Margarete do Socorro Mendonça Gomes

Disseminated histoplasmosis in HIV-infected patients in South America: a neglected killer continues on its rampage.

HIV/AIDS is not a neglected disease. Histoplasmosis is not considered a neglected disease in North America. However, in South America, it should be. It often affects neglected populations and represents a lethal blind spot of the HIV/AIDS data collection systems. Counts of new AIDS cases and AIDS-related deaths are useful to follow the epidemic; however, they overlook the exact cause of death. In the context of the South American pathogen ecology, the systemic mycosis due to Histoplasma capsulatum var. capsulatum is probably on the top of the list of AIDS-defining illnesses and AIDS-related deaths [1], yet it is mostly undiagnosed and is not even on the diagnostic algorithm used by a significant proportion of clinicians facing a febrile, severely immunodepressed patient in the region.

Land cover, land use and malaria in the Amazon: a systematic literature review of studies using remotely sensed data

The nine countries sharing the Amazon forest accounted for 89% of all malaria cases reported in the Americas in 2008. Remote sensing can help identify the environmental determinants of malaria transmission and their temporo-spatial evolution. Seventeen studies characterizing land cover or land use features, and relating them to malaria in the Amazon subregion, were identified. These were reviewed in order to improve the understanding of the land cover/use class roles in malaria transmission. The indicators affecting the transmission risk were summarized in terms of temporal components, landscape fragmentation and anthropic pressure. This review helps to define a framework for future studies aiming to characterize and monitor malaria.

Malaria on the Guiana Shield: a review of the situation in French Guiana.

In a climate of growing concern that Plasmodium falciparum may be developing a drug resistance to artemisinin derivatives in the Guiana Shield, this review details our current knowledge of malaria and control strategy in one part of the Shield, French Guiana. Local epidemiology, test-treat-track strategy, the state of parasite drug resistance and vector control measures are summarised. Current issues in terms of mobile populations and legislative limitations are also discussed.

Implementation of basic quality control tests for malaria medicines in Amazon Basin countries: results for the 2005–2010 period

BackgroundEnsuring the quality of malaria medicines is crucial in working toward malaria control and eventual elimination. Unlike other validated tests that can assess all critical quality attributes, which is the standard for determining the quality of medicines, basic tests are significantly less expensive, faster, and require less skilled labour; yet, these tests provide reproducible data and information on several critical quality attributes, such as identity, purity, content, and disintegration. Visual and physical inspection also provides valuable information about the manufacturing and the labelling of medicines, and in many cases this inspection is sufficient to detect counterfeit medicines. The Promoting the Quality of Medicines (PQM) programme has provided technical assistance to Amazon Malaria Initiative (AMI) countries to implement the use of basic tests as a key screening mechanism to assess the quality of malaria medicines available to patients in decentralized regions.MethodsTrained personnel from the National Malaria Control Programmes (NMCPs), often in collaboration with country’s Official Medicine Control Laboratory (OMCL), developed country- specific protocols that encompassed sampling methods, sample analysis, and data reporting. Sampling sites were selected based on malaria burden, accessibility, and geographical location. Convenience sampling was performed and countries were recommended to store the sampled medicines under conditions that did not compromise their quality. Basic analytical tests, such as disintegration and thin layer chromatography (TLC), were performed utilizing a portable mini-laboratory.ResultsResults were originally presented at regional meetings in a non-standardized format that lacked relevant medicines information. However, since 2008 information has been submitted utilizing a template specifically developed by PQM for that purpose. From 2005 to 2010, the quality of 1,663 malaria medicines from seven AMI countries was evaluated, mostly collected from the public sector, 1,445/1,663 (86.9%). Results indicate that 193/1,663 (11.6%) were found not to meet quality specifications. Most failures were reported during visual and physical inspection, 142/1663 (8.5%), and most of these were due to expired medicines, 118/142 (83.1%). Samples failing TLC accounted for 27/1,663 (1.6%) and those failing disintegration accounted for 24/1,663 (1.4%). Medicines quality failures decreased significantly during the last two years.ConclusionsBasic tests revealed that the quality of medicines in the public sector improved over the years, since the implementation of this type of quality monitoring programme in 2005. However, the lack of consistent confirmatory tests in the quality control (QC) laboratory, utilizing methods that can also evaluate additional quality attributes, could still mask quality issues. In the future, AMI countries should improve coordination with their health authorities and their QC lab consistently, to provide a more complete picture of malaria medicines quality and support the implementation of corrective actions. Facilities in the private and informal sectors also should be included when these sectors constitute an important source of medicines used by malaria patients.

Metemoglobinemia em pacientes com malária por Plasmodium vivax em uso oral de primaquina

INTRODUCAO: A primaquina pode acarretar serios eventos adversos, com destaque para a toxicidade ao sangue. O objetivo deste trabalho e determinar a metemoglobinemia de 20 pacientes com malaria por Plasmodium vivax tratados com primaquina, comparando-os segundo o sexo e a expressao da glicose-6-fosfato desidrogenase. METODOS: Quantificacao da metemoglobina por espectrofotometria visivel e avaliacao qualitativa da glicose-6-fosfato desidrogenase. RESULTADOS: A metemoglobinemia variou de 2,85 a 5,45% nos pacientes do sexo masculino e de 3,77 a 7,34% no feminino. CONCLUSOES: A instituicao da terapia aumentou de maneira significativa os teores de metemoglobina, sem manifestacao clinica evidente e independente do sexo e da atividade enzimatica.

Recurrence of Plasmodium falciparum after treatment with quinine and doxycycline in the Amazon basin.

To investigate whether the recurrence of infection by Plasmodium falciparum in patients from the Brazilian Amazon was caused by an inadequate exposure to quinine.

Primaquine in Plasma and Methemoglobinemia in Patients with Malaria Due to Plasmodium vivax in the Brazilian Amazon Basin

AbstractPrimaquine is the only licensed drug available for the elimination of Plasmodium vivax hypnozoites. Methemoglobinemia is currently reported in the course of treatment. There is evidence that metabolites of primaquine formed by the cytochrome pathway are responsible for methemoglobin formation; a genetic polymorphism of cytochrome isoforms; and a potential influence of gender in the activities of these enzymes requiring the establishment of dose × response curves profiles in different population groups. Concentrations of primaquine in plasma and methemoglobin levels were investigated in 54 patients with malaria due to P. vivax during the course of the standard regimen of chloroquine with primaquine (0.25 mg/kg/day for 14 days). All study subjects lived in an endemic area of the Brazilian Amazon Basin. The blood samples were collected before initiation of treatment and 3 hours (range 2-4 hours) after the administration of antimalarial drugs on days 2, 7, and 14. Plasma primaquine concentrations were similar in both genders (males: range = 164-191 ng/mL, females: range = 193-212 ng/mL). Methemoglobin levels ranged from 3.3% to 5.9% in males and from 3.1% to 6.5% in females. There were no significant correlations between the plasma primaquine concentrations or total dose and methemoglobin levels, suggesting that unidentified metabolites rather than parent drug were likely responsible for changes in methemoglobin levels. There was no significant influence of gender on primaquine concentrations in plasma or methemoglobin levels.

EVALUATION OF CIRCUMSPOROZOITE PROTEIN OF Plasmodium vivax TO ESTIMATE ITS PREVALENCE IN OIAPOQUE , AMAPÁ STATE, BRAZIL, BORDERING FRENCH GUIANA.

SUMMARY Malaria is a major health problem for people who live on the border between Brazil and French Guiana. Here we discuss Plasmodium vivax distribution pattern in the town of Oiapoque, Amapá State using the circumsporozoite (CS) gene as a marker. Ninety-one peripheral blood samples from P. vivax patients have been studied. Of these, 64 individuals were from the municipality of Oiapoque (Amapá State, Brazil) and 27 patients from French Guiana (August to December 2011). DNA extraction was performed, and a fragment of the P. vivax CS gene was subsequently analyzed using PCR/RFLP. The VK210 genotype was the most common in both countries (48.36% in Brazil and 14.28% in French Guiana), followed by the P. vivax-like (1.10% in both Brazil and French Guiana) and VK247 (1.10% only in Brazil) in single infections. We were able to detect all three CS genotypes simultaneously in mixed infections. There were no statistically significant differences either regarding infection site or parasitaemia among individuals with different genotypes. These results suggest that the same genotypes circulating in French Guiana are found in the municipality of Oiapoque in Brazil. These findings suggest that there may be a dispersion of parasitic populations occurring between the two countries. Most likely, this distribution is associated with prolonged and/or more complex transmission patterns of these genotypes in Brazil, bordering French Guiana.

Patient age does not affect mefloquine concentrations in erythrocytes and plasma during the acute phase of falciparum malaria

OBJECTIVE To evaluate whether patient age has a significant impact on mefloquine concentrations in the plasma and erythrocytes over the course of treatment for uncomplicated falciparum malaria. METHODS A total of 20 children aged between 8 and 11 years and 20 adult males aged between 22 and 41 years with uncomplicated falciparum malaria were enrolled in the study. Mefloquine was administered to patients in both age groups at a dose of 20mgkg(-1). The steady-state drug concentrations were measured by reversed-phase high performance liquid chromatography. RESULTS All patients had an undetectable mefloquine concentration on day 0. In adults, the plasma mefloquine concentrations ranged from 770 to 2930ngmL(-1) and the erythrocyte concentrations ranged from 2000 to 6030ngmL(-1). In children, plasma mefloquine concentrations ranged from 881 to 3300ngmL(-1) and erythrocyte concentrations ranged from 3000 to 4920ngmL(-1). There was no significant correlation between mefloquine concentrations in the plasma and erythrocytes in either adults or children. CONCLUSION In the present study, we observed no effect of patient age on the steady-state concentrations of mefloquine in the plasma and erythrocytes. We found that the mefloquine concentration in the erythrocytes was approximately 2.8-times higher than in the plasma. There were no significant correlations between mefloquine concentrations in the erythrocytes and plasma for either age group.

Enteroparasite and vivax malaria co-infection on the Brazil-French Guiana border: Epidemiological, haematological and immunological aspects.

Malaria-enteroparasitic co-infections are known for their endemicity. Although they are prevalent, little is known about their epidemiology and effect on the immune response. This study evaluated the effect of enteroparasite co-infections with malaria caused by Plasmodium vivax in a border area between Brazil and French Guiana. The cross sectional study took place in Oiapoque, a municipality of Amapá, on the Amazon border. Malaria was diagnosed using thick blood smears, haemoglobin dosage by an automated method and coproparasitology by the Hoffman and Faust methods. The anti-PvMSP-119 IgG antibodies in the plasma were evaluated using ELISA and Th1 (IFN-γ, TNF-α and IL-2), and Th2 (IL-4, IL-5 and IL-10) cytokine counts were performed by flow cytometry. The participants were grouped into those that were monoinfected with vivax malaria (M), vivax malaria-enteroparasite co-infected (CI), monoinfected with enteroparasite (E) and endemic controls (EC), who were negative for both diseases. 441 individuals were included and grouped according to their infection status: [M 6.9% (30/441)], [Cl 26.5% (117/441)], [E 32.4% (143/441)] and [EC 34.2% (151/441)]. Males prevailed among the (M) 77% (23/30) and (CI) 60% (70/117) groups. There was a difference in haemoglobin levels among the different groups under study for [EC-E], [EC-Cl], [E-M] and [Cl-M], with (p < 0.01). Anaemia was expressed as a percentage between individuals [CI-EC (p < 0.05)]. In terms of parasitaemia, there were differences for the groups [CI-M (p < 0.05)]. Anti-PvMSP-119 antibodies were detected in 51.2% (226/441) of the population. The level of cytokines evaluation revealed a large variation in TNF-α and IL-10 concentrations in the co-infected group. In this study we did not observe any influence of coinfection on the acquisition of IgG antibodies against PvMSP119, as well as on the profile of the cytokines that characterize the Th1 and Th2 patterns. However, co-infection increased TNF-α and IL-10 levels.