Showing papers in "American Journal of Tropical Medicine and Hygiene in 1989"

An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate.

Abstract: The diagnostic sensitivity and specificity of detection of anti-dengue IgM by antibody capture enzyme-linked immunosorbent assay (ELISA) was investigated in dengue infections in a variety of clinical settings. Sera from uninfected controls were uniformly negative. Serial specimens from experimental and natural infections showed that viremia and fever terminated as anti-dengue IgM became detectable. Anti-dengue IgM appeared in most cases by the 3rd afebrile day of illness and declined to undetectable levels after 30-60 days. Assay sensitivity was 78% in admission sera (924/1,183; 95% CI = 75-81%) and 97% in paired sera (1,030/1,062; 95% CI = 96-98%) thus exceeding or matching the performance of the hemagglutination-inhibition assay. Measurement of the anti-dengue IgM to anti-Japanese encephalitis IgM ratio correctly identified all sera from 112 patients with strictly defined Japanese encephalitis and 98% (307/312; 95% CI = 96-99%) of sera from patients whose dengue infections were confirmed by virus isolation. Dengue infections could be classified as primary or secondary by determining the ratio of units of dengue IgM to IgG antibody. We propose that measurement of dengue and Japanese encephalitis IgM and IgG antibodies upon admission and discharge from hospital care should replace the hemagglutination inhibition assay as the standard dengue serologic technique in regions where these 2 viruses co-circulate.

Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever.

Abstract: Serum specimens collected during a prospective study of dengue infections among schoolchildren in Bangkok were tested for their ability to enhance dengue 2 (DEN-2) virus growth in human monocytes in vitro. Two groups of dengue-immune sera were compared: 32 dengue antibody positive serum specimens from children who subsequently developed asymptomatic secondary dengue infections; and 9 dengue antibody positive serum specimens from children who subsequently developed severe symptomatic secondary dengue infections, 8 of which were clinically diagnosed as dengue hemorrhagic fever. Antibody-dependent enhancement of virus growth was quantitated by measurement of virus yields in supernatant fluids of normal human monocyte cultures that were infected with DEN-2 virus in the presence of undiluted test serum. Only 4 of 32 (12%) preinfection sera from asymptomatic children, but 6 of 9 (67%) preinfection sera from symptomatic children, had significant enhancing activity (P < 0.001). High serum DEN-2 antibody dependent enhancing activity is a significant (relative risk = 6.2) risk factor for severe illness among children in a dengue hemorrhagic fever endemic region. Dengue antibodies can be neutralizing and therefore protective, or they can be enhancing and increase the risk of dengue hemorrhagic fever.

A Review of the Geographic Distribution and Epidemiology of Leishmaniasis in the New World

Abstract: A review of the epidemiologic aspects of the New World leishmaniases, including their known geographic distribution, etiologic agents, zoonotic reservoirs, and insect vectors, based on biological and molecular characterization of Leishmania isolates is presented. Data summarized in this paper on parasite taxonomy and geographic distribution come from our studies of greater than 1,000 New World Leishmania isolates identified by species-specific monoclonal antibodies using an indirect radioimmune binding assay and from scientific literature.

Aedes aegypti and Aedes aegypti-borne disease control in the 1990s: top down or bottom up

Abstract: It is a great honor to be asked to present the Charles Franklin Craig Lecture of this Society. I initially accepted this responsibility with some trepidation, and after reviewing the list of previous Craig Lecturers, I became even more nervous about the prospects of addressing you. It is indeed an honor to be added to that list. I would like to express my sincere thanks to those responsible for my selection as the Craig lecturer, including the committee who selected me for this honor, the many collaborators who over the years have made my work much better than it would have otherwise been, and last, but not least, my wife Bobbie whose understanding and tireless support made it all possible. Charles Franklin Craig helped establish the viral etiology of dengue fever in 1907, so it is appropriate that I talk about this disease today.

Toxocara larva migrans now.

Abstract: It has been nearly 4 decades since Paul Beaver and others first identified Toxocara larvae as the cause of a common disease in children. Our knowledge of the frequency and type of illness produced by Toxocara ssp. has increased greatly during this time. Although under-recognized and under-reported, toxocaral larva migran is now recognized as a widespread and common human infection. Among helminth infections in developed countries, it is perhaps second in frequency only to pinworm. Potential etiologic agents of larva migrans syndromes include a wide range of zoonotic helminths. Toxocara canis and T. cati, the common ascarids of dogs and cats, are incriminated most frequently, at least in temperate climates. This is a result of many factors including the high frequency of pet ownership, the high prevalence of Toxocara species in dogs and cats, and the long persistence of infective Toxocara eggs in the environment.1-3 Widespread environmental contamination with Toxocara eggs, the attraction of children to the animals and their environment, and the play habits of children combine to facilitate human infection with Toxocara ssp.

Treatment with a single dose of albendazole improves growth of Kenyan schoolchildren with hookworm, Trichuris trichiura, and Ascaris lumbricoides infections.

Abstract: We studied the growth of primary schoolchildren with hookworm (87%), T. trichiura (97%), and A. lumbricoides (49%) who received a single 400 mg dose of albendazole or an identical placebo. Children were allocated at random to placebo (PL, n = 72) or albendazole (A, n = 78) groups, treated, and re-examined 6 months later. The A group gained significantly more than the PL group in weight (1.3 kg), percent weight for age (4.5% age points), percent height for age (0.5% age points), percent weight for height (4.3% age points), percent arm circumference (2.9% age points), and in triceps and subscapular skinfold thicknesses (1.2 mm). The PL group showed significant decreases between exams in percent weight for age, percent height for age, percent weight for height, percent arm circumference for age, and skinfold thicknesses for age. The A group had highly significant increases (P less than 0.0002) in all of these parameters except height for age. From Exam 1 to 2, the A group exhibited decreases (P less than 0.0002) in geometric means eggs per gram of feces (epg): for hookworm, means = 1,183 epg at Exam 1 vs. 136 epg at Exam 2 (67% egg reduction); for T. trichiura, means = 2,857 epg at Exam 1 vs. 1,061 epg at Exam 2 (28% egg reduction); and for A. lumbricoides, means = 86 epg at Exam 1 vs. 2 epg at Exam 2 (91% egg reduction). The PL group had a borderline increase in geometric means hookworm egg count, no significant change in T. trichiura egg count, and a small but significant decrease in A. lumbricoides egg count. Decreases in intensities of all infections were significant predictors of growth improvement. Hookworm egg count entered the equations for all 6 measurements, and A. lumbricoides and T. trichiura entered 4/6 equations. Single dose treatment with albendazole, despite continual exposure to infection, can permit improved growth rates in areas where intestinal helminths and protein-energy malnutrition are highly prevalent.

Sensitive determination of circulating anodic antigen in Schistosoma mansoni infected individuals by an enzyme-linked immunosorbent assay using monoclonal antibodies.

Abstract: From a panel of mouse monoclonal antibodies reactive with a repeating epitope of the schistosome circulating anodic antigen, an IgG1 monoclonal antibody was selected. This monoclonal antibody was applied in a sandwich enzyme-linked immunosorbent assay as capture antibody and as alkaline phosphatase labeled conjugate. This assay allowed a sensitive quantitation of circulating anodic antigen in serum samples of infected individuals, detecting less than 1 ng antigen/ml serum. In Schistosoma mansoni infected individuals from Zaire, the level of antigen in serum correlated with fecal egg output. The lower detection level of the immunoassay corresponded to a level of about 10 eggs/gm feces.

Identification of Mycoplasma incognitus infection in patients with AIDS: an immunohistochemical, in situ hybridization and ultrastructural study.

Abstract: Monoclonal antibodies (Mabs) were developed against antigens from a pure culture of Mycoplasma incognitus grown in modified SP-4 medium. All the Mabs obtained were shown to react only with M. incognitus, and not with other species of human mycoplasma. The Mabs identified M. incognitus immunohistologically in thymus, liver, spleen, lymph node, or brain from 22 patients with AIDS, as well as in 2 placentas delivered by patients with AIDS. Using an 35S-labeled DNA probe specific for M. incognitus and in situ hybridization technique, we also identified M. incognitus-specific genetic material in these tissues. Furthermore, ultrastructural studies of the specific areas of tissues which were highly positive for M. incognitus antigens revealed characteristic structures of mycoplasma organisms. These mycoplasma-like particles could be identified intracellularly and extracellularly. Histopathology of the tissues infected by M. incognitus varied from no pathological changes to fulminant necrosis with or without an associated inflammatory reaction. M. incognitus, a novel pathogenic mycoplasma, was cytopathic and cytocidal.

Centrifugation-shell vial technique for rapid detection of Mediterranean spotted fever rickettsia in blood culture.

Abstract: The shell vial technique for isolation of cytomegalovirus was adapted to detect Rickettsia conorii in blood culture using human fibroblast monolayers The inoculation was performed with low speed centrifugation and the rickettsiae demonstrated by immunofluorescence 24–120 hr after inoculation R conorii was identified in 11 of 13 patients with Mediterranean spotted fever in 48–72 hr

Ivermectin for human strongyloidiasis and other intestinal helminths.

Abstract: Since ivermectin, a mixture of 2 closely related macrocyclic lactones, has proven highly effective against animal intestinal nematodes, trials were undertaken to determine its efficacy against human intestinal nematodes. We tested 110 patients with strongyloidiasis and 90 with enterobiasis; many had other intercurrent intestinal nematode infections. Stool examinations were done before and after patients were given a single dose of oral ivermectin capsules (50, 100, 150, or 200 micrograms/kg body wt); 55 recipients of 100 or 200 micrograms/kg doses received a second identical dose the next day. Kato and saline smears, ethyl acetate concentration, modified Baermann's technique, and Harada-Mori cultures were repeated; cure was defined as complete absence of eggs and/or larvae from stools tested 30 days after dosing. Ivermectin was well tolerated. Overall cure rates at all doses 30 days after therapy averaged 88% for strongyloidiasis, 100% for ascariasis, 85% for trichuriasis, and 85% for enterobiasis. Ancylostoma duodenale and Necator americanus were little affected.

Monoclonal antibodies for dengue virus prM glycoprotein protect mice against lethal dengue infection

Abstract: Five murine monoclonal antibodies (Mabs) reactive against the prM glycoproteins of DEN-3 and -4 were used to passively protect mice in vivo against lethal challenge with homologous and heterologous dengue virus serotypes. Four of the 5 prM-reactive monoclonals cross-protected mice against heterologous challenge, whereas 1 protected against challenge with only the homologous serotype. Although in vitro binding to virions was readily demonstrated, only 2 of the prM Mabs had detectable neutralizing activity. The neutralizing activity could not be enhanced by anti-mouse immunoglobulin or complement. However, 4 of the 5 prM Mabs fixed complement. This is the first report of prM-specific Mabs that are protective in mice.

Inhibition of Crimean-Congo hemorrhagic fever viral infectivity yields in vitro by ribavirin.

Abstract: : Ribavirin was evaluated as a potential therapeutic for Crimean-Congo hemorrhagic fever (CCHF). Viral yields for strains of CCHF virus from Europe, Asia, and African in African green monkey kidney (Vero) cells were markedly reduced by this drug. Some CCHF viral strains appeared more sensitive than others, but in general, ribavirin doses as low as 5 ug/ml caused a transient reduction of viral yields. A further reduction in viral yields was induced by a dose of 25 ug/ml, and evidence of viral replication was not demonstrated in cells treated with 50 or 250 ug/ml. In contrast, a dose of ribavirin at least 9 times greater was required to induce a comparable inhibitory effect on the yields of Rift Valley fever virus, for which the drug has been shown to inhibit replication in monkeys and rodents. Keywords: Reprints; Therapy.

A specific diagnostic antigen of Echinococcus granulosus with an apparent molecular weight of 8 kDA.

Abstract: An echinococcus antigen with an apparent molecular weight of 8 kDa was identified as diagnostically important. An immunoblot assay using this antigen was 91% sensitive for surgically confirmed Echinococcus granulosus hydatid disease of the liver. Specificity was 100% for echinococcosis. Marked cross-reactivity was observed with serum specimens from patients with E. multilocularis and E. vogeli infections. The 8 kDa component was not related to the widely recognized echinococcus antigen 5.

Virus-like infectious agent (VLIA) is a novel pathogenic mycoplasma: Mycoplasma incognitus.

Abstract: The newly recognized pathogenic virus-like infectious agent (VLIA), originally reported in patients with AIDS but also known to be pathogenic in previously healthy non-AIDS patients and in non-human primates, was cultured in cell-free conditions using a modified SP-4 medium and classified as a member of the order Mycoplasmatales, class Mollicutes. The infectious microorganism is tentatively referred to as Mycoplasma incognitus. M. incognitus has the unique biochemical properties of utilizing glucose both aerobically and anaerobically, as well as having the ability to metabolize arginine. Among all known human mycoplasmas, these specific biochemical characteristics were found previously only in a rarely isolated species, M. fermentans. In comparison with M. fermentans, M. incognitus appears to be even more fastidious in cultivation requirements and fails to grow in all tested mycoplasma media other than modified SP-4 medium. In addition, M. incognitus grows much more slowly, has a smaller spherical particle size and occasional filamentous morphology, and forms only irregular and very small colonies with diffuse edges on agar plates. Antigenic analysis using polyclonal and monoclonal antibodies and DNA analysis of sequence homology and restriction enzyme mappings in M. incognitus, M. orale, M. hyorhinis, M. hominis, M. pneumoniae, M. fermentans, M. arginini, M. genitalium, M. salivarium, Ureaplasma urealyticum, and Acholeplasma laidlawii revealed that M. incognitus is distinct from other mycoplasmas, but is most closely related to M. fermentans.

Reduced Hepatic Blood Flow and Intestinal Malabsorption in Severe Falciparum Malaria

Abstract: We have studied intestinal function and liver blood flow in Thai adults with complicated and uncomplicated falciparum malaria. The absorption of 3 orally administered test sugars, D-xylose, 3-O-methyl-D-glucose, and L-rhamnose, was greatly reduced in complicated malaria, while the lactulose/rhamnose absorption ratio was significantly increased. Hepatic blood flow was concomitantly reduced in severe malaria. These deviations reverted to normal in convalescence. Neither sugar absorption nor liver blood flow was reduced in uncomplicated falciparum malaria.

Identification of major Trypanosoma cruzi antigenic determinants in chronic Chagas' heart disease.

Abstract: To identify Trypanosoma cruzi target antigens in overt Chagas' heart disease, a parasite lambda gt11 cDNA library was screened with the serum of a patient with a severe chagasic heart involvement (JL). Using a phage dot array immunoassay, 5 highly antigenic clones, JL1, JL5, JL7, JL8, and JL9, were probed with sera from clinically characterized T. cruzi infected subjects. The correlation of cloned T. cruzi antigen recognition with the clinical status of the subjects led to the identification of a recombinant antigen, JL5, that reacted predominantly with sera from patients with Chagas' heart disease. The antigenic determinant of the JL5 recombinant was a small 35 amino acid peptide. The nucleotide and the deduced amino acid sequence, together with other experimental data, allowed identification as the C-terminal portion of a T. cruzi P ribosomal protein. The C-terminal undecapeptide in JL5, EDDDMGFGLFD, was highly homologous to the same region of the human P protein SD(D/E)DMGFGLFD. The latter sequence has been identified as the P protein epitope in systemic lupus erythematosus (SLE). Positive SLE sera reacted with the JL5 recombinant phage, suggesting that the T. cruzi P protein might induce antibodies with a similar specificity to that of P antibodies in SLE.

Suppression of cell-mediated immune responses to malaria antigens in pregnant Gambian women.

Abstract: In malaria endemic areas, pregnancy predisposes previously immune women to clinical and subclinical malaria infection. While parameters of humoral immunity do not seem to be affected to pregnancy, suppression of cellular immunity has been demonstrated for a number of antigens. In this study of women from a rural area of the Gambia where falciparum malaria is holoendemic, we show that lymphoproliferative responses to Plasmodium falciparum antigens are depressed in pregnant women compared to parity matched non-pregnant women, and that this effect is particularly marked in primigravidae. The data also indicate that malaria antigen induced γ-interferon production may be depressed in pregnant women. There was no significant difference in antimalarial antibody titers between the 2 groups.

Plasmodium falciparum associated placental pathology: a light and electron microscopic and immunohistologic study.

Abstract: Pathological changes were studied by light and electron microscopy on term placentas collected in Malawi from 20 P. falciparum infected women (11 primiparas and 9 multiparas). One placenta from an uninfected term primipara and 4 from multiparas were studied as controls. Changes included the presence of parasitized erythrocytes and malarial pigment particles in the intervillous space, excessive syncytial knotting, chronic basal villitis, malarial pigment deposits in the trophoblasts, trophoblastic damage with focal necrosis, partial loss of microvilli, and thickening of the trophoblastic basement membrane. Infected erythrocytes were not seen in the fetal circulation. Severity appeared to correlate with the level of maternal and placental parasitemias, regardless of infant birth weight or placental weight. Differences in the severity of pathological changes between primiparas and multiparas could not be demonstrated. Immunohistochemistry revealed that 45% of the placentas stained strongly for IgG and 15% stained for C3 and for P. falciparum antigens in the trophoblastic cytoplasm and basement membrane.

Diversity of antigens expressed on the surface of erythrocytes infected with mature Plasmodium falciparum parasites in Papua New Guinea.

Abstract: Antigens were detected on the surface of erythrocytes from children with acute falciparum malaria in Madang, Papua New Guinea. These parasite-induced erythrocyte surface antigens (PIESA) were serotyped with convalescent sera from children and hyperimmune sera from adults in parasite infected cell agglutination assays (PICAs) and by inhibition of binding of infected cells to melanoma cells. Extensive serological diversity of PIESA was demonstrated. A significant correlation between serotypes defined by reactivity of immune sera in PICA and inhibition of melanoma cell binding (MCB) was observed. This suggests that both assays measure antibody responses to the same antigen(s). Increased recognition of different PIESA specificities with age is consistent with the hypothesis that repeated exposure to malaria confers immunity against a range of PIESA serotypes and parallels the development of clinical immunity to malaria in this area of Papua New Guinea.

Deciphering western blots of tapeworm antigens (Taenia solium, Echinococcus granulosus, and Taenia crassiceps) reacting with sera from neurocysticercosis and hydatid disease patients.

Abstract: Complex antigen mixtures displayed in Western blots may be immediately and quantitatively categorized with respect to specificity and immunogenicity by immunoplotting. This involves plotting the frequency with which each antigen band reacts with a set of immune sera against the frequency of the same band when reacted with another set of immune sera. Immunoplotting has proven to be a powerful method of analyzing Western blots of reactions between vesicular fluids from the metacestodes of Taenia solium, E. granulosus, and T. crassiceps, and sera from human cases of neurocysticercosis and hydatid disease. Immunoplotting readily sorts out those antigens useful for discriminative immunodiagnosis from the multitude of bands in the sera of sick and healthy people. It aids in assessing the antigenic similarity between the human parasites and the murine parasite T. crassiceps, validating the latter as an alternative source of antigens for immunodiagnosis of cysticercosis and hydatid disease.

Leptospirosis in Chonbuk Province of Korea in 1987: a study of 93 patients.

Abstract: Leptospirosis is a zoonosis with protean clinical manifestation. Diagnosis requires a high index of suspicion and is confirmed by isolation of the organism or, more commonly, by serologic studies. In the fall of 1987, after severe flooding, we saw 93 patients with leptospirosis, confirmed by a microagglutination test. Thirteen percent of the patients had no clinical or laboratory findings except fever and headache, but the rest had mild to severe manifestations. Jaundice, renal failure, and aseptic meningitis were not common, but pulmonary symptoms, when present, were striking. The mortality rate was 5%. The main cause of death was asphyxiation due to massive hemoptysis from pulmonary hemorrhage and acute respiratory failure.

Stage specific actions of antimalarial drugs on Plasmodium falciparum in culture.

Abstract: Chemicals with antimalarial effects show different patterns against ring stages, trophozoites, and schizonts of Plasmodium falciparum in culture. Amodiaquine, mefloquine, quinine, quinacrine, primaquine, qinghaosu, halofantrine, rifampin, antimycin A1, cycloheximide, and actinomycin D were preferentially toxic to the mature stages. Ammonium chloride killed ring stages faster than mature forms, while tetracycline, clindamycin, and halofuginone acted with equal speed on all 3 stages.

Epidemiology of visceral leishmaniasis in Colombia.

Abstract: Epidemiologic studies were conducted during the period 1986–1988 in a small rural community in Colombia (El Callejon) where visceral leishmaniasis is highly endemic. In this community of 185 people, 14 cases of infantile visceral leishmaniasis were diagnosed in the 9 years 1981–1988. Leishmanin skin testing of a sample of the human residents showed that prevalence of Leishmania chagasi infection increased with age; overall, 51.2% of the subjects had a positive reaction. A canine surveillance program was instituted, using introduced sentinel dogs as well as the indigenous dog population. Eleven of 16 sentinel dogs were infected within 8 months of exposure; mean seroconversion time was 4.4 months. Eleven of 25 seronegative local dogs were also infected during the 26 month period; mean seroconversion time was 8 months. Parasites identified by isozyme electrophoresis as L. chagasi were recovered from 18 of 22 seropositive dogs. Collections of wild animals using baited live traps yielded mainly the neotropical opossum, Didelphis marsupialis. Leishmania chagasi was recovered from 12 of 37 (32.4%) opossums. Six of 681 female Lutzomyia longipalpis collected in the community had flagellates in their guts; cultures from 4 were identified as L. chagasi. These data confirmed that active parasite transmission occurred. The relatively high prevalence of L. chagasi infection found among D. marsupialis captured near human dwellings suggests that these animals may be an important peridomestic reservoir.

Characteristic sonographic pattern of schistosomal hepatic fibrosis.

Abstract: The hepatic sonographic patterns from 50 patients undergoing operations for bleeding esophageal varices were compared with the interpretation of the histological findings in a hepatic wedge biopsy obtained during surgery. The sonographic pattern for schistosomiasis periportal fibrosis is characteristic and is not mimicked by other hepatic diseases we have studied. Sonography agreed with pathology in 44 out of 50 patients. Schistosomiasis could be separated from cirrhosis, as well as from combined lesions. Where there was a discordance, we believe that sonography gave a more accurate diagnosis.

Ecologic studies of mosquitoes and birds as hosts of Ockelbo virus in Sweden and isolation of Inkoo and Batai viruses from mosquitoes.

Abstract: Field studies were conducted in central Sweden from 1983 through 1985 to obtain information on the etiologic agent of Ockelbo disease, described in Sweden in the 1960s and probably identical to Pogosta disease in Finland and to Karelian fever in the western USSR. Mosquitoes (63,644) collected during this 3 year period yielded 21 virus strains. Ockelbo virus isolations were from Culiseta morsitans (5 strains), Culex pipiens and/or Cx. torrentium (6 strains), and Aedes cinereus (3 strains). Inkoo (6 strains) and Batai (1 strain) viruses were recovered from Ae. communis. Blood samples collected March-May from migrating birds on the southeast and est coast of Sweden and in July and August from resident birds in east-central Sweden were tested for neutralizing antibody to Ockelbo virus. Antibody was not detected in 328 birds sampled during spring migrations. Two of 58 (3.4%) birds bled in July and 8 of 78 birds (10%) bled in August had antibody to Ockelbo virus. Ockelbo virus circulates in a mosquito-bird-mosquito cycle, with Cs. morsitans and Cx. pipiens and/or Cx. torrentium as enzootic vectors. Antibody was detected in passerine birds. Other classes of birds or other vertebrates were not sampled. Aedes cinereus may serve primarily to transmit virus to people. The role of other mosquito species as vectors for people is unknown.

Uninfected erythrocytes form "rosettes" around Plasmodium falciparum infected erythrocytes.

Abstract: The human malaria parasite, P. falciparum, exhibits cytoadherence properties whereby infected erythrocytes containing mature parasite stages bind to endothelial cells both in vivo and in vitro. Another property of cytoadherence, “rosetting,” or the binding of uninfected erythrocytes around an infected erythrocyte, has been demonstrated with a simian malaria parasite P. fragile which is sequestered in vivo in its natural host, Macaca sinica. In the present study we demonstrate that rosetting occurs in P. falciparum. Rosetting in P. falciparum is abolished by protease treatment and reappears on further parasite growth indicating that, as in P. fragile, it is mediated by parasite induced molecules which are protein in nature. P. vivax and P. cynomolgi, which are not sequestered in the host, did not exhibit rosetting. Rosetting thus appears to be a specific property of cytoadherence in malaria parasites.

The status of ivermectin in the treatment of human onchocerciasis.

Abstract: Ivermectin is a macrocyclic lactone that has widespread antiparasitic activity. Numerous clinical trials have shown that ivermectin is safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction, as is seen with diethylcarbamazine treatment. The drug temporarily interrupts production of microfilaria but has no known long-lasting effects on the adult worms. In patients with onchocerciasis, a single oral dose of ivermectin (150 µg/kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement. At this dose, ivermectin causes minimal side effects and is sufficiently free of severe reactions to be used on a mass scale. It promises to revolutionize the treatment of onchocerciasis.

Experimental transmission of Crimean-Congo hemorrhagic fever virus by Hyalomma truncatum Koch.

Abstract: Larval Hyalomma truncatum ticks were infected with Crimean-Congo hemorrhagic fever (CCHF) virus by allowing them to engorge on viremic newborn mice. The overall tick infection rate was 4.4% (24/542). Virus was detected in specimens for greater than or equal to 160 days postinfection. Transstadial transmission to the adult tick stage was observed and horizontal transmission to a mammalian host was demonstrated. Horizontal transmission of CCHF virus to uninfected adult ticks occurred while feeding with transstadially infected ticks on the same host. No evidence of transovarial virus transmission from infected female ticks to their 1st generation progeny was observed.

The effect of iron therapy on malarial infection in Papua New Guinean schoolchildren.

Abstract: The effect of iron therapy on malarial infection was investigated in Papua New Guinea, where malaria is endemic. Prepubescent schoolchildren with hemoglobin levels of 8-12 g/dl were randomly assigned to receive either 200 mg ferrous sulfate or a placebo twice daily for 16 weeks. Iron status and malarial infection were assessed at baseline, after 6 and 16 weeks of therapy, and 8 weeks after therapy was discontinued. Iron status was significantly improved by the treatment. The treatment did not significantly affect parasite rate, parasite density, or levels of anti-malarial IgG. No changes in spleen size were observed in either group. Furthermore, there was no significant difference between the groups in reported episodes of suspected malaria during the therapy. These results suggest that, in malaria endemic areas, oral treatment for iron deficiency can be carried out in semi-immune or immune schoolchildren without adverse consequences.

Association of the virus-like infectious agent originally reported in patients with AIDS with acute fatal disease in previously healthy non-AIDS patients.

Abstract: We studied 6 patients from 6 different geographic areas who presented with acute flu-like illnesses. The patients developed persistent fevers, lymphadenopathy or diarrhea, pneumonia, and/or heart, liver, or adrenal failure. They died in 1-7 weeks. These patients had no serological evidence of HIV infection and could not be classified as AIDS patients according to CDC criteria. The clinical signs as well as laboratory and pathological studies of these patients suggested an active infectious process, although no etiological agent was found despite extensive infectious disease work-ups during their hospitalization. Post-mortem examinations showed histopathological lesions of fulminant necrosis involving the lymph nodes, spleen, lungs, liver, adrenal glands, heart, and/or brain. No viral inclusion cells, bacteria, fungi, or parasites could be identified in these tissues using special tissue stains. We report that immunohistochemistry using rabbit antiserum raised against VLIA, the virus-like infectious agent previously identified in patients with AIDS and shown to cause fatal systemic infection in primates, revealed VLIA antigens in these necrotizing lesions. In situ hybridization using an 35S labeled VLIA-specific DNA probe also detected VLIA genetic material in the areas of necrosis. Furthermore, virus-like particles closely resembling VLIA were identified ultrastructurally in these histopathological lesions. VLIA was associated with the systemic necrotizing lesions in these previously healthy non-AIDS patients with an acute fatal disease.