Vaccine-preventable diseases and vaccines

General considerations

Vaccination is the administration of agent-specific, but relatively harmless, antigenic components that in vaccinated individuals can induce protective immunity against the corresponding infectious agent. In practice, the terms “vaccination” and “immunization” are often used interchangeably.

Disease prevention

Vaccination is a highly effective method of preventing certain infectious diseases. Vaccines are generally very safe, and serious adverse reactions are uncommon. Routine immunization programmes protect most of the world’s children from a number of infectious diseases that previously caused millions of deaths each year. For travelers, vaccination offers the possibility of avoiding some infectious diseases that may be encountered abroad. However, satisfactory vaccines have not yet been developed against several of the most life-threatening conditions.

Vaccines for routine and selective use.

Recommendations on vaccines for routine use are provided by WHO in regularly updated position papers5. As the information provided in this chapter is limited, readers are encouraged to refer to WHO’s vaccine position papers and to national guidelines on routine vaccinations.

WHO recommendations for routine vaccinations can be found on the WHO website at the web page on WHO’s recommendations for routine immunization – summary tables.

1 International travel and health. See country list updated yearly on WHO’s ITH web page at: https://www.who.int/ith/en/
2 Global Polio Eradication Initiative. See map on website at: https://polioeradication.org
3 International Certificate of Vaccination or Prophylaxis. See: https://www.who.int/ihr/IVC200_06_26.pdf
4 International travel and health, see country list link from https://www.who.int/ith/en/
5 Vaccine position papers. See WHO website at: https://www.who.int/immunization/documents/positionpapers/en/

Information on the vaccine-preventable diseases and the relevant vaccines are set out below.

1) Cholera

Summary of vaccine data	Type of vaccine:	(a) Killed oral O1 whole-cell with B-subunit. (b) Killed oral O1 and O139.
	Number of doses:	(a) For individuals ≥ 6 years of age, two doses, and for children aged 2-5 years, three doses.The interval between doses should be ≥ 7 days and < 6 weeks. Booster doses are recommended after 2 years for individuals ≥ 6 years of age and every 6 months for children aged 2-5 years. If recommended intervals between the primary doses or between the last primary dose and a booster dose are exceeded, primary immunization should be repeated. (b) Two doses 14 days apart for individuals ≥ 1 year. One booster dose is recommended after 2 years for all age groups.
	Contraindications:	Hypersensitivity to previous dose.
	Adverse reactions:	Mild gastrointestinal disturbances.
	Consider for:	Travelers at high risk (e.g. emergency/relief workers), 2weeks before departure
	Special precautions:	None.
Cause		Vibrio cholerae bacteria of serogroups O1 and O139.
Transmission		Infection occurs through ingestion of food or water contaminated directly or indirectly by faeces or vomitus of infected individuals. Cholera affects only human beings; there is no insect vector or animal reservoir host.
Nature of the disease		An acute enteric disease varying in severity. Most infections areasymptomatic (i.e. they do not cause any illness). In mild cases, acute watery diarrhoea occurs without other symptoms. In severe cases, there is sudden onset of profuse watery diarrhoea with nausea and vomiting and rapid development of dehydration. In severe untreated cases, death may occur within a few hours due to dehydration leading to circulatory collapse.
Geographical distribution		Cholera occurs mainly in low-income countries that lack adequate sanitation and clean drinking-water and in areas affected by armed conflict or catastrophe where the infrastructure may have broken down. Many developing countries are affected, particularly in Africa and Asia and, to a lesser extent, in Central and South America.
Risk for travellers		The risk for most travellers is very low, even in countries where cholera epidemics occur, provided that simple precautions are taken. However, humanitarian relief workers in disaster areas and refugee camps may be at risk.
General precautions		As for other diarrhoeal diseases, the consumption of potentially contaminated food, drinks and water should be avoided. Oral rehydration salts should be carried to combat dehydration and electrolyte depletion in case of severe diarrhoea. Cholera vaccination is not required as a condition of entry to any country.
Vaccine		An oral vaccine consisting of killed whole-cell V. cholerae O1 in combination with a recombinant B-subunit of cholera toxin (WC/rBS) has been marketed since the early 1990s. This killed vaccine is well tolerated and confers high-level (about 85%) protection for 6 months after the second dose in all vaccinees aged over 2 years. Two years after immunization, protective efficacy has dropped to about 60%, and after 3 years the level of protection is only 0-18%. Primary immunization consists of two oral doses ≥ 7 days (but < 6 weeks) apart for adults and children aged 6 years and over. For children aged 2–5 years, three doses are recommended. Intake of food and drinks should be avoided for 1 hour before and after vaccination. If the second dose is delayed for more than 6 weeks, vaccination should be restarted. Following primary immunization, protection against cholera may be expected after about 1 week. Booster doses are recommended after 2 years for adults and for children aged 6 years or more, and every 6 months for children aged 2–5 years. The appropriate primary immunization must be repeated for the two groups if > 2 years and > 6 months respectively have passed since administration. The vaccine is not licensed for children under 2 years of age. In studies of travellers to areas reporting cholera outbreaks, WC/rBS was found also to induce short-term protection against diarrhoea caused by enterotoxigenic Escherichia coli in about 50% of those vaccinated. Two closely-related bivalent oral cholera vaccines are available in India and Viet Nam. These killed whole-cell vaccines are based on V. cholerae serogroups O1 and O139 and do not contain the toxin Bsubunit. They are reported to be safe and efficacious in individuals ≥ 1 year of age, providing 66-67% protection for at least 2 years against clinically significant cholera in countries or areas reporting outbreaks.

2) Hepatitis A

Summary of vaccine data	Type of vaccine:	Inactivated or live attenuated hepatitis A virus vaccines are licensed for intramuscular administration in a two-dose series. In addition the live attenuated vaccine can be administered as a single subcutaneous dose.
	Schedule:	The minimum age is 1 year for both inactivated and live attenuated hepatitis A virus vaccines. Inactivated vaccine: a complete vaccination schedule as recommended by the manufacturer consists of two doses. The interval between the first (primary) dose and the second (booster) dose is flexible (from 6 months up to 4–5 years), but is usually 6–18 months. In healthy individuals, a single dose seems to be similarly efficacious and only one dose is recommended for long-term protection. Live vaccine: one dose.
	Contraindications:	Severe allergic reaction to previous dose.
	Boosters:	Not necessary.
	Adverse reactions:	Inactivated vaccine: mild local reaction of short duration, mild systemic reaction. Live vaccine: few reported.
	Recommended for:	Hepatitis A vaccination should be considered for persons aged ≥ 1 year who are travelling to countries or areas of intermediate or high endemicity (given up to the day of travel). Those at high risk of acquiring severe disease, such as immunosuppressed patients and patients with chronic liver disease, should be strongly encouraged to be vaccinated regardless of where they travel. In addition, people at increased risk of hepatitis A including men who have sex with men, those requiring life-long treatment with blood products, and people who inject drugs should be vaccinated.
	Special precautions:	None.
Cause	Hepatitis A virus (HAV).
Transmission	The virus is acquired through close contact with infected individuals or through faecally contaminated food or drinking-water. There is no insect vector or animal reservoir.
Nature of the disease	Acute viral hepatitis is characterized by abrupt onset of fever, malaise, nausea and abdominal discomfort, followed by jaundice a few days later. In very young children infection is usually mild or asymptomatic, whereas in older children symptomatic disease is common. The disease is often more severe in adults and full recovery may take several months. The case-fatality rate is greater than 2% for those over 40 years of age and about 4% for those aged 60 years or more.
Geographical distribution	Worldwide, but most common in areas where sanitary conditions are poor.
Risk for travelers	Non-immune travelers to developing countries are at significant risk of infection, particularly in settings with poor food and drinking-water control and poor sanitation. People born and raised in developing countries, and those born before 1945 in industrialized countries, have usually been infected with HAV in childhood and are likely to be immune.
General precautions	Avoid or boil potentially contaminated food and water. Short-term protection through injection of human immune globulin is gradually being replaced by hepatitis A vaccination.
Vaccine	Two types of hepatitis A vaccines are currently used worldwide, namely formaldehyde-inactivated vaccines and live attenuated vaccines. Both types are safe and highly immunogenic and provide long-lasting, possibly life-long, protection against hepatitis A in both children and adults. 1) Formaldehyde-inactivated vaccines: Inactivated hepatitis A virus vaccines are used in most countries. Monovalent inactivated vaccines are available in both paediatric dose (0.5 mL) for children aged 1–15 years and adult dose (1 mL). Traditionally, a two-dose schedule is recommended, particularly for immunocompromised persons. However, in healthy individuals, comparable effectiveness has been achieved with a single dose. A combined hepatitis A/typhoid (ViCPS) vaccine, administered as a single dose, confers high levels of protection against both of these waterborne 14 diseases. A combination vaccine that provides protection against both hepatitis A and hepatitis B should be considered for travellers who may be exposed to both organisms (see under hepatitis B vaccines). 2) Live attenuated vaccines (based on the H2 or LA-1 strain of HAV): These vaccines are manufactured in China and are available in several other countries. Presence of anti-HAV (IgG) antibodies was documented after 15 years in 72–88% of the vaccinees, implying that, in most cases, long-term protection against hepatitis A is achieved with live attenuated vaccines.

3) Hepatitis B

Summary of vaccine data	Type of vaccine:	Engerix-B or Recombivax HB Heplisav-B HepA-HepB (Twinrix)
	Schedule:	Adults: 2- or 3-dose series (2-dose series Heplisav-B at least 4 weeks apart [2-dose series HepB only applies when 2 doses of Heplisav-B are used at least 4 weeks apart] or 3-dose series Engerix-B or Recombivax HB at 0, 1, 6 months [minimum intervals: dose 1 to dose 2: 4 weeks / dose 2 to dose 3: 8 weeks / dose 1 to dose 3: 16 weeks]) or 3-dose series HepA-HepB (Twinrix at 0, 1, 6 months [minimum intervals: dose 1 to dose 2: 4 weeks / dose 2 to dose 3: 5 months]) Infants: The primary series of vaccination normally consists of one dose of monovalent vaccine at birth followed by two or three doses of monovalent or combined hepatitis B vaccine at intervals of one to several months.
	Contraindications:	Severe allergic reaction to previous dose.
	Boosters:	May take a booster after 10yrs, but generally immunity is life-long.
	Recommended for:	General All people age 18 years and younger. (CDC includes 18-year-olds in their child/teen immunization recommendations.) Anyone 19 years and older who wants to be protected from hepatitis B. People at risk for infection by sexual exposure Sex partners of people who are hepatitis B surface antigen (HBsAg)-positive. Sexually active people who are not in long-term, mutually monogamous relationships. People seeking evaluation or treatment for a sexually transmitted disease. Men who have sex with men. People at risk for infection by percutaneous or permucosal exposure to blood or body fluids Current or recent illegal injection drug users. Household contacts of people who are HBsAg-positive. Residents and staff of facilities for developmentally challenged people. Healthcare and public safety workers with reasonably anticipated risk for exposure to blood or blood-contaminated body fluids. People with end-stage renal disease, including predialysis, hemo-, peritoneal- and home-dialysis patients. Others International travelers to regions with intermediate or high levels of endemic HBV infection. People with chronic liver disease. People with HIV infection. People with diabetes who are age 19 through 59 years. For those age 60 and older, clinicians should make a determination of need for vaccination based on their patients’ situation.
	Special precautions:	None.
Cause	Hepatitis B virus (HBV).
Transmission	May be transmitted perinatally from infected mothers to babies, through injection or transfusion of contaminated blood products, or through penetration of the skin with contaminated needles. In addition, hepatitis B can be transmitted by unprotected sexual intercourse
Nature of the disease	When contracted perinatally or in early childhood, the infection is rarely symptomatic but is likely to develop into chronic liver disease that may develop into cirrhosis and/or cancer in the course of decades. Infection in older children and adults more often causes acute hepatitis, but rarely chronic liver disease.
Geographical distribution	Prevalence assessments are based on presence of hepatitis B virus surface antigen (HBsAg) in serum. The highest prevalences are found in some African and eastern Asian countries with low coverage of hepatitis B vaccination. In well-vaccinated populations of industrialized countries the prevalence of hepatitis B is mostly low. Globally, very high prevalence rates may be found among certain sex workers and injecting drug users.
Risk for travellers	The risk for non-immune travellers depends mainly on personal risktaking behaviour and the prevalence of HBsAg in the concerned population. Except for nosocomial infection during emergency admission to poorly equipped health-care facilities, the risk of contracting hepatitis B is unlikely to be increased for the average traveller.
Vaccine	The active ingredient of hepatitis B vaccine is HBsAg. The primary series of vaccination normally consists of one dose of monovalent vaccine at birth followed by two or three doses of monovalent or combined hepatitis B vaccine at intervals of one to several months. For older children and adults, three doses at appropriate intervals are recommended, using a monovalent or, conveniently, a combined hepatitis A and B vaccine.

4) Human Papilloma Virus (HPV)

Cause	Human papillomavirus (HPV).
Transmission	Sexual contact.
Nature of the disease	Although mostly causing a transient benign mucosal infection, HPV may occasionally lead to the development of anogenital precancerous conditions and cancers. In women, persistent infection with specific oncogenic types of HPV (most frequently types 16 and 18) may lead to precancerous lesions which, if untreated, may progress to cervical cancer. Some types of HPV may cause anogenital warts and recurrent respiratory papillomatosis.
Geographical distribution	HPV is prevalent globally. The incidence of cervical cancer is highest in Latin America and the Caribbean, sub-Saharan Africa, Melanesia, and southern Asia.
Risk for travellers	Transmission of HPV occurs most commonly through sexual activity.
General precautions	As for other diarrhoeal diseases, the consumption of potentially contaminated food, drinks and water should be avoided. Oral rehydration salts should be carried to combat dehydration and electrolyte depletion in case of severe diarrhoea. Cholera vaccination is not required as a condition of entry to any country.
Vaccine	Three vaccines against HPV infection are available: • 2-valent (types 16 and 18) • 4-valent (types 6, 11, 16 and 18) • 9-valent (above plus 5 additional types: 31, 33, 45, 52, and 58). For protection against cervical cancer, vaccination of girls aged 9–14 years is recommended as the vaccines are most efficacious when administered before the start of sexual activity. At least two doses are required, with a minimum interval of 5 months between doses. High vaccination coverage in girls also results in herd protection for boys. The immunization of multiple cohorts of girls aged 9–14 years is recommended when the vaccine is first introduced for faster populationlevel impact. If resources are available, the age range could be expanded up to 18 years.

5) Pneumococcal Disease

Cause	Many serotypes of the bacterium Streptococcus pneumoniae.
Transmission	Inhalation of respiratory droplets containing Streptococcus pneumoniae.
Nature of the disease	The most common non-invasive pneumococcal infections include diseases of the upper respiratory tract and non-bacteraemic pneumonia. Pneumonia with empyema and/or bacteraemia, febrile bacteraemia and meningitis are the commonest manifestations of invasive pneumococcal infection. Resistance of these bacteria to commonly-used antibiotics is of increasing concern. Both non-bacteraemic pneumonia and invasive pneumococcal infections are associated with considerable mortality, particularly in young children, older persons and immunodeficient individuals.
Geographical distribution	Worldwide
Risk for travellers	Before travelling to countries with limited access to modern health-care facilities, vaccination against invasive pneumococcal disease is advisable for children < 2 years of age and for children and adults considered to be at particular risk of serious disease.
Vaccine	1) Conjugate vaccines that include 10 (PCV10) or 13 (PCV13) pneumococcal serotypes. These pneumococcal conjugate vaccines (PCVs) are safe and efficacious and may be used from the age of 6 weeks. PCV10 and PCV13 are licensed for immunization against invasive disease, pneumonia and acute otitis media caused by the 31 respective vaccine serotypes of S. pneumoniae. 2) A pneumococcal polysaccharide vaccine that includes 23 serotypes (PPV23). This vaccine is licensed for individuals aged 2 years or older. It is safe and efficacious against invasive pneumococcal disease and pneumonia in healthy young adults but shows limited efficacy in other age groups, including elderly persons.

6) Poliomyelitis (Polio)

Summary of vaccine data	Type of vaccine:	Orally administered, live attenuated polio vaccine (OPV) and inactivated poliovirus vaccine (IPV) for intramuscular (or subcutaneous) injection.
	Number of doses:	The primary series consists of three doses of OPV plus one of IPV. In countries at high risk of importation and subsequent spread of poliovirus, WHO also recommends an OPV dose at birth (“zero dose”). Provided that there is low risk of importation and a high rate of immunization coverage, routine vaccination using IPV followed by OPV can be used. Routine vaccination with IPV alone is recommended only in countries with immunization coverage > 90% and a low risk of wild poliovirus importation. WHO no longer recommends an OPV-only vaccination schedule.
	Contraindications:	Severe allergy to vaccine components.
	Adverse reactions:	The only serious adverse events associated with OPV are the rare occurrence of vaccineassociated paralytic poliomyelitis (VAPP) and the emergence of vaccine-derived polioviruses (cVDPV). OPV may safely be administered to pregnant women and HIV-infected persons.
	Travellers Info:	Travellers from polio-free to polio-endemic countries should have completed polio vaccination according to their national immunization schedule. Incomplete polio vaccinations should be completed. It is particularly important that persons living in countries with active transmission of poliovirus (including vaccine-derived virus) should be fully vaccinated. In addition, travellers from such countries should receive a dose of OPV or IPV at least 4 weeks before (and within 12 months of) departure.
	Special precautions:	Before issuing an entry visa, some polio-free countries require a certificate of recent polio vaccination from travellers coming from polio affected countries. In some cases, an additional dose of polio vaccine is provided on arrival.
Cause	Poliovirus types 1 and 3 (type 2 has been eradicated)
Transmission	Polioviruses are spread predominantly by the faecal–oral route although the oral–oral route may also be common.
Nature of the disease	Poliomyelitis, also known as polio or infantile paralysis, is a disease of the central nervous system. Following primary asymptomatic infection of the alimentary tract by poliovirus, paralytic disease develops in less than 1% of cases. In developing countries, 65–75% of cases occur in children under 3 years of age and 95% in children under 5 years of age. The resulting paralysis is permanent, although some recovery of function is possible. There is no cure.
Geographical distribution	Worldwide, sustained use of polio vaccines since 1988 has led to a > 99% drop in the global incidence of poliomyelitis and the number of countries with endemic polio has fallen from 125 to 3 (Afghanistan, Nigeria and Pakistan). Globally, the last case of poliomyelitis caused by naturally circulating wild-strain polioviruses type 2 occurred in India in 1999. No case due to wild-strain polioviruses type 3 has been detected since November 2012. In 2015, 73 polio cases were reported, all due to wild-strain poliovirus type 1. This represents the lowest number of any calendar year on record. However, despite a continued downward trend in the number of cases in 2016, the risk of new outbreaks following virus importation into polio-free countries with low population immunity persists as long as transmission continues in the remaining endemic countries.
Risk for travellers	Until the disease has been certified as eradicated globally, the risks ofacquiring polio (for travellers to infected areas) and of reinfection of polio-free areas (by travellers from infected areas) remain. All travellers to and from countries and areas infected by wild poliovirus or circulating vaccine-derived polioviruses (cVDPV) should be adequately vaccinated. Updates on currently or recently infected countries can be found on the website of the Global Polio Eradication Initiative.
General precautions	As for other diarrhoeal diseases, the consumption of potentially contaminated food, drinks and water should be avoided. Oral rehydration salts should be carried to combat dehydration and electrolyte depletion in case of severe diarrhoea. Cholera vaccination is not required as a condition of entry to any country.
Vaccine	Both orally-administered, live attenuated polio vaccines (OPV) and inactivated poliovirus vaccines (IPV) for intramuscular (or subcutaneous) injection are widely used internationally. IPV is considered very safe, and although OPV is a live attenuated vaccine it may safely be administered to pregnant women and HIV-infected persons. However, a rare adverse event associated with OPV is vaccineassociated paralytic poliomyelitis (VAPP), which occurs once in about 2.4 million doses. Outbreaks of polio due to cVDPV continue to be detected occasionally, mainly in areas of low immunization coverage. WHO no longer recommends an OPV-only vaccination schedule. For all countries currently using OPV only, at least one dose of IPV should be added to the schedule. In polio-endemic countries and in countries at high risk of importation and subsequent spread, WHO also recommends an OPV dose at birth (“zero dose”), followed by the primary series of three OPV doses and at least one IPV dose The primary series consisting of three OPV doses plus one IPV dose can be initiated from the age of 6 weeks with a minimum interval of 4 weeks between the OPV doses. Routine vaccination with a sequential schedule using IPV followed by OPV can also be used in countries with a low risk of importation of poliovirus and a high vaccination coverage rate. Routine vaccination with IPV alone should be used only in countries with high vaccination coverage (> 90%) and at low risk of importation and spread of wild poliovirus. Before travelling to areas with active poliovirus transmission, travellers from polio-free countries should ensure that they have completed the age-appropriate polio vaccination series, according to their respective national immunization schedule. Travellers to polio-infected areas who completed an OPV or IPV vaccine series > 12 months previously should be given another one-time booster dose of polio vaccine.Travellers to polio-infected areas who have not received any polio vaccine previously should complete a primary schedule of polio vaccination before departure Before travelling abroad, persons of all ages residing in polio-infected countries (i.e. those with active transmission of a wild or vaccinederived poliovirus) and long-term visitors to such countries (i.e. persons who spend more than 4 weeks in the country) should have completed a full course of vaccination against polio in compliance with the national schedule. Travellers from infected areas should receive an additional dose of OPV or IPV within 4 weeks to 12 months of travel in order to boost intestinal mucosal immunity and reduce the risk of poliovirus shedding, which could lead to reintroduction of poliovirus into a poliofree area. For persons who previously received only IPV, OPV should be the choice for the booster dose, if available and feasible. In case of unavoidable last-minute travel, travellers who have not received a documented dose of polio vaccine within the previous 12 months should still receive one dose of OPV or IPV before departure. Some polio-free countries require resident travellers and long-term visitors from polio-infected countries to provide documentation of recent vaccination against polio in order to obtain an entry visa, or they may require travellers to receive an additional dose of polio vaccine on arrival, or both.

7) Rota Virus

Cause	Strains of highly contagious rotaviruses.
Transmission	Mainly by the faecal-oral route, and by direct or indirect contact.
Nature of the disease	Rotavirus infection is characterized by watery diarrhoea, vomiting and fever mainly in children aged < 2 years. Severe cases may require rapid rehydration therapy, especially in young infants.
Geographical distribution	Worldwide it is a leading cause of dehydrating diarrhoea, but fatal outcomes occur predominantly in low-income countries.
Risk for travellers	Unvaccinated children < 2 years of age are likely to be at increased risk of rotavirus infection in environments of poor hygiene. The risk for older children and adults, most of whom are immune, is negligible.
Vaccine	Two live attenuated oral vaccines are available; one based on a single rotavirus strain (monovalent), the other on five rotavirus strains (pentavalent). When administered according to the respective national recommendations (or following the schedule of routine vaccination against DTP), these vaccines are efficacious and safe.

8) Yellow Fever

Summary of vaccine data	Type of vaccine:	Live attenuated
	Number of doses:	One dose of 0.5 mL.
	Boosters:	A single dose of yellow fever vaccine provides life-long immunity to the disease, making boosters unnecessary. From July 2016 the certificate of vaccination against yellow fever is valid for the life of the person (traveller) vaccinated.
	Contraindications:	Infants aged < 6 months; history of severe allergy to egg or to any of the vaccine components, or hypersensitivity to a previous dose of the vaccine; thymoma or history of thymectomy; immunodeficiency from medication; disease or symptomatic HIV infection.
	Adverse reactions:	Very rare, neurological (encephalitis, acute disseminated encephalomyelitis, Guillain-Barré syndrome etc.) or multi-organ failure resembling wild-type yellow fever.
	Recommended for:	All travellers to countries and areas with risk of yellow fever transmission and when required by countries.
	Special precautions:	Not recommended for infants aged 6–8 months,except during epidemics when the risk of yellow fever virus transmission may be very high. The risks and benefits of vaccination in this age group should be carefully considered before vaccination. The vaccine should be used with precaution during pregnancy or breastfeeding. However, pregnant or breastfeeding women may be vaccinated during epidemics or if travel to a country or area with risk of transmission is unavoidable.
Cause	Yellow fever virus.
Transmission	Yellow fever occurs in urban and rural areas of Africa and Central and South America. In jungle and forest areas, monkeys are the main reservoir of the infection which is spread by mosquitoes from monkey to monkey and, occasionally, to human beings. In urban settings, mosquitoes transmit the virus from person to person, and introduction of infection into densely populated urban areas can lead to large epidemics of yellow fever. In Africa, an intermediate pattern of transmission is common in humid savannah regions where mosquitoes infect both monkeys and human beings, causing localized outbreaks.
Nature of the disease	Although most infections are asymptomatic, some lead to an acute illness characterized by two phases. Initially, there is fever, muscular pain, headache, chills, anorexia, nausea and/or vomiting, often with bradycardia. About 15% of infected persons progress to a second phase after a few days, with resurgence of fever, development of jaundice, abdominal pain, vomiting and haemorrhagic manifestations; up to half of these patients die 10–14 days after the onset of illness.
Geographical distribution	In tropical areas of Africa and Central and South America (see maps) yellow fever virus cannot be transmitted at altitudes > 2300 metres. The number of countries or areas where yellow fever virus is present far exceeds those officially reported. Some countries may have no reported cases simply because of a high level of vaccine coverage against yellow fever, or because of poor surveillance. .
Risk for travellers	Besides areas of high yellow fever endemicity, transmission of yellow fever virus may also take place in areas of low endemicity if the traveller’s itinerary results in heavy exposure to mosquitoes (e.g. during prolonged travel in rural areas). A valid certificate of vaccination against yellow fever may be required for visitors to and from an area at risk of yellow fever transmission.
General precautions	Avoid mosquito bites; the highest risk for transmission of yellow fever virus is during the day and early evening.
Vaccine	Yellow fever vaccine is highly effective (approaching 100%). A single dose of yellow fever vaccine is sufficient to confer sustained life-long protective immunity against yellow fever disease; a booster dose is not necessary. Yellow fever vaccine may be administered simultaneously with other vaccines. As a general rule, any live vaccine may be given either simultaneously or at an interval of 4 weeks. Oral polio vaccine may be given at any time in relation to yellow fever vaccination. Vaccine should be offered to all unvaccinated travellers aged > 9 months, travelling to and from at-risk areas, unless they belong to the group of individuals for whom yellow fever vaccination is contraindicated. Vaccination is recommended, if indicated, for pregnant or breastfeeding women travelling to endemic areas when such travel cannot be avoided or postponed. Yellow fever vaccine may be offered to asymptomatic HIV-infected persons with CD4+ T-cell counts ≥ 200 cells/mm³. Although there are limited data on safety and immunogenicity of yellow fever vaccine when used in HIV-infected children, yellow fever vaccine may be administered to all clinically healthy children. HIV testing is not a prerequisite for vaccination. Adverse reactions Non-serious adverse events, such as headache, myalgia, low-grade fever, discomfort at the injection site, pruritus, urticaria and rash were reported by 7–25% of vaccinees in endemic countries. Very rare, but serious adverse events following vaccination with yellow fever vaccine fall into three categories, as follows: 1) Immediate severe hypersensitivity or anaphylactic reactions. 2) Yellow fever vaccine-associated neurological disease, a group of neurological conditions caused either by direct viral invasion of the central nervous system by the vaccine virus resulting in meningitis or encephalitis, or by an autoimmune reaction resulting in conditions such as Guillain-Barré syndrome or acute disseminated encephalomyelitis. 3) Yellow fever vaccine-associated viscerotropic disease, which is caused by replication and dissemination of the vaccine virus in a manner similar to the natural virus. People with this condition typically develop multi-organ system dysfunction or failure and > 60% of cases have been fatal. The risk of adverse effects looks possibly higher in persons aged ≥ 60 years, but the overall risk remains low. The reported rate for yellow fever vaccine-related adverse events following immunization in mass campaigns in endemic regions was 0.05 per 100 000 administrated doses.

References

1.WHO

2. CDC