The murine model of infection with Leishmania major and its importance for the deciphering of mechanisms underlying differences in Th cell differentiation in mice from different genetic backgrounds.

Mice from the majority of inbred strains are resistant to infection by Leishmania major, an obligate intracellular protozoan parasite of macrophages in the mammalian host. In contrast, mice from BALB strains are unable to control infection and develop progressive disease. In this model of infection, genetically determined resistance and susceptibility have been clearly shown to result from the appearance of parasite-specific CD4+ T helper 1 or T helper 2 cells, respectively. This murine model of infection is considered as one of the best experimental systems for the study of the mechanisms operating in vivo at the initiation of polarised T helper 1 and T helper 2 cell maturation. Among the several factors influencing Th cell development, cytokines themselves critically regulate this process. The results accumulated during the last years have clarified some aspects of the role played by cytokines in Th cell differentiation. They are providing critical information that may ultimately lead to the rational devise of means by which to tailor immune responses to the effector functions that are most efficient in preventing and/or controlling infections with pathogens.

Trypanosoma cruzi: effect of phenothiazines on the parasite and its interaction with host cells

Phenothiazines were observed to have a direct effect on Trypanosoma cruzi and on its in vitro interaction with host cells. They caused lysis of trypomastigotes (50 uM/24 h) and,to a lesser extent, epimastigote proliferation. Treatment of infected peritoneal macrophages with 12.5 uM chlorpromazine or triflupromazine inhibited the infection; this effect was found to be partially reversible if the drugs were removed after 24 h of treatment. At 60 uM, the drugs caused damage to amastigotes interiorized in heart muscle cells. However, the narrow margin of toxity between anti-trypanossomal activity and damage to host cells mitigates against in vivo investigation at the present time. Possible hypothesis for the mechanism of action of phenothiazines are discussed.

A new host of Trypanosoma cruzi from Jujuy, Argentina: octodontomys gliroides (Gervais & D'Orbigny, 1844) (Rodentia, Octodontidae)

To identify wild hosts of Trypanosoma cruzi, surveys were conducted in the subandean valleys of Jujuy Province, Argentina, between June 1986 and March 1987. Seventy two mammals from 13 different species were examined by xenodiagnosis. Fifty two of them were mostly roedents trapped at the localities of Maimará, León and Tilcara, and the remainder had been kept in captivity at the Estación Biológica Experimental, in Jujuy. Trypanosoma cruzi infection was detected only in 2 Octodontomys gliroides (2 pos./8 exam. 25%) from all 72 examined mammals. Isolates were called Octodontomys Argentina 1 and 2 (OA1 and OA2). Both infected animals were caught at the archaelogical ruin of Pucará, at Tilcara. Repeated searches for triatomines in the ruin itself and in neighbour houses rendered negative results. Groups of mice inoculated with either OA1 or OA2 isolates became infected between 7 (OA1) to 12 days (OA2) postinoculation PI. Parasitemia peaks were observed between day 12th - 14th PI. Scarce amastigote nests were found in myocardium and skeletal muscle. Mortality was observed only for mice inoculated with OA1. Isoenzyme patterns of OA1 and OA2 were identical to one found in dogs and slightly different from that of human parasites in Argentina. Bones from Octodontomys sp., were recently found in a cave, dated 10200-8600 BC, in Pumamarca, near Tilcara, Jujuy. There are evidences that O. gliroides cohabited with man in ancient times and was associated to the domestic cycle of T. cruzi transmission, playing a role like that of domestic cavies. in Bolivia.

Rapid diagnostic tests for non-malarial febrile illness in the tropics.

The recent roll-out of rapid diagnostic tests (RDTs) for malaria has highlighted the decreasing proportion of malaria-attributable illness in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low resource settings. This review summarizes the current state of RDT development for several key infections, including dengue fever, enteric fever, leptospirosis, brucellosis, visceral leishmaniasis and human African trypanosomiasis, and highlights many remaining gaps. Most RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent. The sensitivity and specificity of host-antibody detection tests are both inherently limited. Moreover, prolonged antibody responses to many infections preclude the use of most serological RDTs for monitoring response to treatment and/or for diagnosing relapse. Considering these limitations, there is a pressing need for sensitive pathogen-detection-based RDTs, as have been successfully developed for malaria and dengue. Ultimately, integration of RDTs into a validated syndromic approach to tropical fevers is urgently needed. Related research priorities are to define the evolving epidemiology of fever in the tropics, and to determine how combinations of RDTs could be best used to improve the management of severe and treatable infections requiring specific therapy.

Pterigodermatites (Paucipectines) spinicaudatis n.sp. (Nematoda: Rictularidae) from Dromiciops australis (Marsupialia: Microbiotheriidae) in Bariloche, Rio Negro, Argentina, biogeographical distribution and host-parasite relationships

Pterigodermatites (P.) spinicaudatis sp.n. from Dromiciops australis is proposed and described. The simple morphology of the ovijector and the presence of a well developed spine between the two cuticular projections at the caudal extremity of the female distinguish the studied nematode from the remainder species of the genus parasitizing South American Edentata, marsupials and cricetid rodents. The distribution area of the hosts of the different species of P. (P.) are given. The studied genus does not parasitize any Australian marsupials. It was found in the endemic South American Microbiotheriidae. This fact suggests from a parasitological point of view that D. australis is not related to the Australian marsupials but to the South American ones.

Expression of a functional single chain antibody on the surface of extracellular enveloped vaccinia virus as a step towards selective tumour cell targeting.

Recombinant vaccinia virus with tumour cell specificity may provide a versatile tool either for direct lysis of cancer cells or for the targeted transfer of genes encoding immunomodulatory molecules. We report the expression of a single chain antibody on the surface of extracellular enveloped vaccinia virus. The wild-type haemagglutinin, an envelope glycoprotein which is not required for viral infection and replication, was replaced by haemagglutinin fusion molecules carrying a single chain antibody directed against the tumour-associated antigen ErbB2. ErbB2 is an epidermal growth factor receptor-related tyrosine kinase overexpressed in a high percentage of human adenocarcinomas. Two fusion proteins carrying the single chain antibody at different NH2-terminal positions were expressed and exposed at the envelope of the corresponding recombinant viruses. The construct containing the antibody at the site of the immunoglobulin-like loop of the haemagglutinin was able to bind solubilized ErbB2. This is the first report of replacement of a vaccinia virus envelope protein by a specific recognition structure and represents a first step towards modifying the host cell tropism of the virus.

Nomimoscolex touzeti n. sp. (Cestoda), a parasite of ceratophrys cornuta (L.): first record of a monticellidae in an amphibian host

Nomimoscolex touzeti n. sp. is described from one Ceratophrys cornuta (L.) caught in Amazonian Ecuador. Its taxonomic relationships to the others species are discussed. This new species is characterized by a cortical position of vitellaria; by the presence in the uteroduct of conglomerates of 20-40 eggs; by a weak ovary width/proglottis width ratio; by ventral excretory canals anastomosed; by a powerful vaginal sphincter and by a long cirrus. N. touzeti is the first record of Monticellidae in an amphibian host.

New host records and localities of some Monogenea from brazilian marine fishes with scanning electron microscopy of Bicotylophora trachinoti (Mac Callum, 1921)

Bicotylophora trachinoti (Mac Callum, 1921) from Trachinotus carolinus L.; Pseudanthocotyloides heterocotyle (Van Beneden, 1871) from Cetengraulis edentulus (Cuvier), and Decapterus punctatus (Cuvier), new host records; Pseudomazocraes selene Hargis, 1957 from Selene vomer (L.) and Caranx latus Agassiz, new host record, are reported for the first time in Brazil from the coast of Rio de Janeiro State. The marine fishes Diplectrum sp. and Pomatomus saltatrix (L.) are respectively new host records for Pseudotagia cupida (Hargis, 1956) and Macrovalvitrema sinaloense Caballero & Bravo Hollis, 1955. Measurements, original figures and photos in scanning electron microscopy of B. trachinoti are presented. The egg with filaments is reffered for the first time in the genus Pseudanthocotyloides.

The effect of host social system on parasite population genetic structure: comparative population genetics of two ectoparasitic mites and their bat hosts.

BACKGROUND: The population genetic structure of a parasite, and consequently its ability to adapt to a given host, is strongly linked to its own life history as well as the life history of its host. While the effects of parasite life history on their population genetic structure have received some attention, the effect of host social system has remained largely unstudied. In this study, we investigated the population genetic structure of two closely related parasitic mite species (Spinturnix myoti and Spinturnix bechsteini) with very similar life histories. Their respective hosts, the greater mouse-eared bat (Myotis myotis) and the Bechstein's bat (Myotis bechsteinii) have social systems that differ in several substantial features, such as group size, mating system and dispersal patterns. RESULTS: We found that the two mite species have strongly differing population genetic structures. In S. myoti we found high levels of genetic diversity and very little pairwise differentiation, whereas in S. bechsteini we observed much less diversity, strongly differentiated populations and strong temporal turnover. These differences are likely to be the result of the differences in genetic drift and dispersal opportunities afforded to the two parasites by the different social systems of their hosts. CONCLUSIONS: Our results suggest that host social system can strongly influence parasite population structure. As a result, the evolutionary potential of these two parasites with very similar life histories also differs, thereby affecting the risk and evolutionary pressure exerted by each parasite on its host.

On Thelazia anolabiata (Molin, 1860) Railliet & Henry, 1910 (Nematoda, Thelazioidea): a new host record and systematic considerations

Thelazia anolabiata (Molin, 1860) Raillet & Henry, 1910, parasite of eyes of birds, is reported in s new host, Ortalis canicolis pantanalensis Cher & Reich from Salobra, Mato Grosso do Sul State; T. digitata Travassos, 1918 and T. lutzi Travassos, 1918 are considered its synonyms.

Mechanisms of protective immunity against asexual blood stages of Plasmodium falciparum in the experimental host Saimiri

In the Saimiri monkey, an experimental host for human malaria, acquired protection against Plasmodium falciparum blood stages depends on the IgG antibody populations developed. In vivo protective anti-falciparum activity of IgG antibodies is correlated with the in vivo opsonizing activity promoting phagocytosis of parasited red bloood cells. In contrast, non protective antibodies inhibit this mechanism by competing at the target level. A similar phenomenon can be and human infection. Anti-cytoadherent and anti-rosette antibodies developed by Saimiri and humans prevent the development of physiopathological events like cerebral malaria which can also occur in this experimental host. Furthermore, transfer to protective human anti-falciparum IgG antibodies into infected Saimiri monkeys exerts an anti parasite activity as efficient as that observed when it is transfered into acute falciparum malaria patients, making the Saimiri an even more attractive host. Studies on the role of immunocompetent cells in the protective immune reponse are still in their infancy, however the existance of a restricted polymorphism of MHC II class molecules in the Saimiri confers additional theoretical and practical importance to this model.

Influence of the host related factors in the development of the hepatosplenic form of schistosomiasis mansoni

The frequency of hepatosplenomegaly in endemic areas is not proportional to the fecal ova count. This may be explained by epidemiological genetic. The occurrence of two or more cases of schistosomal hepatosplenomegaly in nuclear family is much higher than expected. The concentration is higher among siblings than it is among mothers and children of further and children. It is not significant between father and mother. If the mother, instead of the father has hepatosplenic schistosomiasis the relative risk for the child to acquire hepatosplenomegaly is at least five times (the maternal affect). The inbreeding is highler in the hepatosplenic than in the hepatointestinal patients. In some areas in Brazil the hepatosplenic form of the schistosomiasis mansoni occurs with much higher frequency in whites than in blacks. After treatment, reversion of hepatosplenic schistosomiasis occurs more frequently in non-whithers. It seems that the resistance of blacks to the hepatosplenic form of schistosomiasis may be related to the glyoxalase system , perhaps associated to another genetic marker. The hepatosplenic schistosomiasis is less frequent in longilineal individuals. In some areas the hepatosplenic form of schistosomiasis is more frequent in A blood group of ABO sistem. The family heredograms do not suggest a single mendelian inheritance, but probably a multifactorial and possibility poligenic one.

Parasite enzymes as a tool to investigate immune responses

Previous evidences reported by us and by other authors revealed the presence of IgG in sera of Schistosoma mansoni-infected patients to immunodominant antigens which are enzymes. Besides their immunological interest as possible inductors of protection, several of these enzume antigens might be also intersting markers of infection in antibody-detecting immunocapture assays which use the intrinsic catalytic property of these antigens. It was thus thought important to define some enzymatic and immunological characteristics of these molecules to better exploit their use as antigens. Four different enzymes from adult worms were partially characterized in their biochemical properties and susceptibility to react with antibodies of infected patients, namely alkaline phosphatase (AKP, Mg*+, pH 9.5), type I phosphodiesterase (PDE, pH 9.5), cysteine proteinase (CP, dithiothreitol, pH 5.5) and N-acetyl-ß-D-glucosaminidase (NAG, pH 5.5). The AKP and PDE are distinct tegumental membrane-bound enzymes whereas CP and NAG are soluble acid enzymes. Antibodies in infected human sera differed in their capacity to react with and to inhibit these enzyme antigens. Possibly, the specificity of the antibodies related to the extent of homology between the parasite and the host enzyme might be in part responsible for the above differences. The results are also discussed in view of the possible functional importance of these enzymes.

Mini-review: Specificity and expression of CIITA, the master regulator of MHC class II genes.

The class II transactivator (CIITA) has been referred to as the "master control factor" for the expression of MHC class II (MHCII) genes. As our knowledge on the specificity and function of CIITA grows, it is becoming increasingly evident that this sobriquet is entirely justified. First, despite extensive investigations, the major target genes of CIITA remain those implicated in the presentation of antigenic peptides by MHCII molecules. Although other putative target genes have been reported, the contribution of CIITA to their expression remains indirect, controversial or comparatively minor relative to its decisive role as a regulator of MHCII and related genes. Second, the most important parameter dictating MHCII expression is by far the expression pattern of the gene encoding CIITA (MHC2TA). The vast majority of signals that activate or repress MHCII expression under physiological and pathological situations converge on one or more of the three alternative promoters that drive transcription of the MHC2TA gene. In short, with respect to its specificity and its exquisitely controlled pattern of expression, CIITA is by a long stretch the single most important transcription factor for the regulation of genes required for MHCII-restricted antigen-presentation.

Ecological studies on the intermediate host snails and the relevance to schistosomiasis control

A detailed knoledge of distribution patterns schistosome intermediate hsts and their populations dynamics and factors affecting these patterns will provide useful information about the possibilities and desirability of conducting snail control measures in various transmission situations. On the basis of various case studies the association between the occurence of human water contacts and the presence of schistosome intermediate hosts or infections in the intermediate hosts is illustrated. Other parameters affecting snail distribution patterns and density fluctuations are discussed. It is concluded that ecological studies on the intermediate host are extremely relevant, either to optimally apply existing control measures or to develop alternative measures of snail control, such as ecological or biological control.