6. Emerging and Re-emerging Diseases Chapter 8

Disease is not constant
• Emerging Diseases – are recently “discovered” diseases, or diseases that have become increasingly important. • Some are old diseases just discovered – like Hepatitis C • Some are truly new like HIV • Many are taking advantage of some niche – like air conditioners in large buildings – Legionella pneumophila • Diseases moving to new parts of the world – West Nile Virus • Re-emerging Diseases – are diseases that became less important, but are again increasing in importance. • Tuberculosis is an old disease that is again rapidly increasing in some populations.
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Health Science Microbiology David L. Beck, B.S., A.M., Ph.D.

FYI

Emerging Diseases - Examples

FYI Re-emerging Diseases - Examples

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Known Species
The Tip of the Iceburg
• How many species are there? • 1980 there was 1,792 described species • 1990 there was 3,393 species (173 new per year) • 2000 there was 6,386 species (299 new per year) • 2010 there was 12,926 species (654 new per year) • Oct 2011 there was 13,563 species (Yikes!!!) (Most of these we know nothing about other than their name.) WE KNOW VERY LITTLE 80% of bacteria are unculturable – what you do not know about can hurt you! 61% of the known 1415 species infectious (and counting) to man are from animals (zoonoses)

• • • •

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Want to know the current number of described species? See: http://www.bacterio.cict.fr/number.html Updated daily.

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Normal Flora
The Great Unknown
• • • • First no one knows. NO ONE. Second detection does not mean it is normally there. Detected: Oral Cavity • 700 species (Aas 2005 and others) many sites • 6888 to 10,052 species (Keijser 2008) two sites in 71 people Anderson 2008 • Throat 152 species • Stomach 33 - 262 species • Feces 301 species Most abundant bacteria in the mouth – Veillonella parvula – entire medical literature has 6 papers that have its name in it (as of 8/11). • Reference – Dewhirst et al 2010 J Bact 192:5002-17
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Known Species 2012
• • • • • • • • Eubacteria Archae Fungi Protista Algae Viruses Plantae Animalia
• Insects
• Beetles

(Chromista)

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9,072 281 45,659 14,851 6,571 2,083 321,212 1,072,857
821,670
190,370

All numbers from one website. Others would put the numbers higher, but here the numbers are at least relative to each other. If every mammal has a unique Helicobacter (this seems to be the case) then there should be over 4,000 species in the genus Helicobacter of bacteria alone.

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• • • • •

Spiders 61,923 Mammals 4,835 Birds 9,913 Reptiles 8,656 Fish 30,968 From ‐ http://www.catalogueoflife.org/annual‐checklist/2012/browse/tree

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Infectious Disease The Greater Unknown
• • • We do not know what our normal flora is. We can culture 20% of bacteria. 250 species of bacteria have been cultured from the mouth, but there is greater than 800 species there potentially 1000s of species. We are clearly infected by many bacteria that have yet to be discovered. Some of these will be important and common pathogens. --- and then there are the viruses, fungi, protozoa to consider also ---- there is much to be learned.

Cities and Infectious Diseases
• Cities bring large densities of humans. • Large densities of humans are associated with a lot of feces, etc accumulating. • Large densities of humans are associated with random interactions across diverse groups. There is mixing as you go to work, go out to eat, etc. You may not see anyone you know all day. • Disease can rapidly spread through the population.

• •

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Environmental Interactions
• As humans move into new areas they are exposed to new diseases. • Yellow fever from monkeys in Africa • Poor environmental control – housing, shoes, etc. • Hantavirus – mouse urine • MMTV – house cats eat infected mice, transmits to humans from the cats. • Poor vector control • Dengue – spread by mosquitoes

Food-borne Disease
• It used to be all food was local, the local market, the local butcher. Now it is global. McDonald’s hamburgers come from Argentina. • Large vats of hamburger – one sick cow and the entire vat is contaminated • Machine processing of food • Infections transported 1000s of miles

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Globalization
• The world is incredibly small. Even in the 1800s disease spread efficiently in populations. • Today it can be in 50 cities in 48 hours easily.

Emergence of New Strains
See Below under Influenza

David Harvey, The Condition of Postmodernity, 1989, p241

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A few diseases
• • • • • • • SARS West Nile Virus Viral Hemorrhagic Fever Tuberculosis Influenza “Avian” Influenza Prions

Severe Acute Respiratory Syndrome SARS

• •

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As of Aug 7, 2003: 8422 cases with 916 deaths (11% fatality) Approximate number of passengers that arrived from SARS area - CHINA (including Hong Kong and Taiwan), SINGAPORE, and Hanoi, VIETNAM from March 13, 2003 - April 6, 2003 : 250,000 persons. (Based on the number of SARS cards distributed to incoming passengers.)

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SARS

SARS
23% required intensive care 10% died

SARS

SARS

• The symptoms seem to be: • 1. Fever • 2. Pneumonia with nonproductive cough. • 3. Lymphopenia • 4. Elevevated ALT, AST - liver involvement. • 5. Rigor, malaise • 6. Possibly diarrhea (about 20%). • Signapore reports one child less than 16 out of 106 cases. Canada reports one child less than 16 out of 82 17 Medial Stinal Widening (sort of) cases. It mainly affected adults.

• The simplest explanation for all disease symptoms is a pathogen that can infect the mucosal epithelium and then moves on to internal organ involvement including the liver. • Many people are sick but only a few get infected. • A few super-spreaders infected >90 people in five days.
• A predominantly fecal-oral/oral-oral mucosal pathogen that affects the intestinal and respiratory tract and occasionally with the “right-kind” of lung infection would lead to rapid spread of the disease. This profile is seen for a number of bacterial and viral diseases.
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•

Major issues with SARS:

SARS

Major issues with SARS:

SARS

1. Hospitals were reaching their breaking point in Hong Kong. There was one hospital with 120 patients requiring isolation. No hospital can isolate that many people. Basically all elective and most non-essential surgery was put on hold in Hong Kong. Singapore had a more manageable number of cases and converted a hospital into a SARS suspect cases only hospital. Ontario prepared two hotels with medical equipment to handle the possible surge of SARS patients.

• 2. Surgical masks and gowns started to run out. Ontario had depleted supplies and received shipments from Health Canada. They were looking for suppliers. • The WHO transported thousands of gowns, masks, and gloves into SARS effected regions.

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Major issues with SARS:

SARS

SARS Virus Identification:
• • The currently accepted viral cause is “SARSassociated coronovirus”. Coronoviruses are typically not known to be associated with severe disease, but to be associated with common cold-like diseases.

• 3. If SARS had hit Africa the number of immune-compromised patients with HIV/AIDS may lead to absolute devastation of the African population. A minimal death rate of 4% of the healthy population and 30% of the HIV/AIDS population would kill 14% of Africa or 3 out of 20. • 4. Smoking - smokers beware the highest death toll is again in smokers. This is true of basically all respiratory pathogens.

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Treatment

SARS

Prevention

SARS

• None • Premier of China was highly criticized for going on national TV and telling sick people to stay home and NOT go to the hospital. There was not enough hospital beds to treat them at the hospital. • Home treatment of pneumonia
• Quarantine the patient (family member) • Incline the patient at 20-30° • Encourage the patient to rest as much as possible, even after partial recovery.
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1. Quarantine infected patients early 2. Separation of infected and uninfected patients within the hospital – preferably in separate hospitals. 3. The “police nurse” – essentially guarding the door and making sure EVERYONE entering the quarantine area wears PPE and washes their hands on the way in and on the way out.

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Prevention

SARS

West Nile Virus
• • •

WNV
Flavivirus introduced into New York in 1999. Restricted to tropical and temperate regions West Nile virus has been described in Africa, Europe, the Middle East, Asia (west and central areas), Oceania, and most recently, North America.

1. Smoke little. Heavy smokers are at increased risk for respiratory infection. 2. Contact tracing and temporary quarantine. 3. Mask people arriving at the emergency room with a cough. 4. Identify superspreaders if possible – there are some people that shed shed shed pathogens. 5. Monitor immune compromised patients carefully. They often have atypical disease presentation and delay pathogen clearance. They can serve as a reservoir of infection.
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B. Arambula

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Transmission
• Vector: Mosquitoes infect birds, virus amplifies inside the host, and then further infects other mosquitoes feeding on the host. • The US outbreak revealed novel transmission methods, through blood transfusion, organ transplant, intrauterine exposure, and breast feeding.

http://en.wikipedia.org/wiki/West_nile_virus

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Clinical Symptoms and Presentation

WNV
B. Arambula Junin

Viral Hemorrhagic Fevers
Rift Valley Yellow Fever

• Approximately 90% of West Nile Virus infected patients don’t show any symptoms. • Three outcomes for those infected: – Asymptomatic Infection – West Nile Fever – West Nile Meningitis/Encephalitis • Common symptoms include: fever, headache, chills, excessive sweating, weakness, swollen lymph nodes, drowsiness, pain in the joints. • Occasionally there is a short-lived rash and gastrointestinal symptoms (nausea, vomiting, loss of appetite, or diarrhea) • Treatment – None, palliative care.
2012 Update: It appears that some patients get persistent disease in the kidney, lasting for years.
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Ebola

• There are a large number of viruses that cause hemorrhagic fevers, such as Ebola. • They are quite contagious and have a high fatality rate. • Note people that have recovered from Ebola may remain contagious for months.
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Viral Hemorrhagic Fevers
• • • • • • Symptoms Fever, Bleeding, Circulatory Shock Myalgia with prostration Petechial hemorrhaging (red spots on the skin) Hepatic dysfunction Fatality 5% - 90% depending on virus
• • • •

Disease due to VHF
Lymphocyte depletion – cause unknown Necrosis of the spleen and liver High levels of viremia due to lack of lymphocytes. Reduced blood coagulation and fibrinolysis • Leads to bruising of the skin and bleeding out in some cases. • Thrombocytopenia • DIC – Disseminated intravascular coagulation • Large blood clots lead to organ failure • Depletion of clotting agents leads to increased bruising.

• Transmission • From rodents and arthropods to man. May spread person to person. Often acquired from the dead while preparing the body for burial.

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Model of VHF

Mycobacterium tuberculosis

Case 23
• 63 year old homeless man • 1 month – coughing blood and breathless • Low grade fever, bronchial breathing • Chest X-ray with apical shadowing and large cavitation consistent with tuberculosis • Sputum was collected and ….??
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Case Studies in Infectious Diseases, Lydard et al., 1st Edition

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Mycobacterium tuberculosis
• Acid-fast, nonpigmented, rod • Intracellular pathogen, growth in macrophages. • Very slow growing. • EXTREMELY CONTAGIOUS!!!!!! • Respiratory pathogen, and grows anywhere else in the body too.

Epidemiology

Mycobacterium tuberculosis

• It is estimated that 33% of the worlds population is infected with tuberculosis. 9 million develop active TB every year. About 2 million die. • About 10% of infected individuals develop disease later in life. • Mycobacterium tuberculosis and HIV represents a troublesome dynamic duo. #2 Infectious Deaths Worldwide
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Epidemiology
• •

Mycobacterium tuberculosis
2006 13,779 in USA

Epidemiology

Mycobacterium tuberculosis

In the United States tuberculosis is more common in Asians > African Americans > Hispanics > Native Americans > Caucasians It is more common in New York and the South.
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Epidemiology MDR TB, XDR TB, TDR TB

Mycobacterium tuberculosis

2010 ‐ TB
TB #2

Mycobacterium tuberculosis

• Multidrug Resistant Tuberculsosis –MDR TB • SERIOUS problem and increasing. • 5% of new cases and increasing! • Resistant to first line antibiotics. • Extensively Drug Resistant Tuberculosis – XDR TB • NOW in 50 countries!!!!!! • Resistant to many second line antibiotics. • These patients are VERY dangerous. • This represents the potential for an explosion of cases in any country in the world. • Totally Drug Resistant Tuberculosis – TDR TB • NOW in 4 countries!!!!!! 39 • Resistant to ALL second line antibiotics.

XDR‐ TB 2007 – MDR‐TB
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Transmission

Mycobacterium tuberculosis

Infection to Disease

Mycobacterium tuberculosis

• Airborne - extremely contagious through aerosols. • About 1% of patients develop “fulminant Tb” which is highly contagious. In some populations that number may reach 40%. • Each fulminant Tb patient is estimated to infect 20 others. A sputum smear positive patient will transmit it to as much as 50% of their contacts. A sputum smear negative but sputum culture positive will transmit to about 5% of their contacts.
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• Disease: • There are two stages – TB infection and TB disease. • TB Infection – 30% of people exposed: M. tuberculosis is responsible for the lung disease tuberculosis. • Primary TB infection occurs by inhalation of droplets containing M. tuberculosis. The bacteria grow in the lungs and induce an immune response. • The aggregation of activated macrophages (infected with growing mycobacteria) around the infection forms a tubercle (small lump known as a granuloma) which walls off the infection. `
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Host Response
• T cells activate the macrophages causing the granuloma to be formed.

Mycobacterium tuburculosis

Infection to Disease

Mycobacterium tuberculosis

• Latent TB Infection - 90% of people infected: Bacteria can remain viable within tubercles for years, even decades. If the host is stressed (eg. malnutrition, overcrowding, stress), these bacteria can be released and the infection will spread to other tissues through the blood-disseminated tuberculosis. About 10% of latent infected individuals develop disease later in life.

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Infection to Disease

Mycobacterium tuberculosis

• Fulminant TB Infection – 3-5% of people infected AND 15-35% of latent TB infection (over the course of years): Fulminant TB infection develops slowly over a course of a few months. • Symptoms: Chronic cough, chest pain, high fever, rust colored sputum (bloody), eventually leading to weight loss, and malaise. • EXTREMELY CONTAGIOUS!!!!! • Systemic Infections – can infect bones, joints, liver, spleen, GI tract, brain, etc. Systemic infection can be dormant or progressive. If progressive it is usually fatal. • Fulminant TB - Eventually it will spread throughout the body and damage the liver, kidney, meninges, bone, etc. Known as consumption.
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Fulminant TB

Copyright 2011 – Jones and Bartlett

Diagnosis
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Mycobacterium tuberculosis

Treatment/Management

Mycobacterium tuberculosis

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PPD – Tuberculin antigens are injected subdermally. After 48 hours the radius of inflamed tissue is measured. A positive PPD indicates previous exposure to tuberculosis. It does not indicate if the patient is sick. Chest X-Ray - A patient can then be screened with a chest X-ray. If a person is PPD positive they are typically treated for tuberculosis. This prevents reactivation of tuberculosis later. Once a person is PPD positive they need to be screened every five years with a chest X-ray.

Treatment: The principles of chemotherapy for tuberculosis are: 1) Long-term treatment (6-9 months) to minimize relapse. 2) Combinations of 2 or more drugs because of emergence of antibiotic resistant mycobacteria during the long treatment. 3) Use of drugs able to penetrate macrophages and kill mycobacteria growing in macrophages. Multiple drug resistant TB has appeared and is a serious risk for health workers.

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Treatment/Management

Mycobacterium tuberculosis

XXDR-TB Oswald Juarez and $500,000
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Mycobacterium tuberculosis
Extremely drug resistant tuberculosis (XXDR). Ironically he was treated at the last standing TB sanitarium in the USA. The place is filling up again. He got lucky, the others with this strain have died.
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Directly Observed Therapy – DOT: Basically watching the infected individual take his therapy EVERY single day. Very expensive, and VERY EFFECTIVE! Due to the highly contagious nature of TB this is the only long term effective solution.
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Who Pays?
• Arrived from Peru in Florida to study and became ill. He got to study the inside of an isolation room for 18 months.
• 30 pills a day, and IV drugs 3 times a day.

#2 Infectious Deaths Worldwide
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Mycobacterium tuberculosis

Prevention

Mycobacterium tuberculosis

• TOTALLY DRUG RESISTANT TUBERCULOSIS • IRAN 2009
• Iranian, Iraqi, Afghani

1. Screening – all people need to be screened on a regular basis with the PPD in the USA.
• • All immigrants are screened However anyone can fly in (or walk in)

2. Screening by X-Ray – PPD positive need to be screened every five years. 3. Isolation of infected individuals
• • • •
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• INDIA 2012
• Mumbai
Chest. 2009 Aug;136(2):420‐5 Clin Infect Dis. 2012.

TB Sanitoriums – this is longterm isolation. Wearing of masks by TB patients Negative pressure isolation rooms FORCED isolation at least until sputum negative
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Prevention
• • • • •

Mycobacterium tuberculosis

Influenza virus
• • Overview: Most common cause of acute respiratory infections in adults, particularly in those with chronic conditions and the elderly. Influenza virus is in the orthomyxovirus family - enveloped virions containing 8 helical nucleocapsid segments of negative-strand ssRNA (each coding for one protein) of the segmented genome.

1. Higher rates of screening for at risk individuals
Healthcare workers Zoo Keepers – elephants get TB, etc. HIV patients Cancer, etc patients Homeless People, Illegal Immigrants, Prisoners etc.

2. Wearing of masks in the ER with patients with a cough of unknown origin.
• • • • Masks must be properly fitted!!!!! Directly observed therapy Treatment of all the infected/seroconverted patients Follow up of all seroconverted patients!
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3. Proper therapy!!!

Influenza

Influenza

Virulence Factors
1) A hemagglutinin that binds the virus to a specific respiratory tract receptor.
• 16 known types

Transmission
• Airborne – thought to be primarily through large droplets >5 µm in size. Coughing, sneezing, talking. • Through nasal / oral mucosa. Contagious within 8 hours of infection. Children/immune compromised remain contagious for longer then adults. • Contact • Birds – it there is fecal oral transmission

2) A neuraminidase (which cleaves neuraminic acid residues in the mucus layer on host cell surfaces) that helps the virus penetrate the respiratory epithelium, as well as release budding virus from host cells.
• 9 known types
Birds – all types Humans – H1, H2, H3, (H5), N1, N2
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1918 Spanish Flu

Influenza

Epidemiology

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Influenza

Influenza

Epidemiology

Infection to Disease
Infection: Influenza virus enters the upper respiratory tract in droplets and primarily infects the ciliated epithelial cells. Virus-replication occurs in these cells. • Virus in pneumotropic – from the oropharynx to the alveolar walls. • Receptor for hemagluttin is sialic acid, sialic acid is found on all host cells. Disease: The systemic symptoms of influenza are due to the presence of the virus (which is toxic) and to the liberation of host cell breakdown products. • Generally disease is limited to the respiratory tract (in humans) • It takes the host about 10 days to regenerate enough epithelial cells to restore an intact ciliated epithelium. Loss of the mucus layer allows bacterial invasion and enhanced bacterial adherence to virusinfected cells. • Death can result from influenza infection alone, a secondary bacterial infection alone, or a combination of both infections.
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Influenza

Influenza

Evasion of the Host Response
Influenza viruses undergo two types of antigenic changes: 1) antigenic drift - Results from point mutations that occur randomly and sporadically in the neuraminidase or hemagglutinin genes. Immunity in the population (herd immunity) acts as a selective force for antigenic drift. As the number of susceptible individuals decreases (ie. the number of immune individuals increases), new antigenic variants become the dominant viruses and the population again becomes susceptible to influenza infection. 2) antigenic shift – Only in Influenza A - A major antigenic change in the neuraminidase or hemagglutinin gene. It arises from infection of a single host cell by two different influenza virus strains and genetic reassortment to produce a new virus strain so different from the parental viruses that antibodies against them are not effective against the new strain. Found in animals: aquatic birds, chickens, turkeys, swine, and horses. Antigenic shifts are rare, thought to involve coinfection by human and animal influenza strains (and most have arisen in the Far East), and give rise to pandemics. NOTE: The 1918 strain is thought to have arisen in the USA, and killed 230 million people worldwide.
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Evasion of the Host Response

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Clinical Symptoms

Influenza

Treatment/Management

Influenza

• Fever, headache, myalgia, and respiratory symptoms 14 days after infection, usually abrupt in onset. Fever persists 3-8 days, recovery is in 7-10 days. • Primary influenza pneumonia
• Virus infects from the nose to aveoli • Can result in inflammation, and pneumonia • Can occur in any age group

Treatment: Amantadine and Oseltamivir. Both drugs are antitransmission, they only decrease symptoms by 1-2 days at the most. Major side effects. The drugs are best for managed care facilities. NOTE: The use of aspirin for children is NOT recommended. NOTE: H5N1 - bird flu - is often found to be resistant to these antivirals. NOTE: Amantadine resistance arises in 3 days.

• Secondary Bacterial Pneumonia
• More common in the elderly or those with chronic lung diseases. • Streptococcus pneumoniae, Haemophilus influenzae, 63 Staphylococcus aureus. 63

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Treatment/Management

Influenza

Treatment/Management
Problems with the killed vaccine are:

Influenza

Vaccine: 1. Flu Vaccine - inactivated vaccine given intramuscularly. Each year it is different. 2. Nasal Spray Vaccine – live attenuated vaccine – appears to be more effective in preventing actual flu • Annual vaccination with inactivated strains is recommended for high-risk groups. The vaccine is changed annually to reflect current influenza antigenic types. • Only three strains are vaccinated for any given year. This means that if a new strain emerges, or if the guess is wrong the vaccine has no effect that year.
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1) Pyrogenic reactions and mild flu symptoms are common. 2) IgA’s in respiratory secrections are needed for protection, but are only induced at low levels by a subcutaneous injection of inactivated virus. Protective efficacy is only 70%. 3) Antibodies begin to decrease about three months after vaccination and are gone by six months. 4) Problem of “original antigenic sin”: a vaccinated patient responds only to the strain that caused the patient’s first influenza infection or the first vaccine strain. NOTE: You should not give aspirin to children with influenza.

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Avian Influenza “Bird Flu”

Influenza

Influenza

• All influenza comes from birds, it is the natural reservoir of influenza. • H5N1 – has shown repeated cross species transfer with a high fatality rate in humans and low transmission rate. • It is worldwide. It is drug resistant. It is rare. • It appears to in most cases involve direct contact with birds. • Fatality rate is 20-50% • Consequences would be devastating.
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Prion hypothesis: Prions
1) PrP is a normal host protein having a form PrPc (cellular form), and has normal functions in the host cell. 2) PrP* is an infectious form of the protein, it has an altered shape. This altered shape gives PrP* three properties: a) it can interact with PrPc and convert it to PrP*, thus generating more PrP*. b) PrP* is toxic to host brain cells c) different forms/strains of PrP* have slightly different shapes, which result in having slightly different toxic effects, disease progression and so forth.

• • • • • • •

Infectious protein NO genetic component e.g.: Kuru - New Guinea Fore tribe (cannibals) CWD - Chronic Wasting Disease of mule deer and elk. (Get the deer you shoot tested before you eat.) Scrapie - sheep and goats BSE - mad cow disease
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Prions
Properties: 1) filterable - suggests a virus 2) extremely heat stable - (800C) normal cooking temperatures have little/no effect, even autoclaves can not be trusted completely. 3) radiation resistant 4) nuclease resistant - nucleases chew up viral DNA. Conditions 2-4 would kill all known viruses. Best explanation is that it is an infectious protein. Although there is much debate about this.

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TSE – infection model
• Infective prions can be ingested with prioncontaining material. • These prions can move through the intestinal wall rapidly and enter lymph nodes where they incubate • They are picked up by peripheral nerves and moved to the spinal cord and brain. • Infectious prions can be transmitted between species • Incubation time is significantly longer when they cross between species.

TSE – Transmissible Spongiform Encephalopathy
• Prions produce transmissible • spongiform encephalitis (TSE). • It is a neurodegenerative disease. • It can affect cattle and humans. • There is no test for it in live organisms. • There is no treatment. • There is no cure. • Symptoms include: • Lack of coordination • Staggering • Slurred speech • Dramatic mood swings • Paralysis • Death within one year of symptom onset Biological characteristics of the illness include: • A long incubation time • Plaque deposits in the brain • No antibody response • No inflammatory response
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TSE
Prion Disease

• “Mad cow” disease was first seen in Britain in 1984 • By the year 2000, there were 180,000 confirmed cases in cattle in Britain. • The infection in cattle has been attributed to sheep brain supplement included in cattle feed. • First human case documented in Britain was in 1996. • To date, there have been more than 120 cases documented in humans. • Estimates of the number of new cases in the next few decades vary from a few hundred to 150,000. • Some prion disease are sporadic/familial.
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• Recently shown that it can be transmitted through aerosols. • May explain transmission in deer.

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