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Immunization and vaccines development

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This analytical profile on immunization and vaccine development is structured as follows:

Contents

Analytical summary

Four million unnecessary deaths occur annually from diseases for which vaccines are available. The root of this problem is distribution and supply systems on the one hand, and the difficulty of accessing hard-to-reach and mobile populations on the other. Despite much progress, goals are not yet reached and the absolute numbers of those not consistently immunized remain high. One mechanism adopted to readdress the situation is a strong focus on district-level immunization.

Approaches to improving routine immunization include:

  • prioritizing countries with the largest numbers of non-immunized or under-immunized children
  • using the district-level approach
  • improving data for programme monitoring
  • introducing new vaccines as appropriate
  • enhancing training of health staff
  • resource mobilization.

However, while governments are spending more on buying vaccines, expenditure on routine immunization implementation appears to have changed little over the past 10 years.

Percentage of neonates protected at birth against neonatal tetanus in the WHO African Region, 1990 and 2009
The drive to polio eradication continues, on the understanding that with stronger political and financial commitment, eradication is feasible. The majority of African countries have surveillance systems for measles in place, although large measles outbreaks have occurred in several countries owing to non-immunization of infants.


In general, weak national health systems and fluctuating availability of vaccines produce gaps in immunization coverage. Coupled with funding shortages, these problems continue to challenge successful delivery of immunization programmes in African countries. One review noted that:

  • vaccine stock-outs were affecting some countries;
  • health facilities were found to be inadequately equipped and staffed;
  • gaps were identified in the areas of immunization safety and waste management.

These issues need to be addressed if current initiatives to enhance research capacity at country level in respect of new vaccines development are to play their expected role in reducing vaccine-preventable disease.



Disease burden

Percentage immunization coverage among 1-year-olds for DTP3 in the WHO African Region, 1990 and 2009
Immunization coverage among 1-year-olds for HepB3 in the WHO African Region, 2009

Providing safe and effective vaccines reduces the high burden of communicable diseases in African countries and helps to meet the health-related Millennium Development Goals. Vaccine-preventable diseases contribute significantly to morbidity and mortality; an estimated 4 million people die each year from diseases for which vaccines are available. Pneumonia and diarrhoeal disease, for example, account for approximately 34% of the global 10.4 million deaths among children aged under 5 years.[1] Many of these deaths could be prevented through effective immunization.

Invasive pneumococcal disease has recently been shown to cause about 826 000 deaths in children aged 1–59 months, while rotaviruses are the most common cause of severe diarrhoeal disease in young children throughout the world. According to WHO’s 2004 estimates, 527 000 children aged under 5 years die each year from vaccine-preventable rotavirus infections, most of whom live in low-income countries.[2]

Other vaccine-preventable diseases include cancers caused by the human papilloma virus, and recurrent respiratory papillomatosis. In 2005, there were about 500 000 cases of cervical cancer, and 260 000 related deaths worldwide. Other vaccine-preventable diseases are are meningococcal meningitis and septicaemia caused by various serogroups of Neisseria meningitidis. Major group A epidemics, occurring at intervals of 7–14 years, result in excessive morbidity and mortality among children and young adults in countries located in the African meningitis belt. Meningococcal disease is associated with high case fatality rates even where adequate medical services are available.

Yellow fever, a viral disease that caused major epidemics in Africa and the Americas in the past, is now a serious public health issue again, despite the availability of a vaccine for 60 years.

Immunization schedule

Routine service delivery is the bedrock of any immunization system. In African countries, routine immunization is delivered through the Expanded Programme on Immunization. Global disease control, elimination and eradication efforts depend on strong routine immunization systems, so routine immunization coverage is a good indication of the strength of a national health system.

The immunization schedule recommended by WHO in African countries starts with the Bacille Calmette-Guérin (BCG) and oral polio vaccine (OPV) at birth, followed by diphtheria-tetanus-pertussis (DPT), OPV, Haemophilus influenzae type b (Hib) and hepatitis B (HepB) at 6 weeks, 10 weeks and 14 weeks. Finally, immunization for measles and yellow fever is done at 9 months.

African countries have made great progress in increasing routine immunization coverage rates, but the ambitious Global Immunization Vision and Strategy coverage goals have not yet been reached. Routine immunization coverage for three doses of DPT (DPT3) increased dramatically in the WHO African Region from 2000, when DPT3 coverage was 54%, to 2007 when it stood at 82%.

DPT3 is used as a surrogate for routine immunization coverage. The rates cited are based on the official country estimates reported in the annual Joint Reporting Form. The WHO/United Nations Children's Fund (UNICEF) estimates of DPT3 coverage in the Region were, by contrast, 54% in 2000, 66% in 2004 and 74% in 2007. Because they are based on the official country estimates and the most recent population-based survey results, the WHO/UNICEF estimates are normally lower than the official country estimates.

In 2009, the regional coverage for the third dose of DPT3 was 85%, compared with 82% in 2008. Twenty countries reported at least 90% coverage at national level in 2009, compared with 17 in 2008.

Detailed analysis reveals disparities between and within countries. It is estimated that a total of 4.2 million children throughout the Region did not receive DPT3 vaccine in 2009, compared with 5.2 million in 2008,[3] and that an estimated 80% of these DPT3 under-immunized children reside in only 10 countries (Angola, Cameron, Côte d’Ivoire, Democratic Republic of the Congo, Ethiopia, Kenya, Nigeria, United Republic of Tanzania, Uganda, Zimbabwe).

Achievements against regional targets and other common routine immunization indicators. DTP3, three doses of diphtheria, pertussis and tetanus. 2004 data from Regional Expanded Programme on Immunization Strategic Plan Review

Among the various challenges in routine immunization noted by an external review in 2004 were continuing disparities in immunization coverage at national and subnational levels. DPT3 coverage rates were below 50% in many countries and districts across the Region. Vaccine stock-outs were affecting some countries, health facilities were inadequately equipped and staffed, and gaps were identified in the areas of immunization safety and waste management.

Achieving high levels of population immunity depends on effective routine immunization coverage, and the availability of additional vaccine doses during supplementary immunization activities. Some previously polio-free countries in west and central Africa experienced a resurgence of poliovirus transmission in 2008─2009. Contributing factors include:

  • the inability to achieve optimal coverage during supplementary immunization activities against a background of low routine immunization coverage;
  • disconnection between required activities and available resources;
  • limited sense of ownership and accountability by national and subnational authorities.

Suboptimal routine immunization appears to have contributed to measles outbreaks in many countries in the Region, calling into question the accuracy of some coverage estimates.

In search of new ways to help countries with weak immunization services and low coverage, the WHO Regional Office for Africa and key partners met in 2002 to identify common obstacles to increasing immunization coverage. As a result, the Reaching Every District (RED) Strategy was developed. The five elements of the strategy represent the repackaging and refocusing at district level of critical elements involved in successful routine immunization. The RED strategy components are:

  • planning and management of resources
  • reaching target populations
  • linking services with communities
  • supportive supervision
  • monitoring and use of data for action.

The implementation of the RED approach, together with other innovative strategies such as the Periodic Intensification of Routine Immunization activities, Child Health Days and Immunization Plus Days, have all contributed to improving coverage. In conflict-riven and post-conflict countries, as well as in geographically and culturally hard-to-reach zones, a tailored mix of fixed, outreach and Periodic Intensification of Routine Immunization activities has been key for achieving national and regional coverage goals.

The Regional Office is currently focusing on improving routine immunization performance by:

  • prioritizing countries with large numbers of non-immunized or under-immunized children
  • implementing the revised 2008 RED approach and other innovative strategies
  • improving data quality in programme monitoring
  • using the opportunity provided by the introduction of new vaccines to strengthen immunization systems
  • continuing to train immunization workers to enhance their competence
  • mobilizing resources to close funding gaps.

Efforts continue to improve data quality and use, and an expanded set of coverage indicators has been developed. Both measures will be increasingly important as countries seek and adopt more effective approaches to increasing, sustaining and monitoring routine immunization coverage.

The recent progress in immunization in the African countries was largely made possible due to the availability of international funding, with modest contributions from countries themselves. Eighty five per cent of countries have specific budgets for vaccines procurement. The proportion of government expenditure on vaccines in the Region increased from 48% in 2000 to 53% in 2006, although expenditure on overall routine immunization remained largely unchanged from 45% in 2000 and 43% in 2006.[4]

Percent of target population vaccinated, by antigen

Immunization systems strengthening

Successful immunization programmes rely on a sustainable and efficient supply chain of affordable vaccines of assured quality and its delivery through a reliable cold chain system. Vaccines are temperature-sensitive products that require storage between 2 and 8 degrees Celsius. However, many African countries do not have adequate and optimally decentralized facilities for vaccine cold storage. This has partly hampered the scaling-up of new vaccine introduction.

Efficient vaccine management and logistics systems are of paramount importance. High vaccine quality must be maintained at every stage of the continuum between the vaccine production plant and the ultimate point of administration. The consequences of interrupting the cold chain system can result in financial loss due to damaged vaccines, and the continued spread of vaccine-preventable diseases.

Technical and financial support has been provided to countries through:

  • advice on vaccine procurement systems
  • building capacity for vaccine forecasting at national, provincial and district levels
  • establishing sound cold chain systems and effective vaccine management.

Computerized tools for efficient vaccine forecasting and management have been developed and are now in use in the WHO African Region.

Health Care Waste Management is a key component of health logistics. Poor management of injection-related waste exposes patients, health care workers and other health care waste handlers, as well as members of the community, to potential infections, toxic effects and injury. Additionally, post-immunization waste can be harmful to the environment. An estimated 23 million people become infected each year with life-threatening diseases such as HIV and hepatitis (B and C) due to improper sterilization and inadequate waste disposal practices.

African countries are therefore working towards better ways of managing health care waste by developing protocols, guidelines and training materials for all involved in waste management at both national and subnational levels. The WHO Regional Office for Africa is providing technical and financial support to countries in respect of two principal objectives:

  • development and adoption of a national policy on health care waste management
  • finalization of an ad hoc national strategy and plan of action to implement this policy.

Increasing the capacity of staff at all levels is essential for the optimal delivery of immunization services. Policy-makers, managers and preservice training institutions need to ensure that a health workforce sufficient in numbers, well educated and trained, adequately deployed and motivated is available to provide immunization services of good quality.

Measles pre-elimination

In 2009, 27 of the 46 African countries had attained a coverage rate of 80% or over for the first dose of measles-containing vaccine (MCV1), in accordance with WHO/United Nations Children's Fund coverage estimates, while 15 countries had attained coverage of over 90%.

In 2009, 19 countries conducted measles supplementary immunization activities during which an estimated 29.7 million children between the ages of 6 months and 5 years were vaccinated. Coverage of 95% or more was attained by 11 out of 19 countries. In addition, the measles supplementary immunization activities in all 19 countries were used to deliver additional child survival interventions. The total number of children vaccinated during measles supplementary immunization activities between 2001 and 2009 has reached 425 million.

In 2009, a number of countries reported large measles outbreaks, including Angola, Burkina Faso, Cameroon, Ethiopia, Mali, Namibia, South Africa and Zimbabwe. Programmatic information and outbreak investigation reveals that non-vaccination of infant cohorts, resulting in a critical accumulation of susceptible populations, was a major factor in these outbreaks. Forty African countries have established measles case-based surveillance with laboratory confirmation.

Following the 92% mortality reduction (see figure) in the WHO African Region between 2000 and 2008, the Fifty-ninth Session of the WHO Regional Committee for Africa endorsed a measles elimination goal for 2020.

Figure 1 : Estimated measles deaths in the WHO African Region, 2000─2008
Fig17section404Vaccine PDfig1.png

New and underutilized vaccines introduction

Since the inception of the Global Alliance on Vaccines and Immunization (GAVI) in 2000, 36 eligible African countries have introduced new and underutilized vaccines into their Expanded Programme of Immunization programmes. These are hepatitis B, Haemophilus influenzae type b-containing vaccines and the yellow fever vaccine. Newer vaccines, such as pneumococcal conjugate vaccines, rotavirus vaccines, human papilloma virus vaccines and conjugate meningococcal meningitis A vaccine are also being considered for introduction.

Rotavirus vaccines are an important intervention that can reduce severe rotavirus associated diarrhoea and child mortality. The use of rotavirus vaccines is part of a comprehensive strategy to control diarrhoeal diseases, including other interventions such as:

  • improvements in hygiene and sanitation
  • zinc supplementation
  • community-based administration of oral rehydration solution
  • overall improvements in case management.

Polio eradication

The eradication of poliomyelitis (polio) remains a global priority to which all African countries are committed. Since 1988, when the World Health Assembly resolved that polio should be eradicated, significant progress has been made. Today, only four countries globally are known to have indigenous wild poliovirus transmission. An independent evaluation of the major barriers to interrupting wild poliovirus transmission carried out in 2009 concluded that polio eradication is feasible, provided that managerial, security and technical issues can be addressed.

At its Sixty-first Session in May 2008, the World Health Assembly called for a new plan to complete the eradication. Consequently, a special 1-year Global Polio Eradication Initiative programme of work was developed and implemented in 2009. On evaluation of this Initiative, it was concluded that with stronger political and financial commitments, the remaining barriers to achieving eradication could be addressed. Development of a new 3-year Global Polio Eradication Initiative Strategic Plan from 2010 to 2012 has therefore been agreed, with the goal of interrupting wild poliovirus transmission within that period. This plan was approved by the World Health Assembly in May 2010.

Epidemiology of wild poliovirus

In 2010, a total of 75 wild poliovirus (WPV) cases have been reported in 10 countries, compared with 545 WPV cases in 2009 in 15 countries. This progress is attributable to the marked drop in WPV cases reported from Nigeria, the only African country with indigenous wild poliovirus transmission. Three African countries have re-established polio transmission, namely Angola, Chad and Democratic Republic of the Congo.

Polio eradication in Nigeria has remained problematic, as a large number of children remain unvaccinated in a number of high-risk states and local government areas. This problem is compounded by low routine immunization coverage, gaps in surveillance as evidenced by the presence of orphan viruses, and low political commitment in some areas.

Circulating vaccine-derived polioviruses, largely resulting from low routine immunization coverage, were reported in three countries in 2009, namely Democratic Republic of the Congo, Guinea and Nigeria. Seventeen cases were confirmed in 2010.

A total of 16 annually accredited polio laboratories have been established in African countries as part of the global network.

Polio supplementary immunization activities

In response to circulating WPVs, at least two rounds of polio supplementary immunization activities were implemented in a synchronized manner in 19 countries of west and central Africa. These reached over 86 million children aged under 5 years. Two or more additional rounds and mop-up activities were implemented in priority countries in 2010. Despite commendable efforts to implement high-quality supplementary immunization activities, there have been significant challenges in making available the required quantities of the appropriate vaccine as well as all the necessary funding.

Independent monitoring has been instituted as a way of validating the reported coverage of the polio campaigns. Findings are used to take immediate corrective action, while lessons learned serve to institute corrective measures in subsequent campaigns. Written feedback is provided to each country following analysis of the independent monitoring data. Findings show that the most common reasons for children’s absence during supplementary immunization activities are:

  • limited awareness of caretakers
  • absence of children from home when the vaccinators arrive
  • failure to cover all settlements as a result of inadequate planning.

Surveillance for acute flaccid paralysis

Surveillance for acute flaccid paralysis is fully institutionalized in all 46 countries of the WHO African Region. Acute flaccid paralysis surveillance indicators are monitored and reported weekly. The infrastructure in place for acute flaccid paralysis surveillance also supports surveillance for other vaccine preventable diseases, as well as for other diseases of public health importance. These include measles, yellow fever, and maternal and neonatal tetanus.

Certification of polio eradication

The Africa Regional Certification Commission was established by WHO in 1998. The Commission has successfully constituted national certification committees, national polio expert committees and national task forces to support the polio eradication process.

Twenty-five countries have now been certified polio free by the Africa Regional Certification Commission. However, 11 of these countries experienced importation of wild polioviruses during the 2009 outbreak. Containment measures are taking place.

Remaining challenges

  • Sustaining advocacy at national level and ensuring that commitment at the highest level is translated into action at the operational level.
  • Strengthening health systems to better support routine immunization.
  • Improving the quality of supplementary immunization activities to reduce the number of children missed, especially in hard-to-reach areas.
  • Ensuring availability of the appropriate type of vaccine in the required amounts and in a timely manner.
  • Bridging the financial gap for both surveillance and supplementary immunization activities.

Sentinel surveillance

WHO is currently supporting efforts in African countries to improve surveillance on the three most common causes of bacterial meningitis, namely Hemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. A network of 23 affected countries has been established, coordinated by the WHO Regional Office for Africa.[5] A similar network with 15 participating countries has been established for rotavirus disease surveillance.[6]

These sentinel surveillance networks provide useful data and evidence to support the introduction of new vaccines. They also serve as platforms for impact monitoring of newly introduced vaccines.

Vaccine research and development

Following an assessment of the research capacity of African countries, capacity in regulatory and ethical oversight of vaccine clinical trials has been built and strengthened in 19 Member States (Botswana, Burkina Faso, Cameroon, Ethiopia, Kenya, Gambia, Ghana, Gabon, Mali, Malawi, Mozambique, Nigeria, Rwanda, Senegal, South Africa, United Republic of Tanzania, Uganda, Zambia, Zimbabwe) through the African Vaccine Regulatory Forum. This has significantly improved countries’ ability to undertake vaccine clinical trials.

In recent years, several vaccines have entered phases I, II and III of clinical trials in the WHO African Region, including candidate vaccines against tuberculosis, malaria and HIV/AIDS. On the recommendations of the Strategic Advisory Group of Experts (SAGE) on Immunization and other advisory bodies, other new vaccines have undergone clinical trials to establish their efficacy and safety.

Conjugate Meningococcal A Vaccine

Clinical trials were conducted in the Gambia, Mali and Senegal to establish the safety and efficacy of the conjugate meningococcal A vaccine, which led to its licensure and subsequent WHO prequalification in June 2010. The clinical trials proved that the vaccine is safe and better than existing polysaccharide vaccines currently used for epidemic response. The conjugate meningococcal A vaccine will be used for preventive mass immunization in the age range of 1─29 years. The vaccine will be marketed at an affordable cost of US$ 0.40 per dose.

Subsequent clinical trials are ongoing in Ghana to establish the safety and efficacy of the vaccine for use in infants. This will guide its introduction into the routine Expanded Programme on Immunization programmes of countries in the Region’s meningitis belt.

Candidate Malaria Vaccine

Currently only one candidate, GSK’s RTS,S/AS01E (MosquirixR) malaria vaccine is in phase III clinical trials at 11 sites in seven countries within the Region. These countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, United Republic of Tanzania) conducted a review of the protocol and are receiving support in ethical and regulatory oversight for the clinical trials. WHO has established a policy recommendation pathway in support of the development of this candidate malaria vaccine.

Accelerating HIV vaccine research

The African Aids Vaccine Programme was created to promote the accelerated development of a safe, efficacious and affordable vaccine against HIV/AIDS. The objectives of the Programme are:

  • to develop advocacy and communication tools
  • provide a network of people and institutions
  • promote the development of appropriate candidate HIV vaccines
  • facilitate clinical trials that will ultimately lead to a vaccine against HIV in Africa.

The secretariat for this important advocacy and capacity building effort for HIV vaccines was established at the Uganda Virus Research Institute in 2009.

Programme components

Yellow fever is now endemic in 31 African countries, with 22 at particularly high risk of outbreaks. The total number of outbreaks reported to WHO during this decade increased markedly compared with numbers in the 1990s. The control strategy consists of surveillance for early detection of outbreaks and the effective utilization of the yellow fever vaccine for outbreak prevention and response. The inclusion of the vaccine in the Expanded Programme on Immunization programmes of countries at risk is justified by the high frequency of cases in children, as also observed in the early 1990s. To date, 23 of the 31 countries at risk have incorporated this vaccine into their Expanded Programme on Immunization. Forty-six million people in high-risk districts of 12 countries have been vaccinated.

Challenges in yellow fever control

The challenges of yellow fever control include the need to strengthen surveillance systems against a background of weak national health systems and uncertain availability of vaccine supplies. The global stockpile mechanism set up since 2001 has greatly contributed to the rational distribution of vaccines according to need, and Global Alliance on Vaccines and Immunization (GAVI) support for the yellow fever control programme has greatly improved utilization of the vaccine. However, with only three prequalified manufacturers available and limited annual production capacity, the cost per dose has not significantly reduced. This will continue to be a challenge to countries at risk.

Endnotes: Sources, methods, abbreviations, etc.

The English content will be available soon.

Liste des tableaux / figures

Tableau 1 : réalisations par rapport aux objectifs régionaux et d'autres indicateurs communs de vaccination de routine


Figure 1 : Estimation de la mortalité rougeoleuse dans la Région africaine, 2000 - 2008 (si l'article retenu la rougeole)

Atlas des figures 80 et 81.


Références

1. Le Global Burden of Disease: mise à jour 2004. Organisation mondiale de la Santé, Genève, 2008.

2. Organisation mondiale de la Santé. Décès estimée à rotavirus pour les enfants de moins de 5 ans d'âge, 2004. http://www.who.int/immunization_monitoring/burden/rotavirus_estimates/en/

3. DTC3 est utilisée comme un substitut à la couverture vaccinale de routine. Les taux cités sont basés sur les estimations officielles des pays signalés dans le formulaire de rapport conjoint annuel (JRF). L'OMS / UNICEF estime de couverture en DTC3 dans la région de l'Afrique ont été, en revanche, 54% en 2000, 66% en 2004 et 74% en 2007. Parce qu'elles sont basées sur les estimations officielles des pays et la population basée sur les plus récents résultats de l'enquête, l'OMS / UNICEF estime sont normalement inférieurs aux estimations officielles des pays.

4. Source des données: MS-UNICEF-OMS Formulaires de déclaration commun (FRC)

5. L'Angola, Cameroun, Côte d'Ivoire, République démocratique du Congo, Ethiopie, Kenya, Nigeria, Tanzanie, Ouganda et Zimbabwe.

6. Lyndon P et al. Financement du gouvernement pour la santé et des lignes budgétaires spécifiques nationaux:. Le cas des vaccins et l'immunisation vaccinale 26 (2008) , 6727-6734.

7. Botswana, Burkina Faso, Cameroun, Ethiopie, Kenya, Gambie, Ghana, Gabon, Ouganda, Tanzanie, Mali, Malawi, Nigéria, Afrique du Sud, Sénégal, Rwanda, Mozambique, Zambie, Zimbabwe

8. Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, Tanzanie.

9. Le Réseau pédiatrique surveillance de la méningite bactérienne dans la Région OMS de l'Afrique, 2001-2008: REH n ° 20, 84, 173-184 15 mai 2009.

10. Fardeau et épidémiologie de la diarrhée à rotavirus dans certains pays africains: résultats préliminaires du Réseau de surveillance du rotavirus en Afrique; JID Dans la presse 2010.

References

  1. The global burden of disease 2004 update (pdf 4.85Mb). Geneva, World Health Organization, 2008 http://www.searo.who.int/LinkFiles/Reports_GBD_report_2004update_full.pdf
  2. World Health Organization. Estimated rotavirus deaths for children under 5 years of age, 2004. http://www.who.int/immunization_monitoring/burden/rotavirus_estimates/en/
  3. Ministry of Health─United Nations Children's Fund─WHO Joint Reporting Forms
  4. Lyndon P et al. Government financing for health and specific national budget lines: the case of vaccines and immunization. Vaccine, 2008, 26: 6727─6734
  5. The paediatric bacterial meningitis surveillance network in WHO’s African Region, 2001–2008: Weekly Epidemiological Record, 2009, 84, 20:179–185
  6. Burden and epidemiology of rotavirus diarrhea in selected African countries: preliminary results from the African Rotavirus Surveillance Network. Journal of Infectious Diseases, 2010, 202(Suppl.1):S5–S11