Randomized, controlled, double-blind trial of daily oral azithromycin in adults for the prophylaxis of Plasmodium vivax malaria in Western Thailand.

We assessed the prophylactic efficacy of azithromycin (250 mg/day) against malaria in 276 adults in western Thailand in a randomized, double-blind, placebo-controlled trial. After antimalarial suppressive treatment, volunteers were randomized in a 2:1 ratio to either the azithromycin or placebo, respectively. Study medication was given for an average of 74 days.

Sources of variability in determining malaria parasite density by microscopy.

Enumeration of parasites by microscopic examination of blood smears is the only method available for quantifying parasitemia in infected blood. However, the sources and scale of error inherent in this technique have not been systematically investigated. Here we use data collected in outpatient clinics in Peru and Thailand to elucidate important sources of variation in parasite density measurements.

White blood cell counts and malaria.

White blood cells (WBCs) were counted in 4697 individuals who presented to outpatient malaria clinics in Maesod, Tak Province, Thailand, and Iquitos, Peru, between 28 May and 28 August 1998 and between 17 May and 9 July 1999. At each site and in each year, WBC counts in the Plasmodium falciparum-infected patients were lower than those in the Plasmodium vivax-infected patients, which, in turn, were lower than those in the uninfected patients. In Thailand, one-sixth of the P.

Phase I trial of the SPf66 malaria vaccine in a malaria-experienced population in Southeast Asia.

In preparation for a recently reported, independent field trial of SPf66 malaria vaccine efficacy in Thailand, we first established the safety and immunogenicity of two clinical lots of U.S. manufactured lots of SPf66 in a series of overlapping Phase I studies.

Characterization of naturally acquired antibodies to the non-repetitive flanking regions of the circumsporozoite protein of Plasmodium falciparum.

Antibody responses to the circumsporozoite (CS) protein of Plasmodium falciparum have previously been reported against the central repeating tetrapeptides of this protein. Segments of the protein flanking the repeat region also contain B-cell epitopes, but specific antibody responses have not been previously characterized. Longitudinal serum sets from 16 Thai adults who developed acute falciparum malaria were selected to represent a spectrum of antibody response to the repeat region (R32).

Characterization of naturally acquired antibody responses to a recombinant fragment from the N-terminus of Plasmodium falciparum glycoprotein 195.

Antibody responses to the glycoprotein precursor of the major merozoite surface antigens of Plasmodium falciparum (gp195) were investigated in acutely infected Thai adults. Specific IgG antibody was assayed by enzyme-linked immunosorbent assay using a recombinant fragment derived from the N-terminal region of gp195 as the capture antigen. Two control groups were found to be without significant cross-reacting antibody.

Naturally acquired circumsporozoite antibodies and their role in protection in endemic falciparum and vivax malaria.

The role of naturally acquired circumsporozoite (CS) antibodies in protection against falciparum and vivax malaria was evaluated in a group of Thai endemic villagers using a prospective cohort and a case-control study design. There was no evidence of protection by either the presence of positive CS antibody levels at the presumed time of sporozoite exposure or in individuals who persistently had measurable levels of the antibodies. The study defined levels of CS antibodies that were not protective in natural infection.

Characteristics of natural antibody responses to the circumsporozoite protein of Plasmodium vivax.

The antibody response to the prototype circumsporozoite (CS) protein of Plasmodium vivax (CSPV) was studied in Thai soldiers experiencing occupational malaria. Seventy-four (65%) of 114 men followed during assignment to a malaria transmission area developed blood-stage infection with P. vivax.

Development of immunity in natural Plasmodium falciparum malaria: antibodies to the falciparum sporozoite vaccine 1 antigen (R32tet32).

Antibodies that reacted with a candidate sporozoite vaccine antigen (R32tet32) were found in 20 of 21 patients treated for acute infection with Plasmodium falciparum and monitored longitudinally over 67 days. R32tet32 contains 32 tandem copies of a tetrapeptide sequence that constitutes the immunodominant epitope of the circumsporozoite surface protein. The magnitude of the antibody response varied considerably among individuals and appeared to be independent of the number of previous clinical infections.

Deficient spontaneous cell-mediated cytotoxicity and lectin-induced cellular cytotoxicity by peripheral blood mononuclear cells from Thai adults naturally infected with malaria.

To assess general cytotoxic effector cell capabilities by peripheral blood mononuclear cells from patients with active malaria infections, we examined antibody-dependent cellular cytotoxicity, spontaneous cell-mediated cytotoxicity, and lectin-induced cellular cytotoxicity by using human and chicken erythrocyte, Chang cell line, and K562 cell line targets. By using human erythrocyte and Change cell line targets, we found that Thai adults naturally infected with malaria had significantly impaired lectin-induced cellular cytotoxicity. In addition, spontaneous cell-mediated cytotoxicity was deficient with K562 but not with Chang cell line targets.

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.

Anti-lymphocytotoxic antibodies in sera of Thai adults infected with Plasmodium falciparum or Plasmodium vivax.

Because of the potential for the elimination of lymphocytes through anti-lymphocytotoxic antibodies we examined individual sera of patients infected with falciparum or vivax malaria for the presence of antibodies against normal peripheral blood mononuclear cells. In assays done at 15 degrees C, 95% of the P. falciparum patients and 98% of the P.

Loss of circulating T lymphocytes with normal levels of B and 'null' lymphocytes in Thai adults with malaria.

Peripheral blood mononuclear cells from forty-nine Thai adults infected with either Plasmodium falciparum or Plasmodium vivax were examined in order to determine the percentage of T, B, and Fc-receptor-bearing cells present. In comparison to healthy controls, both the percentage and concentration of peripheral T cells were decreased in the malaria-infected individuals as assessed by formation of rosettes with sheep red blood cells. The percentage of peripheral B cells was increased but their concentration was unchanged, as assessed by two techniques: the presence of surface immunoglobulin and the presence of a complement receptor.