Description of malaria vectors (Diptera: Culicidae) in two agricultural settlements in the Western Brazilian Amazon

The majority of malaria cases in South America occur in rural areas of the Amazon region. Although these areas have a significant impact on malaria cases, few entomological studies have been carried out there. This study aimed to describe entomological parameters in settlements in Rondonia State, Brazil. Collections of anopheles were carried out using the Protected Human Attraction Technique (PHAT). The risk and the potential for malaria transmission were assessed using the human biting rate (HBR), the sporozoite rate (SR) and the entomological inoculation rate (EIR). The results confirmed that Nyssorhynchus darlingi is the predominant species in the two studied locations. Although settlement in the two study sites has occurred at different times, the species richness found was low, showing that environmental changes caused by anthropological actions have probably favor the adaptation of Ny. darlingi species. From the total of 615 anopheline mosquitoes assessed, seven (1.1%) were positive for Plasmodium sp. infections. The EIR revealed that Ny. darlingi contributes to malaria transmission in both locations, as it was responsible for 0.05 infectious bites in humans at night in the old settlement and 0.02 in the recent occupation. In the two study sites, the biting occurred more frequently at dusk. Nyssorhynchus darlingi was prevalent in areas of recent colonization but, even when present in a low density, this species could maintain the transmission of malaria in the older settlement. The entomological information obtained in this study is important and may aid the selection of vector control actions in these locations

Brazil's first free-mating laboratory colony of Nyssorhynchus darlingi.

INTRODUCTION: The lack of highly-productive Nyssorhynchus darlingi laboratory colonies limits some studies. We report the first well-established laboratory colony of Ny. darlingi in Brazil. METHODS: Mosquitoes were collected from Porto Velho and were reared at the Laboratory of Fiocruz/RO. After induced mating by light stimulation in the F1 to F6, the subsequent generations were free mating. Larvae were reared in distilled water and fed daily until pupation. RESULTS: In 11 generations, the colony produced a high number of pupae after the F5 generation. CONCLUSIONS: These results demonstrate the potential for permanently establishing Ny. darlingi colonies for research purposes in Brazil

Estudo de eficácia e segurança de um novo co-blister de cloroquina e primaquina para tratamento de malária por plasmodium vivax não complicada

Made available in DSpace on 2018-05-21T13:34:22Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) dhelio_pereira_ini_dout_2016.pdf: 16506073 bytes, checksum: 198f38539e44a43b55f5218361a796ec (MD5)Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Introdução: O tratamento inadequado e os esquemas terapêuticos de difícil adesão tem efeitos deletérios à efetividade das drogas em uso, favorecendo a transmissão da malária e o surgimento de cepas resistentes. Melhorias na formulação farmacológica e na apresentação do produto, como alteração do sabor pelo revestimento do comprimido e do empacotamento conjunto, em doses adequadas para peso e idade, podem resultar em incremento da adesão, e logo, ampliar a efetividade terapêutica do tratamento da malária causada pelo Plasmodium vivax. Este estudo é proposto para avaliação e registro de um co-blister de antimaláricos. Objetivo: O objetivo geral deste estudo foi avaliar a eficácia terapêutica e segurança do uma nova formulação de cloroquina 150 mg com revestimento administrada em associação com primaquina 15 mg para o tratamento de malária não complicada causada por Plasmodium vivax. Métodos: Este é um estudo de fase II, aberto, realizado em um único centro, localizado em Porto Velho, Brasil, contando com 88 participantes, desenhado para provar taxa de cura superior a 90% em pacientes com malária vivax não complicada. A medida de efeito primária foi definida como a proporção de pacientes com ausência de parasita no dia 28. Para determinar a tolerabilidade deste produto foi considerada como medida de efeito secundária a proporção de pacientes com eventos adversos (EA) clínicos ou laboratoriais. Os dados foram coletados nos dias 0, 1, 2, 3, 7, 14, 21 e 28. A farmacocinética do medicamento teste foi avaliada por níveis séricos de cloroquina em papel de filtro Resultados: A avaliação de cura na população por protocolo (PP) indica resposta clínica e parasitológica adequada em 98,8% (IC 95% 93,4 - 100,0) dos 82 pacientes avaliados. Um total de 74 (84%) pacientes apresentaram 296 EA, classificados, com relações de causalidade com a droga, como possíveis ou prováveis. Cerca de 97,7% dos EA foram classificados como leves, grau I e II. Os EA, com relação provável, com maiores incidências foram prurido (51,1%), erupções cutâneas (8,0%), tosse (6,8%), cefaleia (3,4%), diarreia (2,3%), zumbido (2,3%), desordem do sono (2,3%), dor abdominal (1,1%) e náusea (1,1%). Todos participantes alcançaram a concentração terapêutica efetiva de cloroquina sanguínea. Conclusão: O tratamento é seguro e eficaz na terapêutica da malária vivax não complicada para a população estudada e atende aos objetivos principais propostos no protocolo e às recomendações da OMS para uso de esquema antimalárico no país.Introduction: The inappropriate treatment and therapeutic schemes of difficult adherence favor the maintenance of malaria transmission, collaborating with high rates of disease prevalence. In an environment of incorrect use of the recommended treatments, drug resistance also is more likely to emerge. Given this panorama and considering the interest of public health policies, we designed this study to collect robust data to support the health record of an incremental innovation: a coated chloroquine (Cq) and primaquine (Pq) coblister that can help in the therapeutic effectiveness for malaria treatment caused by Plasmodium vivax. Objective: The aim of this study was to evaluate the therapeutic efficacy and safety of a coated new formulation of Cq 150 mg coated administered in combination with Pq 15 mg for the treatment of uncomplicated malaria caused by Plasmodium vivax. Methods: This was a phase II, open label trial, performed at a single center, designed to prove higher cure rate to 90% in patients with uncomplicated vivax malaria. The primary outcome measured was defined as the proportion of patients with adequate clinical and parasitological response (patients with therapeutic success) at day 28. To determine the tolerability of the product was considered as a secondary effect the proportion of patients with clinical or laboratory adverse events. Data were collected on days 0, 1, 2, 3, 7, 14, 21 and 28. The pharmacokinetics of the test drug was assessed by serum levels of chloroquine on filter paper Results: The per protocol (PP) evaluation in the population indicates cure, clinical and parasitological response adequate in 98.8% (95% CI 93.4 to 100.0) of the 82 patients evaluated. A total of 74 (84%) patients had 296 EA, ranked by causal relationships with the drug as possible or probable. About 97.7% of EA were classified as mild, grade I and II. The EA, ranked probable relationship, with higher incidences were: pruritus (51.1%), rash (8.0%), cough (6.8%), headache (3.4%), diarrhea (2.3%), tinnitus (2.3%), sleep disorder (2.3%), abdominal pain (1.1%) and nausea (1.1%). All participants achieved the effective therapeutic concentration of blood chloroquine. Conclusion: The treatment is safe and effective in the treatment of vivax malaria uncomplicated and meets the main objectives proposed in the protocol and the WHO recommendations for the use of antimalarial regimen in the country

Precisão dos testes sorológico e molecular para diagnóstico do HBV e HCV em pacientes com Insuficiência Renal Crônica em hemodiálise, em Porto Velho, Brasil

Patients under hemodialysis treatment for chronic renal failure (CRF) are among the groups with the highest prevalence of hepatitis B and C viruses due to frequent blood transfusions and nosocomial transmission. A group of CRF patients living in Porto Velho were tested with serological markers for hepatitis B and C using the ELISA test and molecular biology techniques (PCR). The validity parameters for the serological results were measured based on the PCR results. Of the 128 patients on hemodialysis during the study, 12 (9.4%) were HBsAg positive, 69 (53.9%) were anti-HBc positive, 93 (72.7%) were anti-HBs positive, and 22 (17.2%) were anti-HCV positive. The PCR tests result in 12 (9.4%) HBV-DNA positive and 16 (12.5%) HCV-RNA positive. The accuracy, sensitivity and specificity of ELISA for HBsAg were 90.6%, 50% and 94.8%, and the same parameters were 92.2%, 87.5% and 92.9% for anti-HCV. Based on the results just the negative predictive value for anti-HCV (98,2%) is a reliable test in CRF patients on hemodialysis. Beside that, serial serological and/or molecular tests are the indicated methodology to diagnosis HBV and HCV infection in these patients.Pacientes em tratamento com hemodiálise para a Insuficiência Renal Crônica (IRC) estão entre os grupos com maior prevalência da infecção pelo vírus da hepatite B e C, devido às transfusões de sangue e transmissão nosocomial. Um grupo de pacientes com IRC residentes em Porto Velho foi testado com marcadores sorológicos para hepatite B e C utilizando o teste ELISA e técnicas de biologia molecular (PCR). Os parâmetros para a validação dos resultados sorológicos foram medidos com base nos resultados da PCR. Dos 128 pacientes em hemodiálise durante o estudo, 12 (9,4%) eram HBsAg positivos, 69 (53,9%) eram anti-HBc positivos, 93 (72,7%) eram anti-HBs positivos, e 22 (17,2%) eram anti- HCV positivos. Os resultados dos testes com PCR foram de 12 (9,4%) HBV-DNA positivos e 16 (12,5%) HCV-RNA positivos. A precisão, sensibilidade e especificidade do ELISA para o HBsAg foram de 90,6%, 50% e 94,8%, e os mesmos parâmetros foram de 92,2%, 87,5% e 92,9% para anti-HCV. Com base nos resultados, apenas o valor preditivo negativo para anti-HCV (98,2%) mostrou-se confiável em pacientes renais crônicos em hemodiálise. Além disto, testes sorológicos e/ou moleculares representam a metodologia indicada para o diagnóstico da infecção pelo HBV e HCV nestes pacientes

Cross-reactive anti-PfCLAG9 antibodies in the sera of asymptomatic parasite carriers of Plasmodium vivax

Submitted by EMERSON LEAL ([email protected]) on 2016-06-22T14:24:43Z No. of bitstreams: 1 Cross-reactive anti-PfCLAG9.pdf: 858856 bytes, checksum: 2ffe44623a0b886c451e6b51473c40a8 (MD5)Approved for entry into archive by EMERSON LEAL ([email protected]) on 2016-07-14T15:32:27Z (GMT) No. of bitstreams: 1 Cross-reactive anti-PfCLAG9.pdf: 858856 bytes, checksum: 2ffe44623a0b886c451e6b51473c40a8 (MD5)Made available in DSpace on 2016-07-14T15:32:27Z (GMT). No. of bitstreams: 1 Cross-reactive anti-PfCLAG9.pdf: 858856 bytes, checksum: 2ffe44623a0b886c451e6b51473c40a8 (MD5) Previous issue date: 2013Made available in DSpace on 2016-07-15T18:40:36Z (GMT). No. of bitstreams: 3 Cross-reactive anti-PfCLAG9.pdf.txt: 39798 bytes, checksum: 0239dd87d08632acfc502eb84feeeb5c (MD5) Cross-reactive anti-PfCLAG9.pdf: 858856 bytes, checksum: 2ffe44623a0b886c451e6b51473c40a8 (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2013Centro de Pesquisa em Medicina Tropical. Porto Velho, RO, Brasil / Universidade Federal de Rondônia. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Fiocruz Rondônia. Instituto de Pesquisas em Patologias Tropicais. Porto Velho, RO, Brasil.Centro de Pesquisa em Medicina Tropical. Porto Velho, RO, Brasil.Centro de Pesquisa em Medicina Tropical. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Fiocruz Rondônia. Instituto de Pesquisas em Patologias Tropicais. Porto Velho, RO, Brasil.Centro de Pesquisa em Medicina Tropical. Porto Velho, RO, Brasil / Universidade Federal de Rondônia. Porto Velho, RO, Brasil.Centro de Pesquisa em Medicina Tropical. Porto Velho, RO, Brasil.Centro de Pesquisa em Medicina Tropical. Porto Velho, RO, Brasil / Fundação Oswaldo Cruz. Fiocruz Rondônia. Instituto de Pesquisas em Patologias Tropicais. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Fiocruz Rondônia. Instituto de Pesquisas em Patologias Tropicais. Porto Velho, RO, Brasil.Centro de Pesquisa em Medicina Tropical. Porto Velho, RO, Brasil / Fundação Oswaldo Cruz. Fiocruz Rondônia. Instituto de Pesquisas em Patologias Tropicais. Porto Velho, RO, Brasil.The PfCLAG9 has been extensively studied because their immunogenicity. Thereby, the gene product is important for therapeutics interventions and a potential vaccine candidate. Antibodies against synthetic peptides corresponding to selected sequences of the Plasmodium falciparum antigen PfCLAG9 were found in sera of falciparum malaria patients from Rondônia, in the Brazilian Amazon. Much higher antibody titres were found in semi-immune and immune asymptomatic parasite carriers than in subjects suffering clinical infections, corroborating original findings in Papua Guinea. However, sera of Plasmodium vivax patients from the same Amazon area, in particular from asymptomatic vivax parasite carriers, reacted strongly with the same peptides. Bioinformatic analyses revealed regions of similarity between P. falciparum Pfclag9 and the P. vivax ortholog Pvclag7. Indirect fluorescent microscopy analysis showed that antibodies against PfCLAG9 peptides elicited in BALB/c mice react with human red blood cells (RBCs) infected with both P. falciparum and P. vivax parasites. The patterns of reactivity on the surface of the parasitised RBCs are very similar. The present observations support previous findings that PfClag9 may be a target of protective immune responses and raises the possibility that the cross reactive antibodies to PvCLAG7 in mixed infections play a role in regulate the fate of Plasmodium mixed infections

Integration of serial self-testing for COVID-19 as part of contact tracing in the Brazilian public health system: A pragmatic trial protocol.

The coronavirus disease (COVID-19) pandemic has led to an unprecedented public health crisis. Insufficient testing continues to limit the effectiveness of the global response to the COVID-19 pandemic. Molecular testing methods such as reverse transcriptase polymerase chain reaction (RT-PCR) continue to be highly centralized and are a sub-optimal option for population surveillance. Rapid antigen tests (Ag-RDTs) offer multiple benefits including low costs, high flexibility to conduct tests in a wide variety of settings, and faster return of results. Self-test Ag-RDTs (STs) have gained approval in several markets and offer the possibility to expand testing, reaching at-risk populations. While STs have the potential to assist the COVID-19 response, test result integrity, reporting, and appropriate linkage to care continue to hinder the widespread implementation of self-testing programs. This protocol presents a mixed-methods pragmatic trial (ISRCTN91602092) to better understand the feasibility of self-testing as part of a contact tracing strategy within the Brazilian public health system. Approximately 604 close contacts of 150 index cases testing positive for COVID-19 will be enrolled. Index cases will be randomized for their close contacts to participate in either serial (daily) self-testing over a 10-day follow-up period or a more traditional approach to contact tracing with a professional Ag-RDT at one time point post-exposure. Usability workshops and focus group discussions will also be conducted. This study protocol presents a comprehensive plan to assess the effectiveness, operational feasibility, and stakeholder preferences of a serial self-testing strategy for contact tracing within the Brazilian public health system. Our results will contribute to better understanding of the feasibility of a self-testing strategy within the public sector. Potential risks and limitations are discussed. Our findings will have important implications as governments continue working to mitigate the impact of COVID-19, particularly in the context of where to direct limited resources for testing and healthcare infrastructure. Registration: This trial is registered at ISCTRN (ISRCTN91602092)

In vitro and ex vivo antiplasmodial activity of 1-(3-benzyloxy-4-methoxy-phenyl)-3-(3,4,5-trimethoxy-phenyl)-propan-1-one) against circulating strains of Plasmodium spp. in the state of Rondônia, Brazil

Malaria is a disease caused by Plasmodium spp. protozoa. The ability of Plasmodium to develop resistance to current antimalarial drugs makes the study of chemotherapeutic alternatives extremely important. This study aimed to evaluate the antimalarial activity of compound 3286938 (1-(3-benzyloxy-4-methoxy-phenyl)-3-(3,4,5-trimethoxy-phenyl)-propan-1-one), which presents in its structure a 3,4,5-trimethoxyphenyl group, in vitro, using the W2 strain of P. falciparum and against circulating strains of P. vivax and P. falciparum from the state of Rondônia. The compound 3286938 obtained an IC50 of 24.4 µM against the W2 strain of P. falciparum, and against the circulating strains, it presented a median (MD)=38.7 µM for P. vivax and MD=6.7 µM for P. falciparum. As for toxicity, 3286938 showed CC50 > 500 µM for VERO and HepG2 strains with a selectivity index greater than 12.9, a ratio calculated for P. falciparum and P. vivax regarding Vero and HepG2 cells. The compound was not considered hemolytic in in vitro assays, thus indicating the specificity of its antiplasmodial action. Based on the results presented, and considering the unprecedented character of the compound, it can be concluded that 3286938 was shown to be promising for complementary in vitro and in vivo studies aiming to produce effective antiplasmodial action

Immunological characterization of a VIR protein family member (VIR-14) in Plasmodium vivax-infected subjects from different epidemiological regions in Africa and South America.

Plasmodium vivax is a major challenge for malaria control due to its wide geographic distribution, high frequency of submicroscopic infections, and ability to induce relapses due to the latent forms present in the liver (hypnozoites). Deepening our knowledge of parasite biology and its molecular components is key to develop new tools for malaria control and elimination. This study aims to investigate and characterize a P. vivax protein (PvVir14) for its role in parasite biology and its interactions with the immune system. We collected sera or plasma from P.vivax-infected subjects in Brazil (n = 121) and Cambodia (n = 55), and from P. falciparum-infected subjects in Mali (n = 28), to assess antibody recognition of PvVir14. Circulating antibodies against PvVir14 appeared in 61% and 34.5% of subjects from Brazil and Cambodia, respectively, versus none (0%) of the P. falciparum-infected subjects from Mali who have no exposure to P. vivax. IgG1 and IgG3 most frequently contributed to anti-PvVir14 responses. PvVir14 antibody levels correlated with those against other well-characterized sporozoite/liver (PvCSP) and blood stage (PvDBP-RII) antigens, which were recognized by 7.6% and 42% of Brazilians, respectively. Concerning the cellular immune profiling of Brazilian subjects, PvVir14 seroreactive individuals displayed significantly higher levels of circulating atypical (CD21- CD27-) B cells, raising the possibility that atypical B cells may be contribute to the PvVir14 antibody response. When analyzed at a single-cell level, the B cell receptor gene hIGHV3-23 was only seen in subjects with active P.vivax infection where it comprised 20% of V gene usage. Among T cells, CD4+ and CD8+ levels differed (lower and higher, respectively) between subjects with versus without antibodies to PvVir14, while NKT cell levels were higher in those without antibodies. Specific B cell subsets, anti-PvVir14 circulating antibodies, and NKT cell levels declined after treatment of P. vivax. This study provides the immunological characterization of PvVir14, a unique P. vivax protein, and possible association with acute host's immune responses, providing new information of specific host-parasite interaction. Trial registration: TrialClinicalTrials.gov Identifier: NCT00663546 & ClinicalTrials.gov NCT02334462