Performance of four HRP-2/pLDH combination rapid diagnostic tests and field microscopy as screening tests for malaria in pregnancy in Indonesia: a cross-sectional study.
BACKGROUND
Malaria in pregnancy poses a major public health problem in Indonesia with an estimated six million pregnancies at risk of Plasmodium falciparum or Plasmodium vivax malaria annually. In 2010, Indonesia introduced a screen and treat policy for the control of malaria in pregnancy at first antenatal visit using microscopy or rapid diagnostic tests (RDTs). A diagnostic study was conducted in Sumba, Indonesia to compare the performance of four different RDTs in predominately asymptomatic pregnant women under field condition.


METHODS
Women were screened for malaria at antenatal visits using field microscopy and four HRP-2/pLDH combination RDTs (Carestart™, First-Response(®), Parascreen(®) and SD-Bioline(®)). The test results were compared with expert microscopy and nested PCR. End user experience of the RDTs in the field was assessed by questionnaire.


RESULTS
Overall 950 were recruited and 98.7 % were asymptomatic. The prevalence of malaria was 3.0-3.4 % by RDTs, and 3.6, 5.0 and 6.6 % by field microscopy, expert microscopy and PCR, respectively. The geometric-mean parasite density was low (P. falciparum = 418, P. vivax = 147 parasites/µL). Compared with PCR, the overall sensitivity of the RDTs and field microscopy to detect any species was 24.6-31.1 %; specificities were >98.4 %. Relative to PCR, First-Response(®) had the best diagnostic accuracy (any species): sensitivity = 31.1 %, specificity = 98.9 % and diagnostic odds ratio = 39.0 (DOR). The DOR values for Carestart™, Parascreen(®), SD-Bioline(®), and field microscopy were 23.4, 23.7, 23.5 and 29.2, respectively. The sensitivity of Pan-pLDH bands to detect PCR confirmed P. vivax mono-infection were 8.6-13.0 %. The sensitivity of the HRP-2 band alone to detect PCR confirmed P. falciparum was 10.3-17.9 %. Pan-pLDH detected P. falciparum cases undetected by the HRP-2 band resulting in a better test performance when both bands were combined. First Response(®) was preferred by end-users for the overall practicality.


CONCLUSIONS
The diagnostic accuracy to detect malaria among mostly asymptomatic pregnant women and perceived ease of use was slightly better with First-Response(®), but overall, differences between the four RDTs were small and performance comparable to field microscopy. Combination RDTs are a suitable alternative to field microscopy to screen for malaria in pregnancy in rural Indonesia. The clinical relevance of low density malaria infections detected by PCR, but undetected by RDTs or microscopy needs to be determined.
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Rukhsana.Ahmed@lstmed.ac.uk.
Rukhsana
R
Ahmed
Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. elvira.levy9@gmail.com.
Elvira I
EI
Levy
Malaria Laboratory, Eijkman Institute for Molecular Biology, Jakarta, Indonesia. sylvia@eijkman.go.id.
Sylvia S
SS
Maratina
Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. dejong.j.judith@gmail.com.
Judith J
JJ
de Jong
Malaria Laboratory, Eijkman Institute for Molecular Biology, Jakarta, Indonesia. puji@eijkman.go.id.
Puji B S
PB
Asih
Malaria Laboratory, Eijkman Institute for Molecular Biology, Jakarta, Indonesia. eko@eijkman.go.id.
Ismail E
IE
Rozi
UNICEF, Jakarta, Indonesia. whawley@unicef.org.
William
W
Hawley
Malaria Laboratory, Eijkman Institute for Molecular Biology, Jakarta, Indonesia. din@eijkman.go.id.
Din
D
Syafruddin
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Feiko.terkuile@lstmed.ac.uk.
Feiko
F
ter Kuile
D000293:Adolescent; D000328:Adult; D000953:Antigens, Protozoan / Q000097:blood; D002846:Chromatography, Affinity / Q000379:methods*; D003430:Cross-Sectional Studies; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D006801:Humans; D007214:Indonesia; D016778:Malaria, Falciparum / Q000175:diagnosis*; D016780:Malaria, Vivax / Q000175:diagnosis*; D008403:Mass Screening / Q000379:methods*; D008853:Microscopy / Q000379:methods*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000166:cytology / Q000235:genetics / Q000276:immunology; D010966:Plasmodium vivax / Q000166:cytology / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000175:diagnosis*; D055815:Young Adult
D000953:Antigens, Protozoan