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Differential Diagnosis of Illness in Travelers Arriving From Sierra Leone, Liberia, or Guinea: A Cross-sectional Study From the GeoSentinel Surveillance NetworkIllness in Travelers Arriving From Sierra Leone, Liberia, or Guinea

Andrea K. Boggild, MSc, MD; Douglas H. Esposito, MD, MPH; Phyllis E. Kozarsky, MD; Vernon Ansdell, MD; Nicholas J. Beeching, MD; Daniel Campion, MB, MPH; Francesco Castelli, MD; Eric Caumes, MD; Francois Chappuis, MD, PhD; Jakob P. Cramer, MD, MSc; Effrossyni Gkrania-Klotsas, PhD; Martin P. Grobusch, MD, PhD; Stefan H.F. Hagmann, MD; Noreen A. Hynes, MD, MPH; Poh Lian Lim, MD, MPH; Rogelio López-Vélez, MD, PhD; Denis J.M. Malvy, MD, PhD; Marc Mendelson, MD, PhD; Philippe Parola, MD, PhD; Mark J. Sotir, PhD; Henry M. Wu, MD; Davidson H. Hamer, MD, for the GeoSentinel Surveillance Network*
[+] Article, Author, and Disclosure Information

* For a list of GeoSentinel Surveillance Network members, see the Appendix.

This article was published online first at www.annals.org on 12 May 2015.


From the Tropical Disease Unit of Toronto General Hospital, University of Toronto, and Public Health Ontario Laboratory, Toronto, Ontario, Canada; Centers for Disease Control and Prevention and Emory University, Atlanta, Georgia; University of Hawaii, Honolulu, Hawaii; Liverpool School of Tropical Medicine and National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom; InterHealth Worldwide, London, United Kingdom; University of Brescia, Brescia, Italy; Pitié-Salpêtrière Hospital, Pierre and Marie Curie University, Paris, France; Geneva University Hospitals, Geneva, Switzerland; Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany; University of Cambridge, Cambridge, United Kingdom; University of Amsterdam, Amsterdam, the Netherlands; Bronx-Lebanon Hospital Center and Albert Einstein College of Medicine, Bronx, New York; Johns Hopkins University School of Medicine and Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Tan Tock Seng Hospital and Lee Kong Chian School of Medicine, Singapore; Ramón y Cajal Hospital, Madrid, Spain; University of Bordeaux, Bordeaux, France; University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa; Aix-Marseille University, Marseille, France; and Boston University School of Public Health and Boston University School of Medicine, Boston, Massachusetts.

Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the CDC, the National Health Service, the National Institute for Health Research, the Department of Health, or Public Health England.

Financial Support: GeoSentinel, the Global Surveillance Network of the International Society of Travel Medicine, is supported by cooperative agreement U50/CCU412347 from the CDC. Dr. Gkrania-Klotsas was supported by the National Institute for Health Research Cambridge Biomedical Research Centre. Dr. Beeching was funded in part by the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, a partnership among the University of Liverpool, the Liverpool School of Tropical Medicine, and Public Health England.

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0074.

Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.

Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Boggild (e-mail, andrea.boggild@utoronto.ca). Data set: Not available.

Requests for Single Reprints: Davidson H. Hamer, MD, Center for Global Health and Development, Boston University, Crosstown 3rd Floor, 801 Massachusetts Avenue, Boston, MA 02118; e-mail, dhamer@bu.edu.

Current Author Addresses: Dr. Boggild: Tropical Disease Unit, Toronto General Hospital, 200 Elizabeth Street, 13EN-218, Toronto, Ontario M5G 2C4, Canada.

Drs. Esposito and Sotir: Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mail Stop E-03, Atlanta, GA 30333.

Drs. Kozarsky and Wu: Emory Clinic TravelWell, 7th Floor MOT, 550 Peachtree Street, Atlanta, GA 30308.

Dr. Ansdell: Kaiser Permanente Honolulu Clinic, 1010 Pensacola Street, Honolulu, HI 96814.

Dr. Beeching: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom.

Dr. Campion: InterHealth Worldwide, International Health Centre, 63–67 Newington Causeway, London SE1 6BD, United Kingdom.

Dr. Castelli: University Department of Infectious and Tropical Diseases, University of Brescia, Spedali Civili General Hospital, Piazza Spedali Civili 1, 25123 Brescia, Italy.

Dr. Caumes: Hôpital Pitié-Salpêtrière, Service des Maladies Infectieuses et Tropicales, Pavillon Laveran, 47–53 Boulevard de l'Hôpital, 75013 Paris, France.

Dr. Chappuis: Geneva University Hospitals, Division of Tropical and Humanitarian Medicine, Rue Gabrielle-Perret-Gentil 6, CH-1211, Geneva 14, Switzerland.

Dr. Cramer: University Medical Centre Hamburg Eppendorf, Department of Medicine, Division of Infectious Diseases and Tropical Medicine, Bernhard-Nocht-Klinik, Bernhard Nocht Strasse 74, D-20359 Hamburg, Germany.

Dr. Gkrania-Klotsas: Box 25, Department of Infectious Diseases, Cambridge University Hospital NHS Trust, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom.

Dr. Grobusch: Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO Box 22660, 1100 DD Amsterdam, the Netherlands.

Dr. Hagmann: Bronx-Lebanon Hospital Center, Division of Pediatric Infectious Diseases, 1650 Grand Concourse, Bronx, NY 10457.

Dr. Hynes: Johns Hopkins School of Medicine, Division of Infectious Diseases, 1830 East Monument Street, Room 419, Baltimore, MD 21205.

Dr. Lim: Travellers' Health & Vaccination Clinic, Institute of Infectious Diseases & Epidemiology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433.

Dr. López-Vélez: Infectious Diseases Department, Ramón y Cajal Hospital, Carretera de Colmenar km 9.1, Madrid 28034, Spain.

Dr. Malvy: Division of Tropical Medicine and Clinical International Health, Department of Infectious and Tropical Diseases, Chu Pellegrin, Place Amélie Raba-Léon, F-33 075 Bordeaux Cedex, France.

Dr. Mendelson: Division of Infectious Diseases & HIV Medicine, Department of Medicine, University of Cape Town, G16.68 Groote Schuur Hospital, Observatory 7925, Cape Town, South Africa.

Dr. Parola: University Hospital Institute for Infectious Diseases and Tropical Medicine, Aix-Marseille University, Boulevard Jean Moulin, Marseille 13005, France.

Dr. Hamer: Center for Global Health and Development, Boston University, Crosstown 3rd Floor, 801 Massachusetts Avenue, Boston, MA 02118.

Author Contributions: Conception and design: A.K. Boggild, D.H. Esposito, P.E. Kozarsky, V. Ansdell, E. Gkrania-Klotsas, M.P. Grobusch, S.H.F. Hagmann, N.A. Hynes, P.L. Lim, M.J. Sotir, D.H. Hamer.

Analysis and interpretation of the data: A.K. Boggild, D.H. Esposito, P.E. Kozarsky, V. Ansdell, D. Campion, F. Castelli, J.P. Cramer, E. Gkrania-Klotsas, M.P. Grobusch, S.H.F. Hagmann, N.A. Hynes, P.L. Lim, D.J.M. Malvy, M. Mendelson, P. Parola, M.J. Sotir, D.H. Hamer.

Drafting of the article: A.K. Boggild, D.H. Esposito, P.E. Kozarsky, V. Ansdell, N.J. Beeching, M.P. Grobusch, N.A. Hynes, M.J. Sotir, D.H. Hamer.

Critical revision of the article for important intellectual content: A.K. Boggild, D.H. Esposito, P.E. Kozarsky, V. Ansdell, N.J. Beeching, D. Campion, F. Castelli, E. Caumes, F. Chappuis, J.P. Cramer, E. Gkrania-Klotsas, S.H.F. Hagmann, N.A. Hynes, P.L. Lim, D.J.M. Malvy, M. Mendelson, M.J. Sotir, H.M. Wu, D.H. Hamer.

Final approval of the article: A.K. Boggild, D.H. Esposito, P.E. Kozarsky, V. Ansdell, N.J. Beeching, D. Campion, F. Castelli, E. Caumes, J.P. Cramer, E. Gkrania-Klotsas, M.P. Grobusch, S.H.F. Hagmann, N.A. Hynes, P.L. Lim, R. López-Vélez, D.J.M. Malvy, M. Mendelson, P. Parola, M.J. Sotir, H.M. Wu, D.H. Hamer.

Provision of study materials or patients: A.K. Boggild, V. Ansdell, N.J. Beeching, F. Castelli, E. Caumes, F. Chappuis, J.P. Cramer, E. Gkrania-Klotsas, M.P. Grobusch, S.H.F. Hagmann, P.L. Lim, R. López-Vélez, D.J.M. Malvy.

Statistical expertise: A.K. Boggild, M.J. Sotir.

Obtaining of funding: D.H. Hamer.

Administrative, technical, or logistic support: D.H. Esposito, M.J. Sotir, D.H. Hamer.

Collection and assembly of data: A.K. Boggild, V. Ansdell, N.J. Beeching, F. Castelli, E. Gkrania-Klotsas, M.P. Grobusch, P. Parola, H.M. Wu.


Ann Intern Med. 2015;162(11):757-764. doi:10.7326/M15-0074
Text Size: A A A

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.

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Electronic Surveillance System oriented to common symptoms
Posted on June 11, 2015
Carlos Polanco
Faculty of Sciences, Universidad Nacional Autónoma de México, México City, México.
Conflict of Interest: None Declared
I have read the interesting Boggild and colleagues' article (1) related to a cross-sectional study over differential diagnosis in travelers arriving from Sierra Leone, Liberia and Guinea, in the 2009-2014, and on two symptoms: fever and gastrointestinal disorders. The manuscript (1) highlights the need for monitoring other diseases with high mortality rates such as malaria and acute diarrhea, which symptoms are common to Ebola virus disease, and that also deeply affect the African population (2).

In my opinion it is necessary to implement an Electronic Surveillance System (ESS) that alerts the presence of these symptoms among the population, particularly in the region of monsoon forest climate (3). The ESS could perform an initial triage on population located in villages, markets, ports and transport stations. The ESS would identify one symptom among the population, the fever. It would be composed of cameras installed in observation towers, and it would be complemented with drones (4), for areas of difficult access. The information collected by The ESS would alert, in real-time, health care personnel in the site, and it would send this information to the GeoSentinel Surveillance Network (1).

As the technology progresses in visual recognition, these devices will be able to identify other symptoms such as: colorations in the skin, or hemorrhage, which will improve its effectiveness of the initial triage.


Sincerely yours,
Carlos Polanco, Ph.D, D.Sc.
Faculty of Sciences, Universidad Nacional Autónoma de México, México City, México.


REFERENCES

1. Boggild, A.K. et al. Differential Diagnosis of Illness in Travelers Arriving From Sierra Leone, Liberia, or Guinea: A Cross-sectional Study From the GeoSentinel Surveillance Network. Ann Intern Med. Published online 2 June 2015 DOI:10.7326/M14-2002.

2. Butler D, Morello L. Ebola by the numbers: The size, spread and cost of an outbreak. Nature 2015:514; 284–285. DOI: 10.1038/514284a.

3. Hayden E.C. Ebola teaches tough lessons about rapid research. Nature 2015:521; 405-406 DOI:10.1038/521405a.

4. Polanco, C. Comment to: Azarian, T. et al. Impact of spatial dispersion, evolution, and selection on Ebola Zaire Virus epidemic waves. Scientific Reports 2015:10170 DOI:10.1038/srep10170.
Malaria in travellers from West Africa
Posted on July 1, 2015
Emanuele Nicastri, Angela Corpolongo, Francesco Vairo, Nazario Bevilacqua, Giuseppe Ippolito
National Institute for Infectious Diseases INMI “L.Spallanzani”, Rome, Italy
Conflict of Interest: None Declared
Boggild and colleagues (1) provided very useful data on the differential diagnosis in travellers to West Africa Region and highlighted the need of a preventive strategy which include the prompt diagnosis and empirical treatment initiation for malaria also in light of the Ebola Virus disease (EVD) epidemic which can divert the attention from the usual common diseases carried by travellers. We reviewed our experience in Italy as a referral hospital for Infectious Disease and Tropical Medicine. During the period 2009-2014, febrile syndromes due to malaria or dengue were described in 164 patients. Among them mean age was 40.6 years (+13.7) and 116 (69.5%) were mail. Among these patients 37.5% were tourists, 22.1% had business travel and 19.1% visited friends or relatives (VFR). The median interval between the return to Italy and admission to the hospital was 4 days (IQR, 2-6). 62 patients admitted for fever after returning from tropical regions were diagnosed with severe malaria according to WHO criteria: CNS involvement was reporetd in 14 (22.6%) patients and liver involvement in 23 (37.1%) patients. Pl. Falciparum was the cause of malaria in 78.1% followed by Pl. Vivax (17.1%). Dengue infection was diagnosed in 80 cases (all of them with no sign or symptoms of severity.).
There was a clear geographical association between the diagnosis and the respective visiting country: 48 (57.1%) malaria cases returned from West Africa and 69 (85%) dengue cases returned from Latinamerica or Southeast Asia. Among malaria cases from West Africa, 91.5% were caused by Pl. Falciparum.
Malaria infection is the more common tropical infections in person travelling back home from West African countries (2) and malaria can be considered not only as differential diagnosis of a unspecific febrile syndrome but even as a co-infection in patients with clinical suspicion of EVD cases returning home from Ebola-affected countries, Finally, malaria rapid antigen assay can provide false negative results in case of P. vivax infection (3) In our opinion febrile patients returning from West Africa and under investigation for EVD, should receive empirical malaria treatment if neither molecular or microscopy assays are available and concerns on P. vivax infection are raised.

1. Boggild AK, Esposito DH, Kozarsky PE, Ansdell V, Beeching NJ, Campion D, et al.; GeoSentinel Surveillance Network. Differential Diagnosis of Illness in Traveler Arriving From Sierra Leone, Liberia, or Guinea: A Cross-sectional Study From the GeoSentinel Surveillance Network. Ann Intern Med. 2015;162:757-64.

2. Schlagenhauf P, Weld L, Goorhuis A, Gautret P, Weber R, von Sonnenburg F, et al.; EuroTravNet. Travel-associated infection presenting in Europe (2008-12): an analysis of EuroTravNet longitudinal, surveillance data, and evaluation of the effect of the pre-travel consultation. Lancet Infect Dis. 2015;15:55-64.

3. Abba K, Deeks JJ, Olliaro P, Naing CM, Jackson SM, Takwoingi Y, at al. Rapid diagnostic tests for diagnosing uncomplicated P. Falciparum malaria in endemic countries. Cochrane Database Syst Rev. 2011;(7):CD008122
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