Indications for the immunization of selected risk groups

Immunization during pregnancy

Many authors take the conservative position that the use of vaccines during pregnancy should generally be avoided at any stage of the pregnancy, since definitive studies on the level of risk have not been carried out.

Other authors take a more balanced position: They consider that there is no convincing evidence that pregnancy should be an absolute contraindication to the use of standard vaccines. With regard to live vaccines, only smallpox vaccine has been shown to cause fetal malformation. Despite concerns that attenuated rubella vaccine virus might cause congenital abnormalities, rubella vaccine (either monovalent or as MMR) has been given to pregnant women (usually inadvertently) without harm to the fetus. Even though the rubella vaccine virus can infect the fetus if given in early pregnancy, there is no evidence that it causes congenital rubella syndrome in infants born to susceptible mothers immunized during pregnancy, and rubella immunization during pregnancy is not an indication for termination. To date, congenital varicella syndrome has not been identified in women who have been accidentally immunized in early pregnancy. Furthermore, no evidence exists of risk from immunizing pregnant women with inactivated virus or bacterial vaccines or toxoids.

Resulting from these considerations the following is concluded:

- Although only of theoretical concern, pregnancy is a contraindication for measles, mumps, rubella, and varicella vaccines. Women of child-bearing age should avoid becoming pregnant for 1 month after immunization

- Persons who receive MMR vaccine do not transmit the vaccine viruses to contacts; transmission of varicella vaccine virus to contacts has been reported, but is rare. MMR and varicella vaccines could be administered, when indicated, to the children and other household contacts of pregnant women

- If a pregnant woman is likely to be at significant risk of an infection that can be prevented by other live (other than MMR or varicella vaccines), inactivated or toxoid vaccines, then the vaccine should be used: In case of a significant risk of poliomyelitis, IPV can be given if the series of injections can be completed before the anticipated exposure; pregnant women who must travel to areas where the risk for yellow fever is high should receive yellow fever vaccine, because the limited theoretical risk from immunization is substantially outweighed by the risk for yellow fever. Conversely, if the risk of infection from a particular disease is not immediate and significant, then the relevant vaccine should not be used, or its use should be postponed until after the pregnancy. In some cases, changing travel plans can eliminate the risk of exposure and therefore the need for immunization.

- Women in the second and third trimesters of pregnancy have been demonstrated to be at increased risk for hospitalization from influenza. Therefore, routine influenza immunization is recommended for healthy women who will be beyond the first trimester of pregnancy (i.e., a 14 weeks of gestation) during influenza season. Women who have medical conditions that increase their risk for complications of influenza should be immunized before the influenza season, regardless of the stage of pregnancy [8, 17].

Immunization of pre-term babies

Despite their immunological immaturity, pre-term babies should be immunized according to the recommended schedule and precautions at the usual chronological age, provided that they are doing well and that there are no contraindications to vaccination. Birth weight and size are not factors in deciding whether to postpone routine vaccination of a clinically stable premature infant, except for hepatitis B vaccine (see below). OPV, which might spread the live vaccine virus to other babies in the hospital, should not be given until the time of discharge. Alternatively, IPV can be used.

Studies have demonstrated that decreased seroconversion rates might occur among certain premature infants with low birth weights (i.e., < 2000 g) after administration of hepatitis B vaccine at birth. However, by chronological age 1 month, all premature infants, regardless of initial birth weight or gestational age are as likely to respond as adequately as older and larger infants. A premature infant born to HBsAg-positive mothers and mothers with unknown HBsAg-status must receive immunoprophylaxis with hepatitis B vaccine and hepatitis B immunoglobulin (HBIG) s 12 h after birth. If these infants weigh < 2000 g at birth, the initial vaccine dose should not be counted towards completion of the hepatitis B vaccine series, and three additional doses of hepatitis B vaccine should be administered, beginning when the infant is age 1 month. The optimal timing of the first dose of hepatitis B vaccine for premature infants of HBsAg-negative mothers with a birth weight of < 2000 g has not been determined. However, these infants can receive the first dose of the hepatitis B vaccine series at chronological age 1 month. Premature infants discharged from the hospital before chronological age 1 month can also be administered hepatitis B vaccine at discharge, if they are medically stable and have gained weight consistently.

All pre-term babies born at less than 28 weeks of gestation or with chronic lung disease should be offered the 7-valent pneumococcal conjugate vaccine at 2, 4 and 6 months of age with a fourth dose at 12-18 months of age, and a 23-valent pneumococcal polysaccharide vaccine booster during the 3rd year of life [8, 17].

Immunization of individuals with chronic diseases

Chronic diseases (such as asthma, chronic lung and heart diseases, congenital heart diseases, cystic fibrosis; celiac disease; diabetes and other metabolic diseases; renal dysfunction, nephrotic syndrome and other chronic organ failures; stable neurological conditions and Down's syndrome) in children and adults increase the risk from infectious diseases and are known to predispose to complications of infectious diseases.

In general, children and adults belonging to these groups at risk should be immunized according to the schedules recommended in a given country and as a matter of priority. The small potential risk from immunization outweighs by far the much greater risk from complications of vaccine-preventable disease. Although the considerations are valid for the majority of immunizations in children and adults with chronic diseases, the risks from influenza and pneumococcal disease and their prevention through immunization should be considered as a matter of priority. This includes the use of influenza vaccine in severe asthma, chronic lung disease, congenital heart disease and Down's syndrome; pneumococcal conjugate vaccine in children with renal failure, persistent nephrotic syndrome and certain anatomical abnormalities; and pneumococcal polysaccharide vaccine in adults with certain chronic medical conditions mentioned above. Note: Recommendations for use of influenza and pneumococcal polysaccharide vaccine are somewhat similar; the two vaccines can be co-administered at the same visit [7, 8].

Immunization of individuals with impaired immunity

Immunodeficiency conditions are grouped into primary and secondary disorders. Primary disorders are inherited and include humoral (B lymphocyte) immunodeficiencies, cell-mediated (T lymphocyte) immunodeficiencies, disorders of the complement and phagocytic function. Secondary disorders are acquired and occur in individuals with HIV infection, asplenia, malignant neoplasms, transplantation(s) or immunosuppressive or radiation therapy [18].

The immunization of individuals with impaired immune systems presents several problems. Firstly, the immune response to vaccines may be inadequate and, secondly, there is a risk that some live vaccines may themselves cause progressive infection. Degrees of immunodeficiency vary from insignificant to profound, and this should be taken into account when considering a schedule of vaccination, as should the risk of acquisition of the infection one is trying to prevent. Although it may be logical to give higher or more frequent doses of vaccines to these patients, in many cases there are insufficient data to advocate such measures. Because of the uncertainty of the immune response in some immunodeficient patients, it may be useful to measure post-vaccination antibody titers in groups such as children who have received hemopoietic stem cell transplants.

Concerning vaccine response and immunodeficiency, considerable data on immunization in HIV-infected individuals, particularly children, are available, and provide valuable reassurance about immunogenicity, effectiveness and safety of vaccines administrated to the immunocompromised, whereas experience with immunization in persons with other specific disorders is lacking and mainly based on theoretical considerations. Moss and colleagues [19] have recently provided an overview on the most important studies of immunization in HIV-infected children. Table 3 summarizes the data on immunogenicity and effectiveness.

The studies under review show wide variations in the age of immunization, the number of vaccine doses received, the interval between immunization and assay, the type of antibody assay used and the degree of immuno-suppression. In general, seroconversion rates and geometric mean titers are lower in HIV-infected children than in uninfected children and infected children are more likely to lose antibody within few years after immunization. Placental transfer of maternal antibodies may be impaired in HIV-infected women. This correlates with an improved response to measles vaccine administered at 6 months of age. Studies in progress evaluate the immunogenicity of measles immunization at 6 and 9 months of age in HIV-infected children. Experience in southern Africa suggests that the measles incidence can be reduced in regions of high HIV prevalence by maintaining high immunization coverage coupled with periodic supplemental campaigns.

Current general recommendations for vaccine use in immunodeficient individuals

For immunodeficient individuals, the general recommendations are: - BCG and smallpox vaccines are always contraindicated - OPV should not be given to the patient or to the patient's parents or siblings; IPV should be used instead.

Table 3. Immunogenicity and effectiveness of immunization in HIV-infected children (adapted from [19])

Vaccine Sero- Geometrie Antibody per- Booster conversion mean titer sistence response

Effectiveness Studie Field rate


tetanus toxoid

Pertussis (wP/aP)


Lower than in uninfect-ed children

Lower than uninfected children

More rapid decline than in uninfected children

Hepatitis B 25-50%

More rapid decline than in uninfected children

Hib conjugated

Lower than uninfected children

More rapid decline than in uninfected children

No effect in children after extra or higher doses

Rapid antibody increase due to immuno-

logical memory no long-term follow-up studies


No data available

Pneumo- Better antibody response coccal to conjugated vaccine than that of PS vaccine

In Ugandan adults 23-valent PS vaccine did not prevent invasive disease

Polio vaccine

Measles Yellow fever

Tuberculin test not a good predictor of protection; no data to permit definite conclusions re effectiveness of BCG in HIV-infected children

No studies; polio eliminated from several high HIV prevalence countries

17-100%, median value 60%

Much lower than in uninfected children

More rapid decline than in uninfected children

Generally poor

- Immunodeficient travelers should not be given live oral cholera or typhoid vaccines; Vi polysaccharide typhoid vaccine should be used instead.

- Yellow fever vaccine is only indicated if the patient must travel to an area where there is a high risk of yellow fever. Most immunodeficient patients should obtain exemption certificates of immunization ratified by health authorities and immigration departments where international immunization requirements are the only reason for yellow fever immunization. MMR and varicella-zoster vaccines may be given to children with HIV infection who do not have evidence of severe immunosuppression.

- Contacts of immunodeficient patients: healthy siblings and close contacts of immunodeficient children should be immunized with MMR and varicella-zoster vaccines to prevent them from infecting their immunodefi-cient sibling; there is no risk of transmission of the MMR vaccine viruses and there is an almost negligible risk of transmission of varicella-zoster vaccine virus; these close contacts should be given IPV and not OPV when being given routinely scheduled vaccines.

- Morbidity and mortality from influenza and invasive pneumococcal disease are increased in all significantly immunodeficient patients. They should receive annual influenza immunization and either 7-valent pneu-mococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine, depending on their age; although the immune response to pneu-mococcal polysaccharide vaccine may be suboptimal in those individuals, the vaccine is nevertheless strongly recommended [5, 7, 8, 17].

Immunization and corticosteroid administration

In adults, daily doses of oral corticosteroids in excess of 60 mg prednisolone (or equivalent), and in children doses in excess of either 2 mg/kg per day for more than 1 week or 1 mg/kg per day for more than 4 weeks, are associated with significant immunodeficiency. However, even lower doses may be associated with some impairment of immune response. For adults treated with systemic corticosteroids in excess of 60 mg/day, live vaccines (such as MMR, OPV, varicella-zoster and BCG) should be postponed until at least 3 months after treatment has stopped. Children on daily doses of 2 mg/kg per day of prednisolone or equivalent for less than 1 week, and those on lower doses or alternate-day regimens for longer periods, may be given live virus vaccines. The use of inhaled steroids is not a contraindication to the use of live vaccines [8].

Recommendations for immunization of HIV-infected children and women of childbearing age

In collaboration with UNICEF, WHO has established guidelines [20] for immunization of HIV-infected children and women of childbearing age with recommended vaccines (Tab. 4). It is recommended that individuals with known or suspected asymptomatic HIV infection receive all recommended vaccines as early in life as possible, according to the nationally

Table 4. WHO/UNICEF recommendations for immunization of HIV-infected children and women of childbearing age [20]

Vaccine Asymptomatic Symptomatic Optimal timing of

HIV infection HIV infection immunization

Table 4. WHO/UNICEF recommendations for immunization of HIV-infected children and women of childbearing age [20]

Vaccine Asymptomatic Symptomatic Optimal timing of

HIV infection HIV infection immunization








6,10,14 weeks




0, 6, 10, 14 weeks




6 and 9 months

Hepatitis B



As for uninfected children

Yellow fever



Tetanus toxoid



5 doses

*IPV can be used as an alternative for children with symptomatic HIV infection

*IPV can be used as an alternative for children with symptomatic HIV infection recommended schedules. Because of the risk of early and severe measles infection, these infants should receive a dose of standard measles vaccine at 6 months of age with a second dose as soon after age 9 months as possible. Individuals with symptomatic HIV infection can receive all recommended vaccines except BCG and yellow fever vaccines. In asymptomatic children, the decision to give BCG should be based on the local risk of tuberculosis (TB): where the risk of TB is high, BCG is recommended at birth or as soon as possible thereafter, in accordance with standard policies for immunization of non-HIV-infected children; in areas where the risk of TB is low, but BCG is recommended for routine immunization, BCG should be withheld from individuals known or suspected to be infected with HIV.

Similar recommendations exist in many countries, as an example the recommendations of the (US) Advisory Committee on Immunization Practices (ACIP) for immunization of immunocompromised children [21] are provided in Table 5. There are minor differences between recommendations for HIV-infected and other immunodeficient children. Currently, IPV is used as the vaccine of choice without any contraindication due to immunodeficiency.

Immunization of patients with MS

Adults with MS should be given influenza and pneumococcal polysaccha-ride vaccines. There is clear evidence that these patients have an increased risk of complications following natural influenza and pneumococcal disease, whereas the administration of these vaccines is not associated with an increased risk of exacerbations of MS [8, 17].

Table 5. Contraindications for childhood vaccines - ACIP [6, 7]

Vaccines Immunize?


Family history

Note 1: Do not give OPV to a member of a household with a family history of immunodeficiency until the immune status of the recipient and other children in the family is documented Note 2: Varicella vaccine should not be administered to a person with a family history of congenital or hereditary immunodeficiency in parents or siblings unless that person's immune competence has been clinically substantiated or verified by a laboratory

In household contact In recipient

(hematological and solid tumors, congenital immunodeficiency, long-term immunosuppressive therapy, including steroids) Note 3: Varicella vaccine should not be administered to persons who have cellular immunodeficiencies, but persons with impaired humoral immunity may be vaccinated. A protocol exists for use of varicella vaccine in patients with acute lymphoblastic leukemia (ALL).

HIV infection

In recipient (asymptomatic)



Note 4: Varicella vaccination should be considered for


See Note 4

asymptomatic or mildly symptomatic HIV infected children


See Note 5

with age-specific T cell percentages of 25% or higher

All others


Note 5: MMR vaccination is recommended for all

asymptomatic HIV-infected persons who do not have

evidence of severe immunosuppression and for whom

measles vaccination would otherwise be indicated

In recipient (symptomatic)



Note 6: MMR vaccination should be considered for all


See Note 4

symptomatic HIV-infected persons who do not have evidence


See Note 6

of severe immunosuppression or of measles immunity

All others


In household contact



All others


Immunization of patients with bleeding disorders and patients receiving anticoagulant therapy

Intramuscular injection may lead to hematoma formation in patients with bleeding disorders and to pressure necrosis, muscle contractures or nerve compression in patients with severe coagulopathies. On the other hand, these patients have an increased risk for acquiring hepatitis B and at least the same risk as the general population of acquiring other vaccine-preventable diseases. When hepatitis B or any other vaccine is indicated for a patient with a bleeding disorder or a person receiving anticoagulant therapy,

OPV Varicella All others

See Note 1 See Note 2 Yes

OPV All others

OPV MMR Varicella All others

No Yes

No No

See Note 3 Yes the vaccine could be administered intramuscularly if, in the opinion of a physician familiar with the patient's bleeding risk, the vaccine can be administered with reasonable safety by this route. A fine needle (s 23 gauge) should be used for the immunization and firm pressure applied to the site, without rubbing, for a 2 min. The patient or family should be instructed concerning the risk for hematoma from the injection. Patients with platelet counts of less than 50 x 109/L should not receive intramuscular injections. The subcutaneous or intracutaneous route should be considered as an alternative to the intramuscular route in patients with bleeding disorders. Children with inherited coagulopathies should receive factor replacement prior to intramuscular injection [8, 17].

Immunization of recent recipients of human immunoglobulin

With the exception of yellow fever vaccine, the immune response to live viral vaccines may be inhibited by normal human immunoglobulin. Therefore, live virus vaccines should be given 3 weeks before or 3 months after a dose of immunoglobulin. If an individual is under medical treatment with high-dose or intravenous immunoglobulin, the physician who initiated this treatment should be consulted [8].

Immunization and breast-feeding

Breast-fed infants should be immunized according to routinely recommended schedules. Although live vaccines multiply within the mother's body, the majority has not been demonstrated to be excreted in human milk. Rubella vaccine virus might be excreted in human milk. However, the virus usually does not infect the infant. Where infection has occurred in an infant, it has been mild because the virus is attenuated. Inactivated, recombinant, subunit, polysaccharide, conjugate vaccines and toxoids pose no risk for mothers who are breast-feeding or for their infants [8, 17].

Special recommendations for the immunization of hematopoietic stem cell transplant (HSCT) recipients and for solid organ recipients before transplantation exist [22-25].

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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