Effect of weekly versus daily primaquine on Plasmodium vivax malaria recurrences: A real-life cohort study

ABSTRACT Background: Although primaquine (PQ) is indicated for G6PD-deficient patients, data on weekly PQ use in Brazil are limited. Methods: We aimed to investigate malaria recurrences among participants receiving daily and weekly PQ treatments in a real-life setting of two municipalities in the Amazon between 2019 and 2020. Results: Patients receiving weekly PQ treatment had a lower risk of recurrence than those receiving daily PQ treatment (risk ratio: 0.62, 95% confidence interval: 0.41-0.94), using a model adjusted for study site. Conclusions: Weekly PQ use did not increase the risk of malaria recurrence. Further studies with larger populations are warranted.

Pathological findings and morphologic correlation of the lungs of autopsied patients with SARS-CoV-2 infection in the Brazilian Amazon using transmission electron microscopy

Abstract INTRODUCTION: Electron microscopy (EM) is a rapid and effective tool that can be used to create images of a whole spectrum of virus-host interactions and, as such, has long been used in the discovery and description of viral mechanisms. METHODS: Electron microscopy was used to evaluate the pulmonary pathologies of postmortem lung sections from three patients who died from infection with SARS-associated coronavirus 2 (SARS-CoV-2), a new member of the Coronaviridae family. RESULTS: Diffuse alveolar damage (DAD) was predominant in all three patients. The early exudative stage was characterized principally by edema and extravasation of red blood cells into the alveolar space with injury to the alveolar epithelial cells; this was followed by detachment, apoptosis, and necrosis of type I and II pneumocytes. The capillaries exhibited congestion, exposure of the basement membrane from denuded endothelial cells, platelet adhesion, fibrin thrombi, and rupture of the capillary walls. The proliferative stage was characterized by pronounced proliferation of type II alveolar pneumocytes and multinucleated giant cells. The cytopathic effect of SARS-CoV-2 was observed both in degenerated type II pneumocytes and freely circulating in the alveoli, with components from virions, macrophages, lymphocytes, and cellular debris. CONCLUSIONS: Viral particles consistent with the characteristics of SARS-CoV-2 were observed mainly in degenerated pneumocytes, in the endothelium, or freely circulating in the alveoli. In the final stage of illness, the alveolar spaces were replaced by fibrosis.

Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain is conserved in field isolates from Brazilian Amazon

In the present study, we investigated the genetic diversity of Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain in two municipalities of the main malaria hotspot in Brazil, i.e., the Juruá Valley, and observed complete sequence identity among all P. vivax field isolates and the Sal-1 reference strain. Analysis of PvMCA1 catalytic domain in different P. vivax genomic sequences publicly available also revealed a high degree of conservation worldwide, with very few amino acid substitutions that were not related to putative histidine and cysteine catalytic residues, whose involvement with the active site of protease was herein predicted by molecular modeling. The genetic conservation presented by PvMCA1 may contribute to its eligibility as a druggable target candidate in vivax malaria.

Bee sting envenomation severe cases in Manaus, Brazilian Amazon: clinical characteristics and immune markers of case reports

Abstract Bee venom is a natural toxin composed of several peptides. Massive envenoming causes severe local and systemic reactions. We report two cases of severe bee envenomation, of which one was fatal. We also describe clinical characteristics and immune markers. Both victims suffered from respiratory distress, renal failure, rhabdomyolysis, and shock. They required invasive mechanical ventilation, vasoactive drugs, and renal replacement therapy. Moreover, serum levels of chemokines, cytokines, and cell-free circulating nucleic acids demonstrated an intense inflammatory process. Massive envenoming produced systemic injury in the victims, with an uncontrolled inflammatory response, and a more significant chemotactic response in the fatal case.

Confirmed Invasive Pulmonary Aspergillosis and COVID-19: the value of postmortem findings to support antemortem management

Abstract We present postmortem evidence of invasive pulmonary aspergillosis (IPA) in a patient with severe COVID-19. Autopsies of COVID-19 confirmed cases were performed. The patient died despite antimicrobials, mechanical ventilation, and vasopressor support. Histopathology and peripheral blood galactomannan antigen testing confirmed IPA. Aspergillus penicillioides infection was confirmed by nucleotide sequencing and BLAST analysis. Further reports are needed to assess the occurrence and frequency of IPA in SARS-CoV-2 infections, and how they interact clinically.

Do climate changes alter the distribution and transmission of malaria? Evidence assessment and recommendations for future studies

Abstract Malaria, a mosquito-borne infectious disease, is considered a significant global health burden. Climate changes or different weather conditions may impact infectious diseases, specifically those transmitted by insect vectors and contaminated water. Based on the current predictions for climate change associated with the increase in carbon dioxide concentrations in the atmosphere and the increase in atmospheric temperature, the Intergovernmental Panel on Climate Change predicts that in 2050, malaria may threaten some previously unexposed areas worldwide and cause a 50% higher probability of malaria cases. Climate-based distribution models of malaria depict an increase in the geographic distribution of the disease as global environmental temperatures and conditions worsen. Researchers have studied the influence of changes in climate on the prevalence of malaria using different mathematical models that consider different variables and predict the conditions for malaria distribution. In this context, we conducted a mini-review to elucidate the important aspects described in the literature on the influence of climate change in the distribution and transmission of malaria. It is important to develop possible risk management strategies and enhance the surveillance system enhanced even in currently malaria-free areas predicted to experience malaria in the future.

Ascaris lumbricoides coinfection reduces tissue damage by decreasing IL-6 levels without altering clinical evolution of pulmonary tuberculosis or Th1/Th2/Th17 cytokine profile

Abstract INTRODUCTION: Immunological control of Mycobacterium tuberculosis infection is dependent on the cellular immune response, mediated predominantly by Th1 type CD4+ T cells. Polarization of the immune response to Th2 can inhibit the host immune protection against pathogens. Patients with tuberculosis coinfected with helminths demonstrate more severe pulmonary symptoms, a deficiency in the immune response against tuberculosis, and an impaired response to anti-tuberculosis therapy. METHODS: We evaluated the cellular immune response and the impact of the presence of Ascaris lumbricoides on the immune and clinical response in pulmonary tuberculosis patients. Ninety-one individuals were included in the study: 38 tuberculosis patients, 11 tuberculosis patients coinfected with Ascaris lumbricoides and other helminths, 10 Ascaris lumbricoides patients, and 34 non-infected control individuals. Clinical evolution of pulmonary tuberculosis was studied on 0, 30, 60, and 90 days post-diagnosis of Mycobacterium tuberculosis and Ascaris lumbricoides. Furthermore, immune cells and plasma cytokine profiles were examined in mono/coinfection by Mycobacterium tuberculosis and Ascaris lumbricoides using flow cytometry. RESULTS: There were no statistical differences in any of the evaluated parameters and the results indicated that Ascaris lumbricoides infection does not lead to significant clinical repercussions in the presentation and evolution of pulmonary tuberculosis. CONCLUSIONS: The association with Ascaris lumbricoides did not influence the Th1, Th2, and Th17 type responses, or the proportions of T lymphocyte subpopulations. However, higher serum levels of IL-6 in tuberculosis patients may explain the pulmonary parenchymal damage.

Overview of artemisinin effectiveness during outset years of its implementation in the western Brazilian Amazon

BACKGROUND The elimination of malaria depends on the blocking of transmission and of an effective treatment. In Brazil, artemisinin therapy was introduced in 1991, and here we present a performance overview during implementation outset years. METHODS It is a retrospective cohort (1991 to 2002) of patients treated in a tertiary centre of Manaus, with positive microscopic diagnosis of Plasmodium falciparum malaria, under treatment with using injectable or rectal artemisinin derivatives, and followed over 35-days to evaluate parasite clearance, death and recurrence. FINDINGS This cohort outcome resulted 97.6% (1554/1593) of patients who completed the 35-day follow-up, 0.6% (10/1593) of death and 1.8% (29/1593) of follow-up loss. All patients that died and those that presented parasitaemia recurrence had pure P. falciparum infections and received monotherapy. Considering patients who completed 35-day treatment, 98.2% (1527/1554) presented asexual parasitaemia clearance until D4 and 1.8% (27/1554) between D5-D10. It is important to highlight that had no correlation between the five treatment schemes and the sexual parasite clearance. Finally, it is noteworthy that we were able to observe also gametocytes carriage during all follow-up (D0-D35). MAIN CONCLUSIONS Artemisinin derivatives remained effective in the treatment of falciparum malaria during first 12-years of use in north area of Brazil.

Performance of an immuno-rapid malaria Pf/Pv rapid diagnostic test for malaria diagnosis in the Western Brazilian Amazon

Abstract INTRODUCTION: Rapid diagnostic tests (RDTs) for detecting Plasmodium antigens have become increasingly common worldwide. We aimed to evaluate the accuracy of the Immuno-Rapid Malaria Pf/Pv RDT in detecting Plasmodium vivax infection compared to standard thick blood smear (TBS) under microscopy. METHODS: Hundred and eighty-one febrile patients from the hospital's regular admissions were assessed using TBS and RDT in a blinded experiment. RESULTS: RDT showed a sensitivity of 98.9%, specificity of 100%, and accuracy of 99.5% for P. vivax infection when compared to TBS. CONCLUSIONS: The RDT is highly accurate, making it a valuable diagnostic tool for P. vivax infection.

Current vector control challenges in the fight against malaria in Brazil

Abstract In Brazil, malaria is an important public health problem first reported in 1560. Historically, fluctuations in malaria cases in Brazil are attributed to waves of economic development; construction of railroads, highways, and hydroelectric dams; and population displacement and land occupation policies. Vector control measures have been widely used with an important role in reducing malaria cases. In this review article, we reviewed the vector control measures established in the Brazilian territory and aspects associated with such measures for malaria. Although some vector control measures are routinely used in Brazil, many entomological and effectiveness information still need better evidence in endemic areas where Plasmodium vivax predominates. Herein, we outlined some of the needs and priorities for future research: a) update of the cartography of malaria vectors in Brazil, adding molecular techniques for the correct identification of species and complexes of species; b) evaluation of vector competence of anophelines in Brazil; c) strengthening of local entomology teams to perform vector control measures and interpret results; d) evaluation of vector control measures, especially use of insecticide-treated nets and long-lasting insecticidal nets, estimating their effectiveness, cost-benefit, and population acceptance; e) establishment of colonies of malaria vectors in Brazil, i.e., Anopheles darlingi, to understand parasite-vector interactions better; f) study of new vector control strategies with impacts on non-endophilic vectors; g) estimation of the impact of insecticide resistance in different geographical areas; and h) identification of the relative contribution of natural and artificial breeding sites in different epidemiological contexts for transmission.

Implication of Tityus apiacas (Lourenco, 2002) in scorpion envenomations in the Southern Amazon border, Brazil

Abstract Herein, four cases of scorpion stings caused by Tityus apiacas recorded from the municipality of Apuí, in the southern region of the Brazilian Amazon, are described. Patients showed systemic clinical manifestations, described as unusual, involuntary, and generalized tingling and numbness, reported by patients as an electric shock sensation, lasting up to 24 hours after the sting. All patients described local pain and sensation, along with other clinical symptoms including local edema and erythema. Systemic manifestations were not life threatening. Antivenom therapy was administered to all patients, who were discharged without complaints.

Avaliação eosinofílica e soropositividade para anticorpos IgG anti-toxocara em crianças atendidas pelo sistema único de saúde / Eosinophilic count and seropositivity for IgG antibodies to toxocara spp. in children assisted at the public health service / Evaluación eosinófila y suero-positividad para anticuerpos igG anti-toxocara en niños atendidos por el sistema único de salud

OBJETIVO: Verificar a associação entre a presença de eosinofilia e a soropositividade para anticorpos IgG anti-Toxocara spp. em crianças atendidas pelo Sistema Único de Saúde no Noroeste do Paraná, Brasil. MÉTODOS: Estudo retrospectivo com crianças de sete meses a 12 anos, atendidas pelo Sistema Único de Saúde do Noroeste do Paraná, com teste ELISA para a pesquisa de anticorpos IgG anti-Toxocara spp. e contagem de eosinófilos (eosinofilia >600 células/mm³). RESULTADOS: Entre as 1.199 crianças, 386 (32,2 por cento) apresentaram anticorpos IgG anti-Toxocara spp. A soroprevalência e a eosinofilia foram mais frequentes em crianças de sete meses a cinco anos. A eosinofilia foi observada em 7,8 por cento dos pacientes soro-reagentes ao Toxocara spp.. CONCLUSÕES: Foi observada elevada prevalência de anticorpos anti-Toxocara spp., principalmente nos menores de cinco anos. Com exceção de algumas crianças que apresentaram sintomas respiratórios e presença de eosinofilia, a maioria foi assintomática e não mostrava eosinofilia. A pesquisa de eosinófilos é ferramenta secundária para o diagnóstico de toxocaríase.

OBJECTIVE: To study the association between the presence of eosinophilia and IgG antibodies to Toxocara spp. in children assisted by the public health service, in the northwestern region of Parana State, in southern Brazil. METHODS: A retrospective study of children aged seven months to 12 years old assisted by the Public Health Service in northwest state of Paraná, Brazil. ELISA test was performed in all children in order to detect IgG antibodies to Toxocara spp. and eosinophil amounts (eosinophilia > 600 cells/mm3). RESULTS: Among 1,199 screened children, 386 (32.2 percent) had IgG antibodies to Toxocara spp. The seroprevalence of Toxocara spp. and the eosinophilia were more common among children of seven months to five years old. Eosinophilia was observed in 7.8 percent of seropositive patients to Toxocara spp. CONCLUSIONS: There was a high prevalence of anti-Toxocara spp., mainly in children under five years old. With the exception of some children who had respiratory symptoms and eosinophilia, most of them were asymptomatic and did not present eosinophilia. Eosinophilic count is a secondary laboratory finding in the diagnosis of toxocariasis.

OBJETIVO: Verificar la asociación entre la presencia de eosinofilia y una suero-positividad para anticuerpos IgG anti-Toxocara spp. en niños atendidos por el Sistema Único de Salud en el noroeste de Paraná, Brasil. MÉTODOS: Estudio retrospectivo en niños de siete meses a 12 años de edad, atendidos por el Sistema Único de Salud en el noroeste de Paraná, con prueba de ELISA para la investigación de anticuerpos IgG anti-Toxocara spp. y recuento de eosinófilos (eosinofilia > 600 células/mm³). RESULTADOS: Entre los 1.199 niños, 386 (32,2 por ciento) presentaron anticuerpos IgG anti-Toxocara spp. La suero-prevalencia y la eosinofilia fueron más frecuentes en niños de siete meses a cinco años. La eosinofilia fue observada en 7,8 por ciento de los pacientes suero-reactivos al Toxocara spp. CONCLUSIÓN: Se observó elevada prevalencia de anticuerpos anti-Toxocara spp., principalmente en niños menores de cinco años. Excepto por algunos niños que presentaron síntomas respiratorios y presencia de eosinofilia, la mayoría de ellas fue asintomática y mostraban eosinofilia. La investigación de eosinófilos es herramienta adicional a los casos con indicios clínicos de toxocariase.

Mobilidade populacional e produção da leishmaniose tegumentar americana no Estado do Paraná, sul do Brasil / Population mobility and production of American tegumentary leishmaniasis in the State of Paraná, southern Brazil

São escassas as informações sobre o papel da mobilidade populacional na manutenção da leishmaniose tegumentar americana no estado do Paraná. Avalia-se a mobilidade populacional como fator de risco para esta endemia em três mesorregiões do Paraná, utilizando dados gerados na Universidade Estadual de Maringá, no período de 1987 a 2004. Foram notificados 1.933 casos, predominando os casos migrantes (54,4 por cento). Os municípios com maior número de casos notificados foram Maringá (358), Doutor Camargo (108) e Terra Boa (105). Os casos rurais foram predominantemente autóctones (89,8 por cento), enquanto os urbanos, na maioria (84,8 por cento) migrantes (p<0,0001). Para os casos rurais autóctones, não houve predomínio entre os sexos (p=0,127); para os casos urbanos migrantes, prevaleceu o sexo masculino (p<0,0001). Os casos migrantes foram na maioria relacionados com a mobilidade intra e intermunicipal. A mobilidade populacional parece ser uma variável importante na epidemiologia desta doença no Estado do Paraná.

Information on the role of population mobility in maintaining American tegumentary leishmaniasis in the State of Paraná is scarce. Population mobility was evaluated as a risk factor for this endemic disease in three mesoregions of Paraná, using data built up at the State University of Maringá, covering 1987 to 2004. A total of 1,933 cases were notified, mostly among migrants (54.4 percent). The municipalities with the greatest numbers of cases notified were Maringá (358), Doutor Camargo (108) and Terra Boa (105). The rural cases were predominantly autochthonous (89.8 percent), while the urban cases were mostly among migrants (84.8 percent) (p < 0.0001). Among the rural autochthonous cases, there was no difference between the sexes (p = 0.127), whereas among the urban migrant cases, men predominated (p < 0.0001). The migrant cases were mostly related to mobility within and between municipalities. Population mobility seems to be an important variable in the epidemiology of this disease in the State of Paraná.

Análise parasitológica de hortaliças comercializadas na central de abastecimento do município de maringá- Paraná / Parasitological analysis of vegetables commercialized in the Food Supply Center of the municipality of Maringá, Paraná State, Brazil

Este estudo avaliou a contaminação parasitológica de hortaliças consumidas cruas que são comercializadas no CEASA do município de Maringá, Paraná; as condições higiênico-sanitárias do local e dos comerciantes. Foram analisadas 30 amostras de alface crespa; 30 de rúcula; 27 de espinafre e 24 de agrião pela técnica descrita por Oliveira e Germano, em duplicata, e pelo método de Ziehl-Neelsen, modificado por Henriksen-Polenz. A avaliação das condições higiênico-sanitárias do local e dos hábitos dos comerciantes foi efetuada por meio de questionário estruturado, pré-codificado. As hortaliças mais contaminadas foram o agrião e a rúcula, com índices de parasitismo maiores que 80 por cento. Foram encontrados oocistos de coccídeos, ovos e larvas das superfamílias Rhabdiasoidea e Ancylostomatoidea. Não foram encontradas amostras parasitadas por Cryptosporidium sp. A avaliação das condições higiênico-sanitárias do local e dos hábitos dos comerciantes demonstrou que as hortaliças ficavam expostas à poeira e ao trânsito de veículos pesados; a falta de paramentação dos distribuidores e ao manuseio concomitantemente de verduras e dinheiro em 40 por cento dos comerciantes. Conclui-se que as condições de horticultura, transporte, distribuição e manipulação de hortaliças precisam ser constantemente avaliadas e a população, diretamente envolvida.

The aim of this work was to evaluate parasitologicaly the vegeta¬bles that are consumed raw and are marketed in the Food Supply Center of Maringá City (Paraná State-Brazil), the hygienic-sanitary conditions of the place and of the merchants. Thirty samples of curly lettuce, 30 of rocket-salad, 27 of spinach and 24 of watercress were analyzed by Oliveira & Germano technique, in duplicate, and by Ziehl-Neelsen method modified by Henriksen-Polenz. The evaluation of the hygienic-sanitary conditions of the place and of the merchants' habits was made by an epidemiological data collection instrument. Watercress and rocket salad, which contamination index was upper than 80 percent, show the major number of contaminants. Coccidian oocysts, Superfamily Rhabdiasoidea and Ancylostomatoidea eggs and larvae were the mainly parasites found. There were no green vegetables parasited by Cryptosporidium sp. The hygienic-sanitary conditions of the place and of the merchants' habits showed irregularities. The vegetables were exposed to dust and to trucks traffic, the distributors were not appropriately dressed and 40 percente of the merchants handled green veg¬etables and money at the same time. The horticulture conditions, transport, distribution and manipulation of vegetables need to be constantly appraised and the population directly involved enlighten in order to improve the quality of green vegetables.

Qualidade de hortaliças comercializadas no noroeste do Paraná, Brasil / Quality of green vegetables marketed in the northwest of Parana, Brazil

O objetivo deste trabalho foi avaliar parasito-logicamente a qualidade de hortaliças consumidas cruas provenientes de locais de produção e de feiras livres do município de Maringá, Paraná. De julho/2002 a julho/2004, foram coletadas 66 amostras de hortaliças em 13 chácaras e 181 amostras em 17 feiras livres. Pés de alface (variedades lisa, crespa e americana), maços de agrião e rúcula, recolhidos aleatoriamente e em triplicata foram submetidos às técnicas de Oliveira & Germano, Kynioun e à pesquisa de coliformes totais e termotolerantes. O índice total de parasitismo das hortaliças de feiras (63 por cento) e chácaras (71,1 por cento) não diferiu estatisticamente. As hortaliças das chácaras mostraram-se mais parasitadas por protozoários (10/47) que as das feiras (19/114). Larvas de Rhabditoidea e ovos de Ancylostomatoidea encontravam-se igualmente distribuídos nas hortaliças de ambos os locais. Formas parasitárias de outras espécies foram também encontradas. Todas as amostras de alface crespa coletadas nas chácaras estavam contaminadas por bactérias totais e termoto-lerantes em índices não compatíveis com o consumo humano. São discutidos ainda a dificuldade em se diagnosticar laboratorialmente gênero e espécie de parasitas de interesse humano observados em hortaliças e os desafios da vigilância epidemiológica na busca de boa qualidade para hortaliças ingeridas cruas.

This work had the objective of performing a parasitological evaluation of fresh vegetables colleted from production places and free markets of Maringá, Paraná. From July/2002 to July/2004, 66 samples were collected in 13 smallholdings and 181 samples in 17 free markets. Heads of lettuce (varieties flat, curly and American), watercress and rocket salad, picked up randomly and in triplicate, were submitted to Oliveira & Germano's and Kynioun staining techniques and to the research of total and thermotolerant coliforms. The total index of parasitism of the vegetables of free markets (63%) and smallholdings (71.1%) didn't differ statistically. The fresh vegetables from smallholdings have shown more protozoa than (10/47) that from the free markets (19/114). Rhabditoidea larvae and Ancylostomatoidea eggs were equally distributed in the fresh vegetables of both places. Parasitic forms of other species were also found. All the curly lettuce samples collected in the smallholdings presented total and thermotolerant bacteria index incompatible with the human consumption. The difficult in doing laboratorial diagnose at the genre and specie level of the human parasites in fresh vegetables and the sanitary surveillance challenges in the obtaining of good quality products were discussed.

Avaliação da disponibilidade de medicamentos genéricos em farmácias e drogarias de Maringá (PR) e comparação de seus preços com os de referência e similares / An evaluation of generic medicines availability in pharmacies and drugstores in Maringá (PR) and comparison of their prices in relation with the similars and the references

O debate sobre a implementação de genéricos vem sendo realizado no Brasil desde 1976. Entretanto, somente em 1991, foi elaborado um projeto, visando à implantação dos medicamentos genéricos. A lei nº 9787 ("Lei dos genéricos") só foi publicada no Diário Oficial da União em 11 de fevereiro de 1999. Os objetivos deste trabalho foram verificar a disponibilidade de medicamentos genéricos em farmácias e drogarias, bem como comparar os preços destes medicamentos em relação aos similares e aos de referência. Verificou-se a disponibilidade dos medicamentos genéricos em 22 farmácias e drogarias do município de Maringá, estado do Paraná, de 30 de outubro a 22 de novembro de 2002. Dos 222 princípios ativos disponibilizados no Brasil como genéricos, foram encontrados 71 (32 por cento)...