**4.3 Other pathologies**

Chikungunya is not generally considered to be a life-threatening disease. Usually the clinical course is fairly mild, but fatal cases directly or indirectly linked to infection with CHIKV have been observed during the Indian-Ocean outbreak (Josseran et al., 2006). The main evidence of a mortality linked to Chikungunya fever epidemics has been obtained in La Reunion, Mauritius, and India by comparing expected and observed mortality data. In all cases, during the months when the epidemics were raging, the observed mortality significantly exceeded the expected one. In particular, in La Reunion the monthly crude death rates in February and March 2006 were 34.4%and 25.2% higher, respectively, than expected. These corresponded to 260 excess deaths (an increase of 18.4%) with a rough estimate of the case-fatality rate for Chikungunya fever of ≈1/1,000 cases. The case-fatality rate calculated on increased crude death rates in Mauritius and Ahmedabad, India, is substantially higher than that calculated in La Reunion: approximately 4.5% (15,760 confirmed or suspected cases and 743 excess deaths) and 4,9% (60,777confirmed or suspected cases and 2,944 excess deaths), respectively (Beesoon et al., 2008; Mavalankar et al., 2008). These differences may be attributed to many factors (greater disease severity, preexisting patient conditions, different patient management, or coincident excess deaths from other causes) but may also be due to a different efficacy of the surveillance systems for Chikungunya fever, that probably worked poorly in Mauritius and India, leading to underestimating the total number of cases (Fusco et al., 2010). The possible link between CHIKV infection and multiorgan failure is still under investigation.

Neurological complications such as meningo-encephalitis were reported in a few patients during the first Indian outbreak in 1973, and during the 2006 Indian outbreak (Chatterjee et al., 1965; Ravi, 2006). The possible mechanisms underlying these processes remain unknown. Studies performed on animal models showed that CHIKV-infected young mice had weakness and walking difficulties which could be due to necrosis and inflammation of skeletal muscles (Ziegler et al., 2008). CHIKV antigens and viral replication have been detected in human myogenic precursors such as satellite cells but not in muscle fibers (Ozden et al., 2007), suggesting that muscle satellite cells could be potential virus reservoirs. The pathologic symptoms of encephalitis owing to CHIKV infection as well as central nervous system (CNS) infections (Chatterjee & Sarkar, 1965) were expected, since *in vitro* experiments showed that the virus could infect and replicate for extended periods in mouse brain cells (Precious et al., 1974). More recently, it was found that mouse CNS tissues such as the choroid plexi could also be targets of CHIKV, lending more credence to the fact that CHIKV infections do affect CNS cells and tissues (Couderc et al., 2008). Work is currently underway by several research groups around the world to decipher this mechanism in CHIKV infections. Moreover, during the 2006 Indian-Ocean outbreak, rare cases of Guillain-Barré syndrome (GBS) associated with CHIKV infection have been described (Lebrun et al., 2009; Wielanek et al., 2007).

Other rare complications described after CHIKV infection are mild hemorrhage, myocarditis, hepatitis (Lemant et al., 2008) .
