Accuracy of an HRP-2/panLDH rapid diagnostic test to detect peripheral and placental Plasmodium falciparum infection in Papua New Guinean women with anaemia or suspected malaria.
BACKGROUND
The diagnosis of malaria during pregnancy is complicated by placental sequestration, asymptomatic infection, and low-density peripheral parasitaemia. Where intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine is threatened by drug resistance, or is inappropriate due to low transmission, intermittent screening and treatment (ISTp) with rapid diagnostic tests for malaria (RDT) could be a valuable alternative. Therefore, the accuracy of RDTs to detect peripheral and placental infection was assessed in a declining transmission setting in Papua New Guinea (PNG).


METHODS
The performance of a combination RDT detecting histidine-rich protein-2 (HRP-2) and Plasmodium lactate dehydrogenase (pLDH), and light microscopy (LM), to diagnose peripheral Plasmodium falciparum and Plasmodium vivax infections during pregnancy, were assessed using quantitative real-time PCR (qPCR) as the reference standard. Participants in a malaria prevention trial in PNG with a haemoglobin ≤90 g/L, or symptoms suggestive of malaria, were tested. Ability of RDT and LM to detect active placental infection on histology was evaluated in some participants.


RESULTS
Among 876 women, 1162 RDTs were undertaken (anaemia: 854 [73.5 %], suspected malaria: 308 [26.5 %]). qPCR detected peripheral infection during 190 RDT episodes (165 P. falciparum, 19 P. vivax, 6 mixed infections). Overall, RDT detected peripheral P. falciparum infection with 45.6 % sensitivity (95 % CI 38.0-53.4), a specificity of 96.4 % (95.0-97.4), a positive predictive value of 68.4 % (59.1-76.8), and a negative predictive value of 91.1 % (89.2-92.8). RDT performance to detect P. falciparum was inferior to LM, more so amongst anaemic women (18.6 vs 45.3 % sensitivity, Liddell's exact test, P < 0.001) compared to symptomatic women (72.9 vs 82.4 % sensitivity, P = 0.077). RDT and LM missed 88.0 % (22/25) and 76.0 % (19/25) of P. vivax infections, respectively. In a subset of women tested at delivery and who had placental histology (n = 158) active placental infection was present in 19.6 %: all three peripheral blood infection detection methods (RDT, LM, qPCR) missed >50 % of these infections.


CONCLUSIONS
In PNG, HRP-2/pLDH RDTs may be useful to diagnose peripheral P. falciparum infections in symptomatic pregnant women. However, they are not sufficiently sensitive for use in intermittent screening amongst asymptomatic (anaemic) women. These findings have implications for the management of malaria in pregnancy. The adverse impact of infections undetected by RDT or LM on pregnancy outcomes needs further evaluation.
Department of Medicine at the Doherty Institute, The University of Melbourne, Melbourne, Australia. alex.umbers@gmail.com.|Papua New Guinea Institute of Medical Research (PNG IMR), Goroka, Papua New Guinea. alex.umbers@gmail.com.
Alexandra J
AJ
Umbers
Department of Medicine at the Doherty Institute, The University of Melbourne, Melbourne, Australia. hwunger@doctors.org.uk.|Papua New Guinea Institute of Medical Research (PNG IMR), Goroka, Papua New Guinea. hwunger@doctors.org.uk.
Holger W
HW
Unger
Papua New Guinea Institute of Medical Research (PNG IMR), Goroka, Papua New Guinea. arosanas@itg.be.|Institute of Tropical Medicine, Antwerp, Belgium. arosanas@itg.be.
Anna
A
Rosanas-Urgell
Papua New Guinea Institute of Medical Research (PNG IMR), Goroka, Papua New Guinea. wangnapi.regina@yahoo.com.
Regina A
RA
Wangnapi
Papua New Guinea Institute of Medical Research (PNG IMR), Goroka, Papua New Guinea. kattenberg@wehi.edu.au.|Walter and Eliza Hall Institute of Medical Research (WEHI), Melbourne, Australia. kattenberg@wehi.edu.au.
Johanna H
JH
Kattenberg
Papua New Guinea Institute of Medical Research (PNG IMR), Goroka, Papua New Guinea. shadrach.jally@gmail.com.
Shadrach
S
Jally
Papua New Guinea Institute of Medical Research (PNG IMR), Goroka, Papua New Guinea. selina.silim@pngimr.org.pg.
Selina
S
Silim
Papua New Guinea Institute of Medical Research (PNG IMR), Goroka, Papua New Guinea. elvinlufele@gmail.com.
Elvin
E
Lufele
Walter and Eliza Hall Institute of Medical Research (WEHI), Melbourne, Australia. karl@wehi.edu.au.
Stephan
S
Karl
Papua New Guinea Institute of Medical Research (PNG IMR), Goroka, Papua New Guinea. marai.kaius@gmail.com.
Maria
M
Ome-Kaius
Papua New Guinea Institute of Medical Research (PNG IMR), Goroka, Papua New Guinea. robinson@wehi.edu.au.|Walter and Eliza Hall Institute of Medical Research (WEHI), Melbourne, Australia. robinson@wehi.edu.au.
Leanne J
LJ
Robinson
Department of Medicine at the Doherty Institute, The University of Melbourne, Melbourne, Australia. sroger@unimelb.edu.au.
Stephen J
SJ
Rogerson
Walter and Eliza Hall Institute of Medical Research (WEHI), Melbourne, Australia. ivomueller@fastmail.fm.|Barcelona Institute for Global Health (ISGLOBAL), Barcelona, Spain. ivomueller@fastmail.fm.
Ivo
I
Mueller
D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000175:diagnosis*; D000953:Antigens, Protozoan / Q000097:blood; D002846:Chromatography, Affinity / Q000379:methods*; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D016778:Malaria, Falciparum / Q000175:diagnosis*; D016780:Malaria, Vivax / Q000175:diagnosis*; D010219:Papua New Guinea; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000175:diagnosis*; D011446:Prospective Studies; D015800:Protozoan Proteins / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D055815:Young Adult
D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; D007770:L-Lactate Dehydrogenase