Risk factors and attributable mortality of late aspergillosis after T-cell depleted hematopoietic stem cell transplantation

Abstract: Aim. Invasive aspergillosis occurs in 5–15% of allogeneic hematopoietic stem cell transplant (HSCT) recipients. Through the 1990s there has been an increase in the incidence of late aspergillosis (LA). We report on the incidence, risk factors, and attributable mortality of LA in a cohort of 398 adult and pediatric patients at Memorial Sloan-Kettering Cancer Center from January 1999 through December 2003.
Methods. LA was defined as occurring >40 days post HSCT. LA cases were identified by prospective surveillance and examination of a computerized database. Probable or definite aspergillosis was defined by standard EORTC/MSG criteria. Mortality was attributed to LA if it caused or significantly contributed to death.
Results. The overall incidence of LA in our cohort was 4.1%. Median time from stem cell infusion to diagnosis of LA was 164 days (range 68–677) after HSCT. The incidence of LA among unmodified, T-cell depleted, or reduced intensity HSCT was 2.2%, 4%, and 6.8%, respectively ( P not significant). Risk factors for LA were grade II–IV acute graft-versus-host disease (GVHD) ( P =0.002), chronic GVHD ( P =0.01), secondary neutropenia ( P =0.02), and reduced intensity conditioning containing alemtuzumab ( P =0.01). LA was the immediate cause of death in 1 of 10 (10%) T-cell depleted, 2 of 2 (100%) unmodified, and 1 of 4 (25%) of reduced-intensity HSCT.
Conclusions. LA developed a median 164 days post HSCT. All-cause 30-day mortality of LA was 56.3%. The majority of LA cases died of concurrent infections and not from invasive aspergillosis.     

Human metapneumovirus infection after allogeneic hematopoietic stem cell transplantation

Background

The clinical characteristics of human metapneumovirus (hMPV)-associated lower respiratory tract infection (LRTI) after allogeneic hematopoietic stem cell transplantation (HSCT) is not well described. We describe the clinical course in eight HSCT recipients suffering from hMPV infection.

Methods

We prospectively included all patients with hMPV-associated LRTI after allogeneic HSCT during a period of 1?year. hMPV was diagnosed by multiplex polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL).

Results

Eight patients with hMPV-associated LRTI were identified from 93 BAL samples. Three of the eight patients had co-infections with other pathogens. The median age of the patients was 45?years [interquartile range (IQR) 36.8?C53.5], the median time posttransplant was 473?days (IQR 251?C1,165), 5/8 patients had chronic graft-versus-host disease (cGvHD), and 6/8 patients received immunosuppression. Chest computed tomography (CT) scanning showed a ground-glass pattern in 7/8 patients. Seven of eight patients required hospitalization due to severe symptoms and hypoxemia. All were treated with intravenous immunoglobulin (IVIG), which was combined with oral ribavirin in six patients. The mortality rate was 12.5?% (1/8).

Conclusions

hMPV-associated LRTI in allogeneic HSCT recipients are not uncommon and present with unspecific respiratory symptoms, ground-glass pattern in CT scanning, and co-infection.     

Quantification of the influenza virus load by real-time polymerase chain reaction in nasopharyngeal swabs of patients treated with oseltamivir

Influenza A virus load was assessed by real-time polymerase chain reaction (PCR) in nasopharyngeal swabs of infected patients treated with oseltamivir. The mean pretreatment virus load was significantly lower in the 24 patients (group A) who initiated treatment within 24 h of the onset of symptoms than it was in the 26 patients (group B) who initiated treatment between 24 and 48 h (1.6x105 vs. 8.4x105 copies/600 ng of total RNA, P=.04); after 48 h of treatment, twice as many patients in group B still had a positive PCR result, compared with patients in group A (42.3% vs. 20.7%). These virological results support the clinical benefit provided by early therapeutic intervention of influenza illness.     

Oseltamivir Treatment Prevents the Increased Influenza Virus Disease Severity and Lethality Occurring in Chronic Ethanol Consuming Mice

Background: Chronic consumption of ethanol (EtOH) is well recognized to lead to defective innate and adaptive immune responses and increase the severity of pulmonary infections. Our own studies have demonstrated that chronic EtOH consumption decreases CD8 T‐cell immunity to influenza virus infections (IAV) leading to severe infections and mortality. Interestingly, antiviral treatment of IAVs has been shown to be compromised in mice and humans that are immuno‐deficient. It is known that EtOH can alter the pharmacokinetics of antivirals. Therefore, the effectiveness of influenza antiviral therapy during chronic ethanol consumption remains in question. Methods: BALB/c mice were placed on 18% (w/v) EtOH in their drinking water for 8 weeks. Chronic EtOH consuming and water controls were then treated with 10 mg/kg oseltamivir orally and infected intranasally with influenza virus 4 hours post‐oseltamivir treatment. The mice were then treated with oseltamivir twice daily until day 7 postinfection. Influenza disease severity was measured by morbidity and mortality, pulmonary viral titers, and histology. Results: Chronic EtOH consuming mice infected with IAV and treated with oseltamivir have decreased morbidity and mortality, pulmonary viral titers, and pulmonary pathology compared to untreated EtOH mice. Conclusions: Despite the severe immune defect seen in chronic EtOH mice as well as the potential for EtOH to inhibit the conversion of oseltamivir into an active form, treatment with oseltamivir reduces viral shedding as well as disease severity. These data suggest that the combination of a limited adaptive immune response plus the anti‐IAV drug oseltamivir is sufficient to curb high mortality and mediate resolution of IAVs in mice chronically consuming ethanol.     

Five years of monitoring for the emergence of oseltamivir resistance in patients with influenza A infections in the Influenza Resistance Information Study

Background and objectives

The Influenza Resistance Information Study (IRIS) was initiated in 2008 to study the emergence of neuraminidase inhibitor (NAI) resistance and the clinical course of influenza in immunocompetent treated and untreated patients.

Methods

Patients had throat/nose swabs collected on days 1, 3, 6 and 10 for analyses of influenza type, subtype and virus susceptibility to NAIs. RT‐PCR‐positive samples were cultured and tested for NAI resistance by specific RT‐PCR and phenotypic testing. Scores for influenza symptoms were recorded on diary cards (Days 1‐10). This study focuses on influenza A‐infected cases only.

Results

Among 3230 RT‐PCR‐positive patients, 2316 had influenza A of whom 1216 received oseltamivir monotherapy within 2 days of symptom onset (9 seasonal H1N1; 662 H3N2; 545 H1N1pdm2009). Except for 9 patients with naturally resistant seasonal H1N1 (2008/9), no resistance was detected in Day 1 samples. Emergence of resistance (post‐Day 1) was detected in 43/1207 (3.56%) oseltamivir‐treated influenza A‐infected patients, with a higher frequency in 1‐ to 5‐year‐olds (11.8%) vs >5‐year‐olds (1.4%). All N1‐ and N2‐resistant viruses had H275Y (n = 27) or R292K (n = 16) substitutions, respectively. For 43 patients, virus clearance was significantly delayed vs treated patients with susceptible viruses (8.1 vs 10.9 days; P < .0001), and 11 (23.2%) remained RT‐PCR positive for influenza at Day 10. However, their symptoms resolved by Day 6 or earlier.

Conclusions

Oseltamivir resistance was only detected during antiviral treatment, with the highest incidence occurring among 1‐ to 5‐year‐olds. Resistance delayed viral clearance, but had no impact on symptom resolution.     

Detection of influenza A virus in live bird markets in Kenya, 2009–2011

Please cite this paper as: Munyua et al. (2013) Detection of influenza A virus in live bird markets in Kenya, 2009–2011. Influenza and Other Respiratory Viruses 7(2), 113–119. Background Surveillance for influenza viruses within live bird markets (LBMs) has been recognized as an effective tool for detecting circulating avian influenza viruses (AIVs). In Sub‐Saharan Africa, limited data exist on AIVs in animal hosts, and in Kenya the presence of influenza virus in animal hosts has not been described. Objectives This surveillance project aimed to detect influenza A virus in poultry traded in five LBMs in Kenya. Methods We visited each market monthly and collected oropharyngeal and cloacal specimens from poultry and environmental specimens for virological testing for influenza A by real time RT‐PCR. On each visit, we collected information on the number and types of birds in each market, health status of the birds, and market practices. Results During March 24, 2009–February 28, 2011, we collected 5221 cloacal and oropharyngeal swabs. Of the 5199 (99·6%) specimens tested, influenza A virus was detected in 42 (0·8%), including 35/4166 (0·8%) specimens from chickens, 3/381 (0·8%) from turkeys, and 4/335 (1·2%) from geese. None of the 317 duck specimens were positive. Influenza was more commonly detected in oropharyngeal [33 (1·3%)] than in cloacal [9 (0·4%)] specimens. None of the 485 environmental specimens were positive. Virus was detected in all five markets during most (14/22) of the months. Ducks and geese were kept longer at the market (median 30 days) than chickens (median 2 days). Conclusions Influenza A was detected in a small percentage of poultry traded in LBMs in Kenya. Efforts should be made to promote practices that could limit the maintenance and transmission of AIVs in LBMs.     

Invasive fungal infections associated with prior respiratory viral infections in immunocompromised hosts

Background

Increased risk of invasive pulmonary aspergillosis after influenza infection has been reported; however data are limited.

Purpose

To describe Invasive fungal infections (IFI) associated with preceding respiratory viral infection at a large referral center.

Methods

We reviewed all IFI cases among patients with positive influenza and/or RSV nasopharyngeal/lower respiratory tract PCR from October 2015 to December 2016. Cases of pulmonary IFI were classified as possible, probable, and definite based on EORTC-MSG definitions.

Results

We identified 8 cases (4 influenza, 4 RSV); 3 with probable Aspergillosis, 1 possible Aspergillosis, 1 probable Histoplasmosis, 1 probable Mucormycosis, and 2 possible IFI (consistent clinical and imaging findings). Half of our patients were men with a mean age of 64 years (SD 8) and median Charlson Comorbidity Score of 3.5 (IQR 3-7). Most common risk factors were stem cell transplant (75%) and neutropenia (62.5%). Four patients were on antifungal prophylaxis at presentation. All patients received anti-viral therapy with oseltamivir/ribavirin and 50% received empiric antibiotics. Median duration from onset of viral infection to diagnosis of IFI was 8.5 days (IQR 2.5-14) and 75% were diagnosed during the same admission. All received antifungal therapy; 62.5% required ICU care, and 37.5% died during index hospitalization.

Conclusions

Our study supports earlier observations describing IFI following respiratory viral infection in immunocompromised hosts. Secondary IFI occurred in 1.4% of our cohort and most occurred during the index admission. IFI following viral illness is associated with high mortality and early detection and therapy may improve outcomes.

     

Effectiveness of oseltamivir treatment against influenza type A and type B infection in children

We investigated the effectiveness of oseltamivir treatment against influenza virus infection in children. We treated 131 patients (mean age, 5.8 +/- 3.6 years) with oseltamivir (4 mg/kg/day for 5 days) during the 2001-2002 epidemic. All of the patients had been diagnosed with influenza using a rapid diagnosis kit. When treatment was initiated within 48 hours of the onset of fever, 44% of the patients became afebrile (< 37.5 degrees C) within one day, and 86% of them recovered within two days. The average duration of fever after the initiation of oseltamivir treatment was 1.7 days. Oseltamivir was equally effective against both influenza type A and type B. No differences in the effectiveness of oseltamivir treatment were observed between young children (< 4 years of age) and school-aged children (> 6 years of age). No obvious side effects were observed.     

Epidemiology of viral respiratory tract infections in an outpatient haematology facility

Viral respiratory tract infections (VRTI) are an important cause of morbidity and mortality in haematology patients, particularly after haematopoietic stem cell transplantation (HSCT). The incidence, clinical presentation and outcome of symptomatic and asymptomatic VRTI in HSCT outpatient unit were prospectively evaluated during a single influenza season (January–March 2011). Pharyngeal swabs were performed at the first visit and if new symptoms were present. Molecular multiplex assay for 12 respiratory viruses was performed by the regional reference laboratory. Among 264 swabs from 193 outpatients, 58 (22 %) resulted positive for 61 viruses (influenza, n?=?20; respiratory syncytial virus [RSV], n?=?21; rhinovirus, n?=?12; coronavirus, n?=?4; adenovirus, n?=?3; parainfluenza, n?=?1). VRTI were detected more frequently in the presence of symptoms than in asymptomatic patients: 49 out of 162 (30 %) vs. 9 out of 102 (9 %), p?<?0.001. Influenza-like illness syndrome (ILI) was significantly associated with a VRTI if compared to other presentations (42 %), while the European Centre for Disease Prevention and Control definition was not (30 %). Positive predictive value (PPV) of ILI for influenza was 17 %. Influenza and RSV peak periods were contemporary. Influenza prophylaxis was given to 25 patients following exposure. Low rate of progression from upper to lower respiratory tract infection (approximately 5 % for influenza and RSV), no nosocomial epidemics and no VRTI-related deaths were observed. VRTI are very frequent in high-risk haematology outpatients, but symptoms are aspecific and PPV of ILI is low. Symptoms of influenza and RSV overlap. Thus, microbiological diagnosis and contact preventive measures are crucial. Rather than universal influenza prophylaxis, prompt diagnosis and treatment of only documented infections could be pursued.     

Resumption of oral intake following percutaneous endoscopic gastrostomy

Background and Aims:  Percutaneous endoscopic gastrostomy (PEG) provides enteral nutrition to patients who cannot swallow. Few studies have prospectively evaluated its long-term outcomes or eventual resumption of oral intake.
Methods:  Consecutive PEG patients were prospectively recruited from a tertiary hospital over 12 months and followed until all had met the primary endpoints of death or resumption of oral diet with PEG extubation. Data was collected by standardised periodic phone interview.
Results:  Forty patients (24 males, median age 74 years) were followed for up to 8.4 years (median 5.3 months, interquartile range [IQR] 13.6 months). The end-of-study mortality rate was 70% (median 6.8 months, IQR 19.9 months) and the only predictor of mortality was head injury as the indication for PEG (Cox regression HR 5.90, 95% CI: 1.2–28.4). At two years following PEG, 30% of patients had resumed oral intake (median 2.9 months, IQR 7.2 months) and 19% remained on PEG-feeding. Predictors of resumption of oral intake were the ability to tolerate some oral intake at 3 months (HR: 248.5, 95% CI: 8.7–7065.3) and 6 months (HR: 6.3, 95% CI: 1.03–38.9) but not at 12 months. Cumulative survival was highest for ear nose and throat (ENT) tumour and worst for acute head injury (log rank P  = 0.048).
Conclusions:  Half of all PEG patients remained alive at 2 years using PEG or have resumed full oral intake. A supervised trial of oral intake at 3 or 6 months may help predict eventual resumption of per oral diet.     

Neuraminidase Inhibitors in the Treatment of Influenza A and B – Overview and Case Reports

Summary Influenza viruses type A and B can cause a wide spectrum of illness, and they are responsible for considerable mortality and morbidity. With the new neuraminidase inhibitors, of which zanamivir was the first drug to be licensed, the physician has antivirals at his disposal which are safe and effective against both influenza virus type A and type B. Available data from clinical Phase III studies indicate benefits in terms of a reduction in the median time to alleviation of major symptoms by 1.5 to 3 days when treatment is started within 36 to 48h after onset of influenza. Similar results have been obtained with oseltamivir. Neuraminidase inhibitors provide a valuable treatment option, particularly for individuals not protected by vaccination, and those at high risk of influenza-related complications. The study results obtained so far indicate that patients with pre-existing diseases and those with severe influenza symptoms profit most from the treatment. This is confirmed by our own experience in treating severe influenza conditions. Received: March 27, 2000 · Revision accepted: July 12, 2000     

Comparisons of oseltamivir‐resistant (H275Y) and concurrent oseltamivir‐susceptible seasonal influenza A(H1N1) virus infections in hospitalized adults, 2008–2009

In an observational cohort study, we found that adults hospitalized for oseltamivir‐resistant (H275Y) seasonal H1N1 influenza (n = 46) were older than those infected with oseltamivir‐susceptible strains (n = 31) [74(IQR 59–83) versus 64(IQR 48–76) years; P = 0·045], and most had major comorbidities (78% versus 65%). Disease severity and clinical outcomes were comparable between the two groups: radiographic pneumonia 40–42%, supplemental oxygen use 47–48%, critical illness 11–13%, median duration of hospitalization 5–6 days, death rate 6–9%. Failure to receive effective antiviral therapy was associated with progression to critical illness (23% versus 0%, P = 0·016) and death (20% versus 0%, P = 0·033) in hospitalized patients with seasonal H1N1 influenza.     

Outbreak of pandemic 2009 influenza A/H1N1 infection in the hematology ward: fatal clinical outcome of hematopoietic stem cell transplant recipients and emergence of the H275Y neuraminidase mutation

We report an outbreak of pandemic 2009 influenza A/H1N1 virus (2009 H1N1) infection that occurred in the hematology ward of our institution during the 2010-2011 influenza season. A total of seven hospitalized patients with hematologic tumors, including five recipients of hematopoietic stem cell transplantation (HSCT), successively developed rapid influenza detection test (RIDT)-positive influenza A; four patients had laboratory-confirmed 2009 H1N1 infection. Three HSCT recipients required mechanical ventilation support and two were admitted to the intensive care unit; they died of progressive respiratory failure despite receiving available anti-viral drugs. We implemented outbreak-control measures including transferal of RIDT-positive patients to a single-patient room and chemoprophylaxis with oseltamivir. We note that the H275Y neuraminidase mutation was detected in respiratory specimens from three patients, who were administered therapeutic or prophylactic dosages of oseltamivir. The present report demonstrates that the nosocomial 2009 H1N1 outbreak in the hematology ward led to fatal clinical outcomes and the emergence of a resistant virus at a markedly high rate.     

Control of hospital infection of influenza: administration of neuraminidase inhibitor and cohort isolation of influenza patients

Influenza can spread rapidly to patients and staff in hospitals when influenza is introduced by visitors, staff, or patients. In order to prevent and control outbreaks of influenza in hospitals, systematic management is important. This consists of a rapid diagnostic test, cohort isolation and administration of neuraminidase inhibitor. In the 2002-2003 season, 53 elderly patients were admitted to our hospital under the control of the system. The mean age was 78.8 years. We set 2 isolation rooms (10 beds) for influenza patients. Patients were isolated in the room for three days, administered oseltamivir immediately. Oral oseltamivir was well tolerated. Mean hospital stay was 10.7 days. 36 cases developed complications requiring antibiotics, and one patient developed a catheter related infection. Under the system, we could avoid cross infection of influenza. In two cases, nose swabs were taken for virus isolation every 12 hours and a rapid decline in virus shedding was observed after treatment.     

Toxoplasmosis after hematopoietic stem cell transplantation.

Forty-one cases of toxoplasmosis were diagnosed in 15 European transplantation centers in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT) from 1994 through 1998. Most patients (39 [94%]) were seropositive for Toxoplasma gondii before they underwent transplantation, and 30 (73%) had developed moderate to severe acute graft-versus-host disease before they developed toxoplasmosis. Thirty-five (85%) patients had Toxoplasma disease with evidence of organ involvement, whereas 6 (15%) patients had Toxoplasma infection, as defined by fever and a positive polymerase chain reaction (PCR) finding for T. gondii in blood. Nine patients were diagnosed at autopsy. Thirty patients (73%) had not received antimicrobial prophylaxis with anti-Toxoplasma activity after undergoing transplantation. The median day of onset of disease after HSCT was 64. Twenty-two (63%) patients died from toxoplasmosis, and 23 (66%) received adequate anti-Toxoplasma therapy for > or =3 days. Among these 23 patients, 11 (48%) showed a complete response and 3 (13%) showed improvement. In univariate and multivariate analyses, having received adequate therapy and experiencing late infection (>63 days after HSCT) were associated with a lower risk of dying from toxoplasmosis. Toxoplasmosis after HSCT is a severe infection with a high mortality rate even when diagnosed soon after HSCT, and PCR may help establish the diagnosis earlier.     

儿童甲型H1N1流行性感冒病毒相关性肺炎的临床特征

目的 了解儿童甲型H1N1流行性感冒(流感)病毒相关性肺炎的临床流行特征.方法 通过描述性研究对2009年上海复旦大学附属儿科医院收治的30例甲型H1N1流感病毒所致肺炎的患儿做临床及流行病学分析.中位数比较采用秩和检验,率的比较采用精确卡方检验.结果 30例确诊为甲型H1N1流感合并肺炎的患儿中,年龄中位数为5.9岁,5例有基础疾病史,占16.7%.有明确发热病例暴露史的20例,占66.7%.所有患儿均有发热和咳嗽,11例伴气促,占36.7%,10例伴喘息,占33.3%.11例患儿WBC＜4.0×109/L,占36.7%,2例PLT减少,占6.7%.所有患儿入院时胸部X线片提示肺部有单侧或双侧片状渗出性病灶,4例危重症患儿肺部多处大片状渗出伴肺水肿,占13.3%,1例危重症肺炎患儿发病后3个月和9个月复查胸部CT提示不同程度肺纤维化,占3.3%,3例同时伴纵隔积气和皮下积气,占10.0%,6例并发急性呼吸衰竭,占20.0%,3例伴支气管哮喘急性发作,占10.0%,1例合并脑炎,占3.3%.所有患儿均给予奥司他书和抗菌药物治疗,4例接受机械通气,均治愈或好转出院.发病2 d内和2 d后接受奥司他韦治疗的患儿的热程中位数比较差异有统计学意义(2 d比5 d,Z=-8.015,P＜0.01).结论 学龄前和学龄儿童易感染甲型H1N1流感病毒,可并发严重的肺部疾病.在发病早期采用奥司他韦治疗,可缩短热程,降低危重并发症的发生.     

Infections with the 2009 H1N1 influenza virus among hematopoietic SCT recipients: a single center experience

We retrospectively reviewed medical records of 39 hematopoietic SCT (HSCT) recipients who presented at our hospital between 1 October 2009 and 31 January 2010 with the 2009 H1N1 influenza infection. The median age at presentation was 13.8 years (range: 3.3-56.9), infections developed at a median of 585 days (range: 0-2316) post transplant, the majority (n=27, 69%) occurred in allogeneic HSCT recipients, 12 (31%) patients were on immunosuppressive therapy and 12 (31%) had GVHD. Lower airway disease was present in 8 patients (21%). In total, 15 patients (39%) were hospitalized with a median duration of 4.5 days (range: 3-27 days) and 3 (8%) required mechanical ventilation; 2 of whom died.     

Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation

Community-acquired respiratory virus infections are a cause of mortality after stem cell transplantation (SCT). A prospective study was performed at 37 centers to determine their frequency and importance. Additional cases were also collected to allow the analysis of risk factors for severe infection. Forty episodes were collected in the prospective study and 53 additional episodes through subsequent case collection. The frequency of documented respiratory virus infections was 3.5% among 819 allogeneic and 0.4% among 1154 autologous SCT patients transplanted during the study period. The frequency of lower respiratory tract infections (LRTI) was 2.1% among allogeneic and 0.2% among autologous SCT patients. The mortality within 28 days from diagnosis of a respiratory viral infection was 1.1% among allogeneic SCT while no autologous SCT patient died. The deaths of five patients (0.6%) were directly attributed to a respiratory virus infection (three RSV; two influenza A). On multivariate analysis, lymphocytopenia increased the risk for LRTI (P = 0.008). Lymphocytopenia was also a significant risk factor for LRTI in patients with RSV infections. The overall mortality in RSV infection was 30.4% and the direct RSV-associated mortality was 17.4%. For influenza A virus infection, the corresponding percentages were 23.0% and 15.3%. This prospective study supports the fact that community-acquired respiratory virus infections cause transplant-related mortality after SCT.     

Influenza: epidemiology, clinical features, therapy, and prevention

Influenza A and B are important causes of respiratory illness in all age groups. Influenza causes seasonal outbreaks globally and, less commonly, pandemics. In the United States, seasonal influenza epidemics account for >200,000 hospitalizations and >30,000 deaths annually. More than 90% of deaths occur in the elderly population. Interestingly, in the novel 2009 H1N1 influenza pandemic, attack rates were highest among children and young adults. Fewer than 10% of cases occurred in adults >60 years old, likely because preexisting antibodies against other H1N1 viruses afforded protection. Despite concerns about a high lethality rate with the novel 2009 H1N1 strain, most illnesses caused by the 2009 H1N1 viruses were mild (overall case fatality rate <0.5%). Clinical features of influenza infection overlap with other respiratory pathogens (particularly viruses). The diagnosis is often delayed due to low suspicion and the limited use of specific diagnostic tests. Rapid diagnostic tests are widely available and allow detection of influenza antigen in respiratory secretions within 1 hour; however, sensitivity ranges from 50 to 90%. Neuraminidase inhibitors (NAIs) (eg, oseltamivir and zanamivir) are effective for treating influenza A or B and for prophylaxis in selected adults and children. Resistance to NAIs is rare, but influenza strains resistant to oseltamivir have been detected. Vaccines are the cornerstone of influenza control. Currently, trivalent inactivated vaccine (TIV) and live attenuated influenza vaccine (LAIV) are available. These agents reduce mortality and morbidity in high-risk patients (i.e., the elderly or patients with comorbidities), and expanding the use of vaccines to healthy children and adults reduces the incidence of influenza, pneumonia, and hospitalizations due to respiratory illnesses in the community.