TY - JOUR
T1 - Subpatent malaria in a low transmission African setting
T2 - A cross-sectional study using rapid diagnostic testing (RDT) and loop-mediated isothermal amplification (LAMP) from Zambezi region, Namibia
AU - McCreesh, Patrick
AU - Mumbengegwi, Davis
AU - Roberts, Kathryn
AU - Tambo, Munyaradzi
AU - Smith, Jennifer
AU - Whittemore, Brooke
AU - Kelly, Gerard
AU - Moe, Caitlin
AU - Murphy, Max
AU - Chisenga, Mukosha
AU - Greenhouse, Bryan
AU - Ntuku, Henry
AU - Kleinschmidt, Immo
AU - Sturrock, Hugh
AU - Uusiku, Petrina
AU - Gosling, Roland
AU - Bennett, Adam
AU - Hsiang, Michelle S
N1 - Funding Information:
This work was supported by Grants from the Novartis Foundation (A122666), Horchow Family Fund (Grant 5300375400 to MSH), and the Hellen Diller Foundation (Grant to PM).
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/19
Y1 - 2018/12/19
N2 - Background: Subpatent malaria infections, or low-density infections below the detection threshold of microscopy or standard rapid diagnostic testing (RDT), can perpetuate persistent transmission and, therefore, may be a barrier for countries like Namibia that are pursuing malaria elimination. This potential burden in Namibia has not been well characterized. Methods: Using a two-stage cluster sampling, cross-sectional design, subjects of all age were enrolled during the end of the 2015 malaria transmission season in Zambezi region, located in northeast Namibia. Malaria RDTs were performed with subsequent gold standard testing by loop-mediated isothermal amplification (LAMP) using dried blood spots. Infection prevalence was measured and the diagnostic accuracy of RDT calculated. Relationships between recent fever, demographics, epidemiological factors, and infection were assessed. Results: Prevalence of Plasmodium falciparum malaria infection was low: 0.8% (16/1919) by RDT and 2.2% (43/1919) by LAMP. All but one LAMP-positive infection was RDT-negative. Using LAMP as gold standard, the sensitivity and specificity of RDT were 2.3% and 99.2%, respectively. Compared to LAMP-negative infections, a higher portion LAMP-positive infections were associated with fever (45.2% vs. 30.4%, p = 0.04), though 55% of infections were not associated with fever. Agricultural occupations and cattle herding were significantly associated with LAMP-detectable infection (Adjusted ORs 5.02, 95% CI 1.77-14.23, and 11.82, 95% CI 1.06-131.81, respectively), while gender, travel, bed net use, and indoor residual spray coverage were not. Conclusions: This study presents results from the first large-scale malaria cross-sectional survey from Namibia using molecular testing to characterize subpatent infections. Findings suggest that fever history and standard RDTs are not useful to address this burden. Achievement of malaria elimination may require active case detection using more sensitive point-of-care diagnostics or presumptive treatment and targeted to high-risk groups.
AB - Background: Subpatent malaria infections, or low-density infections below the detection threshold of microscopy or standard rapid diagnostic testing (RDT), can perpetuate persistent transmission and, therefore, may be a barrier for countries like Namibia that are pursuing malaria elimination. This potential burden in Namibia has not been well characterized. Methods: Using a two-stage cluster sampling, cross-sectional design, subjects of all age were enrolled during the end of the 2015 malaria transmission season in Zambezi region, located in northeast Namibia. Malaria RDTs were performed with subsequent gold standard testing by loop-mediated isothermal amplification (LAMP) using dried blood spots. Infection prevalence was measured and the diagnostic accuracy of RDT calculated. Relationships between recent fever, demographics, epidemiological factors, and infection were assessed. Results: Prevalence of Plasmodium falciparum malaria infection was low: 0.8% (16/1919) by RDT and 2.2% (43/1919) by LAMP. All but one LAMP-positive infection was RDT-negative. Using LAMP as gold standard, the sensitivity and specificity of RDT were 2.3% and 99.2%, respectively. Compared to LAMP-negative infections, a higher portion LAMP-positive infections were associated with fever (45.2% vs. 30.4%, p = 0.04), though 55% of infections were not associated with fever. Agricultural occupations and cattle herding were significantly associated with LAMP-detectable infection (Adjusted ORs 5.02, 95% CI 1.77-14.23, and 11.82, 95% CI 1.06-131.81, respectively), while gender, travel, bed net use, and indoor residual spray coverage were not. Conclusions: This study presents results from the first large-scale malaria cross-sectional survey from Namibia using molecular testing to characterize subpatent infections. Findings suggest that fever history and standard RDTs are not useful to address this burden. Achievement of malaria elimination may require active case detection using more sensitive point-of-care diagnostics or presumptive treatment and targeted to high-risk groups.
KW - Asymptomatic
KW - LAMP
KW - Malaria
KW - Malaria elimination
KW - Namibia
KW - RDT
KW - Rapid diagnostic test
KW - Subclinical
KW - Submicroscopic
KW - Subpatent
UR - http://www.scopus.com/inward/record.url?scp=85058880624&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058880624&partnerID=8YFLogxK
U2 - 10.1186/s12936-018-2626-5
DO - 10.1186/s12936-018-2626-5
M3 - Article
C2 - 30567537
AN - SCOPUS:85058880624
SN - 1475-2875
VL - 17
JO - Malaria Journal
JF - Malaria Journal
IS - 1
M1 - 480
ER -