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      Submicroscopic malaria infection is not associated with fever in cross-sectional studies in Malawi

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          Abstract

          Background

          Submicroscopic Plasmodium falciparum infections are widespread in many areas. However, the contribution of these infections to symptomatic malaria is not well understood. This study evaluated whether participants with submicroscopic P. falciparum infections have higher prevalence of fever than uninfected participants in southern Malawi.

          Methods

          A total of 16,650 children and adults were enrolled in the course of six cross-sectional surveys during the dry season (October–November) and after the rainy season (April–May) between 2012 and 2014 in three districts in southern Malawi. Demographic and socioeconomic data were collected in conjunction with data on clinical histories, use of malaria preventive measures, and anti-malarial medication taken within 2 weeks of the survey. Axillary temperatures were measured, and blood samples were collected for P. falciparum detection by microscopy and PCR. Participants without malaria parasites detected on microscopy but with a positive PCR for P. falciparum were defined as having submicroscopic infection. Fever was defined as having any one of: reported fever in the past 2 weeks, reported fever in the past 48 h, or a temperature of ≥ 37.5 °C measured at the time of interview.

          Results

          Submicroscopic P. falciparum infections and fever were both detected in 9% of the study population. In the final analysis adjusted for clustering within household and enumeration area, having submicroscopic P. falciparum infection was associated with reduced odds of fever in the dry season (odds ratio = 0.52; 95% CI 0.33–0.82); the association in the rainy season did not achieve statistical significance (odds ratio = 1.20; 95% CI 0.91–1.59). The association between submicroscopic infection and fever was consistent across all age groups. When the definition of fever was limited to temperature of ≥ 37.5 °C measured at the time of interview, the association was not statistically significant in either the rainy or dry season.

          Conclusions

          In this series of cross-sectional studies in southern Malawi, submicroscopic P. falciparum infection was not associated with increased risk of fever. Submicroscopic detection of the malaria parasite is important in efforts to decrease transmission but is not essential for the clinical recognition of malaria disease.

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          Most cited references23

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          The silent threat: asymptomatic parasitemia and malaria transmission.

          Scale-up of malaria control interventions has resulted in a substantial decline in global malaria morbidity and mortality. Despite this achievement, there is evidence that current interventions alone will not lead to malaria elimination in most malaria-endemic areas and additional strategies need to be considered. Use of antimalarial drugs to target the reservoir of malaria infection is an option to reduce the transmission of malaria between humans and mosquito vectors. However, a large proportion of human malaria infections are asymptomatic, requiring treatment that is not triggered by care-seeking for clinical illness. This article reviews the evidence that asymptomatic malaria infection plays an important role in malaria transmission and that interventions to target this parasite reservoir may be needed to achieve malaria elimination in both low- and high-transmission areas.
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            Qinghaosu (artemisinin): the price of success.

            N. White (2008)
            Artemisinin and its derivatives have become essential components of antimalarial treatment. These plant-derived peroxides are unique among antimalarial drugs in killing the young intraerythrocytic malaria parasites, thereby preventing their development to more pathological mature stages. This results in rapid clinical and parasitological responses to treatment and life-saving benefit in severe malaria. Artemisinin combination treatments (ACTs) are now first-line drugs for uncomplicated falciparum malaria, but access to ACTs is still limited in most malaria-endemic countries. Improved agricultural practices, selection of high-yielding hybrids, microbial production, and the development of synthetic peroxides will lower prices. A global subsidy would make these drugs more affordable and available. ACTs are central to current malaria elimination initiatives, but there are concerns that tolerance to artemisinins may be emerging in Cambodia.
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              Submicroscopic Plasmodium falciparum gametocyte densities frequently result in mosquito infection.

              Submicroscopic Plasmodium falciparum gametocytemia (<5,000 gametocytes/mL) is common and may result in mosquito infection. We assessed the relation between gametocyte density and mosquito infection under experimental and field conditions using real-time quantitative nucleic acid sequence-based amplification (QT-NASBA) for gametocyte quantification. Serial dilutions of NF54 P. falciparum gametocytes showed a positive association between gametocyte density and the proportion of infected mosquitoes (beta=6.1; 95% confidence interval [CI], 2.7-9.6; P=0.001). Successful infection became unlikely below an estimated density of 250-300 gametocytes/mL. In the field, blood samples of 100 naturally infected children showed a positive association between gametocyte density and oocyst counts in mosquitoes (beta=0.38; 95% CI, 0.14-0.61; P=0.002). The relative contribution to malaria transmission was similar for carriers with submicroscopic and microscopic gametocytemia. Our results show that transmission occurs efficiently at submicroscopic gametocyte densities and that carriers harboring submicroscopic gametocytemia constitute a considerable proportion of the human infectious reservoir.
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                Author and article information

                Contributors
                mlaufer@som.umaryland.edu
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                29 June 2020
                29 June 2020
                2020
                : 19
                : 233
                Affiliations
                [1 ]GRID grid.411024.2, ISNI 0000 0001 2175 4264, Center for Vaccine Development and Global Health, , University of Maryland School of Medicine, ; Baltimore, MD USA
                [2 ]GRID grid.164295.d, ISNI 0000 0001 0941 7177, School of Public Health, , University of Maryland College Park, ; College Park, MD USA
                [3 ]GRID grid.214458.e, ISNI 0000000086837370, Department of Epidemiology, , University of Michigan School of Public Health, ; Ann Arbor, MI USA
                [4 ]GRID grid.17088.36, ISNI 0000 0001 2150 1785, Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, , Michigan State University, ; East Lansing, MI USA
                [5 ]GRID grid.10595.38, ISNI 0000 0001 2113 2211, Malaria Alert Center, College of Medicine, , University of Malawi, ; Blantyre, Malawi
                [6 ]GRID grid.241116.1, ISNI 0000000107903411, Present Address: Colorado School of Public Health, , University of Colorado, ; Denver, USA
                [7 ]GRID grid.19006.3e, ISNI 0000 0000 9632 6718, Present Address: Fielding School of Public Health, , University of California, ; Los Angeles, USA
                [8 ]GRID grid.416738.f, ISNI 0000 0001 2163 0069, Present Address: US Center for Disease Control and Prevention, ; Atlanta, GA USA
                [9 ]GRID grid.131063.6, ISNI 0000 0001 2168 0066, Present Address: University of Notre Dame, ; Notre Dame, IN USA
                Author information
                http://orcid.org/0000-0001-8300-9593
                Article
                3296
                10.1186/s12936-020-03296-4
                7322713
                32600362
                558febb0-53dd-4028-acb8-a39e60579ae4
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 11 April 2020
                : 17 June 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: D43TW010075
                Award ID: U19AI089683
                Award ID: K24AI114996
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Infectious disease & Microbiology
                malaria,submicroscopic infection,plasmodium falciparum
                Infectious disease & Microbiology
                malaria, submicroscopic infection, plasmodium falciparum

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