A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting.
BACKGROUND
Many countries are scaling up malaria interventions towards elimination. This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities. Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination. A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting.


METHODS
During the survey, 9,491 blood samples were collected and examined by microscopy for Plasmodium species and density, with a subset also examined by polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs). The performances of these diagnostic methods were compared.


RESULTS
A total of 256 samples were positive by microscopy, giving a point prevalence of 2.7%. The species distribution was 17.5% Plasmodium falciparum and 82.4% Plasmodium vivax. In this low transmission setting, only 17.8% of the P. falciparum and 2.9% of P. vivax infected subjects were febrile (≥ 38°C) at the time of the survey. A significant proportion of infections detected by microscopy, 40% and 65.6% for P. falciparum and P. vivax respectively, had parasite density below 100/μL. There was an age correlation for the proportion of parasite density below 100/μL for P. vivax infections, but not for P. falciparum infections. PCR detected substantially more infections than microscopy (point prevalence of 8.71%), indicating a large number of subjects had sub-microscopic parasitemia. The concordance between PCR and microscopy in detecting single species was greater for P. vivax (135/162) compared to P. falciparum (36/118). The malaria RDT detected the 12 microscopy and PCR positive P. falciparum, but failed to detect 12/13 microscopy and PCR positive P. vivax infections.


CONCLUSIONS
Asymptomatic malaria infections and infections with low and sub-microscopic parasite densities are highly prevalent in Temotu province where malaria transmission is low. This presents a challenge for elimination since the large proportion of the parasite reservoir will not be detected by standard active and passive case detection. Therefore effective mass screening and treatment campaigns will most likely need more sensitive assays such as a field deployable molecular based assay.
Harris
Ivor
I
Australian Army Malaria Institute, Weary Dunlop Drive, Gallipoli Barracks Enoggera, Qld 4051, Australia.
Sharrock
Wesley W
WW
Bain
Lisa M
LM
Gray
Karen-Ann
KA
Bobogare
Albino
A
Boaz
Leonard
L
Lilley
Ken
K
Krause
Darren
D
Vallely
Andrew
A
Johnson
Marie-Louise
ML
Gatton
Michelle L
ML
Shanks
G Dennis
GD
Cheng
Qin
Q
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001769:Blood / Q000469:parasitology; D002353:Carrier State / Q000175:diagnosis* / Q000469:parasitology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000469:parasitology / Q000473:pathology; D016780:Malaria, Vivax / Q000175:diagnosis* / Q000469:parasitology / Q000473:pathology; D008297:Male; D008542:Melanesia; D008853:Microscopy / Q000379:methods; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D018512:Parasitemia / Q000175:diagnosis* / Q000469:parasitology / Q000473:pathology; D010274:Parasitology / Q000379:methods*; D010963:Plasmodium falciparum / Q000145:classification / Q000166:cytology / Q000235:genetics / Q000302:isolation & purification*; D010966:Plasmodium vivax / Q000145:classification / Q000166:cytology / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction / Q000379:methods; D015995:Prevalence; D012680:Sensitivity and Specificity; D055815:Young Adult
Exp Parasitol. 1994 Aug;79(1):41-9
8050524
Am J Trop Med Hyg. 2007 Dec;77(6 Suppl):119-27
18165483
Trends Parasitol. 2008 Nov;24(11):525-30
18801702
J Med Entomol. 2004 Mar;41(2):201-8
15061279
Malar J. 2010 Apr 22;9:108
20409349
Am J Trop Med Hyg. 1996 Apr;54(4):325-31
8615441
Malar J. 2008 Jan 28;7:22
18226243
J Clin Microbiol. 2001 Mar;39(3):1025-31
11230422
Trans R Soc Trop Med Hyg. 2001 Mar-Apr;95(2):179-82
11355555
Ann Trop Med Parasitol. 2005 Sep;99(6):553-62
16156968
Bull World Health Organ. 1988;66(5):575-94
3061674
Malar J. 2010 Jul 26;9:218
20659316
Am J Trop Med Hyg. 2007 Mar;76(3):470-4
17360869
Malar J. 2008 Oct 03;7:202
18834523
Trop Med Int Health. 2006 Apr;11(4):432-40
16553926
Am J Trop Med Hyg. 2002 Aug;67(2):141-4
12389937
J Infect Dis. 2009 Nov 15;200(10):1509-17
19848588
Mol Biochem Parasitol. 1993 Apr;58(2):283-92
8479452
Ann Trop Med Parasitol. 2003 Mar;97(2):131-7
12803868
Mol Biochem Parasitol. 1993 Oct;61(2):315-20
8264734