Heritability of human hookworm infection in Papua New Guinea.

Hookworms infect approximately 740 million humans worldwide and are an important cause of morbidity. The present study examines the role of additive genetic effects in determining the intensity of hookworm infection in humans, and whether these effects vary according to the sex of the host. Parasitological and epidemiological data for a population of 704 subjects in Papua New Guinea were used in variance components analysis. The 'narrow-sense' heritability of hookworm infection was estimated as 0.15+/-0.04 (P<0.001), and remained significant when controlling for shared environmental (household) effects. Allowing the variance components to vary between the sexes of the human host consistently revealed larger additive genetic effects in females than in males, reflected by heritabilities of 0.18 in females and 0.08 in males in a conservative model. Household effects were also higher in females than males, although the overall household effect was not significant. The results indicate that additive genetic effects are an important determinant of the intensity of human hookworm infection in this population. However, despite similar mean and variance of intensity in each sex, the factors responsible for generating variation in intensity differ markedly between males and females.

Age- and species-specific duration of infection in asymptomatic malaria infections in Papua New Guinea.

The burden and duration of asymptomatic malaria infections were measured in residents of the malaria endemic village of Gonoa, Madang Province, Papua New Guinea. Plasmodium falciparum, P. vivax and P. malariae infections in people aged 4 years to adulthood were compared. Frequent sampling at 3-day intervals for up to 61 days allowed assessment of individual episodes of infection. Statistical assessment of P. falciparum detection revealed a periodicity consistent with synchronous replication of this species over periods up to 27 days. The duration of P. falciparum episodes was longer across all age groups than that of P. vivax and P. malariae. A trend for decreasing duration with age was also noted in data from each species. This was most prominent in P. falciparum infections: median duration in 4-year-olds was > 48 days compared with a median between 9 and 15 days in older children and adults. The results are consistent with the slow acquisition of immunity to antigenically diverse Plasmodium populations and suggest a faster rate of acquisition to P. vivax and P. malariae than to P. falciparum.

Control of lymphatic filariasis in a hunter-gatherer group in Madang Province.

Diethylcarbamazine (DEC) has been successfully administered to millions of people in established villages and towns, but little or no information exists on the use of this drug to control lymphatic filariasis in isolated seminomadic groups. We have studied the impact of biannual single-dose mass treatment to control filariasis in the Hagahai, an isolated hunter-gatherer, shifting horticulturist group in the fringe highlands of Papua New Guinea. Despite low treatment coverage, 6 mass treatment rounds significantly reduced the overall prevalence of infection with Wuchereria bancrofti, by antigen detection assay, from 55% before treatment to 34% after treatment. Obstructive filarial disease in the form of elephantiasis or hydrocele was not observed among the indigenous population. Anopheles species accounted for 91% of human-biting mosquitoes collected in the area. A total of 1126 mosquitoes were caught and dissected individually but none was infected with third-stage larvae (L3). Our findings support the phenomenon of facilitation, which predicts that Anopheles-transmitted lymphatic filariasis can be interrupted by mass chemotherapy alone in areas of low vector density and low transmission intensity as observed in the Hagahai.

Twelve microsatellite markers for characterization of Plasmodium falciparum from finger-prick blood samples.

Multiple, selectively neutral genetic markers are the most appropriate tools for analysis of parasite population structure and epidemiology, but yet existing methods for characterization of malaria field samples utilize a limited number of antigen encoding genes, which appear to be under strong selection. We describe protocols for characterization of 12 microsatellite markers from finger-prick blood samples infected with Plasmodium falciparum. A two-step, heminested strategy was used to amplify all loci, and products were visualized by fluorescent end-labelling of internal primers. This procedure allows amplification from low levels of template, while eliminating the problem of spurious products due to primer carry over from the primary round of PCR. The loci can be conveniently multiplexed, while accurate sizing and quantification of PCR products can be automated using the GENOTYPER software. The primers do not amplify co-infecting malaria species such as P. vivax and P. malariae. To demonstrate the utility of these markers, we characterized 57 infected finger-prick blood samples from the village of Mebat in Papua New Guinea for all 12 loci, and all samples were genotyped a second time to measure reproducibility. Numbers of alleles per locus range from 4 to 10 in this population, while heterozygosities range from 0.21 to 0.87. Reproducibility (measured as concordance between predominant alleles detected in replicate samples) ranged from 92 to 98% for the 12 loci. The composition of PCR products from infections containing multiple malaria clones could also be defined using strict criteria and scored in a highly repeatable manner.

Mating patterns in malaria parasite populations of Papua New Guinea.

Description of the genetic structure of malaria parasite populations is central to an understanding of the spread of multiple-locus drug and vaccine resistance. The Plasmodium falciparum mating patterns from madang, Papua New Guinea, where intense transmission of malaria occurs, are described here. A high degree of inbreeding occurs in the absence of detectable linkage disequilibrium. This contrasts with other studies, indicating that the genetic structure of malaria parasite populations is neither clonal nor panmictic but will vary according to the transmission characteristics of the region.

Malaria in adult outpatients at Goroka Hospital during 1986.

Of 206 adult outpatients attending Goroka Hospital with suspected malaria during 1986, 40.3% had blood slides positive for malaria (28.2% Plasmodium falciparum, 13.6% P. vivax and 1.9% P. malariae). Parasite densities and proportions of cases with gametocytes were higher than observed in endemic regions. Acquisition of infection during recent coastal travel was implicated in the majority of cases (86%). 6 out of 13 gametocyte carriers tested were infectious to Anopheles farauti mosquitos. Anti-malaria ELISA values in sera were elevated above non-immune values in over 75% of infections, although ELISA values were low compared to those in sera from residents of coastal areas, indicating the low level of previous exposure to malaria.

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.