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Epidemiology of subpatent Plasmodium falciparum infection: implications for detection of hotspots with imperfect diagnostics

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Mosha, Jacklin F, Sturrock, Hugh JW, Greenhouse, Bryan, Greenwood, Brian, Sutherland, Colin J, Gadalla, Nahla, Atwal, Sharan, Drakeley, Chris, Kibiki, Gibson, Bousema, Teun, Chandramohan, Daniel, Gosling, Roly·2013·Malaria Journal
DOI 10.1186/1475-2875-12-221PMC PMC3701503
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Abstract

BACKGROUND: At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. METHODS: Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). RESULTS: Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. CONCLUSION: The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings.

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Crossref · 10.1186/1475-2875-12-221

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Figures

Figure 1 Location of the study site within Tanzania (inset map) and distribution of households included in the study (red points), showing local topography and road network (yellow lines).
Figure 1 Location of the study site within Tanzania (inset map) and distribution of households included in the study (red points), showing local topography and road network (yellow lines).CC BY · PubMed Central
Figure 2 Micro-epidemiology of infection in the study region. A - Household exposure estimated using distance-weighted PCR prevalence with a 1-km window. B - mean household parasite density (infected individuals only).
Figure 2 Micro-epidemiology of infection in the study region. A - Household exposure estimated using distance-weighted PCR prevalence with a 1-km window. B - mean household parasite density (infected individuals only).CC BY · PubMed Central
Figure 3 Relationship between parasite density and household exposure. A – Boxplot of log transformed parasite densities over different exposure categories (based on quintiles). Black lines indicate median values, red lines indicate mean values. B – The proportion of subpatent (<100 parasites/μl) infections over different exposure categories. C – Boxplot of log transformed parasite densities over different age categories. D – The proportion of subpatent (<100 parasites/μl) infections over different age categories.
Figure 3 Relationship between parasite density and household exposure. A – Boxplot of log transformed parasite densities over different exposure categories (based on quintiles). Black lines indicate median values, red lines indicate mean values. B – The proportion of subpatent (<100 parasites/μl) infections over different exposure categories. C – Boxplot of log transformed parasite densities over different age categories. D – The proportion of subpatent (<100 parasites/μl) infections over different age categories.CC BY · PubMed Central
Figure 4 Results of the tMDA simulations assuming different intervention thresholds. The black line represents the percentage of infections that would be correctly treated. The grey line represents the percentage of treatments that would be correctly administered to true positives. The red dashed line indicates the number of treatments that would be administered.
Figure 4 Results of the tMDA simulations assuming different intervention thresholds. The black line represents the percentage of infections that would be correctly treated. The grey line represents the percentage of treatments that would be correctly administered to true positives. The red dashed line indicates the number of treatments that would be administered.CC BY · PubMed Central

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Research works printed but not linked: 1

  1. FIND: Malaria rapid diagnostic test performance. 2012, Geneva, Switzerland: Results of WHO product testing of malaria RDTs: Round 4

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Metadata

Authors
Mosha, J. F., Sturrock, H. J., Greenhouse, B., Greenwood, B., Sutherland, C. J., Gadalla, N., Atwal, S., Drakeley, C., Kibiki, G., Bousema, T., Chandramohan, D., & Gosling, R.
Affiliations
  • National Institute for Medical Research (TZ)
  • University of California, San Francisco (US)
  • London School of Hygiene & Tropical Medicine (GB)
  • Kilimanjaro Christian Medical Centre (TZ)
  • Radboud University Medical Center (NL)
Corresponding author
Mosha, Jacklin F
ORCID
Venue
Malaria Journal
Publisher
Springer Science and Business Media LLC
Published
2013-07-01
Volume
12
Issue
1
Pages
221-221
ISSN
1475-2875 (ISSN-L)
DOI
10.1186/1475-2875-12-221
PMC
PMC3701503
OpenAlex
W2144009871
Cited by
114
References
40
Citations by year
2026: 2 · 2025: 1 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 12 · 2020: 6 · 2019: 5 · 2018: 14 · 2017: 11 · 2016: 18 · 2015: 14 · 2014: 14 · 2013: 1
FWCI
15.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Malaria Journal (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • IHI Repository (acceptedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion, other-oa)
Funders
  • Bill and Melinda Gates Foundation (OPP1013170)
  • Wellcome Trust (084289MA)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Life Sciences › Immunology and Microbiology › Parasitology › Bird parasitology and diseases
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Travel-related health issues
Keywords
Plasmodium falciparum, malaria hotspots, parasite density, household exposure, spatial distribution of infection, rapid diagnostic tests, mass drug administration, screen-and-treat, asymptomatic malaria, parasite reservoir, transmission intensity, northwestern Tanzania
MeSH terms
Adolescent, Adult, Blood, Child, Child, Preschool, Female, Humans, Infant, Male, Middle Aged, Plasmodium falciparum, Tanzania, DNA, Protozoan, Polymerase Chain Reaction, Malaria, Falciparum, Young Adult, Asymptomatic Infections, Parasite Load

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