- Email: [email protected]
Clinical burden of chikungunya virus infection
Reflection and Reaction
Clinical burden of chikungunya virus infection In their update on chikungunya virus infection, Gilles Pialoux and colleagues1 described most clinical manifestations of this two-stage disease. We would like to refine this description by reporting our experience with chikungunya among French soldiers and travellers infected during the 2005–06 outbreak in Réunion (southwest Indian Ocean). Our data highlight the severity of the disease and its effect on quality of life in endemic areas. To determine the clinical impact of chikungunya virus infection in the 757 military policemen on duty on the island, the French Forces Institute of Tropical Medicine undertook a retrospective cohort study in June, 2006. Each volunteer self-completed a detailed questionnaire and provided blood samples for detection of IgM and IgG anti-chikungunya virus antibodies using in-house IgM antibody capture ELISA and IgG capture assays.2 The 662 responders (87·5%) were mostly men (94·7%), with a median age of 40 years (range 19–55 years). Of the 662 responders, 158 (23·9%) self-reported having symptoms that were clinically compatible with
Head 74% Neck 49% Shoulders 61% Arms 42% Elbows 38% Forearms 46%
Chest 12% Back 42% Abdomen 18% Loins 52%
Wrists 74% Hips 29% Fingers and palms 76% Thighs 34%
Knees 58% Legs 50% Ankles 68% Heels 34% Feet 68%
Figure: Frequency of pain by location during acute stage of chikungunya infection Frequencies greater than 66% in bold type.
2
chikungunya fever between January, 2005, and June, 2006. Sex and age were not related to illness. IgM and IgG anti-chikungunya virus antibodies were present in 9·5% and 18·0% of the tested policemen, respectively. Global seroprevalence (ie, positivity for IgM or IgG, or both) in June, 2006 was 19·3%. In our study, the incidence of asymptomatic infections (ie, seropositivity without self-reported illness) was only 3·2%, consistent with other studies.3 The estimated incidence of clinically compatible cases seems very close to the real incidence of chikungunya virus infections based on serology. In terms of public health, the threat of a new outbreak in Réunion, where two-thirds of the population is not infected4 and considered susceptible to the virus, still exists. Our study also contributes to a better description of chikungunya virus features in previously healthy adults. Fever during the acute stage was observed in 86·5% of the self-reported cases (median duration 3 days [range 1–10 days]; mean maximum temperature 39·6°C [SD 0·7°C]), and a rash was documented in 54·4% of cases. Most patients had severe pain in multiple sites (especially in limb extremities) with headache (figure). Moreover, 44·8% of the respondents reported swollen articulations. These self-reported data on acute and disabling chikungunya virus-related polyarthritis are consistent with other medical reports and the description made by Pialoux and colleagues.1,5–8 Haemorrhagic signs were rare in our cohort: 4·1% of cases described spontaneous haematoma and 2·6% minor bleedings (epistaxis and gingival bleedings). The questionnaire did not correlate symptoms with peripheral vascular disorders, such as Raynaud’s phenomenon, which we first described in about 20% of chikungunya virus-infected travellers within the second and third months post-infection.8 The impact of chikungunya virus infection on quality of life during the acute stage was also evaluated by the patients. Tiredness was assessed as totally disabling in 37·2%, very important or important in 47·3%, quite or less important in 15·5%, and missing in 0%. Psychological outlook was also examined: 4·6% declared having been totally depressed, 35·5% were demoralised, 47·4% were morally weakened, and only 12·5% felt normal. http://infection.thelancet.com Vol 8 January 2008
Reflection and Reaction
Most symptomatic patients (93·7%) complained of a chronic stage of the disease, which is characterised by pains in joints or bones, or both, although the inquiry was made 6 months after the epidemic peak. This persisting pain was continuous (41·3%) or discontinuous with alternation of clinical remission and so-called relapses (58·7%). Some infected individuals (11·7%) also mentioned fever at this stage (mean maximum temperature 38·7°C [SD 0·7°C]). The effect of the chronic stage on quality of life was pronounced, since tiredness was self-assessed as totally disabling in 4·6%, very important or important in 42·8%, quite or less important in 50·4%, and missing in 2·3%, while mood was described as totally depressed in 2·0%, demoralised in 37·8%, weakened in 43·9%, and normal in 16·2%. This study clearly demonstrates the severity of clinical symptoms during each stage of chikungunya virus infection. Most working adults are disabled with loss of mobility, hand handicap, and depressive reaction, which can each last for weeks to months. Clinical impact is much more severe in older adults, progressively leading to complete loss of autonomy, health status deterioration, and sometimes death in debilitated or
elderly people.1 Thus, by contrast with dengue fever, chikungunya virus fever is responsible for long-lasting consequences in health, social organisation, and economy in epidemic areas. *Benjamin Queyriaux, Fabrice Simon, Marc Grandadam, Rémy Michel, Hugues Tolou, Jean-Paul Boutin French Forces Institute of Tropical Medicine, Le Pharo, BP 46, 13998 Marseille armées, France [email protected] We declare that we have no conflicts of interest. 1 2 3 4
5 6 7 8
Pialoux G, Gaüzère BA, Jauréguiberry S, Strobel M. Chikungunya, an epidemic arbovirosis. Lancet Infect Dis 2007; 7: 319–27. Peyrefitte CN, Pastorino BA, Bessaud M, et al. Dengue type 3 virus, Saint Martin, 2003–2004. Emerg Infect Dis 2005; 11: 757–61. Boutin JP. Chikungunya fever in La Réunion Island, 2006. Med Trop (Mars) 2006; 66: 221–25 (in French). Institut de Veille Sanitaire. Chikungunya in the world. Situation on September 3, 2007 (in French). http://www.invs.sante.fr/surveillance/ chikungunya (accessed Dec 4, 2007). Lam SK, Chua KB, Hooi PS, et al. Chikungunya infection, an emerging disease in Malaysia. Southeast Asian J Trop Med Public Health 2001; 32: 447–51. Mackenzie JS, Chua KB, Daniels PW, et al. Emerging viral diseases of southeast Asia and the western Pacific. Emerg Infect Dis 2001; 7: 497–504. Hochedez P, Jauréguiberry S, Debruyne M, et al. Chikungunya infection in travelers. Emerg Infect Dis 2006; 12: 1565–67. Simon F, Parola P, Grandadam M, et al. Chikungunya infection, an emerging rheumatism among travellers returned from southwestern Indian Ocean: report of 47 cases. Medicine 2007; 86: 123–37.
Chikungunya and respiratory viral infections An estimated 1·4–6·5 million cases of chikungunya occurred in India during 2006–07, following the outbreak in Réunion,1,2 the largest outbreak reported in the past 43 years with around 2000 cases confirmed by diagnosis.3,4 The outbreak of chikungunya in Pondicherry, south India, occurred from March, 2006, through January, 2007. The epidemic was characterised by a sudden rise in the number of cases in the second half of 2006, along with reported respiratory symptoms, leading to a suspicion that airborne respiratory infections might have been present simultaneously. Spread of infection was rapid, unlike the spread of a vector-borne infection, which is generally gradual. Therefore, we investigated suspected chikungunya cases for co-infection with respiratory viral infections in addition to confirming the suspected outbreak of chikungunya. Blood samples were collected from 110 suspected chikungunya cases from the Pondicherry and Karaikal regions, India. RNA was extracted from serum samples http://infection.thelancet.com Vol 8 January 2008
using the QIAamp Viral RNA Mini Kit (Qiagen, Germany), according to manufacturer’s instructions. One-step RT-PCR was used to amplify the E2 gene fragment of 427 bp from RNA, a diagnostic test for chikungunya virus. The amplicon was sequenced in an automated genetic analyser (ABI 3130xl Genetic Analyzer, Applied Biosystems, Foster City, CA, USA), and the nucleotide sequence was found to be similar to that of the Réunion strain. We also investigated the same serum samples for respiratory syncytial virus (RSV), influenza A and B viruses, and adenoviruses by specific IgM capture ELISA assays (DRG Instruments, Germany), according to the manufacturer’s instructions. Infection with dengue virus was also assessed by IgM capture ELISA (Nova Tech, Germany). Among the 110 patients with suspected chikungunya, 69 (63%) were positive for chikungunya virus (figure). Of the confirmed cases, 60 (87%) were co-infected with RSV (some also positive for other viral infections), 3
Clinical burden of chikungunya virus infection In their update on chikungunya virus infection, Gilles Pialoux and colleagues1 described most clinical manifestations of this two-stage disease. We would like to refine this description by reporting our experience with chikungunya among French soldiers and travellers infected during the 2005–06 outbreak in Réunion (southwest Indian Ocean). Our data highlight the severity of the disease and its effect on quality of life in endemic areas. To determine the clinical impact of chikungunya virus infection in the 757 military policemen on duty on the island, the French Forces Institute of Tropical Medicine undertook a retrospective cohort study in June, 2006. Each volunteer self-completed a detailed questionnaire and provided blood samples for detection of IgM and IgG anti-chikungunya virus antibodies using in-house IgM antibody capture ELISA and IgG capture assays.2 The 662 responders (87·5%) were mostly men (94·7%), with a median age of 40 years (range 19–55 years). Of the 662 responders, 158 (23·9%) self-reported having symptoms that were clinically compatible with
Head 74% Neck 49% Shoulders 61% Arms 42% Elbows 38% Forearms 46%
Chest 12% Back 42% Abdomen 18% Loins 52%
Wrists 74% Hips 29% Fingers and palms 76% Thighs 34%
Knees 58% Legs 50% Ankles 68% Heels 34% Feet 68%
Figure: Frequency of pain by location during acute stage of chikungunya infection Frequencies greater than 66% in bold type.
2
chikungunya fever between January, 2005, and June, 2006. Sex and age were not related to illness. IgM and IgG anti-chikungunya virus antibodies were present in 9·5% and 18·0% of the tested policemen, respectively. Global seroprevalence (ie, positivity for IgM or IgG, or both) in June, 2006 was 19·3%. In our study, the incidence of asymptomatic infections (ie, seropositivity without self-reported illness) was only 3·2%, consistent with other studies.3 The estimated incidence of clinically compatible cases seems very close to the real incidence of chikungunya virus infections based on serology. In terms of public health, the threat of a new outbreak in Réunion, where two-thirds of the population is not infected4 and considered susceptible to the virus, still exists. Our study also contributes to a better description of chikungunya virus features in previously healthy adults. Fever during the acute stage was observed in 86·5% of the self-reported cases (median duration 3 days [range 1–10 days]; mean maximum temperature 39·6°C [SD 0·7°C]), and a rash was documented in 54·4% of cases. Most patients had severe pain in multiple sites (especially in limb extremities) with headache (figure). Moreover, 44·8% of the respondents reported swollen articulations. These self-reported data on acute and disabling chikungunya virus-related polyarthritis are consistent with other medical reports and the description made by Pialoux and colleagues.1,5–8 Haemorrhagic signs were rare in our cohort: 4·1% of cases described spontaneous haematoma and 2·6% minor bleedings (epistaxis and gingival bleedings). The questionnaire did not correlate symptoms with peripheral vascular disorders, such as Raynaud’s phenomenon, which we first described in about 20% of chikungunya virus-infected travellers within the second and third months post-infection.8 The impact of chikungunya virus infection on quality of life during the acute stage was also evaluated by the patients. Tiredness was assessed as totally disabling in 37·2%, very important or important in 47·3%, quite or less important in 15·5%, and missing in 0%. Psychological outlook was also examined: 4·6% declared having been totally depressed, 35·5% were demoralised, 47·4% were morally weakened, and only 12·5% felt normal. http://infection.thelancet.com Vol 8 January 2008
Reflection and Reaction
Most symptomatic patients (93·7%) complained of a chronic stage of the disease, which is characterised by pains in joints or bones, or both, although the inquiry was made 6 months after the epidemic peak. This persisting pain was continuous (41·3%) or discontinuous with alternation of clinical remission and so-called relapses (58·7%). Some infected individuals (11·7%) also mentioned fever at this stage (mean maximum temperature 38·7°C [SD 0·7°C]). The effect of the chronic stage on quality of life was pronounced, since tiredness was self-assessed as totally disabling in 4·6%, very important or important in 42·8%, quite or less important in 50·4%, and missing in 2·3%, while mood was described as totally depressed in 2·0%, demoralised in 37·8%, weakened in 43·9%, and normal in 16·2%. This study clearly demonstrates the severity of clinical symptoms during each stage of chikungunya virus infection. Most working adults are disabled with loss of mobility, hand handicap, and depressive reaction, which can each last for weeks to months. Clinical impact is much more severe in older adults, progressively leading to complete loss of autonomy, health status deterioration, and sometimes death in debilitated or
elderly people.1 Thus, by contrast with dengue fever, chikungunya virus fever is responsible for long-lasting consequences in health, social organisation, and economy in epidemic areas. *Benjamin Queyriaux, Fabrice Simon, Marc Grandadam, Rémy Michel, Hugues Tolou, Jean-Paul Boutin French Forces Institute of Tropical Medicine, Le Pharo, BP 46, 13998 Marseille armées, France [email protected] We declare that we have no conflicts of interest. 1 2 3 4
5 6 7 8
Pialoux G, Gaüzère BA, Jauréguiberry S, Strobel M. Chikungunya, an epidemic arbovirosis. Lancet Infect Dis 2007; 7: 319–27. Peyrefitte CN, Pastorino BA, Bessaud M, et al. Dengue type 3 virus, Saint Martin, 2003–2004. Emerg Infect Dis 2005; 11: 757–61. Boutin JP. Chikungunya fever in La Réunion Island, 2006. Med Trop (Mars) 2006; 66: 221–25 (in French). Institut de Veille Sanitaire. Chikungunya in the world. Situation on September 3, 2007 (in French). http://www.invs.sante.fr/surveillance/ chikungunya (accessed Dec 4, 2007). Lam SK, Chua KB, Hooi PS, et al. Chikungunya infection, an emerging disease in Malaysia. Southeast Asian J Trop Med Public Health 2001; 32: 447–51. Mackenzie JS, Chua KB, Daniels PW, et al. Emerging viral diseases of southeast Asia and the western Pacific. Emerg Infect Dis 2001; 7: 497–504. Hochedez P, Jauréguiberry S, Debruyne M, et al. Chikungunya infection in travelers. Emerg Infect Dis 2006; 12: 1565–67. Simon F, Parola P, Grandadam M, et al. Chikungunya infection, an emerging rheumatism among travellers returned from southwestern Indian Ocean: report of 47 cases. Medicine 2007; 86: 123–37.
Chikungunya and respiratory viral infections An estimated 1·4–6·5 million cases of chikungunya occurred in India during 2006–07, following the outbreak in Réunion,1,2 the largest outbreak reported in the past 43 years with around 2000 cases confirmed by diagnosis.3,4 The outbreak of chikungunya in Pondicherry, south India, occurred from March, 2006, through January, 2007. The epidemic was characterised by a sudden rise in the number of cases in the second half of 2006, along with reported respiratory symptoms, leading to a suspicion that airborne respiratory infections might have been present simultaneously. Spread of infection was rapid, unlike the spread of a vector-borne infection, which is generally gradual. Therefore, we investigated suspected chikungunya cases for co-infection with respiratory viral infections in addition to confirming the suspected outbreak of chikungunya. Blood samples were collected from 110 suspected chikungunya cases from the Pondicherry and Karaikal regions, India. RNA was extracted from serum samples http://infection.thelancet.com Vol 8 January 2008
using the QIAamp Viral RNA Mini Kit (Qiagen, Germany), according to manufacturer’s instructions. One-step RT-PCR was used to amplify the E2 gene fragment of 427 bp from RNA, a diagnostic test for chikungunya virus. The amplicon was sequenced in an automated genetic analyser (ABI 3130xl Genetic Analyzer, Applied Biosystems, Foster City, CA, USA), and the nucleotide sequence was found to be similar to that of the Réunion strain. We also investigated the same serum samples for respiratory syncytial virus (RSV), influenza A and B viruses, and adenoviruses by specific IgM capture ELISA assays (DRG Instruments, Germany), according to the manufacturer’s instructions. Infection with dengue virus was also assessed by IgM capture ELISA (Nova Tech, Germany). Among the 110 patients with suspected chikungunya, 69 (63%) were positive for chikungunya virus (figure). Of the confirmed cases, 60 (87%) were co-infected with RSV (some also positive for other viral infections), 3