Circumsporozoite antibody as a serologic marker of Plasmodium falciparum transmission.

In a longitudinal study of a malaria-endemic village in southeastern Thailand, circumsporozoite (CS) antibody to sporozoites of Plasmodium falciparum was measured by an enzyme-linked immunosorbent assay to determine its usefulness as a seroepidemiologic marker of malaria transmission. The CS anti-(NANP)n antibody level and prevalence during a 25-month period paralleled the pattern of seasonal transmission consistent with conventional parasitologic and entomologic measurements. The prevalence and level of antibody decreased during the non-transmission wet season, and increased over a 1-2-month transition period between the end of monsoon rains and the onset of dry conditions, an interval of maximum vector activity. Antibody increased with age in the population. The prevalence of antibody to the asexual blood stage as measured by conventional indirect fluorescent antibody assay did not coincide with changes in transmission and was sustained throughout the study period. Thus, CS antibody appeared to reflect the relative population exposure to mosquito inoculation of P. falciparum sporozoites and provided a useful measure of malaria transmission dynamics.

Effect of anti-coagulants on cold-reactive anti-lymphocyte activity in the blood of patients with malaria.

The effect of three different anti-coagulants on the level of cold-reactive anti-lymphocyte activity (ALA) in the peripheral blood (PB) of malarious individuals was assessed to determine if plasma could be substituted for serum in assays designed to characterize ALA. Results show that plasma obtained by treating PB with acid-citrate dextrose or ethylenediamine tetraacetic acid can be used instead of serum in these assays but that plasma obtained from heparin-treated blood cannot.

Comparison of a rapid field immunochromatographic test to expert microscopy for the detection of Plasmodium falciparum asexual parasitemia in Thailand.

We assessed a rapid, Plasmodium falciparum histidine rich protein 2 (PfHRP2)-based immunochromatographic test (ICT Malaria Pf Test), for detection of asexual P. falciparum parasitemia in 551 subjects in three groups: (1) symptomatic patients self-referring for diagnosis, (2) villagers in a screening survey, and (3) patients recently treated for P. falciparum malaria. Expert light microscopy was the reference standard. ICT test performance was similar for diagnostic and screening modes. Four findings emerged: (1) test sensitivity correlated directly with parasite density, (2) test band intensity correlated directly with parasite density, (3) persistent test positivity after parasite clearance precludes its use for monitoring early therapeutic responses, and (4) a false negative test at 18,000 parasites/microl is unexplained. We conclude that a strong positive ICT test is highly predictive of falciparum asexual parasitemia for the diagnosis of new cases of falciparum malaria in Thailand, but a negative test result is inadequate to exclude parasitemia < 300/microl, and in some instances, even a higher parasitemia.

Subpopulations of T cells (Tg and Tm) in patients with malaria.

In the present study we utilized rosetting techniques to enumerate the putative suppressor (Tg) and helper (Tm) T-cell subpopulations in the peripheral blood of adult Thais with malaria. A lower percentage of both Tg and Tm subpopulations and a lower number and percentage of total T cells was found in these patients during the acute period of infection than in the peripheral blood of healthy donors. However, the percentages of total T, Tg and Tm cells were higher during the convalescent period and were comparable to the values found in the peripheral blood of healthy donors. The significance of these findings are discussed. No correlations were found between the percentage of these T-cell subpopulations and the level of parasitemia or the hematocrit.

IgM antibody responses to the circumsporozoite protein in naturally acquired falciparum malaria.

The circumsporozoite (CS) protein on the surface of sporozoites is the major target for antibody response(s) to the infective stage of the malaria parasite. Sera from malaria endemic areas contain both IgM and IgG antibodies that react with a dominant epitope in the tetrapeptide repeat region of the CS protein. In order to characterize the IgM CS antibody response in Plasmodium falciparum (PF) malaria, a prospective study was conducted in Thai Rangers. Variable IgM responses against the CS protein were detected in 81% of 47 PF-infected subjects. Similar to IgG response kinetics, IgM levels rose to a peak 6-10 days after detection of parasitemia and showed an apparent serum half-life of less than 25 days. The classic difference in isotype ratio (IgG/IgM) between primary and secondary antibody responses was observed to blood-stage, but not CS, antigens.

Cold-reactive immunoglobulin M antilymphocyte antibodies directed against B cells in Thai children with dengue hemorrhagic fever.

Antilymphocyte antibodies were found in 51 of 83 serum specimens from Thai children with dengue hemorrhagic fever (DHF). The lymphocytotoxic activity was complement dependent, and cytotoxicity was detected in the 19S immunoglobulin M-associated serum fractions at a temperature optimum of 15 degrees C. Sera with lymphocytotoxic activity were cytotoxic to autologous as well as allogeneic lymphocytes from patients and healthy adult donors and were directed primarily against B cells, with some T cell cross-reactivity. This study suggests that infection with DHF induces predominately cold-reactive antilymphocyte antibodies in DHF patients that could potentially interact with peripheral blood cells of patients and modulate the humoral immune responses of patients during infection.