by Osvaldo Tegllia

Introduction

Annually, millions of people cross oceans and continents in search of tourist destinations and, in a globalized world, many others do so for business reasons. The current means of transport allow them to move massively and quickly, connecting extreme points of the Earth in less time than necessary for the incubation of an infectious disease (Table 1).

The geographical characteristics of a certain region, such as humidity, temperature, rainfall, vegetation, latitude and height, determine many of the communicable diseases, since all of them can favor or hinder and even prevent the development of vectors and reservoirs of certain entities, determining the geographical distribution of the pathologies (Figure 1).

Although this chapter has as its primary objective the prevention of diseases through vaccines in the departing traveler, it is necessary to remember that professional practice can put the doctor in front of a traveler who returns and becomes ill. People living in countries with adequate sanitary conditions are destined for others with opposite situations, such as poor sewage services or the provision of safe water. Many are exposed to non-existent diseases at their sites of origin and therefore most likely have no prior immunity. Endemic infections acquired in tropical countries, which a traveler may manifest months after their return and are exotic in their country of origin, They can cause a delay in diagnosis and condition a poor prognosis for your health, putting your life at risk, such as malaria, and sometimes they pose a serious public health problem, as occurs in hemorrhagic fevers. International travelers can literally become importers of exotic diseases. As defined, imported diseases are infectious diseases that are acquired in a country where they are more or less frequent and are diagnosed in another country where they do not exist or are very rare. Despite being an apparently clear definition, it is sometimes difficult to decide what these diseases are. The three most frequent reasons for consultation in travelers who acquire an infectious disease are: diarrhea, fever and skin disease. The exercise of diagnosing a disease outside its borders is sometimes a challenge for the doctor. Incorporating into the interrogation of a patient with suspected infectious symptoms, aspects related to recent trips should be a systematic practice (Table 2). The affirmative answer forces the inclusion of an imported disease in the list of diagnostic possibilities.

The analysis of the traveler's health conditions, their immunization status, the destination or destinations and the nature of the trip, determine the risk of exposure to diseases. Thus, a traveler for business reasons, whose stays are brief and practically without exposure to wild environments, usually constitutes an example of what could be called low risk of acquiring an imported disease, with the exception of those with interhuman transmission (influenza , respiratory syndrome, severe acute - SARS) that can even be acquired before reaching the destination, in waiting rooms of transport terminals or transport booths. In opposition to this, a trip whose nature is adventure tourism or missions, peace or military bodies results in a high exposure to the environment, contact with the sick, crowded communities, animals and vectors, so clearly the risk of disease acquisition is high. As an example, the incidence of hepatitis A, an immuno-preventable disease, in travelers to endemic areas is 7 times higher when comparing adventure tourism (2000 cases / 100,000 travelers / month of stay) with classic tourism (300 cases / 100,000 travelers / month of stay). A specialized evaluation through a prevention program tailored to each traveler can avoid serious problems during and after the trip. An instrument for the prevention of undoubted advantages is that of immunizations. These may become required for entry into a country when local health authorities consider it essential. No less important is that, sometimes, some simple tips related to eating habits, personal hygiene,

The doctor must analyze the health situation of the destination of his patient. There are endemic conditions that can be maintained stable over time, allowing for planning early prevention strategies, but epidemic changes or outbreaks may occur that require adjustment to what has already been planned. Computer resources and internet access facilitate this task. Useful information can be found on the pages of the World Health Organization (http://www.who.ch) or the Centers for Diseases Control (http://www.cdc.gov).

General

Within the context of Traveler Medicine, vaccines can be classified into three categories:

1. Usual: are those that are part of the official vaccination schedule for adults and children in each country. Some within this group are diphtheria, tetanus and pertussis, triple viral, hepatitis A and B, among others.
2. Required or compulsory: they are those that may be legally required by some countries for the entry of travelers to their territory. Some examples are yellow fever, meningococcal vaccination (pilgrims to Mecca), measles (according to epidemiological situation, presence of recent outbreak).
3. Recommended: they are those vaccines that travelers should be advised about the diseases to which they may be exposed. Within this group are hepatitis A and B, typhoid fever, cholera, meningococcus, rabies, polio, among others.

Specific vaccines for the traveler

Hepatitis A

It is the most frequent vaccine-preventable disease in travelers. Produced by a virus of the Picornaviridae family, which is transmitted mainly by the faecal-oral route. The incidence is subject to the sanitary conditions of the place of origin and / or destination of the traveler, adherence to dietary hygiene measures, length of stay and previous immunization. The seroprevalence of hepatitis A in a population is linked to the health level of the place of residence (Figure 2). A better sanitary conditions, lower prevalence in the population and therefore a higher proportion of susceptible people (example: Northern European countries). When a resident of regions with low seroprevalence (natural susceptibles) moves to countries with high prevalence (and therefore high exposure), they have a high risk of acquiring hepatitis A if they are not previously immunized. Immunity to hepatitis A can be passive (gamma globulins) or active (vaccines). The protection offered by gamma globulins is short-lived and vaccines for life. Gamma globulins provide immediate protection, come from a pool of human plasma donors and are administered at the rate of 0.02 ml / kg of weight intramuscularly. An additional advantage is that they can also be used as post-exposure prophylaxis (up to 2 weeks later). The inactivated whole virus vaccine offers high protection (95%) within two weeks of the first dose. It is administered, intramuscularly, over one year of age and a booster dose should be applied between 6 and 18 months later. They should not receive vaccinated pregnant women or lactating women. There is a commercial form of hepatitis A vaccine that combines protection against hepatitis B and is administered in a three-dose schedule (0, 1 and 6 months) intramuscularly in the deltoid region.

Hepatitis B

Hepatitis B, produced by the only member of the Hepadnaviridae family, is a worldwide disease with great socio-sanitary repercussion, whose only reservoir is the sick man or carrier. Several hundred million people in the world are carriers of the hepatitis B virus and the distribution of them is not homogeneous, highlighting some regions with high prevalence (Figure 3). The acquisition of hepatitis B by travelers is closely linked to the sexual behavior that they maintain. It is estimated that between 5 and 20% of travelers have sexual contact abroad and of them, half with more than one partner. The vaccines currently available for hepatitis B are effective and safe. The protection offered to adults with a complete scheme is of the order of 85 to 90%. The classic scheme includes three doses (0.1 and 6 months) administered intramuscularly in the deltoid region. Protection is now known to extend for no less than 20 years in primary responders, and some experts find it unnecessary to add further reinforcements. It is useful to insist that there is a combined formulation of hepatitis A virus plus B commercially available.

Typhoid fever

It is a potentially serious systemic disease caused by Salmonella typhi. The risk of acquiring typhoid fever has been estimated at 30 cases per million travelers, and mortality is low, around 1%. That risk fluctuates depending on the sanitary conditions of the destination site and can reach 300 cases / million travelers to Central African regions. In South America the most affected countries are Mexico, Peru, Bolivia and Chile. In developed countries, such as the United States of America, more than 60% of typhoid cases are linked to a previous trip abroad. This is also an oral fecal transmission disease and therefore hygienic-dietary measures reduce the risk of acquisition. The fact that currently available vaccines offer incomplete protection ranging from 60 to 80%, makes these measures more relevant. There are currently three vaccine formulations available, two parenteral and one oral. The latter, composed of the Ty21a strain, has a good tolerance but its protection is not high (60 to 70%), on the other hand, it should not be administered together with antibiotics or antimalarial drugs and is contraindicated in pregnancy and immunocompromised hosts. The parenteral vaccine consisting of capsular polysaccharides offers somewhat greater protection (60 - 80%) and can be administered to children from two years of age and to immunocompromised hosts. two parenterals and one oral. The latter, composed of the Ty21a strain, has a good tolerance but its protection is not high (60 to 70%), on the other hand, it should not be administered together with antibiotics or antimalarial drugs and is contraindicated in pregnancy and immunocompromised hosts. The parenteral vaccine consisting of capsular polysaccharides offers somewhat greater protection (60 - 80%) and can be administered to children from two years of age and to immunocompromised hosts. two parenterals and one oral. The latter, composed of the Ty21a strain, has a good tolerance but its protection is not high (60 to 70%), on the other hand, it should not be administered together with antibiotics or antimalarial drugs and is contraindicated in pregnancy and immunocompromised hosts. The parenteral vaccine consisting of capsular polysaccharides offers somewhat greater protection (60 - 80%) and can be administered to children from two years of age and to immunocompromised hosts.

Japanese encephalitis

It is a disease due to a flavivirus and transmitted by the Culex mosquito bite, endemic in Southeast and South Asia. Rural and agricultural areas turn out to be the most risky, and in line with the favorable conditions for their vector, the rainy seasons of summer and early autumn, the moments of greatest transmission. The incidence of the disease in travelers is low (1 case / 5000 travelers per month of stay in endemic area) and the majority of infections are asymptomatic (less than 1% of those infected develop encephalitis). It seems obvious to emphasize that it is a disease whose incidence is subject to the degree of exposure and, therefore, to the nature of the trip. Prophylaxis includes measures that prevent mosquito bites and vaccination. The indication of the vaccine is reduced to those travelers whose stay in endemic areas is longer than one month and during the seasons of the year of greatest risk. It is recommended not to vaccinate pregnant women and children under one year of age, as the safety data of vaccines in this population are insufficient.

Yellow fever

Yellow fever is an acute febrile disease whose etiologic agent is an arbovirus of the Flavivirus genus and belonging to the Flaviviridae family, transmitted to humans (urban or epidemic yellow fever) through the Aedes aegypti mosquito, widely spread in sub-Saharan Africa and South America (Figure 1). The yellow fever virus is maintained in nature by transmission from mosquitoes to non-human primates. The clinical manifestations range from a flu-like syndrome to severe hepatitis and hemorrhagic fever. Furthermore, up to 50% of infections can be unapparent. The mortality of symptomatic cases can vary between 5-50%. The World Health Organization estimates that about 200,000 cases are reported annually in Africa alone, with 20,000 deaths. Travelers' risk of acquiring the disease depends on several factors: immunization status, travel destination, season of the year, duration of exposure, work and recreational activities during the trip, and the local rate of virus transmission during the trip. . Therefore, personal protection measures should be taken against exposure to mosquitoes, such as using suitable clothing and repellents if you are going to do outdoor activities, stay in protected rooms, etc. The yellow fever vaccine is the only one that since 1988, according to the WHO, can be required of a traveler and requires an international vaccination certificate. It is composed of an attenuated virus strain and produces immunity in about 95% of the vaccinated population, with a single subcutaneous dose. Revaccination every 10 years is recommended. Common adverse events include headache, fever, and myalgia within 5-10 days after vaccination. Mild allergic reactions are occasional and immediate hypersensitivity phenomena (rash, hives), less common and generally affect people allergic to eggs. Other more severe but rare events may be encephalitis and post-vaccinal viscerotropic syndrome. This vaccine is contraindicated in children under 6 months, pregnant women, immunosuppressed and people with a proven allergy to eggs. less common and generally affect people allergic to eggs. Other more severe but rare events may be encephalitis and post-vaccinal viscerotropic syndrome. This vaccine is contraindicated in children under 6 months, pregnant women, immunosuppressed and people with a proven allergy to eggs. less common and generally affect people allergic to eggs. Other more severe but rare events may be encephalitis and post-vaccinal viscerotropic syndrome. This vaccine is contraindicated in children under 6 months, pregnant women, immunosuppressed and people with a proven allergy to eggs.

Meningococcal disease

Meningococcal disease is caused by a bacteria called Neisseria meningitidis, of which there are 13 serogroups. Among these, those that most commonly cause disease are A, B, C, Y, and W-135, and those related to epidemics are A, B, and C. This disease represents a serious public health problem on several continents, mainly affecting the third world regions. It occurs endemic or epidemic. The only reservoir of meningococcus is the human being. Transmission occurs from nasopharyngeal secretions from asymptomatic carriers and to a lesser extent through contact with secretions from a patient. Among bacterial meningitis, the one caused by Neisseria meningitidis is the one with the greatest capacity to produce epidemic outbreaks, hence the importance of mandatory reporting for epidemiological surveillance systems. In turn, the different serogroups differ in their epidemic potential. Serogroup A is most prevalent in the "meningitis belt" in Africa, the Middle East, and Southeast Asia. Meningococcus B predominates in Europe, the United States, and Australia, and in some countries in South and Central America it shares its prevalence with serogroup C (Figure 4). The manifestations of meningococcal disease are very varied, ranging from benign transient bacteremia, arthritis, to severe neurological conditions, disseminated intravascular coagulation, endotoxic shock, endocarditis, and multi-organ failure. Its severe clinical forms, meningitis and meningococemia, they have a high lethality mainly in children under 4 years of age. Vaccination is the most effective method to prevent meningococcal disease, and should be indicated in travelers to endemic areas, especially to the countries of the "Meningitis Belt" (Figure 4) and to the pilgrimage to Mecca. None of the currently available vaccines provide protection against all serogroups. There are polysaccharide and conjugate meningococcal vaccines. The bivalent capsular polysaccharide vaccine (A + C) is the vaccine available in Argentina, it must be applied in children older than two years, a single dose subcutaneously, it provides protection for short periods (3-5 years) and reinforcements, in case if necessary, they must be carried out every 3 years. The tetravalent conjugate vaccine (A, C, Y, W-135), available in the United States, Provides more durable protection, approximately 8 years. Adverse effects of the vaccine are rare and related to pain, erythema, and local induration. Some occasional systemic reactions may be seen, such as chills, fever, and irritability.

Cholera

Cholera is a communicable endemo-epidemic disease, the etiologic agent of which is Vibrio cholerae. The route of transmission is fecal-oral, through consumption of contaminated food and water. It causes an acute clinical picture characterized by vomiting and uncontrollable diarrhea, with the appearance of "rice water", which can lead to dehydration, hypovolemic shock and sometimes death within a few hours. The prevention of this disease is mainly based on hygienic-dietary measures. Although various types of vaccines have been developed, the WHO does not recommend their use as an effective means of controlling the spread of cholera. Two types of oral vaccines are currently available in some countries (Australia, Canada and the European Union), an attenuated oral vaccine uses live attenuated bacteria,

Measles

It is an acute, potentially serious and communicable viral disease. It remains a common disease in many regions of the world. An estimated 10 million cases and 164,000 deaths occur annually. In Argentina, since the year 2000 there have been no confirmed indigenous cases, but rather imported cases. Complications can be serious and more common in children younger than 5 years of age and in adults over 20 years of age. Thanks to the introduction of the measles vaccine in 1972, its incidence was reduced by more than 78%. The measles virus is a paramyxovirus belonging to the genus Morbillivirus. The mode of transmission is primarily person-to-person, through spread of Flügge droplets by coughing, sneezing, or direct contact with infected nasal or pharyngeal secretions. The clinical picture is characterized by fever, enanthema, cough, rhinitis and conjunctivitis (triple catarrh), and generalized morbilliform rash. Any traveler to areas of viral circulation must be immune to measles before departure, laboratory confirmation (anti-measles IgG) is a correlate of adequate protection. Otherwise, and if the traveler cannot guarantee a vaccination scheme, a dose of measles vaccine (double or triple viral) should be applied subcutaneously. Contraindications are severe allergic reaction (anaphylaxis) after a previous dose or components of the vaccine, pregnancy, known severe immunodeficiency, being in an acute illness with fever, history of thrombocytopenia or thrombocytopenic purpura. and generalized morbilliform rash. Any traveler to areas of viral circulation must be immune to measles before departure, laboratory confirmation (anti-measles IgG) is a correlate of adequate protection. Otherwise, and if the traveler cannot guarantee a vaccination scheme, a dose of measles vaccine (double or triple viral) should be applied subcutaneously. Contraindications are severe allergic reaction (anaphylaxis) after a previous dose or components of the vaccine, pregnancy, known severe immunodeficiency, being in an acute illness with fever, history of thrombocytopenia or thrombocytopenic purpura. and generalized morbilliform rash. Any traveler to areas of viral circulation must be immune to measles before departure, laboratory confirmation (anti-measles IgG) is a correlate of adequate protection. Otherwise, and if the traveler cannot guarantee a vaccination scheme, a dose of measles vaccine (double or triple viral) should be applied subcutaneously. Contraindications are severe allergic reaction (anaphylaxis) after a previous dose or components of the vaccine, pregnancy, known severe immunodeficiency, being in an acute illness with fever, history of thrombocytopenia or thrombocytopenic purpura. Laboratory confirmation (anti-measles IgG) is a correlate of adequate protection. Otherwise, and if the traveler cannot guarantee a vaccination scheme, a dose of measles vaccine (double or triple viral) should be applied subcutaneously. Contraindications are severe allergic reaction (anaphylaxis) after a previous dose or components of the vaccine, pregnancy, known severe immunodeficiency, being in an acute illness with fever, history of thrombocytopenia or thrombocytopenic purpura. Laboratory confirmation (anti-measles IgG) is a correlate of adequate protection. Otherwise, and if the traveler cannot guarantee a vaccination scheme, a dose of measles vaccine (double or triple viral) should be applied subcutaneously. Contraindications are severe allergic reaction (anaphylaxis) after a previous dose or components of the vaccine, pregnancy, known severe immunodeficiency, being in an acute illness with fever, history of thrombocytopenia or thrombocytopenic purpura.

Influenza

Influenza is an acute respiratory disease caused by the influenza virus (RNA virus of the Orthomyxoviridae family) characterized by great genetic variability and the potential to cause epidemics and pandemics. It is classified into three main types: A, B and C. Virus A is the main cause of epidemics that occur each year, while influenza B virus generally occurs in more localized outbreaks. Virus C does not cause epidemics, only asymptomatic or oligosymptomatic infections, and always in the form of isolated cases. It produces an acute febrile illness that mainly affects the upper respiratory tract, generally lasts for a week and, although most recover without requiring medical treatment, it can complicate and even evolve into fatal forms. It is an important health problem both due to the direct or indirect mortality it causes and the complications and socioeconomic costs it causes. An estimated 250,000-500,000 flu-related deaths occur annually worldwide. 80-90% of the mortality associated with this disease occurs in people older than 60 years. Transmission occurs primarily by air via microdroplets that are caused by speaking, coughing, or sneezing. Vaccination is the basic and most effective measure to prevent influenza and reduce the impact of the epidemic. It is recommended in children under 5 years of age, adults 65 years of age and older, patients with chronic cardiovascular or lung diseases, residents of nursing homes or other chronic care institutions, and their caregivers, pregnant women, health workers, people infected with the human immunodeficiency virus, travelers to countries with circulation of the influenza virus. The start date of the vaccination campaign is determined by the time when the virus usually begins to circulate, in the months of October - November in the northern hemisphere and in the southern hemisphere in March - April. The vaccine begins to take effect approximately two weeks after its application. An annual dose is applied intramuscularly. The clinical efficacy in healthy adults under 65 years is 70 to 90%, with a variability that is given by the similarity between the circulating strains and those contained in the vaccine. Although efficacy is lower in older age groups, especially in those over 70 years of age, prevents secondary complications and reduces the risk of hospitalization and death from influenza. Adverse effects are infrequent and can be local (pain, induration and erythema) or general (fever, malaise, myalgia, Guillan-Barré). Vaccination is contraindicated in people allergic to eggs and those who are carrying an acute febrile illness.

Rabies

Rabies is an acute viral infection that affects the central nervous system of humans and other wild or domestic mammals, transmitted by inoculation of the rabies virus, RNA virus belonging to the genus Lyssavirus, of the Rhabdoviridae family, contained in the saliva of the infected animal . The virus is widespread throughout the planet. The importance of rabies for Public Health both in Argentina and in the world does not lie in the number of cases, but in the high lethality that reaches 100% when the patient already has symptoms. America in 1990 presented 251 cases of human rabies, in 2003 they were reduced to 35, which represents a reduction of 86%. Most of them were registered in Northeast Brazil, Northern Argentina (Jujuy province), border with Bolivia and Venezuela. Causes approximately 50.000 deaths annually, most of them in Asia. In the urban cycle, the main reservoirs and sources of infection are cats and dogs. Wild reservoirs include foxes, vampires, and bats.

Rabies vaccination should be indicated to all travelers to endemic-epidemic areas, mainly on adventure tourism trips. There are several types of vaccines available, but the WHO recommended discontinuing those derived from nervous tissue to be replaced by those made in tissue culture. There are two types of prophylaxis:

Pre-exposure: 3 doses of vaccine applied on days 0, 7 and 21 or 28, followed by one booster per year and if the risk continues, one booster every 5 years.

Post-exposure: any person will be indicated in the following circumstances: 1. in the exposures if the attacking animal disappears, dies or there is no certainty in its identification; 2. in exposures, with injuries to the face, neck, fingertips or mucous membranes; 3. in all bite accidents by wild species such as bats, coatis, monkeys, foxes, etc. The treatment consists of an exhaustive cleaning of the wound; rabies vaccine, whose schedule includes 5 doses, on days 0, 3, 7, 14 and 28; and rabies immunoglobulin, which must infiltrate wounds. Immunoglobulin is most effective when administered simultaneously with the first dose of vaccine on day zero, administered at different sites. Post-vaccination events: Local: can cause benign reactions such as pain, edema, erythema and, rarely, abscess; Systemic: mild feverish state. Rarely, a hypersensitivity reaction may occur.

Conclusions

A traveler is a potential importer of disease, which carries an individual and social risk. Specialized consultation before departure and the adoption of preventive measures through vaccines and advice reduce the risks of acquiring diseases. A traveler who becomes ill on his return may be suffering from manifestations of an exotic disease that has contracted thousands of kilometers from his place of residence and could put him at risk of death without early diagnosis. Incorporating a patient's travel history should be a systematic practice of the doctor.

Table 1. INCUBATION PERIODS OF IMPORTED INFECTIONS