LESSON 3.2 WORKBOOK. Lesson 3.2: Reservoirs and vectors - Lyme disease and Malaria

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Borrelia Burgdorferi DEFINITIONS OF TERMS Asymptomatic carrier: is a person or other organism that has contracted an infectious disease, but has no symptoms.

1 Borrelia Burgdorferi DEFINITIONS OF TERMS Asymptomatic carrier: is a person or other organism that has contracted an infectious disease, but has no symptoms. Vector: an organism that transmits a pathogen from reservoir to host. LESSON 3.2 WORKBOOK Lesson 3.2: Reservoirs and vectors - Lyme disease and Malaria In the last lesson, we discussed Ebola and its natural host, the fruit bat. In this lesson, we will explore different methods that pathogens employ to infect their hosts, including the use of more than one host species, and the use of vectors. We will also explore the idea that microbes can evolve to live in their hosts without causing disease, and that a microbe deadly to one host can be an asymptomatic carrier in another. Routes of Transmission Most of the pathogens that we have covered so far can be passed directly from one person to another. However, this is not the only way that diseases can be transmitted. In previous units we discussed Cholera and how it can be contracted through drinking water that is contaminated with feces containing Cholera bacteria. In that case, the cholera bacterium lives in the water in between human hosts. In the case of malaria, the parasite lives inside mosquitoes in between human hosts. As we will see, many pathogens have several stages to their life cycles and these stages can include multiple hosts. Reservoirs When a pathogen does not use humans to complete its entire life cycle, it must have another host, or reservoir. As discussed in the last lesson, reservoirs are carriers of a microbe that are usually asymptomatic. Reservoirs can act as sources of pathogens in the environment and a single microbe may use multiple reservoirs. In the case of Ebola, researchers confirmed that fruit bats acted as a reservoir for the virus since they carry the virus without becoming ill. This means that Ebola can thrive in the bat population for an extended period of time until an unlucky person is exposed. Another example is the plague, which can be carried by prairie dogs. We will see more examples of reservoirs in this lesson. Vectors Many microbes use different hosts for different parts of their lifecycle. But how does a microbe get from one host to another? Most use an animal or an insect vector to transport from host to host. Vectors are living transmitters of disease and are a crucial part of the life cycle for many pathogens. Most vectors are insects and the spread of a disease is often limited by the spread of its vectors. With global warming and the transport of insects by humans numerous vector born diseases are spreading to new places. Perhaps the most famous vector is the mosquito, which transmits Malaria. Warmer weather allows mosquitoes to survive farther north, List four different routes of infection and pathogens that use them _ Can you give an example of a reservoir that can be a vector? so mosquito-borne infections like malaria and Eastern equine encephalitis virus (EEEV) are spreading. In this Lesson 3.2 case eradicating the vectors is a potential means to control the spread of the disease. 1

DEFINITIONS OF TERMS Spirochete - spiral shaped bacterium. LESSON MATERIALS Lyme disease: a complex interaction between reservoirs en route to human infection.

It can be caused by at least 3 different Borrelia bacteria, which are Gram-negative spirochetes (spirilla).

Intensive investigation soon established that Lyme disease is carried by ticks; in fact it is the most common tick-borne disease in the Northern Hemisphere.

2 DEFINITIONS OF TERMS Spirochete - spiral shaped bacterium. LESSON MATERIALS Lyme disease: a complex interaction between reservoirs en route to human infection. Lyme disease is currently one of the Center for Disease Control s Top 10 emerging infectious diseases worldwide. It can be caused by at least 3 different Borrelia bacteria, which are Gram-negative spirochetes (spirilla). Lyme disease is named after the village of Lyme, Connecticut, where a cluster of cases was diagnosed in Intensive investigation soon established that Lyme disease is carried by ticks; in fact it is the most common tick-borne disease in the Northern Hemisphere. Lyme disease is causing focal epidemics as it spreads in the northeastern and upper midwestern US. They are thought to be a result of the large increase in deer in suburban and rural areas. The deer tick needs the whitetailed deer to reproduce successfully. Reducing the numbers of deer hosts may help break the deer tick reproductive cycles and their ability to flourish. In the US it has been suggested that reducing the deer population in areas with the highest Lyme disease rates from current levels of 60 or more per square mile to 8 to 10 per square mile could reduce tick numbers down to levels too low to spread Lyme and other tick-borne diseases. Borellia burgdorferi is transmitted to humans and deer from its natural reservoir in rodents by deer ticks that feed on both humans and deer. Deer are the most common hosts for adult stage ticks; humans are accidental hosts because the bacteria from infected people are not transmitted to other humans or deer. Lyme disease bacteria are transmitted from nymph ticks to rodents like the white-footed mouse, and then back from the mouse to the larval ticks. It works like this: The nymph tick typically feeds on the mouse for several days. If the tick is infected with B. burgdorferi the mouse becomes chronically infected, particularly in the skin where the tick has fed. Then when uninfected ticks feed on the rodent the bacteria passes back to the next generation of ticks. The back and forth transmission is essential because the female tick does not transfer bacteria directly to her offspring. The mice are therefore an essential bridge that allows Lesson 3.2 bacteria to be transmitted from one generation of 2 deer tick to the next. Fig 3.2.1: Borrelia burgdorferi, the major cause of Lyme disease in the US. Fig 3.2.2: Black legged deer ticks maintain the reservoir of B. burgdorferi in nature. The Nymph form is most responsible for human infection because it is so small it often goes unnoticed. When reading, answer the fallowing questions for each disease: Name of disease: Where does it occur?

3 LESSON MATERIALS The vector The nymph tick is also the major vector that transmits the bacteria to humans. When the tick bites a human two important events occur: First, the bacteria in the tick is exposed to warm mammalian blood. This causes it to change a surface protein it produces to a form that helps it transmit to humans. If the feeding ticks are removed before this changeover of protein is complete, i.e. within hours, the bacteria will not transmit successfully to humans. This is why human infection is quite rare - only about 1% of recognized tick bites result in Lyme disease. The second event is that bacteria is injected into the human along with tick saliva. The saliva contains substances that interfere with the immune response at the site of the bite. This prevents the human host feeling an itch or pain from the bite, and provides a protective environment that allows the bacteria to survive. Fig 3.2.3: The life cycle of the deer tick that is the vector for Lyme disease The Life-cycle of Lyme Disease. The 2-year cycle of deer ticks has four stages: eggs, larvae, nymphs, and adults. Larvae hatch in the summer. They are uninfected, but soon acquire B. burgdorferi by feeding on infected mice. The infected larvae molt into nymphs in the fall and are dormant through the winter. Infected nymphs feed on mice in the late spring and early summer. This sets up a natural reservoir of B. burgdorferi. The chronically infected mice then transmit B. How does the life cycle work? burgdorferi to the next generation of uninfected tick larvae. Infected nymph ticks also feed on humans in the late Lesson 3.2 spring and summer causing a peak of human Lyme disease. The nymph ticks then molt into adults. 3

LESSON MATERIALS DEFINITIONS OF TERMS Endemic - persistent. Encephalitis - inflammation of the membranes covering the brain. Cerebrospinal fluid - the fluid that bathes the brain and spinal cord.

4 LESSON MATERIALS DEFINITIONS OF TERMS Endemic - persistent. Encephalitis - inflammation of the membranes covering the brain. Cerebrospinal fluid - the fluid that bathes the brain and spinal cord. The natural cycle of B. burgdorferi is important in how Lyme disease occurs. First, Lyme disease is endemic only in regions were all the players in its life cycle coexist. In the US, this is the northeast and mid-atlantic coastal states, and the Great Lakes regions. Second, most human infections occur in the spring and summer months, when outdoor activities bring people into contact with feeding nymph ticks. Since the ticks are extremely small (approximately 1 mm in length) they are often not discovered for several days, allowing the B. burgdorferi to be activated and transmitted. Lyme Disease Signs and Symptoms Like syphilis, which is also caused by similar bacteria, Lyme disease progresses through several stages and affects many organs. The incubation period from the infection to the onset of symptoms is usually one to two weeks, but can be much shorter (days), or much longer (months to years). The classic sign of Stage 1 infection is a circular bull s eye rash at the site of the bite caused by an inflammatory response to the bacteria (It looks like a bull-s eye because the tick saliva inhibits the inflammation in the area closest to the bite. Only 80% of patients display a bull s eye rash. During Stage 2 the bacteria enter the bloodstream and spread to the joints, heart, nervous system, and distant skin sites where they cause a variety of symptoms such as fever, headache, muscle soreness and fatigue. Some patients also suffer from neurological problems like facial paralysis and encephalitis leading to memory loss. If the infection is untreated, Stage 2 symptoms may progress to Stage 3 with chronic inflammation of the joints, the heart, the central nervous system and the skin. Diagnosing Lyme Disease Lyme disease is usually first diagnosed by the bulls eye rash, facial paralysis or arthritis together with a history of possible exposure to infected ticks. Most but not all patients with Lyme disease will develop the bulls-eye rash, but many may not recall a tick bite. Borrelia bacteria are very hard to grow in the laboratory, so diagnostic tests measure antibodies in the blood or cerebrospinal fluid (CSF) via lumbar puncture. Unfortunately, the blood screens only detect 64% of all infections at early stages of the disease. Although this rises to 100% in people with advanced symptoms, such as arthritis, the disease is much harder to treat at this point. Fig 3.2.4: Stages of Lyme disease: Lyme can persist for many years and infects a large number of organs. How is it diagnosed? What are the symptoms? It can be extremely difficult to eradicate once the Lesson 3.2 bacteria have entered the brain, joints and heart. 4

5 LESSON MATERIALS Treating Lyme disease The antibiotics that are the primary treatment for Lyme disare not always very effective. Up to one third of Lyme disease patients who have completed a course of antibiotic treatment continue to have symptoms. A few doctors believe that the symptoms persist because the Borrelia infection has not been eliminated or because the patient has been co-infected with other tick-borne infections. Other doctors believe that the initial infection may cause an autoimmune reaction that continues to cause serious symptoms even after the bacteria have been eliminated. Lyme disease is causing focal epidemics as it spreads in the northeastern and upper midwestern US. They are thought to be a result of the large increase in deer in suburban and rural areas. The deer tick needs the white-tailed deer to reproduce successfully. Reducing the numbers of deer hosts may help break the deer tick Fig 3.2.5: Adult ticks overwinter on whitetailed deer, which are pests in areas were reproductive cycles and their ability to flourish. In the US it has been suggested that reducing the deer population Lyme disease is endemic in areas with the highest Lyme disease rates from current levels of 60 or more per square mile to 8 to 10 per square mile could reduce tick numbers down to levels too low to spread Lyme and other tick-borne diseases. B. burgdorferi is transmitted to humans and deer from its natural reservoir in rodents by deer ticks that feed on both humans and deer. Deer are the most common hosts for adult stage ticks; humans are accidental hosts because the bacteria from infected people are not transmitted to other humans or deer. Lyme disease bacteria are transmitted from nymph ticks to rodents like the white-footed mouse, and then back from the mouse to the larval ticks. It works like this: The nymph tick typically feeds on the mouse for several days. If the tick is infected with B. burgdorferi the mouse becomes chronically infected, particularly in the skin where the tick has fed. Then when uninfected ticks feed on the rodent the bacteria passes back to the next generation of ticks. The back and forth transmission is essential because the female tick does not transfer bacteria directly to her offspring. The mice are therefore an essential bridge that allows bacteria to be transmitted from one generation of deer tick to the next. What are the public health issues involved with diagnosis, treatment and prevention? Lesson 3.2 5

6 DEFINITIONS OF TERMS Zoonosis- an infectious disease that can be transmitted from animals to humans. LESSON MATERIALS Malaria: The most important of all the parasitic diseases Malaria, the most important of all parasitic diseases, occurs in many tropical and semitropical regions. There are approximately 200 million to 300 million new cases annually, and an estimated 2 million to 3 million people die of malaria each year. About 89% of these deaths occur in Africa, and mostly to children under the age of 5. Of all infectious diseases malaria is considered to have caused the greatest harm to the greatest number of people. Malaria was endemic in some areas of the US in the 1800s but has since been eradicated with DDT (as we will see). Currently, the 1000 or so cases that are diagnosed in the US arise from travelers who have been in an endemic area, or, rarely from infected mosquitoes that have arrived in planes. But this may not necessarily continue. If climate change continues along its current trajectory mosquitoes are expected to regain a foothold in many areas (in red on the map) currently considered too temperate to support them. The Malaria parasite and its vector Malaria in humans is caused by 4 species of parasites: Plasmodium protozoa ( P. falciparum, P. vivax, P. ovale, and P. malariae). The four species vary in their ability to cause disease because they prefer red blood cells of different ages. Plasmodium falciparum is the most deadly because it invades red blood cells of all ages. Transmission of the parasite to humans occurs through the bite of infected female anopheles mosquitoes. The parasite is injected from the mosquito salivary gland into humans when it takes a blood meal. The parasite then travels rapidly to the liver, where it takes up residence in order to mature. Mature plasmodium leaves the liver and enters red blood cells, where it divides so much that the red blood Fig 3.2.6: Climate change and malaria - the red areas show where malaria is expanding to. Fig 3.2.7: Plasmodium falciparum, one of the 4 plasmodium protozoa that can cause malaria seen in a blood culture with red blood cells. When reading answer the fallowing questions for each disease: Where does it occur? Lesson 3.2 cells become full of parasites, and burst. 6

LESSON MATERIALS The Natural Cycle of Malaria How does the life cycle work? DEFINITIONS OF TERMS Sporozite - the form of plamsmodium that replicates in the liver.

The life cycle of the malaria parasite is rich in fascinating detail.

7 LESSON MATERIALS The Natural Cycle of Malaria How does the life cycle work? DEFINITIONS OF TERMS Sporozite - the form of plamsmodium that replicates in the liver. Merozoite - the form of plasmodium that infects red blood cells. The Anopheles mosquito is the vector, transmitting the malaria parasite to humans. Infected humans are the only actual reservoir. The life cycle of the malaria parasite is rich in fascinating detail. Let s start at the beginning of the cycle with an infected female Anopheles mosquito, which has the parasite in her salivary glands. When she feeds on a human the parasite is injected into the bloodstream and immediately travels to the liver. It can enter liver cells within 30 minutes. Over the next week or two the parasite in the form of plasmodium sporozites multiplies in the liver cells generating large numbers. At the same time as the sporozites are dividing they are also maturing to a form that is capable of infecting red blood cells called merozoites. When the merozoite is mature it is released into the bloodstream, where it enters red blood cells. Fig 3.2.7: The female anopheles mosquito that acts as a vector for transmission of the malaria protozoa. Her abdomen is distended with blood. If the blood contains plasmodium she can reinfect another human when she feeds again. Again the parasite divides and matures. After another 2-3 days the infected red blood cells are so full of parasite that they burst, releasing yet more parasites into the blood stream to infect more red blood cells. While this is happening a small number of merozoites develop further into male and female forms. If a mosquito feeds again from the human reservoir it can take in the male and female forms. They then develop in the mosquito into the sporozites and the cycle repeats itself. Fig 3.2.8: The life cycle of plasmodium in the human Lesson 3.2 7

8 DEFINITIONS OF TERMS PCR - a way to detect DNA. Serological testing - testing blood. LESSON MATERIALS Malaria Signs and Symptoms The symptoms of malaria are intense and generally show up within a month of infection as a very high fever, chills and, later on, anemia (low numbers of red blood cells). The symptoms coincide with the release of large numbers of merozoites from the red blood cells, and occur because the immune system has recognized the presence of a foreign invader and has put its defense mechanisms on high alert. After the first parasites replicate in the red blood cells, the infection becomes synchronized so that all infected red blood cells lyse at the same time. Other symptoms of malaria are also caused by the immune system response and resemble influenza (fever, muscle aches and generally feeling ill). Stomach pain can also occur because of liver damage. Patients with symptoms of malaria are often misdiagnosed, especially if they don t live where malaria is endemic and if the physician does not ask about travel. Fig : Detecting P.falciparum merozoites infecting red blood cells Fig 3.2.9: Plasmodium merozoites bursting out of red blood cells Diagnosing Malaria Malaria is diagnosed in the laboratory by taking a thick smear of blood (8-12 cells deep) onto a microscope slide and then using a dye to color the plasmodium merozoites blue. Different types of plasmodia give different patterns of staining. PCR analysis to detect plasmodium is more accurate than blood tests but is expensive and requires expertise. It isn t useful in developing countries. Unlike Lyme disease serological testing for malaria antibodies is of little use for someone with acute infection because antibodies to the parasite do not develop for 3 5 weeks, but treatment must begin within 1 2 days to stop the infection from spreading to the liver. Treatments and Prevention The malaria parasite has evolved several strategies to evade the immune system. As a result, people who have lived where malaria is endemic will still get infected on a regular basis. However their infections are usually less severe, suggesting that the immune system can control the infection even if it cannot eradicate it. Drugs are based on quinine, which accounts for the popularity of gin and tonic in the tropics - tonic contains quinine! Quinine stops the parasite from degrading the hemoglobin in red blood cells, thereby blocking a major source of nutrition. The major antimalarial drug used to be chloroquine. Unfortunately, the parasite can develop resistance to the drug. Chloroquine-resistant malaria is now widespread in most of Southeast Asia, South How is it diagnosed? What are the symptoms? Lesson 3.2 America and Africa, and a cocktail of other anti-malarials a must be used. 8

9 DEFINITIONS OF TERMS WHO - World Health Organization. Serological testing - Testing blood. Carcinogen - able to cause cancer. LESSON MATERIALS Malaria Control - DDT - For and Against Malaria remains a major public health challenge in many parts of the world. The World Health Organization (WHO) estimates that in 2008 there were 243 million cases, resulting in 863,000 deaths. One way to eliminate infection is to eradicate the mosquito vector. Spraying with pesticide, especially DDT has been effective but controversial: It has been called everything from a miracle weapon [that is] like Kryptonite to the mosquitoes, to toxic colonialism. DDT (dichlorodiphenyltrichloroethane) was first used to control malaria in the second half of World War II. In response to its success WHO started an anti-malaria campaign in the 1950s and 1960s that relied heavily on DDT. The results were promising. For example, in Sri Lanka, the program reduced cases from about 3 million per year before spraying to just 29 in Then the program was halted to save money, and malaria rebounded to 600,000 cases in About the same time public awareness about problems with DTT led many governments to restrict or curtail its use. The problems included the realization that people living in sprayed areas have levels of DTT and its breakdown products in their bodies that much higher than people who live elsewhere. Animal studies have shown that DTT is a carcinogen and there is also some evidence in humans that DDT can cause cancer of the liver, pancreas, and breast. Once the mainstay of anti-malaria campaigns, as of 2008 only 12 countries still use DDT, including India and some southern African states. Fig : After DDT was a success against malaria and typhoid in World War 2 the WHO instigated malaria eradication programs to spray mosquitoes. For spraying to be effective, at least 80% of homes and barns must be sprayed, so if enough residents refuse spraying, the whole program can be jeopardized. But there is no doubt that when used properly DTT can significantly curb malaria, however DDT resistance in mosquitoes, which is largely due to its overuse in agriculture, has greatly reduced its effectiveness in many parts of the world. Current WHO guidelines require that before DTT is used in any area it must first be confirmed that local mosquitoes are susceptible to it. Some countries that still use DDT have shown that alternative insecticides are less effective in South Africa malaria incidence increased dramatically when the insecticide was switched, but returning to DDT and introducing new drugs brought malaria back under control. Similarly malaria cases increased in South America after DDT use was stopped. Between 1993 and 1995 Ecuador increased its use of DDT and saw a 61% reduction in malaria rates, while other countries that gradually decreased DDT use at the same time saw large increases in malaria. What are the public health issues involved with diagnosis, treatment and prevention? Lesson 3.2 9

10 DEFINITIONS OF TERMS WHO - World Health Organization. Serological testing - testing blood. Current Recommendations: Currently DDT remains on the WHO s list of recommended insecticides and its policy has shifted from recommending spraying only in areas of seasonal or episodic transmission of malaria, to also advocating it in areas of continuous, intense transmission, so DDT use is expected to rise. The major reason is the failure to curtail malaria through drug treatment to kill the parasite, because of the increasing prevalence of drug-resistant forms.. LESSON MATERIALS Fig : A mosquito bed net soaked in insecticide can give reasonable protection, if used properly, for $5. What are the public health issues involved with diagnosis, treatment and prevention? Lesson

LESSON 3.2 WORKBOOK. Reservoirs and vectors Lyme diseases and Malaria

LESSON 3.2 WORKBOOK. Reservoirs and vectors Lyme diseases and Malaria Reservoir a reservoir typically harbors the infectious agent without injury to itself, and serves as a source from which others can be infecte Asymptomatic carrier is a person or other organism that has