Transfusion-associated babesiosis in the United States: a description of cases.

BACKGROUND: Babesiosis is a potentially life-threatening disease caused by intraerythrocytic parasites, which usually are tickborne but also are transmissible by transfusion. Tickborne transmission of Babesia microti mainly occurs in 7 states in the Northeast and the upper Midwest of the United States. No Babesia test for screening blood donors has been licensed. OBJECTIVE: To ascertain and summarize data on U.S. transfusion-associated Babesia cases identified since the first described case in 1979. DESIGN: Case series. SETTING: United States. PATIENTS: Case patients were transfused during 1979-2009 and had posttransfusion Babesia infection diagnosed by 2010, without reported evidence that another transmission route was more likely than transfusion. Implicated donors had laboratory evidence of infection. Potential cases were excluded if all pertinent donors tested negative. MEASUREMENTS: Distributions of ascertained cases according to Babesia species and period and state of transfusion. RESULTS: 159 transfusion-associated B. microti cases were included; donors were implicated for 136 (86%). The case patients' median age was 65 years (range, <1 to 94 years). Most cases were associated with red blood cell components; 4 were linked to whole blood-derived platelets. Cases occurred in all 4 seasons and in 22 (of 31) years, but 77% (122 cases) occurred during 2000-2009. Cases occurred in 19 states, but 87% (138 cases) were in the 7 main B. microti-endemic states. In addition, 3 B. duncani cases were documented in western states. LIMITATION: The extent to which cases were not diagnosed, investigated, reported, or ascertained is unknown. CONCLUSION: Donor-screening strategies that mitigate the risk for transfusion transmission are needed. Babesiosis should be included in the differential diagnosis of unexplained posttransfusion hemolytic anemia or fever, regardless of the season or U.S. region. PRIMARY FUNDING SOURCE: None.

Toxoplasma gondii and Toxocara spp. co-infection.

Toxoplasma gondii and Toxocara spp. infections can cause systemic and ocular disease. To estimate the prevalence of infection with these organisms, we tested serum samples from persons > or = 12 years of age obtained in the Third National Health and Nutrition Examination Survey (1988-1994). Among those tested for both T. gondii and Toxocara spp. (n = 16,646), the age-adjusted T. gondii antibody prevalence was 23.6% (95% confidence limit [CL] = 22.1-25.1%) and the Toxocara spp. antibody prevalence was 14.0% (95% CL = 12.7-15.4%). Multivariate analysis controlling demographic and risk factors showed that persons infected with Toxocara spp. were more likely to be infected with T. gondii (odds ratio [OR] = 1.93, 95% CL = 1.61-2.31), and similarly, persons infected with T. gondii were more likely to be infected with Toxocara spp. (OR = 1.91, 95% CL = 1.59-2.28). Infection with T. gondii and Toxocara spp. are common and can be prevented by many similar interventions.

High prevalence and presumptive treatment of schistosomiasis and strongyloidiasis among African refugees.

BACKGROUND: Schistosomiasis and strongyloidiasis cause substantial morbidity and mortality among hundreds of millions of infected persons worldwide. In the United States, these infections are most commonly found among international travelers, immigrants, and refugees from areas of endemicity. Refugees resettled to the United States since 2000 include >3800 "Lost Boys and Girls" of Sudan and 8000 Somali Bantu. Many Lost Boys and Girls of Sudan reported chronic abdominal pain only since arrival, and some received diagnoses of schistosomiasis or strongyloidiasis. We assessed seroprevalence of these infections among these refugees and hypothesized an association between infection and abdominal pain. METHODS: We offered a survey assessing chronic abdominal pain and serologic testing for schistosomiasis and strongyloidiasis to all 800 attendees of a Lost Boys and Girls of Sudan reunion in the United States. Serologic testing was performed on preimmigration specimens obtained from 100 United States-bound Somali Bantu refugees. RESULTS: Of the 462 Sudanese refugees (58%) tested, 44% and 46% were seropositive for schistosomiasis (primarily due to Schistosoma mansoni) and strongyloidiasis, respectively; 24% of those who tested positive for schistosomiasis had S. mansoni antigenemia. Forty-six percent reported chronic abdominal pain, which was not associated with either infection. Among 100 Somali Bantu, 73% and 23% tested seropositive for schistosomiasis (primarily due to Schistosoma haematobium) and strongyloidiasis, respectively. CONCLUSIONS: The high seroprevalence of schistosomiasis and strongyloidiasis among Sudanese Lost Boys and Girls and Somali Bantu refugees supports presumptive treatment for these refugees. Current refugee resettlement policies inadequately address these diseases; our data support consideration of predeparture presumptive therapy for all refugees from areas of endemicity.

Hematologic and biochemical changes associated with human T lymphotropic virus type 1 infection in Jamaica: a report from the population-based blood donors study.

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.

Toxoplasma gondii infection in the United States, 1999 2004, decline from the prior decade.

Toxoplasma gondii can cause congenital, neurologic, ocular, and mild or asymptomatic infection. To determine the U.S. prevalence of T. gondii infection, we tested sera collected from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 for T. gondii immunoglobulin G antibodies in persons 6-49 years old and contrasted the results to those comparable in NHANES III (1988-1994) (ages 12-49 years). Of the 17,672 persons examined in NHANES 1999-2004, 15,960 (90%) were tested. The age-adjusted T. gondii seroprevalence among persons 6-49 years old was 10.8% (95% confidence limits [CL] 9.6%, 11.9%), and among women 15-44 years old, 11.0% (95% CL 9.5%, 12.4%). T. gondii seroprevalence declined from 14.1% to 9.0% (P < 0.001) from NHANES III to NHANES 1999-2004 among U.S.-born persons ages 12-49 years. Although T. gondii infects many persons in the U.S., the prevalence has declined in the past decade.

Persistent and untreated tropical infectious diseases among Sudanese refugees in the United States.

A comprehensive medical evaluation to identify persistent and untreated tropical infections among members of the Sudanese group "Lost Boys of Sudan" living in Atlanta, GA, was initiated. Medical examinations and laboratory testing including blood cell counts, liver function tests, stool studies for parasites, hepatitis B serologies, and serologic testing for Schistosoma spp., Strongyloides, and filariae were performed. Preliminary results showed a high prevalence of untreated active schistosomiasis and strongyloidiasis infections in this group, 5 years after their resettlement in the United States. In addition, we found that many of them were infected with onchocerciasis and hepatitis B. We suggest that based on these preliminary results, pre-departure presumptive treatment and/or testing algorithms need to address some of these persistent tropical infections.

Toxoplasma gondii infection in rural Guatemalan children.

To determine the prevalence and risk factors for Toxoplasma gondii infection in Guatemalan children, in 1999 and 2003 we surveyed caretakers and serologically tested children in the San Juan Sacatepequez area using Platelia Toxo IgG TMB enzyme immunoassay kits. In 1999, of 532 children six months to two years old, 66 (12.4%) were antibody positive. In 2003, in 500 children 3-10 years old antibody prevalence increased from 24% to 43% at age five years then leveled off. By multivariate analysis, drinking well water (relative risk [RR] = 1.78, 95% confidence limit [CL] = 1.00, 3.17, P = 0.05) and not cleaning up cat feces (RR = 2.06, 95% CL = 1.00, 4.28, P = 0.05) increased the risk of T. gondii seropositivity. Most T. gondii infections in children from these villages occurred by age five, but half were still not infected by adolescence. Therefore, it is important to educate girls entering child-bearing age about the risks of acute T. gondii infection and the local risk factors for infection.

Schistosome infection among river rafters on Omo River, Ethiopia.

BACKGROUND: Adventure trips to Africa have become more frequent, and rafting on some of the great rivers has become almost commonplace. We describe three rafting trips on the Omo River in Ethiopia, after which most of the participants were diagnosed with schistosomiasis. METHODS: After index cases from the three groups came to medical attention, active surveillance detected outbreaks of illness in a group of American travelers (n = 18 ) in 1993 and in two groups of Israeli travelers in 1997 (n = 26). RESULTS: Of 44 travelers, 37 were screened and 28 (76%) were infected, all with Schistosoma mansoni. Among the infected patients, 16 of 28 (57%) were symptomatic, the most frequent manifestation being fever, which occurred in 14 of 25 (56%); cough occurred in 6 of 18 (33%). Diagnosis was based on FAST-enzyme-linked immunosorbent assay, with confirmation by immunoblot. Other rafting trips on the Omo River sponsored by the same tour companies did not result in symptomatic infection. Investigation of the rafting itineraries suggested the route may have been altered from the usual for these three groups, exposing them to a part of the river that is wider, slower moving, and more densely populated. CONCLUSIONS: Schistosomiasis should be considered in febrile patients following rafting trips in schistosome-endemic areas. As asymptomatic schistosomiasis in travelers is also common (43% in this series), all travelers exposed to freshwater in endemic areas should be encouraged to undergo serologic screening.

Evaluation of reported malaria chemoprophylactic failure among travelers in a US University Exchange Program, 2002.

BACKGROUND: Travelers to malarious areas are at risk of acquiring malaria; however, with chemoprophylaxis and prompt, effective therapy, serious complications of infection are generally preventable. In June 2002, we investigated a report of a cluster of malaria cases among US university staff and students who visited Ghana and were reportedly adherent to appropriate malaria chemoprophylaxis. METHODS: We administered a questionnaire to all participants and collected blood specimens for malaria serological examinations from those reporting malaria infection diagnosed by blood smear in Ghana. RESULTS: Of the 33 participants, 25 completed the questionnaire. Twenty-four took a Centers for Disease Control and Prevention-recommended chemoprophylactic drug; 14 (56%) of 25 reported complete adherence to therapy. Twenty (80%) of 25 subjects reported symptoms consistent with possible malaria. Six of these persons reported a microscopic diagnosis of malaria and were treated in Ghana. Serological examination for malaria was performed using blood samples obtained from 5 of these participants; the results for all were negative, suggesting that incorrect diagnoses of malaria were made. CONCLUSIONS: Misdiagnosis of malaria made while a person is abroad may not only lead to erroneous reports of drug resistance, but it could also result in unnecessary administration of antimalarial treatment. Health care providers and public health authorities must critically evaluate reports of chemoprophylactic failures and disseminate accurate information to travelers.

Survey of clinical laboratory practices for parasitic diseases.

To gain knowledge about laboratory testing practices for parasitic diseases, in 2000 we surveyed 562 laboratories in 9 US states, and 455 (81%) responded. Most laboratories (59%) indicated that they send specimens off site for parasite screening, and most laboratories (89%) did not routinely test fecal specimens for Cryptosporidium species, Cyclospora cayetanensis, or microsporidia, unless testing for these organisms was specifically requested by a physician. Only 39 laboratories offered serological testing for Toxoplasma gondii, and most (78%) that had their results confirmed did so at national commercial laboratories rather than a Toxoplasma reference laboratory. Because most clinical laboratories do not routinely test fecal specimens for Cryptosporidium species, C. cayetanensis, or microsporidia, physicians must request specific testing for these organisms when they are clinically suspected; because of this lack of routine testing, it is difficult to estimate the true burden of disease due to these organisms.

Serology and eosinophil count in the diagnosis and management of strongyloidiasis in a non-endemic area.

Strongyloidiasis is a chronic infection that may result in significant morbidity; however, diagnosis and management remain problematic. The objective of this study was to 1) evaluate the demographic, clinical, and laboratory features of 76 consecutive individuals who had Strongyloides stercoralis larvae identified in their fecal specimens; 2) determine the sensitivity of the Centers for Disease Control and Prevention (CDC) enzyme immunoassay (EIA) for detecting antibodies to Strongyloides in those with confirmed infection; and 3) assess the serologic responses and changes in eosinophil counts following treatment. Most (96%) cases occurred in immigrants, but some patients had immigrated as long as 40 years earlier. The CDC Strongyloides EIA had a sensitivity of 94.6% (95% confidence interval = 92.0-97.2%) in this patient population with proven infection. Serologic and eosinophil counts decreased after therapy, suggesting that they may be useful markers of treatment success.

Outbreak of amebiasis in Tbilisi, Republic of Georgia, 1998.

In 1998, we investigated a suspected outbreak of amebic liver abscesses caused by Entamoeba histolytica in the Republic of Georgia, using a case-control study. A questionnaire was administered and blood samples were obtained from cases and controls for serologic diagnosis. Medical records showed that E. histolytica infections were rarely diagnosed before 1998. However, from July through September 1998, 177 cases of suspected amebiasis were identified. Of 52 persons who had diagnosed liver abscesses, 37 (71%) were confirmed serologically to have antibodies against E. histolytica, compared with 11 of 53 persons (20.8%) diagnosed with intestinal amebiasis. In addition, 9-14% of asymptomatic controls were seropositive. Logistic regression identified the fact that interruptions in the water supply, decreases in water pressure, and increased water consumption were significantly associated with infection. The data support the hypothesis that drinking water was the source of infection, either because of inadequate municipal water treatment or contamination of municipal water in the distribution system.

Cysticercosis: imported and autochthonous infections in Kuwait.

Intracerebral and non-central nervous system (non-CNS) cysticercosis caused by the larval pork tapeworm Taenia solium was diagnosed in patients in an Islamic state. The mode of transmission and challenges in diagnosis are highlighted. Sixteen patients with neurocysticercosis and six with non-CNS lesions were diagnosed by imaging studies (computerized tomography [CT]/magnetic resonance imaging [MRI]) and serology (ELISA and/or enzyme-linked immunoelectrotransfer blot assay [EITB]). Four of 55 family members, including servants, tested for antibodies were positive by the EITB and ELISA. Only one of these sera tested for antibodies to adult T. solium was positive: that of the cook, the probable source of the infection. We postulate a similar mode of transmission in the other Kuwaitis. Evaluation of several commercially available ELISA kits showed they were of poor specificity. Even in countries where pork consumption is proscribed by religious laws, physicians should include cysticercosis in their differential diagnosis in patients with neurological symptoms or non-CNS lesions, especially in non-endemic countries with a large expatriate population such as Kuwait. In children particularly, and in this region, suspected tuberculous lesions on CT must be investigated to rule out cysticerci by a more diligent use of the sensitive and specific EITB assay. Failure to understand the local epidemiology leads to empirical, inappropriate and prolonged therapy for chronic disease.

Multiplex assay detection of immunoglobulin G antibodies that recognize Babesia microti antigens.

Human babesiosis, a blood-borne infection caused by several species of Babesia, including B. microti, is an emerging disease that is endemic in the Northeast, upper Midwest, and Pacific Northwest regions of the United States. Risk factors for babesiosis include exposure to the infected tick vector and blood transfusions from infected donors. In this work, we cloned and expressed two of the immunodominant antigens from B. microti and used them in a multiplex bead format assay (MBA) to detect parasite-specific IgG responses in human sera. The MBA using recombinant B. microti secreted antigen 1 (BmSA1) protein was more specific (100%) and slightly more sensitive (98.7%) than the assay using a truncated recombinant BMN1-17 construct (97.6% and 97.4%, respectively). Although some antibody reactivity was observed among sera from confirmed-malaria patients, only one Plasmodium falciparum sample was simultaneously positive for IgG antibodies to both antigens. Neither antigen reacted with sera from babesiosis patients who were infected with Babesia species other than B. microti. Both positive and negative MBA results were reproducible between assays and between instruments. Additional studies of these recombinant antigens and of the multiplex bead assay using blood samples from clinically defined babesiosis patients and from blood donors are needed to more clearly define their usefulness as a blood screening assay.

Congenital toxoplasmosis.

Approximately 85 percent of women of childbearing age in the United States are susceptible to acute infection with the protozoan parasite Toxoplasma gondii. Transmission of T. gondii to the fetus can result in serious health problems, including mental retardation, seizures, blindness, and death. Some health problems may not become apparent until the second or third decade of life. An estimated 400 to 4,000 cases of congenital toxoplasmosis occur in the United States each year. Serologic tests are used to diagnose acute T. gondii infection in pregnant women. Because false-positive tests occur frequently, serologic diagnosis must be confirmed at a Toxoplasma reference laboratory before treatment with potentially toxic drugs is considered. In many instances, congenital toxoplasmosis can be prevented by educating pregnant women and other women of childbearing age about not ingesting raw or undercooked meat, using measures to avoid cross-contamination of other foods with raw or undercooked meat, and protecting themselves against exposure to cat litter or contaminated soil.

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.

A novel recombinant antigen for immunodiagnosis of human cystic echinococcosis.

A pool of serum samples from mice infected with oncospheres (eggs) of Echinococcus granulosus was used to screen a cDNA library constructed with RNA extracted from protoscolex larvae from sheep hydatid cysts. One immunoreactive clone, designated EpC1, was shown to encode a protein of 76 residues. The complementary DNA (cDNA) fragment was subcloned into an expression vector, pET-41b(+), and the resulting recombinant EpC1 glutathione S-transferase (GST) fusion protein (rEpC1-GST) was expressed in Escherichia coli and was affinity purified against the GST tag. Immunoglobulin G was the dominant antibody isotypes generated against rEpC1-GST. A total of 896 human serum samples were used to evaluate the diagnostic sensitivity and specificity of the fusion protein by immunoglobulin G immunoblotting; 324 serum samples from patients with cystic echinococcosis (CE), 172 from patients with neurocysticercosis, 89 from patients with alveolar echinococcosis, and 241 from patients with other infections or clinical presentations, as well as 70 from confirmed-negative control subjects, yielded an overall sensitivity of 92.2% and an overall specificity of 95.6%. The combined levels of sensitivity and specificity achieved with the rEpC1-GST fusion protein for diagnosis of CE are unprecedented, taking into account the large panel of serum samples that were tested.

Transmission of Babesia microti in Minnesota through four blood donations from the same donor over a 6-month period.

BACKGROUND: Babesiosis is a tick-borne zoonosis caused by intraerythrocytic protozoa. More than 40 US cases of Babesia microti infection acquired by blood transfusion have been reported. This report describes the identification of a transfusion-associated case of babesiosis and the subsequent identification of the infected blood donor and three other infected recipients of cellular blood components from three other donations by this donor. STUDY DESIGN AND METHODS: Serum specimens from the donors of blood that had been made into cellular components received by the index recipient and from other recipients of such components from the implicated donor were tested by the indirect fluorescent antibody (IFA) assay for antibodies to B. microti. Whole blood from IFA-positive persons was tested by PCR for B. microti DNA. RESULTS: IFA testing of serum from 31 of 36 donors implicated a 45-year-old man (titer, 1 in 256), whose donation had been used for RBCs. He likely became infected when bitten by ticks while camping in Minnesota in June 1999 and had donated blood four times thereafter. As demonstrated by PCR, he remained parasitemic for at least 10 months. Of the five other surviving recipients of cellular blood components from the implicated donor, three recipients (one for each of the three other donations) had become infected through either RBC or platelet transfusions. CONCLUSIONS: Babesiosis should be included in the differential diagnosis of posttransfusion febrile illness, and effective means for preventing transmission by blood transfusion are needed.