Seasonal variation in Plasmodium prevalence in a population of blue tits Cyanistes caeruleus

1. Seasonal variation in environmental conditions is ubiquitous and can affect the spread of infectious diseases. Understanding seasonal patterns of disease incidence can help to identify mechanisms, such as the demography of hosts and vectors, which influence parasite transmission dynamics. 2. We examined seasonal variation in Plasmodium infection in a blue tit Cyanistes caeruleus population over 3 years using sensitive molecular diagnostic techniques, in light of Beaudoin et al.'s (1971; Journal of Wildlife Diseases, 7, 5-13) model of seasonal variation in avian malaria prevalence in temperate areas. This model predicts a within-year bimodal pattern of spring and autumn peaks with a winter absence of infection. 3. Avian malaria infections were mostly Plasmodium (24.4%) with occasional Haemoproteus infections (0.8%). Statistical nonlinear smoothing techniques applied to longitudinal presence/absence data revealed marked temporal variation in Plasmodium prevalence, which apparently showed a within-year bimodal pattern similar to Beaudoin et al.'s model. However, of the two Plasmodium morphospecies accounting for most infections, only the seasonal pattern of Plasmodium circumflexum supported Beaudoin et al.'s model. On closer examination there was also considerable age structure in infection: Beaudoin et al.'s seasonal pattern was observed only in first year and not older birds. Plasmodium relictum prevalence was less seasonally variable. 4. For these two Plasmodium morphospecies, we reject Beaudoin et al.'s model as it does not survive closer scrutiny of the complexities of seasonal variation among Plasmodium morphospecies and host age classes. Studies of host-parasite interactions should consider seasonal variation whenever possible. We discuss the ecological and evolutionary implications of seasonal variation in disease prevalence.     

Fitness effects of endemic malaria infections in a wild bird population: the importance of ecological structure

1.?Parasites can have important effects on host populations influencing either fecundity or mortality, but understanding the magnitude of these effects in endemic host-parasite systems is challenging and requires an understanding of ecological processes affecting both host and parasite. 2.?Avian blood parasites (Haemoproteus and Plasmodium) have been much studied, but the effects of these parasites on hosts in areas where they are endemic remains poorly known. 3.?We used a multistate modelling framework to explore the effects of chronic infection with Plasmodium on survival and recapture probability in a large data set of breeding blue tits, involving 3424 individuals and 3118 infection diagnoses over nine years. 4.?We reveal strong associations between chronic malaria infection and both recapture and survival, effects that are dependent on the clade of parasite, on host traits and on the local risk of infection. 5.?Infection with Plasmodium relictum was associated with reduced recapture probability and increased survival, compared to P.?circumflexum, suggesting that these parasites have differing virulence and cause different types of selection on this host. 6.?Our results suggest a large potential survival cost of acute infections revealed by modelling host survival as a function of the local risk of infection. 7.?Our analyses suggest not only that endemic avian malaria may have multiple fitness effects on their hosts and that these effects are species dependent, but also that adding ecological structure (in this case parasite species and spatial variation in disease occurrence) to analyses of host-parasite interactions is an important step in understanding the ecology and evolution of these systems.     

Life history of a malaria parasite (Plasmodium mexicanum): independent traits and basis for variation

Plasmodium mexicanum, a malaria parasite of lizards, exhibits substantial variation among infections in the life-history traits which define its blood-dwelling stages. Such variation in life histories among infections is common in Plasmodium and may influence the ecology and evolution of the parasite's transmission success and virulence. Insight into these issues requires identification of independent traits (some traits may be bound by developmental trade-offs) and the importance of genetic versus host effects producing the variation. We studied 11 life-history traits in 120 induced infections of P. mexicanum in its natural lizard host (20 each from six donor infections). The traits varied among infections and fell into three clusters: rate/peak (rate of increase and peak parasitaemia of asexuals and gametocytes), time (duration of pre-patent period and the infection's growth) and maturity (timing of first gametocytes). Thus, few life-history traits define an infection in the lizard's blood. Donor effects were significant for ten traits and two trait clusters (maturity was the exception) suggesting genetic differences among infections may influence the rate of increase and peak parasitaemia, but not the timing of the first production of gametocytes.     

Within-population variation in prevalence and lineage distribution of avian malaria in blue tits, Cyanistes caeruleus

The development of molecular genetic screening techniques for avian blood parasites has revealed many novel aspects of their ecology, including greatly elevated diversity and complex host-parasite relationships. Many previous studies of malaria in birds have treated single study populations as spatially homogeneous with respect to the likelihood of transmission of malaria to hosts, and we have very little idea whether any spatial heterogeneity influences different malaria lineages similarly. Here, we report an analysis of variation in the prevalence and cytochrome b lineage distribution of avian malaria infection with respect to environmental and host factors, and their interactions, in a single blue tit (Cyanistes caeruleus) population. Of 11 Plasmodium and Haemoproteus cytochrome b lineages found in 997 breeding individuals, the three most numerous (pSGS1, pTURDUS1 and pBT7) were considered separately, in addition to analyses of all avian malaria lineages pooled. Our analyses revealed marked spatial differences in the prevalence and distribution of these lineages, with local prevalence of malaria within the population ranging from over 60% to less than 10%. In addition, we found several more complex patterns of prevalence with respect to local landscape features, host state, parasite genotype, and their interactions. We discuss the implications of such heterogeneity in parasite infection at a local scale for the study of the ecology and evolution of infectious diseases in natural populations. The increased resolution afforded by the combination of molecular genetic and geographical information systems (GIS) tools has the potential to provide many insights into the epidemiology, evolution and ecology of these parasites in the future.     

Loss of forest cover and host functional diversity increases prevalence of avian malaria parasites in the Atlantic Forest

Host phylogenetic relatedness and ecological similarity are thought to contribute to parasite community assembly and infection rates. However, recent landscape level anthropogenic changes may disrupt host-parasite systems by impacting functional and phylogenetic diversity of host communities. We examined whether changes in host functional and phylogenetic diversity, forest cover, and minimum temperature influence the prevalence, diversity, and distributions of avian haemosporidian parasites (genera Haemoproteus and Plasmodium) across 18 avian communities in the Atlantic Forest. To explore spatial patterns in avian haemosporidian prevalence and taxonomic and phylogenetic diversity, we surveyed 2241 individuals belonging to 233 avian species across a deforestation gradient. Mean prevalence and parasite diversity varied considerably across avian communities and parasites responded differently to host attributes and anthropogenic changes. Avian malaria prevalence (termed herein as an infection caused by Plasmodium parasites) was higher in deforested sites, and both Plasmodium prevalence and taxonomic diversity were negatively related to host functional diversity. Increased diversity of avian hosts increased local taxonomic diversity of Plasmodium lineages but decreased phylogenetic diversity of this parasite genus. Temperature and host phylogenetic diversity did not influence prevalence and diversity of haemosporidian parasites. Variation in the diversity of avian host traits that promote parasite encounter and vector exposure (host functional diversity) partially explained the variation in avian malaria prevalence and diversity. Recent anthropogenic landscape transformation (reduced proportion of native forest cover) had a major influence on avian malaria occurrence across the Atlantic Forest. This suggests that, for Plasmodium, host phylogenetic diversity was not a biotic filter to parasite transmission as prevalence was largely explained by host ecological attributes and recent anthropogenic factors. Our results demonstrate that, similar to human malaria and other vector-transmitted pathogens, prevalence of avian malaria parasites will likely increase with deforestation.     

Infection dynamics of endemic malaria in a wild bird population: parasite species-dependent drivers of spatial and temporal variation in transmission rates

1.?Investigating the ecological context in which host-parasite interactions occur and the roles of biotic and abiotic factors in forcing infection dynamics is essential to understanding disease transmission, spread and maintenance. 2.?Despite their prominence as model host-pathogen systems, the relative influence of environmental heterogeneity and host characteristics in influencing the infection dynamics of avian blood parasites has rarely been assessed in the wild, particularly at a within-population scale. 3.?We used a novel multievent modelling framework (an extension of multistate mark-recapture modelling) that allows for uncertainty in disease state, to estimate transmission parameters and assess variation in the infection dynamics of avian malaria in a large, longitudinally sampled data set of breeding blue tits infected with two divergent species of Plasmodium parasites. 4.?We found striking temporal and spatial heterogeneity in the disease incidence rate and the likelihood of recovery within this single population and demonstrate marked differences in the relative influence of environmental and host factors in forcing the infection dynamics of the two Plasmodium species. 5.?Proximity to a permanent water source greatly influenced the transmission rates of P.?circumflexum, but not of P.?relictum, suggesting that these parasites are transmitted by different vectors. 6.?Host characteristics (age/sex) were found to influence infection rates but not recovery rates, and their influence on infection rates was also dependent on parasite species: P.?relictum infection rates varied with host age, whilst P.?circumflexum infection rates varied with host sex. 7.?Our analyses reveal that transmission of endemic avian malaria is a result of complex interactions between biotic and abiotic components that can operate on small spatial scales and demonstrate that knowledge of the drivers of spatial and temporal heterogeneity in disease transmission will be crucial for developing accurate epidemiological models and a thorough understanding of the evolutionary implications of pathogens.     

Island and taxon effects in parasitism revisited: avian malaria in the Lesser Antilles

We identify and describe the distribution of 12 genetically distinct malaria parasite lineages over islands and hosts in four common passerine birds in the Lesser Antilles. Combined parasite prevalence demonstrates strong host effects, little or no island effect, and a significant host-times-island interaction, indicating independent outcomes of host-parasite infections among island populations of the same host species. Host- and/or island-specific parasite lineages do not explain these host-parasite associations; rather, individual lineages themselves demonstrate the same type of independent interactions. Unlike overall prevalence, individual parasite lineages show considerable geographic structure (i.e., island effects) as well as species effects indicating that parasite lineages are constrained in their ability to move between hosts and locations. Together, our results suggest an upper limit to the number of host individuals that malaria parasites, as a community, can infect. Within this limit, however, the relative frequency of the different lineages varies reflecting fine scale interactions between host and parasite populations. Patterns of host-parasite associations within this system suggest both historical co-evolution and ecologically dynamic and independent host-parasite interactions.     

Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study

ABSTRACT: BACKGROUND: Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. METHODS: A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) coadministered with SP (AS + SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. FINDINGS: Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from <1% to 2% between the two sites and across the five survey years. Amultivariable logistic regression model was fitted to adjust for age, socioeconomic status, bed net use and rainfall. In the presence of consistently high coverage and efficacy of SP monotherapy and AS + SP in the comparison and intervention areas, the introduction of ACT in the intervention site was associated with a modest reduction in the adjusted asexual parasitaemia prevalence of 5 percentage-points or 23% (p < 0.0001) relative to the comparison site. Gametocytaemia prevalence did not differ significantly (p = 0.30). Interpretation The introduction of ACT at fixed health facilities only modestly reduced asexual parasitaemia prevalence. ACT is effective for treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly reinfected.     

Ecology and dynamics of the blood parasite, Hepatozoon tuatarae (Apicomplexa), in tuatara (Sphenodon punctatus) on Stephens Island, New Zealand

We explored infection patterns and temporal dynamics of the protozoan blood parasite Hepatozoon tuatarae (Apicomplexa) infecting the tuatara (Sphenodon punctatus), a protected reptile living on Stephens Island, New Zealand. In March 2006, we surveyed tuatara in five study sites to examine spatial variation in infection prevalence, and four times, from May 2005 to November 2006, we recaptured marked individuals within three study sites to examine the temporal dynamics of infection. We also examined how blood-parasite infection patterns were influenced by host sex, body size, and host infestation with ticks (Amblyomma sphenodonti) and mites (Neotrombicula spp.), which are potential vectors of the blood parasite. Infection prevalence (16.9-24% infected) and intensity (<0.01-0.1% blood cells infected) were low in all samples. Infection intensity varied among the five sampled sites in March 2006, but prevalence did not. Neither infection prevalence nor intensity varied with time, and infections were detected in consecutive samples from recaptured individuals for up to 18 mo. Neither survey showed an influence of host sex on infection, but both surveys showed infection intensity declined with increasing host body size, as did infection prevalence in the spatial survey. In the temporal survey, we found a positive relationship between the tick numbers on hosts and blood-parasite infection intensity, which were stronger in two of the sampling periods and among larger hosts. These data suggest that exposure and susceptibility to infection decreases with host size and that ticks, but not mites, are probably the vectors in this ancient host-parasite association of a long-lived (>50 yr) host.     

Coupled population dynamics of endosymbionts within and between hosts

Many insect species are infected with maternally transmitted endosymbionts, the most widely documented being Wolbachia . The rate of spread and equilibrium of prevalence of these infections depend on two parameters – maternal transmission fidelity and relative fitness of infected cytoplasmic lineages. Both transmission fidelity and the phenotypic effect of endosymbionts often increase with endosymbiont density within hosts. Thus, the dynamics of infection prevalence in host populations depends on processes affecting within-host density of endosymbionts. In theory, the equilibrium prevalence of infection by male-killing endosymbionts is much more sensitive to changes in transmission fidelity and relative fitness than is that of endosymbionts that cause cytoplasmic incompatibility. In natural populations, male-killers exhibit much greater temporal and spatial variation in the prevalence of infection than do endosymbionts that cause cytoplasmic incompatibility. Thus, the population dynamics of endosymbiont infections, especially those that cause male-killing, is likely to be governed by environmental and genetic variables that affect within-host density of these infections.     

Primary peak and chronic malaria infection levels are correlated in experimentally infected great reed warblers

SUMMARY Malaria parasites often manage to maintain an infection for several months or years in their vertebrate hosts. In humans, rodents and birds, most of the fitness costs associated with malaria infections are in the short initial primary (high parasitaemia) phase of the infection, whereas the chronic phase (low parasitaemia) is more benign to the host. In wild birds, malaria parasites have mainly been studied during the chronic phase of the infection. This is because the initial primary phase of infection is short in duration and infected birds with severe disease symptoms tend to hide in sheltered places and are thus rarely caught and sampled. We therefore wanted to investigate the relationship between the parasitaemia during the primary and chronic phases of the infection using an experimental infection approach. We found a significant positive correlation between parasitaemia in the primary peak and the subsequent chronic phase of infection when we experimentally infected great reed warblers (Acrocephalus arundinaceus) with Plasmodium ashfordi. The reason for this association remains to be understood, but might arise from individual variation in exoerythrocytic parasite reservoirs in hosts, parasite antigenic diversity and/or host genetics. Our results suggest that the chronic phase parasitaemia can be used to qualitatively infer the parasitaemia of the preceding and more severe primary phase, which is a very important finding for studies of avian malaria in wild populations.     

Epidemiological, evolutionary, and coevolutionary implications of context-dependent parasitism

Abstract Victims of infection are expected to suffer increasingly as parasite population growth increases. Yet, under some conditions, faster-growing parasites do not appear to cause more damage, and infections can be quite tolerable. We studied these conditions by assessing how the relationship between parasite population growth and host health is sensitive to environmental variation. In experimental infections of the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we show how easily an interaction can shift from a severe interaction, that is, when host fitness declines substantially with each unit of parasite growth, to a tolerable relationship by changing only simple environmental variables: temperature and food availability. We explored the evolutionary and epidemiological implications of such a shift by modeling pathogen evolution and disease spread under different levels of infection severity and found that environmental shifts that promote tolerance ultimately result in populations harboring more parasitized individuals. We also find that the opportunity for selection, as indicated by the variance around traits, varied considerably with the environmental treatment. Thus, our results suggest two mechanisms that could underlie coevolutionary hotspots and coldspots: spatial variation in tolerance and spatial variation in the opportunity for selection.     

Migratory behavior of birds affects their coevolutionary relationship with blood parasites

Host traits, such as migratory behavior, could facilitate the dispersal of disease-causing parasites, potentially leading to the transfer of infections both across geographic areas and between host species. There is, however, little quantitative information on whether variation in such host attributes does indeed affect the evolutionary outcome of host-parasite associations. Here, we employ Leucocytozoon blood parasites of birds, a group of parasites closely related to avian malaria, to study host-parasite coevolution in relation to host behavior using a phylogenetic comparative approach. We reconstruct the molecular phylogenies of both the hosts and parasites and use cophylogenetic tools to assess whether each host-parasite association contributes significantly to the overall congruence between the two phylogenies. We find evidence for a significant fit between host and parasite phylogenies in this system, but show that this is due only to associations between nonmigrant parasites and their hosts. We also show that migrant bird species harbor a greater genetic diversity of parasites compared with nonmigrant species. Taken together, these results suggest that the migratory habits of birds could influence their coevolutionary relationship with their parasites, and that consideration of host traits is important in predicting the outcome of coevolutionary interactions.     

The impact of immunization on competition within Plasmodium infections

Evolutionary theory argues that ecological interactions between pathogens within an infection can be a potent source of selection shaping traits such as virulence, drug resistance, and infectiousness. In humans, malaria infections are frequently genetically diverse, with mixed genotype infections the norm. A wide variety of evidence shows that crowding occurs within infections, with the population densities of individual genotypes suppressed by the presence of others. Public health interventions are expected to impact on levels of immunity experienced by pathogens, indirectly by reducing the rate of acquisition of natural immunity by reducing the force of infection, and directly in the case of vaccination programs. Here we ask how enhanced host immunity affects competitive interactions between malaria parasites within hosts and thus the strength of in-host selection on traits such as virulence. We used a model malaria system, Plasmodium chabaudi in laboratory mice, where it has been previously shown that less virulent parasites are competitively suppressed by more virulent strains, generating within-host selection for increased virulence. We found that immunization with either a recombinant antigen or with live parasites suppressed parasite densities, but that there was no evidence that immunization relieved or exacerbated competitive suppression, or affected the relative frequency of clones within infections. There is thus no reason to think that immunization strengthens or alleviates the potentially very potent selection on parasite traits arising from interactions between pathogen genotypes within infections.     

Cross-species regulation of malaria parasitaemia in the human host

Longitudinal genetic analysis of the composition of malaria parasites infecting humans has demonstrated that individuals living in endemic areas are chronically infected with multiple genotypes and species of Plasmodium. The accumulation of infections is a consequence of superinfection from the bites of many infected anopheline mosquitoes. The clinical outcome of infection is determined by the host's ability to regulate the density of malaria parasites in the blood. Interestingly, most infections do not cause symptoms of malarial disease after a degree of immunity is acquired. Here, we review data from the first genetic study of the longitudinal dynamics of multiple Plasmodium species and genotypes in humans. The data show that the total parasite density of Plasmodium species oscillates around a threshold and that peaks of infection with each species do not coincide. We propose that malaria parasitaemia is controlled in a density-dependent manner in these semi-immune children. This implies that a cross-species mechanism of parasite regulation exists. A model of how multiple immune responses could act in concert to explain these within host dynamics is discussed in relation to known regulatory mechanisms.     

Ecological and genetic determinants of multiple infection and aggregation in a microbial host-parasite system

The number of parasites colonizing a host (termed 'multiple infection') is an important determinant of host-parasite interactions. In theory, multiple infection is determined by random mass action in genetically and spatially homogeneous populations of host and parasite. In real populations, deviations from these assumptions may strongly influence levels of multiple infection. We carried out inoculation experiments in microcosms of the freshwater protozoan Paramecium caudatum and its bacterial parasite Holospora undulata. Increasing parasite dose produced higher levels of (multiple) infection; more susceptible host genotypes also were more multiply infected. An overall pattern of parasite aggregation (excess of uninfected individuals and of individuals carrying larger numbers of parasites) indicated deviations from random mass-action transmission. Homogenizing spatial distributions of parasite and host in our microcosms did not affect aggregation, whereas aggregation was more pronounced in old than in new host clones. Thus, variation in susceptibility may arise over time within clonal populations. When sequentially inoculated, already established infections increased the probability of additional infection in generally resistant host clones, but decreased it in more susceptible clones. Hence, the role of multiple infection as a driver of epidemiological or evolutionary processes may vary among populations, depending on their precise genetic composition or infection history.     

The effect of helminth co-infection on malaria in mice: a meta-analysis

The question of how helminths may alter the course of concurrent malaria infection has attracted much interest in recent years. In particular, it has been suggested that by creating an anti-inflammatory immune environment, helminth co-infection may dampen both protective and immunopathological responses to malaria parasites, thus altering malaria infection dynamics and disease severity. Both synergistic and antagonistic interactions are reported in the literature, and the causes of variation among studies are not well understood. Here, meta-analysis of 42 mouse co-infection experiments was used to address how helminths influence malaria parasite replication and host mortality, and explore the factors explaining variation in findings. Most notably, this analysis revealed contrasting effects of helminth co-infection in lethal and resolving malaria models. Whilst co-infection exacerbated mortality and increased peak parasitaemia in ordinarily resolving malaria infections (Plasmodium chabaudi and Plasmodium yoelii), effects among lethal malaria infections (Plasmodium berghei) tended to be in the opposite direction with no change in parasitaemia. In the subset of experiments on cerebral malaria models (P. berghei ANKA strain in a susceptible host), helminth co-infection significantly delayed death. These findings are consistent with the hypothesis that depending on the existing balance of pro- and anti-inflammatory responses mounted against malaria parasites in a given host, immune responses elicited by helminth co-infection may either promote or inhibit malarial disease. However, despite such broad patterns, a prominent feature of this dataset was great heterogeneity in effects across studies. A key future challenge therefore lies in explaining the biological causes of this variation, including a more thorough exploration of non-immunological mechanisms of helminth-malaria interaction.     

The Relationship between Parasite Fitness and Host Condition in an Insect - Virus System

Research in host-parasite evolutionary ecology has demonstrated that environmental variation plays a large role in mediating the outcome of parasite infection. For example, crowding or low food availability can reduce host condition and make them more vulnerable to parasite infection. This observation that poor-condition hosts often suffer more from parasite infection compared to healthy hosts has led to the assumption that parasite productivity is higher in poor-condition hosts. However, the ubiquity of this negative relationship between host condition and parasite fitness is unknown. Moreover, examining the effect of environmental variation on parasite fitness has been largely overlooked in the host-parasite literature. Here we investigate the relationship between parasite fitness and host condition by using a laboratory experiment with the cabbage looper Trichoplusia ni and its viral pathogen, AcMNPV, and by surveying published host-parasite literature. Our experiments demonstrated that virus productivity was positively correlated with host food availability and the literature survey revealed both positive and negative relationships between host condition and parasite fitness. Together these data demonstrate that contrary to previous assumptions, parasite fitness can be positively or negatively correlated with host fitness. We discuss the significance of these findings for host-parasite population biology.     

Assessment of Anopheles salivary antigens as individual exposure biomarkers to species-specific malaria vector bites

The development of parasitological immunity against malaria affects the ability to detect infection, the efficiency of the local human parasite reservoir at infecting mosquitoes, and the response to reintroduction of parasites to previously cleared areas. Observations of similar age-trends in detected prevalence and mean parasitaemia across more than an order-of-magnitude of variation in baseline transmission complicate simple exposure-driven explanations. Mathematical models often employ age-dependent immune factors to match the observed trends, while the present model uses a new detailed mechanistic model of parasite transmission dynamics to explain age-trends through the mechanism of parasite diversity. Illustrative simulations are performed for multiple field sites in Tanzania and Nigeria, and observed age-trends and seasonality in parasite prevalence are recreated in silico, proffering possible mechanistic explanations of the observational data. Observed temporal dynamics in measured parasitaemia are recreated for each location and age-prevalence outputs are studied. Increasing population-level diversity in malaria surface antigens delays development of broad parasitological immunity. A local parasite population with high diversity can recreate the observed trends in age-prevalence across more than an order of magnitude of variation in transmission intensities. Mechanistic models of human immunity and parasite antigen diversity can recreate the observed temporal patterns for the development of parasitological immunity across a wide range of transmission intensities. This has implications for the distribution of disease burden across the population, the human transmission reservoir, design of elimination campaigns, and development and roll-out of potential vaccines.     

Spatially explicit burden estimates of malaria in Tanzania: bayesian geostatistical modeling of the malaria indicator survey data

A national HIV/AIDS and malaria parasitological survey was carried out in Tanzania in 2007-2008. In this study the parasitological data were analyzed: i) to identify climatic/environmental, socio-economic and interventions factors associated with child malaria risk and ii) to produce a contemporary, high spatial resolution parasitaemia risk map of the country. Bayesian geostatistical models were fitted to assess the association between parasitaemia risk and its determinants. bayesian kriging was employed to predict malaria risk at unsampled locations across Tanzania and to obtain the uncertainty associated with the predictions. Markov chain Monte Carlo (MCMC) simulation methods were employed for model fit and prediction. Parasitaemia risk estimates were linked to population data and the number of infected children at province level was calculated. Model validation indicated a high predictive ability of the geostatistical model, with 60.00% of the test locations within the 95% credible interval. The results indicate that older children are significantly more likely to test positive for malaria compared with younger children and living in urban areas and better-off households reduces the risk of infection. However, none of the environmental and climatic proxies or the intervention measures were significantly associated with the risk of parasitaemia. Low levels of malaria prevalence were estimated for Zanzibar island. The population-adjusted prevalence ranges from 0.29% in Kaskazini province (Zanzibar island) to 18.65% in Mtwara region. The pattern of predicted malaria risk is similar with the previous maps based on historical data, although the estimates are lower. The predicted maps could be used by decision-makers to allocate resources and target interventions in the regions with highest burden of malaria in order to reduce the disease transmission in the country.