Viremia and Clinical Presentation in Nicaraguan Patients Infected With Zika Virus, Chikungunya Virus, and Dengue Virus

Waggoner, Jesse J.; Gresh, Lionel; Vargas, María José; Ballesteros, Gabriela; Téllez, Yolanda; Soda, Kenji; Sahoo, Malaya K.; Nunez, Andrea C.; Balmaseda, Ángel; Harris, Eva; Pinsky, Benjamin A.

doi:10.1093/cid/ciw589

Cited by 286 publications

(301 citation statements)

References 30 publications

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“…Back-titrations of each infectious blood-meal on Vero cells estimated ZIKV titers to be 2.0x10 6 PFU/mL and 1.6x10 7 PFU/mL for fresh and frozen virus, respectively. These values are close to the range of viremia that has been previously reported for hospitalized cases of ZIKV infection [18]. …”

Section: Methodssupporting

confidence: 89%

Vector Competence of American Mosquitoes for Three Strains of Zika Virus

et al. 2016

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In 2015, Zika virus (ZIKV; Flaviviridae; Flavivirus) emerged in the Americas, causing millions of infections in dozens of countries. The rapid spread of the virus and the association with disease outcomes such as Guillain-Barré syndrome and microcephaly make understanding transmission dynamics essential. Currently, there are no reports of vector competence (VC) of American mosquitoes for ZIKV isolates from the Americas. Further, it is not clear whether ZIKV strains from other genetic lineages can be transmitted by American Aedes aegypti populations, and whether the scope of the current epidemic is in part facilitated by viral factors such as enhanced replicative fitness or increased vector competence. Therefore, we characterized replication of three ZIKV strains, one from each of the three phylogenetic clades in several cell lines and assessed their abilities to be transmitted by Ae. aegypti mosquitoes. Additionally, laboratory colonies of different Culex spp. were infected with an American outbreak strain of ZIKV to assess VC. Replication rates were variable and depended on virus strain, cell line and MOI. African strains used in this study outcompeted the American strain in vitro in both mammalian and mosquito cell culture. West and East African strains of ZIKV tested here were more efficiently transmitted by Ae. aegypti from Mexico than was the currently circulating American strain of the Asian lineage. Long-established laboratory colonies of Culex mosquitoes were not efficient ZIKV vectors. These data demonstrate the capacity for additional ZIKV strains to infect and replicate in American Aedes mosquitoes and suggest that neither enhanced virus replicative fitness nor virus adaptation to local vector mosquitoes seems likely to explain the extent and intensity of ZIKV transmission in the Americas.

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Section: Methodssupporting

confidence: 89%

Vector Competence of American Mosquitoes for Three Strains of Zika Virus

et al. 2016

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“…Enrolment criteria consisted of age less than 15 years and presentation with an acute febrile illness of fewer than 7 days duration consistent with the case definition for dengue or Zika (the latter, rash with one or more of the following symptoms: conjunctivitis, arthralgia, myalgia and/or periarticular oedema regardless of fever) 37 . ZIKV and DENV infection were confirmed by real-time RT-PCR performed at the National Virology Laboratory of the Ministry of Health in Managua using either of two triplex assays that simultaneously detect ZIKV, CHIKV and DENV infections: the ZCD assay 38 or the CDC Trioplex assay 39 . Patients with acute ZIKV infection (n = 29) or DENV infection (n = 3 DENV2 from 2016 and n = 5 DENV1 from 2012) were selected for our study.…”

Section: Methodsmentioning

confidence: 99%

CD14+CD16+ monocytes are the main target of Zika virus infection in peripheral blood mononuclear cells in a paediatric study in Nicaragua

et al. 2017

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The recent Zika pandemic in the Americas is linked to congenital birth defects and Guillain-Barré syndrome. White blood cells (WBCs) play an important role in host immune responses early in arboviral infection. Infected WBCs can also function as ‘Trojan horses’ and carry viruses into immune-sheltered spaces, including the placenta, testes and brain. Therefore, defining which WBCs are permissive to Zika virus (ZIKV) is critical. Here, we analyse ZIKV infectivity of peripheral blood mononuclear cells (PBMCs) in vitro and from Nicaraguan Zika patients and show CD14+CD16+ monocytes are the main target of infection, with ZIKV replication detected in some dendritic cells. The frequency of CD14+ monocytes was significantly decreased, while the CD14+CD16+ monocyte population was significantly expanded during ZIKV infection compared to uninfected controls. Viral RNA was detected in PBMCs from all patients, but in serum from only a subset, suggesting PBMCs may be a reservoir for ZIKV. In Zika patients, the frequency of infected cells was lower but the percentage of infected CD14+CD16+ monocytes was significantly higher compared to dengue cases. The gene expression profile in monocytes isolated from ZIKV- and dengue virus-infected patients was comparable, except for significant differences in interferon-γ, CXCL12, XCL1, interleukin-6 and interleukin-10 levels. Thus, our study provides a detailed picture of the innate immune profile of ZIKV infection and highlights the important role of monocytes, and CD14+CD16+ monocytes in particular.

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“…Rash was significantly more commonly detected in ZIKVpositive patients (91.4%) than among DENV-and CHIKV-positive patients (50.0% and 56.3%, respectively). In addition, patients with ZIKV infection were significantly less likely to be febrile > 38°C (7.4%) compared to patients with DENV (28.6%) and CHIKV infection (33.7%) [28]. Clinical symptoms reported in our patient (low grade fever, pruritic rash, edema of the legs) were suggestive of ZIKV, rather than DENV and CHIKV infection.…”

Section: Discussionmentioning

confidence: 44%

First detection of Zika virus infection in a Croatian traveler returning from Brazil, 2016

Vilibić-Čavlek¹,

Betica-Radić

Venturi

et al. 2017

J Infect Dev Ctries

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In the last few years, several imported cases of Zika virus (ZIKV) infection were reported in European countries. We report the first imported ZIKV infection case in a Croatian traveler returning from Brazil. The patient presented with a low-grade fever, pruritic rash, general weakness, myalgia, arthralgia and edema of the legs and recovered completely within a week. ZIKV infection was confirmed by detection of IgM/IgG antibodies using enzyme-linked immunosorbent assay (ELISA) and confirmed by plaque-reduction neutralization test (PRNT). ZIKV IgM antibodies cross-reacted with dengue virus (DENV), West Nile virus (WNV) and tick-borne encephalitis virus (TBEV) in ELISA. In indirect immunofluorescence assay (IFA), IgM cross-reactivity was found only with DENV-3. ZIKV IgG antibodies cross-reacted with DENV in both ELISA and IFA. PRNT for DENV was negative. Control serology performed on days 64 and 98 after disease onset showed a decline in crossreactive heterologous DENV IgG antibodies compared to persistently high titer of homologous ZIKV IgG antibodies.

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Viremia and Clinical Presentation in Nicaraguan Patients Infected With Zika Virus, Chikungunya Virus, and Dengue Virus

Abstract: Zika virus, chikungunya virus, and dengue virus result in similar clinical presentations, and coinfections may be relatively common. Accurate, multiplex diagnostics are necessary to detect and differentiate these arboviruses for patient care and epidemiologic surveillance.

Cited by 286 publications

References 30 publications

Vector Competence of American Mosquitoes for Three Strains of Zika Virus

Vector Competence of American Mosquitoes for Three Strains of Zika Virus

CD14+CD16+ monocytes are the main target of Zika virus infection in peripheral blood mononuclear cells in a paediatric study in Nicaragua

First detection of Zika virus infection in a Croatian traveler returning from Brazil, 2016

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