Borrelia burgdorferi sensu lato (s.l.) is maintained in nature by complex zoonotic transmission cycles, involving a large variety of vertebrates as hosts and hard ticks of the genus Ixodes as vectors. Recent studies suggest that the genospecies of B. burgdorferi s.l. and sometimes their subtypes are propagated by different spectra of hosts, mainly birds and rodents. In order to test the concept of host-association, we analysed the relationships between Borrelia genospecies, rodent hosts and I. ricinus ticks in an endemic focus of Lyme borreliosis in western Slovakia. Rodents and questing ticks were collected at a forested lowland locality near Bratislava. Tick infestation levels on rodents were determined, and spirochaete infections in ticks and in ear punch biopsies were analysed by PCR followed by genotyping. Mice were more heavily infested with ticks than bank voles, and a higher proportion of mice was infected with spirochaetes than voles. However, the infectivity of voles was much higher than that of mice. The vast majority of infections detected in the skin and in ticks feeding on the rodents represented B. afzelii. In contrast, more than half of all infections in questing ticks collected in the same region of Slovakia were identified as B. valaisiana and B. garinii. In conclusion, whilst the study reveals that mice and voles play different quantitative roles in the ecology of Lyme borreliosis, it demonstrates that B. afzelii is specifically maintained by European rodents, validating the concept of host-association of B. burgdorferi s.l.

The Kato-Katz method is widely used for diagnosing helminth infections in epidemiological surveys, but is known to have a low sensitivity. In the case of Schistosoma mansoni, statistical methods have been developed to compensate for the poor sensitivity, but the same is not true of any other helminth parasite, or infections with multiple-helminth species. We screened 101 schoolchildren from a rural area of Côte d'Ivoire over 5 consecutive days and made 5 Kato-Katz readings from each stool specimen. We estimated single and dual-species infections with S. mansoni and hookworm based on raw egg count data and after developing a latent-class model. The cumulative prevalence of co-infections was estimated at 9·9% after reading slides on the first day, and 57·0% after reading all 25 slides per person. The latent class model yielded a co-infection prevalence estimate of 79·6%, with marginal prevalence estimates for hookworm and S. mansoni infections of 83·9% and 91·6% respectively. The sensitivities of a single Kato-Katz thick smear for detection of S. mansoni alone, hookworms alone, or S. mansoni plus hookworms were 22·4%, 8·0% and 17·7%, respectively. In the current setting this could be attributable to low infection intensities of both parasites, combined with intra-specimen and day-to-day variation in egg output. If confirmed in other settings, these findings have implications for estimating the prevalence of multiple species helminth infections, and hence the design and implementation of efficacious and cost-effective control programmes.

Foraging strategies of eight species of entomopathogenic nematodes were predicted from their response to host volatile cues and dispersal behaviour on 2-dimensional substrates. Positive directional response to chemical cues and similar distances travelled on smooth (agar) or nictation substrates (agar overlaid with sand grains) by Heterorhabditis bacterio-phora, Heterorhabditis megidis, Steinernema anomali, and Steinernema glaseri suggest their cruising approach to finding hosts. The absence of directional response and less distance travelled on nictation substrate, than on smooth agar by Steinernema carpocapsae and Steinernema scapterisci suggest their ambushing mode of foraging. Steinernema feltiae and Steinernema sp. responded directionally to host volatiles, but travelled less distance on the nictation substrate than on smooth agar; the two species also did not nictate. The cruiser species located hosts more effectively in the sand columns, whereas the ambushers were more effective at finding hosts on filter paper. Steinernema feltiae and Steinernema sp. performed equally on filter paper and in the sand column. We conclude that H. bacteriophora, H. megidis, S. anomali and S. glaseri cruise to find hosts, whereas S. carpocapsae and S. scapterisci ambush hosts. Steinernema feltiae and Steinernema sp. are intermediary in the search continuum sharing some characteristics of both ambush and cruise foragers.

Post-mesocyclic development of Trypanosoma brucei in the tsetse fly in its migration from midgut to salivary glands, was revisited by sequential microdissection, morphometry and DNA-cytofluorometry. This development started by day 6 after the infective feed, with passage of mesocyclic midgut trypomastigotes through proventriculus and upward migration along foregut and proboscis to the salivary gland ducts. Kinetics of salivary gland infection showed that colonization of the salivary glands by epimastigotes occurred only during the time-limited presence of this developmental phase in the foregut and proboscis. Post-mesocyclic trypanosomes in the foregut and proboscis were pleomorphic, with 4 morphological stages in various constant proportions and present all through from proventriculus up to the salivary gland ducts: 67% long trypomastigotes, 27% long epimastigotes, 4% long epimastigotes undergoing asymmetric cell division and 2% short epimastigotes. Measurements of DNA content demonstrated a predominant tetraploidy for 67% of these trypanosomes, the remainder consisting of the homogeneous diploid short epimastigotes and some long epimastigotes. According to the experimental data, the following sequence of trypanosome differentiation in the foregut and proboscis is proposed as the most obvious hypothesis. Incoming mesocyclic trypomastigotes (2N) from the ectoperitrophic anterior midgut start to replicate DNA to a 4N level, are arrested at this point, and differentiate into the long epimastigote (4N) which give rise, by an asymmetric cell division, to 2 unequal, diploid daughter cells: a long, probably dead-end long epimastigote and a short epimastigote. The latter is responsible for the epimastigote colonization of the salivary glands if launched at the vicinity of the gland epithelium by the asymmetric dividing epimastigote.

The unfed tick gains water from humid air or from water in contact with the cuticle, and loses water by evaporation. Whilst attached to the host the tick is gaining water from the ingested blood and losing water in the excrement. The engorged tick usually lacks the ability to take up water from humid air.

The exchange of water takes place mainly through the cuticle. Regulation of the water balance is therefore brought about by the activity of the epidermal cells.

The cuticle comprises two principal layers, the epicuticle and endocuticle. The epicuticle is overlaid by a lipoid possessing important waterproofing properties. The pore canals, which traverse the endocuticle, are occupied by cytoplasm, and may in consequence play an important role in the active -transfer of water through the cuticle: they do not penetrate the epicuticle.

Water loss from the unfed tick is not closely related to saturation deficiency, particularly at high humidities. This departure is due to a physiological cause, namely, to the ability to secrete water. The effects of this activity are such that a state of equilibrium is attained at a relative humidity of about 92%: at lower relative humidities the tick loses water by evaporation, while at higher humidities it takes up water. The retention of water at humidities below the point of equilibrium is due not only to the physical properties of the epicuticle but also to this secretory activity, for water loss increases when the tick is temporarily asphyxiated, poisoned with cyanide or injured through excessive desiccation. Near the point of equilibrium the loss or gain of water over a wide range of temperature is determined by the relative humidity.

The uptake of water from humid air occurs when the tick is in a desiccated condition but ceases as the normal water content is restored. After previous exposure to saturated air the adapted tick at first loses water at relative humidities above the point of equilibrium, but later comes to retain water completely.

Both unfed and engorged ticks possess the ability to prevent or to limit temporarily the entry of water in contact with the cuticle.

The engorging female, originally weighing about 2 mg., ingests about 600 mg. of blood. About 300 mg. or two-thirds of the contained water are usually eliminated before the end of engorgement. Evaporation from the cuticle may account for a considerable fraction of this, for the temperature to which the attached tick is exposed (about 37°C.) is, in Ixodes ricinus, above that temperature at which a marked increase in the permeability of the epicuticular lipoid takes place.

The nine species of ticks examined differ considerably in their powers of limiting evaporation. This may reflect specific differences in the nature of the epicuticular lipoid. The order of their resistance is as follows: Ornithodorus moubata; Dermacentor andersoni; D. reticulatus; Rhipicephalus sanguineus; Amblyomma cajennense and A. maculatum; Ixodes canisuga; I. hexagonus; I. ricinus. In dry air water loss throuǵh the cuticle is 10–15 times more rapid in Ixodes ricinus than in Dermacentor andersoni. The more resistant species also take up water through the cuticle after desiccation; indeed, the rate of uptake over a unit area of cuticle is approximately the same in all species of Ixodidae. Uptake thus appears to be limited by the ability of the epidermal cells to secrete water.

Stocks of Dermacentor andersoni, Rhipicephalus and Amblyomma spp. were kindly supplied by Dr R. A. Cooley, Director of Entomology, Rocky Mountain Laboratory, U.S.A., through the good offices of Prof. P. A. Buxton, F.R.S. I am also indebted to Dr H. H. Green of the Veterinary Laboratory, Weybridge, for providing useful facilities, and to Dr V. B. Wigglesworth, F.R.S., for his generous help throughout the various stages of this work.

Various factors that may influence routine and high levels of mosquito infection with cultured Plasmodium falciparum gametocytes are considered in this paper. One of the most important is the choice of an appropriate isolate, with facilities for cryopreservation and a good technique for initiation of cultures. The use of automated culture systems with strict adherence to detail and routine has eliminated much of the variability. The quality of the serum used for the culture of gametocytes and inclusion in the feed material for mosquitoes is of the highest importance. Blood collection for culture purposes must preferably involve alcohol as an antiseptic for cleaning donor skin or suitable receptacles. Mosquito blood meals should not include plasma with citrate phosphate dextrose or sera collected in microtainer tubes or from volunteers on proguanil-chloroquine prophylaxis. Sera of individuals on chloroquine alone do not influence transmission. Haemato-crits of from 5 to 10% permit the culture of equally infective gametocytes. It was impossible to predict the outcome of an infection in mosquitoes based on the number of female gametocytes or gametes. Within any experiment, the oocyst load initially increased, followed by a decline with progressively lower numbers of gametocytes accompanied by a progressive increase in the efficiency of transmission. Some of the variability of mosquito infection within an experiment was due to individual differences in the speed of blood digestion of the mosquitoes. A new membrane feeder is described with three different sizes to accommodate a variety of goals. The new design permitted more mosquitoes to feed within a limited period compared to the older more widely used feeder of equivalent capacity, and mosquitoes feeding on the new-type feeder were frequently better infected than those fed on the older type.

The taxonomic situation in the genus Tritrichomonas is the subject of controversial discussion: potentially T. foetus and T. suis, the tritrichomonads from cattle and swine, respectively, could belong to the same species. In order to shed some light on this question, a molecular biological analysis was performed. The 5·8S rRNA gene and the flanking internal transcribed spacer regions (ITS1 and ITS2) of 12 different isolates of 3 Tritrichomonas species T. foetus, T. suis and T. mobilensis were enzymatically amplified by PCR and subcloned. Also, the corresponding regions of the trichomonads Trichomonas vaginalis, T. tenax, T. gallinae and Pentatrichomonas hominis were included in this study. Sequence analysis of cloned fragments was used to compare the parasite isolates. The genus Tritrichomonas exhibited an extremely high degree of homogeneity. All T. foetus and T. suis isolates had identical sequences, and only 1 substitution was found in the ITS2 region of T. mobilensis. In contrast, the genus Trichomonas shared more diversity. The results obtained in this study support a possible future revision of the taxonomic classification of tritrichomonads.

This study presents new findings concerning the evolution of the human pathogens, Trypanosoma brucei and T. cruzi, which suggest that these parasites have divergent origins and fundamentally different patterns of evolution. Phylogenetic analysis of 18S rRNA sequences places T. brucei in a clade comprising exclusively mammalian trypanosomes of African origin, suggesting an evolutionary history confined to Africa. T. cruzi (from humans and sylvatic mammals) clusters with trypanosomes specific to Old and New World bats, T. rangeli and a trypanosome species isolated from an Australian kangaroo. The origins of parasites within this clade, other than some of those from bats, lie in South America and Australia suggesting an ancient southern super-continent origin for T. cruzi, possibly in marsupials; the only trypanosomes from this clade to have spread to the Old World are those infecting bats, doubtless by virtue of the mobility of their hosts. Viewed in the context of palaeogeographical evidence, the results date the divergence of T. brucei and T. cruzi to the mid-Cretaceous, around 100 million years before present, following the separation of Africa, South America and Euramerica. The inclusion in this study of a broad range of trypanosome species from various different hosts has allowed long phylogenetic branches to be resolved, overcoming the limitations of many previous studies. Moreover, T. brucei and the other mammalian tsetse-transmitted trypanosomes appear, from these data, to be evolving several times faster than T. cruzi and its relatives.

The role of interspecific interactions in the structure of gastrointestinal helminth communities has been at the core of most research in parasite community ecology, yet there is no consensus regarding their general importance. There have been two different approaches to the study of species interactions in helminths. The first one consists of measuring the responses of helminth species in concomitant infections, preferably in laboratory experiments. Any change in numbers of parasite individuals or in their use of niche space, compared with what is observed in single infections, provides solid evidence that the species are interacting. The second approach can only provide indirect, circumstantial evidence. It consists in contrasting observed patterns either in the distribution of species richness of infracommunities from wild hosts, in their species composition, or in pairwise associations between helminth species among infracommunities, with the random patterns predicted by appropriate null models. In many cases, observed patterns do not depart from predicted ones; when they do, alternative explanations are usually as plausible as invoking the effect of interactions among helminth species. The present evidence suggests that the role of species interactions in helminth community structure is often negligible, but that it must always be evaluated on a case-by-case basis.

By culturing Galleria mellonella, Neoaplectana sp. (DD-136) and Achromobacter nematophilus separately under axenic conditions in the laboratory, it was possible to study the relationship between the bacterium and nematode during nematode parasitism of the insect.

The infective-stage juveniles of the nematode were able to penetrate and kill the insect host without the presence of A. nematophilus or any other bacterium. However, without accompanying bacteria the nematode was unable to reproduce. Only when A. nematophilus or a possible replacement, such as Pseudomonas aeruginosa, was added to the blood did reproduction occur.

The relationship between A. nematophilus and the nematode is considered a mutualistic one, since the bacterium lives and is protected inside the intestine of the free-living stage of the nematode and is transported and released by the nematode to the haemolymph of a host insect. The nematode, in turn, is dependent on the bacterium for reproduction.

A previous analysis of tick infestation patterns on rodents in Slovakia suggested that the key to the focal distribution of western-type tick-borne encephalitis virus (TBEv) in Europe is the geographically variable degree of synchrony in the seasonal activity of larval and nymphal Ixodes ricinus ticks. This prediction is here tested by examining records, from 7 different countries, of the seasonal variation in the abundance of larvae and nymphs feeding on rodents or questing on the vegetation. Larvae consistently started feeding and questing earlier in the year at sites within TBEv foci than elsewhere, so that they appeared in the spring as soon as nymphs were active. Such larval–nymphal synchrony is associated with a rapid fall in ground-level temperatures from August to October as revealed by the satellite-derived index of Land Surface Temperature (LST). Likewise, of 1992 pixels sampled on a grid across Europe, the 418 that fell within TBEv foci were characterized by a higher than average rate of autumnal cooling relative to the peak midsummer LST. It is proposed that such a seasonal temperature profile may cause unfed larvae to pass the winter in quiescence, from which they emerge synchronously with nymphs in the spring.

Human alveolar echinococcosis (AE), caused by the metacestode of the fox tapeworm Echinococcus multilocularis, is the most pathogenic zoonosis in temperate and arctic regions of the northern hemisphere. Prospective collection of human cases in some areas and mass screenings using ultrasound imaging and confirmation with serological techniques have markedly improved our knowledge of the epidemiology of the disease in humans during the past two decades. Transmission occurs when eggs of the tapeworm, excreted by the final hosts (usually foxes but also dogs, wolves and cats), are ingested accidentally by humans or during normal feeding by a variety of rodents and small lagomorphs. However, the species of host animals differ according to regional changes in mammalian fauna. This review mostly focuses on epidemiology of alveolar echinococcosis in those parts of the world where new and more accurate epidemiological data are now available, i.e. China and Europe, as well as on new epidemiological trends that can be suspected from recent case reports and/or from recent changes in animal epidemiology of E. multilocularis infection. The People's Republic of China (PRC) is a newly recognized focus on AE in Asia. Human AE cases were firstly recognized in Xinjiang Uygur Autonomous Region and Qinghai Provinces at the end of 1950s and infected animals were first reported from Ningxia in central China and north-east of Inner Mongolia in the 1980s. E. multilocularis (and human cases of AE) appears to occur in three areas: (1) Northeastern China (northeast focus): including Inner Mongolia Autonomous region and Heliongjiang Province (2) Central China (central focus): including Gansu Province, Ningxia Hui Autonomous Region, Sichuan Province, Qinghai Province and Tibet Autonomous Region and (3) Northwestern China: including Xinjiang Uygur Autonomous Region, bordered with Mongolia, Russia, Kazakhstan and Kyrgyzstan. The highest prevalence of the disease, up to 15 per cent of the population in some villages, is reached in China. In Europe, data from the European Echinococcosis Registry (EurEchinoReg: 1982–2000) show 53 autochthonous cases of AE in Austria, 3 in Belgium, 235 in France, 126 in Germany, 1 in Greece, and 112 in Switzerland, and 15 ‘imported’ cases, especially from central Asia; 14 cases were collected in Poland, a country not previously considered endemic for AE. Improved diagnostic technology, as well as a real increase in the infection rate and an extension to new areas, can explain that more than 500 cases have been reported for these 2 decades while less than 900 cases were published for the previous 7 decades. New epidemiological trends are related to an unprecedented increase in the fox population in Europe, to the unexpected development of urban foxes in Japan and in Europe, and to changes in the environmental situation in many countries worldwide due to climatic or anthropic factors which might influence the host–predator relationship in the animal reservoir and/or the behavioural characteristics of the populations in the endemic areas.

The northern biotype of Echinococcus granulosus occurs in North America and northern Eurasia in life-cycles involving cervids. Previously, cervid isolates of E. granulosus from North America have been characterized using molecular genetic techniques as the G8 genotype. In this study, 5 isolates of E. granulosus were collected from 4 reindeer and 1 moose in north-eastern Finland. DNA sequences within regions of mitochondrial cytochrome c oxidase I (COI) and NADH dehydrogenase I (NDI) genes and the internal transcribed spacer 1 (ITS-1) fragment of the ribosomal DNA were analysed. The mitochondrial nucleotide sequences were identical in all isolates, but high sequence variation was found in the ITS-1 region. Mitochondrial and nuclear sequences of the Finnish cervid E. granulosus and the camel strain (G6) of E. granulosus resembled closely each other. According to phylogenetic analyses, the Finnish isolates have close relationships also with the pig (G7) and cattle (G5) strains. Although some similarities were found with the previously published North American cervid strain (G8), particularly in the NDI sequence and some of the ITS-1 clones, the Finnish E. granulosus form represents a distinct, previously undescribed genotype of E. granulosus. The novel genotype is hereby named as the Fennoscandian cervid strain (G10).

Parasitic helminths excrete or secrete (ES) a variety of molecules into their mammalian hosts. The effects of these ES products on the host's immune responses are reviewed. Investigations into the source of antigenic or immunoregulatory ES products have identified the cuticular and tegumental surfaces of some nematodes and trematodes respectively as being important sources of ES products; other ES molecules are released through specialized excretory or secretory organs. It is proposed that the active shedding of surface antigens may serve as an important source of parasite antigens available to the immune system in a form in which they can be taken up and processed by antigen-presenting dendritic cells, macro-phages and certain B cells for presentation to T helper cells. The ES products of nematodes, trematodes and cestodes contribute to immune evasion strategies of the parasites through mechanisms including shedding of surface-bound ligands and cells, alteration of lymphocyte, macrophage and granulocyte functions and modulation of complement and other host inflammatory responses. Immunopathology may be induced by ES products as in the development of granulomas around entrapped schistosome eggs. In some host – parasite systems ES antigens may induce host-protective immune responses and this source of protective antigens has been utilized in the successful vaccination against helminth infections, particularly against infection with trichurid nematodes and the metacestode stage of cestode parasites. The use of ES antigens in immunodiagnosis of helminth infection is also briefly discussed.

1. Scabies is usually transmitted by intimate personal contact.

2. The young, newly fertilized adult female Sarcoptes is the stage usually responsible for transmission.

3. Patients with a high parasite rate (over 100 adult female mites) are much more likely to spread scabies than those with few parasites.

4. The distribution of the parasites in clinical scabies gives no clue to the original sites of infection.

5. When a volunteer is infected for the first time he gives no reaction for about a month. During this period he may be quite unaware that the parasites are burrowing in his cuticle.

6. After a month the patient becomes sensitized, itching and other symptoms develop.

7. In a first infection the mites increase in numbers far less rapidly than is theoretically possible. A parasite rate of about 25 may be reached in 50 days and of up to 500 in 100 days; after this the number of mites decreases rapidly.

8. The second time an individual has scabies he itches at the sites of infection within 24 hr. His mite population seldom rises to a fraction of the height reached in his first infection.

9. Reinfection of cured cases is much more difficult than infection for the first time.

10. Sarcoptes causes antibody function in man. This causes a partial immunity.

11. The mechanism of immunity is due to three reactions: (a) scratching by the host which removes the parasites mechanically; (b) oedema renders the cuticle unsuitable for colonization and causes the mites to vacate their burrows; (c) scratching produces sepsis which is fatal to Sarcoptes.

12. The partial immunity obtained may account for fluctuations in the incidence of the disease.

In situations where malaria eradication is not an option in the foreseeable future the emphasis must be on the control of morbidity and mortality due to malaria. Under such circumstances drawing a distinction between malarial parasitization and malarial disease may be important for workers in both field and laboratory. This concept is explored from the points of view of the epidemiological picture of malaria in endemic populations, the factors which may influence progression to disease and the processes which mediate disease.

The design of mass and targetted community-based chemotherapy programmes for the control of the major helminth infections of man is discussed in relation to the population and transmission dynamics of the parasites. Rapid reinfection following a single mass or targetted anthelmintic application is shown to be a universal feature of helminth transmission, as a consequence of the regulatory or feed-back mechanisms controlling population abundance within both individuals and the community as a whole. Control of reinfection requires repeated community treatment where the intensity of application and the interval between treatments are dependent on the reproductive life-expectancy of the adult worm, the net force of transmission prior to control (the basic reproductive rate) and the factors which create aggregation in the distribution of parasite loads within the population. Selective or targetted treatment is shown to be most effective for the control of morbidity as opposed to the control of transmission. The impact of targetted treatment depends critically on the factors that generate heterogeneity in parasite burdens and on whether or not selectivity is based on a single or repeated identification of the ‘wormy’ fraction of the community. Monte Carlo simulation studies are employed to assess the likely impacts of different control strategies on average parasite abundance/person and the distributions of parasite loads within populations. Future epidemiological research needs are discussed in relation to theoretical work and recent field studies of predisposition to heavy infection.

1. Defence reactions to metazoan parasites have been reported in fourteen orders of insects. The observations are brought together and reviewed in the first part of the paper.

2. Examination of the various accounts that have been given shows that blood cells are always involved in insect defence reactions. They act by forming a cellular capsule, from which a connective-tissue envelope is usually developed, and in which melanin is often deposited.

3. The reaction of the epidermal cells at perforations made by parasites is of the nature of wound-healing, and plays no part in defence against metazoan parasites after they have entered the body.

4. Although several other tissues have been implicated, there is insufficient evidence to show that any of them make defence reactions, their response being limited to processes of regeneration.

5. It is concluded that the blood cells of insects are their only known agents of defence to internal metazoan parasites.

6. The principal groups of metazoan parasites infesting insects are considered in the third part of the paper, in order to see how the defence reactions made to them are related to their mode of attack and to the nature and consequences of their parasitism.

7. Most parasites elicit a defence reaction when they are in unusual hosts.

8. Some parasites, at certain stages of their life-history, are able to avoid eliciting a defence reaction in their usual hosts.

9. Some parasites elicit a defence reaction in their usual hosts but are able either to endure it in a dormant state or to resist it.

10. General problems of host specificity in relation to defence reactions are discussed. It is concluded that analysis of the stimuli that produce defence reactions has not yet gone far enough to explain the phenomena.

11. The effects of insect defence reactions on metazoan parasites range from no perceptible effect to destruction of the parasite.

12. The defence reactions of insects are influenced by the species, genetic strain, stage, instar, size, health and physiological state of the host; and by the species, genetic strain, physical and physiological activity, and health of the parasite. Environmental temperature and the presence of other parasites of the same or different species also have effects on the reactions.

13. A brief survey of defence reactions made by invertebrates other than insects shows that encapsulation has been reported in Annelida, Mollusca, Crustacea, Acarina, and larval echinoderms. So far as it goes, the survey does not reveal in these other groups any reaction to metazoan parasites of a kind radically different from the reactions observed in insects.

14. The historical development and present state of our knowledge of insect defence reactions is traced.

15. The reactions made by insects to innocuous parasites are of theoretical interest but of little consequence to the species concerned. It is their effect on potentially dangerous parasites that determines the value of defence reactions. Consideration of the evidence suggests that the protection afforded to insects by their defence reactions is greater than has been generally supposed.

16. The review makes apparent many gaps in our knowledge of the phenomena. A few of the outstanding problems are mentioned.

I am indebted to Mr R. T. Hughes of the Balfour Library for helping me to obtain journals not available in Cambridge; to Mr M. J. Ashby for the photography necessary in the preparation of the figures; and to Miss G. M. Edwards for her careful typing from my manuscript. The paper would not have been completed without the goodwill and assistance of two persons: Professor D. Keilin, F.R.S., encouraged me to continue and finish it when my effort flagged; my wife not only gave me positive help in many ways but also exercised great forbearance in allowing me to devote vacations and spare time to it.

Cerebral malaria is a life-threatening complication of malaria infection. The pathogenesis of cerebral malaria is poorly defined and progress in understanding the condition is severely hampered by the inability to study in detail, ante-mortem, the parasitological and immunological events within the brain that lead to the onset of clinical symptoms. Experimental murine models have been used to investigate the sequence of events that lead to cerebral malaria, but there is significant debate on the merits of these models and whether their study is relevant to human disease. Here we review the current understanding of the parasitological and immunological events leading to human and experimental cerebral malaria, and explain why we believe that studies with experimental models of CM are crucial to define the pathogenesis of the condition.

This paper presents a method of estimating the potential global morbidity due to human intestinal nematode infections (Ascaris lumbricoides, Trichuris trichiura and hookworms), based on the observed prevalence of infection. The method relies on the observed relationships between prevalence and intensity of infection, and between worm burden and potential morbidity. This approach is shown to be sensitive to the precision of the original prevalence estimates and, in particular, to the degree of spatial heterogeneity in levels of infection. The estimates presented here indicate that several tens of millions of children are likely to suffer developmental consequences from infection, and suggest that the global disease burden of geohelminthiasis may be significantly greater than was supposed.