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P M Graves

Publications and source records attributed to P M Graves.

At least 19 recordsLinked to original sources
PubMed1999

Lack of association between early childhood immunizations and beta-cell autoimmunity.

OBJECTIVE: To determine whether early childhood immunization history affects the risk of developing the beta-cell autoimmunity that precedes type 1 diabetes. RESEARCH DESIGN AND METHODS: This article describes a case-control study whose participants were 317 children aged < or = 12 years who have a first-degree relative with type 1 diabetes. The children were enrolled in a prospective cohort study of the etiology of beta-cell autoimmunity, the Diabetes Autoimmunity Study in the Young, in Denver, Colorado. The main outcome measure was beta-cell autoimmunity as determined by persistent autoantibodies against insulin, GAD, or islet cell antibody (IA-2) 512. The number of cases with beta-cell autoimmunity was 25, and the number of control subjects (the remainder of the cohort) was 292. RESULTS: There was no difference between cases and control subjects in the proportion receiving hepatitis B (HBV), Haemophilus influenzae b (Hib), polio, or diphtheria tetanus pertussis (DTP) vaccines before 9 months of age; in the proportion receiving HBV at birth rather than later; or in the median age at first HBV, Hib, polio, or DTP vaccination. CONCLUSIONS: The results suggest that changing the early childhood immunization schedule would not affect the risk of developing beta-cell autoimmunity or type 1 diabetes.

Autoantibodies↗
PubMed1998

Comparison of the cost-effectiveness of vaccines and insecticide impregnation of mosquito nets for the prevention of malaria.

The cost-effectiveness of two different methods of prevention of morbidity and mortality due to Plasmodium falciparum malaria, vaccination and impregnation of mosquito nets with permethrin, was compared. The analysis was performed with reference to the cohort of all children born in The Gambia in 1990 and protected for 5 years, using estimates of costs from studies in The Gambia. The vaccine was assumed to be given in three doses before the age of 6 months, through the Expanded Programme of Immunization, and to remain effective up to the age of 5 years. The bednets were assumed to be impregnated at 6-monthly intervals over the 5-year period. The expected number of deaths and attacks due to P. falciparum in the first 5 years of the 1990 cohort's lives were estimated from published literature. The numbers of deaths and attacks averted by the two strategies were then estimated by decision analysis, using the best estimates of effectiveness available in the literature. The vaccine strategy would have averted an estimated 743 deaths and 50,502 malaria attacks, whereas the net impregnation would have averted 1537 deaths and 69,415 attacks. The estimated cost per death averted was U.S. $252 for the vaccine and U.S. $711 for net impregnation. The estimated cost per P. falciparum attack averted was U.S. $3.71 for the vaccine and U.S. $15.75 for net impregnation. Sensitivity analysis, examining the effect of varying the vaccine cost or insecticide cost, the efficacy of the vaccine or net impregnation, and the percentage coverage of the population, confirmed the greater cost-effectiveness of the vaccine strategy for either of the outcomes examined under the conditions of the model. However, limitations on the absolute number of deaths and malaria attacks which can averted by currently available vaccines demonstrate that a vaccine of higher efficacy would be highly desirable.

Bedding and Linens↗
PubMed1997

The role of enteroviral infections in the development of IDDM: limitations of current approaches.

Enteroviruses have been examined for their possible role in the etiology of IDDM for nearly 40 years, yet the evidence remains inconclusive. The mechanism of acute cytolytic infection of beta-cells, proposed by earlier studies, appears to be incompatible with the long preclinical period of autoimmunity preceding IDDM. Advances in molecular biology have improved our understanding of enteroviral biology and of potential alternative pathogenic mechanisms through which enteroviruses may cause diabetes. The focus of future human studies will likely shift from people with IDDM to those with prediabetic autoimmunity to determine whether acute enteroviral infections can promote progression from autoimmunity to overt diabetes. We propose that such studies use assays to detect enteroviral RNA, in addition to IgM serology. RNA assays can overcome sensitivity and type-specificity limitations of IgM assays as well as identify diabetogenic strains of enteroviruses, if such exist. Evaluation of the role of enteroviruses in triggering beta-cell autoimmunity in humans will require large prospective studies of young children. The Diabetes Autoimmunity Study in the Young--one of very few such studies currently underway--is focusing on potential interactions between HLA class II genes and enteroviral infections. Future studies will likely examine interactions between viral infections and non-HLA IDDM candidate genes, including those that may determine beta-cell tropism of candidate viruses.

Amino Acid Sequence↗
PubMed1995

The value of vector-based estimates of malaria transmission.

Estimating malaria transmission in the human is fraught with problems of reconciling clinical illness with parasitological status. It follows that there is a role for entomological assessments as an independent outcome variable and as a process indicator. Advances in DNA technology have expanded our capacity to identify vectors rapidly, while immunoassays allow the inoculation rate to be measured simultaneously in a number of villages with a precision 3-fold greater than measurements of vectorial capacity. The rapid specific identification of parasites in vectors has been utilized to estimate survivorship in mosquitoes per extrinsic incubation period (EIP), circumventing the need for estimates of survivorship per feeding cycle, lengths of feeding cycles or the length of the EIP. While lack of accuracy does not universally preclude the utility of estimates of the components of vectorial capacity in serving as relative estimates of transmission, particularly as process indicators, more accurate estimates of these parameters, particularly for density-dependent variables, may diminish the associated bias in their measurement. When this is accomplished, we will come closer to obtaining true rather than relative estimates of transmission.

Animals↗
PubMed1992

Malaria vaccines.

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Amino Acid Sequence↗
PubMed1992

Human antibody responses to epitopes on the Plasmodium falciparum gametocyte antigen PFS 48/45 and their relationship to infectivity of gametocyte carriers.

Antibodies in human sera recognizing epitopes I, IIa, III, and IV on the Plasmodium falciparum gametocyte antigen Pfs 48/45 have been investigated by competitive enzyme-linked immunosorbent assay. More than one-third of the residents of three villages in Madang, Papua New Guinea responded to epitopes I, IIa and III, with little variation by village or with time. There was a bimodal distribution of positive sera by age, with the highest proportion of responders in the 5-9- and greater than 20-year-old age groups. The data suggest a lower prevalence of antibodies against epitopes IIa and III in P. falciparum gametocyte carriers than in non-carriers. Enhancement of binding of monoclonal antibodies to epitopes IIa and III was also observed more frequently with sera from gametocyte carriers. Sera from gametocyte carriers in Papua New Guinea and Thailand, whose infectivity to mosquitoes had been tested, were used to examine the relationship between recognition of particular epitopes and infectivity. There was a significant association between lack of infectivity of P. falciparum gametocyte carriers and recognition of epitope IIa on Pfs 48/45 by antibodies in their sera.

Adolescent↗
PubMed1992

Antibody detection ELISAS for malaria diagnosis.

Parasite extracts of Plasmodium falciparum and P. chabaudi and three synthetic peptides from the P. falciparum MSA2 merozoite antigen were tested for suitability as antigens in an antibody detection ELISA using sera from malaria patients in Brisbane. The P. chabaudi extract was superior to P. falciparum extract for detecting P. vivax cases, while for P. falciparum cases the two parasite extracts were equivalent. Single peptide antigens were generally less sensitive than parasite extracts; however, peptides G3 and G7 were more sensitive than parasite extracts in detecting first attacks of P. vivax. Examination of isotype specific responses demonstrated that this may be explained by higher IgG responses to these peptides in first than in subsequent P. vivax attacks. Because of the differing antibody specificities in primary and secondary P. falciparum and P. vivax cases, the best sensitivity was achieved by using the combined results of assays with three antigens: P. chabaudi, peptide G3 and peptide G7. The combined sensitivity was 77.1% for P. falciparum and 88.6% for P. vivax acute cases with 91.1% specificity.

Amino Acid Sequence↗
PubMed1991

Antibody responses to Plasmodium falciparum gametocyte antigens during and after malaria attacks in schoolchildren from Madang, Papua New Guinea.

Sera from 49 school children in Madang, Papua New Guinea with malaria and follow-up sera from 40 of these cases were tested by competitive ELISA for antibodies capable of inhibiting binding of eight monoclonal antibodies (MoAbs) to Plasmodium falciparum gametocytes. The proportion of sera inhibiting each MoAb ranged from 31.2% to 85.7%. At follow-up, the proportion of inhibitory sera decreased for 3 MoAbs, did not change significantly for 4 MoAbs and increased for one MoAb. When sera were grouped according to whether the follow-up blood slide was positive or negative, further trends emerged for MoAbs against the gamete surface antigen Pfs 48/45. Antibody levels to the IA3-B8 epitope decreased in follow-up positive cases, but remained unchanged for follow-up negative cases. The converse was observed for the IIC5-B10 epitope with an increase of antibody in follow-up positive cases and no change in the negative cases. Amount of antibody to the 3G12/58 epitope decreased when the follow-up was negative but not when it was positive. Increase in antibody to the 3E12/58 epitope occurred at the follow-up sample irrespective of the blood slide result. Thus four distinct patterns of longitudinal antibody response were observed against four epitopes on the same molecule.

Adolescent↗
PubMed1991

Developmental aspects of the primary process.

The structural-developmental view of primary process initially proposed by Holt (1967) defines primary process as a special system of processing information in the service of "synthetic necessity." Rather than being an archaic, chaotic mode of ideation, primary process follows an independent line of development with specific organizational and synthesizing properties. Vignettes from three phases of the treatment of a severely disturbed child provide clinical evidence to support this viewpoint.

Child↗
PubMed1990

The prevalence of naturally acquired multiple infections of Wuchereria bancrofti and human malarias in anophelines.

Malaria and filaria infection rates were determined for anopheline mosquitoes collected whilst biting and resting in village houses in Papua New Guinea. The number of anophelines infected with both parasites was greater than expected from the infection rates of each parasite and this difference was significant in resting collections. The excess of multiply infected mosquitoes is probably a result of a vector population composed of individuals with differing numbers of opportunities to become infected. Malaria-positive Anopheles punctulatus from resting catches had a significantly greater number of Stage 3 Wuchereria bancrofti larvae than malaria-negative mosquitoes. However, multiply infected mosquitoes appear to suffer greater mortality than non-infected or singly infected mosquitoes when the filarial worm reaches the third stage. Any potential increase in transmission resulting from multiple infections is thereby offset by a greater mortality rate in these mosquitoes.

Animals↗
PubMed1990

The primary antibody response of malaria patients to Plasmodium falciparum sexual stage antigens which are potential transmission blocking vaccine candidates.

Thirty serum samples collected from adult patients attending the Hospital for Tropical Diseases, London, with P. falciparum malaria, were studied. Sera were screened by indirect immunofluorescence for anti-gametocyte antibodies. Twelve of the serum samples taken from 14 patients with primary infections were found to have both IgM and IgG antibodies to gametocyte antigens and total Ig titres comparable with those of patients who had had previous malaria attacks. Sera of individuals from hyperendemic areas have been found to immunoprecipitate the 230 and 48/45 kD gametocyte surface antigens which are known targets of transmission blocking antibodies. To investigate the epitope specificity of the serum samples from our adult patients, competitive ELISAs with 3 monoclonal antibodies (MAbs) that block transmission and recognize different epitopes on the 48/45 Kd antigen, were carried out. Specific antibodies for these epitopes were found in 60% of the sera while nearly a third were able to inhibit the binding of at least two MAbs.

Adult↗
PubMed1990

Properties of epitopes of Pfs 48/45, a target of transmission blocking monoclonal antibodies, on gametes of different isolates of Plasmodium falciparum.

We have studied the properties of epitopes on Plasmodium falciparum gamete surface protein Pfs 48/45, a target antigen of malaria transmission blocking antibodies. Using a two site immunoradiometric assay we have defined three spacially separate, non-repeated, epitope regions on the peptides representing this antigen. Epitope region I is a target of monoclonal antibodies (MoAbs) which strongly suppress infectivity of gametocytes of P. falciparum to mosquitoes; the effect is complement independent and is mediated as effectively by the monovalent Fab fragments as by intact MoAb. Epitope region II consists of two spacially close subregions, IIa and IIb; variant forms of epitopes IIa and IIb occurred in different isolates of P. falciparum. Epitope region III also showed slight structural modification between isolates. MoAbs against regions II or III were relatively ineffective in suppressing gametocyte infectivity compared to MoAbs against region I. However, certain combinations of MoAbs against regions II and III together acted synergistically to suppress infectivity to mosquitoes. All these epitopes failed to react with MoAb when the antigen was presented in reduced form. A fourth epitope, however, was identified which reacted strongly with MoAb when the antigen was presented in reduced form. The MoAb against this epitope had no effect on the infectivity of gametocytes of P. falciparum to mosquitoes.

Animals↗
PubMed1990

High frequency of antibody response to Plasmodium falciparum gametocyte antigens during acute malaria infections in Papua New Guinea highlanders.

Sera from 62 adult Papua New Guinea highlanders with suspected acute malaria were tested by competitive ELISA for the presence of antibodies capable of inhibiting binding of 8 monoclonal antibodies (Mabs) directed against epitopes on gametocytes of Plasmodium falciparum. Between 33% and 72% of the malaria cases were inhibitory, depending on the Mab. There was no difference between the proportion of persons with P. falciparum (asexuals or gametocytes) and P. vivax whose sera inhibited Mab binding, but all 3 categories had a significantly higher proportion of inhibitors than persons who were malaria negative. The amount of gametocyte antibody recognizing epitopes on Pfs 48/45 and Pfs 230 increased with increasing numbers of previous malaria episodes. The proportion of sera from these relatively nonimmune adults which had gamete antibodies was similar to the proportion seen in sera from a highly endemic area, suggesting that antibody responses to these epitopes are a part of the initial response observed after a limited number of malaria episodes.

Acute Disease↗
PubMed1990

Variations in malaria transmission rates are not related to anopheline survivorship per feeding cycle.

Anopheline survivorship, vectorial capacity, and mosquito infection probability estimates from mosquito infection rates were determined 4 times in 1 year in a Papua New Guinea village. Estimates of survivorship over the length of the extrinsic incubation period differed significantly during the year. However, survivorship per feeding cycle, individual mosquito vectorial capacity, and mosquito infection probability did not vary significantly. Estimates of these parameters were then compared to estimates of survivorship, individual vectorial capacity, and mosquito infection probability in mosquito populations in other villages in the study area. Since survivorship per feeding cycle did not vary significantly among the mosquito populations in these villages, changes in malaria transmission potential can be better gauged from estimates of survivorship over the length of the extrinsic incubation period. However, as measurements of relative inoculation rates are easier to perform and have been related to parasite prevalences in children in this area, estimates of inoculation rates are a preferred option for estimating malaria transmission in the Madang area of Papua New Guinea.

Animals↗
PubMed1989

Restricted or absent immune responses in human populations to Plasmodium falciparum gamete antigens that are targets of malaria transmission-blocking antibodies.

We have studied the antibodies to sexual stage antigens of Plasmodium falciparum in human sera from Papua New Guinea where intense transmission of P. falciparum occurs as well as the less prevalent P. malariae and P. vivax. In extracts of gametes of P. falciparum we have studied the reactivity of serum antibodies with antigens labeled with 125I on the surface of the gametes as well as intracellular gamete antigens. A prominent 27-kD sexual stage-specific intracellular protein was recognized more or less in proportion to the general antibody response to gamete proteins. The response to the gamete surface proteins, however, was quite unrepresentative of the general antibody response to the intracellular gamete proteins. No antibodies were detected against Pfs25, a 21-kD protein expressed on zygotes and ookinetes of P. falciparum and known to be a sensitive target of malaria transmission-blocking antibodies. The antibody response to two other target antigens of transmission-blocking antibodies on the surface of gametes of P. falciparum, a 230- and a 48- and 45-kD protein doublet, was very variable and independent of the response to the internal protein antigens. Several possibilities are discussed that may account for the variable response to these gamete surface antigens in individuals with otherwise good antibody responses to internal sexual stage proteins. Among these is the possibility that there is MHC restriction of the immune response to the gamete surface antigens in the human population. This interpretation accords well with evidence for MHC-restricted immune response to the same P. falciparum gamete surface antigens in studies with H-2 congenic mice (24).

Animals↗
PubMed1989

Plasmodium falciparum: an abundant stage-specific protein expressed during early gametocyte development.

A stage-specific protein has been identified in gametocytes of Plasmodium falciparum. The protein is represented on two-dimensional electrophoresis by peptides of two apparent Mr of 27,000 and 25,000, each of which has at least four different isoelectric points between pH 6.0 and 5.0. The protein is designated Pfg 27/25 (P. falciparum gametocyte-specific antigen of 27 and 25 kDa). By indirect immunofluorescence with a monoclonal antibody 1H12 specific for Pfg 27/25, this protein is present in gametocytes within 30 to 40 hr after invasion of a red blood cell by a merozoite and is present throughout subsequent maturation of the gametocyte; Pfg 27/25 is not detectable on the surface of extracellular gametes by immunofluorescence with Mab 1H12. Pfg 27/25 is absent from asexual stages of P. falciparum at any stage in their development. Pfg 27/25 is an abundant protein in gametocytes and represents between 5 and 10% of total protein of these stages. Pfg 27/25 is also a major immunogen in man during P. falciparum infection. Antibodies to this protein were readily detected in human sera from an area of holoendemic P. falciparum and also from an individual following a primary attack of P. falciparum.

Animals↗
PubMed1989

Human host selection by anophelines: no evidence for preferential selection of malaria or microfilariae-infected individuals in a hyperendemic area.

Host selection among humans by Anopheles punctulatus was studied in an area of Papua New Guinea endemic for malaria and filariasis. Blood films were made from the stomach contents of freshly engorged mosquitoes found resting on the walls of houses in which the parasite status of the occupants was known. Engorgement rates on humans were non-random but could not be consistently related to the parasite status of individuals in the houses for either malaria or filaria. In some households, anophelines preferentially fed on parasitaemic individuals while in other households aparasitaemic individuals were significantly more often selected. This finding is believed to reflect the fact that malaria and filarial infections in this endemic area are predominantly asymptomatic. There were no significant differences in axillary temperatures between malaria or microfilariae positive or negative individuals.

Adolescent↗