Trans R Soc Trop Med Hyg 2014; 108: 57–59 doi:10.1093/trstmh/trt110 Advance Access publication 18 December 2013
SHORT COMMUNICATION
Dengue outbreaks: a constant risk for Reunion Island. Results from a seroprevalence study among blood donors Sophie Larrieua,*, Alain Michaultb, Dominique Polycarpec, Franc¸ois Schoonemand, Eric D’Ortenzioa and Laurent Filleula a
*Corresponding author: Tel: +262 262 93 94 58; Fax: +262 262 93 94 57; E-mail: [email protected]
Received 30 August 2013; revised 12 November 2013; accepted 15 November 2013 Background: Immunity against dengue virus (DENV) on Reunion Island could play an important role in the risk of dengue outbreaks but is rather unknown. A study was performed to estimate seroprevalence of antibodies against DENV among blood donors. Methods: An age- and sex-stratified sample of 1825 sera was randomly selected. Results: Overall seroprevalence was 3.1% (95% CI: 2.2–3.9%); seroprevalence increased with age and was much higher in women than in men. Conclusion: The low level of herd immunity is consistent with the absence of an endemic circulation of DENV, and makes it probable that Reunion Island will face future outbreaks. Keywords: Dengue, Outbreaks, Reunion Island, Risk, Seroprevalence
Introduction Reunion Island is a French overseas territory with a population of 840 000 inhabitants located in the South West Indian Ocean, 700 km east of Madagascar. Since the island was hit by the largest chikungunya outbreak ever described,1 arbovirus surveillance and control have become a major public health priority for local authorities. Two dengue outbreaks have also been documented: in 1977–78 with 30% of the population affected, and in 2004 with 228 cases.2 Between these outbreaks, no autochthonous transmission of dengue virus was reported; and since 2004, only sporadic transmission has been detected despite the implementation of an active surveillance system.2 Several factors raise the likelihood of future outbreaks. First, regular arrivals of travellers from dengue endemic areas, particularly from Asia, Pacific islands and the Americas, lead to a constant risk of importation of different serotypes of dengue virus (DENV). Then, Aedes albopictus is present year-round in all densely populated areas of the island and can ensure a rapid dissemination of the virus. Although it is generally considered as less competent than Ae. aegypti for DENV transmission, this vector was responsible for the 1977 and 2004 outbreaks in Reunion Island and other epidemics all over the world.3,4 Due to global
warming, its density could increase during the next few years, and invasion by other mosquito species, such as Aedes aegypti, could also arise. The third factor required in order to assess the risk for major DENV epidemics for the next few years remains unknown, namely immunity of the population. The population growth in Reunion Island, with a high birth rate and constant arrivals of non-immune migrants, increases the risk of future outbreaks. A study was therefore undertaken to estimate the prevalence of antibodies against DENV in a population of blood donors living in Reunion Island.
Materials and methods A seroprevalence study was performed on sera from volunteer blood donors who came to the E´tablissement Franc¸ais du Sang of Reunion Island in 2008 and gave their written consent to participate to research studies. A sex- and age-stratified sample was randomly selected in order to obtain accurate estimations in the different groups. Overall seroprevalence was estimated using the sampling weights so that the estimates are representative of the blood donor population. Dengue IgG were detected by ELISA as originally established by the French National Reference Center for Arboviruses (Paris,
# The Author 2013. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: [email protected].
57
Downloaded from http://trstmh.oxfordjournals.org/ at University of Utah on December 1, 2014
Cire oce´an Indien (Cire OI), Institut de Veille Sanitaire (InVS), 97400 Saint Denis, Re´union, France; bLaboratoire de Bacte´riologieParasitologie-Virologie-Hygie`ne, Centre Hospitalier Universitaire (CHU), 97410 Saint Pierre, Re´union, France; cAgence de Sante´ Oce´an Indien (ARS OI), 97400 Saint Denis, Re´union, France; dEtablissement Franc¸ais du Sang (EFS) de la Re´union, 97400 Saint Denis, Re´union, France
S. Larrieu et al.
France). The technique was automated in an ETIMax 3000 apparatus (DiaSorin, Rome, Italy). Optical density thresholds for the interpretation of results were calculated from a series of 30 negative sera. All statistical analyses were done by using Stata version 11 (StataCorp LP, College Station, TX, USA).
Results and Discussion
Table 1. Number of subjects included in the sample and seroprevalence per age and sex Men, n¼895
Women, n¼930
Total, n¼1825
Age n group, years
Positive (%) n
Positive (%) n
18–29 30–39 40–49 50–65 Total
0 (0) 1 (0.4) 1 (0.4) 5 (2.0) 7 (0.5)
5 (3.5) 2 (0.7) 20 (7.4) 38 (15.8) 65 (5.1)
137 256 256 246 895
143 275 272 240 930
Positive (%)
280 5 (2.0) 531 3 (0.6) 528 21 (4.3) 486 43 (8.8) 1825 72 (3.1)
Figure 1. Age- and sex-specific seroprevalence of anti-DENV IgG among blood donors from Reunion Island, 2008 (n¼1825).
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Downloaded from http://trstmh.oxfordjournals.org/ at University of Utah on December 1, 2014
A total of 1825 samples were included in the study, of which 895 (49.0%) from men and 930 (51.0%) from women. Table 1 gives the number of subjects included and the seroprevalence observed in each group of the sample. Overall weighted seroprevalence of DENV IgG antibodies among blood donors was 3.1% (95% CI: 2.2–3.9%). It was much higher in women (5.1%, 95% CI: 3.6–6.7%) than in men (0.5%, 95% CI: 0.2–0.8%) (p,0.0001), whatever the age group
(Figure 1). Age-specific seroprevalence tended to increase with age: the highest rate was observed among subjects 50–65 years old (8.8%, 95% CI: 6.7–10.8%); whereas it was very low in the youngest age groups (2.0%, 95% CI: 0.3–3.6% and 0.6%, 0.0–1.2% for the 18–29 and 30–39 years, respectively). Our study reveals that only a small minority of blood donors in Reunion Island has already been infected by DENV. Children and elderly people were not represented in our sample, and the proportion of young adults was higher than in the general adult population. Characteristics of blood donors in terms of origin and occupation might have some specificity, but were unknown and could not be explored. However, geographical distribution of our sample was close to that of the general population. Therefore, although our results cannot be directly extrapolated to the general population, they provide useful data on the immune status of the adult population, suggesting that it might be quite low. Furthermore, because of the constant risk of importation of different serotypes in the island, presence of DENV IgG antibodies does not mean that the population is protected against dengue virus; on the contrary, it could increase the likelihood of developing severe dengue if a heterotypic infection occurs.5 Seroprevalence may appear very low compared to the attack rate of 30% estimated in 1977–78. Indeed, as serum IgG after a DENV infection are probably detectable for life, all the subjects included in our study who were affected by that outbreak should still be seropositive. However, population turnover can totally explain this difference. Indeed, Reunion Island population increased 70% between the two periods, with increasing arrivals from continental France which has never been affected by an active arbovirus circulation despite the recent occurrence of autochthonous cases of dengue and chikungunya. The increase of seroprevalence with age is consistent with the absence of endemic circulation of DENV in the island, as suggested by the absence of cases detected by the surveillance system (except for short periods of time when some cases were detected). The
Transactions of the Royal Society of Tropical Medicine and Hygiene
higher seroprevalence among women has previously been reported by others,4,6 and women were also more affected by the chikungunya outbreak that occurred in Reunion Island.1 This difference could be explained by a greater exposure to the vector because of home and gardening activities, or differences between clothing, leading to a greater exposure of the skin in women.
Acknowledgements: Alfred Rochefeuille, Pascal Vilain, Benjamin Larras for their help in blood samples handling; Jimmy Gigan for biological analyses; The Etablissement Franc¸ais du sang for the partnership. Funding: This work was supported by the Agence de Sante´ Oce´an Indien (ARS OI). Competing interests: None declared.
Conclusions
Authors’ contributions: SL, EDO and LF conceived the study, designed the study protocol and carried out the statistical analyses; AM carried out biological analyses; SL and AM drafted the first version of the manuscript; all authors contributed in interpretation of the data, critically revised the manuscript for intellectual content and approved the final manuscript. SL and LF are guarantors of the paper.
Ethical approval: Not required.
References 1 Renault P, Solet JL, Sissoko D et al. A major epidemic of chikungunya virus infection on Reunion Island, France, 2005–2006. Am J Trop Med Hyg 2007;77:727–31. 2 Larrieu S, Dehecq JS, Balleydier E et al. Re-emergence of dengue in Reunion, France, January to April 2012. Euro Surveill 2012;17:20173. 3 Effler PV, Pang L, Kitsutani P et al. Dengue fever, Hawaii, 2001–2002. Emerg Infect Dis 2005;11:742–9. 4 Xu G, Dong H, Shi N et al. An outbreak of dengue virus serotype 1 infection in Cixi, Ningbo, People’s Republic of China, 2004, associated with a traveler from Thailand and high density of Aedes albopictus. Am J Trop Med Hyg 2007;76:1182–8. 5 Zompi S, Montoya M, Pohl MO et al. Dominant cross-reactive B cell response during secondary acute dengue virus infection in humans. PLoS Negl Trop Dis 2012;6:e1568. 6 Allwinn R, Hofknecht N, Doerr HW. Dengue in travellers is still underestimated. Intervirology 2008;51:96–100.
59
Downloaded from http://trstmh.oxfordjournals.org/ at University of Utah on December 1, 2014
Together with the presence of a competent vector and regular connections with countries where dengue is endemo-epidemic with a circulation of various serotypes, in particular South-East Asia, the low level of herd immunity against dengue underlined by this study makes it probable that Reunion Island will face future outbreaks of dengue fever. Continuous epidemiologic surveillance is therefore essential to allow rapid case and cluster detection and to alert immediately public health authorities with the objective to prevent an outbreak by adequate control measures: environment and vector management, and communication towards health practitioners and the general population.
SHORT COMMUNICATION
Dengue outbreaks: a constant risk for Reunion Island. Results from a seroprevalence study among blood donors Sophie Larrieua,*, Alain Michaultb, Dominique Polycarpec, Franc¸ois Schoonemand, Eric D’Ortenzioa and Laurent Filleula a
*Corresponding author: Tel: +262 262 93 94 58; Fax: +262 262 93 94 57; E-mail: [email protected]
Received 30 August 2013; revised 12 November 2013; accepted 15 November 2013 Background: Immunity against dengue virus (DENV) on Reunion Island could play an important role in the risk of dengue outbreaks but is rather unknown. A study was performed to estimate seroprevalence of antibodies against DENV among blood donors. Methods: An age- and sex-stratified sample of 1825 sera was randomly selected. Results: Overall seroprevalence was 3.1% (95% CI: 2.2–3.9%); seroprevalence increased with age and was much higher in women than in men. Conclusion: The low level of herd immunity is consistent with the absence of an endemic circulation of DENV, and makes it probable that Reunion Island will face future outbreaks. Keywords: Dengue, Outbreaks, Reunion Island, Risk, Seroprevalence
Introduction Reunion Island is a French overseas territory with a population of 840 000 inhabitants located in the South West Indian Ocean, 700 km east of Madagascar. Since the island was hit by the largest chikungunya outbreak ever described,1 arbovirus surveillance and control have become a major public health priority for local authorities. Two dengue outbreaks have also been documented: in 1977–78 with 30% of the population affected, and in 2004 with 228 cases.2 Between these outbreaks, no autochthonous transmission of dengue virus was reported; and since 2004, only sporadic transmission has been detected despite the implementation of an active surveillance system.2 Several factors raise the likelihood of future outbreaks. First, regular arrivals of travellers from dengue endemic areas, particularly from Asia, Pacific islands and the Americas, lead to a constant risk of importation of different serotypes of dengue virus (DENV). Then, Aedes albopictus is present year-round in all densely populated areas of the island and can ensure a rapid dissemination of the virus. Although it is generally considered as less competent than Ae. aegypti for DENV transmission, this vector was responsible for the 1977 and 2004 outbreaks in Reunion Island and other epidemics all over the world.3,4 Due to global
warming, its density could increase during the next few years, and invasion by other mosquito species, such as Aedes aegypti, could also arise. The third factor required in order to assess the risk for major DENV epidemics for the next few years remains unknown, namely immunity of the population. The population growth in Reunion Island, with a high birth rate and constant arrivals of non-immune migrants, increases the risk of future outbreaks. A study was therefore undertaken to estimate the prevalence of antibodies against DENV in a population of blood donors living in Reunion Island.
Materials and methods A seroprevalence study was performed on sera from volunteer blood donors who came to the E´tablissement Franc¸ais du Sang of Reunion Island in 2008 and gave their written consent to participate to research studies. A sex- and age-stratified sample was randomly selected in order to obtain accurate estimations in the different groups. Overall seroprevalence was estimated using the sampling weights so that the estimates are representative of the blood donor population. Dengue IgG were detected by ELISA as originally established by the French National Reference Center for Arboviruses (Paris,
# The Author 2013. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: [email protected].
57
Downloaded from http://trstmh.oxfordjournals.org/ at University of Utah on December 1, 2014
Cire oce´an Indien (Cire OI), Institut de Veille Sanitaire (InVS), 97400 Saint Denis, Re´union, France; bLaboratoire de Bacte´riologieParasitologie-Virologie-Hygie`ne, Centre Hospitalier Universitaire (CHU), 97410 Saint Pierre, Re´union, France; cAgence de Sante´ Oce´an Indien (ARS OI), 97400 Saint Denis, Re´union, France; dEtablissement Franc¸ais du Sang (EFS) de la Re´union, 97400 Saint Denis, Re´union, France
S. Larrieu et al.
France). The technique was automated in an ETIMax 3000 apparatus (DiaSorin, Rome, Italy). Optical density thresholds for the interpretation of results were calculated from a series of 30 negative sera. All statistical analyses were done by using Stata version 11 (StataCorp LP, College Station, TX, USA).
Results and Discussion
Table 1. Number of subjects included in the sample and seroprevalence per age and sex Men, n¼895
Women, n¼930
Total, n¼1825
Age n group, years
Positive (%) n
Positive (%) n
18–29 30–39 40–49 50–65 Total
0 (0) 1 (0.4) 1 (0.4) 5 (2.0) 7 (0.5)
5 (3.5) 2 (0.7) 20 (7.4) 38 (15.8) 65 (5.1)
137 256 256 246 895
143 275 272 240 930
Positive (%)
280 5 (2.0) 531 3 (0.6) 528 21 (4.3) 486 43 (8.8) 1825 72 (3.1)
Figure 1. Age- and sex-specific seroprevalence of anti-DENV IgG among blood donors from Reunion Island, 2008 (n¼1825).
58
Downloaded from http://trstmh.oxfordjournals.org/ at University of Utah on December 1, 2014
A total of 1825 samples were included in the study, of which 895 (49.0%) from men and 930 (51.0%) from women. Table 1 gives the number of subjects included and the seroprevalence observed in each group of the sample. Overall weighted seroprevalence of DENV IgG antibodies among blood donors was 3.1% (95% CI: 2.2–3.9%). It was much higher in women (5.1%, 95% CI: 3.6–6.7%) than in men (0.5%, 95% CI: 0.2–0.8%) (p,0.0001), whatever the age group
(Figure 1). Age-specific seroprevalence tended to increase with age: the highest rate was observed among subjects 50–65 years old (8.8%, 95% CI: 6.7–10.8%); whereas it was very low in the youngest age groups (2.0%, 95% CI: 0.3–3.6% and 0.6%, 0.0–1.2% for the 18–29 and 30–39 years, respectively). Our study reveals that only a small minority of blood donors in Reunion Island has already been infected by DENV. Children and elderly people were not represented in our sample, and the proportion of young adults was higher than in the general adult population. Characteristics of blood donors in terms of origin and occupation might have some specificity, but were unknown and could not be explored. However, geographical distribution of our sample was close to that of the general population. Therefore, although our results cannot be directly extrapolated to the general population, they provide useful data on the immune status of the adult population, suggesting that it might be quite low. Furthermore, because of the constant risk of importation of different serotypes in the island, presence of DENV IgG antibodies does not mean that the population is protected against dengue virus; on the contrary, it could increase the likelihood of developing severe dengue if a heterotypic infection occurs.5 Seroprevalence may appear very low compared to the attack rate of 30% estimated in 1977–78. Indeed, as serum IgG after a DENV infection are probably detectable for life, all the subjects included in our study who were affected by that outbreak should still be seropositive. However, population turnover can totally explain this difference. Indeed, Reunion Island population increased 70% between the two periods, with increasing arrivals from continental France which has never been affected by an active arbovirus circulation despite the recent occurrence of autochthonous cases of dengue and chikungunya. The increase of seroprevalence with age is consistent with the absence of endemic circulation of DENV in the island, as suggested by the absence of cases detected by the surveillance system (except for short periods of time when some cases were detected). The
Transactions of the Royal Society of Tropical Medicine and Hygiene
higher seroprevalence among women has previously been reported by others,4,6 and women were also more affected by the chikungunya outbreak that occurred in Reunion Island.1 This difference could be explained by a greater exposure to the vector because of home and gardening activities, or differences between clothing, leading to a greater exposure of the skin in women.
Acknowledgements: Alfred Rochefeuille, Pascal Vilain, Benjamin Larras for their help in blood samples handling; Jimmy Gigan for biological analyses; The Etablissement Franc¸ais du sang for the partnership. Funding: This work was supported by the Agence de Sante´ Oce´an Indien (ARS OI). Competing interests: None declared.
Conclusions
Authors’ contributions: SL, EDO and LF conceived the study, designed the study protocol and carried out the statistical analyses; AM carried out biological analyses; SL and AM drafted the first version of the manuscript; all authors contributed in interpretation of the data, critically revised the manuscript for intellectual content and approved the final manuscript. SL and LF are guarantors of the paper.
Ethical approval: Not required.
References 1 Renault P, Solet JL, Sissoko D et al. A major epidemic of chikungunya virus infection on Reunion Island, France, 2005–2006. Am J Trop Med Hyg 2007;77:727–31. 2 Larrieu S, Dehecq JS, Balleydier E et al. Re-emergence of dengue in Reunion, France, January to April 2012. Euro Surveill 2012;17:20173. 3 Effler PV, Pang L, Kitsutani P et al. Dengue fever, Hawaii, 2001–2002. Emerg Infect Dis 2005;11:742–9. 4 Xu G, Dong H, Shi N et al. An outbreak of dengue virus serotype 1 infection in Cixi, Ningbo, People’s Republic of China, 2004, associated with a traveler from Thailand and high density of Aedes albopictus. Am J Trop Med Hyg 2007;76:1182–8. 5 Zompi S, Montoya M, Pohl MO et al. Dominant cross-reactive B cell response during secondary acute dengue virus infection in humans. PLoS Negl Trop Dis 2012;6:e1568. 6 Allwinn R, Hofknecht N, Doerr HW. Dengue in travellers is still underestimated. Intervirology 2008;51:96–100.
59
Downloaded from http://trstmh.oxfordjournals.org/ at University of Utah on December 1, 2014
Together with the presence of a competent vector and regular connections with countries where dengue is endemo-epidemic with a circulation of various serotypes, in particular South-East Asia, the low level of herd immunity against dengue underlined by this study makes it probable that Reunion Island will face future outbreaks of dengue fever. Continuous epidemiologic surveillance is therefore essential to allow rapid case and cluster detection and to alert immediately public health authorities with the objective to prevent an outbreak by adequate control measures: environment and vector management, and communication towards health practitioners and the general population.
