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Vector competence, vectorial capacity of Nyssorhynchus darlingi and the basic reproduction number of Plasmodium vivax in agricultural settlements in the Amazonian Region of Brazil.

Malar J; 18(1): 117, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30947726


BACKGROUND: Brazilian malaria control programmes successfully reduced the incidence and mortality rates from 2005 to 2016. Since 2017, increased malaria has been reported across the Amazon. Few field studies focus on the primary malaria vector in high to moderate endemic areas, Nyssorhynchus darlingi, as the key entomological component of malaria risk, and on the metrics of Plasmodium vivax propagation in Amazonian rural communities. METHODS: Human landing catch collections were carried out in 36 houses of 26 communities in five municipalities in the Brazilian states of Acre, Amazonas and Rondônia states, with API (> 30). In addition, data on the number of locally acquired symptomatic infections were employed in mathematical modelling analyses carried out to determine Ny. darlingi vector competence and vectorial capacity to P. vivax; and to calculate the basic reproduction number for P. vivax. RESULTS: Entomological indices and malaria metrics ranged among localities: prevalence of P. vivax infection in Ny. darlingi, from 0.243% in Mâncio Lima, Acre to 3.96% in Machadinho D'Oeste, Rondônia; daily human-biting rate per person from 23 ± 1.18 in Cruzeiro do Sul, Acre, to 66 ± 2.41 in Lábrea, Amazonas; vector competence from 0.00456 in São Gabriel da Cachoeira, Amazonas to 0.04764 in Mâncio Lima, Acre; vectorial capacity from 0.0836 in Mâncio Lima, to 1.5 in Machadinho D'Oeste. The estimated R for P. vivax (PvR ) was 3.3 in Mâncio Lima, 7.0 in Lábrea, 16.8 in Cruzeiro do Sul, 55.5 in São Gabriel da Cachoeira, and 58.7 in Machadinho D'Oeste. Correlation between P. vivax prevalence in Ny. darlingi and vector competence was non-linear whereas association between prevalence of P. vivax in mosquitoes, vectorial capacity and R was linear and positive. CONCLUSIONS: In spite of low vector competence of Ny. darlingi to P. vivax, parasite propagation in the human population is enhanced by the high human-biting rate, and relatively high vectorial capacity. The high PvR values suggest hyperendemicity in Machadinho D'Oeste and São Gabriel da Cachoeira at levels similar to those found for P. falciparum in sub-Saharan Africa regions. Mass screening for parasite reservoirs, effective anti-malarial drugs and vector control interventions will be necessary to shrinking transmission in Amazonian rural communities, Brazil.

Avian host composition, local speciation, and dispersal drive the regional assembly of avian malaria parasites in South American birds.

Mol Ecol; 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30959568


Identifying the ecological factors that shape parasite distributions remains a central goal in disease ecology. These factors include dispersal capability, environmental filters, and geographic distance. Using 520 haemosporidian parasite genetic lineages recovered from 7,534 birds sampled across tropical and temperate South America we tested 1) the latitudinal diversity gradient hypothesis and 2) the distance-decay relationship (decreasing proportion of shared species between communities with increasing geographic distance) for this host-parasite system. We then inferred the biogeographic processes influencing the diversity and distributions of this cosmopolitan group of parasites across South America. We found support for a latitudinal gradient in diversity for avian haemosporidian parasites, potentially mediated through higher avian host diversity towards the equator. Parasite similarity was correlated with climate similarity, geographic distance, and host composition. Local diversification in Amazonian lineages followed by dispersal were the most frequent biogeographic events reconstructed for haemosporidian parasites. Combining macroecological patterns and biogeographic processes, our study reveals that haemosporidian parasites are capable of circumventing geographic barriers and dispersing across biomes, although constrained by environmental filtering. The contemporary diversity and distributions of haemosporidian parasites are mainly driven by historical (speciation) and ecological (dispersal) processes, whereas the parasite community assembly is largely governed by host composition and to a lesser extent by environmental conditions. This article is protected by copyright. All rights reserved.

Lack of Evidence of Sylvatic Transmission of Dengue Viruses in the Amazon Rainforest Near Iquitos, Peru.

Artigo em Inglês | MEDLINE | ID: mdl-30964397


Dengue viruses (DENV) are currently responsible for more human morbidity and mortality than any other known arbovirus, and all four DENV are known to exist in sylvatic cycles that might allow these viruses to persist if the urban (Aedes aegypti) cycle could be controlled. To determine whether DENV were being maintained in a sylvatic cycle in a forested area about 14 km southwest of Iquitos, Peru, a city in which all 4 serotypes of DENV circulate, we placed 20 DENV seronegative Aotus monkeys in cages either in the canopy or near ground level for a total of 125.6 months. Despite capturing >66,000 mosquitoes in traps that collected some of the mosquitoes attracted to these monkeys, blood samples obtained once a month from each animal were tested and found to be negative by an enzyme-linked immunosorbent assay for IgM and IgG antibodies to dengue, yellow fever, Venezuelan equine encephalitis, Oropouche, and Mayaro viruses. Although all four DENV serotypes were endemic in nearby Iquitos, the findings of this study did not support a DENV sylvatic maintenance and transmission cycle in a selected area of the Amazon rainforest in northeastern Peru.

Study of the efficacy of N-methyl glucamine antimoniate (Sb ) associated with photodynamic therapy using liposomal chloroaluminium phthalocyanine in the treatment of cutaneous leishmaniasis caused by Leishmania (L.) amazonensis in C57BL6 mice.

Artigo em Inglês | MEDLINE | ID: mdl-30951865


BACKGROUND: Pentavalent antimonials remain first-line drugs in the treatment of cutaneous leishmaniasis (CL); however, adverse effects and drug resistance have led to the search for less toxic and more effective treatments. As an alternative, topical phthalocyanine has been studied and its efficacy and low toxicity demonstrated. We aimed to study the in vivo efficacy of N-methyl glucamine antimoniate (NMG) associated with photodynamic therapy (PDT) with topical liposomal chloroaluminium phthalocyanine (AlClPC) in the treatment of experimental CL by L. amazonensis. METHODS: Experimental study with 54 C57BL6 isogenic mice divided into 9 groups including uninfected control, untreated control, PDT with AlClPC + NMG at doses of 10 and 20 mgSb /Kg/day. The criteria to evaluate the treatment efficacy were: paw diameter, amastigote count, culture, viability test and parasite counts using MTT (3-bromo-4,5-dimethylthiazol-2,5-diphenyl-tetrazolium bromide). RESULTS: Treatment of CL with the association of NMG20 + PDT with AlClPC showed significant reduction of paw diameter, amastigote count, cultures, viability test and parasite counts. Parasite reduction occurred at the 10 and 20 days of treatment and 60 days after treatment ended, indicating that parasites did not multiply again. The NMG10 + PDT group with AlClPC presented results equivalent to gold-standard treatment (20 mgSb /kg/day). Biochemical and histopathological evaluation showed minor changes. CONCLUSION: Treatment of CL caused byL. amazonensis with NMG20 mgSb /kg/day + PDT with AlClPC was more effective than the traditional NMG20 mgSb /kg/day.

American Tegumentary Leishmaniasis in the Brazilian Amazon from 2010 to 2014.

Rev Inst Med Trop Sao Paulo; 61: e22, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30970050


American tegumentary leishmaniasis (ATL) is one of the most important but neglected infectious diseases, and can cause severe deformities. ATL incidence remains high in forest regions, such as in the Amazonas State, Brazil. However, differences within the State and over time have been observed, since infection patterns are not homogeneous, and these aspects need to be clarified. This study aimed to identify the epidemiological profile of ATL and its spatial and temporal distribution in the Brazilian Amazon, from 2010 to 2014. Data were extracted from the Information System for Notifiable Diseases, which descriptively evaluates the incidence rate, as well as the temporal and spatial distribution of the disease. The highest prevalence of ATL was found in men and in the age group of 20-40 years. Approximately 95% of the cases were of cutaneous ATL and they were identified through direct examination. The spatial analysis has shown that ATL was widely distributed, both in rural and urban areas, and more concentrated in the Southern part of the State. Moreover, although there was an expansion in the spatial distribution and an increasing incidence of ATL in Amazonas, the epidemiological profile remained unchanged, suggesting that other factors must be responsible for its widespread distribution and increasing incidence.

Correction to: Use and retention of long-lasting insecticidal nets (LLINs) in a malaria risk area in the Brazilian Amazon: a 5-year follow-up intervention.

Malar J; 18(1): 125, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30967138


Following publication of the original article [1], the corresponding author flagged that the particle 'de' in their name had been placed incorrectly.

Cardiac Evaluation in the Acute Phase of Chagas' Disease with Post-Treatment Evolution in Patients Attended in the State of Amazonas, Brazil.

Arq Bras Cardiol; 112(3): 240-246, 2019 Mar.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30916205


BACKGROUND: In the past two decades, a new epidemiological profile of Chagas' disease (CD) has been registered in the Brazilian Amazon where oral transmission has been indicated as responsible for the increase of acute cases. In the Amazonas state, five outbreaks of acute CD have been registered since 2004. The cardiac manifestations in these cases may be characterized by diffuse myocarditis, with alteration in the electrocardiogram (ECG) and transthoracic echocardiogram (TTE). OBJECTIVE: To perform a cardiac evaluation in autochthonous patients in the acute phase and at least one year after submitted to treatment for acute CD and evaluate the demographic variables associated with the presence of cardiac alterations. METHODS: We evaluated patients diagnosed with acute CD through direct parasitological or serological (IgM) methods from 2007 to 2015. These patients were treated with benznidazole and underwent ECG and TTE before and after treatment. We assumed a confidence interval of 95% (CI 95%, p < 0.05) for all variables analyzed. RESULTS: We observed 63 cases of an acute CD in which oral transmission corresponded to 75%. Cardiac alterations were found in 33% of the cases, with a greater frequency of ventricular repolarization alteration (13%), followed by pericardial effusion (10%) and right bundle branch block and left anterior fascicular block (2%). The follow-up occurred in 48 patients with ECG and 25 with TTE for a mean period of 15.5 ± 4.1 months after treatment. Of these, 8% presented normalization of the cardiac alterations in ECG, 62.5% remained with the normal exams. All of the patients presented normal results in TTE in the post-treatment period. As for the demographic variables, isolated cases presented more cardiac alterations than outbreaks (p = 0.044) as well as cases from Central Amazonas mesoregion (p = 0.020). CONCLUSIONS: Although cardiac alterations have not been frequent in most of the studied population, a continuous evaluation of the clinical-epidemiological dynamics of the disease in the region is necessary in order to establish preventive measures.

Novel benzoxaborole, nitroimidazole and aminopyrazoles with activity against experimental cutaneous leishmaniasis.

Artigo em Inglês | MEDLINE | ID: mdl-30922847


OBJECTIVES: Drugs for Neglected Diseases initiative (DNDi) has identified three chemical lead series, the nitroimidazoles, benzoxaboroles and aminopyrazoles, as innovative treatments for visceral leishmaniasis. The leads discovered using phenotypic screening, were optimised following disease- and compound-specific criteria. Several leads of each series were progressed and preclinical drug candidates have been nominated. Here we evaluate the efficacy of the lead compounds of each of these three chemical classes in in vitro and in vivo models of cutaneous leishmaniasis. METHODS: The in vitro activity of fifty-five compounds was evaluated against the intracellular amastigotes of L. major, L. aethiopica, L. amazonensis, L. panamensis, L. mexicana and L. tropica. The drugs demonstrating potent activity (EC < 5 µM) against at least 4 of 6 species were subsequently evaluated in vivo in different L. major - BALB/c mouse models using a 5 or 10-day treatment with either the oral or topical formulations. Efficacy was expressed as lesion size (measured daily using callipers), parasite load (by quantitative PCR - DNA) and bioluminescence signal reduction relative to the untreated controls. RESULTS: The selected drug compounds (3 nitroimidazoles, 1 benzoxaborole and 3 aminopyrazoles) showed consistent and potent activity across a range of Leishmania species that are known to cause CL with EC values ranging from 0.29 to 18.3 µM. In all cases, this potent in vitro antileishmanial activity translated into high levels of efficacy with a linear dose-response against murine CL. When administered at 50 mg/kg/day, DNDI-0690 (nitroimidazole), DNDI-1047 (aminopyrazole) and DNDI-6148 (benzoxaborole) all resulted in a significant lesion size reduction (no visible nodule) and an approximate 2-log-fold reduction of the parasite load as measured by qPCR compared to the untreated control. CONCLUSIONS: The lead compounds DNDI-0690, DNDI-1047 and DNDI-6148 showed excellent activity across a range of Leishmania species in vitro and against L. major in mice. These compounds offer novel potential drugs for the treatment of CL.

Behavior and abundance of Anopheles darlingi in communities living in the Colombian Amazon riverside.

PLoS One; 14(3): e0213335, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30845198


In the past few years, relative frequencies of malaria parasite species in communities living in the Colombian Amazon riverside have changed, being Plasmodium vivax (61.4%) and Plasmodium malariae (43.8%) the most frequent. Given this epidemiological scenario, it is important to determine the species of anophelines involved in these parasites' transmission. This study was carried out in June 2016 in two indigenous communities living close to the tributaries of the Amazon River using protected human bait. The results of this study showed a total abundance of 1,085 mosquitos, of which 99.2% corresponded to Anopheles darlingi. Additionally, only two anopheline species were found, showing low diversity in the study areas. Molecular confirmation of some individuals was then followed by evolutionary analysis by using the COI gene. Nested PCR was used for identifying the three Plasmodium species circulating in the study areas. Of the two species collected in this study, 21.0% of the An. darlingi mosquitoes were infected with P. malariae, 21.9% with P. vivax and 10.3% with Plasmodium falciparum. It exhibited exophilic and exophagic behavior in both study areas, having marked differences regarding its abundance in each community (Tipisca first sampling 49.4%, Tipisca second sampling 39.6% and Doce de Octubre 10.9%). Interestingly, An. mattogrossensis infected by P. vivax was found for the first time in Colombia (in 50% of the four females collected). Analysis of An. darlingi COI gene diversity indicated a single population maintaining a high gene flow between the study areas. The An. darlingi behavior pattern found in both communities represents a risk factor for the region's inhabitants living/working near these sites. This highlights the need for vector control efforts such as the use of personal repellents and insecticides for use on cattle, which must be made available in order to reduce this Anopheline's abundance.

Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis.

PLoS Negl Trop Dis; 13(3): e0007152, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30845223


Diffuse cutaneous leishmaniasis (DCL) is a rare form of leishmaniasis where parasites grow uncontrolled in diffuse lesions across the skin. Meta-transcriptomic analysis of biopsies from DCL patients infected with Leishmania amazonensis demonstrated an infiltration of atypical B cells producing a surprising preponderance of the IgG4 isotype. DCL lesions contained minimal CD8+ T cell transcripts and no evidence of persistent TH2 responses. Whereas localized disease exhibited activated (so-called M1) macrophage presence, transcripts in DCL suggested a regulatory macrophage (R-Mϕ) phenotype with higher levels of ABCB5, DCSTAMP, SPP1, SLAMF9, PPARG, MMPs, and TM4SF19. The high levels of parasite transcripts in DCL and the remarkable uniformity among patients afforded a unique opportunity to study parasite gene expression in this disease. Patterns of parasite gene expression in DCL more closely resembled in vitro parasite growth in resting macrophages, in the absence of T cells. In contrast, parasite gene expression in LCL revealed 336 parasite genes that were differently upregulated, relative to DCL and in vitro macrophage growth, and these transcripts may represent transcripts that are produced by the parasite in response to host immune pressure.

Investigation of a possible malaria epidemic in an illegal gold mine in French Guiana: an original approach in the remote Amazonian forest.

Malar J; 18(1): 91, 2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30902054


BACKGROUND: In April 2017, Suriname's Ministry of Health alerted French Guiana's Regional Health Agency (RHA) about an increase of imported malaria cases among people coming from an illegal gold mining site called Sophie, in French Guiana, a French overseas territory located in the Amazonian forest. METHODS: Due to safety issues and the remoteness of Sophie, the RHA requested the collaboration of the French Armed Forces for the epidemiological investigation. A medical unit, and six soldiers to ensure the security of the mission, were transported by helicopter. RESULTS: During the investigation, two malaria episodes were diagnosed among 46 persons. Twenty-six of them were from Sophie, where PCR-Plasmodium prevalence was estimated at 60% (15/26). This result was concordant with previous studies revealing high malaria endemicity in the gold miner population. The increase of imported cases in Suriname may have resulted from decreased access to under-the-counter anti-malarials and increased migration of gold miners to Suriname following a decline of the profitability of gold mining in a context of increased repression against illegal mining by the French army. CONCLUSION: This investigation of a suspicious malaria epidemic confirms the importance of malaria among illegal gold miners. Their mobility along the Guiana Shield and their health-seeking behaviour are likely to spread malaria in populations for which significant efforts are undertaken to fight against this disease. Fighting malaria in this population remains more relevant than ever. A pilot study (Malakit project) is currently in progress to evaluate the efficacy of kits for self-diagnosis and self-treatment.

Regional variation in life history traits and plastic responses to temperature of the major malaria vector Nyssorhynchus darlingi in Brazil.

Sci Rep; 9(1): 5356, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30926833


The primary Brazilian malaria vector, Nyssorhynchus darlingi (formerly Anopheles darlingi), ranges from 0°S-23°S across three biomes (Amazonia, Cerrado, Mata Atlântica). Rising temperatures will increase mosquito developmental rates, and models predict future malaria transmission by Ny. darlingi in Brazil will shift southward. We reared F Ny. darlingi (progeny of field-collected females from 4 state populations across Brazil) at three temperatures (20, 24, 28 °C) and measured key life-history traits. Our results reveal geographic variation due to both genetic differences among localities and plastic responses to temperature differences. Temperature significantly altered all traits: faster larval development, shorter adult life and overall lifespan, and smaller body sizes were seen at 28 °C versus 20 °C. Low-latitude Amazonia mosquitoes had the fastest larval development at all temperatures, but at 28 °C, average development rate of high-latitude Mata Atlântica mosquitoes was accelerated and equivalent to low-latitude Amazonia. Body size of adult mosquitoes from the Mata Atlântica remained larger at all temperatures. We detected genetic variation in the plastic responses among mosquitoes from different localities, with implications for malaria transmission under climate change. Faster development combined with larger body size, without a tradeoff in adult longevity, suggests vectorial capacities of some Mata Atlântica populations may significantly increase under warming climates.

A comprehensive analysis of malaria transmission in Brazil.

Pathog Glob Health; 113(1): 1-13, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30829565


Malaria remains a serious public health problem in Brazil despite a significant drop in the number of cases in the past decade. We conduct a comprehensive analysis of malaria transmission in Brazil to highlight the epidemiologically most relevant components that could help tackle the disease. We consider factors impacting on the malaria burden and transmission dynamics including the geographical occurrence of both autochthonous and imported infections, the distribution and abundance of malaria vectors and records of natural mosquito infections with Plasmodium. Our analysis identifies three discrete malaria transmission systems related to the Amazon rainforest, Atlantic rainforest and Brazilian coast, respectively. The Amazonian system accounts for 99% of all malaria cases in the country. It is largely due to autochthonous P. vivax and P. falciparum transmission by mosquitoes of the Nyssorhynchus subgenus, primarily Anopheles darlingi. Whilst P. vivax transmission is widespread, P. falciparum transmission is restricted to hotspot areas mostly in the States of Amazonas and Acre. This system is the major source of P. vivax exportation to the extra-Amazonian regions that are also affected by importation of P. falciparum from Africa. The Atlantic system comprises autochthonous P. vivax transmission typically by the bromeliad-associated mosquitoes An. cruzii and An. bellator of the Kerteszia subgenus. An. cruzii also transmits simian malaria parasites to humans. The third, widespread but geographically fragmented, system is found along the Brazilian coast and comprises P. vivax transmission mainly by An. aquasalis. We conclude that these geographically and biologically distinct malaria transmission systems require specific strategies for effective disease control.

Evaluation of the in vitro and in vivo antileishmanial activity of a chloroquinolin derivative against Leishmania species capable of causing tegumentary and visceral leishmaniasis.

Exp Parasitol; 199: 30-37, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30817917


The treatment against leishmaniasis presents problems, since the currently used drugs are toxic and/or have high costs. In addition, parasite resistance has increased. As a consequence, in this study, a chloroquinolin derivative, namely 7-chloro-N,N-dimethylquinolin-4-amine or GF1059, was in vitro and in vivo tested against Leishmania parasites. Experiments were performed to evaluate in vitro antileishmanial activity and cytotoxicity, as well as the treatment of infected macrophages and the inhibition of infection using pre-treated parasites. This study also investigated the GF1059 mechanism of action in L. amazonensis. Results showed that the compound was highly effective against L. infantum and L. amazonensis, presenting a selectivity index of 154.6 and 86.4, respectively, against promastigotes and of 137.6 and 74.3, respectively, against amastigotes. GF1059 was also effective in the treatment of infected macrophages and inhibited the infection of these cells when parasites were pre-incubated with it. The molecule also induced changes in the parasites' mitochondrial membrane potential and cell integrity, and caused an increase in the reactive oxygen species production in L. amazonensis. Experiments performed in BALB/c mice, which had been previously infected with L. amazonensis promastigotes, and thus treated with GF1059, showed that these animals presented significant reductions in the parasite load when the infected tissue, spleen, liver, and draining lymph node were evaluated. GF1059-treated mice presented both lower parasitism and low levels of enzymatic markers, as compared to those receiving amphotericin B, which was used as control. In conclusion, data suggested that GF1059 can be considered a possible therapeutic target to be tested against leishmaniasis.

Pam3CSK4 adjuvant given intranasally boosts anti-Leishmania immunogenicity but not protective immune responses conferred by LaAg vaccine against visceral leishmaniasis.

Microbes Infect; 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30817996


The use of adjuvants in vaccine formulations is a well-established practice to improve immunogenicity and protective immunity against diseases. Previously, we have demonstrated the feasibility of intranasal vaccination with the antigen of killed Leishmania amazonensis promastigotes (LaAg) against experimental leishmaniasis. In this work, we sought to optimize the immunogenic effect and protective immunity against murine visceral leishmaniasis conferred by intranasal delivery of LaAg in combination with a synthetic TLR1/TLR2 agonist (Pam3CSK4). Intranasal vaccination with LaAg/PAM did not show toxicity or adverse effects, induced the increase of delayed-type hypersensitivity response and the production of inflammatory cytokines after parasite antigen recall. However, mice vaccinated with LaAg/PAM and challenged with Leishmania infantum presented significant reduction of parasite burden in both liver and spleen, similar to those vaccinated with LaAg. Although LaAg/PAM intranasal vaccination had induced higher frequencies of specific CD4 and CD8 T cells and increased levels of IgG2a antibody isotype in serum, both LaAg and LaAg/PAM groups presented similar levels of IL-4 and IFN-y and decreased production of IL-10 when compared to controls. Our results provide the first evidence of the feasibility of intranasal immunization with antigens of killed Leishmania in association with a TLR agonist, which may be explored for developing an effective and alternative strategy for vaccination against visceral leishmaniasis.

Use and retention of long-lasting insecticidal nets (LLINs) in a malaria risk area in the Brazilian Amazon: a 5-year follow-up intervention.

Malar J; 18(1): 100, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30909924


BACKGROUND: Long-lasting insecticidal nets (LLINs) are one of the main vector control strategies recommended by the World Health Organization for the control and elimination of malaria. This study aimed to evaluate the use and retention of LLINs during the 5 years of implementing an integrated control strategy in a malaria-endemic area in the Brazilian Amazon. METHODS: This intervention study was conducted in localities of the municipality of Barcelos, Amazonas, from 2008 to 2014. Four rural localities situated along the Padauiri River were the object of this study. Two localities (Bacabal-rio Aracá and the São Sebastião district) were used as controls. LLINs were distributed to all residents of the Padauiri River; assessments were made regarding their use and retention via a semistructured questionnaire, a household register, and direct observation during 5 years. RESULTS: Overall, 208 individuals participated in the study. In the baseline pilot study (2008), 9.9% of the subjects in the intervention group had slept with mosquito nets the previous night compared with 37.8% of the subjects in the control group. In 2010, this percentage was 43.2% in the intervention group and 50.9% in the control group. Therefore, 1 year after the implementation of the strategy, although there was an increase in the use of mosquito nets in both groups, this increase was significantly higher in the intervention group. This increase in LLINs use did not persist after 5 years of intervention. The households' evaluation in 2014 showed that 80% of the houses in the intervention group owned at least one LLIN compared with 66% in the control group (p = 0.11); 76% of households in the intervention group owned sufficient LLINs for all family members compared with 50% in the control group (p = 0.007). CONCLUSIONS: High ownership and retention of the LLINs was observed in the intervention group. At 1 year after the distribution of these LLINs, there was a significant increase in their use that was not maintained over the long term. Control strategies must be permanent; however, exploring new strategies is necessary to ensure that the knowledge acquired further modifies the attitudes and behaviours.

Modeling asymptomatic infections and work-related human circulation as drivers of unstable malaria transmission in low-prevalence areas: a study in the Northern Peruvian Amazon.

Acta Trop; 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30703339


BACKGROUND: Despite relatively successful control campaigns, malaria remains a relevant public health problem in the Peruvian Amazon. Several studies suggest that malaria persistence in the area can be connected with a high prevalence of asymptomatic infections, which were subsequently shown to be connected with work-related exposure in areas of hyperendemic transmission. In this study, we tested the hypothesis that the infection reservoir represented by asymptomatic carriers in the northern Peruvian Amazon, combined with circular human movement to and from hyperendemic working areas, can capture the observed hypoendemic malaria transmission. METHODS: We designed a set of agent-based models that represent local-scale malaria transmission in a typical riverine community in the northern Peruvian Amazon. The models include asymptomatic individuals as well as a full representation of human movements within the community and between the community and external hyperendemic working places. Several theoretical scenarios are explored to verify if and how malaria clinical immunity prevalence and human work-related movements influence the malaria morbidity registered in the community. RESULTS: Agent-based simulations suggest that malaria incidence observed through passive case detection can be reproduced as exclusively generated by the asymptomatic infection reservoir. Scenarios analysis also show that, even if asymptomatic infections are completely eliminated, human movements to and from hyperendemic working areas generate a flow of imported cases that is enough to permit the persistence of transmission in the community. Simulation results were verified over a wide range of clinical immunity prevalence values and over a wide range of percentages of people working in remote hyperendemic areas. This context of unstable malaria transmission is observed to be vulnerable to severe outbreaks. CONCLUSIONS: Asymptomatic malaria infection and occupational circular human movement to hyperendemic transmission areas are designated by agent-based models as possible exclusive causes of residual hypoendemic malaria transmission observed in the Peruvian Amazon. Control strategies are proposed to decrease asymptomatic infection prevalence and to block transmission from asymptomatic individuals to the malaria susceptible population.

Diethyldithiocarbamate loaded in beeswax-copaiba oil nanoparticles obtained by solventless double emulsion technique promote promastigote death in vitro.

Colloids Surf B Biointerfaces; 176: 507-512, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30711703


Leishmaniasis is considered a neglected tropical disease that represents a Public Health problem due to its high incidence. In the search of new alternatives for Leishmaniasis treatment diethyldithiocarbamate (DETC) has shown an excellent leishmanicidal activity and the incorporation into drug carrier systems, such as solid lipid nanoparticles (SLNs), is very promising. In the present work DETC loaded in beeswax nanoparticles containing copaiba oil were obtained by the double emulsion/melt technique. The nanoparticles were characterized and leishmanicidal activity against L. amazonensis promastigotes forms and cytotoxicity in murine macrophages were evaluated. SLNs presented size below 200 nm, spherical morphology, negative charge surface, high encapsulation efficiency, above 80%, and excellent stability. Moreover, Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses were performed to evaluate the chemical structure and possible interactions between DETC and SLNs. SLNs provided a protection for DETC, decreasing its cytotoxic effects in macrophages, which led to an improvement in the selectivity against the parasites, which almost doubled from free DETC (11.4) to DETC incorporated in SLNs (18.2). These results demonstrated that SLNs had a direct effect on L. amazonensis promastigotes without affect the viability of macrophage cell, can be a promising alternative therapy for the cutaneous treatment of L. amazonensis.

Very severe tungiasis in Amerindians in the Amazon lowland of Colombia: A case series.

PLoS Negl Trop Dis; 13(2): e0007068, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30730885


BACKGROUND: Tungiasis is a parasitic skin disease caused by penetrating female sand fleas. By nature, tungiasis is a self-limiting infection. However, in endemic settings re-infection is the rule and parasite load gradually accumulates over time. Intensity of infection and degree of morbidity are closely related. METHODOLOGY/PRINCIPAL FINDINGS: This case series describes the medical history, the clinical pathology, the socio-economic and the environmental characteristics of very severe tungiasis in five patients living in traditional Amerindian communities in the Amazon lowland of Colombia. Patients had between 400 and 1,300 penetrated sand fleas. The feet were predominantly affected, but clusters of embedded sand fleas also occurred at the ankles, the knees, the elbows, the hands, the fingers and around the anus. The patients were partially or totally immobile. Patients 1 and 3 were cachectic, patient 2 presented severe malnutrition. Patient 3 needed a blood transfusion due to severe anemia. All patients showed a characteristic pattern of pre-existing medical conditions and culture-dependent behavior facilitating continuous re-infection. In all cases intradomiciliary transmission was very likely. CONCLUSION/SIGNIFICANCE: Although completely ignored in the literature, very severe tungiasis occurs in settings where patients do not have access to health care and are stricken in a web of pre-existing illness, poverty and neglect. If not treated, very severe tungiasis may end in a fatal disease course.

Monitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Malaria in the Main Transmission Hotspot of Brazil.

Artigo em Inglês | MEDLINE | ID: mdl-30782991


Emerging resistance to chloroquine (CQ) may undermine malaria elimination efforts in South America. CQ-resistant has been found in the major port city of Manaus, but not in the main malaria hotspots across the Amazon Basin of Brazil, where CQ is routinely co-administered with primaquine (PQ) for radical cure of vivax malaria. Here we randomly assigned 204 uncomplicated vivax malaria patients from Juruá Valley, northwestern Brazil, to receive either sequential (Arm 1) or concomitant (Arm 2) CQ-PQ treatment. Because PQ may synergize the blood schizontocidal effect of CQ and mask low-level CQ resistance, we monitored CQ-only efficacy in Arm 1 subjects, who had PQ administered only at the end of the 28-day follow up. We found adequate clinical and parasitological responses in all subjects assigned to Arm 2. However, 2.2% of Arm 1 patients had microscopy-detected parasite recrudescences at day 28. When PCR-detected parasitemias at day 28 were considered, response rates decreased to 92.1% and 98.8% in Arms 1 and 2, respectively. Therapeutic CQ levels were documented in 6 of 8 recurrences, consistent with true CQ resistance In contrast, assays provided no evidence of CQ resistance in 49 local isolates analyzed. CQ-PQ co-administration was not found to potentiate the antirelapse efficacy of PQ over 180 days of surveillance; however, we suggest that larger studies are needed to examine whether and how CQ-PQ interactions, e.g. CQ-mediated inhibition of PQ metabolism, modulate radical cure efficacy in different -infected populations.
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