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Interactions between worms and malaria: Good worms or bad worms?
Mathieu Nacher
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-259
Abstract: In 1977, it was reported that malnourished patients heavily infected with Ascaris lumbricoides were free of malaria [1]. In 1978, the same team reported that piperazine treatment of patients with a heavy worm burden of Ascaris was followed by an increase in malaria attacks [2]. For the following 20 years, there were no other studies on the subject, perhaps for lack of connections between the fields of nutrition and malaria epidemiology or immunology. In the past decade, the topic was rediscovered, this time from an immunological angle. Depending on which publication one reads, it is not clear if the outcome of this interaction is beneficial [3], neutral [4] or harmful [5]. The studies on the interactions between worms and malaria in humans have been very different in design, in the age groups sampled, in the way the malaria outcome and the exposure to helminths were considered. It is, therefore, impossible to conduct a meta-analysis to settle the matter. Despite these difficulties, the present review aims to synthesize the growing number of studies that have explored the interactions between worms and malaria. Pubmed and google scholar searches were performed for malaria and any of the keywords worms, helminth, Ascaris, hookworm, Trichuris, or Strongyloides. This search identified published papers which were then studied for additional references.When it comes to coinfections between worms and malaria, Ascaris lumbricoides has been the most cited worm. Eight studies found that Ascaris was associated with a reduction of malaria (incidence, prevalence or reduction of parasitemia)[1,2,6-11], two studies found that Ascaris was associated with an increase in malaria prevalence [12,13], and two studies found no relation to malaria [4,14]. For cerebral malaria or renal failure, two studies identified Ascaris lumbricoides as the only individual worm associated with protection from severe malaria in adults [3,15]. One study observed an increase of severe malaria in Ascaris-i
Helminth-infected patients with malaria: a low profile transmission hub?
Nacher Mathieu
Malaria Journal , 2012, DOI: 10.1186/1475-2875-11-376
Abstract: Eclipsed by the debates about malaria incidence and severity in individual patients, malaria transmission in helminth-infected persons has so far received very little attention. Studies in humans have shown increased malaria incidence and prevalence, and a trend for a reduction of symptoms in patients with malaria. This suggests that such patients could possibly be less likely to seek treatment thus carrying malaria parasites and their gametocytes for longer durations, therefore, being a greater potential source of transmission. In addition, in humans, a study showed increased gametocyte carriage, and in an animal model of helminth-malaria co-infection, there was increased malaria transmission. These elements converge towards the hypothesis that patients co-infected with worms and malaria may represent a hub of malaria transmission. The test of this hypothesis requires verifying, in different epidemiological settings, that helminth-infected patients have more gametocytes, that they have less symptomatic malaria and longer-lasting infections, and that they are more attractive for the vectors. The negative outcome in one setting of one of the above aspects does not necessarily mean that the other two aspects may suffice to increase transmission. If it is verified that patients co-infected by worms and malaria could be a transmission hub, this would be an interesting piece of strategic information in the context of the spread of anti-malarial resistance and the malaria eradication attempts.
The role of El Ni?o southern oscillation (ENSO) on variations of monthly Plasmodium falciparum malaria cases at the cayenne general hospital, 1996-2009, French Guiana
Matthieu Hanf, Antoine Adenis, Mathieu Nacher, Bernard Carme
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-100
Abstract: A time series analysis using ARIMA was developed to investigate temporal correlations between the monthly Plasmodium falciparum case numbers and El Ni?o Southern Oscillation (ENSO) as measured by the Southern Oscillation Index (SOI) at the Cayenne General Hospital between 1996 and 2009.The data showed a positive influence of El Ni?o 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%.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.In French Guiana, malaria remains a serious problem with a number of malaria cases observed every year ranging from 3,500 to 4,500. Both Plasmodium falciparum and Plasmodium vivax are prevalent. Since 2000, 60% of the cases are due to P. vivax [1].The ENSO phenomenon refers to the cyclic warming and cooling of the equatorial Pacific Ocean coupled with changes in the atmospheric pressure across the Pacific. This is the most important climatic cycle contributing to worldwide interannual variability in climate and the likelihood of climatic anomalies. The two extremes of ENSO are El Ni?o (a warm event) and La Ni?a (a cold event), which can create rainfall and temperature fluctuations [2].The El Ni?o-Southern Oscillation (ENSO) is the best-known example of quasi-periodic natural climate variability on the interannual time scale. It comprises changes in sea temperature in the Pacific Ocean (El Ni?o) and changes in atmospheric pressure across the Pacific Basin (the Southern Oscillation), together with resultant effects on world weather. El Ni?o events occur at intervals of 2-7 years. In certain countries around the Pacific and beyond, El Ni?o is associated with extreme weather conditions that can cause floods and drought. The other extreme (La Nina) (cooling) is the reverse pattern of clima
Corruption Kills: Estimating the Global Impact of Corruption on Children Deaths
Matthieu Hanf, Astrid Van-Melle, Florence Fraisse, Amaury Roger, Bernard Carme, Mathieu Nacher
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0026990
Abstract: Background Information on the global risk factors of children mortality is crucial to guide global efforts to improve survival. Corruption has been previously shown to significantly impact on child mortality. However no recent quantification of its current impact is available. Methods The impact of corruption was assessed through crude Pearson's correlation, univariate and multivariate linear models coupling national under-five mortality rates in 2008 to the national “perceived level of corruption” (CPI) and a large set of adjustment variables measured during the same period. Findings The final multivariable model (adjusted R2 = 0.89) included the following significant variables: percentage of people with improved sanitation (p.value<0.001), logarithm of total health expenditure (p.value = 0.006), Corruption Perception Index (p.value<0.001), presence of an arid climate on the national territory (p = 0.006), and the dependency ratio (p.value<0.001). A decrease in CPI of one point (i.e. a more important perceived corruption) was associated with an increase in the log of national under-five mortality rate of 0.0644. According to this result, it could be roughly hypothesized that more than 140000 annual children deaths could be indirectly attributed to corruption. Interpretations Global response to children mortality must involve a necessary increase in funds available to develop water and sanitation access and purchase new methods for prevention, management, and treatment of major diseases drawing the global pattern of children deaths. However without paying regard to the anti-corruption mechanisms needed to ensure their proper use, it will also provide further opportunity for corruption. Policies and interventions supported by governments and donors must integrate initiatives that recognise how they are inter-related.
Environmental, entomological, socioeconomic and behavioural risk factors for malaria attacks in Amerindian children of Camopi, French Guiana
Aurélia Stefani, Matthieu Hanf, Mathieu Nacher, Romain Girod, Bernard Carme
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-246
Abstract: 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.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.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.Malaria is a major public health problem in French Guiana, a French overseas region located in South America and separated from Brazil and Suriname by the Oyapock and Maroni Rivers, respectively. The Amazon forest covers 94% of the territory. This area is among the most affected by malaria in South America [1]. To date, French Guiana counts around 3,800 malari
Determination of the Plasmodium vivax relapse pattern in Camopi, French Guiana
Matthieu Hanf, Aurélia Stéphani, Célia Basurko, Mathieu Nacher, Bernard Carme
Malaria Journal , 2009, DOI: 10.1186/1475-2875-8-278
Abstract: 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.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.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.Traditionally, Plasmodium vivax was considered as a relatively benign malaria parasite, which could be easily treated. For the past 10 years, this has been questioned [1]. It has been shown that malaria could be involved in severe disease [2]. Furthermore, P. vivax has recently re-emerged [3] and drug resistances, mainly chloroquino-resistance have developed in several areas[4]. Primaquine treatment, the only therapeutic option against relapse, might also be failing [5]. It requires a 14-day course and G6PD deficiency screening, which is difficult and costly in some areas.In Fre
Is dengue and malaria co-infection more severe than single infections? A retrospective matched-pair study in French Guiana
Lo?c Epelboin, Matthieu Hanf, Philippe Dussart, Sihem Ouar-Epelboin, Félix Djossou, Mathieu Nacher, Bernard Carme
Malaria Journal , 2012, DOI: 10.1186/1475-2875-11-142
Abstract: 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.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 <36% and independent factors significantly associated with co-infections versus malaria were red cells transfusion, low haematocrit < 36%, thrombocytopaenia < 50 109/L and low Plasmodium parasitic load < 0.001%.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.
Discriminating Malaria from Dengue Fever in Endemic Areas: Clinical and Biological Criteria, Prognostic Score and Utility of the C-Reactive Protein: A Retrospective Matched-Pair Study in French Guiana
Lo?c Epelboin ,Charlotte Boullé,Sihem Ouar-Epelboin,Matthieu Hanf,Philippe Dussart,Félix Djossou,Mathieu Nacher,Bernard Carme
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002420
Abstract: Background Dengue and malaria are two major public health concerns in tropical settings. Although the pathogeneses of these two arthropod-borne diseases differ, their clinical and biological presentations are unspecific. During dengue epidemics, several hundred patients with fever and diffuse pain are weekly admitted at the emergency room. It is difficult to discriminate them from patients presenting malaria attacks. Furthermore, it may be impossible to provide a parasitological microscopic examination for all patients. This study aimed to establish a diagnostic algorithm for communities where dengue fever and malaria occur at some frequency in adults. Methodology/Principal Findings A sub-study using the control groups of a case-control study in French Guiana – originally designed to compare dengue and malaria co-infected cases to single infected cases – was performed between 2004 and 2010. In brief, 208 patients with malaria matched to 208 patients with dengue fever were compared in the present study. A predictive score of malaria versus dengue was established using .632 bootstrap procedures. Multivariate analysis showed that male gender, age, tachycardia, anemia, thrombocytopenia, and CRP>5 mg/l were independently associated with malaria. The predictive score using those variables had an AUC of 0.86 (95%CI: 0.82–0.89), and the CRP was the preponderant predictive factor. The sensitivity and specificity of CRP>5 mg/L to discriminate malaria from dengue were of 0.995 (95%CI: 0.991–1) and 0.35 (95%CI 0.32–0.39), respectively. Conclusions/Significance The clinical and biological score performed relatively well for discriminating cases of dengue versus malaria. Moreover, using only the CRP level turned to be a useful biomarker to discriminate feverish patients at low risk of malaria in an area where both infections exist. It would avoid more than 33% of unnecessary parasitological examinations with a very low risk of missing a malaria attack.
HIV-Associated Histoplasmosis Early Mortality and Incidence Trends: From Neglect to Priority
Antoine Adenis ,Mathieu Nacher,Matthieu Hanf,Vincent Vantilcke,Rachida Boukhari,Denis Blachet,Magalie Demar,Christine Aznar,Bernard Carme,Pierre Couppie
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0003100
Abstract: Background Histoplasmosis is an endemic fungal infection in French Guiana. It is the most common AIDS-defining illness and the leading cause of AIDS-related deaths. Diagnosis is difficult, but in the past 2 decades, it has improved in this French overseas territory which offers an interesting model of Amazonian pathogen ecology. The objectives of the present study were to describe the temporal trends of incidence and mortality indicators for HIV-associated histoplasmosis in French Guiana. Methods A retrospective study was conducted to describe early mortality rates observed in persons diagnosed with incident cases of HIV-associated Histoplasma capsulatum var. capsulatum histoplasmosis admitted in one of the three main hospitals in French Guiana between 1992 and 2011. Early mortality was defined by death occurring within 30 days after antifungal treatment initiation. Data were collected on standardized case report forms and analysed using standard statistical methods. Results There were 124 deaths (45.3%) and 46 early deaths (16.8%) among 274 patients. Three time periods of particular interest were identified: 1992–1997, 1998–2004 and 2005–2011. The two main temporal trends were: the proportion of early deaths among annual incident histoplasmosis cases significantly declined four fold (χ2, p<0.0001) and the number of annual incident histoplasmosis cases increased three fold between 1992–1997 and 1998–2004, and subsequently stabilized. Conclusion From an occasional exotic diagnosis, AIDS-related histoplasmosis became the top AIDS-defining event in French Guiana. This was accompanied by a spectacular decrease of early mortality related to histoplasmosis, consistent with North American reference center mortality rates. The present example testifies that rapid progress could be at reach if awareness increases and leads to clinical and laboratory capacity building in order to diagnose and treat this curable disease.
Influence of climate and river level on the incidence of malaria in Cacao, French Guiana
Célia Basurko, Matthieu Hanf, René Han-Sze, Stéphanie Rogier, Philippe Héritier, Claire Grenier, Michel Joubert, Mathieu Nacher, Bernard Carme
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-26
Abstract: 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.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.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.Malaria may be seen as the combination of a Plasmodium, an Anopheles mosquito and a human host. Factors modifying the presence, survival or abundance of any one of these actors are likely to favour the maintenance or breaking of the parasite cycle. Environmental conditions are among the factors likely to affect this parasite cycle. The temperature of the water collecting in hollows, the presence of vegetation or predators and altitude may all favour Anopheles mosquitoes or limit their development within a given geographic zone [1,2].The ecological characteristics of the vectors of malaria in French Guiana have not been completely elucidated [3,4]. In the absence of entomological data, the goal of this study was to investigate the environmental factors conditioning the encounter between humans and parasites, focusing on the incide
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