Chikungunya Fever in Israeli Travelers Returning From Northwestern India

Amir Tanay MD, Eli Schwartz MD, Hanna Bin PhD, Hervé Zeller PhD, Matthias Niedrig PhD, Michael Dan MD
DOI: http://dx.doi.org/10.1111/j.1708-8305.2008.00244.x 382-384 First published online: 1 September 2008

Abstract

Chikungunya fever has been increasingly documented among Western travelers returning from areas with chikungunya virus transmission, which are also popular touristic sites. We describe the case of three Israeli travelers who developed fever, maculopapular rash, and long‐standing arthralgias while visiting northern Indian states not known to be involved in the chikungunya fever epidemic.

Chikungunya virus is a mosquito‐borne alphavirus indigenous to tropical Africa and Asia, where it causes endemic and epidemic infection among humans. Although acute symptoms of the infection usually last a few days, joint symptoms and signs can persist for months and occasionally for years. Immunoglobulin (Ig) M antibodies appear from day 5 after disease onset and can be detected for several months in patients with recurrent arthralgias. In the early days of the disease, the diagnosis can be established by a real‐time polymerase chain reaction assay. 1 Chikungunya fever has been increasingly documented among Western travelers returning from areas with chikungunya virus transmission, which are also popular touristic sites. 2–8 Knowledge of the geographical distribution of exotic infections is a useful tool in establishing the differential diagnosis of an infectious disease in the traveler who returns sick from the tropics. We report the first three cases of chikungunya fever among Israeli travelers, all of whom contracted the infection in north India.

Case report

A married Israeli couple visited the northwestern states of India in October to November 2006. Two weeks after arriving in Rajasthan, while in Bikaner, they became ill: first, the 56‐year‐old wife experienced fever up to 40°C, rigors, myalgias, arthralgias, and loss of appetite; 2 to 3 days after the onset of fever, a nonpalpable maculopapular rash covered predominantly the face and extremities (sparing the palms and soles). A day later, the 58‐year‐old husband started to present the same symptoms, except for skin rash; he also had bilateral conjunctivitis. At the local hospital, malaria was excluded, and the physicians felt that the diagnosis of dengue fever was unlikely. No other specific viral infections were evoked. Fever subsided within 5 days, during which a weight loss of 6 to 9 kg was noted; the arthralgias also regressed. Three weeks after recovering from the acute disease, joint pain reappeared in wrists, metacarpophalangeal joints, ankles, knees, and cervical spine with swelling and morning stiffness of 45 to 120 minutes. The woman also had a new low back pain. The patients consulted a rheumatologist: physical examination revealed symmetric synovitis of wrists, metacarpophalangeal joints, proximal interphalangeal joints, and acromioclavicular joints and tenderness in knees, ankles, and hip joints. The rest of the examination was normal, and their condition improved with nonsteroidal anti‐inflammatory drugs. Laboratory investigation was negative for connective tissue diseases. The possible diagnosis of chikungunya fever was confirmed in both patients by indirect immunofluorescent assay (IFA) serology with IgG titers ≥1:640 and positive IgM (woman 1:10; man 1:80). Serology for other arboviruses (dengue, Sindbis, and Japanese encephalitis) was negative. On the last follow‐up visit (August 2007), both patients were symptom free and have regained full locomotor function.

A 22‐year‐old woman had a 3‐month trip to India from June 29 to October 3, 2006. Before returning back to Israel, she stayed in Delhi for 3 days and in Uttarakhand (Rishikesh) 5 days beforehand. Her symptoms started 2 days after arriving in Israel, consisting of high fever (39.2°C), which lasted for 4 days, a maculopapular rash, and a frontal headache. She also experienced severe arthralgias—mainly in palms and soles—and hardly could walk. On follow‐up 4 weeks later, she continued to complain of significant arthralgias. Chikungunya virus serology was positive for IgM by enzyme‐linked immunosorbent assay and by IFA [2.0 optic density (OD) and 1:80, respectively] and IgG (0.28 OD and 1:160, respectively). Two months thereafter (January 1, 2007), arthralgias were still present, although in a milder form. Repeat chikungunya virus serology by IFA on that occasion showed IgM titers of 1:10 and IgG titers of 1:160. Serology for other arboviruses was negative, although some cross‐reactivity with O’nyong‐nyong was observed (0.39 OD). When contacted a month later, she reported complete disappearance of joint pain.

Chikungunya virus serology was first performed in Institute Pasteur before commercial kits were available. Later, when they became available, IFA slides manufactured by Euroimmune, Gross‐Groenau, Germany, were used. The assays were validated in the laboratories of Drs H. Zeller and M. Niedrig. Tests were performed according to the manufacturer’s instructions.

Discussion

Arthritis has been associated with several viral infections. Joint involvement is a typical manifestation of arthritogenic alphaviruses, rubella virus, and human parvovirus B19. In addition, arthritis can follow infection by cytomegalovirus, Epstein–Barr virus, hepatitis B virus, hepatitis C virus, or human immunodeficiency virus. In alphavirus and human parvovirus B19 infections, arthritis/arthralgia can be prolonged, lasting for months and even years. 9 Of the 10 arthritogenic alphaviruses, 6 are associated with chronic arthralgias. The clinical presentation of these infections is grossly identical, dominated by fever, rash, myalgia, and arthritis/arthralgias. They differ, however, by their geographical distribution: Ross River virus—Australia and West Pacific; Ockelbo virus—Sweden and Norway; Pogosta virus—Finland; Mayaro virus—South America; O’nyong‐nyong virus—Central and East Africa; and chikungunya virus—South and East Asia, Africa, and West Pacific. 9

After a remission of more than 20 years, chikungunya fever has been reported from India and various Indian Ocean Islands. According to a WHO Regional Office for South‐East Asia report, between February 2006 and October 2006, 151 districts in nine states/provinces of India have been affected by chikungunya fever. 10 The affected states were Andaman and Nicobar Islands, Andhra Pradesh, Delhi, Gujarat, Karnataka, Kerala, Madhya Pradesh, Maharashtra, and Tamil Nadu, with more than 1.25 million suspected cases. More recently, the Indian government has reported 1,391,165 suspected chikungunya virus cases in 13 states of the country during 2006. 11,12 The newly added states to the list of affected areas were Rajasthan, Pondicherry, Goa, and Orissa. Because the incubation period of chikungunya fever does not usually exceed 12 days, 1 it is almost certain that the first two patients described in the present report contracted their infection in the newly affected state of Rajasthan. In total, 102 cases were reported in Rajasthan including 24 confirmed cases. 11 In Delhi, of 560 suspected cases in 2006, all of which were tested at the National Institute of Virology, chikungunya fever was confirmed in 67 patients. 11 No cases of chikungunya were reported from the state of Uttarakhand in 2006. Hence, it is possible that our third patient was infected in Delhi as the usual incubation period is 2 to 4 days, 1 although a yet unrecognized focus of chikungunya virus in Uttarakhand cannot be excluded.

Awareness of epidemics in remote areas can help medical practitioners in Western countries recognize infections not commonly seen in their region but rather imported by returning travelers. On the other hand, disease diagnosed in returning travelers may serve as the first indication of its spread to unrecognized foci. For example, malaria in travelers led to the identification of new foci of infection in the Dominican Republic and Bahamas. 13,14 Thus, information gathered from illnesses in travelers may complement local surveillance and assist authorities in areas where public health resources are suboptimal. In two of our cases, the chikungunya fever developed before the announcement of the Indian authorities about the expansion of the disease to Rajasthan and could have served as a sentinel information.

In 2005 to 2006, approximately 800 chikungunya viral infections were reported in France, primarily in travelers returning from Réunion Island. 3 Among 22 travelers with chikungunya infection returning to Paris, France, from the Indian Ocean Islands, 2 fever and joint pain were noted in all patients, while skin manifestations occurred in 77%. Joint pain was mainly distal and symmetric. The main characteristic of the skin eruption was a generalized macular erythematous exanthema, often with a sensation of pruritus. In the United States, 37 imported cases were diagnosed during 2006, 3 most of whom (86%) visited India. Imported cases of chikungunya were reported also in the UK (106 cases), 5 Germany (20), 8 Italy (17), 15 Spain (7), 7 and Taiwan (2). 6

Because joint manifestations of chikungunya fever can persist for months and even years, 1 long after the acute symptoms had resolved and often been forgotten, diagnosis can be missed or delayed if a thorough history is not obtained from the patient. Clinicians should be aware of the late consequences of infection by chikungunya virus and other arthritogenic alphaviruses and recognize the possible association of subacute and chronic arthritic symptoms with travel to endemic areas. Therefore, travel information should be a mandatory part of patient history taking, and chikungunya should be now included in the differential diagnosis of abrupt onset of febrile polyarthralgia in travelers returning from endemic areas.

Declaration of interests

The authors state that they have no conflicts of interest.

References

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