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1.  Are Noroviruses Emerging? 
Emerging Infectious Diseases  2005;11(5):95-102.
PMCID: PMC3320389  PMID: 15898170
Epidemiology; Norovirus; Communicable Diseases; Emerging
2.  Norovirus Transmission on Cruise Ship 
Emerging Infectious Diseases  2005;11(1):154-157.
We documented transmission by food and person-to-person contact; persistence of virus despite sanitization onboard, including introductions of new strains; and seeding of an outbreak on land.
We describe an investigation of a norovirus gastroenteritis outbreak aboard a cruise ship affecting 6 consecutive cruises and the use of sequence analysis to determine modes of virus transmission. Noroviruses (NoV), are the most common cause of infectious acute gastroenteritis and are transmitted feco-orally through food and water, directly from person to person and by environmental contamination (1). These viruses are often responsible for protracted outbreaks in closed settings, such as cruise ships, nursing homes, and hospitals (2,3).
PMCID: PMC3294347  PMID: 15705344
viral gastroenteritis; outbreak; Norwalk; cruise ship; dispatch
3.  Automated, Laboratory-based System Using the Internet for Disease Outbreak Detection, the Netherlands 
Emerging Infectious Diseases  2003;9(9):1046-1052.
Rapid detection of outbreaks is recognized as crucial for effective control measures and has particular relevance with the recently increased concern about bioterrorism. Automated analysis of electronically collected laboratory data can result in rapid detection of widespread outbreaks or outbreaks of pathogens with common signs and symptoms. In the Netherlands, an automated outbreak detection system for all types of pathogens has been developed within an existing electronic laboratory-based surveillance system called ISIS. Features include the use of a flexible algorithm for daily analysis of data and presentation of signals on the Internet for interpretation by health professionals. By 2006, the outbreak detection system will analyze laboratory-reported data on all pathogens and will cover 35% of the Dutch population.
PMCID: PMC3016793  PMID: 14519238
Disease outbreaks; algorithms; Internet; laboratories; data collection
4.  Influenza-associated Hospitalizations and Deaths, Costa Rica, 2009–2012 
Emerging Infectious Diseases  2014;20(5):878-881.
Data needed to guide influenza vaccine policies are lacking in tropical countries. We multiplied the number of severe acute respiratory infections by the proportion testing positive for influenza. There were ≈6,699 influenza hospitalizations and 803 deaths in Costa Rica during 2009–2012, supporting continuation of a national influenza vaccine program.
PMCID: PMC4012819  PMID: 24750897
influenza; hospitalization rate; mortality rate; severe acute respiratory infections; viruses; Costa Rica; tropical; Americas
5.  Clinical differences between influenza A (H1N1) pdm09 & influenza B infections identified through active community surveillance in north India 
Background & objectives:
Most studies on the clinical presentation with influenza viruses have been conducted in outpatient or inpatient medical facilities with only a few studies in community settings. Clinical differences between influenza A (H1N1) pdm 09 and influenza B virus infections have importance for community-based public health surveillance. An active community surveillance at the time of emergence of pandemic influenza provided us with an opportunity to compare the clinical features among patients infected with influenza A (H1N1) pdm09 virus and those with influenza B virus co-circulating in an active community-based weekly surveillance in three villages in Faridabad, Haryana, north India.
Active surveillance for febrile acute respiratory infection (FARI) was carried out in a rural community (n=16,182) in the context of an inactivated trivalent influenza vaccine trial (among children <11 yr). Individuals with FARI were assessed clinically by nurses and respiratory samples collected and tested for influenza viruses by real time RT-PCR from November 2009 to August 2010. Clinical symptoms of patients with influenza A (H1N1) pdm 09 and influenza B infection were compared.
Of the 4796 samples tested, 822 (17%) were positive for influenza virus. Of these, 443 (54%) were influenza A (H1N1) pdm09, 373 (45%) were influenza B and six were other subtypes/mixed infections. The mean age was lower for patients with influenza B (16.4 yr) than influenza A (H1N1) pdm09 infection (18.7 yr; P=0.04). Among children aged 5-18 yr, chills/rigours (OR 4.0; CI 2.2, 7.4), sore throat (OR 6.8; CI 2.3, 27.3) and headache (OR2.0; CI 1.3, 3.3) were more common in influenza A (H1N1) pdm09 infection than in influenza B cases. Chills/rigours (OR 2.4; CI 1.4, 4.0) and headache (OR 1.7; CI 1.0, 2.7) were associated with influenza A (H1N1) pdm09 infection in those >18 yr. No significant differences were seen in children <5 yr.
Our findings show that the differences in the clinical presentation of influenza A(H1N1)pdm09 and influenza B infections are not likely to be of clinical or public health significance.
PMCID: PMC3978989  PMID: 24521643
Diagnosis; influenza A; influenza B; H1N1 subtype; respiratory tract infections; signs and symptoms
6.  Use of National Pneumonia Surveillance to Describe Influenza A(H7N9) Virus Epidemiology, China, 2004–2013 
Emerging Infectious Diseases  2013;19(11):1784-1790.
In mainland China, most avian influenza A(H7N9) cases in the spring of 2013 were reported through the pneumonia of unknown etiology (PUE) surveillance system. To understand the role of possible underreporting and surveillance bias in assessing the epidemiology of subtype H7N9 cases and the effect of live-poultry market closures, we examined all PUE cases reported from 2004 through May 3, 2013. Historically, the PUE system was underused, reporting was inconsistent, and PUE reporting was biased toward A(H7N9)-affected provinces, with sparse data from unaffected provinces; however, we found no evidence that the older ages of persons with A(H7N9) resulted from surveillance bias. The absolute number and the proportion of PUE cases confirmed to be A(H7N9) declined after live-poultry market closures (p<0.001), indicating that market closures might have positively affected outbreak control. In China, PUE surveillance needs to be improved.
PMCID: PMC3837642  PMID: 24206646
pneumonia surveillance; influenza A(H7N9) virus; influenza virus; viruses; influenza; epidemiology; China
7.  Protection by Face Masks against Influenza A(H1N1)pdm09 Virus on Trans-Pacific Passenger Aircraft, 2009 
Emerging Infectious Diseases  2013;19(9):1403-1410.
In response to several influenza A(H1N1)pdm09 infections that developed in passengers after they traveled on the same 2 flights from New York, New York, USA, to Hong Kong, China, to Fuzhou, China, we assessed transmission of influenza A(H1N1)pdm09 virus on these flights. We defined a case of infection as onset of fever and respiratory symptoms and detection of virus by PCR in a passenger or crew member of either flight. Illness developed only in passengers who traveled on the New York to Hong Kong flight. We compared exposures of 9 case-passengers with those of 32 asymptomatic control-passengers. None of the 9 case-passengers, compared with 47% (15/32) of control-passengers, wore a face mask for the entire flight (odds ratio 0, 95% CI 0–0.71). The source case-passenger was not identified. Wearing a face mask was a protective factor against influenza infection. We recommend a more comprehensive intervention study to accurately estimate this effect.
PMCID: PMC3810906  PMID: 23968983
influenza; influenza A virus; influenza A(H1N1)pdm09 virus; viruses; aircraft; trans-pacific passenger aircraft; disease outbreak; face masks; China; Hong Kong; United States; outbreak; air travel; travel
8.  Monitoring Avian Influenza A(H7N9) Virus through National Influenza-like Illness Surveillance, China 
Emerging Infectious Diseases  2013;19(8):1289-1292.
In China during March 4–April 28, 2013, avian influenza A(H7N9) virus testing was performed on 20,739 specimens from patients with influenza-like illness in 10 provinces with confirmed human cases: 6 (0.03%) were positive, and increased numbers of unsubtypeable influenza-positive specimens were not seen. Careful monitoring and rapid characterization of influenza A(H7N9) and other influenza viruses remain critical.
PMCID: PMC3739526  PMID: 23879887
influenza; avian influenza; avian influenza A(H7N9) virus; H7N9; subtype H7N9; China; influenza-like illness; surveillance; viruses
9.  Effect of Winter School Breaks on Influenza-like Illness, Argentina, 2005–2008 
Emerging Infectious Diseases  2013;19(6):938-944.
School closures are used to reduce seasonal and pandemic influenza transmission, yet evidence of their effectiveness is sparse. In Argentina, annual winter school breaks occur during the influenza season, providing an opportunity to study this intervention. We used 2005–2008 national weekly surveillance data of visits to a health care provider for influenza-like illness (ILI) from all provinces. Using Serfling-specified Poisson regressions and population-based census denominators, we developed incidence rate ratios (IRRs) for the 3 weeks before, 2 weeks during, and 3 weeks after the break. For persons 5–64 years of age, IRRs were <1 for at least 1 week after the break. Observed rates returned to expected by the third week after the break; overall decrease among persons of all ages was 14%. The largest decrease was among children 5–14 years of age during the week after the break (37% lower IRR). Among adults, effects were weaker and delayed. Two-week winter school breaks significantly decreased visits to a health care provider for ILI among school-aged children and nonelderly adults.
PMCID: PMC3713818  PMID: 23735682
Influenza; school closure; community mitigation; social isolation; Argentina; winter; viruses; respiratory infections
10.  Demographic Shift of Influenza A(H1N1)pdm09 during and after Pandemic, Rural India 
Emerging Infectious Diseases  2012;18(9):1472-1475.
Population-based active surveillance in India showed higher incidence rates for influenza A(H1N1)pdm09 among children during pandemic versus postpandemic periods (345 vs. 199/1,000 person-years), whereas adults had higher rates during postpandemic versus pandemic periods (131 vs. 69/1,000 person-years). Demographic shifts as pandemics evolve should be considered in public health response planning.
PMCID: PMC3437708  PMID: 22932477
influenza; seasonal influenza; influenza A(H1N1)pdm09; India; pandemic; viruses; H1N1; pH1N1
11.  Enhanced Surveillance of Norovirus Outbreaks of Gastroenteritis in Georgia 
Public Health Reports  2011;126(2):251-258.
The role of noroviruses in both foodborne and person-to-person outbreaks of acute gastroenteritis (AGE) has been difficult to determine in the U.S. because of lack of routine norovirus testing and of national reporting of person-to-person outbreaks. We conducted a prospective study in one state in which enhanced testing for noroviruses was performed to better understand the relative contribution of all gastroenteric pathogens.
During the two-year period, 2000–2001, we took all fecal specimens from AGE outbreaks reported in Georgia that were negative for bacteria and tested these for norovirus.
We investigated 78 AGE outbreaks, from which suitable fecal samples were collected from 57 of them. Norovirus was identified in 25 (44%) outbreaks, bacteria in 20 (35%) outbreaks, and parasites in one (2%) outbreak. Forty-three (75%) of the outbreaks tested were foodborne, of which 17 (40%) were attributable to norovirus and 18 (42%) were attributable to bacteria. Adjusting for incomplete testing, we estimated that 53% of all AGE outbreaks were attributable to norovirus. A total of 2,674 people were reported ill in the 57 outbreaks, and norovirus infections accounted for 1,735 (65%) of these cases. Norovirus outbreaks tended to be larger than bacterial outbreaks, with a median number of 30 vs. 16 cases per outbreak, respectively (p=0.057).
This study provides further evidence that noroviruses are, overall, the most common cause of AGE outbreaks in the U.S. Improved specimen collection, reporting person-to-person outbreaks, and access to molecular assays are needed to further understand the role of these viruses and methods for their prevention.
PMCID: PMC3056038  PMID: 21387955
12.  Early Detection of Pandemic (H1N1) 2009, Bangladesh 
Emerging Infectious Diseases  2012;18(1):146-149.
To explore Bangladesh’s ability to detect novel influenza, we examined a series of laboratory-confirmed pandemic (H1N1) 2009 cases. During June–July 2009, event-based surveillance identified 30 case-patients (57% travelers); starting July 29, sentinel sites identified 252 case-patients (1% travelers). Surveillance facilitated response weeks before the spread of pandemic (H1N1) 2009 infection to the general population.
PMCID: PMC3310083  PMID: 22257637
Bangladesh; H1N1; influenza; viruses; management; outcome; pandemic (H1N1) 2009; pandemic; respiratory infections
13.  Incidence of Acute Gastroenteritis and Role of Norovirus, Georgia, USA, 2004–2005 
Emerging Infectious Diseases  2011;17(8):1381-1388.
TOC summary: Improved clinical assays will guide appropriate case management.
Approximately 179 million cases of acute gastroenteritis (AGE) occur annually in the United States. However, lack of routine clinical testing for viruses limits understanding of their role among persons seeking medical care. Fecal specimens submitted for routine bacterial culture through a health maintenance organization in Georgia, USA, were tested with molecular diagnostic assays for norovirus, rotavirus, astrovirus, sapovirus, and adenovirus. Incidence was estimated by using national health care utilization rates. Routine clinical diagnostics identified a pathogen in 42 (7.3%) of 572 specimens; inclusion of molecular viral testing increased pathogen detection to 15.7%. Community AGE incidence was 41,000 cases/100,000 person-years and outpatient incidence was 5,400/100,000 person-years. Norovirus was the most common pathogen, accounting for 6,500 (16%) and 640 (12%) per 100,000 person-years of community and outpatient AGE episodes, respectively. This study demonstrates that noroviruses are leading causes of AGE among persons seeking medical care.
PMCID: PMC3381564  PMID: 21801613
norovirus; viruses; gastroenteritis; AGE; etiology; incidence; Georgia; United States; research
14.  Foodborne Illness Acquired in the United States—Major Pathogens 
Emerging Infectious Diseases  2011;17(1):7-15.
Each year, 31 pathogens caused 9.4 million episodes of foodborne illness, resulting in 55,961 hospitalizations and 1,351 deaths.
Estimates of foodborne illness can be used to direct food safety policy and interventions. We used data from active and passive surveillance and other sources to estimate that each year 31 major pathogens acquired in the United States caused 9.4 million episodes of foodborne illness (90% credible interval [CrI] 6.6–12.7 million), 55,961 hospitalizations (90% CrI 39,534–75,741), and 1,351 deaths (90% CrI 712–2,268). Most (58%) illnesses were caused by norovirus, followed by nontyphoidal Salmonella spp. (11%), Clostridium perfringens (10%), and Campylobacter spp. (9%). Leading causes of hospitalization were nontyphoidal Salmonella spp. (35%), norovirus (26%), Campylobacter spp. (15%), and Toxoplasma gondii (8%). Leading causes of death were nontyphoidal Salmonella spp. (28%), T. gondii (24%), Listeria monocytogenes (19%), and norovirus (11%). These estimates cannot be compared with prior (1999) estimates to assess trends because different methods were used. Additional data and more refined methods can improve future estimates.
PMCID: PMC3375761  PMID: 21192848
Food poisoning; gastroenteritis; diarrhea; population surveillance; incidence estimates; norovirus; viruses; bacteria; United States; research
15.  Molecular Epidemiology of Genogroup II-Genotype 4 Noroviruses in the United States between 1994 and 2006▿  
Journal of Clinical Microbiology  2009;48(1):168-177.
Human noroviruses (NoVs) of genogroup II, genotype 4 (GII.4) are the most common strains detected in outbreaks of acute gastroenteritis worldwide. To gain insight into the epidemiology and genetic variation of GII.4 strains, we analyzed 773 NoV outbreaks reported to the CDC from 1994 to 2006. Of these NoV outbreaks, 629 (81.4%) were caused by GII viruses and 342 (44.2%) were caused by GII.4 strains. The proportion of GII.4 outbreaks increased from 5% in 1994 to 85% in 2006, but distinct annual differences were noted, including sharp increases in 1996, 2003, and 2006 each associated with newly emerging GII.4 strains. Sequence analysis of the full-length VP1 gene of GII.4 strains identified in this study and from GenBank segregated these viruses into at least 9 distinct subclusters which had 1.3 to 3.2% amino acid variation between strains in different subclusters. We propose that GII.4 subclusters be defined as having >5% sequence variation between strains. Our data confirm other studies on the rapid emergence and displacement of highly virulent GII.4 strains.
PMCID: PMC2812295  PMID: 19864482
16.  Systematic Literature Review of Role of Noroviruses in Sporadic Gastroenteritis 
Emerging Infectious Diseases  2008;14(8):1224-1231.
Noroviruses accounted for 12% of severe gastroenteritis cases among children <5 years of age.
We conducted a systematic review of studies that used reverse transcription–PCR to diagnose norovirus (NoV) infections in patients with mild or moderate (outpatient) and severe (hospitalized) diarrhea. NoVs accounted for 12% (95% confidence interval [CI] 10%–15%) of severe gastroenteritis cases among children <5 years of age and 12% (95% CI 9%–15%) of mild and moderate diarrhea cases among persons of all ages. Of 19 studies among children <5 years of age, 7 were in developing countries where pooled prevalence of severe NoV disease (12%) was comparable to that for industrialized countries (12%). We estimate that each year NoVs cause 64,000 episodes of diarrhea requiring hospitalization and 900,000 clinic visits among children in industrialized countries, and up to 200,000 deaths of children <5 years of age in developing countries. Future efforts should focus on developing targeted strategies, possibly even vaccines, for preventing NoV disease and better documenting their impact among children living in developing countries, where >95% of the deaths from diarrhea occur.
PMCID: PMC2600393  PMID: 18680645
norovirus; Norwalk virus; calicivirus infections; burden of illness; diarrhea; gastroenteritis; epidemiology; research
17.  Norovirus and Foodborne Disease, United States, 1991–2000 
Emerging Infectious Diseases  2005;11(1):95-102.
Analysis of foodborne outbreaks shows how advances in viral diagnostics are clarifying the causes of foodborne outbreaks and determining the high impact of norovirus infections.
Efforts to prevent foodborne illness target bacterial pathogens, yet noroviruses (NoV) are suspected to be the most common cause of gastroenteritis. New molecular assays allow for better estimation of the role of NoV in foodborne illness. We analyzed 8,271 foodborne outbreaks reported to the Centers for Disease Control and Prevention from 1991 to 2000 and additional data from 6 states. The proportion of NoV-confirmed outbreaks increased from 1% in 1991 to 12% in 2000. However, from 1998 to 2000, 76% of NoV outbreaks were reported by only 11 states. In 2000, an estimated 50% of foodborne outbreaks in 6 states were attributable to NoV. NoV outbreaks were larger than bacterial outbreaks (median persons affected: 25 versus 15), and 10% of affected persons sought medical care; 1% were hospitalized. More widespread use of molecular assays will permit better estimates of the role of NoV illness and help direct efforts to control foodborne illness.
PMCID: PMC3294339  PMID: 15705329
research; food; norovirus; disease outbreaks; burden of illness
18.  SARS-associated Coronavirus Transmission, United States 
Emerging Infectious Diseases  2004;10(2):225-231.
To better assess the risk for transmission of the severe acute respiratory syndrome–associated coronavirus (SARS-CoV), we obtained serial specimens and clinical and exposure data from seven confirmed U.S. SARS patients and their 10 household contacts. SARS-CoV was detected in a day-14 sputum specimen from one case-patient and in five stool specimens from two case-patients. In one case-patient, SARS-CoV persisted in stool for at least 26 days after symptom onset. The highest amounts of virus were in the day-14 sputum sample and a day-14 stool sample. Residual respiratory symptoms were still present in recovered SARS case-patients 2 months after illness onset. Possible transmission of SARS-CoV occurred in one household contact, but this person had also traveled to a SARS-affected area. The data suggest that SARS-CoV is not always transmitted efficiently. Laboratory diagnosis of SARS-CoV infection is difficult; thus, sputum and stool specimens should be included in the diagnostic work-up for SARS-CoV infection.
PMCID: PMC3322913  PMID: 15030687
severe acute respiratory syndrome (SARS); outbreak; SARS-associated coronavirus; epidemiology; transmission; natural history
19.  Epidemiology of Urban Canine Rabies, Santa Cruz, Bolivia, 1972–1997 
Emerging Infectious Diseases  2002;8(5):458-461.
We analyzed laboratory data from 1972 to 1997 from Santa Cruz, Bolivia, to determine risk factors for laboratory canine samples’ testing positive for Rabies virus (RABV). Of 9,803 samples, 50.7% tested positive for RABV; the number of cases and the percentage positive has dropped significantly since 1978. A 5- to 6-year cycle in rabies incidence was clearly apparent, though no seasonality was noted. Male dogs had significantly increased odds of testing positive for RABV (odds ratio [OR]=1.14), as did 1- to 2-year-old dogs (OR=1.73); younger and older dogs were at lower risk. Samples submitted from the poorer suburbs of the city were more likely to test positive for RABV (OR=1.71). We estimated the distribution of endemic canine rabies in an urban environment to facilitate control measures in a resource-poor environment.
PMCID: PMC2732486  PMID: 11996678
Epidemiology; rabies; Bolivia; urban health; risk factors; canine
20.  Salmonella enterica Serotype Enteritidis Phage Type 4b Outbreak Associated with Bean Sprouts 
Emerging Infectious Diseases  2002;8(4):440-443.
In November 2000 in the Netherlands, an outbreak of Salmonella enterica serotype Enteritidis phage type 4b was investigated. Eating bean sprouts was the only exposure associated with S. Enteritidis pt 4b infection (matched odds ratio 13.0, 95% confidence interval 2.0-552.5). Contaminated seeds were the most likely cause of contamination of the sprouts. The sprout grower applied a concentration of hypochlorite solution that was too low for seed disinfection.
PMCID: PMC2730240  PMID: 11971783
Salmonella; outbreak investigation; bean sprouts; Enter-net
21.  The Role of Temperature and Humidity on Seasonal Influenza in Tropical Areas: Guatemala, El Salvador and Panama, 2008–2013 
PLoS ONE  2014;9(6):e100659.
The role of meteorological factors on influenza transmission in the tropics is less defined than in the temperate regions. We assessed the association between influenza activity and temperature, specific humidity and rainfall in 6 study areas that included 11 departments or provinces within 3 tropical Central American countries: Guatemala, El Salvador and Panama.
Logistic regression was used to model the weekly proportion of laboratory-confirmed influenza positive samples during 2008 to 2013 (excluding pandemic year 2009). Meteorological data was obtained from the Tropical Rainfall Measuring Mission satellite and the Global Land Data Assimilation System. We found that specific humidity was positively associated with influenza activity in El Salvador (Odds Ratio (OR) and 95% Confidence Interval of 1.18 (1.07–1.31) and 1.32 (1.08–1.63)) and Panama (OR = 1.44 (1.08–1.93) and 1.97 (1.34–2.93)), but negatively associated with influenza activity in Guatemala (OR = 0.72 (0.6–0.86) and 0.79 (0.69–0.91)). Temperature was negatively associated with influenza in El Salvador's west-central departments (OR = 0.80 (0.7–0.91)) whilst rainfall was positively associated with influenza in Guatemala's central departments (OR = 1.05 (1.01–1.09)) and Panama province (OR = 1.10 (1.05–1.14)). In 4 out of the 6 locations, specific humidity had the highest contribution to the model as compared to temperature and rainfall. The model performed best in estimating 2013 influenza activity in Panama and west-central El Salvador departments (correlation coefficients: 0.5–0.9).
The findings highlighted the association between influenza activity and specific humidity in these 3 tropical countries. Positive association with humidity was found in El Salvador and Panama. Negative association was found in the more subtropical Guatemala, similar to temperate regions. Of all the study locations, Guatemala had annual mean temperature and specific humidity that were lower than the others.
PMCID: PMC4067338  PMID: 24956184
22.  Improvements in pandemic preparedness in 8 Central American countries, 2008 - 2012 
In view of ongoing pandemic threats such as the recent human cases of novel avian influenza A(H7N9) in China, it is important that all countries continue their preparedness efforts. Since 2006, Central American countries have received donor funding and technical assistance from the U.S. Centers for Disease Control and Prevention (CDC) to build and improve their capacity for influenza surveillance and pandemic preparedness. Our objective was to measure changes in pandemic preparedness in this region, and explore factors associated with these changes, using evaluations conducted between 2008 and 2012.
Eight Central American countries scored their pandemic preparedness across 12 capabilities in 2008, 2010 and 2012, using a standardized tool developed by CDC. Scores were calculated by country and capability and compared between evaluation years using the Student’s t-test and Wilcoxon Rank Sum test, respectively. Virological data reported to WHO were used to assess changes in testing capacity between evaluation years. Linear regression was used to examine associations between scores, donor funding, technical assistance and WHO reporting.
All countries improved their pandemic preparedness between 2008 and 2012 and seven made statistically significant gains (p < 0.05). Increases in median scores were observed for all 12 capabilities over the same period and were statistically significant for eight of these (p < 0.05): country planning, communications, routine influenza surveillance, national respiratory disease surveillance, outbreak response, resources for containment, community interventions and health sector response. We found a positive association between preparedness scores and cumulative funding between 2006 and 2011 (R2 = 0.5, p < 0.01). The number of specimens reported to WHO from participating countries increased significantly from 5,551 (2008) to 18,172 (2012) (p < 0.01).
Central America has made significant improvements in influenza pandemic preparedness between 2008 and 2012. U.S. donor funding and technical assistance provided to the region is likely to have contributed to the improvements we observed, although information on other sources of funding and support was unavailable to study. Gains are also likely the result of countries’ response to the 2009 influenza pandemic. Further research is required to determine the degree to which pandemic improvements are sustainable.
PMCID: PMC4022548  PMID: 24886275
Pandemic; Influenza; Preparedness; IHR; Central America; Capacity-building; Technical assistance
23.  Population-Based Incidence of Severe Acute Respiratory Virus Infections among Children Aged <5 Years in Rural Bangladesh, June–October 2010 
PLoS ONE  2014;9(2):e89978.
Better understanding the etiology-specific incidence of severe acute respiratory infections (SARIs) in resource-poor, rural settings will help further develop and prioritize prevention strategies. To address this gap in knowledge, we conducted a longitudinal study to estimate the incidence of SARIs among children in rural Bangladesh.
During June through October 2010, we followed children aged <5 years in 67 villages to identify those with cough, difficulty breathing, age-specific tachypnea and/or danger signs in the community or admitted to the local hospital. A study physician collected clinical information and obtained nasopharyngeal swabs from all SARI cases and blood for bacterial culture from those hospitalized. We tested swabs for respiratory syncytial virus (RSV), influenza viruses, human metapneumoviruses, adenoviruses and human parainfluenza viruses 1–3 (HPIV) by real-time reverse transcription polymerase chain reaction. We calculated virus-specific SARI incidence by dividing the number of new illnesses by the person-time each child contributed to the study.
We followed 12,850 children for 279,029 person-weeks (pw) and identified 141 SARI cases; 76 (54%) at their homes and 65 (46%) at the hospital. RSV was associated with 7.9 SARI hospitalizations per 100,000 pw, HPIV3 2.2 hospitalizations/100,000 pw, and influenza 1.1 hospitalizations/100,000 pw. Among non-hospitalized SARI cases, RSV was associated with 10.8 illnesses/100,000 pw, HPIV3 1.8/100,000 pw, influenza 1.4/100,000 pw, and adenoviruses 0.4/100,000 pw.
Respiratory viruses, particularly RSV, were commonly associated with SARI among children. It may be useful to explore the value of investing in prevention strategies, such as handwashing and respiratory hygiene, to reduce respiratory infections among young children in such settings.
PMCID: PMC3934972  PMID: 24587163
24.  Estimation of the National Disease Burden of Influenza-Associated Severe Acute Respiratory Illness in Kenya and Guatemala: A Novel Methodology 
PLoS ONE  2013;8(2):e56882.
Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden.
Methods and Findings
This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons ≥5 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009–July 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129–27,659 for children <5 years old (2.9–4.7 per 1,000 persons) and 6,882–7,836 for persons ≥5 years old (0.21–0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065–2,259 (0.5–1.0 per 1,000 persons) among children <5 years old and 779–2,252 cases (0.1–0.2 per 1,000 persons) for persons ≥5 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases.
Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This method can be performed in most low and lower-middle income countries.
PMCID: PMC3584100  PMID: 23573177
25.  Characteristics of Hospitalized Cases with Influenza A (H1N1)pdm09 Infection during First Winter Season of Post-Pandemic in China 
PLoS ONE  2013;8(2):e55016.
Influenza A (H1N1)pdm09 (2009 H1N1) re-circulated as the predominant virus from January through February 2011 in China. National surveillance of 2009 H1N1 as a notifiable disease was maintained to monitor potential changes in disease severity from the previous season.
Methodology/Principal Findings
To describe the characteristics of hospitalized cases with 2009 H1N1 infection and analyze risk factors for severe illness during the 2010–2011winter season in China, we obtained surveillance data from hospitalized cases with 2009 H1N1 infection from November 2010 through May 2011, and reviewed medical records from 701 hospitalized cases. Age-standardized risk ratios were used to compare the age distribution of patients that were hospitalized and died due to 2009 H1N1 between the 2010–2011winter season to those during the 2009–2010 pandemic period. During the 2010–2011 winter season, children less than 5 years of age had the highest relative risk of hospitalization and death, followed by adults aged 65 years or older. Additionally, the relative risk of hospitalized cases aged 5–14 and 15–24 years was lower compared to children less than 5 years of age. During the winter season of 2010–2011, the proportions of adults aged 25 years or older for hospitalization and death were significantly higher than those during the 2009–2010 pandemic period. Being male, having a chronic medical condition, delayed hospital admission (≥3 days from onset) or delayed initiation of antiviral treatment (≥5 days from onset) were associated with severe illness among non-pregnant patients ≥2 years of age.
We observed a change in high risk groups for hospitalization for 2009 H1N1 during the winter months immediately following the pandemic period compared to the high risk groups identified during the pandemic period. Our nationally notifiable disease surveillance system enabled us to understand the evolving epidemiology of 2009 H1N1 infection after the pandemic period.
PMCID: PMC3564919  PMID: 23393563

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