Pharmacokinetics, safety, tolerability and efficacy of cotadutide, a glucagon-like peptide-1 and glucagon receptor dual agonist, in phase 1 and 2 trials in overweight or obese participants of Asian descent with or without type 2 diabetes.

Aim: To evaluate the safety and pharmacokinetics of cotadutide, a dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist, in overweight Asian participants with or without type 2 diabetes (T2D).

Materials And Methods: In the phase 1, randomized, blinded, single-ascending dose study, 24 Japanese and eight Chinese healthy adults (body mass index [BMI] 23-40 kg/m ) received one subcutaneous dose of cotadutide (50-150 or 100 μg, respectively) or placebo. The primary endpoint was safety.

Efficacy and safety of abrilumab, an α4β7 integrin inhibitor, in Japanese patients with moderate-to-severe ulcerative colitis: a phase II study.

Background/aims: Inhibition of α4β7 integrin has been shown to be effective for induction and maintenance therapy in patients with ulcerative colitis (UC). We investigated the effects of varying doses of the α4β7 inhibitor abrilumab in Japanese patients with moderate-to-severe UC despite conventional treatments.

Methods: In this randomized, double-blind, placebocontrolled study, 45 UC patients were randomized to abrilumab 21 mg (n=11), 70 mg (n=12), 210 mg (n=9), or placebo (n=13) via subcutaneous (SC) injection for 12 weeks.

Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn's Disease: A Phase 2a Study.

Background & Aims: MEDI2070 is a human monoclonal antibody that selectively inhibits interleukin 23 (IL23), a cytokine implicated in the pathogenesis of Crohn's disease (CD). We analyzed its safety and efficacy in treatment of CD in a phase 2a study.

Methods: We conducted a double-blind, placebo-controlled study of 119 adults with moderate to severe CD failed by treatment with tumor necrosis factor antagonists.

Incidence of Medically Attended Respiratory Syncytial Virus and Influenza Illnesses in Children 6-59 Months Old During Four Seasons.

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.

Seasonal incidence of medically attended respiratory syncytial virus infection in a community cohort of adults ≥50 years old.

Background: 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).

Methods: Patients seeking care for acute respiratory illness (ARI) were prospectively enrolled and tested for RSV by multiplex RT-PCR.

Medically attended respiratory syncytial virus infections in adults aged ≥ 50 years: clinical characteristics and outcomes.

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.

Translational sciences approach to RSV vaccine development.

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.

Adults 65 years old and older have reduced numbers of functional memory T cells to respiratory syncytial virus fusion protein.

Respiratory syncytial virus (RSV) infects elderly (≥65 years) adults, causing medically attended illness and hospitalizations. While RSV neutralizing antibody levels correlate inversely with RSV-associated hospitalization in the elderly, the role of RSV-specific T cells in preventing disease in the elderly remains unclear. We examined RSV-specific humoral, mucosal, and cellular immune profiles in healthy elderly (65 to 85 years) and young (20 to 30 years) adults.

Malaria caused by Plasmodium vivax complicated by acalculous cholecystitis.

We report the first adult cases of acute acalculous cholecystitis (AAC) exclusively caused by infections with Plasmodium vivax. We reviewed the previous cases of AAC occurring during malaria, compared and contrasted the variables of previously reported cases with the cases reported here, examined the pathogenic link between malaria and AAC, and considered the diagnostic pitfalls and treatment implications as they applied to clinical outcomes in patients with this serious and potentially underrecognized illness.

A randomized controlled trial of local heat therapy versus intravenous sodium stibogluconate for the treatment of cutaneous Leishmania major infection.

Background: 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.

Methodology/principal Findings: Participants with parasitologically confirmed L.

Alanine mutagenesis of the primary antigenic escape residue cluster, c1, of apical membrane antigen 1.

Antibodies against apical membrane antigen 1 (AMA1) inhibit invasion of Plasmodium merozoites into red cells, and a large number of single nucleotide polymorphisms on AMA1 allow the parasite to escape inhibitory antibodies. The availability of a crystal structure makes it possible to test protein engineering strategies to develop a monovalent broadly reactive vaccine. Previously, we showed that a linear stretch of polymorphic residues (amino acids 187 to 207), localized within the C1 cluster on domain 1, conferred the highest level of escape from inhibitory antibodies, and these were termed antigenic escape residues (AER).

Update on rapid diagnostic testing for malaria.

To help mitigate the expanding global impact of malaria, with its associated increasing drug resistance, implementation of prompt and accurate diagnosis is needed. Malaria is diagnosed predominantly by using clinical criteria, with microscopy as the current gold standard for detecting parasitemia, even though it is clearly inadequate in many health care settings. Rapid diagnostic tests (RDTs) have been recognized as an ideal method for diagnosing infectious diseases, including malaria, in recent years.

A phase I/IIa safety, immunogenicity, and efficacy bridging randomized study of a two-dose regimen of liquid and lyophilized formulations of the candidate malaria vaccine RTS,S/AS02A in malaria-naïve adults.

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.

Sources of variability in determining malaria parasite density by microscopy.

Enumeration of parasites by microscopic examination of blood smears is the only method available for quantifying parasitemia in infected blood. However, the sources and scale of error inherent in this technique have not been systematically investigated. Here we use data collected in outpatient clinics in Peru and Thailand to elucidate important sources of variation in parasite density measurements.

White blood cell counts and malaria.

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.

Hematologic and clinical indices of malaria in a semi-immune population of western Thailand.

This study examines hematologic profiles of persons with acute Plasmodium falciparum or P. vivax infection in Maesod on Thailand's western border with Myanmar compared with febrile, non-parasitemic persons also reporting to malaria clinics. Nine hundred seventy-nine subjects were malaria-negative, 414 were infected with P.

Dependence of malaria detection and species diagnosis by microscopy on parasite density.

Giemsa-stained blood smears from each of 2,190 patients from Thai government-operated clinics on the Thailand-Myanmar border were independently examined by the on-duty microscopists at the clinics and by 2-3 research microscopists, each blinded to the clinics' and each other's reports. Using a strictly defined protocol, a consensus reference-standard blood smear interpretation for each sample was produced by the research microscopists. This result was compared with the clinic's diagnostic interpretation for the corresponding sample with respect to detection of parasitemia and diagnosis of infecting species.

Rapid diagnostic testing for malaria.

Malaria rapid diagnostic devices (MRDD) have been developed with the hope that they would offer accurate, reliable, rapid, cheap and easily available alternatives to traditional methods of malaria diagnosis. The results from early malaria rapid diagnostic studies were quite promising, especially for detecting Plasmodium falciparum at densities of more than 100-500 parasites/microl. Despite the introduction of these devices over a decade ago, only a few target antigens have been introduced.

Rapid diagnostic devices for malaria: field evaluation of a new prototype immunochromatographic assay for the detection of Plasmodium falciparum and non-falciparum Plasmodium.

The NOW ICT Malaria P.f./P.

Devices for rapid diagnosis of Malaria: evaluation of prototype assays that detect Plasmodium falciparum histidine-rich protein 2 and a Plasmodium vivax-specific antigen.

The ParaSight F test was developed as a pioneer industry effort in the large-scale, process-controlled production of a device for the rapid diagnosis of malaria. This device performed well in field settings but was limited to the detection of a single malaria species, Plasmodium falciparum. The ParaSight F+V assay advanced upon the ParaSight F test format by incorporating a monoclonal antibody directed against a proprietary Plasmodium vivax-specific antigen, in addition to the antibody directed against P.