Open Journal Systems

PubMed: http://www.ncbi.nlm.nih.gov/pubmed/25760749

CURRENT ISSUES

Received: October 2^nd 2014

Accepted: October 9^th 2014

Situational panorama of Mexico against the chikungunya virus pandemic

Abisai Martínez-Sánchez,^a Ericay Berenice Martínez-Ramos,^a Manuel Gerardo Chávez-Angeles^b

^aInstituto de Investigación sobre la Salud Pública, Universidad de la Sierra Sur, Miahuatlán de Porfirio Díaz, Oaxaca, México

^bDivisión de estudios de postgrado, Universidad de la Sierra Sur, Miahuatlán de Porfirio Díaz, Oaxaca, México

Comunicación con: Abisai Martínez-SánchezCommunication with: Abisai Martínez-Sánchez

Telephone: (951) 212 0407

Email: abisai01@hotmail.com

Recent outbreaks of emerging diseases emphasize the vulnerability of health systems, as is the the case of chikungunya fever. The wide geographical incidence of the virus in the last years requires alerting systems for the prevention, diagnosis, control and eradication of the disease. Given the ecological, epidemiological and socio-economic characteristic of Mexico, this disease affects directly or indirectly the health of the population and development of agricultural, livestock, industrial, fishing, oil and tourism activities in the country. Due to this situation it is essential to make a brief analysis on the main clinical data, epidemiological and preventive measures with which our country counts with to confront the situation.

Keywords: Chikungunya virus; Emerging diseases; Disease prevention.

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The chikungunya virus (CHIKV) was first described in 1952 during an outbreak in Africa, in a village of the Makonde tribe between Tanzania and Mozambique. The name chikungunya (pronounced/chi kun gu nya /) means disease of the twisted man, because of the strong joint pain causes arthritis and that characterizes the disease.¹

The virus is endemic in Africa, Oceania, and Southeast Asia. In 2006, according to the Centers for Disease Control and Prevention² (CDC), countries in that region had 1.25 million infected people. Since that date, the disease has spread to Europe with imported cases. Subsequently, the first infected patients in the Americas occurred in December 2013 on the island of St. Martin and later cases of indigenous transmission were reported in the Caribbean. So far the Pan American Health Organization³ has reported 580,526 suspected cases, of which 5272 have been confirmed by laboratory tests in 18 countries of the region. The countries with the highest incidence rate are: Guadalupe (15,976), Martinique (14,216.6), San Martin (13,037.3), St. Barthelemy (11,258.4), and Dominica (5068). People’s concern about the possible spread of the virus in countries where the disease is endemic causes annual economic losses of 160 million dollars.⁴

Recently in Mexico, the Sistema Nacional de Vigilancia Epidemiológica (SINAVE) confirmed the first case of a patient with chikungunya fever in Jalisco, imported by attending a sporting event in the Caribbean;⁵ given the eco-epidemiological conditions and the distribution of vectors, the virus spreading to other countries is only a matter of time, especially considering that the attack rates in communities affected by recent outbreaks ranged from 38-63%. It should also be noted that between 3-28% of the population have asymptomatic infections, which contribute significantly to the spread of the disease.^6,7

Characteristics of the virus

The virus belongs to the genus Alphavirus of the family Togaviridae with a genome with single-stranded ribonucleic acid (RNA) of positive polarity of 12,017 bp length.⁸ Given the taxonomy, it shares many genetic traits with the dengue virus (DENV) and even share the same vectors, i.e. natural infection is caused by mosquitoes of the species Aedes aegypti and Aedes albopictus, but it has its own infectivity characteristics, clinical presentation, diagnosis, and treatment.

The capsid is oyster-shaped and has two viral glycoproteins, E1 (50 kd) and E2 (45 kd), of great importance for the recognition of the cell.⁹ The entrance of the viral particle to the host cell is mediated by a protein known as Fuzzy Counterpart (FUZ), which has roles in cell polarity and cilia biogenesis required for internalization of clathrin and a membrane protein tetraspanin (TSPAN9), both of which are critical for the efficient fusion of the virus with the membrane the endosoma.¹⁰ Moreover, the expulsion of viral particles after replication happens through a budding process through the cell membrane, in which the synthesis of four non-structural proteins known as nsP1-4 is essential.

There is evidence that the virus genome has a high mutation rate, especially in specific amino acids in the viral proteins nsP1, nsP3, nsP4, E1, and E2. However, ultrastructural changes induced by viruses in infected cells remain highly conserved between different strains of CHIKV.¹¹ This finding suggests that the virus-cell interaction depends largely on the host’s receiving proteins, the species of the virus, and the evolutionary lineage.

Of equal importance is co-infection between DENV and CHIKV. In recent years coinfection with different serotypes of DENV and CHIKV in patients in Asia, Africa, and most recently Europe, has been demonstrated through clinical and phylogenetic data from partial genomic sequences amplified by RT-PCR.^12,13

Pathophysiology

CHIKV transmission, beyond just happening through the bite of the vector, can also take place by transplacental means, from viremic mother to newborn during childbirth, and it is even suspected that it can cause abortions if it occurs during the first trimester of pregnancy; if it occurs in later stages, the baby does not acquire immunity through the mother nor is there evidence of transfer in breast milk. Similarly, the infection can occur through blood transfusions and organ or tissue transplant, as well as laboratory accidents or injuries from needles with fluids of infected patients in the early days of symptom onset.^4,14

Viral transmission to the mosquito happens through an infected host and later spreads to the epithelial cells of the midgut of the mosquito, to then disperse through the base membrane into the circulation and infect the salivary glands, which establishes viral replication in about 10 days, so that from that date the vector can infect a susceptible host. When the female insect feeds, it secretes saliva containing the pathogen which enters the blood of the host. At this time the virus circulates in the plasma and contacts susceptible cells, such as capillary endothelial cells, macrophages, monocytes, and others from the mononuclear phagocytic system.²

The antibodies that are produced during primary infection are directed towards specific antigenic determinants of the virus, most of which are of the IgM class, but when the formation of the antigen-antibody complex is induced in secondary infection, this process facilitates infection of new mononuclear cells, therefore, infected monocytes become the target of immune mechanisms and upon attack they release chemical mediators that increase capillary permeability, activate the complement, release thromboplastin, and together provoke the pathophysiological changes of the disease itself. Once in circulation, the virus could replicate itself in other cells such as bone marrow, liver, and lymphoid tissue.¹⁵ It is worth mentioning that all individuals previously uninfected with CHIKV, i.e. immunologically virgin individuals, are at risk for infection and developing the disease. It is believed that once exposed to CHIKV, individuals develop lasting immunity that protects against reinfection.¹⁶

The clinical picture appears three to seven days after the bite of an infected mosquito and often includes severe, often disabling, joint pain in the feet and hands, along with high fever, headache, and muscle pain, as well as joint swelling or rash that can persist for a long time, but without jeopardizing the life of the infected individual, as most patients will improve within a week. The main difference between dengue and chikungunya fever is that the latter has a joint condition. Given the symptoms, those at highest risk of serious illness are newborns exposed to the virus, people over 65, and those with chronic conditions such as high blood pressure, diabetes, or heart disease.¹⁷ People with these characteristics should avoid traveling to areas with active outbreaks and, if they are sick, should prevent mosquitoes from biting them to prevent the spread of the virus. As with DENV, clinical manifestations depend on the host’s nutritional status, sex, race, age, and immunological state.¹⁵

Prevention and control measures

So far there is no vaccine or specific antiviral that eliminates or reduces the infection of this virus, so management is exclusively symptomatic. Using painkillers is recommend to reduce pain and swelling, but the use of aspirin should be avoided as it can aggravate symptoms.¹⁸ With this perspective it is imperative to reinforce epidemiological surveillance, especially in prevention and control measures aimed at minimizing exposure to infected mosquitoes, and the timely detection of cases, to guarantee a quick and appropriate response and to prevent the occurrence and spread of outbreaks.

The distribution of the transmitters is associated with ecosystems with tropical climate and rainy seasons. Human activity such as urbanization in endemic areas of mosquito breeding sites, and poor access to water sources that force inhabitants to save the liquid in containers and other inadequately covered objects exposed to the elements, favor the reproduction of these insects.¹⁹ Another important consideration is climate change; the adaptation of species transmitting pathogens to new human systems favors the spread and thus the risk of acquiring infection. 

Although the main reservoir agent of the virus is the human itself, it is suggested that zoonotic transmission between different animal species such as cattle, monkeys, rodents, squirrels, and even birds maintains the cycle of the disease in the jungle.²⁰

Status of control and prevention of CHIKV cases in Mexico

In Mexico, the surveillance system for diseases transmitted by vectors²¹ provides special studies of disease outbreaks, as in the case of entomological studies. In the first instance, in the case of dengue as well as chikungunya fever which share the same vector, a strict inventory must be done of the distribution of the species to understand the biology and behavior of the mosquitoes in areas of transmission or risk. The main entomological indicators are the larval index of homes and/or containers, that is, the proportion of houses and/or containers with positive breeding areas compared with houses and/or containers examined; Breteau larval index, which considers the proportion of positive deposits in relation to houses explored; and bite index, which considers the number of mosquitoes caught for hours in relation to human exposure to the insect. Vector control is essential for disease prevention, especially if we consider that our country ranks fifth for incidence of dengue in Latin America²² with periodic outbreaks of DENV in the states of Chiapas, Oaxaca, Quintana Roo, Campeche, Veracruz, and Jalisco. From this perspective, it is advisable to assess the efficacy of insecticides used (optimal doses, residual, etc.) and estimate population densities and crowding in their immature and adult stages in different seasons. Therefore, it is essential to have close communication with federal authorities through the Laboratorio de Entomología of the Instituto de Diagnóstico y Referencia Epidemiológica to confirm the taxonomy and evaluate the behavior of the specimens collected to predict the migration of species and anticipate possible outbreaks. 

According to the recommendations of the World Health Organization,²³ to avoid bites from mosquitoes, it is necessary to eliminate breeding sites, which often tend to be the recipients of stagnant water that accumulate in the home and work environment. Therefore, it is essential to train staff and organize health programs and the community to carry out the cleaning of rivers and streams, remove obstacles that may create backwaters, and eliminate artificial pools and any other type of vegetation in the localities where mosquitos reproduce, thus eliminating the conditions under which insect larvae proliferate. These actions should be taken at least once a month throughout the year. Moreover, it is suggested to wear clothes that cover the maximum possible area of ​​skin, and use mosquito repellents or, failing that, mosquito nets. 

The diagnosis of this disease is related to the DENV monitoring platform because the clinical manifestations are very similar, that is, in the first place one must consider history of residence or origin in endemic areas, or lacking that, family, community, or work contact with other suspected or confirmed cases; so it is important to inquire about people close to the patient presenting with fever and joint pain. A suspected case should be understood as "a patient with onset of acute fever above 38.5 ° C and severe arthralgia or arthritis not explained by other medical conditions, who resides in or has visited epidemic or endemic areas in the two weeks prior to onset of symptoms".^6,14

To confirm cases, CHIKV detection is done by chain reaction of reverse transcriptase polymerase (RT-PCR). This technique uses different primers and probes used by the CDC in Atlanta and the Pasteur Institute, but it is recommended to standardize and validate these diagnostic tools for local use. Moreover, the determination of IgM may be done by different commercially available techniques (ELISA or IFA). However, it should be considered that the best sensitivity is given by those using whole virus antigen rather than those using recombinant proteins or peptides. Case confirmation must be within 1 or 2 weeks after the first sample and will be given by seroconversion (IgM/IgG) or fourfold or more increase in neutralizing antibody titer.⁶

Laboratories must take into account that since the CHIKV is emerging in the region of the Americas, in addition to its potential infectivity, virus isolation must be done in BSL-3 biosafety conditions.²⁴ Where laboratories do not have the resources and tools for diagnosis, the sample must be sent to the laboratory of reference or PAHO/WHO collaborating center with dry ice or cooling gels during the first 48 hours, always accompanied by its corresponding clinical-epidemiological profile completely filled out.¹⁴

Another important consideration for diagnosis is to rule out dengue in all cases, as well as other possible diseases such as leptospirosis, malaria, exanthematous childhood diseases, HIV primary infection, infectious mononucleosis, juvenile rheumatoid arthritis, and post-infectious arthritis.² When the diagnosis is confirmed, daily laboratory and imaging studies should be done to monitor hemoconcentration, thrombocytopenia, and pleural effusion or ascites. 

According to the Norma para la Vigilancia Epidemiológica,²⁵ control of transmission must be done jointly by the main actors involved in the interruption of disease: health staff, the community, and the authorities.

On the one hand, personnel from the services of the Sistema Nacional de Salud should receive initial training and practice in both health promotion in communities, and in the search for suspected cases by notice and home inspection; similarly, once trained, staff must be able to make the confirmation of clinical diagnosis and laboratory testing, as well as providing timely treatment to minimize the risk of infection for the population and, finally, implementing measures against the vectors. This training should be performed annually, and staff should be trained and evaluated to guide future decisions, whether to maintain or modify actions.

Moreover, the community should be informed about the importance of the disease, its transmission mechanism, and ways to prevent and control it. It is necessary also to orient and train the population in ways to care for their own health. It is also necessary to promote the improvement of housing and basic sanitation, so that community participation is oriented to monitoring the habitat and preventing population contact with the risks for the presence of this virus. Finally, the authorities should be responsible for making decisions and designing control programs that have interdisciplinary participation and collaboration at all levels of government and health, education, environment, social development, and tourism agencies, and encouraging the active participation of individuals and organized groups to facilitate and support surveillance, prevention, and control activities, so as to ensure that the community achieves a culture of individual and family self-care for good health.   

Finally, in the field of research, studies are needed to provide basic and operational information on epidemiological, entomological, and mammalogical aspects as well as in administrative and socio-economic areas, with particular emphasis on risk factors and the evaluation of control and prevention programs. In this sense, some projects that should be addressed immediately are those concerning the behavior of the transmitting species and their reservoirs, in order to predict possible outbreaks in our country, and those that address the symbiotic relationship between DENV and CHIKV to forecast possible mutations, as well as research related to the genome of the virus to ensure the development of accurate and rapid diagnostic tests, alternatives for treatment and prevention through vaccines, and studies related to host genetic factors that condition symptoms, and therefore, the severity of the disease, as well as projects to evaluate prevention programs in accordance with the socio-cultural context of communities to ensure their effectiveness.

To do research according to the country's needs, it is essential to have highly trained human resources in both technical and ethical aspects who accept the necessary commitments to address such contingencies. Similarly, there is a need for the creation of new research centers throughout the country that have innovative tools that facilitate the development and transfer of technology, and that at the same time provide the authorities with accurate and timely information on the epidemiological development, to support them in making decisions to prevent the spread of disease to other areas of risk.

Conclusion

Given the geographical position of Mexico and the trade reflected in the phenomenon of migration to other countries in the area, as well as the presence of mosquitoes involved in CHIKV transmission, the presence of indigenous cases of infection is inevitable. Because of the similarity with DENV virus, the epidemiological surveillance system accordingly has basic programs and resources for prevention of this pathogen. However, the magnitude and seriousness of this global contingency, in terms of extent and infected cases in a relatively short time, entails that the authorities should strengthen control measures in coordination with interdisciplinary institutions, health personnel, and the community to prevent the spread of this virus in our country.  

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