Qadri F.,Center for Vaccine science |
Bhuiyan T.R.,Center for Vaccine science |
Svennerholm A.-M.,Gothenburg University
Vaccine | Year: 2013
Oral mucosal vaccines have great promise for generating protective immunity against intestinal infections for the benefit of large numbers of people especially young children. There however appears to be a caveat since these vaccines have to overcome the inbuilt resistance of mucosal surfaces and secretions to inhibit antigen stimulation and responses. Unfortunately, these vaccines are not equally immunogenic nor protective in different populations. When compared to industrialized countries, children living in developing countries appear to have lower responses, but the reasons for these lowered responses are not clearly defined. The most likely explanations relate to undernutrition, micronutrient deficiencies, microbial overload on mucosal surfaces, alteration of microbiome and microbolom and irreversible changes on the mucosa as well as maternal antibodies in serum or breast milk may alter the mucosal pathology and lower immune responses to interventions using oral vaccines. The detrimental effect of adverse environment and malnutrition may bring about irreversible changes in the mucosa of children especially in the first 1000 days of life from conception to after birth and up to two years of age. This review aims to summarize the information available on lowered immune responses to mucosal vaccines and on interventions that may help address the constraints of these vaccines when they are used for children living under the greatest stress and under harmful adverse circumstances. © 2012 Elsevier Ltd.
Ahmad S.M.,Center for Vaccine science |
Raqib R.,Center for Vaccine science |
Qadri F.,Center for Vaccine science |
Stephensen C.B.,University of California at Davis
Contemporary Clinical Trials | Year: 2014
In recent years, neonatal vitamin A supplementation is considered as an essential infant-survival intervention but the evidence is not conclusive. This randomized controlled clinical trial was conducted to evaluate the effect of vitamin A on immune competence in early infancy. Results would provide a mechanistic basis for understanding the effect of this intervention on infant survival. Within 2. days of birth, infants born at one maternity clinic located in a poor slum area of Dhaka city were supplemented with either 50,000. IU vitamin A or placebo. Live attenuated oral polio vaccine (OPV) and BCG vaccine were provided after supplementation. Infants also receive diphtheria, pertussis, tetanus (TT), hepatitis B (HBV) and Haemophilus influenzae B vaccines (pentavalent combination) along with OPV at 6, 10 and 14. weeks of age. Infant thymus size, anthropometry, feeding practice and morbidity data were collected at regular interval. Infant blood samples were collected to determine T-cell-receptor excision circle (TREC), total, naïve and memory T cells and mucosal targeting lymphocytes including Treg cells. TT-, HBV-, BCG- and OPV-specific T cell blastogenic, cytokine and plasma cell antibody responses were also measured. In 16 mo enrollment period, 306 newborns, equal number of boys and girls, were enrolled. ~. 95% completed the 4-month follow-up period. Baseline characteristics are presented here. Anthropometry and immune assays with fresh blood samples were completed immediately while stored samples were analyzed in single batches at the end of the trial. Connecting different aspects of immunological data in early infancy will help elucidate immune competence for protecting infection. © 2014 Elsevier Inc.
Khan W.A.,Center for Vaccine science |
Griffiths J.K.,Tufts University |
PLoS ONE | Year: 2013
Objective:To determine the clinical manifestations and outcome of shigellosis among children infected with different species of Shigella.Methods:We identified all patients <15 years infected with Shigella admitted to the icddr, b Dhaka hospital during one year. Study staff reviewed admission records and repeated the physical examinations and history of patients daily.Results:Of 792 children with shigellosis 63% were infected with S. flexneri, 20% with S. dysenteriae type 1, 10% with S. boydii, 4% with S. sonnei, and 3% with S. dysenteriae types 2-10. Children infected with S. dysenteriae type 1, when compared to children infected with other species, were significantly (P<0.05) more likely to have severe gastrointestinal manifestations: grossly bloody stools (78% vs. 33%), more stools in the 24 h before admission (median 25 vs. 11), and rectal prolapse (52% vs. 15%) - and extra-intestinal manifestations - leukemoid reaction (22% vs. 2%), hemolytic-uremic syndrome (8% vs. 1%), severe hyponatremia (58% vs. 26%) and neurologic abnormalities (24% vs. 16%). The overall fatality rate was 10% and did not differ significantly by species. In a multiple regression analysis young age, malnutrition, hyponatremia, lesser stool frequency, documented seizure, and unconsciousness were predictive of death.Conclusions:Both severe intestinal disease and extra-intestinal manifestations of shigellosis occur with infection by any of the four species of Shigella, but are most common with S. dysenteriae type 1. Among these inpatient children, the risk of death was high with infection of any of the four Shigella species. © 2013 Khan et al.
Fleckenstein J.,University of Washington |
Fleckenstein J.,Veterans Affairs Medical Center |
Sheikh A.,University of Washington |
Qadri F.,Center for Vaccine science
Expert Review of Vaccines | Year: 2014
Enterotoxigenic Escherichia coli (ETEC) are the most common bacterial pathogens causing diarrhea in developing countries where they lead to hundreds of thousands of deaths, mostly in children. These organisms are a leading cause of diarrheal illness in travelers to endemic countries. ETEC pathogenesis, and consequently vaccine approaches, have largely focused on plasmid-encoded enterotoxins or fimbrial colonization factors. To date these approaches have not yielded a broadly protective vaccine. However, recent studies suggest that ETEC pathogenesis is more complex than previously appreciated and involves additional plasmid and chromosomally encoded virulence molecules that can be targeted in vaccines. Here, we review recent novel antigen discovery efforts, potential contribution of these proteins to the molecular pathogenesis of ETEC and protective immunity, and the potential implications for development of next generation vaccines for important pathogens. These proteins may help to improve the effectiveness of future vaccines by making them simpler and possibly broadly protective because of their conserved nature. © 2014 Informa UK, Ltd.
Sarker A.R.,Center for Vaccine science |
Islam Z.,Center for Vaccine science |
Khan I.A.,Center for Vaccine science |
Saha A.,Center for Vaccine science |
And 5 more authors.
BMC Infectious Diseases | Year: 2013
Background: Cholera poses a substantial health burden to developing countries such as Bangladesh. In this study, the objective is to estimate the economic burden of cholera treatments incurred by households. The study was carried out in the context of a large vaccine trial in an urban area of Bangladesh.Methods: The study used a combination of prospective and retrospective incidence-based cost analyses of cholera illness per episode per household. A total of 394 confirmed cholera hospitalized cases were identified and treated in the study area during June-October 2011. Households with cholera patients were interviewed within 15 days after discharge from hospitals or clinics. To estimate the total cost of cholera illness a structured questionnaire was used, which included questions on direct medical costs, non-medical costs, and the indirect costs of patients and caregivers.Results: The average total household cost of treatment for an episode of cholera was US$30.40. Total direct and indirect costs constituted 24.6% (US$7.40) and 75.4% (US$23.00) of the average total cost, respectively. The cost for children under 5 years of age (US$21.50) was higher than that of children aged 5-14 years (US$17.50). The direct cost of treatment was similar for male and female patients, but the indirect cost was higher for males.Conclusion: Our study suggests that by preventing one cholera episode (3 days on an average), we can avert a total cost of 2,278.50 BDT (US$30.40) per household. Among medical components, medicines are the largest cost driver. No clear socioeconomic gradient emerged from our study, but limited demographic patterns were observed in the cost of illness. By preventing cholera cases, large production losses can be reduced. © 2013 Sarker et al.; licensee BioMed Central Ltd.
Leung D.T.,University of Utah |
Das S.K.,Center for Nutrition and Food Security |
Malek M.A.,Center for Nutrition and Food Security |
Faruque A.S.G.,Center for Nutrition and Food Security |
And 3 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2015
Respiratory and gastrointestinal infections are the top killers of children worldwide, and their co-occurrence is reported but not well understood. Our aim was to determine the risk factors for concurrent presentation of diarrhea and pneumonia (DP) in a resource-limited setting in Bangladesh. We used data from the Diarrheal Disease Surveillance System of the icddr,b Dhaka Hospital to identify children < 60 months of age with diarrhea and concurrent pneumonia, defined as a history of cough, an abnormal lung examination, and tachypnea. For the years 1996-2007, out of total 14,628 diarrheal patients surveyed, there were 607 (4%) patients who satisfied criteria for pneumonia. Those with DP had a higher mortality rate (4% versus 0.05%, odds ratio [OR] = 86, 95% confidence interval [CI] = 26-286) and a longer hospital stay (mean 84 versus 26 hours, difference 58 hours, 95% CI = 52-64 hours) than those with diarrhea (D) only. In multivariable logistic regression comparing cases (N = 607) with controls matched for month and year of admission at a ratio of 1:3 (N = 1,808), we found that DP was associated with younger age, male gender, severe acute malnutrition (SAM), less maternal education, lower family income, and lack of current breast-feeding history. Copyright © 2015 by The American Society of Tropical Medicine and Hygiene.
Ahmad S.M.,Center for Vaccine science |
Hossain M.I.,Center for Nutrition and Food Security |
Bergman P.,Karolinska University Hospital |
Kabir Y.,University of Dhaka |
Raqib R.,Center for Vaccine science
Trials | Year: 2015
Because of limited impact on infant morbidity, mortality, and vitamin A status, the new guideline of the World Health Organization (WHO) does not recommend postpartum vitamin A supplementation (VAS) as a public health intervention in developing countries. However, breast milk contains numerous immune-protective components that are important for infant immune development, and several of these components are regulated by vitamin A. Methods/design: Postpartum women are being enrolled within 3 days (d) of delivery at a maternity clinic located in a slum area of Dhaka city and randomized to one of four postpartum VAS regimens (32/group, total 128). The regimens are as follows: Group 1: 200,000 IU VAS at <3 d and placebo at 6 weeks postpartum; Group 2: placebo at <3 d and 200,000 IU VAS at 6 weeks postpartum; Group 3: 200,000 IU VAS, both at <3 d and 6 weeks postpartum; Group 4: placebo, both at <3 d and 6 weeks postpartum. Breast milk samples at <3 d (before supplementation) and 4 months postpartum will be used to measure vitamin A and bioactive compounds. Infant blood samples at 2 and 4 months of age will be used to measure vitamin A, as well as innate and vaccine-specific immune responses. Dietary, anthropometric, and morbidity data are also being collected. Discussion: This is the first placebo-controlled randomized clinical trial of postnatal vitamin A supplementation to investigate the key bioactive compounds in breast milk, important for infant immunity, in relation to dose and time point of postpartum supplementation and whether such maternal supplementation improves infant immune status during the critical period of early infancy. Trial registration: ClinicalTrials.gov: NCT02043223, 5 December 2013. © Ahmad et al.; licensee BioMed Central.
Seed K.D.,Howard Hughes Medical Institute |
Faruque S.M.,International Center for Diarrhoeal Disease Research |
Mekalanos J.J.,Harvard University |
Calderwood S.B.,Harvard University |
And 2 more authors.
PLoS Pathogens | Year: 2012
The Vibrio cholerae lipopolysaccharide O1 antigen is a major target of bacteriophages and the human immune system and is of critical importance for vaccine design. We used an O1-specific lytic bacteriophage as a tool to probe the capacity of V. cholerae to alter its O1 antigen and identified a novel mechanism by which this organism can modulate O antigen expression and exhibit intra-strain heterogeneity. We identified two phase variable genes required for O1 antigen biosynthesis, manA and wbeL. manA resides outside of the previously recognized O1 antigen biosynthetic locus, and encodes for a phosphomannose isomerase critical for the initial step in O1 antigen biosynthesis. We determined that manA and wbeL phase variants are attenuated for virulence, providing functional evidence to further support the critical role of the O1 antigen for infectivity. We provide the first report of phase variation modulating O1 antigen expression in V. cholerae, and show that the maintenance of these phase variable loci is an important means by which this facultative pathogen can generate the diverse subpopulations of cells needed for infecting the host intestinal tract and for escaping predation by an O1-specific phage. © 2012 Seed et al.
Alam M.J.,Center for Vaccine science |
Rashid M.M.,Center for Vaccine science |
Kabir Y.,University of Dhaka |
Raqib R.,Center for Vaccine science |
Ahmad S.M.,Center for Vaccine science
Vaccine | Year: 2015
In a cross sectional study, we show that infants who received single dose of live attenuated OPV and BCG vaccines within 48. h of birth, have higher excretion of human cathelicidin LL37 (. p<. 0.05) in stool at 6. wk of age. This response remained unchanged in multivariate analysis after adjusting for sex, mode of delivery, infant age, mother age birth weight and breast milk feeding pattern. This analysis also reveals that irrespective of vaccination, girl infants have higher human-beta-defencin2 (HBD2) and exclusively breastfed infants have higher total and anti-polio specific IgA to all three subtypes in stool (. p<. 0.05). However, vaccination induces anti-polio IgA responses only to infants who are exclusively breastfed. Thus on-birth live attenuated vaccination may provide non-specific beneficial effect against infections while exclusive breastfeeding enhance protection by boosting vaccine induced IgA. The result also suggests that in polio endemic area, exclusive breastfeeding may be sufficient for mucosal anti-polio responses during early infancy. © 2014 Elsevier Ltd.
Hasnain M.G.,Center for Vaccine Science |
Ghosh P.,Center for Vaccine Science |
Baker J.,Center for Vaccine Science |
Mondal D.,Center for Vaccine Science
American Journal of Tropical Medicine and Hygiene | Year: 2014
The attack phase of the visceral leishmaniasis (VL) elimination program in Bangladesh aims to decrease the burden of VL incidence from close to 20 cases to less than one case per 10, 000 at sub-district level. The consolidation phase will aim to confirm no increase in VL in endemic areas through active surveillance. During this phase, a reliable diagnostic tool for mass screening is required. Here, we report the diagnostic sensitivity and specificity of a filter paperbased agglutination test (FP-DAT) for diagnosis of VL in patients admitted to an upazila health complex in Mymensingh, a VL-endemic region of Bangladesh. The sensitivity of both the conventional direct agglutination test (DAT) and FP-DAT were 100% and 96%, respectively. The specificity of both assays was 100%. However, when the performances of the two assays were compared using McNamar's test, neither the sensitivity nor the specificity of the FP-DAT differed significantly from conventional DAT. Copyright © 2014 by The American Society of Tropical Medicine and Hygiene.