Vaccines against viral diseases

Summary

• Most vaccines against viral infections are effective at preventing disease
• However, they are not 100% effective for a number of reasons
• Reactions can occur after vaccinations
• The viral vaccines in the national immunisation programme are polio, measles and Hepatitis B

In support of vaccination

It is difficult for many of us today to appreciate the dangers of childhood viral infections. In the 1950’s, hundreds of children were crippled by polio, and as recently as the 1970’s, hundreds more died every year in South Africa from measles. Polio and measles are now rare thanks to successful vaccination programmes, and, because the serious consequences of such diseases are no longer familiar, we have ceased to fear them. Thus we can become blasé about the need to vaccinate our children, or dwell on possible vaccine side effects, both real and rumoured. However, the incidence of polio and measles is still significant in neighbouring countries such as Zimbabwe, Angola and Mozambique, where vaccination programmes have broken down through war and social upheaval. These diseases can rapidly re-enter South Africa if they are given the opportunity - and the opportunity they require is simply enough unvaccinated children.

Routine immunisation schedule in South Africa

• At birth (OPV, BCG)
• 6 weeks (OPV, DTP, HBV, Hib)
• 10 weeks (OPV, DTP, HBV, Hib)
• 14 weeks (OPV, DTP, HBV, Hib)
• 9 months (Measles)
• 18 months (OPV, DTP, Measles)
• 5 years (OPV, DT)

BCG = bacillus Calmette-Guérin (tuberculosis) vaccine primarily preventing TB meningitis in infants
OPV = oral polio vaccine
DTP = diphtheria, tetanus, pertussis (whooping cough) vaccine
DT = diphtheria, tetanus vaccine
HBV = hepatitis B vaccine
Hib = Haemophilus influenza group b (meningitis) vaccine

These vaccines have been grouped together so that they can be conveniently received at regular intervals. They are commonly known as the vaccines belonging to the “Expanded Programme for Immunisation” or EPI which is a strategy supported by the World Health Organisation to prevent childhood infections and ultimately attain the goal of “health for all”. Different countries in the world usually have different EPI programmes. In most developing countries there is an accelerated EPI with a decreased gap between the early vaccinations to ensure that infants receive their vaccines before they are lost to the health care system.

The different vaccine combinations at each time point do not interfere with one another and there is no increased risk of serious side-effects when they are given at the same time.

The EPI schedule includes both bacterial and viral vaccines. In this article, however, only viral vaccines will be discussed. The viral vaccines in the national immunisation programme are:

• Polio
• Measles
• Hepatitis B

Optional extra viral vaccines available in South Africa through the private sector:

• Rubella (German Measles) and Mumps, given with the measles vaccine in the “MMR” vaccine
• Influenza
• Varicella (Chickenpox)
• Hepatitis A
• Rabies

General information about vaccines

How effective are vaccines?

Most of the vaccines in use against viruses are very effective at preventing disease. However, for a variety of reasons, they can fail:

• The vaccine becomes inactive due to incorrect storage, if used past its expiry date, or if incorrectly administered.
• Individuals unpredictably fail to produce an adequate immune response to the vaccine.
• Vaccine immunity “fades” over time.

Overall, about one in 20 people will contract an infection that they were vaccinated against. Usually, such people will get a milder infection than they would have otherwise.

Vaccine reactions

Reactions can occur after vaccinations. The following are the general types of reactions that may occur:

Mild reactions:

• Mildly elevated temperature
• Headache
• Feeling unwell
• Soreness at vaccination site

Severe reactions:

(Rare, but more often associated with pertussis and influenza vaccines.)

These reactions occur within 48 - 72 hours of vaccination and include:

• Extensive, hard, red swelling around the vaccination site
• Fever above 39.5 degrees Celsius
• Convulsions (Pertussis)
• Decreased level of consciousness (Pertussis)
• Prolonged inconsolable screaming (Pertussis)

Anaphylactic (allergic) reactions:

Very rare. Anaphylactic reactions occur within a few minutes to a few hours after vaccination. Similar reactions may also occur after other kinds of drug injections. Anaphylactic reactions are a medical emergency. An anaphylactic reaction may have any of the following symptoms:

• Sudden collapse, with a weak pulse and loss of consciousness (must be distinguished from a faint, which is more common)
• A more gradual onset, with sweating, swelling of the skin (hives), difficulty breathing, swelling of the throat, hoarseness, wheezing, dizziness, fast pulse, paleness

A register of all known side effects with viral vaccines is maintained in the USA and in most European countries. This allows the analysis and follow up of all side effects associated with vaccinations in these countries. Based on data from this register, vaccines are generally regarded as very safe when compared to other medicines.

Risks attached to specific vaccines are mentioned under the descriptions of these in the following section.

Vaccines for specific viral infections

Hepatitis A

The hepatitis A vaccine is a new vaccine that has become available in South Africa relatively recently. A dose of the vaccine contains a minute amount of hepatitis A virus that has been chemically inactivated or “killed”. It is given by injection, usually in two doses one month apart.

Hepatitis A is very common in countries like South Africa and usually occurs in young children between the ages of one and four years. Because hepatitis A tends to be a mild disease in children and does not cause permanent liver damage or become chronic, it is not currently considered a high enough health priority for routine vaccination of children in this country. However, very rarely, in about 1% of cases, hepatitis A infection can be very serious causing severe liver damage and death in infected chilren. Hepatitis A is generally a more unpleasant and potentially serious illness in adults, and vaccination is recommended for the following groups:

• Health care workers
• Staff in centres where young children are cared for
• Clients and staff in institutions for the mentally handicapped
• Workers in the food industry
• Travellers from countries with low rates of hepatitis A who will be visiting countries where the disease is prevalent, namely: Africa, Central and South America, the Caribbean, Mexico, Asia (other than Japan), Southern and Eastern Europe
• Persons with other liver diseases

If given between 24-72 hours after exposure to an infected person, the vaccine may work to prevent hepatitis A, but this use for the vaccine is still being confirmed with large numbers of cases from around the world. In cases of recent exposure, the vaccine can be given concurrently with immunoglobulin (antibodies harvested from blood donors). However, in general, if an individual is exposed to a heptitis A infected person, immunoglobulins are given immediately as a preventative measure.

Hepatitis B

In order to develop immunity to hepatitis B infection, one needs to produce antibodies to the surface protein (surface antigen) or outside coat of the virus that encases it. The hepatitis B vaccine therefore contains only the viral surface antigen known as hepatitis B antigen (HBsAg for short). For one type of vaccine against hepatitis B, the surface antigen is obtained from the blood of people who are chronic carriers of the virus. This is the so-called “plasma-derived” hepatitis B vaccine. During preparation, the surface antigen is highly purified so that there is no risk of catching hepatitis B or other blood-borne infections. For the second type of vaccine, yeast is genetically engineered to produce hepatitis B surface antigen. The surface antigen is collected from the cultured yeast. This is the so-called “recombinant” hepatitis B vaccine. The plasma-derived vaccine costs about a tenth of the recombinant vaccine and is used for routine childhood immunisation in South Africa. The vaccine is given by injection in three doses, each a month apart (see schedule above). It is important to have at least a month between vaccine doses and to make sure that children get all three doses of the vaccine to get a good immune response.

Who should be vaccinated against hepatitis B?

Hepatitis B is very prevalent in children and adults in South Africa, and is highly infectious. About 10% of people who get hepatitis B become chronically infected, with increased risk of kidney disease, liver cirrhosis and liver cancer.

Vaccination against hepatitis B has been part of the routine childhood immunisation programme since 1995. Unvaccinated children under 18 years old, and adults in high risk groups, should also receive the vaccine. High risk groups for hepatitis B include:

• Health care workers
• Family and close contacts of hepatitis B carriers
• Anyone with more than one sexual partner
• People with renal failure receiving haemodialysis
• Haemophiliacs and others who require frequent blood products
• Intravenous drug users

Babies of mothers who are infected with hepatitis B should receive the vaccine and hepatitis B immunoglobulin at birth. This has been shown in the published literature to be the most effective way to prevent transmission of hepatitis B infection from the mother to her infant. However, in South Africa, it is too expensive for the government to provide routine blood tests to screen mothers to check their hepatitis B status and then to also administer hepatitis B immunoglobulin at birth to the infant. This option is therefore only available to mothers and infants being treated at private health care facilities.

Who should not be vaccinated against hepatitis B?

• Persons who have severe allergy to baker’s yeast should not receive the recombinant vaccine.
• If you or your child is extremely ill when the vaccine is due, you can delay vaccination until the child has recovered.

About 95% of people will respond to the full three-dose course of the hepatitis B vaccine. For persons in whom successful vaccination is essential, such as health care workers, a blood test can be done to check the level of antibody to surface antigen (“surface antibody”). A surface antibody level of >100 international units per ml is desirable, however a reponse with an antibody level of >10 international units is considered protective. A fourth booster dose may be necessary to achieve an adequate response in some cases.

Some people who do not respond to the recombinant vaccine may respond to immunisation with the plasma-derived vaccine. There is also a new type of genetically modified vaccine with different parts of the hepatitis B antigen included known as “pre S1, pre S2” vaccines. These vaccines have shown to be particularly useful in individuals that are resistant to the usual hepatitis B immunisation programmes.

The most common reasons why some individuals are resistant to hepatitis B immunisation includes; heavy smokers, obese individuals and unknown or idiopathic reasons. Because one’s surface antibody levels tend to decrease over time, some specialists recommend a booster dose of vaccine every five years for those at high risk.

Although some experimental evidence suggests that boosters may be unnecessary if an initial adequate response was achieved, most immunisation programmes in high risk individuals like health care workers will insist on a booster vaccination.

Rabies

Most people who receive the rabies vaccine do so after potential exposure to animal rabies, usually through animal bites. Not all animal bites result in rabies (the animal must be carrying rabies), and there are guidelines as to when vaccination is necessary. However, rabies is fatal in almost every case, so the vaccine should be given even if there is only a small possibility of exposure. Rabies vaccine is available at public hospitals and through district surgeons.

The rabies vaccine is made of rabies virus grown in cell culture, and is then inactivated and purified. If given in advance of exposure, the rabies vaccine is given as three injections over a month. However, if given after an animal bite in someone who has not been vaccinated before, it is given as a course of five injections over a month. In the case of an animal bite, anti-rabies immunoglobulin is also given, to provide immunity until the vaccine takes effect. If both immunoglobulin and vaccination are given early and correctly, rabies can almost always be prevented.

Who should receive the rabies vaccine?

A person bitten by an animal should consult a health care professional as quickly as possible after the incident, and this should include an assessment of rabies risk. About 10 to 20 human cases of rabies occur in South Africa every year because people fail to seek or receive correct preventive treatment after an animal bite.

The following groups are at risk of rabies exposure and should be vaccinated in advance:

• Veterinarians, game rangers and staff and volunteers of animal welfare organisations
• Travellers (especially back packers) to areas with high levels of rabies such as Thailand, Central and Latin America, and West Africa.

Polio

Over 2000 polio cases were reported in Africa in 1995. An outbreak occurred in Namibia in 1993, with over 50 cases and again in 2006. Although South Africa's last case of polio was notified in 1991, this country has not yet been declared polio-free by the WHO, and therefore surveillance for the disease continues.

The polio virus multiplies in the gut, and only causes the disease “polio” or “infantile paralysis” when it travels from the gut to the spinal cord and brain.

The polio vaccine used in South Africa is the live or “Sabin” vaccine, received orally as “polio drops”. There are three strains of polio, and the vaccine protects against all three, so it is sometimes called “trivalent oral polio vaccine”. The polio vaccine is a weakened form of the natural or “wild” polio virus, which does not cause the disease polio. The vaccine prompts the immune system to produce antibodies in the gut and blood, so that if the wild polio virus should ever enter the gut, it is immediately neutralised and cannot migrate to the brain.

An alternative polio vaccine, the “Salk” vaccine, is used in some European countries and, recently, in the USA. This is a killed virus vaccine, given by injection. For several reasons, the oral trivalent Sabin polio vaccine is regarded as the more effective of the two vaccines, and is recommended for countries that are not polio free. However, the Sabin vaccine carries about a one in 750 000 risk that the live vaccine virus will revert to the virulent form, and cause polio in the vaccine recipient.

Because of this small risk of the oral polio vaccine reverting and causing polio in the vaccine recipient, and because there have been no cases of naturally occurring polio since 1991, the Department of Health in South Africa is considering changing the EPI programme to include the Salk or killed injectable polio vaccine. This adaptation of the EPI programme is commonly used in countries that have eliminated polio and usually entails receiving a combination of the killed injectable polio vaccination first, followed by the oral Sabin polio vaccine. However, this has not been fully implemented as part of the EPI in this country and is still under discussion.

Who should get vaccinated against polio?

All children should receive oral polio vaccine and unvaccinated adults should receive the injectable polio vaccine.

Who should not get vaccinated with OPV (oral polio vaccine)?

• Children with fever or diarrhoea should have vaccination delayed.
• Children with extreme sensitivity to certain antibiotics: the vaccine contains tiny amounts of antibiotics left over from the production process. If your child is allergic to antibiotics, discuss this with your health care professional before OPV vaccination.
• Children with HIV infection or any other type of immune deficiency should receive the Salk (killed) polio vaccine rather than the oral Sabin (live) vaccine.
• Adults should receive the injectable killed Salk polio vaccine.

Varicella (chickenpox)

The vaccine against chickenpox is a live, "handicapped" or attenuated form of the chickenpox virus known as the “Oka strain”. This vaccine, developed in Japan, has been given to over two million healthy children in Japan and Korea. It can be given to children older than 12 months, as a single dose. (It can conveniently be given together with the MMR vaccine.) Teenagers and adults should receive two doses, a month or two apart. Adults should consider being tested to see if they are already immune to varicella before receiving the vaccine, even if they do not recall having had chickenpox.

A small number of children may develop mild chickenpox after receiving the vaccine. The vaccine virus can be transmitted to other children not immune to varicella, who may similarly develop symptoms. A small number of children may develop shingles months to years after receiving the vaccine. There have been rare reported cases of severe side effects like encephalitis, ataxia (cerebellitis), and thrombocytopaenia (low blood platelets) after the vaccine.

Who should receive the chickenpox vaccine?

In some countries, such as the USA, the chickenpox vaccine is being recommended as a routine childhood vaccination or EPI vaccine. In South Africa, receiving the vaccine is a matter of individual choice, or may be recommended by a doctor for certain children who have conditions that put them at increased risk.

Who should not receive the chickenpox vaccine?

• Pregnant women. Non-pregnant women should avoid pregnancy for three months following the vaccine.
• People with an immunocompromising condition, including HIV/AIDS. In immunocompromised persons, the vaccine could cause disease indistinguishable from chickenpox itself. Also, anyone receiving the vaccine should avoid contact with immune compromised persons for six weeks afterwards.
• People on cortisone therapy may safely receive the vaccine, but this must be under medical supervision.
• Children who have acute lymphoblastic leukaemia in remission, may receive the vaccine, under medical supervision.
• People with extreme sensitivity to the antibiotic neomycin or to gelatin.
• People with active, untreated tuberculosis.
• Vaccination should be delayed in anyone with a fever.

Other precautions:

Aspirin and aspirin-containing drugs should be avoided for six months after the varicella vaccine.

Vaccinations for children with HIV/Aids

• Children with HIV/Aids particularly need protection against infections. Most of the childhood vaccines, in the usual doses and at the usual times, are recommended for children with HIV.
• Unfortunately, in HIV-infected children the damaged immune system is often only able to produce a reduced, and shorter-lived, response to vaccines.
• One risk of vaccination in HIV-infected children is that live vaccines, which are safe in other children, may persist and even cause disease. For this reason, the BCG vaccine (against tuberculosis) is not recommended in children who already have signs of immune suppression, and the live oral polio vaccine should be replaced by the killed vaccine. Measles has a live vaccine, but the risk of severe and even fatal natural measles infection in children with HIV is very high, so the measles or MMR vaccine should be given unless the child already has advanced immune suppression (This should be discussed with your health care professional.)
• Some additional vaccines, such as the influenza vaccine, are regarded as beneficial for children with HIV.
• Vaccinations and natural infections can cause a temporary increase in HIV replication and “viral load”, but most specialists believe that the risks associated with natural infections are far greater than the risk attached to vaccination.

A vaccine against HIV/Aids?

Although much hoped for, an effective preventative vaccine against HIV is unlikely to come into use in the next 10 years. Globally over 80 different HIV vaccine trials have been done with different vaccines, only two of these trials were done in Africa (Uganda and Kenya) and none have been done yet in South Africa. In South Africa, early safety trials with three different types of preventative HIV vaccines will be done during 2003. Developing a vaccine against HIV is technically difficult because of certain characteristics of the virus and the human immune response to HIV:

• There are many strains of HIV that would need to be covered by a vaccine
• The virus often enters the body hidden inside human cells. However, new information suggests that this may not be that important and a globally effective HIV vaccine can be made.
• The virus infects the very cells that should eliminate it (white blood cells of the immune system)
• The human immune response to HIV needs to activate two different pathways (antibodies and cellular immunity) in order to control HIV infection. Most other viral infections only require a good antibody response.

Traditional methods of producing vaccines have either proved ineffective (killed vaccine) or are considered too risky in the case of HIV (live vaccine). New ideas are being investigated urgently. The new ideas have included vaccines that will stimulate the human immune response to produce successful antibodies and cellular immune responses and include DNA vaccines and vectored vaccines. Preliminary data with these types of vaccines have been very encouraging. It is likely that the first preventative HIV vaccines will have only modest success (about 40-60% effective) in protecting against HIV infection, or may simply reduce the severity of the disease after infection.

South African scientists are actively involved in the search for an HIV vaccine. An exciting new field of HIV vaccine research is developing a therapeutic vaccine that can be given to already infected individuals to prevent progression of their HIV infection to Aids. These vaccines may have to be used in conjunction with some antiretroviral drugs or they may be used alone.

Reviewed May 2007 by Dr Diana Hardie, Clinical Virologist, employed jointly by the University of Cape Town and the National Health Laboratory Service (NHLS).
Reviewed by Dr Eftyhia Vardas BSc(Hons), MBBCh, DTM&H, DPH, FC Path (Virol), MMed (Virol), Clinical Virologist, Director HIV AIDS Vaccine Division, Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, University of the Witwatersrand and senior lecturer, Department of Infectious Diseases, Faculty of Health Sciences, University of the Witwatersrand.