Active case detection, treatment of falciparum malaria with combined chloroquine and sulphadoxine/pyrimethamine and vivax malaria with chloroquine and molecular markers of anti-malarial resistance in the Republic of Vanuatu.
BACKGROUND
Chloroquine-resistant Plasmodium falciparum was first described in the Republic of Vanuatu in the early 1980s. In 1991, the Vanuatu Ministry of Health instituted new treatment guidelines for uncomplicated P. falciparum infection consisting of chloroquine/sulphadoxine-pyrimethamine combination therapy. Chloroquine remains the recommended treatment for Plasmodium vivax.


METHODS
In 2005, cross-sectional blood surveys at 45 sites on Malo Island were conducted and 4,060 adults and children screened for malaria. Of those screened, 203 volunteer study subjects without malaria at the time of screening were followed for 13 weeks to observe peak seasonal incidence of infection. Another 54 subjects with malaria were followed over a 28-day period to determine efficacy of anti-malarial therapy; chloroquine alone for P. vivax and chloroquine/sulphadoxine-pyrimethamine for P. falciparum infections.


RESULTS
The overall prevalence of parasitaemia by mass blood screening was 6%, equally divided between P. falciparum and P. vivax. Twenty percent and 23% of participants with patent P. vivax and P. falciparum parasitaemia, respectively, were febrile at the time of screening. In the incidence study cohort, after 2,303 person-weeks of follow-up, the incidence density of malaria was 1.3 cases per person-year with P. vivax predominating. Among individuals participating in the clinical trial, the 28-day chloroquine P. vivax cure rate was 100%. The 28-day chloroquine/sulphadoxine-pyrimethamine P. falciparum cure rate was 97%. The single treatment failure, confirmed by merozoite surface protein-2 genotyping, was classified as a day 28 late parasitological treatment failure. All P. falciparum isolates carried the Thr-76 pfcrt mutant allele and the double Asn-108 + Arg-59 dhfr mutant alleles. Dhps mutant alleles were not detected in the study sample.


CONCLUSIONS
Peak seasonal malaria prevalence on Malo Island reached hypoendemic levels during the study observation period. The only in vivo malaria drug efficacy trial thus far published from the Republic of Vanuatu showed chloroquine/sulphadoxine-pyrimethamine combination therapy for P. falciparum and chloroquine alone for P. vivax to be highly efficacious. Although the chloroquine-resistant pfcrt allele was present in all P. falciparum isolates, mutant alleles in the dhfr and dhps genes do not yet occur to the extent required to confer sulphadoxine-pyrimethamine resistance in this population.
Kinzer
Michael H
MH
U,S, Naval Medical Research Unit No,2, Kompleks P2P/PLP-LITBANGKES, Jl, Percetakan Negara No. 29, Jakarta Pusat 10560, Indonesia. mkinzer@gmail.com
Chand
Krisin
K
Basri
Hasan
H
Lederman
Edith R
ER
Susanti
Augustina I
AI
Elyazar
Iqbal
I
Taleo
George
G
Rogers
William O
WO
Bangs
Michael J
MJ
Maguire
Jason D
JD
D000293:Adolescent; D000328:Adult; D000953:Antigens, Protozoan / Q000235:genetics; D000962:Antimalarials / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005819:Genetic Markers; D006801:Humans; D015994:Incidence; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D016780:Malaria, Vivax / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D010966:Plasmodium vivax / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use; D016896:Treatment Outcome; D009514:Vanuatu / Q000453:epidemiology; D055815:Young Adult
D000953:Antigens, Protozoan; D000962:Antimalarials; D004338:Drug Combinations; D005819:Genetic Markers; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine