Blood group phenotypes A and B are risk factors for cerebral malaria in Odisha, India

There is increasing evidence that the ABO blood group phenotypes modulates Plasmodium falciparum rosetting and may influence the clinical manifestation of severe malaria. Whether blood group phenotypes are associated with risk of severe falciparum malaria in Odisha, we analyzed 343 adult malaria patients. The results showed high prevalence of blood group B in both mild (n=110) and severe malaria (cerebral malaria [CM]; n=130 and non-cerebral severe malaria [NCSM]; n=103) categories among the non-O group and while type O is significantly associated with protection against CM, patients with type A and B group had increased risk for developing CM. Further, the strength of association for B group (p=< 0.0001) was high and has double the risk of (OR=5.0) of developing CM compared to blood group A (OR=2.5). Such findings may probably be due to strain specific blood group preferences of P. falciparum and high prevalence of B group. However, the ABO blood group distribution of mild malaria was comparable with that of the NCSM group of patients. The lack of association of ABO phenotypes with NCSM is evidence for the hypothesis that the underlying pathogenesis cascades are different in CM and NCSM clinical presentations.     

Febrile illness experience among Nigerian nomads

Background  

An understanding of the febrile illness experience of Nigerian nomadic Fulani is necessary for developing an appropriate strategy for extending malaria intervention services to them. An exploratory study of their malaria illness experience was carried out in Northern Nigeria preparatory to promoting malaria intervention among them.     

Vaccination of Rhesus monkeys (Macaca mulatta) against Plasmodium knowlesi by the use of nonviable antigen

This study was part of a long-term project with the ultimate goal of developing a malaria vaccine for use in man. Rhesus monkeys that had been vaccinated with a nonviable antigen given in combination with Freund''s adjuvant were protected against a normally lethal challenge of Plasmodium knowlesi. Use of the antigen alone or in combination with other adjuvants was not successful. The fact that monkeys were protected against an infection that is normally lethal suggests that a similarly prepared antigen might be of use against malaria in human beings.     

2006-2012年仪征市疟疾流行现状分析

目的分析江苏省仪征地区疟疾流行现状,为今后制定防治策略提供依据。方法资料来源于仪征市2006--2012年疟疾疫情报表及疟疾流行病学个案调查表;诊断标准为WS259—2006疟疾诊断标准;人口资源来源于仪征统计年鉴。结果仪征市2006--2012年共发生疟疾24例,年平均发病率为0．60／10万。间日疟20例,恶性疟3例,三日疟1例。2006--2009年全是间日疟的病例,2010年出现输入性恶性疟的病例,2011年出现1例输入性的三日疟病例。该地病例2例,输入性病例22例,其中国外输入性病例为7例。结论该市疟疾处于稳定态势,病例以输入性为主,2008年以来国外输入性病例呈上升趋势,且以恶性疟为主,还出现了1例三日疟病例。提示要加强对流动人口及出国务工人员的管理,开展疟疾监测,以防发生暴发疫情。     

High mobility group box 1 (HMGB1) protein: possible amplification signal in the pathogenesis of falciparum malaria

High mobility group box 1 (HMGB1) protein, a DNA-binding protein that can also act as a pro-inflammatory cytokine if released from cells, is an important amplification signal in various forms of inflammation. The concentration of HMGB1 in serum taken at admission was increased in falciparum malaria in sixteen African children, more so in fatal cases than in those who subsequently recovered (P<0.001). Serum from both non-fatal (P=0.0048) and fatal (P<0.001) cases contained significantly more circulating HMGB1 than did serum from healthy Caucasian adults. These data provide an additional argument that malaria is fundamentally a systemic inflammatory state. In keeping with its developing role in sepsis, HMGB1 may enhance and prolong the inflammatory processes, and thus illness, in malaria.     

Socio-economic status and malaria-related outcomes in Mvomero District,Tanzania

While policies often target malaria prevention and treatment – proximal causes of malaria and related health outcomes – too little attention has been given to the role of household- and individual-level socio-economic status (SES) as a fundamental cause of disease risk in developing countries. This paper presents a conceptual model outlining ways in which SES may influence malaria-related outcomes. Building on this conceptual model, we use household data from rural Mvomero, Tanzania, to examine empirical relationships among multiple measures of household and individual SES and demographics, on the one hand, and malaria prevention, illness, and diagnosis and treatment behaviours, on the other. We find that access to prevention and treatment is significantly associated with indicators of households’ wealth; education-based disparities do not emerge in this context. Meanwhile, reported malaria illness shows a stronger association with demographic variables than with SES (controlling for prevention). Greater understanding of the mechanisms through which SES and malaria policies interact to influence disease risk can help to reduce health disparities and reduce the malaria burden in an equitable manner.     

Socio-economic status and malaria-related outcomes in Mvomero District, Tanzania

While policies often target malaria prevention and treatment - proximal causes of malaria and related health outcomes - too little attention has been given to the role of household- and individual-level socio-economic status (SES) as a fundamental cause of disease risk in developing countries. This paper presents a conceptual model outlining ways in which SES may influence malaria-related outcomes. Building on this conceptual model, we use household data from rural Mvomero, Tanzania, to examine empirical relationships among multiple measures of household and individual SES and demographics, on the one hand, and malaria prevention, illness, and diagnosis and treatment behaviours, on the other. We find that access to prevention and treatment is significantly associated with indicators of households' wealth; education-based disparities do not emerge in this context. Meanwhile, reported malaria illness shows a stronger association with demographic variables than with SES (controlling for prevention). Greater understanding of the mechanisms through which SES and malaria policies interact to influence disease risk can help to reduce health disparities and reduce the malaria burden in an equitable manner.     

Program to Eradicate Malaria in Sardinia, 1946�C1950

During 1946–1950, the Rockefeller Foundation conducted a large-scale experiment in Sardinia to test the feasibility of indigenous vector species eradication. The interruption of malaria transmission did not require vector eradication, but with a goal of developing a new strategy to fight malaria, the choice was made to wage a rapid attack with a powerful new chemical. Costing millions of dollars, 267 metric tons of DDT were spread over the island. Although malaria was eliminated, the main objective, complete eradication of the vector, was not achieved. Despite its being considered almost eradicated in the mid-1940s, malaria 60 years later is still a major public health problem throughout the world, and its eradication is back on the global health agenda.     

Environmental risk factors for clinical malaria: a case-control study in the Grau region of Peru

The role of environmental risk factors in clinical malaria has been studied mainly in Africa and Asia, few investigations have been carried out in Latin America. Field observations in northern coastal Peru, where the prevalence of malaria is high during the agricultural season, suggested that the risk of disease varied according to the characteristics of the house and the house environment. Environmental determinants of the risk of clinical malaria were therefore investigated through a case-control study: 323 clinical cases of malaria, recruited through community-based active case-finding, and 969 age-, sex- and village-matched controls were recruited into the study over a period of 12 months ending June 1997. Residual spraying of houses in the previous 6 months, living more than 100 m from a canal, a level of education equal to primary school or above and working in agriculture conferred significant protection from the risk of developing clinical malaria. The presence of spaces between the wall and roof in the subject's bedroom (eaves) and a house aged > 4 years statistically significantly increased the risk of disease. Based on these results we discuss possible control measures for malaria in this area of the country.     

江苏省疟疾流行地理信息系统预测模型的研究

目的 建立江苏省疟疾地理信息系统(GIS)数据库和疟疾流行GIS模型,对江苏省的疟疾流行区进行空间分析。方法 在ArcView3．0a软件中建立江苏省疟疾流行病学GIS数据库,从世界粮农组织的FAOCLIM气象资料库中提取出江苏省及其周边地区的气象数据,计算疟原虫生长发育累积度-日(TGDD),在Arc View3.0a软件支持下对TGDD进行空间分析。结果 获江苏省疟疾TGDD预测分布图,江苏省疟疾流行的程度由西向东逐渐减轻,并可分为3个地带;获江苏省14年疟疾平均发病率分布图,江苏省中部、西部地区疫情较重,江南太湖流域的苏、锡、常地区、南通及江苏北部边界少数县疫情较轻,其他地区的发病率介于两者之间,江苏省14年疟疾平均发病率分布图与江苏省疟疾TGDD预测分布图基本吻合。结论 基于TGDD的GIS预测模型可应用于江苏省疟疾流行的监测。     

Measurement of malaria vaccine efficacy in phase III trials: report of a WHO consultation

In October 2006, the World Health Organisation (WHO) convened a meeting of experts to discuss appropriate methods for evaluating the efficacy of malaria vaccines in pivotal phase III trials. The participants included regulatory, industry and donor representatives and clinical trialists, epidemiologists and statisticians from both developed and developing countries. The consultation also considered the regulatory requirements for registration of a malaria vaccine and public health issues that clinical development plans need to address before deployment of a malaria vaccine in developing countries. This report summarizes the discussions and conclusions reached during the course of the meeting. While the global public health burden of malaria is unquestionable there has been considerable variation in the ways in which a case of clinical disease due to malaria has been defined. In designing trials of malaria vaccines it is important that, to the extent possible, definitions of both clinical malaria and severe malaria are agreed that have high specificity and good sensitivity. There was general agreement on how these definitions should be determined, which should facilitate the clinical evaluation of vaccine candidates in paediatric populations in malaria endemic countries. There was agreement that trials of products that might be expected to have lower efficacy than most other vaccines in routine use for other diseases was justified as even partially effective malaria vaccines may be an important tool for reducing the large burden of disease due to malaria globally. Such products would be most easily deployed if they were designed to be administered with other EPI vaccines, which would be appropriate as the greatest burden of malaria is in infancy and early childhood. The conduct of pivotal trials poses special challenges both because the expected efficacy of immediately foreseeable vaccines is likely to be less than 50% and while malaria is a very common disease, distinguishing it from other conditions is far from straightforward. Therefore, in order to facilitate the interpretation of the results from trials, in particular for regulatory decision-making, it is essential that, insofar as is possible, methods that are used to define the clinical endpoints in such trials are standardised and validated. Cogent cases can be made for using either uncomplicated malaria disease or severe disease as the primary endpoint in pivotal trials, as both impose an enormous public health burden. The decision on which of these is most appropriate will be influenced by both scientific and non-scientific factors. Public health authorities might be more likely to accelerate introduction of a vaccine if an effect on severe disease had been demonstrated in a pivotal trial. Such decisions would also be influenced by knowledge of the efficacy of the vaccine in different malaria endemic settings and by knowledge of the duration of protection conferred post-vaccination. While phase IV studies may be necessary to generate some of this information, it is important to design pivotal trials to provide this information to the extent possible.     

Preventing malaria in pregnancy: a study of perceptions and policy implications in Mukono district, Uganda

Although the efficacy of insecticide-treated nets (ITNs) in malaria prevention is well documented, the low coverage of ITNs in malaria endemic countries necessitates investigation on factors that limit access to this intervention. An exploratory study was conducted in Mukono district, Uganda, to assess perceptions and use of ITNs. Results show that malaria is perceived as a serious illness among pregnant women and children, and there is high awareness on the benefits of ITNs. However, ITNs are used by few people, mainly because of their high cost and the perception that the chemicals used to treat them have dangerous effects on pregnancy and the foetus. Other factors that influence the use of ITNs include low utilization of antenatal care, husband's lack of interest in malaria prevention and the perception that adolescent girls and primigravidae are at a low risk of getting malaria. The policy implications of these findings include demystifying the negative perceptions on the chemicals used to treat nets and subsidizing the cost of ITNs in order to increase access to them. These findings provide important lessons for malaria control programmes that aim at increasing access to ITNs by pregnant women in developing countries.     

Country planning for health interventions under development: lessons from the malaria vaccine decision-making framework and implications for other new interventions

Traditionally it has taken years or decades for new public health interventions targeting diseases found in developing countries to be accessible to those most in need. One reason for the delay has been insufficient anticipation of the eventual processes and evidence required for decision making by countries. This paper describes research into the anticipated processes and data needed to inform decision making on malaria vaccines, the most advanced of which is still in phase 3 trials. From 2006 to 2008, a series of country consultations in Africa led to the development of a guide to assist countries in preparing their malaria vaccine decision-making frameworks. The guide builds upon the World Health Organization's Vaccine Introduction Guidelines. It identifies the processes and data for decisions, when they would be needed relative to the development timelines of the intervention, and where they will come from. Policy development will be supported by data (e.g. malaria disease burden; roles of other malaria interventions; malaria vaccine impact; economic and financial issues; malaria vaccine efficacy, quality and safety) as will implementation decisions (e.g. programmatic issues and socio-cultural environment). This generic guide can now be applied to any future malaria vaccine. The paper discusses the opportunities and challenges to early planning for country decision-making-from the potential for timely, evidence-informed decisions to the risks of over-promising around an intervention still under development. Careful and well-structured planning by countries is an important way to ensure that new interventions do not remain unused for years or decades after they become available.     

Haematinic treatment of anaemia increases the risk of Plasmodium vivax malaria in pregnancy

Nutritional deficiency and malaria are 2 major causes of anaemia during pregnancy in tropical areas. The relationship between anaemia, its treatment with iron and folate, and malaria was studied in a prospective cohort of 2112 pregnant Karen women on the north-western border of Thailand between 1993 and 1997. The development of Plasmodium vivax malaria was associated with a past mean haematocrit > 30% (hazard ratio = 1.5, 95% CI 1.2-2, P = 0.001) and recent (< or = 30 d) iron and folate supplementation (hazard ratio = 1.7, 95% CI 1.1-2.6, P = 0.01). There were no associations with P. falciparum infections. Plasmodium vivax has a predilection for young erythrocytes, and these results suggest that pregnant women with larger numbers of circulating young red cells are at greater risk of developing P. vivax malaria. In P. vivax-endemic areas, systematic iron and folate supplementation confers both benefit and risk in pregnancy.     

Asymptomatic malaria infection prevailing risks for human health and malaria elimination

There has been a consistent rise in malaria cases in the last few years. The existing malaria control measures are challenged by insecticide resistance in the mosquito vector, drug résistance in parasite populations, and asymptomatic malaria (ASM) in healthy individuals.The absence of apparent malaria symptoms and the presence of low parasitemia makes ASM a hidden reservoir for malaria transmission and an impediment in malaria elimination efforts.This review focuses on ASM in malaria-endemic countries and the past and present research trends from those geographical locations. The harmful impacts of asymptomatic malaria on human health and its contribution to disease transmission are highlighted. We discuss certain crucial genetic changes in the parasite and host immune response necessary for maintaining low parasitemia leading to long-term parasite survival in the host. Since the chronic health effects and the potential roles for disease transmission of ASM remain mostly unknown to significant populations, we offer proposals for developing general awareness. We also suggest advanced technology-based diagnostic methods, and treatment strategies to eliminate ASM.     

Case report: severe acute symptomatic hyponatraemia in falciparum malaria

Hyponatraemia is a common finding in malaria, but rarely appears to be of clinical significance. We describe a case of acute, profound, hyponatraemia with confusion and convulsions developing in the context of seemingly uncomplicated Plasmodium falciparum malaria. We draw attention to this rarely reported and poorly documented life-threatening complication and review the limited literature on the subject.     

Recent advances and perspectives on tropical diseases: Malaria

Malaria remains a major health problem in the world. It is a neglected disease because it occurs almost exclusively in poor developing countries, which offer negligible marketable and profitable opportunities. Malaria(together with Tuberculosis), is responsible for an unprecedented global health crisis with devastating effects in developing countries. The 2011 Word Malaria Report indicated that 106 countries showed endemic malaria. Malaria control depends mainly on drug treatment, which is increasingly difficult due to the spread of drug resistant parasites and requires expensive drug combinations. Part of the inability to combat this disease is attributed to an incomplete understanding of its pathogenesis and pathophysiology. Improving the knowledge of the underlying pathogenic mechanisms of malaria transmission and of the exclusive metabolic pathways of the parasites(protozoa of the genus Plasmodium), should promote efficient treatment of disease and help the identification of novel targets for potential therapeutic interventions. Moreover, the elucidation of determinants involved in the spread of malaria will provide important information for efficient planning of strategies for targeted control.     

Report of a Consultation on the Optimization of Clinical Challenge Trials for Evaluation of Candidate Blood Stage Malaria Vaccines, 18–19 March 2009, Bethesda,MD, USA

Development and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing pre-erythrocytic stage vaccines, some researchers believe that the sporozoite challenge model is less appropriate for testing blood stage vaccines. Here we report a consultation, co-sponsored by PATH MVI, USAID, EMVI and WHO, where scientists from all institutions globally that have conducted such clinical challenges in recent years and representatives from regulatory agencies and funding agencies met to discuss clinical malaria challenge models. Participants discussed strengthening and harmonizing the sporozoite challenge model and considered the pros and cons of further developing a blood stage challenge possibly better suited for evaluating the efficacy of blood stage vaccines. This report summarizes major findings and recommendations, including an update on the Plasmodium vivax clinical challenge model, the prospects for performing experimental challenge trials in malaria endemic countries and an update on clinical safety data. While the focus of the meeting was on the optimization of clinical challenge models for evaluation of blood stage candidate malaria vaccines, many of the considerations are relevant for the application of challenge trials to other purposes.     

Why is malaria in Vietnam under control, but Africa is threatened with a malaria disaster?

In Africa malaria parasites are increasingly developing resistance to the 3 affordable and tolerable drugs: chloroquine, amodiaquine and sulfadoxine-pyrimethamine. Alternative products are much more expensive and more toxic. A malaria disaster is looming. On the contrary, in Vietnam a disaster appears to have been averted. Data on malaria epidemiology, on the mosquito, the parasite and the host, man, give insight into the differences and the possibilities of control. Artemisinin derivatives can play an important role in malaria control, also in Africa. Without improvement of care which will require considerable investment and attention, the prospects are bleak.     

The economic consequences of malaria for households: a case-study in Nepal

Increased attention has recently been paid to the impact of illness on the well-being of households in developing countries. This has been a particular theme in the case of malaria, but relatively little evidence is available on how households react to malaria and on its impact on expenditure and time allocation patterns. This paper reports the results of a study designed to investigate the economic consequences of malaria for households in Nepal. A household survey of malaria cases in two districts provided information on use of various sources of treatment, their cost to households, time lost by the person with malaria, the extent to which others inside or outside the household provided assistance with the normal work of the malaria patient, the time spent caring for a child with malaria and any financial losses associated with the malaria episode. Out-of-pocket expenditure on treatment differed greatly between the two districts, for reasons associated with the choice of public or private sources of treatment and the number of visits made per episode. The majority of households appeared to cope without great difficulty with the reduction in labour supply caused by a malaria episode, by drawing largely on the time of adult family members. Caution is advised in extrapolating the results to other situations, given the extent to which local factors are likely to influence the impact on households. Moreover, the findings relate to a situation where a malaria control programme is in place: a relatively greater impact per household would occur in the absence of control. However, it is argued that such surveys have value in informing health policy, particularly in relation to setting priorities and treatment policy.