Update: Temporary Total Depletion of U.S. Licensed Yellow Fever Vaccine for Civilian Travelers Addressed by Investigational New Drug Use of Imported Stamaril Vaccine.

Sanofi Pasteur, the manufacturer of the only yellow fever vaccine (YF-VAX) licensed in the United States, has announced that their stock of YF-VAX is totally depleted as of July 24, 2017. YF-VAX for civilian use will be unavailable for ordering from Sanofi Pasteur until mid-2018, when their new manufacturing facility is expected to be completed. However, YF-VAX might be available at some clinics for several months, until remaining supplies at those sites are exhausted. In anticipation of this temporary total depletion, in 2016, Sanofi Pasteur submitted an expanded access investigational new drug application to the Food and Drug Administration to allow for importation and use of Stamaril. The Food and Drug Administration accepted Sanofi Pasteur's application in October 2016.

Addressing a Yellow Fever Vaccine Shortage - United States, 2016-2017.

Recent manufacturing problems resulted in a shortage of the only U.S.-licensed yellow fever vaccine. This shortage is expected to lead to a complete depletion of yellow fever vaccine available for the immunization of U.S. travelers by mid-2017. CDC, the Food and Drug Administration (FDA), and Sanofi Pasteur are collaborating to ensure a continuous yellow fever vaccine supply in the United States. As part of this collaboration, Sanofi Pasteur submitted an expanded access investigational new drug (eIND) application to FDA in September 2016 to allow for the importation and use of an alternative yellow fever vaccine manufactured by Sanofi Pasteur France, with safety and efficacy comparable to the U.S.-licensed vaccine; the eIND was accepted by FDA in October 2016. The implementation of this eIND protocol included developing a systematic process for selecting a limited number of clinic sites to provide the vaccine. CDC and Sanofi Pasteur will continue to communicate with the public and other stakeholders, and CDC will provide a list of locations that will be administering the replacement vaccine at a later date.

Measles in the 21st Century, a Continuing Preventable Risk to Travelers: Data From the GeoSentinel Global Network.

Measles remains a risk for travelers, with 94 measles diagnoses reported to the GeoSentinel network from 2000 to 2014, two-thirds since 2010. Asia was the most common exposure region, then Africa and Europe. Efforts to reduce travel-associated measles should target all vaccine-eligible travelers, including catch-up vaccination of susceptible adults.

Differential diagnosis of illness in travelers arriving from Sierra Leone, Liberia, or Guinea: a cross-sectional study from the GeoSentinel Surveillance Network.

BACKGROUND: The largest-ever outbreak of Ebola virus disease (EVD), ongoing in West Africa since late 2013, has led to export of cases to Europe and North America. Clinicians encountering ill travelers arriving from countries with widespread Ebola virus transmission must be aware of alternate diagnoses associated with fever and other nonspecific symptoms. OBJECTIVE: To define the spectrum of illness observed in persons returning from areas of West Africa where EVD transmission has been widespread. DESIGN: Descriptive, using GeoSentinel records. SETTING: 57 travel or tropical medicine clinics in 25 countries. PATIENTS: 805 ill returned travelers and new immigrants from Sierra Leone, Liberia, or Guinea seen between September 2009 and August 2014. MEASUREMENTS: Frequencies of demographic and travel-related characteristics and illnesses reported. RESULTS: The most common specific diagnosis among 770 nonimmigrant travelers was malaria (n = 310 [40.3%]), with Plasmodium falciparum or severe malaria in 267 (86%) and non-P. falciparum malaria in 43 (14%). Acute diarrhea was the second most common diagnosis among nonimmigrant travelers (n = 95 [12.3%]). Such common diagnoses as upper respiratory tract infection, urinary tract infection, and influenza-like illness occurred in only 26, 9, and 7 returning travelers, respectively. Few instances of typhoid fever (n = 8), acute HIV infection (n = 5), and dengue (n = 2) were encountered. LIMITATION: Surveillance data collected by specialist clinics may not be representative of all ill returned travelers. CONCLUSION: Although EVD may currently drive clinical evaluation of ill travelers arriving from Sierra Leone, Liberia, and Guinea, clinicians must be aware of other more common, potentially fatal diseases. Malaria remains a common diagnosis among travelers seen at GeoSentinel sites. Prompt exclusion of malaria and other life-threatening conditions is critical to limiting morbidity and mortality. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Outbreak of salmonellosis linked to live poultry from a mail-order hatchery.

BACKGROUND: Outbreaks of human salmonella infections are increasingly associated with contact with live poultry, but effective control measures are elusive. In 2005, a cluster of human salmonella Montevideo infections with a rare pattern on pulsed-field gel electrophoresis (the outbreak strain) was identified by PulseNet, a national subtyping network. METHODS: In cooperation with public health and animal health agencies, we conducted multistate investigations involving patient interviews, trace-back investigations, and environmental testing at a mail-order hatchery linked to the outbreak in order to identify the source of infections and prevent additional illnesses. A case was defined as an infection with the outbreak strain between 2004 and 2011. RESULTS: From 2004 through 2011, we identified 316 cases in 43 states. The median age of the patient was 4 years. Interviews were completed with 156 patients (or their caretakers) (49%), and 36 of these patients (23%) were hospitalized. Among the 145 patients for whom information was available, 80 (55%) had bloody diarrhea. Information on contact with live young poultry was available for 159 patients, and 122 of these patients (77%) reported having such contact. A mail-order hatchery in the western United States was identified in 81% of the trace-back investigations, and the outbreak strain was isolated from samples collected at the hatchery. After interventions at the hatchery, the number of human infections declined, but transmission continued. CONCLUSIONS: We identified a prolonged multistate outbreak of salmonellosis, predominantly affecting young children and associated with contact with live young poultry from a mail-order hatchery. Interventions performed at the hatchery reduced, but did not eliminate, associated human infections, demonstrating the difficulty of eliminating salmonella transmission from live poultry.

Analyzing GeoSentinel surveillance data: a comparison of methods to explore acute gastrointestinal illness among international travelers.

GeoSentinel is a global surveillance network of travel medicine clinics that collect data from ill international travelers. Analyses have relied on proportionate morbidity calculations, but proportionate morbidity cannot estimate disease risk because healthy travelers are not included in the denominator. The authors evaluated the use of a case-control design, controlling for GeoSentinel site and date of clinic visit, to calculate a reporting odds ratio (ROR). The association between region of travel and acute gastrointestinal illness was evaluated. All analyses found that the association with acute gastrointestinal illness was greatest among those who traveled to North Africa and South-Central Asia. There was consistency in the magnitude of the ROR and proportionate morbidity ratio (PMR) in regions such as the Caribbean. However, in other regions, the matched ROR was noticeably different than the PMR. The case-control ROR may be preferred for single-disease/syndrome analytical studies using GeoSentinel surveillance data or other surveillance data.

Economics of malaria prevention in US travelers to West Africa.

BACKGROUND: Pretravel health consultations help international travelers manage travel-related illness risks through education, vaccination, and medication. This study evaluated costs and benefits of that portion of the health consultation associated with malaria prevention provided to US travelers bound for West Africa. METHODS: The estimated change in disease risk and associated costs and benefits resulting from traveler adherence to malaria chemoprophylaxis were calculated from 2 perspectives: the healthcare payer's and the traveler's. We used data from the Global TravEpiNet network of US travel clinics that collect de-identified pretravel data for international travelers. Disease risk and chemoprophylaxis effectiveness were estimated from published medical reports. Direct medical costs were obtained from the Nationwide Inpatient Sample and published literature. RESULTS: We analyzed 1029 records from January 2009 to January 2011. Assuming full adherence to chemoprophylaxis regimens, consultations saved healthcare payers a per-traveler average of $14 (9-day trip) to $372 (30-day trip). For travelers, consultations resulted in a range of net cost of $20 (9-day trip) to a net savings of $32 (30-day trip). Differences were mostly driven by risk of malaria in the destination country. CONCLUSIONS: Our model suggests that healthcare payers save money for short- and longer-term trips, and that travelers save money for longer trips when travelers adhere to malaria recommendations and prophylactic regimens in West Africa. This is a potential incentive to healthcare payers to offer consistent pretravel preventive care to travelers. This financial benefit complements the medical benefit of reducing the risk of malaria.

Acute muscular sarcocystosis: an international investigation among ill travelers returning from Tioman Island, Malaysia, 2011-2012.

BACKGROUND: Through 2 international traveler-focused surveillance networks (GeoSentinel and TropNet), we identified and investigated a large outbreak of acute muscular sarcocystosis (AMS), a rarely reported zoonosis caused by a protozoan parasite of the genus Sarcocystis, associated with travel to Tioman Island, Malaysia, during 2011-2012. METHODS: Clinicians reporting patients with suspected AMS to GeoSentinel submitted demographic, clinical, itinerary, and exposure data. We defined a probable case as travel to Tioman Island after 1 March 2011, eosinophilia (>5%), clinical or laboratory-supported myositis, and negative trichinellosis serology. Case confirmation required histologic observation of sarcocysts or isolation of Sarcocystis species DNA from muscle biopsy. RESULTS: Sixty-eight patients met the case definition (62 probable and 6 confirmed). All but 2 resided in Europe; all were tourists and traveled mostly during the summer months. The most frequent symptoms reported were myalgia (100%), fatigue (91%), fever (82%), headache (59%), and arthralgia (29%); onset clustered during 2 distinct periods: "early" during the second and "late" during the sixth week after departure from the island. Blood eosinophilia and elevated serum creatinine phosphokinase (CPK) levels were observed beginning during the fifth week after departure. Sarcocystis nesbitti DNA was recovered from 1 muscle biopsy. CONCLUSIONS: Clinicians evaluating travelers returning ill from Malaysia with myalgia, with or without fever, should consider AMS, noting the apparent biphasic aspect of the disease, the later onset of elevated CPK and eosinophilia, and the possibility for relapses. The exact source of infection among travelers to Tioman Island remains unclear but needs to be determined to prevent future illnesses.

GeoSentinel surveillance of illness in returned travelers, 2007-2011.

BACKGROUND: International travel continues to increase, particularly to Asia and Africa. Clinicians are increasingly likely to be consulted for advice before travel or by ill returned travelers. OBJECTIVE: To describe typical diseases in returned travelers according to region, travel reason, and patient demographic characteristics; describe the pattern of low-frequency travel-associated diseases; and refine key messages for care before and after travel. DESIGN: Descriptive, using GeoSentinel records. SETTING: 53 tropical or travel disease units in 24 countries. PATIENTS: 42 173 ill returned travelers seen between 2007 and 2011. MEASUREMENTS: Frequencies of demographic characteristics, regions visited, and illnesses reported. RESULTS: Asia (32.6%) and sub-Saharan Africa (26.7%) were the most common regions where illnesses were acquired. Three quarters of travel-related illness was due to gastrointestinal (34.0%), febrile (23.3%), and dermatologic (19.5%) diseases. Only 40.5% of all ill travelers reported pretravel medical visits. The relative frequency of many diseases varied with both travel destination and reason for travel, with travelers visiting friends and relatives in their country of origin having both a disproportionately high burden of serious febrile illness and very low rates of advice before travel (18.3%). Life-threatening diseases, such as Plasmodium falciparum malaria, melioidosis, and African trypanosomiasis, were reported. LIMITATIONS: Sentinel surveillance data collected by specialist clinics do not reflect healthy returning travelers or those with mild or self-limited illness. Data cannot be used to infer quantitative risk for illness. CONCLUSION: Many illnesses may have been preventable with appropriate advice, chemoprophylaxis, or vaccination. Clinicians can use these 5-year GeoSentinel data to help tailor more efficient pretravel preparation strategies and evaluate possible differential diagnoses of ill returned travelers according to destination and reason for travel. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

A novel vehicle for transmission of Escherichia coli O157:H7 to humans: multistate outbreak of E. coli O157:H7 infections associated with consumption of ready-to-bake commercial prepackaged cookie dough--United States, 2009.

BACKGROUND: Escherichia coli O157:H7 is a Shiga toxin-producing E. coli (STEC) associated with numerous foodborne outbreaks in the United States and is an important cause of bacterial gastrointestinal illness. In May 2009, we investigated a multistate outbreak of E. coli O157:H7 infections. METHODS: Outbreak-associated cases were identified using serotyping and molecular subtyping procedures. Traceback investigation and product testing were performed. A matched case-control study was conducted to identify exposures associated with illness using age-, sex-, and state-matched controls. RESULTS: Seventy-seven patients with illnesses during the period 16 March-8 July 2009 were identified from 30 states; 35 were hospitalized, 10 developed hemolytic-uremic syndrome, and none died. Sixty-six percent of patients were <19 years; 71% were female. In the case-control study, 33 of 35 case patients (94%) consumed ready-to-bake commercial prepackaged cookie dough, compared with 4 of 36 controls (11%) (matched odds ratio = 41.3; P < .001); no other reported exposures were significantly associated with illness. Among case patients consuming cookie dough, 94% reported brand A. Three nonoutbreak STEC strains were isolated from brand A cookie dough. The investigation led to a recall of 3.6 million packages of brand A cookie dough and a product reformulation. CONCLUSIONS: This is the first reported STEC outbreak associated with consuming ready-to-bake commercial prepackaged cookie dough. Despite instructions to bake brand A cookie dough before eating, case patients consumed the product uncooked. Manufacturers should consider formulating ready-to-bake commercial prepackaged cookie dough to be as safe as a ready-to-eat product. More effective consumer education about the risks of eating unbaked cookie dough is needed.

Clostridium perfringens infections initially attributed to norovirus, North Carolina, 2010.

We investigated an outbreak initially attributed to norovirus; however, Clostridium perfringens toxicoinfection was subsequently confirmed. C. perfringens is an underrecognized but frequently observed cause of food-borne disease outbreaks. This investigation illustrates the importance of considering epidemiologic and laboratory data together when evaluating potential etiologic agents that might require unique control measures.

Global TravEpiNet: a national consortium of clinics providing care to international travelers--analysis of demographic characteristics, travel destinations, and pretravel healthcare of high-risk US international travelers, 2009-2011.

BACKGROUND: International travel poses a risk of destination-specific illness and may contribute to the global spread of infectious diseases. Despite this, little is known about the health characteristics and pretravel healthcare of US international travelers, particularly those at higher risk of travel-associated illness. METHODS: We formed a national consortium (Global TravEpiNet) of 18 US clinics registered to administer yellow fever vaccination. We collected data regarding demographic and health characteristics, destinations, purpose of travel, and pretravel healthcare from 13235 international travelers who sought pretravel consultation at these sites from January 2009 through January 2011. RESULTS: The destinations and itineraries of Global TravEpiNet travelers differed from those of the overall population of US international travelers. The majority of Global TravEpiNet travelers were visiting low- or lower-middle-income countries, and Africa was the most frequently visited region. Seventy-five percent of travelers were visiting malaria-endemic countries, and 38% were visiting countries endemic for yellow fever. Fifty-nine percent of travelers reported ≥1 medical condition. Atovaquone/proguanil was the most commonly prescribed antimalarial drug, and most travelers received an antibiotic for self-treatment of travelers' diarrhea. Hepatitis A and typhoid were the most frequently administered vaccines. CONCLUSIONS: Data from Global TravEpiNet provide insight into the characteristics and pretravel healthcare of US international travelers who are at increased risk of travel-associated illness due to itinerary, purpose of travel, or existing medical conditions. Improved understanding of this epidemiologically significant population may help target risk-reduction strategies and interventions to limit the spread of infections related to global travel.

Overview of the impact of epidemic-assistance investigations of foodborne and other enteric disease outbreaks, 1946-2005.

Epidemic-assistance investigations (Epi-Aids) in response to outbreaks of foodborne and other enteric pathogens have identified novel pathogens, clinical syndromes, and sequelae; described new reservoirs and vehicles of transmission; evaluated existing prevention strategies; and identified deficiencies in the food safety systems on local, national, and international levels. Since the first Epi-Aid was issued in 1946, approximately 23% (1,023 of 4,484 for which investigations were initiated) of all Epi-Aids have been related to foodborne or other enteric diseases. Epi-Aid results have yielded valuable insights into the epidemiology of these pathogens and have molded prevention strategies for detecting, responding to, and preventing future outbreaks. New challenges, brought about in part by centralization and globalization of the food supply, will continue to emerge. The need for Epi-Aids of such outbreaks undoubtedly will persist as an integral part of future public health response efforts, prevention strategies, and training programs.

Recent multistate outbreaks of human salmonella infections acquired from turtles: a continuing public health challenge.

The federal ban in the United States on the sale of turtles with shell lengths <4 inches that was established in 1975 has reduced the number of turtle-associated human Salmonella infections during subsequent years, especially among children. Although numerous sporadic turtle-associated Salmonella infections in humans have been reported since the ban went into effect, outbreaks were not reported until recently. Since 2006, 3 multistate outbreaks of turtle-associated Salmonella infections have been documented in the United States. This review examines the history of turtle-associated human Salmonella infections in the United States and discusses reasons why an increase in turtle-associated salmonellosis may be occurring and how challenges in enforcement of the ban affect disease control. Additional steps should be considered by the public health community, state governments, and enforcement agencies to prevent turtle-associated Salmonella infections in humans.

Tickborne Powassan virus infections among Wisconsin residents.

INTRODUCTION: Powassan virus (POWV) is a tickborne Flavivirus that causes a rare but potentially life-threatening illness. The first reported case of POWV infection in a Wisconsin resident occurred in 2003. Enhanced surveillance and testing detected 2 additional cases. METHODS: Patient specimens with a positive or equivocal immunoglobulin M (IgM) antibody to an arbovirus were sent from commercial laboratories to the Wisconsin State Laboratory of Hygiene and forwarded to the Centers for Disease Control and Prevention (CDC) for confirmatory testing. Patients with laboratory confirmed POWV infections were interviewed to obtain demographic, clinical, and epidemiologic information. RESULTS: POWV infections were confirmed in 3 adult Wisconsin residents in 2003, 2006, and 2007; illness onsets occurred during May and June. Two patients were hospitalized and all survived. One patient had a dual infection with POWV and Anaplasma phaghocytophilum. Specimens from all 3 patients were initially reported as positive for IgM antibody to either St Louis encephalitis or California serogroup viruses; POWV-specific antibody was detected during confirmatory testing at the CDC. Each patient had exposures to known or likely tick habitats in different counties within 30 days before illness onset. CONCLUSIONS: These are the first diagnosed human POWV infections in Wisconsin. Because all 3 patients were initially identified as having other arboviral infections using commercial screening kits, routine confirmatory testing is essential for proper diagnosis of most arboviral infections. Wisconsin residents should be educated regarding risks of acquiring and ways to prevent POWV infection and other tickborne diseases when spending time outdoors.

Travel-associated Dengue illnesses among Wisconsin residents, 2002-2008.

INTRODUCTION: Dengue infections in humans can result in self-limited illness or conditions that can be severe and life-threatening. Persons traveling to many tropical regions are at risk for dengue infection. This report retrospectively summarizes travel-associated dengue cases occurring among Wisconsin residents from 2002 through 2008. METHODS: We used a surveillance case definition based on the Centers for Disease Control and Prevention (CDC) 1996 dengue illness case definition. Detection of dengue-specific IgM antibody in serum specimens was used for laboratory confirmation of dengue. Clinical and travel histories, mosquito exposure, and repellent use were obtained from patients by interview using arbovirus-specific data collection forms. RESULTS: During 2002-2008, 32 travel-associated dengue illnesses were reported among Wisconsin residents; none met the case criteria of dengue hemorrhagic fever or dengue shock syndrome. Fever (100%), headache (90%), and myalgia (87%) were the most frequently reported signs and symptoms. Nine (28%) patients were hospitalized; no deaths occurred. Onsets in 25 (81%) of 31 patients with reported travel histories occurred after return to Wisconsin. Eighteen (56%) of the 32 patients were female; median age was 35.5 years (range 12 to 68 years). Patients most frequently reported travel to Mexico/Central America (45%) or the Caribbean Islands (39%). Cases occurred during all months. Reported mosquito exposure was high among patients (85%), but consistent repellent use was low (6%). CONCLUSIONS: Dengue illnesses occur in travelers to dengue-endemic tropical areas. Travelers to these areas must take precautions to prevent mosquito bites. Clinicians should consider dengue in travelers who develop febrile illnesses with headache or myalgia within 2 weeks of their return. Arboviral diseases, including dengue, are reportable in Wisconsin.

Parental vaccine refusal in Wisconsin: a case-control study.

INTRODUCTION: Successful immunization programs have diminished parental fear of diseases and increased fear of vaccines. Children with nonmedical exemptions to school immunization requirements are at increased risk of acquiring and transmitting disease. We explored differences in vaccine attitudes, beliefs, and information sources among parents of exempt and vaccinated children. METHODS: Self-administered surveys were mailed to 780 parents of children with nonmedical exemptions (cases) and 1491 parents of fully-vaccinated children (controls). RESULTS: Vaccines most often refused by exempt children were varicella (49%) and hepatitis B (30%). The most common reason for claiming exemptions was vaccine might cause harm (57%). Parents of vaccinated children were less likely than parents of exempt children to report concern about vaccine safety, question the need for immunization, and oppose immunization requirements. Nearly 25% of parents of vaccinated children reported that children get more immunizations than are good for them and 34% expressed concern that children's immune systems could be weakened by too many immunizations. Both groups received information from health care professionals; parents of exempt children were more likely to also consult other sources. CONCLUSIONS: Our findings support the need for improved methods to communicate vaccine safety information. Further studies to explore vaccine safety concerns among parents are needed.

Enabling clinicians to easily find location-based travel health recommendations-is innovation needed?

Background: The types of place names and the level of geographic detail that patients report to clinicians regarding their intended travel itineraries vary. The reported place names may not match those in published travel health recommendations, making traveler-specific recommendations potentially difficult and time-consuming to identify. Most published recommendations are at the country level; however, subnational recommendations exist when documented disease risk varies within a country, as for malaria and yellow fever. Knowing the types of place names reported during consultations would be valuable for developing more efficient ways of searching and identifying recommendations, hence we inventoried these descriptors and identified patterns in their usage. Methods: The data analyzed were previously collected individual travel itineraries from pretravel consultations performed at Global TravEpiNet (GTEN) travel clinic sites. We selected a clinic-stratified random sample of records from 18 GTEN clinics that contained responses to an open-ended question describing itineraries. We extracted and classified place names into nine types and analyzed patterns relative to common travel-related demographic variables. Results: From the 1756 itineraries sampled, 1570 (89%) included one or more place names, totaling 3366 place names. The frequency of different types of place names varied considerably: 2119 (63%) populated place, 336 (10%) tourist destination, 283 (8%) physical geographic area, 206 (6%) vague subnational area, 163 (5%) state, 153 (5%) country, 48 (1%) county, 12 (1%) undefined. Conclusions: The types of place names used by travelers to describe travel itineraries during pretravel consultations were often different from the ones referenced in travel health recommendations. This discrepancy means that clinicians must use additional maps, atlases or online search tools to cross-reference the place names given to the available recommendations. Developing new clinical tools that use geographic information systems technology would make it easier and faster for clinicians to find applicable recommendations for travelers.