Dengue Zika Chikungunya Cuba
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    Autochthonous Chikungunya Fever in Traveler Returning to Japan from Cuba

    To the Editor: Chikungunya fever is a febrile illness caused by
    mosquito-transmitted chikungunya virus CHIKV: (genus Alphavirus, family
    Togaviridae). Clinical signs and symptoms typically begin with
    high-grade fever after an incubation period of 2–4 days (1). Other
    common symptoms include polyarthralgia, which is usually symmetric and
    involves multiple and distal joints, and skin involvement manifesting as
    a macular or maculopapular rash (2). Peripheral lymphadenopathy (most
    often cervical) and conjunctivitis might also occur (3).

    Since late 2013, several outbreaks of illness caused by CHIKV have
    occurred in the Americas, including South America, the Caribbean, and
    the United States, which are outside this virus’s former distribution
    area (3). Although autochthonous transmission of chikungunya fever has
    been reported in most Caribbean islands, only imported cases have been
    previously reported in Cuba (4). As increased numbers of US tourists
    visit Cuba after improved diplomatic relations in July 2015, reports of
    chikungunya fever cases in Cuba are of interest for travelers and
    healthcare providers. We describe a case of autochthonous chikungunya
    fever in a man who had traveled from Japan to Cuba.

    In late February 2016, a previously healthy 27-year-old man visited a
    travel clinic in the National Center for Global Health and Medicine
    (Tokyo, Japan) with fever and rash. In mid-February, he had traveled to
    Havana and Santiago de Cuba in Cuba by way of Toronto, Ontario, Canada,
    for 11 days of sightseeing. He used no insect repellent during the trip
    and was unaware of any mosquito bites. When he sought care, he reported
    a high-grade fever (39°C) for 24 hours and several symptoms since the
    day of his return: retro-orbital pain, malaise, congested conjunctivas,
    and a rash on his anterior chest. Over the previous few days, his knee
    and ankle joints also had mild arthralgia.

    Figure. Phylogenetic analysis of the chikungunya virus sequence obtained
    from a patient returning to Japan (in bold) from Cuba in February 2016,
    compared with reference sequences. Virus lineages are shown at right….

    On physical examination, the patient’s body temperature was 38.7°C, and
    he had congested bulbar conjunctivas, cervical lymphadenopathy, and
    maculopapular rashes on his face, trunk, and extremities (Technical
    Appendix[PDF – 130 KB – 2 pages], Figure, panels A, B). Laboratory tests
    revealed lymphopenia (701 cells/?L) and mild elevation of C-reactive
    protein (0.87 mg/dL). Real-time reverse transcription PCR detected CHIKV
    RNA in his serum sample. Phylogenetic analysis was performed on the
    basis of nucleotide sequences of the E1 gene from the sample by using
    the maximum likelihood method with 1,000 bootstrap replicates and MEGA
    6.0 software (5). This sequence (GenBank accession no. LC146714) was
    99.9% (1,319 of 1,320 sequences) was identical to that of a CHIKV strain
    isolated from the Dominican Republic in 2014 (GenBank accession no.
    KR559498) (Figure; Technical Appendix[PDF – 130 KB – 2 pages] Table).
    The positive-to-negative ratio of CHIKV-specific IgM was negative in a
    serum sample collected on day 4 after fever onset but was positive in a
    sample taken 7 days later (positive-to-negative ratios 5.6 and 21.9,
    respectively; ratios were considered positive if >11). Because the
    patient’s serum samples contained no dengue or Zika virus, infections
    from these viruses were excluded, and chikungunya fever was diagnosed.

    One day after the patient’s first visit to the clinic, rashes on his
    extremities became worse and slightly itchy. Pain also developed in his
    wrists and metacarpophalangeal joints of his hand, followed by cervical
    pain and slight rigidity on the hand’s distal and proximal
    interphalangeal joints. The patient was initially treated with
    acetaminophen (600 mg 3×/d 2 d); after diagnosis of chikungunya fever,
    he was treated with loxoprofen and rebamipide (60 mg and 100 mg,
    respectively, 3×/d 7 d). The congested bulbar conjunctivas and rash on
    his trunk improved; soon thereafter, all symptoms resolved.

    CHIKV was first isolated in 1953 in Tanzania during an epidemic outbreak
    in East Africa (6). Mosquitoes, predominantly Aedes aegypti and Ae.
    albopictus, transmit the virus (2). Aedes spp. are also the common
    vector of dengue and Zika viruses, and localized dengue outbreaks
    occurred in Santiago de Cuba in 1997 and in Havana in 2000–2001 because
    of the persistence of Aedes mosquito infestation in Cuba (7,8).
    Furthermore, autochthonous Zika virus infection in Cuba was first
    reported in March 2016 (9).

    Differentiation between chikungunya fever, dengue fever, and Zika virus
    infection is difficult because of similar signs and symptoms and common
    endemic areas. We suspected chikungunya fever in this patient because of
    high-grade fever and maculopapular rash, although he also had prominent
    conjunctivitis, which is uncommon in CHIKV-infected patients but
    frequent in persons infected with Zika virus (3,10). Phylogenetic
    analysis of the virus isolated from this patient revealed a high
    sequence homology with recent strains discovered in Caribbean and
    Central American countries in 2014. Homology between the isolate from
    this patient and a 2014 Asian lineage isolate from the Dominican
    Republic was 99.92% at the nucleotide level.

    This case highlights the potential threat of a chikungunya fever
    outbreak in Cuba. Physicians should consider chikungunya fever in the
    differential diagnosis for febrile travelers returning from Cuba with a
    rash, similarly to patients returning from other countries in which
    dengue fever, chikungunya fever, and Zika virus infection are endemic.
    Preventive measures, including advice to travelers on proper use of
    insect repellents, are critical for preventing CHIKV infection.

    Motoyuki Tsuboi, Satoshi Kutsuna , Yasuyuki Kato, Eri Nakayama, Ken-ichi
    Shibasaki, Shigeru Tajima, Tomohiko Takasaki, Yuichi Katanami, Kei
    Yamamoto, Nozomi Takeshita, Kayoko Hayakawa, Shuzo Kanagawa, and Norio
    Author affiliations: National Center for Global Health and Medicine,
    Tokyo, Japan (M. Tsuboi, S. Kutsuna, Y. Kato, Y. Katanami, K. Yamamoto,
    N. Takeshita, K. Hayakawa, S. Kanagawa, N. Ohmagari); National Institute
    of Infectious Diseases, Tokyo (E. Nakayama, K.-i. Shibasaki, S. Tajima,
    T. Takasaki)
    The authors thank the clinical staff at the Disease Control and
    Prevention Center, Tokyo, Japan, for their help in completing this study.

    A grant from the National Center for Global Health and Medicine
    (27-6001) supported this work.

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    Source: Autochthonous Chikungunya Fever in Traveler Returning to Japan
    from Cuba – Volume 22, Number 9—September 2016 – Emerging Infectious
    Disease journal – CDC –

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