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Biomedical subjects

K Mendis

Publications and source records attributed to K Mendis.

12 recordsLinked to original sources
PubMed1998

One-day general practice morbidity survey in Sri Lanka.

BACKGROUND: National morbidity surveys provide valuable data for monitoring the health needs of populations, health policy planning and design of medical curricula. In order to meet a long-standing need for such information in Sri Lanka, a nationwide general practice morbidity survey was conducted for the first time in 1996. OBJECTIVES: We aimed to identify people's needs by determining the reasons for encounter or the demand for care with GPs/family physicians, to illustrate the pattern of morbidity in general practice and to determine the average daily workload of GPs in Sri Lanka. METHOD: A random sample of 75 GPs were requested to complete a Practitioner Profile Questionnaire (PPQ) and to record on an encounter form (EF) the reason/s for encounter (RFE) and problems managed during all consultations on 4 July. Central coding of the RFEs and problems defined was done using the International Classification of Primary Care (ICPC). RESULTS: Forty GPs (53.3%) completed the PPQ, while the EF received a response from 34 (43.3%). The GP profile showed a male to female ratio of 7:1, none below 35 years and none qualified after 1984. The average daily workload was 74. It was estimated that GPs handle at least 26.5% of the primary care morbidity. Children accounted for 32% of consultations. There was a significantly higher proportion of children (P < 0.0001) and of the elderly (P < 0.05) in the consulting population compared with the general population. In 2068 encounters, 3448 RFEs and 2087 problems had been recorded. Respiratory and General chapters included 55% of the RFEs. By ICPC rubrics, 27 of the top thirty RFEs were for common symptoms. In addition to acute illnesses, asthma, hypertension and diabetes as well as preventive care activities were within the top 12 problems managed. CONCLUSIONS: The fact that many common illnesses, chronic diseases and preventive treatments are dealt with in general practice shows the necessity to include family medicine in the undergraduate curriculum of all medical schools. Undergraduate and postgraduate training in family medicine should concentrate more on child care and care of the elderly. Suitable incentives may be necessary to motivate younger doctors to become GPs to meet the medical care needs of the community.

Adolescent↗
PubMed1998

Baculovirus merozoite surface protein 1 C-terminal recombinant antigens are highly protective in a natural primate model for human Plasmodium vivax malaria.

A successful anti-blood stage malaria vaccine trial based on a leading vaccine candidate, the major merozoite surface antigen-1 (MSP1), is reported here. The trial was based on Plasmodium cynomolgi, which is a primate malaria parasite which is highly analogous to the human parasite Plasmodium vivax, in its natural host, the toque monkey, Macaca sinica. Two recombinant baculovirus-expressed P. cynomolgi MSP1 proteins, which are analogous to the 42- and 19-kDa C-terminal fragments of P. falciparum MSP1, were tested by immunizing three groups of three animals each with either p42, p19, or both together. The vaccines were delivered subcutaneously in three doses at 4-week intervals with complete and incomplete Freund's adjuvants. Very high antibody titers were obtained against both vaccinating antigens as measured by enzyme-linked immunosorbent assay (10[6] and above) and against whole parasites as measured by indirect immunofluorescence assay (>10[5]), achieving, in most animals, about a 10-fold increase from the first to the last immunization. A blood stage challenge with P. cynomolgi parasites led, in three adjuvant-treated and three naive control animals, to blood infections which were patent for at least 44 days, reaching peak densities of 0.6 and 3.8%, respectively. In contrast, all except one of the nine animals in the three vaccinated groups were highly protected, showing either no parasitemia at all or transient parasitemias which were patent for only 1 or 2 days. When the three p19-vaccinated monkeys were rechallenged 6 months later, the protective efficacy was unchanged. The success of this trial, and striking analogies of this natural host-parasite system with human P. vivax malaria, suggests that it could serve as a surrogate system for the development of a human P. vivax malaria vaccine based on similar recombinant analogs of the P. vivax MSP1 antigen.

Animals↗
PubMed1994

Maternal inheritance of extrachromosomal DNA in malaria parasites.

Plasmodium falciparum has two extrachromosomal genomes, the mitochondrial 6-kb DNA element and the 35-kb circular DNA. The mitochondrial gene cytochrome b on the 6-kb element has been shown to be inherited uniparentally. In order to ascertain whether the route is maternal or paternal we have examined preparations of male and female gametes of the closely related Plasmodium gallinaceum for the presence of extrachromosomal DNA. DNA from purified preparations of gametes was hybridised to probes for both the 6-kb and 35-kb extrachromosomal genomes. Both probes hybridised to the preparation of Plasmodium gallinaceum female gametes but not to that of the males. We conclude that the extrachromosomal DNAs of malaria parasites are transmitted maternally.

Animals↗
PubMed1994

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-gamete 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 gamete 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.

Animals↗
PubMed1993

Transfection of the malaria parasite and expression of firefly luciferase.

The goal of this work is to develop a method for the functional analysis of malaria genes using the method of DNA transfection. We have developed a transient transfection vector by constructing a chimeric gene in which the firefly luciferase gene was inserted in frame into the coding region of the pgs28 gene of Plasmodium gallinaceum. This plasmid DNA was introduced into P. gallinaceum gametes and fertilized zygotes by electroporation, and luciferase expression was assayed after 24 hr. This report of successful introduction and expression of a foreign gene in a malaria parasite demonstrates the feasibility of this approach to developing methods for the functional analysis of parasite genes.

Animals↗
PubMed1993

Plasmodium vivax malaria in Sri Lanka: transmission, disease and immunity.

We have established a study site in a malaria endemic region around Kataragama in the south of Sri Lanka. A population of about 3,000 individuals in a group of villages around Kataragama have been provided with access to a small field clinic enabling us to monitor aspects of malarial infection under conditions of natural transmission. At the present time, both Plasmodium falciparum and Plasmodium vivax are prevalent to a similar degree although prior to about five years ago P. falciparum had been virtually absent for most of the previous ten years.

Animals↗
PubMed1992

Transmission immunity in malaria: reflections on the underlying immune mechanisms during natural infections and following artificial immunization.

Malaria transmission-blocking immunity has been studied in natural malarial infections in man, during infections in animals and following artificial immunization of animals with sexual stage malaria parasites. Effective immunity, which prevents infectivity of a malarial infection to mosquitoes, has been observed under all of these circumstances. Two general types of effector mechanism have been identified. One is an antibody mediated mechanism which acts against the extracellular sexual stages of the parasite within the midgut of a blood feeding mosquito. The other is a cytokine mediated mechanism which inactivates the gametocytes of the parasites while still in the circulation of the vertebrate host. Both effects have been observed during natural infections and following artificial immunization. The basis of induction of transmission-blocking immunity, including the nature of the memory for such immunity, however, may be very different in different host/parasite systems and during natural infection or following artificial immunization. Following artificial immunization a strong immune memory for transmission blocking immunity has been observed in animal systems. By contrast, following natural infections in man immune memory for transmission blocking immunity has been found to be weak and short lived if it occurs at all. It is suggested that the immunogens which induce natural transmission blocking immunity may be CD4+ independent.

Animals↗
PubMed1990

Use of synthetic peptides in the study of the antibody response to Plasmodium vivax sporozoites.

Synthetic peptides reproducing 4 DRADGQPAG (D4) and a sequential array of DRADGQPAG and DRAAGQPAG repeats (DDAAD) of the Plasmodium vivax circumsporozoite (CS) protein were investigated for their potential use in the detection of P. vivax sporozoite antibodies in human sera. These peptides specifically inhibited the binding of monoclonal antibodies to the P. vivax CS protein in Western blots. However, when D4 and DDAAD peptides were used in an enzyme-linked immunosorbent assay (ELISA) for the detection of human antibodies, more sera bound to the DDAAD (61%) than to the D4 peptide (22%). This binding was specific, and suggested that the DDAAD peptide contained epitopes constituted by the sequential array of DRADGQPAG and DRAAGQPAG repeat variants and absent in the D4 peptide. The ELISA using the DDAAD peptide was applied to the detection of P. vivax CS protein antibodies in a large number of sera from Kataragama, an endemic area in Sri Lanka. The prevalence of these antibodies increased with age, reaching 40% in adults greater than 50 years old. The ELISA employing the DDAAD peptide represents a simple and useful tool for the analysis of the antibody response to P. vivax sporozoites in naturally exposed individuals.

Age Factors↗
PubMed1990

Antibody responses to Plasmodium falciparum and P. vivax sporozoites in areas with stable and unstable malaria.

Availability of synthetic and recombinant peptides reproducing the repetitive regions of the circumsporozoite (CS) proteins of Plasmodium falciparum and P. vivax has allowed the development of assays for the detection of specific antibodies and of potential subunit vaccines. Knowledge of the immune responses to malaria sporozoites is a prerequisite for the optimal design of a sporozoite antigen-based vaccine. Studies carried out in areas with stable P. falciparum malaria (United Republic of Tanzania) have shown that antibodies against the synthetic peptide (NANP)40 increase as a function of age. Cluster analysis revealed marked inter-household variation of the anti-sporozoite antibody response, despite comparable risks of exposure to infectious bites. An age-related prevalence of anti-P. vivax sporozoite antibodies has been observed in an area of Sri Lanka with unstable malaria, using a 45-mer synthetic peptide reproducing a defined sequential array of the two main 9-mer variants of the P. vivax CS protein. In this area, anti-(NANP)40 antibodies became detectable after the first epidemic of P. falciparum malaria. Interestingly, their prevalence also increased with age. Since this population had not been exposed to P. falciparum malaria for at least 10 years previously, one can suggest that anti-sporozoite antibodies reflect the relative exposure to infectious bites in the different age groups, and, in turn, the transmission of the disease. This can be particularly useful in areas where entomological indices of transmission tend to be unreliable because of the low vectorial capacity and wide fluctuations in vector densities.

Age Factors↗