Atypical Chikungunya Virus Infections in Immunocompromised Patients

Kee, Adrian; Yang, Samantha Peiling; Tambyah, Paul Anantharajah

doi:10.3201/eid1606.091115

Cited by 50 publications

(34 citation statements)

References 10 publications

(11 reference statements)

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“…Mild or transient arthralgia and fever were the most common symptoms observed in our case series of SOT recipients with CHIKV infection, which is consistent with published reports . Among all case series reviewed, arthralgia lasting more than 5 days was present in 30%‐46% of the SOT recipients with CHIKV infection . This rate is lower than that reported in non‐transplant patients with CHIKV infection, in whom arthralgia lasting more than 5 days has been reported in 80% of patients .…”

Section: Discussionsupporting

confidence: 90%

“…Kee et al reported a case of encephalitis possibly caused by CHIVKV infection in a liver transplant recipient. In this patient, serology was positive for CHIKV, but the serum RT‐PCR was negative .…”

Section: Discussionmentioning

confidence: 99%

“…Given the rising number of SOT performed in Latin American countries and the sparse information on CHIKV infection among transplant recipients, we set out to review the available evidence on this subject, and describe the clinical characteristics of a case series of SOT recipients with post‐transplant CHIKV infection in a reference center in Cali, Colombia.…”

Section: Introductionmentioning

confidence: 99%

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Chikungunya in solid organ transplant recipients, a case series and literature review

Rosso

Rodríguez

Cedano

et al. 2018

Transplant Infectious Dis

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Chikungunya virus is a recent emerging arbovirus in Latin America, and the clinical manifestations can vary from fever and rash to severe chronic inflammatory arthritis. Few reports have been published regarding this infection in immunocompromised patients, including solid organ transplant recipients. We report a case series of solid organ transplant recipients with confirmed Chikungunya infection by positive reverse transcription polymerase chain reaction (RT-PCR), identified between January 2014 and December 2016. In addition, we conducted a literature review searching PubMed, EMBASE, and LILACS databases on Chikungunya infection in solid organ transplant recipients. Ten solid organ transplant recipients were included, consisting of 5 kidney, 4 liver, and 1 liver/kidney transplant recipient. Mean age of the transplant recipients was 47 years, and the most frequent symptoms of Chikungunya infection were arthralgia and fever. None of the patients required treatment in the intensive care unit, no deaths or graft rejection occurred. None of our patients had recurrent arthritis during 3-month follow-up period after the infection. Twenty-one cases of Chikungunya virus were identified in the literature review. Most cases had a benign clinical course with no severe complications, death, or chronic inflammatory arthritis. In conclusion, Chikungunya infection in solid organ transplant recipients has a benign course and has no chronic recurrent arthritis. It is possible that the immunosuppression regimen could decrease the risk of severe or chronic inflammatory manifestations in solid organ transplant recipients infected with Chikungunya.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chikungunya in solid organ transplant recipients, a case series and literature review

Rosso

Rodríguez

Cedano

et al. 2018

Transplant Infectious Dis

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“…Donor-derived transmission of other mosquito-borne viruses with similar epidemiologic and biologic features, notably dengue virus and West Nile virus, has been documented (9,10). Although no cases of CHIKV transmission by transplantation have yet been reported, studies have shown that CHIKV can be isolated from corneas of acutely infected individuals (11), and atypical manifestations of CHIKV infection were reported in a recipient who became infected 7 years after receiving a liver transplant (12). However, the likelihood of CHIKV transmission by transplantation, and what organs/tissues might harbor the virus, remains unknown.…”

mentioning

confidence: 99%

Evaluation of Two Enzyme-Linked Immunosorbent Assay Kits for Chikungunya Virus IgM Using Samples from Deceased Organ and Tissue Donors

Prince¹,

Altrich²,

Nowicki³

2016

Clin Vaccine Immunol

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The identification of nearly 3,500 cases of chikungunya virus (CHIKV) infection in U.S. residents returning in 2014 and 2015 from areas in which it is endemic has raised concerns within the transplant community that, should recently infected individuals become organ and/or tissue donors, CHIKV would be transmitted to transplant recipients. Thus, tests designed to detect recent CHIKV infection among U.S. organ and tissue donors may become necessary in the future. Accordingly, we evaluated 2 enzymelinked immunosorbent assays (ELISAs) for CHIKV IgM readily available in the United States using 1,000 deidentified serum or plasma specimens collected from donors between November 2014 and March 2015. The Euroimmun indirect ELISA identified 38 reactive specimens; however, all 38 were negative for CHIKV IgG and IgM in immunofluorescence assays (IFAs) conducted at a reference laboratory and, thus, were falsely reactive in the Euroimmun CHIKV IgM assay. The InBios IgM-capture ELISA identified 26 reactive samples, and one was still reactive (index > 1.00) when retested using the InBios kit with a background subtraction modification to identify false reactivity. This reactive specimen was CHIKV IgM negative but IgG positive by IFAs at two reference laboratories; plaque reduction neutralization testing (PRNT) demonstrated CHIKV-specific reactivity. The IgG and PRNT findings strongly suggest that the InBios CHIKV IgM-reactive result represents true reactivity, even though the IgM IFA result was negative. If testing organ/tissue donors for CHIKV IgM becomes necessary, the limitations of the currently available CHIKV IgM ELISAs and options for their optimization must be understood to avoid organ/tissue wastage due to falsely reactive results. C hikungunya virus (CHIKV) is an alphavirus transmitted from person to person via mosquito bites (1). Symptoms include fever, rash, and debilitating arthralgia; 15% to 60% of patients develop chronic arthralgia leading to arthritic joint damage (2). After a large CHIKV outbreak in India and southeast Asia in 2004 through 2006, in which nearly 2 million people became infected (3, 4), epidemiologists predicted that CHIKV might move to other geographic areas where the mosquito vectors are found (5). This prediction was realized in December 2013, when local transmission of CHIKV was reported on the Caribbean island of St. Martin (6). CHIKV infection has since spread throughout the Caribbean basin (7) and is now also endemic in Mexico, Central America, and South America and in the Caribbean island nations. In conjunction with this outbreak, 3,490 cases in U.S. residents (from 49 of 50 states) were reported to the CDC during 2014 and 2015; 3,478 cases represented infections acquired during international travel to areas where CHIKV is endemic, whereas 12 cases represented local transmission (8).There is concern within the transplant community that CHIKV could be transmitted from organ and/or tissue donors to recipients. Donor-derived transmission of other mosquito-borne viruses with similar epidemi...

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“…Since 2004, the geographic distribution of CHIKV has increased significantly, reaching immunologically naive populations in islands of the Indian Ocean, Europe, and the Caribbean (8)(9)(10)(11)(12)(13). These epidemics are noteworthy for more severe clinical manifestations, including encephalopathy, hepatitis, meningoencephalitis, and ocular disease and represent the first documented cases of fatal infection (14)(15)(16).…”

mentioning

confidence: 99%

Residue 82 of the Chikungunya Virus E2 Attachment Protein Modulates Viral Dissemination and Arthritis in Mice

Ashbrook

Burrack

Silva

et al. 2014

J Virol

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Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has reemerged to cause profound epidemics of fever, rash, and arthralgia throughout sub-Saharan Africa, Southeast Asia, and the Caribbean. Like other arthritogenic alphaviruses, mechanisms of CHIKV pathogenesis are not well defined. Using the attenuated CHIKV strain 181/25 and virulent strain AF15561, we identified a residue in the E2 viral attachment protein that is a critical determinant of viral replication in cultured cells and pathogenesis in vivo. Viruses containing an arginine at E2 residue 82 displayed enhanced infectivity in mammalian cells but reduced infectivity in mosquito cells and diminished virulence in a mouse model of CHIKV disease. Mice inoculated with virus containing an arginine at this position exhibited reduced swelling at the site of inoculation with a concomitant decrease in the severity of necrosis in joint-associated tissues. Viruses containing a glycine at E2 residue 82 produced higher titers in the spleen and serum at early times postinfection. Using wild-type and glycosaminoglycan (GAG)-deficient Chinese hamster ovary (CHO) cell lines and soluble GAGs, we found that an arginine at residue 82 conferred greater dependence on GAGs for infection of mammalian cells. These data suggest that CHIKV E2 interactions with GAGs diminish dissemination to lymphoid tissue, establishment of viremia, and activation of inflammatory responses early in infection. Collectively, these results suggest a function for GAG utilization in regulating CHIKV tropism and host responses that contribute to arthritis. IMPORTANCECHIKV is a reemerging alphavirus of global significance with high potential to spread into new, immunologically naive populations. The severity of CHIKV disease, particularly its propensity for chronic musculoskeletal manifestations, emphasizes the need for identification of genetic determinants that dictate CHIKV virulence in the host. To better understand mechanisms of CHIKV pathogenesis, we probed the function of an amino acid polymorphism in the E2 viral attachment protein using a mouse model of CHIKV musculoskeletal disease. In addition to influencing glycosaminoglycan utilization, we identified roles for this polymorphism in differential infection of mammalian and mosquito cells and targeting of CHIKV to specific tissues within infected mice. These studies demonstrate a correlation between CHIKV tissue tropism and virus-induced pathology modulated by a single polymorphism in E2, which in turn illuminates potential targets for vaccine and antiviral drug development.

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Atypical Chikungunya Virus Infections in Immunocompromised Patients

Cited by 50 publications

References 10 publications

Chikungunya in solid organ transplant recipients, a case series and literature review

Chikungunya in solid organ transplant recipients, a case series and literature review

Evaluation of Two Enzyme-Linked Immunosorbent Assay Kits for Chikungunya Virus IgM Using Samples from Deceased Organ and Tissue Donors

Residue 82 of the Chikungunya Virus E2 Attachment Protein Modulates Viral Dissemination and Arthritis in Mice

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