Chapter 10
Infectious disease
Infectious diseases
Infectious disease: a disease caused by an organism/pathogen such as a
protoctist, bacterium, or virus and is transmissible, meaning that it can be
spread between individuals within a population.
Non-infectious disease
Diseases that are not caused by pathogens, but that may instead be inherited, or
related to lifestyle factors or life events.
Examples:
1. Lung cancer
2. Sickle cell disease
3. Depression
4. Coronary heart disease, etc.
Pathogen: an organism that causes disease.
Disease transmission: the transfer of a pathogen from a person infected with that
pathogen to an uninfected person; transmission may occur by direct transmission
(direct contact), indirect transmission (through the air, or water), or by animal vectors,
such as insects.
Disease carrier (carrier): a person infected with a pathogen who shows no symptoms,
but can be the source of infection in other people.
Transmission cycle: the passage of a pathogen from one host to another is continually
repeated as the pathogen infects new hosts.
Disease eradication
The complete breakage of the transmission cycle of a pathogen so that there are no more
cases of the disease caused by the pathogen anywhere in the world.
Two diseases have been eradicated so far.
1. Smallpox and
2. Rinderpest, a severe disease of livestock.
Incidence: Incidence is the rate of new cases or events over a specified period
for the population over a certain period of time, usually a week, month, or year.
Prevalence: The prevalence of a disease is the number of people who have that
disease (new + previous cases) at any one time.
Mortality rate: The number of deaths over a particular length of time (usually
a year) is the mortality rate.
Endemic disease: a disease that is always present in a population. Example:
Tuberculosis (TB).
Epidemic disease: An epidemic occurs when there is a sudden increase in the
number of people with a disease. Example: Cholera.
Pandemic disease: A pandemic occurs when there is an increase in the number
of cases throughout a continent or across the world. Example: COVID-19.
Cholera
Cholera is caused by the bacterium Vibrio cholerae.
It is a water-borne or food-borne disease.
Cholera occurs when people do not have access to proper sanitation (clean
water supply) and/or uncontaminated food.
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Transmission of cholera
Infected people pass out large numbers of bacteria in their feces.
If these contaminate the water supply, or if infected people handle food or
cooking utensils without washing their hands, then bacteria are transmitted to
uninfected people.
Bacteria
How does cholera cause diarrohea?
The site of action of Vibrio cholerae is the small intestine.
To reach their site of action in the small intestine, the bacteria have to pass through the
stomach. If the contents are sufficiently acidic (pH less than 4.5), the bacteria are unlikely to
survive.
However, if the bacteria do reach the small intestine, they multiply and secrete the toxin
choleragen. This toxin disrupts the functions of the epithelium lining the intestine, so
that salts and water leave the blood.
The loss of salts and water causes severe diarrhoea. The loss of fluid can be fatal if not treated
within 24 hours.
Treating cholera
The disease can be treated quite cheaply with a solution of salts and glucose.
If people can drink, they are given oral rehydration therapy.
If not, then the solution is given intravenously to rehydrate the body.
Glucose is effective because it is absorbed into the blood and this is linked to the
uptake of sodium and potassium ions.
It is important to make sure that a patient’s fluid intake equals fluid losses in urine and
feces and to maintain the osmotic balance of the blood and tissue fluids.
Using antibiotics in severe cases.
Preventing cholera
Cholera is best controlled by treating sewage effectively, providing a clean water
supply that has been chlorinated to kill bacteria, and maintaining good hygiene in
food preparation.
There is no fully effective vaccine for cholera.
However, an oral vaccine that gives short-term protection against cholera was
approved for use in the USA in 2016 which is used for people traveling to places where
there is a transmission of V. cholera.
The same vaccine has been used in mass vaccination programs in Africa during
epidemics to prevent the spread of the disease.
Malaria
Malaria is caused by a protoctist, Plasmodium.
Genetic analysis of infections shows that some species of Plasmodium that
cause malaria in monkeys also affect humans.
Most cases of malaria are caused by one of four species of the protoctist
Plasmodium.
1. Plasmodium falciparum
2. P. vivax
3. P. ovale, and
4. P. malariae
The predominant parasite species is Plasmodium falciparum, which is the
species that is most likely to cause severe malaria and death.
Transmission of malaria
The female Anopheles mosquito is the disease vector of malaria and she transmits
the disease when she passes the infective stages into an uninfected person.
Malaria may also be transmitted during blood transfusion and when unsterile
needles are reused.
Plasmodium can also pass across the placenta from mother to fetus.
Life cycle of Plasmodium
Female Anopheles mosquitoes feed on human blood to obtain the protein they need to
develop their eggs.
If the person they bite is infected with Plasmodium, they will take up some of the
pathogen’s gametes.
Male and female gametes fuse in the mosquito’s gut (sexual stage) and develop to
form infective stages (sporozoites), which move to the mosquito’s salivary glands.
When the mosquito feeds again, she injects an anticoagulant from her salivary glands
that prevents the blood meal from clotting, so that it flows out of the host into her
body.
At the same time, the infective stages pass from the mosquito’s salivary glands into the
human’s blood to the liver where they grow and multiply first and then in the red cells
of the blood and multiply again until the cells burst (Asexual stage).
Transmission depends on several factors:
Transmission is more intense in places where the mosquito lifespan is longer
and where it prefers to bite humans rather than other animals.
The long lifespan and strong human-biting habit of the species of Anopheles
(P. falciparum).
Transmission also depends on climatic conditions.
In many places, transmission is seasonal, with the peak occurring during and
just after the rainy season.
Malaria epidemics can occur when climate and other conditions suddenly
favour transmission in areas where people have little or no immunity to malaria.
They can also occur when people with low immunity move into areas with
intense malaria transmission.
Treating malaria
All cases of suspected malaria are confirmed by using a test which is
dipstick test for malaria antigens in blood microscopical
examination of blood. The results of these tests can be available
within 30 minutes or less.
Anti-malarial drugs such as quinine and chloroquine are used to
treat infected people.
Chloroquine is also used as a prophylactic (preventative) drug,
stopping an infection from occurring if a person is bitten by an
infected mosquito.
Chloroquine inhibits protein synthesis and prevents the parasite
from spreading within the body.
Quinine works by killing the parasite or preventing it from growing.
Another prophylactic drug is proguanil which inhibits the sexual reproduction of
Plasmodium inside the biting mosquito.
Prophylactic drugs are taken before, during, and after visiting an area where malaria
is endemic.
Newer drugs such as mefloquine which inhibit protein synthesis are used in some
of these areas. However, mefloquine sometimes causes unpleasant side effects.
Currently, the best available treatment, particularly for malaria caused by P.
falciparum, is artemisinin-based combination therapy (ACT) can quickly kill the
majority of malaria parasites. ACT is derived from the plant Artimisia annua and
is used in combination with another drug, such as mefloquine, to treat infections of
P. falciparum.
Preventing malaria
Reduce the number of mosquitoes by removing sources of water in which they can
breed, or by releasing large numbers of sterile males.
Avoid being bitten by mosquitoes by sleeping under a mosquito net, or by wearing
long-sleeved clothing and insect repellant.
Using mosquito nets treated with long-lasting insecticide.
Use prophylactic drugs to prevent Plasmodium from infecting people.
Insecticides are also sprayed inside houses. This control method is effective for
between three and six months, depending on the insecticides used and the type of
surface on which they are sprayed.
Who is at the most risk?
Young children are the most at risk of dying from malaria.
Pregnant women and young children can be treated with drugs that prevent infections
of Plasmodium.
RTS,S/AS01 (RTS,S) – also known as Mosquirix – is an injectable vaccine that
provides partial protection against malaria in young children.
R21/Matrix-M Vaccine provides partial protection against malaria in young children.
The WHO recommends that pregnant women are treated with a prophylactic drug
each time they visit an antenatal clinic in the latter two-thirds of their pregnancy.
Three factors may lead to improvements in the control of malaria:
1. Use of modern techniques in gene sequencing and drug design.
2. Development of vaccines targeted against different stages of the parasite’s life
cycle
3. A renewed international will to remove the burden of malaria from the poorest
parts of the world, allied to generous donations from wealthy individuals and
foundations.
Why are sickle cell patients less prone to malaria?
Sickle cell patients, or individuals with sickle cell trait (carrying one copy of the sickle cell gene), are less
prone to malaria due to the protective effect of the mutated hemoglobin (HbS) in their red blood cells.
Faster Immune Clearance: Sickled cells are recognized as abnormal by the immune system and are
removed more quickly from circulation by the spleen. This rapid clearance reduces the parasite’s ability
to complete its lifecycle and spread.
Reduced Parasite Survival: Individuals with HbS, red blood cells tend to sickle under low oxygen
conditions. This sickling damages the infected cells, making it harder for the parasite to survive and
replicate.
Altered Biochemical Environment: HbS creates a hostile environment for the parasite by causing
oxidative stress and altering the red blood cell's metabolic environment. These changes inhibit the
parasite's growth and development.
Impaired Invasion and Adhesion: The structural and functional changes in sickled red blood cells make
it harder for the malaria parasite to invade or adhere to the cells, reducing the infection rate.
HIV/AIDS
HIV means Human immunodeficiency virus.
AIDS means acquired immunodeficiency syndrome.
The outer lipid membrane forms the envelope, which also
has two glycoproteins: gp120 (helps to attach with the host)
and gp41 (fusion of the viral envelope with the host cell
membrane).
The protein core contains genetic material (RNA) and two
enzymes: a protease and reverse transcriptase.
Reverse transcriptase uses RNA as a template to produce DNA
once the virus is inside a host cell.
Infection with HIV may lead to AIDS.
HIV is a retrovirus, which means that its genetic material is RNA, not DNA. Once
inside a host cell, the viral RNA is converted ‘back’ to DNA (hence ‘retro’) by
reverse transcriptase to be incorporated into human chromosomes.
The virus infects and destroys cells of the body’s immune system so that their
numbers gradually decrease.
These cells, known as T-helper lymphocytes, control the immune system’s
response to infection.
When the number of these cells is low, the body is unable to defend itself against
infection, so allowing a range of pathogens to cause a variety of opportunistic
infections.
Opportunistic infection: an infection caused by pathogens that take advantage of
a host with a weakened immune system.
AIDS is not a disease; it is a collection of these opportunistic diseases
associated with immunodeficiency caused by HIV infection.
For example, Two of these are caused by fungi: oral thrush caused by Candida
albicans, and a rare form of pneumonia caused by Pneumocystis jiroveci.
Transmission of HIV
Transmission is only possible by direct exchange of body fluids from one person to
another through:
Blood from one person entering that of another, for example by sharing the same
needles, or through blood transfusions
Exchange of fluids from the penis, vagina, or anus.
Across the placenta from mother to fetus, or in breast milk, or more often, through
the mixing of blood during birth.
Life cycle of HIV
The virus enters T-lymphocytes, where its RNA is used to make viral DNA, which is
incorporated into the T-lymphocytes’ chromosomes.
A person who has been infected with HIV makes antibodies against the virus and is
said to be HIV-positive.
Usually, nothing more happens for several years after infection, but eventually,
multiple copies of the virus are made inside the T-lymphocytes, which are destroyed
as the viruses break out and infect more cells.
Eventually, there are so few functioning T-lymphocytes that the person is no longer
able to resist infection by other pathogens and develops one or more opportunistic
diseases such as TB. The person has AIDS.
Treating HIV/AIDS
There is as yet no cure for AIDS and no vaccine for HIV.
However, there has been much success in recent years in treating people with
drugs so that they can live with HIV.
Drug therapy can slow down the onset of AIDS quite dramatically. However, the
drugs are expensive and have a variety of side-effects ranging from mild and
temporary (rashes, headaches, diarrhoea) to severe and permanent (nerve damage,
abnormal fat distribution).
For example, using of combination of two or more drugs which prevent the
replication of the virus inside host cells can prolong life, but they are not a cure.
The drugs are similar to DNA nucleotides (e.g., zidovudine is similar to the
nucleotide that contains the base thymine).
Zidovudine binds to the viral enzyme reverse transcriptase and blocks its
action. This stops the replication of the viral genetic material and leads to an
increase in some of the body’s lymphocytes.
A course of combination therapy (taking several drugs) can be very complicated to
follow. The pattern and timing of medication throughout the day must be strictly
followed. People who are unable to keep to this pattern can become susceptible to
strains of HIV that have developed resistance to the drugs.
Preventing HIV/AIDS
All blood to be used in transfusions should be screened to ensure it does not
contain HIV.
All hypodermic needles should be sterile and used only once, and disposed of
carefully.
A person should avoid sexual activity with anyone whose HIV status they do not
know.
If everyone had only one partner, HIV could not be transmitted. Condoms, if properly
used, can prevent the virus passing from one person to another during intercourse.
If a person is diagnosed with HIV, all their sexual contacts should be traced and
informed that they may have the virus.
The chance of HIV passing from an HIV-positive mother to her fetus is greatly
reduced if the mother is treated with appropriate drugs. These drugs can also
greatly increase the length of time between a person becoming infected with HIV
and developing symptoms of AIDS, and can significantly prolong life.
Widespread testing of a population to find people who are HIV+.
Tuberculosis (TB)
TB is caused by the bacterium Mycobacterium tuberculosis or Mycobacterium bovis.
These are pathogens that live inside human cells, particularly in the lungs which is the
first site of infection, but the bacteria can spread throughout the whole body and
even infect bone tissue.
Some people become infected and develop TB quite quickly, while in others the
bacteria remain inactive for many years without showing any symptoms of the
infection; people with this inactive, or latent, infection do not spread the disease
to others.
However, the bacteria can later become active, and this is most likely to happen
when people are weakened by other diseases, suffer from malnutrition, smoke,
have diabetes, consume large quantities of alcohol, or become infected with HIV.
TB is often the first opportunistic infection to strike HIV+ people. HIV
infection may reactivate dormant infections of M. tuberculosis.
TB symptoms
The symptoms of TB disease are:
disease of lungs
coughing,
chest pain,
coughing up of blood,
feelings of sickness or weakness,
weight loss,
fever, etc.
Transmission of TB
TB is spread when infected people cough or sneeze and the bacteria are carried
in the air in tiny droplets of liquid which are inhaled by uninfected people.
This is more likely to happen in places where many people are living in crowded
conditions.
The form of TB caused by M. bovis also occurs in cattle and is spread to humans
in meat and milk.
The incidence in some areas is as high as in less economically developed countries.
This increase is due in part to the following factors:
some strains of TB bacteria are resistant to drugs
the HIV/AIDS pandemic
poor housing in inner cities and homelessness
the breakdown of TB control programs; partial treatment for TB increases the
chance of drug resistance in Mycobacterium.
Treating TB
Test samples of the sputum (mucus and pus) from their lungs are collected for
analysis. The identification of the TB bacteria can be done very quickly by
microscopy.
If TB is confirmed, then patients should be isolated while they are in the most
infectious stage.
The treatment involves using several drugs to ensure that all the bacteria are
killed.
If not killed, drug-resistant forms remain to continue the infection. The
treatment is a long one (six to nine months, or longer) because it takes a
long time to kill the bacteria, which are slow growing and are not very
sensitive to the drugs used.
Unfortunately, many people do not complete their course of drugs, because
they think that they are cured when they feel better. People who do not
complete their treatment may be harboring drug-resistant bacteria and may
spread these to others if the bacteria become active.
To overcome this problem WHO promotes a scheme which is known as DOTS
(direct observation treatment, short course).
In this process, health workers or responsible family members make sure that
patients take their medicine regularly for six to eight months.
The drugs widely used are isoniazid and rifampicin, often in combination with
others. This drug therapy cures 95% of all patients and is twice as effective as
other strategies.
Preventing TB
Contact tracing and the subsequent testing of contacts for the bacterium are
essential parts of controlling TB.
The only vaccine currently available for TB is the BCG (Bacillus Calmette–Guérin)
vaccine, which is derived from M. bovis and protects up to 70–80% of people who
receive it.
The effectiveness of the vaccine decreases with age unless there is exposure to TB.
Many countries with high numbers of people with TB use the BCG vaccine to protect
children.
But some countries use this vaccine for people who are at high risk of becoming
infected because, for example, they live with an adult who is being treated for the
disease.
There are no vaccines that can be administered to protect adults.
To prevent people catching TB from cattle, cattle are routinely tested for TB,
and any found to be infected are destroyed.
TB bacteria are killed when milk is pasteurized, so controlling this method
effectively is very important.
Antibiotics
Antibiotics are substances derived from a living organism that is capable of killing
or inhibiting the growth of a microorganism.
It does not affect human cells, viruses, or fungi.
It is used to treat only bacterial infections.
How do antibiotics work?
Antibiotics interfere with some aspects of the growth or metabolism of the target
bacterium. These include:
synthesis of bacterial cell walls
activity of proteins in the cell surface membrane
enzyme action
DNA synthesis
protein synthesis
Penicillin
Bacterial cells have walls made of peptidoglycans. These are long molecules
containing peptides (chains of amino acids) and sugars.
Peptidoglycans are held together by cross-links that form between them.
Penicillin is an antibiotic that is used to stop bacterial new cell wall
formation by preventing the synthesis of the cross-links between the
peptidoglycan polymers. This means that penicillin is only active against
bacteria while they are growing.
When a newly formed bacterial cell is growing, it
secretes enzymes called autolysins, which make little
holes in its cell wall. These little holes allow the wall to
stretch so that new peptidoglycan chains can link
together.
Penicillin prevents the peptidoglycan chains from
linking up, but the autolysins keep making new holes. As
a result, the cell wall becomes progressively weaker.
Bacteria live in watery environments and take up water
by osmosis. When they are weakened, the cell walls
cannot withstand the turgor pressure exerted on them
by the cell contents, and the cells burst.
However, Penicillin is not effective against all bacteria due to:
1. Thick cell walls which reduce permeability to penicillin. For example, penicillin is not
effective against M. tuberculosis.
2. Bacteria that has a gene that codes for an enzyme which catalyses the breakdown of
penicillin. For example, Penicillin has a structure that can be broken down by β-
lactamase (penicillinase) enzymes.
Antibiotic resistance
Antibiotic resistance occurs when bacteria develop the ability to survive
exposure to antibiotics designed to kill them or stop their growth.
The population of bacteria in the person may contain several million individuals.
Within that population, there are at least one or two individuals that have an
allele (gene) that makes them resistant to penicillin.
So that, these resistant bacteria are able to survive and reproduce asexually
(binary fission) to form a population which contains the allele that helps in
resistance against penicillin.
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Antibiotic resistance
Genes for antibiotic resistance often occur on plasmids, which are small loops of
double-stranded DNA.
Plasmids are quite frequently transferred from one bacterium to another,
even between different species. This happens during conjugation when donor
bacteria form a tube by pili between two bacteria to allow the movement of DNA.
During conjugation, plasmids are transferred from a donor bacterium to a
recipient. Transfer of part of the DNA from the circular DNA also occurs in the
same way.
Thus resistance to a particular antibiotic can arise in one species of bacterium and
be passed on to another.
Vertical and horizontal gene transmission in bacteria
Vertical: The transfer of genetic material from parent to offspring during
reproduction. Example: during binary fission.
Horizontal: The transfer of genetic material between unrelated bacteria, not
involving parent-offspring inheritance. Example: during conjugation.
Consequences of antibiotic resistance
Antibiotic-resistant infections increase the risk of death, and they
are often associated with long stays in hospital, and sometimes
serious complications.
Bacteria living where there is a widespread use of antibiotics may
have plasmids carrying resistance genes for several different
antibiotics, giving multiple resistance.
For example: Previously, there were several antibiotics which can
used to treat Staphylococcus aureus infection, such as: penicillin,
vancomycin oxacillin, amoxicillin, and methicillin but now S. aureus
shows resistance against them. These resistant bacteria of S.
aureus are known as MRSA which is stand for methicillin-resistant
Staphylococcus aureus.
Causes of antibiotic resistance
S. aureus can constantly adapt to antibiotic treatment because of mutation
which gives them new adaption features.
There are several reasons for antibiotic resistance. Such as:
1. Over-prescribing of antibiotics
2. Patient not taking antibiotics as prescribed.
3. Unnecessary antibiotics uses in agriculture.
4. Poor hygiene and sanitization practices.
How can we reduce the development of antibiotic resistance?
Using antibiotics only when appropriate and necessary; not prescribing them for
viral infections
Reducing the use of antibiotics without a doctor’s prescription.
Avoiding the use of so-called wide-spectrum antibiotics.
Making sure that patients complete their course of medication.
Making sure that patients do not keep unused antibiotics for self-medication in the
future or give them to someone else
Changing the type of antibiotics prescribed for certain diseases so that the same
antibiotic is not always prescribed for the same disease
Avoiding using antibiotics in farming to prevent, rather than cure, infections.