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Biomedical subjects

K N Mendis

Publications and source records attributed to K N Mendis.

At least 37 records · Page 2Linked to original sources
PubMed1994

Plasmodium vivax merozoite surface protein 1 C-terminal recombinant proteins in baculovirus.

Recombinant proteins derived from the Plasmodium vivax merozoite surface protein 1 have been produced in the baculovirus expression system. These proteins correspond approximately to the Plasmodium vivax analogs of the 42-kDa or 19-kDa C-terminal processing products previously described for Plasmodium falciparum. Each was produced in two versions, either as a membrane-bound entity located on the cell surface and probably carrying a glycosylphosphatidylinositol addition, or as a secreted entity lacking a membrane anchor. Many native conformational epitopes appear to be accurately reproduced in these molecules. Both the 42-kDa and 19-kDa analogs can be N-glycosylated in the baculovirus system and the N-glycosylation appears to be necessary for efficient secretion of both the 42-kDa and 19-kDa recombinant proteins.

Amino Acid Sequence↗
PubMed1993

Plasmodium vivax:recombination between potential allelic types of the merozoite surface protein MSP1 in parasites isolated from patients.

The merozoite surface protein MSP1, which is one of the most promising candidates for a malaria vaccine directed against erythrocytic stages, has been shown to be polymorphic in different malarial species. Characterization of the Plasmodium vivax MSP1 gene (Pv200) in two strains (Belem and Salvador-1) revealed the existence of several polymorphic regions. One of these regions has been examined here in primary parasite isolates obtained from patients in Sri Lanka. Oligonucleotide primers hybridizing to conserved parts of the gene on either side of a polymorphic region were used to amplify DNA from 22 isolates. Sequence analysis of the amplified portion of the MSP1 gene in five patients showed the existence of three types of polymorphic regions. Two were almost identical either to that of the Belem or to that of the Salvador-1 strain. The third polymorphic type appeared to have resulted from recombination between the two others. This recombination event took place inside a repeated part of the sequence.

Adult↗
PubMed1993

Cytokine-mediated inactivation of malarial gametocytes is dependent on the presence of white blood cells and involves reactive nitrogen intermediates.

Supernatants of human peripheral blood mononuclear cells (PBMC) incubated for 24 hr in the presence of extracts of freeze-thawed blood stage parasites of Plasmodium vivax or P. falciparum mediate inactivation of gametocytes of either species when incubated in vitro with whole human blood cells. Cultured P. falciparum gametocytes incubated with these malaria extract-stimulated PBMC supernatants in the presence of human blood from which white blood cells (WBC) had been removed were not inactivated. Thus the effects of the PBMC supernatants on gametocyte infectivity were dependent upon the presence of WBC. The suppressive effects mediated in the presence of WBC could be partially reversed in the presence of concentrations of 1 mM or higher of the L-arginine analogue NGL-monomethyl arginine acetate (L-NMMA). Our results indicate that the effects of WBC in inactivating gametocytes are due, at least in part, to a mechanism involving an L-arginine-dependent pathway. Previous studies have shown that the mediators of gametocyte inactivation in the stimulated PBMC supernatants comprised tumour necrosis factor (TNF) acting in conjunction with unidentified, but essential, 'complementary factors'. In the present study we show that these mediators, TNF and complementary factors, affect gametocytes indirectly through their interaction with WBC.

Animals↗
PubMed1992

Dynamics of fever and serum levels of tumor necrosis factor are closely associated during clinical paroxysms in Plasmodium vivax malaria.

Paroxysms are sharp episodes of high fever accompanied by chills and rigors that occur periodically, once in every 48 hr in Plasmodium vivax infections. We have measured the changing levels of serum tumor necrosis factor (TNF) during paroxysms in non-immune patients infected with P. vivax malaria. The changes in TNF levels closely paralleled the rise and fall in temperature during the paroxysms but tended to precede them by 30-60 min. These observations suggest that the rise and fall in temperature during P. vivax paroxysm may be directly related to the periodic changes in TNF levels induced during these infections. The peak TNF levels reached during P. vivax infections were much higher than even those which have been recorded during severe and fatal P. falciparum infections in which TNF has been postulated to contribute to the severe manifestations of this disease.

Activity Cycles↗
PubMed1992

Method to estimate relative transmission efficiencies of Anopheles species (Diptera: Culicidae) in human malaria transmission.

A mathematical expression was derived to estimate the relative malaria transmission efficiency of an anopheline species with respect to a standard well-characterized species for which all vector parameters can be sufficiently determined. The method is particularly useful in situations where multiple anopheline species contribute to human malaria transmission and requires the estimation of the man-biting rate, the sporozoite rate, and the human malaria incidence. Under stable conditions of vector abundance, the average sporozoite rate in a species during a transmission season would by itself reflect its relative transmission efficiency. This "efficiency" then was used to calculate the "effective human-biting rate"; i.e., the human-biting rate of that species if it were to have ecological properties identical to those of the standard species. The standard well-characterized species then could be used with the effective human-biting rate of all species to quantify transmission, thus overcoming the need to measure vector parameters for all anopheline species contributing to transmission. An expression also was derived to calculate the relative contribution made by each species to malaria transmission. The usefulness of this method was illustrated using entomological and epidemiological data from Kataragama, Sri Lanka.

Animals↗
PubMed1992

Tumour necrosis factor-dependent parasite-killing effects during paroxysms in non-immune Plasmodium vivax malaria patients.

Plasmodium vivax malaria infections in non-immune individuals manifest as periodic clinical episodes of fever with chills and rigors known as paroxysms. We have demonstrated that in non-immune patients the period of paroxysm is associated with the transient presence of plasma factors which kill gametocytes, the intra-erythrocytic sexual stages of the malaria parasite which transmit the infection from humans to mosquito, rendering them non-infectious to mosquitoes. Gametocyte killing in paroxysm plasma is mediated by tumour necrosis factor (TNF) acting in conjunction with other essential serum factor(s). Plasma TNF levels were elevated during a paroxysm. In semi-immune individuals from a P. vivax-endemic area clinical symptoms of malaria are mild and the parasite killing factors are not induced during paroxysm. Serum TNF levels were correspondingly lower in endemic patients during a paroxysm. Human peripheral blood mononuclear cells (PBMC) can be stimulated in vitro by extracts of P. vivax blood stage parasites to produce TNF and associated parasite killing factor(s), thus simulating in vitro the events that occur during a paroxysm, this being the release of parasite exo-antigens by rupturing schizonts and the subsequent induction of PBMC to produce TNF and other parasite-killing factors. We were able to show that convalescent serum from P. vivax semi-immune individuals block the induction of TNF and parasite-killing factors by malaria antigens in vitro, presumably through antibodies that neutralize parasite exo-antigens. Thus, individuals living in malaria-endemic areas appear to acquire clinical immunity to malaria by avoiding their induction during infection; we have shown that one such mechanism is the neutralization of parasite exo-antigens that induce the production of parasite killing factors.

Animals↗
PubMed1992

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.

Adolescent↗
PubMed1992

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.

Adolescent↗
PubMed1992

Serological relationship of tumor necrosis factor-inducing exoantigens of Plasmodium falciparum and Plasmodium vivax.

Exoantigens of Plasmodium vivax-parasitized erythrocytes stimulated macrophages to secrete tumor necrosis factor, and antisera raised against the exoantigens inhibited this secretion. The antisera also inhibited the activity of Plasmodium falciparum and Plasmodium yoelii exoantigens, and conversely, antisera against the latter cross-reacted with the exoantigens of P. vivax.

Animals↗
PubMed1992

The role of cytokines in Plasmodium vivax malaria.

The cytokine tumor necrosis factor and other as yet unidentified factor(s) which together mediate the killing of intraerythrocytic malaria parasites are transiently elevated in sera during paroxysms in human Plasmodium vivax infections in non-immunes. These factors which included TNF and parasite killing factor(s) are associated with the clinical disease in malaria to the extent that their transient presence in infection sera coincided with paroxysms, the the most pronounced clinical disturbances of P. vivax malaria and secondly because their levels were markedly lower in paroxysm sera of semi-immune patients who were resident of an endemic area. Further, a close parallel was obtained between serum TNF levels and changes in body temperature that occur during a P. vivax paroxysm in non-immune patients, suggesting a causative role for TNF in the fever in malaria. P. vivax rarely if ever cause complicated clinical syndromes. Nevertheless serum TNF levels reached in acutely ill P. vivax patients were as high as in patients suffering from cerebral complications of P. falciparum malaria as reported in studies from the Gambia. Cytokine profiles and other changes accompanying clinical disease in P. vivax and P. falciparum malaria are compared in this paper with a view to discussing the potential role of cytokines in the causation of disease in malaria.

Fever↗
PubMed1991

Cytokines kill malaria parasites during infection crisis: extracellular complementary factors are essential.

Malaria infection crisis, at which the parasitemia drops precipitously and the parasite loses infectivity to the mosquito vector, occurs in many natural malaria systems, and has not been explained. We demonstrate that in a simian malaria parasite (Plasmodium cynomolgi in its natural host, the toque monkey), the loss of infectivity during crisis is due to the death of circulating intraerythrocytic gametocytes mediated by crisis serum. These parasite-killing effects in crisis serum are due to the presence in the serum of cytokines tumor necrosis factor and interferon gamma, which are produced by the host as a result of the malaria infection. The killing activity of each cytokine is absolutely dependent upon the presence of additional, as yet unidentified factor(s) in the crisis serum.

Animals↗
PubMed1991

Antigenic polymorphism in malaria: is it an important mechanism for immune evasion?

Malarial infections do not readily evoke an effective protective immunity against re-infection. Possible reasons for this include the ability of the parasites to interfere with the host's immune response and to evade the response in an immune host, by, for example, exploiting antigenic polymorphism or variation. Antigenic polymorphism undoubtedly exists in malaria parasite populations but does this polymorphism actually contribute to immune evasion by the parasite? Here, Kamini Mendis and colleagues examine the evidence for this and its implications for future malaria vaccines.

Animals↗
PubMed1991

Infectious reservoir of Plasmodium vivax and Plasmodium falciparum malaria in an endemic region of Sri Lanka.

The infectious reservoir of Plasmodium vivax and P. falciparum in a malaria endemic region in Sri Lanka was defined in a population of 3,625 by directly feeding mosquitoes on a sample of infected individuals during a period of 17 months. The malaria case incidence in this population was concurrently monitored. P. vivax gametocyte densities were highest in the youngest age groups, and decreased steadily with increasing age. However, the infectivity per gametocyte appeared to be lower in the younger age groups than in the older ones. There was no significant correlation between the age of patients and their gametocyte densities for P. falciparum, to which this population was only recently exposed, nor was there a discernible trend in the infectivity per gametocyte in different age groups. The average infectivity of patients was lowest in the youngest (0-5 years) and the oldest (greater than 50) age groups. The contribution made by P. vivax patients in the different age groups to the reservoir of infection was estimated. Patients in the 6-25 year age groups made the largest contribution to the reservoir, followed by those in the 26-50 year age group. Patients in the youngest and the oldest age groups contributed least to the infectious reservoir. When population sizes in the different age groups were taken into consideration, the age groups between 6 and 50 years contributed almost equally to approximately 87% of the infectious reservoir. The reservoir of P. falciparum malaria was very small, being confined to 9% of the patients, and this appears to be a characteristic of epidemic malaria, as was the case with P. falciparum.

Acute Disease↗
PubMed1991

Clustering of malaria infections within an endemic population: risk of malaria associated with the type of housing construction.

The occurrence of malaria infections due to Plasmodium vivax and P. falciparum was monitored in a population of 3,023 people living in six contiguous villages in Kataragama, an area of endemic malaria in southern Sri Lanka, over a period of 17 months. The annual incidence of malaria in this population during the study period was 25.8%. Malaria attacks were clustered, occurring more frequently than expected in certain individuals and housing groups and less frequently than expected in others. In one of these villages, the distribution of cases was examined in relation to locality and to the type of house construction. There was a strong association between the malaria incidence and house construction, independent of location. The risk of getting malaria was greater for inhabitants of the poorest type of house construction (incomplete, mud, or cadjan (palm) walls, and cadjan thatched roofs) compared to houses with complete brick and plaster walls and tiled roofs. Houses that were better constructed had a significantly lower malaria incidence rate (10.5%) than those that were poorly constructed (21.2%; P less than 0.01, by Student's t-test). There was also a significantly higher number of indoor resting mosquitoes collected from the poorly constructed houses than from those better constructed; the average (geometric mean) of mosquito densities found in houses of better versus poor construction were 0.97 and 1.89 per collection in the dry season, and 1.95 and 3.42 per collection in the wet season, respectively (P less than 0.05 in both seasons). This indicated that the higher malaria risk associated with poorly constructed houses was at least partly due to higher human-mosquito contact among their inhabitants.

Animals↗
PubMed1991

Immune responses against sexual stages of Plasmodium vivax during human malarial infections in Sri Lanka.

During natural infections of P. vivax malaria a variety of immune responses to the infection affect infectivity of the parasites to mosquitoes. Sexual stage antigens present in the blood stage parasites induce antibodies which may either enhance or suppress the infectivity of the sexual parasites to mosquitoes. Subsequent infections of P. vivax do not, unless occurring within less than 4 months, boost this response indicating a very short immune memory for the relevant antigens. Blood infection also results in the release of cytokines and other non-antibody factors which together can mediate death of the blood stage sexual parasites. These factors are associated with paroxysm in non-immune individuals. In individuals from an endemic area with age-acquired anti-disease immunity clinical symptoms are mild and the parasite killing factors are not induced.

Animals↗