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Summary minor: global health and infectious diseases
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Summary of the minor 'global health and infectious diseases'. Includes information from lectures, practicals and ZSO's.
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GlobalisationGlobalisation: Multidimensional process by which national and international policymakers
promote domestic deregulation and external liberalisation. In short: countries and population
become more and more interconnected.
- Columbus started it in the 14th century (European exploration).
- Globalisation stops barriers between trading countries (policymakers). It’s good for
economy, but is it good for health?
- Technology makes people connect (trains, cars etc.)
- Some (radical) groups protest against globalisation, like IS, because they want to
keep their identity. Brexit is also an example of protest, because the unemployed in
the UK had to make room for Polish people who came to work in the UK.
A better socio-economic status and hygiene reduces the chance of getting diseases.
Migration to the cities caused problems, because of the poor conditions (pollution of water,
bad sanitation). Nowadays, people live longer, but are more sick.
After WO II the difference in life-expectancy between countries decreased, but since 1980
these differences became bigger due to economic globalisation. The difference in life-
expectancy between developing and developed countries increases up to 40 years. Women
have a lower life-expectancy than men, because they mostly die of breast cancer. More
income suggests a longer life-expectancy.
Global burden of disease
Global burden of disease studies described the burden of diseases, injuries and risk factors
as in input to health decision-making and planning processes. This introduced a new metric:
Disability-adjusted life-years (DALYs) to quantify the burden of diseases, injuries and risk
factors.
- DALY is a summation of premature death (years of life lost) and years lived in sub-
optimal quality of life because of the disease (years lived with disabilities).
0 = death, 1 = perfect health (for each disability a number between 0 - 1 is set).
- Middle income countries have the most burden of disease, because the rich suffer
from non-communicable diseases (NCD) and the poor from infectious diseases.
HIV/AIDS kills 1.3 million people per year, TB 1.5 million and malaria < 0.6 million. Most
people die of TB. 1 in 3 is infected with the tuberculosis bacterium. Tuberculosis and malaria
are becoming more resistant against medical treatment. 6 M children < 5 years old died
because of malaria, malnutrition, pneumonia, diarrhoea or measles.
Child mortality is decreasing in all countries due to vaccination programs. Smallpox, polio,
measles and neonatal tetanus are eradicated due to better hygiene and vaccinations. The
ratio of child mortality between developing and developed countries increased a lot.
The prevalence of type 2 diabetes is rapidly increasing due to environmental changes
(inactivity, obesity) in genetically susceptible individuals. It’s a pandemic.
Every disease has risk factors and each risk factor has an underlying factor.
,Globalisation & health risks
More poverty, unregulated pollution of environment, illicit drug trade, unfavorable working
conditions, child labor, violence etc.
This caused a rise in:
- Globalisation has led to the globalised production & marketing of cigarettes, alcohol
and (fast) food.
- Communicable diseases: Foodborne disease (BSE (gekkekoeienziekte) / vCJD
(variant Creutzveldt-Jacob Disease)) and Non-food borne diseases (west nile / zika
virus).
- Irresponsible use of antibiotics
- Immense rise in NCD and injuries
- International mobility of health professionals
Health systems have 3 goals: Improve health, be responsive to population and ensure fair
financing. Health systems can be compared between countries and can be evaluated over
time.
Infectious diseases
Preventable infectious diseases (by vaccines):
- Childhood diseases: DTP (diphtheria, tetanus, polio), MMR (measles, mumps (bof),
rubella virus), pneumonia, rotavirus.
- Hepatitis A, B, C (E) → pigs to human
- Influenza A, B
- These diseases can occur when people have no access to a vaccine or when higher
educated groups resist to give their children vaccines (because when they don’t see
the disease around, they think it’s not necessary to give their children the vaccine).
Emerging diseases, new/existing infectious agents:
- Zoonoses (animal ↔ human), biggest threat, e.g.:
- SARS (coronavirus)
- Q fever: Bacteria in pregnant goats in NL and was present in their feces +
escaped to the outside world through ventilation systems. The feces were
spread among the country. 60% no symptoms = subclinical cases.
- Ebola: Transmission by bats. One boy got infected → Spreads to
Liberia/Sierra Leone, because they have poor health systems → Travelers
got infected (impact rituals + on the run to another country)→ Artsen zonder
grenzen went there. 28k infected, 11.600 died.
- MERS-CoV: Middle East Respiratory Syndrome - coronavirus → in camels in
Korea → humans, infections in hospitals because of low hygiene.
- Vector-borne, e.g.:
- Zika (flue like disease, pregnant women)
- Dengue
- Yellow fever: It was globally under control → sudden outbreak in Angola
‘cause the vaccination program failed over there → Transmission by tiger
mosquitos (= aedes albopictus) and aedes aegypti.
- Chikungunya (caribbean area).
- Varying strains (shift or drift), e.g.:
, - Influenza: Very unstable virus, 1st transmitted from ducks/birds to pigs to
humans, now also from ducks/birds directly to humans.
- Resistant strains of known agents, e.g. malaria or TB.
3000-5000 people die per year of influenza.
Development of infectious diseases (a few waves): Starts slow → little outbreak → looks
under control → big outbreak→ political commitment and communication to the public is
necessary to get it under control.
Pandemic: An infectious disease spreads over the world.
Index case: First case of a disease.
Surveillance is important to know what diseases are around.
3 Major killers: TB, HIV/AIDS and malaria (childhood disease, is getting better).
17 Neglected tropical diseases:
- Bacteria: Leprosy (nerves), buruli ulcer, trachoma, yaws.
- Viruses: Rabies, dengue, chikungunya, zika.
- Protozoa: Trypanosomiasis, chagas ..
- Helminths (lintwormen) ..
- Neglected tropical diseases mostly occur in poor people in poor countries (unsafe
water, poor sanitation, understandard housing/reservoirs for insects). Most people
carry more of these diseases → no/problematic healthcare. Children are most likely
to be affected.
Special cases: Ebola, yellow fever, child mortality.
China: Multiple drug resistant (MDR) TB. There’s a link between HIV and TB infections.
TB:
- 95% of TB deaths occur in low- & middle-income countries.
- Affects lots of children.
- Kills HIV-infected people.
- Diagnosis/screening and treat people are problems.
- MDR TB is hard to treat → Lots of medication needed.
- Estimated number of people falling ill with TB each year is declining very slowly →
the world is on track to achieve the Millenium Development Goal to reverse the
spread of TB by 2015.
Contact tracing: Who has been in contact with infected people → make a map (how are
people connected).
,Options for infectious disease control
- Control: Reduction of incidence, prevalence, mortality, morbidity of an infectious
disease to a locally acceptable level (e.g. influenza, Q fever).
- Elimination: Reduction to zero of the incidence of an infectious disease in a regional
population or the reduction of the global incidence to a negligible level.
- Eradication: Reduction to zero of the worldwide incidence of an infectious disease
(e.g. smallpox / polio, yaws underway).
International health regulations is a legal framework (maakt wetten) that notifies a
potential wide range of events → Public health emergency: seriousness/unexpected/risk to
spread/ risk of travel or trade restrictions. Verification by WHO. It ensures surveillance and
response capacities.
Pandemic preparedness planning especially for new influenza strains, so people know
what to do when there’s an outbreak.
- Phases?
Principles of control:
- Management & coördination
- Surveillance/outbreakmanagement: what’s it doing, changing, is it in the vaccine?
- Prevention/intervention: hygiene/lab measures
- Disasterplanning: only people with permission can go in, stops flights/traffic
- Communication strategy: media plan, no difficult questions
- Research & development: deal with the problem
Trivalent vaccine: Contains 3 types of viruses (AH1, AH3, B for influenza).
A panel tests swabs for 10 viruses.
TB control:
- Better detection rate (64%)
- Directly observed treatment, short course, so people can’t sell medication to others.
- Resistance problems (eastern Europe): admitted to hospital → lots of pills/side
effects, isolation.
- Treatment success is 50%, 30% good diagnosis.
Ebola control:
- Isolation and supportive treatment if there’s an outbreak and no medication in Ebola
treatment centers.
- Contact tracing team and if required quarantaine.
- Health education (hygiene, alarming system).
- Limited restcapacity: treat ebola patients, but malaria patients die.
- Disasterplan incl communication.
- Training of local health workers.
- Staff changes per 1 or 2 months: difficult for staff (suits, alertness, chance on
contamination/dying).
- Distrust government and western doctors.
- Viral load in community high.
- Media.
- Hell and stigma after cure.
, - Radical quarantaine point for debate.
Fear for countries & world:
threat national security, collapse in infrastructure, shutdown democratic process, civil
disobedience (ongehoorzaamheid), loss of trust in authorities.
Principles of elimination:
- Good understanding of natural history of the disease
- Use of health information (disease epidemiology & reservoir)
- Good intervention to break transmission (vaccine)
- Not at the expense of other programmes
- Planning + goals + coördination
- Political commitment + community engagement + funds + communication strategy
Principles of eradication:
- Case finding: find the case + vaccinate family + people around them.
- Recognition card in house so they know who’s been vaccinated.
- Reward to report suspected cases.
- Thermo stable vaccine, easy to administer + lifelong immunity.
Recommendations:
- Keep people conscious for potential danger in infectious diseases
- Develop emergency protocol
- Test operational aspects
- Centralise strategy + coördination
- Take care for international coördination + understanding
- Proactive media strategy
Diagnosis of infectious diseases
Diagnostics of infectious diseases mostly don’t come into the lab. There are 4 key diagnostic
tests (it depends on the pathogen what kind of test will be used):
1) Microscopy: Low-tech, portable, fast, low level of training required, low costs, careful
handling of chemicals needed (expiration date). Problems:
- Sensitivity is limited: detection limit is high → There have to be a lot of
bacteria in the sample to see the bacteria on the microscope.
- Specificity is limited: Bacteria look alike + little artefacts make it hard to see
what kind of bacterium it is.
- Microscopy works on:
1) Malaria: 2 drops of blood + stain needed
2) Pneumonia: gram stain (training required + chemicals/heat needed)
3) Bacterial meningitis: ‘’
4) TB: Auramine (fluorescence stain) or Ziehl-Neelsen stain. Auramine is
more sensitive & Ziehl-Neelsen more specific. For auramine stain you
need a special microscope and lamp → expensive.
5) Cryptococcal meningitis (yeast, related to HIV): Indian ink stain goes
through cerebrospinal fluid → capsule prevents most of the ink to go
inside the yeast → inside color seems gray and capsule is white.
Portable, low sensitivity/high specificity.
,2) Culture: Mostly used in bacteriology. There are more additional tests required to
determine what pathogen is it, besides agar plates → Difficult to set this up in
developing countries, because trained personnel is needed + risks on contamination
for the staff, tests/required stuff arrive too late, takes a lot of time (patients can
die/disappear in the meantime), difficult and expensive, high sensitivity/specificity. It
also requires proper infrastructure, because not all small health centers have the
capacity to culture.
- Susceptibility testing: Test to determine if the bacterium is resistant
to different kinds of antibiotics. Extra costs & complexity → Requires
additional training, specific infrastructure, refrigerator (samples need
to be placed into a cold setting, otherwise the AB will be gone) and
strong standardization (one person has to read the results). 2
Strategies:
1) Apply to individual patient: complex.
2) Do surveys to guide empiric treatment: Send urine
samples of a series of patients from the hospital to the
lab once per year. Lab does all the
culturing/susceptibility tests and then you can do some
statistics: how many patients have AB-resistance
bacteria/how often does it occur? When a lot of
bacteria are resistant, you can change the standard
treatment to another antibiotic where the bacterium is
still susceptible to. Patients benefit indirectly from this.
3) Serology: Detection of antibodies from the patient or antigens from the pathogen.
Mostly used in virology. IgM is detected in the acute phase and IgG in the
convalescence (herstellende) phase. Detection in the acute phase is more difficult.
Especially in developing countries serology is difficult, because there are a lot of
acute infections → There are little antibodies/antigens formed. Sometimes more tests
are needed, because background noise can look like IgM → To make sure it’s IgM or
not, you can test a patient’s blood sample 2 weeks later, but in the meantime the
patient can be gone and you don’t know if the patient wants to pay for additional
tests. Full interpretation requires multiple samples.
- Serology works for HIV/AIDS, because that is treatable.
- Test formats (ELISA etc.) need constant power, the results takes a
while, trained personnel is needed and you can’t set test formats like
ELISA up in earthquake zones. Nowadays, there is a small strip (like a
pregnancy test) that contains the antigens of the virus → If the
antibodies of the patient stick to the antigens, the patient has the
infection. You can only use this for prolonged infections, because
antibodies are needed.
4) PCR/molecular tools: Multiply stretches of DNA/RNA. You can detect a specific trait
or sequence. It used to be out of reach in developing countries, because it’s sensitive
for contamination, specific training & complicated infrastructure is required and it’s
expensive + complicated process. Nowadays, there is a point of care test that costs
about 70 dollars per test and developing countries pay lower prices. It’s a little plastic
box that contains a little PCR machine. You can put the sample in the box and read
the results from a pc: is it positive, how much is positive, what test is positive? There
is no contamination problem and it takes about 2 hours + portable.
,There are different layers that contain different kinds of hospitals. The inner layer is the
dispensary (apotheek)/clinic and they are closest to the patients. Then there’s the district
hospital, regional hospital, national reference center and the supra-national reference center.
Each layer checks the layer below and the supra-ntl ref center checks all other layers. This
one contains all tests, even PCR etc.
Proper use = proper placement of diagnostic tests.
- Where and when do you need access?
- Endemic or epidemic? Doctors see symptoms of an endemic very often, so they
don’t need a diagnostic test to determine what disease a patient has.
- Incidence? How many at risk, transmission possible?
- Diagnostic challenge?
- (Empirical) treatment? If you can’t treat it, you don’t have to know what (bv) kind of
strain it is.
- Goal of testing?
Concepts of molecular diagnostics
Conventional PCR: Amplify the target gene and visualize the fragment on agarose gels.
You can compare the size with controls to see what kind of disease someone has.
Restriction enzymes cut and analyze fragments. The cut out fragments can be used for
sequencing.
Real-time PCR: Probe + primer → Polymerization pushes probe off the DNA target → Light
signal. High intensity means that there’s a lot of DNA present and when it takes a long time
to get a light signal, it means that there’s a little DNA of the e.g. virus present. This can be
important to know, because it can have an influence on the treatment.
Line probe assays: Amplify the DNA of the target gene. There’s DNA present on the paper
strip → Place the amplified DNA on the strip → The monster DNA only binds to
complementary DNA → Colour reaction. It’s important for identification (mycobacteria),
genotyping (hepatitis c) and drug resistance mutations (TB).
Sanger sequencing: Old-fashioned.
, Almost all of these PCR methods were firstly tested on TB, because it remains one of the
biggest killers among infectious diseases, it’s hard to diagnose and it has a complicated
treatment. Culturing is the best option, but it takes a long time (patient can be gone).
Problems: Contamination in the lab leads to false-positives → Strict separation of clean and
dirty rooms, processing (PCR) separated from culture facility + internal & external quality
control programs needed.
Drug resistance can occur in 3 ways:
- Acquisition (verkrijgen) of foreign DNA/resistance genes through plasmids.
- Acquisition of chromosomal mutations in drug target genes.
- Adaptational response: efflux pumps, cell wall composition, metabolism.
TB becomes resistant by chromosomal mutations (no plasmids). It always mutates in the
same way. E. Coli mutates in several different ways and you can’t determine that by PCR,
because PCR only focuses on 1 thing or 1 resistance gene. PCR focuses on 1 thing in the
whole genome, so you can miss other things. You only get what you are looking for.
GA: Diagnostics of infectious diseases
Why do we have to keep screening?
- So you know what’s going on in the population → Make policies
- Quarantine
- Virus can change/mutate → Vaccine can stop working
Sometimes (e.g. when there’s a high chance on transmission) a fast, imprecise policy is
better than a long-time policy, because then you know that you get some fast results (liever
3 negatieve kinderen op IC extra isoleren dan 3 die t wel hebben naar huis sturen met als
gevolg verspreiding). If you want to know if people in a nursing home all have the same or
different strains (transmission/no transmission), it’s better to wait for a good, precise result,
because the chance to spread the disease is limited in a nursing home (enough time +
policy). The task + ordering party can be decisive (bepalend) for what kind of lab work you
will perform.
Positive predictive value (number of false-positives) decreases when the prevalence is low.
Sensitivity and specificity are independent from the prevalence in the population, because
they are characteristics of the device.
What you want to know from the health system in for example Turkmenistan:
- Do the patients come to the place where you have put the diagnostic device? (where
does the device stands in the infrastructure (far/close to the patients?))
- Can you treat the patients?
- Is the standard worldwide treatment effective if someone has MDR TB? You can
culture to see to what antibiotics the bacterium is resistant to. If you want to insert the
diagnostic device into the society, you have to be sure that people can work with it on
that place where you want to insert it.
TB (and resistance) → isolation + medication. You can come out if you are no longer
infectious. The type of TB doesn’t influence the treatment, because people with MDR TB
also go into isolation and will receive medication (policy doesn’t change). Line probe assays
are valid methods to look at resistance of certain cases of TB. Additional test aren’t required.
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