Microbiology Short Notes

1. ENTERIC FEVER (Typhoid Fever)

• Gram-negative, motile, non-spore forming rod (Enterobacteriaceae)
• Has H (flagellar), O (somatic), and Vi (capsular/virulence) antigens

• Ingestion of contaminated food/water
• Organisms pass through intestinal epithelium via M-cells overlying Peyer's patches
• Enter intestinal lymphatics → bloodstream (primary bacteremia)
• Spread to liver, bone marrow, spleen, gallbladder
• Principal lesions: hyperplasia and necrosis of Peyer's patches, focal hepatic necrosis, inflammation of gallbladder

• Week 1: Fever rises gradually to 39-40°C, headache, malaise, relative bradycardia, constipation, myalgia
• Week 2: High plateau fever, splenomegaly, hepatomegaly
• Rose spots (1-4 mm blanching pink macules on chest/abdomen) - seen in <5% of cases
• WBC normal or LOW (unlike bacterial sepsis)
• Abdominal pain, diarrhea or constipation

• Jawetz Melnick & Adelbergs Medical Microbiology 28th Ed, p. 252

2. HIV (Human Immunodeficiency Virus)

• Two types: HIV-1 (worldwide) and HIV-2 (mainly West Africa, less virulent)

• Enveloped, positive-sense ssRNA virus
• Envelope glycoproteins: gp120 (surface, binds CD4) and gp41 (transmembrane, mediates fusion)
• Core proteins: p24 (capsid), p17 (matrix), p7 (nucleocapsid)
• Genome: gag, pol, env + regulatory genes (tat, rev, nef, vif, vpr, vpu)
• Contains reverse transcriptase, integrase, and protease enzymes

1. gp120 binds CD4 receptor on T-helper cells, macrophages, dendritic cells
2. Co-receptor binding: CCR5 (M-tropic, early infection) or CXCR4 (T-tropic, late infection)
3. gp41 mediates fusion; viral nucleocapsid enters cell
4. Reverse transcriptase converts RNA → DNA
5. Integrase incorporates viral DNA (provirus) into host genome
6. Viral RNA and proteins assembled → budding → protease cleaves precursors → mature virion

• Progressive destruction of CD4+ T cells
• Normal CD4 count: >500 cells/µL
• CD4 <200 cells/µL = AIDS-defining

• ELISA (screening) - detects antibodies + p24 antigen (4th generation)
• Western blot (confirmatory)
• CD4 count (monitors immunostatus)
• HIV RNA viral load (monitors treatment response)
• Janeway's Immunobiology 10th Ed, pp. 653-654; Medical Microbiology 9th Ed, pp. 601-602

3. AIDS (Acquired Immunodeficiency Syndrome)

1. Acute HIV syndrome (2-4 weeks post-infection): Flu-like illness, mononucleosis-like syndrome, high viremia, CD4 drops transiently
2. Clinical latency (years): Asymptomatic or Persistent Generalized Lymphadenopathy (PGL); viral replication continues
3. AIDS (CD4 <200, or AIDS-defining illness): Profound immunosuppression

• NRTIs (zidovudine, tenofovir, emtricitabine) - block reverse transcriptase
• NNRTIs (efavirenz, nevirapine) - non-competitively inhibit reverse transcriptase
• Protease inhibitors (lopinavir, ritonavir)
• Integrase inhibitors (dolutegravir - preferred in current regimens)
• Entry/fusion inhibitors (enfuvirtide)
• Standard regimen: 2 NRTIs + integrase inhibitor

4. DENGUE FEVER

• Flavivirus, family Flaviviridae; positive-sense ssRNA
• 4 serotypes (DENV-1 to DENV-4)
• Vector: Aedes aegypti (day-biting mosquito); also A. albopictus

1. Dengue fever (classic): Sudden high fever, severe headache, retro-orbital pain, severe myalgia/arthralgia ("breakbone fever"), rash (morbilliform, trunk → extremities), facial flushing
2. Severe dengue (formerly DHF/DSS): Plasma leakage, hemorrhage, organ impairment; mortality >10% if untreated
   • Preferentially occurs with second infections (different serotype) - antibody-dependent enhancement (ADE)
   • Pleural effusions, bleeding diathesis, thrombocytopenia

• Pre-existing antibodies from first infection bind but do not neutralize new serotype
• Facilitate viral entry into monocytes/macrophages via Fc receptors (ADE)
• Massive cytokine release → vascular leak

• NS1 antigen (days 1-5, most sensitive in febrile phase)
• IgM/IgG ELISA (from day 5 onward)
• PCR (early viremic phase, most specific)
• CBC: Thrombocytopenia + leukopenia + rising hematocrit (hemoconcentration)
• Tourniquet test (Rumpel-Leede test) for capillary fragility

• Tintinalli's Emergency Medicine, p. 1123

5. MALARIA

• P. falciparum - most pathogenic (tertian, malignant), no relapse (no hypnozoites)
• P. vivax - tertian (48h cycle), relapse possible (hypnozoites)
• P. ovale - tertian (48h), relapse possible
• P. malariae - quartan (72h cycle), associated with nephrotic syndrome
• P. knowlesi - zoonotic, Southeast Asia

1. Sporozoites injected by mosquito → liver (exoerythrocytic phase)
2. Sporozoites → merozoites in hepatocytes; rupture liver cells (1-4 weeks)
3. Merozoites enter RBCs → trophozoites → schizonts → merozoites (erythrocytic cycle)
   • Rupture at 48h (P. vivax/falciparum/ovale) or 72h (P. malariae)
4. Some become gametocytes → taken up by mosquito → sexual cycle (sporogony) → sporozoites
5. Hypnozoites (dormant liver forms) only in P. vivax and P. ovale (cause relapse)

• Expresses PfEMP1 on infected RBC surface → binds ICAM-1, VCAM-1, CD36 on endothelium
• Cytoadherence + rosetting → microvascular obstruction in brain, kidney, placenta
• Causes cerebral malaria, blackwater fever (haemoglobinuria), acute renal failure

• Classical paroxysms: Cold stage → Hot stage → Sweating stage
• Tertian fever (48h): P. vivax, P. falciparum, P. ovale
• Quartan fever (72h): P. malariae
• Complications (P. falciparum): Cerebral malaria, pulmonary edema, severe anemia, hypoglycemia, AKI, algid malaria (septicemic)

• Peripheral blood smear (gold standard): Thick smear (detection), thin smear (speciation); Giemsa stain
• Rapid diagnostic tests (RDTs): detect HRP-2 antigen of P. falciparum
• PCR (most sensitive, reference standard)

• P. falciparum: Artemisinin-based combination therapy (ACT) - e.g., artemether + lumefantrine
• P. vivax/ovale: Chloroquine + primaquine (to eliminate hypnozoites/prevent relapse)
• Severe malaria: IV artesunate
• Jawetz Melnick & Adelbergs Medical Microbiology 28th Ed, p. 741; Robbins & Kumar Basic Pathology, pp. 392-393

6. FILARIASIS (Lymphatic Filariasis)

1. Mosquito injects infective larvae (L3) into skin
2. Larvae migrate to lymphatics → develop into adult worms (male + female)
3. Adult females produce microfilariae → enter bloodstream
4. Nocturnal periodicity of W. bancrofti microfilariae (peak in peripheral blood at night, coincides with Culex biting time)
5. Mosquito ingests microfilariae → develop to L3 → cycle continues

• Adult worms in lymphatic vessels → inflammation → obstruction → lymphedema
• Repeated infections + inflammatory responses cause progressive damage

• Asymptomatic (microfilaraemia only)
• Acute: Filarial fevers, acute adenolymphangitis (ADL) with local inflammation, retrograde lymphangitis
• Chronic: Lymphedema, elephantiasis (gross limb/scrotal swelling), hydrocele, chyluria (milky urine from lymph in urine)
• Tropical pulmonary eosinophilia (TPE): Allergic reaction to microfilariae; marked eosinophilia, nocturnal cough, asthma-like

• Nocturnal blood smear (microfilariae detected, best between 10pm-2am)
• Membrane filtration / Knott's concentration technique
• ICT (immunochromatographic card test) for W. bancrofti antigen - no nocturnal sampling needed
• Eosinophilia on CBC
• DEC provocation test (daytime blood after diethylcarbamazine)

• Diethylcarbamazine (DEC): Kills both microfilariae and adult worms
• Ivermectin + albendazole (used in mass drug administration programs)
• Surgical: Excision/eversion for hydrocele; node transfer rarely done for elephantiasis
• Bailey and Love's Short Practice of Surgery 28th Ed, p. 5730

7. INFECTIVE ENDOCARDITIS (IE)

• Pre-existing valvular/endothelial damage → platelet-fibrin thrombus (NBTE)
• Bacteremia seeds the thrombus → colonization → vegetation formation
• High-flow lesions (left side) affected more than right side (except IV drug users)

• Positive blood cultures (2 of 2, or persistent bacteremia with typical organisms)
• Evidence of endocardial involvement on echocardiography (vegetation, abscess, new valvular regurgitation)

• Predisposing heart condition or IV drug use
• Fever >38°C
• Vascular phenomena (emboli, mycotic aneurysm, Janeway lesions)
• Immunologic phenomena (Osler's nodes, Roth's spots, glomerulonephritis, positive rheumatoid factor)
• Microbiological: positive blood culture not meeting major criteria

• Fever (most common), new/changing murmur, splenomegaly
• Peripheral stigmata: Osler's nodes (painful, thenar eminence), Janeway lesions (painless, palms/soles), Roth's spots (retinal hemorrhage with pale center), splinter hemorrhages
• Embolic phenomena: Stroke, renal/splenic infarcts, pulmonary emboli (right-sided)

• Blood cultures x3 (before antibiotics) - cornerstone of diagnosis
• Echocardiography: TTE first; TEE if TTE inconclusive, prosthetic valve, or high suspicion
• CBC, ESR, CRP, urinalysis (microscopic hematuria from immune complex GN)

• Penicillin G (or ampicillin) + gentamicin for streptococcal IE
• Nafcillin/oxacillin for S. aureus; vancomycin if MRSA
• Duration: 4-6 weeks (native valve); 6 weeks minimum (prosthetic valve)
• Surgical indications: Heart failure due to valve dysfunction, uncontrolled infection, large vegetation (>10mm) with embolic risk, fungal IE

• Amoxicillin 2g PO single dose before dental procedures
• Doxycycline as alternative if truly penicillin-allergic (clindamycin no longer recommended due to C. difficile risk)
• Indicated for: Prosthetic valve, previous IE, certain congenital heart defects, heart transplant with valve disease
• Braunwald's Heart Disease 2-Vol Set, p. 1228-1235

Sources: Jawetz Melnick & Adelbergs Medical Microbiology 28E; Janeway's Immunobiology 10E; Medical Microbiology 9E; Robbins & Kumar Basic Pathology; Tintinalli's Emergency Medicine; Bailey and Love's Surgery 28E; Braunwald's Heart Disease; Forensic Medicine & Toxicology 36E