Marianna Wilson

Neurocysticercosis in an Orthodox Jewish community in New York City.

BACKGROUND AND METHODS From June 1990 through July 1991, intracerebral infection with the larval stage of the pork tapeworm Taenia solium was diagnosed in four unrelated persons in an Orthodox Jewish community in New York City. None of the patients had eaten pork, and only one had traveled to a country in which T. solium infection was endemic. We investigated this outbreak, screened serum samples from family members and household contacts for antibodies to cysticercosis, and examined stool specimens from household employees for eggs of taenia species. RESULTS The four patients had recurrent seizures and brain lesions that were radiologically consistent with the presence of cysticerci. The diagnosis was confirmed in two patients by a brain biopsy, and in two by immunoblot assays for cysticercus antibodies. Of 17 immediate family members screened serologically, 7 from two families had cysticercus antibodies. Magnetic resonance imaging of the brain showed cystic lesions in two of the seropositive family members, one of whom had had a seizure. Examinations of six domestic employees from all four households revealed an active infection with taenia species in one and a positive serologic test in another. Since these women had recently emigrated from Latin American countries where T. solium infection is endemic, they were the most likely sources of infection in the members of these households. CONCLUSIONS A diagnosis of neurocysticercosis should be considered in patients with seizures and radiologic evidence of cystic brain lesions, even in those who do not eat pork and who have not traveled to a country in which T. solium infection is endemic. Recent emigrants from countries in which T. solium infection is endemic should be screened for tapeworm infection in their stools before they are employed as housekeepers or food handlers.

Congenital Toxoplasmosis: A Review

Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. In the United States, approximately 85% of women of childbearing age are susceptible to acute infection with T. gondii. Acute infections in pregnant women may cause serious health problems when the organism is transmitted to the fetus (congenital toxoplasmosis), including mental retardation, seizures, blindness, and death. An estimated 400 to 4000 cases of congenital toxoplasmosis occur in the U.S. each year. Manifestations of congenital toxoplasmosis may not become apparent until the second or third decade of life. Serologic tests are used to diagnose acute infection in pregnant women, but false-positive tests occur frequently, therefore, serologic diagnosis must be confirmed at a reference laboratory before treatment with potentially toxic drugs should be considered. Much of congenital toxoplasmosis can be prevented by educating women of childbearing age and pregnant women to avoid eating raw or undercooked meat, to avoid cross-contamination of other foods with raw or undercooked meat, and to use proper cat-litter and soil-related hygiene. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to outline the biology of toxoplasmosis, to explain the methods of transmission of toxoplasmosis, and to identify the methods used to diagnose toxoplasmosis in pregnancy.

Hematologic and Biochemical Changes Associated with Human T Lymphotropic Virus Type 1 Infection in Jamaica: A Report from the Population-Based Blood Donors Study

Background. A quadrivalent (types 6, 11, 16, and 18) human papillomavirus (HPV) L1 virus-like-particle (VLP) vaccine has been shown to be 95%-100% effective in preventing cervical and genital disease related to HPV-6, -11, -16, and -18 in 16-26-year-old women naive for HPV vaccine types. Because most women in the general population are sexually active, some will have already been infected with ≥ 1 HPV vaccine types at the time vaccination is offered. Here, we assessed whether such infected women are protected against disease caused by the remaining HPV vaccine types. Methods. Two randomized, placebo-controlled trials of the quadrivalent (types 6, 11, 16, and 18) HPV vaccine enrolled 17,622 women without consideration of baseline HPV status. Among women infected with 1-3 HPV vaccine types at enrollment, efficacy against genital disease related to the HPV vaccine type or types for which subjects were naive was assessed. Results. Vaccination was 100% effective (95% confidence interval [Cl], 79%-100%) in preventing incident cervical intraepithelial neoplasia 2 or 3 or cervical adenocarcinoma in situ caused by the HPV type or types for which the women were negative at enrollment. Efficacy for preventing vulvar or vaginal HPV-related lesions was 94% (95% CI,81%-99%). Conclusions. Among women positive for 1-3 HPV vaccine types before vaccination, the quadrivalent HPV vaccine protected against neoplasia caused by the remaining types. These results support vaccination of the general population without prescreening.OBJECTIVE We investigated changes in hematologic and biochemical parameters associated with human T lymphotropic virus type 1 (HTLV-1) infection, antibody titer, and provirus load. Additionally, on a subset of participants, we assessed the epidemiologic relationship of HTLV-1 with Strongyloides stercoralis. METHODS Among volunteer blood donors in Jamaica, HTLV-1 carriers (n=482) were frequency matched with HTLV-1 negative subjects (n=355) by age (+/-5 years), sex, and date of blood donation (+/-3 months). HTLV-1 antibody titer, provirus load, S. stercoralis IgG antibodies, complete blood cell count, blood chemistry, and urinalysis parameters were measured. RESULTS HTLV-1 carriers, compared with HTLV-1-negative individuals, had elevated levels of cleaved lymphocytes (24.5% vs. 16.4%), any lymphocyte abnormalities (atypical, cleaved, and reactive lymphocytes combined, 45.7% vs. 35.4%), and gamma-glutamyl transferase levels (21.2 vs. 19.6 IU/L), as well as lower eosinophil count (2.6% vs. 3.1%). Among carriers, HTLV-1 antibody titer (n=482) was inversely correlated with mean corpuscular volume (r=-0.10) and positively correlated with levels of total protein (r=0.16), phosphorus (r=0.12), and lactate dehydrogenase (r=0.24). HTLV-1-provirus load (n=326) was higher among carriers with cleaved lymphocytes and any lymphocyte abnormalities. Provirus load was inversely correlated with hemoglobin (r=-0.11), mean corpuscular volume (r=-0.15), neutrophil (r=-0.12), and eosinophil (r=-0.19) levels and was positively correlated with lactate dehydrogenase levels (r=0.12). Provirus load was significantly higher among male than female subjects. S. stercoralis antibodies were detected in 35 (12.1%) of 288 participants but were not associated with HTLV-1 status, antibody titer, or provirus load. CONCLUSIONS Markers of HTLV-1 infection (infection status, antibody titer, and provirus load) are associated with hematologic and biochemical alterations, such as lymphocyte abnormalities, anemia, decreased eosinophils, and elevated lactate dehydrogenase levels.

National Case-Control Study of Kaposi's Sarcoma and Pneumocystis carinii Pneumonia in Homosexual Men: Part 2, Laboratory Results

The Centers for Disease Control conducted a case-control study to investigate an outbreak of Kaposis sarcoma and Pneumocystis carinii pneumonia in homosexual men. The occurrence of these diseases was found to be associated with certain aspects of lifestyle, including a greater number of male sex partners per year, exposure to feces during sex, history of syphilis and non-B hepatitis, treatment for enteric parasites, and use of various illicit substances. Laboratory studies reflected both this lifestyle and the probable underlying cause of the Kaposis sarcoma and P. carinii pneumonia--cellular immune deficiency. Patients were found to have lymphopenia, specifically a deficiency of the T-helper subpopulation, resulting in a reversal of the T-helper to T-suppressor ratio. Levels of IgG and IgA were increased. When compared with controls, patients were also found to have significantly higher titers of antibody to Epstein-Barr virus and cytomegalovirus, a higher prevalence of antibody to hepatitis A virus and Treponema pallidum, a lower prevalence of antibody to varicella zoster virus, and a higher frequency of isolation of cytomegalovirus.

Babesiosis in Washington State: A New Species of Babesia?

Babesiosis is an intraerythrocytic protozoan infection, transmitted by ticks, and characterized by malaria-like symptoms and hemolytic anemia. The first reported zoonotic cases in Europe and the United States occurred in 1956 [1] and 1966 [2], respectively. In Europe, cases of this infection have generally been in splenectomized persons infected with the cattle parasites Babesia divergens and Babesia bovis [3, 4], which are thought to be maintained by Ixodes ricinus ticks. No national surveillance system for babesiosis exists in the United States, but hundreds of cases have been reported [4, 5]. Most have been attributed to infection with Babesia microti, a rodent parasite maintained by Ixodes dammini ticks, the primary vector of the agent of Lyme disease (Borrelia burgdorferi). Human babesiosis is endemic on various coastal islands in the northeastern United States, such as Nantucket Island and Marthas Vineyard, Block Island, Long Island, and Shelter Island, and in mainland Connecticut [6]. Cases acquired in Wisconsin have been reported as well [7, 8]. Asplenic, immunocompromised, and elderly persons infected with B. microti are at greatest risk for clinical illness [5, 7, 9-13], which may be severe, whereas other infected persons commonly are asymptomatic or only mildly symptomatic. Only three human cases of babesiosis acquired in the western United States have been reported previously, all of which occurred in splenectomized patients in California [2, 14, 15]; the infecting species was not definitively identified for any of these cases. In September 1991, the first recognized case of babesiosis acquired in Washington State was diagnosed. We present the clinical details of this case, which occurred in an apparently immunocompetent person, and provide evidence that it was not caused by B. microti. We also provide results of 1) serologic testing that was done in an attempt to identify the species of the patients Babesia isolate [referred to as WA1]; 2) experimental inoculations of various mammalian species to determine WA1s host specificity; 3) a comparison of the DNA hybridization patterns of WA1, B. microti, and B. gibsoni using a Babesia-specific, ribosomal-DNA (rDNA) probe [16]; 4) a serosurvey of the patients family members and neighbors for antibody to WA1; and 5) attempts to identify WA1s reservoir host and tick vector. Case Report A 41-year-old man from a rural forested area in south-central Washington State went to a local emergency room on 15 September 1991 because of a 1-week history of fever, rigors, anorexia, rhinorrhea, cough, and headache. He had previously been in good health, was not taking any medications, and had never had a blood transfusion. He had a dog, two cats, and two head of cattle and was exposed daily to tick habitats, but he did not recall any tick bites. He had not been outside the Washington-Oregon border region in many years and had never been in areas reported to be endemic for babesiosis or malaria. On evaluation, he had a few rales in his left-lung field and a platelet count of 48 109/L. He was treated for a presumed bronchopneumonia, with intravenous cefazolin to be followed with oral cefixime, and was sent home. He was hospitalized the next day (September 16) because of persistent fever, severe rigors, and dark-colored urine. He had a temperature of 39.5 C, tenderness in both upper quadrants of his abdomen without hepatosplenomegaly, a normal hematocrit (0.44) and leukocyte count, a platelet count of 46 109/L, 1+ occult blood on urine-dipstick analysis with no cells detected microscopically, a normal chest radiograph, and blood and urine culture results that were negative for bacteria. He was treated with cefazolin and gentamicin without improvement. On September 18, his temperature peaked at 40.4 C; his hematocrit was 0.36, his serum lactate dehydrogenase level was 21.34 kat/L (1280 U/L), and his total bilirubin level was 20.5 mol/L (1.2 mg/dL). Intraerythrocytic ring forms attributed to Plasmodium falciparum malaria were noted on his peripheral blood smear. He was treated with mefloquine and sent home at his request. He was rehospitalized the next day (September 19) with a temperature of 40 C, rigors, and vomiting. On re-examination of his blood smears from September 15 and 18, intraerythrocytic ring forms (in 1.2% and 3.0% of the erythrocytes) were noted as well as tetrad forms characteristic of Babesia (Figure 1). Therapy with oral quinine (650 mg, three times daily) and intravenous clindamycin (600 mg, four times daily) was begun on September 20, with symptomatic improvement by the next day. By September 23, he was afebrile, his hematocrit was 0.35, the parasitemia had decreased from 3.7% (September 20) to 0.4%, and his platelet count had increased to 143 109/L. On September 24, he was sent home on oral quinine and clindamycin (600 mg, three times daily) to complete a 10-day course of therapy. Figure 1. Photographs of Giemsa-stained peripheral blood smears from a patient who acquired babesiosis in Washington State. Left. Right. On September 30, he was evaluated because of a diffuse urticarial rash. His blood smear was normal, and he was treated with a 12-day tapering course of prednisone for a presumed hypersensitivity reaction. On November 3, when he felt feverish and had a headache, his temperature was 37.5 C, his hematocrit 0.34, and he had a detectable parasitemia of <1%. Urticaria recurred after a dose of quinine (650 mg). Although he appeared to be improving without further therapy for babesiosis, he was treated with intravenous clindamycin (1.2 grams, twice daily for 10 days). His hematocrit decreased to 0.28 on November 7; his anemia had resolved by December 12. Because of slowly resolving fatigue, he did not return to work until 6 January 1992. No parasites were detected on his blood smear in December 1991 or on smears in January, March, July, and September 1992, during which time he remained asymptomatic. Evaluation of his immunologic status with a Western-blot test for human immunodeficiency virus; a liver-spleen scan; quantitative immunoglobulins (including immunoglobulin-G subtypes); and serologic testing for antibody to tetanus toxoid, rubella virus, and streptolysin O, indicated normal results. Methods Serologic Studies Serum specimens from the patient were tested at the Centers for Disease Control and Prevention (CDC) in serial fourfold dilutions by indirect immunofluorescent antibody (IFA) testing [17] for antibody to B. microti and the patients isolate (WA1), which was propagated in hamsters inoculated with his blood (see below). A titer of at least 64 to B. microti was considered positive. Stored serum specimens from patients in the northeastern United States with B. microti-antibody titers ranging from 64 to greater than 4096 and blood smears with intraerythrocytic ring forms were assayed for IFA reactivity with WA1. In another laboratory (University of California at Davis [UCD]) with a different IFA protocol [18], serum from the patient was assayed in serial twofold dilutions for reactivity with various Babesia isolates maintained by passage in animals (Table 1). A titer of at least 320 to B. microti was considered positive. Fluorescein-labeled, affinity-purified antibody to human IgG (Kirkegaard & Perry, Gaithersburg, Maryland) was used as the secondary antibody. Blood smears from the patient were examined for B. bovis, Babesia equi, and Babesia bigemina antigens by direct immunofluorescence testing with monoclonal antibodies specific for these species [24-26]. Table 1. Indirect Immunofluorescent Antibody Reactivity of Serum from November 1991 from a Patient Who Acquired Babesiosis (Isolate WA1) in Washington State* Animal Inoculations Whole blood specimens from the patient were inoculated intraperitoneally (1-mL inocula) into at least two hamsters (Mesocricetus auratus) or jirds (Mongolian gerbils; Meriones unguiculatus). Giemsa-stained thin smears of blood from the inoculated animals were examined (at least 25 oil-immersion fields per slide) weekly for 6 to 8 weeks. Erythrocytes from hamsters infected with WA1 were washed in Pucks Saline G and were inoculated into a splenectomized 1-year-old female golden Labrador retriever (5.6 109 parasitized erythrocytes were administered intravenously and an equal number, subcutaneously) and into a hamster (9 106 parasitized erythrocytes, intraperitoneally). During the 34-day monitoring period, the dogs clinical status and hematocrit were checked daily for 20 days and then 3 times weekly, and thin smears were examined (>5000 erythrocytes/slide) daily through day 20 and then twice weekly. Pre-and postinoculation serum samples from the dog were assayed for IFA reactivity (UCD) with WA1, B. microti (GI [20] and P20 isolates), and B. gibsoni. Southern-Blot Analysis Babesia-infected erythrocytes (P1 pellets) were obtained as previously described [16]; erythrocytes infected with WA1, a human isolate of B. microti (2Bm) [16], and a canine isolate of B. gibsoni (6Bg) were used. Control mammalian leukocytes were separated from uninfected blood of a hamster and a dog by differential centrifugation (400 x g, 4 C, 20 min) on Ficoll-paque (Pharmacia LDB Biotechnology, Piscataway, New Jersey) gradients. After Babesia and leukocyte DNA samples were prepared [27], approximately 1 g of each DNA sample was digested with restriction endonucleases (HindIII or HaeIII; Boehringer Mannheim, Indianapolis, Indiana), as previously described [16]. DNA fragments were separated by electrophoresis in horizontal 0.8% (weight/volume) agarose gels in 45 mM Tris-borate and 1 mM ethylenediaminetetraacetic acid at 40 V for 16 to 18 hours. A Babesia-specific rDNA probe was hybridized to Southern blots of the restriction-endonuclease- digested DNAs; the probe had been produced by polymerase chain reaction amplification of sequences from B. microti DNA, with universal primers directed against highly conserved portions of the nuclear sma

Epidemiological investigation of Taenia solium taeniasis and cysticercosis in a rural village of Michoacan State, Mexico

We performed a survey for taeniasis and cysticercosis among persons living in a Mexican village where Taenia solium infection in pigs was known to be enzootic. A standardized questionnaire was administered in all 577 households to obtain medical histories and information on demographic and environmental factors and on risk factors associated with transmission of infection. Serum and/or stool specimens were obtained from 1005 volunteers and examined for cysticercosis antibodies and intestinal parasites. Faecal examination of 828 participants revealed infection by Taenia sp. in 2 (0.2%). Three additional cases of taeniasis were detected in individuals who evacuated proglottids after treatment with praziquantel. Of 1005 human serum specimens, 49 (4.9%) were positive in the cysticercosis immunoblot assay. Seropositivity increased with age and reached a peak in subjects aged 46-55 years (P < 0.05). A history of seizures was significantly associated with seropositivity (P < 0.05); approximately 25% of persons with such histories were seropositive. Histories of headache, dizziness, trembling, blurred vision, and vomiting were also significantly associated with positive immunoblot assays. This study has demonstrated previously undiagnosed morbidity associated with T. solium neurocysticercosis and identified community behavioural and environmental practices that must be modified to prevent continued transmission of cysticercosis and taeniasis.

Toxoplasma gondii Infection in the United States, 1999-2000

Infection with Toxoplasma gondii can lead to congenital and acquired disease, resulting in loss of vision and neurologic illness. We tested sera collected in the National Health and Examination Survey (NHANES) from 1999–2000 for T. gondii–specific immunoglobulin G antibodies and compared these results with results from sera obtained in the NHANES III survey (1988–1994). NHANES collects data on a nationally representative sample of the U.S. civilian population. Of 4,234 persons 12–49 years of age in NHANES 1999–2000, 15.8% (age-adjusted, 95% confidence limits [CL] 13.5, 18.1) were antibody positive; among women (n=2,221) 14.9% (age-adjusted, 95% CL 12.5, 17.4) were antibody positive. T. gondii antibody prevalence was higher among non-Hispanic black persons than among non-Hispanic white persons (age-adjusted prevalence 19.2% vs. 12.1%, p=0.003) and increased with age. No statistically significant differences were found between T. gondii antibody prevalence in NHANES 1999–2000, and NHANES III. T. gondii antibody prevalence has remained stable over the past 10 years in the United States.

Schistosomiasis in Lake Malawi

BACKGROUND In 1992 two US Peace Corps volunteers (PCVs) developed central nervous system schistosomiasis due to infection with Schistosoma haematobium following recreational water exposure at Cape Maclear on Lake Malawi, an African lake considered by many to be free of schistosomiasis. To determine the transmission potential and risk for aquiring schistosomiasis in Lake Malawi, a cross-sectional survey of resident expatriates and visitors to Malawi was done during March and April, 1993. METHODS A volunteer cohort of expatriates and visitors representing a cross-section of Malawis foregn population answered detailed questions about freshwater contact and provided blood specimens to determine the seroprevalence of S haematobium and S mansoni by ELISA and immunoblot analyses. A survey for vector snails was conducted along Lake Malawis southwestern shore. FINDINGS The study population of 955 included 305 US citizens and 650 non-US foreign nationals. 303 of the study population had serological evidence of current or past schistosome infection. Seroprevalence was 32% (141/440) among expatriates whose freshwater exposure was limited to Lake Malawi; S haematobium antibodies were found in 135 of 141 (96%) seropositive specimens. Risk of seropositivity increased with the number of freshwater exposures at Lake Malawi resorts. Although many resort areas in the southwestern lake region posed a significant risk, Cape Maclear was the location most strongly associated with seropositivity (OR 2.9, 95% Cl 1.6-5.1). Schistosome-infected Bulinus globosus, the snail vector of S haematobium in Malawi, were found at Cape Maclear and other locations along the lakeshore. INTERPRETATION S haematobium infection is highly prevalent among expatriates and tourists in Malawi. Recreational water contact at popular resorts on Lake Malawi is the most likely source of infection. Transmission of schistosomiasis is occurring in Lake Malawi, a previously under-recognised site of transmission.

Transfusion-Transmitted Babesiosis in Washington State: First Reported Case Caused by a WA1-Type Parasite

Most cases of babesiosis reported in the United States have been tickborne and caused by Babesia microti, the etiologic agent of all previously described transfusion-transmitted cases. A 76-year-old man with the first recognized case of transfusion-transmitted infection with the recently identified WA1-type Babesia parasite is described. The subject received multiple blood transfusions in 1994. Indirect immunofluorescent antibody testing of serum from 57 blood donors implicated a 34-year-old man (WA1 titer, 1:65,536) whose donation had been used for packed red cells. Isolates of the organisms that infected the recipient and the donor, both of whom were spleen-intact residents of Washington State, were obtained by hamster inoculation. The DNA sequence of a 536-bp region of the nuclear small subunit-rRNA gene of both isolates was identical to that of WA1 (isolated in 1991 from the index WA1 case-patient). Effective measures for preventing transmission of babesiosis by blood transfusion are needed.

Comparison of two assays (EIA and EITB) and two samples (saliva and serum) for the diagnosis of neurocysticercosis.

The enzyme immunoassay (EIA), standardized with a crude extract, and the enzyme-linked immunoelectrotransfer blot assay (ETIB) with glycoprotein antigens, were compared by using saliva and serum in the search for specific antibodies against Taenia solium larvae, for the diagnosis of neurocysticercosis. Saliva was slightly more sensitive in EIA (82.1%) than serum (74.1%). In EITB serum was far more sensitive (100%) than saliva (70.4%). The use of EITB with serum is thus an excellent choice for diagnosis of clinical cases of neurocysticercosis, while EIA using saliva represents a useful combination for diagnosis and, especially, epidemiology, because saliva is easily obtained by a painless and non-invasive procedure and the technique is simpler to perform. Furthermore, cross-reactivity of EIA with Echinococcus does not interfere in countries like Mexico where human hydatid disease is not present.