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Introduction to the epidemiology of

infectious diseases: HIV/AIDS,


tuberculosis, malaria
(EC09)
Module: EPM301 Epidemiology of Communicable Diseases
Course: PG Diploma/ MSc Epidemiology

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assisted learning (CAL) session. The first three columns designate which page,
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module CDROM. When studying this session, please ensure you work through
the CDROM material first. This document can then be used for revision purposes
to refer back to specific sessions.
These study materials have been prepared by the London School of Hygiene & Tropical Medicine as part of
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

Section 1: EC09 Introduction to the epidemiology of infectious


diseases: HIV/AIDS, tuberculosis, malaria
Aim

To introduce key epidemiological concepts in the study of three infectious


diseases of global health importance: HIV/AIDS, tuberculosis and malaria

Objectives:
At the end of this session you should be able to:

recognise the public health burden posed by each disease


identify the causative agent responsible for each disease
identify the main modes of transmission
identify the main risk factors for transmission
identify key challenges for the prevention and control of each disease

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/).

Section 3: The global burden of HIV/AIDS

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.

3.1: The global burden of HIV/AIDS


Each year, global estimates of the current HIV/AIDS burden are reported by
UNAIDS.
The information in the next slide was reported by UNAIDS in 2010:

Use this information to answer the following questions:


What percentage of people living with HIV/AIDS are:
a) women
b) children
Interaction: Calculation: The percentage of people living with HIV/AIDS who are women =
Correct Response: 52%:
Women
Well done, the percentage of people living with HIV/AIDS who are women is 52%

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%

3.2: The global burden of HIV/AIDS


Now try and answer the following question:
2) On average, how many HIV-related deaths among men and children
occurred globally every day during 2009?
Interaction: Calculation: The average daily number of HIV-related deaths among
men and children in 2009 =
Correct Response: 4932:
HIV-related deaths
Well done, the average daily number of HIV-related deaths in 2009 was 4932
Incorrect Response:
HIV-related deaths
No, that's not right. The average daily number of HIV-related deaths in 2009 can be
calculated as follows:

(1,540,000 + 260,000)/365 = 4932


Interaction: Cloud bubble:
Remember, these figures are estimates. They should be considered as
useful indicators of the course of the epidemic, rather than as an exact
account of the HIV burden.

Section 4: The prevalence of HIV


There is enormous variation in the prevalence of HIV infection across the world.
Click on the Figure button opposite to see a world map showing the prevalence of
infection in different countries.
Interaction: Button: Figure
HIV prevalence by country, 2009

source: UNAIDS, 2010

4.1: The prevalence of HIV


Look at the map and try to identify the countries with the highest and lowest HIV
prevalence.
You should be able to see that the proportion of HIV-infected individuals is highest in
southern and eastern Africa. HIV prevalence is less than 0.1% in many countries in
North Africa and the Middle East.

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.

Section 5: The causative agent


The human immunodeficiency viruses belong to the lentivirus subgroup of
retroviruses. These viruses cause chronic infections which progress slowly over a
long period.
The virus infects T4 lymphocytes (glossary) and integrates itself into the DNA of the
cell. When the T4 cell is activated, the virus replicates and infects other T4 cells.
The major receptor for HIV is CD4. CD4 is a cellular protein expressed on some
lymphocytes and is crucial for the immune response.
The destruction of infected T4 cells leads to a deficiency of the immune response and
renders the infected person susceptible to opportunistic infections.

5.1: The causative agent


Two types of HIV have been identified: HIV-1 and HIV-2.
Globally, the majority of HIV infections are due to HIV-1. However, HIV-2 is common
in West Africa and Portugal.
Pathogenesis is similar with both viruses, but disease progression with HIV-2 is
slower. HIV-2 is transmitted less easily than HIV-1.
Once infected, there is no cure for HIV infection. Life-long treatment with
antiretroviral drugs reduces the level of virus in the blood, and can prevent the onset
of opportunistic infections.
In the absence of treatment, the average time from infection with HIV-1 to onset of
AIDS-related symptoms and death are similar in developed and developing countries
at around 10 years.

Section 6: Modes of HIV transmission


Understanding the epidemiology of different modes of HIV transmission is important
for developing effective control strategies.

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).

Interaction: Tabs: Mother-to-child:


Mother-to child (or vertical) transmission of HIV can occur:

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.

Interaction: Tabs: Parenteral


Parenteral HIV transmission can occur as a result of:
Transfusions of infected blood or blood products
Injections with contaminated needles either in the context of medical practices or
through drug use
Occupational exposure in clinical settings, particularly from needle-stick injuries
Exposure through unsafe practices involving skin piercing

6.1: Modes of HIV transmission


The main mode of HIV transmission varies between regions.
Globally, and in sub-Saharan Africa (SSA), heterosexual transmission accounts for
most infections. In other regions, such as Eastern Europe and Central Asia, the main
mode of transmission is through intravenous drug use (IDU). By contrast, most
infections in Australia and New Zealand occur among MSM.
However, note that there is very little information on MSM transmission in SSA; as a
consequence of this, the importance of this mode of transmission is unclear in this
region.
In some regions, there are multiple modes of transmission that account for the
spread of HIV.
Interaction: Button: Example

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.

Section 7: Risk factors for HIV transmission


The risk factors for HIV will depend on the mode of transmission.
In the following slides, we will consider the risk factors for heterosexual transmission
of HIV, as this is the main mode of spread in developing countries, and particularly in
sub-Saharan Africa where the majority of all new infections occur.

7.1: Risk factors for HIV transmission


The main risk factors for heterosexual transmission of HIV can be broadly grouped
into behavioural factors, socio-economic and cultural factors and biological factors.
Differences in the presence of these factors within countries may explain some of the
dramatic variations in HIV prevalence in places where the main mode of transmission
is heterosexual.
Interaction: Tabs: Behavioural :
Behavioural factors influence the risk of HIV transmission.

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

Interaction: Tabs: Socio-cultural and economic :


Sexual behaviour patterns are in turn influenced by a range of social, cultural and
economic factors. These include:

Cultural norms
Migration and mobility patterns
Gender inequalities
Civil strife
Urbanisation

Interaction: Tabs: Biological :


There are also various biological factors that influence the probability of heterosexual
transmission of HIV between an infected and uninfected person:

The presence of STIs enhances HIV transmission

Male circumcision has been shown to protect against transmission


Infectiousness varies over time, peaking soon after infection and during the
later stages of disease progression.
Variation in infectiousness between individuals may be due to genetic factors.
Susceptibility to infection may also be determined by genetic factors

7.2: Transmission Probability


Estimates of the per contact transmission probability for HIV based on follow-up
studies of couples who are initially discordant are about 0.001 per contact. Such
data can be used to calculate the probability of being infected with HIV for any given
number of episodes of sexual intercourse with an infected person using the following
calculations:
n = the number of episodes of sexual intercourse
p = the per contact transmission probability for HIV
Risk of not being infected after one episode = 1 - p
Risk of not being infected after n episodes = (1- p)n
Risk of being infected (at least once) after n episodes =1 (1 - p)n
For example, to calculate the probability of infection following 10 episodes of sexual
intercourse based on a per contact transmission probability of 0.001 per contact, we
would do the following calculation:
Risk of not being infected after one episode = 1 0.001 = 0.999
Risk of not being infected after ten episodes = (1- 0.001)10 = 0.99
Risk of being infected (at least once) after ten episodes =1 (1 0.001)10 = 0.01 =
1%
Use the information provided to undertake the following calculations:
Interaction: Tabs: Question 1
Calculate the theoretical probability of infection for an uninfected person following 20
episodes of sexual intercourse with an infected person using a per contact
transmission probability of 0.001 per contact
Interaction: Pull down: Transmission probability of infection following 20 episodes of
sexual intercourse Output:
20%
0.02%
2%
0.01%
Correct response:
Well done. 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%
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%

Section 8: Prevention and control of HIV infection


Effective HIV control requires that infected persons have access to appropriate
treatment, including antiretroviral therapy. Equally, effective strategies are required
to help prevent HIV transmission.
Treatment

10

Antiretroviral therapy (ART) slows down progression to AIDS in HIV-infected


individuals.
ART was introduced in developed countries in 1996 and its widespread use has
resulted in a dramatic reduction in AIDS-related deaths.
Global initiatives have facilitated the introduction of these drugs in developing
countries, but overall coverage is still low. By the end of 2009, approximately 5
million people in middle- and low-income countries were receiving ART, covering
around 1/3 of those estimated to need treatment (based on updated global
guidelines for initiation of ART up to a CD4 cell count of 350)

8.1: Prevention and control of HIV infection


Prevention
Effective strategies to reduce HIV transmission are an urgent priority for controlling
the spread of the virus.
The appropriateness of different prevention strategies will depend on the main mode
of transmission in a particular setting, and the stage of the epidemic (i.e. whether it
is focused among core groups such as IDU or commercial sex workers, or is
generalised within the population).
Consider the different modes of HIV transmission in turn, and use your own
background knowledge to think about potential prevention interventions for each
one.
Now click on the tabs opposite for some of the key strategies that have been
adopted to prevent HIV transmission.
Interaction: Tabs: Heterosexual transmission:
Heterosexual transmission can be reduced through:

Promoting sexual behaviour change


Treatment of sexually transmitted infections (STIs)
Male circumcision

Interaction: Tabs: Mother-to-child transmission:


The risk of mother-to-child transmission of HIV can be reduced through:

Providing ART to the mother during pregnancy and/or labour.


Providing ART to the mother and baby after delivery.
Promoting breast-feeding policies that reduce the risk of HIV transmission
through breast milk (recommendations vary depending on the setting)
Delivery by caesarean section.

Interaction: Tabs: Parenteral transmission:


The risk of HIV transmission through blood can be reduced by:

11

Screening blood donations


Implementing programmes to promote clean needle exchange
Adopting universal precautions to prevent accidental exposure to HIV in
clinical settings.

Other HIV prevention interventions are under development, including:


Vaccination
HIV vaccines are under active development, and some candidate vaccines are under
trial. However, it is unlikely that a safe and effective product will be available for
several years.
Microbicide gels
The evidence on whether vaginal microbicide gels can be used by women to
prevent HIV acquisition remains inconclusive. There was weak evidence from one
trial, which included women from South Africa, Malawi, Zambia, Zimbabwe and the
USA, that the vaginal microbicide PRO2000 was 30% effective in preventing HIV
infection in women (p=0.10) (Abdool Karim, AIDS 2011). However, a subsequent,
larger study found no protective effect of PRO2000 against HIV infection.
Similarly, whilst an RCT from South Africa found evidence that Tenofovir gel
reduced HIV infection by an estimated 39% overall (Abdool Karim, Science 2010),
a later trial also assessing Tenofovir was stopped due to futility (i.e. stopped
because the likelihood of finding an effect of the microbicide on HIV acquisition was
low) .
Male circumcision
In 2005-2007, three randomised controlled trials were conducted to assess
whether circumcision reduced the risk of HIV acquisition in heterosexual men.
Each trial showed that the rate of HIV was approximately 60% less in men
randomised to the intervention (circumcision arm) than the control arm.
Treatment
Interest in the test and treat or treatment as prevention approach, including
immediate initiation of antiretroviral treatment after diagnosis of HIV infection, as a
potential strategy to reduce transmission, was initially raised following modelling
studies (Granich et al, Lancet 2009). Since the results of trial HPTN 052 showing a
96% reduction in transmission from HIV-infected individuals on ART to their
uninfected sexual partners (Cohen et al, NEJM 2011), excitement about this
strategy has grown. However, while some countries have begun to implement
policies that incorporate this approach, there is still wide debate around the
practicalities involved.
Combination prevention measures
The latest HIV prevention research and approaches are trying to use a combination
of these strategies, alongside other social and educational interventions.

8.2: Prevention and control of HIV infection

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

Correct response: 2.46


Well done. The incidence of HIV was 2.46 times higher in uncircumcised, HSV-2
seronegative men compared with circumcised, HSV-2 seronegative men. The rate
ratio is calculated as follows: 0.64/0.26 = 2.46
Incorrect response:
No, thats not right. The incidence of HIV was 2.46 times higher in uncircumcised,
HSV-2 seronegative men compared with circumcised, HSV-2 seronegative men. The
rate ratio is calculated as follows: 0.64/0.26 = 2.46
Interaction: Cloud bubble:
In this data circumcision appears to be protective (associated with lower HIV risk) in
every group, but to be appreciably more protective among HSV2 seronegative than
among HSV2 seropositive individuals. It is important to note that these are not
randomised comparisons, and that there likely to be are many interactions ie
circumcision may protect against HSV2 infection. The published reports on the study
concluded that circumcision is about 50-60% protective against HIV overall, but
devote considerable discussion to the complexities in these data.
See the following paper for further discussion:
Gray et al. Effects of genital ulcer disease and herpes simplex virus type 2 on the
efficacy of male circumcision for HIV prevention: Analysis from the Rakai trials. PLoS
Med 2009 Nov;6(11):e1000187

Section 9: Issues in HIV control


There are many challenges associated with the implementing HIV treatment and
prevention strategies.
Some of the key challenges are listed on the following slides, and you may be able
to think of some of the many others.
Treatment

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.

ART coverage varies considerably by country.


Click on the button below to show a figure of unmet need for antiretroviral therapy.
Interaction: Button: Figure

14

Source: UNAIDS, 2010


Treatment coverage in low- and middle-income countries
Population adjusted averages for treatment coverage in low and middle income
countries by geographical region in 2009 based on 2010 WHO guidelines: Millennium
Development Goal target 6.B (achieve by 2010, universal access to treatment for
HIV/AIDS for all those who need it). The regional figure for North America is not
shown because of lack of data.
Source: WHO Towards Universal Access 2010.

9.1: Issues in HIV control


Prevention of heterosexual transmission

Evidence from many settings has shown that it is difficult to achieve


substantial and sustained changes towards safer sexual behaviour.

Treatment of sexually transmitted infections (STIs) can be difficult to


implement in the absence of diagnostic tools and a low uptake of health
services.

Male circumcision is intimately linked to cultural and religious values and may
be difficult to implement in some settings.

9.2: Issues in HIV control


Prevention of mother-to-child transmission

Undiagnosed HIV in the mother is a major barrier to uptake of MTCT programmes


in many countries.

15

Access to ART for MTCT programmes is still limited in many settings

Provision and access to ART concomitantly with breastfeeding, or alternatively


avoidance of breast-feeding poses challenges for many women in developing
countries, particularly in light of cultural norms, the costs associated with artificial
feeding and a lack of access to clean water.

9.3: Issues in HIV control


Prevention of parenteral transmission

In many countries, blood transfusion services do not select donors appropriately


or provide inadequate HIV screening.

Political opposition to the introduction of clean needle exchange programmes can


hamper efforts to reduce parenteral transmission caused through injecting drug
use.

Adopting universal precautions to prevent accidental exposure to HIV in clinical


settings requires financial resources and training that are not always available in
some settings.

Section 10: Summary

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 prevalence is around 1% globally. However, the prevalence in adults has


reached over 30% in some countries in sub-Saharan Africa.

Although HIV is referred to as a pandemic, it is not a single and homogenous


epidemic, but includes several epidemic patterns varying across regions of the
globe and affecting different core groups.

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.

HIV control focuses on the provision of antiretroviral treatment for HIV-infected


persons, and strategies to prevent infection amongst HIV-negative persons.

Prevention strategies will depend on the main mode of transmission in a


particular setting. Strategies to prevent heterosexual transmission include

16

interventions to promote sexual behaviour change, the treatment of sexually


transmitted infections, male circumcision and providing ART.

Providing ART is complicated in many settings where health systems


infrastructures are limited. Prevention efforts can be hampered in the absence
of political will and financial resources.

Section 11: The global burden of tuberculosis


TB is a worldwide pandemic and a major cause of death. In 2010, there were an
estimated 8.8 million new TB cases and 1.4 million people died of TB.
The vast majority of the new TB cases occurred in Asia and sub-Saharan Africa. The
five countries with the largest numbers of new cases of TB were India, China, South
Africa, Indonesia and Pakistan.
The highest rates of TB disease per capita were in Africa, accounting for about 26%
of all TB cases.
Virtually all TB deaths are in the developing world, affecting mostly young adults in
their most productive years.
Click on the Figure below to see a map of the estimated number of new TB cases
worldwide in 2010.
Interaction: Button: Figure
Estimated number of new TB cases in 2010
Source: WHO, 2011

LHS

17

The incidence of TB varies greatly across countries. The highest incidence is


observed in the African region, which in 2010 had on average 276 new cases per
100,000 population. In contrast, the American region had an estimated average
incidence rate of 29 new cases per 100,000 per year in 2010.
Examples of the estimated TB rates in selected countries in 2010 are presented in
the Table below.
Table: Estimates TB rates in selected countries
Mortality:
Country
Incidence:
new TB cases deaths due to
TB cases per
per 100,000
100,000
population
population
per year
per year
South Africa
981
50
Bangladesh
225
43
Thailand
137
16
Russian Federation
106
18
Brazil
43
3
Source: WHO, 2011

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

11.1: The global burden of tuberculosis


The figure below presents the tuberculosis mortality rates per 100,000 by age, in
males from Massachusetts, USA in 1880 and 1930 (Source: Am J Hyg 1939: 30; 9195).

18

Use this graph to answer the following questions:


Interaction: Tabs: Question 1
What happened to tuberculosis mortality between 1880 and 1930.
Interaction: Pull down: Between 1880 and 1930 tuberculosis mortality Output:
Increased
Decreased
Stayed the same
Correct response: Decreased:
Well done. There was a decrease in tuberculosis mortality between 1880 and 1930.
The decline in the age-specific rates ranges between 65%-95% in different age
groups. The greatest decrease is among 0-4 year olds, and the smallest decline is
among the 40-49 year olds.
Incorrect response:
No, thats not right. There was a decrease in tuberculosis mortality between 1880
and 1930. The decline in the age-specific rates ranges between 65%-95% in
different age groups. The greatest decrease is among 0-4 year olds, and the
smallest decline is among the 40-49 year olds.
Interaction: Tabs: Question 2
Specific anti-tuberculosis drugs (streptomycin and isoniazid) were introduced around
1950. What effect would this have had on these patterns?
Interaction: Pull down: With the introduction of specific anti-tuberculosis drugs,
tuberculosis mortality would have been expected to Output:
Increase
Decrease
Stay the same
Correct response: Decrease:

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.

11.2: The global burden of tuberculosis


Until 2002, the incidence of TB had been growing for around 20 years, but since
2002 the global incidence rate has been falling 1.3%, on average, per year over the
last 20 years. Factors that contributed to the rise of the TB epidemic include:

The HIV/AIDS epidemic


Emergence of drug-resistant strains of Mycobacterium tuberculosis
Insufficient resources for TB control
Deterioration of the public health systems
Poverty and malnutrition
Substance misuse (injecting drug use)
Immigration from countries with high TB burden
Transmission of TB in congregate settings (correctional facilities, homeless
shelters, health care facilities)

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

Source: HPA, 2010


Interaction: Tabs: Example 2: South Africa
South Africa ranks 3rd among the 22 high-burden countries based on the number of
new TB cases. The country is witnessing one of the worst tuberculosis epidemics in
the world, with disease rates up to 60 times higher than those currently seen in the
USA or Western Europe. The incidence of TB in 2010 is estimated at 981 new cases
per 100,000 per year. The spread of HIV/AIDS is driving the TB epidemic. The
HIV/AIDS prevalence rate amongst adults aged 15-49 is estimated to be 21.5% in
2009. About 60% of adult TB cases are infected with HIV. The emergence of multidrug resistant TB and extensively drug-resistant TB (XDR-TB) is associated with high
mortality and demands an urgent response.

21

Interaction: Tabs: Example 3: Russia


Russia ranks 13th among the 22 high-burden countries based on the number of TB
cases. From 1991 to 2000, the notification rate of new TB cases increased from 34 to
95 per 100 000. The estimated incidence for 2010 is 106 per 100,000. A number of
factors have contributed to the resurgence of TB in Russia in the 1990s, including
general socio-economic crisis and dismantling of the health system, high
unemployment rates, widespread poverty, malnutrition, and substance misuse. In
addition, Russia has one of the highest numbers of prisoners in the world and the
poor conditions in the prisons have been conductive for the spread of TB.
Interaction: Button: Figure
Tuberculosis epidemic in Russia in the 1990s

Source: Health for All database, WHO

11.3: The causative agent and clinical features


Causative agent
TB is an infectious disease caused by a group of bacteria referred to as
Mycobacterium tuberculosis complex. The most common of them is Mycobacterium
tuberculosis, or the tubercle bacillus. There are several other related mycobacterial
species which may cause TB but more rarely (M. bovis, M. africanum, M. microti). M.
bovis causes TB in cattle which can be transmitted to humans through drinking of
raw milk from diseased cows.
Common clinical features

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)

11.4: Transmission of tuberculosis


Transmission
From the epidemiological point of view, pulmonary TB is the most important form,
because it is likely to be infectious and can be spread from person to person through
the air.
Droplet nuclei containing M. tuberculosis are expelled in the air when a person with
pulmonary or laryngeal TB coughs, sneezes, speaks or sings. If another person
inhales air containing these droplet nuclei, transmission of M. tuberculosis occurs.
Close contacts are at the highest risk of becoming infected persons who had
prolonged or frequent contact with a case of infectious TB (family members,
roommates, co-workers).
An estimated 2 billion people, equal to one-third of the worlds total population, are
infected with Mycobacterium tuberculosis, the microbes that cause TB. Without
treatment, about 10% of those infected with TB bacillus will develop TB disease at
some point in their lives, if they have normal immune systems.
People who are infected with TB but do not have active TB disease are said to have
latent TB infection (LTBI).

11.5: Risk factors for tuberculosis progression


Risk factors for progression of infection to TB disease
A number of conditions may increase the risk of progression of LTBI to active TB
disease:

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.

11.6: Transmission of tuberculosis


Use the information provided so far to answer the questions below:
Interaction: Tabs: Question 1
How is TB spread? Choose the correct answer.
Interaction: Pulldown: Spread of TB Output:
Sexual transmission
Through the water
Through the air
Correct response:
Well done. TB is spread from person to person through the air.
Incorrect response:
No, thats not right. TB is spread from person to person through the air.
Interaction: Tabs: Question 2
Generally, what percentage of people who have TB infection and normal immune
systems will develop TB disease in some point in their lives? Choose the correct
answer.
Interaction: Pull down: % of infected with TB who will develop TB disease Output:
3%
10%
30%
90%
Correct response:
Well done. 10% of the people infected with M. tuberculosis will develop TB disease in
their lives.
Incorrect response:
No, thats not right. If their immune systems function normally, 10% of the people
with TB infection will develop TB disease at some point in their lives.
Interaction: Tabs: Question 3

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.

11.7: HIV and TB


The risk of tuberculosis
An estimated 9% of the new TB cases in adults were attributable to HIV in 2003.
This proportion was much higher in Africa where more than 30% of the TB cases
were attributable to HIV infection. In Africa, HIV is the single most important factor
contributing to the increase in incidence of TB since 1990.
Worldwide, about a quarter of a million deaths from TB are attributable to HIV.
The following table contains data from a retrospective cohort study carried out on
the workforce of a South African goldmine (Source: AIDS 2000;14: 2759-2768).
Miners with known HIV status were identified through STD clinic records and their
subsequent development of tuberculosis was determined, over two separate periods,
1991-1994 and 1995-1997. The main results are presented in the following table:
Table: Incidence rates of tuberculosis by initial HIV status, over
periods
Time Period
HIV Positive
HIV negative
TB Cases
Person
Rate per TB Cases
Person
100
Years
Years
person
years
1991-1994
18
800
2.2
29
3000
1995-1997
117
1960
5.9
49
4270

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

for tuberculosis would be expected to

26

Correct response: Increase


Well done. If HIV incidence decreases, the RR for tuberculosis would be expected to
increase, as increasing proportions of those with HIV will have been infected for a
very long time and are therefore more likely to be immunosuppressed and
susceptible to TB.
Incorrect response:
No, thats not right. If HIV incidence decreases, the RR for tuberculosis would be
expected to increase, as increasing proportions of those with HIV will have been
infected for a very long time and are therefore more likely to be immunosuppressed
and susceptible to TB.

11.8: Diagnosis of tuberculosis


Diagnosis
Persons suspected of having TB should be referred to medical examination which
should include the following:

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

Diagnosis: 1) Chest X ray


In pulmonary TB, abnormalities on chest radiograph are often seen in the upper
lobes of the lungs. M. tuberculosis is an obligate aerobe, which explains why it tends
to be found in the well-aerated, upper lobes.
However, lesions may appear anywhere in the lungs and vary in size, shape, and
cavitation. Old healed TB may present on X-ray with nodules and fibrotic lesions with
calcification. In HIV-positive persons, any abnormality on chest X-ray may indicate
TB disease.
Radiological abnormalities may be suggestive of TB, but X-ray can never confirm the
diagnosis of TB.
Interaction: Button: Figure
Cavitary pulmonary tuberculosis, right lower lobe

27

11.9: Diagnosis of tuberculosis


Diagnosis: 2) Sputum smear microscopy
Persons suspected of having pulmonary TB should have at least three sputum
specimens examined microbiologically by smear and culture.
Once stained, mycobacteria will retain dyes when treated by acidified organic
compounds. Therefore, they are classified as acidfast bacilli (AFB). The ZiehlNeelsen stain is traditionally used to demonstrate the presence of the bacilli in a
smear. Under the microscope they appear as bright red rods against a contrasting
background.
Detection of AFB in stained smears examined microscopically permits a presumptive
diagnosis of TB. However, this test is not specific because the AFB observed may be
mycobacteria other than M. tuberculosis. Smear microscopy is also not sensitive
enough because a large number of organisms need to be contained in the sputum in
order to be detected. In other words, many patients with pulmonary TB will have
negative AFB smears. The value of smear microscopy is that it is a simple method,
does not require sophisticated laboratory equipment, and the results can be available
on the same day. Furthermore, smear microscopy allows detecting the highly
infectious patients and initiating therapy quickly.
Interaction: Button: Figure
Acid-fast bacilli

28

11.10: Diagnosis of tuberculosis


Diagnosis: 3) Culture
Culture of M. tuberculosis grown on solid or liquid media is a more sensitive and
specific method than microscopy. Positive cultures confirm the diagnosis of TB.
M. tuberculosis grows in Lowenstein-Jensen medium, a solid egg-based medium. It
grows slowly and it takes 4-6 weeks before colonies are visible on the medium.
Results can be available in 4 to 14 days when liquid media systems are used.
Interaction: Button: Figure
Colonies of M. tuberculosis growing on solid media

29

Drug susceptibility testing should be performed on the initial M. tuberculosis isolate.


It is important to identify resistance to any anti-tuberculosis drug as early as
possible, in order to ensure appropriate treatment with drugs to which the strain is
susceptible.
Interaction: Tabs: Question 2
Which of the following confirms the diagnosis of TB?
Click on the box (below) which is the correct answer.
Interaction: Hotspots
Chest X ray
Detection of acid-fast bacilli in smear examination
Positive tuberculin skin test
Positive culture of M. tuberculosis
Correct answer: Positive culture of M. tuberculosisOutput:
Well done. Culture of M.tuberculosis is the only definite finding which confirms the
diagnosis of TB disease.
Incorrect answer: Output:
No, thats not right. Culture of M.tuberculosis is the only definite finding which
confirms the diagnosis of TB disease.

11.11: Calculating the annual risk of infection for tuberculosis


It is possible to estimate incidence rates of TB infections for a given population from
the age pattern of tuberculin positivity using the following calculations:

Therefore:

So:

Annual risk of infection in the Netherlands

30

The tuberculin test is a reasonably good measure of infection with M Tuberculosis in


populations which have not received BCG vaccination or been exposed to other
mycobacteria. The Netherlands has provided some of the worlds best data, because
the country has not used BCG, and for many years all Dutch males were tuberculin
tested when they entered national service at 19 years of age.
Interaction: Button: Figure
Frequency distribution of indurations, in mm, to 1 TU PPD RT23 tuberculin,
in 37,365 Dutch army recruits.

Source: Van Joost and Bleiker, Epidemiology of Tuberculosis, Stafleu, 1966


This figure shows the distributions of tuberculin reactivity in Dutch males tested with
1 Tuberculin unit using the Mantoux method. On the basis of this distribution, 8 mm
was taken as the cut-off for a positive tuberculin, indicating that the individual has
been infected.

11.12: Calculating the annual risk of infection for tuberculosis


As shown in the table below in 1956 21.5% of Dutch national service recruits
(average age 19.5 years) had 8mm or more induration to tuberculin, but this had
fallen to 6% by 1966.
Table: Percentage of Dutch national service recruits who had 8mm or more
induration to Tuberculin in two birth cohorts
% of recruits with Average ARI (%)
Birth Cohort
Year of Survey
8mm induration or during lifetime of
more to 1 TU
cohort
1936/7
1956
21.5
1.2
1946/7
1966
6.0

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.

11.13: Treatment of tuberculosis


Treatment of TB disease
TB disease should always be treated simultaneously with multiple anti-tuberculosis
drugs. A single drug should never be used to treat TB disease, because this leads to
the selection of strains of M. tuberculosis resistant to that drug.

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.

11.14: Treatment of tuberculosis


Multi-drug resistant TB (MDR TB)
Strains resistant to both isoniazid and rifampin are called multi-drug resistant TB
(MDR TB). MDR TB is more difficult to treat and presents a challenge to TB control
globally.
MDR TB can be treated with second line drugs. Most regimens currently used include
an aminoglycoside (e.g. kanamycin, amikacin) or capreomycin, and a
fluoroquinolone, along with other drugs to which the organism is sensitive.
Second line drugs are more costly, more toxic and weaker than first-line drugs.
Second-line treatment must be given for at least 18 months under strict monitoring.
Extensively drug-resistant tuberculosis (XDR TB)
The worldwide emergence of extensively drug-resistant tuberculosis (XDR TB) was
first reported in November 2005. In October 2006, the World Health Organization
convened an Emergency Global Task Force on XDR TB, which specified the case
definition of resistance to at least isoniazid and rifampin among first-line anti-TB
drugs, resistance to any fluoroquinolone, and resistance to at least one second-line
injectable drug (amikacin, capreomycin, or kanamycin).
XDR TB is the result of inappropriate use of second-line anti-TB drugs. It presents a
global threat and a challenge to TB-control activities.
Click on the Figure below to see a map of the worldwide prevalence of MDR TB.
Interaction: Button: Figure
Percentage of MDR Tuberculosis among New Cases of Tuberculosis in 2010

33

Source: WHO, 2011

11.15: Preventing tuberculosis


BCG vaccination
The Bacille Calmette-Gurin (BCG) vaccine is one of the most widely used vaccines in
the world. It is currently given at birth or soon after birth to children in over 100
countries to minimize the potential for serious forms of TB disease. Evidence from
randomized controlled trials and case control studies suggest that BCG provides on
average 80% protection against serious forms of TB in childhood, in particular
disseminated TB and TB meningitis. However, the evidence for protection against
adult pulmonary TB is controversial ranging from 0% to 80%.
Preventive treatment
The Mantoux tuberculin skin test is the preferred method used to identify persons
with latent TB infection (LTBI). Persons with LTBI who are at high risk of developing
TB disease can be offered preventive therapy. Such high-risk groups include for
example:

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.

11.16: Preventing tuberculosis

Principles of TB control
The TB control programmes have two main goals:

Identify and treat all persons with TB disease


Identify contacts to persons with infectious TB and offer therapy to those who
have TB disease and preventive therapy to those with LTBI at risk of
developing TB disease

Key components of a TB programme are:

Overall TB control strategy


Local laws, regulations and policies for TB control
Programme management team responsible for the planning, monitoring,
education and training
Trained health care workers
Functioning laboratory network with mechanisms in place for quality control
System of uninterrupted drug supply and distribution
System for data collection analysis

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

TB is a communicable disease caused by M. tuberculosis complex.


It is a global pandemic with 8.8. million new TB cases and 1.4 million deaths
each year worldwide.
The spread of HIV has been fuelling the TB epidemic over the last 20 years,
particularly in Africa
Identification and appropriate treatment of the TB cases are the most
important principles of TB control
Ensuring adherence to treatment for at least 6 months is difficult and patients
need to be supported to enable them to complete the full course of treatment
Inadequate or incomplete therapy lead to development of drug resistant
forms of TB which are very difficult to treat
The emergence and spread of MDR TB and XDR TB is the greatest challenge
to TB control

35

36

Section 12: The global burden of malaria


Malaria is a parasitic disease that poses a public health problem in more than 90
countries, and affects around 40% of the worlds population.
According to WHO, there were 219 million cases of malaria in 2010 and an estimated
660 000 deaths (WHO World Malaria Report, 2012).
The vast majority of all malaria deaths (about 90%) occur in sub-Saharan Africa,
where the disease is one of the leading causes of under-five mortality.

12.1: The global burden of malaria


Malaria poses a serious obstacle to social and economic development.
The economic cost of the disease is estimated to be between US$3 and US$12
billion dollars per year in Africa alone.
The cost of effective malaria control in the 82 countries with the highest burden
from the disease has been estimated at approximately US$3 billion per year (WHO
2012).

12.2: The global burden of malaria


The highest incidence of clinical malaria occurs in some of the poorest countries in
the world.
Click on the button below to show a map of the global distribution of clinical
malaria.
Interaction: Button: show
Estimated incidence of clinical malaria in 2007

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/

12.3: The global burden of malaria


Exercise: Assume that Ghana has a population of 22 million, and an average
incidence of clinical malaria of 0.45 per person per year. How many cases of clinical
malaria, to the nearest million, would you expect to occur in one year?
Interaction: Calculation: The expected number of cases of clinical malaria cases in
one year =
million
Correct Response: 10:
Well done! The expected number of clinical malaria cases that would occur during
one year is calculated as follows: 22,000,000 * 0.45 = 9,900,000
Incorrect Response:
No, thats not right. The expected number of clinical malaria cases that would occur
during one year is calculated as follows: 22,000,000 * 0.45 = 9,900,000
Interaction: Button: Cloud image

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.

Section 13: The causative agent

Malaria is caused by infection with protozoan parasites, belonging to the genus


Plasmodium.

Malaria parasites are transmitted between hosts by female


mosquitoes, which mainly bite between sunset and sunrise.

Human malaria is caused by infection with one of four species of Plasmodium


protozoa: Plasmodium falciparum, P. vivax, P. ovale (composed of 2
subspecies, P. ovale wallikeri and P. ovale curtisii) and P. malariae.

Plasmodium falciparum causes the most morbidity and mortality, and is most
commonly found in sub-Saharan Africa.

Anopheles

13.1: The causative agent

Malaria is typically characterised by the presence of periodic fevers, anaemia,


headaches, vomiting and other flu-like symptoms.

Some infections with P. falciparum result in serious complications including


cerebral malaria, severe anaemia, renal failure and coma.

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.

In highly endemic areas, repeat infections can result in a degree of immunity


which suppresses most of the clinical symptoms of malaria.

Section 14: Malaria transmission


Modes of transmission

Malaria is most commonly transmitted through the bite of an infected female


Anopheles mosquito.

Malaria can also be transmitted through blood transfusions, and through


contaminated needles and syringes.

Congenital transmission, in which parasites are transmitted from mother to


child before and/or during birth, occurs rarely.

39

14.1: Malaria transmission


The life cycle of the malaria parasite
The life cycle of the malaria parasite is complex and consists of a number of stages
which occur in the human host and mosquito vector.
The following slides provide a brief overview of some of the key stages in this life
cycle.
Infection begins when parasites in the infective or sporozoite stage are injected
into the bloodstream by female Anopheles mosquitoes. Sporozoites circulate in the
blood for around 30 minutes, during which time they travel to the liver.
Having penetrated the liver cells, sporozoites develop and undergo a phase of
asexual reproduction, before entering the bloodstream again in the merozoite
stage. Merozoites attach to and enter red blood cells where further reproduction
takes place.
During this stage, up to 40% of red blood cells become infected, and clinical
manifestations of the disease may occur.

14.2: Malaria transmission


After invading the blood, some merozoites will develop into sexual forms called
gametocytes. It is this form that the malaria parasite that can infect mosquitoes.
The female Anopheles mosquito ingests malaria gametocytes when it takes a blood
meal from an infected person.
The parasite undergoes a further period of development in the mosquito before it
can infect other people. The length of this period, called the sporogonic cycle,
depends on the species of Plasmodium and the ambient temperature.
Click on the button below to see a diagram of the life cycle of a malaria parasite.
Interaction: Button: show

40

Source: http://www.whyfiles.org

Section 15: Risk factors for malaria


Hundreds of millions of infections with P. falciparum occur each year. Most of these
lead to a mild or severe febrile illnesses, while only a relatively small proportion
result in life-threatening complications.
There is a complex interplay of factors that influences the response to malaria
infection. These include:

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.

15.1: Risk factors for malaria


High risk groups
Children, pregnant women and some mobile populations such as migrants and
refugees are considered to be at particularly high risk of malaria.

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:

malaria leads to severe anaemia in infants and young children, particularly in


areas of high transmission

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.

Interaction: Tabs: Pregnant women


In pregnant women with low levels of acquired immunity to malaria, infection is
associated with a high risk of severe malaria, which can result in stillbirths,
spontaneous abortion and maternal mortality.
In areas with moderate or high levels of transmission, pregnant women are
susceptible to asymptomatic malaria, which may not be detected or treated. This can
lead to maternal anaemia and placental parasitaemia, both of which can lead to low
birth weight.
Interaction: Tabs: Mobile populations
Travellers, refugees, displaced persons, and migrants are at particularly high risk of
severe malaria when moving from malaria-free to malaria-endemic areas. In addition
to having lower levels of immunity, mobile populations may have less access to
health care and appropriate malaria treatment options.

15.2: Risk factors for malaria


Epidemic malaria
There are a wide range of epidemiological patterns of malaria in different parts of the
world, with the spatial distribution of malaria being influenced by interactions
between the human host, the mosquito vector and the malaria parasite.
Environmental factors such as climate and geography contribute to these patterns by
producing suitable conditions for these interactions to take place.
A disturbance to the equilibrium between humans, malaria parasites and their
vectors can lead to an increased burden of malaria in a given setting, and to malaria
epidemics in areas where transmission is not always sustained (e.g. the highlands of
East Africa).

15.3: Risk factors for malaria


42

Epidemic malaria

A malaria epidemic is often defined in qualitative terms as an increase in malaria


cases outside the normal range.

Epidemic malaria occurs over a relatively short time span, and unlike endemic
malaria, affects all age groups.

The morbidity and mortality burden during malaria epidemics may be


accentuated by a lack of preparedness within health systems. This may result in
an inability to cope with a higher than usual number of cases, and an insufficient
supply of anti-malarial drugs.

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.

15.4: Risk factors for malaria


Climatic changes can create conditions that are more suitable for malaria
transmission:
Interaction: Button: Example
African malaria outbreaks have occurred following floods associated with El-Nino
rains.
Interaction: Button: Example
Global warming may be one factor resulting in malaria spread into previously
malaria-free mountainous areas of Asia, Africa and South America.
Natural or human-induced changes to the environment can increase opportunities for
malaria transmission:
Interaction: Button: Example
Increased irrigation is one factor believed to have contributed to an epidemic of
malaria in Madagascar in the late 1980s.
Interaction: Button: Example
The construction of small dams has lead to an increase in malaria transmission in
parts of Ethiopia.

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15.5: Risk factors for malaria


Social factors such as war and civil disturbance have led to an increased burden from
malaria in many countries.
Interaction: Button: Example
The collapse of health systems following periods of political change has lead to a
resurgence of malaria in some countries in the former Soviet Union.
Interaction: Button: Example
Malaria epidemics have occurred in several African countries among refugee or
internally-displaced populations who have fled war zones.

Section 16: Malaria control


The control of malaria is a global health priority in areas with a high incidence of the
disease, including many countries in sub-Saharan Africa and south-east Asia.
Current control options include prompt diagnosis and treatment with effective
antimalarial drugs; vector control, including use of long-lasting insecticide treated
nets (LLINs) and indoor residual spraying; preventive chemotherapy for infants,
children living in areas of seasonal transmission and pregnant women..
The implementation of treatment and prevention strategies is often challenging in
the settings where they are most urgently needed.

16.1: Malaria control


Treatment
When malaria is treated promptly with effective anti-malarial drugs, it is rarely fatal.
However, delayed or inadequate treatment can lead to serious complications and
even death.
In the past, anti-malarial drugs included monotherapies (treatment with a single
drug), including chloroquine, quinine, mefloquine, sulfadoxine-pyrimethamine or
amodiaquine. However, the majority of these monotherapies (particularly
chloroquine and sulfadoxine-pyrimethamine) are no longer effective in Africa and
South East Asia. (For more information, including a video of the spread of
chloroquine and SP resistance, visit
http://www.wwarn.org/resistance/malaria/history
More recently, artemisinin combination therapies (ACTs) have been recommended
and adopted as policy in the majority of malaria endemic areas. These drugs
combine an artemisinin component (e.g. artesunate, artemether, dihydroartemisinin) with a longer-lasting partner drug. Common combinations include
artemether-lumefantrine, artesunate-amodiaquine or dihydro-artemisininpiperaquine. These combinations are highly effective, with cure rates over 95%
when used correctly. It is hoped that resistance to these drugs will evolve more
slowly than when the drugs are used separately.

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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.

16.2: Malaria control


Vector control
Many malaria prevention strategies focus on the control of adult and larval
mosquitoes.
The main options that are currently available for malaria vector control include:

Spraying of houses with residual insecticides


Insecticide treated bed-nets
Larval control.

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.

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16.3: Malaria control


Preventive chemotherapy
Drugs have been used to prevent malaria in travellers for many years, but more
recently have been developed for use in populations in endemic areas.
Three approaches are now recommended by the WHO:
-

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

Greenwood provides an open-access review of these approaches (Greenwood,


Malaria Journal, 2010 doi: 10.1186/1475-2875-9-S3-S2). More information on
these approaches is available on the WHO website at
http://www.who.int/malaria/areas/high_risk_groups/en/

16.4: Malaria control


Other interventions for malaria control are under development, including vaccination
and genetic control.
Interaction: Tabs: Vaccination
As for HIV, a safe and effective vaccine would be one of the best approaches for
control of malaria. Ideally, a malaria vaccine would give a strong, long-lasting
immunity that protects against all variants of the parasite species, or better still, give
cross-species immunity.
Malaria vaccines are under active development, and several candidate vaccines have
been tested in field trials. Preliminary results from these studies have suggested
that the leading vaccine candidate, RTS,S, offers moderate protection, but that this
is not as long-lasting as would be considered ideal for use in routine immunization
programs.

Interaction: Tabs: Genetic control

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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.

Section 17: Challenges to malaria control


There are a multitude of challenges associated with implementing strategies for
malaria control.
Some of the key challenges are summarised on the following slides. You may be
able to think of some of the many others.

17.1: Challenges to malaria control


Treatment
Effective treatment of malaria requires rapid diagnosis. Delays by the patient (or
carer) in seeking treatment are a common cause of death. Delays in diagnosis by
a physician can also lead to preventable deaths from malaria.
The cost of anti-malarial drugs represents a barrier to treatment in some settings.
The cost of a course of treatment can vary from $0.1 to over $10.
Multi-drug resistant malaria is now prevalent in many parts of the world, with the
highest rate of drug resistance in Southeast Asia. Inadequate treatment of drug
resistant cases represents an important avoidable cause of death.

17.2: Challenges to malaria control


Click on the button below to see which countries have documented resistance to key
malaria drugs.
Interaction: Button: Figure
Drug resistance and clinical efficacy of antimalarials (1990 to present)

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1) Chloroquine

2) Sulfadoxine-pyrimethamine

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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

17.3: Challenges to malaria control


Vector control
Now consider each of the following methods of vector control: ITNs, larval control
and indoor residual spraying.
What do you think some of the challenges might be in terms of implementing these
strategies in low-income countries?
Click on the tabs opposite to see a summary of current issues in using these
methods for vector control.
Interaction: Tabs: Indoor residual spraying

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.

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Although DDT is one of the cheapest available insecticides, resistance has


evolved in many settings, and alternatives are needed.
Wide-scale use of insectides for malaria control has led to development of
resistance in Anopheles gambiae, An. funestus and An. arabiensis. Pyrethroid
resistance has been reported from 27 countries in sub-Saharan Africa (WHO
World Malaria Report 2011), threatening recent progress made in malaria
control using ITNs and IRS.

Interaction: Tabs: ITNs

Bed-nets need to be regularly retreated in order to ensure that they remain


effective at repelling mosquitoes
Social marketing strategies to encourage rural populations at high risk of
malaria to may not result in high enough coverage to achieve mass effects on
mosquito populations

Interaction: Tabs: Larval control

Larval control will only be effective in protecting a community from malaria if


a very high proportion of local breeding sites can be found and effectively
treated.

Section 18: Summary

Malaria affects 40% of the worlds population, and control of the disease is
one of the most important public health priorities of this century.

Malaria is caused by infection with protozoan parasites, belonging to the


genus Plasmodium.

Malaria parasites are transmitted between hosts by Anopheles mosquitoes,


biting mainly between sunset and sunrise.

Young children, pregnant women and some mobile populations are at


particularly high risk of morbidity and mortality as a result of malaria
infection.

The burden of malaria in any setting may increase as a result of man-made or


natural climatic and environmental changes, and disturbances to the
equilibrium between humans, mosquitoes and the malaria parasite.

Current strategies for malaria control include treatment of clinical cases with
anti-malarial drugs and prevention of malaria transmission through vector
control.

Challenges to effective treatment include delays in seeking treatment, and


lack of access to parasitological diagnosis and treatment with effective and
affordable drugs.

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Challenges to vector control strategies include achieving high coverage with


interventions and the adverse effects caused by some insecticides, and the
spread of resistance to pyrethroids.

This is the end of EC09. When you are happy with the material covered here please
move on to session EC10.

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