Invasive Pneumococcal Disease Among Immunocompromised Persons: Implications for Vaccination Programs.

BACKGROUND: In 2012/2013, a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) was recommended for immunocompromised adults in the United States and Canada. To assess the potential benefits of this recommendation, we assessed the serotype-specific burden of invasive pneumococcal disease (IPD) among immunocompromised individuals. METHODS: From 1995 to 2012, population-based surveillance for IPD was conducted in Metropolitan Toronto and Peel Region, Canada. Disease incidence and case fatality were measured in immunocompromised populations over time, and the contribution of different serotypes determined. RESULTS: Overall, 2115/7604 (28%) episodes of IPD occurred in immunocompromised persons. IPD incidence was 12-fold higher (95% confidence interval [CI], 8.7-15) in immunocompromised compared to immunocompetent persons; the case fatality rate was elevated in both younger (odds ratio [OR] 1.8) and older (OR 1.3) adults. Use of immunosuppressive medications was associated with a 2.1-2.7 fold increase in the risk of IPD. Five years after PPV23 program implementation, IPD incidence had declined significantly in immunocompromised adults (IRR 0.57, 95% CI, .40-.82). Ten years after pediatric PCV7 authorization, IPD due to PCV7 serotypes had decreased by 90% (95% CI, 77%-96%) in immunocompromised persons of all ages. In 2011/2012, 37% of isolates causing IPD in immunocompromised persons were PCV13 serotypes and 27% were PPV23/not PCV13 serotypes. CONCLUSIONS: Immunocompromised individuals comprised 28% of IPD. Both PPV23 and herd immunity from pediatric PCV7 were associated with reductions in IPD in immunocompromised populations. PCV13 vaccination of immunocompromised adults may substantially reduce the residual burden until herd immunity from pediatric PCV13 is fully established.

Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.

IMPORTANCE: Clostridium difficile infection (CDI) is a major burden in health care and community settings. CDI recurrence is of particular concern because of limited treatment options and associated clinical and infection control issues. Fecal microbiota transplantation (FMT) is a promising, but not readily available, intervention. OBJECTIVE: To determine whether frozen-and-thawed (frozen, experimental) FMT is noninferior to fresh (standard) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, noninferiority trial enrolling 232 adults with recurrent or refractory CDI, conducted between July 2012 and September 2014 at 6 academic medical centers in Canada. INTERVENTIONS: Patients were randomly allocated to receive frozen (n = 114) or fresh (n = 118) FMT via enema. MAIN OUTCOMES AND MEASURES: The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events. Noninferiority margin was set at 15%. RESULTS: A total of 219 patients (n = 108 in the frozen FMT group and n = 111 in the fresh FMT group) were included in the modified intention-to-treat (mITT) population and 178 (frozen FMT: n = 91, fresh FMT: n = 87) in the per-protocol population. In the per-protocol population, the proportion of patients with clinical resolution was 83.5% for the frozen FMT group and 85.1% for the fresh FMT group (difference, -1.6% [95% CI, -10.5% to ∞]; P = .01 for noninferiority). In the mITT population the clinical resolution was 75.0% for the frozen FMT group and 70.3% for the fresh FMT group (difference, 4.7% [95% CI, -5.2% to ∞]; P < .001 for noninferiority). There were no differences in the proportion of adverse or serious adverse events between the treatment groups. CONCLUSIONS AND RELEVANCE: Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea. Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01398969.

Fever in a visitor to Canada: a case of mistaken identity.

We report a case of babesiosis in a traveler from India who was diagnosed with malaria on the basis of blood smears. Pan-Plasmodium PCR was positive, though species-specific assays were negative. Reexamination of blood smears and Babesia-specific PCR confirmed babesiosis. We highlight the overlapping clinical and diagnostic features of malaria and babesiosis and the potential cross-reactivity of Plasmodium primers in cases of babesiosis.

An elderly long-term care resident with crusted scabies.

Crusted scabies is a highly contagious form of scabies. Altered immune response, nutritional deficiencies and modified host response are all risk factors for crusted scabies. The authors report a case involving a patient found to have a chronic maculopapular, erythematous rash with large hyperkeratotic, white and grey plaques on the soles of both feet. An ultimate diagnosis of crusted scabies was reached after a delay in diagnosis suspected to be caused by the similarity in appearance to more common skin conditions such as psoriasis. After topical permethrin was unsuccessful, intermittent dosing of oral ivermectin resulted in a rapid reduction in cutaneous plaques.

La gale hyperkératosique est une forme de gale extrêmement contagieuse. Une détérioration de la réponse immunitaire, des carences nutritionnelles et une réponse modifiée de l'hôte en sont toutes des facteurs de risque. Les auteurs rendent compte d'un patient présentant une éruption maculopapuleuse et érythémateuse chronique comportant de grosses plaques hyperkératosiques blanches et grises sur la plante des deux pieds. Le diagnostic de gale hyperkératosique a été posé après un retard de diagnostic qu'on croit attribuable à sa similarité d'aspect avec des troubles cutanés plus courants, tels que le psoriasis. Après avoir essayé la perméthrine topique sans succès, une posologie intermittente d'ivermectine par voie orale a suscité la réduction rapide des plaques cutanées.

Previous antibiotic exposure and antimicrobial resistance in invasive pneumococcal disease: results from prospective surveillance.

BACKGROUND: Estimating the risk of antibiotic resistance is important in selecting empiric antibiotics. We asked how the timing, number of courses, and duration of antibiotic therapy in the previous 3 months affected antibiotic resistance in isolates causing invasive pneumococcal disease (IPD). METHODS: We conducted prospective surveillance for IPD in Toronto, Canada, from 2002 to 2011. Antimicrobial susceptibility was measured by broth microdilution. Clinical information, including prior antibiotic use, was collected by chart review and interview with patients and prescribers. RESULTS: Clinical information and antimicrobial susceptibility were available for 4062 (90%) episodes; 1193 (29%) of episodes were associated with receipt of 1782 antibiotic courses in the prior 3 months. Selection for antibiotic resistance was class specific. Time elapsed since most recent antibiotic was inversely associated with resistance (cephalosporins: adjusted odds ratio [OR] per day, 0.98; 95% confidence interval [CI], .96-1.00; P = .02; macrolides: OR, 0.98; 95% CI, .96-.99; P = .005; penicillins: OR [log(days)], 0.62; 95% CI, .44-.89; P = .009; fluoroquinolones: profile penalized-likelihood OR [log(days)], 0.62; 95% CI, .39-1.04; P = .07). Risk of resistance after exposure declined most rapidly for fluoroquinolones and penicillins and reached baseline in 2-3 months. The decline in resistance was slowest for macrolides, and in particular for azithromycin. There was no significant association between duration of therapy and resistance for any antibiotic class. Too few patients received multiple courses of the same antibiotic class to assess the significance of repeat courses. CONCLUSIONS: Time elapsed since last exposure to a class of antibiotics is the most important factor predicting antimicrobial resistance in pneumococci. The duration of effect is longer for macrolides than other classes.

Cutaneous nocardiosis complicating management of Crohn's disease with infliximab and prednisone.

Infliximab is a chimeric anti-tumour necrosis factor-alpha antibody that is efficacious in treating Crohn's disease. However, its immunomodulatory properties increase susceptibility to opportunistic infections. We present a case of cutaneous Nocardia infection in a patient who was taking infliximab for Crohn's disease. The case illustrates the challenges in the diagnosis and management of this disease and serves as a reminder of the complications associated with the use of immunomodulatory agents.

West Nile virus infection in 2002: morbidity and mortality among patients admitted to hospital in southcentral Ontario.

BACKGROUND: In August and September 2002 an outbreak of West Nile virus (WNV) infection occurred in southern Ontario. We encountered a number of seriously ill patients at our hospitals. In this article we document the clinical characteristics of these cases. METHODS: We conducted a retrospective chart review of patients who came to the attention of infectious disease or neurology consultants or the microbiology laboratories at 7 hospitals in the municipalities of Toronto, Peel and Halton, Ont. Patients were included if they had been admitted to hospital or stayed overnight in the emergency department, had serological evidence of WNV infection and had clinical evidence of WNV fever, aseptic meningitis, encephalomyelitis or motor neuronopathy. RESULTS: In all, 64 patients met the inclusion criteria; 57 had encephalitis or neuromuscular weakness or both, 5 had aseptic meningitis, and 2 had WNV fever. The mean age was 61 years (range 26-87). The patients were predominantly active, middle-aged or elderly people living independently in the community. Seven patients were immunocompromised A febrile prodromal illness preceded the neurological symptoms in almost all cases. The most common neurological abnormality was decreased level of consciousness; this frequently evolved to severe lower motor neuron neuromuscular weakness. Ataxia and swallowing disorders were frequent and important problems. Sixteen patients (25%) required intubation and mechanical ventilation because of a decreased level of consciousness, inability to clear secretions or respiratory muscle weakness; 9 others had disabling muscle weakness of one or more limbs. Ten patients died. The study patients were in hospital a total of 1856 patient-days, including 532 patient-days in an intensive care unit. Only 28% (13/47) of the patients who survived encephalitis or neuromuscular weakness, or both, were discharged home without additional support. Slow turnaround time for serological test results resulted in delayed diagnosis. INTERPRETATION: The 2002 WNV infection outbreak in Ontario caused serious morbidity and mortality in the subset of patients who had encephalitis or neuromuscular weakness severe enough to require hospital admission.