Vaccination to prevent transmission of Plasmodium yoelii malaria

Summary It was possible to block the transmission of infection of the rodent malaria parasite Plasmodium yoelii nigeriensis to Anopheles stephensi mosquitoes by immunizing mice with a vaccine containing formalin-fixed gametes. Both intramuscular and intravenous routes were effective, immunity was achieved with a single dose and the immunity persisted for 6 months at least. Transmission-blocking immunity was found to reside in a serum factor, probably antibody, and to be directed against extracellular gametes, acting on them in the gut of the mosquito, while gametocytes in the circulation of the vertebrate host remained unaffected. The gamete vaccine afforded partial protection against the disease, but immunization with asexual parasites alone showed that this protection was due largely to the presence of asexual forms as contaminants and that anti-gamete immunity is stage specific.     

Anti-circumsporozoite protein antibodies measure age related exposure to malaria in Kataragama, Sri Lanka

Antibodies to two peptides DDAAD and (NANP)40 representing the repetitive sequence of circumsporozoite antigens (CS protein) of P. vivax and P. falciparum respectively were measured in a cohort of 149 and 107 individuals respectively at four, 6 monthly blood surveys performed on residents of Kataragama, a P. vivax malaria endemic region in southern Sri Lanka. The prevalence of antibodies to the CS protein of both species was relatively low being less than 20% to either peptide in the population as a whole, this being consistent with the low entomological inoculation rates in the area. A marked age related prevalence pattern was evident, with the prevalence of antibodies increasing with age to reach between 25 to 30% in the 25-50 year age group in both P. vivax and P. falciparum. The population had had a life long exposure to P. vivax malaria but not to P. falciparum, an epidemic of which occurred in this region a few months prior to the beginning of this study. Nevertheless, the age-related prevalence of these antibodies was identical with respect to the two species. This suggests that the age-related prevalence pattern reflected differences in inoculation rates between the age groups due to differences in exposure to inoculation rather than an age acquired response resulting from a cumulative experience over several years. An analysis of antibody prevalence in individuals showed first, that sporozoite inoculations must have been clustered rather than homogeneously distributed in the population and secondly, that sero-conversion did not correlate with malaria infections in these individuals.     

General intellectual ability of university entrants in Sri Lanka†

Students are admitted to university in Sri Lanka on the basis of aggregate marks above a certain cut-off point obtained at the GCE (advanced level) examination. On this criterion and on a district-quota basis operative for the whole island, high performers are admitted to the medical faculties. Those with lower aggregate marks are admitted to the other life science faculties. High performance at the GCE (advanced level) examination is considered to reflect high general intellectual ability and vice versa. A group of students who failed to obtain university admission on their relatively poor GCE (advanced level) examination performance was used for a preliminary study. This study revealed that several students were of high general intellectual ability. A similar study carried out on groups of new entrants to the life science courses at the University of Peradeniya (which included medical students) showed that the groups did not differ significantly in general intellectual ability from the non-University group. Students of high general intellectual ability were found distributed evenly in all the groups studied.     

Transmission blocking immunity to human Plasmodium vivax malaria in an endemic population in Kataragama, Sri Lanka

Serum effects on gametocyte infectivity, that is, transmission blocking/enhancing immunity, were measured in the sera of 196 acute Plasmodium vivax patients who were residents of a malaria region in Kataragama, southern Sri Lanka. Direct mosquito feedings were also performed on 170 of these patients. Sera of about 48% of patients suppressed gametocyte infectivity significantly (by more than 75%) and of a smaller proportion (12%) had pronounced infectivity enhancing effects. Transmission immunity did not increase with age of patients, rather, immunity tended to be higher in younger patients. Data suggest that immunity levels are boosted by reinfections only if they occur within a period of 4 months from the previous infection, i.e., that immune memory for boosting does not last beyond 4 months. Enhancing effects in the sera of patients correlated with the absence of gametocytes at the time of investigation suggesting that enhancement occurs early during the course of a blood infection, and blocking later, when serum antibodies reach higher levels. The blocking and enhancing effects of serum appears to depend not only on the antibody concentration in serum, but also on the intrinsic infectivity of the parasite isolate against which it is tested: thus, infectivity enhancing effects were potentiated by low intrinsic infectivities of the parasite isolate. The direct infectivity of patients to mosquitoes correlated with transmission immunity indicating that transmission immunity is an influential factor determining infectivity of malaria patients.     

Plasmodium falciparum malaria transmission-blocking immunity under conditions of low endemicity as in Sri Lanka

Sera from acute primary Plasmodium falciparum patients in Sri Lanka were tested for the presence of antibodies against gamete antigens and for their functional effects of transmission blocking activity. Comparisons were made with corresponding data from a previous study from sera of patients from Papua New Guinea where malaria is more highly endemic. Although the prevalence of anti-gamate antibodies in the two groups were broadly similar, the prevalence of infectivity suppressive effects in the Sri Lankan sera (56%) was less than in Papua New Guinea sera (75%), suggesting that the generation of functionally effective transmission blocking antibodies requires prolonged exposure to multiple inoculations of malaria. In Papua New Guinea sera there was a good correlation between transmission blocking effects and antibody responses to Pfs 230, a known target of transmission blocking antibodies. Among the Sri Lankan sera no strong correlation was found between transmission blocking effects and the presence of antibodies to gamete surface antigens Pfs 230 nor Pfs 48/45 as detected by immunoprecipitation of radio-iodinated gamate proteins; a strong correlation was however, found between the intensity of response to gamete surface antigens by IFA and transmission blocking effects of these sera. It is possible therefore, that the antigens identified by IFA include non-protein moieties and that these may be the targets of transmission blocking antibodies in sera from acute primary infections of P. falciparum.     

Tobacco use in a cohort of children in Sri Lanka

This study designed to examine the smoking behaviour and attitude of children were carried out on 3447, 11 to 18 year old Sri Lankan School children. The prevalence of smoking in urban and rural children are 7.2% and 4.3% respectively. 0.5% of children chew tobacco or use tobacco snuff. Friends smoking behaviour and attitude are the best predictors of smoking in children. The knowledge of health hazards of smoking is poor and is related to smoking behaviour.     

A malaria parasite toxin associated with Plasmodium vivax paroxysms

We have previously demonstrated a correlation between clinical paroxysms in Plasmodium vivax malarial infections and the appearance in patients' plasma of factors that kill blood stage parasites (gametocytes). This activity was, as previously shown, dependent on the presence in paroxysm plasma of tumour necrosis factor-alpha (TNF-α), which acts in conjunction with other ‘complementary' factors. Here we have identified a parasite component which is essential for this activity and functions as a ‘complementary' factor together with TNF, and a third component of unknown origin. The P. vivax parasite component present in paroxysm plasma can be substituted for by a blood-stage schizont extract of either P. vivax or P. falciparum. This was demonstrated by restoring the parasite-killing activity to post-paroxysm plasma (from which it was absent) with the addition of the extracts together with TNF. The active materials in these extracts, however, are different from the natural components in P. vivax paroxysm plasma, i.e. while the schizont extracts are immunologically cross-reactive between species, the activity of the natural P. vivax toxin(s) in patients' plasma is neutralized only by the homologous antisera. Plasmodium falciparum infections have neither distinct paroxysms nor parasite-killing activity in plasma. The pronounced paroxysms of P. vivax infections may thus be due in part to a species-specific toxin(s).