Influence of primary infection on the population dynamics of Nematospiroides dubius after challenge infections in mice

Dobson C., Sitepu P. and Brindley P. J. 1985. Influence of primary infection on the population dynamics of Nematospiroides dubius after challenge infections in mice. International Journal for Parasitology15: 353–359. Similar proportions of the inoculum of Nematospiroides dubius larvae reached sexual maturity by 14 days after administration of 50–400 larvae but more adult worms had been expelled by day 63 after infection from those mice infected with 50 vs 400 larvae. There was a significant correlation between time and worm expulsion for all inoculum size groups except for mice given 400 larvae.In mice reinfected with 100 larvae, after termination of primary infections derived from 10 through 400 larvae, more worms from the challenging dose were recovered from mice given greater compared with those given smaller numbers of larvae at primary infection. The N. dubius population size after challenge infection was correlated positively both with number of larvae administered as the primary infection and with the resultant population size during that infection. The serum anti-N. dubius antibody titres after reinfection were higher in mice given 400 compared with those given fewer larvae at primary infection, and the fecundity and female to male sex ratio of the N. dubius populations decreased in proportion to these antibody titres.Protective immunity against challenge N. dubius infection, in mice which had been drenched free of adult worms established from 400 larvae for 5 down to 1 weeks before reinfection, increased from 45% (1 week) to 80% (5 weeks). There was a negative correlation between the population size of N. dubius during challenge infection and the duration between anthelmintic treatment and challenge infection.     

The location of parasites within their hosts: Factors affecting longitudinal distribution of Trichinella spiralis in the small intestine of mice

Inocula of encysted larvae, excysted larvae or infected meat all resulted in aggregated distributions of adults in the anterior small intestine. However, implantation studies indicated that the larvae could establish anywhere between the duodenum and the colon. The site of larval establishment determines the subsequent location of adult T. spiralis; the site of establishment was due largely to influences such as intestinal motility, size of inoculum and the size of the vehicle of infection. Predominantly female inocula were dispersed similarly to heterosexual inocula while male populations were dispersed more widely.     

Effect of host sex on passive immunity in mice infected with Nematospiroides dubius

Dobson C. & Owen M. E. 1978. Effect of host sex on passive immunity in mice infected with Nematospiroides dubius. International Journal for Parasitology8: 359–364. Female C₃H but not Quackenbush (Q) mice harboured fewer Nematospiroides dubius than male C₃H and Q mice. Both strains lost worms 21 days after infection. C₃H and Q mice became progressively immune to infection following 4 sequential doses of N. dubius larvae and showed a sex resistance to infection. Hypothymic nu/nu CBA Balb/c mice did not show these effects on N. dubius infection. The reciprocal transfer of male and female immune mesenteric lymph node cells (IMLNC) to syngeneic male and female recipients showed that the female environment enhanced the protective qualities of both male and female IMLNC but the male environment suppressed these effects. Gonadectomized male and female recipients of male and female IMLNC had levels of infection similar to the entire female recipients. Serum from immune female donor mice protected both male and female recipients better than immune serum from male donors, but female mice in each treatment group were better protected than male mice. Immune serum transferred greater levels of protection then IMLNC to recipient mice against N. dubius infections. These data are consistent with the conclusion that the male environment suppresses lymphocyte activity and the production of protective antibodies and additionally may depress the effectiveness of sensitized lymphocytes and antibodies in ejecting N. dubius. On the other hand the female environment does not appear to adversely affect the mobilization of the protective immune response and may enhance immune effector mechanisms in protecting mice against N. dubius infections.     

Heligmosomoides polygyrus (Nematoda): the dynamics of primary and repeated infection in outbred mice

The population dynamics of Heligmosomoides polygyrus were studied in outbred male MF1 mice subject either to primary or repeated experimental infection. Little variability in susceptibility was observed between mice, but heterogeneity increased with both duration and intensity of primary infection; this result indicates that there are differences in parasite survival between hosts. The rate of parasite-induced host mortality was 4 X 10(-4) per parasite per host per parasite lifespan. The mortality rates of male and female larvae during their development in the intestinal wall were estimated as 0.033 and 0.021 per parasite per day respectively, and estimates of the expected lifespans of the adult male and female parasites in primary infection of 11.22 and 9.92 weeks were obtained. Approximately 40% of female worms were observed in copula at any one time, although this proportion was significantly depressed in hosts harbouring fewer than 50 parasites and during the first four weeks of infection. Parasite fecundity was markedly age-dependent; each female worm produced approximately 31,000 eggs during its lifespan. No density dependence in either worm survival or fecundity in primary infection was apparent. The only detectable effect of worm density was in association with spatial distribution in the intestine; high levels of infection were associated with a posterior shift in the location of a proportion of the parasite population. Characterization of the dynamics of primary infection allowed predictions to be made about the expected dynamics of repeated infection. The comparison of predicted results and observed data revealed unequivocal epidemiological evidence for the density-dependent regulation of parasite population growth during repeated infection, affecting both parasite survival and parasite fecundity. The results also demonstrated the existence of two types of host individual in which the dynamics of repeated infection were markedly different. It is concluded that immunological differences between mice (possibly under genetic control) may be responsible for the observed effects; approximately 25% of MF1 mice seem unable to generate any protective immunity against H. polygyrus, whereas 75% become almost completely refractory to reinfection. This experimental system could be used for quantitative investigation of the impact of acquired immunity and genetic heterogeneity on helminth population dynamics. Both are of obvious relevance with respect to the control of infections of medical and veterinary significance.     

Immunity to adult Heligmosomoides polygyrus (Nematospiroides dubius): survival or rejection of adult worms following transplantation to mice refractory to larval challenge

Experiments were carried out to explore the survival of 14-day adult H. polygyrus following transplantation to mice of four strains, immunized by various protocols. Adult worm establishment and survival was unimpaired in CFLP mice which were totally refractory to larval challenge. Transplanted adult worms were also successful in NIH mice immunized by the 9-day abbreviated infection regime. However, NIH mice exposed to irradiated larvae or subjected to the divided primary infection, expelled transplanted adults. The 9-day abbreviated infection was further examined in SJL and (C57 Bl10 X NIH) F1 mice which expel adult worms during a primary infection and although this regime was unsuccessful in causing NIH mice to reject adult worms, expulsion of adult worms was accelerated in SJL and F1 mice. The survival of adult H. polygyrus was discussed in the context of stage-specific immunity and the delicate balance between the immunogenic stimuli from developing larvae, the immunomodulatory activities of adult stages and the host's genetically determined capacity to respond to these opposing signals.     

Strongyloides ratti: Susceptibility to infection and resistance to reinfection in inbred strains of mice as assessed by excretion of larvae

Eleven inbred strains of mice, and one outbred strain, were infected with Strongyloides ratti and larvae in the faeces were quantitated. Three strains, C57B1/6, CBA and BALB/c mice were susceptible to infection while other strains demonstrated negligible infections as assessed by this method. Larvae were first seen in the faeces on day 5, peak levels were reached on days 6 and 7, and excretion ceased 10 days after infection. Factors influencing intensity of larval excretion were examined in C57B1/6 mice. Young mice (1 month of age) were found to be more susceptible to infection than 2 and 6 month old animals. Male mice were much more susceptible to infection than female animals. There was a direct relationship between the number of S. ratti injected and the number of larvae excreted over the range 200–1600 larvae; subsequent increments in dose of injected larvae failed to increase the larval output. Infection by the percutaneous route resulted in a heavier infection than did subcutaneous injection. Previous exposure to S. ratti induced a profound resistance to reinfection. It is suggested that S. ratti infections of C57B1/6 and CBA mice provide a useful model for the investigation of factors influencing the host-parasite relationship in strongyloidiasis.     

Ocular toxocariasis in mice: distribution of larvae and lesions.

The distribution of Toxocara canis larvae in the eye was determined for mice given a single challenge dose (C-mice) as compared to mice similarily challenged after 2 or 3 previous infections (SC-mice). Controls were mice given only the 2 or 3 previous infections and uninfected mice. Eyes were observed in situ during a 34 day post-challenge period to compare inflammatory responses in the anterior eye; histologic examination of serial sections of the eyes of these mice was done at the end of this period. In situ observations showed that lesions in the anterior eye converted from hemorrhagic to white cell more rapidly in the SC-mice; white cell lesions were predominant in SC-mice as early as day 5, whereas similar predominance in C-mice was not noted until days 16–21. Histology revealed that approximately 90% of these eyes were infected. Worm burdens per eye correlated more closely with total dose per mouse than with the effects of immunization. Histologic study showed that 90% of larvae observed were in the retina, but that most lesions were in the uveal tissues which harbored only 0·8% of the total number of larvae.     

The mode of passive protection against Hymenolepis nana induced by serum transfer

A protective immunity against the cestode Hymenolepis nana was transferred with serum taken from actively immunized mice. All of 17 pooled sera examined, which were taken from mice immunized for 3 or more weeks, were strongly effective. Intraperitoneal injection of a total of 3·0 ml serum made the recipient mice (4–5 weeks old) almost completely immune. In almost all the mice given immune serum no cysticercoids were found on day 4. In mice receiving immune serum, oncospheres hatched, invaded the intestinal villi and differentiated to stage II or III larvae, but failed to develop to fully developed cysticercoids. The degree of protection conferred by serum transfer was similar to, but slightly weaker than that stimulated by active immunization. The major effect of immune serum was damaging hatched oncospheres in both the intestinal lumen and the villi within 1 day post infection.     

Trichinella spiralis: nonspecific resistance and immunity to newborn larvae in inbred mice

The implantation and development of intravenously injected Trichinella spiralis newborn larvae were examined in different strains of inbred mice by determining muscle larvae burden. This was compared to the numbers of muscle larvae that established after a natural infection during which a quantitative assessment of intestinal newborn larvae production was made. In most inbred strains of mice, newborn larvae do not all successfully implant in muscle. Mice of the DBA/1 strain are the most resistant to successful implantation, and C3H mice are the most permissive. This pattern is evident in the strains studied whether newborn larvae are injected intravenously or are produced by intestinal adults. Thus, after a natural infection, 100% of intestinally produced newborn larvae implanted in C3H mice, whereas in NFR 68% and DBA/1 mice 62% successfully matured in muscle. Immunity to newborn larvae could be demonstrated as early as 10 days after exposure to this stage of the life cycle. This immunity was protective against a complete challenge infection given 9 days after newborn larvae had been injected intravenously. Protection against newborn larvae was identical in male and female mice or in mice from 1 to 9 months of age. We conclude that there are two mechanisms by which mice impair newborn larvae establishment or development in muscle. The first appears to be nonimmunological (non-specific resistance), and the second is immunological. Genetically determined variation in strain-specific expression is apparent with both mechanisms. In strains displaying high intrinsic "resistance" (DBA/1), this process is likely to account for most of the 38% reduction in newborn larvae establishment in a primary infection. However, immunity against newborn larvae develops quickly enough to have a significant effect on migratory larvae in primary infections where adults persist in the intestine (e.g., the B10 congenic mice), or when high adult worm burdens delay adult worm rejection. Muscle larvae burden, therefore, reflects systemic nonspecific resistance to newborn larvae as well as immunological processes that occur in the intestine and systemically.     

Histopathological appearances in primary and secondary infections with Strongyloides ratti in mice

Dawkins H. J. S., Muir G. M. & Grove D. I. 1981. Histopathological appearances in primary and secondary infections with Strongyloides ratti in mice. International Journal for Parasitology11: 97–103. The histological appearances of the skin, lungs and small intestines of mice with primary and secondary infections with S. ratti are described. When the skins of mice with a primary infection were examined, larvae were seen scattered throughout the dermis. An inflammatory reaction of neutrophils and eosinophils was first noted around larvae 12 h after infection. By 48 h, mononuclear cells were prominent. The intensity of the inflammatory reaction gradually increased to a maximum on the fifth day and the larvae were destroyed. Very few larvae were seen in the lungs; those observed were located in the alveolar spaces and were not surrounded by an inflammatory infiltrate. Worms in the small intestines were found mostly in the crypts of Leiberkuhn, and were probably located within the epithelial layer; there was no significant villous atrophy or cellular infiltration. Marked differences were found in the tissues of mice with secondary infections. In the skin, oedema and neutrophils and eosinophils were seen around worms as early as 2 h after infection. By 24 h after infection, there was a mixed inflammatory infiltrate and worms were undergoing disintegration. Larvae in the lungs were surrounded by polymorphonuclear and mononuclear cells 48 h and 72 h after infection and the engulfed larvae were undergoing lysis. Only a few worms were seen in the intestines of mice with a secondary infection; the histological appearances were similar to that found in animals with primary infections. It is suggested that the rapid development of an oedematous reaction in the skins of immune mice may facilitate the entry of larvae into the bloodstream and that inflammatory cells destroy many larvae in the lungs of immune mice.     

Effects of Toxoplasma gondii (Gleadle strain) on the host-parasite relationship in trichinosis.

The effects of concurrent infection with Toxoplasma gondii on the host-parasite relationship in trichinosis were studied. Infected mice showed a delay in expulsion of Trichinella spiralis adults from the gut. Persisting adult female worms were fecund but the numbers of larvae recovered from the muscles were not increased. Increased resistance to the systemic phase of trichinosis was shown by reduced numbers of muscle larvae after intravenous injection of newborn larvae in animals with toxoplasmosis as compared with control mice. There were no differences in small bowel pathology of trichinous mice with and without toxoplasmosis but inflammation around muscle cysts of T. spiralis was reduced in mice with toxoplasmosis. The eosinophilia which normally develops in mice with trichinosis was suppressed by concurrent toxoplasmosis. Trichinella infection did not alter the numbers of T. gondii cysts recovered from the brain 4 weeks after infection. It is suggested that the delay in expulsion of adult worms, decrease in muscle inflammation around T. spiralis cysts, and inhibition of eosinophilia result from immune suppression, while the reduction in numbers of muscle larvae after intravenous injection of newborn larvae reflects enhanced nonspecific resistance to infection in toxoplasmosis.     

Kinetics of primary and secondary infections with Strongyloides ratti in mice

Dawkins H. J. S. and Grove D. I. 1981 Kinetics of primary and secondary infections with Strongyloides ratti in mice. International journal for Parasitology11: 89–96. The kinetics of infection with S. ratti were quantitated in normal and previously exposed C57B1 /6 mice. In primary infections, larvae penetrated the skin rapidly and were seen in peak numbers 12 h after infection. By 24 h after infection, larval numbers had declined appreciably and there was a slow decrease in numbers thereafter. Larvae were first observed in the lungs at 24 h and maximal recovery occurred at 48 h. It is thought that larval migration through the lungs is rapid. Worms were first seen in the intestines two days after infection. Maximum numbers were seen on the fifth day and worm expulsion was complete by day 10. Two moults took place in the small intestine during days 3 and 4 after infection. Rhabditiform larvae were first noted on the fourth day after infection. Mice exposed to S. ratti four weeks previously had significantly less larvae in the skin 4 and 12 h after infection but by 24 h there was no difference when compared with mice with primary infections. Peak recovery of larvae from the lungs occurred 24 h after infection; significantly less larvae were recovered on days 2 and 3 when compared with normal mice. There was a marked reduction in the adult worm burden in the gut; the number of worms recovered was less than one fifth of that seen in primary infections. Those worms which did mature were less fecund and were expelled from the intestines within 7 days of infection. It is suggested that in previously exposed animals, the migration of larvae from the skin is hastened, many of these larvae are destroyed in the lungs and that expulsion of worms which do mature in the intestines is accelerated.     

Adoptive transfer of immunity to Trichinella spiralis in mice: generation of effective cells by different life cycle stages

Adoptive transfer of immunity with day 8 mesenteric lymph node cells (MLNC) taken from NIH mice after a chemically abbreviated infection of 3 days duration was as effective as transfer with cells taken from mice which had received an uninterrupted infection. Using a surgical transplantation technique it was demonstrated that adult T. spiralis were not capable of stimulating cells effective upon adoptive transfer. The potent immunogenicity of the early stages of infection was emphasized by data showing that very low numbers of muscle larvae were efficient in stimulating effective mediator cells. Neither the time at which MLNC were taken for transfer after transplantation of adult worms nor the age of adult worms transplanted affected the failure of this life cycle stage to stimulate cells capable of mediating worm expulsion. It is proposed that expulsion of T. spiralis from the gut may be achieved by more than one effector mechanism, and that early and late intestinal stages stimulate these mechanisms differentially.     

Resistance to Taenia pisiformis larvae in rabbits: immunization against infection using non-living antigens from in vitro culture.

Heath D. D. 1976. Resistance to Taenia pisiformis larvae in rabbits: Immunization against infection using non-living antigens from in vitro culture. International Journal for Parasitology6: 19–24. A 97 % protection of rabbits against infection with Taenia pisiformis larvae was stimulated by subcutaneous injections of killed larvae cultured in vitro for 6 or 9 days, combined with the concentrated culture media in which the larvae grew. Larvae cultured in vitro for 3 days or less stimulated only 60% protective immunity.Exogenous antigens produced by 10-day old larvae in vitro were collected free of contaminating macromolecules, and were partially characterized. There appeared to be 6 exogenous antigens. Rabbits were immunized with either frozen larvae, or the exogenous complex, or both, using one subcutaneous injection of antigens adsorbed on aluminium phosphate. Exogenous antigens stimulated an 88% protection against challenge infection 14 days later, while only 52% protection was stimulated by somatic antigens from frozen larvae. The effects of the two antigen complexes were not additive. The protective ability of exogenous antigens was destroyed by exposure to air.     

Growth and development of Hymenolepis nana in mice maintained at different environmental temperatures

Growth and development of Hymenolepis nana in mice maintained at different environmental temperatures. International Journal for Parasitology16: 13–17. On days 3 and 4 post infection (p.i.) the number of Hymenolepis nana cysticercoids in the villi of male mice kept at 5°C did not differ from those in controls (21°C), but fewer larvae were observed in hosts at 35°C. However, on day 10 and 14 p.i. in cysticercoid and egg-induced infections respectively, the incidence of infection was higher and significantly more worms per host were found in mice at 5°C than in those kept at 21 or 35°C. Also, worms from mice maintained at 5°C were significantly heavier and became patent 1 day earlier than those from 21°C, which, in turn, were significantly heavier than those grown in hosts at 35°C.     

Aspects of the life history of Muspicea borreli (Nematoda: Muspiceidae), parasite of the house mouse (Mus domesticus) in Australia

Prevalence of Muspicea borreli (Nematoda) infection in wild populations of Mus domesticus in forests in southeastern New South Wales and in rural Canberra, Australia was variable, relatively low and the parasite occurred predominantly in male mice. Experimental infection of BALB/c mice occurred only via subcutaneous inoculation but was achieved using i) adults containing embryonating eggs, ii) adults containing active larvae and iii) active larvae dissected from the uterus of female worms. Experimental infection was not established using adults containing unembryonated eggs and was not established via intraperitoneal, percutaneous nor oral routes. Evidence indicates that larvae develop to the infective stage in the uterus of the adult worm, suggests that an obligate developmental phase on the host skin does not occur and that autoinfection is possible. Experimental infection predominated in males; females rarely became infected. When male BALB/c mice were inoculated subcutaneously with M. borrelia, immediately paired with an uninoculated female and permitted to breed for 90 days, infection was found in male and female offspring only of the second and subsequent litters or in the breeding female partner. Transmission to the young occurred within 21 days of birth and fifth-stage M. borrelia were found in offspring of the second and subsequent litters only after 35 or more days. However, when a male was inoculated but mating delayed for 23 days, infection was found in progeny of the first and second litters. The life cycle is direct and the prepatent period in BALB/c mice is estimated at 50-60 days. The precise mode of transmission of the parasite in breeding pairs of mice was not determined but larvae remained active for approximately an hour in balanced saline solutions (pH = 7.2) and in human saliva but died under conditions emulating free-living (tap water pH = 7.1) and stomach (pepsin solution pH = 2) environments. Transmission was not effected by transplacental, transmammary nor transseminal routes. Consequently, it is difficult not to conclude that transmission may occur via penetration of skin or mucous membranes, and allogrooming behaviour may be particularly important in this regard.     

The migratory behaviour and survival pattern of Ancylostoma caninum larvae in an adoptively immunised host

The migratory behaviour and survival pattern of a challenge dose of Ancylostoma caninum larvae was found to be affected by the immunological damage caused and the degree of immunity acquired by the adoptively immunised isogenic female Swiss albino mice. In experimental recipients, larval entry into the lungs during migration was prevented by the liver which acts as an immunological barrier; instead they proceeded into the muscles within 4 h after challenge, where they met allergic death in experimental animals only.     

Embryogenesis and the production of males by apterous viviparae of the green peach aphid Myzus persicae in relation to photoperiod

Apterous viviparae of a holocyclic strain of Myzus persicae were given various numbers of prenatal and postnatal exposures to male-inducing, long-night scotophases (15 hr darkness per diem). The sex of the embryos in various positions within their ovarioles was determined from chromosome preparations and correlated with the sequence with which female and male larvae were deposited. An abnormal follicle was found frequently between the female and male embryos in the ovarioles of aphids raised under long nights.Apterous viviparae exposed to long nights from birth or earlier usually produced several females and then switched over to exclusive male production. The more prenatal exposures to long nights given to the aphids, the fewer females were deposited by them and the earlier they started to produce males. When apterae were continuously exposed to long nights from 2 days or more before their birth, some, and occasionally all, their ovarioles were solely androparous. In general, male-producing apterae deposited considerably fewer larvae (female as well as male) than apterae that produced females exclusively. The 1–2 day pause in larviposition that typically occurs between the deposition of the female and male larvae was attributed to a slower rate of development of the male embryos. The results are discussed in relation to the hormonal changes that may be induced by the photoperiodic treatments.     

A Nasal Myiasis in a 76-Year-Old Female in Korea

On July 2009, 5 fly larvae were discovered inside the nose of a 76-year-old female. She was living in Cheonan-si, and in a state of coma due to rupture of an aortic aneurysm. Surgery was performed on the day of admission, and the larvae were found 4 days later. By observing their posterior spiracle, the larvae were identified as Lucilia sericata. Considering the rapid development of this species, the infection was likely acquired during hospitalization. Further investigation on the hospital environment should be needed to know the origin of the infection.