Assessment of the resilience of canine leishmaniasis to control or, more ambitiously, the effort needed to eradicate infection, requires an estimate of the basic case reproduction number (R0). This paper applies the theoretical results of Hasibeder, Dye & Carpenter (1992) to data from a cross-sectional survey on the Maltese island of Gozo in which dogs of known age, sex and occupation (pet, guard etc) were subjected to three different serological tests for the presence of specific antibody (IFAT, DAT and ELISA). Difficulties in interpreting these test results, and hence of determining the proportion of dogs infected, present the main obstacle to estimating R0: estimates are critically dependent on the choice of threshold separating seropositives from seronegatives. The data do, however, allow a robust comparative analysis of risk which shows that the force of infection experienced by working dogs is about three times higher than that of pet dogs, a degree of non-homogeneous contact which actually has little effect on estimates of R0. We suggest a cautious point estimate of R0 ≃ 11, and comment briefly on its significance for leishmaniasis control.

Immunoprecipitation combined with electrophoresis in gelatin-polyacrylamide gels was successfully used for detection of antibodies against numerous proteinases of Trichomonas vaginalis in infected patients. The method proved to be highly specific as anti-proteinase antibodies were absent in women with negative cultivation of T. vaginalis and no history of trichomoniasis. Sera of 71% and vaginal washes of 86% patients with trichomoniasis were positive for these antibodies. In vaginal washes, but not in sera, antibodies were partly complexed with proteinases, possibly of trichomonad origin. It was also shown that serum antibodies as well as local anti-proteinase antibodies persisted for weeks after patients had been cured.

Anti-parasitic drugs may achieve their therapeutic effect either by direct activity against the pathogenic organism, or by altering host factors which lead to parasite killing. In this review, we discuss the evidence for an indirect mode of action for one major anti-filarial drug, diethylcarbamazine (DEC). The interpretation most consistent with existing data is that DEC alters arachidonic acid metabolism in microfilariae and in host endothelial cells. These changes may result in vasoconstriction and amplified endothelial adhesion leading to immobilization of microfilarial parasites, enhanced adherence and cytotoxic activity by host platelets and granulocytes. These events would represent activation of the innate, non-specific immune system, independent of the adaptive, antigen-specific, immune response. This model explains the paradox between rapid clearance in vivo and the lack of an in vitro effect, as well as the efficacy of DEC in non-immune animals.

We describe a new, improved test for the detection of intestinal infection by Entamoeba histolytica. The test depends upon immunoadsorption of the E. histolytica cysteine proteinase, histolysain, from faecal samples, and subsequent visual detection of the enzyme by a colour reaction. With samples from 200 volunteers, results agreed closely with those obtained by the conventional microscopic technique, and there were no false positive reactions with samples containing other parasites. The test is suitable for use either in the laboratory or in the field.

A solid-phase enzyme immunoassay (EIA) was used to detect circulating antibodies to histolysain, the major cysteine proteinase of Entamoeba histolytica. Serum samples from 40 healthy controls, 33 asymptomatic E. histolytica cyst passers and 22 patients with amoebic liver abscess were tested. Antibodies to histolysain were found in 72·7% of cases of amoebic liver abscess, 18·1% of the cyst passers and 2·5% of healthy controls, which suggests that a humoral immune response is induced by histolysain during amoebic liver abscess.

The paper describes a mathematical model for canine leishmaniasis and presents formulae which can be used to estimate the basic reproduction number, R0. The primary concern has been to devise methods of estimation which make best use of those data most easily obtained by fieldwork, e.g. surveys of prevalence in dog (by age) and sandfly populations. A range of formulae are offered which are more or less demanding of data, and which consequently give more or less precise estimates of R0. They include methods for assessing the influence on R0 of heterogeneous biting rates of sandflies on dogs, in which the essence of heterogeneous transmission can be captured merely by measuring relative rather than absolute contact rates.

Cells of Leishmania donovani in co-culture with Trypanosoma brucei, were severely affected in their growth, resulting in swelling and subsequent lysis. Similar effects were also observed when Crithidia luciliae or Phytomonas sp. were co-cultured with T. brucei. Direct contact between the cells under investigation and T. brucei was necessary because T. brucei did not hamper the growth of the other trypanosomatids, when separated by a filter with 0.2 μm pore size. Examination of this phenomenon at the ultrastructural level, in a co-culture of L. donovani and T. brucei, suggests that the plasma membrane permeability is increased in the former, as a result of a close cellular contact between the two cell types.

Malaria is a controllable disease, yet the resources required - human, technical and financial - are massive, and are currently beyond the vast majority of the 96 countries where the disease is endemic. The control measures most widely applied are vector control through spraying or use of insecticide-impregnated bednets, and chemotherapy. The biological problems to add to the resource issues are well known; increasing resistance of anopheline mosquitoes to the most widely used insecticides, and the progressive development of drug resistance in the parasite populations, especially Plasmodium falciparum.

The immune status of a host infected with Trypanosoma spp. or Leishmania spp. can play an important role in successful chemotherapy. In animal models, treatment of African trypanosomiasis with difluoromethylornithine or melarsoprol requires an appropriate antibody-mediated immune response. An intact immune system is also necessary for rapid clearance of trypanosomes from the bloodstream following treatment with suramin or quinapyramine. Similarly, an efficient cell-mediated immune response is required for maximal efficacy of pentavalent antimonials in the treatment of leishmaniasis. However, the potential relationship between parasite-induced or acquired immunosuppression and effective chemotherapy has been poorly studied. Macrophages which have been activated by bacterial cell wall components or gamma-interferon are known to display increased activity against Leishmania donovani or Trypanosoma cruzi. In experimental and clinical visceral leishmaniasis, use of macrophage activators together with pentavalent antimonials has lowered the dose of antimony required to cure the infection.

The complete sequence of the cDNA encoding a 20 kDa calcium-binding protein of Schistosoma mansoni (Sm20) has been determined. The predicted amino acid sequence contains 4 EF hand domains but examination of the predicted secondary structure of Sm20, together with the specific residues in each calcium-binding domain, suggests that only 1 EF hand (domain IV) is functional. Sm20 is most homologous to calmodulin, troponin C and the regulatory light-chain of myosin, particularly those of invertebrates. However, troponin C and the regulatory light-chain of myosin can be distinguished from Sm20 by size and by their differential levels of expression during the life-cycle. Sm20 also appears to be distinct from calmodulin but may be functionally equivalent to the soluble sarcoplasmic calcium-binding proteins of molluscs and crustacea which may act as a reservoir for calcium in muscle. Sm20 is encoded by a small multi-gene family whose members are clustered within a 15 kb region of the genome. A 20 kDa antigen, cross-reactive with Sm20, is expressed in Schistosoma haematobium, Fasciola hepatica and Paragonomus mexicanus.

Fractionation of Schistosoma mansoni cercariae gland secretion on a Sephadex G-150 column followed by a Superose-12 column in an FPLC system, isolated a 47 kDa protease which migrated as a single band on SDS–PAGE gels. A monoclonal antibody (MAb) was produced which recognizes only the 47 kDa protease, and an immuno-affinity column with the MAb was used to isolate the protease. The 47 kDa protease showed activity on several macromolecules such as elastin and collagen type VI besides gelatin and casein. This suggests that this enzyme can be one of the enzymes that might facilitate invasion of the cercariae through host skin. The optimal pH of the protease against the synthetic substrate, Ac-Phe-Arg-Nan, in Tris–HCI buffer was 10. Experiments with protease inhibitors indicate that the purified enzyme is a serine protease.

The ability of Trichomonas vaginalis to adhere to plastic surfaces in the presence of various agents and under different growth conditions was examined in wells of microtitre plates containing unsupplemented TYI medium or the same, with various supplements. Following incubation, the wells were thoroughly washed and adhesion was determined by microscopic counting of the adherent organisms. There was no detectable adhesion in the absence of both serum and carbohydrate. Optimal adhesion (about 10–20% of the total number of parasites) was obtained throughout the growth curve in culture media supplemented with either serum or serum Cohn fractions IV–I (rich in α-globulin) or IV-4 (rich in α + β-globulin) and 25 mM glucose, maltose or fructose, but not in plates pre-coated with the Cohn fractions. Cohn fraction II + III (rich in β + γ-globulin) moderately enhanced adhesion while Cohn fractions II (rich in γ-globulin) or V (albumin), fibronectin, Tamm-Horsfall glycoproteins and polylysine were without effect. Non-metabolizable sugars (methyl derivatives of glucose, mannose or fucose) did not support growth, but, surprisingly, enhanced adhesion. At 4 °C, the trichomonads were not able to adhere and pre-adherent organisms detached from the plastic surface. Optimal adhesion was obtained at a pH range of 6·5–7·5 but was already detectable at pH 5·5. Cytochalasin E markedly suppressed adhesion. The data taken together suggest that the firm, serum-dependent adhesion of T. vaginalis to plastic surfaces is apparently not influenced by the rate of multiplication, requires energy and the binding by the organisms of certain serum proteins, which possibly enhances their hydrophobic interaction with the plastic substratum.

In this in vitro study we investigated whether previously described in vivo plasma-associated effects, that occurred in the period shortly after penetration of Trichobilharzia ocellata into the snail host Lymnaea stagnalis (1.5–72 h post-exposure; p.e.) were direct and/or indirect effects of parasite-derived factor(s). It was investigated whether the effect is mediated by the central nervous system (CNS) of the host. Phagocytic activity of the haemocytes was taken as a parameter for the activity of internal defence of the host. A number of preliminary experiments were performed. When the supernatant of in vitro cultured parasites (33 h; corresponding with their developmental stage in vivo when plasma-associated activation was found) was applied directly to monolayers of haemocytes, it appeared to enhance their phagocytic activity. No direct effect, however, was found with a supernatant of parasites cultured for a longer period of time (72 h; when, in vivo, a plasma-associated suppression was found). In this case, indirect suppression was detected: the parasites appeared to have released a factor that induced the CNS of the host to release material suppressing the activity of the internal defence system of the host. To date the nature of this factor is unknown.

In bovine theileriosis the use of chemotherapy to control an infection sufficiently long to permit the establishment of a solid protective immune response has been developed as a routine vaccination procedure. Infections with Theileria parva and T. annulata can be prevented by the administration of carefully controlled numbers of sporozoites simultaneously with a long acting tetracycline and this form of immunization has been widely used for the control of East Coast fever in Africa with considerable success. In this review, the nature of the chemotherapy, the immune response and the interactions between chemotherapy and immunity in the development of infection-and-treatment immunization procedures are discussed.

We consider two phenomena, related to the host age-intensity profiles of parasitic infections, which have been suggested to be indicative of acquired immunity: (i) a lower age of peak intensity among more intensely infected hosts; and (ii) a decline with age in the dispersion of the distribution of parasites between hosts. We demonstrate that these phenomena occur among Kenyan schoolchildren infected with Schistosoma mansoni, although the magnitude of both is small. We also examine the mathematical models underlying these predictions and conclude that both phenomena are possible in the absence of acquired immunity or, indeed, in the absence of any density-dependent effect. In our opinion, insufficient attention has been focused upon mathematical models, describing the null hypothesis, i.e. density-independent models. In particular, we regard the usual assumptions made for the two stochastic components of these models, describing the heterogeneity between hosts and the probabilistic nature of infection and death of parasites, as too rigid and unrealistic. We demonstrate that deviation from these assumptions undermines the qualitative distinctions between models which describe acquired immunity or density dependence and those which are density-independent.

Two repetitive DNA sequences have been characterized from Schistosoma mansoni which were transcribed into mRNAs and translated to give two families of cross-reactive proteins. One DNA element, which was present as a 230 bp Pst I fragment was arranged in tandem arrays of at least 17 copies in the genome. The second element, which could be localized to a 1800 bp Pst I fragment, was dispersed in the genome. The 1800 bp repeat was found on the mRNA encoding the 45 kDa polypeptide precursor of a potential surface antigen. This precursor was post-translationally modified to give a 50 kDa antigen (Sm50) which was expressed from the cercaria to the adult worm and in the egg. However, a proportion of this antigen was differentially modified in females and eggs to give a 60 kDa form. Two copies of the 230 bp repeat and one copy of the 1800 bp repeat were found on a second cDNA clone. The antiserum raised against the fusion protein of this clone recognized a family of cross-reactive proteins ranging from 14 to 70 kDa in size. The members of this family were also differentially expressed between the sexes. Consequently, two families of antigens have been identified which were both encoded by repetitive DNA elements and whose members were both differentially expressed in adult male and female worms.

The polystomatid Pseudodiplorchis americanus occupies a wider range of habitats and experiences more diverse physiological conditions than any other monogenean. It initially invades the respiratory system of an anuran, Scaphiopus couchii, and then migrates along the alimentary tract while the host is actively feeding, resulting in exposure to digestive enzymes and the surfactant action of bile. Whilst in the urinary bladder, parasites are exposed to wide osmotic fluctuations. This ultrastructural study reveals a set of adaptations unknown elsewhere in platyhelminth biology. During development within the respiratory tract, pre-migratory worms accumulate two types of electron-dense tegumental vesicle. Migration through the gut is accompanied by mass secretion of vesicles which appear to provide protection against digestion. Pre-migrants transferred experimentally to digestive fluids die within minutes unless they have received a specific cue which is responsible for triggering vesicle secretion. Migrants stimulated by this trigger factor can tolerate the same conditions for up to 8 h by continually releasing vesicles to form a protective surface coat. No specific structural adaptations were evident for survival in the lungs or bladder of the host.

Praziquantel is widely used for treatment of schistosomiasis. Elimination of intravascular worms involves a combination of drug-induced changes at the worm surface and a host immune response against exposed parasite components. Loss of spines is a typical feature of schistosomes obtained from praziquantel-treated infected animals. The mechanism for this is unknown. We have considered the possibility that praziquantel treatment involves exposure of surface spines consisting of ‘paracrystalline’ actin and a subsequent host response against actin through mechanisms established in the host independently from schistosomal infection. Drug-induced exposure of actin was demonstrated by fluorescence microscopy using anti-actin antibodies and phallacidin, an actin-binding mushroom toxin. Actin spines remained intact at the schistosome surface after in vitro exposure, but spine morphology was lost after in vivo exposure to praziquantel. Disintegration of spines in vivo was associated with binding of host antibodies. In vitro spine destruction could be seen in the presence of normal human serum. The effect was linked to calcium-dependent binding of actin depolymerizing factor, gelsolin.

An increasing number of antiviral agents are presently in various stages of development and testing, and an increasing number have recently been licensed for use in humans. These drugs have been used extensively to treat viral infections in immunocompromised individuals, and these studies indicate that for many antiviral agents the response to therapy is highly dependent on the integrity of the underlying host immune response. In particular, the response to zidovudine, acyclovir and ganciclovir in persons with HIV-1 infection is highly dependent upon CD4 number, which can be considered a surrogate marker for the state of host immune function in these subjects. Responses to interferons likewise can be shown to depend on the host immune response, with responses due to both direct antiviral effects of this agent as well as immunomodulatory effects mediated through interferon-induced upregulation of HLA molecule expression.

Lysates of Theileria annulata-infected bovine lymphoblastoid cells and their uninfected counterparts were tested for protease activity using gelatin substrate SDS–PAGE. The infected cells produced a number of extra activities at pH 8·0 in the presence of Ca2+. Calcium was found to enhance the activites but was not an absolute requirement. Studies using inhibitors, including E64, 3,4-dichloroisocoumarin, pepstatin and 1, 10-phenanthroline suggested that the activities were metalloproteases. We analysed two vaccine lines; the Ode line from India and the Ankara Pendik line from Turkey. In the Ode line the later passage had very much reduced levels of the enzyme activities. In the case of the Ankara Pendik line both stages analysed had very low protease activities, but a reduction from the early to late passage was also observed. The reduction in the level of protease activity was also observed as a gradual process during on-going culture of lines derived from the Hissar and Ode stocks. In the Ode line we demonstrated a parallel decrease in the production of microschizonts upon temperature shift in vitro.