proportion of children with pneumonia in a population who receive antibiotic treatment, also known as the antibiotic treatment rate. The antibiotic treatment rate is often measured using surveys, such as the Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS), which collect nationally representative data about populations and health in developing countries.
Why Was This Study Done?
Concerns have been raised about whether information collected from DHS and MICS is able to accurately identify cases of pneumonia. In a clinical setting, pneumonia is typically diagnosed based on a combination of physical symptoms, including coughing, rapid breathing, or difficulty breathing, and a chest X-ray. The surveys rely on information collected from interviews of mothers and primary caregivers using structured questions about whether the child has experienced physical symptoms in the past two weeks and whether these were chest-related. The DHS survey labels this condition as “symptoms of acute respiratory infection,” while the MICS survey uses the term “suspected pneumonia.” Thus, these surveys provide a proxy measure for pneumonia that is limited by the reliance on the recall of symptoms by the mother or caregiver. Here the researchers have evaluated the use of these surveys to discriminate physician-diagnosed pneumonia and to provide accurate recall of antibiotic treatment in urban and rural settings in Pakistan and Bangladesh.
What Did the Researchers Do and Find?
The researchers identified caregivers of 950 children under five years with pneumonia and 980 who had a cough or cold but did not have pneumonia from urban and rural settings in Pakistan and Bangladesh. Cases of pneumonia were identified based on a physician diagnosis using World Health Organization guidelines. They randomly assigned caregivers to be interviewed using DHS and MICS questions with either a two- or four-week recall period. They then assessed how well the DHS and MICS questions were able to accurately diagnose pneumonia and accurately recall antibiotic use. In addition, they asked caregivers to complete a pneumonia score questionnaire and showed them a video tool showing children with and without pneumonia, as well as a medication drug chart, to determine if these alternative measures improved the accuracy of pneumonia diagnosis or recall of antibiotic use. They found that both surveys, the pneumonia score, and the video tool had poor ability to discriminate between children with and without physician-diagnosed pneumonia, and there were no differences between using two- or four-week recall. The sensitivity (proportion of pneumonia cases that were correctly identified) ranged from 23% to 72%, and the specificity (the proportion of “no pneumonia” cases that were correctly identified) ranged from 53% to 83%, depending on the setting. They also observed that prescribed antibiotics for pneumonia were correctly recalled by about two-thirds of caregivers using DHS questions, and this increased to about three-quarters of caregivers when using a drug chart and detailed enquiry.
What Do These Findings Mean?
The findings of this study suggest that the current use of questions from DHS and MICS based on mother or caregiver recall are not sufficient for accurately identifying pneumonia and antibiotic use in children. Because these surveys have poor ability to identify children who have true pneumonia, reported antibiotic treatment rates for children with pneumonia based on data from these surveys may not be accurate, and these surveys should not be used to monitor treatment rates. These findings should be interpreted cautiously, given the relatively high rate of loss to follow-up and delayed follow-up in some of the children and because some of the settings in this study may not be similar to other low-income settings.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001422.
More information is available on the United Nations goal to reduce child mortality (MDG 4)
The World Health Organization provides information on pneumonia, its impact on children, and the global action plan for prevention and control of pneumonia
More information is available on Demographic and Health Surveys and Multiple Indicator Cluster Surveys
KidsHealth, a resource maintained by the Nemours Foundation (a not-for-profit organization for children's health) provides information for parents on pneumonia (in English and Spanish)
MedlinePlus provides links to additional information on pneumonia (in English and Spanish)
doi:10.1371/journal.pmed.1001422
PMCID: PMC3646205  PMID: 23667339
5.  Measuring Coverage in MNCH: Challenges in Monitoring the Proportion of Young Children with Pneumonia Who Receive Antibiotic Treatment 
PLoS Medicine  2013;10(5):e1001421.
Pneumonia remains a major cause of child death globally, and improving antibiotic treatment rates is a key control strategy. Progress in improving the global coverage of antibiotic treatment is monitored through large household surveys such as the Demographic and Health Surveys (DHS) and the Multiple Indicator Cluster Surveys (MICS), which estimate antibiotic treatment rates of pneumonia based on two-week recall of pneumonia by caregivers. However, these survey tools identify children with reported symptoms of pneumonia, and because the prevalence of pneumonia over a two-week period in community settings is low, the majority of these children do not have true pneumonia and so do not provide an accurate denominator of pneumonia cases for monitoring antibiotic treatment rates. In this review, we show that the performance of survey tools could be improved by increasing the survey recall period or by improving either overall discriminative power or specificity. However, even at a test specificity of 95% (and a test sensitivity of 80%), the proportion of children with reported symptoms of pneumonia who truly have pneumonia is only 22% (the positive predictive value of the survey tool). Thus, although DHS and MICS survey data on rates of care seeking for children with reported symptoms of pneumonia and other childhood illnesses remain valid and important, DHS and MICS data are not able to give valid estimates of antibiotic treatment rates in children with pneumonia.
doi:10.1371/journal.pmed.1001421
PMCID: PMC3646212  PMID: 23667338
6.  Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis 
Lancet  2013;381(9875):1380-1390.
Summary
Background
The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010.
Methods
We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies.
Findings
We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3–13·9 million) episodes of severe and 3·0 million (2·1–4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265 000 (95% CI 160 000–450 000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals.
Interpretation
Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities.
Funding
WHO.
doi:10.1016/S0140-6736(12)61901-1
PMCID: PMC3986472  PMID: 23369797
7.  Detection and Serotyping of Lyophilized Nonculturable Pneumococcal Isolates 
Journal of Clinical Microbiology  2012;50(10):3388-3390.
One hundred fifty-two nonculturable lyophilized carriage pneumococcal isolates from a vaccine trial were subjected to PCR for serotyping, and 149 (98%) were successfully classified as vaccine or nonvaccine types, which were similar to viable isolates. The methodology will be useful for analysis of this and other studies where stored pneumococcal isolates fail to grow.
doi:10.1128/JCM.01912-12
PMCID: PMC3457436  PMID: 22855517
8.  An assessment of the quality of care for children in eighteen randomly selected district and sub-district hospitals in Bangladesh 
BMC Pediatrics  2012;12:197.
Background
Quality hospital care is important in ensuring that the needs of severely ill children are met to avert child mortality. However, the quality of hospital care for children in developing countries has often been found poor. As the first step of a country road map for improving hospital care for children, we assessed the baseline situation with respect to the quality of care provided to children under-five years age in district and sub-district level hospitals in Bangladesh.
Methods
Using adapted World Health Organization (WHO) hospital assessment tools and standards, an assessment of 18 randomly selected district (n=6) and sub-district (n=12) hospitals was undertaken. Teams of trained assessors used direct case observation, record review, interviews, and Management Information System (MIS) data to assess the quality of clinical case management and monitoring; infrastructure, processes and hospital administration; essential hospital and laboratory supports, drugs and equipment.
Results
Findings demonstrate that the overall quality of care provided in these hospitals was poor. No hospital had a functioning triage system to prioritise those children most in need of immediate care. Laboratory supports and essential equipment were deficient. Only one hospital had all of the essential drugs for paediatric care. Less than a third of hospitals had a back-up power supply, and just under half had functioning arrangements for safe-drinking water. Clinical case management was found to be sub-optimal for prevalent illnesses, as was the quality of neonatal care.
Conclusion
Action is needed to improve the quality of paediatric care in hospital settings in Bangladesh, with a particular need to invest in improving newborn care.
doi:10.1186/1471-2431-12-197
PMCID: PMC3561238  PMID: 23268650
Quality of care; Hospitals; Child health; Bangladesh
10.  Setting Research Priorities to Reduce Global Mortality from Childhood Pneumonia by 2015 
PLoS Medicine  2011;8(9):e1001099.
Igor Rudan and colleagues report the results of their consensus building exercise that identified health research priorities to help reduce child mortality from pneumonia.
doi:10.1371/journal.pmed.1001099
PMCID: PMC3181228  PMID: 21980266
11.  Vulnerability of Newborns to Environmental Factors: Findings from Community Based Surveillance Data in Bangladesh 
Infection is the major cause of neonatal deaths. Home born newborns in rural Bangladeshi communities are exposed to environmental factors increasing their vulnerability to a number of disease agents that may compromise their health. The current analysis was conducted to assess the association of very severe disease (VSD) in newborns in rural communities with temperature, rainfall, and humidity. A total of 12,836 newborns from rural Sylhet and Mirzapur communities were assessed by trained community health workers using a sign based algorithm. Records of temperature, humidity, and rainfall were collected from the nearest meteorological stations. Associations between VSD and environmental factors were estimated. Incidence of VSD was found to be associated with higher temperatures (odds ratios: 1.14, 95% CI: 1.08 to 1.21 in Sylhet and 1.06, 95% CI: 1.04 to 1.07 in Mirzapur) and heat humidity index (odds ratios: 1.06, 95% CI: 1.04 to 1.08 in Sylhet and, 1.03, 95% CI: 1.01 to 1.04 in Mirzapur). Four months (June–September) in Sylhet, and six months in Mirzapur (April–September) had higher odds ratios of incidence of VSD as compared to the remainder of the year (odds ratios: 1.72, 95% CI: 1.32 to 2.23 in Sylhet and, 1.62, 95% CI: 1.33 to 1.96 in Mirzapur). Prevention of VSD in neonates can be enhanced if these interactions are considered in health intervention strategies.
doi:10.3390/ijerph8083437
PMCID: PMC3166752  PMID: 21909316
neonatal; infection; sepsis; community health workers; environment; heat humidity index; Bangladesh
12.  An evaluation of emerging vaccines for childhood pneumococcal pneumonia 
BMC Public Health  2011;11(Suppl 3):S26.
Background
Pneumonia is the leading cause of child mortality worldwide. Streptococcus pneumoniae (SP) or pneumococcus is estimated to cause 821,000 child deaths each year. It has over 90 serotypes, of which 7 to 13 serotypes are included in current formulations of pneumococcal conjugate vaccines that are efficacious in young children. To further reduce the burden from SP pneumonia, a vaccine is required that could protect children from a greater diversity of serotypes. Two different types of vaccines against pneumococcal pneumonia are currently at varying stages of development: a multivalent pneumococcal conjugate vaccine covering additional SP serotypes; and a conserved common pneumococcal protein antigen (PPA) vaccine offering protection for all serotypes.
Methods
We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging SP vaccines relevant to several criteria of interest: answerability; efficacy and effectiveness; cost of development, production and implementation; deliverability, affordability and sustainability; maximum potential for disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%.
Results
The experts expressed very high level of optimism (over 80%) that low-cost polysaccharide conjugate SP vaccines would satisfy each of the 9 relevant CHNRI criteria. The median potential effectiveness of conjugate SP vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 25% (interquartile range 20-38%, min. 15%, max 45%). For low cost, cross-protective common protein vaccines for SP the experts expressed concerns over answerability (72%) and the level of development costs (50%), while the scores for all other criteria were over 80%. The median potential effectiveness of common protein vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 30% (interquartile range 26-40%, min. 20%, max 45%).
Conclusions
Improved SP vaccines are a very promising investment that could substantially contribute to reduction of child mortality world-wide.
doi:10.1186/1471-2458-11-S3-S26
PMCID: PMC3231900  PMID: 21501444
13.  An evaluation of emerging vaccines for childhood meningococcal disease 
BMC Public Health  2011;11(Suppl 3):S29.
Background
Meningococcal meningitis is a major cause of disease worldwide, with frequent epidemics particularly affecting an area of sub-Saharan Africa known as the “meningitis belt”. Neisseria meningitidis group A (MenA) is responsible for major epidemics in Africa. Recently W-135 has emerged as an important pathogen. Currently, the strategy for control of such outbreaks is emergency use of meningococcal (MC) polysaccharide vaccines, but these have a limited ability to induce herd immunity and elicit an adequate immune response in infant and young children. In recent times initiatives have been taken to introduce meningococcal conjugate vaccine in these African countries. Currently there are two different types of MC conjugate vaccines at late stages of development covering serogroup A and W-135: a multivalent MC conjugate vaccine against serogroup A,C,Y and W-135; and a monovalent conjugate vaccine against serogroup A. We aimed to perform a structured assessment of these emerging meningococcal vaccines as a means of reducing global meningococal disease burden among children under 5 years of age.
Methods
We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In the first stage we systematically reviewed the literature related to emerging MC vaccines relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%.
Results
For MenA conjugate vaccine the experts showed very high level of optimism (~ 90% or more) for 7 out of the 12 criteria. The experts felt that the likelihood of efficacy on meningitis was very high (~ 90%). Deliverability, acceptability to health workers, end users and the effect on equity were all seen as highly likely (~ 90%). In terms of the maximum potential impact on meningitis disease burden, the median potential effectiveness of the vaccines in reduction of overall meningitis mortality was estimated to be 20%; (interquartile range 20-40% and min. 8%, max 50 %). For the multivalent meningococcal vaccines the experts had similar optimism for most of the 12 CHNRI criteria with slightly lower optimism in answerability and low development cost criteria. The main concern was expressed over the cost of product, its affordability and cost of implementation.
Conclusions
With increasing recognition of the burden of meningococcal meningitis, especially during epidemics in Africa, it is vitally important that strategies are taken to reduce the morbidity and mortality attributable to this disease. Improved MC vaccines are a promising investment that could substantially contribute to reduction of child meningitis mortality world-wide.
doi:10.1186/1471-2458-11-S3-S29
PMCID: PMC3231902  PMID: 21501447
14.  An evaluation of the emerging vaccines and immunotherapy against staphylococcal pneumonia in children 
BMC Public Health  2011;11(Suppl 3):S27.
Background
Staphylococcus aureus is a commensal of human skin and nares. It is also one of the leading nosocomial pathogens in both developed and developing countries and is responsible for a wide range of life threatening infections, especially in patients who are immunocompromised, post-surgery, undergoing haemodialysis and those who are treated with catheters and ventilators. Over the past two decades, the incidence of nosocomial staphylococcal infections has increased dramatically. Currently there are at least seven vaccine and immunotherapy candidates against S. aureus in the developmental phase targeting both active and passive immunization.
Methods
We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against Staphylococcus aureus relevant to several criteria of interest: answerability; cost of development, production and implementation; efficacy and effectiveness; deliverability, affordability and sustainability; maximum potential impact on disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies) to participate. The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%.
Results
The panel of experts expressed low levels of optimism (score around or below 50%) on the criteria of answerability, efficacy, maximum disease burden reduction potential, low cost of production, low cost of implementation and affordability; moderate levels of optimism (scores around 60 to 80%) that these vaccines could be developed at a low cost, and thus on the deliverability, sustainability and impact on equity; and high levels of optimism (scores above 80%) regarding acceptable of such a product to both the end-users and health workers. While assessing the candidates for passive immunization against S.aureus, the experts were poorly optimistic regarding low production cost, low implementation cost, efficacy, deliverability, sustainability, affordability and equity; moderately optimistic regarding answerability and acceptability to health workers and end-users. They were of the opinion that these interventions would have only a modest impact (3 to 5%) on the burden of childhood pneumonia. .
Conclusion
In order to provide an effective vaccine against S. aureus, a number of unresolved issues in vaccine development relating to optimal antigenic target identification, criteria for acceptable efficacy, identification of target population, commercial development limitations, optimal timing of immunization strategy, storage, cold chain requirements and cost need to be addressed properly. There is still a great deal unknown about the complex interaction between S. aureus and the human host. However, given the nature of S. aureus and the lessons learned from the recent failure of two emerging vaccines, it is clear that a multi-component vaccine is essential. Combating only one virulence factor is not sufficient in the human host but finding the right combination of factors will be very challenging.
doi:10.1186/1471-2458-11-S3-S27
PMCID: PMC3239838  PMID: 21501445
15.  Population-Based Incidence and Etiology of Community-Acquired Neonatal Bacteremia in Mirzapur, Bangladesh: An Observational Study 
The Journal of infectious diseases  2009;200(6):906-915.
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.
Trial registration
ClinicalTrials.gov identifier: NCT00198627.
doi:10.1086/605473
PMCID: PMC2841956  PMID: 19671016
16.  Factors affecting recruitment and retention of community health workers in a newborn care intervention in Bangladesh 
Background
Well-trained and highly motivated community health workers (CHWs) are critical for delivery of many community-based newborn care interventions. High rates of CHW attrition undermine programme effectiveness and potential for implementation at scale. We investigated reasons for high rates of CHW attrition in Sylhet District in north-eastern Bangladesh.
Methods
Sixty-nine semi-structured questionnaires were administered to CHWs currently working with the project, as well as to those who had left. Process documentation was also carried out to identify project strengths and weaknesses, which included in-depth interviews, focus group discussions, review of project records (i.e. recruitment and resignation), and informal discussion with key project personnel.
Results
Motivation for becoming a CHW appeared to stem primarily from the desire for self-development, to improve community health, and for utilization of free time. The most common factors cited for continuing as a CHW were financial incentive, feeling needed by the community, and the value of the CHW position in securing future career advancement. Factors contributing to attrition included heavy workload, night visits, working outside of one's home area, familial opposition and dissatisfaction with pay.
Conclusions
The framework presented illustrates the decision making process women go through when deciding to become, or continue as, a CHW. Factors such as job satisfaction, community valuation of CHW work, and fulfilment of pre-hire expectations all need to be addressed systematically by programs to reduce rates of CHW attrition.
doi:10.1186/1478-4491-8-12
PMCID: PMC2875202  PMID: 20438642
17.  How well does LiST capture mortality by wealth quintile? A comparison of measured versus modelled mortality rates among children under-five in Bangladesh 
International Journal of Epidemiology  2010;39(Suppl 1):i186-i192.
Background In the absence of planned efforts to target the poor, child survival programs often favour the rich. Further evidence is needed urgently about which interventions and programme approaches are most effective in addressing inequities. The Lives Saved Tool (LiST) is available and can be used to model mortality levels across economic groups based on coverage levels for child survival interventions.
Methods We used LiST to model neonatal and under-5 mortality levels among the highest and the lowest wealth quintiles in Bangladesh based on national and wealth-quintile-specific coverage of child survival interventions. The cause-of-death structure among children under-5 was also modelled using the coverage levels. Modelled rates were compared to the rates measured directly from the 2004 Bangladesh Demographic and Health Survey and associated verbal autopsies.
Results Modelled estimates of mortality within wealth quintiles fell within the 95% confidence intervals of measured mortality for both neonatal and post-neonatal mortality. LiST also performed well in predicting the cause-of-death structure for these two age groups for the poorest quintile of the population, but less well for the richest quintile.
Conclusions LiST holds promise as a useful tool for assessing socio-economic inequities in child survival in low-income countries.
doi:10.1093/ije/dyq034
PMCID: PMC2845873  PMID: 20348120
Child survival; Neonatal mortality; Under-five mortality; Modelling; Causes of death; Wealth quintiles; LiST
18.  Impact of 4.0% chlorhexidine cleansing of the umbilical cord on mortality and omphalitis among newborns of Sylhet, Bangladesh: design of a community-based cluster randomized trial 
BMC Pediatrics  2009;9:67.
Background
The World Health Organization recommends dry cord care for newborns but this recommendation may not be optimal in low resource settings where most births take place in an unclean environment and infections account for up to half of neonatal deaths. A previous trial in Nepal indicated that umbilical cord cleansing with 4.0% chlorhexidine could substantially reduce mortality and omphalitis risk, but policy changes await additional community-based data.
Methods
The Projahnmo Chlorhexidine study was a three-year, cluster-randomized, community-based trial to assess the impact of three cord care regimens on neonatal mortality and omphalitis. Women were recruited mid-pregnancy, received a basic package of maternal and neonatal health promotion messages, and were followed to pregnancy outcome. Newborns were visited at home by local village-based workers whose areas were randomized to either 1) single- or 2) 7-day cord cleansing with 4.0% chlorhexidine, or 3) promotion of dry cord care as recommended by WHO. All mothers received basic messages regarding hand-washing, clean cord cutting, and avoidance of harmful home-base applications to the cord. Death within 28 days and omphalitis were the primary outcomes; these were monitored directly through home visits by community health workers on days 1, 3, 6, 9, 15, and 28 after birth.
Discussion
Due to report in early 2010, the Projahnmo Chlorhexidine Study examines the impact of multiple or single chlorhexidine cleansing of the cord on neonatal mortality and omphalitis among newborns of rural Sylhet District, Bangladesh. The results of this trial will be interpreted in conjunction with a similarly designed trial previously conducted in Nepal, and will have implications for policy guidelines for optimal cord care of newborns in low resource settings in Asia.
Trial Registration
ClinicalTrials.gov (NCT00434408)
doi:10.1186/1471-2431-9-67
PMCID: PMC2770449  PMID: 19845951
19.  Setting Priorities in Child Health Research Investments for South Africa 
PLoS Medicine  2007;4(8):e259.
Nearly 100,000 children under 5 years die annually in South Africa. This paper defines health research priorities to address this unacceptably high mortality rate.
doi:10.1371/journal.pmed.0040259
PMCID: PMC1952202  PMID: 17760497
20.  Molecular Basis of Resistance Displayed by Highly Ciprofloxacin-Resistant Salmonella enterica Serovar Typhi in Bangladesh 
Journal of Clinical Microbiology  2006;44(10):3811-3813.
Highly ciprofloxacin-resistant (MIC, 512 μg/ml) strains of Salmonella enterica serovar Typhi were isolated from the blood of typhoid patients in Dhaka, Bangladesh. The strains were indistinguishable by their antibiograms, biotypes, and variable-number tandem repeat types and had matching point mutations at positions 83 and 87 of the gyrA gene. The isolation of these strains in an area of high endemicity indicates the need for continuous surveillance of antibiotic resistance of S. enterica serovar Typhi and for the rationalized use of ciprofloxacin.
doi:10.1128/JCM.01197-06
PMCID: PMC1594770  PMID: 17021117
21.  Comparison of Antibiotic Resistance and Serotype Composition of Carriage and Invasive Pneumococci among Bangladeshi Children: Implications for Treatment Policy and Vaccine Formulation 
Journal of Clinical Microbiology  2003;41(12):5582-5587.
The nasopharyngeal carriage of Streptococcus pneumoniae is thought to pose a risk for invasive pneumococcal diseases, and the evaluation of carriage strains is thus often used to inform antibiotic treatment and vaccination strategies for these diseases. In this study, the age-specific prevalences, resistance to antibiotics, and serotype distributions of 1,340 carriage strains were analyzed and compared to 71 pneumococcal strains isolated from the cerebrospinal fluid of children under 5 years old with meningitis. Overall, the nasal carriage rate was 47%. One-fourth (26%) of the infants under 1 month of age and one-half (48%) of the infants under 12 months of age were colonized with S. pneumoniae. Rural children were colonized earlier than those from urban areas. Approximately one-fourth and one-half of the cases of pneumococcal meningitis occurred in the first 3 and 6 months of life, respectively. The respective rates of resistance for carriage and meningitis strains to penicillin (7 and 3%), cotrimoxazole (77 and 69%), and erythromycin (2 and 1%) were similar, whereas chloramphenicol resistance was lower among carriage strains (3%) than among meningitis strains (15.5%). The predominant serogroups of carriage and invasive isolates were variable and widely divergent. Thus, hypothetical 7-, 9-, and 11-valent vaccines, based on the predominant carriage strains of the present study, would cover only 23, 26, and 30%, respectively, of the serotypes causing meningitis. Further, currently available 7-, 9-, and 11-valent vaccines would protect against only 26, 43, and 48%, respectively, of these meningitis cases. In conclusion, while the surveillance of carriage strains for resistance to antibiotics appears useful in the design of empirical treatment guidelines for invasive pneumococcal disease, data on the serotypes of carriage strains have limited value in vaccine formulation strategies, particularly for meningitis cases.
doi:10.1128/JCM.41.12.5582-5587.2003
PMCID: PMC308982  PMID: 14662944
22.  Setting Priorities in Global Child Health Research Investments: Addressing Values of Stakeholders 
Croatian medical journal  2007;48(5):618-627.
Aim
To identify main groups of stakeholders in the process of health research priority setting and propose strategies for addressing their systems of values.
Methods
In three separate exercises that took place between March and June 2006 we interviewed three different groups of stakeholders: 1) members of the global research priority setting network; 2) a diverse group of national-level stakeholders from South Africa; and 3) participants at the conference related to international child health held in Washington, DC, USA. Each of the groups was administered different version of the questionnaire in which they were asked to set weights to criteria (and also minimum required thresholds, where applicable) that were a priori defined as relevant to health research priority setting by the consultants of the Child Health and Nutrition Research initiative (CHNRI).
Results
At the global level, the wide and diverse group of respondents placed the greatest importance (weight) to the criterion of maximum potential for disease burden reduction, while the most stringent threshold was placed on the criterion of answerability in an ethical way. Among the stakeholders’ representatives attending the international conference, the criterion of deliverability, answerability, and sustainability of health research results was proposed as the most important one. At the national level in South Africa, the greatest weight was placed on the criterion addressing the predicted impact on equity of the proposed health research.
Conclusions
Involving a large group of stakeholders when setting priorities in health research investments is important because the criteria of relevance to scientists and technical experts, whose knowledge and technical expertise is usually central to the process, may not be appropriate to specific contexts and in accordance with the views and values of those who invest in health research, those who benefit from it, or wider society as a whole.
PMCID: PMC2213572  PMID: 17948948
25.  Setting Priorities in Global Child Health Research Investments: Guidelines for Implementation of the CHNRI Method 
Croatian Medical Journal  2008;49(6):720-733.
This article provides detailed guidelines for the implementation of systematic method for setting priorities in health research investments that was recently developed by Child Health and Nutrition Research Initiative (CHNRI). The target audience for the proposed method are international agencies, large research funding donors, and national governments and policy-makers. The process has the following steps: (i) selecting the managers of the process; (ii) specifying the context and risk management preferences; (iii) discussing criteria for setting health research priorities; (iv) choosing a limited set of the most useful and important criteria; (v) developing means to assess the likelihood that proposed health research options will satisfy the selected criteria; (vi) systematic listing of a large number of proposed health research options; (vii) pre-scoring check of all competing health research options; (viii) scoring of health research options using the chosen set of criteria; (ix) calculating intermediate scores for each health research option; (x) obtaining further input from the stakeholders; (xi) adjusting intermediate scores taking into account the values of stakeholders; (xii) calculating overall priority scores and assigning ranks; (xiii) performing an analysis of agreement between the scorers; (xiv) linking computed research priority scores with investment decisions; (xv) feedback and revision. The CHNRI method is a flexible process that enables prioritizing health research investments at any level: institutional, regional, national, international, or global.
doi:10.3325/cmj.2008.49.720
PMCID: PMC2621022  PMID: 19090596

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