Maria das Graças Vale Barbosa

Chloroquine-Resistant Plasmodium vivax, Brazilian Amazon

To the Editor: Plasmodium vivax is the protozoan that causes the second most common form of malaria. Some resistant strains to chloroquine (CQ) occur in a few places in Asia and the Indo-Pacific Region (1–4). Although resistance of P. vivax to CQ has already been described in South America (5–7), there are limited data regarding this issue. CQ plus primaquine is the standard treatment for vivax malaria worldwide. Presently, this drug regimen exhibits satisfactory efficacy in the Brazilian Amazon. However, in recent years several treatment failures presumably related to CQ resistance, have been reported in the city of Manaus (Amazonas) where vivax malaria predominates (7). This observation warrants local attention despite these cases having no confirmation of CQ blood levels on the basis of the appearance of asexual parasites against CQ plus desethylchloroquine levels exceeding the minimally effective plasma concentration proposed for sensitive parasite strains (>10 ng/mL) (8), according to Pan American Health Organization recommendations (9). From September 2004 to February 2005, a 28-day in vivo test was conducted at the Foundation for Tropical Medicine of Amazonas (FMTAM) in Manaus, Brazil, to assess the efficacy of standard supervised CQ therapy. The test involved 166 volunteers with uncomplicated vivax malaria. Each volunteer was administered uncoated, scored, 150-mg CQ tablets (10 + 7.5 + 7.5 mg/kg at 24-hour intervals) (9). Primaquine was withheld until day 28 (dose regimen of 30 mg/day for 7 days). Among the 109 volunteers who completed the in vivo test, 19 had positive blood smears within the 28-day follow-up (1 on day 14, 3 on day 21, and 15 on day 28). All were required to undergo alternative therapy (mefloquine). Adequate CQ absorption was confirmed in these cases on day 2 with a mean ± SD CQ plasma concentration of 785.4 ± 800.1 ng/mL) (10) Suspected therapeutic failure (P. vivax CQ resistance) was confirmed in 11 (10.1%) of 109 persons with a mean isolated choloroquine plasma concentration >10 ng/mL (356.6 ± 296.1 ng/mL) (9). Desethylchloroquine levels in plasma were not measured. Previously, a CQ efficacy study demonstrated that 4.4% of those tested had CQ-resistant P. vivax (7). In comparison, the proportion of failures (10.1%) in the current study seems to be relevant; even though most of the P. vivax infections (98, 89.9%) were successfully evaluated and adequate clinical and parasitologic responses were obtained. Currently, the FMTAM Manaus Outpatient Clinic is detecting patients from different areas of the city who show parasitologic recurrences after correct treatment within 28 days of the routine clinical follow-up. This observation is an indirect indicator of the possible regional spread of P. vivax CQ-resistant strains (unpub. data). We believe our findings are important and merit the attention of local public health authorities. Considering the possibility of emerging underestimated P. vivax CQ resistance in Manaus, we feel it is essential to quickly clarify whether such documented resistance can copromote vivax malaria outbreaks in malaria-endemic areas within the Amazon.

Epidemiologia da leishmaniose tegumentar na Comunidade São João, Manaus, Amazonas, Brasil

In Manaus, Amazonas State, Brazil, the degree of individual exposure to leishmaniasis is related to disorganized land occupation. In order to evaluate predisposing factors for an outbreak, confirm the parasitological diagnosis, treat patients, and assess etiological agents, reservoirs, and vectors, a 12-month study was conducted in Manaus in a community located along the BR-174 federal highway. Some 451 individuals were studied, among whom 17 cases of American tegumentary leishmaniasis (ATL) were diagnosed (six women and 11 men). Age varied from one to 64 years. Eleven patients had from one to three lesions. As for reservoirs, three opossums were captured. No hemoflagellates were found in the blood tests. Lutzomyia umbratilis was the predominant vector species captured. Many ATL patients were engaged in activities that exposed them to Leishmania vectors. Some patients may have been infected in the household and peridomiciliary environments. The epidemiological profile of ATL in this community is similar that of other foci in the region. This case series characterizes ATL as an endemic local public health problem.

Expansão urbana e distribuição espacial da malária no município de Manaus, Estado do Amazonas

In the municipality of Manaus, intensification of the migratory process, along with precarious epidemiological and entomological surveillance, resulted in reintroduction of malaria transmission on the urban perimeter (in the eastern zone), in July 1988, after 13 years without any records of autochthonous disease. This study reports on the epidemiological situation relating to malaria and to the areas that were subjected to human actions (deforestation, human settlement, fish-rearing activity, etc) in Manaus, between 1986 and 2005. In this municipality, the population increase from 1986 to 2005 was 105.2%. This resulted from occupation of space, in the form of invasions and housing projects. From 2003, the increase in relation to 1986 was more than 2,000%. In these areas, there were increases in disease incidence. The annual parasitic index in the municipality ranged from low to medium risk and, between urban zones, it ranged from no risk to high risk. In the eastern, western and northern zones, which still contain areas with agricultural characteristics, there was greater receptivity and vulnerability to transmission.

In vivo susceptibility to benznidazole of Trypanosoma cruzi strains from the western Brazilian Amazon

To assess the susceptibility of Trypanosoma cruzi strains from Amazon to benznidazole.

Outbreak of acute Chagas disease associated with oral transmission in the Rio Negro region, Brazilian Amazon

INTRODUCTION Chagas disease is considered as emerging in the Brazilian Amazon, usually occurring in acute outbreaks. METHODS We describe 17 cases of acute Chagas disease in Rio Negro, Amazonas. RESULTS There were 15 males (average age, 31.3 years), all positive for Trypanosoma cruzi in fresh blood smear examination, and 14 positive by xenodiagnosis and PCR. The top clinical manifestations were fever, asthenia, abdominal pain, and palpitations. Electrocardiograms featured low-voltage QRS, anterosuperior divisional block, and right bundle branch block associated with anterosuperior divisional block. CONCLUSIONS All patients had consumed açaí products from Monte Alegre in the rural area around Santa Izabel do Rio Negro, Brazil.

American Tegumentary Leishmaniasis and HIV-AIDS Association in a Tertiary Care Center in the Brazilian Amazon

American tegumentary leishmaniasis (ATL) and human immunodeficiency virus (HIV) are both common infectious diseases in the Brazilian Amazon with overlapping expansion areas, which leads to the occurrence of Leishmania/HIV coinfection. Most ATL/HIV-acquired immunodeficiency syndrome (AIDS) association cases have been reported from areas where Leishmania (Viannia) braziliensis is the main pathogen; this finding is in contrast with the Amazon region, where L. (V.) guyanensis is the most implicated agent, implying distinct clinical and therapeutic aspects. We describe 15 cases of ATL/HIV coinfection treated in a tertiary care center in the Brazilian Amazon between 1999 and 2008. Thirteen patients presented with diverse clinical manifestations of cutaneous leishmaniasis, and four of them had disseminated forms; two patients presented with mucosal leishmaniasis (ML). Seven patients required more than one course of treatment. The particularities of ATL/HIV-AIDS association in L. (V.) guyanensis-endemic areas require efforts for an increased understanding of its burden and subsequent improvements in case management.

Integrated vector management targeting Anopheles darlingi populations decreases malaria incidence in an unstable transmission area, in the rural Brazilian Amazon.

BackgroundStudies on vector behaviour should be conducted in order to evaluate the effectiveness of vector control measures on malaria protection in endemic areas of Latin America, where P. vivax predominates. This work aims to investigate the fauna of anopheline mosquitoes and verify the impact of integrated vector management in two colonization projects in the Careiro Municipality, Western Brazilian Amazon.MethodsFour mosquitoes’ captures were carried out from August 2008 to March 2010, with an interval of six months between each collection. Since September 2009 a large programme to reduce the burden of malaria has started in the two communities by distribution of insecticide-treated bed nets (ITN) and intensification of indoor residual spraying (IRS). Human biting rates (HBRs), entomological inoculation rates (EIRs), malaria incidence rate (MIR) and Plasmodium carrier’s prevalence were used as outcomes to estimate the impact of the control measures.ResultsA total of 3,189 anophelines were collected, belonging to 13 species. Anopheles darlingi was the predominant species in the period (42.6%), followed by Anopheles albitarsis (38.4%). An. darlingi HBRs showed a notable decreasing trend from the start to the end of the study. Conversely, An. albitarsis increased its contribution to overall HBRs throughout the study. For An. darlingi there was a significant positive correlation between HBRs and MIR (p = 0.002). Anopheles albitarsis HBRs showed a significant negative correlation with the corresponding MIR (p = 0.045). EIR from total anophelines and from An. darlingi and An. albitarsis presented decreasing patterns in the successive collections. Four species of anophelines (An. darlingi, An. albitarsis, Anopheles braziliensis and Anopheles nuneztovari) were naturally infected with Plasmodium, albeit at very low infection rates. There were a decrease in the MIR for both vivax and falciparum malaria and in the prevalence of Plasmodium vivax and Plasmodium falciparum carriers during the period of study.ConclusionsThere is strong evidence of association between the density of An. darlingi and the incidence of malaria in the studies sites, further highlighting the importance of this vector in malaria transmission in this region. An. darlingi susceptibility to control using ITN and IRS is likely to be high in the rural settlements studied.

Glucose-6-phosphate dehydrogenase deficiency in an endemic area for malaria in Manaus: a cross-sectional survey in the Brazilian Amazon.

Background There is a paucity of information regarding glucose-6-phosphate dehydrogenase (G6PD) deficiency in endemic areas for malaria in Latin America. Methodology/Principal Findings This study determined the prevalence of the G6PD deficiency in 200 male non-consanguineous individuals residing in the Ismail Aziz Community, on the outskirts of Manaus (Brazilian Amazon). Six individuals (3%) were deficient using the qualitative Brewers test. Gel electrophoresis showed that five of these patients were G6PD A−. The deficiency was not associated with the ethnic origin (P = 0.571). In a multivariate logistic regression analysis, G6PD deficiency protected against three or more episodes of malaria (P = 0.049), independently of the age, and was associated with a history of jaundice (P = 0.020) and need of blood transfusion (P = 0.045) during previous treatment for malarial infection, independently of the age and the previous malarial exposure. Conclusions/Significance The frequency of G6PD deficiency was similar to other studies performed in Brazil and the finding of a predominant G6PD A− variant will help the clinical management of patients with drug-induced haemolysis. The history of jaundice and blood transfusion during previous malarial infection may trigger the screening of patients for G6PD deficiency. The apparent protection against multiple malarial infections in an area primarily endemic for Plasmodium vivax needs further investigation.

Trypanosoma cruzi TcIII/Z3 genotype as agent of an outbreak of Chagas disease in the Brazilian Western Amazonia.

Chagas’ disease is an emerging and neglected disease in the Brazilian Amazon region, where T. cruzi I predominates among the acute cases of the disease; and T. cruzi III/Z3, a population cluster from sylvatic areas of the Amazon basin, is rarely associated with human infections. On 23rd April 2007, the Foundation for Health Surveillance of the State of Amazonas, Brazil reported an outbreak of acute Chagas disease in the municipality of Coari on the Solimões River banks. Fresh blood examination confirmed the infection in 25 patients. Parasite culture in LIT medium was successful for 18 isolates. Molecular characterization was performed by PCR of the non‐transcribed spacer of the mini‐exon and by sequencing of the mitochondrial cytochrome c oxidase subunit II (COII) gene. The T. cruzi isolates were all from genotype Z3, and sequencing revealed that all isolates had equal COII sequences compatible with TcIII type, suggesting a single source of infection. To our knowledge, this is the first outbreak of acute cases caused uniquely by the genotype TcIII/Z3. Wild vectors harbouring TcIII stocks contribute to transmission when the triatomine species reaches human food chain or when humans invade the forest environment, where sylvatic cycle constitutes a reservoir of parasites that might be associated with specific epidemiological and clinical traits of the emergent Chagas disease in the Amazon.

Trypanosoma cruzi I and IV Stocks from Brazilian Amazon Are Divergent in Terms of Biological and Medical Properties in Mice

Background In the Brazilian Amazon, clinical and epidemiological frameworks of Chagas disease are very dissimilar in relation to the endemic classical areas of transmission, possibly due to genetic and biological characteristics of the circulating Trypanosoma cruzi stocks. Twenty six T. cruzi stocks from Western Amazon Region attributed to the TcI and TcIV DTUs were comparatively studied in Swiss mice to test the hypothesis that T. cruzi clonal structure has a major impact on its biological and medical properties. Methodology/Principal Findings Seventeen parameters were assayed in mice infected with 14 T. cruzi strains belonging to DTU TcI and 11 strains typed as TcIV. In comparison with TcI, TcIV stocks promoted a significantly shorter pre-patent period (p<0.001), a longer patent period (p<0.001), higher values of mean daily parasitemia (p = 0.009) and maximum of parasitemia (p = 0.015), earlier days of maximum parasitemia (p<0.001) and mortality (p = 0.018), higher mortality rates in the acute phase (p = 0.047), higher infectivity rates (p = 0.002), higher positivity in the fresh blood examination (p<0.001), higher positivity in the ELISA at the early chronic phase (p = 0.022), and a higher positivity in the ELISA at the late chronic phase (p = 0.003). On the other hand TcI showed higher values of mortality rates in the early chronic phase (p = 0.014), higher frequency of mice with inflammatory process in any organ (p = 0.005), higher frequency of mice with tissue parasitism in any organ (p = 0.027) and a higher susceptibility to benznidazole (p = 0.002) than TcIV. Survival analysis showing the time elapsed from the day of inoculation to the beginning of the patent period was significantly shorter for TcIV strains and the death episodes triggered following the infection with TcI occurred significantly later in relation to TcIV. The notable exceptions come from positivity in the hemocultures and PCR, for which the results were similar. Conclusion/Significance T. cruzi stocks belonging to TcI and TcIV DTUs from Brazilian Amazon are divergent in terms of biological and medical properties in mice.