Zika virus RNA excretion in sweat with concomitant detection in other body fluid specimens

We evaluated sweat, blood and urine specimens obtained from an ongoing cohort study in Brazil. Samples were collected at pre-established intervals after the initial rash presentation and tested for Zika virus (ZIKV) RNA presence by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). From 254 participants with confirmed infection, ZIKV RNA was detected in the sweat of 46 individuals (18.1%). Sweat presented a median cycle threshold (Ct) of 34.74 [interquartile range (IQR) 33.44-36.04], comparable to plasma (Ct 35.96 - IQR 33.29-36.69) and higher than urine (Ct 30.78 - IQR 28.72-33.22). Concomitant detection with other specimens was observed in 33 (72%) of 46 participants who had a positive result in sweat. These findings represent an unusual and not yet investigated virus shedding through eccrine glands.

Key words:
Zika virus; diagnosis; persistence

Authorship

Armando Menezes-Neto

Fundação Oswaldo Cruz-Fiocruz, Instituto Aggeu Magalhães, Recife, PE, BrasilFundação Oswaldo Cruz-FiocruzBrazilRecife, PE, BrazilFundação Oswaldo Cruz-Fiocruz, Instituto Aggeu Magalhães, Recife, PE, Brasil

Marcia da Costa Castilho

Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, AM, BrasilFundação de Medicina Tropical Doutor Heitor Vieira DouradoBrazilManaus, AM, BrazilFundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, AM, Brasil

Guilherme Amaral Calvet

Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, RJ, BrasilInstituto Nacional de Infectologia Evandro ChagasBrasilRio de Janeiro, RJ, BrasilInstituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, RJ, Brasil

Edna Oliveira Kara

World Health Organization, Geneva, SwitzerlandWorld Health OrganizationSwitzerlandGeneva, SwitzerlandWorld Health Organization, Geneva, Switzerland

Camila Helena Aguiar Bôtto-Menezes

Universidade do Estado do Amazonas, Manaus, AM, BrasilUniversidade do Estado do AmazonasBrazilManaus, AM, BrazilUniversidade do Estado do Amazonas, Manaus, AM, Brasil

Marcus Vinícius Guimarães Lacerda

Fundação Oswaldo Cruz-Fiocruz, Manaus, AM, BrasilFundação Oswaldo Cruz-FiocruzBrazilManaus, AM, BrazilFundação Oswaldo Cruz-Fiocruz, Manaus, AM, Brasil

Gerson Fernando Mendes Pereira

Ministério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis, Brasília, DF, BrasilMinistério da SaúdeBrazilBrasília, DF, BrazilMinistério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis, Brasília, DF, Brasil

Silvana Pereira Giozza

Ximena Pamela Diaz Bermudez

Organização Pan Americana de Saúde/Organização Mundial da Saúde, Universidade de Brasília, Departamento de Saúde Pública, Brasília, DF, BrasilOrganização Pan Americana de Saúde/Organização Mundial da SaúdeBrasilBrasília, DF, BrasilOrganização Pan Americana de Saúde/Organização Mundial da Saúde, Universidade de Brasília, Departamento de Saúde Pública, Brasília, DF, Brasil

Noemia Santana Lima

Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USAHenry M Jackson Foundation for the Advancement of Military MedicineUSABethesda, MD, USAHenry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA

Walter Reed Army Institute of Research, Silver Spring, Maryland, USAWalter Reed Army Institute of ResearchUSASilver Spring, Maryland, USAWalter Reed Army Institute of Research, Silver Spring, Maryland, USA

Kayvon Modjarrad

Nathalie Broutet

World Health Organization, Geneva, SwitzerlandWorld Health OrganizationSwitzerlandGeneva, SwitzerlandWorld Health Organization, Geneva, Switzerland

Ana Maria Bispo de Filippis

Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz-FiocruzBrazilRio de Janeiro, RJ, BrazilFundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brasil

Rafael Freitas Oliveira Franca ⁺+ Corresponding author: rafael.franca@cpqam.fiocruz.br

http://orcid.org/0000-0002-1846-6007

Study Team ZIKABRA

+ Corresponding author: rafael.franca@cpqam.fiocruz.br

AM-Neto and MCC performed laboratory procedures and data collection; GAC, EOK, CHAB-M, MVGL, GFMP, SPG, XPDB, NSL, KM, NB, AMBF and RFOF performed data analysis and study supervision; AM-Neto and RFOF wrote the manuscript. All authors reviewed and approved the final version of the manuscript. The authors declare they have no conflict of interests, and the funders had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript. *ZIKABRA Study Team members (in alphabetical order): Ana Izabel Costa de Menezes, Ana Maria Bispo de Filippis, André Luiz de Abreu, Anna Thorson, Armando Menezes Neto, Camila Helena Aguiar Bôtto-Menezes, Carlos Alexandre Antunes Brito, Casey Storme, Cristina Pimenta, Edna Oliveira Kara, Gerson Fernando Mendes Pereira, Guilherme Amaral Calvet, Kayvon Modjarrad, Lydie Trautman, Maeve Brito de Mello, Marcia da Costa Castilho, Marcus Vinicius Guimarães Lacerda, Morganna Costa Lima, Nathalie Jeanne Nicole Broutet, Ndema Habib, Noemia Lima, Patrícia Brasil, Rafael Freitas Oliveira Franca, Sihem Landoulsi, Silvana Pereira Giozza, Ute Ströher, Ximena Pamela Diaz Bermudez.

SCIMAGO INSTITUTIONS RANKINGS

World Health Organization, Geneva, SwitzerlandWorld Health OrganizationSwitzerlandGeneva, SwitzerlandWorld Health Organization, Geneva, Switzerland

Universidade do Estado do Amazonas, Manaus, AM, BrasilUniversidade do Estado do AmazonasBrazilManaus, AM, BrazilUniversidade do Estado do Amazonas, Manaus, AM, Brasil

Fundação Oswaldo Cruz-Fiocruz, Manaus, AM, BrasilFundação Oswaldo Cruz-FiocruzBrazilManaus, AM, BrazilFundação Oswaldo Cruz-Fiocruz, Manaus, AM, Brasil

Figures | Tables

Figures (2)
Tables (1)

Thumbnail

Fig. 1:
(A) Zika virus (ZIKV) infection confirmation by real time reverse transcriptase polymerase chain reaction (rRT-PCR). ZIKV RNA detection in sweat samples from 46 participants of 254 confirmed infection cases in Manaus, northern Brazil, analyzed at different time points (according to days of rash report). Detections in sweat at two distinct time points were reported for five participants: (participant IDs 6, 25, 27, 34, and 37). A single participant was defined as asymptomatic household contact (participant 12 - asterisk). Blue dots - ZIKV detection in sweat. Gray dots - detection at other body fluid (blood, urine, or semen, not specified on the figure) according to days post rash.

Thumbnail

Fig. 2:
(A) Zika virus (ZIKV) RNA detection by real time reverse transcriptase polymerase chain reaction (rRT-PCR) according to the days of symptoms onset (days post rash report - “x” axis), Cycle threshold (Ct) rRT-PCR value (“y”axis) and body fluid specimen (urine, plasma and sweat) (figure legend colors). (inset) Median Ct value from 46 participants with positive rRT-PCR result in urine, plasma, and sweat body fluid specimens. Cut-off values were set above Ct 38 on rRT-PCR result. Ct - cycle threshold. NS: not significant; ***p < 0.001 analyzed by One-way ANOVA. (B) ZIKV RNA concomitant detection according to the body fluid specimen analyzed. rRT-PCR concomitant detection (“y” axis) refers to an individual positive detection on that specimens from the same participant (as specified on figure legend) according to its study number identification.

Thumbnail

TABLE
Participants characteristics and clinical data reported at screening visit (defined as rash presentation or Zika virus (ZIKV) initial positive detection for household/sexual asymptomatic subjects). Clinical data was collected at outpatients study clinic, only those participants with a positive detection at sweat are presented

Fig. 1: (A) Zika virus (ZIKV) infection confirmation by real time reverse transcriptase polymerase chain reaction (rRT-PCR). ZIKV RNA detection in sweat samples from 46 participants of 254 confirmed infection cases in Manaus, northern Brazil, analyzed at different time points (according to days of rash report). Detections in sweat at two distinct time points were reported for five participants: (participant IDs 6, 25, 27, 34, and 37). A single participant was defined as asymptomatic household contact (participant 12 - asterisk). Blue dots - ZIKV detection in sweat. Gray dots - detection at other body fluid (blood, urine, or semen, not specified on the figure) according to days post rash.

Fig. 2: (A) Zika virus (ZIKV) RNA detection by real time reverse transcriptase polymerase chain reaction (rRT-PCR) according to the days of symptoms onset (days post rash report - “x” axis), Cycle threshold (Ct) rRT-PCR value (“y”axis) and body fluid specimen (urine, plasma and sweat) (figure legend colors). (inset) Median Ct value from 46 participants with positive rRT-PCR result in urine, plasma, and sweat body fluid specimens. Cut-off values were set above Ct 38 on rRT-PCR result. Ct - cycle threshold. NS: not significant; ***p < 0.001 analyzed by One-way ANOVA. (B) ZIKV RNA concomitant detection according to the body fluid specimen analyzed. rRT-PCR concomitant detection (“y” axis) refers to an individual positive detection on that specimens from the same participant (as specified on figure legend) according to its study number identification.

TABLE Participants characteristics and clinical data reported at screening visit (defined as rash presentation or Zika virus (ZIKV) initial positive detection for household/sexual asymptomatic subjects). Clinical data was collected at outpatients study clinic, only those participants with a positive detection at sweat are presented

Participants	Total 46	Age (mean ± SD)
Male	16	30 (± 10.9)
Female	30	43 (± 12.2)
Symptoms reported at screening visit
Rash		97.8% (45/46)
Fever		84.7% (39/46)
Itchiness		91.3% (42/46)
Conjunctival hyperemia		78.2% (36/46)
Arthralgia		80.4% (37/46)
Periarticular edema		67.4% (31/46)

SD: standard deviation.

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Instituto Oswaldo Cruz, Ministério da Saúde Av. Brasil, 4365 - Pavilhão Mourisco, Manguinhos, 21040-900 Rio de Janeiro RJ Brazil, Tel.: (55 21) 2562-1222, Fax: (55 21) 2562 1220 - Rio de Janeiro - RJ - Brazil
E-mail: memorias@fiocruz.br

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Zika virus RNA excretion in sweat with concomitant detection in other body fluid specimens

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[1] + Corresponding author: rafael.franca@cpqam.fiocruz.br