Treatment and outcomes among patients with Cryptococcus gattii infections in the United States Pacific Northwest.

BACKGROUND: Cryptococcus gattii is a fungal pathogen causing an emerging outbreak in the United States Pacific Northwest (PNW). Treatment guidelines for cryptococcosis are primarily based on data from C. neoformans infections; applicability to PNW C. gattii infection is unknown. We evaluated the relationship between initial antifungal treatment and outcomes for PNW C. gattii patients. METHODS: Cases were defined as culture-confirmed invasive C. gattii infections among residents of Oregon and Washington States during 2004-2011. Clinical data were abstracted from medical records through one year of follow-up. Recommended initial treatment for central nervous system (CNS), bloodstream, and severe pulmonary infections is amphotericin B and 5-flucytosine; for non-severe pulmonary infections, recommended initial treatment is fluconazole. Alternative initial treatment was defined as any other initial antifungal treatment. RESULTS: Seventy patients survived to diagnosis; 50 (71%) received the recommended initial treatment and 20 (29%) received an alternative. Fewer patients with pulmonary infections [21 (64%)] than CNS infections [25 (83%)] received the recommended initial treatment (p = 0.07). Among patients with pulmonary infections, those with severe infections received the recommended initial treatment less often than those with non-severe infections (11% vs. 83%, p<0.0001). Eight patients with severe pulmonary infections received alternative initial treatments; three died. Four patients with non-severe pulmonary infections received alternative initial treatments; two died. There was a trend towards increased three-month mortality among patients receiving alternative vs. recommended initial treatment (30% vs. 14%, p = 0.12), driven primarily by increased mortality among patients with pulmonary disease receiving alternative vs. recommended initial treatment (42% vs. 10%, p = 0.07). CONCLUSIONS: C. gattii patients with pulmonary infections--especially severe infections--may be less likely to receive recommended treatment than those with CNS infections; alternative treatment may be associated with increased mortality. Reasons for receipt of alternative treatment among C. gattii patients in this area should be investigated, and clinician awareness of recommended treatment reinforced

Assessment of Quadrivalent Human Papillomavirus Vaccine Safety Using the Self-Controlled Tree-Temporal Scan Statistic Signal-Detection Method in the Sentinel System

Abstract The self-controlled tree-temporal scan statistic—a new signal-detection method—can evaluate whether any of a wide variety of health outcomes are temporally associated with receipt of a specific vaccine, while adjusting for multiple testing. Neither health outcomes nor postvaccination potential periods of increased risk need be prespecified. Using US medical claims data in the Food and Drug Administration’s Sentinel system, we employed the method to evaluate adverse events occurring after receipt of quadrivalent human papillomavirus vaccine (4vHPV). Incident outcomes recorded in emergency department or inpatient settings within 56 days after first doses of 4vHPV received by 9- through 26.9-year-olds in 2006–2014 were identified using International Classification of Diseases, Ninth Revision, diagnosis codes and analyzed by pairing the new method with a standard hierarchical classification of diagnoses. On scanning diagnoses of 1.9 million 4vHPV recipients, 2 statistically significant categories of adverse events were found: cellulitis on days 2–3 after vaccination and “other complications of surgical and medical procedures” on days 1–3 after vaccination. Cellulitis is a known adverse event. Clinically informed investigation of electronic claims records of the patients with “other complications” did not suggest any previously unknown vaccine safety problem. Considering that thousands of potential short-term adverse events and hundreds of potential risk intervals were evaluated, these findings add significantly to the growing safety record of 4vHPV

Initial therapy received by <i>Cryptococcus gattii</i> patients.

<p>Initial therapy received by <i>Cryptococcus gattii</i> patients.</p

Three-month mortality among patients by site of infection and by initial therapy received^*.

<p>*Mortality measured from date of diagnosis; 4 patients died prior to diagnosis and receipt of antifungal therapy and are not included in this table.</p

Characteristics of patients with invasive <i>Cryptococcus gattii</i> infection in United States Pacific Northwest who survived to diagnosis (N = 70).

a<p>VGII molecular type isolates include isolates from the three outbreak genotypes, VGIIa, VGIIb, and VGIIc.</p>b<p>n = 69.</p>c<p>Categories not mutually exclusive.</p

Epidemic Cholera in a Crowded Urban Environment, Port-au-Prince, Haiti

We conducted a case–control study to investigate factors associated with epidemic cholera. Water treatment and handwashing may have been protective, highlighting the need for personal hygiene for cholera prevention in contaminated urban environments. We also found a diverse diet, a possible proxy for improved nutrition, was protective against cholera