Skin changes occurs after bcg vaccine
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Skin Changes After BCG Vaccination
Normal (Expected) Local Reaction - Sequence of Events
After a correct intradermal BCG injection, the following sequence of skin changes occurs at the injection site:
| Timeline | Change |
|---|---|
| Immediately after injection | A wheal of 5 mm diameter appears (confirms correct intradermal placement) |
| 2-3 weeks | A papule develops at the site |
| ~5 weeks | Papule slowly increases to 4-8 mm in diameter |
| 5-12 weeks | Papule subsides or breaks into a shallow ulcer, usually covered with a crust |
| 6-12 weeks | Spontaneous healing with a permanent, tiny, round scar (4-8 mm in diameter) |
| By 8 weeks (sometimes up to 14 weeks) | Individual becomes Mantoux-positive |
This entire progression is a normal, expected immune response to the live attenuated vaccine. - Park's Textbook of Preventive and Social Medicine
Note on overdosage: If an excessive dose is given, the local lesion and the resulting scar may be considerably larger and irregular in size.
Note on newborns (< 4 weeks): The dose is halved to 0.05 ml because the skin of newborns is thin - a full 0.1 ml dose may penetrate deeper tissue and cause local abscess formation and enlarged axillary (regional) lymph nodes.
Complications (Abnormal Skin/Local Reactions)
These occur in a minority of cases and depend on the BCG strain, dose, age, injection technique, and immune status of the recipient:
- Prolonged severe ulceration at the vaccination site (beyond normal healing)
- Suppurative lymphadenitis - occurs in 1-10% of vaccinations
- Local abscess formation - more likely if vaccine is injected subcutaneously instead of intradermally
- Osteomyelitis - rare
- Disseminated BCG infection - occurs in <1 per million vaccinations; usually associated with severe cellular immune deficiencies
Management of local abscess:
- First: Aspiration (if it does not clear spontaneously)
- If aspiration fails: Incision + daily local application of PAS or INH powder
- Systemic INH is NOT required
- The vaccination site should be strictly intradermal to prevent these complications
- No other injection should be given into the same arm for at least 6 months
Key Points to Remember
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The scar confirms vaccine receipt and is used by health surveyors - this is why BCG is given on the left upper arm (for uniformity and easy verification)
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No scar = not necessarily vaccine failure - there is no need to re-vaccinate even if no scar appears
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BCG is contraindicated in persons with primary or secondary immunodeficiencies, burns, or skin infections
-
Park's Textbook of Preventive and Social Medicine
Live vaccine Killed vaccine Conjugate vaccine
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Types of Vaccines: Live, Killed, and Conjugate
1. Live Attenuated Vaccines
Definition
Vaccines that use virus (or bacteria) mutants that antigenically overlap with wild-type pathogen but are restricted in some step in the pathogenesis of disease. They are attenuated (weakened) by repeated serial passages in animals or cell cultures of a different species, during which mutations accumulate.
How Attenuation Works
The pathogen is grown in non-human host cells until it can only grow poorly in human cells - it replicates enough to stimulate immunity but not enough to cause disease.
Advantages
- Single dose usually sufficient
- No adjuvant needed
- Longer-lasting immunity (acts like natural infection)
- Induces IgA + IgG (both mucosal and systemic antibodies)
- Good cell-mediated immunity (CD4 and CD8 T cells)
- Induces mucosal immunity at the portal of entry
Disadvantages
- Risk of reversion to virulence (e.g., OPV - Sabin polio vaccine can revert in immunodeficient hosts)
- Contraindicated in immunocompromised patients (can cause severe opportunistic infection)
- Limited shelf life - requires cold chain; low stability at room temperature
- Possible excretion and transmission to non-immune contacts
- May be interfered with by other viruses in the host
Examples
| Live Bacterial | Live Viral |
|---|---|
| BCG (tuberculosis) | Measles (MMR) |
| Typhoid (oral, Ty21a) | Mumps |
| Cholera (oral) | Rubella |
| Varicella (chickenpox) | |
| Yellow fever | |
| OPV (oral polio - Sabin) | |
| Rotavirus | |
| Influenza (intranasal) | |
| Zoster | |
| Smallpox (vaccinia) |
2. Killed (Inactivated) Vaccines
Definition
Made by purifying viral/bacterial preparations and then inactivating infectivity with minimal damage to the structural proteins. Mild formalin treatment is the most common method.
Mechanism
Stimulate the development of circulating antibody against coat proteins, conferring resistance. However, they do NOT replicate in the host.
Advantages
- No risk of reversion to virulence
- Can be made when no acceptable attenuated strain is available
- Safe in immunocompromised patients
- High stability at room temperature
Disadvantages
- Multiple doses required (need for boosters)
- Shorter duration of immunity
- Poor cell-mediated response
- Adjuvant required to boost immunogenicity
- Poor mucosal immunity
- Occasional hypersensitivity to subsequent infection
- Primarily induces IgG only
Examples
| Killed Bacterial | Killed Viral |
|---|---|
| Whole-cell pertussis | IPV (inactivated polio - Salk) |
| Typhoid (injectable) | Influenza (flu shot, intramuscular) |
| Cholera (injectable) | Hepatitis A |
| Plague | Rabies |
| Japanese encephalitis |
Comparison: Live vs Killed Vaccines
| Characteristic | Killed Vaccine | Live Vaccine |
|---|---|---|
| Number of doses | Multiple | Single |
| Need for adjuvant | Yes | No |
| Duration of immunity | Shorter | Longer |
| Mimics natural infection | Lower | Greater |
| Immunoglobulins produced | IgG only | IgA and IgG |
| Mucosal immunity | Poor | Yes |
| Cell-mediated immunity | Poor | Yes |
| Reversion to virulence | No | Possible |
| Vaccine virus transmission | No | Possible |
| Stability at room temperature | High | Low |
- Jawetz, Melnick & Adelberg's Medical Microbiology, Table 30-9
3. Conjugate Vaccines
The Problem They Solve
Bacteria like Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis have polysaccharide capsules that are the main virulence factor. The best defense is opsonizing antibody against the polysaccharide coat.
However, polysaccharides are T cell-independent antigens - they stimulate B cells directly but:
- Produce only short-lived IgM response (no memory)
- Children under 2 years cannot make good T cell-independent antibody responses
- No affinity maturation or isotype class switching
The Solution: Conjugation
The bacterial polysaccharide is chemically conjugated (linked) to a protein carrier (e.g., diphtheria toxoid, tetanus toxoid, CRM197 - a non-toxic diphtheria protein).
How It Works (Linked Recognition)
- B cell recognizes and binds the polysaccharide portion
- It internalizes and degrades the whole conjugate
- It presents peptides from the carrier protein on MHC class II
- Carrier-specific helper T cells (pre-primed by prior vaccination, e.g., DPT) recognize the peptide-MHC complex
- T cell delivers co-stimulatory signals (CD40L - CD40 interaction + cytokines)
- B cell activates, undergoes affinity maturation, isotype switching - producing high-affinity IgG against the polysaccharide
This converts a T cell-independent response into a T cell-dependent response - generating immunological memory and effective immunity even in infants <2 years. - Janeway's Immunobiology 10e
Examples of Conjugate Vaccines
| Vaccine | Polysaccharide | Carrier Protein |
|---|---|---|
| Hib vaccine | H. influenzae type b | Tetanus toxoid |
| PCV7/PCV13/PCV20 | Pneumococcal (7, 13, 20 serotypes) | Diphtheria CRM₁₇₇ protein |
| MenACWY | Meningococcal A, C, W, Y | Diphtheria toxoid or tetanus toxoid |
| MenC | Meningococcal group C | Diphtheria CRM₁₉₇ |
| Typhoid Vi conjugate | Salmonella typhi Vi antigen | Protein carrier |
Key Advantage Over Plain Polysaccharide Vaccines
-
Effective in children under 2 years (plain polysaccharide vaccines are NOT)
-
Generates immunological memory (plain polysaccharide vaccines do not)
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Booster effect - subsequent doses give stronger responses
-
Produces longer-lasting protection
-
Goodman & Gilman's The Pharmacological Basis of Therapeutics; Sherris & Ryan's Medical Microbiology; Janeway's Immunobiology 10e
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