Chickenpox, Measles, Mumps & Diphtheria

1. CHICKENPOX (Varicella)

Definition

Problem Statement

• Global annual burden: ~4.2 million severe complications leading to hospitalization and ~4,200 deaths.
• In the pre-vaccine era in high-income countries, case fatality rate (CFR) was ~3 per lakh cases.
• In India (2018): 66,963 cases and 50 deaths (CFR ~0.074%). Kerala reported the highest cases (34,785); West Bengal the most deaths (31).
• Herpes zoster incidence increases markedly after age 50 years; about half of those who reach 85 years will suffer at least one episode.

Epidemiological Determinants

• (a) Agent: V-Z virus. Primary infection causes chickenpox. After recovery, virus lies latent in cranial nerve sensory ganglia and spinal dorsal root ganglia. Reactivation (when cell-mediated immunity wanes) causes herpes zoster in 10-30% of persons.
• (b) Source of infection: A case of chickenpox (oropharyngeal secretions and skin/mucosal lesions). Rarely a herpes zoster patient. Virus isolated from vesicular fluid in first 3 days; scabs are NOT infective.
• (c) Infectivity/Communicability: From 1-2 days before rash appearance until 4-5 days after. Patient ceases to be infectious once lesions crust.
• (d) Secondary attack rate: About 87% (high).

• (a) Age: Most common in children aged 5-9 years. Adults can also be affected; disease is more severe in adults.
• (b) Immunity: One attack confers lifelong immunity. Maternal antibodies protect infants up to ~6 months.

• Worldwide distribution; endemic and epidemic forms.
• Peak incidence in late winter and spring.
• Overcrowding favors spread.

• Droplet infection and direct contact with vesicular lesions.
• Airborne spread also documented.

Clinical Features

• Prodrome: Mild fever, malaise (usually mild in children, more severe in adults).
• Rash: Starts as macules → papules → vesicles → pustules → crusts. Rash is:
  • Centripetal (more on trunk, less on extremities)
  • Pleomorphic (different stages visible simultaneously, because rash appears in successive crops)
  • Superficial, unilocular vesicles with a "dew-drop" appearance
  • Accompanied by surrounding area of inflammation/erythema
  • Palms and soles are seldom affected; axilla is commonly involved
• Scabs begin to form 4-7 days after rash appears.
• Temperature rises with each fresh crop.

Complications

• Haemorrhagic varicella, Varicella pneumonia (most common serious complication in neonates, adults, immunocompromised)
• Encephalitis, Acute cerebellar ataxia
• Reye's syndrome (acute encephalopathy with fatty degeneration of viscera, especially liver)
• Congenital varicella syndrome (if mother infected in pregnancy): cutaneous scars, limb atrophy, microcephaly, cataract, microphthalmia, chorioretinitis, deafness, cerebrocortical atrophy.
• Secondary bacterial infections (Group A beta-haemolytic streptococci, Staphylococcus aureus): cellulitis, erysipelas, epiglottitis, osteomyelitis.
• Acute retinal necrosis / progressive outer retinal necrosis - especially in AIDS patients.
• Neonatal risk if mother develops varicella within 5 days before or 2 days after delivery - VZIG must be given.

Treatment

• Antiviral: Acyclovir - drug of choice; reduces duration and severity if given within 24-48 hours of rash onset.
• Symptomatic: antipyretics (avoid aspirin - risk of Reye's syndrome), antihistamines for itching.
• Calamine lotion for local application.
• Antibiotics for secondary bacterial infections.

Prevention and Control

1. Isolation of cases until all lesions have crusted.
2. Active immunization: Varicella vaccine (live attenuated) - 2 doses; also available as MMRV.
3. Passive immunization: Varicella-zoster immunoglobulin (VZIG) - for susceptible high-risk contacts (immunocompromised, neonates, pregnant women).
4. Concurrent disinfection of articles soiled with nasal/throat secretions.

2. MEASLES (Rubeola)

Definition

Problem Statement

• Measles is endemic virtually worldwide. Epidemics occur when susceptible children reach ~40% of the population.
• In a virgin community, >90% of those exposed will be infected.
• Pre-vaccine era (1980): ~2.6 million deaths annually worldwide.
• By 2018: ~9.7 million cases and >140,000 deaths globally (a 73% decline in deaths and 76% decline in cases from 2000 to 2018).
• Responsible for ~2% of under-five mortality worldwide.
• India (2018): 20,895 cases and 34 deaths (down from ~2.47 lakh cases in 1987 pre-UIP).

Epidemiological Determinants

• (a) Agent: Measles virus - an RNA paramyxovirus with a single serotype. The virus is relatively unstable outside the host. Remains infective in air or on surfaces for up to 2 hours.
• (b) Source: Exclusively humans (no animal reservoir). Both clinical and subclinical cases.
• (c) Communicability: From 1-2 days before symptom onset (4 days before rash) until 4 days after rash appearance. Most infectious during the prodromal (catarrhal) stage.
• (d) Secondary attack rate: About 90% among susceptibles in household (extremely high).

• (a) Age: Mainly affects children <5 years. Most common in 6 months - 3 years in unimmunized populations.
• (b) Immunity: One attack confers lifelong immunity. Maternal antibodies protect infants up to ~6 months.
• (c) Risk factors: Malnutrition (especially Vitamin A deficiency), overcrowding, immunodeficiency.

• Peak incidence in late winter and spring.
• Overcrowding is a major risk factor.

• Airborne droplet transmission (most important).
• Direct contact with nasal/throat secretions.

Clinical Features (Stages of Measles)

• High fever, coryza, cough, conjunctivitis ("4 Cs": Cough, Coryza, Conjunctivitis, Koplik's spots)
• Koplik's spots (pathognomonic): Bluish-white spots with a red areola on the buccal mucosa, opposite the lower molars. Appear 1-2 days before the rash.

• Maculopapular rash begins on the face (behind the ears, hairline) → spreads downward to trunk and extremities over 3-4 days (cephalocaudal progression).
• Rash is morbilliform (irregular blotchy), initially red, later brownish.
• Rash lasts 5-6 days then fades in order of appearance.
• Branny desquamation may follow.

• Recovery phase; susceptibility to secondary infections is high.

Complications

• Respiratory: Pneumonia (most common cause of death, especially in young children), otitis media, laryngitis/croup.
• Neurological: Encephalitis (1 in 1000 cases; 10-15% mortality), Subacute Sclerosing Panencephalitis (SSPE) - a fatal late complication occurring years after measles infection.
• Nutritional: Precipitates/worsens malnutrition; causes Vitamin A deficiency - can cause blindness (xerophthalmia), especially in developing countries.
• Immunosuppression: Measles causes a prolonged state of immune suppression ("immune amnesia"), predisposing to other infections.
• Diarrhea, stomatitis, cancrum oris (noma).

Treatment

• No specific antiviral treatment.
• Vitamin A supplementation (recommended by WHO for all children with measles in developing countries):
  • <6 months: 50,000 IU
  • 6-11 months: 100,000 IU
  • ≥12 months: 200,000 IU
  • A third dose if clinical signs of Vitamin A deficiency present.
• Supportive treatment; antibiotics for secondary bacterial infections.

Prevention and Control

1. Active immunization (cornerstone of control):
   • Live attenuated measles vaccine (only type recommended by WHO).
   • Available as monovalent or combined: MR, MMR, MMRV vaccines.
   • Store at 2-8°C; sensitive to heat and light; reconstituted vaccine must be used within 4 hours.
   • India (UIP): MCV1 at 9 months; MCV2 at 15-18 months.
   • High-income/low-transmission countries: MCV1 at 12-15 months.
2. Passive immunization: Normal human immunoglobulin (0.25 ml/kg IM) given within 6 days of exposure for susceptible contacts.
3. Isolation of cases for 4 days from onset of rash.
4. Concurrent disinfection; ventilation of rooms.

3. MUMPS (Epidemic Parotitis)

Definition

Problem Statement

• Occurs throughout the world; endemic in most countries.
• Annual incidence (without immunization): 100-1000 cases per 100,000 population; epidemic peaks every 2-5 years.
• 30-40% of infections are subclinical.
• Natural infection confers lifelong protection.

Epidemiological Determinants

• (a) Agent: Myxovirus parotiditis (RNA virus of the myxovirus family). Only one serotype exists; no significant antigenic variation. Can be grown in chick embryo or tissue culture.
• (b) Source of infection: Both clinical and subclinical cases. Subclinical cases (30-40% of all cases) maintain the cycle of infection. Virus isolated from saliva or swabs from Stenson's duct; also found in blood, urine, human milk, and occasionally CSF.
• (c) Period of communicability: 4-6 days before symptom onset to a week or more thereafter. Maximum infectivity is just before and at the onset of parotitis. Non-infectious once gland swelling subsides.
• (d) Secondary attack rate: ~86%.

• (a) Age and sex: Most common in children aged 5-9 years (higher average age than measles, chickenpox, or whooping cough). No age is exempt if no prior immunity. Disease more severe in adults.
• (b) Immunity: One attack (clinical or subclinical) induces lifelong immunity. Only one antigenic type - no significant antigenic variation. Maternal antibodies protect infants below 6 months.

• Largely endemic, year-round occurrence.
• Peak incidence in winter and spring.
• Epidemics associated with overcrowding.

• Droplet infection.
• Direct contact with an infected person.

Clinical Features

• 30-40% of infections are subclinical (inapparent).
• In apparent cases: pain, swelling of one or both parotid glands; may also involve sublingual and submandibular glands.
• Child often complains of "earache" on the affected side before swelling.
• Pain and stiffness on opening the mouth before visible swelling.
• Fever, headache, malaise.
• Swelling peaks at 1-3 days, then subsides over 7-10 days.

Complications

• Orchitis/Epididymitis: Most common complication in post-pubertal males (~20-30%); rarely leads to sterility.
• Oophoritis: In post-pubertal females (~5%).
• Aseptic Meningitis/Meningoencephalitis: Most common CNS complication; usually self-limiting.
• Pancreatitis: Abdominal pain, nausea, vomiting.
• Deafness: Unilateral sensorineural hearing loss - rare but permanent.
• Myocarditis: Rare.
• Thyroiditis, Arthritis.
• Mumps during first trimester of pregnancy may increase risk of spontaneous abortion.

Surveillance Case Definitions (WHO)

• Suspected mumps: Sudden onset of unilateral or bilateral tender self-limited swelling of the parotid or other salivary glands, lasting ≥2 days, without other apparent cause.
• Laboratory-confirmed mumps: Clinical case + positive mumps IgM antibody OR 4-fold rise in IgG titre OR isolation of mumps virus from saliva/urine/CSF.
• Epidemiologically confirmed: Clinical case epidemiologically linked to a laboratory-confirmed case.

Prevention and Control

• Isolation until clinical manifestations subside.
• Concurrent disinfection of articles used by the patient.
• Contacts under surveillance.
• Control is difficult because the disease is infectious before diagnosis can be made, and subclinical cases are numerous.
• Active immunization: MMR vaccine (combined Measles-Mumps-Rubella); live attenuated; part of UIP in India. Given at 12-15 months and booster at 4-6 years.

Note: "The control of mumps is difficult because the disease is infectious before a diagnosis can be made." - Park's Textbook

4. DIPHTHERIA

Definition

• (a) Formation of a greyish/yellowish "false membrane" (pseudo-membrane) over tonsils, pharynx, larynx - with well-defined edges; cannot be wiped away.
• (b) Marked congestion, oedema, and local tissue destruction.
• (c) Enlargement of regional lymph nodes ("bull neck").
• (d) Signs and symptoms of toxaemia.

Problem Statement

• World: Rare in developed countries due to routine vaccination. However, outbreaks occur among unimmunized groups and adults with waning immunity.
• Key epidemic drivers: decreasing immunization coverage, waning immunity in adults, population movement, irregular vaccine supply.
• Global (2016): ~7,097 cases reported.
• India: Endemic disease with declining trend due to UIP. In 2018: 11,720 cases and 180 deaths. Assam reported the most cases (9,083); Delhi had the highest deaths (156).

Epidemiological Determinants

• (a) Agent: C. diphtheriae - a Gram-positive, non-motile organism. Has no invasive power but produces a powerful exotoxin.
  • 4 types: gravis, mitis, belfanti, intermedius (all pathogenic).
  • Gravis tends to cause more severe disease than mitis.
  • Not all strains are toxigenic. A non-toxigenic strain can become toxigenic by acquiring the beta phage (bacteriophage carrying the toxin gene).
  • Toxin affects: heart (myocarditis) and nerves (neuropathy/polyneuritis).
• (b) Source of infection: Cases and carriers (nasal and pharyngeal carriers); skin diphtheria is less common.
• (c) Carrier state: Healthy carriers are common and important in disease transmission. Carriers can be detected only by culture methods (swabs from both nose and throat).
• (d) Communicability: Variable; from 2-4 weeks until bacilli disappear from lesions. Penicillin/erythromycin treatment terminates communicability.

• (a) Age: All ages affected; predominantly children in unimmunized populations. In vaccinated populations, older children and adults form a larger proportion of cases (waning immunity).
• (b) Immunity:
  • Natural immunity is acquired gradually through subclinical infections.
  • Active immunity by toxoid vaccination.
  • Passive immunity by antitoxin.
  • Schick test: used to determine susceptibility. A positive Schick test indicates susceptibility (no protective antitoxin present). Nowadays rarely used - replaced by serology.
  • Immunity to toxin does NOT prevent the carrier state.

• Overcrowding and poor sanitation favor transmission.
• Common in cold months (autumn/winter).

• Droplet infection (most common).
• Direct contact with cases or carriers.
• Fomites (contaminated articles).
• Rarely through raw milk.

Clinical Features

• Faucial (tonsillar/pharyngeal) diphtheria: Most common form. White-grey pseudo-membrane forms on tonsils, spreads to pharynx. Membrane is tough, adherent, bleeds on removal. Toxaemia with fever, malaise, cervical lymphadenopathy ("bull neck").
• Laryngeal diphtheria: Dangerous due to airway obstruction. Hoarseness, croup, stridor, risk of suffocation.
• Nasal diphtheria: Mildest form; serosanguineous discharge; carrier state common.
• Myocarditis: Due to toxin; occurs in 2nd week; can be fatal.
• Neuropathy/Polyneuritis: Palatal palsy (nasal voice, regurgitation), oculomotor palsy, peripheral neuropathy (weeks later).

Treatment

• Diphtheria antitoxin (DAT): Given urgently without waiting for lab confirmation. Dose:
  • Mild/early pharyngeal-laryngeal: 20,000-40,000 units IM
  • Moderate nasopharyngeal: 40,000-60,000 units
  • Severe/extensive/late (≥3 days): 80,000-100,000 units IM or IV
  • Always give a preliminary test dose of 0.2 ml subcutaneously to detect horse serum sensitization.
• Antibiotics: Penicillin or erythromycin for 5-6 days (to clear throat of C. diphtheriae and reduce toxin production).

• Oral erythromycin for 10 days (most effective for carriers).

Control of Diphtheria (Park's Three-Level Approach)

• Early detection by culture (nose + throat swabs).
• Isolation for at least 14 days or until 2 consecutive negative swabs (taken 24 hours apart).
• Treatment as above.

• Throat swab + immunity status determined.
• If immunized within past 5 years: no further action.
• If immunized >5 years ago: booster dose of diphtheria toxoid.
• Non-immunized close contacts: prophylactic penicillin or erythromycin + 1,000-2,000 units DAT + active immunization.
• Daily surveillance of contacts for at least 1 week; bacteriological surveillance (repeated swabbing) for several weeks.

• Active immunization with diphtheria toxoid as early in life as possible.
• Aim to immunize before maternal immunity wanes (no gap in protection from birth).
• Booster doses every 10 years.
• Important: Immunization does NOT prevent carrier state; therefore immunization rates must remain high.

• DPT / DTPw (Diphtheria-Pertussis-Tetanus whole cell)
• DTPa (acellular pertussis)
• DT (Diphtheria-Tetanus toxoid for children)
• dT (adult-type low-dose diphtheria-Tetanus)
• Pentavalent vaccine (DTP + Hep B + Hib) - part of India's UIP

Summary Comparison Table

Rubella, Influenza, Pertussis & Meningococcal Meningitis

1. RUBELLA (German Measles)

Definition

Historical Note (Park): Rubella was considered a benign disease until 1941, when Norman Gregg, an Australian ophthalmologist, reported an epidemic of congenital cataracts and other defects in children born to mothers who had rubella during pregnancy. This discovery revealed the teratogenic potential of rubella. The virus was isolated in 1962; an attenuated vaccine was developed in 1967.

Problem Statement

• Worldwide, over 100,000 babies are born with CRS every year.
• Extent and periodicity are highly variable across industrialized and developing countries.

Epidemiological Determinants

• (a) Agent: RNA virus of the Togavirus family. Only one antigenic type exists. Recovered from nasopharynx, throat, blood, CSF, and urine. Propagated in cell culture.
• (b) Source of infection: Clinical or subclinical cases (20-50% of infections are subclinical - a major difference from measles). No known carrier state for postnatally acquired rubella. Infants with congenital rubella may shed virus for many months. Vaccine virus is NOT communicable.
• (c) Period of communicability: From 1 week before symptoms to about 1 week after rash appears. Infectivity is greatest 1-5 days after rash appearance. Rubella is much less communicable than measles (no coughing).

• (a) Age: Mainly a disease of children aged 3-10 years. In developed countries (post-immunization), persons older than 15 years now account for >70% of cases (same pattern as measles after immunization campaigns).
• (b) Immunity: One attack confers lifelong immunity; second attacks are rare. Infants of immune mothers protected for 4-6 months. Without immunization, 10-40% of the population could reach adulthood susceptible.

• Seasonal pattern: late winter and spring in temperate zones.
• Epidemics every 4-9 years.

• Droplet and droplet nuclei (aerosols) from nose and throat.
• Portal of entry: respiratory tract.
• Vertical (transplacental) transmission - infects the foetus in utero, leading to Congenital Rubella.

Clinical Features

• 20-50% of infections are asymptomatic.
• (a) Prodrome: Coryza, sore throat, low-grade fever (mild and often insignificant, especially in children).
• (b) Lymphadenopathy: Characteristic enlargement of post-auricular, occipital, and posterior cervical lymph nodes - appears 5-10 days before the rash; persists for 10-14 days after. Not pathognomonic (can be absent).
• (c) Rash: Often the first sign in children. Appears on the face first, spreads rapidly to trunk and extremities - often cleared from face by the time it reaches extremities. The rash is:
  • Minute, discrete, pinkish, macular
  • NOT confluent (unlike measles)
  • May be pruritic
  • Disappears completely by the 3rd day (much faster than measles)
  • Absent in 25% of infections (inconstant feature)
• (d) Complications (rare):
  • Arthralgia/arthritis - especially in adult women
  • Encephalitis (very rare)
  • Thrombocytopenic purpura

Congenital Rubella Syndrome (CRS)

1. Cataracts (and other eye defects: glaucoma, retinopathy)
2. Cardiac defects (Patent Ductus Arteriosus, pulmonary artery stenosis, ventricular septal defect)
3. Sensorineural deafness (most common single defect)

Diagnosis

• Definitive diagnosis by virus isolation (throat swabs) or serology.
• HI (Haemagglutination Inhibition) test is the standard serological test (serum must be pretreated to remove non-specific inhibitors).
• ELISA preferred - no pretreatment required; can detect specific IgM.
• Detection of IgG = evidence of immunity.
• To confirm recent infection: rising titre in two samples ≥10 days apart OR rubella-specific IgM in a single sample.

Prevention and Control

• Based on the live attenuated RA 27/3 strain.
• Available as: monovalent, MR (Measles-Rubella), MMR, MMRV vaccines.
• Single dose provides >95% efficacy; vaccine-induced immunity persists for lifetime.
• Storage: 2-8°C, protected from light. Single dose = 0.5 ml, subcutaneous injection.
• One dose is sufficient to achieve rubella elimination if high coverage is achieved.
• All non-pregnant women of reproductive age who are seronegative should receive one dose.

• Should not be given in pregnancy (theoretical teratogenic risk - though never demonstrated in practice). Women should avoid pregnancy for 1 month after vaccination.
• Avoid in severe immunodeficiency, active TB, symptomatic HIV/AIDS.
• Inadvertent vaccination during pregnancy is NOT an indication for termination.
• Wait ≥3 months after blood products before giving RCV.

2. INFLUENZA

Definition

Problem Statement

• A truly international disease affecting millions every year.
• Pandemic pattern: Every 10-40 years due to major antigenic changes - 1918 (Spanish flu, H1N1), 1957 (Asian flu, H2N2), 1968 (Hong Kong flu, H3N2), 2009 (Swine flu, H1N1pdm).
• Epidemic pattern: Every 2-3 years for influenza A and 3-6 years for influenza B.
• Annual epidemics cause ~3-5 million cases of severe illness and 290,000-650,000 deaths worldwide.
• Epidemic character: few early cases → sudden outburst → increased hospitalization → peak in 3-4 weeks → decline. Attack rate: 5-10% in adults; 20-30% in children.
• Currently 3 strains circulating: A(H1N1), A(H3N2), and B viruses.

Epidemiological Determinants

• (a) Agent: Family Orthomyxoviridae. Types A, B, C, D; antigenically distinct with no cross-immunity.
  • Influenza A has 2 surface antigens:
    • Haemagglutinin (H): Initiates infection by attaching to susceptible cells. 18 HA subtypes identified.
    • Neuraminidase (N): Responsible for release of virus from infected cell. 11 NA subtypes identified.
  • Humans generally infected by H1, H2 or H3, and N1 or N2.
  • Type B - does not undergo antigenic shift; not divided into subtypes.
  • Type C - antigenically stable.
• Antigenic Variation (KEY CONCEPT):
  • Antigenic Shift: Sudden, complete/major change - results from genetic recombination of human with animal/avian virus. Causes pandemic involving all age groups.
  • Antigenic Drift: Gradual change over time due to point mutations in the gene, driven by selection pressure of host immunity. Causes epidemics (less severe than pandemics).
• (b) Reservoir: A major reservoir exists in animals and birds (swine, horses, dogs, cats, domestic poultry, wild birds). Animal reservoirs provide new strains through recombination.
• (c) Source: Cases and subclinical cases. Respiratory tract secretions are infective.
• (d) Period of infectivity: Virus present in nasopharynx from 1-2 days before until 1-2 days after onset of symptoms.

• (a) Age and sex: All ages and both sexes affected. Attack rate lower in adults. Children are important links in transmission. High-risk groups for mortality: elderly (>65 years), children <18 months, persons with diabetes, chronic heart/kidney/respiratory disease.
• (b) Human mobility: Important factor in spread.
• (c) Immunity:
  • Immunity is subtype-specific.
  • Antibody against H (HA) - neutralizes virus; resists initiation of infection.
  • Antibody against N (NA) - decreases severity; decreases ability to transmit virus.
  • Local secretory IgA in nasal secretions: important in preventing infection; shorter-lived (months) than serum antibodies.
  • Serum antibodies appear in 7 days, peak at 2 weeks, then drop to pre-infection level in 8-12 months.
  • Immunity is incomplete; reinfection with same virus is possible.

• (a) Season: Epidemics in winter in Northern Hemisphere; winter/rainy season in Southern Hemisphere. In tropical countries, year-round circulation with 1-2 peaks during rainy season.
• (b) Overcrowding: Enhances transmission; high attack rates in schools, institutions, ships.

• Droplet infection and droplet nuclei (sneezing, coughing, talking).
• Portal of entry: respiratory tract.

Clinical Features

• Virus enters respiratory tract → inflammation and necrosis of tracheal and bronchial mucosa → secondary bacterial invasion. No viraemia.
• Sudden onset: fever, chills, aches and pains, coughing, generalized weakness.
• Fever lasts 1-5 days (average 3 days in adults).
• Complications:
  • Acute sinusitis, otitis media, purulent bronchitis.
  • Pneumonia (most dreaded complication) - suspect if fever persists beyond 4-5 days OR recurs after convalescence ("herald wave" pneumonia).
  • In immunocompromised and elderly: increased severity and mortality.

Avian Influenza (H5N1)

• Caused by influenza A viruses that normally infect birds.
• Human infections usually through direct contact with infected poultry.
• High case fatality rate (~60%).
• Not yet efficient human-to-human transmission.

Prevention and Control

• Inactivated Influenza Vaccines (IIVs): Most widely used; safe even in pregnancy and immunocompromised. Trivalent (TIV) or Quadrivalent (QIV). Given by IM injection. Must be updated annually based on circulating strains (WHO recommendations).
• Live Attenuated Influenza Vaccine (LAIV): Intranasal; for healthy non-pregnant persons 2-49 years.
• Target groups for vaccination: Elderly (>65), chronic disease patients, healthcare workers, pregnant women, children 6 months - 5 years.
• Vaccine composition is updated each year to match circulating strains.

• Oseltamivir (Tamiflu) and Zanamivir - neuraminidase inhibitors; effective against A and B if given within 48 hours of onset.

• WHO Global Influenza Surveillance and Response System (GISRS) monitors circulating strains.

• Isolation of cases; hand hygiene; respiratory etiquette.
• Avoid crowding during epidemics.
• Concurrent disinfection.

3. WHOOPING COUGH (Pertussis)

Definition

Problem Statement

• Important cause of infant death worldwide; public health concern even in countries with high vaccination coverage.
• Global (2018): ~151,000 cases reported to WHO; DPT3 immunization coverage was 86%.
• One of the most lethal diseases in unimmunized infants, especially with underlying malnutrition and respiratory infections.
• Increasingly reported in older children, adolescents, and adults (waning vaccine immunity). A US study showed 21% of adults with prolonged cough (>2 weeks) had pertussis.
• India (2018): 18,006 cases and 8 deaths - a decline of ~89% from 1.63 lakh cases (1987) pre-UIP.

Epidemiological Determinants

• (a) Agent: Bordetella pertussis (causative agent in most cases). B. parapertussis responsible in <5% of cases. Occurs in smooth/rough phases, capsulated/non-capsulated forms. Elaborates exotoxin (pertussis toxin) and endotoxin. Has 3 major agglutinogens (1, 2, 3). Survives only briefly outside the human body.
• (b) Source: B. pertussis infects only man. Source is a case of pertussis; often mild/unrecognized cases. No subclinical infection (unlike measles, rubella). No chronic carrier state.
• (c) Infective material: Nasopharyngeal and bronchial secretions; freshly contaminated objects.
• (d) Infective period: Most infectious during catarrhal stage. Communicability extends from 1 week after exposure to ~3 weeks after onset of paroxysmal stage; diminishes rapidly after catarrhal stage.
• (e) Secondary attack rate: ~90% in unimmunized household contacts.

• (a) Age: Most susceptible: infants and young children.
  • <1 year: most severe and highest mortality.
  • Rarely seen in adults in non-immunized populations (immunity from natural infection lasts ~15 years; from vaccine ~6-12 years).
• (b) Sex: No significant difference.
• (c) Immunity: Natural infection provides longer-lasting immunity (~15 years) than vaccination (~6-12 years). No passive maternal immunity (no transplacental transfer of adequate levels).

• Worldwide distribution; endemic/epidemic patterns.
• No striking seasonal variation (unlike measles or chickenpox).
• Overcrowding and poor housing increase transmission.

• Droplet infection from close contact.
• Portal of entry: respiratory tract.

Clinical Features (Three Stages)

• Mild coryza, low-grade fever, mild irritating cough.
• Most infectious stage - indistinguishable from common cold.
• Bacilli are most abundant in secretions.

• Characteristic paroxysms of coughing - 5-10 or more rapid coughs per paroxysm, ending with a loud crowing "whoop" (inspiratory stridor).
• Post-tussive vomiting (often ends the paroxysm).
• Cyanosis during paroxysms.
• "Whoop" may be absent in infants <6 months, adults, and immunized individuals.
• Face may become red/congested; subconjunctival hemorrhages.
• Between paroxysms: child appears well.

• Paroxysms decrease in frequency and severity.
• Cough may recur with subsequent respiratory infections ("Hundred Day Cough").

Complications

• Respiratory: Pneumonia (most common cause of death - secondary bacterial infection), bronchiectasis, atelectasis.
• CNS: Convulsions, encephalopathy (from anoxia during paroxysms or from toxin).
• Physical: Subconjunctival hemorrhage, epistaxis, umbilical hernia, rectal prolapse (from severe straining during paroxysms).
• Nutritional: Weight loss due to post-tussive vomiting and poor feeding.
• Pertussis in infants <6 months can be rapidly fatal.

Treatment

• Drug of choice: Erythromycin (30-50 mg/kg/day in 4 divided doses for 10 days).
• Alternatives: Azithromycin, Clarithromycin.
• If given during incubation or early catarrhal stage: may prevent or moderate the disease.
• During paroxysmal stage: antibiotics do NOT change clinical course but eliminate bacteria from nasopharynx and reduce transmission.
• Useful for controlling secondary bacterial infections.

Prevention and Control

• Early diagnosis by nasopharyngeal swab for culture (best within 10-14 days of onset; isolation rate <60% after this).
• Fluorescent antibody technique for rapid diagnosis.
• Isolation until non-infectious.
• Contacts (especially infants/young children): prophylactic erythromycin or azithromycin for 10 days.
• Best protection for newborn: booster dose of DPT given to siblings before birth.

• Given as DPT, DTPw, or DTaP (combined vaccine).
• India (UIP): 3 doses at 6, 10, 14 weeks, each 0.5 ml IM; booster at 18-24 months.
• Interrupted series: resume without repeating previous doses.
• Efficacy: Most efficacious vaccines (whole-cell or acellular) protect ~85% from clinical disease.
• Duration of protection: ~6-12 years (for both whole-cell and acellular).
• Acellular pertussis vaccines used for older children and adults (fewer side effects).
• All infants, including HIV-positive, should be immunized.
• Acellular pertussis combination vaccines may include: diphtheria toxoid, tetanus toxoid, Hib, HepB, and IPV.

4. MENINGOCOCCAL MENINGITIS (Cerebrospinal Fever)

Definition

Problem Statement

• Worldwide distribution - sporadic cases and small outbreaks in most of the world.
• African Meningitis Belt (Sub-Saharan Africa, Senegal to Ethiopia, ~400 million population): Devastating unpredictable epidemics; WHO epidemic definition = >100 cases/100,000 population/year.
• Endemicity levels: >10 cases = high; 2-10 cases = moderate; <2 cases = low (per 100,000/year).
• Europe: 0.2-14 cases/100,000; mostly serogroup B.
• Americas: 0.3-4 cases/100,000; serogroups B, C, Y.
• Asia: Mostly serogroups A or C.
• India (2018): 3,382 cases and 152 deaths, mostly from Andhra Pradesh (758 cases), UP, Rajasthan.

Epidemiological Determinants

• (a) Agent: Neisseria meningitidis (meningococcus) - Gram-negative diplococcus.
  • At least 13 serogroups based on polysaccharide capsule; 6 main disease-causing groups: A, B, C, W-135, X, Y.
  • Serogroup A: responsible for large epidemics in Africa and Asia.
  • Serogroups B and C: dominant in Europe and Americas.
  • Strains produce an endotoxin responsible for toxaemia, haemorrhage, and circulatory collapse.
• (b) Source of infection: Cases and carriers. Carrier rate is high (5-25% of population); meningococcal disease is actually rare compared to the frequency of nasopharyngeal carriage. Infants are too young to have acquired natural immunity; higher risk.
• (c) Communicability: Spread by close contact with respiratory secretions. Portal of entry: nasopharynx.

• (a) Age: All ages; highest incidence in infants <1 year and young children. Susceptibility decreases with age (acquisition of natural immunity through subclinical infection). Peaks again in adolescents (due to risk behaviors - crowding in dormitories, military barracks).
• (b) Predisposing conditions: Asplenia, HIV infection, complement deficiencies, immunoglobulin deficiency.
• (c) Immunity: Acquired through subclinical infection (mainly), clinical disease, or vaccination. Infants derive passive immunity from mother.

• Seasonal: Outbreaks more frequent in dry and cold months (December to June).
• Overcrowding (schools, barracks, refugee camps).
• Low socioeconomic status, poor housing, exposure to tobacco smoke.
• Travel to endemic areas.

• Droplet infection (mainly).
• Portal of entry: nasopharynx.

Clinical Course

• Most infections do NOT cause clinical disease - many become asymptomatic nasopharyngeal carriers.
• Susceptibility to meningococcal disease decreases with age.
• Meningococcal Meningitis: Sudden onset of intense headache, fever, nausea, vomiting, photophobia, stiff neck and neurological signs. Can be fatal within 24-48 hours in 5-10% of cases even with treatment.
• Survivors: Up to 15-20% have permanent neurological sequelae (deafness, mental retardation, motor deficits, seizures).
• Meningococcal Septicaemia: Less common but more severe - rapid bacteraemia, circulatory collapse, haemorrhagic skin rash (petechiae/purpura), high fatality rate.

Prevention and Control

• Antibiotics can save 95% of patients if started within the first 2 days.
• Drug of choice: Penicillin (IV).
• Penicillin-allergic: Ceftriaxone or other 3rd-generation cephalosporins.
• In sub-Saharan Africa epidemics: single dose of long-acting chloramphenicol or ceftriaxone.
• Management challenges: septicaemic shock and raised intracranial pressure.
• Isolation of cases is of limited usefulness in controlling epidemics (carriers far outnumber cases).

• Penicillin does NOT eradicate the carrier state.
• Rifampicin needed to eradicate carrier state.

• Close contacts (household, child care, preschool) are at increased risk - most secondary cases occur within the first 72 hours.
• Risk decreases to near baseline by 10-14 days.
• Chemoprophylaxis for contacts: Rifampicin, ciprofloxacin, ceftriaxone, or azithromycin. Treatment should ideally start within 24 hours of identifying the index case.

• Recommended only for closed, medically supervised communities.
• Causes immediate drop in incidence and carrier proportion.
• Drugs of choice: ciprofloxacin, minocycline, spiramycin, ceftriaxone.
• Efficacy depends on population coverage.

• Meningococcal vaccines available: polysaccharide vaccines (A, C, W-135, Y) and conjugate vaccines.
• MenA conjugate vaccine (MenAfriVac): Used for serogroup A epidemics in sub-Saharan Africa.
• Quadrivalent conjugate vaccines (MCV-4): Cover A, C, W, Y; recommended for travelers to high-risk areas, military recruits, persons with asplenia/complement deficiency.
• Currently no broadly effective vaccine against serogroup B (outer membrane vesicle vaccines used in some countries; MenB vaccine available).
• Vaccines are part of national immunization programmes in many countries.

Summary Comparison Table