Summary Keuzevak Infectieziekten pre-master Health Sciences blok 7
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Infectieziekten (AP_470905)
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Vrije Universiteit Amsterdam (VU)
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Microbiology
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Vrije Universiteit Amsterdam (VU)
Health Sciences pre-master
Infectieziekten (AP_470905)
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Chapter 8 (153-154 & 161-166): Emerging and Re-Emerging Infectious diseases
Globalization and transmission
Changing patterns in human behavior and a changing ecology contribute to the emergence
of infectious diseases in two ways:
- Increased opportunity for animal-to-human infection because of greater exposure.
- Increased opportunity for the transmission from person-to-person once a person is
infected.
Genetic changes in pathogens can occur through a process known as re-assortment. This is a
type of gene shuffling in which an organism’s genes rearrange themselves and cause changes
in the characteristics of the organism. Re-assortment can also take place between different
pathogens, which can give rise to new, rapidly spreading strains of pathogens.
Some of the most sinister infections are latent ones that have long incubation periods, such
as HIV. By the time these diseases are recognized, the infection is already established in
humans, potentially out of control, and the pathogen has been spread.
If we combine all factors, especially travel, the potential for deadly infections to appear
quickly worldwide is not small. Keep in mind that the immunodeficiency associated with HIV
as well as increasing numbers of compromised hosts can amplify the entire process by
presenting an increasing number of potential targets.
Hurdles to interspecies transfer
Crossing the species barrier is not a simple task. A pathogen must overcome two major
hurdles to replicate successfully in a human host:
- It must adapt in such a way that it can replicate in human cells.
- It must be able to configure itself so that it can be easily transmitted from
person-to-person.
Many pathogens, such as hantavirus and avian influenza, have overcome the first hurdle and
have jumped from animals to humans, but they have not yet been able to overcome the
second. Other pathogens, such as HIV or swine influenza, successfully cleared both.
For a pathogen to clear these two hurdles it must undergo extensive genetic changes.
Viruses are prone to mutation because of the lack of fidelity in replication, making it easier
for them to acquire genetic changes.
Re-emerging infectious diseases
Several diseases we once thought were no longer a threat have bounced back in recent
years. All of them present important challenges to health care. For example, tuberculosis and
influenza.
1. Tuberculosis:
It is estimated that 1/3 of the world’s population is infected with mycobacterium tuberculosis
and about 10% will develop tuberculosis. Even though there has been a slight decrease,
1
,mycobacterium tuberculosis is still a leading killer of young adults worldwide. In people living
with HIV, tuberculosis causes death in 1/4th. More than 95% of tuberculosis deaths occur in
low-income and middle-income countries.
Symptoms of active lung tuberculosis are cough (producing sputum and blood), chest pains,
weakness, weight loss, fever and night sweats but may be mild for many months.
Tuberculosis can infect up to 15 others over the course of a year due to airborne
transmission.
The development of antibiotics in the 1950’s slowed the spread of tuberculosis for some
years, and the death rate had dropped significantly, but by 2000 the incidence had begun to
rise again. Several factors are behind the resurgence of tuberculosis.
Immune status and fitness of the host
People with HIV are particularly vulnerable to tuberculosis and to develop the active form of
tuberculosis rather than the more common latent form. Elderly people are also at risk.
Increased poverty and homelessness helps tuberculosis spread rapidly in crowded shelters
and prisons, where people are weakened by poor nutrition, drug addiction, tobacco use and
alcoholism.
Virulence/fitness of the pathogen
Drug-sensitive tuberculosis is usually treated for 6 months with a combination of four
antimicrobial drugs. Patients who do not complete the required drug treatment can stay
infectious for longer periods and spread the infection to more people. In addition, failure to
follow treatment protocols can result in the evolution of mycobacterium tuberculosis strains
that are resistant to standard treatment. The primary cause of multidrug resistant
tuberculosis (MDR-TB), is inappropriate treatment. MDR-TB is now seen in all countries
surveyed. Almost 60% of MDR-TB cases are reported in India, China and the Russian
Federation.
MDR-TB does not respond to first-line drugs (such as isoniazid or rifampicin), but is still
curable by using second-line drugs. Further drug resistance can develop, first cases of
extensively drug-resistant tuberculosis (XDR-TB) were reported in 2006 in Italy. These do not
respond to second-line drugs either. About 9% of MDR-TB cases are XDR-TB and a global
spread is ongoing. In 2009 clinical isolates resistant to all anti-tuberculosis drugs were found
in Iran. In India in 2011 and 2012, extremely drug-resistant (XXDR-TB) and totally
drug-resistant tuberculosis (TDR-TB) cases were reported.
2. Influenza:
Although seasonal influenza does not usually result in high death rates, it remains a major
public health problem that causes losses in work and school time. The outcome depends on
both the viral and health status of the host. A host’s previous exposure can lead to partial
protection, but in a naïve host it is the virulence of the influenza subtype that determines the
outcome of the infection. The virus has what are called gene constellations, clusters of genes
that determine its virulence and single mutations in these constellations can affect the level
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, of virulence of the strain. Influenza is caused by an RNA virus that is constantly undergoing
mutations that change the characteristics of the virus. When we couple this high mutation
rate with the fact that the virus has a stable animal reservoir (aquatic birds), it becomes
apparent that new epidemics and pandemics are likely to occur and eradication would be
very hard.
The influenza virus contains eight segments of RNA and has two major glycoproteins on its
surface, hemagglutinin and neuraminidase, which are required for successful infection. There
are at least 17 hemagglutinin subtypes and 10 neuraminidase subtypes. Human infection has
been linked to hemagglutinin H1, H2 and H3 and neuraminidases N1 and N2. All other
subtypes are found primarily in birds. As a result of changes in the surface glycoprotein,
there have been epidemics and pandemics in humans, and major epizootics in poultry, pigs,
horses, seals and even camels.
There were three influenza pandemics in the past century. The 1918 pandemic of Spanish
influenza was the most contagious and deadly and had a major global impact affecting
mainly young adults. It was caused by a virus containing H1 and N1 surface glycoproteins,
killing an estimated 30-50 million people in less than a year. The outbreak in 1957, Asian
influenza, was characterized by H2 and N2 glycoproteins. Because these proteins were
different, there was no herd immunity and mainly children were infected. It is estimated that
the Asian influenza caused up to 4 million deaths worldwide. In 1968, Hong Kong influenza
killed an estimated 34.000 people in the USA. The virus contained H3 and N2 glycoproteins.
All age groups were affected this time.
An outbreak of the influenza known as swine flu emerged in Mexico in 2009. Cases were first
seen in Europe and within days had been recorded on five continents. In a couple of months
there had been over 27.000 reported cases worldwide and the WHO declared the outbreak a
pandemic, making it the first influenza pandemic of the 21th century. Person-to-person
transmission was confirmed in Europe.
Swine flu is subtype H1N1, but not a human virus and therefore would not normally infect
humans. Initially humans were exposed to infected pigs, in hosts infected with influenza
viruses from different species these viruses mixed and through re-assortment created a new
virus that could spread from person-to-person. Such a change is known as antigenic shift and
can cause pandemics. In the 2009 pandemic a H1N1 virus with swine, avian and human
genes had emerged. Fortunately, it caused only a moderate illness and mild symptoms.
Influenza vaccines against human influenza viruses usually do not protect from swine
influenza viruses. A vaccine was subsequently developed and included in seasonal flu
vaccines.
Avian influenza
The avian influenza virus has already overcome the first hurdle, but not yet cleared the
second hurdle. Serious infections seen in people are a result of direct or indirect contact with
infected live or dead poultry. The avian virus has subtype H5N1 and uses birds as a reservoir.
The H5N1 virus mutates at an extremely high rate and can acquire genes from other viruses.
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