Genetic Counseling in PSM (Preventive & Social Medicine)

Definition

• Park's Textbook of Preventive and Social Medicine, p. 931
• Thompson & Thompson Genetics and Genomics in Medicine, 9th ed., p. 387

Types of Genetic Counseling

1. Prospective Genetic Counseling

• Allows for the true prevention of disease - this is the most important form from a PSM standpoint
• Requires identifying heterozygous (carrier) individuals by screening procedures before marriage or conception
• Explains the risk of having affected children if they marry another carrier of the same gene
• If heterozygous marriage is prevented or reduced, the incidence of affected children diminishes
• Classic applications: sickle cell anaemia and thalassemia
• May be extended to other recessive defects in future

2. Retrospective Genetic Counseling

• Most genetic counseling currently is retrospective - the hereditary disorder has already occurred in the family
• WHO survey showed genetic advice is chiefly sought for:
  • Congenital abnormalities
  • Mental retardation
  • Psychiatric illness
  • Inborn errors of metabolism
  • Only a few seek premarital advice
• Methods that may be suggested under retrospective counseling:
  1. Contraception
  2. Pregnancy termination
  3. Sterilization - depending on attitudes and cultural environment of the couple
• Park's Textbook of Preventive and Social Medicine, p. 931-932

The Genetic Counseling Process (Case Management)

• Help patients understand how heredity contributes to the condition
• Explain available reproductive options for mitigating genetic risks
• Identify the values, beliefs, and goals affected by the condition
• Help the individual choose the course of action most appropriate to them (respecting autonomy)
• Make referrals to specialists, social services, and support groups
• Thompson & Thompson Genetics and Genomics in Medicine, 9th ed., p. 388

Common Indications for Genetic Counseling

• Personal/family history of a hereditary condition (e.g., cystic fibrosis, fragile X, congenital heart defect, hereditary cancer)
• Previous child with multiple congenital anomalies, intellectual disability, or isolated birth defect (neural tube defect, cleft lip/palate)
• Pregnancy at risk for chromosomal or hereditary condition
• Consanguinity (marriages between blood relatives)
• Teratogen exposure (chemicals, medications, alcohol)
• Repeated pregnancy loss or infertility
• Newly diagnosed condition with genetic etiology
• Before or after genetic testing
• Positive newborn screening result (e.g., PKU)
• Carrier screening
• Abnormal prenatal screening result (maternal serum screen, cell-free fetal DNA, abnormal fetal ultrasound)
• Thompson & Thompson, p. 388

Preventive and Social Measures in Medical Genetics (PSM Framework)

1. Health Promotional Measures

(a) Eugenics

• Proposed by Francis Galton - science aimed at improving the genetic endowment of a population
• Negative eugenics: Reducing frequency of hereditary disease by sterilizing or preventing reproduction of affected individuals. Even with eugenic sterilization, new cases will continue due to fresh mutations and carrier alliances
• Positive eugenics: Encouraging carriers of "desirable" genotypes to reproduce - very limited application; most socially valuable traits are multifactorial and not simply inherited

(b) Euthenics

• Environmental manipulation to allow the genotype to express itself optimally
• Example: environmental stimulation can improve IQ in mildly mentally retarded children
• Solution lies not in opposing heredity vs. environment, but in their mutual interaction

(c) Genetic Counseling (as above)

(d) Other Preventive Measures

• Consanguineous marriages: Blood relative marriages increase risk of autosomal recessive traits and polygenic diseases (albinism, alkaptonuria, PKU). Lowering consanguinity is advantageous - offspring mortality from first cousin unions is significantly higher
• Late marriages: Early female marriage is favored to prevent Down syndrome (Trisomy 21). Risk rises sharply with maternal age: ~1:3,000 at age 20 vs. ~1:40 at age 40

2. Specific Protection

• Protection against mutagens - ionizing radiation (X-rays, nuclear), chemical mutagens
• Protecting gonads from unnecessary X-ray exposure
• Avoiding X-ray of pregnant uterus unnecessarily
• Rh haemolytic disease - now preventable with anti-D immunoglobulin

3. Early Diagnosis

• Genetic screening programs (newborn screening, carrier screening)
• Prenatal diagnosis (amniocentesis, CVS)
• Antenatal screening for chromosomal abnormalities

4. Treatment

• Gene therapy: introduction of a gene sequence into a cell to correct a mutation, kill a cell (cancer), or modify susceptibility
  • Delivery vehicles: retroviruses, adenoviruses, lipid or receptor targeting
  • Somatic gene therapy is now universally accepted as ethical
• Park's Textbook of Preventive and Social Medicine, p. 930-932

Principles of Genetic Counseling

WHO Recommendations on Genetic Counseling Services

• Establish genetic counseling centers in sufficient numbers in:
  1. Regions where infectious disease and nutritional disorders have been brought under control
  2. Areas where genetic disorders constitute a serious public health problem (e.g., sickle cell anemia and thalassemia endemic areas)

Risk Communication in Genetic Counseling

• Calculating risks using mendelian principles, Bayesian analysis, and empirical data
• Many adults have limited numeracy - only ~10% score in upper levels of numeric understanding; counselors should use proportions, visual aids, and tailored formats
• Factors affecting risk perception include: seriousness of condition, personal attributes, familial experience, media attention, stress, beliefs about prognosis

Ethical and Eugenics Concerns

• Thompson & Thompson Genetics and Genomics in Medicine, 9th ed., p. 395
• Emery's Elements of Medical Genetics and Genomics

Genetic counseling = Prospective (prevention-oriented, carrier screening) + Retrospective (post-occurrence in family). Key diseases: sickle cell, thalassemia. WHO recommends genetic counseling centers in endemic areas. Preventive levels: Health promotion (eugenics, euthenics, genetic counseling) → Specific protection (anti-radiation, anti-D) → Early diagnosis (screening, prenatal) → Treatment (gene therapy). Always nondirective and autonomy-respecting.

Measles (Rubeola) - Epidemiology, Clinical Features, Control and Prevention

Definition

• Park's Textbook of Preventive and Social Medicine

Problem Statement (Global Burden)

• Endemic virtually in all parts of the world
• Epidemics occur when the proportion of susceptible children reaches about 40%
• In a virgin community, more than 90% will be infected if the disease is introduced
• In 1980, before widespread vaccine use: estimated 2.6 million measles deaths/year worldwide
• By 2018: ~9.7 million cases and >140,000 deaths - a 73% decline in deaths from 2000-2018
• Measles accounts for about 2% of under-five mortality worldwide
• WHO/UNICEF 2010 targets: MCV1 coverage ≥90% nationally, ≥80% in every district; annual incidence <5 cases/million; 95% reduction in mortality vs. 2000

EPIDEMIOLOGICAL DETERMINANTS

Agent Factors

Host Factors

Environmental Factors

• Overcrowding favors spread
• Seasonal pattern: in temperate climates, peaks in late winter/spring; in tropical areas, post-harvest/dry season
• Herd immunity threshold: ~92-95% vaccination coverage needed to prevent outbreaks

CLINICAL FEATURES

Stage 1: Prodromal (Pre-eruptive) Stage

• Begins 10 days after infection, lasts until day 14
• The classic 3 Cs: Coryza (sneezing, nasal discharge), Cough, Conjunctivitis (redness, lacrimation, photophobia)
• Fever (sometimes high)
• Vomiting or diarrhoea may occur
• Koplik's spots (pathognomonic):
  • Appear 1-2 days before the rash
  • Small, bluish-white spots on a red base, like grains of table salt
  • Located on the buccal mucosa opposite the first and second lower molars
  • Smaller than the head of a pin
  • Pathognomonic of measles

Stage 2: Eruptive Phase

• Dusky-red, macular or maculopapular rash
• Begins behind the ears → spreads over the face and neck → down the trunk → reaches lower extremities over 2-3 days (cephalocaudal spread)
• Rash may be discrete or confluent and blotchy
• Rash and fever disappear in 3-4 days (in absence of complications)
• Rash fades in the same order of appearance, leaving a brownish discoloration persisting for up to 2 months
• During prodromal phase and first 2-5 days of rash: virus present in tears, nasal/throat secretions, urine, and blood
• As maculopapular rash appears: circulating antibodies become detectable, viraemia disappears, fever falls
• In patients with defective cell-mediated immunity: NO rash develops

Stage 3: Post-Measles Stage

• Child loses weight and remains weak
• May deteriorate into chronic illness due to increased susceptibility to secondary infections (bacterial superinfections)

DIAGNOSIS

• Clinical: Typical rash + Koplik's spots. The diagnosis would normally be incorrect in any febrile exanthem in which red eyes and cough are absent.
• Laboratory (used in developed countries where measles is uncommon):
  • Specific IgM antibodies by ELISA
  • RT-PCR for measles virus RNA in throat swabs, oral fluid, nasopharyngeal mucus, or urine

COMPLICATIONS

• Children aged <5 years (especially <1 year)
• Adults >30 years
• Malnourished children (especially Vitamin A deficiency)
• Immunocompromised patients (HIV/AIDS: CFR up to 50%)
• Overcrowded populations

• Developing countries: 3-6% (up to 30% in displaced/naive populations)
• Developed countries: 0.01-0.1%

TREATMENT

1. Supportive care: antipyretics, cough relief, treatment of conjunctivitis, sore mouth
2. Nutritional support: prevent malnutrition; encourage breastfeeding
3. Oral rehydration salts for dehydration
4. Vitamin A (for all severe cases and in areas with high case-fatality):
   • Dose given immediately on diagnosis AND repeated the next day
   • <6 months: 50,000 IU
   • 6-11 months: 100,000 IU
   • ≥12 months: 200,000 IU
   • If clinical signs of Vitamin A deficiency: third dose after 4 weeks
5. Antibiotics: only for proven bacterial superinfections
6. Patient isolation: for 7 days from onset of rash

PREVENTION AND CONTROL

A. Prevention of Measles

• Achieving an immunization rate of >95%
• Ongoing immunization through successive generations of children

1. Measles Vaccination (Primary Prevention)

• Available as: Monovalent (measles only), MR (measles-rubella), MMR (measles-mumps-rubella), MMRV (measles-mumps-rubella-varicella)
• Each dose (0.5 ml): ≥1,000 viral infective units
• Contains sorbitol, hydrolysed gelatin (stabilizers) and small amount of neomycin; no thiomersal
• No person-to-person transmission of vaccine strains ever documented

• Freeze-dried; stored at 2-8°C in colored glass vials (sensitive to sunlight)
• After reconstitution: use within 4 hours, store at 2-8°C in dark
• Loses ~50% potency after 1 hr at 20°C; almost all potency after 1 hr at 37°C

• 1 dose at 11-12 months: 95% protection
• 2 doses: 98% protection
• Infants vaccinated at 9 months: ~90% seroconversion
• Immunity develops 11-12 days after vaccination, probably lifelong

• Susceptible contacts >9-12 months can be protected if vaccine is given within 3 days of exposure (vaccine incubation ~7 days vs. natural measles ~10 days)

• HIV-infected with severe immunosuppression (MMRV absolutely contraindicated in HIV)
• Moderate/severe acute illness (minor illness is NOT a contraindication)
• Recent receipt of antibody-containing blood products (delay vaccination: 3 months post-IG for hepatitis A prophylaxis; 7-11 months post-IVIG)
• Severe immunosuppression (congenital immunodeficiency, leukaemia, lymphoma, high-dose immunosuppressive therapy)

• Mild "measles illness" (fever + rash) 5-10 days after immunization in 15-20% of vaccinees; fever lasts 1-2 days, rash 1-3 days - no cause for alarm
• Toxic Shock Syndrome (TSS): occurs with contaminated vaccine or reuse of vials beyond 4 hours - preventable

2. Passive Immunization (Immunoglobulin)

• For those who cannot receive live vaccine (immunocompromised, <6 months)
• Human immunoglobulin: 0.25 ml/kg body weight
• Must be given within 3-4 days of exposure
• Live vaccine may then be given 8-12 weeks later

B. Outbreak Control Measures

1. Isolation: Isolate patient for 7 days after onset of rash
2. Immunization of contacts: Within 2 days of exposure (if vaccine contraindicated: immunoglobulin within 3-4 days)
3. Prompt immunization at the beginning of an epidemic to limit spread

C. Specific Protection

• Protection against mutagens (radiation, chemicals) that could impair immunity
• Nutritional support programs to reduce malnutrition-related severity
• Integration with other child health interventions (Vitamin A supplementation programs)

ERADICATION PROSPECTS

• Only one serotype of measles virus
• Only two doses of vaccine needed
• No animal reservoir
• Heat-stable vaccines now available

• Immunization coverage of at least 96% of children under one year
• Prevention of cumulation in the immunity gap
• Challenges: weak immunization systems, high infectivity (R₀ = 12-18), anti-vaccination movements, conflict zones, changing epidemiology (shift to adolescents/adults)

GLOBAL MEASLES & RUBELLA STRATEGIC FRAMEWORK 2021-2030

1. Incorporate measles activities as key components of Primary Health Care (PHC) in support of Universal Health Coverage
2. Improve community demand for MCV uptake
3. Identify and close immunity gaps - reach under-served populations
4. Use life-course approach for MCV2 and catch-up vaccination
5. Ensure outbreak preparedness for timely detection and response
6. Ensure sustainable financing and quality vaccine supply
7. Foster research and innovation to overcome barriers

• Park's Textbook of Preventive and Social Medicine, pp. 166-170