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state of worlds vaccines and immunization

state of worlds vaccines and immunization

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Published by: apoorvsood on Mar 22, 2011
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Often referred to as one of humankind’s “most devastating diseases”, cholera was for
centuries a permanent feature of life in the slums and poverty-stricken villages of India,
where outbreaks have occurred since the early 1800s. Ships sailing from the Bay of
Bengal during an 1817 epidemic are believed to have brought the disease to Europe in
bilge water contaminated with the causative organism, Vibrio cholerae. From there, the
disease spread eastwards throughout Europe and Asia, and westwards to the Americas.
Since 1817, there have been seven major cholera pandemics in areas of South America,
Africa, Europe, and Asia (60). The seventh pandemic, which is still ongoing, began in
1961 in Indonesia, then spread through Asia and Africa, and fnally reached Latin America
early in 1991 (60).

V. cholerae is transmitted by contaminated water and food and, like typhoid fever, is
associated with poverty, poor hygiene, and inadequate sanitation. The disease typically
begins with an acute attack of diarrhoea and copious vomiting, rapidly followed by
dehydration, and, in the absence of treatment, renal failure and death (1). About 80% of
cholera episodes are of mild-to-moderate severity. Cholera usually responds to prompt
administration of oral rehydration salts to replace lost fuids. In the past, before the advent
of fuid replacement therapy, up to 50% of infected people died from the disease. Today,
the risk of death is less than 3%, on a global average (61).

The number of cholera cases reported to WHO annually has remained relatively constant
since 1995, varying from 100 000 to 300 000 cases per year, with Africa accounting for
more than 94% of the total. In 2006, a total of 236 896 cases were notifed to WHO from
52 countries: 31 out of 46 African countries experienced an outbreak of cholera and
reported a total number of 202 407 cases with 5259 deaths (62). Globally, the actual
number of cholera cases is known to be much higher; the discrepancy is the result of
underreporting due to fear of unjustifed travel and trade-related sanctions, limitations
of surveillance systems, such as inconsistency in the case defnition and a lack of a
standard vocabulary (61), and this perhaps represents 10-20% of all cases (63). The
problem may be less acute following the change, in 2005, in the International Health
Regulations (IHR) that replaces compulsory public notifcation of cholera with a more
discreet outbreak response arrangement between affected countries and WHO. Today,
no country requires proof of cholera vaccination as a condition for entry.

The causative agent of cholera was frst discovered in 1854 by the Italian scientist
Filippo Pasini, and “re-discovered”, seemingly independently, in 1884 by the German
microbiologist Robert Koch. In that year, the frst cholera vaccine was made and
began to be used in Spain. It consisted of the killed whole cholera bacterium and was
administered by injection. Over subsequent years, several injectable whole-cell cholera


State of the world’s vaccines and immunization

vaccines made their appearance and were used in millions of people in several countries,
including India and Russia. Reported effcacy of these early vaccines varied widely.

The year 1959 saw licensure of the frst cholera vaccine to beneft from modern
manufacturing technology, and the frst to be submitted to reliable scientifc scrutiny.
However, several well-designed studies in Asia found that the vaccine possessed only
limited effcacy and caused a signifcant number of side-effects.

The search for a safer, more effective cholera vaccine produced three new-generation
vaccines, of which only one is available for widespread use today. This vaccine, frst
licensed in Argentina in 1997 and code-named WC/rBS, is made from the whole-cell
V. cholerae linked to a genetically engineered (recombinant) fragment (B-subunit) of the
cholera toxin. Field trials in Bangladesh, Mozambique, and Peru found the vaccine to be
effective and safe. It does have shortcomings, though. First, it requires two doses given
one week apart and taken with liquid (a buffer solution to neutralize stomach acid) – two
factors that complicate its use, particularly in epidemics. Second, its protective capability
takes about three weeks to develop after administration of the frst dose. Protection is
highest during the frst six months after vaccination but lasts for up to three years (64).
Third, it is effective only against the 01 V. cholerae strain (serogroup): until recently, this
strain was the most frequent cause of epidemics but in 1992 a second serogroup, 0139,
was identifed as the cause of epidemics in Bangladesh and India, and has since been
implicated in a growing number of outbreaks in Asia.

From a public health standpoint, the WC/rBS vaccine, despite its shortcomings, is the
only new-generation cholera vaccine recommended for use by travellers to cholera-
endemic areas, and the only one to have been used in mass vaccination campaigns.
Over the period 2003–2006, it was successfully deployed in mass campaigns carried out
in Indonesia, Mozambique, and the Sudan. Since 2006, WHO has recommended that in
complex emergencies, the use of cholera vaccine should be considered by governments
in the context of other public health priorities (61, 65).

As of mid-2008, WHO’s cholera control policy (61) calls, in the frst instance, for the
improvement of basic sanitary conditions and hygiene. Guided by its Global Task Force
on Cholera Control, WHO is weighing how best vaccines might be used to supplement
these basic measures, particularly in areas, such as urban slums, or in conditions, such
as epidemics, where these measures are particularly diffcult to apply.

Meanwhile, the vaccine R&D pipeline holds the promise of several new vaccines which,
if they fulfl their promise, would confer long-lasting immunity against all predominant
strains of V. cholerae after oral administration of a single dose, would be affordable by
developing countries, and would not require or overload current cold-chain facilities.


Part 2: Diseases and their vaccines

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