Vaccination in Practice and Public Health — Questions

• Severe combined immunodeficiency (SCID): a live vaccine can cause prolonged or disseminated infection.
• Previous intussusception, or an uncorrected congenital gastrointestinal malformation predisposing to it.
• Severe hypersensitivity to a previous dose or to a vaccine component.
• Outside the age window: the course must not be started or completed late (no dose after 24 weeks of age), a timing restriction rather than a true contraindication but applied strictly.

• (a) False. Inactivated influenza vaccine is recommended, not contraindicated, in pregnancy and in HIV at any CD4 count; it is non-live and safe, and both pregnancy and HIV raise the risk of severe influenza.
• (b) True. HPV vaccination is recommended for HIV-infected people regardless of CD4 count, ART use or viral load, including men who have sex with men up to about 40 years, because of their high HPV-associated cancer risk.
• (c) True. Hepatitis A vaccine is inactivated and safe in HIV; the standard two-dose schedule is appropriate, and chronic liver disease is itself an indication. Checking post-vaccination antibody is reasonable, as the response may be reduced.
• (d) False. The varicella vaccine is live and contraindicated at a CD4 count of 150 cells/uL. Give varicella-zoster immunoglobulin (VZIG) for post-exposure prophylaxis instead.

A complete answer first checks existing immunity, then separates live from inactivated vaccines and sequences the doses within the time available.

Assessment first. Take a vaccination history and, where useful, check serology (measles, rubella, varicella, hepatitis B). Do a pregnancy test: the live vaccines (MMR and varicella) are contraindicated in pregnancy, and pregnancy should be avoided for one month after them.

Live vaccines (give on the same day, or at least 4 weeks apart).

• MMR: one or two doses depending on documented immunity.
• Varicella: two doses 4 to 8 weeks apart if there is no history or evidence of immunity.

Inactivated vaccines (flexible timing, may be co-administered at separate sites).

• Hepatitis A: two doses at 0 and 6 to 12 months.
• Hepatitis B: three doses at 0, 1 and 6 months (an accelerated 0, 7, 21 days plus a 12-month dose if time is short). Combined hepatitis A and B is an option.
• Typhoid: single-dose Vi polysaccharide (inactivated).
• Polio: an inactivated polio (IPV) booster.
• dTaP: a single adult Tdap dose, reviewing tetanus and diphtheria status.

A workable sequence. Day 0: MMR, varicella (1), hepatitis A (1), hepatitis B (1), IPV, Tdap and typhoid together at separate sites. Then varicella (2) at 4 to 8 weeks; hepatitis B (2) at 1 month and (3) at 6 months; hepatitis A (2) at 6 to 12 months. Document everything for the destination country’s entry requirements.

A complete answer gives the rationale, the vaccine and its evidence, the alternative passive approach, and the caveats.

Rationale. RSV causes its most severe disease in the first months of life, before an infant can mount a good vaccine response. Maternal IgG crosses the placenta, so immunising the mother in pregnancy delivers protective antibody to the newborn at exactly the vulnerable time.

The vaccine. A recombinant pre-fusion F protein vaccine given in pregnancy (around 28 to 36 weeks) raises maternal neutralising antibody that is transferred to the fetus.

Evidence. Maternal vaccination reduces severe RSV lower-respiratory-tract disease in the first months of life.

The alternative. A long-acting monoclonal antibody given to the infant (nirsevimab) provides the same protection passively and directly, and is an option where maternal vaccination is not used.

Caveats. The timing window matters for adequate antibody transfer, preterm infants may receive less, and safety in pregnancy and around gestational age has been a focus of evaluation.

A complete answer lists the priority groups, gives the rationale, and critiques the strategy.

Priority groups. Pregnant women; people living with HIV; those with chronic cardiac, pulmonary, renal or metabolic disease; the elderly; and healthcare workers. The very young are also at higher risk.

Rationale. The inactivated vaccine is safe in pregnancy and in HIV, and reduces severe disease and complications in exactly these higher-risk groups, where influenza adds to an already heavy respiratory and HIV/TB burden.

Critique. Influenza vaccine sits outside the routine EPI, so delivery and coverage are limited; the egg-based vaccine can mismatch the circulating strain; and annual reformulation and re-vaccination are needed. In a resource-constrained system a targeted risk-group strategy, rather than universal vaccination, is the appropriate use of limited doses, though cell-based and mRNA vaccines may improve the match in future.

A complete answer states the disease burden, explains how the vaccine works and its proven efficacy and safety, describes the local programme, and directly addresses common concerns.

The disease burden

Cervical cancer is a leading cause of cancer death among South African women, and the burden is amplified by HIV, which accelerates HPV-driven disease. HPV types 16 and 18 cause about 70% of cervical cancer, and almost all cervical cancer is caused by persistent high-risk HPV infection.

How the vaccine works and its efficacy

The vaccine is a non-infectious virus-like particle that raises type-specific neutralising antibody, preventing the persistent infection that leads to precancer and cancer. Vaccinated populations show large falls in high-risk HPV infection, genital warts and high-grade precancer, and early evidence of falling cervical cancer.

Safety

The HPV vaccine has an extensive safety record across tens of millions of doses. It does not cause infertility, does not affect future sexual behaviour, and the common complaints are transient injection-site reactions. Safety is continuously monitored and reported.

The South African programme

The public programme vaccinates girls through schools, at an age that protects them before exposure. Vaccinating before sexual debut gives the greatest benefit.

Addressing hesitancy

Vaccination is a means of preventing a cancer, not a statement about a child’s future behaviour; high uptake also protects the wider community, and transparent safety surveillance is what allows rare problems to be detected and acted on.

Circulating vaccine-derived poliovirus (cVDPV) arises when the live oral vaccine strain reverts toward virulence and spreads in under-immunised communities. It drives the move to newer oral vaccine strains and to inactivated vaccine.

The other terms describe naturally circulating virus or unrelated immunological phenomena.

Measles has a very high basic reproduction number (R0) of roughly 12 to 18, so the herd-immunity threshold, approximately 1 minus 1/R0, is about 95%. This is why measles is the first disease to return when coverage slips.

Lower figures suffice for less transmissible viruses but leave measles able to spread.

South Africa gives the hepatitis B birth dose only to infants of HBsAg-positive mothers (a targeted policy), with routine hepatitis B otherwise delivered inside the hexavalent vaccine from 6 weeks. A universal birth dose, which the World Health Organization recommends, is not yet policy and is a recognised gap.

The other options misstate the current schedule.

Immune pressure can select hepatitis B surface-antigen (HBsAg) escape mutants whose altered surface antigen is less well recognised by vaccine-induced and therapeutic antibody.

The effect is limited where the surface antigen is structurally constrained; the other options do not occur.

The oral rotavirus course must be completed early, with no dose given after 24 weeks of age, because the small risk of intussusception rises with age at first dose. South Africa uses a two-dose schedule at 6 and 14 weeks.

The other options are not contraindications to the vaccine.

The public programme gives HPV vaccine to girls only, as a single dose, delivered through schools.

Boys are not covered in the public sector, and the private sector offers multi-dose schedules to both sexes.

Cocooning is vaccinating those around a vulnerable person who cannot be effectively vaccinated, so the virus cannot reach them.

Ring vaccination targets the contacts around a case during an outbreak; herd immunity is the population-level version of the same idea.

Phase III trials, in thousands to tens of thousands of participants, test protective efficacy and detect less common adverse events. Phase I addresses first-in-human safety and dose, phase II the immune response and schedule, and phase IV post-licensure surveillance.

Manufacturing scale-up is not the trial’s purpose.

NAGI is South Africa’s national immunisation technical advisory group, providing the evidence-based advice that shapes the EPI schedule and policy.

Adverse events are handled by SAHPRA and the National Immunisation Safety Committee, and polio certification sits with separate committees.

Smallpox is the only eradicated human disease, declared in 1980. The animal morbillivirus rinderpest followed in 2011. Polio and measles are current eradication targets but are not yet eradicated.

The others remain in circulation.

The Global Influenza Surveillance and Response System (GISRS) monitors circulating influenza worldwide and recommends each season’s vaccine strains, twice a year, once per hemisphere.

The other bodies handle polio, vaccine safety, routine immunisation delivery and acute flaccid paralysis surveillance respectively.

Eradication is permanent worldwide reduction to zero, after which vaccination can stop; elimination is zero cases in a defined area, sustained by continued vaccination because the virus persists elsewhere.

The other options reverse or conflate the two.

Inactivated influenza vaccine is recommended in every pregnancy, protecting the mother and, through transferred antibody, the newborn.

The live vaccines (intranasal influenza, MMR, varicella and yellow fever) are all contraindicated in pregnancy.

The early 6-month dose is a deliberate measles-control measure in a setting of intense transmission and high HIV prevalence, protecting infants sooner. It is off-label against the 9-month licensed minimum and does not replace the later dose.

The other options are not the rationale.

Passively acquired maternal IgG neutralises the live measles vaccine in early infancy, causing primary vaccine failure, so the first dose is delayed until maternal antibody has waned. South Africa gives it at 6 months as a measles-control compromise.

The vaccine is live rather than inactivated, and the other options are not the reason.

• Oral poliovirus (bivalent OPV) at birth, and inactivated poliovirus (IPV) within the hexavalent vaccine.
• Hepatitis B: within the hexavalent vaccine from 6 weeks, plus a birth dose for infants of HBsAg-positive mothers.
• Rotavirus: at 6 and 14 weeks.
• Measles-rubella (MR): at 6 and 12 months.
• HPV: girls, single dose, from around 9 years.

(The hexavalent vaccine carries the polio and hepatitis B components alongside the bacterial diphtheria, tetanus, pertussis and Hib antigens.)

Withheld live vaccines: BCG, oral poliovirus vaccine, rotavirus vaccine and the measles-containing vaccine.

Why: in symptomatic HIV or AIDS the impaired cellular immunity cannot reliably control even an attenuated vaccine strain, risking disseminated vaccine-strain infection.

Children with asymptomatic HIV receive all EPI vaccines, and an additional early measles dose is given to HIV-infected infants because of their higher risk of severe measles.