The relevance of non-human primate and rodent malaria models for humans

At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material.     

“Tazomoka Is Not a Problem”. Local Perspectives on Malaria,Fever Case Management and Bed Net Use in Madagascar

Background

Although its incidence has been decreasing during the last decade, malaria is still a major public health issue in Madagascar. The use of Long Lasting Insecticidal Nets (LLIN) remains a key malaria control intervention strategy in Madagascar, however, it encounters some obstacles. The present study aimed to explore the local terminology related to malaria, information channels about malaria, attitude towards bed nets, and health care seeking practices in case of fever. This article presents novel qualitative findings about malaria. Until now, no such data has been published for Madagascar.

Methods

A comparative qualitative study was carried out at four sites in Madagascar, each differing by malaria epidemiology and socio-cultural background of the populations. Seventy-one semi-structured interviews were conducted with biomedical and traditional caregivers, and members of the local population. In addition, observations of the living conditions and the uses of bed net were conducted.

Results

Due to the differences between local and biomedical perspectives on malaria, official messages did not have the expected impact on population in terms of prevention and care seeking behaviors. Rather, most information retained about malaria was spread through informal information circulation channels. Most interviewees perceived malaria as a disease that is simple to treat. Tazomoka (“mosquito fever”), the Malagasy biomedical word for malaria, was not used by populations. Tazo (“fever”) and tazomahery (“strong fever”) were the terms more commonly used by members of the local population to refer to malaria related symptoms. According to local perceptions in all areas, tazo and tazomahery were not caused by mosquitos. Each of these symptoms required specific health recourse. The usual fever management strategies consisted of self-medication or recourse to traditional and biomedical caregivers. Usage of bed nets was intermittent and was not directly linked to protection against malaria in the eyes of most Malagasy people.

Conclusions

This article highlights the conflicting understanding of malaria between local perceptions and the biomedical establishment in Madagascar. Local perceptions of malaria present a holistic vision of the disease that includes various social and cultural dimensions, rather than reflecting one universal understanding, as in the biomedical image. The consideration of this “holistic vision” and other socio-cultural aspects surrounding the understanding of malaria is essential in implementing successful control intervention strategies.     

Malaria and social health determinants: a new heuristic framework from the perspective of Latin American social medicine

Traditionally, malaria research and study have followed the positivist scientific paradigm and its biomedical conception of disease. From this perspective, diverse control actions and strategies have been designed. However, despite a century of scientific experience and the depth and thoroughness achieved in the knowledge of malaria, this has not been translated into a constant and progressive decrease of its epidemiological burden. This essay argues for the need for a change in malaria conception, reconfiguring it as a process of biological and social character, where the geno-phenotypical possibilities of the host-parasite relationship and of the diseases clinical expression are articulated with the historic and social dynamics of the spaces in which they occur. In addition, it proposes rethinking the epidemiological research of this entity on the basis of the visualization of the dynamic, heterogeneous, dialectic and complex character of biosocial organizations that constitute the reality of malaria (from the social structure to the genetic and phenotypic level of parasite individuals, vectors and humans). To achieve this, it is suggested that: 1) the Latin American perspective on the social determinants of health be adopted; 2) new analytical categories (for instance, malaria social territory) and new investigation tools (matrices of critical processes of social determination) be incorporated, and 3) the conventional epidemiological categories of infectious diseases such as the transmission and infectiousness be reinterpreted.     

Malaria Prevalence,Spatial Clustering and Risk Factors in a Low Endemic Area of Eastern Rwanda: A Cross Sectional Study

Background

Rwanda reported significant reductions in malaria burden following scale up of control intervention from 2005 to 2010. This study sought to; measure malaria prevalence, describe spatial malaria clustering and investigate for malaria risk factors among health-centre-presumed malaria cases and their household members in Eastern Rwanda.

Methods

A two-stage health centre and household-based survey was conducted in Ruhuha sector, Eastern Rwanda from April to October 2011. At the health centre, data, including malaria diagnosis and individual level malaria risk factors, was collected. At households of these Index cases, a follow-up survey, including malaria screening for all household members and collecting household level malaria risk factor data, was conducted.

Results

Malaria prevalence among health centre attendees was 22.8%. At the household level, 90 households (out of 520) had at least one malaria-infected member and the overall malaria prevalence for the 2634 household members screened was 5.1%. Among health centre attendees, the age group 5–15 years was significantly associated with an increased malaria risk and a reported ownership of ≥4 bednets was significantly associated with a reduced malaria risk. At the household level, age groups 5–15 and >15 years and being associated with a malaria positive index case were associated with an increased malaria risk, while an observed ownership of ≥4 bednets was associated with a malaria risk-protective effect. Significant spatial malaria clustering among household cases with clusters located close to water- based agro-ecosystems was observed.

Conclusions

Malaria prevalence was significantly higher among health centre attendees and their household members in an area with significant household spatial malaria clustering. Circle surveillance involving passive case finding at health centres and proactive case detection in households can be a powerful tool for identifying household level malaria burden, risk factors and clustering.     

International funding for malaria control in relation to populations at risk of stable Plasmodium falciparum transmission

Background

The international financing of malaria control has increased significantly in the last ten years in parallel with calls to halve the malaria burden by the year 2015. The allocation of funds to countries should reflect the size of the populations at risk of infection, disease, and death. To examine this relationship, we compare an audit of international commitments with an objective assessment of national need: the population at risk of stable Plasmodium falciparum malaria transmission in 2007.

Methods and Findings

The national distributions of populations at risk of stable P. falciparum transmission were projected to the year 2007 for each of 87 P. falciparum–endemic countries. Systematic online- and literature-based searches were conducted to audit the international funding commitments made for malaria control by major donors between 2002 and 2007. These figures were used to generate annual malaria funding allocation (in US dollars) per capita population at risk of stable P. falciparum in 2007. Almost US$1 billion are distributed each year to the 1.4 billion people exposed to stable P. falciparum malaria risk. This is less than US$1 per person at risk per year. Forty percent of this total comes from the Global Fund to Fight AIDS, Tuberculosis and Malaria. Substantial regional and national variations in disbursements exist. While the distribution of funds is found to be broadly appropriate, specific high population density countries receive disproportionately less support to scale up malaria control. Additionally, an inadequacy of current financial commitments by the international community was found: under-funding could be from 50% to 450%, depending on which global assessment of the cost required to scale up malaria control is adopted.

Conclusions

Without further increases in funding and appropriate targeting of global malaria control investment it is unlikely that international goals to halve disease burdens by 2015 will be achieved. Moreover, the additional financing requirements to move from malaria control to malaria elimination have not yet been considered by the scientific or international community.     

An exploratory study of community factors relevant for participatory malaria control on Rusinga Island, western Kenya

Background

Capacity strengthening of rural communities, and the various actors that support them, is needed to enable them to lead their own malaria control programmes. Here the existing capacity of a rural community in western Kenya was evaluated in preparation for a larger intervention.

Methods

Focus group discussions and semi-structured individual interviews were carried out in 1,451 households to determine (1) demographics of respondent and household; (2) socio-economic status of the household; (3) knowledge and beliefs about malaria (symptoms, prevention methods, mosquito life cycle); (4) typical practices used for malaria prevention; (5) the treatment-seeking behaviour and household expenditure for malaria treatment; and (6) the willingness to prepare and implement community-based vector control.

Results

Malaria was considered a major threat to life but relevant knowledge was a chimera of scientific knowledge and traditional beliefs, which combined with socio-economic circumstances, leads to ineffective malaria prevention. The actual malaria prevention behaviour practiced by community members differed significantly from methods known to the respondents. Beside bednet use, the major interventions implemented were bush clearing and various hygienic measures, even though these are ineffective for malaria prevention. Encouragingly, most respondents believed malaria could be controlled and were willing to contribute to a community-based malaria control program but felt they needed outside assistance.

Conclusion

Culturally sensitive but evidence-based education interventions, utilizing participatory tools, are urgently required which consider traditional beliefs and enable understanding of causal connections between mosquito ecology, parasite transmission and the diagnosis, treatment and prevention of disease. Community-based organizations and schools need to be equipped with knowledge through partnerships with national and international research and tertiary education institutions so that evidence-based research can be applied at the grassroots level.     

Practical Implications of the Non-Linear Relationship between the Test Positivity Rate and Malaria Incidence

Background

The test positivity rate (TPR), defined as the number of laboratory-confirmed malaria tests per 100 suspected cases examined, is widely used by malaria surveillance programs as one of several key indicators of temporal trends in malaria incidence. However, there have been few studies using empiric data to examine the quantitative nature of this relationship.

Methods

To characterize the relationship between the test positivity rate and the incidence of malaria, we fit regression models using the confirmed malaria case rate as the outcome of interest and TPR as the predictor of interest. We varied the relationship between the two by alternating linear and polynomial terms for TPR, and compared the goodness of fit of each model.

Results

A total of 7,668 encounters for malaria diagnostic testing were recorded over the study period within a catchment area of 25,617 persons. The semi-annual TPR ranged from 4.5% to 59% and the case rates ranged from 0.5 to 560 per 1,000 persons. The best fitting model was an exponential growth model (R² = 0.80, AIC = 637). At low transmission levels (TPR<10%), the correlation between TPR and CMCR was poor, with large reductions in the TPR, for example from 10% to 1%, was associated with a minimal change in the CMCR (3.9 to 1.7 cases per 1,000 persons). At higher transmission levels, the exponential relationship made relatively small changes in TPR suggestive of sizeable change in estimated malaria incidence, suggesting that TPR remains a valuable surveillance indicator in such settings.

Conclusions

The TPR and the confirmed malaria case rate have a non-linear relationship, which is likely to have important implications for malaria surveillance programs, especially at the extremes of transmission.     

Distribution of the species of the Anopheles gambiae complex and first evidence of Anopheles merus as a malaria vector in Madagascar

BACKGROUND: Members of the Anopheles gambiae complex are amongst the best malaria vectors in the world, but their vectorial capacities vary between species and populations. A large-scale sampling of An. gambiae sensu lato was carried out in various bioclimatic domains of Madagascar. Local abundance of an unexpected member of this complex raised questions regarding its role in malaria transmission. METHODS: Sampling took place at 38 sites and 2,067 females were collected. Species assessment was performed using a PCR targeting a sequence in the IGS of the rDNA. Analysis focused on the relative prevalence of the species per site, bioclimatic domain and altitude. Infectivity of Anopheles merus was assessed using an ELISA to detect the presence of malarial circumsporozoite protein in the head-thorax. RESULTS: Three species were identified: An. gambiae, Anopheles arabiensis and An. merus. The distribution of each species is mainly a function of bioclimatic domains and, to a lesser extent, altitude. An. arabiensis is present in all bioclimatic domains with highest prevalence in sub-humid, dry and sub-arid domains. An. gambiae has its highest prevalence in the humid domain, is in the minority in dry areas, rare in sub-humid and absent in sub-arid domains. An. merus is restricted to the coastal fringe in the south and west; it was in the majority in one southern village. The majority of sites were sympatric for at least two of the species (21/38) and two sites harboured all three species.The role of An. merus as malaria vector was confirmed in the case of two human-biting females, which were ELISA-positive for Plasmodium falciparum. CONCLUSION: Despite the huge environmental (mainly man-made) changes in Madagascar, the distribution of An. gambiae and An. arabiensis appears unchanged for the past 35 years. The distribution of An. merus is wider than was previously known, and its effectiveness as a malaria vector has been shown for the first time; this species is now on the list of Malagasy malaria vectors.     

Modelling the cost-effectiveness of mass screening and treatment for reducing Plasmodium falciparum malaria burden

Background

Past experience and modelling suggest that, in most cases, mass treatment strategies are not likely to succeed in interrupting Plasmodium falciparum malaria transmission. However, this does not preclude their use to reduce disease burden. Mass screening and treatment (MSAT) is preferred to mass drug administration (MDA), as the latter involves massive over-use of drugs. This paper reports simulations of the incremental cost-effectiveness of well-conducted MSAT campaigns as a strategy for P. falciparum malaria disease-burden reduction in settings with varying receptivity (ability of the combined vector population in a setting to transmit disease) and access to case management.

Methods

MSAT incremental cost-effectiveness ratios (ICERs) were estimated in different sub-Saharan African settings using simulation models of the dynamics of malaria and a literature-based MSAT cost estimate. Imported infections were simulated at a rate of two per 1,000 population per annum. These estimates were compared to the ICERs of scaling up case management or insecticide-treated net (ITN) coverage in each baseline health system, in the absence of MSAT.

Results

MSAT averted most episodes, and resulted in the lowest ICERs, in settings with a moderate level of disease burden. At a low pre-intervention entomological inoculation rate (EIR) of two infectious bites per adult per annum (IBPAPA) MSAT was never more cost-effective than scaling up ITNs or case management coverage. However, at pre-intervention entomological inoculation rates (EIRs) of 20 and 50 IBPAPA and ITN coverage levels of 40 or 60%, respectively, the ICER of MSAT was similar to that of scaling up ITN coverage further.

Conclusions

In all the transmission settings considered, achieving a minimal level of ITN coverage is a “best buy”. At low transmission, MSAT probably is not worth considering. Instead, MSAT may be suitable at medium to high levels of transmission and at moderate ITN coverage. If undertaken as a burden-reducing intervention, MSAT should be continued indefinitely and should complement, not replace, case management and vector control interventions.     

Social determinants of long lasting insecticidal hammock use among the Ra-glai ethnic minority in Vietnam: implications for forest malaria control

Background

Long-lasting insecticidal hammocks (LLIHs) are being evaluated as an additional malaria prevention tool in settings where standard control strategies have a limited impact. This is the case among the Ra-glai ethnic minority communities of Ninh Thuan, one of the forested and mountainous provinces of Central Vietnam where malaria morbidity persist due to the sylvatic nature of the main malaria vector An. dirus and the dependence of the population on the forest for subsistence - as is the case for many impoverished ethnic minorities in Southeast Asia.

Methods

A social science study was carried out ancillary to a community-based cluster randomized trial on the effectiveness of LLIHs to control forest malaria. The social science research strategy consisted of a mixed methods study triangulating qualitative data from focused ethnography and quantitative data collected during a malariometric cross-sectional survey on a random sample of 2,045 study participants.

Results

To meet work requirements during the labor intensive malaria transmission and rainy season, Ra-glai slash and burn farmers combine living in government supported villages along the road with a second home at their fields located in the forest. LLIH use was evaluated in both locations. During daytime, LLIH use at village level was reported by 69.3% of all respondents, and in forest fields this was 73.2%. In the evening, 54.1% used the LLIHs in the villages, while at the fields this was 20.7%. At night, LLIH use was minimal, regardless of the location (village 4.4%; forest 6.4%).

Discussion

Despite the free distribution of insecticide-treated nets (ITNs) and LLIHs, around half the local population remains largely unprotected when sleeping in their forest plot huts. In order to tackle forest malaria more effectively, control policies should explicitly target forest fields where ethnic minority farmers are more vulnerable to malaria.     

Prospects for malaria control

Malaria control strategies have to be established locally according to epidemiological situations, including socio-economic factors and to resources available for their implementation. It has been stressed that all antimalaria activities be integrated in PHC.Stratification of malaria is the introduction to malaria control and serves as a basis for the planning which should be established by a body of experts on malaria at the central level (epidemiologist, entomologist, specialists in social sciences, sanitary engineer) who later will guide, supervise and evaluate the activities.Case treatments, sometimes presumptive, are the most basic activities of control. They are cheap and they can be carried out by PHC which insures the coverage of the entire population at risk. Drug resistance of Plasmodium falciparum is a growing and threatening problem. In a number of areas cheap and harmless chloroquine has to be replaced by drugs or combinations of drugs which can only be delivered by experienced personnel. Chemoprophylaxis is recommended for pregnant women but questioned for infants and young children because the risk of side-effects and resistance selection and the difficulties of maintaining a good coverage for a long time.Vector control by house-spraying remains the best means of reducing transmission and is still the basis of malaria control in countries in Asia and America where the disease has been seriously reduced. In some areas resistance to DDT lead to the use of more expensive organophosphates and/or carbamates. Resistance to these compounds has also been reported in several countries. House-spraying is probably one of the malaria activities which is the most difficult to integrate in PHC. Some attempts have been successful.Integrated vector control with community participation is not a simple task nor a panacea. To be efficient it needs to be established on a strong scientific basis. Tools and technics have to be selected for each area according to the vector ecology and socio-cultural habits of the population. Maintaining community interest in a long lasting activity is a problem which has never been really explored. Self-protection against vectors (mainly by using impregnated mosquito nets) has shown promise and is currently being evaluated at an operational scale with community involvement. There is great hope for a vaccine but more advances are necessary before its place in malaria control can be established.Intersectorial approach is the best way to counteract undesirable effects of development schemes like irrigation. There is a need for training in the scope of interdisciplinary actions for high level personnel. PHC agents need special training whatever they are, specialized or multipurpose. Special attention must be paid to malaria in health education for communities at risk. Some researches dealing with the most immediate problems are suggested.     

Ecologists can enable communities to implement malaria vector control in Africa

Background

Malaria imposes significant costs on households and the poor are disproportionately affected. However, cost data are often from quantitative surveys with a fixed recall period. They do not capture costs that unfold slowly over time, or seasonal variations. Few studies investigate the different pathways through which malaria contributes towards poverty. In this paper, a framework indicating the complex links between malaria, poverty and vulnerability at the household level is developed and applied using data from rural Kenya.

Methods

Cross-sectional surveys in a wet and dry season provide data on treatment-seeking, cost-burdens and coping strategies (n = 294 and n = 285 households respectively). 15 case study households purposively selected from the survey and followed for one year provide in-depth qualitative information on the links between malaria, vulnerability and poverty.

Results

Mean direct cost burdens were 7.1% and 5.9% of total household expenditure in the wet and dry seasons respectively. Case study data revealed no clear relationship between cost burdens and vulnerability status at the end of the year. Most important was household vulnerability status at the outset. Households reporting major malaria episodes and other shocks prior to the study descended further into poverty over the year. Wealthier households were better able to cope.

Conclusion

The impacts of malaria on household economic status unfold slowly over time. Coping strategies adopted can have negative implications, influencing household ability to withstand malaria and other contingencies in future. To protect the poor and vulnerable, malaria control policies need to be integrated into development and poverty reduction programmes.     

Differential induction of functional IgG using the Plasmodium falciparum placental malaria vaccine candidate VAR2CSA

Background

In Plasmodium falciparum malaria endemic areas placental malaria (PM) is an important complication of malaria. The recurrence of malaria in primigravidae women irrespective of acquired protection during childhood is caused by the interaction between the parasite-expressed VAR2CSA antigen and chondroitin sulfate A (CSA) in the placental intervillous space and lack of protective antibodies. PM impairs fetal development mainly by excessive inflammation processes. After infections during pregnancy women acquire immunity to PM conferred by antibodies against VAR2CSA. Ideally, a vaccine against PM will induce antibody-mediated immune responses that block the adhesion of infected erythrocytes (IE) in the placenta.

Principal Findings

We have previously shown that antibodies raised in rat against individual domains of VAR2CSA can block IE binding to CSA. In this study we have immunized mice, rats and rabbits with each individual domain and the full-length protein corresponding to the FCR3 VAR2CSA variant. We found there is an inherently higher immunogenicity of C-terminal domains compared to N-terminally located domains. This was irrespective of whether antibodies were induced against single domains or the full-length protein. Species-specific antibody responses were also found, these were mainly directed against single domains and not the full-length VAR2CSA protein.

Conclusions/Significance

Binding inhibitory antibodies appeared to be against conformational B-cell epitopes. Non-binding inhibitory antibodies reacted highly against the C-terminal end of the VAR2CSA molecule especially the highly polymorphic DBL6ε domain. Differential species-specific induction of antibody responses may allow for more direct analysis of functional versus non-functional B-cell epitopes.     

Modeling the Cost Effectiveness of Malaria Control Interventions in the Highlands of Western Kenya

Introduction

Tools that allow for in silico optimization of available malaria control strategies can assist the decision-making process for prioritizing interventions. The OpenMalaria stochastic simulation modeling platform can be applied to simulate the impact of interventions singly and in combination as implemented in Rachuonyo South District, western Kenya, to support this goal.

Methods

Combinations of malaria interventions were simulated using a previously-published, validated model of malaria epidemiology and control in the study area. An economic model of the costs of case management and malaria control interventions in Kenya was applied to simulation results and cost-effectiveness of each intervention combination compared to the corresponding simulated outputs of a scenario without interventions. Uncertainty was evaluated by varying health system and intervention delivery parameters.

Results

The intervention strategy with the greatest simulated health impact employed long lasting insecticide treated net (LLIN) use by 80% of the population, 90% of households covered by indoor residual spraying (IRS) with deployment starting in April, and intermittent screen and treat (IST) of school children using Artemether lumefantrine (AL) with 80% coverage twice per term. However, the current malaria control strategy in the study area including LLIN use of 56% and IRS coverage of 70% was the most cost effective at reducing disability-adjusted life years (DALYs) over a five year period.

Conclusions

All the simulated intervention combinations can be considered cost effective in the context of available resources for health in Kenya. Increasing coverage of vector control interventions has a larger simulated impact compared to adding IST to the current implementation strategy, suggesting that transmission in the study area is not at a level to warrant replacing vector control to a school-based screen and treat program. These results have the potential to assist malaria control program managers in the study area in adding new or changing implementation of current interventions.     

Periodical abstracts

Abstract

In a sample of 51 like‐sex DZ twin pairs (22 male, 29 female) 49 quantitative traits were analyzed for association with, and linkage to, each of 7 informative blood systems. Nine associations were found to be significant at the 0.01 level, and a further 27 significant at the 0.05 level, whereas the numbers expected to be significant by chance alone are about 3 and 17 respectively. The most consistent associations are those of Rh with the scores obtained with Paul Griéger's characterological test. The associations may be due to a factor present in the physical or social environment that influences both characteristics simultaneously; alternative explanations are pleiotropy, epistasis, or heterogeneity of the populations. Only 12 of the tests for linkage were significant at the 0.05 level, less than would be expected by chance alone; these results are therefore inconclusive. The most significant linkage is that between Hp and activity, one of the 3 scores in Griéger's characterological test. In vew of independent data suggesting evidence of linkage between Hp and depression spectrum disease, further study of this possible linkage in larger families would be warranted.     

Loss of Population Levels of Immunity to Malaria as a Result of Exposure-Reducing Interventions: Consequences for Interpretation of Disease Trends

Background

The persistence of malaria as an endemic infection and one of the major causes of childhood death in most parts of Africa has lead to a radical new call for a global effort towards eradication. With the deployment of a highly effective vaccine still some years away, there has been an increased focus on interventions which reduce exposure to infection in the individual and –by reducing onward transmission-at the population level. The development of appropriate monitoring of these interventions requires an understanding of the timescales of their effect.

Methods & Findings

Using a mathematical model for malaria transmission which incorporates the acquisition and loss of both clinical and parasite immunity, we explore the impact of the trade-off between reduction in exposure and decreased development of immunity on the dynamics of disease following a transmission-reducing intervention such as insecticide-treated nets. Our model predicts that initially rapid reductions in clinical disease incidence will be observed as transmission is reduced in a highly immune population. However, these benefits in the first 5–10 years after the intervention may be offset by a greater burden of disease decades later as immunity at the population level is gradually lost. The negative impact of having fewer immune individuals in the population can be counterbalanced either by the implementation of highly-effective transmission-reducing interventions (such as the combined use of insecticide-treated nets and insecticide residual sprays) for an indefinite period or the concurrent use of a pre-erythrocytic stage vaccine or prophylactic therapy in children to protect those at risk from disease as immunity is lost in the population.

Conclusions

Effective interventions will result in rapid decreases in clinical disease across all transmission settings while population-level immunity is maintained but may subsequently result in increases in clinical disease many years later as population-level immunity is lost. A dynamic, evolving intervention programme will therefore be necessary to secure substantial, stable reductions in malaria transmission.     

Developing an agent-based model for simulating the dynamic spread of Plasmodium vivax malaria: A case study of Sarbaz,Iran

Malaria is a vector-borne disease that is considered a major public health problem in tropical and semi-tropical areas. The transmission of malaria is associated with the interactions among environment, Anopheles mosquitoes (vectors), and humans (hosts). Plasmodium vivax is one of the four species of malaria parasites that commonly infect humans in Asia, Latin America, and in some parts of Africa. The major difference between this and other parasites is the recurrence of malaria. The main objective of this study is to develop an agent-based model (ABM) for simulating the dynamic spread of P. vivax malaria, based on the interactions of these three elements represented as agents. The SEIRS model is used to simulate the transmission of malaria. The model explanation follows the ODD (Overview, Design concepts, Details) protocol. The transmission of malaria depends on various factors consisting of temperature, humidity, vegetation, altitude, distance from rivers, and the human population density. The main innovation of this study is that the first three factors are assumed changeable and are entered dynamically to the model during the simulation process. In the study area, the malaria occurrence data were available only for each month and only at the county level. Therefore, the processes of calibration and validation of the model were merely based on the temporal pattern of malaria incidence and the Root-Mean-Square-Error (RMSE). After the calibration of the model, the best value of RMSE calculated for the temporal pattern of malaria spread was 3.155 infected people. The map of critical locations of malaria spreading resulted from this research can be helpful to the policymakers to plan the malaria-control interventions.     

Malaria: medical and surgical complications

The resurgence of malaria in Venezuela as an epidemic has caused an increase in the number of cases of this disease. 898 cases were registered in 1962 in contrast to 46,279 cases in 1988. This reality implies that all hospitals will have to face the increase of patients with this disease. Ten cases of malaria have been described and analyzed. These have been chosen for their medical and surgical complications, for which they were admitted to the "Hospital Universitario de Caracas" and "Hospital de Clínicas Caracas". Of these ten cases, eight were acquired in a natural way and two in an induced form. In six cases, the agent was P. falciparum; in three, P. vivax; in one, P. ovale and P.vivax combined. Five of the cases by P.falciparum were resistant to chloroquine, being necessary to treat them with a combination of quinine and other antimalaric drugs. Among the 10 described patients, there were: one case of splenic rupture in malaria by P. vivax, a severe case of anemia in a child with malaria by this same species and a case of relapse produced by P.vivax in another child with an insufficient radical treatment. The usual mistakes are observed in the management of malaria, such as a delay in the diagnosis and inappropriate radical treatment. As conclusion, publication of epidemiological, clinical and parasitological problems which are causing the actual epidemic, is recommended. This will be a guide in the fight against malaria, that must be considered again a national emergency.     

Multi-Step Polynomial Regression Method to Model and Forecast Malaria Incidence

Malaria is one of the most severe problems faced by the world even today. Understanding the causative factors such as age, sex, social factors, environmental variability etc. as well as underlying transmission dynamics of the disease is important for epidemiological research on malaria and its eradication. Thus, development of suitable modeling approach and methodology, based on the available data on the incidence of the disease and other related factors is of utmost importance. In this study, we developed a simple non-linear regression methodology in modeling and forecasting malaria incidence in Chennai city, India, and predicted future disease incidence with high confidence level. We considered three types of data to develop the regression methodology: a longer time series data of Slide Positivity Rates (SPR) of malaria; a smaller time series data (deaths due to Plasmodium vivax) of one year; and spatial data (zonal distribution of P. vivax deaths) for the city along with the climatic factors, population and previous incidence of the disease. We performed variable selection by simple correlation study, identification of the initial relationship between variables through non-linear curve fitting and used multi-step methods for induction of variables in the non-linear regression analysis along with applied Gauss-Markov models, and ANOVA for testing the prediction, validity and constructing the confidence intervals. The results execute the applicability of our method for different types of data, the autoregressive nature of forecasting, and show high prediction power for both SPR and P. vivax deaths, where the one-lag SPR values plays an influential role and proves useful for better prediction. Different climatic factors are identified as playing crucial role on shaping the disease curve. Further, disease incidence at zonal level and the effect of causative factors on different zonal clusters indicate the pattern of malaria prevalence in the city. The study also demonstrates that with excellent models of climatic forecasts readily available, using this method one can predict the disease incidence at long forecasting horizons, with high degree of efficiency and based on such technique a useful early warning system can be developed region wise or nation wise for disease prevention and control activities.     

Estimating physical splenic filtration of Plasmodium falciparum‐infected red blood cells in malaria patients

Splenic filtration of Plasmodium falciparum‐infected red blood cells has been hypothesized to influence malaria pathogenesis. We have developed a minimum cylindrical diameter (MCD) filtration model which estimates physical splenic filtration during malaria infection. The key parameter in the model is the MCD, the smallest tube or cylinder that a red blood cell (RBC) can traverse without lysing. The MCD is defined by a relationship between the RBC surface area and volume. In the MCD filtration model, the MCD filtration function represents the probability of a cell becoming physically removed from circulation. This modelling approach was implemented at a field site in Blantyre, Malawi. We analysed peripheral blood samples from 120 study participants in four clinically defined groups (30 subjects each): cerebral malaria, uncomplicated malaria, aparasitaemic coma and healthy controls. We found statistically significant differences in the surface area and volumes of uninfected RBCs when healthy controls were compared with malaria patients. The estimated filtration rates generated by the MCD model corresponded to previous observations in ex vivo spleen experiments and models of red blood cell loss during acute malaria anaemia.There were no differences in the estimated splenic filtration rates between cerebral malaria and uncomplicated malaria patients. The MCD filtration model estimates that at time of admission, one ring‐stage infected RBC is physically filtered by the spleen for each parasite that remains in peripheral circulation. This field study is the first to use microfluidic devices to identify rheological diversity in RBC populations associated with malaria infection and illness in well‐characterized groups of children living in a malaria endemic area.