The host—parasite relationship of<i>Schistosoma haematobium</i>in CBA mice

Agnew, Alison; Lucas, Sebastian; Doenhoff, Michael J.

doi:10.1017/s0031182000058820

Cited by 19 publications

(16 citation statements)

References 35 publications

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“…Our data agree with published data on worm recovery from mice, i.e., 16% (Fripp 1968) and 18% (Taylor and Andrews 1973) for S. rodhaini and 26% (Taylor and Andrews 1973) for S. intercalatum. Our rates of recovery of S. haematobium worms (about 5%) were similar to those reported by Dean et al (1996;3±5% in four experiments) and Taylor and Andrews (1973;7±9%) but lower than those reported by Agnew et al (1988Agnew et al ( , 1993, Imbert-Establet et al (1992;10±13%), and Dean et al (1996;14% in one experiment). The above-mentioned results, together with the data from directly comparable infections of mice with S. japonicum and S. mansoni (Gui et al 1995), demonstrate the greatly varying ability of cercariae of dierent schistosome species to develop into adult worms.…”

Section: Discussionsupporting

confidence: 89%

Schistosoma haematobium , S. intercalatum , S. japonicum , S. mansoni , and S. rodhaini in mice: relationship between patterns of lung migration by schistosomula and perfusion recovery of adult worms

Rheinberg

Moné

Caffrey

et al. 1998

Parasitology Research

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The development of five schistosome species was compared in mice by the recovery of schistosomula from chopped lung tissue and of adult worms by portal perfusion. Three developmental patterns appeared. (1) Schistosoma japonicum was unique in showing an early establishment of schistosomula in and a rapid departure from the lungs together with the highest worm recovery; (2) S. haematobium contrasted by establishing later and persisting in the lungs for at least 2 weeks while yielding the lowest adult worm recovery; and (3) S. intercalatum, S. mansoni, and S. rodhaini had an intermediate pattern--they resided in the lungs for several days, then disappeared and produced intermediate numbers of adults. Lung petechiae, known to accompany the migration of S. japonicum, were never detected after infection with the other species. We speculate that the three migration patterns of schistosomes are related to the size of the relative spectra of naturally infected definitive hosts.

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Section: Discussionsupporting

confidence: 89%

Schistosoma haematobium , S. intercalatum , S. japonicum , S. mansoni , and S. rodhaini in mice: relationship between patterns of lung migration by schistosomula and perfusion recovery of adult worms

Rheinberg

Moné

Caffrey

et al. 1998

Parasitology Research

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“…Promisingly, no species-specific sensitivity was observed with all three lead candidates (mefloquine, enpiroline, and WR7930), revealing comparable activities against S. mansoni and S. haematobium. However, since the mouse is a poor host for drug testing against S. haematobium (as evidenced by the very low worm recoveries in mice), the results obtained for enpiroline and WR7930 should be confirmed in hamsters (as was done for mefloquine), since it is the better host for rodent S. haematobium infections (1,5).…”

Section: Discussionmentioning

confidence: 99%

Antischistosomal Activities of Mefloquine-Related Arylmethanols

Ingram

Ellis

Keiser

2012

Antimicrob Agents Chemother

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H uman schistosomiasis is a neglected tropical disease whose burden is mainly concentrated in sub-Saharan Africa and affects approximately 207 million people (30). The three main schistosome species parasitizing humans are Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum. Today, treatment with praziquantel is the core component of schistosomiasis control programs (32,34,35). There is no question that heavy reliance on a single drug bears a risk of drug resistance development. Indeed, in different regions of endemicity, lower cure rates have already been observed (9). An additional disadvantage of praziquantel is its stage-dependent susceptibility, showing only poor efficacy against immature schistosome stages (23). Therefore, drug discovery in the field of schistosomiasis remains an important task. Antischistosomal properties of the antimalarial drug mefloquine were first mentioned in 2008, when it was shown that a dosage of 150 mg/kg of body weight significantly reduced the egg burden in S. mansoni-infected mice (33). Further investigations revealed that mefloquine possesses good in vivo efficacy, with a single oral dosage of 200 mg/kg resulting in a total worm burden reduction of 72.3% in S. mansoni-infected mice. Another interesting characteristic of mefloquine is its efficacy against the juvenile immature stage (13). Finally, a randomized clinical trial that investigated the effect of mefloquine and mefloquine-artesunate in S. haematobium-infected patients was recently performed. It was shown that a combination therapy of mefloquine-artesunate resulted in moderate cure and high egg reduction rates (15).Based on these promising findings, we were motivated to test mefloquine-related compounds belonging to the three major groups of arylmethanols well described in antimalarial research, namely, 4-quinolinemethanols, 9-phenanthrenmethanols, and 4-pyridinemethanols (4), in order to elucidate their potential as antischistosomal lead candidates. In addition, a study on mefloquine-related compounds might provide us with a deeper understanding of structural features needed for antischistosomal activity of arylmethanols. The selected nine arylmethanols were first tested against S. mansoni schistosomula and adults in vitro. Promising compounds were followed up in vivo. Candidates characterized by high in vivo activity against S. mansoni were tested against S. haematobium. In addition, promising candidates were incubated in the presence of hemoglobin, hemin, or red blood cells to compare drug activities in relation to the postulated mechanistic heme dependency of arylmethanols (6). Finally, isothermal microcalorimetry (IMC) was used to investigate the antischistosomal properties of lead candidates in greater detail and to compare their levels of activity with mefloquine.

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“…Rate of accumulation is considered to reflect worm fecundity since during the periods of study here egg excretion in S . hnrmatobium-infected mice is negligible, as is rate of degradation in the tissues (Agnew, Lucas & Doenhoff 1988). Changes in S. bovis fecundity in mice cannot be estimated because both egg excretion rates and adult worm burdens are affected by T-cell deprivation (Murare & Doenhoff 1987).…”

Section: Parasite Survival and Fecundity In Infected Immunologically mentioning

confidence: 99%

Immune attrition of adult schistosomes

Agnew

Murare²,

Doenhoff

1993

Parasite Immunology

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Mouse infection models are described that demonstrate reduction in the rate of egg production in Schistosoma haematobium worms 6-10 weeks after the onset of oviposition and loss of Schistosoma bovis worms around 10 weeks after infection. Neither phenomenon has been shown in Schistosoma mansoni- or Schistosoma japonicum-infected mice. The immunological basis for these anti-adult responses was inferred by comparison with infections in T-cell deprived mice and by transference of the ability to reduce a S. bovis worm burden in immuno-compromised hosts with immune serum. Vaccination with irradiation-attenuated parasites of S. haematobium was also shown to have consequences for the adults of challenge infections of either S. haematobium or of S. bovis, but not of S. mansoni. Thus, prior vaccination resulted in an abrogation of the reduced egg production by S. haematobium and S. bovis worms and also of the adult worm elimination that occurred in non-vaccinated S. bovis-infected mice. These models are being used to define the targets and mechanisms involved in the attrition of adult worms of schistosomes with terminal spined eggs.

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The host—parasite relationship ofSchistosoma haematobiumin CBA mice

Cited by 19 publications

References 35 publications

Schistosoma haematobium , S. intercalatum , S. japonicum , S. mansoni , and S. rodhaini in mice: relationship between patterns of lung migration by schistosomula and perfusion recovery of adult worms

Schistosoma haematobium , S. intercalatum , S. japonicum , S. mansoni , and S. rodhaini in mice: relationship between patterns of lung migration by schistosomula and perfusion recovery of adult worms

Antischistosomal Activities of Mefloquine-Related Arylmethanols

Immune attrition of adult schistosomes

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