Hymenolepis nana-An Emerging Intestinal Parasite Associated with Anemia in School Children from the Bolivian Chaco.

Tropical anemia can have multiple causes, whether socioeconomic, dietary, or infectious. In the Bolivian Chaco, soil-transmitted helminthiases (STH), malaria, and Chagas disease are potential infectious causes of anemia among school-aged children (SAC). Following years of preventive chemotherapy with mebendazole, the prevalence of STH among SAC living in that area is now negligible, whereas protozoan infections are still highly prevalent (81%); Hymenolepis nana is the most frequent intestinal helminth (∼13%). We present results of hemoglobin (Hb) assessment and the association between parasitic infections and Hb levels of that SAC population. Overall, 511 SAC (girls:boys ratio 1:1, mean age 9.4 years [95% confidence interval {CI}: 9.3-9.5]) had Hb levels measured by using a point of care testing (HemoCue® Hb 301 System; HemoCue, Angelhome, Sweden). The prevalence of anemia was 23% (117/511), with mean and median Hb level = 12.2 g/dL (95% CI: 12.1-12.3; range 9.2-15.4 g/dL). By multivariate analysis, H. nana infection was associated with an increased risk of anemia (odds ratio 2.9, 95% CI: 1.5-5.7, P = 0.002). Two samples (0.5%) were positive for Trypanosoma cruzi and none for Plasmodium spp. by polymerase chain reaction of the 439 children tested. Anemia is still a concern among SAC living in the Bolivian Chaco. Our findings call for a greater attention to fecal-oral emerging pathogens, such as H. nana, and highlight the importance of water, sanitation, and hygiene improvements for disadvantaged population such as those living in the Bolivian Chaco.

Non-Human Cancers in AIDS Patients.

Neoplasms are more frequent in HIV-positive persons than in non-infected individuals. The incidence of malignancies associated to oncoviruses increases with low CD4 counts in HIV carriers. This is the case for Kaposi sarcoma, Castleman disease or effusive cavity lymphomas due to HHV-8, anorectal or cervical cancer due to human papillomavirus, and Burkitt lymphoma or large B-cell lymphoma due to Epstein-Barr virus.

Murine autoimmune arthritis is exaggerated by infection with the rat tapeworm, Hymenolepis diminuta.

Infection with helminth parasites triggers strong and stereotypic immune responses in humans and mice, which can protect against specific experimentally-induced autoimmune diseases. We have shown that infection with the rat tapeworm, Hymenolepis diminuta, confers a protective effect on FCA-induced joint inflammation. Here, we investigated the effect of a prophylactic infection with H. diminuta on the K/BxN-serum model of polyarthritis in BALB/c mice. Mice were infected with 10 cysticercoids of H. diminuta by oral gavage and 8 days later arthritis was induced by i.p. injection of K/BxN arthritogenic serum. Joint swelling and pain measurements were recorded throughout a 13 day time course. At necropsy, joints and blood serum were collected. K/BxN-treated mice developed joint inflammation in the front paws, hind paws and knees as shown by increased swelling, mechanical allodynia and myeloperoxidase activity. Mice infected with H. diminuta had more severe disease, with increased eosinophil peroxidase activity in their paws and greater inflammatory infiltrate and synovitis in the knee joints. Hymenolepis diminuta-infected mice displayed significant increases in serum levels of C5a and mast cell protease-1 compared with K/BxN-serum only treatment, the latter being indicative of mast cell activation. In contrast to the protective effect of infection with H. diminuta in FCA-induced monoarthritis, infection with this helminth exacerbated K/BxN serum-induced polyarthritis in BALB/c mice. This correlated with increases in C5a and mast cell activation: factors critical in the development of K/BxN-induced arthritis. Thus, while data accumulate from animal models showing that infection with helminth parasites may be beneficial for a variety of auto-inflammatory diseases, our findings demonstrate the potential for helminths to exacerbate disease. Hence care is needed when helminth therapy is translated into a clinical setting.

Exacerbation of oxazolone colitis by infection with the helminth Hymenolepis diminuta: involvement of IL-5 and eosinophils.

Substantial data show that infection with helminth parasites ameliorates colitis; however, oxazolone-induced colitis is exaggerated in mice infected with the tapeworm, Hymenolepis diminuta. We tested the hypothesis that the IL-5 response to helminth infection enhances the severity of oxazolone-induced colitis. Mice were infected with H. diminuta and 8 days later were treated with oxazolone ± anti-IL-5 antibodies. Colitis was assessed 72 hours postoxazolone treatment by disease activity scores, myeloperoxidase activity, and histopathology. Other mice received injections of a replication-deficient adenovirus that carried the IL-5 (Ad.IL-5) gene or a control adenovirus (Ad.delete) ± oxazolone. The effect of H. diminuta+oxazolone in CCL11/CCL22 (eotaxin-1 and 2) knockout (KO) mice was determined. Helminth infection and Ad.IL-5 treatment increased IL-5 and eosinophil numbers. In vivo neutralization of IL-5 significantly reduced the severity of colitis in H. diminuta+oxazolone-treated mice, and H. diminuta did not exaggerate oxazolone-induced colitis in CCL11/CCL22 KO mice. Mice receiving Ad.IL-5 only had no colitis, while oxazolone-induced colitis was more severe in animals cotreated with Ad.IL-5 (Ad.delete + oxazolone was not significantly different from oxazolone only). Thus, while there is much to be gleaned about antiinflammatory mechanisms from rodent-helminth model systems, these data illustrate the caveat that infection with helminth parasites as a therapy could be contraindicated in patients with eosinophilia or elevated IL-5 unless coupled to appropriate measures to block IL-5 and/or eosinophil activity.

A human case of Hymenolepis diminuta in a child from eastern Sicily.

We report a case of Hymenolepis diminuta infection in a 2-year-old child living in a suburban area of Catania, Italy. This case was initially referred to us as Dipylidium caninum infection, which was not cured after being treated twice with mebendazole. However, by analyzing the clinical presentation and stool samples we arrived to the diagnosis of H. diminuta infection. The case presented with atypical allergic manifestations which had never been reported as clinical features of symptomatic H. diminuta infection; remittent fever with abdominal pain, diffuse cutaneous itching, transient thoracic rash, and arthromyalgias. The patient was treated with a 7-day cycle of oral niclosamide, which proved to be safe and effective. This case report emphasizes that a correct parasitological diagnosis requires adequate district laboratories and trained personnel. In addition, we recommend the importance of reporting all H. diminuta infection cases, in order to improve knowledge on epidemiology, clinical presentation, and treatment protocols.

Acetic acid induced ulceration in rats is not affected by infection with Hymenolepis diminuta.

Analysis of rodent models of inflammatory bowel disease, airways hyper-reactivity, diabetes, and multiple sclerosis has shown that infection with helminth parasites can significantly reduce the severity of the disease. Here, we assessed whether rats infected with the tapeworm Hymenolepis diminuta were protected from gastric ulceration induced by the serosal application of acetic acid. All rats gavaged with infective cysticercoids harbored adult worms when assessed 6 wk later, and acetic acid evoked the expected gastric ulceration. However, infection with H. diminuta did not affect the degree of gastric ulceration at either 3 or 7 days post-acetic acid application, as gauged by ulcer area or histopathology. While the data do not dismiss the possibility that infection with other helminths could be anti-ulcerogenic, they illustrate that 'helminth therapy' for inflammatory disease is likely to be both disease- and helminth-specific.

Food additives and Hymenolepis nana infection: an experimental study.

The effect of sodium benzoate (SB) on the pathogenesis of Hymenolepis nana (H. nana) and its neurological manifestations was studied in the present work. One hundred and thirty five mice were classified into three groups. GI: received SB alone. GII: received SB before & after infection with H. nana and GIII: infected with H. nana. All groups were subjected to parasitological, histopathological, immunohistochemical and biochemical assays. The results revealed a significant decrease in IL-4 serum level with a significant increase in gamma amino butyric acid (GABA) and decrease in zinc brain levels in GI, while GII showed non significant increase in IL-4 level that resulted in a highly significant increase in the mean number of cysticercoids and adult worms with delayed expulsion as compared to GIII. This was reflected on histopathological and immunohistochemical changes in the brain. Also, there was a highly significant increase in GABA and decrease in zinc brain levels in GII to the degree that induced behavioral changes. This emphasizes the possible synergistic effect of SB on the neurological manifestations of H. nana and could, in part, explain the increased incidence of behavioral changes in children exposed to high doses of SB and unfortunately have H. nana infection.

The findings of capsule endoscopy in patients with common variable immunodeficiency syndrome.

BACKGROUND/AIMS: Common variable immunodeficiency syndrome (CVIS) is a primary immunodeficiency disorder characterized by reduced serum immunoglobulins and heterogeneous clinical features. Parasitic and bacterial infections are very common complications of the syndrome. Capsule endoscopy (CE) represents a new and highly innovative method of demonstrating the small intestinal diseases. We evaluated the practical usefulness and diagnostic yield of CE in three patients with CVIS. METHODOLOGY: Between January 2003 and September 2004 CE was performed in 31 patients for different indications including mostly obscure gastrointestinal bleeding. We particularly evaluated 3 patients with CVIS whose diagnosis was based on serum immunoglobulins levels, clinical features and intestinal biopsy. The three CVIS patients with a median age of 25.6 years (ranged 21-34 years) have been followed-up for a period of 6.3 years (range 3-9 years). After introduction of CE in our medical center, this technique was performed with a Given M2A video capsule system in three patients to explain chronic severe and refractory diarrhea and iron deficiency anemia. RESULTS: All three patients were able to complete the study. In one of the three patients, CE demonstrated unlimited sessile and sometimes pedunculated polyp-like lesions of 2 to 6mm in diameter starting from antrum of the stomach to terminal ileum without escaping fashion and a parasite, Hymenolepsis nana that was located in the ileum of the patient. Biopsy obtained by conventional endoscopy from small intestine and antrum demonstrated typical nodular lymphoid hyperplasia. In the second patient, the same capsule endoscopic and histological findings were found on the mucosa of the duodenum and jejunum but not ileum and the stomach. In the third patient in whom the follow-up period was 3 years, CE revealed no abnormality through the small intestine. CONCLUSIONS: Our data indicated that CE may be necessary for the patients with CVIS to evaluate not only the complications but also extension of the small intestinal involvement.

Helminth infection enhances disease in a murine TH2 model of colitis.

BACKGROUND & AIMS: There is convincing evidence from animal and human studies that infection with parasitic helminths can alleviate the histopathology and symptoms of colitis. Here the ability of the rat tapeworm Hymenolepis diminuta to affect the course of oxazolone-induced colitis (a TH2 model) was assessed. METHODS: Mice were infected with H diminuta and 8 days later they received oxazolone (3 mg in 50% EtOH, intrarectal). On autopsy (3 or 7 days postoxazolone), disease severity was assessed by macroscopic clinical scores, histologic damage scores, myeloperoxidase and eosinophil peroxidase activity, and cytokine synthesis. RESULTS: As gauged by all markers of gut function, infection with H diminuta caused a significant exacerbation of oxazolone-induced colitis. Indeed, while mice receiving oxazolone only began to recover approximately 3-4 days posttreatment, the cotreated group continued to deteriorate. Helminth infection, independent of oxazolone administration, enhanced IL-4, IL-5, IL-10, and IL-13 production from in vitro stimulated immune cells and evoked increases in colonic eosinophil peroxidase of cotreated mice. Finally, while knockout of natural killer (NK) and NK-T cells by administration of a neutralizing NK1.1 antibody reduced the inflammation in oxazolone and oxazolone + H diminuta-treated animals, mice in the latter group still displayed significant colitis. CONCLUSIONS: We have shown that H diminuta infection is beneficial in other models of colitis. The current data is presented as a caveat to the position that parasitic helminths in general can be considered as a therapy for heterogeneous inflammatory disorders without careful analysis of the immunologic basis of the condition.

Intestinal permeability in Hymenolepis nana as reflected by non invasive lactulose/mannitol dual permeability test and its impaction on nutritional parameters of patients.

Assessment of Hymenolepis nana infection among 102 children and adults of both sexes (5-16 years) residing 2 Welfare Institutes (Giza and Cairo) showed a prevalence of 22.33%. The effect of H. nana on intestinal permeability and on nutritional parameters of patients was studied. A total of 46 subjects were divided into 2 groups: GI (20 H. nana patients) and GII (26 parasite-free control). Both groups were subjected to lactulose/mannitol dual permeability test, anthropometric study, estimation of vitamin B12 and folate levels in plasma and estimation of haemoglobin (HB)%, RBCs and WBCs counts and haematocrite value (HCT%) for anaemia. The H. nana patients showed significant higher percent (P = 0.04) of altered intestinal permeability versus controls denoting intestinal leakage, significant means lower levels of vitamin B12 (P = 0.01) and folate (P < 0.04) in blood plasma versus control denoting liability to vitamin B12 & folate deficiencies. Means value of HB%, RBC & WBC counts and HCT% showed generalized decrease but without significant difference in H. nana patients and control denoting anaemia liability. The percent of stunting (HAZ < or =2) and of wasting (WAZ < or =2) were higher among H. nana patients versus controls but without significant difference (P = 0.19 & P = 0.47 respectively).

[Transmission of schistosomiasis in an urban population and prevalence of intestinal helminthiasis in Bamako, Mali ]. / Transmission de la schistosomose urbaine et prévalence des helminthoses intestinales à Bamako, Mali.

Parasitological, malacological and anthropological studies were performed to assess the prevalence of Schistosoma haematobium and S. mansoni in schoolchildren living in the suburban area of Bamako. A total of 1017 schoolchildren aged 6-14 years were selected in two different areas between September 1997 and December 1999. In Djikoroni, the prevalence of S. haematobium and S. mansoni was 80.7% (339/420) and 22.8% (85/372) respectively. There was no significant difference of prevalence and intensity of infection with S. haematobium between schools, gender and age (p > 0.05), whereas, those of S. mansoni were higher in the vicinity of (+/- 100 m from) major sites where infected Biomphalaria pfeifferi were found (p < 0.001). In Niomirambougou, S. haematobium was prevalent in 46.7% (279/597) and S. mansoni in 28.2% (134/475). Boys and children aged 11-14 years were more infected (p < 0.001). Associated intestinal helminths (Hymenolepis nana, Necator americanus and Ascaris lumbricoides) were relatively scarce (prevalence < 1%). The prevalences of schistosome infected snails intermediate host were relatively high, 49.3% (100/203) in B. pfeifferi, 20.6% (88/138) in B. truncatus and 24.1% (7/29) in B. globosus. We recorded a total of 2514 water contacts about which 1130 in December and 1384 in January. Most of the children, 42.9% (1077/2511) were attracted to water bodies for bathing, swimming and playing, suggesting the lack of recreational facilities in these areas. Developing local control programmes in schools located in the vicinity of water bodies would contribute to break the parasite transmission cycle in Bamako.

Hymenolepis nana: a common cause of paediatric diarrhoea in urban slum dwellers in India.

The prevalence of intestinal parasitic infections was studied for a period of 5 years (April 1996-April 2001) among urban slum dwellers. All age groups were represented in the study. Parasitological examinations were performed on 939 faecal specimens collected on a household basis. The total prevalence of pathogenic parasites was 33.6 per cent. No significant age and sex differences in pathogenic parasites were observed. The prevalence of intestinal helminths and pathogenic protozoa was as follows: Hymenolepis nana (9.9 per cent), Ascaris lumbricoides (8.5 per cent), Giardia lamblia (8.4 per cent) and Entamoeba histolyticaldispar (3.7 per cent). Thirty-four E. histolytica/dispar positive samples were cultured and speciation was done using polymerase chain reaction (PCR). The predominant isolate was E. dispar compared to E. histolytica. The notable finding of the present study was high prevalence of Hymenolepis nana compared with other parasitic infections in slum dwellers.

Endoscopic evaluation of chronic human immunodeficiency virus-related diarrhea: is colonoscopy superior to flexible sigmoidoscopy?

OBJECTIVES: In patients with chronic human immunodeficiency virus (HIV)-related diarrhea undergoing lower endoscopy, the decision to perform flexible sigmoidoscopy or colonoscopy is controversial. The purpose of this study is twofold: 1) to evaluate the diagnostic yield of colonoscopy in a large group of patients with chronic HIV-related diarrhea and negative stool studies, and 2) to determine whether colonoscopy is superior to flexible sigmoidoscopy in this setting. METHODS: All HIV-infected patients with chronic diarrhea who were referred for diagnostic colonoscopy at Bellevue Hospital Center between January 1992 and December 1996 were identified. Patient charts, pathology reports, and endoscopy records were reviewed. RESULTS: During the 5-yr study period, 317 consecutive patients with chronic unexplained diarrhea undergoing colonoscopy were identified. A potential cause of diarrhea was found in 116 patients (36.6%). Cytomegalovirus was the most common pathogen detected (24%). The yield of colonoscopy was significantly higher in patients with a CD4 count of <100 cells/mm3 than in those with higher CD4 counts (44.8% vs 6.4%, p < 0.0001). Thirty percent of pathogens and 75% of lymphomas were identified only on biopsies taken from the proximal colon, well beyond the reach of the flexible sigmoidoscope. Importantly, 94% of the pathogens that were found only in the proximal colon were organisms for which effective therapy is currently available. CONCLUSIONS: Colonoscopy is superior to flexible sigmoidoscopy in HIV-infected patients with chronic unexplained diarrhea. If flexible sigmoidoscopy had been performed instead of colonoscopy, 30% of pathogens would have been missed and 75% of lymphomas would have escaped detection.