AS03B-adjuvanted H5N1 influenza vaccine in children 6 months through 17 years of age: a phase 2/3 randomized, placebo-controlled, observer-blinded trial.

BACKGROUND: This phase 2/3, randomized, placebo-controlled, observer-blinded study assessed the immunogenicity, reactogenicity, and safety of an inactivated, split-virion H5N1 influenza vaccine (A/Indonesia/5/2005) in children aged 6 months through 17 years. METHODS: Children received 2 influenza vaccine doses 21 days apart, each containing 1.9 µg of hemagglutinin and AS03B adjuvant (5.93 mg of α-tocopherol). The randomization ratio was 8:3 for vaccine to placebo, with equal allocation between 3 age strata (6-35 months, 3-8 years, and 9-17 years). Immunogenicity against the vaccine strain was assessed 21 days after the first and second vaccine doses for all vaccinees, at day 182 for half, and at day 385 for the remaining half. Reactogenicity after each dose and safety up to 1 year after vaccination were evaluated. RESULTS: Within each age stratum, the lower limit of the 98.3% confidence interval for the day 42 seroprotection rate was ≥70%, thus fulfilling the US and European licensure criteria. The immune responses elicited by vaccine persisted well above baseline levels for 1 year. The vaccine was more reactogenic than placebo, but no major safety concerns were identified. CONCLUSIONS: AS03B-adjuvanted H5N1 influenza vaccine was immunogenic and showed an acceptable safety profile in all age groups studied. Clinical Trials Registration: NCT01310413.

Safety and long-term humoral immune response in adults after vaccination with an H1N1 2009 pandemic influenza vaccine with or without AS03 adjuvant.

BACKGROUND: In this study (NCT00985088) we evaluated different formulations of an H1N1 2009 pandemic influenza vaccine that deliver various viral hemagglutinin (HA) doses with or without AS03 (a tocopherol-based oil-in-water adjuvant system). METHODS: A total of 1340 healthy subjects aged ≥18 years were randomized to receive 1 or 2 doses of an adjuvanted (3.75-µg HA/AS03(A) or 1.9-µg HA/AS03(B)) or nonadjuvanted vaccine formulation. Safety and immunogenicity (by hemagglutination-inhibition [HI] assay) after each dose and 6 months after dose 1 are reported here. RESULTS: A single dose of AS03(A)-adjuvanted 3.75-µg HA H1N1 2009 induced the strongest immune responses in subjects aged 18-64 years (seroprotection rate [SPR], 97.2%; seroconversion rate [SCR], 90.1%) as well as in subjects aged >64 years (SPR, 91.1%; SCR, 78.2%) 21 days after vaccination. Six months after dose 1, subjects who received 2 doses of either the adjuvanted formulation or 1 dose of the adjuvanted 3.75-µg HA formulation continued to meet all Center for Biologics Evaluation and Research and Committee for Medicinal Products for Human Use criteria. All formulations had clinically acceptable safety profiles. CONCLUSION: A single dose of the 3.75-µg HA AS03(A)-adjuvanted H1N1 2009 influenza vaccine was highly immunogenic in both age strata (18-64 and >64 years), inducing long-term persistence of the immune response until at least 6 months after dose 1.

Monkeypox (hMPXV Infection): A Practical Review.

Monkeypox, a neglected disease previously confined to Africa, is causing a worldwide outbreak affecting predominantly males who have sex with males, especially those who are infected with HIV. The clinical presentation during the current outbreak differs from endemic cases. Treatment with tecovirimat and other antivirals is available. Immunization may be used as preexposure and postexposure prophylaxis.

COVID-19 infection in the developing world: the Peruvian perspective.

COVID-19 infections have spread widely in Peru, causing severe societal and health impact. We describe the evolution of the epidemics, the reasons for high transmission and the way the disease is diagnosed and managed in the Andean country.

A probable case of human neurotrichinellosis in the United States.

Human neurotrichinellosis is seldom reported. This is likely the result of the low incidence of parasites from the genus Trichinella in the United States domestic food supply, as well as difficulties in diagnosing the disease, especially when neither the organism nor the source of the infection are readily available. Although trichinellosis from domestic food supplies has been decreasing for many years, a resurgence has occurred in cases derived from the consumption of wild game. We report a rare case of neurotrichinellosis in the United States and implicate wild game as the source of the infection. These results suggest that clinicians should consider the potential for Trichinella infection in cases where wild game is common in the diets of the patients.

Trichosporon asahii fungemia in a patient with non-hematological malignancy.

Trichosporon fungemia is usually seen in neutropenic patients with underlying hematological malignancies. In this report we describe a fatal case of Trichosporon asahii fungemia in a non-neutropenic patient with a non-hematological malignancy. For 1 week the patient exhibited hematuria, weakness, easy fatigability and headaches. At admission she had anemia, renal failure and evidence of right hydronephrosis and bladder wall masses as detected by CT scan. She did not have a history of tobacco abuse, contact with urinary carcinogens or Schistosoma infestation; her clinical picture was suggestive of bladder cancer. After some investigations the patient underwent radical cystectomy and ileal conduit surgery because of transitional cell carcinoma in the urinary bladder. After an initial uneventful improvement postoperatively the patient deteriorated and died of septic shock despite all reanimation efforts and antibiotherapy including fluconazole. The blood culture obtained 4 days before the patient died revealed T. asahii, which was isolated on the day she died and found to be resistant to fluconazole and caspofungin. This report suggests that clinicians remain aware that T. asahii fungemia may develop in clinically deteriorated patients even if they do not have a hematological malignancy.

Learning by doing: developing fellows' academic skills through collaborative research.

Physicians in postgraduate training are expected to learn research methods but how best to achieve that curricular goal is unclear. This article describes a novel educational approach to develop research skills among infectious disease fellows. Five infectious disease fellows and two faculty members participated in a collaborative research project as a vehicle for active, problem-based learning. During the learning experience several tasks with specific learning objectives were achieved. The authors evaluated the weaknesses and strengths of the collaborative research project as an educational program. This problem-based approach for learning research methods seems more effective than traditional methods and may be applicable to a broad range of training programs.

Chikungunya: bending over the Americas and the rest of the world.

Chikungunya is an arthropod-borne virus transmitted by Aedes mosquito bites. A viral mutation has allowed Aedes albopictus to become the preferred vector extending the geographic spread of the condition. The virus causes an acute febrile illness occasionally followed by a chronic rheumatic condition causing severe impairment. The diagnosis is usually confirmed with serology. No specific treatment is currently available. This article reviews the condition with emphasis on his dissemination in the Americas.

Ebola Virus Disease: A Perspective for the United States.

Ebola virus caused an epidemic of unprecedented extension in West Africa. There was concern that the outbreak would not be controlled for a prolonged period of time. Two cases of infected returning travelers have been reported in the US. One of the cases has been associated with secondary transmission and other infected subjects have been repatriated for treatment. This article reviews the etiology, pathogenesis, transmission, clinical manifestations, diagnosis, treatment, and prevention of the disease with emphasis on the identification and management in the US.

Immunogenicity and safety of AS03A-adjuvanted H5N1 influenza vaccine prepared from bulk antigen after stockpiling for 4 years.

BACKGROUND: Stockpiling vaccine for deployment in the event of an influenza pandemic is an important mitigation strategy. A necessary aspect of stockpiling is to determine the shelf-life of the stored vaccine. METHODS: In this Phase II, open-label study we assessed the immunogenicity and safety of H5N1 A/Indonesia/5/2005 vaccine adjuvanted with AS03A. The AS03A-H5N1 vaccine was prepared from bulk antigen that had been stored for 4 years, and adjuvant that had been stored for 2.5 years. Both the antigen and adjuvant were filled in separate multi-dose vials within 4 months of use, and on the day of vaccination, the contents of antigen and adjuvant vials were mixed. Seventy-eight adults aged 18-64 years were scheduled to receive two doses of hemagglutinin-antigen (3.75µg) given 21 days apart. Antibody responses were assessed by hemagglutination-inhibition (HI) assay according to age (18-30 years, 31-40 years, 41-50 years, and 51-64 years). Reactogenicity was assessed for 7 days after each vaccination, and safety was assessed for 385 days post-vaccination (NCT01416571). RESULTS: The vaccine was immunogenic. Twenty-one days after the second dose of vaccine in the overall population, the HI seroconversion rate and seroprotection rate (SPR; titer ≥1:40) was 96.0% and 98.7%, respectively. At Day 182 after vaccination, the SPR was 76.7% in the overall population. Injection site pain was the most frequent solicited adverse event (91.0%), and no safety concerns were raised. CONCLUSION: The immunogenicity and safety observed with AS03A-H5N1 vaccine formulated with bulk antigen which had been stockpiled before vialing and administration was consistent with that previously observed with newly manufactured AS03A-H5N1 vaccine. This suggests that stockpiling bulk antigen for 4 years does not compromise the immunogenicity or reactogenicity of the vaccine.

Why don't they listen? Adherence to recommendations of infectious disease consultations.

The effectiveness of an infectious diseases (ID) consultation is dependent on adherence to the recommendations. To delineate the factors that affect adherence, we conducted a prospective cohort study of 465 consultations at 2 academic institutions in which we evaluated the consultation process, patient and consultant characteristics, types of recommendations, and compliance with recommendations. The overall compliance rate was 80%, with 85% adherence to crucial recommendations. Multivariate analysis revealed that adherence to ID recommendations was higher when the recommendations were therapeutic instead of diagnostic, when they related to a specific clinical question, when recommendations were deemed crucial by the ID service, if the primary service was medicine, and if the consultation note was legible and organized. Whether modification of consultant practice will lead to improved recommendation compliance and patient outcomes warrants further study.

Q fever: a biological weapon in your backyard.

Coxiella burnetii, which causes Q fever, is a highly infectious agent that is widespread among livestock around the world. Although the culture process for coxiella is laborious, large amounts of infectious material can be produced. If used as an aerosolised biological weapon, coxiella may not cause high mortality, but could provoke acute disabling disease. In its late course, Q fever can be complicated by fatal (eg, endocarditis) or debilitating (eg, chronic fatigue syndrome) disorders. The diagnosis of Q fever might be delayed because of non-specific and protean presentations. Effective antibiotic treatment is available for the acute form of disease but not for the chronic complications. Vaccination and chemoprophylaxis in selected individuals may be used in the event of bioterrorism.

Polymyositis-like syndrome in hypothyroidism: review of cases reported over the past twenty-five years.

Polymyositis-like syndrome, with proximal muscle weakness and elevation of muscle enzymes, may be a clinical manifestation of hypothyroidism. To define the clinical, biochemical, electromyographic, and pathologic characteristics of patients with this syndrome, we identified and reviewed by MEDLINE all cases reported in the English literature from January 1, 1975 through December 31, 2000. Thirty-two cases were considered. Fifty-nine percent of the patients were male with a mean age of 54.7 +/- 22.6 years, (+/- 1 standard deviation [SD]). Weakness was described in 100% of patients. Other common clinical manifestations were: delayed tendon reflexes with slow relaxation phase (41%), muscle tenderness (25%), and muscle induration (9%). The mean creatine kinase (CK) was 2164 +/- 1954 U/L (+/- 1 SD) and the mean thyroid-stimulating hormone (TSH) was 114.8 +/- 85.6 mIU/L (+/- 1 SD). Fifty percent of patients had electromyography; half of the studies were normal while the other half showed nonspecific myopathic changes. Biopsies were performed in 80% of the patients. The most common findings were type II fiber atrophy, type I fiber hypertrophy, central nuclei disposition, necrosis, increased percentage of type I fibers, and decreased percentage of type II fibers, inflammatory infiltrate and the presence of core-like structures. The characteristics of polymyositis-like syndrome in hypothyroidism did not differ from those of nonspecific hypothyroid myopathy. Clinical judgment alone may not be sufficient to suspect and detect these patients. Serum TSH levels should be routinely determined in all patients with muscle weakness or elevation of creatine kinase.

Long-term immunogenicity of an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine in young and elderly adults: an observer-blind, randomized trial.

BACKGROUND: This study (NCT00979602) evaluated the immunogenicity and relative protective efficacy of one dose of influenza A(H1N1)pdm09 vaccine with or without AS03 (an α-tocopherol oil-in-water emulsion based Adjuvant System). METHODS: Four thousands and forty-eight healthy adults aged ≥ 18 years were randomized (1:1) to receive one dose of either the adjuvanted split virion (3.75 µg hemagglutinin antigen [HA]/AS03) or non-adjuvanted (15 µg HA) vaccine. Hemagglutination inhibition [HI] antibody response was evaluated before vaccination and at Days 21, 42 and 182 (Month 6). Safety of the study vaccines was evaluated during the entire study duration. RESULTS: At Day 21, both study vaccines induced HI immune responses meeting the US regulatory criteria in subjects 18-64 years (seroprotection rate [SPR]: 98.0% [97.1-98.6]; seroconversion rate [SCR]: 89.7% [88.0-91.2] in the AS03-adjuvanted group; SPR: 91.4% [89.9-92.8]; SCR: 74.6% [72.3-76.9] in the non-adjuvanted group) and >64 years of age (SPR: 86.0% [82.5-89.0]; SCR: 75.3% [71.1-79.2] in the AS03-adjuvanted group; SPR: 69.1% [64.6-73.3]; SCR: 56.7% [52.0-61.3] in the non-adjuvanted group). The AS03-adjuvanted vaccine induced higher HI geometric mean titers than the non-adjuvanted vaccine at all time points. At Month 6, only subjects 18-64 years of age from both vaccine groups still met the US regulatory criteria (SPR: 82.1% [80.0-84.1]; SCR: 62.3% [59.6-64.8] in the AS03-adjuvanted group; SPR: 75.3% [72.9-77.5]; SCR: 53.7% [51.0-56.4] in the non-adjuvanted group). Protective efficacy was not evaluated due to low number of RT-qPCR-confirmed A(H1N1)pdm09 influenza cases. Through Month 12, 216 serious adverse events (in 157 subjects: 84 in the AS03-adjuvanted and 73 in the non-adjuvanted group) and 12 potentially immune mediated diseases (5 in the AS03-adjuvanted and 7 in the non-adjuvanted group) were reported. CONCLUSION: A single dose of either adjuvanted or non-adjuvanted influenza A(H1N1)pdm09 vaccine induced protective HI antibody levels against the A/California/7/2009 strain that persisted through Month 6 in the 18-64 years population.