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      High-Sensitivity C-Reactive Protein: A Potential Ancillary Biomarker for Malaria Diagnosis and Morbidity

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          Abstract

          Background

          Malaria remains an important cause of morbidity and mortality in Africa. Previous studies that assessed C-reactive protein (CRP) have centered on the conventional method. This study evaluated the usefulness of high-sensitivity CRP (hs-CRP) in malaria diagnosis and morbidity in a pediatric population in Ghana.

          Methodology

          A total of 267 subjects (100 microscopically proven nonmalarial parasitaemics as controls and 167 plasmodium parasitaemic subjects as cases), between the ages of 7 months and 18 years, were recruited for this case-control study. Blood samples were collected for malaria parasite density by microscopic examination; full blood count, electrolytes, and liver function tests using an automated analyzer; and hs-CRP levels by sandwich ELISA method.

          Results

          The median hs-CRP concentration was lowest in the control group and increased significantly from low to high parasitaemia. The median hs-CRP level was significantly higher in high malaria parasitaemia compared to moderate and low malaria parasitaemia. Increasing hs-CRP cutoff (3.12-4.64 mg/L) presented with increasing specificity (79.3-93.1%) and sensitivity (96.4%-97.4%), except for moderate parasitaemia where a decline in sensitivity (80.9%) was observed. However, hs-CRP had relatively lower PPV but high NPV at low parasitaemia while both the PPV and NPV were moderate in moderate parasitaemia.

          Conclusion

          hs-CRP yielded a high sensitivity, specificity, and accuracy for low, moderate, and high-grade malaria, respectively, and thus may serve as an effective supplementary diagnostic and prognostic biomarker for Plasmodium parasite infection. However, hs-CRP might not be readily useful yet for diagnostic purposes in hospitals due to the relatively low PPV and NPV for low and moderate parasitaemia and thus necessitates further studies in larger cohorts.

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          Most cited references34

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          Function of C-reactive protein.

          T Du Clos (2000)
          C-reactive protein (CRP) is an ancient highly conserved molecule and a member of the pentraxin family of proteins. CRP is secreted by the liver in response to a variety of inflammatory cytokines. Levels of CRP increase very rapidly in response to trauma, inflammation, and infection and decrease just as rapidly with the resolution of the condition. Thus, the measurement of CRP is widely used to monitor various inflammatory states. CRP binds to damaged tissue, to nuclear antigens and to certain pathogenic organisms in a calcium-dependent manner. The function of CRP is felt to be related to its role in the innate immune system. Similar to immunoglobulin (Ig)G, it activates complement, binds to Fc receptors and acts as an opsonin for various pathogens. Interaction of CRP with Fc receptors leads to the generation of proinflammatory cytokines that enhance the inflammatory response. Unlike IgG, which specifically recognizes distinct antigenic epitopes, CRP recognizes altered self and foreign molecules based on pattern recognition. Thus, CRP is though to act as a surveillance molecule for altered self and certain pathogens. This recognition provides early defense and leads to a proinflammatory signal and activation of the humoural, adaptive immune system.
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            Epidemiology of malaria in the forest-savanna transitional zone of Ghana

            Background Information on the epidemiology of malaria is essential for designing and interpreting results of clinical trials of drugs, vaccines and other interventions. As a background to the establishment of a site for anti-malarial drugs and vaccine trials, the epidemiology of malaria in a rural site in central Ghana was investigated. Methods Active surveillance of clinical malaria was carried out in a cohort of children below five years of age (n = 335) and the prevalence of malaria was estimated in a cohort of subjects of all ages (n = 1484) over a 12-month period. Participants were sampled from clusters drawn around sixteen index houses randomly selected from a total of about 22,000 houses within the study area. The child cohort was visited thrice weekly to screen for any illness and a blood slide was taken if a child had a history of fever or a temperature greater than or equal to 37.5 degree Celsius. The all-age cohort was screened for malaria once every eight weeks over a 12-month period. Estimation of Entomological Inoculation Rate (EIR) and characterization of Anopheline malaria vectors in the study area were also carried out. Results The average parasite prevalence in the all age cohort was 58% (95% CI: 56.9, 59.4). In children below five years of age, the average prevalence was 64% (95% CI: 61.9, 66.0). Geometric mean parasite densities decreased significantly with increasing age. More than 50% of all children less than 10 years of age were anaemic. Children less than 5 years of age had as many as seven malaria attacks per child per year. The attack rates decreased significantly with increasing cut-offs of parasite density. The average Multiplicity of Infection (MOI) was of 6.1. All three pyrimethamine resistance mutant alleles of the Plasmodium falciparum dhfr gene were prevalent in this population and 25% of infections had a fourth mutant of pfdhps-A437G. The main vectors were Anopheles funestus and Anopheles gambiae and the EIR was 269 infective bites per person per year. Conclusion The transmission of malaria in the forest-savanna region of central Ghana is high and perennial and this is an appropriate site for conducting clinical trials of anti-malarial drugs and vaccines.
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              Emergency department management of mosquito-borne illness: malaria, dengue, and West Nile virus.

              Up to 700 million people are infected and more than a million die each year from mosquito-borne illness. While the vast majority of cases occur in endemic tropical and subtropical regions, international travel and migration patterns have increased their prevalence in North America. This review discusses the diagnosis and treatment of the 3 most common mosquito-borne illnesses seen in the United States: Plasmodium falciparum malaria, dengue, and West Nile virus. With no pathognomonic findings, it is critical that emergency clinicians in nonendemic areas maintain a high index of suspicion, conduct a thorough history/travel history, and interpret indirect findings to initiate prompt and appropriate treatment. This review gathers the best evidence from international public health resources, surveillance studies, guidelines, and academic research to give emergency clinicians tools to combat these potentially lethal infections.
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                Author and article information

                Contributors
                Journal
                Dis Markers
                Dis. Markers
                DM
                Disease Markers
                Hindawi
                0278-0240
                1875-8630
                2019
                4 April 2019
                : 2019
                : 1408031
                Affiliations
                1Department of Medical Laboratory Technology, Faculty of Allied Health Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
                2Department of Molecular Medicine, School of Medical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
                3Department of Physiology, School of Medical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
                Author notes

                Academic Editor: Michael Hawkes

                Author information
                http://orcid.org/0000-0001-9225-5876
                http://orcid.org/0000-0003-1369-3750
                http://orcid.org/0000-0003-0252-3190
                http://orcid.org/0000-0001-9023-6612
                http://orcid.org/0000-0003-4499-0678
                Article
                10.1155/2019/1408031
                6476067
                214ff88f-cb9b-40e8-85d9-d2c603543a88
                Copyright © 2019 Otchere Addai-Mensah et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 September 2018
                : 21 February 2019
                : 12 March 2019
                Categories
                Research Article

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