The Struggle with Infectious Disease Lecture 5
Tropical Diseases Life and infectious disease began in the rift valley/rain forest of Eastern Africa Peoples migrated North to temperate regions
Tropical Diseases Diseases that thrive in a hot, humid climate Sometimes extended to hot regions eg sub-sahara Types of infections more common in these areas: More complex life forms Soil or water stages More complex stages in insects (no over-winter problem)
WHO identifies the most common tropical diseases as: Malaria, Leishmaniasis Schistosomiasis Onchocerciasis Lymphatic filariasis Chagas disease African trypanosomiasis Dengue. Tropical Diseases
Tropical Diseases Types of disease Single cell parasites Single/multi-cell parasites Nematodes Worms Virus/bacteria
Cost of Tropical Diseases Difficult to accurately compute Impact on agricultural work (30% decrease for some single diseases) Impact on school attendance Estimated cost of Trachoma $1.5 billion/yr
Cost of Tropical Diseases Generally chemotherapy medications are inexpensive $0.50 - $0.05
Malaria A parasitic disease Caused by single cell organism plasmodium 4 types that infect people (~16 total) Spread by Anopheles mosquito
Malaria: why we should care Common in tropical and sub-tropical regions around the world Residents develop some level of immunity Naive hosts react much more severely Treatment options are limited
Malaria: why we should care 300 to 500 million cases per year (WHO) Over 1 million deaths per year annually 85% of deaths are children under the age of 5 90% of deaths are in Africa
Outside Africa malaria is concentrated in 8 countries in SE Asia Malaria
Symptoms High fever Shaking chills Flu-like symptoms Anemia Symptoms usually occur within 10 days to 4 weeks (up to 1 year) Symptoms last 48 72 hours (recurrent) Malaria
Malaria Death is usually due to anemia due to burst blood cells Plasmodium falcparum is the most serious and can lead to death within hours of the first symptoms
Malaria Disease is transmitted from person to person by mosquito Separate life stages in people and insect Three distinct life stages First: Injected by mosquito into blood stream and migrate to liver and multiply
Rupture kidney cell and enter blood stream Second: parasite infects red blood cell (erythrocyte) and multiples over ~ 48 hours Red cell ruptures releasing further parasites Malaria
Malaria Two types of reproduction take place Asexual (more efficient) Gametes (evolutionary) Parasites are returned to mosquito through a blood meal Third: parasite reproduces in mosquito
Treatment: Drug treatments can only be effective when parasite in not hiding in another cell Drug resistance has developed In part due to incomplete treatment of infection Multi-drug treatments are currently being used successfully Malaria
Malaria Prevention Prevention becomes key strategy Mosquito control Mosquitos have become insecticide resistant Mosquito habitat control Mosquito bite control Bed net programs Vaccines have been unsuccessful
Malaria Prevention Mosquito control Mosquitos have become insecticide resistant Mosquito habitat control
Malaria Prevention Mosquito bite control Bed net programs
Reduction in deaths since 2000 by 25% worldwide and 33% in Africa Malaria Prevention
Malaria Vaccine Development Possibilities (Pro) Plasmodium is in the size range where the immune system functions well It is a single cell organism in all stages Issues (Con) Plasmodium more complex than bacteria or virus Life cycle complex, many stages and forms Sexual & asexual Reproduction rate in blood borne stage greatly exceeds the need for survival Have to kill off nearly all
Malaria Vaccine Development Potential targets for vaccine: Pre-erythrocyte Blood stage Transmission blocking Currently 41 vaccines under development
One vaccine has made it to phase 3 clinical trial Has proved somewhat effective ~30% - 50% Less effective in young children (where it is most needed) than in older children We are not there yet
Dengue Fever Also know as Breakbone Fever Viral infection with 4 serotypes Transmission by mosquito Aedes aegypti Widely distributed throughout the world Also spread Yellow Fever and Chikungunya
Developed in monkeys Jumped to humans in Africa/SW Asia 100-800 years ago Second world war transported mosquito and disease around the world 100 million infected annually Dengue Fever
Dengue Fever
Dengue Fever
Dengue Fever Symptoms Symptoms start 3-10 days after bite Skin rash High fever: 104-105 for 4-7 days Febrile seizures: can be extremely severe hence the name breakbone fever Usually resolves after 10 days
Dengue Fever No vaccine available No treatment Prevention has been partially successful
Dengue Fever Prevention
Dengue Hemorrhagic Fever 4 Serotypes of Dengue Infection with one serotype does not provide immunity to other three In fact infection with a second serotype is much more serious
Dengue Hemorrhagic Fever Symptoms: Similar course to Dengue Fever But with fever shock-like symptoms develop Crisis period lasts 1 day Bleeding occurs in patches under the skin Sometimes bleeding from nose & mouth
Dengue Hemorrhagic Fever Shock-like symptoms develop Can cause death 100,000 deaths each year due to Dengue and Dengue Hemorrhagic Fever Increased capillary permeability and reduced clotting ability are believed to be due to over-reaction of the immune system Antibody-dependent Enhancement (ADE)
Dengue Fever is one of the fastest spreading (geographically) vector borne infectious diseases Cases have been reported in Southern Texas (2005) Endemic throughout Caribbean Dengue Fever
Dengue Fever Range could be impacted by climate change Dengue seems to be more ubiquitous than yellow fever
Ebola Virus Ebola, previously known as Ebola hemorrhagic fever, is a rare and deadly disease caused by infection with one of the Ebola virus strains. Ebola can cause disease in humans and nonhuman primates (monkeys, gorillas, and chimpanzees). Ebola is caused by infection with a virus of the family Filoviridae, genus Ebolavirus. There are five identified Ebola virus species, four of which are known to cause disease in humans: Ebola virus (Zaire ebolavirus); Sudan virus (Sudan ebolavirus); Taï Forest virus (Taï Forest ebolavirus, formerly Côte d Ivoire ebolavirus); and Bundibugyo virus (Bundibugyo ebolavirus). The fifth, Reston virus (Reston ebolavirus), has caused disease in nonhuman primates, but not in humans. Ebola viruses are found in several African countries. Ebola was first discovered in 1976 near the Ebola River in what is now the Democratic Republic of the Congo. Since then, outbreaks have appeared sporadically in Africa. The natural reservoir host of Ebola virus remains unknown. However, on the basis of evidence and the nature of similar viruses, researchers believe that the virus is animal-borne and that bats are the most likely reservoir. Four of the five virus strains occur in an animal host native to Africa. CDC Atlanta, USA
5 known Ebola viruses 4 infect humans Clinically almost identical to Marburg virus First recorded epidemic: August 26, 1976 in Yambuku on the Ebola River DRC Zaire EBOV Ebola Virus
May have the highest case mortality of any known disease: 90% in some epidemics; 83% overall With treatment as low as 50% Sporadic outbreaks in remote villages usually in or near to rainforest Ebola Virus
Ebola Virus Fruit bats are considered the natural host Contact with blood, secretions, organs or other body fluids Chimps, gorillas, monkeys, forest antelope, porcupines
Ebola Virus Human to human transmission through infected tissue of fluids Family members Funerals Health care workers (poorly protected) Transmission via infected serum can occur up to 7 weeks
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
Ebola Virus Symptoms 2 21 days following infection Stage 1: fever, intense weakness, muscle pain, headache, sore throat Stage 2: vomiting, diarrhoea, rash impaired kidney function, internal & external bleeding Infectious up to 61 days
Ebola Virus Virus enters monocytes in the blood stream and multiplies Breakup of cells causes cytokine response (fever, inflammation) Endothelial cells, hepatocytes are targets Death of endothelial cells causes blood leakage ad clotting problems
Ebola Outbreak 2014
Ebola Outbreak 2014
Fighting Ebola Support the patient so that the immune system can fight the virus Improve the immune system convalescent serum Anti-viral When will it work? Vaccines Why is it taking so long?
Above all Prevent spread of the virus How many times in history, how many diseases Increase understanding of disease transmission How many theories Education to overcome cultural beliefs What other cultural beliefs
Have we come so far?
Supplementary Material
Leishmaniasis Single cell parasite Transmitted by sand fly Person to person or mammal to person (dog, rodent) 20 species of parasite 30 species of sand fly Range: S America, Africa Occasionally Texas Cutaneous 0.7 to 1.2 mm sores 1.2 million cases/year Visceral Spleen, liver, kidney, bone marrow 400,00 cases/year Life threatening Difficult to treat
Schistosomiasis Second most devastating parasitic disease 280,00 deaths/yr Parasitic worm Reservoir: freshwater snails Fecal/urinary transmission of eggs to water Penetrates skin & reproduces in blood stream Symptoms are due to the reaction to the eggs Inflammation/scaring in bladder and small intestine 1-2 months following infection Skin reaction within days Chronic symptoms: Enlarged liver, abdominal pain, intestinal/urinary, growth, mental capcity Medication is available (1-2 day treatment)
Onchocerciasis (River Blindness) Parasitic worm (nematode) Transmitted by black flies: Larvae develop in black fly 37 million infected Two stages: Transmissible 200-400µ Resident 30-50cm long Treatable with medication For lifetime of worm (15yr) New med attacks bacterial food source Live in nodules under the skin for <15yr May not induce immune response Respond to dead larvae 1000/day per nematode Blotchy skin Reversible corneal/optic nerve damage
African trypanosomiasis (Sleeping Sickness) Single cell parasite (rather like malaria) Spread by Tetsi fly Largely human reservoir (some animals) Endemic in rural Africa 10,000 cases/yr Multiplies in body fluids (blood,lymph,spinal fluid) Second stage crosses blood/brain barrier Leads to neuro problems
Chagas Transmission through feces of kissing bug Enters through skin or wound Enters tissue near wound and differentiates Gametes multiply by binary fusion Does not differentiate in blood stream Central and South America Acute phase: immediate to several months Mild/asymptomatic, swelling Chronic stage No parasites in blood Asymptomatic Complications: Heart rhythm (sudden death) Dilated heart, esophogus/colon