Malaria, TB, Syphilis, Gonorrhea

1. Malaria, TB, Syphilis, Gonorrhea And more, Oh my!

2. 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, 1-2 million deaths per year. • Many people contract malaria several times in their lifetime. • Range of disease has expanded.

3. 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).

5. Other Species • P. vivax – prevalent in Asia. • Can survive in liver for months. • P. ovale

6. Plasmodium vivax

7. 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.

8. Anti-Malarials • Quinine • Chloroquine, primaquine, mefloquine • Resistance is evident • Malarone is newer • Derivatives of artemisinin. • ACT = Artemesinin-based Combination Therapy.

9. Plasmodium lifecycle

10. Malaria Vaccine Trials • Proteins from Plasmodium sporozoite. • Add adjuvant. • Live, Attenuated parasites. • Cultured in mosquitoes. 3. Transmission-blocking Vaccines. • Proteins from gametocyte or from mosquito.

11. Tuberculosis (TB) • “Consumption” • Mycobacterium tuberculosis • 20 hour generation time • Acid-fast • Can survive for weeks in dried sputum • Resistant to chemical disinfectants

12. M. avium in AIDS lymph node

13. Most Common Human Infection • 33% of world population is infected • Immigrants, teachers, health care workers are screened

14. Vaccine • Live M.bovis • Inconsistent effectiveness • Vaccinated people will test positive for TB

15. Diagnosis • Tuberculin Skin Test • Detects T cell response • Bacterial protein is injected under skin • Response detected within 48 hours

16. TB X-ray

17. 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

20. 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

21. 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???

22. 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.

23. United States, 1940s

25. Syphilis • Treponema pallidum – spirochete • Cannot be cultured without host cells • Incubation: 3 weeks to several months • Spirochetes do not last long outside of body

26. Microscopy • T. pallidum is best observed with dark-field microscopy • Do not stain well • 0.2 mm diameter • Previous diagram is EM • Important in early stages since antibodies do not form until a few weeks after infection

27. Dark field T.pallidum

28. Primary syphilis chancre

29. Syphilis chancres

30. Primary Stage Syphilis • Chancre at the site of infection • External or internal • Painless, but highly infectious • Can enter bloodstream

32. Secondary Stage Syphilis • Several weeks later • Symptoms can be very subtle • Skin rashes, mild fever, loss of some hair in patches • Rash can also be in mucous membranes • Rashes are also highly infectious • Lasts for a few weeks

33. Latent Period • No symptoms • Can last for several years • Not usually infectious (except to fetus) • Most cases do not go beyond latent period

34. Tertiary Stage Syphilis • Probably due to a T cell response • Not very infectious • Resulting lesions are called gummas – skin and organs • Can affect mouth, aorta, nervous system

35. Congenital Syphilis • From mother to fetus • Mostly interferes with neurological development

36. Treatment • T. pallidum is slow growing • Requires long antibiotic treatment • Benzathine penicllin – slow-acting • Tetracylcines also work

37. Tuskegee Syphilis Study • Conducted by U.S. Public Health Service from 1932 – 1972 • 399 poor black men from Macon County, Alabama • Each already had syphilis • Doctors told them they had “bad blood” • None were told that they had syphilis • No one was treated for syphilis • Doctors wanted to see what would happen

38. Tuskegee • 28 men died directly from syphilis • 100 died of complications stemming from syphilis • 40 wives were infected • 19 children born with congenital syphilis • 1972 – story break in newspapers • Out-of-court settlement for $10M • May 1997 – President Clinton offers apology

39. 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

42. N.gonorrhea in human fallopian tube

45. Diagnosis • Pus from male  smear • N. gonorrhea seen in WBCs • Cervical culture from female  cultivate • Difficult to grow (fastidious) • CO2 enrichment • ELISA

47. Systemic Cases • Joints – gonorrheal arthritis • Heart – gonorrheal endocarditis • Meninges – gonorrheal meningitis • Eyes – especially in babies born to infected mothers (opthalmia neonatorum) • Pharynx • Anus

48. Reinfection • Immunity is rare because of antigenic variation Antibiotics • Penicillin-resistant strains • Now: fluoroquinolones

49. Antibiotic Resistance • Fluoroquinilones and Cephalosporins!! • New treatments (experimental): • azithromycin + gentamicin • azithromycin + gemifloxacin