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      False-negative malaria rapid diagnostic test results and their impact on community-based malaria surveys in sub-Saharan Africa

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          Abstract

          Surveillance and diagnosis of Plasmodium falciparum malaria relies predominantly on rapid diagnostic tests (RDT). However, false-negative (FN) RDT results are known to occur for a variety of reasons, including operator error, poor storage conditions, pfhrp2/3 gene deletions, poor performance of specific RDT brands and lots, and low-parasite density infections. We used RDT and microscopy results from 85 000 children enrolled in Demographic Health Surveys and Malaria Indicator Surveys from 2009 to 2015 across 19 countries to explore the distribution of and risk factors for FN-RDTs in sub-Saharan Africa, where malaria’s impact is greatest. We sought to (1) identify spatial and demographic patterns of FN-RDT results, defined as a negative RDT but positive gold standard microscopy test, and (2) estimate the percentage of infections missed within community-based malaria surveys due to FN-RDT results. Across all studies, 19.9% (95% CI 19.0% to 20.9%) of microscopy-positive subjects were negative by RDT. The distribution of FN-RDT results was spatially heterogeneous. The variance in FN-RDT results was best explained by the prevalence of malaria, with an increase in FN-RDT results observed at lower transmission intensities, among younger subjects, and in urban areas. The observed proportion of FN-RDT results was not predicted by differences in RDT brand or lot performance alone. These findings characterise how the probability of detection by RDTs varies in different transmission settings and emphasise the need for careful interpretation of prevalence estimates based on surveys employing RDTs alone. Further studies are needed to characterise the cost-effectiveness of improved malaria diagnostics (eg, PCR or highly sensitive RDTs) in community-based surveys, especially in regions of low transmission intensity or high urbanicity.

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          Most cited references 26

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          GeoDa: An Introduction to Spatial Data Analysis

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            A new world malaria map: Plasmodium falciparum endemicity in 2010

            Background Transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations. Maps of transmission intensity are necessary to identify populations at different levels of risk and to evaluate objectively options for disease control. To remain relevant operationally, such maps must be updated frequently. Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010. This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (PfEIR) and the basic reproductive number (PfR). Methods Annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (PfPR) surveys were used in a model-based geostatistical (MBG) prediction to create a continuous contemporary surface of malaria endemicity within these limits. A suite of transmission models were developed that link PfPR to PfEIR and PfR and these were fitted to field data. These models were combined with the PfPR map to create new global predictions of PfEIR and PfR. All output maps included measured uncertainty. Results An estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively. The majority of the endemic world was predicted with a median PfEIR of less than one and a median PfR c of less than two. Values of either metric exceeding 10 were almost exclusive to Africa. The uncertainty described in both PfEIR and PfR was substantial in regions of intense transmission. Conclusions The year 2010 has a particular significance as an evaluation milestone for malaria global health policy. The maps presented here contribute to a rational basis for control and elimination decisions and can serve as a baseline assessment as the global health community looks ahead to the next series of milestones targeted at 2015.
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              Caregivers’ treatment-seeking behaviour for children under age five in malaria-endemic areas of rural Myanmar: a cross-sectional study

              Background A community-based malaria intervention was introduced through fixed and mobile clinics in rural Myanmar. This study attempted to identify treatment-seeking behaviour of caregivers for children under five and the determinants of appropriate treatment-seeking behaviour in mobile clinic villages (MV) and non-mobile clinic villages (NMV) in malaria-endemic rural areas in Myanmar. Methods A cross-sectional study was conducted in 23 MV and 25 NMV in Ingapu Township, Myanmar. Appropriate treatment-seeking behaviour was operationally defined as seeking treatment from trained personnel or at a health facility within 24 hours after the onset of fever. Multiple logistic regression analyses were conducted to identify the determinants of appropriate treatment-seeking behaviour. Results Among the 597 participants in both types of villages, 166 (35.3%) caregivers sought appropriate treatment. No significant difference in appropriate treatment-seeking behaviour was found between the two types of villages (adjusted odds ratio (AOR), 0.80; 95% confidence interval (CI), 0.51-1.24). Determinants of behaviour include proximity to public health facilities (AOR, 5.86; 95% CI, 3.43-10.02), knowledge of malaria (AOR, 1.90; 95% CI, 1.14-3.17), malaria prevention behaviour (AOR, 1.76; 95% CI, 1.13-2.76), treatment at home (AOR, 0.26; 95% CI, 0.15-0.45), and treatment and transportation costs (AOR, 0.52; 95% CI, 0.33-0.83). Conclusions Caregivers’ treatment-seeking behaviour was poor for fever cases among children under age five, and did not differ significantly between MV and NMV. It is necessary to educate caregivers, particularly for early treatment seeking and appropriate use of health care options for fever, and catering to their medical needs. These findings can help promote awareness and prevention, and improve the quality of interventions at the community level.
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                Author and article information

                Journal
                BMJ Glob Health
                BMJ Glob Health
                bmjgh
                bmjgh
                BMJ Global Health
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2059-7908
                2019
                29 July 2019
                : 4
                : 4
                Affiliations
                [1 ] departmentMRC Centre for Global Infectious Disease Analysis , Imperial College London , London, UK
                [2 ] departmentDepartment of Epidemiology, Gillings School of Global Public Health , University of North Carolina , Chapel Hill, North Carolina, USA
                [3 ] departmentGlobal Health Institute , Duke University , Durham, North Carolina, USA
                [4 ] departmentDepartment of Geography , University of North Carolina , Chapel Hill, North Carolina, USA
                [5 ] departmentDivision of Infectious Diseases, Department of Medicine , University of North Carolina , Chapel Hill, North Carolina, USA
                Author notes
                [Correspondence to ] Oliver J Watson; o.watson15@ 123456imperial.ac.uk

                OJW and KMS are joint first authors.

                Article
                bmjgh-2019-001582
                10.1136/bmjgh-2019-001582
                6666813
                10417976-9a46-43a7-9e23-6ae2faebe7ec
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

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                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: 1R01AI13254701A1
                Funded by: FundRef http://dx.doi.org/10.13039/100000104, National Aeronautics and Space Administration;
                Award ID: NNX15AP74g
                Funded by: American Society for Tropical Medicine and Hygiene-Burroughs Wellcome Fund;
                Funded by: FundRef http://dx.doi.org/10.13039/501100000761, Imperial College London;
                Funded by: FundRef http://dx.doi.org/10.13039/501100000272, National Institute for Health Research;
                Award ID: R21AI126024
                Funded by: FundRef http://dx.doi.org/10.13039/501100000265, Medical Research Council;
                Funded by: FundRef http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: OPP1068440
                Funded by: FundRef http://dx.doi.org/10.13039/501100000278, Department for International Development;
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 109312/Z/15/Z
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                1506
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