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Revisão Produção Nacional Revisado por pares

BIBTEX RIS

Vaccine Recommendations for Solid-Organ Transplant Recipients and Donors

2018; Wolters Kluwer; Volume: 102; Issue: 2S Linguagem: Inglês

10.1097/tp.0000000000002012

1534-6080

R.S.B. Stucchi, Marta Heloísa Lopes, Deepali Kumar, Oriol Manuel,

Virology and Viral Diseases

Vaccine-preventable infections represent a significant burden of disease in solid-organ transplant (SOT) recipients. Respiratory infections caused by Streptococcus pneumoniae and influenza viruses are more prevalent and associated with worse outcomes compared with the general population1,2 Chickenpox and herpes zoster are associated with significant morbidity in these patients. Meningococcal disease, although rare in SOT recipients, is at greater risk in patients receiving the terminal complement inhibitor eculizumab.3 In addition, SOT recipients live longer and have better quality of life; and therefore, they are more likely to travel to tropical regions.4 Together with increasing activity of transplant centers located in tropical regions, SOT recipients have a greater potential to be exposed to vaccine-preventable infections. General Principles of Immunization Immunosuppressive drugs administered after transplant impair vaccine immune responses. Also, live-attenuated vaccines may have safety concerns in immunocompromised patients. Therefore, it is highly recommended to vaccinate patients before transplantation; particularly, at early stages of the underlying disease to avoid any effect of end-organ disease on vaccine immunogenicity.5 Because there is a risk of no response to the vaccine, it is also recommended to perform vaccine serology after vaccination when available. Vaccination of healthcare workers and households is also of importance to decrease exposure to the pathogen. This review will discuss routine vaccination for candidates and recipients in Latin American (LA) and specific consideration for candidates and recipients traveling to/from LA. Routine Vaccination Some routine vaccines are recommended to candidates and recipients of SOT who live in endemic regions or who will return to live in endemic regions. Recommendations are based on the routine schedule for immunocompetent individuals, according to a persons age, vaccination, and exposure history.6 The routine recommendation for vaccination in adults transplant candidates or recipients is summarized in Table 1.TABLE 1: Recommendation for vaccination in adults transplant candidates or recipientsTetanus, Diphtheria, and Pertussis Vaccine The complete vaccination schedule against tetanus/diphtheria/pertussis in LA countries consists of 3 primary doses for all candidates with a booster dose of tetanus/diphtheria-containing vaccine every 10 to 20 years. Bordetella pertussis is the main causative agent of pertussis, also known as whooping cough, which remains a serious public health problem worldwide. In LA, the annual number of suspected pertussis cases over the last 10 years has ranged from 1500 to 43000 with significant increases in the number of cases in Argentina, Brazil, Mexico, Chile, Colombia, Paraguay, Peru, and Uruguay, among others. Possible reasons for the increasing number of pertussis cases are the suboptimal coverage rates of vaccination, the waning of immunity conferred by vaccination and/or natural infection, the reduction in the number of natural boosters, and the adaptability of the bacteria to the immunity conferred by the vaccines. Other more noticeable causes are the higher awareness of the disease, and the improvements in epidemiological surveillance and diagnostic tests.8 Also, divergence between vaccine strains and local isolates could contribute to the described pertussis epidemiology.9 In many countries including some from LA, pertussis is now increasing in adolescents and adults, probably due to the fast waning immunity postimmunization.8 The assessment in the burden of pertussis in LA is complex, especially in regard of comparisons between countries. This may be mainly due to the differences in vaccination (type of vaccine and/or producer of vaccines) and the quality of the surveillance systems adopted. Data from other countries of LA (Argentina, Brazil, Chile, Colombia, and Mexico) have evidence of an increase in pertussis-related morbidity in recent years, as compared to previous periods.8 Immunization against pertussis (combined with tetanus and diphtheria-containing vaccine) has been included in the World Health Organization's (WHO) Expanded Programme on Immunization in 1974 for children. In recent years, an increasing number of cases have been registered in older children, adolescents, and adults. Based on this, the current Centers for Disease Control and Prevention (CDC) recommendation is that adolescents and adults receive a 1-time booster dose of tetanus toxoid, reduced diphtheria toxoid, and reduced acellular pertussis (Tdap) vaccine. After receiving Tdap, individuals should continue to receive Td for routine booster vaccination against tetanus and diphtheria, in accordance with previously published guidelines.10 Influenza Vaccine Influenza disease affects up to 10% of the world's population every year. Transplant recipients belong to the high-risk group of complications and death compared to general population, and should receive an annual influenza vaccine.11 The WHO Global Influenza Surveillance and Response System define the vaccine composite for the following influenza season in the northern and southern hemisphere in February and September, based on the influenza viruses circulating in the last influenza season. Influenza occurs year-round in the tropics; although, recent data suggests that there are also specific epidemic peaks in tropical countries.12 The updated annual influenza vaccine distribution usually starts from April to May. There are 2 types of influenza vaccine, the trivalent (or quadrivalent) inactivated influenza vaccine (TIV) and the live-attenuated influenza vaccine (LAIV). Because of safety concerns, LAIV is contraindicated in immunocompromised patients. A significant amount of data has confirmed that TIV in SOT recipients is safe and immunogenic.13 Although antibody responses are expected to be lower in SOT recipients, studies found that vaccinated patients have lower rates of complications and improved allograft and patient survival14,15 Although some studies correlated influenza vaccination with production of anti-HLA antibodies, this has not confirmed in subsequent larger studies.16 The exact timing of administration of influenza vaccine after transplant has not been completely defined; whereas, immunogenicity may be reduced during the first weeks posttransplant, which is the period when influenza is associated with impaired outcomes. Recommendations suggest that 1 to 3 months is the minimal period for vaccination.13 However, the influenza vaccine can be administered 1 month after transplantation during a community influenza outbreak,6 and revaccination 3 to 6 months after transplantation could be considered if influenza activity persists after this period. Recent clinical trials have studied alternative immunization scheme for SOT recipients, such as administration of a booster doses, a double dose of antigen, intradermal preparations and adjuvanted vaccine, in an attempt to improve the efficacy of the vaccine.17-19 Although these strategies have yet to be validated in large clinical trials, adjuvanted and high-dose vaccines have been well tolerated and may have increased immunogenicity compared with the standard dose.18-20 Households and close contacts of transplant recipients should receive influenza vaccine yearly, preferably the inactivated vaccine. However, if only LAIV is available, they must be aware of handwashing frequently for a 2-week period after vaccination.5 Although antiviral prophylaxis with neuraminidase inhibitors is not recommended in high-risk or unvaccinated patients, patients can be given empiric antiviral therapy if symptoms compatible with influenza appear while waiting for a confirmatory diagnosis.21 Measles-Mumps-Rubella Vaccine Severe cases of measles, including the development of subacute measles encephalopathy, have been described in SOT recipients.22 Seronegative pediatric transplant candidates should receive 2 doses of the vaccine 1 month apart and seronegative adult transplant candidates should receive 1 dose of the vaccine, with seroconversion confirmation after 1 month (and a booster dose in case of undetectable antibody levels).5 These patients should be put on temporary hold for transplant for a minimum interval of 28 days. Experience with the use of MMR vaccine in the posttransplant period is limited to selected cases of pediatric liver transplant recipients on low doses of immunosuppression.23 Otherwise, MMR vaccine should not be used in SOT recipients. Households and close contacts of transplant recipients should also receive MMR vaccine.5 Pneumococcal Vaccines S. pneumoniae causes a wide range of diseases such as pharyngitis, acute otitis media, meningitis, septic arthritis, and bacteremia beyond pneumonia. Invasive pneumococcal disease (IPD) is a vaccine-preventable disease that causes around a million deaths each year worldwide; approximately 90% of these deaths occur in developing countries.24 In LA and the Caribbean, WHO reports that 1.6 million children younger than 5 years suffer an episode of IPD each year and among 12 000 to 28 000 deaths occur annually.24S. pneumoniae is the most prevalent agent associated with pneumonia cases in LA, accounting for at least 11% of all disease causes. Pneumococcal meningitis is also a relevant issue in LA with an incidence of 8.34 per 100 000 in children aged 0 to 23 months, and 4.62 per 100 000 in the age group of up to 5 years. The mortality rate is high among the elderly reaching 80%.25 Two types of pneumococcal vaccines are available: polysaccharide (PPV) and conjugate vaccines (PCV). Pneumococcal vaccines in different age groups can reduce the burden of disease, morbidity, mortality, and hence the high costs in healthcare attention of the affected patients, providing protection against the most common serotypes. In LA and the Caribbean regions, PCV has been incorporated as part of the universal immunization programs for children under 2 years. It has also been approved for use in adult patients with underlined risk factors for IPD.24 The immunization of high-risk population against IPD aged between 2 and 65 years has been conducted in several countries with the administration of PPV23. However, immunocompromised patients do not present a good response to polysaccharide vaccines, conjugate vaccines are the best option for this group.26 PCV7 was licensed in 2000 to provide protection against 7 of the most common pneumococcal serotypes. In early 2010, new formulations with protection against 10 and 13 serotypes have become available for use. Serotypes 1, 3, 5, 6A/B, 7F, 9V, 14, 18C, 19A/F, and 23F are the most frequently found in LA. These serotypes are covered by both conjugate vaccines (PCV7 contains 4, 6B, 9V, 14, 18C, 19F, and 23F serotypes; PCV10 also covers serotypes 1, 5 and 7F in addition to PCV7; and PCV13 contains serotypes 1, 3, 5, 6A, 7F and 19A in addition to PCV7) and the polysaccharide vaccine PPV23 (serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F).25 Thus, despite the high incidence of IPD, available vaccines show potential efficacy in this scenario, setting up a preventable health problem in these countries. Studies comparing PCV7 and PPV23 in the adult organ transplant population show that there is a trend to greater vaccine immunogenicity with PCV7; however, a longer-term follow-up of this cohort showed that titers declined to baseline by 3 years regardless of vaccine type.27 In addition, no boosting effect was seen with PPV23 after PCV7 was administered.28 One dose of PCV13 is recommended for adult transplant candidates or recipients, followed by a dose of PPV23 after a minimum interval of 8 weeks to expand serotype coverage.29 In some countries, where there is little additional coverage of the invasive serotypes with the PPV23, a second dose of the PCV13 is recommended. Immunocompromised adults aged 19 years or older who previously have received at least 1 PPV23 vaccine dose should be given a PCV13 vaccine dose at least 1 year interval after last PPV23 vaccine.29 For those who require additional doses of PPSV23, the first such dose should be given no sooner than 8 weeks after PCV13 and at least 5 years after the most recent dose of PPSV23.29 Meningococcal Vaccine Neisseria meningitidis remains a major cause of invasive bacterial disease worldwide and is associated with substantial morbidity and overall case fatality rates of around 10%. In LA, incidence rates and serogroup distribution of meningococcal disease are highly variable (from <0.1 to almost 2 cases per 100 000 inhabitants), with the highest burden of disease reported in Brazil and the Southern Cone countries (Argentina, Chile, and Uruguay)30; very limited data are available from the Andean region, Mexico, and Central America. Overall, in LA, there is a need to improve the surveillance system (including case definition, laboratory procedures and surveillance). According to the SIREVA surveillance (Sistema de Redes de Vigilancia de los Agentes Responsables de Neumonías y Meningitis Bacterianas), since 2000 in LA and the Caribbean, the most prevalent meningococcal serogroups circulating are B and C, with 69% and 26% of the total group, and there is a progressive increase in circulation of serogroups W and Y.31 Meningococcal outbreaks occur periodically in some parts of LA. The recent emergence and spread of serogroup W disease in Argentina and Chile have determined the changes in routine meningococcal vaccination programs.30 Meningococcal polysaccharide vaccines (MPV against N. meningitidis serotypes A, C, Y and W) are important to control outbreaks and epidemics. They are not used, however, in the routine immunization because they stimulate immune response T cell-independent and do not induce immunological memory and protection is short-lived. The conjungation of polysaccharide to a protein carrier (meningococcal conjugate vaccines, MCV) provides a T cell dependent immune response, immune memory and long-term protection. A recent N. meningitidis serotype B vaccine obtained by reverse vaccinology was recently licensed in some countries, but there is still no data on its use in immunocompromised patients.32 Both MCV4 and MPV4 (against serotypes A, C, W, and Y) are recommended for use in control of meningococcal outbreaks caused by vaccine-preventable serogroups. Specific recommendations should be reinforced for vaccination of high-risk groups.33 The Brazilian current recommendation is to vaccinate with MCV-C all SOT candidates and recipients.34 The recommended schedule in SOT recipients or candidates for meningococcal vaccine is 2 doses 2 months apart. Meningococcal disease does not seem to occur at higher rates after transplantation, with only a few case reports published.35 Therefore, meningococcal vaccination has not routinely been recommended in SOT recipients, except in patients with risk factors (eg, splenectomy, military recruits), or those who travel to high-risk areas (Hajj) (see below). Cases of meningococcal disease have been recently reported; however, in patients receiving eculizumab, a terminal complement pathway inhibitor, which is authorized for the treatment of atypical hemolytic-uremic syndrome, and is increasingly used for the treatment of antibody-mediated rejection posttransplant.3 Few studies have evaluated the immunogenicity of meningococcal vaccine in SOT recipients. Humoral responses to the polysaccharide vaccine appear to be worse compared to the conjugated vaccine, so that this latter vaccine is preferred.36 Because of the potential impaired responses to meningococcal vaccine in the early posttransplant period (usually when eculizumab is administered), vaccination in transplant candidates with a higher immunological risk before transplant (ie, highly sensitized, high panel of reactive antibody) may be a more effective strategy to protect against meningococcal disease, although there are no data to support this recommendation.37 Varicella and Zoster Vaccines Both varicella and zoster vaccines are live-attenuated vaccines and should be given before transplant. Varicella vaccine is indicated for those that are VZV IgG negative and do not have documented proof of receipt of 2 doses of varicella vaccine. Zoster vaccine contains approximately 14 times the amount of attenuated virus than varicella vaccine and is indicated for before transplant in those candidates aged 50 years or older who are VZV IgG positive and not on immunosuppressive drugs.38 However, the effect of pretransplant zoster vaccination on posttransplant protection from shingles is largely unknown. Although the varicella vaccine is live-attenuated, it has been administered safely posttransplant in selected long-term transplant (primarily pediatric) recipients on low-dose immunosuppression.39,40 Because there are no large studies, the risk and benefits of this approach need to be carefully weighed on a case-by-case basis. A recent study suggested that zoster vaccine was generally well tolerated in patients receiving chronic/maintenance corticosteroids, as is the case of SOT recipients.41 Households and close contacts of transplant recipients should also receive varicella vaccine.5 A subunit inactivated vaccine containing VZV glycoprotein E (also called HZ/su) is under study in renal transplant recipients. In nonimmunocompromised older adults (≥50 years of age), a randomized placebo-controlled phase 3 study was recently conducted in 18 countries, showing the safety and efficacy of the HZ/su vaccine to reduce the risk of herpes zoster.42 Hepatitis B Vaccine In LA, the majority countries are considered low prevalence (<2%) regions for hepatitis B virus (HBV). For more epidemiological information concerning HBV, please refer to the review on Viral Hepatitis in this supplement. Hepatitis B vaccine should be given as a 3-dose series before transplantation when possible and anti-HBs titers should be checked 4 to 8 weeks postvaccination to confirm immunity.5 In previously vaccinated patients (in particular during childhood), anti-HBs titers should be also checked to decide whether booster doses are needed. Since nonresponse to hepatitis B vaccine can occur in end-stage renal disease and patients on immunosuppression, high dose hepatitis B (40 μg) vaccine should be administered to patients on dialysis and all posttransplant patients. Although the standard schedule for vaccination is 0, 1, and 6 months, accelerated schedules at 0, 7, 21, and 28 days and 0, 1, 2 months (with a booster dose at 6 months) have been studied and are immunogenic. The Brazilian current recommendation for immunocompromised patients is a 4-dose schedule with double-dose according to the age group standard dose.34 Although serial hepatitis B surface antibody titers should be routinely monitored after transplantation and booster doses given if protective titers wane,5 a recent systematic review concluded that randomized clinical trials are needed to evaluate the benefits of booster dose vaccination for preventing HBV.43 Hepatitis A Vaccine Risk factors for hepatitis A virus (HAV) infection include intravenous drug use, men who have sex with men, travel to high-risk areas, and certain ethnic or religious groups. LA is a moderate- to high-risk area for HAV. For more epidemiological information concerning HAV, please refer to the review on Viral Hepatitis in this supplement. Vaccine against hepatitis A is an inactivated virus vaccine, which has demonstrated safety and high immunogenicity in the general population. Hepatitis A vaccine is already introduced in routine vaccination schedule (only 1 dose) in some countries of LA, such as Brazil and Argentina.34,44 The vaccine schedule includes 2 doses, 6 months apart, but the first dose is usually enough to ensure initial protection in immunocompetent patients. Studies evaluating the immunogenicity of HAV vaccine in SOT recipients have generally showed a lower antibody response after vaccination as compared with healthy volunteers.45 Vaccination against HAV in seronegative patients before transplant (alone or together with the HBV vaccine) is recommended.46 Polio Vaccine The Americas region, which includes LA, Caribbean, and North America (Canada and the United States), interrupted the indigenous transmission of wild poliovirus in 1991 by using oral polio vaccine (OPV) and was certified as free of polio in 1994; most LA and Caribbean countries rely on the OPV to maintain elimination.47 Only the inactivated vaccine by intramuscular injection (IPV) can be administered to SOT recipients as a single dose. The oral live-attenuated virus vaccine (OPV) is formally contraindicated in transplant recipients and their household contacts due to the risk of transmission of poliovirus.5 Human Papillomavirus Vaccine Disease caused by human papillomavirus (HPV) including anogenital warts and cervical cancer occurs with greater frequency in SOT recipients.48 Because HPV vaccine is recommended before viral exposure, routine immunization with a 3-dose series at 0, 2, 6 months should be followed according to the current guidelines: 2vHPV, 4vHPV, or 9vHPV for routine vaccination of females aged 9 to 14 years to 26 years who have not been vaccinated previously or who have not completed the 3-dose series; and 4vHPV or 9vHPV for routine vaccination of males aged 11 to 12 years to 21 years who have not been vaccinated previously or who have not completed the 3-dose series49,50 Additionally, 4vHPV or 9vHPV vaccination is recommended for men who have sex with men and for immunocompromised men through age 26 years if not vaccinated previously. Although routine immunization with 2-dose series has been used as an alternative to the standard 3-dose series,51 it has not been studied yet in immunocompromised patients. HPV vaccine is an inactivated virus-like particle vaccine based on the L1 protein of HPV and can be offered to either pretransplantation or posttransplantation. Although immunogenicity or efficacy has not been studied in the pretransplant period, studies in the posttransplant setting showed good immunogenicity in pediatrics but lower immunogenicity in adults.52 Neither the bivalent adjuvanted nor the nonavalent vaccines have been studied in transplant recipients, although could be used if recommended in population-based programs. Vaccination for Travelers Vaccination for SOT recipients should ideally be initiated several months before travel to/from LA. The vaccination schedule planning needs to consider the risk of exposure to vaccine-preventable disease in the country of travel, as well as the travel conditions. Vaccines containing live, attenuated viruses (varicella, measles, mumps, rubella, yellow fever [YF]) are contraindicated for SOT recipients even if there is a potential risk of exposure in a susceptible patient. It is therefore recommended that live-attenuated vaccines be administered during pretransplant period. Pretravel consultation is a good opportunity for healthcare providers to review the immunization status of patients. All travelers should be up to date with routine vaccinations before the trip. Thus, vaccines previously described must be within the protection timeframe established or should be updated (tetanus, diphtheria, pertussis, pneumococcus, influenza). However, some vaccines are not routinely indicated and should be administered in case of exposure during trips. Although it is advisable for travelers to have an official record of their immunization history during their trip, an official certificate of specific immunization is required only for polio for those traveling to Saudi Arabia, and YF vaccine for those traveling to countries that require proof of vaccination. The recommendation for vaccination in adults transplant candidates or recipients traveling to LA is summarized in Table 2. For more detailed information please see specific section below or the specific review of routine vaccination. More information can be additionally found in the CDC Health Information for International Travel.53TABLE 2: Recommendation for vaccination in adults transplant candidates or recipients traveling to Latin AmericaInfluenza Vaccine As previously mentioned, seasonality patterns are less defined in the tropics, with multiple peaks and year-round activity.12 Therefore, influenza immunization should be given to all SOT recipients who were not vaccinated within the past year, before traveling to LA and from LA to the northern hemisphere during the autumn-winter period.7 Meningococcal Vaccine Vaccination with quadrivalent meningococcal vaccines is required by all international travelers going to Saudi Arabia, including pilgrims to the Hajj, and is recommended for those traveling to the meningitis belt in sub-Saharan Africa. WHO regularly provides update information with list of countries facing epidemics.54 Hepatitis A Vaccine Susceptible HAV individuals that have expressed their interest in potential travel to endemic areas should receive the HAV vaccine. For optimal protection, in case of short time from vaccination to travel (<2 weeks), patients should receive intramuscular pooled immunoglobulin in addition to 1 vaccine dose at a separate injection site.53 Susceptible travelers who are exposed to HAV should be administered 1 dose of hepatitis A vaccine or immunoglobulin as soon as possible, ideally within 2 weeks of exposure.53 Polio Vaccine For everyone traveling to countries where the wild poliovirus is still circulating, it does not include LA countries. For SOT recipients traveling from LA to certain parts of Africa and Asia, which may be at risk for polio, 1-time polio inactivated vaccine booster is recommended.55 YF Vaccine YF is not present in all parts of LA, and in most of the countries the virus is restricted to sylvatic cycle. For more epidemiological information concerning YF, please refer to the review on Arboviruses in this supplement. Vaccination is the most important preventive measure against YF. The YF vaccine is recommended to all susceptible individuals if traveling to endemic areas, it is required for entrance and transit in some countries from all arriving travelers or depending of origin of traveler. The YF vaccine requirements are regulated by international law. Further country-specific information is available from the CDC Yellow Book.53 YF vaccine is a live-attenuated virus vaccine contraindicated in the posttransplant setting. Some SOT recipients have inadvertently received the vaccine with no major complications reported.56 However, the immunogenicity of YF vaccine on these patients is unknown, and because of the potential development of the disease by the vaccine viral strain, it is not recommended in SOT recipients. A single dose of YF vaccine is sufficient to confer lifelong protective immunity in immunocompetent hosts, and booster doses every 10 years are no longer necessary.57 Patients that have been vaccinated before transplant are probably still protected years after transplant.58 Visits to YF risk areas are generally not recommended for SOT recipients, particularly in case of YF outbreaks. SOT recipients who have to travel to YF risk areas should be advised to use methods to prevent mosquito bites including wearing full-sleeved clothing and using mosquito repellent. Travel to countries requiring a YF vaccine certificate in those with a medical contraindication to vaccination requires a waiver letter stating the contraindication reason (an International Certificate of Vaccination or Prophylaxis).59 Japanese Encephalitis Vaccine Japanese encephalitis (JE) is a flaviviral infection transmitted by mosquito bites and is endemic in several Asian countries, especially in rural areas. Mortality if encephalitis develops ranges 20% to 30%. Therefore, JE vaccination must be considered only for those considering prolonged travel (≥1 month) from LA to endemic areas. The inactivated JE virus vaccine can be administered to SOT recipients and is given as a 2-dose series, 28 days apart.23 A booster dose might be recommended for anyone who was vaccinated more than a year ago and remains at risk for exposure. There is a JE vaccine containing live-attenuated viruses available in Asia that is contraindicated for SOT recipients. Rabies Vaccine Rabies incidence in LA and the Caribbean has decreased and several countries (Uruguay, Chile, Costa Rica, Mexico, and Panama), and there are certain areas to which this disease is still endemic. The higher-risk areas for human rabies transmitted by dogs are Haiti, Bolivia, Guatemala, Dominican Republic, and parts of Brazil (Maranhão State) and Peru (Puno Region). Unfavorable conditions in these areas maintain rabies transmission.60 In LA and the Caribbean, around 40% of cases of rabies are transmitted by dogs and 60% by bats. Although rabies control in LA and the Caribbean has been successful, travelers should be oriented for avoid animal exposure. Transplant recipients who anticipate intense exposure to animals during travel should receive preexposure rabies vaccination. Where available, rabies vaccine titer should be checked after vaccination. If preexposure rabies vaccination has not been given and the transplant recipient is exposed to the rabies virus, they should be oriented for postexposure prophylaxis; immunoglobulin and the full vaccine schedule should be administered, independent of the severity of the wound and the animal's condition.61 Patients with preexposure rabies vaccination who are exposed to rabies virus should complete the vaccination schedule after exposure. Typhoid Fever Vaccine Typhoid and paratyphoid (enteric) fever remain important public health problems globally and major causes of morbidity in the developing world. The estimated prevalence of typhoid fever in LA ranges from 10 to 100 000 cases year, but there is scarce information about the real incidence due to the lack of surveillance systems.62 Enteric fever is a particular problem in travelers to endemic areas, especially those visiting friends and relatives. Currently, the 2 main vaccines recommended for travelers are the inactivated vaccine containing bacterial capsule polysaccharide and the live-attenuated bacteria oral Ty21a vaccine. These internationally licensed vaccines are safe and effective against Salmonella Typhi. However, there is currently no commercially available vaccine against Salmonella enterica Typhi, which is increasingly reported as a cause of enteric fever.63 Moreover, enteric fever remains a common cause of fever in returned travelers, even for those who report having been immunized.64 TF vaccination is indicated for everyone traveling to endemic areas.65 The live-attenuated bacteria vaccine is contraindicated for SOT recipients. The inactivated polysaccharide vaccine is indicated for SOT recipients traveling to typhoid endemic regions and is administered as a single dose. A booster dose is recommended for anyone vaccinated more than 2 years ago and still at risk of exposure. TF vaccination does not preclude the use of other protection measures to prevent food-borne diseases. Cholera Vaccine The cholera epidemic still presents high morbidity and mortality due to socioeconomic and climatic factors. The reemergence of cholera in LA highlight the need for development and strengthening of regional prevention and control strategies. In LA, the most affected countries have been Peru between 1991 and 2002, with a maximum annual cumulative incidence of 1452.72 cases per 100 000 population but a low case fatality rate (0.72%), and Haiti between 2010 and 2011, with a maximum annual cumulative incidence of 3319.13 per 100 000 population and a case fatality rate of 1.32%.66 Cholera vaccination is indicated for everyone traveling to endemic areas during cholera outbreaks, but it is not routinely recommended otherwise. Three orally administered vaccines are available. The Dukoral vaccine contains the B-subunit of the cholera toxin, which is similar to the Escherichia coli thermolabile toxin and thus offers cross protection preventing infection by enterotoxigenic E. coli. The Shanchol vaccine contains killed whole-cells from 2 strains of Vibrio cholerae.67 Both cholera vaccines can be administered to SOT recipients as a 2-dose series (at least 1 week apart). A booster dose is recommended for anyone who was vaccinated more than 2 years ago and is still at risk of exposure. Again, because the vaccine efficacy may be suboptimal, additional measures for prevention of food-borne diseases should be maintained. Vaxchora is a live vaccine against disease caused by V. cholerae serogroup O1 that it is indicated for adults 18 to 64 years of age traveling to cholera-affected areas, but it is contraindicated in SOT recipients.68 Dengue Vaccine Despite efforts to control dengue, based primarily on individual protection against mosquito bites and vector control, 96 million cases of dengue occur annually worldwide. Sixty percent of them in Americas, predominantly LA, where the mosquito-borne viral disease is largely distributed in the urban areas and where circulate the 4 serotype of the virus (DEN-1, DENV-2, DENV-3, and DENV-4).69 For more epidemiological information concerning dengue, please refer to the review on Arboviruses in this supplement. Therefore, dengue fever vaccine is a public health priority and an ideal vaccine is a quadrivalent vaccine that induces protective immunity against the 4 serotypes. The first licensed dengue vaccine is the Dengvaxia (CYD-TV), a live attenuated tetravalent chimeric vaccine developed by Sanofi Pasteur, that uses the YF virus as a backbone, carrying prM and E protein genes from wild type DENV-1-4. Vaccine efficacy estimate was 56.6%; the serotype specific efficacy for DENV-2 was not statistically significant.70 CYD-TV is currently approved by Philippines, Mexico, and Brazil, for people aged 9 to 45 years. The vaccine is not recommended under age 9 years; data from phase III clinical trials showed that among children younger than 9 years, the risk of vaccinated children being hospitalized for a dengue infection increased 1.6-fold.71 Other vaccine candidates are in clinical stages of development, including a phase III study of TV003 in Brazil, a live-attenuated vaccine produced by the partnership between the Butantan Institute in Brazil and the National Institutes of Health of the United States.72 As well as all other attenuated vaccines, dengue vaccine is contraindicated for SOT recipients.