Abstract
Background. The performance of Plasmodium falciparum-specific histidine-rich protein 2-based rapid diagnostic tests (RDTs) to evaluate suspected malaria in low-endemicity settings has not been well characterized. Methods. Using dried blood spot samples from patients with suspected malaria at 37 health facilities from 2012 to 2014 in the low-endemicity country of Swaziland, we investigated the diagnostic accuracy of histidine-rich protein 2-based RDTs using qualitative polymerase chain reaction (PCR) (nested PCR targeting the cytochrome b gene) and quantitative PCR as reference standards. To explore reasons for false-negative and/or false-positive results, we used pfhrp2/3-specific PCR and logistic regression analyses of potentially associated epidemiological factors. Results. From 1353 patients, 93.0% of RDT-positive (n = 185) and 31.2% of RDT-negative samples (n = 340) were available and selected for testing. Compared with nested PCR, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RDTs were 51.7%, 94.1%, 67.3%, and 89.1%, respectively. After exclusion of samples with parasite densities <100/ μL, which accounted for 75.7% of false-negative results and 33.3% of PCR-detectable infections, the sensitivity, specificity, PPV, and NPV were 78.8%, 93.7%, 62.3%, and 97.1%. Deletions of pfhrp2 were not detected. False-positivity was more likely during the second year and was not associated with demographics, recent malaria, health facility testing characteristics, or potential DNA degradation. Conclusions. In the low-transmission setting of Swaziland, we demonstrated low sensitivity of RDT for malaria diagnosis, owing to an unexpectedly high proportion of low-density infection among symptomatic subjects. The PPV was also low, requiring further investigation. A more accurate point-of-care diagnostic may be needed to support malaria elimination efforts.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1221-1227 |
| Number of pages | 7 |
| Journal | Clinical Infectious Diseases |
| Volume | 64 |
| Issue number | 9 |
| DOIs | |
| State | Published - 2017 |
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Keywords
- Diagnostic accuracy
- Low transmission
- Malaria
- Rapid Diagnostic Test
- Subpatent infection
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases
Cite this
Limitations of rapid diagnostic testing in patients with suspected malaria : A diagnostic accuracy evaluation from Swaziland, a low-endemicity country aiming for malaria elimination. / Ranadive, Nikhil; Kunene, Simon; Darteh, Sarah; Ntshalintshali, Nyasatu; Nhlabathi, Nomcebo; Dlamini, Nomcebo; Chitundu, Stanley; Saini, Manik; Murphy, Maxwell; Soble, Adam; Schwartz, Alanna; Greenhouse, Bryan; Hsiang, Michelle S.
In: Clinical Infectious Diseases, Vol. 64, No. 9, 2017, p. 1221-1227.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Limitations of rapid diagnostic testing in patients with suspected malaria
T2 - A diagnostic accuracy evaluation from Swaziland, a low-endemicity country aiming for malaria elimination
AU - Ranadive, Nikhil
AU - Kunene, Simon
AU - Darteh, Sarah
AU - Ntshalintshali, Nyasatu
AU - Nhlabathi, Nomcebo
AU - Dlamini, Nomcebo
AU - Chitundu, Stanley
AU - Saini, Manik
AU - Murphy, Maxwell
AU - Soble, Adam
AU - Schwartz, Alanna
AU - Greenhouse, Bryan
AU - Hsiang, Michelle S.
PY - 2017
Y1 - 2017
N2 - Background. The performance of Plasmodium falciparum-specific histidine-rich protein 2-based rapid diagnostic tests (RDTs) to evaluate suspected malaria in low-endemicity settings has not been well characterized. Methods. Using dried blood spot samples from patients with suspected malaria at 37 health facilities from 2012 to 2014 in the low-endemicity country of Swaziland, we investigated the diagnostic accuracy of histidine-rich protein 2-based RDTs using qualitative polymerase chain reaction (PCR) (nested PCR targeting the cytochrome b gene) and quantitative PCR as reference standards. To explore reasons for false-negative and/or false-positive results, we used pfhrp2/3-specific PCR and logistic regression analyses of potentially associated epidemiological factors. Results. From 1353 patients, 93.0% of RDT-positive (n = 185) and 31.2% of RDT-negative samples (n = 340) were available and selected for testing. Compared with nested PCR, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RDTs were 51.7%, 94.1%, 67.3%, and 89.1%, respectively. After exclusion of samples with parasite densities <100/ μL, which accounted for 75.7% of false-negative results and 33.3% of PCR-detectable infections, the sensitivity, specificity, PPV, and NPV were 78.8%, 93.7%, 62.3%, and 97.1%. Deletions of pfhrp2 were not detected. False-positivity was more likely during the second year and was not associated with demographics, recent malaria, health facility testing characteristics, or potential DNA degradation. Conclusions. In the low-transmission setting of Swaziland, we demonstrated low sensitivity of RDT for malaria diagnosis, owing to an unexpectedly high proportion of low-density infection among symptomatic subjects. The PPV was also low, requiring further investigation. A more accurate point-of-care diagnostic may be needed to support malaria elimination efforts.
AB - Background. The performance of Plasmodium falciparum-specific histidine-rich protein 2-based rapid diagnostic tests (RDTs) to evaluate suspected malaria in low-endemicity settings has not been well characterized. Methods. Using dried blood spot samples from patients with suspected malaria at 37 health facilities from 2012 to 2014 in the low-endemicity country of Swaziland, we investigated the diagnostic accuracy of histidine-rich protein 2-based RDTs using qualitative polymerase chain reaction (PCR) (nested PCR targeting the cytochrome b gene) and quantitative PCR as reference standards. To explore reasons for false-negative and/or false-positive results, we used pfhrp2/3-specific PCR and logistic regression analyses of potentially associated epidemiological factors. Results. From 1353 patients, 93.0% of RDT-positive (n = 185) and 31.2% of RDT-negative samples (n = 340) were available and selected for testing. Compared with nested PCR, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RDTs were 51.7%, 94.1%, 67.3%, and 89.1%, respectively. After exclusion of samples with parasite densities <100/ μL, which accounted for 75.7% of false-negative results and 33.3% of PCR-detectable infections, the sensitivity, specificity, PPV, and NPV were 78.8%, 93.7%, 62.3%, and 97.1%. Deletions of pfhrp2 were not detected. False-positivity was more likely during the second year and was not associated with demographics, recent malaria, health facility testing characteristics, or potential DNA degradation. Conclusions. In the low-transmission setting of Swaziland, we demonstrated low sensitivity of RDT for malaria diagnosis, owing to an unexpectedly high proportion of low-density infection among symptomatic subjects. The PPV was also low, requiring further investigation. A more accurate point-of-care diagnostic may be needed to support malaria elimination efforts.
KW - Diagnostic accuracy
KW - Low transmission
KW - Malaria
KW - Rapid Diagnostic Test
KW - Subpatent infection
UR - http://www.scopus.com/inward/record.url?scp=85019991172&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019991172&partnerID=8YFLogxK
U2 - 10.1093/cid/cix131
DO - 10.1093/cid/cix131
M3 - Article
VL - 64
SP - 1221
EP - 1227
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 9
ER -