Brugia pahangi: Antibodies and microfilaremias in Lewis rats

Male and female Lewis rats were inoculated subcutaneously in the left groin with 75 infective larvae of Brugia pahangi and microfilaremias were followed for as long as 420 days postinoculation. Patent infections developed in 64% of the female rats and 95% of the male rats. Mean prepatent periods were similar (65.9 and 63.9 days, respectively), but mean microfilaremias in males rose much higher, to a mean of 218 mf/0.25 ml blood at 270 days postinoculation. IgG titers, as measured by enzyme-linked immunosorbent assay (ELISA), to adult worm somatic antigen were higher than those to microfilariae in almost all rats. For both sexes, the most consistently microfilaremic rats had highest titers to these antigens. Granulomas with degenerating microfilaria were present in the spleen of male rats with high microfilaremias (>100–300 mf/0.25 ml blood). Ouchterlony precipitin reactions suggested that most rats with spleen granulomas responded to microfilarial antigen components to which most rats without granulomas did not. Neither spleen granulomas nor antibody responses measured in this study appeared to have protective (microfilaremia-lowering) value. As measured by microfilaremias, the male Lewis rat is not as susceptible as some conventional hosts of B. pahangi, but it does consistently become infected and remains microfilaremic for more than a year. Preferential male susceptibility indicates that this model may be useful for studying this aspect of human lymphatic filariasis.     

Brugia pahangi: infections and their effect on the lymphatic system of Mongolian jirds (Meriones unguiculatus)

Brugia pahangi has been found to be primarily a lymphatic-dwelling parasite in jirds when infections are induced by the subcutaneous injection of infective larvae or by allowing infected Aedes aegypti to feed.Migration to the regional lymphatics occurred as early as 1–4 days. Although some injected larvae remained in the skin for as long as 30 days and some became localized in the heart, lungs, pleural cavity, or peritoneal cavity, about three-fourths of the recovered filariae were found in the regional lymphatics. In contrast, when larvae were injected peritoneally they remained largely in the peritoneal cavity for at least 30 days.The relevant lymphatics and their drainage patterns in jirds have been described.The major pathological changes noted in jirds involved the regional lymphatic vessels and nodes, which were severely affected when they contained dead worms. Pulmonary granulomas due to dead microfilariae and occasionally to dead larvae or adult worms were noted.Observations are included on the susceptibility and course of B. pahangi infections in jirds.     

Dipetalonema viteae: Response of spleen cells in experimental mouse filariasis to mitogens and antigens

Balb/c mice were infected by transplanting 3, 5, 10, or 20 female adult Dipetalonema viteae under the dorsal skin. The microfilaremias resulting from infections with 3 or 5 adult worms were of lesser magnitude and of shorter duration than those produced in infections with 10 or 20 worms. Spleen cells taken from these mice at various intervals after infection were assayed in vitro for their ability to respond to phytohemagglutinin (PHA) or lipopolysaccharide (LPS). There was no depression in the response to LPS or to PHA in mice given infections of 3 or 5 D. viteae adult worms. In contrast, the response to PHA was significantly depressed in groups receiving 10 or 20 adult female worms 12 days after infection and by Day 25, the depression was severe. Thereafter the PHA responsiveness recovered gradually to reach control values on Day 60. In mice transplanted with 10 or 20 D. viteae adult worms there was no significant depression in the response to LPS at any time during the infection, but the response was increased slightly sporadically during infection. These results indicate that in mice, this infection causes an initial suppression in the function of PHA-sensitive T cells but has little effect on the B cells which respond to LPS. A factor present in serum taken on Day 25 from mice infected with 10 or 20 adult worms inhibited the proliferative response to PHA by spleen cells from normal mice. The recovery of PHA responsiveness in mice given the heavier infections coincided with death of the adult worms, but mitogen reactivity and microfilaremia were unrelated. Antigens from male or female worms induced cell division in spleen cells taken from infected mice after microfilaremia had ceased whether they were implanted with 3 or 10 adult worms.     

Dipetalonema viteae: primary, secondary and tertiary infections in hamsters.

Hamsters were given primary infections of 100, 200, and 300 D. viteae larvae and groups killed at various intervals after infection. In addition, hamsters were sequentially infected with 100, 200, and 300 larvae and groups killed at 100 or 75 days after the secondary and tertiary infection, respectively. Blood microfilariae were detected on Day 60 following a primary infection, reached a maximum on Day 75, declined to low levels by Day 105, and were negative on Day 120. No microfilariae reappeared in the blood of hamsters given secondary or tertiary infections.Between 20–30% of the infecting larval dose had reached the adult stage by Days 75 or 100 postinfection in hamsters given primary, secondary, or tertiary infections. There was no evidence of arrested larval development in hamsters receiving a second or third challenge infection. Almost half of the tertiary infection hamsters developed subcutaneous nodules and their numbers varied greatly among individual animals. The nodules variously contained living worms, pus, and fragmented worms, or pus only. Hamsters given primary infections of 100, 200, or 300 larvae and killed 375 days after infection had no subcutaneous nodules; however, hamsters given the 200 and 300 larval infections were seen to have dead worms in the subcutaneous tissues. No stunting of adult worms was noted and all female worms had uteri packed with microfilariae.     

Dipetalonema viteae: Microfilariae production in various mouse strains and in nude mice

Adult female Dipetalonema viteae worms obtained from hamsters were introduced beneath the dorsal skin of $\text{Balb}\text{c}$, $\text{C}{}_{57}\text{Bl}\text{6}$, and $\text{C}{}_3\text{H}\text{He}$ mice. The microfilaraemia from the transplanted worms in $\text{Balb}\text{c}$ mice was higher and persisted longer than in $\text{C}{}_{57}\text{Bl}\text{6}$, and in $\text{C}{}_3\text{H}\text{He}$ mice was intermediate between these two strains. The transplanted adult worms were killed earlier in $\text{C}{}_{57}\text{Bl}\text{6}$ compared to $\text{Balb}\text{c}$ mice; adult worms were killed before the microfilariae were cleared from the circulation. D. viteae infective larvae did not reach maturity in mice but when female worms were implanted into mice which had been infected with third-stage infective larvae 6 or 19 days previously, microfilarial production was inhibited. Outbred as well as inbred nude mice infected with 10 or 20 infective larvae died by Day 15, whereas the normal littermate control mice that received the same number of infective larvae remained alive and healthy. There was no difference in the duration and level of microfilaraemia from implanted female worms in outbred nudes and their heterozygous littermate control mice. In contrast, microfilaraemia in inbred $\text{Balb}\text{c}$ Nu+ was similar to that of inbred $\text{Balb}\text{c}\text{Nu}\text{Nu}$ only until Day 45; thereafter the microfilaraemia declined to zero around Day 160 in the Nu+, at which time it was still high and persisted longer in the $\text{Balb}\text{c}\text{Nu}\text{Nu}$. Transplanted adults were viable in inbred $\text{Balb}\text{c}\text{Nu}\text{Nu}$ for a longer time than in $\text{Balb}\text{c}$ Nu+. When infected, amicrofilaraemic nudes, littermate controls, and three strains of mice were challenged, a very low level short-lasting microfilaraemia resulted.