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CHIKUNGUNYA RE-EMERGES AS A GLOBAL HEALTH THREAT

Without a vaccine or medicine, infected travelers may be bringing this neglected tropical disease home

In 2014, a total of 2,788 travelers returning to the US, nearly all from the Caribbean and Latin America, were infected with the Chikungunya virus (Fig.1). International travel to disease endemic regions, the growing geographic distribution of the mosquito vectors, climate change, human demographics and behavior, agricultural and environmental pollution and the adaptation of the epidemic strain of the Chikungunya virus to the mosquito species Aedes albopictus have probably enabled the repeated emergence of Chikungunya epidemics. This article focuses on the growing global distribution of Chikungunya epidemics following early outbreaks, transmission patterns amid concomitant incidences of related viral diseases in the same location, disease patterns in different age groups and diagnostic issues, as well as the genotypes currently transmitted worldwide.

Figure 1: Countries and territories where Chikungunya cases have been reported (without imported cases, as of March 10, 2015, CDC)

Early Outbreaks

While dengue fever and yellow fever viruses have been re-emerging in many tropical areas since the 1980s, new epidemics have recently been caused by lesser-known arthropod-borne viruses (arboviruses): the Chikungunya virus since 2005, and the Zika virus since 2007. The Chikungunya and Zika viruses share common epidemiological features, such as transmission by the same vector, presence in the same environment, and observation by the same surveillance systems. Chikungunya, first identified and isolated in 1952-1953 during an outbreak along the border between Tanzania and Mozambique, is a Makonde name, meaning “that which bends up.”’ Numerous small outbreaks, originally noted in Africa, spread to Asia in the late 1950s and early 1960s, when massive outbreaks were observed in Thailand. Up to 31% of the population of Bangkok was infected during the 1962 outbreak. Outbreaks in India also were reported in the 1960s and 1970s. High attack rates were noted in Madras (40%) in 1962-1964 and in Barsi (37%) in 1973. Following these, outbreaks in India abruptly stopped, not to reoccur for the next 32 years. In 2006, the East Central South African (ECSA) genotyope caused an outbreak across India again. Another outbreak this year (2016) was found to be due to the same genotype and had caused 15 deaths up to October 1 from complications triggered by the disease.

Re-emergence of Current Epidemics

Since 2004, massive urban outbreaks have been reported again, causing morbidity in tropical and subtropical areas of Africa, Asia, Europe, the Pacific archipelago, and the Americas. Similar to trends in the 1960s and 1970s, outbreaks in India have moved from place to place for nearly a decade now, since 2006. According to a municipal report, 6,667 cases of Chikungunya had been reported in Delhi through September of this year. Of these, the total number of confirmed cases stands at 5,293. This is in sharp contrast to 2015, when only 64 cases of Chikungunya were reported in the city.

Transmission

In Africa, where the Chikungunya virus originated, the transmission cycle is sylvatic, occurring in or affecting wild animals, and completed by the mosquito vectors, Aedes aegypti and Aedes albopictus. While the transmission cycle may be maintained by animals such as monkeys during inter-epidemic periods, humans are the principal reservoirs during epidemics. As with the arboviruses dengue, yellow fever and Zika, humans complete the transmission cycle by infecting Aedes aegypti mosquitoes and causing outbreaks in urban areas. In Asia, previous outbreaks have occurred mostly in urban areas, with the continuous introduction of the virus in new areas and new naive human populations. There is evidence of a sylvatic transmission cycle also in Asia, and the involvement of both the vector species.

Comparing Chikungunya, Zika and Dengue Transmission in Same Locations

In French Polynesia, Zika virus outbreaks occurred from October 2013 to March 2014, followed a year later by Chikungunya outbreaks (October 2014 to March 2015). Overall, there were about 30,000 observed clinical cases of Zika and 69,000 of Chikungunya, corresponding to an observed cumulated incidence of 11% and 26%, respectively. In the French West Indies, Chikungunya virus outbreaks occurred first (between December 2013 and April 2015) and Zika virus outbreaks started in January 2016 and were still ongoing by August 2016. Overall, there were 159,000 clinical cases of Chikungunya and 62,000 of Zika through July 2016. The Chikungunya virus epidemic lasted 47 to 73 weeks, with an observed cumulated incidence between 15% and 20%.

A joint model of Chikungunya and Zika transmission, based on the time-dependent susceptible-infectious-recovered (TSIR) framework, studied the main factors impacting the spread of both the diseases. The relative transmissibility between the two viruses was 1.04, in favor of Zika, suggesting a small difference in transmission. The epidemic dynamics of the two viruses seemed to be controlled more by factors such as the denseness of mosquito presence, and local environmental, socio-economic and meteorological conditions, rather than the actual difference between the two viruses.

Similarly in India, dengue and Chikungunya virus infections are presently widespread diseases that call for close attention. Chikungunya causes high fever and joint pain, and while dengue symptoms are similar, the latter disease causes severe complications and sudden death from uncontrolled bleeding. The All India Institute of Medical Sciences (AIIMS) is treating 112 people for Chikungunya, 11 of whom have dengue as well. Reports claim that vector-borne diseases have claimed 40 lives in Delhi this year; 18 people have died of Chikungunya, 17 people have succumbed to dengue, while malaria has claimed another five lives. A total of 2,133 cases of dengue had been reported in the city up until October 1 this year. In all, 29 cases of malaria have surfaced so far this season. In 2015, Delhi saw the highest number of dengue cases in 20 years with 15,867 such cases being reported. As many as 60 people died due to this vector-borne disease last year.

Imported Disease

Imported Chikungunya virus cases have been reported in numerous non-endemic regions, including Japan, the USA, and Europe. The susceptibility of mosquitoes in non-endemic areas such as Australia and North America, and the occurrence of autochthonous outbreaks in Italy (2007) and France, confirm that the virus can no longer be considered as a problem of tropical countries. Following outbreaks in December 2013 in the Caribbean Islands, the Americas, and Micronesia, 1.7 million cases and 240 deaths were reported from 45 of the 53 countries/territories reporting to the Pan American Health Organization by September 2015.

Disease Burden by Age

Among adults, Chikungunya virus causes a fever-rash-painful-arthritis syndrome, with symptoms usually occurring in 72% to 97% of the infected patients. Congenital Chikungunya (mother-to-child Chikungunya virus infection) can occur with almost 50% surety, if the mother is infected with a high viral load during the early stages of labor. Unlike dengue infections, Chikungunya fever does not confer an increased risk for obstetric hemorrhage, preterm birth or low birth weight. Children born with low virus levels may show clinical disease (fever, pain, and suckling difficulties) within a week. Life-threatening complications such as Chikungunya virus-associated central nervous system disease (encephalopathy) or multiple organ dysfunction (MOD) may occur in about half of these newborns.

Among infants, up to 57% presented circulatory collapse and 80% febrile seizures, as reported in a study from Kerala, India. A separate series in the same state displayed symptoms of fever (100%), skin rash (100%), acrocyanosis (75%), diarrhea (41%), atypical febrile seizures (39%), irritability (26%), lethargy/poor feeding (21%), and limb edema (11%). Skin involvement included an abrupt onset of generalized erythematous rash (day 0 to 2 of fever), maculopapular rash (day 2 to 4), vesiculobullous lesions (day 3 to 6), peeling (day 6 to 10), and hypo- or hyperpigmentation (after day 10).

Older children present with fever as the main symptom, which is usually high grade, of sudden onset (within 24 hours) and single-spiked. In contrast to adults, arthritis is uncommon in children.

Diagnostic issues

The differential diagnosis of a febrile child or pregnant woman with recent travel to or residency in tropical areas affected by the Chikungunya virus can include malaria, dengue, influenza, hepatitis, typhoid fever, leptospirosis, and rickettsial infections. Moreover in regions with both Zika and Chikungunya transmission, only 20% of all Zika cases end up being reported (vs. 40% of Chikungunya cases), given the high asymptomatic rates of Zika virus infections (around 80%) compared to Chikungunya virus infections (around 30%), as reported in serological studies in Yap Island and French Polynesia.

Figure 2: Control measures to prevent Chikungunya virus infections.

Genotypes

Chikungunya is a positive-sense, single-stranded RNA virus that originated from Africa and was subsequently introduced to Asia. Three chikungunya viral genotypes are recognized: West African genotype, ECSA genotype, and Asian genotype. Both ECSA and Asian genotype viruses, sometimes together, have been responsible for the epidemics, depending on location. Mutations in the envelope glycoproteins E1 and E2 led to increased infectivity and dissemination of CHIKV in Ae. albopictus. The ECSA virus containing the E1: A226V mutation spread from La Reunion Island to India by 2006, where more than 1 million cases were reported in the first year alone. Activity in India still continues almost a decade later. From India, the Indian Ocean lineage strain spread to Southeast Asia and to northern Italy.

The Asian genotype has spread throughout the Pacific in recent years. The Asian genotype subsequently was noted during outbreaks in the following locations: Papua New Guinea (2012); Yap Island, Federated States of Micronesia (2013); Tonga, Samoa, American Samoa, Tokelau, French Polynesia (2014); and Kiribati and the Cook Islands (2015).

Conclusions

The current outbreak of Chikungunya virus infection in (South) Delhi is claiming lives. In an environment where parallel infections with other arboviruses are not uncommon, the identification of the genotype responsible, together with healthcare utilization, can help to decrease the morbidity associated with this virus infection (Fig.2.). Chikungunya virus infections are said to confer lifelong immunity, although some patients do not recover well and will perform at 60% of their capacity for months or even years. What separates chikungunya from other viral illnesses is the acute pain in joints. "We have seen youngsters coming in wheelchairs as they can't take the joint pain. Chikungunya may not be deadly, but it is definitely debilitating," Personnel attending to the infected patients (assistants and nurses) need to take precautions against getting infected themselves. South Delhi might become the first-ever megapolis hit by a Chikungunya outbreak, which in itself poses questions as to the potential sylvatic nature of the ESCA genotype, as well as the growing mosquito population in the city. While it is not a life-threatening disease, complications may prove fatal, especially in children and the elderly, therefore strict measures for control and treatment are imperative.

Review the excerpted Chikungunya virus disease summary here for further detail, and learn more about the Incidence & Prevalence Database from Clarivate Analytics.