Anti-malaria humoral responses in children exposed to Plasmodium falciparum and Schistosoma haematobium

Antibody responses directed against the Plasmodium falciparum antigens, total extract, anti-merozoite surface protein-3 (MSP3b) and glutamate-rich protein (Glurp-R0) were studied in 42 children exposed to both Schistosoma haematobium and P. falciparum infections. The association between levels of the anti-malaria IgG subclasses and IgM with host age, sex, schistosome infection intensity and schistosome specific antibodies was studied before chemotherapeutic treatment of schistosome infections. This showed a significant negative association between schistosome infection intensity and levels of IgG1, IgG3, and IgG4 directed against malaria total extract antigen, and a positive association between levels of anti-schistosome soluble egg antigen IgG2, IgG3, and IgG4 and levels of the same subclasses directed against malaria total extract antigens. The effect of treating schistosome infections with praziquantel on malaria specific responses was also studied. This treatment resulted in increases in significant IgG4 levels against MSP3b and IgM against Glurp R0. Treatment also resulted in a significant decrease in IgG4 levels against Glurp R0. Host age, sex or pre-treatment infection intensity was not associated with the magnitude of change in the two IgG4 responses while males showed a significantly higher increase in levels of IgM. The results suggest cross reactivity between schistosome and malaria antigens in this population.

How reliable are models for malaria vaccine development? Lessons from irradiated sporozoite immunizations.

Models occupy a key position in the development of anti-parasitic vaccines, yet their relevance has been seldom addressed. It is customary to admit that malaria vaccine development requires easy-to-handle, laboratory models. Animal models involving predominantly inbred rodents and primates as parasite hosts are currently the basic tools for the study of host-parasite interactions. Literature however indicates that the induction of host protection is more difficult in natural host-parasite pairs than in experimental models of parasite infection. Moreover different models delineate a wide range of host-pathogen relationship profiles providing a mosaic of contradictory informations, yet there is little incentive to delineate their relevance or to exploit recent advances to develop improved model systems. In this context the analysis of natural host-parasite interactions between Plasmodium berghei and its mammalian host and reservoir, the tree rat Grammomys surdaster could ge of relevance in the study of host-parasite interactions.

Well-breeding Anopheles dirus and their role in malaria transmission in Myanmar.

Mosquitos were collected with human and animal baits from March 1996 to January 1998 in four villages located along the Yadana gas pipe line in Yepyu township, Dawae district, Tanintharyi Division, southern Myanmar. A total of 23 anopheline species were collected. Anopheles dirus were abundant in pre-monsoon (May/June) an post-monsoon (October) months. All An. dirus caught both humans and cattle were assayed with specific, sporozoite enzyme-linked immunosorbent assays (ELISAs). A total of 5/250 (2%) caught with human bait was found positive with Plasmodium vivax from Eindayaza, Ohnbinkwin and Thaechaung during rainy and cool-dry months. Larval surveys also showed An. dirus larvae/pupae were caught from domestic wells (6 to 46% found positive). Clinical surveys indicated that transmission is hyperendemic and occur all year round in all four villages.

Chimpanzees and supporting models in the study of malaria pre-erythrocytic stages

Chimpanzees are being used in the study of immune response to Plasmodium falciparum malaria pre-erythrocytic stages (MPES). Responses induced by immunisation with recombinant/synthetic antigens and by irradiated sporozoites are being evaluated in a model system that is phylogenetically close to humans and that is amenable to limited manipulation not possible in humans. The value of chimpanzees for the in-depth study of immunological mechanisms at work in MPES-induced protection are discussed. A total number of 7 chimpanzees have been used to evaluate the immune response to recombinant antigens, and 5 have been challenged with large numbers of sporozoites, followed by surgical liver-wedge resection, in order to generate infected liver tissue for histological and immunological studies. As a complementary model, SCID mice carrying live, transplanted human and primate hepatocytes have been inoculated with sporozoites and infection of transplanted cells has been monitored by histological and immunological methods. In ongoing experiments chimpanzees are being immunised with MPES-derived lipopeptides that have been shown to overcome MHC restriction in mice, and with irradiated sporozoites.

Pharmacokinetics of quinine, quinidine and Cinchonine when given as combination.

Pharmacokinetics of quinine, quinidine and cinchonine when given as a combination were evaluated in Thai patients with falciparum malaria during acute infection and convalescence. The combination of quinine, quinidine and cinchonine was randomly given to thirteen patients at 400 mg or 600 mg (consisting of one-third of each component; 7 patients were enrolled in 400 mg regimen and 6 in 600 mg regimen) intravenously every 8 hours for 7 days. The drug combination was given again at day 35 to define the pharmacokinetics of each drug during convalescence. All patients with the 600 mg regimen had good response with 100% cure rate while patients with the 400 mg regimen had a good initial response but one patient recrudesed on day 46. This particular patient had plasma concentrations of all three drugs lower than the mean values of patients with sensitive responses. The plasma levels of quinine and quinidine obtained from the present study were higher than that expected from one-third of the conventional dose (600 mg) when given alone, suggesting drug combination interaction. The terminal half-lives of each of the three components were prolonged during acute malaria when compared to those obtained during convalescence.

Mefloquine resistant malaria in cameroon and correlation with resistance quinine

Based on the results of in vitro sensitivity of Plasmodium falciparum to chloroquine, quinine and mefloquine, and evaluation of drug consumption conducted in 1987-1988 in four areas in the noth and south-west of Cameron, two opposite situations were encountered in this country. In northern Cameron where mefloquine resistance is prevalent a close correlation was found between the responses of P. falciparum to mefloquine and to quinine, but not between mefloquine and chloroquine. In the south, where chloroquine resistance is highly prevalent, no correlation was found neither between mefloquine and chloroquine nor mefloquine and quinine, but the responses to quinine and chloroquine appear partly correlated. These lead to formulate the hypothesis of a "southern" type of P. falciparum submitted to a high chloroquine drug pressure inducing a secondary cross resistance, whilst a "northern"type submitted to a relatively high and abortive quinine drug pressure inducing a primary quinine resistance and a secondary cross resistance with mefloquine

Immunological evaluation of cell-mediated and humoral immunity in Thai patients with cerebral and non-cerebral Plasmodium falciparum malaria: I. Cutaneous delayed hypersensitivity, blood leukocytes and in vitro lymphocyte responses.

In Thai patients with acute P. falciparum malaria including cerebral cases, cell mediated immune functions were studied in vivo and in vitro. Initial cutaneous delayed reactions to phytohaemagglutinin and soluble protein antigens were negative in most cerebral malaria patients. No major alteration of the number of circulating T and B cells was observed. In lymphocytes cultures, proliferatives responses to lectins or protein antigens were generally found within normal ranges. This study shows a direct role of P. falciparum on the impairment of cell mediated immunity.

Immunological evaluation of cell-mediated and humoral immunity in Thai patients with cerebral and non cerebral Plasmodium falciparum malaria: II. Evolution of serum levels of immunoglobulins, antimalarial antibodies, complement fractions and alpha interferon.

In Thai patients with Plasmodium falciparum malaria, IgG and IgM values were elevated, whereas IgA levels were within normal ranges. No association of Ig values with parasitaemia was noted. IFA-IgM antibody levels were lower in cerebral malaria (CM) than in the non cerebral malaria (NCM) group. IFA-IgG antibodies were present in all patients. The mean C3 and C4 values were similar among patients from the CM and NCM groups. Interferon like activity was detected in all CM and NCM patients, and no correlation was found with either antimalarial antibodies, complement or parasitaemia.

Anti-P1, allohemagglutinins associated with Clonorchis sinensis and opisthorchis viverrini infections in patients from Southeast Asia.

An automated assay of anti-P1 allohemagglutinins has been carried out on sera of 61 individuals from Southeast Asia : 28 with clonorchiasis, 18 with opisthorchiasis and 15 control subjects. Anti-P1 activity was detected in 61% of the opisthorchiasis sera, 57% of the clonorchiasis sera and in 26.6% of the control subjects. Their concentration, in the sera, was low in control subjects and exceptionally high in clonorchiasis and opisthorchiasis (up to 13 and 22 times the maximum concentration of the control subjects, respectively). In all cases the anti-P1 antibodies were of IgM class. The results suggested that Clonorchis and Opisthorchis were responsible for immunization of the patients, with P1 alloantigen.