The evolution of respiratory Cryptosporidiosis: evidence for transmission by inhalation.

The protozoan parasite Cryptosporidium infects all major vertebrate groups and causes significant diarrhea in humans, with a spectrum of diseases ranging from asymptomatic to life-threatening. Children and immunodeficient individuals are disproportionately affected, especially in developing countries, where cryptosporidiosis contributes substantially to morbidity and mortality in preschool-age children. Despite the enormous disease burden from cryptosporidiosis, no antiprotozoal agent or vaccine exists for effective treatment or prevention. Cryptosporidiosis involving the respiratory tract has been described for avian species and mammals, including immunocompromised humans. Recent evidence indicates that respiratory cryptosporidiosis may occur commonly in immunocompetent children with cryptosporidial diarrhea and unexplained cough. Findings from animal models, human case reports, and a few epidemiological studies suggest that Cryptosporidium may be transmitted via respiratory secretions, in addition to the more recognized fecal-oral route. It is postulated that transmission of Cryptosporidium oocysts may occur by inhalation of aerosolized droplets or by contact with fomites contaminated by coughing. Delineating the role of the respiratory tract in disease transmission may provide necessary evidence to establish further guidelines for prevention of cryptosporidiosis.

Hyperimmune bovine colostrum as a novel therapy to combat Clostridium difficile infection.

BACKGROUND: Clostridium difficile is a primary cause of antibiotic-associated diarrhea that typically develops when gut microbiota is altered. Conventional treatment for C. difficile infection (CDI) is additional antimicrobial administration, which further disrupts normal intestinal microbiota, often resulting in poor treatment outcomes. METHODS: A pregnant dairy cow was repeatedly immunized with recombinant mutants of toxins A and B produced by C. difficile, and the resultant hyperimmune bovine colostrum (HBC) was evaluated for therapeutic efficacy in gnotobiotic piglets with diarrhea due to CDI. Control piglets received nonimmune colostrum. To determine the impact of HBC on gut microbiota, 1 of 2 groups of piglets transplanted with normal human gut microbiota was treated with HBC. RESULTS: Nonimmune colostrum-treated piglets developed moderate to severe diarrhea and colitis. In contrast, HBC-treated piglets had mild or no diarrhea and mild or no colitis. Lyophilization had no detectable impact on HBC efficacy. HBC had no discernible effect on the composition of normal human gut microbiota in the porcine intestinal tract. CONCLUSIONS: HBC provides an oral, cost-effective, and safe alternative to antibiotic therapy for CDI. By preserving intestinal microbiota, HBC may be more efficacious than antibiotics. Additional studies are warranted to establish HBC as a viable immunotherapeutic agent for human use against CDI.

Field assessment of potential exposure of dogs to leptospirosis by measuring antibody titers in dogs: a multisite study in five geographic regions of the United States.

Leptospirosis vaccine for dogs in the United States is considered a lifestyle or non-core vaccine, making individual veterinary practitioners responsible for determining if vaccination is necessary for their patients. Veterinary professionals often base their vaccination decisions on local rates of clinical cases. However, even subclinical leptospirosis infections have zoonotic potential. The microscopic agglutination test (MAT) is effective for screening unvaccinated animals, but previous vaccination can lead to inconsistent results and variable MAT titers over time. This prospective research survey evaluated if local experience was sufficient to justify selective vaccination for leptospirosis. MAT analyses were performed on sera collected from well-cared-for, unvaccinated dogs residing in five different geographies across the United States: South-Central (East Texas), New England, the Mid-Atlantic (North Carolina and Virginia), Midwest (Wisconsin/northern Illinois), and Southwest (southern California). Thirty-eight clinics participated, submitting a total of 1345 qualified samples from unvaccinated dogs over 1 year of age. 11.6% of these unvaccinated dogs had MAT titers for one or more serogroups of Leptospira. While seropositivity does not necessarily indicate that disease will result or that a specific serovar is involved, these MAT-positive cases do indicate that the potential for exposure exists and clinical signs or a carrier-state could result from infection. These survey results would indicate that a more aggressive vaccination protocol for leptospirosis should be considered.

Clinical Significance of Respiratory Involvement in Cryptosporidiosis: Cross-Sectional Study of Children with Diarrhea and Respiratory Symptoms in Uganda.

Respiratory cryptosporidiosis is considered an occasional, late-stage complication of HIV/AIDS. This study aimed to assess the clinical importance of respiratory cryptosporidiosis in children with diarrhea and respiratory symptoms at Mulago Hospital, Kampala, Uganda. Children aged 9 to 36 months presenting with diarrhea and cough or unexplained tachypnea (N = 1,918) were screened for fecal Cryptosporidium using polymerase chain reaction (PCR). Children with positive stool samples were eligible for further diagnostic tests, including sputum induction. Sputum samples were subjected to PCR for Cryptosporidium, as well as routine microbiology (culture and gram stain) and auramine stain for tuberculosis. Regression analyses were used to investigate 1) factors associated with respiratory cryptosporidiosis and 2) whether respiratory cryptosporidiosis was independently associated with hospitalization. Prevalence of enteric cryptosporidiosis was 260/1,918 (13.6%) (>80% Cryptosporidium hominis). Of the 236 children who had sputum available for analysis, 62 (26.3%) had Cryptosporidium in the sputum, only two of whom had HIV infection. Children with Cryptosporidium in the sputum were more likely to have abnormal oxygen saturation at presentation (SpO2 <96%; P = 0.053); no other differences in frequency or severity of respiratory signs were noted. No alternative bacterial cause of respiratory symptoms was identified in 37.7% of children with respiratory cryptosporidiosis, compared with 23.6% of children without (P = 0.04). Sputum-positive children had twice the odds of hospitalization compared with children without Cryptosporidium infection at this site (adjusted odds ratio = 2.08, 95% confidence interval: 1.02-4.22; P = 0.043). Respiratory tract involvement is common in children with intestinal cryptosporidiosis who are experiencing respiratory symptoms. Such children may experience some degree of respiratory compromise and may be at increased risk for hospitalization.

Expectoration of Cryptosporidium Parasites in Sputum of Human Immunodeficiency Virus-Positive and -Negative Adults.

Respiratory cryptosporidiosis is thought to be a rare, end-stage complication of HIV. Few studies have systematically examined the frequency of such infection in adults. Sputum specimens submitted for tuberculosis (TB) testing at Mulago Hospital, Uganda, were anonymously retested for Cryptosporidium using real-time polymerase chain reaction (PCR). Visual confirmation using immunofluorescence confocal microscopy was performed for a subset of PCR-positive samples. Of 824 sputum samples tested, 24 (2.9%) were Cryptosporidium positive. Prevalence in sputum ranged between 0% and 10% in each month of the study and exceeded TB prevalence in some months. In this referral population, respiratory Cryptosporidium prevalence was lower in people with HIV (1.3% versus 4.4% without HIV, P = 0.028) and higher in those with TB (6.8% versus 2.6% without TB, P = 0.086). The weak association between respiratory Cryptosporidium infection and TB persisted after controlling for HIV (odds ratio = 3.2, 95% confidence interval: 0.9, 11.8; P = 0.080). This is the first study to document adult respiratory tract cryptosporidiosis in a referral population with presumed TB. These findings 1) confirm that Cryptosporidium respiratory infection occurs in HIV-negative and -positive adults; 2) suggest there is potential for Cryptosporidium to be disseminated or transmitted by coughing or expectoration; and 3) identify possible synergy between Cryptosporidium and TB in the respiratory tract.

Hyperimmune bovine colostrum for treatment of GI infections: a review and update on Clostridium difficile.

Hyperimmune bovine colostrum (HBC), produced by vaccination of a cow during gestation, is rich in targeted immunoglobulins, and can be used to treat a variety of diseases. The published history of HBC use for treating gastrointestinal infections in humans has developed over the past several decades and demonstrates the promise of this type of therapeutic for GI infectious disease. HBC, or purified derivative products, have been used successfully for treatment or prevention of cryptosporidiosis, shigellosis, rotavirus, enterotoxigenic E. coli, and C. difficile infection (CDI). Given the positive results of previous studies using HBC for treatment of CDI, we have produced HBC with antibodies against the two most important virulence factors of C. difficile, TcdA and TcdB, using a novel recombinant vaccine. Our preliminary results demonstrate efficacy of the HBC product for treatment of CDI in the gnotobiotic piglet model, and warrant more thorough investigation. HBC may provide an effective treatment alternative to antibiotics, which can spare the normal gut microflora, and reduce rates of recurrence and antibiotic resistance.