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      Epidemiology and Clinical Burden of Malaria in the War-Torn Area, Orakzai Agency in Pakistan


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          Military conflict has been a major challenge in the detection and control of emerging infectious diseases such as malaria. It poses issues associated with enhancing emergence and transmission of infectious diseases by destroying infrastructure and collapsing healthcare systems. The Orakzai agency in Pakistan has witnessed a series of intense violence and destruction. Military conflicts and instability in Afghanistan have resulted in the migration of refugees into the area and possible introduction of many infectious disease epidemics. Due to the ongoing violence and Talibanization, it has been a challenge to conduct an epidemiological study.

          Methodology/Principal Findings

          All patients were sampled within the transmission season. After a detailed clinical investigation of patients, data were recorded. Baseline venous blood samples were taken for microscopy and nested polymerase chain reaction (nPCR) analysis. Plasmodium species were detected using nested PCR (nPCR) and amplification of the small subunit ribosomal ribonucleic acid (ssrRNA) genes using the primer pairs. We report a clinical assessment of the epidemic situation of malaria caused by Plasmodium vivax (86.5%) and Plasmodium falciparum (11.79%) infections with analysis of complications in patients such as decompensated shock (41%), anemia (8.98%), hypoglycaemia (7.3%), multiple convulsions (6.7%), hyperpyrexia (6.17%), jaundice (5%), and hyperparasitaemia (4.49%).


          This overlooked distribution of P. vivax should be considered by malaria control strategy makers in the world and by the Government of Pakistan. In our study, children were the most susceptible population to malaria infection while they were the least expected to use satisfactory prevention strategies in such a war-torn deprived region. Local health authorities should initiate malaria awareness programs in schools and malaria-related education should be further promoted at the local level reaching out to both children and parents.

          Author Summary

          The malaria epidemic and endemic in Pakistan is a present and ongoing threat to public health which could have an impact in the nearby regions as well. For the first time, we report a clinical assessment of malaria endemicity in the Orakzai Agency, which is Pakistan’s most neglected area due to Talibanization and war in Afghanistan. Febrile patient blood samples of the area were investigated to report the clinical assessment of malaria caused by Plasmodium vivax and P. falciparum infections. The nested polymerase chain reaction (nPCR) examination detected 154 (86%) and 21 (12%) P. vivax and P. falciparum infections, respectively. We found worsening hygiene conditions in FATA, likely caused by poor socioeconomics and the collapse of the public health infrastructure. Decompensated shock was a common and prominent clinical feature of malaria among all the clinical presentations caused by both P. vivax (53%) and P. falciparum (42.9%). Our results have significant implications for both public health and malaria control in FATA and Pakistan. Our findings illustrate higher prevalence of malaria in children compared to other age groups. Further research on sensible estimates of refugees is required, as well as resistance to anti-malarials.

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          Most cited references 23

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          Factors in the emergence of infectious diseases.

           S. S. Morse (1995)
          "Emerging" infectious diseases can be defined as infections that have newly appeared in a population or have existed but are rapidly increasing in incidence or geographic range. Among recent examples are HIV/AIDS, hantavirus pulmonary syndrome, Lyme disease, and hemolytic uremic syndrome (a foodborne infection caused by certain strains of Escherichia coli). Specific factors precipitating disease emergence can be identified in virtually all cases. These include ecological, environmental, or demographic factors that place people at increased contact with a previously unfamiliar microbe or its natural host or promote dissemination. These factors are increasing in prevalence; this increase, together with the ongoing evolution of viral and microbial variants and selection for drug resistance, suggests that infections will continue to emerge and probably increase and emphasizes the urgent need for effective surveillance and control. Dr. David Satcher's article and this overview inaugurate Perspectives, a regular section in this journal intended to present and develop unifying concepts and strategies for considering emerging infections and their underlying factors. The editors welcome, as contributions to the Perspectives section, overviews, syntheses, and case studies that shed light on how and why infections emerge, and how they may be anticipated and prevented.
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            Severe Plasmodium vivax malaria: a report on serial cases from Bikaner in northwestern India.

            Epidemiologic studies and clinical description of severe Plasmodium vivax malaria in adults living in malaria-endemic areas are rare and more attention is needed to understand the dynamics and its interaction with the immune system. This observational study included 1,091 adult patients admitted to medical wards of S. P. Medical College and associated group of hospitals in Bikaner, India from September 2003 through December 2005. The diagnosis of P. vivax malaria was established by peripheral blood film (PBF), rapid diagnostic test (RDT), and polymerase chain reaction (PCR), and severe malaria was categorized as per World Health Organization guidelines. Of 1,091 patients with malaria, 635 had P. falciparum malaria and 456 had P. vivax malaria. Among patients with severe manifestations, 40 had evidence of monoinfection of P. vivax malaria diagnosed by PBF, RDT, and PCR. Complications observed were hepatic dysfunction and jaundice in 23 (57.5%) patients, renal failure in 18 (45%) patients, severe anemia in 13 (32.5%) patients, cerebral malaria in 5 patients (12.5%), acute respiratory distress syndrome in 4 patients (10%), shock in 3 patients (7.5%), and hypoglycemia in 1 (2.5%) patient. Thrombocytopenia was observed in 5 (12.5%) patients, and multi-organ dysfunction was detected in 19 (47.5%) patients. Further large-scale multicentric epidemiologic studies are needed to define the basic pathology of this less known entity.
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              A trial of combination antimalarial therapies in children from Papua New Guinea.

              Malaria control is difficult where there is intense year-round transmission of multiple plasmodium species, such as in Papua New Guinea. Between April 2005 and July 2007, we conducted an open-label, randomized, parallel-group study of conventional chloroquine-sulfadoxine-pyrimethamine and artesunate-sulfadoxine-pyrimethamine, dihydroartemisinin-piperaquine, and artemether-lumefantrine in children in Papua New Guinea 0.5 to 5 years of age who had falciparum or vivax malaria. The primary end point was the rate of adequate clinical and parasitologic response at day 42 after the start of treatment with regard to Plasmodium falciparum, after correction for reinfections identified through polymerase-chain-reaction (PCR) genotyping of polymorphic loci in parasite DNA. Secondary end points included the rate of adequate clinical and parasitologic response at day 42 with regard to P. vivax without correction through PCR genotyping. Of 2802 febrile children screened, 482 with falciparum malaria and 195 with vivax malaria were included. The highest rate of adequate clinical and parasitologic response for P. falciparum was in the artemether-lumefantrine group (95.2%), as compared with 81.5% in the chloroquine-sulfadoxine-pyrimethamine group (P=0.003), 85.4% in the artesunate-sulfadoxine-pyrimethamine group (P=0.02), and 88.0% in the dihydroartemisinin-piperaquine group (P=0.06). The rate of adequate clinical and parasitologic response for P. vivax in the dihydroartemisinin-piperaquine group (69.4%) was more than twice that in each of the other three treatment groups. The in vitro chloroquine and piperaquine levels that inhibited growth of local P. falciparum isolates by 50% correlated significantly (P<0.001). Rash occurred more often with artesunate-sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine than with chloroquine-sulfadoxine-pyrimethamine (P=0.004 for both comparisons). The most effective regimens were artemether-lumefantrine against P. falciparum and dihydroartemisinin-piperaquine against P. vivax. The relatively high rate of treatment failure with dihydroartemisinin-piperaquine against P. falciparum may reflect cross-resistance between chloroquine and piperaquine. (Australian New Zealand Clinical Trials Registry number, ACTRN12605000550606.) 2008 Massachusetts Medical Society

                Author and article information

                Role: Editor
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                25 January 2016
                January 2016
                : 10
                : 1
                [1 ]National Leading Research Laboratory, Department of Biological Sciences, Myongji University, Yongin, Gyeonggido, Republic of Korea
                [2 ]Department of Zoology, Kohat University of Science and Technology, Kohat, Pakistan
                [3 ]Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, Pakistan
                [4 ]University of British Columbia, Vancouver, Canada
                [5 ]Department of Natural Science, North Shore Community College, Danvers, Massachusetts, United States of America
                University of California San Diego School of Medicine, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AMK IH SKM JHL IHC SHL. Performed the experiments: AMK IH SKM JHL. Analyzed the data: AMK IH SKM JHL IHC YBK. Contributed reagents/materials/analysis tools: SHL. Wrote the paper: AMK IH SKM YBK SHL.

                © 2016 Karim et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 3, Tables: 2, Pages: 12
                The work was supported by research grants from the National Research Laboratory Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (grant no. 2011-0027928); and the Next Generation BioGreen 21 Program (grant no. PJ01103103) of Rural Development Administration in Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Research Article
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                Infectious disease & Microbiology


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