The American Journal of Tropical Medicine and Hygiene - Volume 23, Issue 1, January 1974

A strain of Plasmodium falciparum isolated in the Republic of Panama in March 1972 was transferred to the Unit on Human Malaria (LPD, NIAID, NIH) in Atlanta, Georgia. Studies in eight non-immune prisoner volunteers demonstrated that infections with this Panama II strain of P. falciparum recrudesced following treatment with chloroquine 1.5 g (base), amodiaquine 1.4 g (base), chlorguanide 1.3 g (base) over 5 days, or quinine 11.34 g (base) over 7 days. Parasitemia increased during therapy with pyrimethamine 150 mg over 3 days. Infections were cured by treatment with quinine for 10 days (16.2 g base) or by combination therapy with sulfadiazine (10 g in 5 days) plus pyrimethamine (150 mg in 3 days).

Toxoplasma antibody was not detected in, or was found in less than 2% of, primitive New Guineans inhabiting areas where either felids had never been present or where domestic cats had been recently introduced but were still limited in number and distribution. However, Toxoplasma antibody was detected in 14% to 34% of New Guineans living in areas where cats were more numerous and had been present longer. In comparison, Toxoplasma antibody was detected in 50% of Nonama Indians, a primitive people living in the Pacific jungles of Colombia, who also had no domestic cats but who hunt and eat neotropical Felidae.

Rhesus monkeys infected with Trypanosoma rhodesiense developed a proliferative glomerulonephritis associated with glomerular deposits consisting of the third component of complement (C3), properdin, and IgM. None of the glomerular deposits contained IgG or IgA. The pattern of deposits as revealed by immunofluorescence was granular. Sera from animals with glomerulonephritis were hypocomplementemic; by radial immunodiffusion some animals showed depression of C3 but not C4 levels. These findings suggest that the glomerulonephritis associated with trypanosomal infections in monkeys is related to deposition of immunologically important serum proteins, two of which represent components in an alternate pathway of complement activation. Trypanosomiasis in the rhesus monkey appears to be a valuable model for studies on the pathogenesis of glomerular injury.

The counterimmunoelectrophoresis (CIEP) technique was compared with other serologic tests in regard to sensitivity, specificity and its use as a diagnostic aid for amebic disease. Sera used were from patients with amebic dysentery and amebic liver abscess and from uninfected control persons from the same socio-economic group. Results from indirect hemagglutination, immunodiffusion and immunoelectrophoresis were compared with those from CIEP. The sensitivity and specificity of the CIEP test compared well with the hemagglutination test and was superior to immunodiffusion. The principal advantages of the test are ease in setting up, simplicity of reagents and rapidity of obtaining results.

Two cases of successfully treated amebic liver abscess are reported in which hepatic tomograms following intravenous infusion of Hypaque® visualized the walls of amebic abscesses. The low incidence of amebic abscess in this area prevents further evaluation of this finding in our hospital. With more clinical experience, the authors suggest that this technique might be of value of diagnosing amebic abscess of the liver.

The possible role of Onchocerca volvulus infections in the pathogenesis of elephantiasis of the lower extremities was explored in an Ethiopian population using standard skin-snip and fluorescent antibody techniques. All subjects studied (44) with the deformity who lived outside areas endemic for onchocerciasis were skin-snip negative and lacked specific antibody to onchocercal antigen. Positive skin-snip rates and mean microfilarial densities in 95 subjects with elephantiasis from areas endemic for the parasite were similar to those in subjects without elephantiasis from the same areas. No significant difference in mean sero-titers was found between infected subjects with elephantiasis and those without. The conclusion was drawn that, in this population, onchocerciasis was not related etiologically to elephantiasis of the lower extremities.

A rapid, accurate immunodiagnostic test for trichinosis has been developed. The test employs particle-associated antigens derived from cell-free homogenates of muscle larvae of Trichinella spiralis in the technique of counterelectrophoresis (CE). A supplementary test using agar gel diffusion (AGD) serves to confirm results obtained by CE. Using these two tests, we showed that 4% (8/189) of normal human sera were positive by CE, and 3% (10/334) of normal human sera were positive by AGD. Both of these values are well within the 5% incidence range of human trichinosis in the United States. Moreover, 90% (94/104) of Trichinella sera which were positive by the bentonite flocculation test were also positive by both the AGD and CE tests. Sera from patients with parasitic infections other than trichinosis were tested for the presence of cross-reacting antibodies. Included in this group were sera from patients with amebiasis, echinococcosis, filariasis, and schistosomiasis. Among these sera some gave false positive tests when first tested by AGD, but few gave false positives when tested further by CE.

An American Foreign Service family of three was found to have Schistosoma intercalatum infection upon their return from residence in Kisangani, Zaire. Only one case was possibly symptomatic, infections appeared to be light, and all were apparently cured with a course of niridazole. Outside of the two recognized foci of S. intercalatum in Africa, infection has been described in Europe almost exclusively in immigrant Africans from these foci. The present three cases are the first reported in this country. Clinical, biological, and epidemiological evidence is cited for regarding S. intercalatum as a distinct species and the disease produced by it is reviewed.

The parasitologic and pathologic features of Schistosoma japonicum infection were studied in capuchin, grivet, and rhesus monkeys, and in baboons. Animals were killed 3 and 7 months after exposure to 50, 100, or 200 cercariae per kg body weight. Heavy infections developed in all monkey species, and moderately heavy infections in baboons. Rhesus and grivet monkeys became immune, and in these hosts many worms died between the 3rd and 7th months of infection. The fecundity of surviving worms was also markedly decreased in immune rhesus monkeys. The magnitude and rapidity of development of host immunity were much greater in the more heavily infected animals. Moderate hepatic portal fibrosis developed by the 3rd month after infection in capuchin monkeys, but 4 months later these lesions had not progressed to unequivocal pipe-stem fibrosis in spite of continued active infection. Portal pressure remained normal and portal-systemic collateral veins were not seen. Only focal portal fibrosis was seen in the other host species. Marked segmental lesions of the intestine were observed in all infected primates. These regressed rapidly in immune animals, and host destruction of S. japonicum eggs appeared to be rapid in all infected animals.

In rhesus monkeys (Macaca mulatta) infected with Schistosoma japonicum (Japanese strain), derived from cercariae obtained from the natural molluscan host Oncomelania hupensis nosophora, a single treatment with the purine nucleoside antibiotic tubercidin (7-deazadenosine) seemed to be as effective as two treatments 1 month apart. The high efficacy of a single treatment with tubercidin against schistosomiasis japonica in monkeys was comparable to that found previously against schistosomiasis mansoni in monkeys. However, the second treatment with tubercidin apparently was responsible for the eradication of the few deformed female worms which presumably survived the first treatment.

The tegument of Schistosoma mansoni in situ in mesenteric veins was observed in mice with and without horseradish peroxidase injections. No evidence of incorporation of horseradish peroxidase into the tegument was noted after 45 minutes of high serum levels of peroxidase. Scant endogenous peroxidase was noted in multilaminate vesicles of the tegument. No evidence of significant endothelial changes, activation of coagulation or cellular response was associated with worms in situ. Endothelia in adjacent worms showed no increased permeability to horseradish peroxidase.

Eight baboons (Papio cynocephalus) were percutaneously exposed at 3-month intervals to small numbers of Schistosoma mansoni cercariae until a total of 700 was reached over a 3-year period. Fecal egg excretion in all had passed peak levels and was fairly steady or even depressed by about 40 months after the initial exposure. At this time 5 were challenged with 1,000 cercariae each. The other 3, serving as controls, were killed and their worms were counted. The 5 experimental baboons were killed 175 days after challenge and their worm burdens were determined. Post-challenge fecal egg excretion was not increased over pre-challenge levels. The difference in mean percent recoveries of penetrating cercariae in the two groups (experimental, 28.7%; control, 46.2%) was highly significant (P > 0.99 < 0.999). These data indicate that baboons can acquire immunity to S. mansoni, as reflected in fecal egg excretion and worm burdens. The immunity is partial in that neither are all worms destroyed nor is reproduction terminated in the survivors.

Immunofluorescent “banding” of the dermal-epidermal junction of skin was demonstrated in 3 of 7 patients with lepromatous leprosy by direct immunofluorescence microscopy. The “banding” was caused specifically by deposition of IgM. Within the glomeruli of one patient, dense, amorphous deposits in subendothelial and intramembranous position were also demonstrated by electron microscopy. These preliminary findings suggest that lepromatous leprosy may be associated with immunologic disturbances of both skin and glomerular basement membranes.

Transmission of paracoccidioidomycosis infection from the patient to close family members has been indicated by comparing dermal sensitivity reactions to paracoccidioidin and histoplasmin in households of patients and controls. The wives of patients were 3 to 5 times more at risk than other adult women. These findings suggest that a common source of infection other than the environment or occupation occurs in the patients' households. This source may be the patient himself. Active disease was not diagnosed in any family member studied.

Studies were conducted from July 1969 through January 1972 in an outdoor recreation and conservation education area in the Tennessee Valley region to provide information on the occurrence and bionomics of ticks involved in the maintenance and transmission of spotted fever and tularemia in nature. A total of 22,832 ticks of seven species was collected; Amblyomma americanum and Dermacentor variabilis accounted for 95% of the total. Ticks were collected both by dragging and by examination of collected mammals: 16,851 were taken by dragging and 5,981 were taken from 951 animal hosts. The American dog tick, D. variabilis, and the lone star tick, A. americanum, the two established vectors of Rickettsia rickettsi and Francisella tularensis to man in Eastern and Southeastern United States, were found abundantly throughout Land Between the Lakes and were associated with large numbers of deer and raccoons. Other species, such as Haemaphysalis leporispalustris, D. albipictus, Ixodes dentatus, I. cookei, and I. texanus, were also recorded but in small numbers. Data on host relationships and seasonal activities are presented.

A survey was conducted from July 1969 through January 1972 in Land Between the Lakes, an outdoor recreation and conservation education area in the Tennessee Valley Region, to determine the occurrence of Rickettsia rickettsi and Francisella tularensis, the agents of spotted fever and tularemia, respectively, in wild mammals and their ticks. Serologic evidence suggested that both pathogens are widely distributed among a large variety of medium-sized mammals throughout the area. Fifty-five of 666 sera comprising 8 of 22 animal species had complement-fixing antibodies to spotted fever antigens, with cottontail rabbits (32 of 66), raccoons (8 of 163), and woodchucks (6 of 49) giving the largest number of seropositives. Antibodies to tularemia were detected in 117 of 620 sera with highest prevalence among striped skunks (11 of 16), gray foxes (37 of 72), raccoons (73 of 161), and woodchucks (17 of 48). Dermacentor variabilis was the only species of tick from which R. rickettsi and F. tularensis were isolated. Of 931 adults collected off host animals or by dragging, 51 were infected with spotted fever rickettsiae; 39 of these yielded strains pathogenic for laboratory animals. Seven ticks, two of them also infected with R. rickettsi, contained F. tularensis. An unidentified bacterium-like microorganism was detected by hemolymph examination in 80 D. variabilis. This organism appeared unrelated to rickettsiae and proved nonpathogenic for meadow voles. A rickettsia-like organism antigenically related to the spotted fever group was noted in 64 of 545 Amblyomma americanum; it, too, failed to produce detectable infection or antibodies to spotted fever group antigens in meadow voles.

Squirrel monkeys, cynomolgus monkeys, rhesus monkeys and chimpanzees produced very broad and high hemagglutination-inhibition (HI) responses against group B arbovirus antigens when vaccinated with the sequential immunization procedure consisting of live 17D yellow fever virus, live attenuated strain of Langat virus followed by a live attenuated strain of dengue 2 virus. All such primates were protected against challenges with dengue viruses (dengue 1 virus in the case of squirrel monkeys and dengue 4 virus for the other three primate species) as determined by viremia studies and lack of HI antibody booster responses after challenges. The four vaccinated primate species were also protected against challenges with St. Louis encephalitis virus as determined by viremia studies and absence of histologic lesions in the central nervous system. Chimpanzees who had acquired group B arbovirus antibodies in nature responded with very broad and high HI antibodies against group B arbovirus antigens when vaccinated with the 3-virus sequential immunization and were immune to challenges with dengue 4 virus and St. Louis encephalitis virus. The protection against dengue viruses is discussed.

An evaluation of the susceptibility of eight mosquito species to Sindbis virus was conducted as a prelude to studies on the mechanisms of arbovirus infection in mosquitoes at the cellular and molecular level. Culex tritaeniorhynchus was the most susceptible mosquito tested, with an ID10 of 2.42 log10 TCID50. Considerably higher infectivity thresholds were observed with C. salinarius (4.41) and Aedes aegypti (4.46), but these species did show persistence of virus which may indicate multiplication. Anopheles quadrimaculatus, An. stephensi, Aedes taeniorhynchus and Ae. triseriatus became infected only at high doses and all showed reduced virus titers after 7 days post-infection. Armigeres subalbatus were refractory to infection at all doses tested.

The in vitro neutralization capacity of the sea snake antivenin (equine anti-Enhydrina schistosa) manufactured at Commonwealth Serum Laboratories, Melbourne, Australia, was tested against four heterologous venoms. Venoms of four sea snakes used were Praescutata viperina from the Gulf of Thailand, Pelamis platurus from the Pacific coast of Costa Rica, Central America, Laticauda semifasciata from Gato Island, Philippines, and Laticauda laticaudata from Amami Island, Japan. The antivenin effectively neutralized these venoms. Immunoelectrophoretic properties of these four venoms were also investigated and compared with homologous venom from Enhydrina schistosa.

Catalog of the Diptera of the Oriental Region, A. Volume 1. Suborder Nematocera, compiled and edited by Mercedes D. Delfinado and D. Elmo Hardy. 618 pages. The University of Press of Hawaii, Honolulu. 1973. $18.50.

Evaluation of Environmental Health Programmes. Report of a WHO Scientific Group. WHO Technical Report Series No. 528, 64 pages. 1973. $1.50.

Flies and Diseases. Volume II. Biology and Disease Transmission, by Bernard Greenberg. x + 447 pages, illustrated. Princeton University Press, Princeton, New Jersey 08540. 1973. $18.00.

Principles of Immunology, edited by Noel R. Rose, Felix Milgrom, and Carel J. van Oss. x + 468 pages, illustrated. Macmillan Publishing Co. Inc., 866 Third Avenue, New York 10022. 1973. $14.95 hardcover; $9.95 paperback.

Tumours in a Tropical Country, edited by A. C. Templeton. Recent Results in Cancer Research, Volume 41. xii + 345 pages, illustrated. Springer-Verlag, New York, Inc., 175 Fifth Avenue, New York 10010. 1973. $32.40.