Medicine Marrow Pg No 1055-1064 (Infectious Diseases)

Viral Replication Steps

• Viral entry occurs when gp120 on the virus binds to the CD4 receptor on lymphocytes.
• gp120 undergoes a conformational change, allowing co-receptor binding to CXCR4 (lymphocytes) or CCR5 (macrophages).
• gp41 undergoes a conformational change, leading to fusion and uncoating of the virus.
• Reverse transcription converts viral RNA into DNA.
• Viral DNA integrates into host DNA.
• Viral RNA creates viral proteins, leading to the formation of immature virions on the cell surface.
• Mature virus is released after cleavage by protease.

Disease Progression

• Primary infection: Incubation period of 3-6 weeks.
• Acute infectious syndrome/Acute HIV infection: Fever, sore throat, diarrhea, lymphadenopathy, and rash.
• 90% of patients experience resolution of symptoms.
• 10% experience a fulminant stage (meningoencephalitis).
• Establishment of infection in the gastrointestinal tract (GALT).
• Subclinical replication occurs for a long period (clinical latency).

Scrub Typhus

• Infectious agent: Orientia tsutsugamushi.
• Endothelial proliferation leads to loss of endothelial integrity.
• Micro infarcts occur in the kidneys, leading to acute tubular necrosis and a thrombotic microangiopathic pattern.
• Eschar is a characteristic feature.
• Lymphadenopathy develops after one week.
• Untreated cases can lead to CNS involvement within one week, presenting with sensorineural deafness (reversible) and opsoclonus, myoclonus.

Malaria

• Sporozoites are the infective form of the parasite.
• Sporozoites travel through the blood to the liver and undergo pre-erythrocytic schizogony.
• Fever and rupture of red blood cells occur, releasing merozoites that undergo erythrocytic schizogony.
• Merozoites are released into the bloodstream, continuing the cycle.

Clinical Features of Malaria

• High-grade fever with chills and rigors.
• Extreme fatigue.

Complications of Malaria

• Sequestration of infected red blood cells in vital organs causes organ ischemia.

Miscellaneous Information about Malaria

• Parasites bind to glycophorin A receptors on red blood cells.
• Duffy-negative red blood cells provide protection against P.vivax.
• Sequestration of red blood cells within vital organs is caused by cyto-adherence, rosetting, and agglutination of red blood cells.
• Sickle cell trait and G-6PD deficiency protect against P.falciparum.
• The spleen is the major organ involved in trapping red blood cells.

Characteristics of Plasmodium Species

• P. falciparum: 48-hour erythrocytic cycle, younger cell preference, black pigment, no relapses.
• P. vivax: 48-hour erythrocytic cycle, reticulocytes and younger cells, yellow-brown pigment, relapses possible.
• P. ovale: 50-hour erythrocytic cycle, reticulocytes, dark-brown pigment, relapses possible.
• P. malariae: 72-hour erythrocytic cycle, older cells, brown-black pigment, no relapses.

Uncomplicated Malaria

• Fever with chills, fatigue, and diaphoresis.
• Tachypnea, tachycardia, and splenomegaly.
• Myalgia (not severe).

Complicated Malaria

• Anemia.
• Acidosis (lactic acidosis due to anaerobic metabolism).
• Renal failure (due to red blood cell sequestration).
• Non-cardiogenic pulmonary edema (ARDS).
• Jaundice.
• Cerebral malaria (convulsions, seizures).
• Hypoglycemia.
• Hypotension/shock.
• Hemoglobinuria (black water fever).

HIV Structural Genes

• Env: Codes for gp160 (spike protein).
• Gag: Codes for gp41 (transmembrane pedicle protein).
• Pol: Codes for enzymes (reverse transcriptase, integrase, protease).
• Other Genes: p17, gp41, matrix protein, core protein, nucleocapsid protein.

HIV Non-Structural Genes

• Nef/p2: Negative effector that downregulates host CD4 cells.
• Vif: Viral infectivity factor.
• Rev: Regulation of viral expression.
• Tat: Transcription activator.
• Vpr: Viral protein R.
• Vpu/vpx.

HIV Infection Sources

• High Concentration: Blood, semen, vaginal fluid, pus from sores, cerebrospinal fluid (CSF).
• Low Concentration: Sweat, tears, urine, saliva (SLIP: Salivary lymphocyte inhibitory protein), breast milk.

Modes of Transmission

• Sexual.
• Parent to child.
• Intravenous drug abuse.
• Blood transfusion.
• Needle stick.

Risk of Acquiring HIV per 10,000 Exposures

• Maximum: Blood transfusion (9250/10,000).
• Parent to child.
• Intravenous drug abuse.
• Needle stick.

Maximum Risk in Pregnancy

• During delivery (20-30%).

Note on HIV

• Delta32 mutation in the CCR5 receptor on macrophages renders resistance to HIV infection.
• DC sign refers to C-type lectin receptors on dendritic cells that bind to HIV.

Leptospirosis & Scrub Typhus

• Transmission Agent: Rodents.
• Incubation Period: 10 days.

Clinical Presentation of Leptospirosis

• Abrupt onset fever (low to intermediate grade).
• Myalgia.
• Calf muscle tenderness.
• Conjunctival congestion.

Complications of Leptospirosis

• Hepatorenal syndrome: Hepatitis with jaundice and acute tubular necrosis.
• Thrombocytopenia.
• Myocarditis.
• Secondary mitral regurgitation/aortic regurgitation.
• Aseptic meningitis.

Diagnosis of Leptospirosis

• Modified Faine's criteria.
• Gold standard test: Microscopic agglutination test (MAT).
• Lepto IgM ELISA positive after 7 days.

Treatment of Leptospirosis

• Doxycycline + Inj. Ceftriaxone 2g IV OD.

Diagnosis of Malaria

• Microscopy: Thick smear is the gold standard, using Giemsa staining and light microscopy. Thin smear is not sensitive.
• QBC test: Uses acridine orange stain for detection, three tests are conducted 12 hours apart.
• Rapid diagnostic test: HRP2 (not validated).

Treatment of Malaria

• Uncomplicated Malaria (Oral therapy): Artemether 20mg + Lumefantrine 120mg (first line), 4 tablets BID x 3 days. Alternative regimens include Atovaquone + Proguanil, Clindamycin + Mefloquine, Doxycycline + Quinine, Artesunate + Amodiaquine, Artesunate + Mefloquine.
• Complicated Malaria (IV therapy): Day 1: Three doses of IV Artesunate (120mg/2.4mg per kg) at 0, 12, and 24 hours. Day 2 and 3: Single dose of 2.4 mg/kg.

HIV History

• First reported case: 1981.
• AIDS (Acquired Immunodeficiency Syndrome) term coined by CDC: 1982.
• First isolation of the virus: 1983 by Luc Montagnier and colleagues, named as Lymphadenopathy Associated Virus (LAV) from an African patient.
• World Aids Day: 1 December (since 1987).

CDC Staging of HIV Infection

Pathogenesis of Salmonella

• Transmission: Feco-oral route.
• Salmonella invade the small intestine through the bloodstream (WBC).
• Salmonella multiply in the liver, spleen, and bone marrow, re-entering the bloodstream.
• Invasion and multiplication occur in the gallbladder, biliary system, and lymphatic system of the bowel.
• Salmonella pass into the intestinal tract, causing ileocoecal hyperplasia.

Treatment of Salmonella

• Uncomplicated cases: Cotrimoxazole (DS) BD x 14 days, or Azithromycin 1g OD x 7 days.
• Complicated cases: Ceftriaxone 2g IV OD x 14 days.

Dengue

• Incubation period: 7-10 days.

Disease Course of Dengue

• Day 1-3: NS-1 antigen positive. Symptoms include high-grade fever, headache, retro-orbital pain, and vomiting.
• Day 4 onwards: NS-1 antigen negative. Symptoms include subsiding fever, decreased platelet counts, and potential for dengue with warning signs/organ failure.

Active Space (Opportunistic Infections)

• Parasites: Cryptosporidiosis (chronic intestinal > 1 month), Isosporiasis (disseminated or extrapulmonary), Toxoplasmosis of the brain.
• Bacterial infections: Mycobacterium avium complex, Mycobacterium tuberculosis, Salmonella septicemia.

Category B (Not AIDS-Defining Illnesses)

• Vulvovaginal candidiasis.
• Oropharyngeal candidiasis (thrush).
• Pelvic inflammatory disease.
• Cervical dysplasia/carcinoma in-situ.
• Idiopathic thrombocytopenic purpura.
• Herpes zoster (shingles).
• Peripheral neuropathy.
• Hairy leukoplakia.
• Fever (>38.5°C) or diarrhea lasting >1 month.

Features of HIV in India

• First case detected (Chennai): 1986.

Retroviridae Family

• Delta virus: HTLV-I, responsible for adult T-cell lymphoma/leukemia and tropical spastic paraparesis.
• Lentivirus Serotypes: HIV-1 and HIV-2.

HIV-1 Groups

• M (most common).
• N.
• O.
• P (total: 10). Most common subtype: C. Subtype B spreads through blood and homosexuals.

HIV-1 Structure

• Envelope: Composed of glycoproteins gp41 and gp120.
• Nucleocapsid: Contains RNA, protease, reverse transcriptase, integrase, and p17.

HIV-2

• Less virulent.
• Belongs to the simian viridae family.
• West African virus.