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Biomedical subjects

P H David

Publications and source records attributed to P H David.

At least 19 recordsLinked to original sources
PubMed1995

Transmission blocking immunity in Plasmodium vivax malaria: antibodies raised against a peptide block parasite development in the mosquito vector.

One approach towards the development of a vaccine against malaria is to immunize against the parasite sexual stages that mediate transmission of the parasite from man to mosquito. Antibodies against these stages, ingested with the blood meal, inhibit the parasite development in the mosquito vector, constituting "transmission blocking immunity." Most epitopes involved in transmission-blocking immunity depend on the tertiary conformational structure of surface antigens. However, one of the transmission-blocking monoclonal antibodies we have raised against Plasmodium vivax reacts with a linear epitope on both asexual stages and gametes. This monoclonal antibody (A12) is capable of totally blocking development of the parasite in the mosquito host when tested in membrane feeding assays with gametocytes from P. vivax-infected patients. Immune screening of a P. vivax lambda gt11 genomic expression library with A12 led to the isolation of a clone to which was mapped the six-amino acid epitope recognized by A12. Antisera raised in mice against a 12-mer synthetic peptide containing this epitope coupled to bovine serum albumin not only had high titers of antipeptide antibodies as measured by enzyme-linked immunosorbent assay, but in addition recognized the same 24- and 57-kD parasite components as A12 on Western blots and reacted with the parasite by immunofluorescence. When tested in membrane feeding assays, these antibodies have significant suppressive effects on parasite development in the mosquito.

Amino Acid Sequence↗
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

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 2. Mortality and morbidity from malaria in the study area.

Background data on child mortality and morbidity from malaria were obtained in a new study area in the centre of The Gambia, south of the river, chosen as the site for a malaria intervention trial. Infant and child mortality rates were 120 and 41 per 1000 respectively. Results obtained using post-mortem questionnaires suggested that malaria was an uncommon cause of death in children under the age of one year but responsible for about 40% of deaths in children aged 1-4 years. Ninety-two percent of deaths attributed to malaria occurred during or immediately after the rainy season. Parasite and spleen rates in children aged 1-5 years at the end of the malaria transmission season were 66% and 64% respectively. Malariometric indices were similar in primary health care (PHC) villages, selected as sites for an intervention with insecticide-treated bed nets and targeted chemoprophylaxis, and in smaller, non-PHC, control villages.

Cause of Death↗
PubMed1993

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 6. The impact of the interventions on mortality and morbidity from malaria.

The effects of insecticide-impregnated bed nets on mortality and morbidity from malaria have been investigated during one malaria transmission season in a group of rural Gambian children aged 6 months to 5 years. Sleeping under impregnated nets was associated with an overall reduction in mortality of about 60% in children aged 1-4 years. Mortality was not reduced further by chemoprophylaxis with Maloprim given weekly by village health workers throughout the rainy season. Episodes of fever associated with malaria parasitaemia were reduced by 45% among children who slept under impregnated nets. The addition of chemoprophylaxis provided substantial additional benefit against clinical attacks of malaria; 158 episodes were recorded among 946 children who slept under impregnated nets but who also received chemoprophylaxis. Chemoprophylaxis reduced the prevalence of splenomegaly and parasitaemia at the end of the malaria transmission season by 63% and 83% respectively. Thus, insecticide-impregnated bed nets provided significant protection in children against overall mortality, mortality attributed to malaria, clinical attacks of malaria, and malaria infection. The addition of chemoprophylaxis provided substantial additional protection against clinical attacks of malaria and malaria infection but not against death.

Antimalarials↗
PubMed1991

The effect of insecticide-treated bed nets on mortality of Gambian children.

Insecticide treatment of bed nets ("mosquito nets") may be a cheap and acceptable method of reducing the morbidity and mortality caused by malaria. In a rural area of The Gambia, bed nets in villages participating in a primary health-care (PHC) scheme were treated with permethrin at the beginning of the malaria transmission season. Additionally, children aged 6 months to 5 years were randomised to receive weekly either chemoprophylaxis with maloprim or a placebo throughout the malaria transmission season. We measured mortality in children in PHC villages before and after the interventions described, and compared this with mortality in villages where no interventions occurred (non-PHC villages). About 92% of children in PHC villages slept under insecticide-treated bed nets. In the year before intervention, mortality in children aged 1-4 years was lower in non-PHC villages. After intervention, the overall mortality and mortality attributable to malaria of children aged 1-4 in the intervention villages was 37% and 30%, respectively, of that in the non-PHC villages. Among children who slept under treated nets, we found no evidence of an additional benefit of chemoprophylaxis in preventing deaths. Insecticide-treated bed nets are simple to introduce and can reduce mortality from malaria.

Antimalarials↗
PubMed1991

Primary structure of the merozoite surface antigen 1 of Plasmodium vivax reveals sequences conserved between different Plasmodium species.

Merozoite surface antigen 1 (MSA1) of several species of plasmodia has been shown to be a promising candidate for a vaccine directed against the asexual blood stages of malaria. We report the cloning and characterization of the MSA1 gene of the human malaria parasite Plasmodium vivax. This gene, which we call Pv200, encodes a polypeptide of 1726 amino acids and displays features described for MSA1 genes of other species, such as signal peptide and anchoring sequences, conserved cysteine residues, number of potential N-glycosylation sites, and repeats consisting here of 23 glutamine residues in a row. When the nucleotide and deduced amino acid sequences of the MSA1 of P. vivax are compared to those of another human malaria parasite, Plasmodium falciparum, and to those of the rodent parasite Plasmodium yoelii, 10 regions of high amino acid similarity are observed despite the very different dG + dC contents of the corresponding genes. All of the interspecies conserved regions reside within the conserved or semiconserved blocks delimited by the sequences of different alleles of the MSA1 gene of P. falciparum.

Amino Acid Sequence↗
PubMed1991

Using routine surveys to measure mortality: a tool for programme managers.

Aid donors and recipients have begun to demand timely, population-based information for programme planning and for measuring health programme performance. Results from trials in Jordan, Syria, Djibouti and People's Democratic Republic of Yemen show that widely-used routine surveys for estimating vaccination coverage can be adapted to collect data on health indicators such as child and maternal mortality. Estimation methods must be robust and fieldwork well-supervised. Adding questions about total children ever born and surviving, the survival of the preceding birth, and the survival of sisters to such surveys, population-based estimates of the trend and recent level of childhood mortality and of the lifetime risk of maternal death can be obtained. These trials indicate that the need to monitor selected health indicators could be met through inexpensive, low-technology surveys.

Adult↗
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↗
PubMed1990

Human T cell proliferative responses to Plasmodium vivax antigens: evidence of immunosuppression following prolonged exposure to endemic malaria.

Human T cell proliferative responses, of 33 adult Sri Lankans convalescing from Plasmodium vivax infections, to several P. vivax antigens (i.e. a soluble extract of asexual erythrocytic stage parasites and two cloned antigens that are potential vaccine candidates PV200 and GAM-1) were assessed. The peripheral blood mononuclear cell proliferative responses to the soluble extract of P. vivax, as assessed by studying both the proportion of responders and the degree of the response, were significantly lower in a group of individuals resident in a malaria endemic area in Sri Lanka than in another group that did not have a life-long exposure to malaria but had acquired the disease on a visit to an endemic region. Individuals of both groups responded equally well to mitogen. The responses to a non-malarial antigen such as purified protein derivative of tuberculin were only marginally lower in residents of the malaria-endemic region. These findings suggest that exposure to endemic P. vivax malaria leads to a specific immunosuppression to P. vivax antigens. Immunosuppression of a much lower degree was evident to a non-malarial antigen.

Adolescent↗
PubMed1990

Human immune responses against sexual stages of malaria parasites: considerations for malaria vaccines.

Studies on the natural immune responses to the sexual stages of malaria parasites have been reviewed in the context of human malaria transmission-blocking vaccines. Antibodies against the sexual stages of the malaria parasite, gametocytes and gametes, are readily evoked by natural malaria infections. These antibodies that suppress infectivity at high concentrations can, at low concentrations, enhance the development of the parasite in the mosquito; however, because enhancing antibodies are prevalent during natural malaria infections, it is likely that a vaccine would rapidly boost these antibodies to blocking levels. The immunogenicity of sexual stage antigens appears to be constrained in the human host, probably due to T epitope polymorphism and MHC restriction in humans. These constraints apply mainly to those antigens that are sensitive targets of host immunity such as the gamete surface antigens and not to internal gamete antigens, indicating that antigenic polymorphism may have evolved in response to immune selection pressure. Evidence for immunosuppression of the host by exposure to endemic malaria is presented and its consequences on vaccine development are discussed.

Animals↗
PubMed1990

Genetic complexity of Plasmodium vivax parasites in individual human infections analyzed with monoclonal antibodies against variant epitopes on a single parasite protein.

Monoclonal antibodies against variant epitopes of a highly polymorphic protein (PV200) in schizonts of Plasmodium vivax have been used to analyze the variety of genetically distinct populations of parasites present in the peripheral blood of individual P. vivax infections in Sri Lanka. In 9 out of 10 isolates of freshly drawn P. vivax infected blood from different individuals, parasites of only 1 PV200 serotype was found within each individual infection, even though parasites were serotypically distinct between individuals. In 1 isolate parasite population, 3 distinct PV200 serotypes were identified. Thus, most P. vivax infections appeared to consist of a single genetically homogeneous population of parasites within the detection limits of the technique. The prevalence of P. vivax infections in an area of malaria transmission in southern Sri Lanka and the densities of oocysts in mosquitoes fed on P. vivax infected individuals indicated that parasite populations would be transmitted many times before encountering parasites of other origins, and that individual populations would tend to reduce to genetic homogeneity during transmission. These expectations are consistent with the high proportion of genetically homogeneous P. vivax isolates observed.

Adult↗
PubMed1989

Uninfected erythrocytes form "rosettes" around Plasmodium falciparum infected erythrocytes.

The human malaria parasite, P. falciparum, exhibits cytoadherence properties whereby infected erythrocytes containing mature parasite stages bind to endothelial cells both in vivo and in vitro. Another property of cytoadherence, "rosetting," or the binding of uninfected erythrocytes around an infected erythrocyte, has been demonstrated with a simian malaria parasite P. fragile which is sequestered in vivo in its natural host, Macaca sinica. In the present study we demonstrate that rosetting occurs in P. falciparum. Rosetting in P. falciparum is abolished by protease treatment and reappears on further parasite growth indicating that, as in P. fragile, it is mediated by parasite induced molecules which are protein in nature. P. vivax and P. cynomolgi, which are not sequestered in the host, did not exhibit rosetting. Rosetting thus appears to be a specific property of cytoadherence in malaria parasites.

Animals↗
PubMed1989

Continuous monitoring of child mortality from clinic records.

A simple method is described for estimating childhood mortality when mothers are seen at or soon after a birth. The main bias in the method arises from omission of reports from mothers not contacted in the immediate postnatal period. Recent work indicates that the key question on the survival of the preceding born child might be usefully included in household surveys. A comparison between data from Tari, Papua New Guinea on childhood mortality collected as part of a regular community surveillance scheme and the results from asking the supplementary question in clinics indicates that the simpler preceding birth technique appears to give good results quickly and cheaply.

Actuarial Analysis↗
PubMed1988

Plasmodium vivax: karyotype polymorphism of field isolates.

Pulse-field gradient electrophoresis (PFG) has been applied to the karyotype analysis of Plasmodium vivax isolates obtained directly from infected patients in Sri Lanka. Detection of separated chromosomes was performed either by ethidium bromide staining of gels or by hybridization with a telomer specific probe. Each of the 15 different isolates examined exhibited a different chromosome migration pattern, indicating that a high level of polymorphism prevailed in wild populations of P. vivax. Chromosome size variation was further confirmed using a P. vivax chromosome-specific probe which also demonstrated that, in each isolate, the parasite population appeared to be homogeneous. These observations were made directly on parasites from infected blood, without the necessity for culture amplification, indicating that PFG can be used on a large scale for the epidemiological analysis of wild parasite populations.

Animals↗
PubMed1988

Plasmodium vivax: cloning and expression of a major blood-stage surface antigen.

Plasmodium vivax is a highly prevalent malaria pathogen of man; the following report is the first to describe the cloning and expression of a major asexual erythrocytic stage antigen of this species. The screening of a genomic DNA expression library with a monoclonal antibody directed against a 200-kDa surface component (Pv200) of the more mature schizonts of P. vivax led to the selection of a recombinant bacterial clone which produced a fusion protein. Mouse and rabbit immune sera raised against the purified fusion protein recognized the 200-kDa parasite antigen on Western blots and reacted with the surface of segmenters by immunofluorescence. Sequencing of the 1.9-kb P. vivax DNA insert coding for this fusion protein revealed a 45-47% homology at the nucleotide level with the P. falciparum gene of a parasite surface antigen, Pf195, which has been shown to be a promising candidate for a malaria vaccine in primates and in man.

Amino Acid Sequence↗