Role of macrophages in experimental malaria: VII--studies on adoptive transfer of macrophages.

Adoptive transfer of purified macrophages harvested from normal, Plasmodium berghei infected and latent/cured mice and also macrophages exposed to parasites in vitro were carried out to see the role of macrophages in transferring immunity against P. berghei infection. Macrophages obtained from mice having high parasitaemia at a dose of one million cells/animal showed significant increase in survival period (SP) and K values, compared to controls. Macrophages exposed to low parasite density conferred significant K values only. There was a decrease in prepatent period (PP) in the animal which received macrophages from animals cured 7-11 months compared to controls. The adoptive transfer studies with macrophages conditioned in vitro to parasite contributed towards increased protection of host against P. berghei as expressed by K values only. These studies showed that the macrophages harvested from infected mice were capable of acting as immunogen against P. berghei infection.

A rapid immunochromatographic test (ICT) for diagnosis of Plasmodium falciparum.

A field study was conducted to assess the sensitivity and specificity of rapid immunodiagnostic test based on detection of Plasmodium falciparum histidine-rich protein-2 (PfHRP-2) in peripheral blood for diagnosis of P. falciparum infection. Evaluation in 173 patients showed that the assay was 98.59% sensitive and 97.1% specific. There was no cross-reactivity with P. vivax. The test was positive in few patients who were found to be negative by microscopy showing the presence of antigen after curative chemotherapy. The test is a valuable diagnostic tool for falciparum malaria, especially in emergency/field situations requiring rapid diagnosis.

Role of macrophages in experimental malaria: IV--Bioassay of silica in immunity against Plasmodium berghei infection.

Silica treated mice when challenged with Plasmodium berghei showed increase in duration of prepatent(PP) and survival period (SP) and median survival day(MSD) as compared with controls. Daily parasite density curve during the course of infection was similar to control. Response to the parasite challenge, however, was dependent on the dose of silica. No increase in SP at 0.7 mg and in PP at 35 mg (cumulative doses) dose was observed. A dose upto 5 mg per mouse before challenge resulted in protection of the animal. No mortality was recorded in mice which received silica alone (35 mg; 5 mg/day x 7 days). Death due to lethal P.berghei infection could be delayed or prevented by altering/reducing the functional activities of macrophages during the course of infection.

Role of macrophages in experimental malaria: V--Effect of ethyl palmitate on macrophages in Plasmodium berghei infected mice.

Ethyl palmitate (EP) was used as a macrophage cytotoxin. The response of P. berghei after exposing the macrophage to EP was opposite to what was seen with other agents like Silica, Antimacrophage serum and Freund's complete adjuvant. EP at dose of 5 mg and above decreased the survival period (SP), median survival day (MSD) and parasite density 24 hrs. before death (K values). Prepatent period (PP) was lower at doses 10 mg and 20 mg per day for 5 days before challenge compared to their corresponding controls. EP at a dose of 5 mg and above was found to be toxic to host, mice. EP in dosage of 3 mg per mouse administered 48 hrs. before challenge resulted in an increase in the mean survival period, survival rate (30%) and decrease in the mean parasitaemia per day when compared with the corresponding control. The interfering agents affected differently both the host and/or parasite. A proper modulation of the macrophage during the course of infection may help the host in surviving this lethal infection.

High prevalence of chloroquine resistant Plasmodium falciparum infection in Rajasthan epidemic.

Plasmodium falciparum is the main killer among all human malaria parasites. In 1994, there was a falciparum malaria epidemic in Rajasthan, India, with many deaths. We have investigated active falciparum malaria cases from this epidemic and found that most of the parasite isolates (95%) were resistant to chloroquine. Nevertheless, all the tested isolates from the epidemic, were sensitive to mefloquine and quinine and ninety percent were also susceptible to sulfadoxine/pyrimethamine. Most individuals had moderate levels of TNF-alpha (20-220 pg/ml) and anti-parasite IgM antibodies compared to IgG levels which were relatively lower. In conclusion, the high transmission rate of the chloroquine resistant P. falciparum parasite could be the probable cause of the disease epidemic in Rajasthan. The timely drug sensitivity test and availability of appropriate antimalarial drugs are, therefore, warranted.