Université Antilles Guyane, Equipe EA 3593 Epidemiologie des Parasitoses et Mycoses tropicales; Centre Hospitalier de Cayenne, Centre d'Investigation Clinique Epidémiologie Clinique INSERM CIE 802, Coordination Régionale de lutte contre le VIH
mathieu.nacher1966@gmail.com
Curent : Professor of epidemiology & public health at the université Antilles Guyane Chairman of the HIV Coordination committee of French Guiana Researcher at the Clinical investigation center, INSERM CIE 802 Research topics: in the interactions between worms and malaria, HIV, histoplasmosis, leishmaniasis...
Abstract: In order to determine the predictive value of a rash during dengue fever, a cohort study was conducted in children hospitalized for dengue during an epidemic in French Guiana. A rash was predictive of uncomplicated dengue: the HR of developing a severe form of disease was 0.43 (95% CI 0.21-0.88; p-value=0.021) for patients with rash.
Abstract: French Guiana is the French territory where the HIV epidemic is most preoccupying. In Cayenne, the mother to child HIV transmission rate was 6% in 2006-2008. Despite free testing and treatment, HIV pregnant women often have delayed or insufficient access to care. The aim of this study was to identify predictive factors of antiretroviral treatment<4 weeks in HIV pregnant women in Cayenne (French Guiana) and then to describe their attitudes, practices, and beliefs regarding HIV/AIDS. A case control study was conducted including all deliveries in Cayenne from 2003 to 2010. For each case, a standardized questionnaire including epidemiological, clinical, and biological data was administered. The analysis first described the summary statistics and then bivariate analysis studied the relation of each variable with the outcome. Multivariate analysis adjusted for the confounding factors. Thirty-three women in the first group and 96 in the control group were included in the study. Women born in French Guiana (OR = 5, IC95% = 1.22-20.86, p=0.027) had a high risk of treatment<4 weeks. The other factors associated with treatment<4 weeks in our study were benefiting from food parcels (OR = 12.72, IC95% = 2.07-78.14, p=0.006), consulting a traditional healer when sick (OR = 9.86, IC95% = 2.57-37.88, p= < 0.001), and drug use (OR = 6.27, IC95% = 1.26-31.13, p=0.025). These predictive factors should be considered in prevention programs against mother to child transmission of HIV.
Abstract: 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.
Abstract: For the first time, the incidence of cervical cancer was estimated in French Guiana, an overseas French Territory of South America. A certified cancer registry collected exhaustive data on cervical cancer between 2003 and 2005. The age-standardized rate of invasive cervical cancer was 30.3 per 100,000 women. Women from rural areas had lesions with a significantly greater extension than women from urban areas. Compared to South American figures, the standardized incidence of cervical cancer seemed relatively high when viewed in comparison with the gross domestic product per capita. The curative orientation of the health system should move from opportunistic screening for cervical cancer to organized screening, with an emphasis on the rural parts of French Guiana.
Abstract: 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.
Abstract: The variables influencing the interval between diagnosis and effective access to specialized care were studied in a cohort of 2,661 human immunodeficiency virus (HIV)-positive patients in French Guiana between 1992 and 2008. Patients with a subsequent follow-up interruption were significantly more likely to have a delayed first consultation after the HIV diagnosis. Ordinal logistic regression showed that younger persons, women, and French citizens were independently associated with greater delays between the HIV diagnosis and the first specialized consultation. However, persons with acquired immunodeficiency syndrome (AIDS) were less likely to have a delay between the HIV diagnosis and the first specialized consultation. Focusing on the link between the private sector and specialized health care may shorten delays and improve care and follow-up.
Abstract: The pathogen ecology of Amazonian regions may lead to specific differences in the most frequent clinical presentations of acquired immunodeficiency syndrome (AIDS). A retrospective cohort study was thus conducted to describe the main AIDS-defining events in French Guiana. Disseminated histoplasmosis was the most frequent opportunistic infection (15.4/1000 person years).
Abstract: Cryptococcosis is a common opportunistic systemic mycosis caused by members of the encapsulated yeast genus Cryptococcus. The aetiological agents of the disease are classified into two species, i.e., Cryptococcus neoformans (serotypes A, D, and AD) affecting mainly immunocompromised patients and Cryptococcus gattii (serotypes B and C) usually found in immunocompetent individuals. Limited data exist on Cryptococcus infections in French Guiana, the department with the highest HIV incidence in the French territories. A retrospective study between January 1998 and December 2008 was performed on all patients with cryptococcosis, admitted to hospitals in French Guiana. Epidemiological data, clinical forms and diagnosis methods were studied. Of the 43 patients with cryptococcosis, 29 (67.4%) had HIV infections. Among the HIV-negative patients, two (4.7%) presented identified risk factors for cryptococcosis. This study has shown a high frequency of patients with HTLV-1 positive serology (12.1%). C. neoformans var. grubii was recovered with a frequency of 77.3% and was mainly isolated from patients with AIDS (13/17), whereas C. gattii (22.7%) was strictly isolated from HIV-negative patients with no apparent risk factors. Despite a socio-economic environment closer to western countries, the overall epidemiology of cryptococcosis in French Guiana is more similar to that found in South America, particularly with reference to the serotypes of the causative yeasts. Indeed, French Guiana presents an especially high proportion of cases caused by C. gattii, which may explain the significant incidence of this disease, particularly in HIV-negative and immunocompetent patients.
Abstract: In Cayenne, French Guiana, 80% of HIV-positive patients followed at the hospital are migrants. Behavioural information is crucial for optimising HIV testing for this vulnerable group. Predictors of ignorance of the existence of free voluntary counselling and testing (VCT) centre and willingness to get tested were investigated in 2006 among 398 migrants from Haiti, Guyana, Suriname and Brazil using a structured questionnaire. Only 27% of migrants knew simultaneously about the existence of free VCT, its localisation and its operating hours. Factors associated with ignorance of the existence of free VCT centre were birthplace in Haiti, being in French Guiana for less than three years, not thinking one's birth country as strongly affected by HIV and not thinking to be personally at risk for HIV. Factors independently associated with willingness to get tested were thinking to be at risk for HIV, birthplace in Brazil and Haiti, having a high-integration level and fear of suffering if HIV test was positive. In order to improve testing among migrants, the accessibility of testing facilities and the knowledge of their whereabouts and operating hours must be improved to promote the desired behaviour among the majority of migrants which is often willing to do the test.
Abstract: 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.
Abstract: Leishmania species of the subgenus Viannia and especially Leishmania Viannia guyanensis are responsible for a large proportion of New World leishmaniasis cases. Since a recent publication on Leishmania Viannia braziliensis, the debate on the mode of reproduction of Leishmania parasites has been reopened. A predominant endogamic reproductive mode (mating with relatives), together with strong Wahlund effects (sampling of strains from heterogeneous subpopulations), was indeed evidenced. To determine whether this hypothesis can be generalized to other Leishmania Viannia species, we performed a population genetic study on 153 human strains of L. (V.) guyanensis from French Guiana based on 12 microsatellite loci. The results revealed important homozygosity and very modest linkage disequilibrium, which is in agreement with a high level of sexual recombination and substantial endogamy. These results also revealed a significant isolation by distance with relatively small neighbourhoods and hence substantial viscosity of Leishmania populations in French Guiana. These results are of epidemiological relevance and suggest a major role for natural hosts and/or vectors in parasite strain diffusion across the country as compared to human hosts.
Abstract: In the past decade there have been an increasing number of studies on co-infections between worms and malaria. However, this increased interest has yielded results that have been at times conflicting and made it difficult to clearly grasp the outcome of this interaction. Despite the heterogeneity of study designs, reviewing the growing body of research may be synthesized into some broad trends: Ascaris emerges mostly as protective from malaria and its severe manifestations, whereas hookworm seems to increase malaria incidence. As efforts are made to de-worm populations in malaria endemic areas, there is still no clear picture of the impact these programmes have in terms of quantitative and qualitative changes in malaria.
Abstract: 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.
Abstract: Prurigo nodularis and herpes zoster frequently lead to the diagnosis of HIV in tropical areas. The WHO has established a clinical definition of AIDS for undeveloped countries. Prurigo and herpes zoster are both classified as stage 2. The main objective of this study was to compare the level of immunosuppression of patients diagnosed as HIV-positive after consulting for prurigo nodularis or herpes zoster in French Guiana. A retrospective study was conducted including patients consulting at the Department of Dermatology, Cayenne Hospital (French Guiana) for prurigo nodularis or herpes zoster between 1989 and 2007 for which the systematic HIV test was positive. Demographic data and CD4 counts of both groups were compared. Analysis of 346 patients consulting for herpes zoster (n=192) or prurigo nodularis (n=154) led to the discovery of 129 HIV infections. The positive predictive value (PPV) for HIV positivity was 38.5% for herpes zoster and 36% for prurigo nodularis. The median lymphocyte count was 302/mm(3) in herpes zoster and 87/mm(3) in prurigo nodularis (P<0.001). The PPV for having a CD4 lymphocyte count<200/mm(3) was 26.5% for herpes zoster and 72% for prurigo nodularis. Prurigo nodularis was predictive of advanced immunosuppression. This questions the pertinence of the WHO clinical classification of AIDS. In the absence of CD4 count, the present results suggest that for patients with prurigo nodularis, antiretrovirals should be initiated without delay.
Abstract: 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.
Abstract: In order to determine whether HIV-associated disseminated histoplasmosis was a recent infection or a reactivation, time series of first episodes of disseminated histoplasmosis were analyzed. Climatic variables were associated with histoplasmosis incidence. This suggested an important proportion of cases were due to recent exposure, and therefore primary prophylaxis may be warranted in French Guiana.
Abstract: We described hepatitis B surface antigen (HBsAg) prevalence among 2,347 pregnant women having delivered at the Cayenne hospital in 2007 according to ethnicity. With 11.0% HBsAg prevalence, Asian women (Hmong and Chinese) were the group with the highest risk of hepatitis B virus (HBV) perinatal transmission compared with other ethnic groups.
Abstract: Thirty years after the first HIV case in French Guiana, the drivers of the epidemic are not clearly known, but the epidemic is usually conceptualized as generalized. Cross-linking results from a study in the general population and a study in the HIV-infected population in Cayenne suggests that in the general population of HIV-positive men, 45% of HIV cases are attributable to having sex with someone they paid. Similarly, for HIV-positive women exchanging sex for presents or money, 10.7% of HIV cases are attributable to transactional sex. A surprising finding was that 16.8% of HIV patients had tried crack cocaine before. On the Maroni river, the female-biased sex ratio suggests the drivers in that remote area may be related to cultural polygyny. These observations have important consequences on communication and prevention strategies.
Abstract: A retrospective cohort study was conducted to determine the predictive factors and the incidence of anxiety and depression in a cohort of patients followed in French Guiana. A total of 2315 patients were followed for a total of 9116 years of follow-up. The incidence rate of first observed depression was 1.89 per 100 person years. The incidence rate of first observed generalized anxiety was 1.27 per 100 person years. A single failure Cox proportional hazards model showed that patients diagnosed <1 year (Hazard ratio (HR)=4.15; 95% CI=1.15-14.9; P=0.029), patients treated <one year (HR=3.2; 95% CI=1.7-6.2; P<0.001), patients with anxiety (HR=37; 95% CI=19-72; P<0.001), females (HR=2.5; 95% CI=1.5-4; P<0.001), French citizens (HR=1.6; 95% CI=1.05-2.5; P=0.029), and patients with severe immunodeficiency (HR=3.7; 95% CI=1.7-7.8; P=0.001) were at increased risk of depression. For anxiety, recently diagnosed patients (HR=11.7; 95% CI=3.2-42; P<0.001) and females (HR=3; 95% CI=1.6-5.8; P=0.001) were at increased risk. The hazard function showed that there were three peaks for anxiety (2, 6, and 11 years) and depression (2, 7, and 14 years). Incidence of anxiety and depression in this HIV cohort is high. Knowledge of this pattern may help physicians be more vigilant to psychological distress at certain phases of life with HIV.
Abstract: The clays consumed by geophagous individuals contain large quantities of aluminum, a known neurological and hematological toxin. This is the first study to evaluate the risk of aluminum poisoning in geophagous individuals. Blind determinations of plasma and urinary aluminum concentrations were carried out in 98 anemic geophagous pregnant women and 85 non-anemic non-geophagous pregnant women. Aluminum concentrations were significantly higher (P < 0.0001) in the geophagous anemic women than in the controls, with odds ratios of 6.83 (95% confidence interval [CI] = 2.72-19.31) for plasma concentrations (13.92 ± 14.09 μg/L versus 4.95 ± 7.11 μg/L) and 5.44 (95% CI = 2.17-14.8) for urinary concentrations (92.83 ± 251.21 μg/L versus 12.11 ± 23 μg/L). The ingested clay is the most likely source of this overexposure to aluminum. If confirmed, the clinical consequences of this absorption for pregnant women and their offspring should be explored.
Abstract: Deworming is recommended by the WHO in girls and pregnant and lactating women to reduce anaemia in areas where hookworm and anaemia are common. There is conflicting evidence on the harm and the benefits of intestinal geohelminth infections on the incidence and severity of malaria, and consequently on the risks and benefits of deworming in malaria affected populations. We examined the association between geohelminths and malaria in pregnancy on the Thai-Burmese border.
Abstract: Dengue-malaria co-infection reports are scarce. Of 1,723 consecutive febrile patients in Cayenne Hospital, 238 had dengue (174 early dengue fever cases) and 393 had malaria (371 acute malaria); 17 had both. Diagnosis of 1 of these 2 infections should not rule out testing for the other infection.
Abstract: A retrospective cohort study was conducted to determine whether the incidence of leprosy varied with the duration of antiretroviral therapy (ART). Between 1992 and 2006, seven cases of leprosy were observed. The incidence of leprosy in untreated patients was 0.7 per 1000 person-years, 13 per 1000 person-years in persons receiving HAART for more than 3 months and 0.9 per 1000 person-years for persons receiving HAART for more than 3 months. The adjusted hazard ratio was 18.5 (95% confidence interval, 1.6-217) with P = 0.02. In tropical areas where HAART is increasingly available, physicians should be aware of the possibility of incident leprosy shortly after HAART initiation.
Abstract: We conducted a retrospective cohort study to determine the influence of crack cocaine use on the outcomes of HIV infection. The use of crack cocaine was associated with an increased incidence of AIDS: 27.8 per 100 person-years versus 6.6 per 100 person-years for nonusers, adjusted hazard ratio = 3.8 (1.9-7.5), P < 0.001. More specifically, crack users had a greater incidence of disseminated histoplasmosis, pneumocystosis, pulmonary tuberculosis, bacterial pneumonia, oesophageal candidiasis, cerebral toxoplasmosis, salmonellosis, and genital herpes. The care of HIV-infected crack users is particularly challenging and requires additional efforts to reduce the high morbidity of these patients.
Abstract: 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.
Abstract: Histoplasma capsulatum var. capsulatum infection is a major AIDS-defining illness in French Guiana. Although it affects South and Central American countries, the number of published cases is low. We present the largest series of AIDS-related histoplasmosis. The aim of this work is to describe clinical features and to help optimize investigations in settings where antigen detection methods are not available.
Abstract: For thousands of years the deadliest human parasite, Plasmodium falciparum, has been evolving in populations also infected by the most prevalent parasites, worms. This is likely to have shaped the genome of all 3 protagonists--man, worms and malaria. Observational studies in Thailand have shown that although P. falciparum malaria incidence increased two-fold in helminth-infected patients, there was a 64% reduction of cerebral malaria and an 84% reduction of acute renal failure in helminth-infected patients relative to those without helminths. In addition, it was suggested that mixed infections, anaemia and gametocyte carriage were more frequent in helminth-infected patients. On the contrary, fever was lower in helminth-infected patients. The present hypotheses, their implications and the limitations of the results described and of those from studies in Africa are discussed.
Abstract: We report the onset of an urban epidemic of human myiasis caused by Dermatobia hominis. To our knowledge, this is the first urban epidemic described for D. hominis. The epidemic was most likely related to exceptional weather conditions and notably high rainfall in January 2000, which may have facilitated the maturation of the pupae.
Abstract: Malaria is a major public health problem in French Guiana. This study was conducted in children <1-5 years of age in Camopi, an Amerindian village in eastern French Guiana. Medical, environmental, and behavioral predictive factors of malaria were studied using the Kaplan-Meier method and Cox modeling. Variables included were clearing vegetation around the home (hazard ratio [HR] = 0.62, 95% confidence interval [CI] = 0.43-0.88 for 50-75% cleared and HR = 0.5, 95% CI = 0.31-0.81 for > 75% cleared) relative to homes surrounded by vegetation; distance of a home from a river (HR = 0.56, 95% CI = 0.37-0.85 for distances between 20 and 40 meters, HR = 0.72, 95% CI = 0.47-1.09 for distances between 40 and 80 meters, HR = 0.52, 95% CI = 0.28-0.94 for distances between 80 and 120 meters, and HR = 0.5, 95% CI = 0.30-0.86 for distances > 120 meters) relative to distances < 20 meters; the number of occupants in the home (HR = 1.54, 95% CI = 0.98-2.44 for 7 occupants, HR = 1.9, 95% CI = 1.29-2.81 for 8-11 occupants, and HR = 2.03, 95% CI = 1.27-3.23 for > 11 occupants); clothing (HR = 0.64, 95% CI = 0.46-0.90 for children wearing western-style clothes relative to those wearing the traditional kalimbe), and ethnicity (Wayampi children had a lower hazard of malaria relative to Emerillon children: HR = 0.55, 95% CI = 0.40-0.80). The environment near the home was strongly associated with malaria. This suggests that simple pragmatic protection measures would be useful in Camopi.
Abstract: We report the occurrence of myiasis owing to Dermatobia hominis (Dh) in a HIV-infected subject. HIV infection did not modify the pathogenicity of myiasis. However, the clinical presentation seemed unusual with voluminous inflammatory nodules. Use of topical ivermectin killed the larvae and facilitated their extraction.
Abstract: Risk factors for death in an HIV-infected cohort in French Guiana were studied in 1374 patients between 1996 and 2005. Of these patients, 48.5% were male and 76% were immigrants. Covariates were measured at the time of consultation. There were 223 deaths. Addictions [adjusted hazard ratio (HR)=13; 95% confidence interval (CI) 5.5-30.6; P<0.001], age>60 years (HR=1.5; 95% CI 0.9-2.5; P=0.13), male gender (HR=1.5; 95% CI 1.03-2.5; P=0.03) and CD4 count<50 cells/microL (HR=9.1; 95% CI 5.1-16.3; P<0.001) were independently associated with death. These results suggest that strategies promoting early diagnosis and better follow-up of addicted patients would have a significant impact on mortality.
Abstract: Cutaneous leishmaniases are endemic over the entire territory of French Guiana. At least 5 distinct Leishmania species coexist in the sylvatic ecotopes of this French territory. The present paper checks the advances in the ecological research field during the past 5 years. The current epidemiological situation and trends are detailed successively Links between the recrudescence of leishmaniases and gold-mining are highlighted. The potential adaptation of the pathogenic complexes to the newly anthropized habitats is also described.
Abstract: Immune reconstitution disease (IRD) has been associated with many pathogens after the initiation of antiretroviral therapy for advanced HIV infection. A retrospective cohort study was conducted to determine whether cutaneous mycoses were also associated with IRD. After adjusting for various confounding factors, the recent initiation of HAART was found to be associated with an increased incidence of cutaneous mycoses when compared with untreated patients.
Abstract: Immune reconstitution after HAART initiation is often complicated by adverse clinical manifestations caused either by the unmasking of preexisting untreated opportunistic infections or the clinical deterioration of a known and treated opportunistic infection. The present study was conducted to determine whether the initiation of HAART was followed by an increase in the incidence of mucosal candidiases, a possible manifestation of immune reconstitution disease of the unmasking type.
Abstract: To determine whether the initiation of highly active antiretroviral therapy (HAART) had any influence on the incidence of disseminated histoplasmosis, a retrospective cohort study was performed on 1551 patients followed for up to 12 years. After controlling for CD4 counts, age, and sex, patients taking HAART for 2 months or less were more likely to develop disseminated histoplasmosis than untreated patients (respectively, hazard ratio, 3.7 [95% confidence interval, 1.57-8.7]; P = 0.003). In contrast, after 6 months of HAART, treated patients were less likely to develop disseminated histoplasmosis than untreated patients (hazard ratio, 0.6 [95% confidence interval, 0.37-0.98], P = 0.04). This increased incidence suggests that the initiation of HAART and the subsequent immune reconstitution may reveal undiagnosed latent disseminated histoplasmosis.
Abstract: At least 13 characterized Leishmania species are known to infect humans in South America. Five of these parasites are transmitted in the sylvatic ecotopes of the whole French Guianan territory and responsible for cutaneous leishmaniasis. For the diagnosis of cutaneous leishmaniasis, restriction fragment length polymorphism (RFLP) analyses have shown promising results. Thus, the end of the small subunit and internal transcribed spacer 1 of the rRNA genes were sequenced and targeted by PCR-RFLP analysis in the 10 main New World (NW) Leishmania species from the two subgenera. Then, the procedure was tested on 40 samples from patients with cutaneous leishmaniasis, and its results were compared with those of conventional methods. (i) The results of this simple genus-specific method were in agreement with those of previous isoenzyme analyses. (ii) This method distinguished the most medically relevant Leishmania species with only one enzyme (RsaI). (iii) This method could be performed directly on human biopsy specimens (sensitivity of 85.7%). Performing NW Leishmania species typing rapidly and easily in the field constitutes a very valuable improvement for detection of Leishmania spp. Revealing great diversity with several enzymes, this method could also be useful for taxonomic, ecological, and epidemiological studies in space and time.
Abstract: Little information is available about the genetic variability of Leishmania populations and the possible correlations with ecoepidemiological features of leishmaniases. The present study was carried out in French Guiana, a country where cutaneous leishmaniases (CL) are endemic over the whole territory. The genetic polymorphism of a nuclear sequence encompassing the end of the ribosomal small subunit and the internal transcribed spacer 1 of 265 isolates from patients with CL was examined by restriction fragment length polymorphism analysis. Genotypes based on the fingerprinting phenetic integration were compared to epidemiological, clinical, and geographical data. In agreement with previous reports, five different Leishmania species were identified, but Leishmania (Viannia) guyanensis represented 95.8% of the samples. Two distinct L. (V.) guyanensis populations were found to originate in two ecologically characterized regions. Higher lesional parasite densities and the need for additional treatments were significantly linked to genotype group I. Parasites of genotype group II were more likely to cause chronic and disseminated cutaneous forms in patients. L. (V.) guyanensis was previously said not to be very polymorphic; however, the present analysis resulted in a significant degree of discrimination among L. (V.) guyanensis isolates from diverse ecological areas and with different clinical implications.
Abstract: French Guiana is the region of France where the HIV epidemic is most prevalent. To determine the risk factors for being lost for follow-up, we followed a cohort of 1,213 patients between 1992 and 2002 and determined which variables were related to two definitions of being lost to follow-up: permanently disappearing from HIV clinics and coming back after more than 1 year of missed appointments. The incidence rate for permanent follow-up interruption was 17.2 per 100 person-years. The median time to lost to follow-up was 4.3 years (interquartile range = 1.4-8.4 years). Cox modeling showed that the younger age groups, foreigners, patients with initial CD4 counts at the time of HIV diagnosis less than 500/mm3, and patients followed before the availability of highly active antiretroviral therapy (HAART) were significantly more likely to be permanently lost to follow-up, suggesting that some of the patients may have died. When looking at temporary loss to follow-up, younger age groups, untreated patients, patients consulting before the availability of HAART, and patients with CD4 counts more than 500/mm3 were more likely to not come back for a period of more than 1 year.
Abstract: Demodecidosis is an ectoparasitosis that is infrequently observed in subjects with human immunodeficiency virus (HIV) infection. It has a rosacea-like presentation. We present three cases in patients with acquired immunodeficiency syndrome (AIDS). Two of these patients had a profuse eruption, and all three cases were cured by ivermectin. The single-dose treatment could be repeated in cases of subsequent recurrence. Ivermectin thus seems to be a good alternative in the treatment of demodecidosis in patients with HIV infection.
Abstract: Histoplasmosis due to Histoplasma capsulatum var capsulatum is a frequent systemic fungal infection in the Americas. Diagnostic and therapeutic options differ between North and South America. Disseminated histoplasmosis is an AIDS-defining infection. Prognostic factors of potentially severe presentations must be evaluated in order to facilitate the initial therapeutic choice.
Abstract: In a retrospective study set in French Guiana, the efficacy and tolerance of the intramuscular treatment of cutaneous leishmaniasis (CL) with a single injection of pentamidine isethionate, at 7 mg/kg, were compared with those observed, earlier, using two such injections (given 48 h apart). Although 83.6% of the 281 patients given two injections each were cured, the single-injection protocol was generally as effective, curing 78.8% of 137 patients. The single-injection protocol was also associated with fewer adverse effects than the two-injection. In the treatment of "difficult" cases (those with satellite papules or relatively high numbers of amastigotes in their lesions), however, the two-injection protocol appeared significantly more effective than the single-injection. In French Guiana, therefore, patients with CL should be given one injection with pentamidine isethionate and only be given a second, 48 h later, if they have satellite papules and/or relatively high numbers of amastigotes in their lesions.
Abstract: Clinical presentation of Plasmodium falciparum malaria reflects a continuum from asymptomatic to multi-organ manifestation and death. Severe malaria is defined by the World Health Organization as a qualitative variable. We used the multi-organ dysfunction score (MODS) as a quantitative approach for severity in 29 patients with severe and complicated P. falciparum malaria to test its usefulness in discriminating different severity levels. The MODS on admission was highly correlated with the duration of symptoms after admission (r = 0.73, P < 0.001) and the serum level of tumor necrosis factor alpha (r = 0.41, P = 0.03). In addition, the simplified MODS, based mainly on clinical findings, was also correlated with liver and renal dysfunction during hospitalization (alanine transaminase, r = 0.42, P = 0.02; blood urea nitrogen, r = 0.45, P = 0.015). A score >or= 16 was associated with significantly longer disease duration (P = 0.018). Thus, this score might provide a predictive value for morbidity in P. falciparum malaria.
Abstract: The two week period that stretches between the absorption of gametocytes from a malaria patient by a mosquito and the subsequent injection of sporozoites in another human host is a most fragile segment of the malaria cycle. There is non-randomness in the blood meal choice of anopheline vectors. Manipulations of the host by the parasite to satisfy the preferences of the vector might have contributed to the robustness of the malaria cycle. Indeed, although gametocytes do not directly cause symptoms, the acute and chronic clinical manifestations caused by asexual forms seem to be organized around their transmission: fever patterns and behavior modification, anemia and thrombocytopenia converge towards making malarious individuals a preferred and safer source of blood for the vector than non-malarious individuals. Malaria symptoms offer the vector its favorite cues: increased skin temperature, increased lactates, sweating, and CO(2) expiration. In addition, this tempting menu seems easier to absorb because of thrombocytopenia and reduced blood viscosity during anemia, and because behavior modification reduces mosquito avoidance and the risk of dying. The attractive cues may be characteristic symptoms of malaria but also slight infraclinical changes that mostly go unnoticed by the doctor but not by the vector. The manifestations of malaria are often seen as adaptive for the host, this article argues that on average they may also be adaptive for malaria parasites. Examining malaria as the extended phenotype of Plasmodium leads to new research questions.
Abstract: Immune reconstitution syndrome (IRIS) is an unusual inflammatory reaction to an opportunistic infection in an HIV-positive patient. This syndrome occurs when immunity is restored in the first months of an effective highly active antiretroviral treatment (HAART). First, we described all patients with a cutaneous form of IRIS. Then, between 1992 and 2004 we conducted a retrospective cohort study comparing Herpes Zoster and Herpes Simplex infections among untreated patients, patients treated by HAART for < or = six months, and patients treated for > six months. We observed three cases of atypical leprosy and three original observations: two of these were fistulisation of lymph node histoplasmosis and tuberculosis, the third one reports the recurrence of a treated cutaneous leishmaniasis. Multivariate analysis showed that, after controlling for age, sex and CD4 counts, patients receiving HAART for < or = six months were more likely to develop Herpes Zoster or herpes simplex infections (p < 0.005). Herpes Simplex and Herpes Zoster infections are the two most frequent dermatological manifestations in our tropical setting. Although mycobacterial infections are more rarely observed than in visceral IRIS, the increased incidence of leprosy may be quite significant when the availability of HAART spreads to developing countries.
Abstract: Risk factors for delayed HIV diagnosis in French Guiana were studied in 1952 patients between 1992 and 2003. At the time of diagnosis, 30% of patients had less than 200 CD4 lymphocytes/mm3; age, male sex, and foreign nationality were independently associated with a low CD4 cell count. The availability of highly active antiretroviral therapy was not associated with an earlier HIV diagnosis. Promoting HIV information and testing should be done in several languages to reach minorities.
Abstract: Between January 2000 and December 2002 monthly rainfall was correlated with the proportion of patients with hyperparasitaemic Plasmodium falciparum malaria and with the proportion of patients with P. falciparum gametocytes. During the observation period 6953 cases of P. falciparum malaria were treated at the Shoklo Malaria Research Unit in Maela refugee camp on the Thai-Burmese border. Three hundred and seventy-five of these patients had >/=4% of parasitized red blood cells. Although there were more monthly malaria cases in the rainy season, rainfall was negatively correlated with the proportion of patients with hyperparasitaemia (Spearman's rho = -0.59, P < 0.001 ), and the proportion of gametocyte carriers among P. falciparum cases, (Spearman's rho = -0.39, P = 0.018). After controlling for age and the origin of the patient, the odds ratio for developing hyperparasitaemia during the dry season was 1.6 (95% CI 1.14-2.2; P = 0.006). The adjusted odds ratio for gametocyte carriage during the dry season was 1.3 (95% CI 1.03-1.6; P = 0.02). Migrations, changes in transmission patterns, the haematological burden of cumulative infections, and ultraviolet immunosuppression are discussed as potential explanations for these observations.
Abstract: To study the influence of season on Plasmodium vivax gametocyte carriage, the relationship between monthly rainfall and the proportion of P. vivax patients with detectable gametocytaemia was analysed. Most of the data used came from 6807 aggregated observations collected, in a refugee camp on the Thai-Burmese border, between January 2000 and December 2002. There was a positive correlation between rainfall and the incidence of P. vivax infection (Spearman's rho=+0.42; P =0.01) but the prevalence of gametocyte carriage among those with P. vivax infection was negatively correlated with rainfall (Spearman's rho=-0.58; P <0.001). The latter, negative correlation remained significant after controlling for the proportion of visitors relative to camp residents (P =0.003). Migrations, changes in transmission patterns, seasonal haematological changes, and ultraviolet immunosuppression are discussed as potential explanations for these observations.
Abstract: Helminths are the most prevalent parasitic infections and malaria is the deadliest parasitic disease. Helminths have been reported to be protective against the severe forms of malaria but they were also possibly linked to increased malaria-incidence and gametocyte carriage. Connecting the dots between observations suggests that statistical regularities throughout the evolution of worms and malaria parasites in the same hosts, may have led to the emergence of non-zero interactions as observed in iterated prisoners dilemma games. Thus by protecting the host, helminths protect themselves and their reproductive potential, but also favor the dissemination and reproduction of Plasmodium falciparum. The proximate causes of this evolutionarily stable strategy might be mediated by IgE and the CD23/NO pathway, the protective role of IL10 in helminth-infected patients, and possibly the hematological consequences of worms. The chronic activation of the CD23/NO pathway might be instrumental in downregulating the expression of cytoadherence receptors thus reducing sequestration of parasitized red blood cells in the deep organs. Mild anemia in helminth-infected patients might favor gametocytogenesis and send attractive cues to the vector. This framework leads to numerous testable hypotheses and could explain certain singularities regarding the double edged role of IgE and NO. Among these hypotheses, there are 2 practical ones: the impact of helminths on malaria vaccine candidates, and the theoretical risk of increasing the severity of malaria after anthelmintics. The capacity for increased IgE responses could thus have been vital in our ancestor's wormy and malarious past. Allergies may be what remains of it in the modern world.
Abstract: The gametocytes of Plasmodium falciparum have a characteristic banana-shape. One could wonder if this shape has been retained by selection forces because it favored transmission. By increasing the surface to volume ratio, the elongation that takes place during the maturation of P. falciparum gametocytes increases the susceptibility of gametocytes to rheological forces. This may facilitate their exit from the bone marrow and their subsequent impaction in the cutaneous capillaries that are lined with sequestered asexual parasites. The asymmetric curvature of gametocytes may tend to present gametocytes perpendicularly to the axis of the blood flow, thus increasing their chance to be retained and accumulate where they can be absorbed by the vector.
Abstract: To determine if intestinal helminths and the CD23/nitric oxide pathway had an influence on liver size, we conducted a cross-sectional study on 438 patients with confirmed P. falciparum malaria admitted at the Hospital for Tropical Diseases in Bangkok. For all patients the liver size was measured as number of centimeters below the rib cage, a stool examination was conducted, and CD23 and reactive nitrogen intermediates were measured. The median liver size was smaller in helminth-infected patients than in helminth-free patients (chi2 for trend = 9.1, p = 0.003). Liver size significantly increased with the concentration of sCD23 (p < 0.0001). The median sCD23 concentration (OD) was significantly lower in helminth-infected patients than in helminth-free patients, respectively 0.33 (quartiles 0.24-0.57) and 0.45 (quartiles 0.27-0.59), (p = 0.01). There was a negative correlation between sCD23 concentrations and RNI (Spearman's rho = -0.40, p < 0.0001). All the above results remained significant after controlling for potential confounders. These results are compatible with a CD23/NO-mediated decrease in liver size in helminth-infected patients.
Abstract: To study the risk factors for Plasmodium vivax gametocyte carriage, the presence or absence of gametocytes was determined in 2,125 patients with P. vivax malaria participating in clinical trials at the Hospital for Tropical Diseases in Bangkok, Thailand. Stepwise logistic regression models were used to determine which variables were significantly related to gametocyte carriage. On admission, 615 patients (29%) had detectable gametocytes (before treatment). After treatment had started, an additional 245 patients (11%) developed patent gametocytemia. The variables retained by multivariate analysis were highest observed temperature (adjusted odds ratio [AOR] per degrees C increase = 0.82, 95% confidence interval [CI] = 0.71-0.94, P = 0.006), asexual parasitemia > 9,200/muL (AOR = 2.8, 95% CI = 1.9-4.2, P < 0.0001), erythrocyte counts (AOR = 0.8/million/muL increase, 95% CI = 0.67-0.95, P = 0.01), monocyte percentage (AOR = 0.93 per % increase, 95% CI = 0.89-0.96, P < 0.0001), lymphocyte percentage (AOR = 0.98 per % increase, 95% CI = 0.97-0.99, P = 0.006), albumin (AOR = 0.67 per 10 g/mL increase, 95% CI = 0.5-0.9, P = 0.007), and anion gap (AOR = 1.1 per unit increase, 95% CI = 1.02-1.14, P = 0.009). The possible significance of these observations is discussed.
Abstract: The gametocidal activities of chloroquine and artesunate were compared. The relative risk (RR) of having detectable gametocytes appear after treatment initiation was lower in artesunate-treated patients (n = 792) than in chloroquine-treated patients (n = 695) (RR = 0.29; 95% CI = 0.2 to 0.40; P < 0.0001). The duration and magnitude of gametocyte carriage were also lower for artesunate than chloroquine. By reducing the transmission of Plasmodium vivax to the vector, artesunate could therefore reduce the incidence of P. vivax malaria.
Abstract: In recent years, several rapid diagnostic tests for falciparum malaria have been developed. KAT test results were compared with microscopy on 90 consecutive patients hospitalized at the Hospital for Tropical Diseases, Bangkok, Thailand. Fifty-one patients had P. falciparum infections while 49 had malaria due to other plasmodium species. For a geometric mean +/-SD (Min;Max;range) parasitemia of 11,481 +/- 5.0 (88;713,838;713,750), the sensitivity of the KAT test was 96% (95% CI = 86-99.5), the specificity was 92% (95% CI = 80-99), the accuracy was 94% and the reliability was 85%. These findings suggest that the KAT test is of potential interest in the diagnosis of falciparum malaria in Thailand.
Abstract: The usual criteria for severe malaria are not always sufficient to identify patients who subsequently develop this disease. The multi-organ dysfunction score (MODS) was assessed in 22 patients with uncomplicated Plasmodium falciparum malaria to test its usefulness in discriminating different severity levels. The MODS on admission was highly correlated with the baseline concentration of tumor necrosis factor--alpha (r = 0.83, P < 0.001) and the duration of symptoms after admission (r = 0.54, P = 0.01). The MODS was also correlated with parasite count (r = 0.52, P = 0.014), parasite clearance time (r = 0.54, P = 0.009), and fever clearance time (r = 0.58, P = 0.005). The above correlations remained significant after controlling for the initial parasitemia (P = 0.03 and 0.005). The MODS is simple and easy to apply and needs a recording time of less than three minutes. Thus, this score might provide a quantitative approach for determining severity in Plasmodium falciparum malaria.
Abstract: Nutritional deficiency and malaria are 2 major causes of anaemia during pregnancy in tropical areas. The relationship between anaemia, its treatment with iron and folate, and malaria was studied in a prospective cohort of 2112 pregnant Karen women on the north-western border of Thailand between 1993 and 1997. The development of Plasmodium vivax malaria was associated with a past mean haematocrit > 30% (hazard ratio = 1.5, 95% CI 1.2-2, P = 0.001) and recent (< or = 30 d) iron and folate supplementation (hazard ratio = 1.7, 95% CI 1.1-2.6, P = 0.01). There were no associations with P. falciparum infections. Plasmodium vivax has a predilection for young erythrocytes, and these results suggest that pregnant women with larger numbers of circulating young red cells are at greater risk of developing P. vivax malaria. In P. vivax-endemic areas, systematic iron and folate supplementation confers both benefit and risk in pregnancy.
Abstract: To evaluate the effect of long-term storage of sample filters on the sensitivity of polymerase chain reaction (PCR) detection of malaria, 252 blood spots from patients with microscopically confirmed Plasmodium falciparum malaria were analyzed and stratified by storage duration. The spots were collected between 1996 and 2000 on filter paper and stored at room temperature. A Chelex-based method was used to extract the DNA. Unexpectedly, after the first purification, the sensitivity of the PCR from recently stored samples was low and showed progressively increased with time storage (P = 0.003, by chi-square test for linear trend). This suggested that PCR inhibitors were easier to dissolve from the more recent blood spots (< 4 years old) than from blood spots > or = 4 years old, thus leading to a time-dependent increase in PCR sensitivity. However, if DNA was purified again (when the first PCR result was negative), the cumulative sensitivity was not influenced by storage duration. This indicated that length of storage is not a critical issue providing purification is sufficient.
Abstract: In concurrent infections in vivo, the blood stages of Plasmodium vivax suppress those of Plasmodium falciparum. To see if the paroxysm (i.e. the periodic febrile episode) of P. vivax infection contributes to this suppression, sera from a P. vivax-infected volunteer were added to cultures of whole blood taken from cases of P. falciparum malaria. The crude 'rate' of schizont generation from the ring forms, measured as the percentage of all asexual parasites that were schizonts after incubation for 24 h, was similar whether the cultures contained serum samples collected during paroxysms or those collected, from the same volunteer, at other times (19.1% v. 18.9%; P=0.842). After a random-effect linear regression was used to adjust for disparities between the P. falciparum isolates, however, the degree of schizont maturation, measured as the mean number of nuclei per schizont, was significantly lower for the cultures with 'paroxysm serum' than for those with 'non-paroxysm serum' (4.8 v. 5.3; P=0.002). The proportion of schizonts considered mature was also significantly lower when 'paroxysm serum' was used (3.7% v. 6.3%: P=0.03). This appears to be the first in-vitro study in which sera collected during a paroxysm of P. vivax have been shown to inhibit the maturation of P. falciparum schizonts. The role of this mechanism in intra- and inter-specific competition is discussed.
Abstract: To determine factors influencing gametocyte carriage, a cross-sectional study was conducted among 512 patients admitted for Plasmodium falciparum malaria. After adjustments for potential confounders, hemoglobin concentrations were lower in gametocyte carriers 10.5 (+/-2.5) than in patients without gametocytes 12.5 (+/-2.3) (P < 0.0001). Hemoglobin concentrations were negatively correlated with peak gametocyte counts (Spearman's p = -0.37, P < 0.0001) and gametocyte carriage durations (Spearman's p = -(0.30, P < 0.0001). Adjustments for the duration of the malaria episode and other potential confounders did not alter the association (P < 0.0001). After adjustment for potential confounders, the median asexual parasitemia was higher in patients with gametocytes than in patients without gametocytes (P = 0.003). Severe malaria cases were more likely to have gametocytes (65%) than malaria with hyperparasitemia (38%) or mild malaria (31%) (P = 0.0001). These findings suggest that events surrounding anemia and tissue hypoxia stimulate Plasmodium falciparum gametocytogenesis.
Abstract: In a prospective study of the total population of 5 hamlets on the western border of Thailand, all subjects were screened for helminth infections; during the following year, the incidence of malaria was recorded. Patients were not treated for helminth infections. Among 731 villagers, helminth-infected subjects were more likely to develop falciparum malaria during the following year (adjusted risk ratio 2.24, range 1.4-3.6; P = 0.001). The risk of developing falciparum malaria increased with the number of helminth species (P =0.036). Whereas in other studies helminths were associated with protection from severe complications of malaria, it seemed here that helminth-infected patients were more likely to develop malaria. It is suggested that a helminth-mediated Th2 shift may have complex consequences on malaria, decreasing antisporozoite immunity, but protecting against severe malaria.
Abstract: Although human infection with Ascaris appears to be associated with protection from cerebral malaria, there are many potential socio-economic and nutritional confounders related to helminth infection that need to be considered. In a hospital-based study, 37 cases of cerebral malaria and 61 cases of non-severe malaria with high parasite biomass (i.e. hyperparasitaemia and/or circulating schizonts) answered a structured questionnaire and were screened for intestinal helminths. Logistic regression was then used to adjust for the potential confounders. The adjusted odds ratios (OR) and their 95% confidence intervals (CI) still showed a significant protective association for helminths (OR = 0.24; CI = 0.07-0.78, P = 0.02) and malnutrition (OR = 0.11; CI = 0.02-0.58; P = 0.01), with no evidence of interaction between the two. There was also a significant dose-effect trend for the helminth infections (P = 0.048). These results, despite coming from a hospital-based study, indicate that the apparent association between helminths and protection from cerebral malaria is not the result of socio-economic or nutritional confounders.
Abstract: The burden of malaria mortality has been a major evolutionary influence on human immunity. The selection of the most successful immune responses against malaria has been in populations concomitantly infected by intestinal helminths. Animal models have shown that coinfections with helminths and protozoa in the same host elicit a range of antagonist and synergistic interactions. Recent findings suggest similar interactions take place between helminths, Plasmodium falciparum and humans. However, as the threat of HIV and tuberculosis becomes a major selective force, what used to be a successful ecological system may now prove detrimental. Nevertheless, the understanding of the ecological forces at play may expose new intervention targets for malaria control, and give a new perspective on our shortcomings against the deadliest of human parasites.
Abstract: Following a study showing an association between Ascaris and protection from cerebral malaria, we hypothesized helminths may have induced protection through immunoglobulin E (IgE) and the CD23/NO pathway. We compared the prevalence of helminth infections in 67 cerebral malaria patients and 217 hyperparasitemic controls with no complications. For 24 cerebral malaria cases and 56 controls, we compared reactive nitrogen intermediates (RNI) concentrations and their correlations to total IgE and sCD23 concentrations in helminth-infected and noninfected patients. We observed a dose-dependent association between helminth infections and protection from cerebral malaria (adjusted odds ratio [OR] = 0.36, 95% CI = 0.19-0.7, P = 0.002, linear trend P = 0.0007). Helminth-infected controls had higher RNI concentrations than those without helminths: 72 OD +/- 19 SD and 57 OD +/- 20 SD, respectively (P = 0.006). Logistic regression, including interaction terms between RNI and sCD23, showed that an increase of RNI could be both protective and pathogenic depending on the concentration of sCD23. Helminths increasing both the CD23 receptor and its ligand may have a role in the establishment of malaria tolerance through the CD23/NO pathway.
Abstract: To search for evidence of a protective role of the CD23/NO pathway against cerebral malaria, concentrations of reactive nitrogen intermediates (RNI) and sCD21, total immunoglobulin (Ig)E and sCD23 were compared between 17 cases of cerebral malaria and 33 controls. The geometric mean of sCD23 concentration was higher among cerebral malaria cases than among controls (optical density 2643/1495, P = 0.01). The ratio between sCD21 and sCD23 was significantly lower in cerebral malaria cases than in controls (0.67 +/- 0.02 versus 0.77 +/- 0.02, respectively, P = 0.009). Multiple linear regression analysis showed that, among cerebral malaria cases, there was a clear correlation between RNI and both IgE (P = 0.007) and sCD21 (P < 0.0001). Among controls, there was a strong negative correlation between RNI and sCD23 concentrations (r = -0.61, P < 0.0001). However, multivariate analysis unmasked the fact that, in controls, there was also a positive correlation between RNI and IgE (P = 0.045). Logistic regression showed that increased RNI concentrations were associated with a cerebral malaria adjusted odds ratio of 1.05 per unit increase [95% confidence interval (CI) 1.006-1.1, P = 0.02] and that an increased ratio between sCD21 and sCD23 was associated with protection from cerebral malaria (adjusted OR = 0.00001 per unit increase (95% CI 0-0.03, P = 0.005). These different immunological profiles suggest that, among controls, the CD23/NO pathway was chronically stimulated whereas, in cerebral malaria, its stimulation was acute, which could explain why some patients developed cerebral malaria and others did not.
Abstract: In French Guiana, marked seasonal fluctuations have been observed in the numbers of individuals who present with cutaneous leishmaniasis (CL). To investigate the seasonal trends further, the clinical characteristics and responses to treatment of 455 cases of CL, who presented over a 3-year period (1995-1998), were compared against data on the weather for the calendar month of presentation (month 0) and for the month before presentation (month-1). Several statistically significant associations were observed. The number of sunlight hours in month -1 was lower for the treatment successes than for the treatment failures [adjusted odds ratio (AOR) for successful treatment=0.28; 95% confidence interval (CI)=0.13-0.6; P=0.001] and for those with long incubation periods than for those with relatively short incubation periods (multiple-regression coefficient=-0.003; P=0.002). However, the radiation intensity for month-1 was higher for the treatment successes than for the treatment failures (AOR=2.1; CI=1.1-3.8; P=0.02). Relatively high numbers of hours of sunlight on month-1 were associated with relatively high numbers of parasites on the skin smears (AOR=1.03; CI=1.01-1.04; P<0.001). Relatively high numbers of hours of sunlight during month 0 were associated with lymphangitis (AOR=0.4; CI=0.19-0.8; P=0.01). These results indicate that meteorological parameters may influence the evolution of CL, at least in French Guiana.
Abstract: Despite the apparent frailty of a complex cycle, Plasmodium falciparum seems remarkably fit in its ability to escape human interventions. The red blood cell is central in a number of aspects of the cycle. Hence, hematocrit reduction is of paramount importance in vector survival and reproduction, gametocyte induction and infectiousness, and host pathology. Here, in the light of recent observations, the importance of anemia for P. falciparum is emphasized, suggesting that among populations at risk for malaria, the subgroup of anemic patients may be preferential amplifiers of the plasmodial cycle.
Abstract: Malaria's pyrogenic threshold seems to depend on factors such as age and transmission patterns. We studied the temperature at admission of 200 patients with mild malaria and observed that after adjusting for body mass index, the presence of other helminths, and other confounders, only hookworm-infected patients had lower fever at admission that those without hookworm infection (37.5 +/- 0.9 and 38 +/- 0.8, respectively; P < 0.001). Thus, we suggest the age dependence of the pyrogenic threshold could have been confounded by the epidemiology of iron deficiency.
Abstract: Following an investigation suggesting a protective role for Ascaris against cerebral malaria, possibly through immunomodulation, we examined whether Ascaris had any impact on mixed Plasmodium falciparum and Plasmodium vivax infections. We studied a cross section of 928 patient files between 1991 and 1999. Forty patients had contemporaneous mixed infections and 40 patients had P. falciparum infections, followed by P. vivax infections. There was a significant association between Ascaris infection and risk of having both contemporaneous or successive mixed P. falciparum and P. vivax infections (adjusted odds ratios respectively 6 [2-18] P = 0.001 and 3.6 [1.2-11.1] P = 0.02). There was a positive linear trend between the burden of Ascaris and the risk of mixed infections P < 0.0001. These results suggested the possibility that pre-existing Ascaris infection may increase tolerance of the host to different Plasmodium spp., thus facilitating their coexistence.
Abstract: The cure 'rates' achieved using intramuscular pentamidine isethionate (two injections of 4 mg/kg separated by an interval of 48 h) were investigated in French Guiana, in 198 consecutive patients with cutaneous leishmaniasis caused by Leishmania braziliensis guyanensis. One aim was to see if initial clinical presentation could be used to predict treatment failure. The cure rate after one course of pentamidine isethionate was 87% and almost all (80%) of the treatment failures responded to an identical second course. Although many of the patients complained of adverse effects, most commonly of pain at the injection site (54%), none of these effects was severe. Although frequently associated with discomfort, the two-injection course, giving a total of 8 mg pentamidine isethionate/kg, appears to be an effective treatment for cutaneous leishmaniasis in French Guiana. The observation of satellite papules on presentation was associated with a significantly increased risk of failure of the first course of treatment (P = 0.01), with an odds ratio (and 95% confidence interval) estimated at 3.5 (1.3-11.1), after adjusting for other clinical presentations and lesion size and number. The presence of satellite papules perhaps indicates that the patient's immune system is unable to control the progression of the parasite. Patients with more than three lesions were also less likely to be cured after one course of pentamidine than those with fewer lesions (P = 0.01).
Abstract: Although molecular biology has illustrated the phenotypic heterogeneity of Plasmodium falciparum, there are still no specific markers of virulence. As parasite virulence is an important determinant of severe malaria, the choice of comparison groups in the study of host factors influencing severity is a delicate issue. Ignoring parasite factors in the selection of controls potentially leads to biased comparisons between a majority of cases with virulent parasites and a majority of controls with non-virulent parasites. This article discusses how to avoid this virulence bias in the absence of specific markers of virulence.
Abstract: Following a study showing an association between Ascaris and protection from cerebral malaria, we conducted a cross-sectional study comparing admission hemoglobin concentrations in relation to exposure to helminth infection in 2 separate groups of patients: 111 cerebral malaria cases and 180 mild Plasmodium falciparum malaria cases. Hookworm infections were excluded. Mean hemoglobin concentrations were significantly lower in helminth-infected patients compared to those without helminths, both in the cerebral malaria group (10.1+/-3 [n = 47] versus 11.2+/-2.4 g/dl [n = 64], P = 0.04) and the mild malaria group (11+/-2.5 [n = 89] vs 12.2+/-2.7 g/dl [n = 91], P = 0.004). Median reticulocyte counts, only available in the cerebral malaria group, were lower in helminth-infected patients compared to those without helminths (15,340/23,760 per microl, P = 0.03). Adjustments for confounders such as body mass index did not alter these associations. These data are consistent with a mechanism causing anemia linked to differences in the immune response of helminth-infected patients during malaria.
Abstract: We conducted a cross-sectional study to identify the socio-economic and environmental protective/risk factors for severe malaria in Thailand. Forty-six cases of severe malaria, 72 cases of non-severe malaria with high parasite biomass and 40 mild malaria cases were included. When comparing severe malaria and non-severe malaria with high parasite biomass, specific logistic regression models showed a significant protective effect for helminths, adjusted odds ratio 0.24 (0.07-0.78) for low body mass index (BMI), adjusted odds ratio 0.11 (0.02-0.58). When comparing severe and mild malaria, a longer residence duration, adjusted odds ratio 0.36 (0.09-0.83) and the use of antimalarial self-medication, adjusted odds ratio 0.08 (0.009-0.84) were associated with protection from severe malaria. Using stepwise logistic regression with all the variables inserted in the model yielded similar results. These findings suggest specific immunity and self-medication control parasite multiplication whereas helminths and malnutrition more specifically affect the pathogenesis of severe malaria.
Abstract: Following studies showing an association between helminth infections and protection from cerebral malaria, we compared 22 patients with malaria-associated acute renal failure with 157 patients with moderately severe malaria. Helminths were associated with protection from renal failure (adjusted odds ratio [AOR], 0.16 [0.03-0.85], P = 0.03). Helminth-infected controls were less likely to have jaundice (AOR, 0.39 [0.16-0.96], P = 0.04) or to have peripheral mature schizonts (AOR, 0.2 [0.07-0.62], P = 0.005) than controls without helminths. This suggested that preexisting helminth infections may have been protective by influencing sequestration and obstructive jaundice, 2 possible determinants of acute tubular necrosis.
Abstract: An investigation was conducted to determine whether seasonal variations affected the development of cutaneous leishmaniasis. Data from 499 cases treated between July 1994 and December 1998 were analyzed. The interval between infection and consultation and between treatment and clinical cure varied significantly between cases with an incubation period during the dry season compared with the rainy season (P < 0.001). When the incubation period occurred during the dry season, the standard pentamidine isethionate treatment seemed to be less effective (i.e.. the odds ratio for failure was 1.9 [1.1-3.4], P = 0.01). The presence of lymphangitis was more frequent during the dry season (i.e., the odds ratio was 0.26 [0.15-0.45], P < 0.001). These results suggested that the observed seasonal variations were due to variations in the host/parasite balance. Converging indirect elements that suggest a role for variations in solar ultraviolet radiation are discussed.
Abstract: We conducted a case record study comparing liver tests abnormalities in 20 malaria-related acute renal failure cases without cerebral malaria, 52 cerebral malaria cases without other organ impairment, 189 cases of nonsevere malaria associated with a high parasite burden, and 131 cases of mild Plasmodiumfalciparum malaria. Jaundice and hepatomegaly were significantly associated with renal failure (adjusted odds ratio [AOR], 3.3, 95% confidence interval [CI], 1.3-8.6, P = 0.01; and AOR, 1.7 95% CI, 1.13-2.4, P = 0.01) but not with cerebral malaria (AOR, 1, 95% CI, 0.5-2, P = 0.8; and AOR, 1.08, 95% CI, 0.8-1.8, P = 0.5). Patients with acute renal failure were significantly older and had increased liver abnormalities compared with other groups. Although an increase in the proportion of mature schizonts over ring forms was significantly associated with cerebral malaria, it did not seem to have affected acute renal failure. These results suggested that cytoadherence was not the main determinant for renal failure and that jaundice itself may have potentiated the effects of hypovolemia.
Abstract: The objective of this study was to determine whether pre-existing helminth infections could affect sexual forms of Plasmodium falciparum. A cross-sectional case record study compared 120 mild P. falciparum malaria cases with patent gametocyte carriage and 187 without gametocytes for helminth exposure. Relevant crude odds ratios and potential confounders were included in a logistic regression model. Helminth infections were associated with the presence of gametocytes with a crude odds ratio of 1.9 (95% confidence interval = 1.1-3.3) (P = 0.01). A positive linear trend was observed between the odds of having patent gametocytemia and the number of different helminth species (P = 0.003). However, when adjusting for hemoglobin concentration the significance of the association between helminths and gametocytes disappeared (P = 0.15). Pre-existing helminth infections may increase the severity of malarial anemia and therefore increase the likelihood of carrying gametocytes. At a population level, helminth infections may thus have a significant influence on malaria transmission.
Abstract: The role of the spleen during Plasmodium falciparum malaria in humans is unclear. In Thailand, malaria transmission is low and splenomegaly is rarer than in high transmission areas. We compared the prevalence of splenomegaly between 52 cerebral malaria patients and 191 patients without complications despite a high parasite biomass. We also measured concentrations of reactive nitrogen intermediates (RNIs) in a fraction of these cases recruited in 1998 (24 cerebral malaria and 56 controls). Splenomegaly was significantly associated with cerebral malaria (adjusted odds ratio = 2.07 [95% confidence interval = 1-4.2]; P = 0.048). There was a linear trend for this association (P = 0.0003). After adjusting for potential confounders, concentrations of RNIs were significantly lower in the presence of splenomegaly (P = 0.01). These results suggest that in humans, as in animal models, the spleen may be involved in the pathogenesis of cerebral malaria. The relationship between RNI concentrations and the spleen suggest that nitric oxide may have a regulating role in the complex physiology of the spleen during malaria.
Abstract: Following reports of increased IgE in severe malaria and hypothesizing that helminth coinfections could modify its outcome, we conducted a retrospective case-control study to establish whether helminths affect the evolution of Plasmodium falciparum malaria. Some 182 severe cases, 315 mild controls and 40 controls with circulating schizonts were examined for intestinal helminths. Comparing cerebral malaria with mild controls, Ascaris lumbricoides was associated with a protective adjusted odds ratio (OR) of 0.58 (0. 32-1.03) P = 0.06, for coinfection with Ascaris and Necator americanus, OR = 0.39 (0.17-0.88) P = 0.02. Protection followed a dose-effect trend (P = 0.008). When comparing cerebral malaria cases and controls with circulating schizonts the OR was 0.25 (0.009-0.67) P = 0.006. We hypothesized that Ascaris infected patients may have had decreased cyto-adherence, possibly through endothelial cell receptor downregulation and/or decreased splenic clearance leading to the absence of selection of virulent P. falciparum strains. IgE-anti-IgE immune complexes resulting from helminth preinfection may have an important role in influencing clinical presentation of severe malaria, and in establishing malaria tolerance, through the CD23/NO pathway.
