Cost-effectiveness analysis of malaria chemoprophylaxis for travellers to West-Africa

Background: The importation of malaria to non-endemic countries remains a major cause of travel-related morbidity and a leading cause of travel-related hospitalizations. Currently they are three priority medications for malaria prophylaxis to West Africa: mefloquine, atovaquone/proguanil and doxycycline. We investigate the cost effectiveness of a partial reimbursement of the cheapest effective malaria chemoprophylaxis (mefloquine) for travellers to high risk areas of malaria transmission compared with the current situation of no reimbursement. Methods: This study is a cost-effectiveness analysis based on malaria cases imported from West Africa to Switzerland from the perspective of the Swiss health system. We used a decision tree model and made a literature research on the components of travel related malaria. The main outcome measure was the cost effectiveness of malaria chemoprophylaxis reimbursement based on malaria and deaths averted. Results: Using a program where travellers would be reimbursed for 80% of the cost of the cheapest malaria chemoprophylaxis is dominant (i.e. cost saving and more effective than the current situation) using the assumption that currently 68.7% of travellers to West Africa use malaria chemoprophylaxis. If the current usage of malaria chemoprophylaxis would be higher, 82.4%, the incremental cost per malaria case averted is (sic) 2'302. The incremental cost of malaria death averted is (sic) 191'833. The most important factors influencing the model were: the proportion of travellers using malaria chemoprophylaxis, the probability of contracting malaria without malaria chemoprophylaxis, the cost of the mefloquine regimen, the decrease in the number of travellers without malaria chemoprophylaxis in the reimbursement strategy. Conclusions: This study suggests that a reimbursement of 80% of the cost of the cheapest effective malaria chemoprophylaxis (mefloquine) for travellers from Switzerland to West Africa is highly effective in terms of malaria cases averted and is cost effective to the Swiss health system. These data are relevant to discussions about the cost effectiveness of malaria chemoprophylaxis reimbursement for vulnerable groups such as those visiting friends and relatives who have the highest risk of malaria, who are least likely to use chemoprophylaxis

Changing pattern of malaria in Bissau, Guinea Bissau.

OBJECTIVE: To describe the epidemiology of malaria in Guinea-Bissau, in view of the fact that more funds are available now for malaria control in the country. METHODS: From May 2003 to May 2004, surveillance for malaria was conducted among children less than 5 years of age at three health centres covering the study area of the Bandim Health Project (BHP) and at the outpatient clinic of the national hospital in Bissau. Cross-sectional surveys were conducted in the community in different malaria seasons. RESULTS: Malaria was overdiagnosed in both health centres and hospital. Sixty-four per cent of the children who presented at a health centre were clinically diagnosed with malaria, but only 13% of outpatient children who tested for malaria had malaria parasitaemia. Only 44% (963/2193) of children admitted to hospital with a diagnosis of malaria had parasitaemia. The proportion of positive cases increased with age. Among hospitalized children with malaria parasitaemia, those less than 2 years old were more likely to have moderate anaemia (RR = 1.27; 95% CI: 1.02-1.56) (P = 0.03) or severe anaemia (RR = 1.67; 95% CI: 1.25-2.24) (P = 0.0005) than older children. The prevalence of malaria parasitaemia in the community was low (3%, 53/1926). CONCLUSION: In Bissau, the prevalence of malaria parasitaemia in the community is now low and malaria is over-diagnosed in health facilities. Laboratory support will be essential to avoid unnecessary use of the artemisinin combination therapy which is now being introduced as first-line treatment in Bissau with support from the Global Fund

Clinical malaria case definition and malaria attributable fraction in the highlands of western Kenya.

BackgroundIn African highland areas where endemicity of malaria varies greatly according to altitude and topography, parasitaemia accompanied by fever may not be sufficient to define an episode of clinical malaria in endemic areas. To evaluate the effectiveness of malaria interventions, age-specific case definitions of clinical malaria needs to be determined. Cases of clinical malaria through active case surveillance were quantified in a highland area in Kenya and defined clinical malaria for different age groups.MethodsA cohort of over 1,800 participants from all age groups was selected randomly from over 350 houses in 10 villages stratified by topography and followed for two-and-a-half years. Participants were visited every two weeks and screened for clinical malaria, defined as an individual with malaria-related symptoms (fever [axillary temperature≥37.5°C], chills, severe malaise, headache or vomiting) at the time of examination or 1-2 days prior to the examination in the presence of a Plasmodium falciparum positive blood smear. Individuals in the same cohort were screened for asymptomatic malaria infection during the low and high malaria transmission seasons. Parasite densities and temperature were used to define clinical malaria by age in the population. The proportion of fevers attributable to malaria was calculated using logistic regression models.ResultsIncidence of clinical malaria was highest in valley bottom population (5.0% cases per 1,000 population per year) compared to mid-hill (2.2% cases per 1,000 population per year) and up-hill (1.1% cases per 1,000 population per year) populations. The optimum cut-off parasite densities through the determination of the sensitivity and specificity showed that in children less than five years of age, 500 parasites per μl of blood could be used to define the malaria attributable fever cases for this age group. In children between the ages of 5-14, a parasite density of 1,000 parasites per μl of blood could be used to define the malaria attributable fever cases. For individuals older than 14 years, the cut-off parasite density was 3,000 parasites per μl of blood.ConclusionClinical malaria case definitions are affected by age and endemicity, which needs to be taken into consideration during evaluation of interventions

Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria

Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria

Developing Ontology Support for Human Malaria Control Initiatives

Malaria is one of the most common infectious diseases and an enormous public health problem in Sub-Sahara Africa, Asia and parts of America. In this paper, we discuss the development of the Human Malaria Control Ontology (HMCO) which contains general information on Malaria and epidemiological information that can help in the formulation of effective malaria control policies. The HMCO is aimed at providing interoperability support for the knowledge management of malaria control initiatives, and serve as an open semantic web infrastructure for malaria research and treatment

Malaria mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.

BACKGROUND: Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies. OBJECTIVE: To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions. DESIGN: From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992-2012, but two-thirds of the observations related to 2006-2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality. RESULTS: Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level. CONCLUSIONS: The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology

Increased risk for malaria in chronically malnourished children under 5 years of age in rural Gambia.

Malaria and malnutrition cause high morbidity and mortality in rural sub-Saharan Africa. To explore the relationship between nutritional status and malaria, a cohort of Gambian children under 5 years of age was followed weekly during one malaria season. Anthropometric measurements were made at the beginning and at the end of the season. A total of 55/107 (51.4 per cent) children with baseline stunting, defined as having a height-for-age z-score below -2 standard deviations, subsequently experienced malaria episodes, compared to 145/380 (38.2 per cent) children who were not stunted (RR = 1.35; 95 per cent CI, 1.08-1.69; p value = 0.01). Neither wasting (weight-for-height z-score below -2 standard deviations) nor undernutrition (weight-for-age z-score below -2 standard deviations) influenced susceptibility to malaria. Adjustment for characteristics of age, sex, and ethnicity did not significantly change the risk ratios. Malaria had no effect on the nutritional status from the beginning to the end of the malaria season. Our findings suggest that chronically malnourished children may be at higher risk for developing malaria episodes

Malaria Diagnosis and the Plasmodium Life Cycle: the BFO Perspective

Definitive diagnosis of malaria requires the demonstration through laboratory tests of the presence within the patient of malaria parasites or their components. Since malaria parasites can be present even in the absence of malaria, and since symptoms of malaria can be manifested even in the absence of malaria parasites, malaria diagnosis raises important issues for the adequate understanding of disease, etiology and diagnosis. One approach to the resolution of these issues adopts a realist view, according to which the needed clarifications will be derived from a careful representation of the entities on the side of the patient which form the ultimate truthmakers for clinical statements. We address a challenge to this realist approach relating to the diagnosis of malaria, and show how this challenge can be resolved by appeal to Basic Formal Ontology (BFO) and to the Ontology for General Medical Science (OGMS) constructed in its terms

The immune response to malaria in utero.

Malaria causes tremendous early childhood morbidity and mortality, providing an urgent impetus for the development of a vaccine that is effective in neonates. However, the infant immune response to malaria may be influenced by events that occur well before birth. Placental malaria infection complicates one quarter of all pregnancies in Africa and frequently results in exposure of the fetus to malaria antigens in utero, while the immune system is still developing. Some data suggest that in utero exposure to malaria may induce immunologic tolerance that interferes with the development of protective immunity during childhood. More recently, however, a growing body of evidence suggests that fetal malaria exposure can prime highly functional malaria-specific T- and B-cells, which may contribute to postnatal protection from malaria. In utero exposure to malaria also impacts the activation and maturation of fetal antigen presenting cells and innate lymphocytes, which could have implications for global immunity in the infant. Here, we review recent advances in our understanding of how various components of the fetal immune system are altered by in utero exposure to malaria, discuss factors that may tilt the critical balance between tolerance and adaptive immunity, and consider the implications of these findings for malaria prevention strategies

Developing Ontology Support for Human Malaria Control Initiatives

Malaria is one of the most common infectious diseases and an enormous public health problem in Sub-Sahara Africa, Asia and parts of America. In this paper, we discuss the development of the Human Malaria Control Ontology (HMCO) which contains general information on Malaria and epidemiological information that can help in the formulation of effective malaria control policies. The HMCO is aimed at providing interoperability support for the knowledge management of malaria control initiatives, and serve as an open semantic web infrastructure for malaria research and treatment