Ideally, vaccination should occur when an individual is healthy, thus minimizing the risk of an adverse host reaction and/or vaccine failure. However, a current or recent infection does not necessarily preclude the use of vaccines, depending on the severity of the patient's symptoms and their etiology. Superficial infections and minor acute illnesses such as a mild upper respiratory infection with or without low-grade fever do not contraindicate immunization, particularly if prompt administration of a vaccine is deemed necessary or beneficial. In fact, when vaccines are administered during the course of a minor illness, the risk of adverse events is not increased, and serum antibody response is not often diminished. On the other hand, if fever or symptoms suggest a moderate or severe illness, it is usually appropriate to withhold vaccination until the patient has recovered. In addition to the potential risks already mentioned, evolving signs and symptoms of the illness can sometimes confound the diagnosis of a vaccine reaction if it develops. In the presence of any infection, the decision to administer or withhold/defer immunization should take into consideration the benefits versus the risks to an individual patient.

In patients with thrombocytopenia or coagulation disorders, intramuscular injections may produce bleeding and hematomas. Patients with a platelet count less than 50,000/mm3 are at an increased risk. Caution is advised if the vaccine (e.g., plague vaccine, hepatitis A and B vaccines, and aluminum-adsorbed DTaP, DTP, DT, or Td) must be administered intramuscularly. The risk of bleeding may be minimized by vaccination immediately after the administration of replacement factor, use of a 23-gauge (or smaller) needle, and immediate application of direct pressure to the vaccination site for at least 2 minutes.

Hepatitis B vaccine (adult and pediatric) is usually for intramuscular administration. However, it may be administered subcutaneously to persons at risk for hemorrhage following intramuscular injections (e.g., hemophiliacs), although it may result in lower antibody response. Additionally, when other aluminum- absorbed vaccines have been administered subcutaneously, an increased incidence of local reactions including subcutaneous nodules has been observed. Therefore, consider subcutaneous administration only in persons who are at risk of hemorrhage following intramuscular injections.

Hepatitis B vaccine should be deferred for infants with a birth weight less than 2,000 grams if the mother is documented to be HBsAg negative at the time of the infant's birth. If the mother is HBsAg positive (or the status cannot be determined), the infant should receive the vaccine within 12 hours after birth.
Apnea following intramuscular vaccination has been observed in some infants born prematurely and the decision to administer any intramuscular vaccine, including hepatitis B vaccine, should be based on consideration of the infant's medical status, and the potential benefits and risks of vaccination. Close monitoring is recommended.

The expected serum antibody responses may not be obtained when vaccines and/or toxoids are administered to patients with primary or acquired immunodeficiency, including those with severe combined immunodeficiency, hypogammaglobulinemia or agammaglobulinemia, HIV infection, altered immune states (due to diseases such as leukemia, lymphoma, or generalized malignancy), or immunosuppression due to drug or other treatments (e.g., corticosteroids, alkylating agents, antimetabolites, or radiation).