Mycobacteria and spirochaetes
Mycobacteria, spirochaetes, chlamydia, rickettsia and mycoplasma for FCPS
Tuberculosis, leprosy, syphilis, leptospirosis, chlamydia, rickettsiae, Q fever and mycoplasma for FCPS Part 1: stains, pathology, serology and drugs. These organisms stain poorly with Gram stain or live inside cells, so the exam tests their staining, culture, pathology, serology and drug choice.
*Mycobacterium tuberculosis*: the organism
- Acid-fast bacillus: mycolic acids hold carbol fuchsin against acid-alcohol (Ziehl–Neelsen; auramine fluorescence). Strict aerobe, slow growing (about 18–24 hours per division): Löwenstein–Jensen culture takes 6–8 weeks, liquid culture (MGIT) 1–3 weeks. Cord factor gives serpentine growth and virulence.
- Spread by airborne droplet nuclei from an open pulmonary case, typically to household members in close, prolonged contact. It survives inside macrophages by blocking phagosome–lysosome fusion.
- Pathology: Th1 cells release IFN-γ, turning macrophages into epithelioid cells and Langhans giant cells; the caseating granuloma is the diagnostic microscopic lesion, and in a biopsy you look for acid-fast bacilli to confirm it. A tuberculous skin ulcer has undermined edges.
Primary and secondary tuberculosis
| Feature | Primary TB | Secondary (post-primary) TB |
|---|---|---|
| Who | First infection, often children | Reactivation (or reinfection) in adults; diabetes, HIV, steroids |
| Lung site | Ghon focus: subpleural, lower part of the upper lobe or upper part of the lower lobe (where most inhaled air goes) | Apical and posterior segments of the upper lobe (Assmann focus) |
| Nodes | Hilar node involved: Ghon complex; calcified: Ranke complex | Little node involvement |
| Course | Usually heals; progressive or miliary in infants and the immunosuppressed | Cavitation, caseation, haemoptysis, night sweats, weight loss |
- Why the apex: the apex is ventilated relatively more than it is perfused (high V/Q), so alveolar oxygen tension is highest there, which suits this strict aerobe; lymphatic drainage is also poorer. Bacilli seeded there during primary infection lie dormant (Simon foci) and later reactivate.
- Extrapulmonary: lymph nodes (commonest; cervical scrofula, cold abscess), pleura, ileocaecal region (commonest abdominal site; strictures, right iliac fossa mass), peritoneum (lymphocytic exudative ascites), spine (Pott disease: anterior vertebral bodies and disc, gibbus, psoas abscess, paraplegia), meningitis (basal exudate, cranial nerve palsies, hydrocephalus), genitourinary (sterile pyuria), adrenal, pericardium (constriction), miliary.
Diagnosis and prevention
- Sputum smear (two or three samples), GeneXpert MTB/RIF (rapid, detects rifampicin resistance; first test in Pakistan's programme), culture and sensitivity (gold standard), histology.
- Mantoux: 5 TU PPD intradermally, induration read at 48–72 hours; 10 mm or more is positive generally, 5 mm or more in HIV, contacts and the immunosuppressed. False negatives: miliary TB, HIV, malnutrition, measles, steroids, sarcoidosis. IGRA (QuantiFERON) is not affected by BCG.
- BCG (live attenuated *M. bovis*) at birth is most effective against severe childhood TB: TB meningitis and miliary TB. Protection against adult pulmonary TB is variable and modest.
- Why combination therapy: a large bacterial population always contains a few mutants resistant to any one drug; several drugs together prevent resistance emerging. Key toxicities:
| Drug | Classic side effect |
|---|---|
| Isoniazid | Peripheral neuropathy (give pyridoxine), hepatitis |
| Rifampicin | Orange-red urine, tears; enzyme induction (oral contraceptive failure, warfarin); hepatitis |
| Pyrazinamide | Hepatitis, gout (raised urate) |
| Ethambutol | Optic neuritis: red–green colour blindness first |
| Streptomycin | Ototoxicity and nephrotoxicity; avoided in pregnancy (fetal deafness) |
- Drug-induced hepatitis on ATT: stop the hepatotoxic drugs, let liver tests settle, then reintroduce one at a time.
- Non-tuberculous (atypical) mycobacteria live in water and soil and are not spread person to person: *M. avium* complex (HIV with CD4 below 50), *M. marinum* (fish-tank granuloma), *M. ulcerans* (Buruli ulcer), *M. fortuitum* and *M. abscessus* (infection after surgery and cosmetic procedures).
*Mycobacterium leprae*
- Acid-fast, obligate intracellular, prefers cool tissues (skin, peripheral nerves, nose, testes). It cannot be grown on artificial media (mouse footpad, armadillo only). Spread by nasal droplets after long contact; incubation years. Diagnosed by slit-skin smear and biopsy; early sign is an anaesthetic hypopigmented patch with a thickened nerve.
| Feature | Tuberculoid | Lepromatous |
|---|---|---|
| Cell-mediated immunity | Strong (Th1) | Weak (Th2) |
| Lesions | Few, well-defined, anaesthetic, hypopigmented; thick nerves | Many symmetrical nodules, leonine facies, loss of lateral eyebrows, saddle nose |
| Bacilli | Few (paucibacillary) | Many (multibacillary; foamy Virchow cells, globi) |
| Lepromin test | Positive | Negative |
- Nerves: ulnar (claw hand, commonest), median, common peroneal (foot drop), facial, greater auricular (visibly thickened), posterior tibial.
- Lepra reactions:
| Reaction | Who | Mechanism and picture |
|---|---|---|
| Type 1 (reversal) | Borderline leprosy | Rising cell-mediated immunity; existing lesions become red and swollen, acute neuritis |
| Type 2: erythema nodosum leprosum | Lepromatous, often on treatment | Immune complexes (type III); fever, arthralgia, crops of new painful red nodules while old lesions are unchanged; neuritis, iritis, orchitis |
- Treat reactions with prednisolone (thalidomide for severe ENL, never in pregnancy) and continue multidrug therapy.
Spirochaetes
| Organism | Disease and key points |
|---|---|
| *Treponema pallidum* | Syphilis; cannot be cultured; dark-ground microscopy. Primary: painless indurated chancre. Secondary (6–12 weeks): rash including palms and soles, condylomata lata, snail-track mouth ulcers. Tertiary: gummas, aortitis (ascending aneurysm, aortic regurgitation), tabes dorsalis, Argyll Robertson pupils. Congenital: Hutchinson teeth, saddle nose, sabre shins, interstitial keratitis, deafness. Treat with benzathine penicillin; Jarisch–Herxheimer reaction (fever, rigors within hours of the first dose) |
| *Leptospira* | Rat urine in flood water; fever, calf tenderness, conjunctival suffusion; Weil disease: jaundice, AKI, pulmonary haemorrhage; penicillin or doxycycline |
| *Borrelia burgdorferi* | Lyme disease (*Ixodes* tick): erythema migrans, facial palsy, heart block, arthritis; doxycycline |
| *Borrelia recurrentis* | Louse-borne relapsing fever; antigenic variation; spirochaetes on blood film |
- Syphilis serology: non-treponemal (VDRL, RPR) for screening and monitoring; they fall after treatment and give false positives in SLE, antiphospholipid syndrome, pregnancy, malaria, leprosy, EBV. Treponemal (TPHA, FTA-ABS, EIA) confirm and stay positive for life.
*Chlamydia*
- Obligate intracellular: the infectious elementary body enters cells and becomes the replicating reticulate body; diagnose by NAAT.
| Serovars | Disease |
|---|---|
| *C. trachomatis* A–C | Trachoma: the leading infectious cause of blindness worldwide (follicles, scarring, trichiasis); SAFE strategy, azithromycin |
| *C. trachomatis* D–K | Commonest bacterial STI and commonest cause of PID (tubal infertility, ectopic): urethritis, cervicitis, Fitz-Hugh–Curtis perihepatitis, reactive arthritis; neonatal conjunctivitis (days 5–14) and afebrile pneumonia; doxycycline (azithromycin in pregnancy) |
| *C. trachomatis* L1–L3 | Lymphogranuloma venereum: transient painless ulcer, then painful inguinal buboes (groove sign), proctitis |
| *C. pneumoniae*, *C. psittaci* | Atypical pneumonia; psittacosis from parrots |
- For combined gonorrhoea and chlamydia the current approach is ceftriaxone plus doxycycline; older schemes used a fluoroquinolone such as ofloxacin, now limited by resistance.
Rickettsiae and Coxiella
| Organism | Disease | Clue |
|---|---|---|
| *R. rickettsii* | Rocky Mountain spotted fever (tick) | Rash starts at wrists and ankles, spreads inwards, palms and soles |
| *R. prowazekii* | Epidemic typhus (louse) | Rash on trunk, spares palms and soles; Brill–Zinsser relapse |
| *R. typhi* | Endemic typhus (flea) | |
| *Orientia tsutsugamushi* | Scrub typhus (mite; South Asia) | Eschar at the bite, fever, nodes, pneumonitis |
| *Coxiella burnetii* | Q fever (inhaled from livestock and birth products) | No rash, no vector; pneumonia, hepatitis, culture-negative endocarditis |
- Weil–Felix test: antibodies to rickettsiae cross-react with *Proteus* OX antigens; a historical, cheap test for rickettsial infections (negative in Q fever). Serology or PCR is used now. Treatment: doxycycline, at any age for serious disease.
*Mycoplasma pneumoniae*
- No cell wall (sterols in the membrane), so beta-lactams cannot work and Gram stain shows nothing; fried-egg colonies; smallest free-living organism.
- "Walking" pneumonia in young adults (schools, barracks): dry cough, headache, X-ray worse than the signs; cold agglutinins (IgM anti-I) cause haemolysis; erythema multiforme, bullous myringitis, Guillain–Barré. Macrolide or doxycycline.
A related mimic: infectious mononucleosis
- The atypical lymphocytes in EBV glandular fever are activated CD8 cytotoxic T cells responding to infected B cells; heterophile (Monospot) antibodies confirm it. It enters this chapter because fever, lymphadenopathy and atypical cells mimic TB and other intracellular infections.
Remember Mycobacteria are slow aerobes: the apex for oxygen, weeks on Löwenstein–Jensen, several drugs to beat resistance.
Exam trap Lepromin is positive in tuberculoid and negative in lepromatous leprosy; *M. leprae* cannot be cultured.
Exam trap The Ghon focus is not apical; reactivation TB is, because apical oxygen tension is highest.
How FCPS asks about this
- Why secondary TB is apical: highest alveolar oxygen tension; Ghon focus is subpleural in the mid-zone.
- BCG: protects best against TB meningitis and miliary TB in children.
- ATT side effects: ethambutol red–green blindness; rifampicin orange urine and OCP failure; streptomycin avoided in pregnancy.
- Leprosy: cannot be cultured; ENL is an immune-complex reaction with new tender nodules; continue MDT.
- Syphilis: painless chancre; VDRL falls after treatment, TPHA stays positive; Jarisch–Herxheimer reaction.
- Rickettsia: Weil–Felix uses *Proteus* OX antigens; scrub typhus eschar; Q fever has no rash or vector.
- Mycoplasma and chlamydia: no cell wall so no beta-lactams; chlamydia is the commonest cause of PID and of infectious blindness.
Test yourself on this topic
5 of the 96 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A man has a single painless ulcer on the penis with an indurated base and painless rubbery inguinal nodes. What is the best immediate test on fluid from the ulcer?
Answer: Dark-ground microscopy
Primary syphilis (Treponema pallidum) causes a painless, indurated, clean-based chancre with painless regional lymphadenopathy, about 3 weeks after exposure. Treponemes are too thin for Gram staining and cannot be grown on ordinary media; dark-ground microscopy of serum from the chancre shows motile spirochaetes, and PCR is also used. Serology may still be negative early. Painful ulcers suggest herpes (Tzanck smear shows multinucleated giant cells) or chancroid (Haemophilus ducreyi).
Primary syphilis
- Painless indurated chancre + painless nodes
- Test: dark-ground microscopy
- Painful ulcers: herpes, chancroid
- Treat: benzathine penicillin
Remember Syphilis ulcer does not hurt.
Why the other options are wrong
- Gram stain Spirochaetes stain poorly with Gram.
- Ziehl–Neelsen stain For acid-fast bacilli.
- Tzanck smear Herpes simplex.
- Culture on blood agar T. pallidum cannot be cultured on ordinary media.
A stone-cutter has upper-lobe nodular fibrosis and eggshell calcification of hilar lymph nodes. Which infection is he especially prone to?
Answer: Tuberculosis
Silicosis follows inhalation of crystalline silica (quarrying, sandblasting, stone cutting, mining). Silica particles are ingested by macrophages, damage their lysosomes and activate the inflammasome, releasing fibrogenic mediators. It causes upper-lobe silicotic nodules, eggshell calcification of hilar nodes and progressive massive fibrosis. Silica impairs macrophage killing of mycobacteria, so tuberculosis is much commoner (silicotuberculosis). It is also a lung carcinogen.
Silicosis
- Upper lobes, nodules
- Eggshell calcification of hilar nodes
- Macrophage damage → TB risk
Remember Silica and TB walk together.
Why the other options are wrong
- Aspergilloma only Can colonise cavities, but TB is the classic association.
- Pneumocystis pneumonia Seen in HIV with low CD4.
- Legionnaires' disease Linked to water systems.
- Hydatid disease Linked to dogs and sheep.
BCG vaccine is given at birth in Pakistan. Against which outcome is it most effective?
Answer: Severe childhood TB
BCG is a live attenuated Mycobacterium bovis vaccine given intradermally (left upper arm) at birth in high-burden countries. It protects best against disseminated and meningeal TB in young children (about 70–80%), with variable and often poor protection against adult pulmonary TB, so it has limited effect on transmission. It also gives some protection against leprosy. Complications: local ulcer, suppurative lymphadenitis, rarely disseminated BCG in immunodeficient infants (contraindicated in symptomatic HIV and SCID). It causes a positive Mantoux test.
BCG
- Live M. bovis, intradermal, at birth
- Protects against TB meningitis and miliary TB in children
- Poor against adult pulmonary TB
- Avoid in immunodeficiency
Remember BCG protects the baby's brain more than the adult's lungs.
Why the other options are wrong
- Adult pulmonary TB everywhere Protection is variable and often poor.
- Latent TB reactivation Little effect.
- Multidrug-resistant TB Not specific to MDR.
- Leprosy only Partial protection only; not its main purpose.
Which lesion of tertiary syphilis is a destructive granulomatous mass with central necrosis, commonly in bone, liver or skin?
Answer: Gumma
Tertiary syphilis appears years after infection. Gummas are granulomatous lesions with central coagulative necrosis surrounded by macrophages, lymphocytes and plasma cells; they occur in bone, skin, liver (hepar lobatum), testis and other organs. Cardiovascular syphilis causes aortitis (endarteritis obliterans of vasa vasorum, 'tree-bark' intima), ascending aortic aneurysm and aortic regurgitation. Neurosyphilis includes tabes dorsalis (dorsal column degeneration), general paresis and Argyll Robertson pupils. Plasma cells are prominent in all syphilitic lesions.
Tertiary syphilis
- Gumma: granuloma with necrosis
- Aortitis: tree-bark intima, aneurysm, AR
- Neuro: tabes dorsalis, Argyll Robertson pupil
- Hallmark cell: plasma cell
Remember Gumma: syphilis's late granuloma.
Why the other options are wrong
- Chancre Primary syphilis.
- Condyloma latum Secondary syphilis.
- Hutchinson's teeth Congenital syphilis.
- Tabes dorsalis Neurosyphilis; dorsal column degeneration, not a mass.
A 25-year-old woman has 3 months of back pain, night sweats and a kyphus. Which part of the spine does this disease most often affect?
Answer: Lower thoracic and upper lumbar
Back pain with constitutional symptoms and a kyphus (gibbus) in a young adult in Pakistan points to Pott disease. The lower thoracic and upper lumbar (thoracolumbar) vertebrae are involved most often. Infection usually starts next to the disc (paradiscal) and destroys two adjacent bodies, which collapse forward to give the angular kyphus. Cervical and sacral disease are much less common.
Pott spine
- Commonest site: thoracolumbar
- Starts paradiscal, two bodies involved
- Anterior collapse gives a gibbus
- May form a cold abscess
Remember Pott spine: thoracolumbar, paradiscal, gibbus.
Exam trap Metastases usually spare the disc; TB typically destroys the disc space with the adjacent bodies.
Why the other options are wrong
- Upper cervical (atlantoaxial) Atlantoaxial TB occurs but is uncommon.
- Lower lumbar and sacral Lumbosacral disease is less common.
- Mid cervical vertebrae Cervical TB is uncommon; may cause a retropharyngeal abscess.
- Upper thoracic only The upper thoracic spine is a less common site.
Where this sits in the CPSP syllabus
- Paper 1: Microbiology, Mycobacteria, spirochaetes, chlamydia, rickettsia, mycoplasma
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