Asymptomatic Orthopoxvirus Circulation in Humans in the Wake of a Monkeypox Outbreak among Chimpanzees in Cameroon.

Monkeypox virus is a zoonotic Orthopoxvirus (OPXV) that causes smallpox-like illness in humans. In Cameroon, human monkeypox cases were confirmed in 2018, and outbreaks in captive chimpanzees occurred in 2014 and 2016. We investigated the OPXV serological status among staff at a primate sanctuary (where the 2016 chimpanzee outbreak occurred) and residents from nearby villages, and describe contact with possible monkeypox reservoirs. We focused specifically on Gambian rats (Cricetomys spp.) because they are recognized possible reservoirs and because contact with Gambian rats was common enough to render sufficient statistical power. We collected one 5-mL whole blood specimen from each participant to perform a generic anti-OPXV ELISA test for IgG and IgM antibodies and administered a questionnaire about prior symptoms of monkeypox-like illness and contact with possible reservoirs. Our results showed evidence of OPXV exposures (IgG positive, 6.3%; IgM positive, 1.6%) among some of those too young to have received smallpox vaccination (born after 1980, n = 63). No participants reported prior symptoms consistent with monkeypox. After adjusting for education level, participants who frequently visited the forest were more likely to have recently eaten Gambian rats (OR: 3.36, 95% CI: 1.91-5.92, P < 0.001) and primate sanctuary staff were less likely to have touched or sold Gambian rats (OR: 0.23, 95% CI: 0.19-0.28, P < 0.001). The asymptomatic or undetected circulation of OPXVs in humans in Cameroon is likely, and contact with monkeypox reservoirs is common, raising the need for continued surveillance for human and animal disease.

Update: Influenza Activity - United States and Worldwide, May 19-September 28, 2019, and Composition of the 2020 Southern Hemisphere Influenza Vaccine.

During May 19-September 28, 2019,* low levels of influenza activity were reported in the United States, with cocirculation of influenza A and influenza B viruses. In the Southern Hemisphere seasonal influenza viruses circulated widely, with influenza A(H3) predominating in many regions; however, influenza A(H1N1)pdm09 and influenza B viruses were predominant in some countries. In late September, the World Health Organization (WHO) recommended components for the 2020 Southern Hemisphere influenza vaccine and included an update to the A(H3N2) and B/Victoria-lineage components. Annual influenza vaccination is the best means for preventing influenza illness and its complications, and vaccination before influenza activity increases is optimal. Health care providers should recommend vaccination for all persons aged ≥6 months who do not have contraindications to vaccination (1).

Investigation of an Outbreak of Variant Influenza A(H3N2) Virus Infection Associated With an Agricultural Fair-Ohio, August 2012.

BACKGROUND: In 2012, one third of cases in a multistate outbreak of variant influenza A(H3N2) virus ([H3N2]v) infection occurred in Ohio. We conducted an investigation of (H3N2)v cases associated with agricultural Fair A in Ohio. METHODS: We surveyed Fair A swine exhibitors and their household members. Confirmed cases had influenza-like illness (ILI) and a positive laboratory test for (H3N2)v, and probable cases had ILI. We calculated attack rates. We determined risk factors for infection, using multivariable log-binomial regression. RESULTS: We identified 20 confirmed and 94 probable cases associated with Fair A. Among 114 cases, the median age was 10 years, there were no hospitalizations or deaths, and 82% had swine exposure. In the exhibitor household cohort of 359 persons (83 households), we identified 6 confirmed cases (2%) and 40 probable cases (11%). An age of <10 years was a significant risk factor (P < .01) for illness. One instance of likely human-to-human transmission was identified. CONCLUSIONS: In this (H3N2)v outbreak, no evidence of sustained human-to-human (H3N2)v transmission was found. Our risk factor analysis contributed to the development of the recommendation that people at increased risk of influenza-associated complications, including children aged <5 years, avoid swine barns at fairs during the 2012 fair season.

Influenza activity - United States, 2013-14 season and composition of the 2014-15 influenza vaccines.

During the 2013-14 influenza season in the United States, influenza activity increased through November and December before peaking in late December. Influenza A (H1N1)pdm09 (pH1N1) viruses predominated overall, but influenza B viruses and, to a lesser extent, influenza A (H3N2) viruses also were reported in the United States. This influenza season was the first since the 2009 pH1N1 pandemic in which pH1N1 viruses predominated and was characterized overall by lower levels of outpatient illness and mortality than influenza A (H3N2)-predominant seasons, but higher rates of hospitalization among adults aged 50-64 years compared with recent years. This report summarizes influenza activity in the United States for the 2013-14 influenza season (September 29, 2013-May 17, 2014†) and reports recommendations for the components of the 2014-15 Northern Hemisphere influenza vaccines.

Update: influenza activity - United States, September 29, 2013-February 8, 2014.

Influenza activity in the United States began to increase in mid-November and remained elevated through February 8, 2014. During that time, influenza A (H1N1)pdm09 (pH1N1) viruses predominated overall, while few B and A (H3N2) viruses were detected. This report summarizes U.S. influenza activity* during September 29, 2013-February 8, 2014, and updates the previous summary.

Outbreak of variant influenza A(H3N2) virus in the United States.

BACKGROUND: Variant influenza virus infections are rare but may have pandemic potential if person-to-person transmission is efficient. We describe the epidemiology of a multistate outbreak of an influenza A(H3N2) variant virus (H3N2v) first identified in 2011. METHODS: We identified laboratory-confirmed cases of H3N2v and used a standard case report form to characterize illness and exposures. We considered illness to result from person-to-person H3N2v transmission if swine contact was not identified within 4 days prior to illness onset. RESULTS: From 9 July to 7 September 2012, we identified 306 cases of H3N2v in 10 states. The median age of all patients was 7 years. Commonly reported signs and symptoms included fever (98%), cough (85%), and fatigue (83%). Sixteen patients (5.2%) were hospitalized, and 1 fatal case was identified. The majority of those infected reported agricultural fair attendance (93%) and/or contact with swine (95%) prior to illness. We identified 15 cases of possible person-to-person transmission of H3N2v. Viruses recovered from patients were 93%-100% identical and similar to viruses recovered from previous cases of H3N2v. All H3N2v viruses examined were susceptible to oseltamivir and zanamivir and resistant to adamantane antiviral medications. CONCLUSIONS: In a large outbreak of variant influenza, the majority of infected persons reported exposures, suggesting that swine contact at an agricultural fair was a risk for H3N2v infection. We identified limited person-to-person H3N2v virus transmission, but found no evidence of efficient or sustained person-to-person transmission. Fair managers and attendees should be aware of the risk of swine-to-human transmission of influenza viruses in these settings.

Estimates of the number of human infections with influenza A(H3N2) variant virus, United States, August 2011-April 2012.

BACKGROUND: Thirteen human infections with an influenza A(H3N2) variant (H3N2v) virus containing a combination of gene segments not previously associated with human illness were identified in the United States from August 2011 to April 2012. Because laboratory confirmation of influenza virus infection is only performed for a minority of ill persons and routine clinical tests may not identify H3N2v virus, the count of laboratory-confirmed H3N2v virus infections underestimates the true burden of illness. METHODS: To account for this underascertainment, we adapted a multiplier model created at the beginning of the influenza A(H1N1) 2009 pandemic to estimate the true burden of H3N2v illness. Data to inform each of these parameters came from the literature and from special projects conducted during the 2009 H1N1 pandemic and the 2010-2011 influenza season. The multipliers were calculated as the simple inverses of the proportions at each step, and we accounted for variability and uncertainty in model parameters by using a probabilistic or Monte Carlo approach. RESULTS: We estimate that the median multiplier for children was 200 (90% range, 115-369) and for adults was 255 (90% range, 152-479) and that 2055 (90% range, 1187-3800) illnesses from H3N2v virus infections may have occurred from August 2011 to April 2012, suggesting that the new virus was more widespread than previously thought. CONCLUSIONS: Illness from this variant influenza virus was more frequent than previously thought. Continued surveillance is needed to ensure timely detection and response to H3N2v virus infections.

Human infections with influenza A(H3N2) variant virus in the United States, 2011-2012.

BACKGROUND. During August 2011-April 2012, 13 human infections with influenza A(H3N2) variant (H3N2v) virus were identified in the United States; 8 occurred in the prior 2 years. This virus differs from previous variant influenza viruses in that it contains the matrix (M) gene from the Influenza A(H1N1)pdm09 pandemic influenza virus. METHODS. A case was defined as a person with laboratory-confirmed H3N2v virus infection. Cases and contacts were interviewed to determine exposure to swine and other animals and to assess potential person-to-person transmission. RESULTS. Median age of cases was 4 years, and 12 of 13 (92%) were children. Pig exposure was identified in 7 (54%) cases. Six of 7 cases with swine exposure (86%) touched pigs, and 1 (14%) was close to pigs without known direct contact. Six cases had no swine exposure, including 2 clusters of suspected person-to-person transmission. All cases had fever; 12 (92%) had respiratory symptoms, and 3 (23%) were hospitalized for influenza. All 13 cases recovered. CONCLUSIONS. H3N2v virus infections were identified at a high rate from August 2011 to April 2012, and cases without swine exposure were identified in influenza-like illness outbreaks, indicating that limited person-to-person transmission likely occurred. Variant influenza viruses rarely result in sustained person-to-person transmission; however, the potential for this H3N2v virus to transmit efficiently is of concern. With minimal preexisting immunity in children and the limited cross-protective effect from seasonal influenza vaccine, the majority of children are susceptible to infection with this novel influenza virus.

Using routine surveillance data to estimate the epidemic potential of emerging zoonoses: application to the emergence of US swine origin influenza A H3N2v virus.

BACKGROUND: Prior to emergence in human populations, zoonoses such as SARS cause occasional infections in human populations exposed to reservoir species. The risk of widespread epidemics in humans can be assessed by monitoring the reproduction number R (average number of persons infected by a human case). However, until now, estimating R required detailed outbreak investigations of human clusters, for which resources and expertise are not always available. Additionally, existing methods do not correct for important selection and under-ascertainment biases. Here, we present simple estimation methods that overcome many of these limitations. METHODS AND FINDINGS: Our approach is based on a parsimonious mathematical model of disease transmission and only requires data collected through routine surveillance and standard case investigations. We apply it to assess the transmissibility of swine-origin influenza A H3N2v-M virus in the US, Nipah virus in Malaysia and Bangladesh, and also present a non-zoonotic example (cholera in the Dominican Republic). Estimation is based on two simple summary statistics, the proportion infected by the natural reservoir among detected cases (G) and among the subset of the first detected cases in each cluster (F). If detection of a case does not affect detection of other cases from the same cluster, we find that R can be estimated by 1-G; otherwise R can be estimated by 1-F when the case detection rate is low. In more general cases, bounds on R can still be derived. CONCLUSIONS: We have developed a simple approach with limited data requirements that enables robust assessment of the risks posed by emerging zoonoses. We illustrate this by deriving transmissibility estimates for the H3N2v-M virus, an important step in evaluating the possible pandemic threat posed by this virus. Please see later in the article for the Editors' Summary.

Outbreak of influenza A (H3N2) variant virus infection among attendees of an agricultural fair, Pennsylvania, USA, 2011.

During August 2011, influenza A (H3N2) variant [A(H3N2)v] virus infection developed in a child who attended an agricultural fair in Pennsylvania, USA; the virus resulted from reassortment of a swine influenza virus with influenza A(H1N1)pdm09. We interviewed fair attendees and conducted a retrospective cohort study among members of an agricultural club who attended the fair. Probable and confirmed cases of A(H3N2)v virus infection were defined by serology and genomic sequencing results, respectively. We identified 82 suspected, 4 probable, and 3 confirmed case-patients who attended the fair. Among 127 cohort study members, the risk for suspected case status increased as swine exposure increased from none (4%; referent) to visiting swine exhibits (8%; relative risk 2.1; 95% CI 0.2-53.4) to touching swine (16%; relative risk 4.4; 95% CI 0.8-116.3). Fairs may be venues for zoonotic transmission of viruses with epidemic potential; thus, health officials should investigate respiratory illness outbreaks associated with agricultural events.

Expanding the recommendations for annual influenza vaccination to school-age children in the United States.

BACKGROUND: Despite long-standing recommendations to vaccinate children who have underlying chronic medical conditions or who are contacts of high-risk persons, vaccination coverage among school-age children remains low. Community studies have indicated that school-age children have the highest incidence of influenza and are an important source of amplifying and sustaining community transmission that affects all age groups. METHODS: A consultation to discuss the advantages and disadvantages of a universal recommendation for annual influenza vaccination of all children age ≥6 months was held in Atlanta, Georgia, in September 2007. Consultants provided summaries of current data on vaccine effectiveness, safety, supply, successful program implementation, and economics studies and discussed challenges associated with continuing a risk- and contact-based vaccination strategy compared with a universal vaccination recommendation. RESULTS: Consultants noted that school-age children had a substantial illness burden caused by influenza, that vaccine was safe and effective for children aged 6 months through 18 years, and that evidence suggested that vaccinating school-age children would provide benefits to both the vaccinated children and their unvaccinated household and community contacts. However, implementation of an annual recommendation for all school-age children would pose major challenges to parents, medical providers and health care systems. Alternative vaccination venues were needed, and of these school-located vaccination programs might offer the most promise as an alternative vaccination site for school-age children. CONCLUSIONS: Expansion of recommendations to include all school-age children will require additional development of an infrastructure to support implementation and methods to adequately evaluate impact.

Influenza viruses in Thailand: 7 years of sentinel surveillance data, 2004-2010.

BACKGROUND: The re-emergence of avian influenza A (H5N1) in 2004 and the pandemic of influenza A (H1N1) in 2009 highlight the need for routine surveillance systems to monitor influenza viruses, particularly in Southeast Asia where H5N1 is endemic in poultry. In 2004, the Thai National Institute of Health, in collaboration with the U.S. Centers for Disease Control and Prevention, established influenza sentinel surveillance throughout Thailand. OBJECTIVES: To review routine epidemiologic and virologic surveillance for influenza viruses for public health action. METHODS: Throat swabs from persons with influenza-like illness and severe acute respiratory illness were collected at 11 sentinel sites during 2004-2010. Influenza viruses were identified using the standard protocol for polymerase chain reaction. Viruses were cultured and identified by immunofluorescence assay; strains were identified by hemagglutination inhibition assay. Data were analyzed to describe frequency, seasonality, and distribution of circulating strains. RESULTS: Of the 19,457 throat swabs, 3967 (20%) were positive for influenza viruses: 2663 (67%) were influenza A and able to be subtyped [21% H1N1, 25% H3N2, 21% pandemic (pdm) H1N1] and 1304 (33%) were influenza B. During 2009-2010, the surveillance system detected three waves of pdm H1N1. Influenza annually presents two peaks, a major peak during the rainy season (June-August) and a minor peak in winter (October-February). CONCLUSIONS: These data suggest that March-April may be the most appropriate months for seasonal influenza vaccination in Thailand. This system provides a robust profile of the epidemiology of influenza viruses in Thailand and has proven useful for public health planning.

Surveillance for influenza during the 2009 influenza A (H1N1) pandemic-United States, April 2009-March 2010.

The emergence in April 2009 and subsequent spread of the 2009 pandemic influenza A (H1N1) virus resulted in the first pandemic of the 21st century. This historic event was associated with unusual patterns of influenza activity in terms of the timing and persons affected in the United States throughout the summer and fall months of 2009 and the winter of 2010. The US Influenza Surveillance System identified 2 distinct waves of pandemic influenza H1N1 activity--the first peaking in June 2009, followed by a second peak in October 2009. All influenza surveillance components showed levels of influenza activity above that typically seen during late summer and early fall. During this period, influenza activity reached its highest level during the week ending 24 October 2009. This report summarizes US influenza surveillance data from 12 April 2009 through 27 March 2010.

Effects of adverse events on the projected population benefits and cost-effectiveness of using live attenuated influenza vaccine in children aged 6 months to 4 years.

OBJECTIVE: To evaluate the effect of adverse events associated with live attenuated influenza vaccine (LAIV) in children younger than 5 years on the cost-effectiveness of influenza vaccination. DESIGN: A decision analytic model was developed to predict costs and health effects of no vaccination, vaccination with LAIV, and vaccination with inactivated influenza vaccine (IIV). Probabilities, costs, and quality adjustments for uncomplicated influenza, outpatient visits, hospitalizations, deaths, vaccination, and vaccine adverse events were based on primary and published data. The analysis included the possible increased incidence of adverse events following vaccination with LAIV for children younger than 5 years, including fever, wheezing, and hospitalization. A societal perspective was used. Sensitivity analyses, including probabilistic sensitivity analysis, were conducted. SETTING: Vaccination in the physician office setting in the United States. PARTICIPANTS: Hypothetical cohorts of healthy children aged 6 months to 4 years. INTERVENTION: Vaccination with LAIV or IIV. MAIN OUTCOME MEASURE: Incremental cost-effectiveness ratio in dollars per quality-adjusted life-year (QALY). RESULTS: Cost-effectiveness ratios ranged from $20 000/QALY (age 6-23 months) to $33 000/QALY (age 3-4 years) for LAIV and from $21 000/QALY to $37 000/QALY for IIV for healthy children aged 6 months to 4 years. Inclusion of possible new adverse events for LAIV had varying effects on cost-effectiveness results. Results were not sensitive to the inclusion of wheezing as an adverse event but were sensitive to a possible increase in the probability of hospitalization. CONCLUSION: Live attenuated influenza vaccine had comparable cost-effectiveness compared with IIV for children younger than 5 years under a wide range of assumptions about the incidence of adverse events.

Episodic illness, chronic disease, and health care use among homeless persons in Metropolitan Atlanta, Georgia, 2007.

BACKGROUND: Homeless persons are at higher risk for morbidity and mortality from both chronic and episodic illness than the general population. Few data are available on the prevalence of these conditions and uptake of vaccination for prevention. METHODS: In March 2007, we administered a cross-sectional survey to a convenience sample of homeless persons in Atlanta. RESULTS: Approximately half (46.2%) of the survey participants reported at least one chronic medical condition. Acute respiratory symptoms within the previous 30 days were reported by up to 57.7% of survey participants. Receipt of influenza vaccination was reported by 31.9% of survey participants, receipt of pneumococcal vaccine by 18.7%. Vaccination rates varied by age and risk group. DISCUSSION: The survey demonstrated high rates of morbidity in this population. Influenza and pneumococcal vaccination rates were suboptimal. Culturally appropriate interventions must be developed to prevent respiratory and other diseases in this important group.

Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States.

CONTEXT: During the 2007-2008 influenza season, oseltamivir resistance among influenza A(H1N1) viruses increased significantly for the first time worldwide. Early surveillance data suggest that the prevalence of oseltamivir resistance among A(H1N1) viruses will most likely be higher during the 2008-2009 season. OBJECTIVES: To describe patients infected with oseltamivir-resistant influenza A(H1N1) virus and to determine whether there were any differences between these patients and patients infected with oseltamivir-susceptible A(H1N1) virus in demographic or epidemiological characteristics, clinical symptoms, severity of illness, or clinical outcomes. DESIGN, SETTING, AND PATIENTS: Influenza A(H1N1) viruses that were identified and submitted to the Centers for Disease Control and Prevention by US public health laboratories between September 30, 2007, and May 17, 2008, and between September 28, 2008, and February 19, 2009, were tested as part of ongoing surveillance. Oseltamivir resistance was determined by neuraminidase inhibition assay and pyrosequencing analysis. Information was collected using a standardized case form from patients with oseltamivir-resistant A(H1N1) infections and a comparison group of patients with oseltamivir-susceptible A(H1N1) infections during 2007-2008. MAIN OUTCOME MEASURES: Demographic and epidemiological information as well as clinical information, including symptoms, severity of illness, and clinical outcomes. RESULTS: During the 2007-2008 season, influenza A(H1N1) accounted for an estimated 19% of circulating influenza viruses in the United States. Among 1155 influenza A(H1N1) viruses tested from 45 states, 142 (12.3%) from 24 states were resistant to oseltamivir. Data were available for 99 oseltamivir-resistant cases and 182 oseltamivir-susceptible cases from this period. Among resistant cases, median age was 19 years (range, 1 month to 62 years), 5 patients (5%) were hospitalized, and 4 patients (4%) died. None reported oseltamivir exposure before influenza diagnostic sample collection. No significant differences were found between cases of oseltamivir-resistant and oseltamivir-susceptible influenza in demographic characteristics, underlying medical illness, or clinical symptoms. Preliminary data from the 2008-2009 influenza season identified resistance to oseltamivir among 264 of 268 influenza A(H1N1) viruses (98.5%) tested. CONCLUSIONS: Oseltamivir-resistant A(H1N1) viruses circulated widely in the United States during the 2007-2008 influenza season, appeared to be unrelated to oseltamivir use, and appeared to cause illness similar to oseltamivir-susceptible A(H1N1) viruses. Circulation of oseltamivir-resistant A(H1N1) viruses will continue, with a higher prevalence of resistance, during the 2008-2009 season.