Epidemiology of Typhoid and Paratyphoid: Implications for Vaccine Policy.

BACKGROUND: Typhoid and paratyphoid remain the most common bloodstream infections in many resource-poor settings. The World Health Organization recommends typhoid conjugate vaccines for country-specific introduction, but questions regarding typhoid and paratyphoid epidemiology persist, especially regarding their severity in young children. METHODS: We conducted enteric fever surveillance in Bangladesh from 2004 through 2016 in the inpatient departments of 2 pediatric hospitals and the outpatient departments of 1 pediatric hospital and 1 private consultation clinic. Blood cultures were conducted at the discretion of the treating physicians; cases of culture-confirmed typhoid/paratyphoid were included. Hospitalizations and durations of hospitalizations were used as proxies for severity in children <12 years old. RESULTS: We identified 7072 typhoid and 1810 paratyphoid culture-confirmed cases. There was no increasing trend in the proportion of paratyphoid over the 13 years. The median age in the typhoid cases was 60 months, and 15% of the cases occurred in children <24 months old. The median age of the paratyphoid cases was significantly higher, at 90 months (P < .001); 9.4% were in children <24 months old. The proportion of children (<12 years old) hospitalized with typhoid and paratyphoid (32% and 21%, respectively) decreased with age; there was no significant difference in durations of hospitalizations between age groups. However, children with typhoid were hospitalized for longer than those with paratyphoid. CONCLUSIONS: Typhoid and paratyphoid fever are common in Dhaka, including among children under 2 years old, who have equivalent disease severity as older children. Early immunization with typhoid conjugate vaccines could avert substantial morbidity, but broader efforts are required to reduce the paratyphoid burden.

Designing Comprehensive Public Health Surveillance for Enteric Fever in Endemic Countries: Importance of Including Different Healthcare Facilities.

Background: Designing comprehensive surveillance to generate credible burden estimates of enteric fever in an endemic country can be challenging because care-seeking behavior is complex and surveillance in different healthcare facilities may lead to documentation of different epidemiological characteristics. Methods: We conducted retrospective surveillance in 3 healthcare facilities to identify culture-confirmed enteric fever cases in Dhaka, Bangladesh, from January 2012 through December 2016. The study settings included (1) hospital in-patient department (IPD), (2) hospital out-patient department (OPD), and (3) private consultation center OPD. We analyzed the cases to understand their distribution, age ranges, and antibiotic susceptibility patterns across the settings. Results: Of the 1837 culture-confirmed enteric fever cases, 59% (1079 of 1837) were OPD cases. Children with enteric fever hospitalized in the IPDs were younger than children seeking care at the hospital OPD (median age: 45 vs 60 months) or private OPD (median age: 45 vs 72 months). Multidrug resistance rates were slightly higher in hospital IPD cases than in private OPD cases (26% vs 24%). Conclusions: In each facility, we identified different epidemiological characteristics, and lack of consideration of any of these may result in misinterpretation of disease burden, identification of different age groups, and/or antibiotic susceptibility patterns.

Epidemiology and risk factors for pneumonia severity and mortality in Bangladeshi children <5 years of age before 10-valent pneumococcal conjugate vaccine introduction.

BACKGROUND: Pneumonia is the leading infectious cause of morbidity and mortality in young children in Bangladesh. We present the epidemiology of pneumonia in Bangladeshi children <5 years before 10-valent pneumococcal conjugate vaccine introduction and investigate factors associated with disease severity and mortality. METHODS: Children aged 2-59 months admitted to three Bangladeshi hospitals with pneumonia (i.e., cough or difficulty breathing and age-specific tachypnea without danger signs) or severe pneumonia (i.e., cough or difficulty breathing and ≥1 danger signs) were included. Demographic, clinical, laboratory, and vaccine history data were collected. We assessed associations between characteristics and pneumonia severity and mortality using multivariable logistic regression. RESULTS: Among 3639 Bangladeshi children with pneumonia, 61% had severe disease, and 2% died. Factors independently associated with severe pneumonia included ages 2-5 months (adjusted odds ratio [aOR] 1.60 [95% CI: 1.26-2.01]) and 6-11 months (aOR 1.31 [1.10-1.56]) relative to 12-59 months, low weight for age (aOR 1.22 [1.04-1.42]), unsafe drinking water source (aOR 2.00 [1.50-2.69]), higher paternal education (aOR 1.34 [1.15-1.57]), higher maternal education (aOR 0.74 [0.64-0.87]), and being fully vaccinated for age with pentavalent vaccination (aOR 0.64 [0.51-0.82]). Increased risk of pneumonia mortality was associated with age <12 months, low weight for age, unsafe drinking water source, lower paternal education, disease severity, and having ≥1 co-morbid condition. CONCLUSIONS: Modifiable factors for severe pneumonia and mortality included low weight for age and access to safe drinking water. Improving vaccination status could decrease disease severity.

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

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

Improving access to family planning services through community pharmacies: Experience from The Challenge Initiative in three counties in Kenya.

Pharmacies play a vital role in improving access to family planning (FP) services in urban areas. They complement the resource-limited public health system and are viewed as key access points for contraceptives among young people (10-24 years) and the general population. The Challenge Initiative East Africa (TCI EA), in collaboration with the health management teams of Mombasa, Kilifi, and the Nairobi counties in Kenya and the Kenya Pharmaceutical Association (KPA) piloted an innovative public-private partnership (PPP) engagement to improve access to quality FP services offered at pharmacies in urban areas. The pilot project built the capacity of pharmacists, strengthened the referral system to public health facilities, and made FP data accessible and visible to drive informed decision-making. This paper describes the strategies employed and the outcomes. The initiative targeted 150 pharmacies across the three counties from June 2019 to December 2020 period. Our assessment shows that this intervention delivered FP commodities to 43,632 FP client visits; 71% for female clients and 21% for males. Adjusting for couple years of protection and seasonality, this translates to about 2,800 annual FP clients obtaining modern contraception in a 12-month period, including 48% injectables, 25% oral contraception, 24% emergency contraception, and 3% condoms. The majority of clients (75%) were older than 24 years, 21% were 20-24 years, 3% were 15-19 years, and 1% were less than 15 years. In addition, 327 clients were referred to a public sector facility for other methods. This intervention demonstrates the potential of pharmacies in contributing to FP uptake and provides a framework for improving access to quality FP services by pharmacies. There is potential to scale such an approach beyond the 3 counties, given the involvement and reach of KPA and the Ministry of Health (MoH) health management teams.

Pediatric Hypertension: Parental Perception and Knowledge.

The prevalence of hypertension (HTN) among youngsters has increased recently. Often, it is underrecognized owing to a lack of routine blood pressure measurement in many health centers, partly due to the unavailability of instruments and possibly because of this perception that it is not the foremost problem in children. There is less information about the parental perception of childhood HTN from Bangladesh. We aimed to conduct this survey among parents to see the perception and knowledge about this childhood HTN, which can be served as a baseline for future reference. This cross-sectional study was carried out in Dr. MR Khan Shishu Hospital and ICH from April 2021 to September 2021 over 6 months. Parents who visited our hospital, both in outpatient and inpatient, for their children aged (3 years-17 years) were included in this study. Parents who did not give permission were excluded. Purposive sampling was done during the study period. Parents were interviewed with a structured questionnaire. Parents' educational status and the idea about HTN in children were recorded. The data were analyzed and expressed as frequency and percentage. A total of 352 respondents were interviewed with a mean age of 28 ± 11 years. Among these respondents, 187 (53.2%) were male, and 165 (46.8%) were female. In this study, most of the participant parents are literate; only a negligible proportion, 5.6%, are illiterate. Eighty-nine percent of participants know high blood pressure is HTN and 83.5% know HTN can be detected by measuring BP. Among the participants, 83% think children do not develop HTN, and only 17% responded that children could develop HTN. This study offers insight into parents' lack of awareness of childhood HTN. Hence, proper knowledge and understanding of pediatric HTN play a crucial role in early detection and management.

Trends in antimicrobial resistance amongst Salmonella Paratyphi A isolates in Bangladesh: 1999-2021.

BACKGROUND: Typhoid and paratyphoid remain common bloodstream infections in areas with suboptimal water and sanitation infrastructure. Paratyphoid, caused by Salmonella Paratyphi A, is less prevalent than typhoid and its antimicrobial resistance (AMR) trends are less documented. Empirical treatment for paratyphoid is commonly based on the knowledge of susceptibility of Salmonella Typhi, which causes typhoid. Hence, with rising drug resistance in Salmonella Typhi, last-line antibiotics like ceftriaxone and azithromycin are prescribed for both typhoid and paratyphoid. However, unlike for typhoid, there is no vaccine to prevent paratyphoid. Here, we report 23-year AMR trends of Salmonella Paratyphi A in Bangladesh. METHODS: From 1999 to 2021, we conducted enteric fever surveillance in two major pediatric hospitals and three clinics in Dhaka, Bangladesh. Blood cultures were performed at the discretion of the treating physicians; cases were confirmed by culture, serological and biochemical tests. Antimicrobial susceptibility was determined following CLSI guidelines. RESULTS: Over 23 years, we identified 2,725 blood culture-confirmed paratyphoid cases. Over 97% of the isolates were susceptible to ampicillin, chloramphenicol, and cotrimoxazole, and no isolate was resistant to all three. No resistance to ceftriaxone was recorded, and >99% of the isolates were sensitive to azithromycin. A slight increase in minimum inhibitory concentration (MIC) is noticed for ceftriaxone but the current average MIC is 32-fold lower than the resistance cut-off. Over 99% of the isolates exhibited decreased susceptibility to ciprofloxacin. CONCLUSIONS: Salmonella Paratyphi A has remained susceptible to most antibiotics, unlike Salmonella Typhi, despite widespread usage of many antibiotics in Bangladesh. The data can guide evidence-based policy decisions for empirical treatment of paratyphoid fever, especially in the post typhoid vaccine era, and with the availability of new paratyphoid diagnostics.

Long COVID-19 Syndrome: Insights From a Major Tertiary Center in the UK on Who Is at Greater Risk.

INTRODUCTION: The COVID-19 pandemic triggered the unprecedented 'long COVID' crisis, with persistent symptoms beyond two months post-infection. This study explores the nexus between long COVID symptoms, patient demographics such as age, gender, and smoking, and clinical factors like vaccination, disease severity, and comorbidities. METHODS: A retrospective analysis of records was conducted between September 2021 and December 2022. The analysis covered adults with confirmed COVID-19 diagnoses. Data encompassed demographics, medical history, vaccination, disease severity, hospitalization, treatments, and post-COVID symptoms, analyzed using logistic regression. RESULTS: Among 289 participants, the average age was 51.51 years. Around 62.6% were females, and 93% received the COVID-19 vaccination, i.e., primarily the mRNA vaccine (48.4%) and the adenovirus vector-based vaccine (34.8%). Reinfections occurred in 11.76% of cases. Disease severity varied, with 75% having mild, 15% having moderate, and 10% having severe infections. Hospitalization rates were significant (25.6%), including 10.7% requiring intensive care. Thirteen distinct post-COVID symptoms were reported. Fatigue, shortness of breath upon exertion, and brain fog emerged as the most prevalent symptoms. Notably, females exhibited higher symptom prevalence. Significant correlations were established between higher BMI and smoking with augmented symptomatology. Conversely, a link between booster doses and symptom reduction was discerned. Using multinomial regression analysis, gender and smoking were identified as predictors of post-COVID-19 symptoms. CONCLUSION: The study underscores obesity, smoking, and the female gender's impact on long COVID symptoms; boosters show promise in alleviation. Respiratory pathology might underlie persistent symptoms in cases with radiological abnormalities and abnormal spirometry. Findings contribute to risk stratification, intervention strategies, and further research.

Assessment of the Link of ABCB1 and NR3C1 gene polymorphisms with the prednisolone resistance in pediatric nephrotic syndrome patients of Bangladesh: A genotype and haplotype approach.

Introduction: Nephrotic syndrome is a common pediatric kidney disease. Investigations on several genetic polymorphisms revealed an inconsistent influence on the resistance of patients to steroids. Objectives: This study aimed to identify the association of ABCB1 (1236C > T, 2677G > T, 3435C > T), NR3C1 (rs10482634, rs6877893), and CYP3A5 (CYP3A5*3) gene polymorphism as well as sociodemographic and clinicopathological parameters with the risk of developing prednisolone resistance in pediatric patients with nephrotic syndrome. Methods: A case-control analysis was performed on 180 nephrotic syndrome patients. Among them, 30 patients were classified as prednisolone resistant group, and 150 were classified as prednisolone sensitive group. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: No significant association of 1236C > T polymorphism with the risk of prednisolone resistance (p > 0.05) was found. The GT heterozygous of 2677G > T was found to be significantly associated with the development of prednisolone resistance (OR = 3.9, p = 0.034). In the case of 3435C > T, a statistically significant association was observed in TC heterozygous and TT mutant homozygous genotypes (OR = 0.38, p = 0.047; OR = 3.06, p = 0.038, respectively) with prednisolone resistance. For rs10482634 polymorphism, the AG heterozygous and AG+GG genotypes were significantly linked with prednisolone resistance (OR = 2.40, p = 0.033; OR = 2.36, p = 0.034, respectively). We found no association with the risk of prednisolone resistance with rs6877893 and CYP3A5*3 polymorphism (p > 0.05). CTC and TGT haplotypes of ABCB1 and GA haplotype of NR3C1 were also associated with the increased risk of pediatric prednisolone resistance (OR = 4.47, p = 0.0003; OR = 2.71, p = 0.03; and OR = 4.22, p = 0.022, consecutively). We also observed the correlation of different sociodemographic and clinicopathological factors with prednisolone resistance in pediatric nephrotic syndrome. Conclusion: Our findings showed a significant association of ABCB1 and NR3C1 gene polymorphisms with prednisolone resistant pediatric nephrotic syndrome.

Pediatric Continuous Renal Replacement Therapy (PCRRT) expert committee recommendation on prescribing prolonged intermittent renal replacement therapy (PIRRT) in critically ill children.

INTRODUCTION: Recently, prolonged intermittent renal replacement therapies (PIRRT) have emerged as cost-effective alternatives to conventional CRRT and their use in the pediatric population has started to become more prominent. However, there is a lack of consensus guidelines on the use of PIRRT in pediatric patients in an intensive care setting. METHODS: A literature search was performed on PubMed/Medline, Embase, and Google Scholar in conjunction with medical librarians from both India and the Cleveland Clinic hospital system to find relevant articles. The Pediatric Continuous Renal Replacement Therapy workgroup analyzed all articles for relevancy, proposed recommendations, and graded each recommendation for their strength of evidence. RESULTS: Of the 60 studies eligible for review, the workgroup considered data from 37 studies to formulate guidelines for the use of PIRRT in children. The guidelines focused on the definition, indications, machines, and prescription of PIRRT. CONCLUSION: Although the literature on the use of PIRRT in children is limited, the current studies give credence to their benefits and these expert recommendations are a valuable first step in the continued study of PIRRT in the pediatric population.

Invasive Pneumococcal Infections in Children with Nephrotic Syndrome in Bangladesh.

INTRODUCTION: Children with nephrotic syndrome are susceptible to invasive bacterial infections. In this study, we aimed to: (1) determine the pathogens associated with infections in children with nephrotic syndrome and (2) describe antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae to guide evidence-based treatment and prevention policies. METHODS: From June 2013 to March 2015, we collected blood and/or ascitic fluid from children hospitalized with nephrotic syndrome and suspected bacterial disease in the largest pediatric hospital of Bangladesh. We cultured all samples and performed polymerase chain reaction (PCR) and immunochromatographic test on ascitic fluid for detection of S. pneumoniae. Pneumococcal isolates were tested for antibiotic susceptibility using disc diffusion and serotyped using Quellung reaction and PCR. RESULTS: We identified 1342 children hospitalized with nephrotic syndrome. Among them, 608 children had suspected bacterial disease from whom blood and/or ascitic fluid were collected. A pathogen was identified in 8% (48/608) of cases, 94% (45/48) of which were S. pneumoniae. Most (73%, 33/45) pneumococcal infections were identified through culture of blood and ascitic fluid and 27% (12/45) through immunochromatographic test and PCR of ascitic fluid. In total, 24 different pneumococcal serotypes were detected; 51% are covered by PCV10 (+6A), 53% by PCV13 and 60% by PPSV23. All pneumococcal isolates were susceptible to penicillin. CONCLUSIONS: Because S. pneumoniae was the primary cause of invasive infections, pneumococcal vaccines may be considered as a preventive intervention in children with nephrotic syndrome. Additionally, penicillin can be used to prevent and treat pneumococcal infections in children with nephrotic syndrome in Bangladesh.

Fractional excretion of magnesium, a marker of aminoglycoside induced nephrotoxicity in neonates.

Aminoglycoside is a widely used antibiotic in neonatal age group at hospital setting in Bangladesh. It has underlying side effect and toxicity which is mostly unseen and ignored. The aim of the study was to evaluate the nephrotoxic effect of aminoglycoside in neonates. This study was conducted in fifty hospital admitted neonates of Dhaka Shishu Hospital from January 2012 to December 2013. Serum creatinine, blood urea nitrogen, and fractional excretion of magnesium (FEMg) were measured before starting and after seven days of aminoglycoside treatment. Statistical analyses of the results were obtained by window-based computer software devised with Statistical Packages for Social Sciences (SPSS version 16). Statistical tests for significance of difference were done using Student's paired t-test. Serum creatinine and blood urea nitrogen were not significantly changed after drug administration (P = 0.092, P = 0.247, respectively). None of the neonates in our study group had abnormal serum creatinine and blood urea nitrogen after aminoglycoside therapy. FEMg was significantly increased (P <0.001) after aminoglycoside treatment. In this study, conventional renal function test such as blood urea and serum creatinine did not reflect the nephrotoxicity of aminoglycoside. However, a biomarker of tubular damage, FEMg detected nephrotoxicity of aminoglycoside therapy.

Correlation of fractional excretion of magnesium with steroid responsiveness in children with nephrotic syndrome.

Steroid-resistant nephrotic syndrome (SRNS) patients are candidates for other alter-native drug regimes, and the non-responsiveness to steroid is more common among glomerulo-nephritides other than minimal change disease. Without performing biopsy and proper renal histology, progression of the disease cannot be assessed. Fractional excretion of magnesium (FE Mg) has been found to correlate directly with various renal histologies. The aim of this study is to evaluate the relationship of FE Mg in children with the histological pattern in SRNS. In this prospective observational study, 40 children of nephrotic syndrome, both with the first episode as well as relapse, aged 1-12 years were included in the study. Of them, 20 were steroid-responsive cases and 20 were steroid-resistant cases. FE Mg was determined in all the patients and renal histology was performed in the steroid-resistant cases. A correlation was found between FE Mg and renal histology. Data were analyzed in SPSS program version-16. Comparison of two groups was performed by the Fisher exact test and unpaired t test. P-value less than 0.05 were considered to be significant. The results of histo-pathology showed that the mean difference in FE Mg was significant (P <0.001), as FE Mg was 7.0 ± 2.3% in mesangiocapillary glomerulonephritis, 6.9 ± 1.3% in focal segmental glomerulosclerosis, 4.7 ± 0.6% in immunoglobulin M nephropathy, 4.5 ± 1.2% in focal segmental proliferative glomerulo-nephritis, 4.4 ± 1.6% in minimal change disease, 4.2 ± 0.4% in diffuse mesangial proliferative glome-rulonephritis and 3.8 ± 1.3% in mesangial proliferative glomerulonephritis. There was a statistically significant difference between FE Mg in steroid-resistant nephrotic syndrome (4.9 ± 1.9) and steroid-responsive syndrome (1.2 ± 0.3). FE Mg is a simple, minimally invasive screening marker for SRNS, and is an early predictor of clinical outcome. It can be considered as an initial investigation where biopsy cannot be performed or indications are not clear.

Markers of progenitor cell recruitment and differentiation rise early during ischemia and continue during resuscitation in a porcine acute ischemia model.

Clinical administration of bone marrow-derived stem cells in the setting of acute myocardial infarction (AMI) leads to improved left ventricular ejection fraction. Thymosin beta-4 (TB4) and vascular endothelial growth factor (VEGF) are linked to adult epicardial progenitor cell mobilization and neovascularization and is cardioprotective after myocardial ischemia. This study investigated the time course of TB4 and VEGF during AMI, cardiac arrest, and resuscitation. Fifteen anesthetized and instrumented domestic swine underwent balloon occlusion of the proximal left anterior descending coronary artery. During occlusion, venous blood samples were collected from the right atrium at 5-min intervals until 15 min after the onset of cardiopulmonary resuscitation (CPR). Plasma levels of TB4, VEGF, and matrix metalloproteinase-9 (MMP-9, selected as a marker for remodeling and repair) were measured by ELISA. Generalized linear mixed models were employed to model the time-dependent change in plasma concentration. All variables were natural log transformed, except TB4 values, to normalize distributions. Fifteen animals successfully underwent balloon occlusion of the left anterior descending coronary artery and samples were collected from these subjects. The average onset of spontaneous ventricular fibrillation was 28 min. TB4, VEGF, and MMP-9 demonstrated a statistically significant, time-dependent increase in concentration during ischemia. Following arrest and throughout the first 15 min of resuscitation, MMP-9 had an unchanged rate of rise when compared with the prearrest, ischemic period, with VEGF showing a deceleration in its time-dependent concentration trajectory and TB4 demonstrating an acceleration. Endogenous TB4 and VEGF increase shortly after the onset of AMI and increase through cardiac arrest and resuscitation in parallel to remodeling proteases. These markers continue to rise during successful resuscitation and may represent an endogenous mechanism to recruit undifferentiated stem cells to areas of myocardial injury.

Endothelin-1 attenuates the hemodynamic response to exogenous epinephrine in a porcine ischemic ventricular fibrillation cardiac arrest model.

Endothelin-1 (ET-1) increases in the ischemically induced ventricular fibrillation (VF) swine model of cardiac arrest and affects outcome by potentially attenuating the hemodynamic response to epinephrine. Fifty-one swine underwent percutaneous left anterior descending occlusion. Seven minutes postonset of ischemic VF, cardiopulmonary resuscitation (CPR) was initiated. If VF persisted after 3 shocks, 1 mg of epinephrine was given. ET-1 (collected at baseline and every 5 min until VF onset) was assayed with ELISA. Bayesian multivariate logistic regression analysis compared peak ET-1 levels with the binary outcome of a positive coronary perfusion pressure response of >20 mmHg following epinephrine. Sixteen animals (31%) failed to achieve a positive response. Restoration of spontaneous circulation (ROSC) was observed in 1/16 (6.3%) of epinephrine nonresponders and 20/35 (57.1%) of epinephrine responders (P = 0.0006). The median peak ET-1 level was 2.71 pg/mL [interquartile range (IQR) 1.06-4.40] in nonresponders and 1.69 pg/mL (IQR 0.99-2.35) in responders. ET-1 levels were inversely associated with epinephrine response with a median posterior odds ratio (OR) of a coronary perfusion pressure response of 0.72 (95% confidence interval [CI] 0.48-1.06) for each one-unit increase in ET-1 and a probability that the associated OR is <1 of 0.95. Peak ET-1 levels predict a lack of a hemodynamic response to epinephrine during treatment of cardiac arrest during ischemic VF.

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.

Might gene therapy offer symptomatic relief for patients with 'no option' angina?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the use of gene therapy could relieve angina symptoms in patients who are not amenable to conventional revascularisation strategies. Altogether 60 papers were identified using the search below. Seven papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of the papers are tabulated. We conclude that, gene therapy for ischaemic heart disease is in its infancy with evaluation trials of novel vectors, delivery methods and targeted patient population. The initial results from the randomised clinical trials using gene therapy for severe CHD are interesting but clear benefits are yet to be demonstrated. Longer term outcomes from the AGENT trial and VIVA trials are awaited.

Invasive Haemophilus influenzae type B diseases in Bangladesh, with increased resistance to antibiotics.

OBJECTIVE: To determine the prevalence, age-group distribution, serotype, and antibiotic susceptibility patterns of invasive Haemophilus influenzae type b (Hib) isolates in Bangladeshi children because data regarding Hib diseases in developing countries are scarce, which has led to delay of the introduction of Hib vaccine in these countries. METHODS: Children diagnosed with meningitis (n = 1412) and pneumonia (n = 2434) were enrolled in this surveillance study for Hib invasive diseases. Cerebrospinal fluid (CSF) and blood specimens, and the subsequent isolates, were processed using standard procedures. RESULTS: During 1993 to 2003, 455 H influenzae strains were isolated from patients with meningitis (n = 425) and pneumonia (n = 30), and an additional 68 Hib meningitis cases were detected by latex agglutination (LA) testing. Overall, 35% of pyogenic meningitis cases were a result of H influenzae, 97.1% of which were Hib. Most (91.4%) cases occurred during the first year of life. Resistance to ampicillin, chloramphenicol, and cotrimoxazole was 32.5%, 21.5%, and 49.2%, respectively. There was a trend toward increasing resistance for all three drugs. Resistance to ampicillin and chloramphenicol was almost universally coexistent and was associated with increased sequelae compared with the patients infected with susceptible strains (31% [23/75] vs 11% [21/183]; P <.001). CONCLUSION: Hib is the most predominant cause of meningitis in young Bangladeshi children. Resistance to ampicillin and chloramphenicol and the high cost of third-generation cephalosporin highlight the importance of disease prevention through vaccination against Hib.

Are prophylactic beta-blockers of benefit in reducing the incidence of AF following coronary bypass surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether prophylactic beta-blockers effectively reduces the incidence of atrial fibrillation post-cardiac surgery. Altogether 113 papers were found using the reported search, of which 8 represented the best evidence on this topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses were tabulated. We conclude that prophylactic beta-blockers clearly reduce the incidence of AF with a number needed to treat of only seven to prevent one episode of AF. The optimal beta-blocker or the benefits to patients with impaired ejection fraction are less clear.