• View in gallery

    Outcomes of 11 Yellow Fever Vaccine-Associated Viscerotropic Disease (YEL-AVD) case-patients by steroid dose, United States, 1996–2004.

  • View in gallery

    Outcomes and steroid dose of 11 Yellow Fever Vaccine-Associated Viscerotropic Disease (YEL-AVD) case-patients by year, United States, 1996–2004.

  • 1

    World Health Organization, fact sheet no. 100. Yellow Fever. 2001. Available at: http://www.who.int/topics/yellow_fever/en. Accessed October 11, 2005.

  • 2

    Monath TP, 2001. Yellow Fever: An Update. Lancet Infect Dis 1 :11–20.

  • 3

    Monath TP, Tsai TF, 1997. Flaviviruses. Richman DD, Whitley RJ, Hayden FG, eds. Clinical Virology. New York: Churchill-Livingstone, 1133.

  • 4

    Tsai TF, Vaughn DW, Solomon T, 2005. Flaviviruses (Yellow Fever, Dengue, Dengue Hemorrhagic Fever, Japanese Encephalitis, West Nile Encephalitis, St. Louis Encephalitis, Tick-Borne Encephalitis). Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. Sixth edition. Philadelphia: Churchill Livingstone, Inc., 1927–1951.

  • 5

    Monath TP, 2003. Yellow fever. Plotkin SA, Orenstein WA, eds. Vaccines. Fourth Edition. Philadelphia: W. B. Saunders, 1095–1176.

  • 6

    Monath TP, Nichols R, Archambault WT, Moore L, Marchesani JT, Shope RE, Thomas N, Schrader R, Furby D, Bedford P, 2002. Comparative safety and immunogenicity of two yellow fever 17D vaccines (Arilvax and YF-VAX) in a phase III multicenter, double-blind clinical trial. Am J Trop Med Hyg 66 :533–541.

    • Search Google Scholar
    • Export Citation
  • 7

    Belmusto-Worn VE, Sanchez JL, McCarthy K, Nichols R, Bautista CT, Magill AJ, Pastor-Cauna G, Echevarria C, Laguna-Torres VA, Samame BK, Baldeon ME, Burans JP, Olson JG, Bedford P, Kitchener S, Monath TP, 2005. Randomized Double-blind, Phase III, Pivotal Field Trial of the Comparative Immunogenicity, Safety, and Tolerability of Two Yellow Fever 17D Vaccines (Arilvax and YF-VAX) in Healthy Infants and Children in Peru. Am J Trop Med Hyg 72 :189–197.

    • Search Google Scholar
    • Export Citation
  • 8

    Advisory Committee on Immunization Practices, 2002.Yellow Fever Vaccine: Recommendations of the Advisory Committee on Immunization Practices, 2002. Morbidity and Mortality Weekly Report 51 :1–12.

    • Search Google Scholar
    • Export Citation
  • 9

    Martin M, Weld LH, Tsai TF, Mootrey GT, Chen RT, Niu M, Cetron MS, GeoSentinel Yellow Fever Working Group, 2001. Advanced age a risk factor for illness temporally associated with yellow fever vaccination. Emerg Infect Dis 7 :94–95.

    • Search Google Scholar
    • Export Citation
  • 10

    Barwick RS, 2004. History of Thymoma and Yellow Fever Vaccination. Correspondence in the Lancet 364 :936.

  • 11

    Chen RT, Rastogi SC, Mullen JR, 1994. The Vaccine Adverse Event Reporting System (VAERS). Vaccine 12 :542–550.

  • 12

    Centers for Disease Control and Prevention. Adverse events associated with 17D-derived Yellow Fever vaccination—United States, 2001–2002. Morbidity and Mortality Weekly Report 51 (44):989–993.

    • Search Google Scholar
    • Export Citation
  • 13

    Martin M, Tsai TF, Cropp B, Chang GJJ, Holmes DA, Tseng J, Shieh WJ, Zaki SR, As-Sanouri I, Cutrona AF, Ray G, Weld LH, Cetron MS, 2001. Fever and multisystem organ failure associated with 17D-204 Yellow Fever vaccination: a report of four cases. Lancet 358 :98–104.

    • Search Google Scholar
    • Export Citation
  • 14

    Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E, 2002. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288 :862–871.

    • Search Google Scholar
    • Export Citation
  • 15

    Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM, 2004. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 32 :858–873.

    • Search Google Scholar
    • Export Citation
  • 16

    Munford RS, 2005. Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. Sixth edition. Philadelphia: Churchill Livingstone, Inc., 906–924.

  • 17

    Annane D, Bellisant E, Cavaillon JM, 2005. Septic shock. Lancet 365 :63–78.

  • 18

    Minneci PC, Deans KJ, Banks SM, Elchacker PQ, Natanson C, 2004. Meta-Analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 141 :47–56.

    • Search Google Scholar
    • Export Citation
  • 19

    World Health Organization, WHO/AFRO Yellow Fever. 2004. Available at: http://www.afro.who.int/yellowfever/. Accessed October 11, 2005.

 

 

 

 

YELLOW FEVER VACCINE-ASSOCIATED VISCEROTROPIC DISEASE (YEL-AVD) AND CORTICOSTEROID THERAPY: ELEVEN UNITED STATES CASES, 1996–2004

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  • 1 National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia; Logistics Health Inc., La Crosse, Wisconsin; Boston Combined Residency Program in Pediatrics, Children’s Hospital Boston and Boston Medical Center, Boston, Massachusetts; Immunization Safety Office, Office of the Chief Science Officer, Centers for Disease Control and Prevention, Atlanta, Georgia; National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

During 1996 through 2004, 29 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) have been reported worldwide; 17 were fatal. Stress-dose corticosteroid (SDS) therapy has recently been found to improve survival among patients with septic shock but benefit for the treatment of YEL-AVD patients in septic shock is unknown. We retrospectively reviewed medical records of 11 U.S. YEL-AVD cases reported to the Vaccine Adverse Event Reporting System (VAERS) from 1996 through 2004. Four of 11 case-patients received SDS; 3 of these 4 (75%) survived. Seven patients did not receive SDS and 2 (29%) survived. Altered mental status was documented on admission for 5 of the 11 patients; 4 of these 5 did not receive SDS and died, whereas one received SDS and survived. The use of stress-dose steroids might be a factor that influenced the survival of these YEL-AVD patients and should be further evaluated in the management of both YEL-AVD and wild-type yellow fever septic shock.

INTRODUCTION

Yellow fever is a viral hemorrhagic febrile illness caused by a flavivirus and transmitted by mosquitoes. It is endemic in tropical South America and sub-Saharan Africa; the World Health Organization (WHO) estimates that 200,000 cases occur annually, but only a small percentage of these cases are identified due to underreporting.1 Most cases occur in sub-Saharan Africa and during epidemics the incidence of infection can be as high as 20%.2 Clinical presentation ranges from a mild febrile illness to a serious infection leading to hepatic and renal failure, myocardial injury, hemorrhage, and shock with a case fatality rate of 20–30%.3,4 Prevention with a live attenuated vaccine, first developed in 1936, has been considered highly effective and safe.5

The yellow fever live virus vaccine is prepared from the 17D yellow fever virus strain, grown in chick embryos. Within 30 days of vaccination, over 90% of individuals develop neutralizing antibodies to yellow fever.5,6 Immunity is long lasting, possibly lifelong .7 The Advisory Committee on Immunization Practices (ACIP) currently recommends revaccination every 10 years in persons 9 months of age and older traveling to or living in endemic areas.8 Since 1996 through 2004, 29 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) (previously called multiple organ system failure) have been reported to the Centers for Disease Control and Prevention (CDC) after yellow fever vaccination worldwide (CDC unpublished data). The pathogenesis of YEL-AVD is unknown but older age and thymic dysfunction may be risks factors for the development of this adverse event.9,10 Eleven of these cases occurred in the United States and were reported to the Vaccine Adverse Event Reporting System (VAERS), a federally mandated national passive surveillance system established in 1990 that receives reports of adverse events after immunization with U.S.-licensed vaccines.11 Six of the 11 cases have previously been reported in detail in the literature.12,13

Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) is clinically indistinguishable from wild-type yellow fever illness. Most YEL-AVD reports describe patients with fever and multiple organ system failure, and often death (17 deaths/29 cases worldwide). This clinical presentation is frequently identified and managed as septic shock. Since 2002 there has been evidence to support the use of stress-dose steroid (SDS) treatment (200–300 mg/day) in the management of septic shock.14 In 2003 the Surviving Sepsis Campaign Management Guidelines Committee (a committee of critical care and infectious disease experts representing 11 international organizations) recommended the use of SDS for the treatment of septic shock to reverse shock and increase survival rate.15 This committee also strongly discouraged the use of high-dose steroids (> 300 mg/day) in the management of septic shock since this has been shown to decrease survival.15 We describe the use of corticosteroids in the management of the 11 YEL-AVD reported U.S. cases and their clinical outcomes.

METHODS

Medical records were obtained for all 11 U.S. YEL-AVD cases reported to VAERS from 1996 through 2004. We retrospectively reviewed medical records and determined the dates of vaccination, onset of adverse event (onset of illness following vaccination), and hospital admission. We searched the medical records for the use of steroids in the treatment of the case-patient and, if administered, we recorded the initiation date, dosage, and duration. We also abstracted clinical and laboratory data and the clinical outcome. We describe the relationship between clinical findings, clinical outcome, and steroid administration.

RESULTS

Of the 11 case-patients we reviewed, 4 received stress-dose steroids (SDS), 4 received high-dose steroids (> 300 mg/day), 1 received low-dose steroids (< 200 mg/day), and 2 received no steroids during the course of illness. Three (75%) of the 4 case-patients who received SDS survived. Only 2 (29%) of the 7 case-patients who did not receive SDS survived (Figure 1); 1 received high-dose steroids and the other received no steroids. All of the case-patients who were treated with SDS were vaccinated after 2002 (Figure 2).

The time interval from date of vaccination (DOV = day 0) to onset of adverse event (mean = 4, median = 4.5) and the time interval from DOV to initiation of steroids (mean = 9, median = 8.5) were similar for those receiving SDS and not receiving SDS (Table 1). Past medical and surgical histories were also similar for those receiving SDS and not receiving SDS. The mean ages were 54 and 62 years, respectively. Both groups had one case-patient with a history of thymic disease (see Table 1).

All case-patients had hepatic and renal injury; the case-patients not receiving SDS had much higher mean and median peak aspartate aminotransaminase (AST) levels than those case-patients who received SDS (mean = 44.5, median = 28.9 units/L in multiples of the normal [i.e., the mean is 44.5 times higher than the upper limit of normal] and mean = 8.1, median = 8.5 units/L in multiples of normal, respectively). However, the median AST on admission was lower among those who were not treated with SDS (2.2 units/L in multiples of normal) compared with the median AST for those who received SDS (3.6 units/L in multiples of normal). We found that steroids of any dose were started among 6 case-patients after the admission serum samples for AST were obtained; 3 of these case-patients received SDS. It was not possible to determine whether the serum samples were obtained immediately upon admission and prior to the initiation of SDS for the other 3 case-patients who received steroids. It was also not possible to discern the timing of serum collection resulting in peak AST levels in relationship to the initiation of steroid treatment. Peak serum creatinine levels were only slightly higher among those not receiving SDS (mean 5.7 mg/dL versus 4.3 mg/dL). We found documentation that all but one case-patient experienced hypotension requiring pressors; information about treatment with pressors in this case-patient’s medical record was not available, but this case-patient was intubated and had a temperature of 105°F (case-patient #8, see Table 1). All but 2 case-patients were intubated (these 2 case-patients received SDS and both survived), all had thrombocytopenia, and all but 1 experienced a peak temperature of > 103°F. The peak temperature of 1 case-patient was unknown; this case-patient received high-dose steroids and survived.

Altered mental status was documented on admission for 4 of the 7 (57%) case-patients who did not receive SDS and only 1 of the 4 (25%) who received SDS. The case-patient with mental status changes who received SDS survived, whereas the 4 case-patients with mental status changes who did not receive SDS all died. In contrast, an initial diagnosis of sepsis or septic shock was given to 3 of the 4 (75%) case-patients receiving SDS, but only 2 (30%) of those who did not receive SDS (see Table 1).

DISCUSSION

Our review of 11 case-patients having YEL-AVD accompanied by shock has led us to question whether SDS treatment might be beneficial in the management of these cases. This is in accordance with the recently published recommendation to treat septic shock with SDS rather than high-dose steroids.

Sepsis is defined as a clinical syndrome characterized by the presence of both infection and a systemic inflammatory response, which would include at least 2 of the following clinical features: body temperature > 100.4°F or < 96.8°F, increased heart rate (> 90 beats/min), hyperventilation (respiratory rate > 20 breaths/min or Pa CO2 < 32 mm of Hg), and white blood cell count > 12,000 cells/mm3, < 4000 cells/mm3, or > 10% immature (band) forms.16 Septic shock is characterized by persistent arterial hypotension in a patient with sepsis.16 Patients presenting to an emergency room with fever, hypotension, multiorgan system dysfunction, and hematologic diathesis are usually diagnosed as, and treated for septic shock. An etiology may not always be determined. Two to four percent of septic shock cases are the result of viral infections17 and in up to 50% of patients with septic shock, no microbial etiology is found.16 Clinically and pathophysiologically, patients with YEL-AVD can present in septic shock; 10 of the 11 cases we investigated received pressor therapy for hypotension (meeting the criteria for shock) and 5 were given an admitting diagnosis of septic shock.

Approximately half of the patients with septic shock display deficiencies in adrenal function,17 and evidence indicates that SDS are of benefit in the management of septic shock. A 2004 meta-analysis of 14 randomized controlled trials revealed that while short doses of high-dose glucocorticoids actually decrease survival in septic shock, physiologic stress-doses equivalent to 200–300 mg of hydrocortisone daily for 5–7 days reduced mortality and promoted earlier shock reversal.18 Current (2004) guidelines developed by the Surviving Sepsis Campaign Management Guidelines Committee recommend the administration of stress-dose steroids for 7 days in patients with septic shock.15

Corticosteroids have not been evaluated in treatment of yellow fever,2 and our review is the first description of their use for the management of YEL-AVD. Results of the first studies evaluating SDS treatment of septic shock became available after 2002 at which time we might expect changes in the management of septic shock; our findings of the use of SDS are consistent with the timing of these studies and the subsequent recommendations published in 2004. All 4 case-patients who received yellow fever vaccine and developed YEL-AVD after 2002 were treated with SDS (see Fig. 2).

The timing of initiation of steroid treatment, of any dose, after vaccination did not appear to affect the clinical outcomes of the case-patients overall. All but one of the case-patients who were started on steroids were given the initial dose about 8–9 days after vaccination, regardless of the dates of hospitalization or onset of the adverse event. This finding suggests that the dose, rather than the timing of steroid therapy, may be more important in survival.

Although 75% (3/4) of the case-patients who received SDS survived and only 29% (2/7) of those who did not receive SDS survived, our numbers are still too small to determine if SDS therapy contributed to a better outcome. Several other factors may have been responsible for the greater percentage of survivors among the case-patients who received SDS. Advanced age (≥ 60 years) appears to be a risk factor for developing YEL-AVD9 and the case-patients who did not receive SDS had a greater mean age, possibly contributing to fewer survivors. Four (57%) of those not receiving SDS were admitted with signs of altered mental status, which usually occurs in the late stages of illness.4 The peak median AST levels were also many times higher among the case-patients not receiving SDS (although on admission the median AST levels were actually lower), another possible indicator of illness severity among this group. Furthermore, we found that 3 of the 4 case-patients who received SDS were given an admitting diagnosis of sepsis and had slightly higher median AST levels upon hospital admission, which may have triggered more aggressive management and support, including the adoption of current recommendations for steroid dosing in septic shock. We also found that those who received SDS were among the more recent cases (all occurred after 2001). In more recent years it is possible that the overall management of intensive care patients has improved resulting in a decrease in mortality of all patients with septic shock. With these limitations we can not determine if the case-patients who did not receive SDS simply had a more fulminant illness and therefore less chance of survival, and/or whether the management of those receiving SDS was more rigorous, improving their survival.

Thymic dysfunction also appears to be a risk factor for developing YEL-AVD,10 and it is interesting to note that we found 1 case-patient in each group (those receiving SDS and all others) had a history of thymic dysfunction; the case-patient who received SDS survived, whereas the other case-patient received low-dose steroids (< 200–300 mg/day) and did not survive.

We obtained our data from a retrospective review of medical records, and at times the data was difficult to interpret; we could not always determine baseline health and accurate past medical history. Furthermore, reports of an adverse event after yellow fever vaccination were captured through a passive surveillance system (VAERS), which is known to be limited by underreporting;11 there may have been cases that were not reported but were diagnosed and treated as septic shock and possibly given steroid treatment. Nevertheless, we believe that our report supports the need for further study of the use of SDS in the management of YEL-AVD. Future YEL-AVD surveillance with standardized, “real time” data collection should include data regarding steroid treatment.

Our review of these 11 cases of YEL-AVD and the use of SDS may also stimulate studies that have broader public health implications. Since YEL-AVD and wild-type yellow fever illnesses have the same clinical findings it might be worthwhile to evaluate the impact of using SDS among patients with wild-type yellow fever. The worldwide burden of wild-type yellow fever illness is great. From 1990 through 1999 over 13,000 cases of yellow fever with over 3,500 deaths were reported from Africa and South America2; however, WHO estimates the annual incidence to be 200,0001 and an increase in the number of cases has been observed over the past two decades.19 The use of SDS in the management of septic shock as a result of wild-type yellow fever illness should be evaluated.

This small case series of patients suggests that a change in the management of YEL-AVD has occurred over time, as demonstrated by our finding of increased usage of stress-dose steroids since 2002. Although we cannot fully determine all of the factors that may have influenced the survival of these patients, we believe our data points out that the benefit of SDS should be further evaluated in the management of both YEL-AVD and wild-type yellow fever septic shock.

Table 1

Characteristics, medical history, interval from date of vaccination to adverse event and start of steroid use, select laboratory findings, and outcomes of case patients reported to VAERS with YEL-AVD comparing those treated with stress does steroids and others,* United States, 1996–2004

Number of medical conditionsNumber of past surgeryInterval (days) from DOV to:AST†
Case patientYear vaccinatedAge in yearsSexDocumented mental status changes on admissionInitial assessment of sepsis/septic shock0–2≥3≥1Onset adverse eventStart of steroid treatmentOn admissionPeakPeak creat (mg/dl)Peak temp (°F)Survived
* Patients who received high dose (HD), low dose (LD), or no steroids (0); †Aspartate aminotransaminase in multiples of normal units/liter; includes: ‡Ulcerative colitis; χCrohn disease; ||Thymic disease; ¶Bowel resection. DOV, date of vaccination; SDS, stress dose steroids.
Received SDS
    1200270M++||+5112.910.87.3103.3Yes
    2200222F+482.56.61.9106.1No
    3200463M+++2957.6103.2Yes
    4200460M+++584.39.53.6103.2Yes
All others*
    5 (LD)199867F++‡||382.140.93.7103No
    6 (HD)200125M+2912.510.4Yes
    7 (HD)199879F+++181.39.73.0103No
    8 (HD)199663M+++583.116.85.7105No
    9 (HD)199956M++792.244.34.4105.9No
    10 (0)199876M++χ4n/a13.37.1104Yes
    11 (0)200376M+++4n/a100.91525.6103.5No
Figure 1.
Figure 1.

Outcomes of 11 Yellow Fever Vaccine-Associated Viscerotropic Disease (YEL-AVD) case-patients by steroid dose, United States, 1996–2004.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 75, 2; 10.4269/ajtmh.2006.75.333

Figure 2.
Figure 2.

Outcomes and steroid dose of 11 Yellow Fever Vaccine-Associated Viscerotropic Disease (YEL-AVD) case-patients by year, United States, 1996–2004.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 75, 2; 10.4269/ajtmh.2006.75.333

*

Address correspondence to Claudia Vellozzi, National Immunization Program, Centers for Disease Control and Prevention, MS E-05, 1600 Clifton Rd., Atlanta, GA 30333. E-mail: cvellozzi@cdc.gov

Other members of The Yellow Fever Vaccine Safety Working Group include T.L. Smith, Robert Chen, Martin Cetron, Michelle Russell, Jennifer Lehman, Katrin Kohl, and Nicholas Crass (Centers for Disease Control and Prevention), Neil Halsey and Anna Durbin (Johns Hopkins, Bloomberg School of Public Health), Elizabeth Barnett (Boston Universiity School of Medicine), Dirk Teuwen (Sanofi Pasteur), Thomas Monath (Acambis), R. Dana Bradshaw (Department of Defense), and Mary Elizabeth Wilson (Harvard School of Public Health).

Authors’ addresses: Claudia Vellozzi, Centers for Disease Control and Prevention; MS E-05, 1600 Clifton Rd, Atlanta, GA 30333; Telephone: (404) 639-6364, Fax: (404) 639-6258, Email: cvellozzi@cdc.gov. Tarissa Mitchell, Boston Combined Residency Program in Pediatrics, Boston Medical Center; One Boston Medical Center Place, Boston, MA 02118-2999; Email: tarissa.mitchell@gmail.com. Elaine Miller and Christine G. Casey, Centers for Disease Control and Prevention, MS E-61, 1600 Clifton Rd, Atlanta, GA 30333, Telephone (404) 639-8268, Fax: (404) 639-8834, Email: emiller@cdc.gov. Rachel Barwick Eidex, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS E03, Atlanta, GA 30333, Telephone: (404) 639-4503, Fax: (404) 639-4441, Email: REidex@cdc.gov. Edward B. Hayes, Centers for Disease Control and Prevention, TFCL Bldg TRAIL, Room 1, MS P02, Fort Collins, CO 80521, Telephone: (970) 266-3517, Fax: (970) 221-6476, Email: NHayes1@cdc.gov.

Acknowledgments: The authors thank Frank Destefano and Francisco Averhoff for their valuable input and revisions of the manuscript.

REFERENCES

  • 1

    World Health Organization, fact sheet no. 100. Yellow Fever. 2001. Available at: http://www.who.int/topics/yellow_fever/en. Accessed October 11, 2005.

  • 2

    Monath TP, 2001. Yellow Fever: An Update. Lancet Infect Dis 1 :11–20.

  • 3

    Monath TP, Tsai TF, 1997. Flaviviruses. Richman DD, Whitley RJ, Hayden FG, eds. Clinical Virology. New York: Churchill-Livingstone, 1133.

  • 4

    Tsai TF, Vaughn DW, Solomon T, 2005. Flaviviruses (Yellow Fever, Dengue, Dengue Hemorrhagic Fever, Japanese Encephalitis, West Nile Encephalitis, St. Louis Encephalitis, Tick-Borne Encephalitis). Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. Sixth edition. Philadelphia: Churchill Livingstone, Inc., 1927–1951.

  • 5

    Monath TP, 2003. Yellow fever. Plotkin SA, Orenstein WA, eds. Vaccines. Fourth Edition. Philadelphia: W. B. Saunders, 1095–1176.

  • 6

    Monath TP, Nichols R, Archambault WT, Moore L, Marchesani JT, Shope RE, Thomas N, Schrader R, Furby D, Bedford P, 2002. Comparative safety and immunogenicity of two yellow fever 17D vaccines (Arilvax and YF-VAX) in a phase III multicenter, double-blind clinical trial. Am J Trop Med Hyg 66 :533–541.

    • Search Google Scholar
    • Export Citation
  • 7

    Belmusto-Worn VE, Sanchez JL, McCarthy K, Nichols R, Bautista CT, Magill AJ, Pastor-Cauna G, Echevarria C, Laguna-Torres VA, Samame BK, Baldeon ME, Burans JP, Olson JG, Bedford P, Kitchener S, Monath TP, 2005. Randomized Double-blind, Phase III, Pivotal Field Trial of the Comparative Immunogenicity, Safety, and Tolerability of Two Yellow Fever 17D Vaccines (Arilvax and YF-VAX) in Healthy Infants and Children in Peru. Am J Trop Med Hyg 72 :189–197.

    • Search Google Scholar
    • Export Citation
  • 8

    Advisory Committee on Immunization Practices, 2002.Yellow Fever Vaccine: Recommendations of the Advisory Committee on Immunization Practices, 2002. Morbidity and Mortality Weekly Report 51 :1–12.

    • Search Google Scholar
    • Export Citation
  • 9

    Martin M, Weld LH, Tsai TF, Mootrey GT, Chen RT, Niu M, Cetron MS, GeoSentinel Yellow Fever Working Group, 2001. Advanced age a risk factor for illness temporally associated with yellow fever vaccination. Emerg Infect Dis 7 :94–95.

    • Search Google Scholar
    • Export Citation
  • 10

    Barwick RS, 2004. History of Thymoma and Yellow Fever Vaccination. Correspondence in the Lancet 364 :936.

  • 11

    Chen RT, Rastogi SC, Mullen JR, 1994. The Vaccine Adverse Event Reporting System (VAERS). Vaccine 12 :542–550.

  • 12

    Centers for Disease Control and Prevention. Adverse events associated with 17D-derived Yellow Fever vaccination—United States, 2001–2002. Morbidity and Mortality Weekly Report 51 (44):989–993.

    • Search Google Scholar
    • Export Citation
  • 13

    Martin M, Tsai TF, Cropp B, Chang GJJ, Holmes DA, Tseng J, Shieh WJ, Zaki SR, As-Sanouri I, Cutrona AF, Ray G, Weld LH, Cetron MS, 2001. Fever and multisystem organ failure associated with 17D-204 Yellow Fever vaccination: a report of four cases. Lancet 358 :98–104.

    • Search Google Scholar
    • Export Citation
  • 14

    Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E, 2002. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288 :862–871.

    • Search Google Scholar
    • Export Citation
  • 15

    Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM, 2004. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 32 :858–873.

    • Search Google Scholar
    • Export Citation
  • 16

    Munford RS, 2005. Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. Sixth edition. Philadelphia: Churchill Livingstone, Inc., 906–924.

  • 17

    Annane D, Bellisant E, Cavaillon JM, 2005. Septic shock. Lancet 365 :63–78.

  • 18

    Minneci PC, Deans KJ, Banks SM, Elchacker PQ, Natanson C, 2004. Meta-Analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 141 :47–56.

    • Search Google Scholar
    • Export Citation
  • 19

    World Health Organization, WHO/AFRO Yellow Fever. 2004. Available at: http://www.afro.who.int/yellowfever/. Accessed October 11, 2005.

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