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the PG Diploma/MSc Epidemiology distance learning course. This material is not licensed either for resale
or further copying.
London School of Hygiene & Tropical Medicine September 2013 v1.0
Objectives:
At the end of this session you should be able to:
This session should take you about 60 to 90 minutes to complete. Please also
check out the Virtual Lecture Theatre series for more information on control of
infectious
diseases:
http://www.lshtm.ac.uk/dl/programme/student/ep/student/vlt.htm
Section 2: Introduction
This session provides a brief overview of the key characteristics relevant to the
epidemiology and control of three infectious diseases of global importance: AIDS,
tuberculosis and malaria. You should read through the three articles that are
provided in the reader for EC09 before starting this session.
You will be able to learn much more about the clinical aspects, epidemiology and
control of each of these infectious diseases if you choose to take any of the
following study units later in the course:
You may prefer to skip this session if you feel that you already have a good basic
knowledge of the epidemiology of these three diseases. The WHO website
(http://www.who.int/topics/en/) also provides detailed information on most
infectious diseases. This includes an update on the current status of infections,
control strategies, diagnostic tools and future developments (e.g. vaccine
developments: http://www.who.int/topics/vaccines/en/).
The first few cases of acquired immune deficiency syndrome (AIDS) were reported
in the USA in 1981. Since then, the human immunodeficiency virus (HIV) epidemic
has spread rapidly throughout the world, infecting almost 60 million adults and
children, and causing more than 20 million deaths.
HIV/AIDS is now the fourth leading cause of death globally, and the leading cause
of death in Africa. Control of the epidemic represents one of the most important
public health challenges of the 21st century.
Incorrect Response:
Women
No, that's not right. The proportion of people living with HIV/AIDS who are women is
calculated as follows:
(16/(14.8+16+2.5)) x 100 = 52%
Interaction: Calculation: The proportion of people living with HIV/AIDS who are
children =
Correct Response: 7.5%:
Children
Well done, the proportion of people living with HIV/AIDS who are children is 7.5%
Incorrect Response:
Children
No, that's not right. The proportion of people living with HIV/AIDS who are children
is calculated as follows:
(2.5/(14.8+16+2.5)) x 100 = 7.5%
The epidemic pattern varies widely across the globe in terms of prevalence and also
the most affected population groups. Epidemics patterns have often been grouped in
3 main categories:
- Low level epidemics: settings in which the HIV prevalence has not
consistently exceeded 5% in any define sub-population (e.g. sex workers,
truck drivers, Intravenous Drug Users (IDU), Men having sex with men
(MSM)).
- Concentrated epidemics: settings in which the HIV prevalence is consistently
over 5% in at least one defined sub-population, but do not exceed 1% in
pregnant women in urban areas.
- Generalised epidemics: Settings in which the HIV prevalence is consistently
higher than 1% in pregnant women.
HIV is transmitted from person to person through the exchange of bodily fluids,
including blood, semen, vaginal secretions and breast milk.
Based on this, and using your own background knowledge of HIV, can you identify
the three main modes of HIV transmission?
The three main modes of transmission are sexual, mother-to-child and parenteral.
Interaction: Tabs: Sexual :
Sexual HIV transmission can occur through:
Heterosexual sex
Among men who have sex with men (MSM).
Prior to labour if the barrier of placental cells protecting the foetus is damaged
During birth, when the membranes protecting the foetus from the virus present
in cervico-vaginal secretions are ruptured
During breast-feeding as HIV can be present in breast milk.
Intravenous drug use, heterosexual transmission and transmission among MSM are
all important in HIV transmission in Latin and North America, and in East Asia.
The relative importance of different modes of transmission may change over time.
Interaction: Button: Example
In the UK, HIV prevalence used to be highest among IDU, but recent data suggest
the main mode of transmission is now heterosexual.
Sexual mixing patterns, including the rate of sexual partner change, are
important determinants of HIV spread
(Lack of) condom use is a key behavioural risk factor in the sexual
transmission of HIV
Cultural norms
Migration and mobility patterns
Gender inequalities
Civil strife
Urbanisation
Risk of being infected (at least once) after twenty episodes =1 (1 0.001)20 =
0.0198 = 2%
Incorrect response:
No, thats not right. The transmission probability of infection following 20 episodes of
sexual intercourse is 1.98%, or approx 2%. It is calculated as follows:
Risk of not being infected after one episode = 1 0.001 = 0.999
Risk of not being infected after twenty episodes = (1- 0.001)20 = 0.9802
Risk of being infected (at least once) after twenty episodes =1 (1 0.001)20 =
0.0198 = 2%
Interaction: Tabs: Question 2
Using the same per contact transmission probability calculate what is the probability
of infection following 200 episodes of sexual intercourse.
Interaction: Pull down: Transmission probability of infection following 200 episodes
of sexual intercourse Output:
1.8%
18%
15%
1.5%
Correct response:
Well done. The transmission probability of infection following 200 episodes of sexual
intercourse is 18.14%, or approx 18%. It is calculated as follows:
Risk of not being infected after one episode = 1 0.001 = 0.999
Risk of not being infected after 200 episodes = (1- 0.001)200 = 0.82
Risk of being infected (at least once) after 200 episodes =1 (1 0.001)200 =
0.1814 = 18%
Incorrect response:
No, thats not right. The transmission probability of infection following 200 episodes
of sexual intercourse is 18.14%, or approx 18%. It is calculated as follows:
Risk of not being infected after one episode = 1 0.001 = 0.999
Risk of not being infected after 200 episodes = (1- 0.001)200 = 0.82
Risk of being infected (at least once) after 200 episodes =1 (1 0.001)200 =
0.1814 = 18%
10
11
12
Male circumcision
The table below contains a selection of data from one of the trials conducted to
assess whether circumcision reduced HIV acquisition. It shows HIV incidence rates
amongst men by circumcision status, and evidence of Herpes simplex virus type 2
(HSV-2). HSV-2 is a common STI.
Rank
Status
1.
2.
3.
4.
5.
6.
HSV2
HSV2
HSV2
HSV2
HSV2
HSV2
seroconvertor*, uncircumcised
seroconvertor*, circumcised
seropositive, uncircumcised
seropositive, circumcised
seronegative, uncircumcised
seronegative, circumcised
HIV
incidence
per 100 person
years
3.13
1.95
1.45
1.37
0.64
0.26
*HSV2 seroconverter means that the individual converted from seronegative to seropositive
for HSV2 during the course of the trial follow-up
Use the data presented in this table to answer the following questions.
Interaction: Tabs: Question 1
Calculate the rate ratio comparing HIV incidence in men who are uncircumcised
compared to men who are circumcised amongst men who are HSV seropositive.
Interaction: Pull down: The rate ratio comparing HIV incidence amongst men who
are uncircumcised compared to men who are circumcised amongst men who are HSV
seropositive is Output:
1.61
0.62
1.06
Correct Response: 1.06:
Well done. The incidence of HIV was 1.06 times higher in uncircumcised, HSV-2
seropositive men compared with circumcised, HSV-2 seropositive men. The rate ratio
is calculated as follows: 1.45/1.37 = 1.06
Incorrect response:
No, thats not right. The incidence of HIV was 1.06 times higher in uncircumcised,
HSV-2 seropositive men compared with circumcised, HSV-2 seropositive men. The
rate ratio is calculated as follows: 1.45/1.37 = 1.06
Interaction: Tabs: Question 2
Calculate the rate ratio comparing HIV incidence in men who are uncircumcised
compared to men who are circumcised amongst men who are HSV seronegative.
Interaction: Pull down: The rate ratio comparing HIV incidence amongst men who
are uncircumcised compared to men who are circumcised amongst men who are HSV
seronegative is Output:
1.06
2.46
0.20
13
Treatment with ART is life-long, and failure to strictly adhere to daily medication
regimens can cause drug-resistant strains of HIV to emerge.
A lack of human and financial resources and health systems infrastructure poses
serious barriers to the delivery of ART in many developing countries.
14
Male circumcision is intimately linked to cultural and religious values and may
be difficult to implement in some settings.
15
There are currently around 34 million people infected with HIV/AIDS globally.
Controlling the spread of the epidemic represents a key public health challenge
for the 21st century.
HIV is a lentivirus, causing chronic infections which progress slowly over a long
period. Survival time post-infection in the absence of antiretroviral therapy is
around 10 years.
There are three main modes of HIV transmission: sexual, mother-to-child and
parenteral.
Risk factors for heterosexual transmission of HIV include behavioural, sociocultural and biological factors.
16
LHS
17
Prevalence:
existing TB
cases per
100,000
population
per year
795
411
182
136
47
Prevalence of
HIV in
incident TB
cases in
adults
60.0
0.2
16.0
5.3
23.0
18
19
Well done. There was a dramatic decrease in tuberculosis mortality in all age groups
with the introduction of anti-tuberculosis drugs.
Incorrect response:
No, thats not right. There was a dramatic decrease in tuberculosis mortality in all
age groups with the introduction of anti-tuberculosis drugs.
The relative contribution of each of these factors varies among different countries.
Click on the tabs below for some examples of countries with different TB burden.
Interaction: Tabs: Example 1: UK
Since the late 1980s, the number of new cases of TB reported each year has
increased gradually in the UK. In 2009, the notification rate was 14.6 per 100,000
population. The number of cases reported increased by 4.9% between 2008 and
2009. The London region accounted for 38% of cases reported in 2009, and had the
highest rate of disease (44.4 per 100,000). The highest rates were observed among
non-UK born population. Those belonging to the Indian, Pakistani and Bangladeshi
ethnic groups accounted for the highest number of cases, while the highest rates
occurred in the Black African ethnic group (273.0 per 100,000).
Interaction: Button: Figure
Tuberculosis case numbers and rates by place of birth (UK born vs. non-UK
born), England, Wales and Northern Ireland, 2000 to 2009
20
21
22
TB disease most commonly affects the lungs: 73% of TB cases are exclusively
pulmonary. Typical symptoms of pulmonary TB are prolonged productive cough for
more than 3 weeks, chest pain and hemoptysis (blood in the sputum). Systemic
symptoms of TB include fever, chills, night sweats, weight loss and fatigue.
TB can affect any other organ in the body. Approximately 19% of all TB cases are
exclusively extrapulmonary. Extrapulmonary TB is more common in young children
and immunosuppressed persons. The specific symptoms of extrapulmonary TB
depend on the site of the disease.
Click on the button below to see the most common sites of extrapulmonary TB.
Interaction: Button: Common sites of extrapulmonary TB
Output:
pleura
central nervous system
lymphatic system
genitourinary system
bones and joints
disseminated disease (miliary TB)
23
HIV infection
Substance abuse (especially drug injection)
Recent infection with M. tuberculosis (within the past 2 years)
Chest radiograph findings suggestive of previous TB (in a person who
received inadequate or no treatment)
Diabetes mellitus
Silicosis
Prolonged corticosteroid therapy or other immunosuppressive therapy
Low body weight (10% or more below the ideal)
HIV infection is the strongest known risk factor for development of TB disease in
persons with LTBI.
24
What is the strongest known risk factor for development of TB disease in persons
with latent TB infection?
Interaction: Pull down: The strongest risk factor for developing TB disease is
Output:
Diabetes mellitus
Low body weight
HIV infection
Substance abuse (injecting drugs)
Correct response:
Well done. HIV is the strongest known risk factor for progression of TB infection to
TB disease. For people infected with HIV the risk of developing TB may be more than
100 times higher than that for people without HIV.
Incorrect response:
No, thats not right. HIV is the strongest known risk factor for progression of TB
infection to TB disease. For people infected with HIV the risk of developing TB may
be more than 100 times higher than that for people without HIV.
two time
Rate per
100
person
years
1.0
1.1
Use the information provided in this table to answer the following questions:
Interaction: Tabs: Question 1
Between the two time periods what appears to have happened with HIV prevalence
in this population? Choose the correct answer.
25
Interaction: Pull down: The HIV prevalence between 1991-1994 and 1995-1997
Output:
Increased
Decreased
No change
Correct Response: Increased:
Well done. An increase in HIV prevalence during the 1990s is suggested by the
greater increase in person years amongst the HIV positives compared to the HIV
negatives between the two time periods.
Incorrect response:
No, thats not right. An increase in HIV prevalence during the 1990s is suggested by
the greater increase in person years amongst the HIV positives compared to the HIV
negatives between the two time periods.
Interaction: Tabs: Question 2
The rate of TB was 2.2 times higher in HIV positive individuals compared with those
without HIV in 1991-1994. Calculate the rate ratio for the 1995-1997 time period
and think about why there might be a difference in the rate ratios between the two
time periods.
Interaction: Pull down: The rate ratio for TB in HIV positive compared with HIV
negative is Output:
5.4
0.2
2.6
Correct response: 5.4
Well done. HIV positive miners had a 5.4 higher rate of TB compared with HIV
negative miners in 1995-1997. The rate ratio is calculated as follows: 5.9/1.1 = 5.4
Incorrect response:
No, thats not right. HIV positive miners had a 5.4 higher rate of TB compared with
HIV negative miners in 1995-1997. The rate ratio is calculated as follows: 5.9/1.1 =
5.4
Interaction: Cloud bubble:
The increase in the rate ratio from 2.2 to 5.4 during the 1990s suggests that most of
the HIV-infected miners in the early 1990s had recently become infected and they
had yet to suffer appreciable immunosuppression.
Interaction: Tabs: Question 3
What would you expect to happen to the rate ratio for tuberculosis if the incidence of
HIV decreases?
Interaction: Pull down: The
Output:
Increase
Decrease
No change
rate ratio
26
Medical history (symptoms consistent with TB, history of close contact with
TB, medical conditions associated with higher risk of developing TB)
Physical examination
Mantoux tuberculin skin test
Chest X-ray
Bacteriologic examination (sputum smear microscopy, culture, drug
sensitivity testing) or Histologic examination
27
28
29
Therefore:
So:
30
31
Given that 21.5% of recruits had been infected with TB at 19.5 years old, the
average annual risk of infection (ARI) during lifetime of the 1936/7 cohort is
calculated as:
= 0.012
= 1.2%
Use the information provide in the table to calculate the average ARI for the 1946/7
cohort (rounded to one decimal place).
Interaction: Calculation: The average ARI for the 1946/7 cohort is = %
Correct Response: 0.3:
Well done! The average ARI for the 1946/7 cohort is calculated as follows:
= 0.003
= 0.3%
Incorrect Response:
No, thats not right. The average ARI is calculated as follows:
Given that 6% of recruits had been infected with TB at 19.5 years old, the average
annual risk of infection (ARI) for the 1946/7 cohort is:
= 0.003
= 0.3%
Interaction: Cloud bubble:
Remember, the prevalence of infection in 19.5 year old recruits represents their
cumulative lifetime exposure, and the estimate infection risk (ARI) is thus a measure
of the average risk over their lifetimes.
32
The preferred regimen for treating TB disease consists of an initial 2-month intensive
phase of treatment with four drugs: isoniazid, rifampin, pyrazinamide, and
ethambutol (or streptomycin), followed by a 4-month continuation phase of isoniazid
and rifampin.
These drugs are called first-line drugs and are used for treating most cases of TB.
The infectiousness of patients (related to the number of bacteria expelled into the
air) usually declines rapidly after adequate therapy is started.
Treatment of TB should continue for at least 6 months. Ensuring adherence to
treatment for the whole period is a major problem in TB control. Patients should be
supported with incentives and enablers to help them complete the full course of
therapy. WHO recommends directly observed therapy short course (DOTS) where a
health care worker (or another trained person) directly observes the intake of each
dose of treatment by the patient.
Incomplete treatment or using inappropriate treatment regimens may lead to
developing of drug resistant strains of M. tuberculosis.
33
HIV-positive persons
Recent close contacts of an infectious TB case
Children and adolescents in contact with TB
Health care workers serving high-risk clients
34
A commonly used treatment for latent TB infection is Isoniazid. In clinical trials, daily
Isoniazid treatment for 12 months reduced the risk of TB disease by more than 90%.
Careful assessment to rule out TB disease is necessary before initiating treatment for
LTBI.
Principles of TB control
The TB control programmes have two main goals:
Read the paper Lienhardt et al (Nature Reviews Microbiology, 2012) for a recent
overview of the global efforts to control tuberculosis
11.17: Summary
Summary
35
36
37
Map shows estimated incidence per 10,000 population for the year 2007 [Hay et
al., 2010]; this map and others available at http://www.map.ox.ac.uk/browseresources/
38
Remember, a simple calculation like this can only provide a rough estimate
of expected malaria cases. In reality, the incidence of clinical malaria will
vary by age-group, with the highest incidence typically occurring among
under 5 year olds. Furthermore, some individuals will experience multiple
episodes of clinical malaria during one year, and others may not
experience malaria.
Plasmodium falciparum causes the most morbidity and mortality, and is most
commonly found in sub-Saharan Africa.
Anopheles
The incubation period for malaria depends on the infecting species. The time
between the infective bite and the appearance of clinical symptoms is around 914 days for P.falciparum, 12-18 days for P.vivax and P.ovale and 18-40 days for
P.malariae. The incubation period may last as long as 8-10 months for some
strains of P.vivax.
39
40
Source: http://www.whyfiles.org
host factors such as genetic resistance, and the degree of immunity attributable
to previous malaria exposure
parasite factors such as the dose of infecting sporozoites, their subsequent
multiplication rate, and drug resistance
geographic factors that influence transmission intensity, seasonality and
infectious bites per year
socio-economic factors which influence access to diagnostics and treatment.
41
Click on the tabs opposite to see some of the reasons for this.
Interaction: Tabs: Children
The vast majority of malaria deaths occur among young children who have not
developed immunity from previous exposure to malaria infection.
Malaria morbidity also poses a particular risk for young children:
Children may also suffer from cerebral malaria a condition with a high fatality
rate. Around 10% of children who survive cerebral malaria will experience
neurological defects which can have serious implications for their education and
future employment prospects.
Fever caused by malaria can reduce appetite and accentuate the risk of
malnutrition.
Epidemic malaria
Epidemic malaria occurs over a relatively short time span, and unlike endemic
malaria, affects all age groups.
The unexpected nature of malaria epidemics can have significant social, political
and economic implications.
Using your own background knowledge, try and think of some of the causes for
recent epidemics of malaria.
Interaction: Button: Cloud image
Hint: Think how climatic, environmental and social factors might contribute to an
increased burden of malaria in a given setting.
Now look at the following slides to see some examples of events that have
contributed to recent malaria epidemics.
43
44
Treatment decisions depend on the species of malaria parasite involved, the age of
the patient, and the severity of disease. Special considerations are needed for
treating pregnant women, as several anti-malarials are contraindicated in pregnancy.
The choice of drug or combination will often also depend on the availability and cost
of the different options. ACTs have previously been rather expensive but have
become more affordable, at least in some countries, due to subsidies or donations to
reduce costs.
Click on the tabs opposite to see the objectives and control agents for each of these
methods.
Interaction: Tabs: Residual house spraying
Indoor residual spraying (IRS), using insecticides such as DDT, malathion or
pyrethroids, aims to reduce survival of adult mosquitoes and population density, and
to divert mosquitoes out of houses.
Interaction: Tabs: ITNs
Bed-nets treated with pyrethroids aim to reduce the survival of adult mosquitoes,
reduce population density and divert mosquitoes from biting humans.
The use of bed-nets is particularly effective because it places the insecticide directly
in the path of the blood-seeking mosquito.
ITNs can have both individual and community-level benefits. The use of an ITN will
protect an individual user from mosquitoes, and if enough people in the locality use
ITNs, then the overall vectorial capacity may also be reduced, resulting in public
health benefits for the community.
Interaction: Tabs: Larval control
The objective of larval control is to reduce the population density of Anopheles
larvae.
Possible methods of larval control include water management, the use of chemical
larvicides and bacterial toxins, and the introduction of larvivorous fish.
45
intermittent preventive treatment in pregnancy (IPTp) using sulfadoxinepyrimethamine given at antenatal contacts
intermittent preventive treatment in infancy (IPTi) using sulfadoxinepyrimethamine given at the time of routine vaccinations in infancy. This
approach is currently recommended in high burden areas of Africa, where
there is no high-level resistance to SP.
seasonal malaria chemoprevention (SMC) involving monthly administration of
SP+amodiaquine to all children under 5 years of age, during the transmission
season. This approach currently recommended only in areas of Africa with
highly seasonal transmission
46
Genetic control methods involve introducing the control agent into the mosquito
population through mating.
The genetic control of mosquitoes is still at the research stage. However, one
potential method involves rearing males which are then sterilized and released to
mate with wild females, causing the female to lay sterile eggs.
Another possible method is to introduce genes into wild mosquito populations that
prevent infection by malaria parasites.
47
1) Chloroquine
2) Sulfadoxine-pyrimethamine
48
3) Artemisinins
Note the lower efficacy in SE Asia, this is now considered a serious threat to malaria
treatment world wide, and efforts are underway to contain resistance.
Source: Worldwide Antimalarial Resistance Network (WWARN), 2013. Visit
http://www.wwarn.org/ for more information
Some insecticides used for indoor residual spraying have adverse effects. For
example, DDT may accumulate in breast-milk, and illegal diversion to
agriculture can lead to unacceptable residues.
49
Malaria affects 40% of the worlds population, and control of the disease is
one of the most important public health priorities of this century.
Current strategies for malaria control include treatment of clinical cases with
anti-malarial drugs and prevention of malaria transmission through vector
control.
50
This is the end of EC09. When you are happy with the material covered here please
move on to session EC10.
51