**1. Introduction**

116 Current Topics in Tropical Medicine

Although all animals develop strong humoral responses, antibodies appear more rapidly in survivors and are directed against GP(1), GP(2), and NP. Activated T lymphocytes circulate

A single injection of ML29 reassortant vaccine for **Lassa fever** induces **low**, transient viremia, and **low** or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cellmediated immunity. DNA array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ML29 revealed that gene expression patterns in ML29 exposed PBMC and **control**, media-exposed PBMC, clustered together confirming safety profile of the ML29 in non-human primates. The ML29 reassortant is a promising vaccine

Baize S, Marianneau P, Loth P, et al. Early and strong immune responses are associated with

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Donaldson, Ross I. (2009). The Lassa Ward:One Man's Fight Against One of the World's Deadliest Diseases. St. Martin's Press. ISBN 0312377002. ISBN 978-0312377007. Frame JD, Baldwin JM, Gocke DJ, Troup JM. Lassa fever, a new virus disease of man from

Granjon, L., Lavrenchenko, L., Corti, M., Coetzee, N. & Rahman, E.A. Mastomys natalensis.

Inegbenebor, U, Okosun, J, Inegbenebor, J. Prevention of Lassa fever in Nigeria. Trans R. Soc

Lukashevich IS, Carrion R, Salvato MS, et al. Safety, immunogenicity, and efficacy of the

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in survivors, whereas T-cell activation is **low** and delayed in fatalities

candidate for **Lassa fever**.

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**10. References** 

Until recently, very few physicians in industrialized countries had heard the word "Chikungunya", and fewer knew how to spell it. Chikungunya, a viral infection transmitted by mosquitoes, derives its name from Makonde, a language spoken in south Tanzania, and means "that which bends up", referring to the posture of patients afflicted with severe joint paints characterizing this infection. Chikungunya virus (CHIKV) was first isolated in Tanzania in 1952 (Robinson, 1955) and has come to the world attention recently, when it caused a massive outbreak in the Indian Ocean region and India (Enserik, 2006). Since 1952, CHIKV has caused a number of epidemics, both in Africa and Southeast Asia, many of them having involved hundreds-of-thousands people. In 2005 the largest Chikungunya fever epidemic on record occurred. The most affected region was La Reunion Island, where CHIKV infected more than a third of the population and killed hundred of people. The 2005/2006 outbreak, started from Comoro Islands, rapidly spread to several countries in the Indian Ocean and India (Enserik, 2006; Mavalankar et al., 2007). Compared to earlier outbreaks, this episode was massive, occurred in highly medicalized areas such as La Reunion, and had very significant economic and social impact. More than 1000 imported CHIKV cases have been detected among European and American travellers returning from the affected areas since the beginning of the outbreak in the Indian Ocean region (Fusco et al., 2006; Taubiz et al., 2007), giving rise, in 2007, to the first autochthonous European outbreak in Italy (Charrel & de Lambellerie, 2008; Rezza et al., 2007). Since 2006, the Regional Office of the French Institute For Public Health Surveillance in the Indian Ocean has conducted epidemiological and biological surveillance for CHIKV infection. During the period December 2006-july 2009, no confirmed case was detected on Reunion Island and Mayotte, but new outbreak were reported in Madacascar. After few years of relative dormancy in Réunion Island, CHIKV transmission has restarted in 2009 and 2010, with one case imported in France (May 2010) (D'Ortenzio et al., 2010). This episode has refreshed the concerns about the possibility of renewed autochthonous transmission in Mediterranean countries.

<sup>\*</sup> Meschi Silvia1, Selleri Marina1, Lalle Eleonora1, Castilletti Concetta1, Carletti Fabrizio2, Di Caro Antonino2 and Capobianchi Maria Rosaria1

<sup>1</sup>*Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy* 

*<sup>2</sup>Laboratory of Microbiology and Infectious Disease Biorepository, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy*

The Re-Emergence of an Old Disease: Chikungunya Fever 119

they can become perfect "incubators" for mosquito eggs, where the ideal conditions of

Human beings serve as the Chikungunya virus reservoir during epidemic periods. In Africa some animals (monkeys, rodents, and birds) constitute the virus reservoir during not-epidemic periods, sustaining virus circulation in the environment in the absence of human cases. Outbreaks might occur in monkeys when herd immunity is low; the animals develop viraemia but no pronounced physical manifestations (Inoue et al., 2003; Wolfe et al., 2001). An animal

After infection with Chikungunya virus, there is a silent incubation period lasting 2–4 days on average (range 1–12 days) (Lam et al., 2001). Clinical onset is abrupt, with high fever, headache, back pain, myalgia, and arthralgia; the latter can be intense, affecting mainly the extremities (ankles, wrists, phalanges) but also the large joints (Hochedez et al., 2006; Lam et al., 2001; Quatresous, 2006; Robinson, 1955; Saxena et al., 2006). Skin involvement present in about 40–50% of cases, and consists of (1) a pruriginous maculopapular rash predominating on the thorax, (2) facial oedema, or (3) in children, a bullous rash with pronounced sloughing, and (4) localised petechiae and gingivorrhagia (mainly in children) (Brighton et al., 1983; Fourie & Morrison, 1979). Radiological findings are normal, and biological markers of inflammation (erythrocyte sedimentation rate and C-reactive protein) are normal or moderately elevated (Fourie & Morrison, 1979; Kennedy et al., 1980). Iridocyclitis and retinitis are the most common ocular manifestations associated with Chikungunya fever; less frequent ocular lesions include episcleritis. All ocular manifestations have a benign course with complete resolution and preservation of vision. Retinitis shows gradual resolution over a period of 6 to 8 weeks (Mahendradas et al., 2008). CHIKV infection seems to elicit long-lasting protective immunity, and experiments performed using animal models have shown a partial cross-protection among CHIKV and other alphaviruses (Edelman et

Erratic, relapsing, and incapacitating arthralgia is the hallmark of Chikungunya, although it rarely affects children. These manifestations are normally migratory and involve small joints of hands, wrists, ankles, and feet with pain on movement. Symptoms generally resolve within 7–10 days, except for joint stiffness and pain: up to 12% of patients still have chronic arthralgia three years after onset of the illness. Arthralgia experienced by CHIKF patients closely resembles the symptoms induced by other viruses like Ross River Virus (RRV) and Barmah Forest virus (BFV) (Jacups et al, 2008; Mahalingam et al., 2002). Such alphavirusinduced arthralgia mirrors rheumatoid arthritis, a condition which is characterised by severe joint pains due to inflammation and tissue destruction caused by inflammatory cytokines such as IL-1b, IL-6 and TNF-a (Barksby et al., 2007). It is thus plausible that CHIKV infection induces similar pro-inflammatory cytokines that cause arthralgia, explaining why joint pains are constant ailments of many patients infected with CHIKV even years after recovery from the initial febrile phase (Lakshmi et al., 2008). More recently, global analyses on the specific involvement of cytokines and chemokines have showed that IL-1b, IL-6, and RANTES were associated with disease severity (Ng et al.,

reservoir has not been identified in Asia, where humans appear to be the only host.

temperature and humidity are achieved easily and naturally.

**4. Clinical manifestation** 

al., 2000; Hearn Jr. & Rainey, 1963).

**4.2 Arthralgia** 

**4.1 General features** 
