Infectious Diseases

1. What is a Disease?

Disease: an abnormal condition that reduces the effectiveness of the functions of an organism (body acts out of the normal, overall performance ↓).

Diseases are classified into 2 categories:

E.g. non-infectious: cancers, genetic disorders, Alzheimer's, Parkinson's.

How a pathogen causes disease: another species enters the body and hijacks its chemical, metabolic & protein-synthesis machinery ⇒ body behaves abnormally.

Contagious example: sharing a drink / food with someone with flu or tonsillitis — infected saliva/food carries the pathogen to you.

Non-infectious example	Real cause (NOT a pathogen)
Cancer	body cells divide rapidly & indefinitely by mitosis → irregular mass = tumour
Diabetes (type 2)	strong family / genetic history – if father & grandfather had it, you are more prone
Sickle-cell anaemia	gene mutation → biconcave RBCs become sickle-shaped
Alzheimer's	old age – nerve cells (neurons degenerate) → memory loss
Parkinson's	nervous-system disorder – body shivers / jitters (ion imbalance, teacher unsure of exact ion)

2. Classification of Infectious Diseases

↳ on the basis of the pathogen

Pathogen	Disease type	Notes
(1) Bacteria	bacterial disease	treated with antibiotics (very common infections)
(2) Viruses	viral disease	e.g. AIDS; antibiotics don't work
(3) Protozoa	protozoal disease	e.g. malaria (Plasmodium)
(4) Fungi	fungal infection	usually skin infections
(5) Worms (helminths)	helminth infection	"worms in stomach": appetite loss, blood in stool, stomach pain
(6) Prions	—	abnormal proteins that become disease-causing; not in syllabus

3. The 6-Point Checklist (for every disease)

Whenever you study a disease, fill in this chart:

Step	Meaning (from teacher)
① Causative agent	which species / pathogen causes it
② Mode of transmission	Airborne (breathing dirty air) · droplet (sneeze, saliva, sweat – e.g. Covid) · body fluids (blood from infected → uninfected person) · water-/food-borne
③ Signs & symptoms	how we identify / guess the disease (e.g. malaria vs dengue)
④ Diagnosis	the test / procedure that confirms it
⑤ Treatment	how to cure / treat
⑥ Prevention & control	stop the spread (Covid SOPs: isolation, quarantine)

4. CHOLERA ⇒ bacterial infection

① Causative agent: Vibrio cholerae (bacterium).

② Mode of transmission: Faecal–oral route

• (i) infected person contaminates water supply through infected faeces → uninfected person drinks the contaminated water → gets V. cholerae.
• (ii) person passes infected faeces, doesn't wash hands, eats food with unwashed hands → ingests V. cholerae.

How cholera makes you ill

• Some V. cholerae are destroyed by HCl in the stomach – many succumb to the low pH.
• Those that breach the acid barrier attack the epithelial cells of the small intestine by releasing a toxin called choleragen.
• Choleragen promotes loss of salts (electrolytes) from the small intestine ⇒ rapid dehydration (water follows the salts).

③ Signs & symptoms

watery diarrhoea (rice-water stool) · vomiting · fever · lethargy · sunken eyes · dry mouth & skin (due to dehydration) · increased thirst

④ Diagnosis: microscopic stool examination

⑤ Treatment

Condition	Treatment
mild – moderate	Oral rehydration therapy (ORT)
severe dehydration	Intravenous fluid → faster rehydration

• Main cause of death = dehydration ⇒ main target = prompt rehydration + normalising salt (electrolyte) levels.
• Avoid anti-vomiting or anti-diarrhoeal medicines.
• Antibiotics shorten the duration of illness & lessen severity of symptoms.

⑥ Prevention & control

• Clean food and water supply
• Proper sanitation
• Vaccination
• Strict hygiene rules (hand washing)
• Boiled water
• Chlorinated water
• Educational awareness

5. TUBERCULOSIS (TB) ⇒ bacterial infection

① Causative agents: (1) Mycobacterium tuberculosis (MTB)   (2) Mycobacterium bovis

Species	Affects	Transmission
M. tuberculosis	humans	aerosol droplets – infected person coughs / sneezes → uninfected person inhales MTB from the air
M. bovis	mainly cattle	unpasteurised milk, undercooked / uncooked (cattle) meat
Both – vertical	—	across the placenta in a pregnant woman (RARE)

④ Diagnosis: (1) Chest X-ray (lungs show patchy spots/lesions)   (2) Sputum culture

③ Signs & symptoms

• persistent cough · bloody phlegm · chest pain
• fever · weight loss · night sweats

DOTS — Directly Observed Treatment, Short-course

Many sufferers in the developing world have limited financial resources and are possibly less literate. Any mistake in TB treatment is likely to increase the chance of drug / antibiotic resistance. So WHO developed the DOTS policy. Main points:

1. commitment of the local authority / government
2. diagnosis & monitoring using sputum smear microscopy
3. standardised treatment for at least the first 2 months
4. a regular medicinal drug supply
5. a standardised recording & reporting system that allows assessment of treatment results

BCG vaccine (against Mycobacterium)

Contains an attenuated (weakened) pathogen → it does not cause disease; instead it triggers the immune system to produce antibodies against the pathogen → develops immunity if the same pathogen naturally invades in future.

⑤ Treatment of TB

• TB is a prolonged chronic disease → minimum duration 6 months (6–8 / 6–12 months).
• Multiple antibiotics are prescribed because:
  (i) kill the bacteria so no reservoir of infection remains
  (ii) reduce the chance of developing antibiotic resistance
  (iii) to overcome antigenic concealment (MTB hides inside cells)

Antibiotics for TB: (1) Isoniazid (2) Rifampicin (3) Ethambutol (4) Pyrazinamide — these 4 = first-line drugs.

If the pathogen is resistant to all first-line drugs → 2nd-line drugs are prescribed.

⑥ Prevention & control

• Detect infected individuals + appropriate treatment / quarantine so the disease doesn't spread
• Mass vaccination programme → develop herd immunity

6. AIDS (Acquired Immuno-Deficiency Syndrome)

① Causative agent: HIV (human immunodeficiency virus) – belongs to the family of retroviruses.

• Host cell: T-helper cells (T_H)
• HIV is an enveloped virus
• HIV contains enzymes: (1) reverse transcriptase (2) protease (also integrase shown in diagram)
• Role of glycoproteins (gp41, gp120): allow the virus to attach to the host (T_H) cells

② Mode of transmission: exchange of body fluids

1. Unprotected sexual intercourse
2. Sharing of contaminated needles
3. Unscreened blood transfusion
4. Vertical transmission – placenta → fetus, or mother → baby via breastfeeding. NOT RARE! (unlike TB & malaria)

④ Diagnosis: (i) ELISA (enzyme-linked immunosorbent assay) – screening test   (ii) Western blot – confirmatory test

③ Signs & symptoms

AIDS makes the patient immunocompromised ⇒ vulnerable to all kinds of opportunistic infections. General symptoms: (1) fever (2) rashes / ulcers (3) fatigue (4) muscle pain / body aches

⑤ Treatment

• There is no cure for advanced AIDS; treatment is generally effective in HIV-positive people who don't yet have AIDS.
• Treatment = HAART (Highly Active Antiretroviral Therapy): 2–3 antiretrovirals in combination against HIV.

Drug class	How it works	E.g.
NRTI (nucleotide reverse transcriptase inhibitor)	competitive inhibitor of reverse transcriptase – drug shape is similar to a nucleotide	Zidovudine
nNRTI (non-nucleotide RTI)	non-competitive inhibitor of reverse transcriptase	Efavirenz
Protease inhibitor	blocks the viral enzyme protease	Indinavir

⑥ Prevention & control

• avoid unprotected sex · stick to one sexual partner
• avoid contaminated needles
• screen blood for HIV before transfusions
• always screen pregnant & breastfeeding mothers
• educational campaigns on spread & transmission
• screen for symptomless carriers and trace contacts of infected individuals

7. MALARIA ⇒ protozoa (protoctista)

① Causative agents: Plasmodium – (i) P. falciparum (75% of cases) (ii) P. malariae (iii) P. ovale (iv) P. vivax

Vector: an organism that carries a disease (pathogen) from one person to another. Malaria needs a vector → female Anopheles mosquito.

② Mode of transmission

1. Mosquito bite (infected → uninfected): female Anopheles bites an infected person and releases an anticoagulant to prevent clotting → it ingests the parasite with the blood → later bites an uninfected person and transmits the parasite (with anticoagulant + saliva).
2. Transfusion of unscreened blood.
3. Vertical transmission (rare) – across the placenta or during breastfeeding.

Life cycle of Plasmodium

1. Plasmodium gametes fuse, multiply and form infective stages in the mosquito (gut → salivary glands).
2. When the mosquito takes a blood meal, the parasite enters the host with the mosquito's anticoagulant and saliva.
3. Infective stages enter the bloodstream and then liver cells.
4. Parasite matures in liver cells, then leaves the liver to enter RBCs.
5. Parasites multiply in RBCs, causing RBCs to lyse.
6. Parasites are released and infect other RBCs.
7. Parasites are picked up by another mosquito in a blood meal.

③ Symptoms

• high fever with chills · headache · vomiting · excessive sweating · diarrhoea · fatigue
• anaemic → ↓ number of RBCs / ↓ Hb (the "lack of iron" feeling)

④ Diagnosis: peripheral blood smear

⑤ Treatment: antimalarial drugs – e.g. chloroquine; also a combination of antimalarial drugs.

⑥ Prevention & control

Strategy	Methods
(1) Mosquito eradication (vector control)	insecticide spray · indoor residual sprays · spread oil over stagnant water to disrupt breeding sites · introduce fish (guppy) in ponds to kill larval stages
(2) Prevent mosquito bites	mosquito repellents · mosquito nets · insecticide-treated nets · keep pet animals in the house (mosquitoes prefer animal blood)
(3) Prophylactic drugs	medicinal drugs you take to prevent infection
(4) Educational awareness	—

8. Antibiotics

Antibiotics protect us against bacterial infections (they do NOT work on viruses – no target sites).

Mode of action – antibiotics inhibit the synthesis of: ① cell wall ② cell membrane ③ nucleic acid ④ protein synthesis

Penicillin

→ bactericidal (kills bacteria) → competitive inhibitor of the enzyme glycoprotein peptidase.

• Glycoprotein peptidase makes the cross-links between peptidoglycan chains in the peptidoglycan cell wall → essential for bacterial cell-wall synthesis.
• Penicillin blocks the enzyme ⇒ no cross-links ⇒ weak wall ⇒ osmotic lysis of the bacterial cell (water enters, cell bursts).

Antibiotic resistance (ABR)

Example: antibiotic A was very effective on bacterium A, but after a few months bacterium A grows normally – same antibiotic, same bacterium, no change in manufacture ⇒ the bacterium has developed resistance. The genes are the "law book" of any organism – it now has antibiotic-resistance genes.

Spread of ABR

Bacteria divide every ~20 min (binary fission) – so resistance spreads fast.

Vertical transmission	Horizontal transmission
parent → genetically identical daughter cells by binary fission (gene copied along with circular DNA)	genetic recombination – gene passes to same or different species, no parent→offspring needed: transformation · transduction · conjugation

Horizontal transmission – 3 methods

R = antibiotic-resistance gene

Reasons for development & spread of ABR

1. Overprescribing of antibiotics by doctors (rushed OPD – same drug to everyone) → community-wide exposure.
2. Patients don't finish the prescribed course as instructed (bacterial reservoir survives).
3. Overuse – same antibiotics given to humans and livestock; also self-medication / re-using an old prescription.
4. Poor infection control in hospitals and clinics.
5. Lack of new antibiotics being developed.

How can antibiotics be used effectively to prevent ABR?

1. Prescribe narrow-spectrum antibiotics
2. Antibiotics available only when prescribed
3. Take the entire course
4. Use multiple antibiotics in combination (bacterium faces different drugs at once → very hard to resist all)
5. Don't use the same antibiotics in humans and animals
6. Avoid prescribing antibiotics for viral diseases

Antibiotic susceptibility testing

Susceptibility: a state of being likely to be influenced or harmed by a particular thing.

Antibiotic A is tested against bacteria B_α, B_β, B_γ: it kills B_α and B_γ but B_β is resistant – so doctors pick the antibiotic the pathogen is susceptible to.

Disk diffusion method

• Paper disks soaked in different antibiotics (Ab A, B, C) are placed on an agar plate with a bacterial lawn/colony.
• Clear zone of inhibition around Ab A ⇒ bacteria susceptible to A (growth inhibited/killed).
• No zone of inhibition around B and C ⇒ bacteria resistant to Ab B and C.
• Bigger zone = more effective antibiotic.