M.A. Haseeb

Reduced cognitive function in children with toxocariasis in a nationally representative sample of the United States

Toxocariasis has recently been recognised as a potentially important neglected infection in developed countries, particularly those that experience substantive health disparities such as the United States. Given a relatively high prevalence of infection, an association between Toxocara infection and cognitive function may elucidate an important mechanism by which toxocariasis could contribute significantly to morbidity while still remaining hidden and, thus, neglected. To assess the potential relationship between toxocariasis and cognitive function, this investigation measured differences in components of both the Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Wide Range Achievement Test-Revised (WRAT-R) in children seropositive and in children seronegative for Toxocara antibodies in the Third National Health and Nutrition Examination Survey, a large, nationally-representative survey of the United States population. Seropositive children scored significantly lower on the WISC-R and WRAT-R compared with the seronegative children. Moreover, this relationship was independent of socioeconomic status, ethnicity, gender, rural residence, cytomegalovirus infection and blood lead levels. These results identify an important association that may reflect morbidity attributable to a genuine neglected infection. Nevertheless, longitudinal data are required to confirm an etiological connection between toxocariasis and cognitive function, as well as the true population attributable risk for toxocariasis and its chronic sequelae.

Schistosoma mansoni: Female-dependent lipid secretion in males and corresponding changes in lipase activity

Eight to 10-week old Schistosoma mansoni males from unisexual infections were examined histochemically for neutral lipids and lipase activity. In addition, in situ fixed pairs were examined for lipase activity. Neutral lipid content of males from unisexual infections was variable and lipase activity was minimal. Following 1 h incubation at 37 degrees C in Earles balanced salt solution (EBSS) in which females had previously been maintained for 1 h, males showed moderate increase in lipid content and diminished lipase activity. In contrast, unisexually developed males incubated for 1 h with females from bisexual infections showed increased lipid accumulation and lipase activity. Unisexually developed males incubated for 1 h in EBSS showed both lipid accumulation and release from the dorsal surface. Worm-pairs fixed in situ showed greater lipase activity in females than in males. These observations suggest that a factor(s) released by females affects the physiology of males.

Toxocariasis and lung function: Relevance of a neglected infection in an urban landscape

Toxocariasis has been highlighted as a potentially important neglected infection of poverty in developed countries that experience substantive health disparities such as the United States. An association between Toxocara infection and lung function, in concert with a relatively high prevalence of infection, may mark an important mechanism by which this infection could contribute significantly to the differential morbidity across different socioeconomic groups and landscapes. To assess the potential relevance of this infection in a dense urban environment, we measured the association between forced expiratory volume in 1 second (FEV1) and serology diagnosed Toxocara infection in a sample of US-born New York City residents. We identified a significant independent association between Toxocara infection and lung function, wherein those with previous Toxocara infection had a 236.9 mL reduced FEV1 compared to those without Toxocara infection even after adjusting for age, sex, ethnicity, level of education, smoking status, body mass index, and pet ownership. These findings from New York City corroborate similar findings in a national sample and, while the cross-sectional data preclude a direct causal relationship, this study identifies a potentially important neglected infection in a dense urban landscape.

Modeling the ecologic niche of plague in sylvan and domestic animal hosts to delineate sources of human exposure in the western United States

Plague has been established in the western United States (US) since 1900 following the West Coast introduction of commensal rodents infected with Yersinia pestis via early industrial shipping. Over the last century, plague ecology has transitioned through cycles of widespread human transmission, urban domestic transmission among commensal rodents, and ultimately settled into the predominantly sylvan foci that remain today where it is maintained alternatively by enzootic and epizootic transmission. While zoonotic transmission to humans is much less common in modern times, significant plague risk remains in parts of the western US. Moreover, risk to some threatened species that are part of the epizootic cycle can be quite substantive. This investigation attempted to predict the risk of plague across the western US by modeling the ecologic niche of plague in sylvan and domestic animals identified between 2000 and 2015. A Maxent machine learning algorithm was used to predict this niche based on climate, altitude, land cover, and the presence of an important enzootic species, Peromyscus maniculatus. This model demonstrated good predictive ability (AUC = 86%) and identified areas of high risk in central Colorado, north-central New Mexico, and southwestern and northeastern California. The presence of P. maniculatus, altitude, precipitation during the driest and wettest quarters, and distance to artificial surfaces, all contributed substantively to maximizing the gain function. These findings add to the known landscape epidemiology and infection ecology of plague in the western US and may suggest locations of particular risk to be targeted for wild and domestic animal intervention.

Characterization of Trypanosoma cruzi infectivity, proliferation, and cytokine patterns in gut and pancreatic epithelial cells maintained in vitro

Trypanosoma cruzi infects all nucleated cells in both humans and experimental animals. As a prelude to our studies of T. cruzi pathogenesis in the gastrointestinal system, we have initiated in vitro cultures of gut (Caco-2 and HT-29) and pancreatic (Panc-1) epithelial cells. We show that along with primary human fibroblasts, all three cell lines are susceptible to infection and support proliferation of T. cruzi. Infection with T. cruzi modified dramatically the cytokines elaborated by these cells. Substantially greater quantities of IL-5 and TGF-β1 were produced by fibroblasts and Caco-2 and Panc-1 cells, whereas secretion of IFN-γ and TNF-α was greatly reduced in all three cell types. Since these cells are not known to be the primary sources of IFN-γ, we examined IFN-γ mRNA expression in these cells. Both Caco-2 and Panc-1 cells were found to express IFN-γ mRNA, validating its secretion. These findings may provide insight into signaling pathways that mediate innate immunity to T. cruzi and pathogenesis of gastrointestinal and pancreatic alterations in Chagas disease.

Determinants of reactivation of inapparent Strongyloides stercoralis infection in patients hospitalized for unrelated admitting diagnosis.

Background Clinical presentation of strongyloidiasis in humans is highly variable, ranging from clinically inapparent infection to life-threatening multisystem disease. The course of infection is dependent on the immune status of the patient. Our objective was to ascertain the clinical characteristics of patients who developed reactivated strongyloidiasis from a primary infection acquired in the past, and to evaluate risk factors that contributed to its exacerbation. Methods We identified 31 patients diagnosed with strongyloidiasis by stool examination at our institution from January 2007 to June 2012. We reviewed their clinical records and selected eight patients whose admitting diagnosis was not suggestive of strongyloidiasis-associated gastrointestinal disease. However, they developed symptoms consistent with strongyloidiasis during their hospitalization, and stool examinations revealed diagnostic larvae. Results and conclusion We have identified immunosuppressive therapy, viral infection-associated immunodeficiency, alcoholism, and diabetes mellitus as risk factors for reactivation of chronic inapparent strongyloidiasis. Analysis of hemogram data suggests the low sensitivity of hypereosinophilia to be a marker for this helminthiasis.

Schistosoma japonicum: Changes in lipase activity in adults maintained in vitro

Schistosoma japonicum (Chinese strain) adult worm pairs (10-12 weeks old) were fixed in 4 degrees C absolute acetone or neutral buffered formalin either immediately after recovery from mice, or following incubation for 0.5 or 1.0 h. Males and females were incubated individually in Earles balanced salt solution at 37 degrees C. Lipase activity was determined in frozen sections by Gomoris method using Tween 80 as substrate. In unincubated males, lipase activity was localized only in the parenchyma; in females it was present in the vitellaria and parenchyma subjacent to the tegument. After 0.5 h incubation, males showed less lipase activity in the parenchyma than unincubated males, and females showed increased activity in the parenchyma subjacent to the tegument, but not in the vitellaria. Following 1.0 h incubation, males showed less lipase activity than previously, and females showed a marked increase in activity, particularly in the parenchyma subjacent to the tegument.

Abstract 3406: Enhancer of zeste homolog 2 (EZH2) expression and proliferation index (Ki-67) in neuroendocrine tumors of the gastrointestinal tract and pancreas

EZH2 is a polycomb group protein that is involved in the progression of multiple human cancers including prostatic, endometrial, and colonic adenocarcinomas. Its expression has been shown to increase from typical carcinoid to atypical carcinoid and further to small cell/large cell neuroendocrine carcinomas of the lung. Here we examine the EZH2 expression and the proliferation index (PI) by Ki-67 expression in neuroendocrine tumors of the gastrointestinal tract (GI) and pancreas. We retrieved 72 cases of GI and pancreatic neuroendocrine tumors of grades G1 (n = 56), G2 (n = 6) and G3 (n = 10) which were graded according to the WHO classification. Expression of EZH2 and Ki-67 was analyzed by immunohistochemistry using monoclonal antibodies (EZH2 at 1:200; Ki-67 at 1:70). Expression of EZH2 was determined to be low (10%), and was compared with the respective PI. All G1 tumors had low EZH2 expression and a low PI (20%). In G2 tumors, EZH2 expression was intermediate (1-10%) and PI was between 0-8%. One of the G2 tumors had a low PI of 0, however, the EZH2 expression was intermediate (3%). There was increased EZH2 expression relative to increasing tumor grade from G1 to G3 (p EZH2 expression increases incrementally from G1 neuroendocrine tumors to G2 and further to G3 tumors, suggesting an association or a role in progression of neuroendocrine tumors. There is strong correlation between the expression of EZH2 and PI in G1, G2 and G3 tumors. EZH2 appears to be a better predictor of tumor grade in G2 tumors as compared to PI. Thus, EZH2 could be used as an additional diagnostic marker in examining atypical GI neuroendocrine tumors. Citation Format: Jia Qin, Raag Agrawal, Miguel G. Echevarria, LAura A. Martello, M.A Haseeb, Raavi Gupta. Enhancer of zeste homolog 2 (EZH2) expression and proliferation index (Ki-67) in neuroendocrine tumors of the gastrointestinal tract and pancreas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3406. doi:10.1158/1538-7445.AM2015-3406