106 research outputs found

    Optimal dose finding for novel antimalarial combination therapy*

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    A recent discussion meeting convened by the Medicines for Malaria Venture examined how best to manage the discovery and preclinical pipeline to achieve novel combination therapies which would address the key clinical needs in malaria. It became clear that dose optimisation of components within combination therapy was a key issue in achieving antimalarial efficacy and for preserving that efficacy against parasite resistance emergence. This paper outlines some of the specific issues in malaria that cause dose-ranging and dose-optimisation studies to be particularly challenging and discusses the potential of factorial study design to address such challenges

    Malaria control in Bhutan: case study of a country embarking on elimination

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    <p>Abstract</p> <p>Background</p> <p>Bhutan has achieved a major reduction in malaria incidence amid multiple challenges. This case study seeks to characterize the Bhutan malaria control programme over the last 10 years.</p> <p>Methods</p> <p>A review of the malaria epidemiology, control strategies, and elimination strategies employed in Bhutan was carried out through a literature review of peer-reviewed and grey national and international literature with the addition of reviewing the surveillance and vector control records of the Bhutan Vector-Borne Disease Control Programme (VDCP). Data triangulation was used to identify trends in epidemiology and key strategies and interventions through analysis of the VDCP surveillance and programme records and the literature review. Enabling and challenging factors were identified through analysis of socio-economic and health indicators, corroborated through a review of national and international reports and peer-review articles.</p> <p>Findings</p> <p>Confirmed malaria cases in Bhutan declined by 98.7% from 1994 to 2010. The majority of indigenous cases were due to <it>Plasmodium vivax </it>(59.9%) and adult males are most at-risk of malaria. Imported cases, or those in foreign nationals, varied over the years, reaching 21.8% of all confirmed cases in 2006.</p> <p>Strategies implemented by the VDCP are likely to be related to the decline in cases over the last 10 years. Access to malaria diagnosis in treatment was expanded throughout the country and evidence-based case management, including the introduction of artemisinin-based combination therapy (ACT) for <it>P. falciparum</it>, increasing coverage of high risk areas with Indoor Residual Spraying, insecticide-treated bed nets, and long-lasting insecticidal nets are likely to have contributed to the decline alongside enabling factors such as economic development and increasing access to health services.</p> <p>Conclusion</p> <p>Bhutan has made significant strides towards elimination and has adopted a goal of national elimination. A major challenge in the future will be prevention and management of imported malaria infections from neighbouring Indian states. Bhutan plans to implement screening at border points to prevent importation of malaria and to targeted prevention and surveillance efforts towards at-risk Bhutanese and migrant workers in construction sites.</p

    Trends in malaria research in 11 Asian Pacific countries: an analysis of peer-reviewed publications over two decades

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    Background: Quantitative data are lacking on published malaria research. The purpose of the study is to characterize trends in malaria-related literature from 1990 to 2009 in 11 Asian-Pacific countries that are committed to malaria elimination as a national goal. Methods. A systematic search was conducted for articles published from January 1990 to December 2009 in PubMed/MEDLINE using terms for malaria and 11 target countries (Bhutan, China, North Korea, Indonesia, Malaysia, Philippines, Solomon Islands, South Korea, Sri Lanka, Thailand and Vanuatu). The references were collated and categorized according to subject, Plasmodium species, and whether they contained original or derivative data. Results: 2,700 articles published between 1990 and 2009 related to malaria in the target countries. The annual output of malaria-related papers increased linearly whereas the overall biomedical output from these countries grew exponentially. The percentage of malaria-related publications was nearly 3% (111/3741) of all biomedical publications in 1992 and decreased to less than 1% (118/12171; p < 0.001) in 2009. Thailand had the highest absolute output of malaria-related papers (n = 1211), followed by China (n = 609) and Indonesia (n = 346). Solomon Islands and Vanuatu had lower absolute numbers of publications, but both countries had the highest number of publications per capita (1.3 and 2.5 papers/1,000 population). The largest percentage of papers concerned the epidemiology and control of malaria (53%) followed by studies of drugs and drug resistance (47%). There was an increase in the proportion of articles relating to epidemiology, entomology, biology, molecular biology, pathophysiology and diagnostics from the first to the second decade, whereas the percentage of papers on drugs, clinical aspects of malaria, immunology, and social sciences decreased. Conclusions: The proportion of malaria-related publications out of the overall biomedical output from the 11 target Asian-Pacific countries is decreasing. The discovery and evaluation of new, safe and effective drugs and vaccines is paramount. In addition the elimination of malaria will require operational research to implement and scale up interventions

    Malaria in Sri Lanka: one year post-tsunami

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    One year ago, the authors of this article reported in this journal on the malaria situation in Sri Lanka prior to the tsunami that hit on 26 December 2004, and estimated the likelihood of a post-tsunami malaria outbreak to be low. Malaria incidence has decreased in 2005 as compared to 2004 in most districts, including the ones that were hit hardest by the tsunami. The malaria incidence (aggregated for the whole country) in 2005 followed the downward trend that started in 2000. However, surveillance was somewhat affected by the tsunami in some coastal areas and the actual incidence in these areas may have been higher than recorded, although there were no indications of this and it is unlikely to have affected the overall trend significantly. The focus of national and international post tsunami malaria control efforts was supply of antimalarials, distribution of impregnated mosquito nets and increased monitoring in the affected area. Internationally donated antimalarials were either redundant or did not comply with national drug policy, however, few seem to have entered circulation outside government control. Despite distribution of mosquito nets, still a large population is relatively exposed to mosquito bites due to inadequate housing. There were no indications of increased malaria vector abundance. Overall it is concluded that the tsunami has not negatively influenced the malaria situation in Sri Lanka

    Irregular Migration as a Potential Source of Malaria Reintroduction in Sri Lanka and Use of Malaria Rapid Diagnostic Tests at Point-of-Entry Screening

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    Background. We describe an irregular migrant who returned to Sri Lanka after a failed people smuggling operation from West Africa. Results. On-arrival screening by Anti-Malaria Campaign (AMC) officers using a rapid diagnostic test (RDT) (CareStart Malaria HRP2/PLDH) indicated a negative result. On day 3 after arrival, he presented with fever and chills but was managed as dengue (which is hyperendemic in Sri Lanka). Only on day 7, diagnosis of Plasmodium falciparum malaria was made by microcopy and CareStart RDT. The initially negative RDT was ascribed to a low parasite density. Irregular migration may be an unrecognized source of malaria reintroduction. Despite some limitations in detection, RDTs form an important point-of-entry assessment. As a consequence of this case, the AMC is now focused on repeat testing and close monitoring of all irregular migrants from malaria-endemic zones. Conclusion. The present case study highlights the effective collaboration and coordination between inter-governmental agencies such as IOM and the Ministry of Health towards the goals of malaria elimination in Sri Lanka

    Temporal correlation between malaria and rainfall in Sri Lanka

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    <p>Abstract</p> <p>Background</p> <p>Rainfall data have potential use for malaria prediction. However, the relationship between rainfall and the number of malaria cases is indirect and complex.</p> <p>Methods</p> <p>The statistical relationships between monthly malaria case count data series and monthly mean rainfall series (extracted from interpolated station data) over the period 1972 – 2005 in districts in Sri Lanka was explored in four analyses: cross-correlation; cross-correlation with pre-whitening; inter-annual; and seasonal inter-annual regression.</p> <p>Results</p> <p>For most districts, strong positive correlations were found for malaria time series lagging zero to three months behind rainfall, and negative correlations were found for malaria time series lagging four to nine months behind rainfall. However, analysis with pre-whitening showed that most of these correlations were spurious. Only for a few districts, weak positive (at lags zero and one) or weak negative (at lags two to six) correlations were found in pre-whitened series. Inter-annual analysis showed strong negative correlations between malaria and rainfall for a group of districts in the centre-west of the country. Seasonal inter-annual analysis showed that the effect of rainfall on malaria varied according to the season and geography.</p> <p>Conclusion</p> <p>Seasonally varying effects of rainfall on malaria case counts may explain weak overall cross-correlations found in pre-whitened series, and should be taken into account in malaria predictive models making use of rainfall as a covariate.</p

    Models for short term malaria prediction in Sri Lanka

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    <p>Abstract</p> <p>Background</p> <p>Malaria in Sri Lanka is unstable and fluctuates in intensity both spatially and temporally. Although the case counts are dwindling at present, given the past history of resurgence of outbreaks despite effective control measures, the control programmes have to stay prepared. The availability of long time series of monitored/diagnosed malaria cases allows for the study of forecasting models, with an aim to developing a forecasting system which could assist in the efficient allocation of resources for malaria control.</p> <p>Methods</p> <p>Exponentially weighted moving average models, autoregressive integrated moving average (ARIMA) models with seasonal components, and seasonal multiplicative autoregressive integrated moving average (SARIMA) models were compared on monthly time series of district malaria cases for their ability to predict the number of malaria cases one to four months ahead. The addition of covariates such as the number of malaria cases in neighbouring districts or rainfall were assessed for their ability to improve prediction of selected (seasonal) ARIMA models.</p> <p>Results</p> <p>The best model for forecasting and the forecasting error varied strongly among the districts. The addition of rainfall as a covariate improved prediction of selected (seasonal) ARIMA models modestly in some districts but worsened prediction in other districts. Improvement by adding rainfall was more frequent at larger forecasting horizons.</p> <p>Conclusion</p> <p>Heterogeneity of patterns of malaria in Sri Lanka requires regionally specific prediction models. Prediction error was large at a minimum of 22% (for one of the districts) for one month ahead predictions. The modest improvement made in short term prediction by adding rainfall as a covariate to these prediction models may not be sufficient to merit investing in a forecasting system for which rainfall data are routinely processed.</p

    What clinicians who practice in countries reaching malaria elimination should be aware of: lessons learnt from recent experience in Sri Lanka

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    Following progressive reduction in confirmed cases of malaria from 2002 to 2007 (41,411 cases in 2002, 10,510 cases in 2003, 3,720 cases in 2004, 1,640 cases in 2005, 591 cases in 2006, and 198 cases in 2007). Sri Lanka entered the pre-elimination stage of malaria in 2008. One case of indigenous malaria and four other cases of imported malaria are highlighted here, as the only patients who presented to the Professorial Medical Unit, Colombo North Teaching Hospital, Ragama, Sri Lanka over the past eight years, in contrast to treating several patients a week about a decade ago. Therefore, at the eve of elimination of malaria from Sri Lanka, it is likely that the infection is mostly encountered among travellers who return from endemic areas, or among the military who serve in un-cleared areas of Northern Sri Lanka. They may act as potential sources of introducing malaria as until malaria eradication is carried out. These cases highlight that change in the symptomatology, forgetfulness regarding malaria as a cause of acute febrile illness and deterioration of the competency of microscopists as a consequence of the low disease incidence, which are all likely to contribute to the delay in the diagnosis. The importance regarding awareness of new malaria treatment regimens, treatment under direct observation, prompt notification of suspected or diagnosed cases of malaria and avoiding blind use of anti-malarials are among the other responsibilities expected of all clinicians who manage patients in countries reaching malaria elimination
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