Principles of Medical Microbiology and Parasitology LAQs & SAQs

- **Trimethoprim-sulfamethoxazole (TMP-SMX)**: First-line prophylaxis for both PCP and toxoplasmic encephalitis, especially when CD4 count <200 cells/μL or <100 cells/μL with positive *Toxoplasma* IgG. - **Alternative agents**: Dapsone, atovaquone, or aerosolized pentamidine may be used in TMP-SMX-intolerant patients. - **CD4 Monitoring**: Regular CD4+ T-cell count assessment to guide initiation and discontinuation of prophylaxis. - **ART initiation**: Early antiretroviral therapy helps restore immunity and prevent opportunistic infections. - **Adherence counseling**: Ensures compliance with prophylactic regimens and ART. - **Leucovorin (folinic acid) supplementation**: To prevent bone marrow suppression from pyrimethamine. - **Regular hematologic monitoring**: Monitor CBC for neutropenia, anemia, and thrombocytopenia. - **Renal function monitoring**: Sulfadiazine can cause crystalluria or renal toxicity. - **Hydration**: Ensure adequate fluid intake to prevent renal complications. - **Allergy surveillance**: Watch for hypersensitivity reactions or rash, especially from sulfonamides. - **Cutaneous lesions**: Ulcerated or nodular skin lesions at the site of sandfly bite, often painless. - **Regional lymphadenopathy**: Enlargement of nearby lymph nodes. - **Disfiguring scars**: Chronic or healing lesions may result in visible scarring. - **Secondary bacterial infection**: May complicate ulcerated lesions. - **Systemic symptoms** *(in some cases)*: Low-grade fever and malaise, depending on the species and immune status. - **Bactericidal effect** occurs when an antibiotic kills bacteria directly. This is typically seen:At higher drug concentrations. - In rapidly dividing bacterial populations. - In infections where immune clearance is inadequate (e.g., endocarditis, meningitis, neutropenia). - **Bacteriostatic effect** inhibits bacterial growth and replication without killing, relying on the host immune system to eliminate the organism. - **Effect depends on the drug, dose, organism, and host immunity.**For example, chloramphenicol may be bacteriostatic for some organisms and bactericidal for others. - **Avoid in immunocompromised patients**: These patients may require bactericidal agents due to reduced immune clearance. - **Avoid combination with bactericidal drugs**: Some combinations (e.g., bactericidal + bacteriostatic) can lead to antagonism and reduced efficacy. - **Pathogenesis**:Prions are misfolded proteins (PrP^Sc) that induce conformational changes in normal cellular prion proteins (PrP^C) to the abnormal form. - PrP^Sc accumulates in neural tissue, forming amyloid plaques. - This accumulation leads to neuronal death, spongiform degeneration, and progressive neurodegeneration. - There is no immune response or inflammation due to the host-derived nature of prions. - **Human prion diseases**:**Creutzfeldt-Jakob disease (CJD)** – the most common prion disease, often sporadic. - **Variant CJD** – associated with consumption of BSE (mad cow disease)-infected beef. ##### **A. Life Cycle** *(Illustration-friendly — include with diagram if submitting)* . Click to see Life Cycle - **Mosquito stage (Definitive host)**Female *Anopheles* mosquito inoculates **sporozoites** during a blood meal. - **Human liver stage (Pre-erythrocytic)**Sporozoites enter hepatocytes → multiply asexually → form **schizonts** → release **merozoites** into bloodstream. - **Human blood stage (Erythrocytic cycle)**Merozoites invade RBCs → mature into **trophozoites** → form **schizonts** → rupture RBCs, releasing more merozoites. - Some trophozoites form **gametocytes** (sexual forms). - **Back to mosquito (sexual cycle)**Mosquito ingests gametocytes → gamete fusion → **zygote** → **ookinete** → **oocyst** → sporozoites → cycle continues. **Illustration tip**: Use a circular flow chart with human and mosquito phases clearly labeled. --- ##### **B. Pathogenesis** - **RBC Destruction** → Hemolytic anemia, jaundice. - **Cytoadherence** → *P. falciparum* causes infected RBCs to adhere to endothelium (via PfEMP1) → **microvascular obstruction**, **cerebral malaria**, **placental malaria**. - **Immune response** → Fever, chills, cytokine release. - **Sequestration** → In spleen/liver; can lead to organomegaly and immune evasion. --- ##### **C. Treatment** - **Uncomplicated malaria**:**Artemisinin-based combination therapies (ACTs)**: e.g., artemether-lumefantrine, artesunate-amodiaquine. - **Severe malaria**:**IV artesunate** (preferred), followed by oral ACT. - **Supportive care**:Manage hypoglycemia, anemia, renal failure, cerebral edema. Note: Chloroquine is **ineffective** due to resistance. --- ##### **D. Control and Prevention** - **Vector control**: Insecticide-treated nets (ITNs), indoor residual spraying (IRS). - **Chemoprophylaxis**: E.g., atovaquone-proguanil, doxycycline (travelers). - **Surveillance**: Rapid diagnostic tests (RDTs), microscopy. - **Vaccination**: RTS,S/AS01 (Mosquirix)