Yellow Fever

Yellow Fever (YF) is a mosquito-borne viral disease of humans and other primates, and is currently endemic in over 43 countries in the tropical regions of Africa and The Americas. Infection with the YF virus can be asymptomatic or cause a wide spectrum of disease, from mild symptoms to severe illness with bleeding, jaundice and, ultimately, death. Over 30,000 deaths occur each year and this figure would be much higher without vaccination. Aedes aegypti, is the most important vector. Transmission is complex with different characteristics in different endemic areas.

All currently available yellow fever vaccines are live, attenuated and based on the 17D attenuation variant. Vaccines from four manufacturers are currently prequalified by WHO.

Yellow fever vaccination is carried out for 3 reasons: to protect populations living in areas subject to endemic and epidemic disease; to protect travellers visiting these areas; and to prevent international spread by minimizing the risk of importation of the virus by viraemic travellers.

A single dose of YF vaccine is sufficient to confer sustained life-long protective immunity against YF disease. In view of the ongoing transmission of YF virus, and the proven efficacy and safety of YF vaccination, WHO recommends that all endemic countries should introduce YF vaccine into their routine immunization programmes. Vaccine should be offered to all unvaccinated travellers aged >9 months, travelling to and from at-risk areas, unless they belong to the group of individuals for whom YF vaccination is contraindicated.

Well designed and adequately powered studies are needed to assess co-administration of YF vaccine with other live vaccines, including MMR, and to assess safety and immunogenicity of YF vaccine in pregnant women, in people aged ≥60 years, and in HIV positive adults with CD4 T cell values >200 per mm(3).

Typhoid

Typhoid fever is an infection caused by the Salmonella typhi bacterium, usually through ingestion of contaminated food or water. The acute illness is characterized by prolonged fever, headache, nausea, loss of appetite, and constipation or sometimes diarrhoea. However, clinical severity varies and severe cases may lead to serious complications or even death. WHO estimates that 21 million typhoid cases and 216 000–600 000 typhoid-related deaths occur annually worldwide. A similar but often less severe disease is caused by Salmonella paratyphi bacteria.

Two typhoid vaccines are available internationally and both are considered safe and effective:

• An injectable polysaccharide vaccine based on the purified Vi antigen (known as Vi-PS vaccine) for children under two years of age.
• A live attenuated oral Ty21a vaccine currently available in capsules for those over five years of age.

WHO recommends the use of the Vi-PS and Ty21a vaccines to control endemic disease and for outbreak control. WHO further recommends that all typhoid fever vaccination programmes should be implemented in the context of other efforts to control the disease, including health education, water quality and sanitation improvements, and training of health professionals in diagnosis and treatment.

Several Vi polysaccharide–protein conjugate vaccine candidates are under development (or are nationally licensed but not on the international market) and anticipated to be available in the future for infant immunization.

Rubella

Under the Global Vaccine Action Plan, measles and rubella are targeted for elimination in 5 WHO Regions by 2020. WHO is the lead technical agency responsible for coordination of immunization and surveillance activities supporting all countries to achieve this goal.

Transmitted in airborne droplets when infected people sneeze or cough, rubella is an acute, usually mild viral disease traditionally affecting susceptible children and young adults worldwide. Rubella infection just before conception and in early pregnancy may result in miscarriage, foetal death or congenital defects 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.

In 1996, an estimated 22 000 babies were born with CRS in Africa, an estimated 46 000 in South-East Asia and close to 13 000 in the Western Pacific. Very few countries in these regions had introduced rubella-containing vaccine by the year 2008, and therefore the current burden of CRS in these settings is thought to be similar to that estimated for 1996.

Rubella vaccines are available either in monovalent formulation or in combinations with other vaccine viruses, as rubella-containing vaccines (RCVs). Commonly used RCVs are combinations with vaccines against measles (MR), measles and mumps (MMR), or measles, mumps and varicella (MMRV).

Large-scale rubella vaccination during the last decade has drastically reduced or practically eliminated rubella and CRS in many developed and in some developing countries. Indeed, the western hemisphere and several European countries have eliminated rubella and CRS.

WHO recommends that countries take the opportunity of accelerated measles control and elimination activities to introduce rubella-containing vaccines. All countries that have not yet introduced rubella vaccine, and are providing two doses of measles vaccine using routine immunization and/or supplementary immunization activities should consider the inclusion of RCV in their immunization programme.

Rotavirus

Rotaviruses are the most common cause of severe diarrhoeal disease in young children throughout the world. According to WHO 2008 estimates, about 450 000 children aged <5 years die each year from vaccine-preventable rotavirus infections; the vast majority of these children live in low-income countries.

Two oral, live, attenuated rotavirus vaccines, Rotarix™ (derived from a single common strain of human rotavirus) and RotaTeq™ (reassorted bovine-human rotavirus), are available internationally; and both vaccines are considered highly effective in preventing severe gastrointestinal disease. In low income countries, vaccine efficacy can be lower than in industrialized settings, similar to other live oral vaccines, but even with this lower efficacy a greater reduction in absolute numbers of severe gastroenteritis and death was seen, due to the higher background rotavirus disease incidence.

WHO recommends that rotavirus vaccines should be included in all national immunization programmes and considered a priority particularly in countries in South and Southeast Asia and sub-Saharan Africa. WHO continues to recommend that the first dose of either RotaTeq™ or Rotarix™ be administered as soon as possible after 6 weeks of age, along with DTP vaccination. Apart from a low risk of intussusception (about 1-2 per 100 000 infants vaccinated) the current rotavirus vaccines are considered safe and well tolerated.

The public health impact of rotavirus vaccination has been demonstrated in several countries. For example, in the USA, a measurable decrease was seen in the number of rotavirus gastroenteritis hospitalizations accompanied by a suggested herd effect protecting older non-vaccinated children, while in Mexico a decline of up to 50% in diarrhoeal deaths in children < 5 years of age was attributed directly to the use of the vaccine.

WHO reiterates that the use of rotavirus vaccines should be part of a comprehensive strategy to control diarrhoeal diseases with the scaling up of both prevention (promotion of early and exclusive breastfeeding, handwashing with soap, improved water and sanitation) and treatment packages (including low-osmolarity ORS and zinc).

Rabies

Rabies is a zoonotic viral disease which infects domestic and wild animals. It is transmitted to other animals and humans through close contact with saliva from infected animals (i.e. bites, scratches, licks on broken skin and mucous membranes). Once symptoms of the disease develop, rabies is fatal to both animals and humans.

Approximately 60 000 people die from rabies each year. The vast majority of these deaths occur in Asia and Africa. Children are at particular risk.

Two types of vaccines to protect against rabies in humans exist - nerve tissue and cell culture vaccines. WHO recommends replacement of nerve tissue vaccines with the more efficacious, safer vaccines developed through cell culture as soon as possible. Cell culture vaccines which are more affordable and require less vaccine have been developed in recent years.

Intradermal immunization using cell-culture-based rabies vaccines is an acceptable alternative to standard intramuscular administration. Intradermal vaccination has been shown to be as safe and immunogenic as intramuscular vaccination, yet requires less vaccine, for both pre- and post-exposure prophylaxis, leading to lower direct costs. This alternative should thus be considered in settings constrained by cost and/or supply issues.

Pre-exposure prophylaxis is recommended for anyone at continual, frequent or increased risk of exposure to rabies virus, either by nature of their residence or occupation.

Periodic booster injections are recommended as an extra precaution only for people whose occupation puts them at continual or frequent risk of exposure. If available, antibody monitoring of personnel at risk is preferred to the administration of routine boosters.

Recommendations for post-exposure depend on the type of contact with the suspected rabid animal. For category I exposure (touching or feeding animals, licks on intact skin), no prophylaxis is required; for category II (nibbling of uncovered skin, minor scratches or abrasions without bleeding), immediate vaccination; and for category III (single or multiple transdermal bites or scratches, contamination of mucous membrane with saliva from licks, licks on broken skin, exposures to bats), immediate vaccination and administration of rabies immunoglobulin are recommended.

Poliomyelitis

Polio (poliomyelitis) is a highly infectious disease caused by a virus. It invades the nervous system and can cause irreversible paralysis in a matter of hours. Polio is spread through person-to-person contact. When a child is infected with wild poliovirus, the virus enters the body through the mouth and multiplies in the intestine. It is then shed into the environment through the faeces where it can spread rapidly through a community, especially in situations of poor hygiene and sanitation. If a sufficient number of children are fully immunized against polio, the virus is unable to find susceptible children to infect, and dies out.

Most infected people (90%) have no symptoms or very mild symptoms and usually go unrecognized. In others, initial symptoms include fever, fatigue, headache, vomiting, stiffness in the neck and pain in the limbs.

There is no cure for polio, only treatment to alleviate the symptoms. Heat and physical therapy is used to stimulate the muscles and antispasmodic drugs are given to relax the muscles. While this can improve mobility, it cannot reverse permanent polio paralysis.

Polio can be prevented through immunization. Polio vaccine, given multiple times, almost always protects a child for life. The development of effective vaccines to prevent paralytic polio was one of the major medical breakthroughs of the 20th century. With the development and evaluation of bivalent oral polio vaccine in 2009, the Global Polio Eradication Initiative now has an armory of five different vaccines to stop polio transmission:

• Oral polio vaccine (OPV)
• Monovalent oral polio vaccines (mOPV1 and mOPV3)
• Bivalent oral polio vaccine (bOPV)
• Inactivated polio vaccine (IPV)

If enough people in a community are immunized, the virus will be deprived of susceptible hosts and will die out. High levels of vaccination coverage must be maintained to stop transmission and prevent outbreaks occurring.

In May 2012, the World Health Assembly declared the completion of polio eradication a programmatic emergency for global public health and requested the Director-General to rapidly finalize a comprehensive eradication and endgame strategy for the period 2013-2018. The draft strategic plan and current status of the global polio eradication program were presented to SAGE. Noting the substantive progress made in implementing polio emergency action plans in the remaining polio infected countries, detailed attention to oral polio vaccine (OPV) campaign planning in the field, and new evidence in improving performance, SAGE was alarmed by the considerable funding shortfalls at a time when eradication is in sight, with OPV campaigns already cancelled or scaled back in over 25 high risk countries in 2012.

In November 2012, SAGE endorsed the four major objectives and milestones in the new strategic plan. SAGE also recommended that all countries should introduce at least one dose of inactivated polio vaccine (IPV) in their routine immunization program to mitigate the risks and consequences associated with the eventual withdrawal of the type 2 component of OPV (OPV2). SAGE will review progress on achieving the pre-requisites for OPV2 withdrawal, including the availability of affordable IPV products, every six months to ensure the earliest possible date for OPV2 withdrawal but with sufficient advance notification to ensure programmatic readiness and vaccine availability.

In the new Eradication and Endgame strategy, research is a vital component of the Global Polio Eradication Initiative, providing the necessary evidence to guide the final steps to a lasting polio-free world and beyond. The Global Polio Eradication Initiative coordinates and supports an extensive program of research from a wide range of core scientific disciplines. The research program has two broad objectives:

• to identify, develop and evaluate new tools and tailored approaches to maximize the impact of eradication efforts
• to inform long-term policy for the post-eradication era.

Malaria

Malaria is a preventable and treatable mosquito-borne illness. In 2013, 97 countries had ongoing malaria transmission. There were an estimated 207 million cases of malaria in 2012 (uncertainty range: 135 – 287 million) and an estimated 627 000 deaths (uncertainty range: 473 000 – 789 000). 90% of all malaria deaths occur in sub-Saharan Africa, and 77% occur in children under five. Between 2000 and 2012, an estimated 3.3 million lives were saved as a result of a scale-up of malaria interventions. 90%, or 3 million, of these lives saved are in the under-five age group, in sub-Saharan Africa.

There is currently no commercially available malaria vaccine, despite many decades of intense research and development effort. The most advanced vaccine candidate against Plasmodium falciparum is RTS,S/AS01. A large clinical trial with 15 460 children is ongoing in the following seven countries in sub-Saharan Africa: Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and the United Republic of Tanzania.

The clinical trial data for WHO to consider making a policy recommendation is expected to be made available to WHO in late 2014. Depending on these full phase 3 results, the first WHO policy recommendations on use may occur in 2015. The policy timings depend on the outcome of the regulatory process with the European Medicines Agency.

Originally launched in 2006, The Malaria Vaccine Technology Roadmap has been updated in November 2013. The updated Roadmap represents a blueprint for second generation malaria vaccine development, including a new Vision, two new Strategic Goals and 13 priority activities, funding of which will be critical for successful development of a next generation of malaria vaccines by 2030.