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      Clustering symptoms of non-severe malaria in semi-immune Amazonian patients

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          Abstract

          Malaria is a disease that generates a broad spectrum of clinical features. The purpose of this study was to evaluate the clinical spectrum of malaria in semi-immune populations. Patients were recruited in Mâncio Lima, a city situated in the Brazilian Amazon region. The study included 171 malaria cases, which were diagnosed via the use of a thick blood smear and confirmed by molecular methods. A questionnaire addressing 19 common symptoms was administered to all patients. Multiple correspondence analysis and hierarchical cluster analysis were performed to identify clusters of symptoms, and logistic regression was used to identify factors associated with the occurrence of symptoms. The cluster analysis revealed five groups of symptoms: the first cluster, which included algic- and fever-related symptoms, occurred in up to 95.3% of the cases. The second cluster, which comprised gastric symptoms (nausea, abdominal pain, inappetence, and bitter mouth), occurred in frequencies that ranged between 35.1% and 42.7%, and at least one of these symptoms was observed in 71.9% of the subjects. All respiratory symptoms were clustered and occurred in 42.7% of the malaria cases, and diarrhea occurred in 9.9% of the cases. Symptoms constituting the fifth cluster were vomiting and pallor, with a 14.6% and 11.7% of prevalence, respectively. A higher parasitemia count (more than 300 parasites/mm 3) was associated with the presence of fever, vomiting, dizziness, and weakness ( P < 0.05). Arthralgia and myalgia were associated with patients over the age of 14 years ( P < 0.001). Having experienced at least eight malaria episodes prior to the study was associated with a decreased risk of chills and fever and an increased risk of sore throat ( P < 0.05). None of the symptoms showed an association with gender or with species of Plasmodium. The clinical spectrum of malaria in semi-immune individuals can have a broad range of symptoms, the frequency and intensity of which are associated with age, past exposure to malaria, and parasitemia. Understanding the full spectrum of nonsevere malaria is important in endemic areas to guide both passive and active case detection, for the diagnosis of malaria in travelers returning to non-endemic areas, and for the development of vaccines aimed to decrease symptom severity.

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          Análise de dados qualitativos: estratégias metodológicas para ciências da saúde, humanas e sociais

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            Amazonian malaria: asymptomatic human reservoirs, diagnostic challenges, environmentally driven changes in mosquito vector populations, and the mandate for sustainable control strategies.

            Across the Americas and the Caribbean, nearly 561,000 slide-confirmed malaria infections were reported officially in 2008. The nine Amazonian countries accounted for 89% of these infections; Brazil and Peru alone contributed 56% and 7% of them, respectively. Local populations of the relatively neglected parasite Plasmodium vivax, which currently accounts for 77% of the regional malaria burden, are extremely diverse genetically and geographically structured. At a time when malaria elimination is placed on the public health agenda of several endemic countries, it remains unclear why malaria proved so difficult to control in areas of relatively low levels of transmission such as the Amazon Basin. We hypothesize that asymptomatic parasite carriage and massive environmental changes that affect vector abundance and behavior are major contributors to malaria transmission in epidemiologically diverse areas across the Amazon Basin. Here we review available data supporting this hypothesis and discuss their implications for current and future malaria intervention policies in the region. Given that locally generated scientific evidence is urgently required to support malaria control interventions in Amazonia, we briefly describe the aims of our current field-oriented malaria research in rural villages and gold-mining enclaves in Peru and a recently opened agricultural settlement in Brazil. Copyright © 2011 Elsevier B.V. All rights reserved.
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              Malaria, erythrocytic infection, and anemia.

              Malaria is a major world health problem. It results from infection of parasites belonging to the genus Plasmodium. Plasmodium falciparum and Plasmodium vivax cause the major human malarias, with P falciparum being the more virulent. During their blood stages of infection, both P falciparum and P vivax induce anemia. Severe malarial anemia caused by P falciparum is responsible for approximately a third of the deaths associated with disease. Malarial anemia appears to be multi-factorial. It involves increased removal of circulating erythrocytes as well as decreased production of erythrocytes in the bone marrow. The molecular mechanisms underlying malarial anemia are largely unknown. Over the last five years, malaria parasite ligands have been investigated for their remodeling of erythrocytes and possible roles in destruction of mature erythrocytes. Polymorphisms in cytokines have been associated with susceptibility to severe malarial anemia: these cytokines and malaria "toxins" likely function by perturbing erythropoiesis. Finally a number of co-infections increase susceptibility to malarial anemia, likely because they exacerbate inflammation caused by malaria. Because of the complexities involved, the study of severe malarial anemia may need a "systems approach" to yield comprehensive understanding of defects in both erythropoiesis and immunity associated with disease. New and emerging tools such as (i) mathematical modeling of the dynamics of host control of malarial infection, (ii) ex vivo perfusion of human spleen to measure both infected and uninfected erythrocyte retention, and (iii) in vitro development of erythroid progenitors to dissect responsiveness to cytokine imbalance or malaria toxins, may be especially useful to develop integrated mechanistic insights and therapies to control this major and fatal disease pathology.
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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                PeerJ
                PeerJ
                PeerJ
                PeerJ Inc. (San Francisco, USA )
                2167-8359
                13 October 2015
                2015
                : 3
                : e1325
                Affiliations
                [1 ]Health Sciences Center, Federal University of Acre , Rio Branco, Acre, Brazil
                [2 ]Tropical Medicine Institute, University of São Paulo , São Paulo, Brazil
                [3 ]Scientific Computation Programm, Oswaldo Cruz Foundation , Rio de Janeiro, Rio de Janeiro, Brazil
                Article
                1325
                10.7717/peerj.1325
                4614890
                26500831
                4c2e083b-6163-4d47-92d1-bc25bd1ea0b5
                © 2015 Martins et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 4 August 2015
                : 24 September 2015
                Funding
                Funded by: UFAC (Brazil)
                Funded by: FUNTAC
                Award ID: Edital FDCT 2011 grant # 14/2013
                Award ID: Edital PIBIC 01/2014
                Funded by: CNPq (Edital Universal 2011)
                Funded by: FAPAC (Edital PPSUS 2013)
                Award ID: 14/2013
                Funded by: UFAC Master’s Program
                This study received financial support from UFAC (Brazil), FUNTAC (Edital FDCT 2011), CNPq (Edital Universal 2011) and FAPAC (Edital PPSUS 2013) as well as support from the UFAC Master’s Program in Public Health. Research fellowships were awarded by CNPq, UFAC and FAPAC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Global Health
                Infectious Diseases

                malaria,symtoms,amazon,clustering
                malaria, symtoms, amazon, clustering

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