ABSTRACT
With the appearance of strains of Plasmodium falciparum in the Trat Province, eastern Thailand, reported to have developed resistance to mefloquine there is a need for an alternative drug. This comparative trial with mefloquine and halofantrine has demonstrated extremely low cure rates with both drugs (33.3% and 28.13% respectively), cross-resistance is suggested.
Subject(s)
Administration, Oral , Adult , Antimalarials/administration & dosage , Drug Resistance , Female , Humans , Malaria, Falciparum/drug therapy , Male , Mefloquine/administration & dosage , Phenanthrenes/administration & dosage , Thailand/epidemiology , Treatment OutcomeABSTRACT
A competitive antibody binding inhibition ELISA to detect Plasmodium falciparum-infected cells in clinical specimens was developed. Optimum conditions developed included: 12.5 micrograms/ml of P. falciparum antigen for plate coating, 25 micrograms/ml of polyclonal rabbit anti-P. falciparum IgG, 30 minute incubation of a mixture of infected red blood cell extract with anti-P. falciparum IgG, dilution of 1:500 of alkaline phosphatase-conjugated anti-rabbit IgG, and reading of the absorbance values 60 min after adding the p-nitrophenyl phosphate substrate. Reproducibility of the assay against cultured P. falciparum-infected red blood cells varied according to parasitemia, the higher the parasitemia, the better the reproducibility. The sensitivity of the assay was approximately 110 parasites/10(6) red blood cells. The assay was applied to field conditions involving 103 cases with falciparum malaria, 38 cases with vivax malaria and 30 healthy controls. With the 10% antibody binding inhibition as a cutoff, 87.4% of falciparum cases and 26.3% of vivax cases were positive. After treatment, the majority of cases became parasitologically negative with the corresponding negative assay. Regression analysis showed only weak but statistically significant correlation between the percent inhibition with parasitemia (r = 0.38, p less than 0.001), and this was more clearly shown in patients with high parasitemia.
Subject(s)
Animals , Antibodies, Monoclonal/diagnosis , Binding Sites, Antibody , Binding, Competitive , Enzyme-Linked Immunosorbent Assay , Humans , Malaria/diagnosis , Plasmodium falciparum , Reproducibility of Results , Sensitivity and Specificity , Thailand/epidemiologyABSTRACT
Sera from clinically immune individuals comprising 10 hospitalised patients (Group I), 30 persons residing in a malaria endemic area in Thailand (Group II) and 8 persons from a hyperendemic area in Ivory Coast (Group III) were tested by the parasite growth inhibition (PGI), indirect fluorescent antibody test of ring-infected erythrocyte surface antigen (RESA-IFA), urease-ELISA and Western blot. Paired sera from patients recovering from malaria (Group IV) as well as sera from blood donors were also tested. In the PGI test, sera were tested against three uncloned isolates of P. falciparum comprising SO, I4 and AE9 (PGI-SO, PGI-I4 and PGI-AE9 respectively). When growth inhibition of greater than or equal to 30% against any one of the three isolates was considered positive, the positive rate for the combined Groups I, II and III was 78.7%. Further analysis showed that the positive rates for PGI-SO, PGI-I4 and PGI-AE9 were 63.8%, 59.5% and 59.5% respectively and were not significantly different (p greater than 0.05). Comparison between PGI-SO, PGI-I4 and PGI-AE9 activities of Groups I, II and III sera showed no significant differences in any comparison groups except with PGI-AE9 in which Group III sera were more frequently positive than Group II sera (p = 0.004). Follow-up of PGI-SO and PGI-AE9 activities in Group IV patients showed mostly a decrease or no change in the activities of the convalescent sera taken 63 days later. RESA-IFA positive rate in the combined Groups I, II and III sera was 91.7%. There were no significant differences either in the seropositive rates or in the geometric mean antibody titers (GMT) between Groups I, II and III sera. Follow-up in Group IV patients showed no change in antibody titers in 64% of cases, decrease and increase in titers in 29% and 7% of cases respectively. The urease-ELISA seropositive rate in the combined Groups (I, II and III) was 89.5% which is not significantly different from that of RESA-IFA (p greater than 0.05). Comparison between individual Groups (I, II and III) likewise showed no significant differences in both GMT and seropositive rates. Follow-up in Group IV sera showed either no change or a decrease in antibody titers in 55.6% and 44.4% of cases respectively.(ABSTRACT TRUNCATED AT 400 WORDS)