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Pathogens, which have recently colonized a new host species or new populations of the same host, are interesting models for understanding how populations may evolve in response to novel environments. During its colonization of South America from Africa, Plasmodium falciparum, the main agent of malaria, has been exposed to new conditions in distinctive new human populations (Amerindian and populations of mixed origins) that likely exerted new selective pressures on the parasite's genome. Among the genes that might have experienced strong selective pressures in response to these environmental changes, the eba genes (erythrocyte-binding antigens genes), which are involved in the invasion of the human red blood cells, constitute good candidates. In this study, we analysed, in South America, the polymorphism of three eba genes (eba-140, eba-175, eba-181) and compared it to the polymorphism observed in African populations. The aim was to determine whether these genes faced selective pressures in South America distinct from what they experienced in Africa. Patterns of genetic variability of these genes were compared to the patterns observed at two housekeeping genes (adsl and serca) and 272 SNPs to separate adaptive effects from demographic effects. We show that, conversely to Africa, eba-140 seemed to be under stronger diversifying selection in South America than eba-175. In contrast, eba-181 did not show any sign of departure from neutrality. These changes in the patterns of selection on the eba genes could be the consequence of changes in the host immune response, the host receptor polymorphisms and/or the ability of the parasite to silence or express differentially its invasion proteins.

The origin of Plasmodium falciparum in South America is controversial. Some studies suggest a recent introduction during the European colonizations and the transatlantic slave trade. Other evidence--archeological and genetic--suggests a much older origin. We collected and analyzed P. falciparum isolates from different regions of the world, encompassing the distribution range of the parasite, including populations from sub-Saharan Africa, the Middle East, Southeast Asia, and South America. Analyses of microsatellite and SNP polymorphisms show that the populations of P. falciparum in South America are subdivided in two main genetic clusters (northern and southern). Phylogenetic analyses, as well as Approximate Bayesian Computation methods suggest independent introductions of the two clusters from African sources. Our estimates of divergence time between the South American populations and their likely sources favor a likely introduction from Africa during the transatlantic slave trade.

Despite a wide overlap between malaria- and dengue-endemic areas, published reports of co-infections are scarce in the literature. The first 2 patients with concurrent malaria (Plasmodium falciparum) and dengue were [...]

French Guiana is a French territory in South America; the Amazon rain forest covers 92% of the territory. Toxoplasmosis is a cosmopolitan parasitic disease. It is usually benign in patients [...]

Abstract Background High circulating parasite load is one of the WHO criteria for severe falciparum malaria. During a period of 11 years (2000–2010), the frequency of hyperparasitaemia (HP) (≥4% infected erythrocytes) during bouts of malaria due to Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae in patients referred to Cayenne General Hospital (CGH) in French Guiana and the frequency of their admission to the Intensive Care Unit (ICU) were evaluated. Methods A mean of 1,150 malaria cases were referred to the Parasitology Laboratory of CGH each year over the last decade. During this period, malaria diagnostic (microscopy) and parasitaemia evaluation have remained unchanged: determination of the parasitized erythrocytes percentage with asexual forms on thin blood smears for all cases of parasitaemia exceeding 0.1%. Patients admitted to the ICU can be counted by origin of the request for malaria testing. All the data collected retrospectively were anonymized in a standardized case report form and in database. Results Between 2000 and 2010, 12,254 bouts of malaria were confirmed at the Parasitology Laboratory of CHG: P. vivax: 56.2%, P. falciparum: 39.5%, co-infection with both species: 3.4%, P. malariae: 0.9%. HP was observed in 262 cases, at a frequency of 4.9% for P. falciparum and only 0.041% for P. vivax, with no recorded cases for P. malariae. The need for intensive care was correlated with P. falciparum parasite load: 12.3% of cases for parasitaemia of 4-9%, 21.2% for parasitaemia 10-19%, 50% for parasitaemia 20-29% and 77.8% for parasitaemia ≥30% (n=9). The patient with the highest parasitaemia (75% infected erythrocytes with asexual form) presented a major concomitant lupus flare-up treated with corticoids. He survived without obvious sequelae. Conclusions In French Guiana during bouts of malaria, HP was observed at a frequency of ~ 5% for P. falciparum and two orders of magnitude less frequent for P. vivax. HP is a severity criterion for falciparum malaria in this endemic area. However, two of the patients with HP ≥30% were not admitted to the ICU and sequel-free cure in malaria patients with 75% parasitaemia is, therefore, possible.

Abstract Background Dengue and malaria are two major arthropod-borne infections in tropical areas, but dual infections were only described for the first time in 2005. Reports of these concomitant infections are scarce and there is no evidence of more severe clinical and biological pictures than single infections. Methods To compare co-infections to dengue alone and malaria alone, a retrospective matched-pair study was conducted between 2004 and 2010 among patients admitted in the emergency department of Cayenne hospital, French Guiana. Results 104 dengue and malaria co-infection cases were identified during the study period and 208 individuals were matched in two comparison groups: dengue alone and malaria alone. In bivariate analysis, co-infection clinical picture was more severe than separated infections, in particular using the severe malaria WHO criteria. In multivariate analysis, independent factors associated with co-infection versus dengue were: masculine gender, CRP level > 50 mg/L, thrombocytopaenia < 50 109/L, and low haematocrit 9/L and low Plasmodium parasitic load < 0.001%. Conclusions In the present study, dengue and malaria co-infection clinical picture seems to be more severe than single infections in French Guiana, with a greater risk of deep thrombocytopaenia and anaemia.

Abstract Background Malaria remains a major health problem in French Guiana, with a mean of 3800 cases each year. A previous study in Camopi, an Amerindian village on the Oyapock River, highlighted the major contribution of environmental features to the incidence of malaria attacks. We propose a method for the objective selection of the best multivariate peridomestic landscape characterisation that maximises the chances of identifying relationships between environmental features and malaria incidence, statistically significant and meaningful from an epidemiological point of view. Methods A land-cover map, the hydrological network and the geolocalised inhabited houses were used to characterise the peridomestic landscape in eleven discoid buffers with radii of 50, 100, 200, 300, 400, 500, 600, 700, 800, 900 and 1000 metres. Buffer-based landscape characterisations were first compared in terms of their capacity to discriminate between sites within the geographic space and of their effective multidimensionality in variable space. The Akaike information criterion (AIC) was then used to select the landscape model best explaining the incidences of P. vivax and P. falciparum malaria. Finally, we calculated Pearson correlation coefficients for the relationships between environmental variables and malaria incidence, by species, for the more relevant buffers. Results The optimal buffers for environmental characterisation had radii of 100 m around houses for P. vivax and 400 m around houses for P. falciparum. The incidence of P. falciparum malaria seemed to be more strongly linked to environmental features than that of P. vivax malaria, within these buffers. The incidence of P. falciparum malaria in children was strongly correlated with proportions of bare soil (r = -0.69), land under high vegetation (r = 0.68) and primary forest (r = 0.54), landscape division (r = 0.48) and the number of inhabited houses (r = -0.60). The incidence of P. vivax malaria was associated only with landscape division (r = 0.49). Conclusions The proposed methodology provides a simple and general framework for objective characterisation of the landscape to account for field observations. The use of this method enabled us to identify different optimal observation horizons around houses, depending on the Plasmodium species considered, and to demonstrate significant correlations between environmental features and the incidence of malaria.

Abstract Background Malaria is a major health issue in French Guiana. Amerindian communities remain the most affected. A previous study in Camopi highlighted the predominant role of environmental factors in the occurrence of malaria. However, all parameters involved in the transmission were not clearly identified. A new survey was conducted in order to clarify the risk factors for the presence of malaria cases in Camopi. Methods An open cohort of children under seven years of age was set up on the basis of biologically confirmed malaria cases for the period 2001-2009. Epidemiological and observational environmental data were collected using two structured questionnaires. Data were analysed with a multiple failures multivariate Cox model. The influence of climate and the river level on malaria incidence was evaluated by time-series analysis. Relationships between Anopheles darlingi human biting rates and malaria incidence rates were estimated using Spearman's rank correlation. Results The global annual incidence over the nine-year period was 238 per 1,000 for Plasmodium falciparum, 514 per 1,000 for Plasmodium visa and 21 per 1,000 for mixed infections. The multivariate survival analysis associated higher malaria incidence with living on the Camopi riverside vs. the Oyapock riverside, far from the centre of the Camopi hamlet, in a home with numerous occupants and going to sleep late. On the contrary, living in a house cleared of all vegetation within 50 m and at high distance of the forest were associated with a lower risk. Meteorological and hydrological characteristics appeared to be correlated with malaria incidence with different lags. Anopheles darlingi human biting rate was also positively correlated to incident malaria in children one month later. Conclusions Malaria incidence in children remains high in young children despite the appearance of immunity in children around three years of age. The closeness environment but also the meteorological parameters play an important role in malaria transmission among children under seven years of age in Camopi.

Abstract Background Malaria remains a serious problem in French Guiana, which is at potential risk for drought linked with the El Niño Event and where there could be a risk of malaria epidemic after the onset of an El Niño event. Methods A time series analysis using ARIMA was developed to investigate temporal correlations between the monthly Plasmodium falciparum case numbers and El Niño Southern Oscillation (ENSO) as measured by the Southern Oscillation Index (SOI) at the Cayenne General Hospital between 1996 and 2009. Results The data showed a positive influence of El Niño at a lag of three months on P. falciparum cases (p < 0.001). The incorporation of SOI data in the ARIMA model reduced the AIC by 4%. Conclusions Although there is a statistical link, the predictive value of ENSO to modulate prevention intervention seems marginal in French Guiana. However, additional work should refine the regional dependence of malaria on the ENSO state.

Abstract Background The epidemiological profiles of vector-borne diseases, such as malaria, are strongly associated with environmental conditions. An understanding of the effect of the climate on the occurrence of malaria may provide indirect insight into the anopheles mosquito vectors endemic to a particular region. The association between meteorological and hydrographical factors and the occurrence of malaria was studied in a village in French Guiana during an epidemic caused essentially by Plasmodium vivax. Methods A cohort of confirmed cases of P. vivax malaria occurring between 2002 and 2007 was studied to search for an association between the number of new infection episodes occurring each month, mean, maximum and minimum monthly temperatures, cumulative rainfall for the month and the mean monthly height of the river bordering the village, with the aid of time series. Cross-correlation analysis revealed that these meteorological factors had large effects on the number of episodes, over a study period of 12 months. Results Climatic factors supporting the continuance of the epidemic were identified in the short-term (low minimum temperatures during the month), medium-term (low maximum temperatures two months before) and long-term (low maximum temperatures nine months before and high lowest level of the river 12 months before). Cross-correlation analysis showed that the effects of these factors were greatest at the beginning of the short rainy season. Conclusion The association between the river level and the number of malaria attacks provides clues to better understand the environment of malaria transmission and the ecological characteristics of the vectors in the region.

An investigation on whether the initiation of highly active antiretroviral therapy (HAART) has any influence on the incidence of disseminated histoplasmosis is presented. Results reveal that after controlling for the confounding effect of CD4 counts, the incidence of symptomatic disseminated histoplasmosis in the 2 months after HAART initiation is higher than in untreated patients.

Abstract Should the Kalimbe (a traditional Amerindian loincloth) be banned, based on its association with an increased risk of malaria? Studies on malaria conducted on Amerindian children in the Oyapock region, French Guiana suggest that there is an argument for replacing the Kalimbe with a modern alternative. However, the wider issue of how the positive (risk reduction and related benefits) and negative effects (exacerbation of acculturation processes and associated consequences) should be assessed needs to be considered before suggesting a change in ancestral behaviour for medical purposes. A multidisciplinary approach is needed, together with caution and humility from epidemiologists.

Abstract Background Malaria is a major public health problem in French Guiana, where Plasmodium vivax has become the dominant malaria species since 2000. As in others endemic areas, it is important to specify the pattern of vivax malaria relapses and to try to discriminate efficiently re-infections from relapses. Methods This study was conducted in children born between January 1, 2001 and December 31, 2008 in Camopi, an Amerindian village located in the Amazon forest (n = 325), using an open cohort design. Primary and secondary attack rates of P. vivax were calculated using survival analysis. With the difference between the primary and secondary rates, this study aimed to estimate indirectly P. vivax relapse rate and evaluate its time evolution. Results Of the 1042 malaria attacks recorded, 689 (66%) were due to P. vivax (without mixed infection). One hundred and fifty one children had their primary attack with P. vivax and 106 had their two first attacks with P. vivax. In the absence of primaquine treatment, it was shown that P. vivax relapses mainly occurred during the first three months after the first attack. Thirty percent of children never had a relapse, 42% had a relapse before the first month after primary attack, 59% before the second month and 63% before the third month. Conclusion This study confirmed that the relapse pattern in Camopi was compatible with the pattern described for the P. vivax Chesson (tropical) strain. In addition, due to the relapse rate time evolution, a simple arbitrary classification rule could be constructed: before 90 days after the primary attack, the secondary attack is a relapse; after 90 days, it is a re-infection. Adapted management of malaria cases based on these results could be devised.

Abstract Background Reliable molecular typing tools are required for a better understanding of the molecular epidemiology of Plasmodium vivax. The genes msp3a and msp1_block5 are highly polymorphic and have been used as markers in many P. vivax population studies. These markers were used to assess the genetic diversity of P. vivax strains from French Guiana (South America) and to develop a molecular typing protocol. Methods A total of 120 blood samples from 109 patients (including 10 patients suffered from more than one malaria episode, samples were collected during each episode) with P. vivax infection were genotyped. All samples were analysed by msp3a PCR-RFLP and msp1_b5 gene sequencing was performed on 57 samples. Genotyping protocol applied to distinguish between new infection or relapse from heterologus hypnozoites and treatment failure or relapse from homologus hypnozoites was based on analysing first msp3a by PCR-RFLP and secondly, only if the genotypes of the two samples are identical, on sequencing the msp1_b5 gene. Results msp3a alleles of three sizes were amplified by PCR: types A, B and C. Eleven different genotypes were identified among the 109 samples analysed by msp3a PCR-RFLP. In 13.8% of cases, a mixed genotype infection was observed. The sequence of msp1_b5 gene revealed 22 unique genotypes and 12.3% of cases with mixed infection. In the 57 samples analysed by both methods, 45 genotypes were found and 21% were mixed. Among ten patients with two or three malaria episodes, the protocol allowed to identify five new infections or relapses from heterologous hypnozoites and six treatment failures of relapses from homologous hypnozoites. Conclusion The study showed a high diversity of msp3a and msp1_b5 genetic markers among P. vivax strains in French Guiana with a low polyclonal infection rate. These results indicated that the P. vivax genotyping protocol presented has a good discrimination power and can be used in clinical drug trials or epidemiological studies.