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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
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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
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•
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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
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•
•
•
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