The American Journal of Tropical Medicine and Hygiene - Volume 23, Issue 4, 1974

Clinical and laboratory results and pathological findings are presented for 12 cases of acute pulmonary insufficiency due to falciparum malaria. Renal and cerebral complications were also seen in all cases. Hematologic studies indicate disseminated intravascular coagulation in all cases, and hemorrhagic diathesis was noted in ten cases. Nine patients died, and intracapillary fibrin clots were seen in internal organs in 2 of 8 postmortems. Disseminated intravascular coagulation is probably an important mechanism causing serious complications, particularly acute pulmonary insufficiency. A high degree of parasitemia, massive intravascular hemolysis, and delay in recognition and treatment of disseminated intravascular coagulation are important in the outcome. The survival of three cases is believed to be the highest reported survival rate of this lethal complication.

A clinical trial comparing the efficacy and toxicity of WR 33063, a phenanthrenemethanol derivative, and quinine sulfate, was undertaken in adult Thai males with Plasmodium falciparum infections hospitalized in Prachinburi, Thailand. A 6-day course of WR 33063, 1.8 g daily, in divided doses, cured 23 of 25 patients. Quinine sulfate, in a course of 1.95 g daily in divided doses for 6 days, cured 21 of 22 patients. WR 33063 treatment was accompanied by a smaller number of side effects than treatment with quinine sulfate. Hematologic and biochemical abnormalities were not detected during or following treatment with either drug. An extended trial of WR 33063 and WR 30090, a quinolinemethanol derivative, is in progress.

The efficacy of clindamycin, a slow acting antimalarial, in combination with a rapid acting schizonticidal drug, quinine, was determined against three multidrug-resistant strains of Plasmodium falciparum (Cambodian I, Burma [Thau] and Panama II). No recrudescences occurred after treatment with quinine 650 mg orally every 8 hours for 3 days and clindamycin 450 mg orally every 6 hours for 3 days, when administered either simultaneously or sequentially. Quinine alone for 3 days was not curative against infections with these strains. During a 3-day course of therapy, blood levels of quinine or clindamycin were not influenced by administration of the other drug.

Significant structural differences are observed between the chloroquine-resistant Vietnam (Smith) strain and the chloroquine-sensitive Malaya (Camp-Sadun) strain of Plasmodium falciparum. The Vietnam strain shows subpellicular microtubules in the gametocyte, granular aggregates of the nucleus and enlargement of food vacuoles in the gametocyte and asexual form, while the Malaya (Camp-Sadun) strain lacks such findings. These differences are attributable to genetic variation rather than to drug resistance.

Sera from 60 Burkitt's lymphoma patients and from 60 matched controls were tested for antibodies to Plasmodium falciparum by the indirect immunofluorescent and indirect hemagglutination tests. Although the studies failed to show marked differences in sera from patients and controls, they could not exclude malaria infection as a predisposing factor for development of Burkitt's lymphoma.

Anemia, splenomegaly and glomerulonephritis in acute Plasmodium gallinaceum infections of chickens were studied in association with cold-active hemagglutinin for trypsinized human “O” erythrocytes, serum antigen, and the concurrent presence of antibody to serum antigen, as well as with the parasitemia of acute infection. Anemia with splenic enlargement was produced in normal chickens within 24 hours by intravenous injection of malarious chicken plasma that contained high titers of hemagglutinin, serum antigen, and antibody. A similar anemia and splenic engorgement resulted in normal birds injected with eluates from the washed blood cells of malarious chickens. Within 24 hours, the malarious plasma produced an acute glomerulonephritis similar to that which had been observed on the 5th day of infection. The concurrent presence of the hemagglutinin, serum antigen, and its antibody in the injected plasma, and the failure of the plasma to produce nephritis in immunized chickens, suggested that immune substances might be causal in acute malarial anemia and nephritis.

A controlled clinical trial with three amebicidal regimens was undertaken in the treatment of amebic liver abscess. Twenty patients in each of three groups received either niridazole, metronidazole, or emetine hydrochloride combined with chloroquine. Niridazole was found to produce toxic reactions. Metronidazole was ineffective in seven patients and emetine combined with chloroquine was ineffective in one patient.

Mice infected with Trichuris muris and then challenged with Entamoeba histolytica trophozoites by intracecal injection showed a higher rate of amebic infection and were more susceptible to amebic tissue invasion compared with controls. Amebic ulceration occurred principally at the site of attachment of the Trichuris worms to the cecal mucosa. The possible mechanisms of this interaction and its relevance in man are discussed.

A female Onchocerca was found in a nodular swelling removed from the wrist of a 48-year-old woman who had not been outside the area of Illinois, Wisconsin, and Missouri. Detailed examination of Onchocerca from man, horse, and cow demonstrated that on the basis of cuticle morphology the worm from the patient was distinguishable from O. volvulus obtained from subcutaneous nodules from man, O. lienalis from the gastrosplenic ligament of cattle, O. reticulata from the ligaments and flexor tendons of the legs of horses, and an Onchocerca species from the stifle joint of cattle. It closely resembled O. gutturosa and O. cervicalis from the ligamentum nuchae of the cow and horse, respectively. Its location in dense connective tissues possibly favors the likelihood of its being eventually identified as O. cervicalis. Neither O. gutturosa or O. cervicalis has been reported from the immediate locality of the patient's residence but both species probably occur there as do also their respective vectors, Culicoides and Simulium species. Three authentic cases of zoonotic onchocerciasis have been reported previously, one each from Switzerland, Crimea (USSR), and Canada.

Renal glomeruli of 9 dogs and 5 cats infected with Dirofilaria immitis and 19 hamsters infected with Dipetalonema viteae were studied ultrastructurally. Other major organs from infected hamsters were studied with the light microscope. One or more of the following pathological changes were found in the infected dogs: glomerular basement membrane (GBM) thickenings, GBM dense deposits, GBM holes, fusion of epithelial cell foot process, increased numbers of epithelial cell microvilli, increased numbers of mesangial cells, and occurrence of lysosome-like residual bodies in mesangial cells. Glomerular basement membrane thickenings, GBM dense deposits, GBM holes, GBM nodules and subendothelial dense deposits occurred in heavily infected hamsters. Amyloid fibrils and virus-like inclusions were also found in some infected hamster glomeruli. The pathological changes in hamster glomeruli appear to be associated with microfilaremia. Abnormalities were not found in cat glomeruli examined. Light microscopy revealed mononuclear and eosinophilic cellular infiltrations in the liver of all infected hamsters. These liver lesions were not found in any of 12 control animals examined. The observations made in this study suggest that glomerular lesions are another complication of filariasis.

Dogs infected with Dirofilaria immitis produced at least two types of skinsensitizing antibodies detectable by homologous passive cutaneous anaphylaxis (PCA) using adult soluble antigens. Reaginic antibodies (IgE-like) were demonstrated in 15 out of 36 dogs (42%) using 48- to 72-hour skin sensitization periods. Short term skin-sensitizing antibodies were found in 17 out of 36 dogs (47%) with 2- to 3-hour latent periods. The IgE-like reaginic antibodies were inactivated at 56°C for 4 to 6 hours. They were capable of inducing PCA reactions in the skin of rabbits and to a lesser extent in the skin of rhesus monkeys but not of guinea pigs and rats. No precipitating antibodies were demonstrated in the positive sera by immunodiffusion techniques. Rabbits appear to be good PCA recipients for determination and titration of canine reaginic antibodies.

A study of the morbidity of schistosomiasis mansoni was made in 138 school-children (age range, 7–16 years) in St. Lucia. The study was based on quantitative egg excretion data collected over a 4-year period before the study and included a comparable uninfected control group. All examinations were carried out “blind.” Infected subjects were divided into three levels of intensity of infection: heavy, 400 or more eggs/ml of feces; moderate, 100 to 300 eggs/ml; and light, 10 to 75 eggs/ml. The children were hospitalized for medical histories and physical and laboratory examinations. Gastrointestinal symptoms were present at relatively high levels in all groups, and were no more frequent in the Schistosoma mansoni-infected subjects than in the controls. Anthropometric measurements showed no differences among the groups. Hepatomegaly and splenomegaly were significantly more frequent in the heavy-moderate infection group, and extension of the liver below the costal margin was found to increase with intensity of infection. Serum globulin level and skin-test reactivity were directly related to intensity of infection; serum albumin level was inversely related. It was clear that in this St. Lucian study, infection with S. mansoni did not result in disease in most of the school-age subjects investigated; assessment of possible long-term (>4 years) effects was not made. This study provides a method for assessing morbidity of schistosomiasis based on quantitative egg excretion and demonstrates the relation of objective morbidity to intensity of infection.

The susceptibility of Liberian and Puerto Rican strains of Schistosoma mansoni to antischistosomal drugs was compared. The Liberian strain was more sensitive than the Puerto Rican strain to lucanthone · HCl, SQ 18,506, and stibophen. Parameters tested 90 days after treatment were hatching of eggs, parasitological cures, and extent of worm reductions.

In order to obtain information on whether established bilharzial lesions in various organs are persistent or reversed after treatment, 10 chimpanzees were infected with Schistosoma japonicum and treated 2 to 4.5 months later with a nitrovinylfuran derivative. Nine others were kept as controls. Regardless of timing, treatment resulted in the prompt reversal of most clinical symptoms as well as hematological and biochemical abnormalities, with the notable exception of the elevated immunoglobulin levels and only partial correction of hypoalbuminemia. No deleterious effects of treatment were noted. Treatment had a pronounced effect on the extent of colonic lesions, and on the degree of schistosomal nephropathy; in the liver inflammatory activity was significantly reduced, but the degree of portal fibrosis and of vascular abnormalities remained comparable to those observed at the time treatment was begun. Thus clinical or parasitological improvement did not reliably reflect the degree of pathological changes persisting after treatment. In the chimpanzees treated 2 months after exposure anatomical schistosome lesions were minimal and completely inactive. In the remaining animals the lesions were only partly inactivated. Portal liver fibrosis was prevented by early treatment; with later treatment it was stabilized but not reversed. On the other hand, treatment did not at any time aggravate the clinical or pathological status of the infected animals.

A specific and characteristic precipitation band appeared in immunoelectrophoresis tests with sera from hydatidosis patients, when fluid from either fertile or sterile bovine liver cysts of Echinococcus granulosus was used as antigen. No “false positives” were found using this test on sera from normal subjects and from patients with tuberculosis, aspergillosis, acute pneumonia, hepatic cirrhosis or pulmonary carcinoma. The immuno-electrophoresis test showed a higher sensitivity than the indirect hemagglutination test in the preoperative diagnosis of pulmonary hydatidosis in 54 patients whose infections were subsequently confirmed at surgery. It was possible to classify hydatid cysts into four categories based upon the physical integrity of cyst membranes observed at surgery and the histopathological response of the host. In individuals having recently broken cysts the immunoelectrophoresis test was uniformly positive whereas in those with only remnants or unbroken cysts, the proportion of positive reactors was markedly less. It is postulated that the physical status of the hydatid cyst membranes influences the degree of antigen stimulation of the immune system of the host and therefore affects the success or otherwise of immunodiagnostic tests.

From three different habitats in North Dakota 5,638 deer mice, Peromyscus maniculatus, were examined for larval Echinococcus multilocularis infections during 1965 through 1972. Infection was found in 224 (4%) of these mice. Yearly differences in prevalence were evident, with a low of 1.1% during 1971 and a high of 7.8% in 1968. These yearly differences were partially attributable to host density, habitat sampled, and climatic season during which the mice were taken. Since the year was not a legitimate variable, the total over-years data were used to assess the relative influence of sex and age of the host, habitat, and climatic season on the prevalence of the larval parasite. The rate of infection varied significantly with habitat. Seasonally, the highest prevalence was observed during spring (6.5%), followed by summer (5.5%), autumn (2.2%), and winter (2.0%). The prevalence in adult mice was over 10 times greater than in juveniles (4.5% vs. 0.4%), while more males were infected than females (4.6% vs. 3.1%). A factorial analysis of variance showed the order of importance of these variables to be 1) age, 2) habitat, 3) season, 4) age by season, 5) age by habitat, and 6) habitat by season. A mathematical model based on the functions of these variables and accounting for about 74% of the variation is suggested for the prediction of prevalences of larval E. multilocularis in this intermediate host.

A 32-year-old woman developed severe and protracted intrahepatic cholestasis following the oral ingestion of thiabendazole (Mintezol®). The cholestatic reaction was associated with nausea, intense pruritus, and a generalized rash. The jaundice persisted for more than 1 month without signs of remission. A transhepatic cholangiogram was followed by a massive hemorrhage which ultimately led to her death. Postmortem examination revealed completely patent ducts and liver histology was indicative of a cholestatic drug reaction. Cholestasis due to hypersensitivity to thiabendazole has not previously been reported.

An outbreak of scrub typhus occurred in Chinese Army personnel in the eastern part of Taiwan during 1970. This is the first outbreak of this disease documented on the main island of Taiwan since 1932. Of 21 hospitalized patients examined during the convalescent stage, 19 had antibody titers of from one to 640 to one to 10,240 as measured by indirect immunofluorescence to the Karp, Kato and Gilliam stains of Rickettsia tsutsugamushi. All were males of from 35 to 51 years and all had high fever by history. Eleven patients had eschars, six with typical black necrotic scabs. In addition, serologic evidence of prior scrub typhus infection was found in 59 of 241 other men from the two military companies involved in the outbreak. All men had been working clearing an area in hills 300 to 500 meters high. This land was originally cleared for agricultural use, but had been abandoned over 4 years previously. Rickettsia tsutsugamushi was recovered from rodents and chiggers (Leptotromibidium deliense) captured in the area.

Immunization programs constitute one of the most economical and efficient approaches to preventive medicine in developing countries. Costs can be reduced further by administering several antigens simultaneously. Available evidence suggests it is safe and effective to administer the usual range of antigens utilized in developing countries at one time. Likewise, operational experiences in the past 5 years indicate the delivery of multiple antigens is logistically feasible. Mobile vaccination teams can be expected to reach a high percentage of children and by means of objective screening systems, vaccine wastage and duplication can be avoided without the need for individual immunization records.

Clinical and prevalence studies of Chagres virus (Phlebotomus-fever group of arboviruses) infections in Panamanian residents were performed. Clinical cases of Chagres virus infection in three persons are described. Antibody conversions and virus reisolations were demonstrated in all cases. The distribution of Chagres hemagglutination-inhibition antibodies in different regions of Panama were as follows: western region 0.4% of 1,329 samples; central region 4.3% of 2,829; eastern region 2.9% of 276; Perlas Islands 10.9% of 174 (including 17.8% of 107 from San Miguel Island), giving an overall rate of 3.3% in 4,608 samples. These results indicate a widespread distribution of Chagres virus in Panama, with a particularly high rate of antibody prevalence on one of the offshore islands.