In the accompanying manuscript Saul (1998) points out that a model of within-host malaria population dynamics (Anderson, May & Gupta, 1989) can exhibit unrealistically large growth rates. He suggests that this error can be avoided by replacing the parameter r, which is the number of merozoites produced by each parasite at schizogony, with the value ln (r)+1. This substitution does not, however, address the true underlying problem with the model, namely that whilst in reality there is small variation in the distribution of Plasmodium spp. life-spans, the use of the constant rate α assumes an exponential, and hence much more variable, distribution. This can allow the population to increase, over the time period of the average life-span (48 h in the case of Plasmodium falciparum), by factors considerably larger than r. Saul identifies this assumption as unrealistic in terms of the biology of malaria, but it is not remedied in the proposed model.

Within the structure of the original model there are two ways of addressing the growth rate problem. Firstly, the ‘growth constant’ r can be replaced by the value ln (r)+1, so that if all parasites reinvade, the model increases by a factor r over 1 generation. As pointed out by Saul, this is an artificial device since it means that each parasite produces a reduced number of merozoites. Alternatively, a parasite can produce the observed number of merozoites, r, many of which do not reinvade. This is the situation in the original paper and Gravenor, McLean & Kwiatkowski (1995). In these papers the model does grow at a reasonable rate because the parameter β is estimated directly from observed growth rates. These points, however, are only an aside. Both the original and Saul's modified model can grow at the same rate and they both have the same distributional assumptions concerning parasite life-span.

Relapse of infection after trypanocidal drug treatment of trypanosome infections is normally attributed to drug resistance on the part of the parasite, under-dosage of the drug, or reinfection of the host. We have demonstrated relapse infections in goats arising from none of these. Fourteen goats infected with Trypanosoma brucei suffered severe illness and 3 died within 45 days. Despite treatment with the trypanocidal drug Berenil, a 4th goat died 2 days later. Recovery of the remainder followed chemotherapy, and in 2 goats, necropsiecl 45 days after treatment, no trypanosomes or abnormalities were detected. However 2–3 months after Berenil chemotherapy, despite trypanosomes being undetectable in the blood during the intervening period, infections in 4 of the remaining 8 animals relapsed. At all stages of the primary and relapse infections, trypanosomes isolated from the blood of the goats were completely susceptible to Berenil when tested in mice, as were parasites isolated from cerebrospinal fluid and brain tissue at necropsy. At the time of treatment, only minimal cellular infiltration was found in the central nervous system (CNS), but death from the relapse infection was associated with a very severe meningoencephalitis. We conclude that the relapse infections were caused by the re-emergence of trypanosornes from the CNS, where sequestered parasites were inaccessible to the trypanocidal effects of the drug.

The expression of the Schistosoma mansoni 28 kDa glutathione S-transferase (Sm28) was studied using molecular (PCR, in situ hybridization), and immunocytochemical techniques. The presence of Sm28 was demonstrated in all developmental stages of the parasite except the intra-uterine immature egg. In the parenchyma of male and female adult worms the distribution of Sm28 was limited to a subpopulation of parenchymal cells and to the dorsal tubercles of the male. The tegument, the muscles, the digestive tract, the neural mass, the vitelline glands, and mature gametes were not immunoreactive. Immature germinal cells in both sexes, and the ootype in the female genital system, were found to express Sm28. Deposits of immunoreactive material on host skin following cercarial penetration, exfoliation from the male tubercles, and especially emission of Sm28 from eggs in hepatic granulomas are suspected to be a source of antigen during the parasite infection. The reduction in worm fecundity previously observed in immunization experiments may result from an antibody response directed against Sm28 present in the ootype. There was no cross-reactivity observed, under the experimental conditions used, between the anti-Sm28 sera and either vertebrate or invertebrate host tissue.

Cortisone acetate, given to mice on two days during a primary infection with the nematode Trichuris muris, suppressed the development of acquired immunity to the parasite. The proportion of mice in which suppression occurred was greatest when the drug was given (at 2.5 mg per mouse) on days 14 and 15 of the infection. Suppression of the response prevented the elimination of larvae, which otherwise occurs during the third week, and allowed the parasite population to mature and survive for at least a further 3 weeks. Similar treatment given during a challenge infection in resistant mice prevented the elimination of the challenge larvae for 2 or 3 days only. Mice in which cortisone treatment had prevented the elimination of a primary infection were not only found to be fully susceptible to subsequent challenge, but showed no development of immunity to the challenge infection itself. This long-lasting suppression of the immune response to T. muris is discussed and the possibility of the induction of a specific immunological unresponsiveness to the parasite is considered.

“Piranabú,” “Piranampú” or “Piranampú” (the last according to Goeldi, 1898) are local names on the Amazon applied to the siluroid fish which, so far as it is possible to determine from memory and from the rough sketches and notes which I made at the time, is the modern Pirinampus pirinampus (Spix). This fish, of which I examined eight examples, attains a length of at least 60 cm., has an elongated adipose fin more than one-third the length of the entire body, microscopic scales, possesses maxillary barbels about half the length of the body, and in general appearance closely resembles the figure (Tab. VIII, a) of “Pimelodus ctenodus” provided by Spix (1829). I am much indebted to Mr J. R. Norman, of the British Museum, for his kind assistance in identification.

The circadian migration of Hymenolepis diminuta in the small intestine of the rat may be correlated with a circadian variation in 5-hydroxytryptamine levels present in worm tissue, in the intestinal lumen, in the intestinal mucosa, with the amount of food present in the small intestine and in arterial blood. The 5-HT and food levels in uninfected animals were also determined. The 16.00 h stage in the circadian cycle marks both the commencement of host feeding, followed by rising 5-HT levels in both worm and host tissues, and initiation of an anteriad migration of worm biomass. It was found that 5-HT levels in the intestine of parasitized animals were significantly higher than in the intestine of uninfected controls. This is the first report of circadian variation in mucosal and luminal 5-HT levels. The similarity in the circadian patterns of worm migration and worm luminal, mucosal and blood 5-HT levels were striking. Fasting eliminated the circadian rise in intestinal 5-HT levels and the worms did not migrate. Luminal 5-HT levels were significantly lower in fasted animals than in the comparable rats fed ad libitum. When the intestine was ligatured at the pyloric sphincter, worm anteriad migration still occurred after feeding, indicating that the presence of exogenous food in the intestine is not a factor in the initial migration of the worms.

It will be convenient at this point, before proceeding to a more general discussion of the findings, to summarize all the experiments recorded in the eight preceding subsections. Briefly the results are as follows:

(i) An attempt to infect a Macacus rhesus by feeding it with Trichomonas isolated from a monkey of the same species failed completely.

(ii) Four similar attempts to infect a Macacus sinicus with the same Trichomonas (from M. rhesus) were equally unsuccessful.

(iii) Two attempts to infect another M. sinicus by intra-intestinal inoculation with the same flagellate were likewise wholly negative.

(iv) One attempt to infect a man per os with the same strain of Trichomonas (from M. rhesus) did not succeed.

(v) A strain of Trichomonas from Man, when fed to a Macacus rhesus, produced no infection.

(vi) The same strain (T. hominis) fed to a Macacus sinicus likewise failed to infect.

(vii) A strain of Trichomonas from Macacus nemestrinus, however, when fed to M. rhesus, gave rise to a temporary infection lasting about a month.

(viii) This Trichomonas (from M. nemestrinus, after passage through M. rhesus) produced, nevertheless, a permanent infection—lasting 4½ years to date—when fed to a man.

(ix) The same strain of Trichomonas (from M. nemestrinus), after passage through M. rhesus and Man, when fed to a Macacus sinicus gave rise to an infection which endured for approximately 1½ months and then died out. But

(x) The very same Trichomonas (which was derived from M. nemestrinus, and which produced a temporary intestinal infection in M. rhesus and M. sinicus, and a permanent intestinal infection in Man) when introduced into the vagina of M. sinicus established itself enduringly as a typical “T. vaginalis.” The infection has now persisted for ome 3⅓ years.

(xi) The monkey (M. sinicus) in which a permanent vaginal infection with an intestinal Trichtomonas was established, has probably since reacquired no permanent intestinal infection—despite every natural opportunity for such reinfection.

(xii) No macaque suffered any harm whatsoever as a result of inoculation with any strain of Trichomonas–whether successful or unsuccessful.

(xiii) The one man successfully infected with Trichomonas (from M. nemestrinus) has likewise remained normal ever since.

The epidemiology of Ostertagia ostertagi and other gastrointestinal nematodes in yearling beef cattle was examined in each of 2 successive years. During each year 50 head of newly weaned beef calves were given a single dose of thiabendazole and then placed on experimental pastures. Twenty-four of the animals were designated for monthly slaughter (n = 2) and analysis of worm population characteristics and 25 were designated for blood and faecal collection and for weighing. Parasite-free tracer calves were grazed alongside the yearling cattle each month (n = 2) throughout the 2 years and were also slaughtered for analysis of worm populations. Faecal egg counts, plasma pepsinogen determinations, herbage larval counts, and animal liveweight changes were recorded monthly. Results of this work substantiated previous observations on seasonal changes of populations of the different nematode genera, but greater continuity and definition of patterns was possible in the present work. Ostertagia ostertagi was the predominant nematode present. While minimal numbers of inhibited larvae were observed from autumn into winter, most of the population was adult at this time. Acquisition of inhibition-prone larvae begins in late winter and peak numbers are acquired between March and June. Little transmission of O. ostertagi occurs between June and September. Trichostrongylus axei had a similar seasonal prevalence to O. ostertagi. A major difference in the 2 years was in the pattern of maturation of inhibited larvae. This occurred early, during May 1981, following below average temperatures in May and above average rainfall in May and June. Overt type II disease was not associated with a smaller level of maturation in autumn 1981. In contrast, maturation of large burdens of inhibited larvae did not occur until autumn 1982 following a protracted period of dry and hot weather from spring. Acute type II disease was observed in autumn 1982. Reasons for the differences in maturation pattern, based on worm counts from yearling cattle and tracer calves and association of these with faecal egg counts, herbage larval counts, clinical condition, and liveweight changes are discussed.

In the year 1915 the flies caught in traps baited with various materials and placed in different situations were recorded, and charts constructed showing the effects of various meteorological conditions on flies. “These charts showed that the curve for flies caught in traps corresponded most closely to the curve for the maximum temperature recorded by a thermometer exposed to the sun” (1916, 497 and Chart 5). During the years 1916 and 1917 traps baited daily with human excrement were exposed in sunny situations, and the flies caught in them recorded. Records of the hours of bright sunshine, of the rainfall, the velocity of the wind, the maximum temperatures indicated by thermometers exposed to the sun and in. the screen, the minimum temperatures in the screen and on the grass were kept. From these observations it was possible to compare the effects of meteorological conditions on flies in three consecutive seasons.

Farm-reared Leuciscus idus were experimentally infected with the intestinal tapeworm Caryophyllaeus laticeps, and maintained at different temperatures. At 12 °C and lower temperatures there was an initial loss of parasites after infection, but the survivors persisted for up to 1 month. At 18 °C only temporary survival of the parasite was possible, and worms were killed and rejected after 3 days. Experimental transplants to fresh hosts after 2 days indicated that the factors responsible for the death of the parasites became effective within this period.Neither inhibition of peristalsis nor host starvation affected the parasite's survival. The speed of the response to the parasite indicates that circulating antibodies produced in response to C. laticeps and directed specifically against it cannot be involved in the rejection. Other possible mechanisms of rejection are discussed, together with the significance of the results to the interpretation of data based on field observations.

I should like to thank Mr J. Harris for allowing me to refer to some of his unpublished data and for helpful discussions.

The base compositions of DNA from some species of malarial parasite have been estimated by measurement of density in CsCl gradients and of thermal denaturation temperatures. Species from avian (Plasmodium gallinaceum) and rodent (P. berghei and P. vinckei) hosts – often used as model systems in malarial studies – contain single DNA components with base compositions of about 20% G + C. By contrast, species from primate hosts (P. knowlesi and P. falciparum) contain major DNA components of about 40% G + C and minor ones of about 20% G + C. These differences could be reflexions of markedly different genomes within these two groups of the genus Plasmodium.

Apart from differences in base composition, the physico-chemical properties of the main components of DNA from primate and rodent malarial parasites are very similar to those of DNA from mammalian cells. DNA from avian malarial parasites appears to have some unusual properties.

One of us (P.I.T.) received financial assistance from the World Health Organization. We thank Dr F. Hawking and Dr J. Williamson for many helpful discussions, Dr W. H. G. Richards, Dr A. Voller and Dr D. C. Warhurst for the provision of some of the strains and Miss Jane Dunnett, Mrs A. C. Gutteridge and Mr T. Scott-Finnigan for technical assistance.

The following notes deal with nine species of parasitic nematodes from the Yangtze Valley and an additional one from North China. Of these ten species, one belongs to the super-family Rhabdiasoidea, three to Oxyuroidea, and six to Spiruroidea; three species have been previously described; therefore in these cases the writer gives only their measurements and a description of the particulars in which he found them to differ from the original description. Seven species Rhabdias annulosa n.sp., Pingus sinensis n.g. et n.sp. (Pingidae n.f.), Omeia hoepplii n.g. et n.sp., Thelazia chungkingensis n.sp., Oxyspirura kaitingensis n.sp., Oxyspirura peipingensis n.sp., Oxyspirura tsingchengensis n.sp., are new to science.

Observations are reported on the life history of Amplicaecum robertsi, in relation to the mode of infection as it occurs under natural conditions. Some of the natural intermediate hosts are listed, as compiled from observations on natural infection with third-stage larvae in Queensland mammals. Various natural intermediate hosts were experimentally infected by means of eggs, and observations on the growth and development of the larvae are described.

It was found that the second-stage larvae have a wide range of hosts, including earthworms, snails, fish, tadpoles, reptiles, birds, and mammals. Development to the third-stage was only observed to occur in birds and mammals. Third-stage larvae exhibited a wide variation in the degree of growth attained in different animals. In birds, growth was slight, not extending beyond 3–4 mm.; in mammals, growth varied considerably in different species; it was greater in the indigenous species, reaching 70–80 mm. No development beyond the third-stage occurred, except in reptiles.

Second-stage larvae in the tissues of invertebrates and lower vertebrates could be transferred by feeding to reptiles, birds and mammals. Development proceeded in these hosts to the same extent as occurred following egg infection.

Third-stage larvae could be transferred to certain snakes and lizards by feeding liver of infected rodents, but third-stage larvae over 3 mm. could not be transferred to mammals. Third-stage larvae were found to be uninfective at all stages of growth for birds.

The third moult occurred in the carpet snake when fed with third-stage larvae in the liver of Trichosurus caninus, Rattus assimilis and Melomys cervinipes infected 1 month previously. This was in contrast to previous findings with laboratory rodents, in which maturation of the third-stage larva took considerably longer.

Besides the carpet snake, the third and fourth moult was observed to occur in the goanna (Varanus spp.), the blue-tongued lizard (Tiliqua scincoides) and the bearded dragon (Amphibolurus barbatus). No growth in length was observed and no eggs were evident. As far as is known, none of these lizards is a definitive host of A. robertsi.

The results are discussed in relation to the food chain involved in the natural habitat of the carpet snake. The snake is depicted as the apex of a food pyramid, whose base comprises a variety of animals ranging from earthworms to herbivorous mammals. It is concluded that A. robertsi has adapted its life history in such a way as to enable the parasite to ascend the pyramid by transference through a series of predatory episodes, which culminate in the infection of the natural prey of the snake.

The life history is thus regarded, not as a life cycle, but as a life pyramid; development proceeds according to a pattern of diminishing host-specificity. Host-specificity is wide at the base of the pyramid, so that second-stage larvae occur in a wide variety of paratenic hosts. Host specificity narrows at the second moult which may occur in birds and mammals. It narrows still further in the third stage, because this larva, though it will survive in reptiles, birds and mammals, will not grow to a length at which it is capable of further development in the snake, except in certain mammals. At the third moult, host specificity shifts to certain reptiles, but becomes eventually restrictive to the carpet snake, because this host alone appears to provide a suitable environment for maturation of the eggs.

This work was financed by a research grant from the University of Queensland. The writer's sincere thanks are due to Miss Ann Pritchard and Mr J. Ballantyne for their valuable assistance.

Genetically defined, live attenuated Salmonella vaccines are proving useful both as oral vaccines against salmonellosis and for the development of multivalent vaccines based on the expression of heterologous antigens in such strains. Several candidate attenuated S. typhi strains are at present being evaluated as new single dose oral typhoid vaccines in human volunteers. The emergence of such a vaccine will facilitate the development of multivalent vaccines for humans. Many antigens from different infectious organisms have been expressed in attenuated Salmonella. A focus of this work has been on developing vaccines against parasitic diseases. This review will summarize the efforts that have been made in this area.

The diversity of the genes encoding 2 merozoite surface proteins (MSP-1 and MSP-2) of Plasmodium falciparum has been examined in parasites infecting members of 4 households in a village in Tanzania. The polymerase chain reaction (PCR) was used to characterize allelic variants of these genes by the sizes and sequences of regions of tandemly repeated bases in each gene. In each household extensive polymorphism was detected among parasites in the inhabitants and in infected mosquitoes caught in their houses. Similar frequencies of the alleles of these genes were observed in all households. Capture-recapture data indicated that both Anopheles gambiae and A.funestus freely dispersed among households in the hamlet. The results confirm that cross-mating and gene flow occur extensively among the parasites, and are discussed within the context of spatial clustering of natural populations of P. falciparum.

The larvae of Brugia pahangi recovered from the jird have been shown to grow continuously between moults, their length increasing at least 5-fold during the 4th instar. This intermoult growth is achieved without an increase in the surface area of larvae. The cuticle of very early 4th and 5th-stage worms is highly folded and intermoult growth is accommodated by an expansion of surface annular folds. The major increases in the surface area of larvae occur only through ecdysis, with an 8-fold increase in the surface area being achieved at the 3rd moult. The growth curve of these worms is therefore sigmoidal but the surface area curve is stepped. The relationship between the cuticles of nematodes and insects is discussed

Acquired immunity influences the severity of parasitic disease, but modelling the effects of acquired immunity in helminth infections has proved challenging. This may be due to a lack of suitable immunological data, or to the perceived complexity of modelling the immune response. We have developed a model of T. circumcincta infection in domestic sheep that incorporates the effects of acquired immunity on parasite establishment and fecundity. A large data set from commercially managed populations of Scottish Blackface sheep was used, which included relationships between IgA activity and worm length, and between worm length and fecundity. Use was also made of a recently published meta-analysis of parasite establishment rates. This realistic but simple model of nematode infection emulates observed patterns of faecal egg counts. The end-of-season faecal egg counts are remarkably robust to perturbations in the majority of the parameters, possibly because of priming of the immune system early in the season, reducing parasite establishment and growth and, therefore, faecal egg counts. Lowering the amount of early infection leads to higher end-of-season egg counts. The periparturient rise in egg counts in ewes appears to have an important role in supplying infection for the priming of the immune response. This feedback in the immune priming suggests that nematode infections may be difficult to eliminate.

The 14-3-3 protein is a key player in signal transduction processes in various species. We have previously cloned and expressed the 14-3-3 of Schistosoma mansoni. Using the purified protein we have now raised antibodies against it. A highly specific, affinity-purified antibody preparation was employed for the localization of the 14-3-3 protein in the parasite, by both immunohistochemistry and immunoelectron microscopy. The results demonstrate wide distribution of this protein. It was observed in the female excretory system, the nephridia as well as in the genital systems of both sexes, namely in the vitelline gland of female and in the testis of the male. It is also present in the parenchyma and muscle of both male and female worms. Immunoelectron microscopy demonstrated the presence of immunogold-labelled protein in the tegument, subtegument, muscle, parenchyma and in the female reproductive system, in both the cytoplasm and nucleus of vitelline cells, and oocytes. The possible role of the 14-3-3 protein in the genital organs is discussed.

One of the most important public health problems in the world today is the emergence and dissemination of drug-resistant malaria parasites. Plasmodium falciparum is the causative agent of the most lethal form of human malaria. New anti-malarial strategies are urgently required, and their design and development require the identification of potential therapeutic targets. However, the molecular mechanisms controlling the life cycle of the malaria parasite are still poorly understood. The published genome sequence of P. falciparum and previous studies have revealed that several homologues of eukaryotic signalling proteins, such as protein kinases, are relatively conserved. Protein kinases are now widely recognized as important drug targets in protozoan parasites. Cyclic AMP-dependent protein kinase (PKA) is implicated in numerous processes in mammalian cells, and the regulatory mechanisms of the cAMP pathway have been characterized. P. falciparum cAMP-dependent protein kinase plays an important role in the parasite's life cycle and thus represents an attractive target for the development of anti-malarial drugs. In this review, we focus on the P. falciparum cAMP/PKA pathway to provide new insights and an improved understanding of this signalling cascade.

This study describes, for the first time, the characterization of excretory–secretory antigens (ES-Ag) from Echinococcus granulosus protoscoleces, evaluating their usefulness in the immunodiagnosis of human cystic echinococcosis. ES-Ag were obtained from the first 50 h maintenance of protoscoleces in vitro. This preparation contained over 20 major protein components which could be distinguished by 1-dimensional SDS–PAGE with apparent masses between 9 and 300 kDa. The culture of of protoscoleces from liver produced a greater variety of excretory–secretory protein components than those from lung. Determination of enzymatic activities of secreted proteins revealed the presence of phosphatases, lipases and glucosidases, but no proteases. These findings were compared to those obtained from somatic extracts of protoscoleces and hydatid cyst fluid products. Immunochemical characterization was performed by immunoblotting with sera from individuals infected by cystic echinococcosis (n=15), non-hydatidic parasitoses (n=19), various liver diseases (n=24), lung neoplasia (n=16), and healthy donors (n=18). Antigens with apparent masses of 89, 74, 47/50, 32, and 20 kDa showed specificity for immunodiagnosis of human hydatidosis. The 89 and 74 kDa components corresponded to antigens not yet described in E. granulosus, whereas proteins of 41–43 kDa and 91–95 kDa were recognized by the majority of the non-hydatid sera studied.