An overview of animal models in experimental schistosomiasis and refinements in the use of non-human primates

Farah, Idle O.; Kariuki, Thomas; King, Christopher L.; Hau, Jann

doi:10.1258/0023677011911570

Cited by 38 publications

(26 citation statements)

References 34 publications

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“…Is that an acceptable philosophy or not is still a matter of debate. In case of schistosomiasis, the complex nature of schistosomes and their complicated interaction with the mammalian host necessitates the use of live animal models in various aspects of schistosomiasis research (Farah et al 2001). Schistosome infections in experimental animals, including murine hosts, are less complex, or at least more readily studied, than infections in humans (Cheever et al 1994a).…”

Section: Justification For Murine Modelingmentioning

confidence: 99%

Murine schistosomiasis as a model for human schistosomiasis mansoni: similarities and discrepancies

Abdul‐Ghani

Hassan

2010

Parasitol Res

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Human schistosomiasis has been studied extensively since its discovery by Theodore Bilharz in 1851. Because of its medical importance as a chronic debilitating disease in the tropics and subtropics, continuing research efforts are still going on. The use of animal models still represents a major cornerstone in this field, with murine hosts, especially mice, as the most preferable experimental units. Murine schistosomiasis has been employed as a model for studying various aspects of human schistosomiasis, including biology, pathogenesis, immunology, chemotherapy screening, and vaccine development. However, there may be differences between murine and human schistosomiasis. The present article tries to explore some of these aspects that may help researchers in the field of schistosomiasis.

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Section: Justification For Murine Modelingmentioning

confidence: 99%

Murine schistosomiasis as a model for human schistosomiasis mansoni: similarities and discrepancies

Abdul‐Ghani

Hassan

2010

Parasitol Res

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“…The pathology and immune responses to chronic S. mansoni in baboons mimic those observed in humans (27,28). The nonhuman primate malaria P. knowlesi readily infects baboons, producing symptoms of severe malaria similar to those seen in humans (29).…”

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confidence: 95%

Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi

et al. 2016

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c Malaria and schistosomiasis coinfections are common, and chronic schistosomiasis has been implicated in affecting the severity of acute malaria. However, whether it enhances or attenuates malaria has been controversial due the lack of appropriately controlled human studies and relevant animal models. To examine this interaction, we conducted a randomized controlled study using the baboon (Papio anubis) to analyze the effect of chronic schistosomiasis on severe malaria. Two groups of baboons (n ‫؍‬ 8 each) and a schistosomiasis control group (n ‫؍‬ 3) were infected with 500 Schistosoma mansoni cercariae. At 14 and 15 weeks postinfection, one group was given praziquantel to treat schistosomiasis infection. Four weeks later, the two groups plus a new malaria control group (n ‫؍‬ 8) were intravenously inoculated with 10 5 Plasmodium knowlesi parasites and monitored daily for development of severe malaria. A total of 81% of baboons exposed to chronic S. mansoni infection with or without praziquantel treatment survived malaria, compared to only 25% of animals infected with P. knowlesi only (P ‫؍‬ 0.01). Schistosome-infected animals also had significantly lower parasite burdens (P ‫؍‬ 0.004) than the baboons in the P. knowlesi-only group and were protected from severe anemia. Coinfection was associated with increased spontaneous production of interleukin-6 (IL-6), suggesting an enhanced innate immune response, whereas animals infected with P. knowlesi alone failed to develop mitogen-driven tumor necrosis factor alpha and IL-10, indicating the inability to generate adequate protective and balancing immunoregulatory responses. These results indicate that chronic S. mansoni attenuates the severity of P. knowlesi coinfection in baboons by mechanisms that may enhance innate immunity to malaria. P olyparasitism is common in low-resource countries, especially in sub-Saharan Africa. Coinfections may alter disease outcomes and affect both drug and vaccine efficacies (1, 2). The majority of studies on coinfections have focused on interactions between malaria and chronic helminth infections. Interest in studying malaria and schistosomiasis, in particular, comes from the major overlap of the two diseases in areas where they are endemic and the fact that these infections account for a large proportion of global morbidity and mortality (3, 4). Because of the chronicity of schistosome infection, most studies have focused on its impact on susceptibility to clinical malaria.Studies on malaria and schistosomiasis coinfections in human and animal models have generated contradicting results. Although some animal studies have shown that chronic schistosomiasis protects against severe malaria (5), others have reported that a concurrent schistosome infection enhances the severity of malaria (6-10). Many factors may account for these differences, including mouse strain, duration and intensity of the helminth infection, Plasmodium strain or species, inoculum size, or route of malaria infection (skin or blood stage) (11). An important limitat...

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“…[6][7][8][9] Mouse models of Schistosoma mansoni infection vary widely with some inbred strains showing pathology similar to human disease (e.g., C57BL/6), whereas others develop more severe manifestations (e.g., CBA). [10][11][12][13] Regardless of the model used, the acute stage of murine schistosomiasis typically starts within 6-8 weeks of infection when active granulomas begin to form around eggs deposited in the colonic wall or swept up the portal circulation into the liver. At 12-14 weeks postinfection, mice enter the chronic stage and granuloma size tends to decrease.…”

Section: Introductionmentioning

confidence: 99%

“…These changes occur primarily in the liver and intestines in the case of S. mansoni infection. [10][11][12] Schistosoma mansoni infection in humans ranges from asymptomatic to severe hepatosplenic fibrosis with portal hypertension, gastrointestinal hemorrhage, and death. [10][11][12] Because of the similarities between murine and human disease manifestations, we used the C57BL/6 model to study protein profiles after S. mansoni infection to look for candidate biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Serum Carbonic Anhydrase 1 is a Biomarker for Diagnosis of Human Schistosoma mansoni Infection

Kardoush

Ward

Ndao

2017

The American Society of Tropical Medicine and Hygiene

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Abstract. Schistosoma mansoni is a major public health threat in many parts of the world. The current diagnostic tests for schistosomiasis are suboptimal, particularly early in infection, when the parasite burden is low and with reinfection after treatment. We sought to identify novel biomarkers of active infection by studying serum proteins in a mouse model of schistosomiasis followed by confirmation in chronically infected patients. Acute (6 weeks) and chronic (12 weeks) sera from S. mansoni-infected C57Bl/6 mice as well as sera from chronically infected patients were assessed using two proteomic platforms: surface-enhanced, laser desorption and ionization, time-of-flight mass spectrometry and Velos Orbitrap mass spectrometry. Several candidate biomarkers were further evaluated by Western blot and/or enzyme-linked immunosorbent assay (ELISA). Among the most promising was carbonic anhydrase 1 (CA1), a host protein found primarily in red blood cells and enterocytes that proved to be a negative biomarker for schistosomiasis in both mouse and human samples. Reduced serum CA-1 levels were confirmed by both Western blot (murine and human: both P < 0.001) and ELISA (human: P < 0.01). Western blots of serial mouse sera revealed a progressive reduction in serum CA1 levels over the 12-week infection period. CA1 is a promising negative serum biomarker for the diagnosis of S. mansoni infection.

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An overview of animal models in experimental schistosomiasis and refinements in the use of non-human primates

Cited by 38 publications

References 34 publications

Murine schistosomiasis as a model for human schistosomiasis mansoni: similarities and discrepancies

Murine schistosomiasis as a model for human schistosomiasis mansoni: similarities and discrepancies

Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi

Serum Carbonic Anhydrase 1 is a Biomarker for Diagnosis of Human Schistosoma mansoni Infection

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