Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 40 Records) |
Query Trace: Wilkins PP[original query] |
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Development of a Multiplex Bead Assay To Detect Immunoglobulin G Antibodies to Babesia duncani in Human Serum.
Wang Y , Aderohunmu T , Bishop H , McAuliffe I , Rivera HN , Smith D , Wilkins PP , Bowden KE , Reed MS , Svoboda P , Stuchlik O , Pohl J , Wiegand RE , Handali S . J Clin Microbiol 2021 59 (11) Jcm0045821 Babesia duncani is the causative agent of babesiosis in the western United States. The indirect fluorescent antibody (IFA) assay is the diagnostic test of choice for detection of B. duncani specific antibodies. However, this test requires parasitized red blood cells harvested from infected hamsters and test results are often difficult to interpret. To simplify serological testing for B. duncani, a proteomics approach was employed to identify candidate immunodiagnostic antigens. Several proteins were identified by electrospray ionization (ESI) mass spectrometric analysis and four recombinant protein constructs were expressed and used in a multiplex bead assay (MBA) to detect B. duncani-specific antibodies. Two antigens, AAY83295.1 and AAY83296.1, performed well with high sensitivities and specificities. AAY83295.1 had a higher sensitivity (100%) but lower specificity (89%) in comparison to AAY83296.1, which had a sensitivity of 90% and a specificity of 96%. Combining these two antigens did not improve the performance of the assay. This MBA could be useful for diagnosis, serosurveillance, and blood donor screening for B. duncani infection. |
Taenia solium cysticercosis and taeniasis in urban settings: Epidemiological evidence from a health-center based study among people with epilepsy in Dar es Salaam, Tanzania
Schmidt V , O'Hara MC , Ngowi B , Herbinger KH , Noh J , Wilkins PP , Richter V , Kositz C , Matuja W , Winkler AS . PLoS Negl Trop Dis 2019 13 (12) e0007751 In Africa, urbanization is happening faster than ever before which results in new implications for transmission of infectious diseases. For the zoonotic parasite Taenia solium, a major cause of acquired epilepsy in endemic countries, the prevalence in urban settings is unknown. The present study investigated epidemiological, neurological, and radiological characteristics of T. solium cysticercosis and taeniasis (TSCT) in people with epilepsy (PWE) living in Dar es Salaam, Tanzania, one of the fastest growing cities worldwide. A total of 302 PWE were recruited from six health centers in the Kinondoni district of Dar es Salaam. Serological testing for T. solium cysticercosis-antigen (Ag) and -antibodies (Abs) and for T. solium taeniasis-Abs was performed in all PWE. In addition, clinical and radiological examinations that included cranial computed tomography (CT) were performed. With questionnaires, demographic data from study populations were collected, and factors associated with TSCT were assessed. Follow-up examinations were conducted in PWE with TSCT. T. solium cysticercosis-Ag was detected in three (0.99%; 95% CI: 0-2.11%), -Abs in eight (2.65%; 95% CI: 0.84-4.46%), and taeniasis-Abs in five (1.66%; 95% CI: 0.22-3.09%) of 302 PWE. Six PWE (1.99%; 95% CI: 0.41-3.56%) were diagnosed with neurocysticercosis (NCC). This study demonstrates the presence of TSCT in Dar es Salaam, however, NCC was only associated with a few cases of epilepsy. The small fraction of PWE with cysticercosis- and taeniasis-Abs may suggest that active transmission of T. solium plays only a minor role in Dar es Salaam. A sufficiently powered risk analysis was hampered by the small number of PWE with TSCT; therefore, further studies are required to determine the exact routes of infection and risk behavior of affected individuals. |
Distribution of Taenia solium diagnostic glycoproteins in the different developmental stages of the parasite
Cruz-Rivera M , Torres J , Carrillo-Farga J , Wilkins PP , Flisser A , Mendlovic F . J Parasitol 2019 105 (4) 642-650 Taenia solium is a helminth parasite that causes 2 diseases in humans: cysticercosis and taeniasis. The establishment of T. solium metacestodes in the central nervous system causes neurocysticercosis, while development of the adult tapeworm in the small intestine causes taeniasis. Serological diagnosis of neurocysticercosis is performed by Western blot with an enriched fraction of glycoproteins that has been extensively used for clinical diagnosis and epidemiological surveys. The lectin-bound fraction that is used for this assay contains 7 antigenic glycoproteins. These antigenic proteins are considered to be highly specific for cysticercosis when tested with heterologous parasitic diseases. However, recent studies show that people with taeniasis have cross-reactive antibodies against the neurocysticercosis diagnostic glycoproteins and vice versa. Nevertheless, it is not known if these diagnostic proteins are expressed in the adult stage of the parasite. In this paper, we describe the location of 3 of these glycoproteins in T. solium adults and cysticerci using polyclonal antibodies raised against a synthetic peptide based on the amino acid sequence of TS14, a recombinant protein T24H, and the native GP50. The glycoproteins' distribution was different in invaginated and evaginated cysticerci as well as in adult tapeworms. Specifically, the 3 glycoproteins studied were differentially expressed during embryogenesis. Our findings indicate that expression of the diagnostic glycoproteins is developmentally regulated; this is noteworthy since these glycoproteins are considered specific for the diagnosis of neurocysticercosis but nevertheless are present in different structures throughout the development of T. solium. Here we describe the glycoprotein expression and localization, which can be important in understanding their biological functions. In addition, our results help clarify the cross-reaction observed between people with neurocysticercosis and taeniasis to TS14, T24H, and GP50, which are used as diagnostic antigens for neurocysticercosis. |
Human seroprevalence to 11 zoonotic pathogens in the U.S. Arctic, Alaska
Miernyk KM , Bruden D , Parkinson AJ , Hurlburt D , Klejka J , Berner J , Stoddard RA , Handali S , Wilkins PP , Kersh GJ , Fitzpatrick K , Drebot MA , Priest JW , Pappert R , Petersen JM , Teshale E , Hennessy TW , Bruce MG . Vector Borne Zoonotic Dis 2019 19 (8) 563-575 BACKGROUND: Due to their close relationship with the environment, Alaskans are at risk for zoonotic pathogen infection. One way to assess a population's disease burden is to determine the seroprevalence of pathogens of interest. The objective of this study was to determine the seroprevalence of 11 zoonotic pathogens in people living in Alaska. METHODS: In a 2007 avian influenza exposure study, we recruited persons with varying wild bird exposures. Using sera from this study, we tested for antibodies to Cryptosporidium spp., Echinococcus spp., Giardia intestinalis, Toxoplasma gondii, Trichinella spp., Brucella spp., Coxiella burnetii, Francisella tularensis, California serogroup bunyaviruses, and hepatitis E virus (HEV). RESULTS: Eight hundred eighty-seven persons had sera tested, including 454 subsistence bird hunters and family members, 160 sport bird hunters, 77 avian wildlife biologists, and 196 persons with no wild bird exposure. A subset (n = 481) of sera was tested for California serogroup bunyaviruses. We detected antibodies to 10/11 pathogens. Seropositivity to Cryptosporidium spp. (29%), California serotype bunyaviruses (27%), and G. intestinalis (19%) was the most common; 63% (301/481) of sera had antibodies to at least one pathogen. Using a multivariable logistic regression model, Cryptosporidium spp. seropositivity was higher in females (35.7% vs. 25.0%; p = 0.01) and G. intestinalis seropositivity was higher in males (21.8% vs. 15.5%; p = 0.02). Alaska Native persons were more likely than non-Native persons to be seropositive to C. burnetii (11.7% vs. 3.8%; p = 0.005) and less likely to be seropositive to HEV (0.4% vs. 4.1%; p = 0.01). Seropositivity to Cryptosporidium spp., C. burnetii, HEV, and Echinococcus granulosus was associated with increasing age (p </= 0.01 for all) as was seropositivity to >/=1 pathogen (p < 0.0001). CONCLUSION: Seropositivity to zoonotic pathogens is common among Alaskans with the highest to Cryptosporidium spp., California serogroup bunyaviruses, and G. intestinalis. This study provides a baseline for use in assessing seroprevalence changes over time. |
Seroprevalence of Baylisascaris procyonis Infection among Humans, Santa Barbara County, California, USA, 2014-2016
Weinstein SB , Lake CM , Chastain HM , Fisk D , Handali S , Kahn PL , Montgomery SP , Wilkins PP , Kuris AM , Lafferty KD . Emerg Infect Dis 2017 23 (8) 1397-1399 Baylisascaris procyonis (raccoon roundworm) infection is common in raccoons and can cause devastating pathology in other animals, including humans. Limited information is available on the frequency of asymptomatic human infection. We tested 150 adults from California, USA, for B. procyonis antibodies; 11 were seropositive, suggesting that subclinical infection does occur. |
Identifying wildlife reservoirs of neglected taeniid tapeworms: Non-invasive diagnosis of endemic Taenia serialis infection in a wild primate population
Schneider-Crease I , Griffin RH , Gomery MA , Dorny P , Noh JC , Handali S , Chastain HM , Wilkins PP , Nunn CL , Snyder-Mackler N , Beehner JC , Bergman TJ . PLoS Negl Trop Dis 2017 11 (7) e0005709 Despite the global distribution and public health consequences of Taenia tapeworms, the life cycles of taeniids infecting wildlife hosts remain largely undescribed. The larval stage of Taenia serialis commonly parasitizes rodents and lagomorphs, but has been reported in a wide range of hosts that includes geladas (Theropithecus gelada), primates endemic to Ethiopia. Geladas exhibit protuberant larval cysts indicative of advanced T. serialis infection that are associated with high mortality. However, non-protuberant larvae can develop in deep tissue or the abdominal cavity, leading to underestimates of prevalence based solely on observable cysts. We adapted a non-invasive monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) to detect circulating Taenia spp. antigen in dried gelada urine. Analysis revealed that this assay was highly accurate in detecting Taenia antigen, with 98.4% specificity, 98.5% sensitivity, and an area under the curve of 0.99. We used this assay to investigate the prevalence of T. serialis infection in a wild gelada population, finding that infection is substantially more widespread than the occurrence of visible T. serialis cysts (16.4% tested positive at least once, while only 6% of the same population exhibited cysts). We examined whether age or sex predicted T. serialis infection as indicated by external cysts and antigen presence. Contrary to the female-bias observed in many Taenia-host systems, we found no significant sex bias in either cyst presence or antigen presence. Age, on the other hand, predicted cyst presence (older individuals were more likely to show cysts) but not antigen presence. We interpret this finding to indicate that T. serialis may infect individuals early in life but only result in visible disease later in life. This is the first application of an antigen ELISA to the study of larval Taenia infection in wildlife, opening the doors to the identification and description of infection dynamics in reservoir populations. |
Association between Taenia solium infection and HIV/AIDS in northern Tanzania: A matched cross sectional-study
Schmidt V , Kositz C , Herbinger KH , Carabin H , Ngowi B , Naman E , Wilkins PP , Noh J , Matuja W , Winkler AS . Infect Dis Poverty 2016 5 (1) 111 BACKGROUND: The frequency of Taenia solium, a zoonotic helminth, is increasing in many countries of sub-Saharan Africa, where the prevalence of the human immunodeficiency virus (HIV) is also high. However, little is known about how these two infections interact. The aim of this study was to compare the proportion of HIV positive (+) and negative (-) individuals who are infected with Taenia solium (TSOL) and who present with clinical and neurological manifestations of cysticercosis (CC). METHODS: In northern Tanzania, 170 HIV+ individuals and 170 HIV- controls matched for gender, age and village of origin were recruited. HIV staging and serological tests for TSOL antibodies (Ab) and antigen (Ag) were performed. Neurocysticercosis (NCC) was determined by computed tomography (CT) using standard diagnostic criteria. Neurological manifestations were confirmed by a standard neurological examination. In addition, demographic, clinical and neuroimaging data were collected. Further, CD4+ cell counts as well as information on highly active antiretroviral treatment (HAART) were noted. RESULTS: No significant differences between HIV+ and HIV- individuals regarding the sero-prevalence of taeniosis-Ab (0.6% vs 1.2%), CC-Ab (2.4% vs 2.4%) and CC-Ag (0.6% vs 0.0%) were detected. A total of six NCC cases (3 HIV+ and 3 HIV-) were detected in the group of matched participants. Two individuals (1 HIV+ and 1 HIV-) presented with headaches as the main symptom for NCC, and four with asymptomatic NCC. Among the HIV+ group, TSOL was not associated with CD4+ cell counts, HAART duration or HIV stage. CONCLUSIONS: This study found lower prevalence of taeniosis, CC and NCC than had been reported in the region to date. This low level of infection may have resulted in an inability to find cross-sectional associations between HIV status and TSOL infection or NCC. Larger sample sizes will be required in future studies conducted in that area to conclude if HIV influences the way NCC manifests itself. |
Baylisascaris procyonis roundworm seroprevalence among wildlife rehabilitators, United States and Canada, 2012-2015
Sapp SG , Rascoe LN , Wilkins PP , Handali S , Gray EB , Eberhard M , Woodhall DM , Montgomery SP , Bailey KL , Lankau EW , Yabsley MJ . Emerg Infect Dis 2016 22 (12) 2128-2131 Baylisascaris procyonis roundworms can cause potentially fatal neural larva migrans in many species, including humans. However, the clinical spectrum of baylisascariasis is not completely understood. We tested 347 asymptomatic adult wildlife rehabilitators for B. procyonis antibodies; 24 were positive, suggesting that subclinical baylisascariasis is occurring among this population. |
Cross-reactivity of the 31 kDa antigen of Angiostrongylus cantonensis - dealing with the immunodiagnosis of meningoencephalitis
Morassutti AL , Rascoe LN , Handali S , DASilva AJ , Wilkins PP , Graeff-Teixeira C . Parasitology 2016 144 (4) 1-5 The primary causative agent of eosinophilic meningoencephalitis (EoM) in endemic regions is the nematode Angiostrongylus cantonensis. The occurrence of EoM was previously restricted to countries in Southeast Asia and the Pacific Islands; however, more recently, it has been reported from other regions, including Brazil. The commonly used diagnosis is detection of specific antibody reactivity to the 31 kDa antigen, which is derived from female worm somatic extracts. Here we report the occurrence of cross-reactivity to this antigen in sera from other parasitic infections, especially those that may cause EoM, such as gnathostomiasis, toxocariasis, hydatidosis and strongyloidiasis. We also demonstrated that the cross-reactivity, in part, is dependent of the concentration of antigen used in Western blot assays. We discuss the importance of these findings on the interpretation of this test. |
Transmission of Babesia microti parasites by solid organ transplantation
Brennan MB , Herwaldt BL , Kazmierczak JJ , Weiss JW , Klein CL , Leith CP , He R , Oberley MJ , Tonnetti L , Wilkins PP , Gauthier GM . Emerg Infect Dis 2016 22 (11) 1869-76 Babesia microti, an intraerythrocytic parasite, is tickborne in nature. In contrast to transmission by blood transfusion, which has been well documented, transmission associated with solid organ transplantation has not been reported. We describe parasitologically confirmed cases of babesiosis diagnosed approximately 8 weeks posttransplantation in 2 recipients of renal allografts from an organ donor who was multiply transfused on the day he died from traumatic injuries. The organ donor and recipients had no identified risk factors for tickborne infection. Antibodies against B. microti parasites were not detected by serologic testing of archived pretransplant specimens. However, 1 of the organ donor's blood donors was seropositive when tested postdonation and had risk factors for tick exposure. The organ donor probably served as a conduit of Babesia parasites from the seropositive blood donor to both kidney recipients. Babesiosis should be included in the differential diagnosis of unexplained fever and hemolytic anemia after blood transfusion or organ transplantation. |
Experimental transfusion-induced Babesia microti infection: dynamics of parasitemia and immune responses in a rhesus macaque model
Gumber S , Nascimento FS , Rogers KA , Bishop HS , Rivera HN , Xayavong MV , Devare SG , Schochetman G , Amancha PK , Qvarnstrom Y , Wilkins PP , Villinger F . Transfusion 2016 56 1508-19 BACKGROUND: Babesiosis is an emerging tick-borne infection in humans. The increasing numbers of reported cases of transfusion-associated babesiosis (TAB), primarily caused by Babesia microti, represents a concern for the safety of the US blood supply. STUDY DESIGN AND METHODS: This study investigated kinetics of parasitemia and innate immune responses and dynamics of antibody responses during B. microti infection in rhesus macaques (RMs) using blood smears, quantitative polymerase chain reaction (qPCR), flow cytometry, and indirect fluorescent antibody testing. A total of six monkeys were transfused with either hamster or monkey-passaged B. microti-infected red blood cells (two and four monkeys, respectively) simulating TAB. RESULTS: The prepatent period in monkeys inoculated with hamster-passaged B. microti was 35 days compared with 4 days in monkeys transfused with monkey-passaged B. microti; the latter monkeys also had markedly higher parasitemia levels. The duration of the window period from the first detected parasitemia by qPCR analysis to the first detected antibody response ranged from 10 to 17 days. Antibody responses fluctuated during the course of the infection. Innate responses assessed by the frequencies of monocytes and activated B cells correlated with the kinetics and magnitude of parasitemia. On Day 14, additional activation peaks were noted for CD14+CD16+ and CD14-CD16+ monocytes and for CD11c+ myeloid dendritic cells, but only in animals transfused with monkey-passaged B. microti. Parasitemia persisted in these immunocompetent animals, similar to human infection. CONCLUSION: The results suggest that transfusion-associated transmission of B. microti leads to rapid onset of parasitemia (Day 4) in RMs, detectable antibody response 14 days later, and persistent parasitemia. |
Identification of antigenic glycans from Schistosoma mansoni using a shotgun egg glycan microarray
Mickum ML , Prasanphanich NS , Song X , Dorabawila N , Mandalasi M , Lasanajak Y , Luyai A , Secor WE , Wilkins PP , Van Die I , Smith DF , Nyame AK , Cummings RD , Rivera-Marrero CA . Infect Immun 2016 84 (5) 1371-1386 Infection of mammals by the parasitic helminth Schistosoma mansoni induces antibodies to glycan antigens in worms and eggs, but the differential nature of the immune response among infected mammals is poorly understood. To better define these responses we used a shotgun glycomics approach, in which N-glycans from schistosome egg glycoproteins were prepared, derivatized, separated, and used to generate an egg shotgun glycan microarray. This array was interrogated with sera from infected mice, rhesus monkeys, humans, and with glycan-binding proteins and antibodies to gather information about the structures of antigenic glycans, which were also analyzed by mass spectrometry. A major glycan antigen targeted by IgG from different infected species is the FLDNF epitope [Fucalpha3GalNAcbeta4(Fucalpha3)GlcNAc-R], which is also recognized by the IgG monoclonal F2D2. The FLDNF antigen is expressed by all life stages of the parasite in mammalian hosts and F2D2 can kill schistosomula in vitro in a complement-dependent manner. Different antisera also recognized other glycan determinants including core beta-xylose and highly fucosylated glycans. Thus, the natural shotgun glycan microarray of schistosome eggs is useful in identifying antigenic glycans and in developing new anti-glycan reagents that may have diagnostic applications and contribute to developing new vaccines against schistosomiasis. |
Development of a Luminex bead based assay for diagnosis of toxocariasis using recombinant antigens Tc-CTL-1 and Tc-TES-26
Anderson JP , Rascoe LN , Levert K , Chastain HM , Reed MS , Rivera HN , McAuliffe I , Zhan B , Wiegand RE , Hotez PJ , Wilkins PP , Pohl J , Handali S . PLoS Negl Trop Dis 2015 9 (10) e0004168 The clinical spectrum of human disease caused by the roundworms Toxocara canis and Toxocara cati ranges from visceral and ocular larva migrans to covert toxocariasis. The parasite is not typically recovered in affected tissues, so detection of parasite-specific antibodies is usually necessary for establishing a diagnosis. The most reliable immunodiagnostic methods use the Toxocara excretory-secretory antigens (TES-Ag) in ELISA formats to detect Toxocara-specific antibodies. To eliminate the need for native parasite materials, we identified and purified immunodiagnostic antigens using 2D gel electrophoresis followed by electrospray ionization mass spectrometry. Three predominant immunoreactive proteins were found in the TES; all three had been previously described in the literature: Tc-CTL-1, Tc-TES-26, and Tc-MUC-3. We generated Escherichia coli expressed recombinant proteins for evaluation in Luminex based immunoassays. We were unable to produce a functional assay with the Tc-MUC-3 recombinant protein. Tc-CTL-1 and Tc-TES-26 were successfully coupled and tested using defined serum batteries. The use of both proteins together generated better results than if the proteins were used individually. The sensitivity and specificity of the assay for detecting visceral larval migrans using Tc-CTL-1 plus Tc-TES-26 was 99% and 94%, respectively; the sensitivity for detecting ocular larval migrans was 64%. The combined performance of the new assay was superior to the currently available EIA and could potentially be employed to replace current assays that rely on native TES-Ag. |
Identification of immunodominant antigens for the laboratory diagnosis of toxocariasis
Zhan B , Ajmera R , Geiger S , Goncalves MT , Liu Z , Wei J , Wilkins PP , Fujiwara R , Gazzinelli-Guimaraes PH , Bottazzi ME , Hotez P . Trop Med Int Health 2015 20 (12) 1787-96 OBJECTIVES: To identify immunodominant antigens of Toxocara canis recognized by Toxocara-infected sera as recombinant reagents for immunodiagnosis of toxocariasis.. METHODS: Pooled sera from human cases of toxocariasis were used to identify immunodominant antigens by immunoscreening a T. canis larval expression cDNA library. The positive clones were sequenced to reveal the identity of the antigens. The recombinant proteins were expressed in E. coli and then used to confirm their immunoreaction with sera of humans with toxocariasis. Two chosen antigens were also used to differentiate Toxocara infection from other helminth infections in mice. RESULTS: 11 antigens with immunodiagnostic potential were identified, including two C-type lectins (CTLs) that reacted strongly with the Toxocara-positive serum pool. The first CTL (Tc-CTL-1) is the same as TES-32, previously identified as a major immunodominant component of TES; the second CTL (Tc-CTL-2) is a novel C-type lectin sharing 83% amino acid sequence identity within the functional domain of Tc-CTL-1. The E. coli expressed recombinant Tc-CTL-1 was strongly recognized by the Toxocara-positive serum pool or sera from animals experimentally infected with T. canis. Reactivity with recombinant Tc-CTL-1 was higher when the unreduced protein was used in an ELISA, Dot blot assay or Western blot test compared to the protein under reduced condition. Both recombinant Tc-CTL-1 and Tc-CTL-2 based ELISAs were able to differentiate T. canis infection from other helminth infections in experimentally infected mice. CONCLUSIONS: Both Tc-CTL-1 and Tc-CTL-2 were able to differentiate Toxocara infection from other helminth infections and could potentially be used as sensitive and specific immunodiagnostic antigens. |
Taeniasis among refugees living on Thailand-Myanmar border, 2012
McCleery EJ , Patchanee P , Pongsopawijit P , Chailangkarn S , Tiwananthagorn S , Jongchansittoe P , Dantrakool A , Morakote N , Phyu H , Wilkins PP , Noh JC , Phares C , O'Neal S . Emerg Infect Dis 2015 21 (10) 1824-6 We tested refugee camp residents on the Thailand-Myanmar border for Taenia solium infection. Taeniasis prevalence was consistent with that for other disease-endemic regions, but seropositivity indicating T. solium taeniasis was rare. Seropositivity indicating cysticercosis was 5.5% in humans, and 3.2% in pigs. Corralling pigs and providing latrines may control transmission of these tapeworms within this camp. |
Cysticercosis and epilepsy in rural Tanzania: a community-based case-control and imaging study
Hunter E , Burton K , Iqbal A , Birchall D , Jackson M , Rogathe J , Jusabani A , Gray W , Aris E , Kamuyu G , Wilkins PP , Newton CR , Walker R . Trop Med Int Health 2015 20 (9) 1171-1179 OBJECTIVE: To assess the contribution of neurocysticercosis (NCC) to the burden of epilepsy in a rural Tanzanian population. METHODS: We identified adult people with epilepsy (PWE) in a door-to-door study in an established demographic surveillance site. PWE and community controls were tested for antibodies to Taenia solium, the causative agent of NCC, and all PWE were offered a computed tomography (CT) head scan. Data on household occupancy and sanitation, pig-keeping and pork consumption were collected from PWE and controls and associations with epilepsy were assessed using chi-square or Fisher's exact tests. RESULTS: Six of 218 PWE had antibodies to T. solium (2.8%; 95% CI 0.6-4.9), compared to none of 174 controls (Fisher's exact test, P = 0.04). Lesions compatible with NCC were seen in eight of 200 CT scans (4.0%; 95% CI 1.3-6.7). A total of 176 PWE had both investigations of whom two had positive serology along with NCC-compatible lesions on CT (1.1%; 95% 0.3-4.0). No associations between epilepsy and any risk factors for NCC were identified. CONCLUSIONS: Neurocysticercosis is present in this population but at a lower prevalence than elsewhere in Tanzania and sub-Saharan Africa. Insights from low-prevalence areas may inform public health interventions designed to reduce the burden of preventable epilepsy. |
Ring-screening to control endemic transmission of Taenia solium
O'Neal SE , Moyano LM , Ayvar V , Rodriguez S , Gavidia C , Wilkins PP , Gilman RH , Garcia HH , Gonzalez AE . PLoS Negl Trop Dis 2014 8 (9) e3125 BACKGROUND: Taenia solium is a major cause of preventable epilepsy in developing nations. Screening and treatment of human intestinal stage infection (taeniasis) within high-risk foci may reduce transmission and prevent epilepsy by limiting human exposure to infective eggs. We piloted a ring-strategy that involves screening and treatment for taeniasis among households located nearby pigs heavily-infected with the larval stage (cysticercosis). These pigs mark areas of increased transmission and can be identified by tongue examination. METHODOLOGY: We selected two villages in northern Peru for a controlled prospective interventional cohort pilot study. In the intervention village (1,058 residents) we examined the tongues of all pigs every 4 months for nodules characteristic of cysticercosis. We then screened all residents living within 100-meters of any tongue-positive pig using enzyme-linked immunosorbent assay to detect Taenia antigens in stool. Residents with taeniasis were treated with niclosamide. In both the intervention and control (753 residents) we measured incidence of exposure by sampling the pig population every 4 months for serum antibodies against cysticercosis using enzyme-linked immunoelectrotransfer blot. PRINCIPAL FINDINGS: Baseline seroincidence among pigs born during the study was 22.6 cases per 100 pigs per-month (95% confidence interval [CI] 17.0-30.0) in the intervention and 18.1 (95% CI 12.7-25.9) in the control. After one year we observed a 41% reduction in seroincidence in the intervention village compared to baseline (incidence rate ratio 0.59, 95% CI 0.41-0.87) while the seroincidence in the control village remained unchanged. At study end, the prevalence of taeniasis was nearly 4 times lower in the intervention than in the control (prevalence ratio 0.28, 95% CI 0.08-0.91). CONCLUSIONS/SIGNIFICANCE: Ring-screening reduced transmission of T. solium in this pilot study and may provide an effective and practical approach for regions where resources are limited. However, this strategy requires validation in larger populations over a greater period of time. |
Neglected parasitic infections: what every family physician needs to know
Woodhall D , Jones JL , Cantey PT , Wilkins PP , Montgomery SP . Am Fam Physician 2014 89 (10) 803-11 Neglected parasitic infections, including Chagas disease, toxocariasis, cysticercosis, and toxoplasmosis, affect millions of persons in the United States. Relatively few resources have been devoted to surveillance, prevention, and treatment of these diseases. Chagas disease primarily affects Latin American immigrants and can cause heart failure and death if not treated. Immediate antiparasitic treatment is indicated for most patients with acute Chagas disease. Treatment is recommended for patients younger than 18 years who have chronic Chagas disease and is generally recommended for adults younger than 50 years who do not have advanced cardiomyopathy; treatment decisions for other patients should be made on an individual basis. Toxocariasis primarily affects children and can cause gastrointestinal, respiratory, and ophthalmologic disease. Treatment options include albendazole and mebendazole. Patients with ocular infection require referral to an ophthalmologist. Neurocysticercosis, a form of cysticercosis, is the most common infectious cause of seizures in some parts of the United States. Initial treatment should focus on symptom control. Humans generally acquire toxoplasmosis by eating undercooked contaminated meat or ingesting things that have been contaminated with cat feces. Congenital infection can result in miscarriage or adverse fetal effects. Treatment is recommended for immunosuppressed persons, pregnant women, and immunocompetent persons with severe symptoms. |
Exposure to multiple parasites is associated with the prevalence of active convulsive epilepsy in sub-Saharan Africa
Kamuyu G , Bottomley C , Mageto J , Lowe B , Wilkins PP , Noh JC , Nutman TB , Ngugi AK , Odhiambo R , Wagner RG , Kakooza-Mwesige A , Owusu-Agyei S , Ae-Ngibise K , Masanja H , Osier FH , Odermatt P , Newton CR . PLoS Negl Trop Dis 2014 8 (5) e2908 BACKGROUND: Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa. METHODS AND FINDINGS: A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95%CI: 1.52-2.58, p<0.001), Toxocara canis (OR = 1.52; 95%CI: 1.23-1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95%CI: 1.04-1.56, p = 0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95%CI: 1.30-2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas. CONCLUSION: This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated. |
Recombinant protein- and synthetic peptide-based immunoblot test for diagnosis of neurocysticercosis
Noh J , Rodriguez S , Lee YM , Handali S , Gonzalez AE , Gilman RH , Tsang VC , Garcia HH , Wilkins PP . J Clin Microbiol 2014 52 (5) 1429-34 One of the most well-characterized tests for diagnosing neurocysticercosis (NCC) is the enzyme-linked immunoelectrotransfer blot (EITB) assay developed at the CDC, which uses lentil lectin-bound glycoproteins (LLGP) extracted from Taenia solium cysticerci. Although the test is very reliable, the purification process for the LLGP antigens has been difficult to transfer to other laboratories because of the need for expensive equipment and technical expertise. To develop a simpler assay, we previously purified and cloned the diagnostic glycoproteins in the LLGP fraction. In this study, we evaluated three representative recombinant or synthetic antigens from the LLGP fraction, individually and in different combinations, using an immunoblot assay (recombinant EITB). Using a panel of 249 confirmed NCC-positive and 401 negative blood serum samples, the sensitivity of the recombinant EITB assay was determined to be 99% and the specificity was 99% for diagnosing NCC. We also tested a panel of 239 confirmed NCC-positive serum samples in Lima, Peru, and found similar results. Overall, our data show that the performance characteristics of the recombinant EITB assay are comparable to those of the LLGP-EITB assay. This new recombinant- and synthetic antigen-based assay is sustainable and can be easily transferred to other laboratories in the United States and throughout the world. |
Neglected parasitic infections in the United States: cysticercosis
Cantey PT , Coyle CM , Sorvillo FJ , Wilkins PP , Starr MC , Nash TE . Am J Trop Med Hyg 2014 90 (5) 805-9 Cysticercosis is a potentially fatal and preventable neglected parasitic infection caused by the larval form of Taenia solium. Patients with symptomatic disease usually have signs and symptoms of neurocysticercosis, which commonly manifest as seizures or increased intracranial pressure. Although there are many persons living in the United States who emigrated from highly disease-endemic countries and there are foci of autochthonous transmission of the parasite in the United States, little is known about burden and epidemiology of the disease in this country. In addition, despite advances in the diagnosis and management of neurocysticercosis, there remain many unanswered questions. Improving our understanding and management of neurocysticercosis in the United States will require improved surveillance or focused prospective studies in appropriate areas and allocation of resources towards answering some of the key questions discussed in this report. |
Toxoplasma gondii seroprevalence in the United States 2009-2010 and comparison with the past two decades
Jones JL , Kruszon-Moran D , Rivera H , Price C , Wilkins PP . Am J Trop Med Hyg 2014 90 (6) 1135-9 Toxoplasma gondii is a ubiquitous parasite that can cause neurologic and ocular disease. We tested sera from 7,072 people ≥ 6 years of age in the 2009-2010 National Health and Nutrition Examination Survey (NHANES) for immunoglobulin G antibodies and compared these results with two previous NHANES surveys. The overall T. gondii antibody seroprevalence among persons ≥ 6 years of age in 2009-2010 was 13.2% (95% confidence limit [CL] 11.8%, 14.5%) and age-adjusted seroprevalence was 12.4% (95% CL 11.1%, 13.7%); age-adjusted seroprevalence among women 15-44 years of age was 9.1% (95% CL 7.2%, 11.1%). In U.S. born persons 12-49 years of age, the age-adjusted T. gondii seroprevalence decreased from 14.1% (95% CL 12.7%, 15.5%) in NHANES III (1988-1994) to 9.0% (95% CL 7.6%, 10.5%) in NHANES 1999-2004 to 6.7% (95% CL 5.3%, 8.2%) in NHANES 2009-2010 (P < 0.001 linear trend). Although T. gondii antibody presence is still relatively common, the prevalence in the United States has continued to decline. |
Interlaboratory optimization and evaluation of a serological assay for diagnosis of human baylisascariasis
Rascoe LN , Santamaria C , Handali S , Dangoudoubiyam S , Kazacos KR , Wilkins PP , Ndao M . Clin Vaccine Immunol 2013 20 (11) 1758-63 A Western blot assay using a recombinant protein, recombinant Baylisascaris procyonis RAG1 protein (rBpRAG1), was developed for the diagnosis of human baylisascariasis concurrently by the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the National Reference Centre for Parasitology (NRCP) in Montreal, Canada. Assay performance was assessed by testing 275 specimens at the CDC and 405 specimens at the NRCP. Twenty specimens from 16 cases of baylisascariasis were evaluated. Eighteen were positive, with the assay correctly identifying 14 of 16 patients. The rBpRAG1 Western blot assay showed no cross-reactivity with Toxocara-positive serum and had an overall sensitivity of 88% and a specificity of 98%. |
Concurrent parasitic infections in a renal transplant patient
Visvesvara GS , Arrowood MJ , Qvarnstrom Y , Sriram R , Bandea R , Wilkins PP , Farnon E , Weitzman G . Emerg Infect Dis 2013 19 (12) 2044-5 Protozoan pathogens, including Entamoeba histolytica, Giardia, Cryptosporidium, Cyclospora, Cystoisospora, and microsporidia such as Enterocytozoon bieneusi, are well-known agents of diarrhea and a major public health problem in developing countries. Infection with Cyclospora cayetanensis and E. bieneusi can occur in immunocompromised and immunocompetent persons. Severe diarrhea and weight loss along with anorexia, nausea, and low-grade fever occur in immunocompromised persons, particularly those with HIV/AIDS and transplant recipients who are taking immunosuppressive drugs (1,2). However, transient diarrhea occurs in immunocompetent persons, notably in travelers returning from countries with poor hygienic standards (1–3). | | We report on a kidney transplant recipient who had uncontrollable diarrhea and weight loss in whom C. cayetanensis and E. bieneusi were detected in biopsy specimens; the diarrhea resolved after treatment with drugs that act specifically on these 2 parasites. The patient was a 55-year-old man from the Dominican Republic living in New York, NY, USA; he had a history of long-term diabetes, coronary disease, and alcoholism. He had undergone a cadaveric renal transplant 14 months earlier and had an uneventful posttransplant course. After returning from visiting family in the Dominican Republic, he sought treatment for acute, profuse watery diarrhea in early November, 2009. He had >10 watery bowel movements daily that were associated with a 20-lb weight loss. His symptoms persisted for 2 months, and he required 2 hospitalizations for the diarrhea. |
Immunodiagnosis of CNS parasitic infections
Wilkins PP . Handb Clin Neurol 2013 114 23-36 The nature of many parasitic infections of the central nervous system (CNS) requires immunodiagnosis to confirm presumptive diagnoses. The CNS is the primary site of parasite infection for some parasitic organisms and for others, neurological infection occurs only in immunocompromised hosts. Still other parasites cause ectopic infections of the CNS and occur very rarely. This review concentrates on laboratory diagnosis of diseases that are caused by parasites with a primary predilection for the CNS. Emphasis is placed on laboratory diagnostic methods that are used and suitable for clinical diagnosis, rather than a comprehensive review of all the experimental methods that have been reported in the literature. Immunodiagnosis is not appropriate for the diagnosis of all parasitic infections of the CNS; in those cases, alternative diagnostic methods are presented, but not discussed in detail. In some instances potential new antigens or methods are presented, particularly if adoption of these methods is expected in the near future. |
The current status of laboratory diagnosis of Angiostrongylus cantonensis infections in humans using serologic and molecular methods.
Wilkins PP , Qvarnstrom Y , Whelen AC , Saucier C , da Silva AJ , Eamsobhana P . Hawaii J Med Public Health 2013 2 55-57 Laboratory diagnosis of angiostrongyliasis relies on serological techniques, since definitive diagnosis is insensitive. Modern antibody detection methods focus on antibodies to the 29 and 31 kDa proteins of the parasite. Antigen detection may ultimately prove to be more reliable than antibody detection but no method has been adopted for clinical diagnostic use. Diagnosis using PCR amplification of DNA sequences specific to Angiostrongylus cantonensis have been developed but have not yet been validated for clinical use. Diagnostic tests have not been developed commercially and in the United States tests developed experimentally by non-commercial laboratories have to be approved by the Food and Drug Administration before they can be sold to other laboratories for diagnostic purposes. |
Serological diagnosis of North American paragonimiasis by Western blot using Paragonimus kellicotti adult worm antigen
Fischer PU , Curtis KC , Folk SM , Wilkins PP , Marcos LA , Weil GJ . Am J Trop Med Hyg 2013 88 (6) 1035-40 We studied the value of an IgG Western blot (WB) with Paragonimus kellicotti (Pk) antigen for diagnosis of North American paragonimiasis. The test was evaluated with sera from patients with Pk and Paragonimus westermani infections, with control sera from patients with other helminth infections, and sera from healthy Americans. All 11 proven Pk infection sera and two samples from suspected cases that were negative by P. westermani WB at Centers for Disease Control and Prevention (CDC) contained antibodies to antigens at 34 kDa and at 21/23 kDa. Seven of 7 P. westermani sera contained antibodies to the 34 kDa antigen, but only 2 recognized the 21/23 kDa doublet. No control samples were reactive with these antigens. Antibody reactivity declined after praziquantel treatment. Thus, the P. kellicotti WB appears to be superior to P. westermani WB for diagnosing Pk infections, and it may be useful for assessing responses to treatment. |
Geographic correlation between tapeworm carriers and heavily infected cysticercotic pigs
O'Neal SE , Moyano LM , Ayvar V , Gonzalvez G , Diaz A , Rodriguez S , Wilkins PP , Tsang VC , Gilman RH , Garcia HH , Gonzalez AE . PLoS Negl Trop Dis 2012 6 (12) e1953 BACKGROUND: Neurocysticercosis is a leading cause of preventable epilepsy in the developing world. Sustainable community-based interventions are urgently needed to control transmission of the causative parasite, Taenia solium. We examined the geospatial relationship between live pigs with visible cysticercotic cysts on their tongues and humans with adult intestinal tapeworm infection (taeniasis) in a rural village in northern Peru. The objective was to determine whether tongue-positive pigs could indicate high-risk geographic foci for taeniasis to guide targeted screening efforts. This approach could offer significant benefit compared to mass intervention. METHODS: We recorded geographic coordinates of all village houses, collected stool samples from all consenting villagers, and collected blood and examined tongues of all village pigs. Stool samples were processed by enzyme-linked immunosorbent assay (ELISA) for presence of Taenia sp. coproantigens indicative of active taeniasis; serum was processed by enzyme-linked immunoelectrotransfer blot for antibodies against T. solium cysticercosis (EITB LLGP) and T. solium taeniasis (EITB rES33). FINDINGS: Of 548 pigs, 256 (46.7%) were positive for antibodies against cysticercosis on EITB LLGP. Of 402 fecal samples, 6 (1.5%) were positive for the presence of Taenia sp. coproantigens. The proportion of coproantigen-positive individuals differed significantly between residents living within 100-meters of a tongue-positive pig (4/79, 5.1%) and residents living >100 meters from a tongue-positive pig (2/323, 0.6%) (p = 0.02). The prevalence of taeniasis was >8 times higher among residents living within 100 meters of a tongue-positive pig compared to residents living outside this range (adjusted PR 8.1, 95% CI 1.4-47.0). CONCLUSIONS: Tongue-positive pigs in endemic communities can indicate geospatial foci in which the risk for taeniasis is increased. Targeted screening or presumptive treatment for taeniasis within these high-risk foci may be an effective and practical control intervention for rural endemic areas. |
Schistosomiasis serology is valuable and reliable
Wilkins PP , Keystone JS . Clin Infect Dis 2012 56 (2) 312 We read the photo quiz authored by Bagdure and Khasawneh with interest [1]. The authors described a case of schistosomiasis colitis caused by Schistosoma mansoni, which was diagnosed after review of hematoxylin-eosin–stained colonic biopsy sections. This case emphasizes the challenges associated with obtaining a laboratory diagnosis of schistosomiasis based on examination of ova and parasites in stool specimens. | The authors suggested that serology for schistosomiasis is neither sensitive nor specific. In fact, although serologic tests vary widely in their sensitivity and specificity, based on the antigen and test used, reliable antibody detection assays for schistosomiasis are available that are both sensitive and specific [2]. The Centers for Disease Control and Prevention employs a combination of tests that are based on detection of antibodies to species-specific proteins produced by the adult worms of S. mansoni, Schistosoma haematobium, and Schistosoma japonicum. This serologic testing algorithm for schistosomiasis begins with screening using the S. mansoni Falcon assay screening test (FAST)–enzyme-linked immunosorbent assay (ELISA) [3]; a positive result indicates infection with Schistosoma species. The specificity of the FAST-ELISA is 99%, and its sensitivity is 99% for S. mansoni, 95% for S. haematobium, and approximately 50% for S. japonicum infection. Because the sensitivity of the FAST-ELISA is lower for schistosome infections other than those caused by S. mansoni, species-specific immunoblot tests are also used that can identify the causal schistosome species of the infection if results are positive. Immunoblot tests for S. mansoni, S. haematobium, and S. japonicum are assigned based on travel history. |
Zoonotic infections among employees from Great Smoky Mountains and Rocky Mountain National Parks, 2008-2009
Adjemian J , Weber IB , McQuiston J , Griffith KS , Mead PS , Nicholson W , Roche A , Schriefer M , Fischer M , Kosoy O , Laven JJ , Stoddard RA , Hoffmaster AR , Smith T , Bui D , Wilkins PP , Jones JL , Gupton PN , Quinn CP , Messonnier N , Higgins C , Wong D . Vector Borne Zoonotic Dis 2012 12 (11) 922-31 U.S. National Park Service employees may have prolonged exposure to wildlife and arthropods, placing them at increased risk of infection with endemic zoonoses. To evaluate possible zoonotic risks present at both Great Smoky Mountains (GRSM) and Rocky Mountain (ROMO) National Parks, we assessed park employees for baseline seroprevalence to specific zoonotic pathogens, followed by evaluation of incident infections over a 1-year study period. Park personnel showed evidence of prior infection with a variety of zoonotic agents, including California serogroup bunyaviruses (31.9%), Bartonella henselae (26.7%), spotted fever group rickettsiae (22.2%), Toxoplasma gondii (11.1%), Anaplasma phagocytophilum (8.1%), Brucella spp. (8.9%), flaviviruses (2.2%), and Bacillus anthracis (1.5%). Over a 1-year study period, we detected incident infections with leptospirosis (5.7%), B. henselae (5.7%), spotted fever group rickettsiae (1.5%), T. gondii (1.5%), B. anthracis (1.5%), and La Crosse virus (1.5%) in staff members at GRSM, and with spotted fever group rickettsiae (8.5%) and B. henselae (4.3%) in staff at ROMO. The risk of any incident infection was greater for employees who worked as resource managers (OR 7.4; 95% CI 1.4,37.5; p=0.02), and as law enforcement rangers/rescue crew (OR 6.5; 95% CI 1.1,36.5; p=0.03), relative to those who worked primarily in administration or management. The results of this study increase our understanding of the pathogens circulating within both parks, and can be used to inform the development of effective guidelines and interventions to increase visitor and staff awareness and help prevent exposure to zoonotic agents. |
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