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Diagnostic testing for respiratory syncytial virus (RSV) is not routinely performed in adults. We estimated medically attended RSV seasonal incidence in a community cohort of adults ≥50 years old during four influenza seasons (2006-07 through 2009-10). Patients seeking care for acute respiratory illness (ARI) were prospectively enrolled and tested for RSV by multiplex RT-PCR. Results from enrolled patients were used to estimate projected cases among non-enrolled patients with ARI. The seasonal incidence of medically attended RSV was the sum of actual and projected cases divided by the community cohort denominator. Since each enrollment period did not include the entire RSV season, incidence estimates were adjusted to account for the statewide proportion of RSV occurring outside the study enrollment period. There were 16,088 to 17,694 adults in the cohort each season and 164 RSV cases in all 4 seasons. The overall seasonal incidence of medically attended RSV was 154 episodes (95% CI, 132-180) per 10,000 persons; the incidence was highest in 2007-08 (179) and lowest in 2006-07 (110). Among persons 50-59, 60-69, and ≥70 years old, RSV incidence was 124 (95% CI, 99-156), 147 (95% CI, 110-196), and 199 (95% CI, 153-258), respectively. The incidence of medically attended RSV increased with age and was similar during four seasons.

Background. Few studies have examined respiratory syncytial virus (RSV) infections in adults. We assessed the characteristics and outcomes of RSV relative to other viral infections. Methods. Patients ≥50 years old with acute respiratory illness were recruited for studies of influenza vaccine effectiveness from 2004 through 2010. Nasopharyngeal swabs from enrollees were analyzed for the presence of RSV and other respiratory viruses by multiplex reverse transcription polymerase chain reaction. Clinical data were obtained from interview and medical records. Results. A total of 2225 samples were tested across all seasons. The mean age was 64.2 (SD, 10.7) years; the mean interval from illness onset to sample collection was 4 (SD, 2.2) days. One or more viruses were detected in 1202 (54%) participants. In a multivariable logistic regression model, RSV was associated with ages 65–79 years (vs 50–64 years), symptoms of cough, nasal congestion and wheezing, and longer interval from illness onset to clinical encounter. RSV was not associated with the presence of chronic obstructive pulmonary disease or congestive heart failure in univariate analyses. Hospital admission within 30 days after illness onset was less common among patients with RSV compared to those with influenza (unadjusted odds ratio = 0.54 [95% confidence interval, .29–1.01], P = .06). Conclusions. RSV is a common cause of acute respiratory illness in adults aged ≥50 years; the risk of infection increases with age. Delays in healthcare seeking and reduced risk of hospital admission in patients with RSV suggest a milder course of illness relative to influenza.

White blood cells (WBCs) were counted in 4697 individuals who presented to outpatient malaria clinics in Maesod, Tak Province, Thailand, and Iquitos, Peru, between 28 May and 28 August 1998 and between 17 May and 9 July 1999. At each site and in each year, WBC counts in the Plasmodium falciparum–infected patients were lower than those in the Plasmodium vivax–infected patients, which, in turn, were lower than those in the uninfected patients. In Thailand, one-sixth of the P. falciparum–infected patients had WBC counts of <4000 cells/μL. Leukopenia may confound population studies that estimate parasite densities on the basis of an assumed WBC count of 8000 cells/μL. For instance, in the present study, use of this conventional approach would have overestimated average asexual parasite densities in the P. falciparum–infected patients in Thailand by nearly one-third

Cutaneous Leishmania major has affected many travelers including military personnel in Iraq and Afghanistan. Optimal treatment for this localized infection has not been defined, but interestingly the parasite is thermosensitive. Participants with parasitologically confirmed L. major infection were randomized to receive intravenous sodium stibogluconate (SSG) 20mg/kg/day for ten doses or localized ThermoMed (TM) device heat treatment (applied at 50 degrees C for 30 seconds) in one session. Those with facial lesions, infection with other species of Leishmania, or more than 20 lesions were excluded. Primary outcome was complete re-epithelialization or visual healing at two months without relapse over 12 months. Fifty-four/56 enrolled participants received intervention, 27 SSG and 27 TM. In an intent to treat analysis the per subject efficacy at two months with 12 months follow-up was 54% SSG and 48% TM (p = 0.78), and the per lesion efficacy was 59% SSG and 73% TM (p = 0.053). Reversible abdominal pain/pancreatitis, arthralgias, myalgias, headache, fatigue, mild cytopenias, and elevated transaminases were more commonly present in the SSG treated participants, whereas blistering, oozing, and erythema were more common in the TM arm. Skin lesions due to L. major treated with heat delivered by the ThermoMed device healed at a similar rate and with less associated systemic toxicity than lesions treated with intravenous SSG. ClinicalTrials.gov NCT 00884377.

We conducted an open-label safety and immunogenicity bridging study that compared liquid and lyophilized formulations of the candidate malaria vaccine RTS,S formulated in AS02A in 34 healthy, malaria-naïve adults at WRAIR. Volunteers received two doses of either formulation on a 0, 1-month schedule. Both vaccines were well tolerated and similarly immunogenic. Nineteen of 25 subjects who received the lyophilized formulation and six infectivity controls underwent sporozoite challenge to assess vaccine efficacy. All six controls had parasitemia detectable by thick blood smear by day 13 (mean pre-patent period 12.3 days; range 11–13). In the vaccine group, 8 of 19 vaccinees did not develop malaria and were completely protected (i.e., 42%). Among the 11 vaccinees who did become infected, the mean pre-patent period was delayed (14.4 days; range 13–18). The two formulations of RTS,S were equally safe and immunogenic, and the lyophilized formulation showed similar levels of efficacy against sporozoite challenge to that conferred by the liquid formulation in previous studies.

Introduction: Brazikumab (MEDI2070), a human monoclonal antibody that is an anti-p19 subunit inhibitor of interleukin-23, was shown to be effective over 8 weeks of treatment for patients with moderate-to-severe active Crohn's disease.[1] Here, we report the long-term safety and tolerability of brazikumab. Methods: The Phase 2a study (NCT01714726) consisted of a 12-week double-blind induction period with randomization to intravenous brazikumab (700 mg) or placebo, followed by the open-label (OL) period where all patients were administered subcutaneous brazikumab (210 mg) every 4 weeks. Patients were aged 18-65 years, had a ≥6-month history of moderate-to-severe active Crohn's disease, had failed on or were intolerant to ≥1 anti-tumor necrosis factor alpha (TNFa) agent, successfully completed the double-blind period, and signed consent for inclusion in the OL period. Adverse events (AEs) and vital signs were recorded every 4 weeks until patients discontinued or completed the study at 100 weeks. Results: 104 patients entered (n=52 from placebo to brazikumab and n=52 from brazikumab to brazikumab) and 57 (54.8%) patients completed the OL period. Overall, 87 (83.7%) patients experienced ≥1 treatment-emergent AE (TEAE); 12 (11.5%) experienced ≥1 TEAE leading to permanent discontinuation of study drug and 20 (19.2%) experienced ≥1 serious AE (SAE). The most common TEAEs were headache (22.1%), nasopharyngitis (22.1%), abdominal pain (18.3%), and Crohn's disease (16.3%) [Table]. Half of the SAEs observed were gastrointestinal disorders associated with Crohn's disease. Five SAEs of infection were reported, none of which were opportunistic, such as herpes zoster or tuberculosis; all resolved and the investigational product was permanently discontinued for only one patient. No cases of cancer were reported. The AE profile was similar between patients who completed a previous 12-week course of either placebo or brazikumab treatment. Conclusion: In this 100-week OL period, brazikumab was well tolerated in patients with moderate-to-severe active Crohn's disease, warranting future studies in larger patient populations.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and the elderly. Despite its relatively low degree of antigenic variation, it causes frequent reinfection throughout life. Clinical manifestations of RSV disease and the immune response to infection differ in infants and the elderly, suggesting that vaccines designed to protect these two populations may require different attributes. Here, the authors describe the translational approach of utilizing data from epidemiology studies performed in these populations, the use of RSV diagnostics in clinical practice, lessons learned from previous vaccine clinical trials and the success of palivizumab in prevention of RSV disease in premature and high-risk infants to aid the development of safe and effective RSV vaccines.

RSV was the most common viral agent causing acute respiratory illness in children 6 to 59 months old during the influenza season. Children in the 6-23 month age range had a higher incidence of RSV compared to those aged 24-59 months.Abstract Background.  Respiratory syncytial virus (RSV) and influenza are significant causes of seasonal respiratory illness in children. The incidence of influenza and RSV hospitalization is well documented, but the incidence of medically attended, laboratory-confirmed illness has not been assessed in a well defined community cohort. Methods.  Children aged 6–59 months with medically attended acute respiratory illness were prospectively enrolled during the 2006–2007 through 2009–2010 influenza seasons in a Wisconsin community cohort. Nasal swabs were tested for RSV and influenza by multiplex reverse-transcription polymerase chain reaction. The population incidence of medically attended RSV and influenza was estimated separately and standardized to weeks 40 through 18 of each season. Results.  The cohort included 2800–3073 children each season. There were 2384 children enrolled with acute respiratory illness; 627 (26%) were positive for RSV and 314 (13%) for influenza. The mean age was 28 months (standard deviation [SD] = 15) for RSV-positive and 38 months (SD = 16) for influenza-positive children. Seasonal incidence (cases per 10 000) was 1718 (95% confidence interval [CI], 1602–1843) for RSV and 768 (95% CI, 696–848) for influenza. Respiratory syncytial virus incidence was highest among children 6–11 (2927) and 12–23 months old (2377). Influenza incidence was highest (850) in children 24–59 months old. The incidence of RSV was higher than influenza across all seasons and age groups. Conclusions.  The incidence of medically attended RSV was highest in children 6–23 months old, and it was consistently higher than influenza. The burden of RSV remains high throughout the first 2 years of life.

Background. Clinical symptoms of mixed-species malaria infections have been variously reported as both less severe and more severe than those of single-species infections. Methods. Oral temperatures were taken from and blood slides were prepared for 2308 adults who presented at outpatient malaria clinics in Tak Province (Thailand) during May–August 1998, May–July 1999, and May–June 2001 with malaria infections diagnosed by 2 expert research microscopists, each of whom was blinded to the other's reports. Results. In each year, temperatures of patients with mixed Plasmodium vivax—Plasmodium falciparum infections were higher than temperatures of patients with P. vivax or P. falciparum infections. In every mixed-species case, P. falciparum parasitemia was higher than P. vivax parasitemia, but patient temperature was not correlated with the parasitemia of either species or with the total parasitemia. Conclusions. Among adults who self-report to malaria clinics in western Thailand, patients with mixed P. vivax—P. falciparum infections have higher fevers than patients with single-species infections, a distinction that cannot be attributed to differences in parasitemia. This observation warrants more detailed investigations, spanning wider ranges of ages and transmission environments.

The efficacy and toxicity of sodium stibogluconate (SSG) at a dosage of 20 mg/(kg×d) for either 20 days (for cutaneous disease) or 28 days (for visceral, mucosal, or viscerotropic disease) in the treatment of leishmaniasis is reported. Ninety-six U.S. Department of Defense health care beneficiaries with parasitologically confirmed leishmaniasis were prospectively followed for 1 year. One patient was infected with human immunodeficiency virus; otherwise, comorbidity was absent. Clinical cure occurred in 91% of 83 cases of cutaneous disease and 93% of 13 cases of visceral/viscerotropic disease. Adverse effects were common and necessitated interruption of treatment in 28% of cases, but they were generally reversible. These included arthralgias and myalgias (58%), pancreatitis (97%), transaminitis (67%), headache (22%), hematologic suppression (44%), and rash (9%). No subsequent mucosal leishmaniasis was identified, and there were no deaths attributable to SSG or leishmaniasis.