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Revising rates of asymptomatic Zika virus infection based on sentinel surveillance data from French Overseas Territories

Open AccessPublished:October 25, 2017DOI:https://doi.org/10.1016/j.ijid.2017.10.009

      Highlights

      • Asymptomatic Zika virus infections have been overestimated.
      • Surveillance data confirm the results from seroprevalence studies.
      • The use of easy-to-implement surveys to estimate ZIKV circulation during outbreaks is proposed.

      Abstract

      French Polynesia and the French Territories of the Americas (FTAs) have experienced outbreaks of Zika virus (ZIKV) infection. These territories used similar sentinel syndromic surveillance to follow the epidemics. However, the surveillance system only takes into account consulting patients diagnosed with ZIKV disease, while non-consulting cases, as well as asymptomatic cases, are not taken into account. In the French territories under study, the ratio of consulting to non-consulting patients was found to likely be as low as 1/3 to 1/4, and rough estimates of the ZIKV asymptomatic infections indicated a lower rate than previously reported (i.e., not more than half).

      Keywords

      Introduction

      The first documented outbreak of Zika virus (ZIKV), a mosquito-borne flavivirus associated with neurological complications (
      • Cao-Lormeau Van-Mai
      • Blake Alexandre
      • Mons Sandrine
      • Lastère Stéphane
      • Roche Claudine
      • Vanhomwegen Jessica
      • et al.
      Guillain-Barrè Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study.
      ,
      • de Araújo Thalia Velho Barreto
      • Rodrigues Laura Cunha
      • de Alencar Ximenes Ricardo Arraes
      • de Barros Miranda-Filho Demócrito
      • Montarroyos Ulisses Ramos
      • de Melo Ana Paula Lopes
      • et al.
      Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study.
      ), was reported in 2007. This outbreak involved 70% of the population (5300 individuals) of Yap islands, in the Federated States of Micronesia (
      • Duffy Mark R.
      • Chen Tai-Ho
      • Hancock W. Thane
      • Powers Ann M.
      • Kool Jacob L.
      • Lanciotti Robert S.
      • et al.
      Zika virus outbreak on Yap Island, Federated States of Micronesia.
      ). In 2013–2014, French Polynesia experienced a larger Zika outbreak with an estimated 11.5% of the population (over 30 000 people) having consulted a doctor for suspected ZIKV infection (
      • Musso Didier
      • Gubler Duane J.
      Zika virus.
      ). In 2015–2016, ZIKV spread throughout the Americas and the Caribbean region (
      • World Health Organization
      Zika situation report.
      ).
      Based on data from the Yap outbreak, it was assumed that asymptomatic ZIKV infections account for 80% of the overall infections (
      • Duffy Mark R.
      • Chen Tai-Ho
      • Hancock W. Thane
      • Powers Ann M.
      • Kool Jacob L.
      • Lanciotti Robert S.
      • et al.
      Zika virus outbreak on Yap Island, Federated States of Micronesia.
      ). However, recently published serological data from French Polynesia and Martinique have estimated it to be less than half of the overall infections (
      • Aubry Maite
      • Teissier Anita
      • Huart Michael
      • Merceron Sébastien
      • Vanhomwegen Jessica
      • Roche Claudine
      • et al.
      Zika virus seroprevalence, French Polynesia, 2014-2015.
      ,
      • Gallian Pierre
      • Cabié André
      • Richard Pascale
      • Paturel Laure
      • Charrel Rémi N.
      • Pastorino Boris
      • et al.
      Zika virus in asymptomatic blood donors, Martinique: 2016.
      ). In this study, a rough estimate of the level of asymptomatic infections was performed using the sentinel syndromic surveillance data available from three comparable French Overseas Territories that experienced Zika outbreaks: French Polynesia, Martinique, and Guadeloupe.

      The study

      French Polynesia, Martinique, and Guadeloupe have comparable syndromic surveillance systems, which include a network of 35–55 general practitioners (GPs) or consultation sites reporting the number of patients that fit the case definition for a given syndrome on a weekly basis. During the Zika outbreaks, these sentinel networks were considered as representative of all private and public GP consultations in the three territories, as they provided 16–25% of the overall medical consultations in the community, with a regular geographic distribution (Table 1).
      Table 1Sentinel surveillance data to estimate ZIKV asymptomatic infection rates.
      French PolynesiaMartiniqueGuadeloupe (except North Islands)
      Number of inhabitants270 000

      (Tahiti: 180 000)
      390 000400 000
      Surface (km2)∼4200

      (Tahiti: ∼1000)
      ∼1100∼1600
      Date of emergence (first confirmed case)2013-412015-502016-02
      Dates of the outbreakOct 2013–Apr 2014Jan 2016–Oct 2016Apr 2016–Sept 2016
      Length of the outbreak (weeks)283522
      Peak week (from first confirmed case)91815
      Number of GPS or sites participating in the sentinel network during the outbreak455535
      SN representativeness (ratio of SN sites reported to total consultation sites)30%25%16%
      Total estimated number of symptomatic consulting cases32 00038 35030 560
      Consultation rate in the population11.5%9.8%7.6%
      Estimated ratio of consulting/non-consulting among symptomatic cases1:3 to 1:4
      Estimated attack rate of symptomatic cases in the population34–46%29–39%23–30%
      ZIKV overall attack rate from seroprevalence data49% (general population) (
      • Aubry Maite
      • Teissier Anita
      • Huart Michael
      • Merceron Sébastien
      • Vanhomwegen Jessica
      • Roche Claudine
      • et al.
      Zika virus seroprevalence, French Polynesia, 2014-2015.
      )
      42% (blood donors, in early June) (
      • Gallian Pierre
      • Cabié André
      • Richard Pascale
      • Paturel Laure
      • Charrel Rémi N.
      • Pastorino Boris
      • et al.
      Zika virus in asymptomatic blood donors, Martinique: 2016.
      )
      ND
      Highest estimate of ZIKV overall attack rate86% (
      • Kucharski Adam J.
      • Funk Sebastian
      • Eggo Rosalind M.
      • Mallet Henri-Pierre
      • Edmunds W. John
      • Nilles Eric J.
      Transmission dynamics of Zika virus in Island populations: a modelling analysis of the 2013-14 French Polynesia Outbreak.
      )
      NDND
      Estimated rate of asymptomatic cases3–51.5%3–57%ND
      ZIKV, Zika virus; GPS, global positioning system; SN, sentinel network; ND, not determined.
      Cases were reported according to local clinically suspected case definitions (
      • Daudens-Vaysse Elise
      • Ledrans Martine
      • Gay Noellie
      • Ardillon Vanessa
      • Cassadou Sylvie
      • Najioullah Fatiha
      • et al.
      Zika emergence in the French Territories of America and description of first confirmed cases of Zika virus infection on Martinique, November 2015 to February 2016.
      ,
      • Mallet H.P.
      • Vial A.L.
      • Musso D.
      Bilan de l’épidémie à virus Zika survenue en Polynésie française entre octobre 2013 et mars 2014. De la description de l’épidémie aux connaissances acquises après l’évènement.
      ). These case definitions, using a combination of a minimum of three symptoms, met those proposed by the European Centre for Disease Prevention and Control and the Pan-American Health Organization, and have proven to be fairly specific and sensitive (
      • Chow Angela
      • Ho Hanley
      • Win Mar-Kyaw
      • Leo Yee-Sin
      Assessing sensitivity and specificity of surveillance case definitions for Zika virus disease.
      ). Consultations in emergency structures (hospitals and mobile emergency services) were accounted for in the global surveillance network in French Polynesia, in Martinique, and in Guadeloupe. The total number of clinically suspected cases for the whole country was estimated by summation of these sources and extrapolation. This surveillance system was implemented to monitor the space–time evolution of the epidemic, but in the case of ZIKV, it failed to estimate the total number of infected people. As ZIKV infection mostly causes a mild illness, a significant proportion of infected people may not consult a GP. Furthermore, many cases are asymptomatic.
      During the Zika outbreaks, the total estimated proportion of individuals who sought medical care with symptoms compatible with ZIKV infection in the three French Territories ranged from 7.6% to 11.5% of the overall population (Table 1). Based on the ZIKV serosurvey conducted in French Polynesia (
      • Aubry Maite
      • Teissier Anita
      • Huart Michael
      • Merceron Sébastien
      • Vanhomwegen Jessica
      • Roche Claudine
      • et al.
      Zika virus seroprevalence, French Polynesia, 2014-2015.
      ), a blood donor study in Martinique (
      • Gallian Pierre
      • Cabié André
      • Richard Pascale
      • Paturel Laure
      • Charrel Rémi N.
      • Pastorino Boris
      • et al.
      Zika virus in asymptomatic blood donors, Martinique: 2016.
      ), and data from a cross-sectional survey conducted in Guadeloupe (Table 2), the estimated ratio of consulting to non-consulting symptomatic suspected cases was found to be in the range of 1:3 to 1:4. Information from the survey in Guadeloupe, which used quota sampling, was gathered through telephone-based interviews of a sample of 501 individuals aged >15 years. The questionnaire was mainly focused on knowledge of the disease and reported infectious episodes, including specific symptoms (
      • IPSOS Antilles
      Study on the impact of prevention communication and information about Zika.
      ). The resulting attack rates of symptomatic ZIKV infection ranged from 23% to 46% (Table 1). Using available estimates of ZIKV overall attack rates from (1) seroprevalence studies (
      • Aubry Maite
      • Teissier Anita
      • Huart Michael
      • Merceron Sébastien
      • Vanhomwegen Jessica
      • Roche Claudine
      • et al.
      Zika virus seroprevalence, French Polynesia, 2014-2015.
      ,
      • Gallian Pierre
      • Cabié André
      • Richard Pascale
      • Paturel Laure
      • Charrel Rémi N.
      • Pastorino Boris
      • et al.
      Zika virus in asymptomatic blood donors, Martinique: 2016.
      ), and (2) a modeling study in French Polynesia (
      • Kucharski Adam J.
      • Funk Sebastian
      • Eggo Rosalind M.
      • Mallet Henri-Pierre
      • Edmunds W. John
      • Nilles Eric J.
      Transmission dynamics of Zika virus in Island populations: a modelling analysis of the 2013-14 French Polynesia Outbreak.
      ), it was found that surveillance data indicated asymptomatic infection rates not exceeding half of the overall infections.
      Table 2Estimate of consultation rates from a cross-sectional study based on telephone interviews with individuals aged >15 years (n = 501) recruited by quota sampling at the end of the Zika outbreak—Guadeloupe, October 2016.
      Data courtesy of IPSOS Antilles. For details (in French): http://www.ireps.gp/data/IMG/Rapport_Impact_Comm_Zika_ARS_Mai_2016.pdf.
      Percentage
      ZIKV reported symptoms
       Yes (consulted a GP)31 (9)
       No69
      Consultation rate of symptomatic cases29
      ZIKV, Zika virus; GP, general practitioner.
      a Data courtesy of IPSOS Antilles. For details (in French): http://www.ireps.gp/data/IMG/Rapport_Impact_Comm_Zika_ARS_Mai_2016.pdf.

      Discussion

      The estimated ZIKV asymptomatic infection rates reported here are lower than that found during the 2007 Yap outbreak. This inconsistency with the data from Yap may be due to the limited sample representativeness of the Yap study (
      • Duffy Mark R.
      • Chen Tai-Ho
      • Hancock W. Thane
      • Powers Ann M.
      • Kool Jacob L.
      • Lanciotti Robert S.
      • et al.
      Zika virus outbreak on Yap Island, Federated States of Micronesia.
      ). Alternatively, unknown risk factors, such as environmental or individual conditions, may have affected the ZIKV asymptomatic rate.
      Taking into consideration the underlying assumptions and limitations, the estimated asymptomatic case rates from sentinel surveillance data reported here, which are compatible with those from seroprevalence studies (
      • Aubry Maite
      • Teissier Anita
      • Huart Michael
      • Merceron Sébastien
      • Vanhomwegen Jessica
      • Roche Claudine
      • et al.
      Zika virus seroprevalence, French Polynesia, 2014-2015.
      ,
      • Gallian Pierre
      • Cabié André
      • Richard Pascale
      • Paturel Laure
      • Charrel Rémi N.
      • Pastorino Boris
      • et al.
      Zika virus in asymptomatic blood donors, Martinique: 2016.
      ), are important in order to improve surveillance systems: they give a more realistic idea of the true number of susceptible individuals throughout the outbreak, because they consider individuals who have experienced asymptomatic infection as immunized. Together with the estimate of the outbreak-specific consultation rate, the new ZIKV asymptomatic infection rate allows a rough prediction of the overall intensity of ZIKV circulation. This is particularly important on islands, where attack rates often reach high percentages (
      • Aubry Maite
      • Teissier Anita
      • Huart Michael
      • Merceron Sébastien
      • Vanhomwegen Jessica
      • Roche Claudine
      • et al.
      Zika virus seroprevalence, French Polynesia, 2014-2015.
      ).
      Zika outbreak surveillance should be improved by implementing simple cost-effective surveys during outbreaks to assess the outbreak-specific consultation rate and the asymptomatic infection rate, in order to obtain a less error-prone estimate of viral circulation. The first could be estimated using telephone-based interviews and the second by analyzing blood donor samples. Ideally, to be confident that estimates are not biased, a population-based survey using probability sampling rather than quota sampling should be performed. However, such surveys are often difficult to implement during outbreaks as they are costly and time-consuming. Standardized protocols should be available to allow the rapid implementation of these surveys in any country or territory where ZIKV is likely to (re-)emerge.
      In conclusion, the ZIKV asymptomatic infection rate should be taken into account to estimate the level of ZIKV circulation in a country or territory. Determining viral circulation is, in turn, essential to guide public health action. Past reference studies may have overestimated the true ZIKV asymptomatic infection rate, which in the present study settings, corresponds to, at most, half of the infected people.

      Conflict of interest

      None declared

      Acknowledgements

      We thank IPSOS Antilles for sharing data.

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