MEASLES

Measles (Rubeola) is the commonest vaccine-preventable illness, characterized by fever, upper respiratory tract infection and generalized maculopapular rash with self­limiting course, but high morbidity and mortality.

India contributes to highest number of measles cases in the world, though incidence has substantially declined in recent years. However, intermittent outbreaks are common, recent ones in Mumbai (2022) and Hyderabad (2023).

Epidemiology: Measles virus is an RNA virus of only one known serotype, present in nasopharyngeal secretions of infected clinical/sub-clinical human case. Infection is transmitted by droplet infection. Disease is highly contagious with secondary attack rate of as high as 80%, and period of infectivity extends from 4 days before to 5 days after the appearance of rash.

Maximum cases are seen in preschool children. Maternal antibodies in endemic regions protect infants till 4-6 months. Immunization or natural infection usually provides life-long immunity. Overcrowding and poor immunization coverage are two important predisposing factors for measles outbreaks in a community, more common in winter or spring season.

Pathogenesis: The sequence of events in pathogenesis of measles are: (a) local viral multiplication at the site of entry, i.e. nasopharynx, for short period, (b) transient, asymptomatic primary viremia, spreading virus to distant sites, specially lymphoid tissue, (c) active multiplication in lymphoid tissue for ~1 week, (d) symptomatic secondary viremia with development of clinical disease.

Essential pathology in measles is a generalized inflammatory reaction with perivascular infiltration, specially in skin (rash) and mucus membranes (Koplik spots) and lymphoid hyperplasia, specially in appendix with multinucleated giant cells (Warthin-Finkeldey cells).

Clinical manifestations: While subclinical infections are common, typical case presents after an incubation period of ~10-12 days, with three stages:

a. Prodromal phase (4-5 days) with mild to moderate fever, upper respiratory illness with cough, coryza, etc. and conjunctivitis. Conjunctivitis is characterized by a transverse line of inflammation across the bulbar conjunctiva, sharply demarcated along the lid margins. Koplik spots are pathognomic lesions in this stage, seen as grayish-white sandy dots surrounded by slightly reddish areola, usually opposite the lower molars on oral mucosa. These spots are present from 2-3 days before to 24 hours after the appearance of rash, and herald the onset of skin rash (Fig. 10.8).

b. Eruptive phase (5-7 days): Skin rashes appear on 4-5th day with transient rise of fever, starting as faint blanching macules, first along the hair-line behind the ears, face and neck. These rashes rapidly turn maculopapular and extend downward, involving whole body in next 2-3 days (Fig. 10.8). Rashes may be associated with moderate cervical lymphadenopathy, constitutional symptoms, e.g. anorexia/malaise, GIT upsets, e.g. diarrhea, vomiting or abdominal pain due to mesenteric lymphadenopathy.

c. Convalescent phase: Rashes disappear in the same sequence after 5-7 days, leaving behind a branny brown desquamation (post-measles staining) for next 10-15 days.

Fig. 10.8: Measles: (A) Active disease; (B) Post-measles staining.

GBS: Guillain-Barre syndrome

*due to blocked lumen by lymphoid hyperplasia **usually in second week, incidence ~ 1-2 per 1000 cases

Atypical presentations of measles include:

• Hemorrhagic (black) measles, a life-threatening illness in immunocompromised children, characterized by high fever, confluent ecchymotic rashes, altered sensorium and bleeding diathesis.

• Modified measles with transient, few and faint macu­lar rashes with minimal fever and constitutional symptoms, seen in immunized cases, young infants lt;9 months (due to maternal antibodies), or children who have received immunoglobulin prophylaxis in incubation period.

Complications: Although most cases recover spon­taneously, complications are common in older or mal­nourished children, specially during convalescent phase (Table 10.33).

Subacute sclerosing panencephalitis (SSPE) is a unique, rare and late complication of measles infection or vaccination, with an estimated incidence of ~ 8/ million cases or lt;1/million doses of vaccine. Clinically presenting as a neurodegenerative disease after at least 4 years of primary infection, SSPE represents slow viral infection of CNS (see Ch.18.15).

Diagnosis of measles is mainly clinical, based on: (a) history of ongoing outbreak and unimmunized child, (b) typical rash after 4^th-5^th day of prodromal illness, (c) presence of Koplik spots for early diagnosis, and (d) post­measles staining for retrospective diagnosis.

Laboratory confirmation is rarely required and includes: (a) serological testing with gt;4-fold rise in IgM antibodies after 15 days, (b) viral culture on human embryonic or rhesus monkey kidney cells, (c) supportive evidences, e.g. leucopenia with relative lymphocytosis and presence of multi-nuclear giant cells or intracellular inclusion bodies in infected tissues after 5-10 days.

D/D include other causes of maculopapular rash (Ch

25.5), specially: (a) other exanthematous fevers (Table

10.5), (b) allergic or drug rash, and (c) miliaria.

Treatment is mainly symptomatic with no specific antiviral therapy and includes: (a) maintenance of nutrition and hygiene, (b) antipyretics, (c) humidification to relieve cough, and (d) treatment of complications. Two doses of vitamin A at 24 hours interval (PO 50,000 IU lt; 6 mo age, 1 lac IU in 6-12 mo infants and 2 lac IU in older children), are known to reduce the mortality and morbidity in measles by about 50%.

Prevention involves avoidance of contact with an infec­ted case along with universal immunization with two doses of a live-attenuated combination vaccine (MR) at the age of 9-12 months and 16-24 months, as per NIS. IAP recommends three doses of MMR at 9 mo, 15 mo and 4-6 years. (Ch 9.2.1).

Outbreak-control measures in measles include:

• Supplementary immunization rounds in outbreak areas, including additional dose to previously immunized children and the immunization in 6-9 months age group (zero dose).

• Post-exposure prophylaxis to reduce severity/duration of disease, only if received within 3-5 days of exposure. It is indicated only in high-risk household contacts, as follows:

- Unimmunized infants (immunoglobulins* with vaccine)

- Older unimmunized children without past history of disease (only vaccine)

- Immunocompromised or pregnant contact (only immunoglobulin*)

*(0.25 ml/kg of human immunoglobulin)

• Isolation of the case and susceptible contacts during infectivity period (7 days after exposure to 5 days after appearance of rash).

Measles-Rubella (MR) Elimination Plan in India by 2023 rests on four pillars: (a) 95% coverage with two doses of Measles-containing vaccine, (b) sensitive case-based MR surveillance, (c) rapid response to MR outbreaks, and (d) augmentation of the laboratory network for confirmation of diagnosis and virus typing.

Some other close mimics of Measles with Exanthe­matous fevers are also discussed as follows.

Rubella (German Measles) is a common RNA viral infection, with asymptomatic or mild self-limiting illness in children/adults. However, maternal infection in first trimester has serious consequences to fetus, e.g. fetal death or congenital rubella syndrome (Ch 12.15.3).

During 2017-2021, India adopted a National Strategic Plan for MR elimination (discussed below) and intro­duced rubella vaccination in National Immunization Schedule, replacing Measles vaccine with MR (Measles + Rubella) vaccine, apart from intensified surveillance.

Epidemiology: Rubella is a RNA virus, present in nasopharynx, throat, and urine of infected person. Infec­tion is usually acquired in school-age as droplet infection from a clinical or subclinical case, who is infective from 7 days before to 14 days after the rash.

As ~80% of Indian population is infected by late adolescence and conferred life-long immunity, 15-20% of pregnant mothers are still susceptible for rubella and consequent risk of CRS.

Pathologically, virus replicates in local epithelium and spreads to regional lymph nodes followed by viremia lasting for about 10-14 days. Fetal infection occurs transplacentally during the viremia, leading to extensive tissue damage, specially in brain, heart and auditory nerve.

Clinically, postnatal rubella is either asymptomatic or presents as mild, self-limiting viral illness, with: (a) prodromal phase (4-5 days) with mild catarrhal symptoms, and (b) exanthematous phase (2-3 days) with transient morbilliform or scarlatiniform rash and generalized lymphadenopathy, specially involving occipital and post-auricular nodes. Other features, e.g. Forchheimer spots—a rose-colored enanthem on soft palate and arthralgia, are common in adolescent girls.

Complications, other than congenital rubella syn­drome after infection during pregnancy are extre­mely rare and include: (a) early complications, e.g. thrombocytopenia or Guillain-Barre syndrome, and (b) late complication, e.g. progressive rubella encephalitis. Diagnosis is clinical, often missed due to nonspecific, transient illness. Laboratory confirmation requires elevated specific IgM antibodies or rising IgG titers on repeat testing.

Management: Rubella is self-limiting with no specific therapy, except symptomatic care.

Prevention of infection is specially important in pros­pective mothers and includes:

• Routine MR/MMR immunization at or after 15 months of age. (Ch 9.2.1).

• Exposed pregnant and unimmunized women of reproductive age should be serologically screened immediately and after four weeks of exposure. Risk of congenital rubella syndrome is very low if mother is seropositive at the time of exposure. Seronegative mother, who turns seropositive after 4 weeks, carry maximum risk of congenital rubella syndrome and should be counseled accordingly. If abortion is not an option, immunoglobulin prophylaxis is indicated immediately after exposure, to reduce the risk of congenital rubella syndrome.

Erythema infectiosum (fifth disease) is the prototype illness of Parvoviral B19 infection in healthy children. Infection is acquired as droplet infection from a clinical or sub-clinical case, usually in school-age.

Clinically, infection is asymptomatic or presents as a mild febrile illness, followed by hallmark rash. Typical rash evolves in three stages:

a. Initial, transient facial flush (slapped-cheek appearance).

b. Discrete macular lesions over trunk and proximal extremities, sparing palm and soles.

c. Central clearing of macular lesions, with a lacy, reticular appearance.

Rash resolves spontaneously within 1-3 weeks, without desquamation, but may recur for a few weeks after sun exposure, heat, exercise and stress.

Diagnosis is mainly clinical, based on: (a) hallmark rash without fever and sick-appearance. Laboratory confirmation is not easily available, but includes: (a) elevated specific IgM titers, or (b) PCR testing. Virus cannot be isolated by culture.

Treatment is supportive and non-specific.

Other parvoviral illnesses: B₁₉ is the only serotype of parvovirus, known to cause of human disease. It mainly targets erythroid cell line and other Parvovirus B₁₉- associated illnesses are:

• Transient aplastic crisis in hemolytic anemia, e.g. sickle cell disease,

• Chronic anemia or pancytopenia in immuno­compromised host,

• A self-limiting arthropathy in female adolescents or adults, and

• Non-immune hydrops fetalis due to bone marrow depression and anemia in maternal infection.

Roseola infantum (exanthem subitum) is the prototype manifestation of a human herpesvirus type 6 or 7 (HHV 6/7) infection, characterized by a mild exanthematous febrile illness in infants and toddlers (d/d fifth disease in older children).

HHV 6/7 virus is present in saliva of infected humans and transmitted by close contact, e.g. kissing. Conse­quently, infection rate is highest in early infancy.

Clinically, it is characterized by:

• Sudden onset of high fever (gt;39-40°C) for 3-5 days that resolves with a crisis (suddenly). Typically, baby is apparently normal and active despite high fever. Roseola is one of the commonest causes of febrile seizures.

• Transient, discrete, maculopapular or rose-colored rash after 24-36 hours of defervescence, with centri­petal distribution, most prominent on trunk and proximal extremities. Rash disappears rapidly within 1-3 days.

Complications are rare, except in immunocompromised host, who may develop aseptic meningitis or encephalitis. Diagnosis is clinical, though laboratory confirmation is possible with—(a) elevated specific IgM titers, and (b) viral detection by culture or PCR amplification.

Treatment is supportive and non-specific. Ganciclovir and Foscarnet may be used for severe CNS disease in immunocompromised host.

Other HHV 6/7 illnesses, presumably associated with life­long persistence of these infections are:

• Blood disorders, e.g. hemophagocytic syndrome, histiocytosis and immune thrombocytopenia.

• Intussusception.

• Pityriasis rosea.

• Multiple sclerosis in adults.

• It is also considered as a co-factor in progression of HIV/AIDS infection.

10.19