Q&A: New Vaccine Window Decision
Dhaka, Bangladesh – Nov 16-17, 2011
1. HPV VACCINE
What has the GAVI Board agreed to?
The GAVI Board has opened a funding window for human papillomavirus (HPV) country
proposals provided that:


the Secretariat secures acceptable price commitments from industry for HPV vaccines;
HPV proposals demonstrate the ability of the country to deliver HPV vaccines to the new
target population, including through a successful demonstration project, and a communication
strategy is in place in that country.
The Board also requested that the GAVI Secretariat work with technical partners to develop a
programme to provide support for an HPV demonstration project if the country is not yet ready for
national roll out.
Thus the HPV vaccine joins the pentavalent, yellow fever, meningitis A, rotavirus, pneumococcal, and
other life-saving vaccines that GAVI supports.
Unlike the other GAVI-supported vaccines, the HPV vaccine targets girls between the ages of 10
to 13. And in this respect, it requires new delivery strategies. GAVI will support countries’
implementation strategies, which may include a combination of health centre-based and school-based
delivery.
Because HPV has a different implementation strategy, GAVI will also support countries with pilot
implementation to help with planning and costing.
What are the next steps?
The GAVI Secretariat will




Work with technical partners to guide countries in the development of HPV demonstration
project
Negotiate with the help of partners to secure a sustainable price point from vaccine
manufacturers
Plan a call for applications in 2012, with clear eligibility guidelines including a successful
demonstration project and a clear communication strategy
An Independent Review Committee would review the applications and recommend funding
proposals to the GAVI Board
Is this the first cancer vaccine in GAVI’s portfolio?
GAVI has already had significant success with immunisation against cancer with the hepatitis B
vaccine, projected to cut millions of deaths from liver cancer. But by providing HPV vaccine, GAVI will
have a stronger impact on women’s and reproductive health too.
What is the potential impact?
By 2015, up to nine countries may have rolled out the vaccines to close to two million (girls aged 1013, according to country demand. GAVI estimates that by 2023, it may have supported the
immunisation of 62 million girls in 40 countries.
Why this vaccine? What is the disease burden?
The vaccine against human papillomavirus (HPV) is one of four vaccines that were prioritised in
October 2008 for GAVI support. This prioritisation was based on the potential health impact as well as
the costs and challenges of introducing each vaccine in developing countries.
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HPV continues to take an enormous toll on some of the world’s poorest countries. HPV is the cause
of virtually all cervical cancer, which kills 275,000 women every year. Nearly 90% of those
deaths and three quarters of new cervical cancer cases are in developing countries. 1 Every
year, 500,000 new cases are diagnosed.
These numbers are growing especially in the developing world. If left unchecked, by 2030
cervical cancer will kill an estimated 430,000 women every year. 2 Without intervention, the developing
world will account for 99% of the world’s cervical cancer deaths. 3
What will countries have to do to demonstrate they can deliver HPV vaccines to the target
population?
To be approved, HPV applications will need to demonstrate the ability of the country to deliver
HPV vaccines to the target population, including through a successful demonstration project and
that a communication strategy is in place in that country.
GAVI will not offer support unless country applications comply with a series of criteria that confirm the
ability of the country to delivery HPV vaccines. Countries that do not meet these criteria will be
eligible to participate in a demonstration programme.
When will funding start?
The funding process is contingent on securing an affordable and sustainable price from a
manufacturer. Therefore a specific date has not been established for the initiation of funding. The
next step will be for the GAVI Alliance to engage industry partners in negotiations, and open a call for
applications.
Which countries are likely to receive funding?
Any country may apply and this is solely the country’s decision. However countries will need to
demonstrate capacity to effectively and sustainably deliver the vaccines.
GAVI surveys countries intents quarterly, and the recent survey shows that 9 countries expect to
introduce the vaccine before 2015. Should all qualify for funding, this would help reach close to 2
million girls.
At countries’ request, we do not disclose specific elements of our survey such as the names of
the countries considering introductions, although countries may chose to make this information
public.
Is this not an expensive vaccine? How much does the vaccine cost? How will the Secretariat
ensure vaccine manufacturers offer HPV vaccine at an “acceptable price”? How much will it
cost GAVI, 2011 to 2015? Will it be cost-effective for GAVI to support this vaccine?
Prices are a critical issue for introducing the HPV vaccine sustainably. They have certainly been a
major obstacle to introducing the vaccine so far into developing countries. In western countries, the
vaccine is available at US$120 per dose therefore $360 per course (per girl), which is prohibitive
for developing economies.
That’s why reducing vaccine prices is a core part of GAVI’s mission and GAVI engages in dialogs with
the vaccine industry and uses a variety of supply and procurement strategies. In June 2011, GAVI
received an offer at US$5 per dose or $15 a course, a 67% drop on the next lowest publicly
available price anywhere and a significant mark down from the US and European prices cited above.
1
GAVI messaging on HPV, November 2, 2011
Globocan 2008, http://globocan.iarc.fr/burden.asp?selection_pop=220900&Textp=World&selection_cancer=4152&Text-c=Cervix+uteri&pYear=22&type=1&window=1&submit=%A0Execute%A0
3 Vivien Tsu, Director, PATH HPV vaccines project, Tech Tuesday presentation to GAVI Alliance, 3 May 2011
2
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This $5 a dose ($15 dollars a course) is a welcome offer, but it is not a final price. The price of
the HPV vaccine to developing countries through GAVI is yet to be negotiated.
The WHO group of experts refers to several models indicate that HPV vaccination in low-income and
middle-income countries where quality screening is not widespread may be cost-effective if the cost
per vaccinated girl (including 3 doses of vaccine and programmatic costs) is less than US$10-25.4
Hence GAVI’s plan to seek new price points from industry partners.
Are we taking resources away from other important disease issues?
Individual countries decide on their own whether or not HPV should be prioritised for their population,
based on their own assessment of epidemiologic priorities, cost-effectiveness and other factors. At
this stage, nine countries have expressed interest the HPV vaccine by 2015. We expect 40 countries
to have introduced by 2020.
What is HPV?
Human papillomavirus (HPV) is common, highly transmissible, and the cause of virtually all
cervical cancer cases. HPV infections are transmitted through sexual contact. Using condoms may
not be sufficient to prevent infection.
Most HPV infections cause no symptoms, but persistent genital HPV infection can cause cervical
cancer in women. HPV can also cause other genital cancers in both sexes and benign genital warts.
Most sexually-active individuals become infected at some point in their lives, but cervical cancer
occurs only in a small fraction of those infected and may take decades to develop. Cervical cancer
incidence rates vary from 1-50 per 100,000 females. 5 Most cases of cervical cancer are diagnosed in
women over the age of 40.6
Cervical cancer is one of the most common cancers among women. The toll of HPV is
heaviest in sub-Saharan Africa, Latin America, and South / Southeast Asia. 7
Countries with well-organised screening and treatment programmes can prevent up to 80% of these
cancers. However, effective screening programmes and follow-up of women with abnormal screening
tests have been difficult to implement in low-resource and middle-resource settings. Mortality rates
from cervical cancer are therefore much higher in the developing world. 8
When cervical cancer strikes women in developing countries it has a terrible economic and social
impact. And stigmatisation sometimes accompanies cervical cancer.
In low-resource settings, vaccination is by far the most effective approach to reducing disease
incidence. This is why developing countries are demanding this vaccine. Meanwhile, we encourage
countries to continue screening programmes even after the introductions of new vaccines.
What vaccines are available?
4
Human papillomavirus vaccines, WHO position paper (November 15, 2009),
http://www.who.int/wer/2009/wer8415.pdf
5 Human papillomavirus vaccines, WHO position paper (November 15, 2009),
http://www.who.int/wer/2009/wer8415.pdf
6 Human papillomavirus vaccines, WHO position paper (November 15, 2009),
http://www.who.int/wer/2009/wer8415.pdf
7 PATH, RHO cervical cancer website: http://www.rho.org/about-cervical-cancer.htm
8 Human papillomavirus vaccines, WHO position paper (November 15, 2009),
http://www.who.int/wer/2009/wer8415.pdf
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Two HPV vaccines have received WHO pre-qualification and by May 2011 were licensed in more
than 100 countries9. The vaccines are both highly effective against HPV types 16 and 18, responsible
for about 70% of cervical cancers. Both vaccines are safe and effective.
The vaccines are recommended by WHO for girls aged between 10 and 13, requiring three doses
within six months.
The current available vaccines are produced by Merck and Glaxo Smithkline (GSK). The GSK
vaccine is called Cervarix and it protects against HPV types 16 and 18. It is available to GAVI in 2dose vials.10 Merck’s vaccine is called Gardasil and it protects against HPV types 6, 11, 16, and 18.
HPV types 6 and 11 cause anogenital warts and recurrent respiratory papillomatosis. It is presented
in a 1-dose vial.
Several emerging manufacturers are currently developing HPV vaccines too.
How safe is this vaccine? What are the side effects?
Both vaccines now available on the market are safe. By pre-qualifying the vaccine, WHO gives its
seal of approval to both the safety and efficacy of the vaccine.
The US Centers for Disease Control and Prevention (CDC) 11 says: “Clinical trials and monitoring
data shows that both vaccines are very safe.”
What does WHO say about HPV immunisation?
The WHO position paper (2009) recommends that routine HPV vaccination should be introduced into
national immunisation programmes where (a) prevention of cervical cancer is a public health priority,
(b) the introduction is programmatically feasible, (c) the introduction is economically sustainable, and
where (d) cost-effectiveness aspects have been duly considered. In addition, HPV vaccine
introduction should not undermine or divert funding from effective screening programmes for cervical
cancer.
Immunisation is only effective before a person is infected with the targeted virus. Therefore, it is
optimal to immunise with the HPV vaccine prior to sexual debut.
WHO recommends the vaccine for girls between the ages of 10 and 13. In low income countries, on
grounds of cost-effectiveness, WHO does not recommend routine immunisation for boys with existing
HPV vaccines.
Who is using HPV vaccines already? What experience do we have?
Both existing vaccines have been extensively tested before pre-qualification and approval by WHO.
By the end of 2010, five years since the first HPV vaccine was licensed, some 37 countries had
introduced HPV vaccine (including four in parts of the country only).
The HPV vaccine targets young women to prevent a sexually transmitted infection and cervical
cancer. Therefore, organisations in reproductive health, adolescent health, women’s health, and
cancer all have an interest in, or experience of, this vaccine.
In developing countries, several initiatives to introduce HPV vaccines inform our knowledge-base,
mostly demonstration projects, a one national introduction (Rwanda). With funding from the Bill &
Melinda Gates Foundation, PATH12 ran demonstration projects in India, Peru, Uganda, and Vietnam
9
Vivien Tsu, Director, PATH HPV vaccines project, Tech Tuesday presentation to GAVI Alliance, 3 May 2011.
The GSK vaccine also comes in 1-dose vials, but these are not available to GAVI.
11 CDC website. http://www.cdc.gov/vaccinesafety/Vaccines/HPV/index.html
12 “Human papillomavirus vaccine delivery strategies that achieved high coverage in low – and middle- income
countries”, published in Bulletin of the World Health Organisation, http://www.who.int/bulletin/volumes/89/11/11089862/en/
10
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between 2006 and 2010 to generate knowledge and understanding about the introduction of HPV
vaccines. Demonstration projects operated for 1 or 2 years in each country. Vaccine delivery
strategies were evaluated, including school-based, health-centre-based or vaccination combined with
other health interventions.
These projects confirmed the feasibility and acceptability of each of these strategies to achieve high
rates of coverage.
What about the developing countries themselves? Is GAVI pushing this vaccine onto
developing countries? How does GAVI decide who will get this vaccine? To what extent is
GAVI pushing this vaccine on developing countries? Do LDCs really want this vaccine?
GAVI’s approach is country-led. If a country does not want the vaccine, it will not apply to GAVI for
HPV vaccine support. In addition, GAVI will only accept an application if it passes through several
criteria. These criteria range from an assessment of the acceptability of HPV vaccines by community
and health providers through to documentation that the education ministry signs off on the HPV
vaccine application documentation
Many developing countries are showing strong demand for the HPV vaccine. In our quarterly surveys
of governmental plans, nine countries have expressed intent to introduce the HPV vaccine by 2015.
Up to 40 countries may introduce by 2020.
Civil society groups in these countries and worldwide are also calling for the introduction of the
vaccine. Cervical Cancer Action, the International Union for Cancer Control, and PATH compiled a
dossier of more than 390 letters and articles from political and social leaders around the world, but
especially from Africa, demanding support for improved cervical cancer prevention. The dossier can
be found online at: http://www.rho.org/files/PATH_CCA_UICC_dossier_intro.pdf
Why buy the vaccines instead to inviting manufacturers to donate it?
A few HPV vaccination demonstration projects relied on private sector donations. However this is
neither scalable nor sustainable for national rollout.
GAVI policy does not support vaccine donations. Instead, we seek to deliver sustainable access to
affordable vaccines, guided by its supply and procurement strategy.
How old are the girls that receive this vaccine? How do communities view this vaccine?
WHO recommends the vaccine for girls between the ages of 10 and 13.
GAVI’s work is country-led. GAVI invites countries to follow the WHO recommendations as well as
best practices in the design of programs owned and coordinated by the country whose coordination
mechanisms address issues of appropriate community communication and of parental consent.
However, to be funded, programs must demonstrate a strong communication strategy to address
potential socio-cultural barriers to HPV vaccines. Indeed, sensitivities exist about vaccines against
sexually transmitted infections and vaccines only targeting girls.
What about the men? What if WHO recommends the vaccine for boys?
Vaccinating boys is not considered cost-effective in the developing world. For these reasons, WHO
does not recommend national routine immunisation with the HPV vaccine for boys in low-income
settings.
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2. RUBELLA VACCINE
What is rubella?
Rubella is a vaccine-preventable disease caused by the rubella virus. It is sometimes called German
measles or three-day measles and is spread by drops of fluid from the nose and mouth that are
breathed in by others. Symptoms include fever, swollen lymph nodes and a rash that starts on the
face and neck before moving down the body.
Rubella infection is often harmless for children, but infection during early pregnancy may result in
miscarriage, stillbirths, or, in 90% of cases, infants born with birth defects such as heart disease,
deafness, or blindness. These birth defects are known as Congenital Rubella Syndrome (CRS). The
highest risk of CRS is found in countries with high rates of susceptibility to rubella among women of
childbearing age.13
Why is GAVI addressing rubella?
By vaccinating children between the ages of 9 months and 14 years with rubella containing vaccine,
the spread of rubella virus is markedly reduced. This immediately reduces the risk of rubella virus
exposure and subsequent rubella infection among women of childbearing age thereby preventing
CRS and improving maternal health by reducing miscarriage and stillbirth.
What has the GAVI Board agreed to for the rubella vaccine? What has the GAVI board voted to
do? Why was this decision taken now?
The November 2011 GAVI Board has opened a funding window for rubella vaccines. The GAVI
Secretariat will invite proposals for support from countries in 2012.
By opening a new funding window for the rubella vaccine, GAVI will support countries to use the
rubella vaccine in combination with a measles vaccine, focusing GAVI support on catch-up
campaigns targeting children between the ages of 9 months and 15 years. Implementation of these
campaigns will enable the countries to introduce routine infant immunization against this disease.
Rubella vaccines are inexpensive and in-line with the price of other traditional vaccines. Supporting
catch-up campaigns will allow countries to follow through with routine introduction.
The decision to open a funding window for Rubella Containing Vaccine (RCV) supports the UN
Secretary-General’s Global Strategy on Women and Children’s Health by increasing access to
life‐saving vaccines for women and children in the world’s poorest countries.
By supporting an immunisation programme that supports the replacement of measles antigens with a
combined measles/rubella vaccine, GAVI can contribute to the dual goals of measles and rubella
elimination.
What are the next steps?
In 2012 the GAVI secretariat will invite country proposals for rubella vaccine support.
Six GAVI countries have already introduced rubella.14 Thus, out of GAVI’s 57 eligible countries, 51 are
eligible to apply. GAVI forecasts that all 51 countries will introduce the vaccine by 2018. 15
GAVI would support large-scale catch-up campaigns that have been demonstrated to drastically
reduce rubella and CRS in developing and developed countries.
13
WHO rubella position paper, 2011
Haiti, Tajikistan, Kyrgyzstan, Uzbekistan, Nicaragua and some states in India, Devi Aung
15 Report to the GAVI Alliance Board, November 2011
14
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Countries would pay for routine introduction of the vaccine and would be eligible for an introduction
grant in the first year.
What is the impact of rubella in developing countries? Where is the disease burden heaviest?
CRS is a major public health issue with an estimated 112,000 cases occurring globally of
which 80% are in GAVI-eligible countries. .16
Of these three regions, only the Western Pacific region had significantly increased its coverage with
rubella containing vaccines by 201017. Africa and Southeast have the highest estimated number of
rubella cases and lack goals for rubella control or elimination. 18
In developed and developing countries that have implemented wide scale rubella vaccination during
the past decade, rubella and CRS have been drastically reduced or practically eliminated. 19
Who is affected by rubella?
For children and young adults, rubella is often mild and may go unnoticed initially.
However, when a woman is infected with the rubella virus, particularly in early pregnancy, serious
consequences may include: miscarriages, stillbirths, and infants being born with severe birth defects
leading to life-long disabilities (such as sight, hearing impairments, and heart defects) known as
Congenital Rubella Syndrome (CRS). Of women infected with rubella virus during the first 11 weeks
of gestation, she has up to a 90% chance of passing the virus on to her fetus and deliver an infant
with CRS.
The last large-scale epidemic in the United States during 1964-65 saw an estimated 12.5 million
cases of rubella and 2,000 cases of encephalitis, 11,250 fetal deaths, and 20,000 infants born with
CRS 8,000 cases of deafness, 3,580 deaf-blind children, and 2,100 neonatal deaths.2021
Is the vaccine considered safe and effective? What is the duration of protection it gives?
Rubella vaccine is safe, effective, and gives long-term protection. Adverse reactions following
vaccination are generally mild and transient. Visit http://www.who.int/wer/2011/wer8629.pdf for
details.
What is the market for rubella vaccines? What is GAVI doing to shape the market for rubella
vaccine?
Out of the three suppliers that produce MR vaccine two22 have WHO-prequalified vaccines. One
(Crucell) has decided to cease production but a new MR producer may enter the market and
potentially gain WHO-prequalification around 2016. The other (Serum Institute India) has more than
adequate supply to meet demand but GAVI will take steps to hedge against the risk of price increases
in the absence of competition.23
16
WHO rubella position paper, 2011
Comment from Susan Reef, CDC, via e-mail, 16 Nov 2011
18 Report to the GAVI Alliance Board, November 2011
19 WHO rubella position paper, 2011
20 Plotkin S et al. Rubella vaccine. In: Plotkin S, Orenstein W, Offit P, eds. Vaccines, 5th ed. Philadelphia, cited in
the WHO rubella position paper, 2011
Saunders, 2008: 467-517, cited in WHO rubella position paper, 2011
21 Susan Reef, CDC, by email, 16 November 2011
22 Serum Institute of India and Crucell
23 Report to the GAVI Alliance Board, November 2011
17
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How much does the vaccine cost?
Measles-containing vaccines are considered one of the most cost-effective public health interventions
across a range of development settings. 24 The 2011 MR vaccine price is US$0.50 per dose when
purchased through UNICEF. A potential future price range for MR vaccine could be between $0.300.60 per dose. This would be no more than 25% above the price of a single antigen rubella vaccine. 25
In order to apply for GAVI funding countries must show they can achieve and maintain immunisation
coverage of 80% or greater with rubella-containing vaccines given through routine immunisation or
regular supplementary immunisation strategies.
In the 12-year timeframe from 2012 to 2023 the projected total GAVI cost (vaccine cost, campaign
operational cost and routine introduction cost) for a catch-up campaign targeting 9- to 12-month- olds
and 14-year-olds is US $554 million.
What is measles? What is GAVI doing to address measles?
Measles is highly contagious and one of the leading causes of death among young children. It is
caused by a virus and spread by coughing or sneezing. Severe measles is more likely among
malnourished children or those whose immune systems have been compromised by other diseases.
Adults can contract measles as well.
Measles vaccination policy and delivery strategies vary considerably by country. As of 2008, 132 of
193 WHO member states use a routine two-dose schedule26. Countries with ongoing measles
transmission and measles first dose vaccine delivered at 9 months should administer the routine
measles vaccine second dose at age 15-18 months.27 The remaining 61 countries use mass
vaccination campaigns to provide a second dose of measles vaccine. 28
In 1980, an estimated 2.6 million deaths were caused before measles vaccination was widespread. 29
However, Measles deaths worldwide fell by 78% between 2000 and 2008, from an estimated 750,000
to 164,000 per year, according to the Measles Initiative 30.
GAVI works to address measles in two ways.
First, GAVI has provided direct support to the Measles Initiative, a global partnership dedicated to
reducing measles mortality. Between 2004 and 2007, GAVI contributed US $176 million to the
Measles Initiative to purchase measles vaccine, syringes and other supplies and fund operational
costs.
Second, GAVI provides support for the measles vaccine second dose. Providing a second
opportunity for measles vaccination is a way to reach children who missed the first opportunity and to
produce immunity in the small number of persons who failed to develop measles immunity after the
first dose.
Countries can apply and receive support for measles second dose through the new vaccine support
(NVS) window.31
How is measles related to rubella?
Measles immunisation presents a platform for addressing rubella at the same time with MR (MeaslesRubella) or MMR (Measles-Mumps-Rubella) vaccines.
24
WHO measles position paper, 2009
Report to the GAVI Alliance Board, November 2011
26 WHO measles position paper, 2009
27 WHO measles position paper, 2009
28 Peter Strebel, WHO, via e-mail, 15 November 2011
29 WHO measles fact sheet, 2011
30 GAVI website
31 GAVI website
25
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3. JAPANESE ENCEPHALITIS
What is Japanese encephalitis?32
Endemic in many parts of Asia, Japanese encephalitis (JE) is the main cause of viral encephalitis, an
inflammation of the brain. Symptoms include high fever, headache, sensitivity to light, stiff neck and
back, vomiting, confusion and, in severe cases, seizures, paralysis and coma. Infants and elderly
people are particularly at risk of severe illness.
Overall, the disease is considered under-reported, and annual mortality is estimated to range from 1015,000 deaths. A recent literature review estimates a total number of 68,000 clinical cases of JE
(Bulletin of WHO, October 2011). Of these cases, 30% or more result in permanent neuropsychiatric
sequelae.
The disease is endemic with seasonal distribution in parts of China, the Russian Federation’s southeast, and South and Southeast Asia. All year transmission is observed in tropical climate zones.
Currently, JE is considered hyperendemic in northern India and southern Nepal as well as in parts of
central and southern India, and authorities have responded with immunization campaigns. The spread
of JE in new areas has been correlated with agricultural development and intensive rice cultivation
supported by irrigation programmes.
The infection is mosquito-borne and caused by the JE virus, a flavivirus related to dengue, yellow
fever and West Nile viruses.
What did the Board decide?
The November 2011 GAVI Board noted that:


Japanese Encephalitis (JE) is a critically important vaccine, particularly for Southeast Asia;
GAVI should consider opening a window once an appropriate vaccine is prequalified.
At the same time, continued efforts are needed on surveillance.
Earlier this year, the PPC had noted the crucial importance the vaccine could play in catalyzing
vaccine uptake throughout the region but felt that it would be inappropriate to open a window until a
cost-effective and suitable vaccine received WHO requalification.
How close is a JE vaccine to prequalification?
With support from PATH, an effective JE vaccine has been developed in China and used for many
years in Asia. It is expected to be prequalified by 2013. This vaccine is significantly more costeffective than other vaccines expected to be WHO prequalified in the coming years.
WHO recommends JE immunization in all regions where the disease is a recognized public health
problem. But until recently, the use of vaccine has been limited due to vaccine price, cumbersome
immunization schedules, and lack of recognition of the burden of disease.
32
WHO - http://www.who.int/nuvi/je/en/ and http://www.who.int/topics/encephalitis_viral/en/
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4. TYPHOID
What did the Board decide?
The November 2011 Board confirmed its earlier decision to not open support for a typhoid vaccine
until an appropriate conjugate vaccine has been developed.
The Board also noted that the Alliance looks forward to the development of an appropriate conjugate
vaccine.
What about the existing typhoid vaccine?
A polysaccharide typhoid vaccine does exist. But its duration of protection is not clear. And in any
case, options for treatment do exist.
What is typhoid?33
Typhoid fever is a bacterial disease, caused by Salmonella typhi. It is transmitted through the
ingestion of food or drink contaminated by the faeces or urine of infected people.
Symptoms usually develop 1–3 weeks after exposure, and may be mild or severe. They include high
fever, malaise, headache, constipation or diarrhoea, rose-coloured spots on the chest, and enlarged
spleen and liver. Healthy carrier state may follow acute illness.
Typhoid fever can be treated with antibiotics. However, resistance to common antimicrobials is
widespread. Healthy carriers should be excluded from handling food.
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33
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http://www.who.int/topics/typhoid_fever/en/
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