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1.  Community-based cross-sectional seroprevalence study of hepatitis A in Bangladesh 
AIM: To elucidate the age-distribution of anti-hepatitis A virus (HAV) seroprevalence across different socioeconomic status (SES) categories in Bangladesh which, despite scarce data, is generally deemed to have high endemicity.
METHODS: Blood samples of 818 subjects from a stratified sample of schools and hospitals, comprising different age categories and SES were collected. They were assayed for total anti-HAV antibodies. Social and medical history data were obtained using a questionnaire.
RESULTS: Overall anti-HAV seroprevalence was 69.6%, increasing with age from 1-5 years (40.4%) to > 30 years (98.4%). Seroprevalence was lowest (49.8%) in the high SES group and highest (96.5%) in the rural lower-middle SES group. Among subjects aged 6-20 years, anti-HAV seroprevalence was lowest in urban private school children (43.0%), followed by urban government school children (76.2%) and rural school children (96.5%) (P < 0.01). Within the high SES group, anti-HAV seroprevalence was 32.3% in subjects < 10 years and 51.7% in those aged 11-20 years. Until now Bangladesh has been deemed to have high endemicity for HAV.
CONCLUSION: The transition from high to intermediate HAV endemicity may be underway; high SES adolescents and adults remain particularly at risk of symptomatic illness. Preventive measures need consideration.
PMCID: PMC2764972  PMID: 19842225
Age groups; Hepatitis A virus; Hepatitis A virus seroprevalence; Anti-hepatitis A virus antibodies; Socioeconomic groups
2.  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.
PMCID: PMC3457436  PMID: 22855517
3.  Biomarkers for diagnosis of neonatal infections: A systematic analysis of their potential as a point-of-care diagnostics 
Journal of Global Health  2011;1(2):201-209.
Neonatal infections annually claim lives of 1.4 million neonates worldwide. Until now, there is no ideal diagnostic test for detecting sepsis and thus management of possible sepsis cases often depends on clinical algorithm leading to empirical treatment. This often results in unnecessary antibiotic use, which may lead to emergence of antibiotic resistance. Biomarkers have shown great promise in diagnosis of sepsis and guiding appropriate treatment of neonates. In this study, we conducted a literature review of existing biomarkers to analyze their status for use as a point-of-care diagnostic in developing countries.
PubMed and EMBASE database were searched with keywords, ‘infections’, ‘neonates’, and ‘biomarkers’ to retrieve potentially relevant papers from the period 1980 to 2010. Leading hospitals and manufacturers were communicated to inquire about the cost, laboratory requirements and current standing of biomarkers in clinical use.
The search returned 6407 papers on biomarkers; 65 were selected after applying inclusion and exclusion criteria. Among the studies, C-reactive protein (CRP), procalcitonin (PCT) and interleukin 6 (IL-6) were the most widely studied biomarkers and were considered to be most promising for diagnosing neonatal infections. About 90% of the studies were from developed countries; more than 50% were from Europe.
Extensive work is being performed to find the diagnostic and prognostic value of biomarkers. However, the methodologies and study design are highly variable. Despite numerous research papers on biomarkers, their use in clinical setting is limited to CRP. The methods for detection of biomarkers are far too advanced to be used at the community level where most of the babies are dying. It is important that a harmonized multi-site study is initiated to find a battery of biomarkers for diagnosis of neonatal infections.
PMCID: PMC3484777  PMID: 23198119
4.  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.
To devise treatment strategies for neonatal infections, the population-level incidence and antibiotic susceptibility of pathogens must be defined.
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.
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.
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 identifier: NCT00198627.
PMCID: PMC2841956  PMID: 19671016
5.  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.
PMCID: PMC3001156  PMID: 17591349
Delivery of healthcare; Health services; Care-seeking; Referral and consultation; Community health workers; Neonatal health; Maternal health; Bangladesh
6.  Feature tracking measurement of dyssynchrony from cardiovascular magnetic resonance cine acquisitions: comparison with echocardiographic speckle tracking 
Analysis of left ventricular (LV) mechanical dyssynchrony may provide incremental prognostic information regarding cardiac resynchronization therapy (CRT) response in addition to QRS width alone. Our objective was to quantify LV dyssynchrony using feature tracking post processing of routine cardiovascular magnetic resonance (CMR) cine acquisitions (FT-CMR) in comparison to speckle tracking echocardiography.
We studied 72 consecutive patients who had both steady-state free precession CMR and echocardiography. Mid-LV short axis CMR cines were analyzed using FT-CMR software and compared with echocardiographic speckle tracking radial dyssynchrony (time difference between the anteroseptal and posterior wall peak strain).
Radial dyssynchrony analysis was possible by FT-CMR in all patients, and in 67 (93%) by echocardiography. Dyssynchrony by FT-CMR and speckle tracking showed limits of agreement of strain delays of ± 84 ms. These were large (up to 100% or more) relative to the small mean delays measured in more synchronous patients, but acceptable (mainly <25%) in those with mean delays of >200 ms. Radial dyssynchrony was significantly greater in wide QRS patients than narrow QRS patients by both FT-CMR (radial strain delay 230 ± 94 vs. 77 ± 92* ms) and speckle tracking (radial strain delay 242 ± 101 vs. 75 ± 88* ms, all *p < 0.001).
FT-CMR delivered measurements of radial dyssynchrony from CMR cine acquisitions which, at least for the patients with more marked dyssynchrony, showed reasonable agreement with those from speckle tracking echocardiography. The clinical usefulness of the method, for example in predicting prognosis in CRT patients, remains to be investigated.
PMCID: PMC4016574  PMID: 24134158
Strain; Dyssynchrony; Echocardiography; Cardiovascular magnetic resonance
7.  Optimization of Multiple Pathogen Detection Using the TaqMan Array Card: Application for a Population-Based Study of Neonatal Infection 
PLoS ONE  2013;8(6):e66183.
Identification of etiology remains a significant challenge in the diagnosis of infectious diseases, particularly in resource-poor settings. Viral, bacterial, and fungal pathogens, as well as parasites, play a role for many syndromes, and optimizing a single diagnostic system to detect a range of pathogens is challenging. The TaqMan Array Card (TAC) is a multiple-pathogen detection method that has previously been identified as a valuable technique for determining etiology of infections and holds promise for expanded use in clinical microbiology laboratories and surveillance studies. We selected TAC for use in the Aetiology of Neonatal Infection in South Asia (ANISA) study for identifying etiologies of severe disease in neonates in Bangladesh, India, and Pakistan. Here we report optimization of TAC to improve pathogen detection and overcome technical challenges associated with use of this technology in a large-scale surveillance study. Specifically, we increased the number of assay replicates, implemented a more robust RT-qPCR enzyme formulation, and adopted a more efficient method for extraction of total nucleic acid from blood specimens. We also report the development and analytical validation of ten new assays for use in the ANISA study. Based on these data, we revised the study-specific TACs for detection of 22 pathogens in NP/OP swabs and 12 pathogens in blood specimens as well as two control reactions (internal positive control and human nucleic acid control) for each specimen type. The cumulative improvements realized through these optimization studies will benefit ANISA and perhaps other studies utilizing multiple-pathogen detection approaches. These lessons may also contribute to the expansion of TAC technology to the clinical setting.
PMCID: PMC3689704  PMID: 23805203
8.  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.
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.
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
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
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)
PMCID: PMC3646205  PMID: 23667339
9.  Left atrial reservoir function predicts atrial fibrillation recurrence after catheter ablation: a two-dimensional speckle strain study 
Predictors of atrial fibrillation (AF) recurrence after catheter ablation (CA) are not fully defined. We hypothesized that 2D left atrial (LA) regional strain maps would help identify abnormal atrial substrate that increases susceptibility to AF recurrence post-CA.
Methods and Results
Sixty-three patients (63±10 years, 60% male) underwent CA for symptomatic paroxysmal (75%) or persistent (25%) AF. Baseline LA mechanical function determined using speckle tracking echocardiography was compared between those with AF recurrence (AFR) and no recurrence post-CA. Bi-dimensional global and regional maps of LA wall velocity, strain, and strain rate (SR) were obtained during end ejection and early diastole. After 18±12 months of follow-up, 34 patients were free of AFR post-CA. There were no differences in clinical characteristics, LA and LV volumes, and Doppler estimates of LV diastolic function and filling pressures at baseline between patients with recurrent AF and those that maintained sinus rhythm. However, the LA emptying fraction (55±17% vs. 64±14%, p=0.04), global and regional systolic and diastolic strains, SR, and velocities were reduced in patients with recurrent AF. There was marked attenuation of peak LA lateral wall longitudinal strain (LS; 11±7% vs. 20±14%, p=0.007) and SR (0.9±0.4 vs. 1.3±0.6 s−1, p=0.01). Multivariate analysis revealed lateral wall LS (odds ratio=1.15, 95% CI=1.02–1.28, p=0.01) as an independent predictor of AFR.
Regional LA lateral wall LS is a pre-procedural determinant of AFR in patients undergoing CA, independent of LA enlargement. Characterization of atrial myocardial tissue properties by speckle tracking echo may aid the appropriate selection of adjunctive strategies and prognostication of patients undergoing CA.
PMCID: PMC3153595  PMID: 21424845
Atrial fibrillation; Catheter ablation; Strain and strain rate; Atrial size
10.  Streptococcus pneumoniae Serotype-2 Childhood Meningitis in Bangladesh: A Newly Recognized Pneumococcal Infection Threat 
PLoS ONE  2012;7(3):e32134.
Streptococcus pneumoniae is a leading cause of meningitis in countries where pneumococcal conjugate vaccines (PCV) targeting commonly occurring serotypes are not routinely used. However, effectiveness of PCV would be jeopardized by emergence of invasive pneumococcal diseases (IPD) caused by serotypes which are not included in PCV. Systematic hospital based surveillance in Bangladesh was established and progressively improved to determine the pathogens causing childhood sepsis and meningitis. This also provided the foundation for determining the spectrum of serotypes causing IPD. This article reports an unprecedented upsurge of serotype 2, an uncommon pneumococcal serotype, without any known intervention.
Methods and Findings
Cases with suspected IPD had blood or cerebrospinal fluid (CSF) collected from the beginning of 2001 till 2009. Pneumococcal serotypes were determined by capsular swelling of isolates or PCR of culture-negative CSF specimens. Multicenter national surveillance, expanded from 2004, identified 45,437 patients with suspected bacteremia who were blood cultured and 10,618 suspected meningitis cases who had a lumber puncture. Pneumococcus accounted for 230 culture positive cases of meningitis in children <5 years. Serotype-2 was the leading cause of pneumococcal meningitis, accounting for 20.4% (45/221; 95% CI 15%–26%) of cases. Ninety eight percent (45/46) of these serotype-2 strains were isolated from meningitis cases, yielding the highest serotype-specific odds ratio for meningitis (29.6; 95% CI 3.4–256.3). The serotype-2 strains had three closely related pulsed field gel electrophoresis types.
S. pneumoniae serotype-2 was found to possess an unusually high potential for causing meningitis and was the leading serotype-specific cause of childhood meningitis in Bangladesh over the past decade. Persisting disease occurrence or progressive spread would represent a major potential infection threat since serotype-2 is not included in PCVs currently licensed or under development.
PMCID: PMC3316528  PMID: 22479314
11.  Nosocomial Sepsis Risk Score for Preterm Infants in Low-resource Settings 
Journal of Tropical Pediatrics  2009;56(2):82-89.
Sepsis is a leading cause of mortality for neonates in developing countries; however, little research has focused on clinical predictors of nosocomial infection of preterm neonates in the low-resource setting. We sought to validate the only existing feasible score introduced by Singh et al. in 2003 and to create an improved score. In a secondary analysis of daily evaluations of 497 neonates ≤33 weeks gestational age admitted to a tertiary care NICU in Dhaka, Bangladesh, we tested the Singh score and then constructed and internally validated our own bedside predictive score. The Singh score had low sensitivity of 56.6% but good positive predictive value (PPV) of 78.1% in our sample. Our five-sign model requiring at least one clinical sign of infection (apnea, hepatomegaly, jaundice, lethargy and pallor) had an area under the receiver operating characteristic of 0.70, sensitivity of 77.1%, and PPV of 64.9%. Our clinical sepsis score is the first bedside clinical screen exclusively for hospitalized, very premature neonates in a low-resource setting, and warrants external validation.
PMCID: PMC3115678  PMID: 19622712
neonate; sepsis; prematurity; very low birth-weight; developing countries; nosocomial
12.  Evaluation of a Cluster-Randomized Controlled Trial of a Package of Community-Based Maternal and Newborn Interventions in Mirzapur, Bangladesh 
PLoS ONE  2010;5(3):e9696.
To evaluate a delivery strategy for newborn interventions in rural Bangladesh.
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.
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.
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 NCT00198627
PMCID: PMC2844410  PMID: 20352087
13.  Causes of Early Childhood Deaths in Urban Dhaka, Bangladesh 
PLoS ONE  2009;4(12):e8145.
Data on causes of early childhood death from low-income urban areas are limited. The nationally representative Bangladesh Demographic and Health Survey 2007 estimates 65 children died per 1,000 live births. We investigated rates and causes of under-five deaths in an urban community near two large pediatric hospitals in Dhaka, Bangladesh and evaluated the impact of different recall periods. We conducted a survey in 2006 for 6971 households and a follow up survey in 2007 among eligible remaining households or replacement households. The initial survey collected information for all children under five years old who died in the previous year; the follow up survey on child deaths in the preceding five years. We compared mortality rates based on 1-year recall to the 4 years preceding the most recent 1 year. The initial survey identified 58 deaths among children <5 years in the preceding year. The follow up survey identified a mean 53 deaths per year in the preceding five years (SD±7.3). Under-five mortality rate was 34 and neonatal mortality was 15 per thousand live births during 2006–2007. The leading cause of under-five death was respiratory infections (22%). The mortality rates among children under 4 years old for the two time periods (most recent 1-year recall and the 4 years preceding the most recent 1 year) were similar (36 versus 32). The child mortality in urban Dhaka was substantially lower than the national rate. Mortality rates were not affected by recall periods between 1 and 5 years.
PMCID: PMC2779865  PMID: 19997507
14.  Simplified Dosing of Gentamicin for Treatment of Sepsis in Bangladeshi Neonates 
Extended-interval dosing of gentamicin has several advantages over conventional multiple-daily dosing for the treatment of sepsis. The study was conducted to evaluate the pharmacokinetics of gentamicin for the treatment of neonatal sepsis in predetermined doses at 24- or 48-hour intervals, according to weight category, and to develop a simplified protocol for use in peripheral healthcare settings in developing countries. This prospective observational study was conducted among 59 neonates admitted to the Special Care Nursery at Dhaka Shishu Hospital, Bangladesh, with suspected sepsis and treated with antibiotics, including gentamicin. Intravenous dosing of gentamicin according to weight category was: 10 mg every 48 hours if the infant weighed <2,000 g (n=23), 10 mg every 24 hours if the infant weighed 2,000–2,249 g (n=12), or 13.5 mg every 24 hours if the infant weighed 2,500–3,000 g (n=24). Peak and trough concentrations of gentamicin and the presence of signs of nephrotoxicity and ototoxicity were determined. The mean±standard deviation peak concentration of gentamicin was 12.3±3.7 µg/mL in infants weighing <2,000 g, 9.6±3.1 µg/mL in infants 2,000–2,249 g, and 10.0±3.4 µg/mL in infants 2,500–3,000 g. Initial peak concentration of gentamicin was >12 µg/mL in 28.8% and initial trough concentration was >2 µg/mL in 6.8% of the subjects. No signs of nephrotoxicity or ototoxicity were detected. Favourable pharmacokinetic parameters found with the simplified dosing regimen suggest that it is safe for the treatment of neonatal sepsis.
PMCID: PMC2928089  PMID: 19902799
Aminoglycoside; Antibiotics; Gentamicin; Infection; Newborns; Observational studies; Pharmacokinetics; Prospective studies; Sepsis; Bangladesh
15.  Determining Gestational Age in a Low-resource Setting: Validity of Last Menstrual Period 
The validity of three methods (last menstrual period [LPM], Ballard and Dubowitz scores) for assessment of gestational age for premature infants in a low-resource setting was assessed, using antenatal ultrasound as the gold standard. It was hypothesized that LMP and other methods would perform similarly in determining postnatal gestational age. Concordance analysis was applied to data on 355 neonates of <33 weeks gestational age enrolled in a topical skin-therapy trial in a tertiary-care children's hospital in Bangladesh. The concordance coefficient for LMP, Ballard, and Dubowitz was 0.878, 0.914, and 0.886 respectively. LMP and Ballard underestimated gestational age by one day (±11) and 2.9 days (±7.8) respectively while Dubowitz overestimated gestational age by 3.9 days (±7.1) compared to ultrasound finding. LMP in a low-resource setting was a more reliable measure of gestational age than previously thought for estimation of postnatal gestational age of preterm infants. Ballard and Dubowitz scores are slightly more reliable but require more technical skills to perform. Additional prospective trials are warranted to examine LMP against antenatal ultrasound for primary assessment of neonatal gestational age in other low-resource settings.
PMCID: PMC2761790  PMID: 19507748
Gestational age; Last menstrual period; Neonatal health; Obstetrics; Bangladesh
16.  Identification of Serotype in Culture Negative Pneumococcal Meningitis Using Sequential Multiplex PCR: Implication for Surveillance and Vaccine Design 
PLoS ONE  2008;3(10):e3576.
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.
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.
This PCR approach, could improve ascertainment of pneumococcal serotype distributions, especially for meningitis in settings with high prior use of antibiotics.
PMCID: PMC2571985  PMID: 18974887
17.  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.
PMCID: PMC2754003  PMID: 17985826
Bathing; Emollient; Oil massage; Prospective studies; Skin; Bangladesh
18.  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.
PMCID: PMC1594770  PMID: 17021117
19.  Assessment of atrial regional and global electromechanical function by tissue velocity echocardiography: a feasibility study on healthy individuals 
The appropriate evaluation of atrial electrical function is only possible by means of invasive electrophysiology techniques, which are expensive and therefore not suitable for widespread use. Mechanical atrial function is mainly determined from atrial volumes and volume-derived indices that are load-dependent, time-consuming and difficult to reproduce because they are observer-dependent.
To assess the feasibility of tissue velocity echocardiography (TVE) to evaluate atrial electromechanical function in young, healthy volunteers.
Subjects and methods
We studied 37 healthy individuals: 28 men and nine women with a mean age of 29 years (range 20–47). Standard two-dimensional (2-D) and Doppler echocardiograms with superimposed TVE images were performed. Standard echocardiographic images were digitized during three consecutive cardiac cycles in cine-loop format for off-line analysis. Several indices of regional atrial electrical and mechanical function were derived from both 2-D and TVE modalities.
Some TVE-derived variables indirectly reflected the atrial electrical activation that follows the known activation process as revealed by invasive electrophysiology. Regionally, the atrium shows an upward movement of its walls at the region near the atrio-ventricular ring with a reduction of this movement towards the upper levels of the atrial walls. The atrial mechanical function as assessed by several TVE-derived indices was quite similar in all left atrium (LA) walls. However, all such indices were higher in the right (RA) than the LA. There were no correlations between the 2-D- and TVE-derived variables expressing atrial mechanical function. Values of measurement error and repeatability were good for atrial mechanical function, but only acceptable for atrial electrical function.
TVE may provide a simple, easy to obtain, reproducible, repeatable and potentially clinically useful tool for quantifying atrial electromechanical function.
PMCID: PMC550667  PMID: 15717936
atrial mechanical function; atrial electrical impulse spreading; left ventricular function; tissue Doppler echocardiography
20.  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.
PMCID: PMC308982  PMID: 14662944
21.  Rapid Identification and Antibiotic Susceptibility Testing of Salmonella enterica Serovar Typhi Isolated from Blood: Implications for Therapy 
Journal of Clinical Microbiology  2001;39(10):3583-3585.
The turnaround time (TAT) for Salmonella enterica serovar Typhi identification and reporting of the antibiotic susceptibility profile was determined for 391 cases of typhoid fever, using the lysis direct plating or lysis centrifugation method of blood culture along with rapid antimicrobial susceptibility testing. The TAT was more rapid (TAT for 90% of the patients [TAT90] = 30 h; TAT100 ≤ 67 h) than was possible with conventional methodologies and was equivalent to that reported previously using more advanced, costly technologies that are largely unavailable in developing countries. Antibiotic susceptibility profiles, determined by the rapid antimicrobial susceptibility testing method, of randomly selected 60 S. enterica serovar Typhi isolates were identical to those determined by overnight conventional testing. Preliminary assessment of the impact of the reduced TAT on physician practices revealed that initial empirical therapy was prescribed at the time of presentation in most cases (87 of 108 [81%]) despite awareness that the final report would be available on the following day. Patients treated empirically with first-line antibiotics and shown subsequently to be infected with a multidrug-resistant strain benefited most (8 cases), since therapy was changed appropriately on the following day. In an additional 21 cases, therapy with an appropriate antibiotic was initiated after culture results were available. Thus, in approximately one-fourth (29 of 108 [27%]) of the cases, a change in management to an agent active for treatment of the isolate was made after receipt of the test results. However, in no case was therapy changed from a second-line to a first-line agent, even if the isolate was reported on the day after presentation to be sensitive to first-line therapy (33 cases). Ways in which to utilize rapid-TAT result reporting in order to positively influence physicians' prescribing in Bangladesh are the subject of ongoing research.
PMCID: PMC88392  PMID: 11574576
22.  Antimicrobial Resistance and Serotype Distribution of Streptococcus pneumoniae Strains Causing Childhood Infections in Bangladesh, 1993 to 1997 
Journal of Clinical Microbiology  1999;37(3):798-800.
Three hundred sixty-two Streptococcus pneumoniae strains were isolated from children under 5 years of age at Dhaka Shishu (Children) Hospital from 1993 to 1997. The strains were isolated from blood (n = 105), CSF (n = 164), ear swab (n = 61), eye swab (n = 20), and pus (n = 12). Of the 362 isolates, 42 (11.6%) showed intermediate resistance (MIC, <0.1 μg/ml) and only 4 (1.1%) showed complete resistance (MIC, >2.0 μg/ml) to penicillin. Penicillin resistance exhibited a strong relationship with serotype 14; 47.8% of the penicillin-resistant strains belonged to this type. A remarkably high (64.1%) resistance to co-trimoxazole was observed, along with a significant increase during the time period studied; there was no relationship to capsular type. By way of contrast, penicillin resistance did not show any significant change during the study period. Resistance to chloramphenicol (2.2%) and erythromycin (1.1%) was rare. The high resistance to co-trimoxazole and its increasing trend demand elucidation of the clinical impact of pneumonia treatment by this antimicrobial and reconsideration of the World Health Organization recommendation for co-trimoxazole administration to children with community-acquired pneumonia at the health care worker level in Bangladesh.
PMCID: PMC84560  PMID: 9986858

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