An influenza A (H3N2) virus outbreak in the Kingdom of Cambodia during the COVID-19 pandemic of 2020.

BACKGROUND: Global influenza virus circulation decreased during the COVID-19 pandemic, possibly due to widespread community mitigation measures. Cambodia eased some COVID-19 mitigation measures in June and July 2020. On 20 August a cluster of respiratory illnesses occurred among residents of a pagoda, including people who tested positive for influenza A but none who were positive for SARS-CoV-2. METHODS: A response team was deployed on 25 August 2020. People with influenza-like illness (ILI) were asked questions regarding demographics, illness, personal prevention measures, and residential arrangements. Respiratory swabs were tested for influenza and SARS-Cov-2 by real-time reverse transcription PCR, and viruses were sequenced. Sentinel surveillance data were analyzed to assess recent trends in influenza circulation in the community. RESULTS: Influenza A (H3N2) viruses were identified during sentinel surveillance in Cambodia in July 2020 prior to the reported pagoda outbreak. Among the 362 pagoda residents, 73 (20.2%) ILI cases were identified and 40 were tested, where 33/40 (82.5%) confirmed positive for influenza A (H3N2). All 40 were negative for SARS-CoV-2. Among the 73 residents with ILI, none were vaccinated against influenza, 47 (64%) clustered in 3/8 sleeping quarters, 20 (27%) reported often wearing a mask, 27 (36%) reported often washing hands, and 11 (15%) reported practicing social distancing. All viruses clustered within clade 3c2.A1 close to strains circulating in Australia in 2020. CONCLUSIONS: Circulation of influenza viruses began in the community following the relaxation of national COVID-19 mitigation measures, and prior to the outbreak in a pagoda with limited social distancing. Continued surveillance and influenza vaccination are required to limit the impact of influenza globally.

Progress toward sustainable influenza vaccination in the Lao Peoples' Democratic Republic, 2012-2018.

Despite global recommendations for influenza vaccination of high-risk, target populations, few low and middle-income countries have national influenza vaccination programs. Between 2012 and 2017, Lao PDR planned and conducted a series of activities to develop its national influenza vaccine program as a part of its overall national immunization program. In this paper, we review the underlying strategic planning for this process, and outline the sequence of activities, research studies, partnerships, and policy decisions that were required to build Laos' influenza vaccine program. The successful development and sustainability of the program in Laos offers lessons for other low and middle-income countries interested in initiating or expanding influenza immunization.

Utility of state-level influenza disease burden and severity estimates to investigate an apparent increase in reported severe cases of influenza A(H1N1) pdm09 - Arizona, 2015-2016.

The Arizona Department of Health Services identified unusually high levels of influenza activity and severe complications during the 2015-2016 influenza season leading to concerns about potential increased disease severity compared with prior seasons. We estimated state-level burden and severity to compare across three seasons using multiple data sources for community-level illness, hospitalisation and death. Severity ratios were calculated as the number of hospitalisations or deaths per community case. Community influenza-like illness rates, hospitalisation rates and mortality rates in 2015-2016 were higher than the previous two seasons. However, ratios of severe disease to community illness were similar. Arizona experienced overall increased disease burden in 2015-2016, but not increased severity compared with prior seasons. Timely estimates of state-specific burden and severity are potentially feasible and may provide important information during seemingly unusual influenza seasons or pandemic situations.

Do animal exhibitors support and follow recommendations to prevent transmission of variant influenza at agricultural fairs? A survey of animal exhibitor households after a variant influenza virus outbreak in Michigan.

Influenza A viruses circulate in swine and can spread rapidly among swine when housed in close proximity, such as at agricultural fairs. Youth who have close and prolonged contact with influenza-infected swine at agricultural fairs may be at increased risk of acquiring influenza virus infection from swine. Animal and human health officials have issued written measures to minimize influenza transmission at agricultural exhibitions; however, there is little information on the knowledge, attitudes, and practice (KAP) of these measures among animal exhibitors. After an August 2016 outbreak of influenza A(H3N2) variant ("H3N2v") virus infections (i.e., humans infected with swine influenza viruses) in Michigan, we surveyed households of animal exhibitors at eight fairs (including one with known H3N2v infections) to assess their KAP related to variant virus infections and their support for prevention measures. Among 170 households interviewed, most (90%, 151/167) perceived their risk of acquiring influenza from swine to be low or very low. Animal exhibitor households reported high levels of behaviours that put them at increased risk of variant influenza virus infections, including eating or drinking in swine barns (43%, 66/154) and hugging, kissing or snuggling with swine at agricultural fairs (31%, 48/157). Among several recommendations, including limiting the duration of swine exhibits and restricting eating and drinking in the animal barns, the only recommendation supported by a majority of households was the presence of prominent hand-washing stations with a person to monitor hand-washing behaviour (76%, 129/170). This is a unique study of KAP among animal exhibitors and highlights that animal exhibitor households engage in behaviours that could increase their risk of variant virus infections and have low support for currently recommended measures to minimize infection transmission. Further efforts are needed to understand the lack of support for recommended measures and to encourage healthy behaviours at fairs.

Evaluating interest in an influenza A(H5N1) vaccine among laboratory workers who work with highly-pathogenic avian influenza viruses in the United States.

BACKGROUND: Highly pathogenic avian influenza A (HPAI) viruses found in poultry and wild birds occasionally infect humans and can cause serious disease. In 2014, the Advisory Committee on Immunization Practices (ACIP) reviewed data from one licensed ASO3-adjuvanted influenza A(H5N1) vaccine for consideration of use during inter-pandemic periods among persons with occupational exposure. To guide vaccine policy decisions, we conducted a survey of laboratory workers to assess demand for HPAI vaccination. METHODS: We designed an anonymous web survey (EpiInfo 7.0) to collect information on demographics, type of work and time spent with HPAI viruses, and interest in HPAI vaccination. Eligible participants were identified from 42 entities registered with United States Department of Agriculture's Agricultural Select Agent program in 2016 and emailed electronic surveys. Personnel with Biosafety Level 3 enhanced (BSL-3E) laboratory access were surveyed. Descriptive analysis was performed. RESULTS: Overall, 131 responses were received from 33 principal investigators, 26 research scientists, 24 technicians, 15 postdoctoral fellows, 6 students, and 27 others. The estimated response rate was 15% among the laboratory personnel of responding principal investigators. One hundred respondents reported working in a BSL-3E area where HPAI experiments occurred with a mean time of 5.1-11.7 h per week. Overall, 49% were interested in receiving an A(H5N1) vaccine. By role, interest was highest among students (80%) and among those who spent >50% of their time in a BSL-3E area (64%). Most (61%) of those who said they might be or were not interested in vaccine believed it would not provide additional protection to current safety practices. CONCLUSIONS: Half of responding laboratory workers was interested in receiving an influenza A(H5N1) vaccine. HPAI vaccination of laboratory workers at risk of occupational exposure could be used along with existing safety practices to protect this population.

Pneumococcal antigen testing of blood culture broth to enhance the detection of Streptococcus pneumoniae bacteremia.

The purpose of this investigation was to enhance the detection of pneumococcal bacteremia cases using the Binax NOW® immunochromatographic test (ICT) on blood culture broth as part of surveillance in two rural Thailand provinces. Blood cultures were collected as clinically indicated from hospitalized patients. ICT was performed on broth from culture bottles flagged as positive by BactT/ALERT® (alarm-positive) but which failed to grow organisms on subculture. During the period May 2005-June 2007, ICT was positive on 43 (24%) of 182 alarm-positive blood cultures with no growth on subculture. Compared to pneumococcal bacteremia cases confirmed by culture, cases detected only by ICT had a longer median time from culture collection to incubation and a longer median time from alarm positivity to subculture, and were more likely to be from patients pretreated with antibiotics. In a subsequent surveillance period (July 2007-December 2009), ICT continued to detect additional pneumococcal cases, but in a lower proportion of samples (7 of 221, 3.2%). Recently, as part of a separate study, ICT applied to uninoculated blood culture broth produced weak-positive results, mandating caution if testing broth from patient blood cultures. The antigen testing of blood culture broth appears to enhance the detection of pneumococcal bacteremia, but a controlled evaluation is needed.

Incidence of respiratory pathogens in persons hospitalized with pneumonia in two provinces in Thailand.

Although pneumonia is a leading cause of death from infectious disease worldwide, comprehensive information about its causes and incidence in low- and middle-income countries is lacking. Active surveillance of hospitalized patients with pneumonia is ongoing in Thailand. Consenting patients are tested for seven bacterial and 14 viral respiratory pathogens by PCR and viral culture on nasopharyngeal swab specimens, serology on acute/convalescent sera, sputum smears and antigen detection tests on urine. Between September 2003 and December 2005, there were 1730 episodes of radiographically confirmed pneumonia (34·6% in children aged <5 years); 66 patients (3·8%) died. A recognized pathogen was identified in 42·5% of episodes. Respiratory syncytial virus (RSV) infection was associated with 16·7% of all pneumonias, 41·2% in children. The viral pathogen with the highest incidence in children aged <5 years was RSV (417·1/100,000 per year) and in persons aged ≥50 years, influenza virus A (38·8/100,000 per year). These data can help guide health policy towards effective prevention strategies.

High dose single-agent paclitaxel in a hemodialysis patient with advanced ovarian cancer: a case report with pharmacokinetic analysis and review of the literature.

There exists only scarce data on the pharmacokinetics of paclitaxel in patients with renal insufficiency. A 53-year-old woman on hemodialysis was treated with paclitaxel for relapsed ovarian cancer. Paclitaxel was administered as a 3-h infusion at 175, 225, and 300 mg/m(2) on nonhemodialysis days. The pharmacokinetic analysis revealed independence of the pharmacokinetic parameters for paclitaxel from the extent of renal (dys-)function. The peak plasma concentration of the 300 mg/m(2) dose level before and after dialysis was 23.05 and 21.01 ng/mL, respectively, proving that paclitaxel was not dialysable. The area under the plasma concentration versus time curve for the standard and highest dose of paclitaxel was 12,200 ng.h/mL in mean and 40,936 ng.h/mL, respectively. The absence of marked side effects at all dose levels was in line with the independence of the pharmacokinetic parameters for paclitaxel from renal function. No objective response was found, but a marked improvement of symptoms from gastrointestinal obstruction as well as a decrease in the serum CA125 level were observed. Patients with terminal renal failure undergoing hemodialysis tolerate conventional and even high doses of paclitaxel without experiencing severe toxicity.

Evaluation of community-based serologic screening for identification of chronic Salmonella typhi carriers in Vietnam.

OBJECTIVES: To determine the utility of screening anti-Vi antibodies to detect chronic Salmonella Typhi carriers in an endemic community. METHODS: We conducted a community-based serologic survey for anti-Vi antibodies to identify chronic Salmonella Typhi carriers in a typhoid endemic region in Vietnam. RESULTS: We tested sera from 3209 (67.2%) of 4772 eligible adults. The median age was 37 years (range 20-92), 57.3% were female, 4.6% reported a history of typhoid fever and 0.3% reported typhoid vaccination. Anti-Vi antibody titers tested in Vietnam were < 1:40 in 2759 (86.0%), 1:40 in 194 (6.0%), 1:80 in 168 (5.2%), 1:160 in 57 (1.8%), and > or = 1:320 in 31 (1.0%). On re-testing in the USA, an additional 19 sera with titers > or = 1:160 were identified. We collected 589 rectal swabs from 103 (96.3%) of 107 persons with Vi antibody titers > or = 1:160 and 183 swabs from 33 persons with antibody titers < 1:80. No Salmonella Typhi was isolated. CONCLUSIONS: Community-based serologic screening is a feasible, but impractical method for identifying chronic Salmonella Typhi carriers. Background levels of anti-Vi antibody titers in this endemic area may be high despite a low prevalence of chronic carriers.

Assessment of the use and feasibility of video to supplement the genetic counseling process: a cancer genetic counseling perspective.

Cancer genetic counselors use a variety of teaching modalities for patient education. This survey of cancer genetic counselors assessed their use of educational videos and their recommendations for content of future videos. Thirty percent of respondents use videos for patient education. Cited benefits included reinforcement of information for clients and increased counselor efficiency. Of the 70% who do not use videos, predominant barriers included the perceived lack of an appropriate video, lack of space and/or equipment, and concern that videos are impersonal. Most respondents desired a video that is representative of the genetic counseling session, but emphasized the importance of using broad information. Content considered critical included the pros and cons of genetic testing, associated psychosocial implications, and genetic discrimination. The results of this exploratory study provide data relevant for the development of a cancer genetics video for patient education, and suggestions are made based on aspects of information processing and communication theories.

Outbreaks of typhoid fever in the United States, 1960-99.

Although the incidence of typhoid fever in the United States has been low since the 1940s, Salmonella Typhi continues to cause outbreaks. We reviewed reported outbreaks of typhoid fever from 1960 to 1999. There were 60 outbreaks; in 54, exposure occurred within the United States. These 54 outbreaks accounted for 957 total cases (median 10) and 4 deaths. In 36 (67%) outbreaks the route of transmission was identified, and in 16 (62%) of the 26 foodborne outbreaks an asymptomatic carrier was identified by culture or serology. The median incubation period was 2 weeks. Isolates from 10 (40%) of 25 outbreaks were phage type E1. The average frequency of outbreaks decreased from 1.85/year during 1960-79 to 0.85/year during 1980-99 (P=0.0001). S. Typhi outbreaks in the United States are generally small in size but can cause significant morbidity, and are often foodborne, warranting thorough investigation.

Evaluation of methods for subtyping Campylobacter jejuni during an outbreak involving a food handler.

In October 1998, the Centers for Disease Control and Prevention (CDC) assisted in an investigation of an outbreak of campylobacteriosis at a school in Salina, Kansas. Twenty-two isolates were submitted from the Kansas state public health laboratory to CDC, 9 associated with the outbreak and 13 epidemiologically unrelated sporadic isolates. Pulsed-field gel electrophoresis (PFGE) using SmaI and SalI was initially used to validate the epidemiologic data. We then tested the ability of other subtyping techniques to distinguish the outbreak-associated isolates from unrelated sporadic isolates. The methods employed were somatic O serotyping, PCR-restriction fragment length polymorphism (RFLP) analysis of flaA, DNA sequence analysis of 582 bp of flaA that included the short variable region (SVR), and sequencing of the entire flaA gene. PFGE was the most discriminatory technique, yielding 11 SmaI and 10 SalI restriction profiles. All outbreak isolates were indistinguishable by PFGE, somatic O serotyping, and sequencing of the 582-bp region of the flaA gene. fla typing by PCR-RFLP grouped one sporadic isolate with the outbreak strain. Analysis of the DNA sequence of a 582-bp segment of flaA produced strain groupings similar to that generated by PCR-RFLP but further differentiated two flaA PCR-RFLP types (with a 1-bp difference in the 582-bp region). Two sporadic strains were distinct by flaA PCR-RFLP but differed only by a single base substitution in the 582-bp region. The entire flaA gene was sequenced from strains differing by a single base pair in the 582-bp region, and the data revealed that additional discrimination may in some cases be obtained by sequencing outside the SVR. PFGE was superior to all other typing methods tested for strain discrimination; it was crucial for understanding the Kansas outbreak and, when SmaI was used, provided adequate discrimination between unrelated isolates.

A nosocomial outbreak of fluoroquinolone-resistant salmonella infection.

BACKGROUND: Infection with fluoroquinolone-resistant strains of salmonella is rare, as is nosocomial salmonella infection. We describe the first recognized outbreak of fluoroquinolone-resistant salmonella infections in the United States, which occurred in two nursing homes and one hospital in Oregon. METHODS: We interviewed medical staff and reviewed patients' charts and death certificates. In Nursing Home A we conducted a case-control study. Patients were defined as residents of the nursing home from whom fluoroquinolone-resistant Salmonella enterica serotype Schwarzengrund was isolated between February 1996 and December 1998. Controls were residents with similar medical conditions whose cultures did not yield salmonella. We compared isolates using pulsed-field gel electrophoresis and sequence analysis. We reviewed pharmacy records to compare the use of fluoroquinolone among several nursing homes. RESULTS: Eleven patients with fluoroquinolone-resistant salmonellosis were identified at two nursing homes. The index patient had been hospitalized in the Philippines and had probably acquired the infection there. Transmission was probably direct (from patient to patient) or through contact with contaminated surfaces. Treatment with fluoroquinolones during the six months before a culture was obtained was associated with a significant risk of salmonella infection (4 of 5 patients had taken fluoroquinolones, as compared with 2 of 13 controls; odds ratio, 22.0; 95 percent confidence interval, 1.06 to 1177). The patients were not significantly more likely than the controls to have taken other antibiotics. More fluoroquinolones were used at Nursing Home A than at similar nursing homes in Oregon. The isolates from the outbreak had similar patterns on pulsed-field gel electrophoresis and the same gyrA mutations. The isolates from the outbreak were also similar to the only previous isolate of fluoroquinolone-resistant salmonella in the United States, which came from a patient in New York who had been transferred from a hospital in the Philippines. CONCLUSIONS: We describe a prolonged nosocomial outbreak of infection with fluoroquinolone-resistant S. enterica serotype Schwarzengrund. More such outbreaks are likely in institutional settings, particularly those in which there is heavy use of antimicrobial agents.

The changing epidemiology of salmonella: trends in serotypes isolated from humans in the United States, 1987-1997.

Salmonellosis is a major cause of illness in the United States. To highlight recent trends, data for 1987-1997 from the National Salmonella Surveillance System were analyzed. A total of 441,863 Salmonella isolates were reported, with the highest age-specific rate among infants (159/100,000 infants at 2 months). Annual isolation rates decreased from 19 to 13/100,000 persons; however, trends varied by serotype. The isolation rate of Salmonella serotype Enteritidis increased until 1996, whereas declines were noted in Salmonella serotypes Hadar and Heidelberg. Overall, serotypes that increased in frequency were significantly more likely than those that decreased to be associated with reptiles (P=.008). Salmonella infections continue to be an important cause of illness, especially among infants. Recent declines in food-associated serotypes may reflect changes in the meat, poultry, and egg industries that preceded or anticipated the 1996 implementation of pathogen-reduction programs. Additional educational efforts are needed to control the emergence of reptile-associated salmonellosis.

An outbreak of Campylobacter jejuni infections associated with food handler contamination: the use of pulsed-field gel electrophoresis.

In 1998, an outbreak of Campylobacter jejuni infections occurred in Kansas among persons attending a school luncheon; community cases were also reported. In a cohort study of luncheon attendees, 27 (17%) of 161 persons reported illness. Consuming gravy (relative risk [RR], 4.2; 95% confidence interval [CI], 1.5-11.7) or pineapple (RR, 2.4; 95% CI, 1.0-5.7) was associated with illness. Both foods were prepared in a kitchen that served 6 other schools where no illness was reported. A cafeteria worker at the luncheon had a diarrheal illness and was the likely source of the outbreak. The pulsed-field gel electrophoresis (PFGE) patterns of the isolates from the food handler and those of 8 lunch attendees were indistinguishable. Isolates from 4 community patients differed. This was the first use of PFGE in a Campylobacter outbreak in the United States; its use was critical in determining that community cases were not linked.

Restaurant-associated outbreak of Salmonella typhi in Nauru: an epidemiological and cost analysis.

Typhoid fever is endemic in the South Pacific. We investigated an outbreak in Nauru. Through interviews and medical records, we identified 50 persons with onset between 1 October 1998 and 10 May 1999, of fever lasting > or = 3 days and one other symptom. Salmonella Typhi was isolated from 19 (38%) cases. Thirty-two (64%) patients were school-aged children, and 17 (34%) were in four households. Case-control studies of (a) culture-confirmed cases and age- and neighbourhood-matched controls; and (b) household index cases and randomly selected age-matched controls implicated two restaurants: Restaurant M (matched OR [MOR] = 11, 95% confidence interval [CI] = 1.3-96) and Restaurant I (MOR = 5.8, 95% CI = 1.2-29). Food-handlers at both restaurants had elevated anti-Vi antibody titres indicative of carrier state. The annual incidence was 5.0/1000 persons. Outbreak-associated costs were $46,000. Routine or emergency immunization campaigns targeting school-aged children may help prevent or control outbreaks of typhoid fever in endemic disease areas.

Hereditary colorectal cancer.

This article summarizes the genetics of colorectal cancer (CRC), a disease in which 15% to 20% of cases are inherited. Familial adenomatous polyposis and hereditary nonpolyposis CRC represent the two most common forms of inherited CRC. One particular mutation, APC11307K, is associated with CRC in certain Jewish populations. Inherited cancers can be prevented with careful attention to regular and frequent sigmoidoscopy or colonoscopy screening intervals and the prompt removal of premalignant polyps. The role of the nurse should include the prompt identification and referral of high-risk individuals. Ongoing patient and family counseling and education, multidisciplinary collaboration, support for primary prevention, and intensive screening are essential.

Evaluation of the latency-associated nuclear antigen (ORF73) of Kaposi's sarcoma-associated herpesvirus by peptide mapping and bacterially expressed recombinant western blot assay.

Kaposi's sarcoma (KS)-associated herpesvirus open-reading frame (ORF) 73 encodes a latency-associated nuclear antigen (LANA) that is the basis for several serologic assays. Immunoreactive epitopes were searched for by peptide mapping, and 171 cleavable, biotinylated 17-mer peptides offset by 5 residues were synthesized and screened with human serum samples by ELISA. The initial screen, which used highly reactive serum diluted 1:500, identified 38 immunoreactive peptides. These were subsequently tested on additional serum samples diluted 1:40. Thirteen peptides were more reactive with serum samples from patients with KS than with control serum samples. No single epitope was recognized by most KS patient serum samples. Combined use of these peptides did not increase test sensitivity to that of current indirect immunofluorescence assays for LANA (80%-90%). For comparison, full-length ORF73 was expressed in bacteria and analyzed by Western blot. The overall sensitivity was 67% (range, 100% among US patients with classic KS to 52% among Italian patients with classic KS). These studies suggest that LANA immunoreactivity may be due to variations in patient response or conformational epitopes.