Parasitic worm infections are amongst the most widespread of all chronic human infections. It is estimated that there are more than 3 billion infections in the world today. In many low income countries it is often more common to be infected than not to be. Indeed, a child growing up in an endemic community can expect be infected soon after weaning, and to be infected and constantly reinfected for the rest of her or his life. Infection is most common amongst the poorest and most disadvantaged communities, and is typically most intense in children of school going age. As the risk of morbidity is directly related to intensity of infection, it follows that children are the most at risk from the morbid effects of disease. Multiparasite infections are also common in such communities and there is evidence that individuals harbouring such infections may suffer exacerbated morbidity, making children even more vulnerable. Thus, these infections pose a serious threat to the health and development of children in low income countries. For many years, the need to control these infections has lain uncontested, and with the advent of broad-spectrum anthelminthic drugs that are cheap, safe and simple to deliver, control has at last become a viable option for many communities. Furthermore, there is now increased emphasis being placed on a multispecies approach as a cost-effective mechanism to control the morbidity of virtually all the major helminthic infections of humans.

Sporozoites of P. falciparum and other Plasmodia appear to be fairly simple antigenically, in that there is a dominant antigen, the circumsporozoite (CS) protein that forms the sporozoite surface coat (Potocnjak, Yoshida, Nussenzweig & Nussensweig, 1980; Santoro et al. 1983). Consequently, the CS protein and the gene encoding it have now been studied in considerable detail (Ellis et al. 1983; Godson et al. 1983; Ozaki et al. 1983; Dame et al. 1984; Enea et al. 1984). In contrast to sporozoites, the asexual blood stages of P. falciparum are antigenically complex. Two-dimensional gel analyses of immunoprecipitated, biosynthetically labelled antigens indicate that repeated infection with P. falciparum results in the synthesis of antibodies against a large number of distinct antigens (Perrin & Dayal, 1982; Brown et al. 1981, 1983). In further contrast to the sporozoite, the asexual blood stages of different P. falciparum isolates exhibit a high degree of antigenic heterogeneity (Brown et al. 1983; Hall et al. 1983; McBride, Walliker & Morgan, 1982). Much of this antigenic diversity is no doubt due to allelic differences but clonal populations of parasites may also have the capacity to undergo antigenic variation (Hommel, David & Oligino, 1983).

The aims of this study were to characterize human American tegumentary leishmaniasis, which includes cutaneous, mucocutaneous and mucosal leishmaniasis, in Northwest Argentina, to determine the prevalence of double infection with Trypanosoma cruzi and to identify the species of Leishmania in this area. Most of the 330 leishmaniasis patients presented cutaneous ulcers (96·1%), 2·4% mucocutaneous and 1·5% the mucosal form (‘espundia’). The aetiological agents, determined by isoenzyme electrophoresis, were identified as Leishmania (Viannia) braziliensis in 16 out of 20 isolates and in the remaining 4 as Leishmania (Leishmania) amazonensis, the first ever-documented in Argentina. Sera analysed by ELISA and IFA using complex antigen from both T. cruzi and L. braziliensis showed a very high percentage of positives (66·3–78·2%). When antigens for specific diagnosis of Chagas' disease were used, 40·9% of the leishmaniasis patients were also found to be infected by T. cruzi. These results indicate that the strong immune response against T. cruzi gave no protection to Leishmania, in spite of the serological cross-reaction between these parasites. In addition, we showed that more than 40% of the patients would be misdiagnosed as chagasic if complex antigens, as epimastigotes or soluble fraction from epimastigotes, were used in IFA or ELISA. This is of paramount importance not only because patients' treatment would be associated to misdiagnosis but the fact that in many countries in Central and South America, a positive test for Chagas' disease means a rejection for those seeking employment.

Transmission of the malaria parasite Plasmodium is influenced by many different host, vector and parasite factors. Here we conducted a field study at Mbita, an area of endemic malaria in Western Kenya, to test whether parasite transmission to mosquitoes is influenced by the severity of malaria infection in its human host at the time when gametocytes, the transmission forms, are present in the peripheral blood. We examined the infectivity of 81 Plasmodium falciparum gametocyte carriers to mosquitoes. Of these, 21 were patients with fever and other malaria-related symptoms, and 60 were recruited among apparently healthy volunteers. Laboratory-reared Anopheles gambiae s.s. (local strain) were experimentally infected with blood from these gametocyte carriers by membrane-feeding. The severity of the clinical symptoms was greater in febrile patients. These symptomatic patients had higher asexual parasitaemia and lower gametocyte densities (P=0·05) than healthy volunteers. Ookinete development occurred in only 6 out of the 21 symptomatic patients, of which only 33·3% successfully yielded oocysts. The oocyst prevalence was only 0·6% in the 546 mosquitoes that were fed on blood from this symptomatic group, with mean oocyst intensity of 0·2 (range 0–2) oocysts per mosquito. In contrast, a higher proportion (76·7%) of healthy gametocyte carriers yielded ookinetes, generating an oocyst rate of 12% in the 1332 mosquitoes that fed on them (mean intensity of 6·3, range: 1–105 oocysts per mosquito). Statistical analysis indicated that the increased infectivity of asymptomatic gametocyte carriers was not simply due to their greater gametocyte abundance, but also to the higher level of infectivity of their gametocytes, possibly due to lower parasite mortality within mosquitoes fed on blood from healthy hosts. These results suggest that blood factors and/or conditions correlated with illness reduce P. falciparum gametocyte infectivity.

Blood flukes in the genus Schistosoma are important human parasites in tropical regions. A substantial amount of genetic diversity has been described in populations of these parasites using molecular markers. We first consider the extent of genetic variation found in Schistosoma mansoni and some factors that may be contributing to this variation. Recently, though, attempts have been made to analyze not only the genetic diversity but how that diversity is partitioned within natural populations of schistosomes. Studies with non-allelic molecular markers (e.g. RAPDs and mtVNTRs) have indicated that schistosome populations exhibit varying levels of gene flow among component subpopulations. The recent characterization of microsatellite markers for S. mansoni provided an opportunity to study schistosome population structure within a population of schistosomes from a single Brazilian village using allelic markers. Whereas the detection of population structure depends strongly on the type of analysis with a mitochondrial marker, analyses with a set of seven microsatellite loci consistently revealed moderate genetic differentiation when village boroughs were used to define parasite subpopulations and greater subdivision when human hosts defined subpopulations. Finally, we discuss the implications that such strong population structure might have on schistosome epidemiology.

The biodiversity of insect trypanosomes is largely unknown, resulting in significant gaps in the understanding of pathogen evolution. A culture-independent preliminary survey of trypanosomatid fauna was conducted for the parasites of Heteroptera (Hemiptera) from several localities in Costa Rica. Trypanosomatid infections were detected by light microscopy of smeared gut contents. Out of 257 insects representing 6 families, infections were found in 62 cases; cultures were obtained for 29 new isolates. Gut material from infected hosts was preserved in the field using an SDS–EDTA buffer solution for subsequent DNA extraction in the laboratory. PCR amplification of the trypanosomatid-specific spliced leader (SL) RNA gene repeats was successful for 60 field samples. Eighteen distinct SL RNA typing units were identified in a set of 28 samples analysed in detail. Cluster analysis indicated that these typing units were unique and thus could represent new species and, in some cases, new genera. This study reveals only a minor fraction of the trypanosomatid biodiversity, which is anticipated to be high.

Just as human helminth infections are vitally influenced by the way in which people live, so the helminthiases of domestic animals depend on how these are managed.Veterinary helminthology is a branch of agriculture. The agricultural industry changes quickly, more quickly than the ideas of scientists. Ideas, in their turn change more rapidly than their practical implications are understood. A discussion of anthelmintic use must therefore be partly agricultural, partly historical.

Although the biological control of medically important snails has been suggested from time to time during the past quarter of a century (Nagano, 1927; Bequaert, 1928; Mozely, 1939, 1951; McMullen, 1952), the subject has, as yet, received but little serious consideration. Upon the initiation of our studies (Chernin, Michelson & Augustine, 1956a, b) the literature was searched for references to predators, parasites and diseases of molluscs which might furnish leads for experimental investigation.

Previously quoted figures for the frequency of antigen switching in Trypanosoma brucei are based on incorrect assumptions. In order to determine the correct switching frequency, an equation was derived that takes the growth rates of the newly expressed antigen types into consideration as well as the proportion of switched trypanosomes and the number of generations since the population was antigenically homogeneous. When this equation was applied to published in vitro data, variable values were obtained for the switching frequency in clonal populations originally expressing one antigen type. The calculated most likely switching frequencies ranged from 1·4×10−7 to 3·5×10−6. This variation was probably caused by differences in the growth rates of the new antigen types in the population and failure to detect slow growing variants. To overcome these problems, an experimental procedure was developed to analyse the switching frequency in vitro. Trypanosomes were cloned and grown in parallel cultures. After an appropriate number of generations, cells expressing the original antigen type were destroyed and, from the proportion of cultures that contained new antigen types, the switching frequency was calculated. The technique minimized subculturing or other procedures that could distort the results. Although the method was optimized for analysing switching frequency, the values differed between experiments, ranging from 2·2×10−7 to 2·6×10−6 for one variant. Possible causes for the variations in switching frequency are discussed.

Plasmodium knowlesi merozoites were prepared by the polycarbonate sieving method of Dennis, Mitchell, Butcher & Cohen (1975). Merozoite function was assayed by their attachment to and invasion of rhesus erythrocytes at 37 °C. The early merozoites from the culture chamber were the most invasive, although maximum numbers of merozoites appeared later. Merozoites were most stable when incubated at room temperature (23 °C). At 37 and 0 °C invasiveness rapidly declined to zero. Attachment was rapidly lost at 37 °C but was retained at 0 °C. Attachment was unchanged in the pH range 6·8–7·9 but invasion was reduced at pH 7·9. The presence of l-fucose, d-galactose, d-glucose, d-mannose, N-acetyl-d-galactosamine or N-acetyl-D-glucosamine did not reduce invasion. Attachment and invasion were greatly reduced or abolished by the presence of 2·5 mm EDTA or EGTA, by lactoper-oxidase-catalysed iodination of the merozoites, or by treatment of the merozoites with trypsin at a concentration of 1 μg/ml or greater for 10 min at 23 °C.

The moulting behaviour of nymphal Rhipicephalus appendiculatus from the laboratory colony and 3 field strains from Kenya was greatly influenced by constant temperatures between 18 and 37 °C but was not significantly different for the 4 tick strains. Six batches of R. appendiculatus (Muguga laboratory) nymphs which had engorged on cattle parasitaemic with 4 stocks of Theileria parva (Kiambu 4, Kiambu 5, Muguga and Mbita 4) isolated in Kenya were incubated at constant temperatures between 18 and 37 °C during their pre-moult and post-moult periods. The Theileria infections in the salivary glands of the resultant adult ticks were assessed by staining with Feulgen's stain. Two stocks (Muguga and Kiambu 5) developed their highest infections in ticks incubated at 28 °C while the other two (Kiambu 4 and Mbita 4) developed their highest infections at 23 °C. Constant temperatures of 18, 33 and 37 ° C were detrimental to the development of salivary gland infections. Temperature influenced the rate of development and numbers of the earlier Theileria stages in the ticks. Engorged nymphal ticks incubated for 4 days at 37 °C during their pre-moult period developed lower infections than ticks exposed at 4 °C for 4 days.

The influence of density-dependent processes on the transmission of parasitic helminths is determined by both the severity of the regulatory constraints and the degree of parasite overdispersion among the host population. We investigate how overdispersed parasite distributions among humans influence transmission levels in both directly- and indirectly-transmitted nematodes (Ascaris lumbricoides and Onchocerca volvulus). While past work has assumed, for simplicity, that density dependence acts on the average worm load, here we model density-dependence as acting on individual parasite burdens before averaging across hosts. A composite parameter, which we call the effective transmission contribution, is devised to measure the number of transmission stages contributed by a given worm burden after incorporating overdispersion in adult worm mating probabilities and other density-dependent mechanisms. Results indicate that the more overdispersed the parasite population, the greater the effect of density dependence upon its transmission dynamics. Strong regulation and parasite overdispersion make the relationship between mean worm burden and its effective contribution to transmission highly non-linear. Consequently, lowering the intensity of infection in a host population using chemotherapy may produce only a small decline in transmission (relative to its initial endemic level). Our analysis indicates that when parasite burden is low, intermediate levels of parasite clustering maximize transmission. Implications are discussed in relation to existing control programmes and the spread of anthelmintic resistance.

Trypanosomes in the dissection-positive proboscis of Glossina pallidipes were identified by PCR using species-specific primers. Of the 3741 flies dissected 643 were proboscis positive. PCR was performed on 406 dissection-positive probosces giving positive identifications in 352 (86·7%) and infection rates of 14·8% for congolense-type infections, 2·8% for vivax- type infections and 1·4% for the unidentified group. Of the 352 PCR identified infections 225 were single, 111 were double, 13 were triple infections and there were 3 quadruple infections. Statistical analysis suggests that mixed infections group into 3 largely separate divisions among the tsetse population (i) Trypanosoma congolense savannah and T. congolense Kenya coast, (ii) T. simiae, T. congolense Tsavo and T. godfreyi and (iii) T. vivax. We conclude that either differing feeding patterns among members of the fly population or the ability of the trypanosomes in each of the infection categories to significantly influence the maturation of trypanosomes in the other categories are the most likely causes of the groupings noted. Chi-squared analysis of dissection and PCR methods of trypanosome identification revealed profound differences (χ = 19·1; D.F. = 1; P > 0·05). If confirmed in other studies these findings have serious implications for our understanding of trypanosome epidemiology in tsetse flies, much of which is founded on data from dissection-based trypanosome identifications.

To investigate the quantitative distribution of Plasmodium falciparum gametocytes into the vector bloodmeal, Anopheles arabiensis mosquitoes were fed on 3 volunteers naturally infected with gametocytes. The content of each mosquito midgut was smeared on a microscope slide and Giemsa stained. The distribution of gametocytes ingested by mosquitoes followed a negative binomial distribution, with apparently constant overdispersion (parameter k±S.E. = 3·105±0·392) for the 3 series. This aggregation of gametocytes in some midguts probably facilitates the conjunction of gametes and fertilization. This suggests that P. falciparum gametocytes in the peripheral blood flow of infected man do not follow an independent, homogeneous pattern but show a significant aggregation.

In recent years there has been a steadily growing interest in the immunology of schistosomiasis. Much work has been carried out using a variety of experimental hosts and many attempts have been made to vaccinate these hosts against schistosomes, both by exposing them to irradiated cercariae and by injecting them with various antigens derived from the parasites. These attempts have been attended by varying degrees of success. The ultimate object of much of this work has been its possible application to the disease in man. We believe, however, that work of this kind cannot really be profitably undertaken unless there already exists a sound understanding of the basic host-parasite relations between the schistosomes and their hosts. This knowledge is essential in order to decide whether a finding in one host is likely to be applicable in others. With this idea in mind, we report here our findings on naturally acquired resistance to Schistosoma mansoni in the rhesus monkey.

Within the last few years several books and numerous papers have been published dealing with various problems relating to the life-histories, and disease-spreading capacities, of house-frequenting and other nonbiting flies. An intimate knowledge of the habits of flies is essential if the most suitable methods are to be devised in order to diminish their numbers, yet it is only too evident that many of the accepted hypotheses are founded on the most superficial observations, and that extensive and carefully planned experiments, with a few notable exceptions, are conspicuously absent.

Variations in the amount of water contact made by individuals and in the amount of water contact made at different sites may have significant impacts on patterns of human schistosome infection. Previous studies have reported variations in the rate of water contact and differences in the sites used between age/sex classes, but there is limited information on variations in individual water contact behaviour. In this paper we report and analyse observations of essentially all water contacts made over a two week period by all individuals in a rural community in eastern Zimbabwe. The mean rate of water contact was 0.43 contacts/person/day. These data were over-dispersed, ranging from zero to 3.3 contacts/person/day; 90% of contacts were made by only 37% of the population. Contact rates were related to age (highest in 8 to 10-year-olds) but not sex, with substantial variation unaccounted for by these variables. Age and sex classes differed in types of water-related activities and the time of day of contact. A greater diversity of sites was used by children than by adults and by males than by females. Individual contact rates were correlated with intensities of infection, although the risk of infection per contact was estimated to be highest in 2 to 4-year-old children and higher for males than females. Five contact sites were used during the study period, with more than 50% of contacts occurring at just 2 sites. Different age and sex classes used different sites and there were additional site-related differences in types of activity and the time of day of use. The implications of these water contact patterns for schistosome epidemiology are discussed. In particular the results provide strong quantitative support for control programmes aimed at heavily used sites (e.g. focal mollusciciding) or at the minority of individuals making most water contacts (e.g. targeted chemotherapy).

This paper presents a model-based analysis of longitudinal data describing the impact of integrated vector management on the intensity of Wuchereria bancrofti infection in Pondicherry, India. The aims of this analysis were (1) to gain insight into the dynamics of infection, with emphasis on the possible role of immunity, and (2) to develop a model that can be used to predict the effects of control. Using the LYMFASIM computer simulation program, two models with different types of immunity (anti-L3 larvae or anti-adult worm fecundity) were compared with a model without immunity. Parameters were estimated by fitting the models to data from 5071 individuals with microfilaria-density measurement before and after cessation of a 5-year vector management programme. A good fit, in particular of the convex shape of the age-prevalence curve, required inclusion of anti-L3 or anti-fecundity immunity in the model. An individual's immune-responsiveness was found to halve in ~10 years after cessation of boosting. Explanation of the large variation in Mf-density required considerable variation between individuals in exposure and immune responsiveness. The mean life-span of the parasite was estimated at about 10 years. For the post-control period, the models predict a further decline in Mf prevalence, which agrees well with observations made 3 and 6 years after cessation of the integrated vector management programme.

Antimicrobial proteins were purified from acid extracts of rainbow trout (Oncorhynchus mykiss) and sunshine bass (Morone saxatilis male×M. chrysops female) skin, gill and spleen by reverse-phase HPLC. Mass spectrometry and amino acid sequence data suggest that these proteins are closely related to histone H2B and histone H1 and thus they were designated histone-like proteins (HLPs). These proteins were lethal to Amyloodinium ocellatum, which is one of the most important parasitic agents affecting fish. Antibiotic concentrations as low as 12·5 μg/ml were inhibitory. Activity was directed against the trophont (feeding) stage of the parasite, while the disseminative (dinospore) stage was unaffected. Thus, HLPs act unlike typical drugs used to treat amyloodiniosis, which usually target the dinospore. Both the ability of the parasite to infect host cells, as well as the ability to grow and differentiate after infection were severely inhibited. This is in contrast to magainin 2, which was similarly toxic to both the dinospore and trophont stages. These findings provide further evidence that histone-like proteins may be important defensive molecules in fish.

Gametocytes are the specialized form of Plasmodium parasites that are responsible for human-to-mosquito transmission of malaria. Transmission of gametocytes is highly effective, but represents a biomass bottleneck for the parasite that has stimulated interest in strategies targeting the transmission stages separately from those responsible for clinical disease. Studying targets of naturally acquired immunity against transmission-stage parasites may reveal opportunities for novel transmission reducing interventions, particularly the development of a transmission blocking vaccine (TBV). In this review, we summarize the current knowledge on immunity against the transmission stages of Plasmodium. This includes immune responses against epitopes on the gametocyte-infected erythrocyte surface during gametocyte development, as well as epitopes present upon gametocyte activation in the mosquito midgut. We present an analysis of historical data on transmission reducing immunity (TRI), as analysed in mosquito feeding assays, and its correlation with natural recognition of sexual stage specific proteins Pfs48/45 and Pfs230. Although high antibody titres towards either one of these proteins is associated with TRI, the presence of additional, novel targets is anticipated. In conclusion, the identification of novel gametocyte-specific targets of naturally acquired immunity against different gametocyte stages could aid in the development of potential TBV targets and ultimately an effective transmission blocking approach.