Campak (Measles)

01Pathophysiology

Measles is caused by the Morbillivirus, a member of the Paramyxoviridae family. It is a single-stranded, negative-sense RNA virus with an envelope containing two critical surface glycoproteins: the hemagglutinin (H) protein, which binds to host cell receptors (CD46, SLAM/CD150, and nectin-4), and the fusion (F) protein, which mediates viral entry by fusing with the host cell membrane.

Transmission occurs through aerosolized respiratory droplets, and the virus can remain suspended in air for up to 2 hours after an infected person leaves the room. This explains why measles is extraordinarily contagious, with a basic reproductive number (R0) of 12 to 18, meaning a single infected individual can transmit the virus to 12-18 susceptible contacts. After inhalation, the virus initially infects epithelial cells of the respiratory tract and local dendritic cells and alveolar macrophages. These immune cells then carry the virus to regional lymph nodes, where the first round of viral replication occurs.

This is followed by a primary viremia (days 2-3 post-infection), during which the virus disseminates via the bloodstream to the reticuloendothelial system (spleen, liver, bone marrow, and additional lymph nodes). A secondary viremia (days 5-7) then spreads the virus to the skin, respiratory tract, and other organs, producing the clinical disease. The incubation period from exposure to symptom onset is typically 10 to 14 days.

The prodromal phase (lasting 2-4 days) is characterized by the "3 C's": cough, coryza, and conjunctivitis, along with high fever. These symptoms reflect direct viral cytopathic damage to respiratory and conjunctival epithelium. During this phase, Koplik spots appear on the buccal mucosa, which represent focal areas of epithelial necrosis and are considered pathognomonic for measles. Koplik spots typically appear 1-2 days before the rash and fade 1-2 days after the rash emerges.

The maculopapular rash that follows is largely an immune-mediated phenomenon. It results from the host's T-cell response targeting virus-infected endothelial cells in dermal capillaries, producing perivascular inflammation. The rash characteristically begins on the face and behind the ears (post-auricular region), then spreads downward to the trunk and extremities over 3-4 days. This craniocaudal progression is a key discriminator from other febrile exanthems. The rash typically fades in the same order it appeared (face first), sometimes leaving a brownish discoloration or fine desquamation.

A critical concept is measles-induced immune suppression. The virus has a tropism for CD150/SLAM-expressing memory lymphocytes, and infection leads to the destruction of pre-existing memory B and T cells. This phenomenon, called "immune amnesia," can persist for months to years after acute infection and leaves the patient vulnerable to secondary bacterial infections. This explains why post-measles pneumonia and otitis media are so common and why measles is associated with increased all-cause mortality for 2-3 years following infection.

Complications vary by age and immune status. Pneumonia (either primary viral or secondary bacterial) is the most common cause of measles-related death. Acute post-infectious encephalitis occurs in approximately 1 in 1,000 cases, typically 1-2 weeks after the rash, and is caused by an autoimmune demyelinating process. A rare but uniformly fatal late complication is subacute sclerosing panencephalitis (SSPE), a progressive degenerative CNS disease that manifests 7-10 years after the initial infection, caused by persistent defective measles virus in the brain.

02Classification and Clinical Manifestation

Clinical Phases of Measles

Classification by Severity

Complications

03Diagnostic Workup

The standard approach to diagnosing measles begins with clinical recognition of the classic triad (cough, coryza, conjunctivitis) with a craniocaudal maculopapular rash and high fever, particularly in an unvaccinated patient or one with known exposure. In most clinical and public health settings, measles-specific IgM serology is the best initial test. It should be drawn at the time of rash onset. However, a key caveat is that IgM can be falsely negative if obtained within the first 72 hours of rash onset, so if clinical suspicion remains high and the initial IgM is negative, repeat testing 3-4 days later is recommended.

RT-PCR from a nasopharyngeal or throat swab (or urine) is the most accurate confirmatory test. It is highly sensitive and allows genotyping, which is critical for distinguishing between wild-type measles and vaccine-strain virus, and for epidemiologic surveillance. RT-PCR can detect viral RNA from the prodromal phase through approximately 7-10 days after rash onset. For this reason, public health guidelines recommend obtaining both serology (IgM) and a viral specimen for RT-PCR whenever measles is suspected.

A paired acute and convalescent IgG titer showing a 4-fold rise provides retrospective confirmation, which is useful in diagnostically challenging cases but is less practical in acute management.

On laboratory studies, expect to see leukopenia (white blood cell count often below $4,000\mathrm{/}\mu L4,000/\backslash mu\; L$) with a predominant lymphocytopenia, reflecting the virus's tropism for lymphocytes. This finding can help distinguish measles from bacterial infections that typically produce leukocytosis. Thrombocytopenia may also be present in severe cases.

Histopathology is rarely needed for diagnosis, but when tissue is examined, Warthin-Finkeldey giant cells (multinucleated reticuloendothelial giant cells formed by fusion of virus-infected lymphoid cells) are pathognomonic. These can be found in the tonsils, adenoids, appendix, and respiratory epithelium.

Imaging is generally unnecessary unless complications are suspected. A chest radiograph should be obtained if the patient has persistent fever, tachypnea, or hypoxia suggesting pneumonia. Findings in measles pneumonia can range from interstitial infiltrates to lobar consolidation (if secondary bacterial pneumonia is present).

04Management and Treatment

Acute Stabilization and Supportive Care: There is no antiviral therapy with proven efficacy for routine measles. Management is primarily supportive. Fever should be treated with acetaminophen (paracetamol) 10-15 mg/kg/dose every 4-6 hours or ibuprofen 10 mg/kg/dose every 6-8 hours as needed. Adequate fluid intake must be maintained, especially in children at risk for dehydration due to fever, poor oral intake, or diarrhea.

Vitamin A Supplementation: This is one of the most tested points in exam vignettes. Vitamin A significantly reduces morbidity and mortality from measles, particularly in children with vitamin A deficiency. The WHO and AAP recommend vitamin A for all children with measles, regardless of their country of residence.

The dosing schedule is age-based and given orally once daily for 2 consecutive days:

• Children >= 12 months of age: 200,000 IU per dose

• Children 6-11 months of age: 100,000 IU per dose

• Children < 6 months of age: 50,000 IU per dose

A third dose should be given 2-4 weeks later if there is clinical evidence of vitamin A deficiency (e.g., xerophthalmia, Bitot spots). The mechanism of benefit relates to vitamin A's role in maintaining mucosal epithelial integrity and supporting T-cell-mediated immune responses.

Management of Complications: For secondary bacterial infections (pneumonia, otitis media), antibiotics should be chosen based on the most likely pathogen. Amoxicillin is a reasonable first-line agent for otitis media. For community-acquired bacterial pneumonia superimposed on measles, empirical coverage for Streptococcus pneumoniae and Staphylococcus aureus with an appropriate beta-lactam (e.g., amoxicillin-clavulanate or a parenteral cephalosporin if hospitalized) is indicated.

Ribavirin is an antiviral agent that has shown in vitro activity against measles virus. Its clinical use is limited to severe measles in immunocompromised patients, such as those with HIV/AIDS or patients on immunosuppressive therapy. It is not standard care for uncomplicated measles.

Acute post-infectious encephalitis is managed with supportive care, seizure management, and monitoring for elevated intracranial pressure. There is no established antiviral treatment for measles encephalitis. SSPE has no curative therapy; intrathecal interferon-alpha and inosiplex have been tried with limited benefit.

Post-Exposure Prophylaxis (PEP): This is a high-yield management question. The choice of PEP depends on the time since exposure and the patient's immune status:

• MMR vaccine should be given within 72 hours of exposure to susceptible individuals aged >= 6 months (this includes the early "zero dose" at 6-11 months, which does not count as a routine vaccine dose and requires re-vaccination at 12-15 months).

• Immunoglobulin (IG) should be given within 6 days of exposure for individuals who cannot receive MMR, including: infants < 6 months, pregnant women, and severely immunocompromised patients. The dose is 0.5 mL/kg IM (maximum 15 mL) or 400 mg/kg IV for immunocompromised patients.

• If more than 6 days have passed since exposure, neither MMR nor IG is effective as PEP.

Infection Control: All patients with suspected or confirmed measles must be placed on airborne isolation precautions (negative-pressure room, N95 respirators for healthcare workers). The infectious period extends from 4 days before to 4 days after rash onset. Immunocompromised patients may shed virus for a prolonged period and should remain in isolation for the entire duration of their illness.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The most common way students get measles questions wrong is by failing to recognize the chronologic relationship between Koplik spots and the rash. Koplik spots appear during the prodromal phase, 1-2 days before the rash, and fade shortly after the rash emerges. If the vignette describes a child in the prodromal phase (fever, cough, coryza, conjunctivitis with white spots on the buccal mucosa), the diagnosis is measles even though the rash has not yet appeared. Students who are anchored to the rash as the defining feature will miss this.

A second common trap involves the direction of rash spread. Measles rash spreads craniocaudally (head to toe). If a vignette describes a rash starting on the trunk or extremities and spreading upward, this should point away from measles and toward alternative diagnoses such as atypical measles, drug eruption, or secondary syphilis.

Students also frequently forget that vitamin A is indicated for all children with measles, not just those in developing countries or those with malnutrition. The exam tests whether you know to include vitamin A supplementation as part of the standard management plan.

Another tested concept is the timing of post-exposure prophylaxis. The critical cutoffs are: MMR vaccine within 72 hours and immunoglobulin within 6 days of exposure. Knowing who qualifies for which (pregnant women and immunocompromised patients get IG, not MMR) is a frequently examined decision point.

The concept of immune amnesia is increasingly tested in more advanced board-style questions. Students should understand that measles does not simply resolve. The destruction of memory lymphocytes leaves the patient immunologically vulnerable for months to years afterward, which is why measles vaccination prevents not only measles itself but also reduces overall childhood mortality from other infections.

Finally, be aware of the SSPE trap: if a vignette presents an adolescent with progressive cognitive decline, myoclonus, and behavioral changes with a history of measles in infancy, the answer is SSPE. Students may be drawn toward other neurodegenerative conditions, but the history of early measles infection combined with the long latency period is the critical clue.

The core competency being tested with measles questions is the ability to recognize the disease based on its clinical staging (prodrome with Koplik spots followed by craniocaudal rash), to distinguish it from other childhood exanthems using key discriminators, and to apply the correct management (vitamin A for all, PEP timing, and isolation precautions).