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Biomedical subjects

T R Burkot

Publications and source records attributed to T R Burkot.

At least 55 records · Page 3Linked to original sources
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

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↗
PubMed1989

Differential antibody responses to Plasmodium falciparum and P. vivax circumsporozoite proteins in a human population.

Papua New Guineans exposed to hyperendemic malaria in the Madang area showed different antibody responses to Plasmodium falciparum and Plasmodium vivax sporozoites despite comparable entomological inoculation rates. Although there was a significant trend of increasing prevalence of anti-P. falciparum circumsporozoite (CS) protein immunoglobulin G (IgG) with age, there was no significant increase in the antibody units of IgG recognizing P. falciparum CS proteins. Antibodies recognizing P. vivax CS proteins steadily increased in prevalence and antibody units with age. Significant trends of increasing prevalence of antibody responders (both IgG and IgM) with increasing splenic enlargement were found in the younger age groups for P. falciparum CS proteins but not for P. vivax CS proteins. When antibody responders were analyzed by quartiles, there was a trend of increasing antibody response with age against P. vivax CS peptide, but not for P. falciparum CS protein. There was no evidence for increasing protection against blood-stage infections with increasing antibody levels for either P. falciparum or P. vivax. Neither were any significant relationships found between entomological inoculation rates and either CS antibody prevalence or concentration among the villages studied.

Adolescent↗
PubMed1989

An analysis of some factors determining the sporozoite rates, human blood indexes, and biting rates of members of the Anopheles punctulatus complex in Papua New Guinea.

The degree to which Anopheles punctulatus complex members feed on humans in different Papua New Guinea villages has a significant effect on sporozoite rates. Among villages, the human blood index (HBI) of the members of the complex varied with the average number of persons sharing a bednet. Although dogs are the preferred hosts by the 3 malaria vector species, the number of dogs did not significantly affect the HBI. The HBI was dependent upon the human-biting rate, implying increased avoidance of anophelines by people relative to other hosts at times of greater mosquito numbers. Human-biting rates and HBIs were also influenced by the distribution of alternative hosts relative to people.

Animals↗
PubMed1989

Association between HLA type and antibody response to malaria sporozoite and gametocyte epitopes is not evident in immune Papua New Guineans.

HLA-A,B,C and DR types were determined for 46 adults living in the Madang area of Papua New Guinea. Sera from these individuals were tested by ELISA for antibodies against: (i) sonicated schizont extract of Plasmodium falciparum; (ii) circumsporozoite repeat regions of P. falciparum and P. vivax; and (iii) epitopes on the 230 and 48/45 kD gametocyte antigens of P. falciparum. All sera were from highly immune individuals and reacted strongly to the schizont antigen. The proportions responding to circumsporozoite repeat regions were 60.7% and 23.9% for P. falciparum and P. vivax, respectively. Between 32.6 and 47.8% of adults responded to each gametocyte epitope as assessed by inhibition of monoclonal antibodies. The limited number of alleles present at each HLA locus which is characteristic of coastal Papua New Guinea was observed. Five HLA-DR alleles were detected, of which only three (HLA-DR2, 4 and w5) were present at frequencies over 0.12. All individuals possessed at least one DR2,4 or w5 allele, and 96% of individuals possessed DR2, or 4 or both. There was no evidence for association between HLA type and antibody response to circumsporozoite repeat regions or the gametocyte epitopes. Homozygotes for DR2 and 4 were able to respond to each antigen. These results imply that either there is no HLA restriction of the response to these antigens or that each DR type is responding to a different variant of the T-epitope. Even in the latter case the results are encouraging for the prospects of inclusion of an HLA-restricted T-epitope in a malaria vaccine for Papua New Guinea since a limited number of versions would be required to cover a population with an HLA profile similar to that in Madang.

Animals↗
PubMed1988

Non-random host selection by anopheline mosquitoes.

Malaria represents a complex system. Transmission depends on a multitude of factors - of which vector density may not be the most important (see Box 1). The classical Ross-Macdonald model of malaria transmission (Box 2) reveals two dominant factors: the probability that a mosquito will survive long enough for the parasite to develop to its infective stage, and the likelihood that the mosquito will feed on man. An important assumption however, is that all individuals will be at equal risk from mosquito attack. In fact, host-vector contact is far from randomly distributed. In this review, Tom Burkot explains the biological causes of non-random host selection by anopheline vectors, and Chris Dye discusses some of the epidemiological implications of this selection for malaria transmission (Box 3).

Journal Article↗
PubMed1988

Measurement of malarial infectivity of human populations to mosquitoes in the Madang area, Papua, New Guinea.

The proportion of blood meals taken on humans which are infectious to mosquitoes in the Madang area, Papua New Guinea was estimated by two methods. In the first, laboratory reared Anopheles farauti were fed on individuals of all ages at village surveys. The results showed that 3.8% of people were infectious and that the mean percentage of mosquitoes which became infected by feeding on these people was 37.9%. From the average proportion of mosquitoes infected, the probability that a mosquito feeding on a human would pick up infection was 0.013 +/- 0.005. In the second approach mosquitoes were fed on identified Plasmodium falciparum, P. vivax and P. malariae gametocyte carriers. The results indicated that 46% of gametocyte carriers were infectious and that the mean probability of a mosquito becoming infected after feeding on a gametocyte carrier was 0.151 +/- 0.029. Gametocyte prevalence rates in all ages measured over 18 months in three villages averaged 3.3% P. falciparum, 4.0% P. vivax and 0.7% P. malariae, totalling 8.0 +/- 0.7%. Combining gametocyte prevalence rates with the probability of a mosquito becoming infected from a gametocyte carrier, the probability of a mosquito becoming infected following a blood meal on a member of the human population was estimated to be 0.012 +/- 0.003.

Age Factors↗
PubMed1988

Antibodies to Plasmodium falciparum gamete surface antigens in Papua New Guinea sera.

Sera from individuals living in malaria endemic areas of Papua New Guinea were tested for their effect on infectivity of Plasmodium falciparum gametocytes grown in culture to Anopheles freeborni mosquitoes. Consistent reduction of infectivity to less than 5% of control was observed with nine out of the 41 sera from the endemic area tested and also with three out of seven sera tested from individuals rarely exposed to malaria infection. Gamete surface antigens recognized by the sera were investigated by immunoprecipitation from 125I surface-labelled gametes extracted in SDS and Triton X-100. The main antigens recognized were of the same mol. wt (230, 48 and 45 kD) as those known to be targets of transmission-blocking monoclonal antibodies. A significant negative correlation was observed between the total ct/min immunoprecipitated from surface-labelled gametes by the sera and the average number of oocysts per gut observed in membrane feeding experiments with these sera. Spearmann's rank correlation coefficient indicated that suppression of infectivity correlated strongly with the presence of antibodies against the 230 kD protein; there was no significant correlation between suppression and antibodies to the 48/45 kD proteins. The antibody response to the different gamete surface antigens varied greatly in sera from the endemic areas suggesting that individuals respond differently to each gamete antigen.

Animals↗
PubMed1988

Naturally occurring antibodies to an epitope on Plasmodium falciparum gametes detected by monoclonal antibody-based competitive enzyme-linked immunosorbent assay.

The antibody response to an epitope on gamete antigens of Plasmodium falciparum in persons naturally exposed to malaria has been investigated by competitive enzyme-linked immunosorbent assay. The assay detects antibodies to an epitope on the 48/45-kilodalton (kDa) gamete surface antigen by competition with horseradish peroxidase-labeled monoclonal antibody IIC5-B10. Five sera previously shown to immunoprecipitate the 230- and 48/45-kDa antigens significantly inhibited IIC5-B10 binding to an average of 24.2% of control. The one serum which precipitated only the 48/45-kDa antigen did not inhibit IIC5-B10 binding. For 26 sera which were negative by immunoprecipitation, mean binding in the assay was 112.7% of control (pooled London nonimmune sera). Recognition of both 230-kDa and 48/45-kDa antigens was associated with a titer of 1:9 or greater (reciprocal geometric mean titer, 27.6) for inhibition to more than 2 standard deviations from the mean of the negative sera. The results show that the IIC5-B10 binding site is a naturally immunogenic epitope recognized by the majority of persons who had antibodies to the 48/45-kDa protein. An additional finding was enhancement of binding of IIC5-B10 to an average of 154.4% of control by five sera which recognized only the 230-kDa antigen, presumably due to conformational alteration of the gamete antigen complex.

Animals↗
PubMed1988

Human malaria transmission studies in the Anopheles punctulatus complex in Papua New Guinea: sporozoite rates, inoculation rates, and sporozoite densities.

Malaria sporozoite rates and inoculation rates were measured over periods up to 25 months in the different anopheline species biting humans in 13 villages in Madang Province, Papua New Guinea. Analysis of three members of the Anopheles punctulatus complex, 68,458 An. farauti, 36,779 An. koliensis, and 11,667 An. punctulatus caught in landing catches was made using monoclonal antibody based ELISAs to detect sporozoites of Plasmodium falciparum and P. vivax. Sporozoite rates ranged from 0%-5.5% in An. farauti, 0.2%-3.8% in An. koliensis, and 0%-3.3% in An. punctulatus. In addition, over 3,000 An. longirostris were analyzed and sporozoites were not detected in this species. No significant differences were observed between the three vector species in the densities of P. falciparum sporozoites (geometric mean 2,320). However, the geometric mean P. vivax sporozoite density was significantly higher in An. punctulatus (350) than in either An. koliensis (160) or An. farauti (150). An. koliensis was less susceptible to infections of P. falciparum or P. vivax than either An. farauti or An. punctulatus. Variations in average sporozoite and inoculation rates were found among different villages, despite their close geographic proximity. Sporozoite and inoculation rates varied greatly within a village over time, but malaria transmission was perennial with a higher transmission during the wet season by An. koliensis and An. punctulatus.

Animals↗
PubMed1988

Detection of circulating parasite antigen and specific antibody in Toxocara canis infections.

Serological surveys, measuring humoral antibody responses, have indicated significant levels of human infection with the zoonotic nematode Toxocara canis, and raised concern about the resultant risk of ocular and neurological damage. Such measurements do not distinguish with certainty current infection from past exposure. Thus, we have developed a test for circulating Toxocara antigen released by parasites in the host. This monoclonal antibody-based two-site 'sandwich' assay discriminates between T. canis and the related feline ascarid T. cati, and has been used, in tandem with the standard ELISA, to examine experimental and human infections. In experimental animals, antigen is transiently detectable, disappearing when immunocomplexed with host antibody. Antigen was also found in sera from UK patients diagnosed with visceral or ocular toxocariasis, and in four asymptomatic Papua New Guinean children. In the latter population, individuals positive for parasite antigens were not necessarily positive for antibody, implying that some infected cases may be negative in the current diagnostic ELISA. The antibody test was also adapted to measure host antibody directed to single monoclonal antibody-defined epitopes, revealing evidence of differential temporal regulation of distinct antibody specificities.

Animals↗
PubMed1987

Genetic analysis of the human malaria parasite Plasmodium falciparum.

Malaria parasites are haploid for most of their life cycle, with zygote formation and meiosis occurring during the mosquito phase of development. The parasites can be analyzed genetically by transmitting mixtures of cloned parasites through mosquitoes to permit cross-fertilization of gametes to occur. A cross was made between two clones of Plasmodium falciparum differing in enzymes, drug sensitivity, antigens, and chromosome patterns. Parasites showing recombination between the parent clone markers were detected at a high frequency. Novel forms of certain chromosomes, detected by pulsed-field gradient gel electrophoresis, were produced readily, showing that extensive rearrangements occur in the parasite genome after cross-fertilization. Since patients are frequently infected with mixtures of genetically distinct parasites, mosquito transmission is likely to provide the principal mechanisms for generating parasites with novel genotypes.

Adenosine Deaminase↗
PubMed1987

The efficiency of sporozoite transmission in the human malarias, Plasmodium falciparum and P. vivax.

Reported are malaria sporozoite and inoculation rates over a 1-year period in eight epidemiologically defined villages of different endemicity in Madang Province, Papua New Guinea. In the study, more than 41 000 wild-caught mosquitos were analysed for Plasmodium falciparum and P. vivax sporozoites by ELISA. In a given village the entomological inoculation rates correlated strongly with the prevalences of both these malarial parasites in children. However, the prevalence of P. falciparum infections in children was much higher than that of P. vivax, despite similar inoculation rates for the two species. These data suggest that in Papua New Guinea P. falciparum is more efficiently transmitted than P. vivax from mosquito to man. The increased efficiency of transmission of P. falciparum may be due to the heavier sporozoite densities in wild-caught mosquitos naturally infected with P. falciparum sporozoites that were tenfold greater than the sporozoite densities in mosquitos infected with P. vivax.

Animals↗
PubMed1987

Reduction in incidence and prevalence of Plasmodium falciparum in under-5-year-old children by permethrin impregnation of mosquito nets.

The malaria incidence and prevalence rates among children who slept under permethrin-impregnated mosquito nets in four villages near Madang, Papua New Guinea, were compared with the rates among children who slept under unimpregnated nets in four paired control villages. Immediately following a parasitological survey in the eight villages, malaria parasites were cleared from the children with chemotherapy, and the mosquito nets in the four experimental villages were impregnated with permethrin. Follow-up parasitological surveys were performed 4 and 10 weeks later. Sporozoite rates in female mosquitos of the Anopheles punctulatus complex decreased significantly in two of the experimental villages after impregnation. Also, the incidence of Plasmodium falciparum between the 4-week and 10-week surveys was significantly lower among the 0-4-year olds in villages with impregnated nets than in those with unimpregnated nets, leading to reduced prevalence of P. falciparum in this age group. Use of permethrin-impregnated nets had no effect on the incidence or prevalence of P. falciparum among 5-9-year olds or on that of P. vivax among the 0-4- or 5-9-year olds.

Animals↗
PubMed1987

Comparative testing of monoclonal antibodies against Plasmodium falciparum sporozoites for ELISA development.

Ten monoclonal antibodies developed against Plasmodium falciparum sporozoites at four institutions were evaluated for use in an enzyme-linked immunosorbent assay (ELISA). Four of the antibodies were eliminated because of their low sensitivity or requirement for high concentrations of capture antibody, while an additional four were rejected because they exhibited cross-reactivity with P. berghei sporozoites. Of the two remaining monoclonal antibodies, that designated 2A10 had the highest sensitivity, a requirement for lower concentrations of capture antibody, and had been tested successfully against sporozoites from a wider range of geographical areas than the others. Use of this monoclonal antibody in a standardized ELISA method gave a test ten times more sensitive than previously reported for P. falciparum sporozoites and its detection limit was less than 100 sporozoites per mosquito.

Animals↗