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The Struggle with Infectious Disease Lecture 6 Emerging Diseases Diseases of Developing Nations Deaths due to Infectious Disease Annual Deaths (in millions) Disease Deaths Respiratory Infections 3.9 Malaria 1.3 - 3.0 HIV/AIDS 2.5 Diarrheal Diseases 1.8 Tuberculosis 1.7 Neglected Tropical Diseases 0.5 Global Situation Vaccine Preventable Diseases • Measles – 91% decrease from 2000 to 2006 • • • • • • Meningitis Diphtheria Polio Pertussis Yellow fever (Rotavirus) – causes diarrhea Tropical Diseases Tropical Diseases • Diseases that thrive in a hot, humid climate – Sometimes extended to hot regions e.g. 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) Tropical Diseases • WHO identifies the most common tropical diseases as: – – – – – – – – Malaria, Leishmaniasis Schistosomiasis Onchocerciasis Lymphatic filariasis Chagas disease African trypanosomiasis Dengue. Tropical Diseases • Types of disease – Single cell parasites – Single/multi-cell parasites – Nematodes – Worms – Virus/bacteria Leishmaniasis • Single cell parasite • Transmitted by sand fly • Person to person or mammal to person (dog, rodent) • 20 species of parasites • 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 Leishmaniasis Distribution 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 capacity • Medication is available (12 day treatment) Schistosomiasis Distribution 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 Onchocerciasis Distribution 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 African Trypanosomiasis Ditribution 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 • 24% of global disease burden is accounted for by sub-Saharan Africa • Area represents 3% of the world’s workforce 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 Malaria • 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 • 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 Malaria • Rupture liver cell and enter blood stream • Second: parasite infects red blood cell (erythrocyte) and multiplies over ~ 48 hours • Red cell ruptures releasing further parasites 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 Malaria • 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 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 Malaria Prevention • Reduction in deaths since 2000 by 25% worldwide and 33% in Africa 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 Malaria Vaccine 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 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 Dengue Fever • 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 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 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 • 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 • Range could be impacted by climate change – Dengue seems to be more ubiquitous than yellow fever Impacts of Climate Change • Diseases transmitted by Asus Egyptus : Dengue Yellow Fever Zika Impacts of Climate Change • Other mosquito borne infections – – – – West Nile Chikungunya Filariasis Japanese encephalitis • More species of mosquitoes are infective Asian Tiger Mosquito Impacts of Climate Change • Other impacts of climate change: – Severe weather • Impacts mosquito populations • Impacts areas for waterborne diseases • Impacts costal areas – Change in habitat • Change is range of species • Change in ecological habitat – Deforestation Ebola Early Epidemiology Ebola Outbreak 2014 Key Factors in Disease Reduction • Education: – Cultural practices, particularly funeral practices – Identification of symptoms – Reducing stigma – Seeking medical care • Reduction in spread can be related directly to: – Community driven education programs – Availability of medical care SARS SARS • Outbreak started November 2002 in Hong Kong • Jumped from wild animal (civet cat) • Case fatality 9.6% • High transmission rate person to person • First serious coronavirus SARS • Spread to 37 countries • 8,237 cases • 775 deaths Supplementary Material • Ebola • SARS • Chagas 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 Ebola Virus • 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 • 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 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 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 Outbreak 2014 Ebola Outbreak 2014 Chronology • Index Case: 18 month boy in Meliandou – Sparsely populated area – Only 31 households – Located in the ‘forest district’ (Gueckedou) – Largely deforested (up to 80%) for resource development • Brings animals in closer contact with people -Seen playing near a hollow tree infested with bats Chronology • Died December 26, 2013 – Vomiting, black stools, fever • Early January family members, traditional healers, midwives in village had died • Spread to 4 other sub districts • First report January 24, 2014 district health clinic investigated by MSF – ‘5 cases of severe diarrhoea: rapidly fatal outcome’ Chronology • Ebola had never been seen in East Africa • General belief put area at low risk • Cholera and Lassa Fever are widespread • Based on symptoms only Cholera would be expected • Bacteria were found in post mortem samples – Probably endemic infection Chronology • Carried to capital city Conakry by member of boy’s extended family • Died in hospital Feb 5 • Doctors had no reason to suspect Ebola – No measures were taken • Disease spread to 4 cities and along routes Chronology • Ministry of Health issued alert on ‘unidentified disease’ March 13, 2015 • WHO/AFRO, WHO, MSF investigation March 14-25 – Epidemiology and Outbreak tracing – Laboratory analysis • 21 March Pasture Institute identified flavivirus • 22 Identified Zaire strain of Ebola virus Chronology • March 23, 2015 outbreak was announced by WHO – 49 cases – 29 deaths reported Early Epidemiology Current Status • 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 • Education: – Cultural practices, particularly funeral practices – Identification of symptoms – Reducing stigma – Seeking medical care • Reduction in spread can be related directly to: – Community driven education programs – Availability of medical care What Have We Learned? • 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 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 SARS SARS • Severe Acute Respiratory Syndrome • Caused by a coronavirus – Causes upper respiratory tract infection and gastrointestinal tact infection in mammals and birds – 5-6 strains infect humans SARS • Outbreak started November 2002 in Hong Kong • Jumped from wild animal (civet cat) • Case fatality 9.6% • High transmission rate person to person • First serious coronavirus SARS • Spread to 37 countries • 8,237 cases • 775 deaths SARS • Feb 23, 2003 first case in Canada: vacationing in Hong Kong – Died at home March 5 – Victims son reported to hospital March 7 with unknown illness – Potentially infected many health workers and visitors • Identified as TB and isolated – Patient in next bed in ER returned to hospital March 15 and died • Unknown disease • Unknown mode of transmission – Highly transmissable SARS • Only precautionary measure was isolation • Disease was described March 31, 2003 • Work started on a vaccine – There were confounding factors noted in cats • Convalescent serum was considered • Second outbreak May – June 2003 Novel Coronavirus Infection • A second novel coronavirus has appeared – First cases early 2012 in Saudi Arabia and Jordan – Presents as pneumonia but also renal failure – Recently 3 cases have been reported in UK with no history of travel Novel Coronavirus Infection • 12 confirmed cases with 5 deaths • Seems less contagious than SARS – Mode of transfer is not known – Fatality rate was highest in earliest cases • Global surveillance is underway