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A review of clinical trials of treatments for visceral leishmaniasis in the Indian subcontinent (India, Bangladesh and Nepal)]]>http://journal.tropika.net/scielo.php?script=sci_arttext&pid=S2078-86062010000100001&lng=en&nrm=iso&tlng=en
BACKGROUND: India, Bangladesh and Nepal share nearly 60% of the global burden of the 500,000 annual cases of visceral leishmaniasis (VL, kala-azar). In 2005, the three countries and the World Health Organization (WHO) signed an agreement to eliminate VL as a public health problem from this region by 2015. OBJECTIVES: To conduct a review of clinical trials of the treatment of VL in India, Bangladesh and Nepal, in order to contribute to the evidence base for the treatment options to be used in the VL elimination programme. METHODS: We searched PubMed and trial registry databases and contacted clinical investigators to identify published and unpublished comparative, non-comparative and dose-finding trials of amphotericin deoxycholate or liposomal (AmBisome®), miltefosine, paromomycin, sodium stibogluconate and paromomycin + sodium stibogluconate for the treatment of VL in the three countries. Efficacy evaluation was based on final cure at six months of follow up or longer. We reviewed reported serious adverse effects or adverse effects and laboratory changes. The methodological quality of studies was assessed. Six-month success rates were recalculated with 95% confidence intervals (95%CI) on both an intention-to-treat (ITT) and a per-protocol (PP) basis. Relative risks (RR, fixed effect) with 95%CI for failure were calculated for comparative studies. MAIN RESULTS: Twenty-three (23) clinical trials enrolling 5,730 patients met the inclusion criteria: 11 comparative, four non-comparative, eight dose-finding. Both plain and liposomal amphotericin B (AmBisome®) were effective in these trials. Miltefosine is as effective as amphotericin B and is the only drug that has been tested in a Phase 4 study; in these conditions, effectiveness was lower than efficacy. Paromomycin is effective both alone and combined with sodium stibogluconate, and was shown not to be different from amphotericin B using a non-inferiority trial design. Sodium stibogluconate is lost to parasite resistance in Bihar; recent data from other areas were not available. The major adverse events were cardiotoxicity with sodium stibogluconate; ototoxicity and nephrotoxicity for paromomycin; vomiting and diarrhoea for miltefosine; nephrotoxicity, vomiting and diarrhoea for amphotericin B deoxycholate and infusion-related fever and chills with AmBisome. CONCLUSIONS: AmBisome, miltefosine and paromomycin are effective options for treatment of VL in the Indian subcontinent. Other factors, such as costs, and practicalities of care and delivery need to be considered for policy decisions. The majority of available evidence was from Bihar, India with very limited evidence from Bangladesh and Nepal, except on sodium stibogluconate. More studies are needed in these countries to test the efficacy, safety and effectiveness of the various treatment options.Dengue outbreak response: documented effective interventions and evidence gaps]]>http://journal.tropika.net/scielo.php?script=sci_arttext&pid=S2078-86062010000100002&lng=en&nrm=iso&tlng=en
BACKGROUND: 2.5 billion people, two-fifths of the world's population, are at risk from dengue with 50 million cases of dengue infection worldwide every year. OBJECTIVES: To review the effectiveness of interventions employed during dengue outbreaks, to recommend an evidence-based strategy for the management of dengue outbreak response programmes, and to identify areas for further research. METHODS: We searched for literature containing different terms for dengue (including dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS)) combined with the terms "outbreak", "epidemic" and "intervention", "response", "control", "management" and "treatment" in the Cochrane Database of Systematic Reviews, PubMed, EMBASE, LILACS, WHO library database, grey literature, and through manual reference searching. Studies were included that measured the outcome of interventions implemented during outbreaks by entomological and/or human disease epidemiological parameters. RESULTS: A total of 24 (out of 1134) studies met all the inclusion criteria. Different strategies in the organization of outbreak response were identified that clearly emphasized an intersectoral approach. Studies that managed the outbreak response by creating multidisciplinary response teams, including vector control teams working on a door-to-door basis, and studies that monitored and evaluated their activities, showed successful outbreak control. Combining interventions that use 1) vector control (elimination of larval habitats with community involvement; appropriate use of insecticides in and around houses) and 2) capacity training of medical personnel in combination with laboratory support, were crucial for the successful control of outbreaks. Spatial spraying of insecticides alone proved ineffective in achieving outbreak control and its usefulness in combination with other interventions remains doubtful. CONCLUSION: Further research is needed that links the effectiveness of interventions used during the outbreak response to human disease epidemiology. However, available evidence indicates that, in order to achieve rapid control, the outbreak response must employ a multidisciplinary approach combined with monitoring and evaluation.Insecticide resistance in dengue vectors]]>http://journal.tropika.net/scielo.php?script=sci_arttext&pid=S2078-86062010000100003&lng=en&nrm=iso&tlng=en
BACKGROUND: Most national dengue control programmes rely extensively on insecticides to control the mosquito vectors of this disease. OBJECTIVES: The objective of this review is to describe current knowledge of the extent of insecticide resistance in dengue vectors and the potential impact of this resistance on control activities. METHODS: We searched Web of Science and PubMed for studies that included data on resistance to the four major classes of insecticides: organochlorines, carbamates, organophosphates and pyrethroids, in the dengue vectors Aedes aegypti and Aedes albopictus. Insecticide bioassay data were extracted from the published literature and the methods used to obtain, analyse and interpret this data were critically evaluated. Emphasis was placed on the two insecticide classes most widely used in dengue control, organophosphates and pyrethroids. The use of biochemical and molecular tools for resistance monitoring was also reviewed. RESULTS: 103 studies met our inclusion criteria, of which 65 contained bioassay data which we uploaded on to a public database (IRBase). There is a strong geographical bias in published studies with nearly half originating from three countries (Thailand, India and Brazil). Bioassay data demonstrate that resistance to the organophosphate temephos and to pyrethroids is widespread in Ae. aegypti and resistance has also been reported in Ae. albopictus. Assessing the impact of insecticide resistance on vector control is complicated by variations in the methodology used to measure and report resistance, and by the lack of studies into the epidemiological consequences of insecticide resistance. CONCLUSIONS: The lack of publicly accessible standardized data sets documenting levels of insecticide resistance in many dengue endemic countries, and the absence of studies on the operational impact of resistance, precludes a comprehensive analysis of the current global threat that insecticide resistance poses to dengue control. However, several countries with active resistance monitoring programmes have shown that insecticide resistance is reducing our ability to control dengue vectors. This situation is likely to worsen unless effective strategies are rapidly implemented to mitigate these effects.Review of delivery strategies for insecticide treated mosquito nets: are we ready for the next phase of malaria control efforts?]]>http://journal.tropika.net/scielo.php?script=sci_arttext&pid=S2078-86062010000100004&lng=en&nrm=iso&tlng=en
BACKGROUND: The renewed interest in malaria elimination using long-lasting insecticidal nets (LLIN) for malaria prevention has shifted from targeted distributions of vulnerable groups to universal access. Many countries are now reaching high net coverage levels and need to consider options for sustained control. OBJECTIVES: This review addresses the question: which LLIN distribution mechanisms might be best suited for these approaches? METHODS: We searched PudMed, EMBASE, Popline, BIDS, African Journals Online, and SciELO using a board list of search terms to identify studies on bed nets. Additional searches were conducted in Google and through reference tracking. The net distribution mechanisms in the included studies were categorized using an open system of six characteristics with the distribution channel serving as the primary descriptive element. Studies were then further evaluated on net coverage, equity and cost per net delivered. RESULTS: Searches of the eight electronic databases produced 258 articles. The secondary search using reference lists and other search engines revealed an additional 44 sources. After an initial screening, 174 reports and studies were included in the detailed review. Community-based distributions (campaigns) achieve rapid increases in net coverage of 30-80%-points among the targeted population and no differences between different implementation models (stand-alone or integrated, house-to-house or distribution point) was found. Equity ratios post distribution were found to be around the 1.0 mark of perfect equity and remained high. However, following the campaign distributions a drop in coverage can be observed in the range of 5-13%-points per year for the first two years. Continuous distribution mechanisms through routine services and/or retail outlets avoid coverage fluctuations but are much slower in build-up, ranging between 3-5%-points increase/year for the unassisted commercial sector and 6-25%-points/year for combination of commercial market with free or highly subsidized nets through routine services. These delivery mechanisms can eventually achieve high equity when they reach high levels of coverage but this can take up to eight years. Cost per net delivered for campaigns appeared slightly better than other distribution mechanisms but no definite advantage can be stated for either mechanism, given methodological and within-study variability. CONCLUSION: Campaign distributions that target the general population are best suited for the scale-up phase of universal access to LLIN, but more work is needed to define the best distribution algorithms for full intra-household coverage, as well as indicators to measure it. For the phase of sustained control and LLIN replacement, a mix of continuous delivery mechanisms through community, routine services and retail outlets is suitable as long as equity issues are addressed with subsidies. Whether and how campaigns can also be used for replacement strategies can not be answered adequately until the concept of "useful life of a net" is better understood and more data available.How pro-poor are infectious disease programmes?]]>http://journal.tropika.net/scielo.php?script=sci_arttext&pid=S2078-86062010000100005&lng=en&nrm=iso&tlng=en
BACKGROUND: Poor and deprived groups benefit less from preventive and curative interventions than the general population, despite the availability of a range of interventions that are generally considered effective. OBJECTIVES: This review assesses the evidence on the degree to which infectious disease programmes benefit the poor and the mechanisms that potentially determine pro-poor effectiveness. METHODS: A combination of search strings was used to identify infectious diseases studies that describe programmes targeted on the poor in MEDLINE and ScienceDirect databases. An additional online search was conducted in Google Scholar. Further literature and research reports were retrieved by reference tracking ("snowballing") and upon recommendation from experts. The literature was reviewed independently by the authors in a two-step process. The findings of the extremely diverse set of studies were extracted and conclusions drawn after a series of discussions with colleagues in the field. REUSLTS: 89 studies were selected on the basis of previously agreed inclusion and exclusion criteria. Hardly any evidence was found on programmes with a particular focus on the poorest and most vulnerable beyond malaria, TB, and HIV/AIDS. CONCLUSION: Our review demonstrates that the pro-poor effectiveness of infectious disease interventions has neither been a priority in programme development nor has it been addressed articulately in research. In order for an infectious disease programme to be considered pro-poor, the endpoints should be measurable as long-term health gains for the poor and vulnerable. Programmes designed as integrated approaches addressing environmental factors, health risks, health care and poverty alleviation have the most potential to yield pro-poor outcomes.