Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni.

Infections by the zoonotic foodborne bacterium Campylobacter jejuni (C. jejuni) are among the most frequent causes of bacterial gastroenteritis worldwide. The aim was to evaluate the relationship between epithelial barrier disruption, mucosal immune activation, and vitamin D (VD) treatment during C. jejuni infection, using intestinal epithelial cells and mouse models focused on the interaction of C. jejuni with the VD signaling pathway and VD treatment to improve C. jejuni-induced barrier dysfunction. Our RNA-Seq data from campylobacteriosis patients demonstrate inhibition of VD receptor (VDR) downstream targets, consistent with suppression of immune function. Barrier-preserving effects of VD addition were identified in C. jejuni-infected epithelial cells and IL-10-/- mice. Furthermore, interference of C. jejuni with the VDR pathway was shown via VDR/retinoid X receptor (RXR) interaction. Paracellular leakiness of infected epithelia correlated with tight junction (TJ) protein redistribution off the TJ domain and apoptosis induction. Supplementation with VD reversed barrier impairment and prevented inhibition of the VDR pathway, as shown by restoration of transepithelial electrical resistance and fluorescein (332 Da) permeability. We conclude that VD treatment restores gut epithelial barrier functionality and decreases bacterial transmigration and might, therefore, be a promising compound for C. jejuni treatment in humans and animals.

The role of infectious agents, antibiotics, and antiviral therapy in the treatment of extranodal marginal zone lymphoma and other low-grade lymphomas.

OPINION STATEMENT: There is strong evidence to corroborate the association with Helicobacter pylori (Hp) to gastric extranodal marginal zone lymphoma (ENMZL) and hepatitis C virus (HCV) to splenic/nodal marginal zone lymphoma. Koch's postulates generally hold for these two associations and eradication of the infectious agent is well supported. Hp eradication (HPE) is recommended as front-line therapy for early stage gastric ENMZL regardless of Hp status. Complete response (CR) rate for Hp-negative patients is not as high as for Hp-positive patients; however, the benign nature of HPE and high rates of salvage allow this strategy to be safe while sparing some Hp-negative patients from systemic therapy or radiation. Similarly for HCV-seropositive patients, treatment with antivirals should be strongly considered as first-line for those who do not require immediate cytoreductive therapy or at some point even after completing chemoimmunotherapy. The controversy regarding the role for antibiotics is greatest for primary ocular adnexal lymphoma (POAL). Considering the low incidence of Chlamydia psittaci (Cp) infection with OAL and the challenges to reliably identifying Cp, we typically do not consider doxycycline in POAL treatment. Involved-field radiotherapy (IFRT) remains the treatment of choice for most with unilateral POAL. However, if reliable detection of Cp is available and Cp is identified, patients with unilateral low tumor stage POAL who do not require immediate radiotherapy could be considered for doxycycline as front-line treatment. Other infectious associations to indolent lymphomas have been made, including Borrelia borgdorferi (Bb) in cutaneous lymphoma and Campylobacter in immunoproliferative small intestinal disease (IPSID), but these associations are not as strong and primary treatment targeting the infectious agents is not recommended.

Brucellosis, genital campylobacteriosis and other factors affecting calving rate of cattle in three states of Northern Nigeria.

BACKGROUND: Reproductive diseases limit the productivity of cattle worldwide and represent an important obstacle to profitable cattle enterprise. In this study, herd brucellosis and bovine genital campylobacteriosis (BGC) status, and demographic and management variables were determined and related to predicted calving rate (PrCR) of cattle herds in Adamawa, Kaduna and Kano states, Nigeria. Serum samples, preputial scrapings, questionnaire data, trans-rectal palpation and farm records were used from 271 herds. The Rose-Bengal plate test and competitive enzyme-linked immunosorbent assay were used for Brucella serology and culture and identification from preputial samples for BGC. A herd was classified as positive if one or more animals tested positive. The PrCR was determined as the number of calvings expected during the previous 6 and next 6 months as a percentage of the number of postpubertal heifers and cows in the herd. A multilevel linear regression model was used to estimate the herd-level effect of Brucella abortus seropositivity, Campylobacter fetus infection and other factors on calculated PrCR. RESULTS: The reproductive performance of the cattle herds was generally poor: Only 6.5% of the nursing cows were pregnant and 51.1% were non-pregnant and acyclic; the mean annual PrCR was 51.4%. Brucella abortus and C. fetus infection of herds were independently associated with absolute reduction in PrCR of 14.9% and 8.4%, respectively. There was also a strong negative association between within-herd Brucella seroprevalence and PrCR. Presence of small ruminants, animal introduction without quarantine and the presence of handling facilities were associated with lower PrCR, whereas larger herd size, supplementary feeding, routine mineral supplementation and care during parturition were associated with higher PrCR. CONCLUSIONS: Brucellosis and BGC may be largely responsible for the poor reproductive performance of indigenous Nigerian cattle. Farmer education and measures to improve the fertility of cattle herds are suggested.

Burden of laboratory-confirmed Campylobacter infections in Guatemala 2008-2012: results from a facility-based surveillance system.

INTRODUCTION: Campylobacteriosis is one of the leading causes of gastroenteritis worldwide. This study describes the epidemiology of laboratory-confirmed Campylobacter diarrheal infections in two facility-based surveillance sites in Guatemala. METHODS: Clinical, epidemiologic, and laboratory data were collected on patients presenting with acute diarrhea from select healthcare facilities in the departments of Santa Rosa and Quetzaltenango, Guatemala, from January 2008 through August 2012. Stool specimens were cultured for Campylobacter and antimicrobial susceptibility testing was performed on a subset of isolates. Multidrug resistance (MDR) was defined as resistance to ≥3 antimicrobial classes. RESULTS: Campylobacter was isolated from 306 (6.0%) of 5137 stool specimens collected. For children <5 years of age, annual incidence was as high as 1288.8 per 100,000 children in Santa Rosa and 185.5 per 100,000 children in Quetzaltenango. Among 224 ambulatory care patients with Campylobacter, 169 (75.5%) received metronidazole or trimethoprim-sulfamethoxazole, and 152 (66.7%) received or were prescribed oral rehydration therapy. Antimicrobial susceptibilities were tested in 96 isolates; 57 (59.4%) were resistant to ciprofloxacin and 12 (12.5%) were MDR. CONCLUSION: Campylobacter was a major cause of diarrhea in children in two departments in Guatemala; antimicrobial resistance was high, and treatment regimens in the ambulatory setting which included metronidazole and trimethoprim-sulfamethoxazole and lacked oral rehydration were sub-optimal.

Empiric antimicrobial therapy and infectious diarrhea. Do we need local guidelines?

BACKGROUND: In the management of acute diarrhea, administration of antibiotics may be indicated. Appropriate antimicrobial therapy can shorten illness, reduce morbidity and can be life-saving in invasive infections. Emergence of microbial strains resistant to commonly used antibiotics means that treatment failures may become common. Because of changing patterns of resistance, knowledge of recent local patterns of susceptibility can guide the initial choice of antibiotics. METHODS: A retrospective study was conducted to investigate the epidemiology of infective gastroenteritis in patients over 14years old in the region of Chania (Crete). We reviewed all positive stool cultures and susceptibilities of the pathogens recovered from patients with symptoms of acute diarrhea, from 2003 until October 2010. RESULTS: Out of 194 positive stool cultures, we observed 139 cases of Salmonella enterica and 48 cases of Campylobacter jejuni. During the last 3years of observation there was an increased incidence of C. jejuni, especially after the tap water outbreak that occurred in our region in 2009. DISCUSSION: In the vast majority of acute diarrhea in adults, antibiotics are of no benefit and overprescription may confer to side effects, costs and emergence of resistance. Antibiotics are initiated in cases of febrile diarrheas especially those believed to have moderate to severe disease. Considering the increased incidence of C. jejuni and the resistance of the great majority of isolated strains to quinolones as well as the sensitivity of Salmonella spp. to azithromycin, administration of azithromycin empirically for acute diarrhea, when indicated, could be appropriate in our region.

[Immune-pharmacology study on the immunoregulatory effects of Dabuyin Wan in autoimmune mice induced by Campylobacter jejuni].

OBJECTIVE: To study the immunoregulatory effect of Dabuyin Wan (DBYW) on cytokines of IFN-gamma and IL-4 and proliferation of T, B lymphocytes in autoimmune mice induced by Campylobacter jejuni. METHODS: Healthy female ICR mice were divided into 8 groups at random: normal control group (N), model group (M), model control group (MC), five different time administration groups (30 min, 1h, 1.5h, 2h, 3h). The mice were induced by Campylobacter jejuni with Complete Freund's Adjuvant as autoimmune animal model except N group. From the fifteenth day after primary immunization, the administration groups were given DBYW through gastric route in a dosage of 0.4 g/ml. At the same time, MC group were given physiological saline instead. All the administration lasted for 10 days. Blood samples were taken 30 min, 1h, 1.5h, 2h and 3h respectively after the last administration to detect the proliferation of T, B lymphocytes and to cultivate T lymphocytes which were taken from M group. The concentrations of gamma-interferon (IFN-gamma) and interleukin-4 (IL-4) in culture supernantants were measured by an enzyme-linked immunosorbent asay (ELISA) after 48h. The drug efficacy was evaluated by marking the curve of time-effect relationship in the chart. RESULTS: It was found that the concentrations of IFN-gamma was significantly lower in cultures with the drug-containing serum taken at 1-1.5 h after the treatment than that in cultures with the MC control serum (P < 0.01). Only the serum taken at 1.5h was found to enhance the production of IL-4 (P < 0.05). The proliferation of T, B lymphocytes was markedly inhibited by the drug-containing serum taken at 1-1.5 h after the treatment (P < 0.01). CONCLUSION: The drug-containing serum in mice taken at 1-1.5 h after ingestion of DBYW can regulate the immunologic function of autoimmune mice induced by Campylobacter jejuni.

Persistent diarrhea, arthritis, and other complications of enteric infections: a pilot survey based on California FoodNet surveillance, 1998-1999.

Numerous complications of enteric infections have been described, including persistent diarrhea, reactive arthritis, and Guillain-Barre syndrome. We determined the frequency of self-reported complications of enteric infections in a pilot study in the California site of the Foodborne Diseases Active Surveillance Network. From 1 April 1998 through 31 March 1999, active surveillance identified 1454 infections in Alameda and San Francisco counties, of which 52% were Campylobacter infections, 22% were Salmonella infections, 15% were Shigella infections, 6% were Cryptosporidium infections, 2% were Escherichia coli O157:H7 infections, 2% were Yersinia infections, and 1% were Vibrio infections. We mailed surveys to 1331 eligible participants, and 571 (43%) were returned. A new health problem following infection was reported by 153 (27%) of the respondents: 12 (8%) reported new onset of joint pain and 53 (35%) reported new gastrointestinal symptoms, of whom 38 reported persistent diarrhea, including 2 who reported irritable bowel syndrome. Three respondents reported hair loss. The frequency, nature, and etiology of these complications merit further investigation.

Treatment of infectious diarrhea in children.

Diarrheal diseases remain an important cause of childhood morbidity and death in developing countries, although diarrheal deaths have significantly declined in recent years, mostly due to successes in the implementation of oral rehydration therapy (ORT), which is the principal treatment modality. Diarrhea may occur for varied reasons; however, most episodes of diarrhea in developing countries are infectious in origin. Three clinical forms of diarrhea (acute watery diarrhea, invasive diarrhea, and persistent diarrhea) have been identified to formulate a management plan. Acute diarrhea may be watery (where features of dehydration are prominent) or dysenteric (where stools contain blood and mucus). Rehydration therapy is the key to management of acute watery diarrhea, whereas antimicrobial agents play a vital role in the management of acute invasive diarrhea, particularly shigellosis and amebiasis. In persistent diarrhea, nutritional therapy, including dietary manipulations, is a very important aspect in its management, in addition to rehydration therapy. Rehydration may be carried out either by the oral or intravenous route, depending upon the degree of dehydration. Oral rehydration salts (ORS) solution (World Health Organization formula) is recommended for ORT. Intravenous fluid is recommended for initial management of severe dehydration due to diarrhea, followed by ORT with ORS solution for correction of ongoing fluid losses. Antimicrobial therapy is beneficial for cholera and shigellosis. Antiparasitic agents are indicated only if amebiasis and giardiasis are present. Appropriate feeding during diarrhea is recommended for nutritional recovery and to prevent bodyweight loss. Antidiarrheal agents do not provide additional benefit in the management of infectious diarrhea. Although some probiotics have been shown to be beneficial in the treatment of acute diarrhea due to rotavirus, their use in the treatment of diarrhea is yet to be recommended, even in developed countries. The children of developing countries might benefit from zinc supplementation during the diarrheal illness, but its mode of delivery and cost effectiveness are yet to be decided.

An unusual case of refractory Campylobacter jejuni infection in a patient with X-linked agammaglobulinemia: successful combined therapy with maternal plasma and ciprofloxacin.

An unusual hippurate-negative strain of Campylobacter jejuni caused a chronic refractory infection in a patient with X-linked agammaglobulinemia; this infection persisted for > 2 years despite therapy with various antibiotics and immunoglobulins (Igs). To characterize the defense status of this patient, several in vitro studies, including those with T cells and polymorphonuclear leukocytes (PMNLs), were performed. T cell responses specific for C. jejuni were only weak in this patient. Chemiluminescence and bacterial killing studies with PMNLs revealed that the bactericidal activity of PMNLs against Campylobacter was enhanced more vigorously by maternal serum than by commercial Ig preparations. On the basis of these results, combined treatment with ciprofloxacin and maternal plasma was initiated, and the C. jejuni infection was rapidly cured. This case report shows that in vitro immunologic assays may be useful for characterizing immune functions of patients with chronic or refractory C. jejuni infections, thus leading to individual treatment strategies.

Use of ciprofloxacin for successful eradication of bacteremia due to Campylobacter cinaedi in a human immunodeficiency virus-infected person.

A 36-year-old homosexual man who was infected with human immunodeficiency virus presented with a 2-month history of fever and intermittent diarrhea. Stool cultures were negative for bacterial pathogens, ova, parasites, and acid-fast organisms. An initial blood culture became positive after 5 days for a curved, gram-negative rod that was identified later as Campylobacter cinaedi. The patient received a series of antibiotic regimens, including a 2-week course of erythromycin followed by a 2-week course of tetracycline, but follow-up blood cultures continued to yield C. cinaedi. The patient was then treated with a 2-week course of oral ciprofloxacin; he remained asymptomatic 11 weeks later, at which time a blood culture was negative for C. cinaedi. To the best of our knowledge, this is the first documented case of symptomatic bacteremia due to C. cinaedi that was successfully treated with ciprofloxacin.

The presence of Campylobacter pylori in nonsteroidal antiinflammatory drug associated gastritis.

Although Campylobacter pylori has recently been causally linked to active chronic gastritis and peptic ulcer disease, its relationship to nonsteroidal antiinflammatory drug (NSAID) associated gastritis is unclear. We performed a case-control study of 100 patients who had undergone gastritis biopsy. Blinded review of Giemsa stained slides demonstrated the presence of C. pylori in 32% of 19 NSAID treated cases with active chronic gastritis vs 3% of 36 controls with chronic gastritis not taking NSAID, and 69% of 45 "positive" controls with active chronic gastritis not taking NSAID (p less than 0.001). Our results suggest a possible multifactorial etiology of NSAID associated gastritis.