Sherlock Holmes and tropical medicine: a centennial appraisal.

Sir Arthur Conan Doyle incorporated an unidentified tropical disease as a murder weapon in the Sherlock Holmes story, "The Dying Detective," written in 1913. Documentary and circumstantial evidence suggests that the disease mentioned was melioidosis. The description of the newly identified disease occurred shortly before Doyle's death. Doyle's other works at the time reflect a consistent interest in tropical disease.

Biomphalaria glabrata in Haiti.

Biomphalaria glabrata, an intermediate host for Schistosoma mansoni, was first reported in Haiti in 1891 at one location in the Départment du Nord and in 1977 it was reported at several sites in one additional watershed. Our study identifies two additional locations each on a different watershed plus a third possible site. A wide but discontinuous distribution of the snail on the north coast of Haiti is confirmed (no autochthonous infections with S. mansoni have been reported). While there are many possible explanations for this discontinuous distribution, a role for the competitor Thiara granifera in shaping the current distribution of B. glabrata is suggested. The incursion of B. glabrata into Haiti is not recent but at the same time is not expanding.

Summer research program for medical students.

The decrease in the number of physician investigators is a serious national problem. Direct participation in research by medical students is widely regarded as a valuable component of medical education and as a stimulus to a career in research. A voluntary summer research program was implemented at the Medical College of Ohio at Toledo with student participation exceeding 20 percent for the classes entering in 1980 and 1981 and reaching 40 percent for the freshman class that entered in 1982. The research program was planned along with implementation of a new four-year curriculum. First-year students were encouraged to participate in research projects during the summer between their first and second year. Interested students were matched with faculty members by mutual agreement. An evaluation of the program based on publications and presentations by medical students and on responses of students and faculty members to a questionnaire was made.

Effect of immune reconstitution on resistance to Brugia pahangi in congenitally athymic nude mice.

The dichotomy of resistance to Brugia pahangi (Nematoda: Filarioidea) between nonsusceptible, euthymic C3H/HeN mice, heterozygotic for the "nu" gene (+/nu), and susceptible, congenitally-athymic "nude" (nu/nu) C3H/HeN mice, suggests that resistance is thymus-dependent. To test this hypothesis, the effect of syngeneic neonatal thymus grafts and neonatal thymus cell suspensions on recovery of worms at day 40 PI, and responses to Concanavalin A (Con A) were examined in reconstituted nudes. Nude recipients of a thymus graft 7 or 14 wk before subcutaneous inoculation with 50 infective larvae (L3) yielded no worms and responded strongly to Con A. Serum from these mice reacted in two lines of identity with serum from similarly-infected heterozygotes by double radial immunodiffusion against an adult worm saline extract. Nude recipients of a thymus 2 days or 3 wk before inoculation harbored an average of three or two worms, respectively. Intravenous injection of nude recipients with 10(7) or 10(8) neonatal thymus cells seven weeks before inoculation was less effective in conferring resistance to B. pahangi and responsiveness to Con A. Complete resistance to B. pahangi could be adoptively transferred to nude mice by 10(8) spleen cells obtained from infection-primed heterozygotes and injected intravenously on the day of larval inoculation. The same numbers of worms were significantly reduced. less effective when injected 3 wk before inoculation, although numbers of worms were significantly reduced. Passive transfer of primed heterozygote serum, containing high titers of antibodies to adult worm and larval antigens, failed to protect nude recipients against a larval inoculum in the absence of cellular reconstitution.(ABSTRACT TRUNCATED AT 250 WORDS)

Life cycle of Brugia pahangi (Nematoda) in nude mice, C3H/HeN (nu/nu).

The development of Brugia pahangi (Nematoda: Filarioidea) was studied in nude (congenitally athymic) mice C3H/HeN (nu/nu) and in their phenotypically normal littermates (nu/+). Nude mice were highly susceptible to this parasite. As in the natural host (the cat), the nematodes' third molt in nude mice occurred at 7 to 10 days. The final molt occurred at about 24 days for male worms and 33 days for female worms. Adult worms were smaller than those from other hosts, such as the cat. After inoculation of various numbers of infective larvae, recoveries of adult worms averaged about 15% of the inoculum. In long-term infections initiated with 100 larvae, about 75% of the worms localized in the heart or lungs. Patent infections were seen as early as day 50 PI. Microfilaremia developed in most nude mice given 100, 50, or 25 infective larvae, but was less frequent in those given only 10. Mean filaremias generally rose during the first 6 mo, but in individuals usually did not exceed 500-600/20 mm3 of blood. As in the Mongolian jird, intraperitoneal inoculations yielded large quantities of worms and microfilariae. Few worms could be recovered from normal mice after day 40, even when large (1,000 larvae) inocula were used. Microfilaremia was not detected in normal mice. Although recoveries of adult worms from some nude females were not as high as those from nude males, neither nude nor normal mice showed consistent evidence of a differential susceptibility based on sex. Given the strong, consistent dichotomy of response to B. pahangi between nude and normal mice, this system may be useful in studies of protective immune responses in filariasis.

The lymphatic pathology of Brugia pahangi in the Mongolian jird.

We studied the sequence of histopathologic changes associated with Brugia pahangi (Nematoda: Filarioidea) infections in lymphatic vessels in the spermatic cord of the Mongolian jird (gerbil), Meriones unguiculatus. Intravascular granulomas caused mainly by disintegrating worms were seen in 67% of jirds necropsied on, or after, 35 days postinoculation, whereas none of 20 jirds examined before this day showed dying larvae. These granulomas usually evolved without vascular occlusion. Other granulomatous foci, often with a thrombuslike core, sometimes harbored microfilariae or microfilarialike materials. The perilymphatic cellular infiltrate consisted mostly of eosinophils, lymphocytes, and plasma cells. Large numbers of eosinophils were seen in the early weeks, but later declined, while lymphocytes increased to become the predominant cell in old infections. Irregular fibrosis of some valves and portions of the lymphatic walls were seen as early as the 2nd wk postinoculation. Lymphatic changes in the jird are similar to those described in other hosts infected with filariae, but remained moderate. Living worms appeared to be the stimulus for many observed changes. Most pathologic alterations were well established by 3 or 4 mo and showed little qualitative change during the remaining 4 mo of the study.

The Mongolian gerbil in aging research.

The authors have explored the suitability of the Mongolian gerbil as a model in aging research and reviewed data on major factors in gerbil morbidity and mortality. The gerbil is a semi-desert rodent, introduced relatively recently into biomedical research. It is moderately prolific, has a maximum survival of about 208 weeks and is easily maintained. Maternal neglect, fighting and epidemic diseases (Tyzzer's disease, salmonellosis, pneumonia) are potential causes of mortality in gerbil colonies. Obese or breeding gerbils may exhibit hyperadrenocorticism, diabetes, non-lipoid arteriosclerosis and secondary lesions in several organs. There is a high prevalence of spontaneous neoplasms in aged gerbils, especially tumors of the adrenal cortex, ovary and skin. The gerbil is a useful model of experimentally-induced stroke, but has proven unsuitable for studies of cholesterol-induced atherosclerosis. The normal and pathological anatomy of periodontal disease in the gerbil is similar in many respects to that of man.

Lampyridae larva: a natural predator of schistosome vector snails in Liberia.

A lampyrid larva (Coleoptera) was found during snail collecting in Liberia, West Africa to be a natural predator of Biomphalaria pfeifferi and Bulinus globosus.

The pathology of the Mongolian Gerbil (Meriones unguiculatus): a review.

Both naturally occurring disease processes and experimental models of human disease in the Mongolian gerbil were reviewed. The gerbil was highly susceptible to cerebral infarction following unilateral ligation of one common carotid artery and was useful in studies of the pathogenesis of stroke. Spontaneous epileptiform seizures mimicked those of human idiopathic epilepsy, and both seizure-sensitive and resistant strains have been bred. Perhaps because of its more efficient nephron, the gerbil accumulated four to six times as much renal lead as the rat, and the gerbil has been proposed as an experimental model of lead nephropathy. On standard diets, about 10% of the animals became obese, and some showed decreased glucose tolerance, elevated serum immunoreactive insulin and diabetic changes in the pancreas and other organs. Some breeders exhibited hyperactivity of the adrenal cortex associated with hyperglycemia, hyperlipidemia and degenerative vascular disease. Although dietary supplements of cholesterol were toxic and did not induce atherosclerosis, the gerbil was useful in other studies of cholesterol absorption and metabolism. Spontaneous, insidious periodontal disease became evident after about 6 months on standard diets, and dental caries were induced by cariogenic diets or by pathodontic streptococci. Spontaneous neoplasia occurred in 8.4--24% of gerbils, usually after 2 years of life. Adrenal cortical, ovarian and cutaneous tumors were the most consistently reported neoplasms.