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The Source-Sink Dynamics of Plasmodium vivax May Undermine Malaria Elimination Efforts in the Amazon: An Epidemiological and Population Genomic Study.

BACKGROUND: Brazil's progress toward malaria elimination has stalled and 163 000 new cases (more than 80% caused by Plasmodium vivax) were recorded in the Brazilian Amazon in 2023. We hypothesize that human mobility continues to disperse parasites from hotspots to areas with decreasing endemicity. METHODS: We analyzed 5.5 million malaria case notifications between 2003 and 2023 to describe malaria case mobility and identify sources and sinks of P. vivax in the Brazilian Amazon. We leveraged whole-genome sequence data from 408 P. vivax isolates sampled from across South America to characterize parasite gene flow and infer likely regional routes of parasite dispersal. RESULTS: We found that nearly one-third of the P. vivax infections diagnosed in residents in the Brazilian Amazon over 21 years were acquired outside the locality or municipality of residence, but only 1.7% were imported from other countries in South America, mostly from the Guiana Shield. We show that large cities with residual malaria transmission-such as Manaus and Porto Velho-are receptive parasite sinks surrounded by high-risk source rural localities. Although the genetic relatedness of parasites tended to decrease with geographic distance, parasites from sites more than 1000 km apart often remained genetically connected. CONCLUSIONS: Understanding parasite source-sink dynamics on different geographic scales is crucial to target high-risk mobile populations and source localities along with receptive sinks within low-transmission municipalities, with the goal of eliminating malaria transmission and preventing its reintroduction into malaria-free areas.

Humans↗

Etiology of cancer in humans and animals.

Cancer is a multistep disease with a multifactorial aetiology. Among the avoidable causes of human cancer are exposure to environmental carcinogens, ionizing and non-ionizing radiation, chronic inflammatory states (viruses and parasites) and life style factors, in particular diet. There is increasing evidence that these aetiologic factors may interact with each other resulting in a more than additive cancer risk. This has been demonstrated for example with hepatitis B virus and aflatoxins in hepatocellular carcinoma and alcohol and tobacco in cancer of the esophagus. The integration of molecular markers of exposure, biological effect and individual susceptibility into epidemiological studies can contribute to strengthening the causal link between exposure and disease and thus help assess the relative contribution of multiple risk factors to the aetiology of a specific cancer. For some genotoxic carcinogens the sequence of events leading to tumour formation is well understood from exposure, to metabolism and ultimately to specific mutations in transformation-associated genes. The mechanisms of action of carcinogens which do not interact directly with DNA but exert adverse effects through receptor-mediated modulation of intercellular signal pathways is far less well understood and an example of this is the interaction between diet and hormones. Furthermore, there is increasing awareness that individual response to environmental agents may depend to a significant extent on the genetic background of the individual or population. This has long been known from animal experiments but human cancer susceptibility is a complex genetic trait involving genes responsible for carcinogen metabolism, DNA repair and as yet unidentified cell specific susceptibility genes. Phenotypic changes observed during tumour progression reflect the sequential acquisition of genetic alterations. To assess the contribution of mutations in the various genes involved in the carcinogenic process may require their expression in transgenic animals or knock out mice. This has again placed animal experimentation into the forefront of mainstream cancer research.

Animals↗

Simultaneous transient expression assays of the trypanosomatid parasite Leishmania using beta-galactosidase and beta-glucuronidase as reporter enzymes.

We describe a transient transfection protocol for cultured Leishmania major promastigotes, utilizing Escherichia coli genes encoding beta-galactosidase and beta-glucuronidase inserted into an expression vector derived from the dihydrofolate reductase-thymidylate synthase locus. Less than 0.1 pg of either reporter enzyme can be detected with a simple fluorimetric assay, and transfection of 10 micrograms of either reporter construct yields activities at least 100-fold over background. Simultaneous introduction of both constructs showed that the activity of each reporter gene was unaffected by the presence of the other, allowing one reporter construct to serve as a control for experimental variability in test gene constructs containing the second reporter gene. These results show that it is feasible to apply transient expression assays to the identification of cis-acting elements of genes encoding nonabundant mRNAs in the genus Leishmania.

Animals↗

Biochemical and immunological properties of a viral hybrid particle expressing the Plasmodium vivax merozoite surface protein 1 C-terminal region.

BACKGROUND: Mammalian cells expressing the small hepatitis B virus surface protein (HBs) secrete highly immunogenic 20 nm lipoprotein particles. Previous studies demonstrated that the fusion of foreign sequences into certain regions of HBs leads to chimeric particles carrying epitopes for the foreign peptide, as well as for HBs. The present study investigates immunologic and biochemical properties of the fusion of the C-terminal region of the merozoite surface 1 protein of P. vivax, the most widely distributed human malaria parasite, and HBs (PvMSP1(19)-HBs). MATERIALS AND METHODS: COS7 cells were transfected with a plasmid coding for PvMSP1(19)-HBs. The hybrid products were analyzed by density gradient centrifugation and electron microscopy or detected by metabolic labeling and immunoprecipitation with anti-HBs and patient-derived anti-P. vivax serum. Mice were immunized with the vector and the antibody response was checked by ELISA. RESULTS: The fusion PvMSP1(19)-HBs formed particles of 20-45 nm size, which were secreted from COS7 cells. The particles were immunoprecipitable with anti-HBs and serum of different P. vivax-positive individuals. Immunization of mice with the construct as a genetic vaccine showed that antibodies were raised mostly against the PvMSP1(19) domain and recognized the native protein. CONCLUSION: Due to its biochemical and antigenic properties, the hybrid particle will be useful in future vaccine trials against the asexual blood stages of P. vivax as a genetic and/or a proteic subunit candidate.

Animals↗

Separation and mapping of multiple genes that control IgE level in Leishmania major infected mice.

The strain BALB/cHeA (BALB/c) is a high producer, and STS/A (STS) a low producer of IgE after Leishmania major infection. We analyzed this strain difference using 20 recombinant congenic (RC) BALB/c-c-STS/Dem (CcS/Dem) strains that carry different random subsets of 12.5% of genes of the strain STS on the BALB/c background. Strains CcS-16 and -20 exhibit a high and a low IgE level, respectively. In their F(2) hybrids with BALB/c we mapped nine Leishmania major response (Lmr) loci. Two of them we previously found to influence IgE level in CcS-5. IgE production in CcS-16 is controlled by loci on chromosomes 2, 10, 16 and 18 and in CcS-20 by loci on chromosomes 1, 3, 4, 5 and 8. The STS alleles of loci on chromosomes 1, 4, 5, 8 and 10 were associated with a low, whereas the STS alleles on chromosomes 16 and 18 with a high IgE production. The loci on chromosomes 2 and 3 have no apparent individual effect, but interact with the loci on chromosomes 10 and 1, respectively. The loci on chromosomes 10 and 18 were mapped in the regions homologous with the human regions containing genes that control total serum IgE and intensity of infection by Schistosoma mansoni, suggesting that some Lmr loci may participate in the pathways influencing atopic reactions and responses to several parasites. The definition of genes controlling anti-parasite responses will permit a better understanding of pathways and genetic diversity underlying the disease phenotypes.

Animals↗

Different roles for interleukin-4 during the course of Toxoplasma gondii infection.

The course of Toxoplasma gondii infection from initiation of disease perorally until day 28 postinfection was compared between interleukin-4 (IL-4) gene knockout (IL-4-/-) mice and their wild-type (IL-4+/+) counterparts on a disease-susceptible genetic background. The rate of mortality was significantly greater in mice deficient in Il-4 than in the immunocompetent controls. Although levels of T. gondii-specific spleen cell proliferation measured in vitro were similar between groups at all time points examined throughout infection, the quantities of cytokines released into the culture supernatant differed. Culture supernatants from spleen cells derived from IL-4-deficient mice contained significantly more gamma interferon than those derived from IL-4+/+ mice at day 7 postinfection. Conversely, IL-10 production was significantly greater from the spleen cells derived from wild-type mice at day 28 postinfection. Splenocytes from both groups of mice had a marked inhibition of proliferation in response to soluble tachyzoite antigen as well as reduced proliferation in response to concanavalin A between days 7 and 14 postinfection and marked proliferation on days 21 and 28 postinfection. At day 28 postinfection, histological examination of the brains indicated that IL-4+/+ mice had more severe pathological changes and more cysts than IL-4-/- mice. In addition, although many nonencysted single organisms were present in IL-4+/+ mice within both necrotic lesions and microglial nodules, few nonencysted parasites were found, and no necrotic lesions were present in IL-4-deficient animals. These results suggest that the observed reduction in mortality during the early acute phases of infection may be due to the down-regulatory effects of Il-4 or associated Th2-derived products on proinflammatory cytokines such as gamma interferon. However, the long-term effects of IL-4 are detrimental, possibly because of the ability of this cytokine to inhibit proinflammatory antiparasitic products. This may explain the increased parasite multiplication with cysts observed in the brains of IL-4+/+ mice.

Animals↗

The high background immune reactivity of mice to polymorphic determinants on xenogeneic erythrocytes: theoretical and practical implications.

Background responses have been assessed by fusing lipopolysaccharide- (LPS) stimulated spleen cells from unimmunized mice with MOPC 315.43 myeloma cells and screening the hybrids for the production of antibody against chicken red blood cells (CRBC). Clones specific for CRBC represented about 1% of total hybrid clones (1000 to 5000 clones were obtained per mouse). The majority of the anti-CRBC clones (greater than 95%) secreted antibody against polymorphic CRBC determinants (present on CRBC from some but not all chickens) rather than species-specific determinants present on all CRBC. Some of the polymorphic determinants were linked to the B locus (the MHC of the chicken) and some were non-B antigens. The relative amount of these 2 categories varied slightly according to the mouse strain. These results agree well with the specificities of natural mouse antibody and rosette-forming spleen cells. The response of immunized mice against CRBC and human RBC was also selective for polymorphic determinants. These results have considerable importance for the use of xenogeneic RBC as "standard" antigens, and are interpreted in terms of a model for the advantages of genetic polymorphism as a protection against antigen mimicry by parasites.

Animals↗

Quantitative trait loci in Anopheles gambiae controlling the encapsulation response against Plasmodium cynomolgi Ceylon.

BACKGROUND: Anopheles gambiae females are the world's most successful vectors of human malaria. However, a fraction of these mosquitoes is refractory to Plasmodium development. L3-5, a laboratory selected refractory strain, encapsulates transforming ookinetes/early oocysts of a wide variety of Plasmodium species. Previous studies on these mosquitoes showed that one major (Pen1) and two minor (Pen2, Pen3) autosomal dominant quantitative trait loci (QTLs) control the melanotic encapsulation response against P. cynomolgi B, a simian malaria originating in Malaysia. RESULTS: We have investigated the response of L3-5 to infection with P. cynomolgi Ceylon, a different but related parasite species, in crosses with the susceptible strain 4Arr. Refractoriness to this parasite is incompletely recessive. Infection and genotyping of F2 intercross females at genome-spanning microsatellite loci revealed that 3 autosomal QTLs control encapsulation of this species. Two loci map to the regions containing Pen2 and Pen3. The novel QTL maps to chromosome 3R, probably to polytene division 32 or 33. Thus the relative contribution of any QTL to oocyst encapsulation varies with the species of parasite. Further, different QTLs were most readily identified in different F2 families. This, like the F1 data, suggests that L3-5 is not genetically homogeneous and that somewhat different pathways may be used to achieve an encapsulation response. CONCLUSION: We have shown here that different QTLs are involved in responses against different Plasmodium parasites.

Animals↗

Host-microbe relationships in chronic respiratory infection.

Infection of the upper and lower respiratory tracts accounts for 85% of the respiratory disease seen by primary-care physicians. Acute infection is usually attributable to microbial virulence but may occur on a background of immune deficiency. Recurrent acute bronchial and pneumonic infection is associated with considerable immunological abnormality (up to 75%) for which a high index of suspicion must be maintained. Chronic bronchial sepsis, on the other hand, has a paradoxically low prevalence of immune deficiency (less than 10%) and the pathogenesis depends on initially compromised mucociliary clearance (by exogenous agents or underlying genetic disease) allowing certain microbes to be selected for airway colonisation according to their ability to release cilio-inhibitory factors and factors damaging ciliated epithelium. Once microbial colonisation is established, the host responds exuberantly with non-specific and immune inflammatory responses which fail to clear the microbial flora but damage the 'innocent bystander' lung. This further compromises bronchial clearance mechanisms in a 'vicious circle' of events whose end result is progressive lung damage and cardio-respiratory failure.

Acute Disease↗

A Plasmodium vivax vaccine candidate displays limited allele polymorphism, which does not restrict recognition by antibodies.

BACKGROUND: The 19 kDa C-terminal region of the merozoite surface protein 1 (MSP1(19)) has been suggested as candidate for part of a subunit vaccine against malaria. A major concern in vaccine development is the polymorphism observed in different plasmodial strains. The present study examined the extension and immunological relevance of the allelic polymorphism of the MSP1(19) from Plasmodium vivax, a major human malaria parasite. MATERIALS AND METHODS: We cloned and sequenced 88 gene fragments representing the MSP1(19) from 28 Brazilian isolates of P. vivax. Subsequently, we evaluated the reactivity of rabbit polyclonal antibodies, a monoclonal antibody, and a panel of 80 human sera to bacterial and yeast recombinant proteins representing the two allelic forms of P. vivax MSP1(19) described thus far. RESULTS: We observed that DNA sequences encoding MSP1(19) were not as variable as the equivalent region of other species of Plasmodium, being conserved among Brazilian isolates of P. vivax. Also, we found that antibodies are directed mainly to conserved epitopes present in both allelic forms of the protein. CONCLUSIONS: Our findings suggest that the use of MSP1(19) as part of a subunit vaccine against P. vivax might be greatly facilitated by the limited genetic polymorphism and predominant recognition of conserved epitopes by antibodies.

Alleles↗

IL-4 is required to prevent filarial nematode development in resistant but not susceptible strains of mice.

The murine Litomosoides sigmodontis model of filarial infection provides the opportunity to elucidate the immunological mechanisms that determine whether these nematode parasites can establish a successful infection or are rejected by the mammalian host. BALB/c mice are fully susceptible to L. sigmodontis infection and can develop patent infection, with the microfilarial stage circulating in the bloodstream. In contrast, mice on the C57BL background are largely resistant to the infection and never produce a patent infection. In this study, we used IL-4 deficient mice on the C57BL/6 background to address the role of IL-4 in the development of L. sigmodontis parasites in a resistant host. Two months after infection, adult worm recovery and the percentage of microfilaraemic mice in infected IL-4 deficient mice were comparable with those of the susceptible BALB/c mice while, as expected, healthy adults were not recovered from wild type C57BL/6 mice. The cytokine and antibody responses reveal that despite similar parasitology the two susceptible strains (BALB/c and IL-4 deficient C57BL/6) have markedly different immune responses: wild type BALB/c mice exhibit a strong Th2 immune response and the IL-4 deficient C57BL/6 mice exhibit a Th1 response. We also excluded a role for antibodies in resistance through infection of B-cell deficient C57BL/6 mice. Our data suggest that the mechanisms that determine parasite clearance in a resistant/non-permissive host are Th2 dependent but that in a susceptible/permissive host, the parasite can develop in the face of a Th2 dominated response.

Animals↗

The Arabidopsis downy mildew resistance gene, RPP13-Nd, functions independently of NDR1 and EDS1 and does not require the accumulation of salicylic acid.

RPP13-Nd-mediated resistance prevents parasitism by five isolates of Peronospora parasitica (At) in a transgenic Arabidopsis. Columbia background. We tested the effect of a number of known disease resistance mutations on the RPP13-Nd function and found that resistance remained unaltered in plants carrying mutations in either EDS1 or NDR1 and in double ndr1-1/eds1-2 mutant lines. Furthermore, we found that pbs2, pad4-1, npr1-1, and rps5-1, which compromise resistance to a number of P. parasitica (At) isolates, had no affect on RPP13-Nd function. In addition, RPP13-Nd-mediated resistance remained unchanged in a background of salicylic acid depletion (nahG). We conclude that RPP13-Nd is the first Arabidopsis R gene product reported to act via a novel signaling pathway that is independent of salicylic acid-mediated responses and is completely independent of NDR1 and EDS1.

Arabidopsis↗

Use of the green fluorescent protein as a marker in transfected Leishmania.

We have tested the suitability of the green fluorescent protein (GFP) of Aequorea victoria as a marker for studies of gene expression and protein targeting in the trypanosomatid parasite Leishmania. Leishmania promastigotes expressing GFP from episomal pXG vectors showed a bright green fluorescence distributed throughout the cell, readily distinguishable from control parasites. Transfection of a modified GFP gene containing GC-rich synonymous codons and the S65T mutation (GFP+) yielded a much higher fluorescence. FACS analysis revealed a clear quantitative separation between GFP-transfected and control parasites, with pXG-GFP+ transfectants showing fluorescence signals more than 100-fold background. Episomal DNAs could be recovered from small numbers of fixed cells, showing that GFP could be used as a convenient screenable marker for FACS separations. GFP was fused to the C-terminus of the LPG1 protein, which retained its ability to restore LPG expression when expressed in the lpg- R2D2 mutant of L. donovani. The LPG1(GFP) fusion was localized to a region situated between the nucleus and kinetoplast; its pattern was similar to that of LPG2, which is known to be located in the Golgi apparatus. This is notable as LPG1 participates in the biosynthesis of the glycan core of the LPG GPI anchor, whereas protein GPI anchor biosynthesis occurs in the endoplasmic reticulum. These studies suggest that the GFP will be a broadly useful marker in Leishmania.

Amino Acid Sequence↗

Th1-cytokine induction and anti-tumor effect of 55 kDa protein isolated from Aeginetia indica L., a parasitic plant.

We have isolated a 55 kDa protein from the seed extract of Aeginetia indica L. (AIL), a parasitic plant, by affinity chromatography on an N-hydroxysuccinimide-activated Sepharose High Performance column bound with F3, a monoclonal antibody that neutralizes the cytokine-inducing and anti-tumor effect of AIL. In the present study, we examined this protein (AILb-A) for cytokine induction and anti-tumor effects by animal study, using syngeneic Meth-A tumor-bearing BALB/c mice, in which the Th2 response is genetically dominant. AILb-A administration resulted in markedly increased levels of Th1 cytokines [interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-12 and IL-18] in the sera derived from Meth-A-bearing mice. The in vitro re-stimulation with AILb-A of splenocytes derived from AILb-A-primed mice also selectively induced Th1-type cytokines and antigen-specific killer cell activity. The neutralizing test using cytokine-specific antibodies revealed that AILb-A-induced IL-18 plays a most significant role for and killer cell-inducing activities. Furthermore, IL-12 and IL-18 induced by AILb-A inhibited specifically IL-10 and IL-4 production, respectively. Finally, we examined the anti-tumor effect of AILb-A in both Meth-A-bearing BALB/c mice and Meth-A-bearing nude mice with BALB/c background. AILb-A exhibited a striking anti-tumor effect in normal BALB/c mice inoculated with Meth-A cells. In athymic nude mice, the anti-tumor effect of AILb-A was relatively weak. These findings strongly suggested that AILb-A is a potent Th1 inducer and may be a useful immunotherapeutic agent for patients with malignant diseases.

Animals↗

Use of Coniothyrium minitans transformed with the hygromycin B resistance gene to study survival and infection of Sclerotinia sclerotiorum sclerotia in soil.

A Coniothyrium minitans strain (T3) co-transformed with the genes for beta-glucuronidase (uidA) and hygromycin phosphotransferase (hph), the latter providing resistance to the antibiotic hygromycin B, was used to investigate the survival and infection of sclerotia of Sclerotinia sclerotiorum by C. minitans over time in four different soils. Infection of sclerotia was rapid in all cases, with the behaviour of transformant T3 and wild type parent A69 being similar. Differences were seen between the soils in the rate of infection of sclerotia by C. minitans and in their indigenous fungal populations. Amendment of agar with hygromycin B enabled the quantification of C. minitans in soil by dilution plating where there was a high background of other microorganisms. In Lincoln soil from New Zealand, which had a natural but low population of C. minitans, the hygromycin B resistance marker allowed the umambiguous discrimination of the applied transformed isolate from the indigenous hygromycin B sensitive one. In this soil, although the indigenous C. minitans population was detected from sclerotia, none were recovered on the dilution plates, indicating the increased sensitivity of C. minitans detection from soil using sclerotial baiting. C. minitans was a very efficient parasite, being able to infect a large proportion of sclerotia within a relatively short time from an initially low soil population. The addition of hygromycin B to agar also allowed the detection of C. minitans from decaying sclerotia by inhibiting secondary fungal colonisers. This is the first report to show that fungi colonising sclerotia already infected by C. minitans mask the detection of C. minitans from sclerotia rather than displacing the original parasite.

Ascomycota↗

The identification and characterization of new immunogenic egg components: implications for evaluation and control of the immunopathogenic T cell response in schistosomiasis.

In schistosomiasis, granuloma formation to parasite eggs signals the beginning of a chronic and potentially life-threatening disease. Granulomas are strictly mediated by CD4+ T helper (Th) cells specific for egg antigens; however, the number and identity of these T cell-sensitizing molecules are largely unknown. We have used monoclonal T cell reagents derived from egg-sensitized individuals as probes to track down, isolate and positively identify several egg antigens; this approach implicitly assures that the molecules of interest are T cell immunogens and, hence, potentially pathogenic. The best studied and most abundant egg component is the Sm-p40 antigen. Sm-p40 and its peptide 234-246 elicit a strikingly immunodominant Th-1-polarized response in C3H and CBA mice, which are H-2k strains characterized by severe egg-induced immunopathology. Two additional recently described T cell-sensitizing egg antigens are Schistosoma mansoni phosphoenolpyruvate carboxykinase (Sm-PEPCK) and thioredoxin peroxidase-1 (Sm-TPx-1). In contrast to Sm-p40, both of these molecules induce a more balanced Th-1/Th-2 response, and are relatively stronger antigens in C57BL/6 mice, which develop smaller egg granulomas. Importantly, Sm-p40 and Sm-PEPCK have demonstrated immunogenicity in humans. The findings in the murine model introduce the important notion that egg antigens can vary significantly in immunogenicity according to the host's genetic background. A better knowledge of the principal immunogenic egg components is necessary to determine whether the immune responses to certain antigens can serve as indicators or predictors of the form and severity of clinical disease, and to ascertain whether such responses can be manipulated for the purpose of reducing pathology.

Animals↗

Analysis of egg antigens inducing hepatic lesions in schistosome infection.

In schistosomiasis, granuloma formation to parasite eggs signals the beginning of a chronic and potentially life-threatening disease. Granulomas are strictly mediated by CD4+ T helper (Th) cells specific for egg antigens; however, the number and identity of these T cell-sensitizing molecules are largely unknown. We have used monoclonal T cell reagents as probes to track down, isolate and positively identify several egg antigens; this approach implicitly assures that the molecules of interest are T cell immunogens and, hence, potentially pathogenic. The best-studied egg component is the Sm-p40 antigen. Sm-p40 elicits a strikingly immunodominant Th-1-polarized response in C3H and CBA mice, which are characterized by severe egg-induced immunopathology. Two additional described T cell-sensitizing egg antigens are Schistosoma mansoni phosphoenolpyruvate carboxykinase (Sm-PEPCK) and thioredoxin peroxidase-1 (Sm-TPx-1). In contrast to Sm-p40, both of these molecules induce a more balanced Th-1/Th-2 response, and are relatively stronger antigens in C57BL/6 mice, which develop smaller egg granulomas. Other components, including moieties with molecular weights of 25 kDa (Sm-p25), 150/166 kDa (Sm-p155/166), and 29 kDa (Sm-GST29), are also found to stimulate specific T cells. These findings in the murine model introduce the important notion that egg antigens can vary significantly in immunogenicity according to the host's genetic background. A better knowledge of the principal immunogenic egg components is necessary to ascertain whether such responses can be manipulated for the purpose of reducing pathology.

Animals↗

A review of the biology and transmission ecology of African bovine species of the genus Schistosoma.

The present paper reviews the information available concerning the biology and transmission ecology of the African bovine species Schistosoma bovis, S. mattheei, S. margrebowiei and S. leiperi. Criteria for species identification (egg morphology, intermediate host spectra, definitive host-parasite relationships, etc.) are listed and the geographical distribution of the four species and factors determining the relative occurrence within their overall distributional ranges are described. S bovis and S. mattheei occur north and south of 10 degrees S, respectively, and S. margrebowiei occurs mainly, and S. leiperi only, in southern central Africa. Definitive host-related factors (susceptibility, water contact pattern, ect.) providing the background for being a primary definitive host and the primary definitive host spectra for the four schistosome species are described. The primary definitive host spectrum for S. margrebowiei and S. leiperi comprise lechwe, puku and waterbuck, for S. mattheei lechwe, puku, waterbuck plus cattle, and for S. bovis cattle and possibly also some of the listed antelope species. In addition, wild bovines and cattle may provide a reservoir of S. mattheei and S. margrebowiei in humans, but wild bovines and domestic stock play no major role in the transmission of other human species of schistosomes. The intermediate snail host spectra of S. mattheei and S. leiperi only comprise members of the Bulinus africanus species complex; S. bovis is transmitted by members of the B. truncatus, B. africanus and B. forskalii species groups, and S. margrebowiei is transmitted by members of the B. forskalii species group and possibly also by members of the B. tropicus and B. truncatus species groups. Factors determining the transmission ecology of the four schistosome species, and thereby the epidemiology of bovine schistosomiasis, are discussed. Influential factors comprise environmental conditions mediated via the effect of these on the size of the snail host population and on the rate of the intramolluscan development, behavioural patterns of the definitive host population and the course of the infection in the definitive host as related to aspects of susceptibility and level of endemicity. The epidemiological pattern (prevalence and intensity of infection, seasonality of transmission, etc.) is described and exemplified, and it is finally concluded that the increasing water conservation and changing methods of husbandry may result in bovine schistosomiasis becoming a major veterinary problem in Africa.

Africa↗