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CORE I Infectious Diseases Disease: disorder of the body, preventing it working at maximum efficiency. It produces special symptoms which are detectable. The disorder has a specific cause, even if this is not understood. Infectious disease VS non-infectious disease: Infectious disease: Transmissible/communicable Caused by pathogen Can spread from infected to uninfected people via direct contact (as pathogen cannot survive outside the human body) or via indirect transmission through food, water, faeces or animals (insect vectors) Transmission cycle: way in which pathogen passes from one host to another Non-infectious disease: NOT caused by pathogens Includes deficiency diseases (scurvy: lack of Vit C, rickets: lack of Vit D), inherited diseases (cystic fibrosis, sickle cell anaemia), degenerative diseases (lung cancer, CHD), mental diseases (dementia, Alzheimer’s), social diseases (obesity) and self-inflicted diseases (smoking, sunbathing, drug abuse diseases). Carriers: people who do not show symptoms of the disease BUT carry the pathogens and are able to spread them IREVE SUI 1 CORE I Infectious Diseases CHOLERA CAUSES AND EFFECTS Caused by bacterium Vibrio cholerae (in writing, underline the Latin name + capitalise V only) Site of action of bacteria is small intestine. Bacteria will hence, have to pass through stomach. If stomach pH environment is < 4.5, bacteria destroyed. Or else, bacteria can proceed to small intestine. At small intestine, bacterium multiply/reproduce and secrete toxin choleragen. Choleragen disrupts epithelium of small intestine. Usually, small intestine is absorptive (absorbs salts and water that enters blood). Instead, choleragen makes water and salts leave the blood and enter the small intestine. After about 24 hours of infection, watery and highly infectious diarrhoea (‘rice water’) may begin. If not treated, the excess loss of fluid causes dehydration. It can be fatal. Effects of cholera: dehydration (loss of water and salts), severe diarrhoea and weakness. TRANSMISSION Ingestion of contaminated food. Oysters and mussels are filter feeders that may live in contaminated waters. Sewage pumped directly into the sea can contain Vibrio cholerae bacteria that are taken up by oysters and mussels. Eating them without thorough cooking can cause infection. Flies can also spread Vibrio cholarae from faeces to food. Drinking or cooking with contaminated water. Water may be contaminated with sewage or faeces of infected people. Vibrio cholerae can survive outside the human body, in water very well. IREVE SUI 2 CORE I Infectious Diseases TREATMENT Death from cholera can be avoided. Treatment in the form of oral rehydration therapy can be given, if the patient can drink. The therapy involves drinking a solution of salts and glucose. If the patient cannot drink, the solution can be administered intravenously. Glucose is cotransported into blood together with salts (Na+ and K+). It is important that fluid intake = fluid losses (urine + diarrhoea). This is to maintain osmotic balance of blood and tissue fluids. PREVENTION AND CONTROL Proper sanitation and health practices Purification of water for consumption (drinking, cooking, washing) Good personal hygiene (thorough handwashing) Good irrigation system and agricultural practices Vaccination. This provides only short-term protection (~6 months). Used to be recommended for travellers going from cholera-free area to an endemic area. However, the vaccine is not so helpful as it is hard to concentrate the action of the vaccine at the small intestine. Scientists are trying to develop oral medicine that can act at the intestine. GLOBAL IMPORTANCE OF CHOLERA Developing regions Asia, Africa and Latin America These areas have rapidly growing population. However, development of infrastructure/sewage systems is slow or non-existent due to financial problems. Also, in these areas, people have been displaced due to war or natural disasters (famine, drought). Cholera infection is widespread as clean water is not available. IREVE SUI 3 CORE I Infectious Diseases MALARIA CAUSES AND EFFECTS Caused by protoctist Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale and Plasmodium vivax. An insect vector, the female Anopheles mosquito, transmits the protoctist from an infected person to an uninfected person. Effects: fever, anaemia, nausea, headaches, muscle pain, shivering, sweating and enlarged spleen. People who are infected continuously may become immune to malaria, but only after around five years of exposure. The first five years of life is when mortality of malaria is high. The immunity lasts as long as they are in contact with the disease. This explains why mortality is higher in areas not previously exposed to malaria. Also, malaria is more dangerous in those areas where it only occurs during and after the rainy season. (Mosquitoes lay their eggs in stagnant water; common during and after the rainy season). During and after the rainy season, agricultural activity increases. If people are infected and ill with malaria, they will not be able to cultivate land. Hence, there will be disastrous economic effects. TRANSMISSION The female Anopheles mosquitoes feed on human blood. If the person being bitten is infected with Plasmodium, the mosquito in her blood meal will take some of the protoctists’ gametes up. These gametes will mature to the infective stage and move to the mosquito’s salivary glands. The next time the mosquito feeds on a human, using its saliva, it injects an anticoagulant into the human to prevent blood from clotting. Together with the anticoagulant, the infective stages pass out into the blood. The human IREVE SUI 4 CORE I Infectious Diseases host is now infected as the parasites (infective stages) enter the red blood cells and liver cells and multiply. Plasmodium multiplies in both the human host and the insect vector/host. There is a huge increase in the number of parasites each time and this increases the chances of infecting another mosquito or human host. Plasmodium may also be transmitted through blood transfusion. Plasmodium can be spread through the use of unsterelised needles. Malaria can also be transmitted through the placenta, from mother to foetus. TREATMENT Anti-malarial drugs, quinine and chloroquine, are used to treat infected people. These drugs are also used as prophylactic/preventive drugs to stop infection in a person bitten by an infectious mosquito. These drugs are taken before, during and after visiting an endemic region. Chloroquine inhibits protein synthesis and stops the parasite from spreading within the body. However, wise usage of chloroquine in S. America, Africa and New Guinea has led to the evolution of drug-resistant strains of Plasmodium. In these areas, a newer drug, mefloquine, is used but it is expensive and may have unpleasant side effects (e.g. dizziness, restlessness, vomiting and disturbed sleep). Proguanil is an anti-malarial drug that additionally inhibits sexual reproduction of Plasmodium inside the biting mosquito. PREVENTION AND CONTROL There are three main ways of controlling malaria: o Reduce number of mosquito vectors o Avoid being bitten by mosquitoes o Use drugs to prevent parasite infecting people Killing all mosquitoes may break the transmission cycle. IREVE SUI 5 CORE I Infectious Diseases Mosquitoes lay their eggs in stagnant water bodies, and the larvae breathe air by coming to the surface. Spraying the surface with oil will cause suffocation and hence the mosquito larvae and pupae will not be able to breathe. Wet marshes can be drained and vegetation cleared to reduce breeding sites for mosquitoes. However, with the rainy season, there will always be small puddles around. Two biological controls can be implemented: o Placing fish in ponds, irrigation and drainage ditches that will feed on mosquito larvae o Spraying a solution containing the bacterium Bacillus thuringiensis that kills mosquito larvae. The bacterium is harmless to other species. Prevention is better than cure: avoid being bitten by mosquitoes. o Sleep under insecticide-treated mosquito nets (Soak mosquito nets in insecticide every 6 months) o Use insect-repellent spray o Avoid exposing skin at dusk, when mosquitoes are most active o Sleep with a dog or a pig, as mosquitoes prefer biting them! GLOBAL IMPORTANCE OF MALARIA World Health Organisation (WHO) tried to eradicate malaria in the 1950s. It was not successful. o Plasmodium became resistant to drugs used to control it o Mosquitoes became resistant to DDT and other insecticides used Malaria is causing worldwide concern. o Increase in drug-resistant Plasmodium strains o Increase in malaria cases caused by P. falciparum, the strain that causes severe, often fatal malaria o Difficulties in developing effective and cheap vaccine o Increase in number of epidemics due to change in climate and environment that favours spread of mosquitoes IREVE SUI 6 CORE I Infectious Diseases o Migration of infected and potential uninfected hosts from one place to another due to civil unrest and war. 40% of the world’s population live in areas where malaria is a risk (91 countries). These areas include mostly tropical and sub-tropical countries (rainy season + hot, humid weather). Every 20 seconds, a child dies of malaria… IREVE SUI 7 CORE I Infectious Diseases TUBERCULOSIS (TB) CAUSES AND EFFECTS Caused by bacterium Mycobacterium tuberculosis and Mycobacterium bovis. They infect the lungs first, then may spread throughout the whole body (infect lymph nodes and gut) and may even affect bone tissue. Effects: racking cough, coughing blood, chest pain, shortness of breath, fever, sweating and weight loss. TRANSMISSION Some people become infected and develop TB quickly. Others may have the bacteria that remain inactive/dormant for a long period of time before causing disease. These people are infected but are not infectious (cannot spread TB) and do not show any symptoms. They show symptoms when their immune system is weakened by other diseases, as that is when TB strikes. TB is often the first opportunistic infection that occurs in an HIV-positive patient. It is now the leading cause of death in HIV-positive patients. TB is spread through airborne droplets of liquid containing bacteria expelled from the sneeze or cough of an infected person. Hence, TB spreads rapidly in overcrowded areas, areas where lots of people live together and in the homeless population where the people are likely to suffer from malnutrition and weakened immune systems (due to being HIVpositive). TB caused by M. bovis is found in cattle and can spread to humans in meat and milk. IREVE SUI 8 CORE I Infectious Diseases DIAGNOSIS AND TREATMENT Doctor analyses sputum samples for presence of M. tuberculosis or M. bovis. If the bacteria are present and are in most infectious stage (the first 2-4 weeks after infection), the patient is isolated/quarantined. Treatment involves a combination of several drugs to ensure: o All bacteria are killed o Reduction of chances of drug-resistant strains developing Drugs must be consumed for 9 months to one year. Bacteria are slow growing and are not very sensitive to drugs used. Problem arises when people do not continue taking drugs for 9 months to one year, believing that they are cured. These are the people who may harbour drug-resistant forms. Antibiotics kill the more sensitive ones and leave the resistant ones behind. Drug resistance occurs as a result of mutation in bacterial DNA. Occurs about once in every 1000 bacteria. Stopping treatment early allows bacteria to develop resistance to all the drugs used in the combination. WHO promoted a scheme called DOTS (Direct Observation Treatment, Short Course). It involves health workers or responsible family members making sure that patients take their medication regularly for the prescribed period of time. Two of the drugs in the combination are isoniazid and rifampicin. The drug treatment cures 95% of patients and helps to reduce multiple drugresistant strains. PREVENTION AND CONTROL Once thought to be eradicated, Tb is now showing resurgence. o Some strains of TB bacteria are drug-resistant o AIDS pandemic o Poor housing and rising homelessness IREVE SUI 9 CORE I Infectious Diseases o Breakdown of TB control programs; partial treatment (not complete 9 months to one year) increases the chance of drug resistance in Mycobacterium o Migration of people from developing countries to large cities that are more populated/overcrowded Contact tracing is essential in the combat of TB. Contacts that may have interacted or been in close proximity to an infected patient are screened for symptoms of TB (via lung X-rays and microscopic sputum analysis). Spread of TB is prevented in young children by the BCG vaccine given to 1314 year olds. The vaccine is derived from M. bovis and is effective, but effectiveness decreases with age unless there is exposure to the disease. TB can also be transmitted between humans and cattle. So, cattle are routinely tested for TB. If infected, they are killed. Pasteurisation of milk kills the TB bacteria so pasteurised milk will not be able to spread the disease. GLOBAL IMPORTANCE OF TUBERCULOSIS Widespread throughout developing countries as well as among homeless and poor areas in developed countries. Especially common amongst immigrants from developing countries. IREVE SUI 10 CORE I Infectious Diseases HUMAN IMMUNODEFFICIENCY VIRUS and ACQUIRED IMMUNE DEFICIENCY SYNDROME CAUSES AND EFFECTS Caused by human immunodeficiency virus. Virus targets and attacks helper T lymphocytes, macrophages and brain cells. Virus has an outer lipid envelope with glycoprotein spikes (gp 41 and gp120) and a protein core (refer to Page 171, Figure 13.5 to familiarize yourself with what HIV looks like). HIV is a retrovirus. This means it uses RNA to produce a single strand of DNA, called copy DNA (cDNA) inside the host cell, using resources of the host cell. The enzyme that catalyses formation of cDNA is reverse transcriptase. HIV can remain latent for 7-8 years (incubation period). When activated, it will start to replicate and cause damage to the target host cells listed above. Initially after infection, patients start to develop flu-like illness, swollen lymph glands and high body temperature. Damage to the target host cells, especially the T helper lymphocytes, reduces their number and causes the host immune system to weaken. The body will be unable to defend itself. AIDS develop when the weakened immune system allows opportunistic infections to attack the body. Cancers may also appear. Effects of HIV infection: flu-like symptoms and then symptomless. Effects of AIDS: opportunistic infections (TB, pneumonia, cancers), weight loss, diarrhoea, fever, sweating, dementia. TRANSMISSION Virus is spread through direct, intimate human contact. There is no vector and the virus cannot survive outside the human body. Transmission is possible via direct exchange of body fluids. Exchange of body fluids occur: o During sexual intercourse IREVE SUI 11 CORE I Infectious Diseases o When sharing of infected needles among drug (ab)users o At blood donations o Through placenta from HIV-positive mother to foetus DIAGNOSIS AND TREATMENT Diagnosis is via blood tests to check for presence of HIV antibodies. There is no cure for AIDS and no vaccine for HIV yet (waiting for you as the next generation of scientists to discover these cures and vaccines!) As HIV is able to change its surface proteins, it is difficult for the host immune system to recognize and destroy it. This is also one of the reasons that it is hard to develop an effective vaccine targeting HIV. Drug treatment can delay onset of full-blown AIDS. In many developed countries, where people can afford and have access to drug treatment, it has extended their life expectancies greatly. The drugs are similar to DNA nucleotides. The best-known drug so far is zidovudine (AZT). AZT stops HIV replication by binging with the reverse transcription enzyme and blocking its action. Hence, no cDNA is made from RNA. The drugs have to be taken in a complicated regime. Failing to follow it can lead to development of drug-resistant HIV strains. These drugs have some unpleasant side effects. They are headaches, rashes and perhaps permanent nerve damage. PREVENTION AND CONTROL As the cost of effective drug treatment is great, they are usually outside the economic abilities of HIV-positive patients in developing nations. In these areas, it is most important to prevent HIV/AIDS then cure. People must be prepared to have lifestyles that help control the AIDS epidemic. Some prevention methods include: o Not engaging in sexual intercourse. IREVE SUI 12 CORE I Infectious Diseases o Staying with one faithful sexual partner who you know very well. Avoid prostitutes. o Avoid sexual intercourse with persons at risk of HIV infections. o Avoid trauma/wounds to the genitalia and rectum. Small breaks in the skin and mucous membrane allow HIV to infect. o Not engaging in sexual intercourse when sores from herpes simplex or other causes are present. They represent sites for HIV infection. o Not engaging in anal intercourse. It carries a high risk of HIV infection (initial epidemic in North America and Europe was amongst male homosexuals who practised anal intercourse and had many sexual partners). o Using latex condoms (male) or femidoms (female) from beginning to end of sexual intercourse. However, condoms may not be fully effective at preventing HIV infection because they can split when in use or may not be put on correctly. o Do not get pregnant if you are a HIV-positive woman. If unsure of HIV status, get blood tested. o Avoid needles, razors and toothbrushes that could be contaminated with someone else’s blood. (You shouldn’t be sharing these personal belongings anyway!) Contact tracing: This is an important part of HIV control. If someone has been recently diagnosed with HIV, people who they have had sexual intercourse or shared needles with will be offered a blood test. Needle exchange: Drug (ab)users are urged to give up drugs and stop sharing unsterile needles. In some areas, needle exchange schemes exist. Blood screening: In developed countries, blood is routinely screened for HIV. In developing nations, such procedures are not often followed, and people are advised to donate some of their own blood in advance of an operation. Testing: In developed countries, HIV testing in promoted to high-risk groups (male homosexuals, drug users and prostitutes). If they test positive, they will be given medical and psychological support. In developing nations, HIV- IREVE SUI 13 CORE I Infectious Diseases positive patients tend to discover that they are infected only when they have developed full-blown AIDS. Breast feeding: In developed countries, mothers are advised against breast feeding because of the risk of transmitting the viral particles and infected lymphocytes which may be found in breast milk. GLOBAL IMPORTANCE OF HIV/AIDS Widespread testing of a population to identify HIV-positive people is not expensive, but governments are reluctant to implement this as it may be seen as an invasion of personal freedom. In developed world, HIV testing is encouraged for high risk groups, such as male homosexuals, prostitutes, drug users and their sexual partners. In developing nations of Africa and South-East Asia, HIV/AIDS is not restricted to such easily identifiable groups. There is no widespread testing due to high cost of traveling to reach majority of population who live in remote areas as well as the difficulty in organising a test. IREVE SUI 14 CORE I Infectious Diseases ROLES OF ANTIBIOTICS IN TREATMENT OF INFECTIOUS DISEASES Antibiotics: drugs used to treat or cure infections. Antibiotics may be derived from living organisms or may be synthetic. There is a wide range of antibiotics to treat bacterial and fungal infections but only a few for viral infections. Effective antibiotics show selective toxicity: killing or inhibiting the growth of the pathogen but having little or no effect on the host cells. (Important: Figure 13.10, p177, Main textbook) Antibiotics interfere with: o Bacterial wall synthesis (Core A) o Protein synthesis (transcription and translation) (Core F) o Plasma membrane function (Core D) o Enzyme action (Core C) Different diseases treated with different antibiotics. Broad spectrum antibiotics are effective against a wide range of bacteria. Narrow spectrum antibiotics are only effective against a few bacteria. ANTIBIOTIC RESISTANCE Penicillin: inhibits the enzymes involved in bacterial cell wall formation (synthesizing peptidoglycan cross-links). Bacteria with weak cell walls die due to leakage of the cell contents. o This means penicillin is only active against bacteria while they are growing and synthesizing cell wall. o Many bacteria are penicillin-resistant (meaning penicillin has no effect on them) as they have enzymes that can break down the penicillin antibiotic. The enzymes are called penicillinase. SCREENING ANTIBIOTICS Antibiotics to be used should be chosen carefully. It should be the most effective against the particular strain of bacteria or fungus. This choice can be made by screening. IREVE SUI 15 CORE I Infectious Diseases For example, if patient is suffering from food poisoning, an antibiotic sensitivity test can be carried our on the pathogenic strain of the human gut bacterium, Escherichia coli (O157). o Collect bacteria from faeces, food or water. o Grow on agar medium. o A selection of antibiotics are absorbed onto filter paper discs and placed on the agar. o Incubate the agar plate. The antibiotics diffuse out of each filter paper disc, killing the microbe and producing a clear region: inhibition zone. o Diameters of the inhibition zones where no bacteria are growing are measured. o The larger the diameter of the inhibition zone, the more sensitive the bacteria are towards the antibiotic. This antibiotic should be chosen. (Refer to Fig 13.11 and Table 13.5 on p178, Main textbook). It is important to screen antibiotics. Currently, antibiotic resistance is increasing and patients cannot be treated with drugs that were previously effective. This increases mortality rates. Some hospitals carry MRSA (methichillin-resistant Staphylococcus aureus) that is resistant to at least FOUR antibiotics due to their previous inappropriate and widespread use. It is advisable to use some antibiotics as a ‘last resort’ when everything else has failed. This lessens the chances of resistance development. IREVE SUI 16