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Malaria, TB, Ebola, Gonorrhea And more, Oh my! Malaria • Chills, fever, vomiting, headache last 2-3 days; alternates with asymptomatic period. • Anopheles mosquitoes (night feeders) carry Plasmodium protozoan. • Tropical areas report 300-500 million cases, 12 million deaths per year. • Many people contract malaria several times in their lifetime. • Range of disease has expanded. Plasmodium falciparum • Most dangerous species. • Destroys RBCs – anemia. • Some RBCs stick to capillary walls, clogging them. • Within 30 minutes of bite, parasite infects liver. • Liver releases many merozoite forms (RBC destroyers). Other Species • P. vivax – prevalent in Asia. – Can survive in liver for months. • P. ovale Plasmodium vivax Plasmodium • Many stages to its life cycle. • Merozoite stage infects RBCs. • Different stages enable it to evade immune system and anti-malarial drugs. • Antigenic variation in sporozoite. • People with sickle-cell anemia (or carriers) have some resistance. Anti-Malarials • • • • • Quinine Chloroquine, primaquine, mefloquine Resistance is evident Malarone is newer Derivatives of artemisinin. – ACT = Artemesinin-based Combination Therapy. Plasmodium lifecycle Malaria Vaccine Trials 1. Proteins from Plasmodium sporozoite. • Add adjuvant. 2. Live, Attenuated parasites. • Cultured in mosquitoes. 3. Transmission-blocking Vaccines. • Proteins from gametocyte or from mosquito. Tuberculosis (TB) • “Consumption” • Mycobacterium tuberculosis • 20 hour generation time • Acid-fast • Can survive for weeks in dried sputum • Resistant to chemical disinfectants M. avium in AIDS lymph node Most Common Human Infection • 33% of world population is infected • Immigrants, teachers, health care workers are screened Vaccine • Live M.bovis • Inconsistent effectiveness • Vaccinated people will test positive for TB Diagnosis • • • • Tuberculin Skin Test Detects T cell response Bacterial protein is injected under skin Response detected within 48 hours TB X-ray Pathogenesis • Destruction by macrophage is avoided • As immune cells arrive to infection, they wall if off in a tubercle • These lesions can be seen in X-ray • If the tubercle ruptures, bacteria can be released in bloodstream • Loss of energy, Coughing (blood), hemoptysis Exposure • Does not always result in disease • Enters body by inhalation • 1926: Big mistake in Germany where babies were inoculated with virulent M. tuberculosis instead of vaccine – 76 of 249 died; rest showed few symptoms Treatment of TB • Antibiotics must be administered for months – Slow growth, bacteria hidden in macrophages – May be cause of emergence of resistant strains (MDR-TB) • Rifampin + Isoniazid • Streptomycin, ethambutol • Moxifloxacin??? MDR-TB • About 5% of active cases of TB. • Second-line drugs are expensive. – But many patents have expired. • Major outbreak in NY State Prisons in 1990s. • Partners in Health in Lima, Peru. • Russian prisons. Ebola Viral Disease – November 21, 2014 • • • • • • • • • • Guinea 2047 cases/1214 deaths. Liberia 7082/2963. Sierra Leone 6190/1267. Mali 6/6. Nigeria 20/8. Senegal 1/0. Spain 1/0. U.S. 4/1 Total: 15,351/5459. Health Care Workers: 588/337. Suspected, probable, & confirmed. http://www.who.int/csr/disease/ebola/situation-reports/en/ Ebola Virus Strains • Zaire, Sudan, Bundibugyo. – Ape-to-human transmission. – Deadly • Reston – Pig-to-human transmission in Philippines? – Not dangerous. Host immune responses to Ebola virus and cell damage due to direct infection of monocytes and macrophages cause the release of cytokines associated with inflammation and fever (A). Sullivan N et al. J. Virol. 2003;77:9733-9737 Ebola Virus (Filoviridae) https://microbewiki.kenyon.edu/index.php/Infection_Mechanism_of_Genus_Ebolavirus https://www.bcm.edu/departments/molecular-virology-and-microbiology/emerging-infections-and-biodefense/ebola-virus Marburg Virus • Similar to Ebola. • Recent outbreak in Angola & Uganda. – Dutch woman brought it home with her from Uganda in 2008. United States, 1940s Gonorrhea • • • • Neisseria gonorrhea – gram-negative Fimbriae attach to mucosal cells Named in AD 150 in Greece 300,000 cases per year in U.S. (reported) – 800,000 estimated by CDC. • Symptoms in males – pus discharge, painful urination • Subtle symptoms in females – more dangerous (true for many STIs), infects cervix – Infection can spread to other areas N.gonorrhea in human fallopian tube Diagnosis • Pus from male smear – N. gonorrhea seen in WBCs • Cervical culture from female cultivate – Difficult to grow (fastidious) – CO2 enrichment – ELISA Systemic Cases • • • • Joints – gonorrheal arthritis Heart – gonorrheal endocarditis Meninges – gonorrheal meningitis Eyes – especially in babies born to infected mothers (opthalmia neonatorum) • Pharynx • Anus Reinfection • Immunity is rare because of antigenic variation Antibiotics • Penicillin-resistant strains • Now: fluoroquinolones Antibiotic Resistance • Fluoroquinilones and Cephalosporins!! • New treatments (experimental): – azithromycin + gentamicin – azithromycin + gemifloxacin