micro unit 7

disease and symptoms

central -headache systemic -fever muscular -fatigue -pain back -pain skin -chills -sweating respiratory -dry cough spleen -enlargement stomach -nausea -vomiting

"More people will be at risk"

current distribution and yellow and I think that's red for the regions that it will become susceptible to malaria infection. which is near the EQUATOR

zoonotic disease

disease that can be passed between animals and humans -70% of diseases are zoonotic -example: HIV/AIDS

Ebola: Bats

they carry Ebola and a natural reservoir

Contact tracing

the identification and diagnosis of people who may have come into contact with an infected person and can also figure out how a disease started

Areas of Malaria Transmission and Antimalarial Drug Resistance

these resistances are not static because the population is continually evolving. So it is important that whenever you are going to prescribe something to treat the patient for malaria, that you will, we look up what the correct treatment for their area where they got infected is. And the CDC routinely updates their website and provides information about how to correctly treat malaria from different regions

news figure post VIAGRA MAY HELP CURE MALARIA RESEARCH SUGGESTS

viagra can actually have some useful effects in the treatment of malaria. It alters the permeability of red blood cells, making them less susceptible to infection with the merozoites -Researchers were actually trying to develop drugs for treating heart failure because Viagra dilates arteries to increase blood flow. The intent was to treat heart failure, not erectile dysfunction. So when this drug came out, uninformed people were quick to criticize. Well, why did we make a drug for erectile dysfunction on to other things that we should be devoting our drug developmental resources to (SERENDIPITOUS story)

zika, nipah, mers

virus that spill over aniamls to humans

3 diseases spread by mosquitoes

zika, dengue, chikungunya fever

Malaria control using vaccines?

•An effective vaccine is not yet available •Early efforts were limited by availability of Plasmodium samples to work with •Genomic studies have helped overcome this hurdle •New vaccines targeting protein subunits are promising

RVAH2O

•Drinking water treatment plant •Built in 1924 •Up to 130 million gallons a day •Treats water from the James for drinking water •https://www.rva.gov/public-utilities/water-utility

E. Coli has been shown to be the best indicator organisms

•E. coli make up a large portion of the bacteria in the human gut •Their presence is a great indicator of other pathogens. •EPA has guidelines for water safety based on the abundance of E. coli in water. •Looking for E. coli is way cheaper than looking for all the possible pathogens in water. •But I thought you said an indicator organism is never a pathogen?!?! -Most E. coli are not pathogenic organisms.

Climate Change

•Global temperatures increase of 0.8°C •Contributes to sea level rise •Changes in distribution and range of plants and animals •Alters plant and animal cycles (blooming, migration) •Affect seasonality •Increases frequency of severe weather events

Key methods for prevention of malaria

•Long lasting insecticide impregnated nets (LLINs) •Indoor residual spraying •Mosquito repellents •Preventative drugs treatments

waterborne (Classification of water-related illnesses)

-Originate in fecal material, transmitted by ingestion -Cholera & Typhoid fever

Drinking Water Treatment

1)Coagulation and flocculation - Chemicals are added to the water. They bind with the dirt and dissolved particles, forming larger particles called floc. 2)Sedimentation - The floc is heavy, so it settles to the bottom of the tank. 3) Filtration - The clear water on top passes through filters composed of sand, gravel and charcoal to remove dissolved particles such as dust, parasites, bacteria, viruses and chemicals. 4)Disinfection - Chlorine or chloramine is added to kill parasites, bacteria, viruses and germs.Fluorine is added to prevent tooth decay

Atmospheric Withdraws -arid air environments? -air has low water yield

Air well - stones cool overnight and encourage condensation from the warm air during the day (© Michel Royon / Wikimedia Commons) Fog fence - work best in areas near water. Cool moisture laden air moves inland and the moisture is collected in the fog fence Dew harvester - collects dew and provides water to grow plants despite drought conditions (https://techxplore.com/news/2015-03-dew-collector-greenhouse-food-growth.html)

5. Treatment & Prevention

Drug choice and treatment success depend on: •Type of infecting parasite •Region where the infection was acquired and its drug-resistance status •Clinical status of the patient •Any accompanying illness or condition •Pregnancy •Drug allergies, or other medications taken by the patient

Where are we at this point in class? ****the disease is actually separate from the pathogen that causes that -The pathogen is the causal organism that causes the disease. There's the environment where you came in contact with the pathogen that caused the disease. And then there's the host organism, which sometimes there might be more than one if you're working with a vector-borne diseases

Environmentally-transmitted pathogens Route of infection: -****Water based ******* (cholera, nikolai) -Soil borne -Airborne spread -Vector (where another organism transmits the pathogen to a person-malaria) -Zoonoses (a spillover event where the pathogen develops in an animal population and then humans come in contact with that animal. And that pathogen spreads like wildfire through the human population)

water cycle steps Abbreviated Water Cycle Diagram from the USGS: https://www.usgs.gov/special-topic/water-science-school/science/water-cycle-adults-and-advanced-students?qt-science_center_objects=0#qt-science_center_objects

Evaporation, condensation, precipitation, run off, transpiration, infiltration

Disinfection: Pros and Cons

Ozone •Fast acting and more effective than chlorine •No residual chemicals •Ozone decomposes rapidly •Generated on site so no shipping and handling •No residual also means no protection during water transport •Expensive equipment •Corrosive •Doesn't work if there is lots of organic matter

Marburg virus

The causative agent of Marburg haemorrhagic fever. The virus is closely related to Ebola and originates in Uganda and Eastern Congo. Egyptian fruit bats are suspected of being the reservoir host. -kills up to 90% of those infected

water cycle

The continuous process by which water moves from Earth's surface to the atmosphere and back

Nipah virus

The first outbreak was in Malaysia in 1998, caused severe respiratory and neurological disease in pigs, 105 human deaths. Fruit bats excrete the virus in urine but are unaffected by it. Pigs spread the infection to humans. Human to human transmission occurs. -zoonotic disease -mutation when changing host?? from village to global -some raw date sap that is consumed by people was infected by a bat -causes fever, malaise, flu-like symptoms and can have a loss of consciousness -3/4 of people infected die -passed though person saliva

disease and symptoms

Uncomplicated •Attacks last 6-10 hours, occur every 2-3 days •Cold stage (sensation of cold, shivering) •Hot stage (fever, headaches, vomiting; seizures in young children) •Sweating stage (sweats, return to normal temperature, tiredness) Severe •Can develop from uncomplicated malaria in a few hours •Medical emergency, immediate treatment needed •Potential for organ failure

2. Disease & Symptoms

Vector: Female Anopheles mosquito the female anopheles mosquito transmits protozoan parasite Protozoan parasite: Plasmodium falciparum -Most life threatening P. vivax and P. ovale -Can remain dormant in the liver -Sometimes up to 20 years P. malariae -3 day rather than 2 day cycle

Intercepting the Water Cycle

Withdraws from water cycle •Air Well •Fog Fence •Dehumidifier •Rain barrel •Reservoir •Water pumps •Groundwater wells

Chickungunya

a disease that causes debilitating joint pain in the Caribbean and South America -fever, paralysis etc

Today I was asked to prepare for you lecture as if I would give in an environmental microbiology course. Thought that before doing so, would be good to tell you what I consider environmental microbiology to be:

maybe add a tree of life and say "this include the study of organisms from all 3 domains of life"

spillover event

moment the disease transfers from one species to another -lots of these events are happening because we are outgrowing the global world. forcing interaction between live stick and wild animals causing disease to transfer and spread

viruses

tiny particles, smaller than bacteria and other pathogens, which must invade living cells (species) in order to reproduce; when they invade, the cells are damaged or destroyed in the process releasing new particles to infect other cells -infectious agents that straddle the fence between living and nonliving things

Zika

- first isolated from a rhesus macaque in Zika forest, Uganda (Africa - 1947) then went to yap ( pacific island) then french polynesia then brazil - caused an infection from a viral strain - symtoms in adults at like the common cold which can be solved by fluids and rest (rash, fever, tired etc)

protozoa: eukaryotic organisms that can infect people through a waterborne route, including Plasmodium species, genus that contains malaria causing eukaryotes (Major Infectious Agents)

-Giardia lamblia, Naegleria fowleri, Cryptosporidium parvum, Plasmodium spp.

water based (Classification of water-related illnesses)

-Originate in the water. (grow in water/moister) Come in direct contact with humans in water or by inhalation -Schistosomiasis & Legionella

water realted (Classification of water-related illnesses)

-Pathogens life cycle associated with insects that live or breed in water -Malaria & Yellow fever (mosquitoes make these diseases related to standing water)

viruses (Major Infectious Agents)

-Poliovirus, Hepatitis A, Rotaviruses, Norovirus

ebola

-S/S: sore throat, headache, high temprature, nausea, vomiting, diarrhea, internal and external bleeding, shock -treatment: no cure -supportive care: minimize invasive procedures -prevention: vaccine

bacteria (Major Infectious Agents)

-Salmonella typhi, Campylobacter, Shigella, E. coli, Vibrio cholerae

zika in babies

-causes microcephaly, sight and hearing can be affected (lifetime) -affects tissue in fetus brain, the brain contains calcium deposits and empty space -affected thousands of babies in brazil

fives species of genus ebolavirus

-reston ebolavirus -sudan ebolavirus -zaire ebolavirus -THE MOST DANGEROUS -cause of 2014 outbreak -tai forest ebolavirus -bundibygyo ebolavirus

Ebola in Africa

-sometimes isolated in villages but can spread easily -many didnt know about it or prepared -

Coagulation and Sedimentation

1.Chemicals are added to the water to encourage sedimentation -adding a chemical is a positive charge encouraging sedimentation) •Alum is a great flocculant •Alum is a cation •Most sediment particles have a negative charge 2.The water is allowed to sit •Flocculant makes particles stick together •Larger aggregates settle •Water is removed from the top of the tank

Filtration

3.Water from the top of the sedimentation tank move on to the filtration tank Layers of gravel, sand, and charcoal are used to remove impurities •Dust •Parasites •Bacteria •Viruses •Chemicals

Disinfection

4.Disinfection •Treatment to kill pathogens Chlorine Chloramine Ozone UV light •Fluorine added to prevent tooth decay •Ozone and UV light do not provide a residual •Chlorine added as residual to protect water in transit

ebola

A contagious viral disease originating in Africa. It is transmitted by blood and body fluids and causes body organs and vessels to leak blood, usually resulting in death. -1976 first discovered -person to person contact -when body dies the virus is still alive for a period of time -kills 90% of the people infected

Meliandou

A small village in southeastern Guinea; location in which a toddler was responsible for an Ebola outbreak

5. Treatment & Prevention -prophylactic treatment is the preventative to stop infection before it happens -Chloroquine targets the detoxification of the heme generated from hemoglobin digestion by Plasmodium. Chloroquine based drugs prevent the heme groups from polymerizing and forming a black pigment. As a result, the Fe concentration inside the red blood cell rises until it is toxic to the plasmodium Artemisinin interferes with heme detoxification

Anti-malarial drugs •Artemisinin combination therapies recommended by WHO •Chloroquine and primaquine are older treatments, but still in use

Disinfection: Pros and Cons

Chloramine •Group of compounds containing chlorine and ammonia •Monochloramine used to treat drinking water •Alternative to chlorine •4 mg per liter allowed in drinking water •Lower concentration of regulated biproducts formed •Unregulated biproducts are being studied

Disinfection: Pros and Cons

Chlorination •Cheap and effective •Two Forms: -Gas -Hypochlorite solution (aka bleach) Disadvantages •Can produce trihalomethanes •Ineffective against Cryptosporidium and Giardia •Mostly removed by sand filtration

Surface Water

Cobbs Creek Reservoir Project •In Henrico County •$280 Million •store 15 billion gallons of water •1,100 acre reservoir •Diverts water from the James during overflow -surface water source

E. coli

EHEC: Enterohemorrhagic E. coli •Strain O157:H7 is the most common cause of EHEC •Bloody diarrhea •Uses fimbriae for attachment •Causes an inflammatory response •Very similar to Shigella, has phage encoded genes •Produces Shiga toxin •Moderately invasive •Also produces intimin •Hemolytic Uremic Syndrome (HUS) •Taking antibiotics increases the risk of HUS EHEC: Enterohemorrhagic E. coli •Can cause Hemolytic-uremic syndrome (HUS) •Shiga toxin can damage blood vessels leading to HUS •Shiga toxin binds to a GB3 receptor on human cells •Stimulates -Apoptosis of human cells -Binding of leukocytes •Renal system has more GB3 •Other mammals (e.g. cows, deer) do not have GB3 receptors •The CDC does *not* recommend antibiotics for EHEC EHEC: Enterohemorrhagic E. coli (O157:H7) •Antibiotics are contraindicated for EHEC •Might increase production of shiga toxin •Might increase residence time of E. coli in the intestinal tract

E. coli

ETEC: Enterotoxigenic E. coli •Fimbrial adhesins to bind cells in the small intestine •Produces heat-labile (LT) enterotoxin similar to cholera •Can also produces heat stabile (ST) enterotoxin which causes cells leak fluids and salts into the intestine. •Common cause of travelers' diarrhea Enteroaggregative E. Coli (EAEC) •Produces a stable enterotoxin similar to ETEC •A non-invasive pathogen that causes watery diarrhea •Forms aggregates of bacterial cells stacked on intestinal cells of the host. EPEC: Enteropathogenic E. coli •No fimbriae or toxins •An adhesin known as intimin •Responsible for pedestal formation in intestinal cells •Pedestal formation is similar to shiga-toxin producing E. coli Cause of infantile diarrhea EIEC: Enteroinvasive E. coli •Responsible for ruffling in intestinal cells •Invades the cell •Causes an inflammatory response including fever

Macaques monkey

Group of Old World monkeys comprising several species, including rhesus monkeys. -they carry diseases such as herpes

4. pathogenesis •Plasmodium (merozoites) infects red blood cells. •Synchronized release of merozoites causes classic symptoms of malaria. •Inside the host, different Plasmodium cells will express different proteins. •This diversity of proteins makes it difficult for the host to develop immunity. •Also confounds vaccine development.

Malaria is a major disease worldwide. Plasmodium falciparum (colorized TEM). Schizont after completion of division. A residual body of the organism (yellow-green) is left over after division. The erythrocyte has lysed and only a ghost cell remains; no cytoplasm is seen surrounding the merozoites just being released. Free merozoites are seen outside the membrane. The disease is caused by four species of Plasmodium: P. falciparum (the most deadly), P. malariae, P. vivax, and P. ovale. The life cycle of Plasmodium, discussed in detail in Chapter 20, is complex and involves two cycles: an asexual erythrocytic cycle in the human and a sexual cycle in the mosquito (see Fig. 20.40). In the erythrocytic cycle, the organisms enter the bloodstream through the bite of an infected female Anopheles mosquito (the mosquito injects a small amount of saliva containing Plasmodium). The haploid sporozoites travel immediately to the liver, where they undergo asexual fission to produce merozoites. Released from the liver, the merozoites attach to and penetrate red blood cells, where Plasmodium consumes hemoglobin and enlarges into a trophozoite. The protist nucleus divides, so that the cell, now called a schizont, contains up to 20 or so nuclei. The schizont then divides to make the smaller, haploid merozoites (Fig. 26.22B). The glutted red blood cell eventually lyses, releasing merozoites that can infect new red blood cells (see Fig. 20.39). Sudden, synchronized release of the merozoites and red blood cell debris triggers the telltale symptoms of malaria: violent, shaking chills followed by high fever and sweating. The erythrocytic cycle, and thus the symptoms, repeats every 48-72 hours. After several cycles, the patient goes into remission lasting several weeks to months, after which there is a relapse. Much of today's research focuses on why malarial relapse happens. Why does the immune system fail to eliminate the parasite after the first episode? When Plasmodium invades the red blood cells, it lines the blood cells with a protein, PfEMP1, which causes the parasite to stick to the sides of blood vessels. The parasite is thereby removed from circulation, but the protein cannot protect the parasite from patrolling macrophages, which eventually detect the invader and recruit other immune cells to fight it. So, during a malarial infection, a small percentage of each generation of parasites switches to a different version of PfEMP1 that the body has never seen before. In its new disguise, Plasmodium can invade more red blood cells and cause another wave of fever, headaches, nausea, and chills. The antigenic shift happens when the parasite alters the PfEMP1 gene that is expressed. The body now has to repeat the recognition and attack responses all over again. The parasite has 60 cloaking genes, called var, that can be turned on and off individually, changing the organisms' antigenic structure, like a criminal repeatedly changing his disguise to elude police. In April 2005, Australian scientists Alan Cowman, Brendan Crabb, and colleagues at the Walter and Eliza Hall Institute of Medical Research showed that var genes are regulated by chromosome packaging, which unwraps one gene to be expressed at a time and literally packs away the inactive genes. DNA can be encased so securely by some proteins that other proteins cannot access the nucleic acid for transcription—a process known as epigenetic silencing. Becoming immune to all the types of malaria can take upwards of 5 years and requires constant exposure; otherwise the immunity is lost. Many children do not live long enough to gain immunity to malaria in all its forms. Diagnosis of malaria involves microscopic demonstration of the protist within erythrocytes (Wright stain) or serology to identify antimalarial antibodies. Treatment regimens include chloroquine or mefloquine, which kill the organisms in their erythrocytic asexual stages, and primaquine, effective in the exoerythrocytic stages. The chloroquine family of drugs acts by interfering with the detoxification of heme generated from hemoglobin digestion. Malaria parasites accumulate the hemoglobin released from red blood cells in plasmodial lysosomes, where digestion occurs. The parasites use the amino acids from hemoglobin to grow but find free heme toxic. To prevent eating itself to death (from accumulating too much heme), the organism detoxifies heme via polymerization, which produces a black pigment. Many antimalarial drugs, such as chloroquine, prevent polymerization by binding to the heme. As a result, the increased iron level (from heme) kills the parasite.Chloroquine is given prophylactically to persons traveling to endemic areas. Unfortunately, Plasmodium has been developing resistance to these drugs, forcing the development of new ones. The antigenic shape-shifting carried out by this parasite has so far stymied development of an effective vaccine.

E. coli type III secretion and cell-cell interaction

Model of cytoskeletal components within the EPEC pedestal. EPEC injects Tir protein into the host cell, where it moves to the membrane and acts as a receptor for intimin. Tir also communicates through phosphorylation with other host proteins to cause a change in actin cytoskeleton, which leads to pedestal formation.

Burden of water-related disease 4.6 million deaths in 2004 39% diarrheal disease 13% other 14% malaria 21% malnutrition complications etc etc etc

Overlaying the issues of water stress both from flooding and drought is the fact that waterborne and foodborne diseases continue to be significant causes of morbidity and mortality world-wide. Among the wide spectrum of diseases that are associated with food and especially water, gastroenteritis is the most commonly identified illness. These diarrheal diseases contribute to as many as 4 million cases annually and 1.8 million deaths. Of these cases, 88% can be linked to poor water quality (World Health Organization, 2009). DALYs = Disability Adjusted Life Years.

E. coli type III secretion and cell-cell interaction

Pedestal formation (SEM).

What is environmental microbiology?

Study of microbes within all habitats, and their beneficial and detrimental impacts on human health and welfare.

Where does water come from?

The sky •Perciptation •Rain, snow Condensation •Fog, mist, dew Groundwater •Aquifers Surface water •Reservoirs, lakes, rivers, oceans, glaciers

Disinfection: Pros and Cons

Trihalomethane •Biproduct of chlorination -Chlorine reacts with naturally occurring organic matter -Forms chloroform (CCl3H) -Can also be formed by other halides •Absorbed through skin, ingested, or inhaled •Chloroform is a carcinogen •EPA Regulation = 100 micrograms total trihalomethanes per liter of water

Disinfection: Pros and Cons

UV Light •Effective on viruses, spores, and protists •Physical process making it safer •Shorter contact time for treatment •No residual - no harmful biproducts but no protection during transport

Areas of Malaria Transmission and Antimalarial Drug Resistance

if we look at areas of malaria transmission and antimalarial drug resistance, we're going to see that the areas that are most impacted by malaria are near the equator (tropical areas that have water and heat) regionally: resistance to different malaria treatment drugs changes depending on the region of the world that you're in. Because these malarial population of Plasmodium that cause malaria are isolated and evolving

6. Environmental Interactions

in the face of climate change, the spread of warm weather is happening. Standing water from rain events to encourage mosquito growth. Mosquito population growth is happening. The regions where malaria is a problem, where the anopheles mosquito can thrive are changing. And that is a challenge in controlling the spread of malaria

transmission

lifecycle of Plasmodium (a) Anopheles mosquito feeds on a human transmitting Malaria sporozoites (b) Sporozoites cells infect the liver and reproduce (c) Merozoites cells exit the liver and infect red-blood cells. Red-blood cells lyse, releasing more merozoites and gametocytes (d) Mosquito bites infected host picking up gametocytes.Gametocytes reproduce in the gut of the mosquito producing sporozoites

zika virus

spread by Aedes mosquito (aedes aegypti) or by sexual transmission and blood influsions -horrific phenomenon that invades the fetal brain and destroys brain tissue in the fetus

Summary

•Malaria is caused by several species of Plasmodium, a protist pathogen. •Transmitted by a Anopheles mosquito. •Climate change will impact the range of the disease, and the frequency of the outbreaks. •Multiple strategies for treatment and prevention targeting different life stages of Plasmodium.

Insecticides for Prevention? -DDT, which was a very long-lasting pesticide. In fact, it would bioaccumulate up the food chain and create health issues for tertiary predators. So they stopped making long-lasting insecticides

•Most common is DDT (negative affect on environmental health) -Dichloro-diphenyl-trichloro-ethane •Negative effect on human health and environment •Potential vector resistance •Alternative insecticides

Monitoring Pathogens

•Most microbes are okay!! •There are a lot of different kinds of pathogens (too expensive to monitor individually) •Viruses •Protists •Worms •Bacteria •Fungi ^Indicator organisms are non-pathogenic organisms that indicate the presence of pathogens.

Microbes affect our daily lives

•Overall health of the planet •What infects us •What heals us •What we drink •What we eat •What we breathe (aerosolized pathogenic organism)

Will climate change affect malaria?

•Plasmodium species grow faster at higher temperatures (optimal: 27-30°C) •Capacity of mosquitoes to transmit Plasmodium increases as temperature increases (optimal: 22-30°C) •Mosquito lifespan increases with higher temperatures •Aquatic life cycle of mosquitoes reduced (20 à 7 days)

Treatment - Artemesinins

•Rapidly kills P. falciparum inside red blood cells •Dose varies with preparation •Possible neurotoxicity •Increasing evidence of safety during pregnancy

Why is malaria a big deal? So what does this really mean? Well, these diseases that are preventable are occupying a rather large chunk of health resources. So It's going to have a cascade effect on health resource availability

•Significant economic impact on countries with high levels of transmission. •109 countries where it is routinely transmitted, with a combined population of 3.3 billion people. •In these countries, disease accounts for: -40% of public health drug expenditure -30-50% of in-patient hospital admissions -up to 60% of outpatient health clinic visits

Indicator Organisms

•present whenever pathogens present in water •absent in uncontaminated water •does not reproduce in contaminated water •better survival in water than pathogens •easy to analyze (cheap, accurate, reliable) -the less indicator organisms the less risk of being exposed to a pathogen

1. Significance of Malaria

•~1500 cases reported each year in the US -Most often people who travel to infected regions •863,000 people died globally in 2008 (WHO) -89% of deaths are in Africa -Every minute, one child in Africa dies from malaria •5th leading cause of death from infectious diseases (worldwide) •2nd leading cause of death from infectious disease in Africa -DDT: a chemical that wiped out all the mosquitoes, and in doing so, reduced the prevalence of vector-borne diseases USED in high populated areas with mosquitoes