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Haque U.,International Center for Diarrhoeal Disease Research Bangladesh | Haque U.,Nagasaki University | Sunahara T.,Nagasaki University | Hashizume M.,Nagasaki University | And 2 more authors.
PLoS ONE | Year: 2011

Background: Malaria is a major public health concern in Bangladesh and it is highly endemic in the Chittagong Hill Tracts where prevalence was 11.7% in 2007. One sub-district, Rajasthali, had a prevalence of 36%. Several interventions were introduced in early 2007 to control malaria. This study was undertaken to evaluate the impacts of these intensive early stage interventions on malaria in Bangladesh. This prevalence study assesses whether or not high malaria prevalence remains, and if so, which areas and individuals remain at high risk of infection. Methods and Principal Findings: A 2-stage cluster sampling technique was used to sample 1,400 of 5,322 (26.3%) households in Rajasthali, and screened using a rapid diagnostic test (Falci-vax). Overall malaria prevalence was 11.5%. The proportions of Plasmodium falciparum, Plasmodium vivax and infection with both species were 93.2%, 1.9% and 5.0%, respectively. Univariate, multivariate logistic regression, and spatial cluster analyses were performed separately. Sex, age, number of bed nets, forest cover, altitude and household density were potential risk factors. A statistically significant malaria cluster was identified. Significant differences among risk factors were observed between cluster and non-cluster areas. Conclusion and Significance: Malaria has significantly decreased within 2 years after onset of intervention program. Both aspects of the physical and social environment, as well as demographic characteristics are associated with spatial heterogeneity of risk. The ability to identify and locate these areas provides a strategy for targeting interventions during initial stages of intervention programs. However, in high risk clusters of transmission, even extensive coverage by current programs leaves transmission ongoing at reduced levels. This indicates the need for continued development of new strategies for identification and treatment as well as improved understanding of the patterns and determinants of parasitaemia. © 2011 Haque et al.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP-SICA | Phase: HEALTH.2011.2.3.3-2 | Award Amount: 7.70M | Year: 2011

The overall concept of this research project is to assemble a consortium of international experts working together to develop new and innovative tools to be applied to the control of dengue in a global context. The core of the application focuses on parallel strategies aimed at: improving diagnosis and clinical management of dengue through two linked work packages designed a) to identify readily available clinical and laboratory parameters and/or viral and immunological markers, that differentiate between dengue and other common febrile illness within 3 days of fever onset, and b) to identify any of the available markers that are predictive of the likelihood of evolving to a more severe disease course assessing the risk of dengue spread though linked work packages focused on a) mapping and modelling techniques to define the current extent of dengue disease globally and to evaluate possible scenarios of spread or risk to previously uninfected regions in the future, and b) developing effective and affordable early warning and outbreak response systems. These four work packages are supported by a fifth work package dedicated to networking and translational activities to ensure that outputs from the various research activities are used to maximal advantage.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP-SICA | Phase: HEALTH.2010.2.3.4-1 | Award Amount: 16.04M | Year: 2010

To contribute to the development of vaccines against Shigella and ETEC for children of the developing world, STOPENTERICS will provide novel solutions by imposing a two-fold paradigm switch: (i) to break the dogma of serotype-specificity by inducing a cross-protective immunity (ii) to improve the immunogenicity of Shigella glycoconjugates by using synthetic oligosacharides mimicking the lipopolysaccharide O-antigen. The possibilities offered by genomics/proteomics and bacterial outer membrane blebs (OMB) will be exploited to identify virulence proteins conserved throughout Shigella or ETEC isolates. For ETEC, the development of a safe, immunogenic ST (heat stable) toxoid is a priority. State-of-the-art glycochemistry and sugar-protein carrier conjugation will allow engineering optimal Shigella glycoconjugates with focus on the five most prevalent serotypes. The ultimate aim is to optimize chances for the best coverage by combining cross-protective and serotype-specific antigens, thus ensuring the development of efficient multivalent vaccines that will help reduce the burden of diarrheal diseases. At all stages of the R & D process, candidate antigens will be considered in light of immunomonitoring data obtained in naturally-infected individuals, and volunteers undergoing vaccine trials. Regarding the latter, Phase-1 clinical trials with two vaccine candidates are planned as proofsof-concept of (i) a synthetic oligosaccharides approach mimicking Shigella O-antigens, and (ii) a Shigella OMB-based vaccines to be tested after validation of preclinical studies. STOPENTERICS is a unique combination of laboratories, platforms, vaccinology centres from academia and industry in the North and the South, integrated to successfully develop new vaccines, from R&D toward clinical trials. By promoting high-standard training capacity for young investigators, it will foster a new generation of researchers in neglected infectious diseases.


Ali I.K.M.,University of Virginia | Haque R.,International Center for Diarrhoeal Disease Research Bangladesh | Alam F.,Rajshahi Medical College | Kabir M.,International Center for Diarrhoeal Disease Research Bangladesh | And 2 more authors.
Clinical Microbiology and Infection | Year: 2012

The results of Entamoeba histolytica infections range from asymptomatic colonization to variable disease outcomes. However, markers that may predict infection outcomes are not known. Here, we investigated sequence types of a non-coding tRNA-linked locus R-R to identify surrogate markers that may show association with infection outcomes. Among 112 clinical samples-21 asymptomatic, 20 diarrhoea/dysentery and 71 liver abscesses-we identified 11 sequence types. Sequence type 5RR was mostly associated with asymptomatic samples, and sequence type 10RR was predominantly associated with the symptomatic (diarrhoea/dysentery and liver abscess) samples. This is the first report that identifies markers that may predict disease outcomes in E. histolytica infection. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.


Ali I.K.M.,University of Virginia | Haque R.,International Center for Diarrhoeal Disease Research Bangladesh | Siddique A.,International Center for Diarrhoeal Disease Research Bangladesh | Kabir M.,International Center for Diarrhoeal Disease Research Bangladesh | And 4 more authors.
PLoS Neglected Tropical Diseases | Year: 2012

Background: The category B agent of bioterrorism, Entamoeba histolytica has a two-stage life cycle: an infective cyst stage, and an invasive trophozoite stage. Due to our inability to effectively induce encystation in vitro, our knowledge about the cyst form remains limited. This also hampers our ability to develop cyst-specific diagnostic tools. Aims: Three main aims were (i) to identify E. histolytica proteins in cyst samples, (ii) to enrich our knowledge about the cyst stage, and (iii) to identify candidate proteins to develop cyst-specific diagnostic tools. Methods: Cysts were purified from the stool of infected individuals using Percoll (gradient) purification. A highly sensitive LC-MS/MS mass spectrometer (Orbitrap) was used to identify cyst proteins. Results: A total of 417 non-redundant E. histolytica proteins were identified including 195 proteins that were never detected in trophozoite-derived proteomes or expressed sequence tag (EST) datasets, consistent with cyst specificity. Cyst-wall specific glycoproteins Jacob, Jessie and chitinase were positively identified. Antibodies produced against Jacob identified cysts in fecal specimens and have potential utility as a diagnostic reagent. Several protein kinases, small GTPase signaling molecules, DNA repair proteins, epigenetic regulators, and surface associated proteins were also identified. Proteins we identified are likely to be among the most abundant in excreted cysts, and therefore show promise as diagnostic targets. Major Conclusions: The proteome data generated here are a first for naturally-occurring E. histolytica cysts, and they provide important insights into the infectious cyst form. Additionally, numerous unique candidate proteins were identified which will aid the development of new diagnostic tools for identification of E. histolytica cysts. © 2012 Ali et al.


Schmidt W.-P.,London School of Hygiene and Tropical Medicine | Arnold B.F.,University of California at Berkeley | Boisson S.,London School of Hygiene and Tropical Medicine | Genser B.,Federal University of Bahia | And 5 more authors.
International Journal of Epidemiology | Year: 2011

Background: Diarrhoea remains a leading cause of morbidity and mortality but is difficult to measure in epidemiological studies. Challenges include the diagnosis based on self-reported symptoms, the logistical burden of intensive surveillance and the variability of diarrhoea in space, time and person. Methods: We review current practices in sampling procedures to measure diarrhoea, and provide guidance for diarrhoea measurement across a range of study goals. Using 14 available data sets, we estimated typical design effects for clustering at household and village/neighbourhood level, and measured the impact of adjusting for baseline variables on the precision of intervention effect estimates. Results: Incidence is the preferred outcome measure in aetiological studies, health services research and vaccine trials. Repeated prevalence measurements (longitudinal prevalence) are appropriate in high-mortality settings where malnutrition is common, although many repeat measures are rarely useful. Period prevalence is an inadequate outcome if an intervention affects illness duration. Adjusting point estimates for age or diarrhoea at baseline in randomized trials has little effect on the precision of estimates. Design effects in trials randomized at household level are usually <2 (range 1.0-3.2). Design effects for larger clusters (e.g. villages or neighbourhoods) vary greatly among different settings and study designs (range 0.1-25.8). Conclusions: Using appropriate sampling strategies and outcome measures can improve the efficiency, validity and comparability of diarrhoea studies. Allocating large clusters in cluster randomized trials is compromized by unpredictable design effects and should be carried out only if the research question requires it. © The Author 2011; all rights reserved.


Larance B.,University of New South Wales | Ambekar A.,All India Institute of Medical Sciences | Azim T.,International Center for Diarrhoeal Disease Research Bangladesh | Murthy P.,National Institute of Mental Health and Neuro Sciences | And 3 more authors.
Drug and Alcohol Review | Year: 2011

Aims. To provide an overview of the availability of pharmaceutical opioids and the evidence on the extent of diversion and injection in South Asia. Methods. This paper reviews existing peer-reviewed and 'grey' literature on the extramedical use and injection of pharmaceutical opioids in Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka. Results. Reports indicate that prescribing for all types of pain is inadequate. There is a paucity of empirical data across South Asia regarding the mechanisms and extent of the diversion and misuse of pharmaceutical opioids, although the problem is widely acknowledged. India is believed to account for significant large-scale diversion within the region and further afield through poor regulation of licit opioid production and pharmacies. A recent decline in use of natural opiates has been accompanied by an increase in pharmaceutical opioid misuse and increasingly, injection, particularly in Bangladesh, India, Nepal and Pakistan. The medications are typically buprenorphine preparations and/or other lower potency opioids, such as codeine, nalbuphine and dextropropoxyphene. Opioid substitution treatment and needle-syringe programs are available in some countries, but better coverage is needed. Studies identify a lack of comprehensive knowledge regarding HIV and high prevalence of risk behaviours among at-risk populations in the region. Conclusions. It is imperative for the region to rapidly facilitate access to opioids for the treatment of pain and opioid dependence, ensuring effective systems that maintain quality care, regulate and monitor retail pharmacies, and minimise diversion. Prevention of HIV among people who inject pharmaceutical opioids is essential.[Larance B, Ambekar A, Azim T, Murthy P, Panda S, Degenhardt L, Mathers B. The availability, diversion and injection of pharmaceutical opioids in South Asia. Drug Alcohol Rev 2011;30:246-254] © 2011 Australasian Professional Society on Alcohol and other Drugs.


Powell-Jackson T.,London School of Hygiene and Tropical Medicine | Hoque M.E.,International Center for Diarrhoeal Disease Research Bangladesh
Health Economics (United Kingdom) | Year: 2012

We use panel data on household consumption combined with information taken from the medical records of women who gave birth in health facilities to explore the economic consequences of maternal ill health, in the context of a rural population in Bangladesh. The findings suggest that there is a large reduction in household resources associated with maternal illness, driven almost entirely by spending on health care. In spite of this loss of resources, we find that households are able to fully insure consumption against maternal ill health, although confidence intervals are unable to rule out a small effect. Households in our study area are shown to have good access to informal credit (whether it be from local money lenders or family relatives), and this appears critical in helping to smooth consumption in response to these health shocks, at least in the short term. Copyright © 2011 John Wiley & Sons, Ltd.


Koehlmoos T.P.,International Center for Diarrhoeal Disease Research Bangladesh | Anwar S.,International Center for Diarrhoeal Disease Research Bangladesh | Cravioto A.,International Center for Diarrhoeal Disease Research Bangladesh
Infectious Disease Clinics of North America | Year: 2011

Infectious diseases have had a decisive and rapid impact on shaping and changing health policy. Noncommunicable diseases, while not garnering as much interest or importance over the past 20 years, have been affecting public health around the world in a steady and critical way, becoming the leading cause of death in developed and developing countries. This article discusses emergent issues in global health related to noncommunicable diseases and conditions, with focus on defining the unique epidemiologic features and relevant programmatic, health systems, and policy responses concerning noncommunicable chronic diseases, mental health, accidents and injuries, urbanization, climate change, and disaster preparedness. © 2011 Elsevier Inc.


Khan M.G.M.,International Center for Diarrhoeal Disease Research Bangladesh | Bhaskar K.R.H.,International Center for Diarrhoeal Disease Research Bangladesh | Salam M.A.,Rajshahi Medical College | Akther T.,International Center for Diarrhoeal Disease Research Bangladesh | And 2 more authors.
Parasites and Vectors | Year: 2012

Background: Visceral leishmaniasis (VL) remains as one of the most neglected tropical diseases with over 60% of the world's total VL cases occurring in the Indian subcontinent. Due to the invasive risky procedure and technical expertise required in the classical parasitological diagnosis, the goal of the VL experts has been to develop noninvasive procedure(s) applicable in the field settings. Several serological and molecular biological approaches have been developed over the last decades, but only a few are applicable in field settings that can be performed with relative ease. Recently, loop-mediated isothermal amplification (LAMP) has emerged as a novel nucleic acid amplification method for diagnosis of VL. In this study, we have evaluated the LAMP assay using buffy coat DNA samples from VL patients in Bangladesh and compared its performance with leishmania nested PCR (Ln-PCR), an established molecular method with very high diagnostic indices. Methods. Seventy five (75) parasitologically confirmed VL patients by spleen smear microcopy and 101 controls (endemic healthy controls -25, non-endemic healthy control-26, Tuberculosis-25 and other diseases-25) were enrolled in this study. LAMP assay was carried out using a set of four primers targeting L. donovani kinetoplast minicircle DNA under isothermal (62 °C) conditions in a heat block. For Ln-PCR, we used primers targeting the parasite's small-subunit rRNA region. Results: LAMP assay was found to be positive in 68 of 75 confirmed VL cases, and revealed its diagnostic sensitivity of 90.7% (95.84-81.14, 95% CI), whereas all controls were negative by LAMP assay, indicating a specificity of 100% (100-95.43, 95% CI). The Ln-PCR yielded a sensitivity of 96% (98.96-87.97, 95% CI) and a specificity of 100% (100-95.43, 95% CI). Conclusion: High diagnostic sensitivity and excellent specificity were observed in this first report of LAMP diagnostic evaluation from Bangladesh. Considering its many fold advantages over conventional PCR and potential to be used as a simple and rapid test in the VL endemic areas of the Indian subcontinent, our findings are encouraging, but further evaluation of LAMP is needed. © 2012 Khan et al.; licensee BioMed Central Ltd.

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