Newsletter

Volume XXXIV Number 5 Immunize and Protect Your Family October 2012 XX TAG Meeting Paving the Way for Immunization Bolivian Uru Chipaya Community Receives PAHO The XX Meeting of the Technical Advisory Group (TAG) on - Immunization Award preventable Diseases of the Pan American Health Organization The Uru Chipaya Ethnic Group of the Oruro (PAHO) was held from 17-19 October 2012 in Washington, D.C. Department of Bolivia received the 2011 Pan The twentieth TAG Meeting addressed several topics including polio ; use of thiom- American Health Organization (PAHO) Im- ersal in vaccines; age restriction on administration; Decade of Vaccines; evi- munization Award for their activities to keep dence on pertussis; proposal for standardizing PAHO’s TAG procedures; PAHO’s Revolving immunization coverage close to 100% in Fund in the current global vaccine market; improving regional vaccine production capacity their area. The group was presented with a to meet the needs of the Americas; measles, rubella and Congenital Rubella Syndrome (CRS) certificate of recognition, as well as a mon- elimination in the Region of the Americas; Haiti’s immunization program; and vaccina- etary gift in the amount of three thousand US tion in the Americas. dollars at the twentieth Meeting of PAHO’s Technical Advisory Group (TAG) on Vac- The slogan for the meeting, “Paving the Way for Immunization,” reflected the Region’s leader- cine-preventable Diseases. PAHO created the ship in immunization in the global context. The purpose of the meeting was to draft TAG recom- Immunization Award to recognize outstand- mendations on how to address current and future challenges facing immunization programs in ing contributions to a national immunization the Americas. The following is a summary of TAG’s technical deliberation and recommenda- program and to the control and/or elimination tions as presented in the final report. of vaccine-preventable diseases. Despite extreme poverty conditions, mar- ginalization and inequity, the Uru Chipaya Ethnic Group of Bolivia made extraordinary contributions in the control and elimination of vaccine-preventable diseases. In the last 15 years, the municipality reached more than 95% coverage, even reaching 100% coverage in some years. Since 2000, the community no longer has confirmed cases of measles, rubella or neonatal tetanus, in ad- dition to other vaccine preventable diseases, such as polio and , which have not occurred in 24 years. Their achievements were made possible by making immunization and health promo- tion a top priority. In 2001, the community put nearly 60% of its financial resources into health, education and basic hygiene. The group established and maintained a strong alliance with the community, indigenous au- thorities and health personnel. Other activi- Members of the Uru Chipaya Ethnic Group of the Oururu Department of Bolivia receiving the 2011 PAHO Immunization Award ties to increase success in health included the In This Issue development and use of creative tactics to 1 XX TAG Meeting -Paving the Way for Immunization 5 Cholera Vaccination in the Americas prevent morbidity and mortality in the com- 1 Bolivian Uru Chipaya Community Receives PAHO 6 Thimerosal-Containing Vaccines Continue to be Safe munity; ensuring vaccination completion for Immunization Award 7 The PAHO Revolving Fund and the Current Global Vaccine teenagers, senior citizens and migrant groups; 2 Polio Vaccines Market 3 Rotavirus 8 Improving Regional Vaccine Production Capacity to Meet increasing vaccination hours; and promoting 3 Measles, Rubella and CRS Elimination the Needs of the Americas health in schools. 3 Evidence on Pertussis 8 WANTED: Trinidad and Tobago’s East Leo Club 1982 4 Decade of Vaccines: From Planning to Action 2 Immunization Newsletter Volume XXXIV Number 5 October 2012 Pan American Health Organization Polio Vaccines At its most recent meeting held in Geneva on the development, scientific vetting, and rapid age conditions recommended during TAG’s 10-12 April, the Strategic Advisory Group finalization of a comprehensive polio eradi- previous meeting (Argentina 2011). If a of Experts (SAGE) on Immunization recom- cation “endgame” strategy, and inform Mem- country does not meet these basic conditions, mended that, the World Health Organization ber States of the potential timing of a switch it should conduct at least two annual vacci- (WHO) should promote switching from the from trivalent to bivalent oral poliovirus vac- nation campaigns, administering the tOPV 2 to every child aged <5 years, without taking trivalent oral polio vaccine (tOPV) to the bi- cine for all routine immunization programs . into account their previous vaccination sta- valent oral (bOPV) for routine PAHO’s TAG discussed the implications of tus. Countries making plans to introduce the vaccination. This change should take place a potential change in vaccination recommen- IPV should be able to guarantee its long-term in a synchronized manner in order to mini- dations, noting that the Region of the Ameri- supply, in addition to considering the price of mize the risk of cVDPV2 circulation and out- cas managed to eliminate wild poliovirus in the vaccine. breaks, as well as to accelerate the elimina- 1991; and since then has remained free of • Countries should reinforce surveillance of tion of type 1 and type 3 wild , since polio without outbreaks due to importation, AFP, attain adequate levels in all basic sur- the bivalent vaccine provides better protec- using the tOPV vaccine. veillance indicators, and continue working tion against those types than the triva- to achieve ≥95% polio coverage in every 1 Recommendations: lent vaccine . municipality. • TAG awaits the World Health Organiza- During its 65th meeting in May 2012, the • As IPV will be considered for use in the po- tion’s comprehensive polio eradication and World Health Assembly (WHA) adopted lio endgame requested by the WHA, it will endgame strategy, as well as results from Resolution WHA65.5, which states that be important for WHO to maintain a fluid ongoing and planned research to revisit dialogue with vaccine manufacturers to en- “substantial planning is required for a glob- its recommendations for the Region of the sure an adequate IPV supply at an afford- ally synchronized switch from trivalent to bi- Americas. At the present time, the trivalent able price for countries of all income levels, valent oral poliovirus vaccine for routine im- oral poliomyelitis vaccine (tOPV) remains as this will be a factor in the rapid adoption munization and, potentially, the introduction the vaccine of choice for the Americas. of the vaccine. beforehand of one or more doses of inacti- To this end, PAHO, in collaboration with • PAHO is in an advantageous position to vated poliovirus vaccine. In 2012, the SAGE WHO, should negotiate with providers to work with the GPEI, in the development will provide recommendations on the actual ensure sufficient supply of tOPV for coun- of the endgame strategy and for the syn- implementation of this strategy based on tries of the Americas. chronized cessation of vaccines containing broad-based consultations across a number of • Countries considering the introduction of the poliovirus type 2, and supporting cost-ef- work streams.” In the Resolution, the WHA inactivated polio vaccine (IPV) should first fectiveness studies for different scenarios. asks WHO’s Director-General to undertake fulfill the sanitation and vaccination - cover Additionally, the World Immunization Week 1 Available at: http://www.who.int/wer/2012/ 2 Available at: http://apps.who.int/gb/ebwha/pdf_files/ could be used as an effective platform for wer8721.pdf WHA65/A65_R5-en.pdf globally coordinated actions.

Polio3 coverage in children under 1 year of age and Polio cases in the Americas, 1975- 2011

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2000 30 20 1000 10 0 0 75 77 79 81 83 85 87 89 91 93 95 97 99 01 03 05 07 09 11 Sabin-derived outbreak in DOR and HAI Source: country reports Immunization Newsletter Volume XXXIV Number 5 October 2012 Pan American Health Organization 3 Rotavirus Vaccination Schedule Currently, the vaccination schedules used in from the benefits of rotavirus vaccines could immunization of children at greater risk of Latin America and the Caribbean follow the be immunized, and it is likely that these in- morbidity and mortality due to rotavirus di- most recent WHO position paper, which rec- clude some of the children most vulnerable arrhea. However, in areas of difficult access ommends administering the first dose of the to this serious disease. Thousands of deaths and /or high diarrheal mortality, vaccine can vaccine between 6 and 15 weeks of age and could be averted, with just a minimal increase be administered later, at any time of immu- the last dose no later than 32 weeks of age (2nd in cases of intestinal intussusception. SAGE nization contact and before 1 year of age. dose for the monovalent rotavirus vaccine and also stated that based on the age distribution • TAG encourages countries that have not 3rd dose of the pentavalent rotavirus vaccine)1. of rotavirus disease, vaccinating children over introduced rotavirus vaccine to reassess More importantly, risk/benefit analysis con- 24 months of age would have few beneficial the burden of disease in order to consider tinues to favor early immunization, but cur- effects. the introduction of rotavirus immuniza- rent age-related restrictions on administration tion. This in light of the current evidence Recommendations: demonstrating the huge impact of rotavirus of the first dose (<15 weeks) and the last dose • In the Region of the Americas, countries (<32 weeks) prevent vaccinating many vulner- vaccine administered in the current sched- should continue making efforts to admin- ule in reducing the morbidity and mortality able children. If these restrictions were elimi- ister rotavirus vaccines on their routine im- nated, children who are currently excluded from rotavirus diarrhea in the Region of the munization schedules, at the recommended Americas. 1 Available at: http://www.who.int/wer/2009/ ages, usually at 2 and 4 months or 2,4, and wer8451_52.pdf 6 months. This schedule favors the early

Measles, Rubella and CRS Elimination in the Region of the Americas On 20 September 2012, ministers of health for the next two years to address weaknesses part of the emergency action plan, countries of the Region approved an emergency plan identified in the immunization and surveil- should integrate the proposed activities for of action to keep the Americas free of mea- lance programs during the process to docu- maintaining measles, rubella, and CRS elimi- sles, rubella, and congenital rubella syndrome ment and verify measles and rubella elimina- nation in their annual plans of action for na- (CRS) at the 28th Pan American Sanitary Conference. Given the continuing circulation tion. To sustain and build on this elimination tional immunization programs. of measles and rubella viruses in other regions achievement, PAHO has urged Member Recommendation: of the world, countries of the Region continue States to maintain high-quality, elimination- to be exposed to high risk of virus importa- standard surveillance and high population The TAG endorses and urges countries to tions. Moreover, some countries have reported immunization coverage against measles and implement the Emergency Plan of Action to weaknesses and failures in their national sur- rubella (>95%). Full implementation of in- maintain the elimination of measles, rubella veillance systems and routine immunization tensified vaccination activities to maintain and CRS in the Americas, as stated in Reso- programs, making them vulnerable to the rein- elimination status will be essential to ensure lution CSP28.R14 of the Pan American Sani- troduction of viruses that can cause outbreaks. high immunization coverage, especially in tary Conference 2012. The emergency plan of action was formulated areas that have susceptible populations. As

Evidence on Pertussis

Pertussis continues to be a significant cause sued recommendations. It also clearly stated countries in the Region participated in a meet- of child mortality worldwide and a disease that in order to change or issue new recom- ing called by PAHO to define what informa- that causes serious public health concern, mendations, it requires new epidemiological tion is needed or could be presented to request even in countries with high levels of vac- information to support them. In response to that the TAG issue new recommendations or to cination coverage. The WHO estimates that this call for action, a project titled “Improv- implement the current recommendations. The in 2008, there were nearly 16 million cases ing Epidemiological Surveillance of Pertus- countries were invited to present new epidemi- worldwide, 195,000 of which resulted in sis in Latin America” is now being carried ological evidence. The conclusion drawn from death. out in Argentina, Mexico and Panama, with the meeting was that the disease continues In the Region of the Americas, coverage with support from the Sabin Vaccine Institute, the to appear among children under five without DPT3 among children aged <1 year is over US Centers for Disease Control and Preven- completed vaccination schedules for their age. 90%, and the annual number of cases has tion (CDC) in Atlanta, the and PAHO. Its No additional new evidence was presented to ranged from 15,000 to 34,000 over the last 10 objectives include: improving diagnostic ca- support new recommendations. The goal con- years, with significant increases in the num- pacity, developing a reliable and valid method tinues to be adequate implementation of the ber of cases in Argentina, Brazil, Chile, Co- of improving surveillance of pertussis in Latin current recommendations. lombia and the United States in the last year. America, and making the project findings and results available by the end of 2012. During this meeting, the TAG received an During its last two meetings, the TAG dis- update on the global pertussis situation, new cussed matters related to this disease and is- In March 2012, 32 professionals from 12 trends in vaccination policies such as the “co- 4 Immunization Newsletter Volume XXXIV Number 5 October 2012 Pan American Health Organization coon” strategy and vaccination of pregnant this time there is insufficient evidence to sup- the regular vaccination program in every women, and a report on the current status of port the use of a 5th DTP dose. It is expected country, and the coverage attained with this the “Improving Epidemiological Surveillance that SAGE will review pertussis vaccination dose (as with all vaccine doses) should be of Pertussis in Latin America” project. Argen- strategies in use at upcoming meetings. the object of careful recording, monitoring, tina, Chile, Mexico, and the United States pre- reporting and evaluation. sented information on recent pertus- • Every pertussis outbreak should be sis outbreaks and the measures taken Reported DTP1 and DTP4 Coverage, thoroughly investigated to improve for their control. It was highlighted Selected Countries of the Americas, 2011 the understanding of the current epi- that a significant proportion of cases 100 demiology of the disease in the Re- and deaths occur among infants, of- 90 gion of the Americas. PAHO should ten in the first months of life. 80 provide countries with specific guid- ance for outbreak investigation. There is growing evidence of an 70 (%) 60 • Countries should improve surveil- increase in the incidence of the dis- ge 50 lance and the use of adequate diag- ease in adolescents in some settings, ver a nostic tools. The present surveillance o 40 which suggests that the C 30 pilot project being implemented in conferred by the acellular vaccine 20 Argentina, Mexico and Panama by is short-lived. In September 2012, 10 the Sabin Vaccine Institute, CDC and WHO convened an informal expert 0 PAHO should be expanded to other I L T T X R R R R C A U G N

meeting to discuss the current situ- I H E E C O A C U countries of the Region. R R U O C N L P V B CO L P S GR E EC U BR A CO R VE A G U D ation of pertussis in Australia, Can- M • Considering new evidence suggest- ada, the United Kingdom, and the DTP1 DTP4 ing that the immunity conferred by the United States. The experts conclud- Only includes countries reporting DTP4 coverage in the 2012 PAHO/WHO-UNICEF Join Reporting Form on Immunization acellular vaccine may be shorter-lived ed that there are limitations to aP, than the immunity conferred by wP but that the problem remains poorly defined. Recommendations: vaccines, countries that are using whole-cell At that meeting, it also was highlighted that • Countries should ensure vaccination cover- vaccine (wP) should not switch to an acel- countries are utilizing a range of strategies, in- age ≥95% with 3 doses of pertussis-contain- lular vaccine (aP). Similarly, countries cur- cluding maternal vaccination and ; ing vaccines in children aged <1 year; and rently using aP should not switch back to the and that use of aP or the Tdap booster is being encourage timely vaccination and comple- use of wP until more evidence is available contemplated. However, the data available to tion of the schedule. The 4th dose of the to support changes in vaccination strategies support these strategies is weak. Similarly, at DPT vaccine should be incorporated into for pertussis. Decade of Vaccines: From Planning to Action

The Global Vaccine Action Plan (GVAP) is accountability framework for the DoV, and (SO3): The benefits of immunization are eq- the result of global consultation efforts, which mobilize resources to ensure the vision for uitably extended to all people gathered input from more than 1,100 people the DoV becomes a reality. (SO4): Strong immunization systems are an from 142 countries and 297 organizations in In the Americas, the GVAP will complement integral part of a well-functioning health sys- Asia, Africa, the Americas, Europe, the Mid- the existing Regional Immunization Vision tem dle East and the Western Pacific. The GVAP and Strategy (RIVS), which was developed builds on the success of the WHO/UNICEF (SO5): Immunization programs provide sus- to translate the GIVS into regional priorities 2006-2015 Global Immunization Vision and tainable access to predictable funding, qual- in the late 2000s. The RIVS has three stra- Strategy (GIVS), which was launched in ity supply and innovative technologies tegic areas to guide the implementation of 2005 as the first 10 year strategic framework successful immunization programs in Latin (SO6): Country, regional and global research for immunization. The plan reiterates exist- America and the Caribbean, including strate- and development innovations maximize the ing goals and sets new goals for the Decade gies for: maintaining the achievements; com- benefits of immunization of Vaccines (DoV) 2010-2020, proposes six pleting the unfinished immunization agenda, The six strategic objectives set forth in the strategic objectives and provides an initial with the control of vaccine-preventable dis- GVAP will help bring new focus to the ex- estimate of resource requirements and return eases; and facing new challenges, such as the isting RIVS. PAHO’s regional immunization on investments. introduction of new vaccines. Likewise, the program will work to incorporate the six stra- On May 25, 2012, the 65th World Health GVAP encompasses these same strategies but tegic objectives described in the GVAP into Assembly (WHA) endorsed the GVAP and with a more horizontal approach, highlighted its existing RIVS framework by developing a passed resolution 65.17 in support of it. Be- in its six strategic objectives (SOs): regional vaccination action plan to 2020 and yond the action plan, country, regional and (SO1): All countries commit to immuniza- beyond. For this regional action plan, PAHO global stakeholders need to take responsibil- tion as a priority will lead discussions with Member States to ity for specific actions, translate the action develop and define indicators to track pro- plan into detailed operational plans, com- (SO2): Individuals and communities under- gress towards achieving regional goals and plete the development of the monitoring and stand the value of vaccines and demand targets. Immunization Newsletter Volume XXXIV Number 5 October 2012 Pan American Health Organization 5 Cholera Vaccination in the Americas Deployment of oral (OCV) of cholera transmission elimination, TAG up to 2–4 million doses in 2013 and to has been considered since October 2010. considers that several short-term actions 10–20 million doses in 2014 and thereafter. At that time, also considering the rapidly should also be considered, including the ex- Therefore, a phased introduction based on spreading epidemic and the limited vaccine panded use of OCV. However, if water and global supply will need to be used in Haiti. supplies, PAHO recommended focusing sanitation are not improved in the long run, OCV deployment could be prioritized in the emergency efforts on time-tested measures the Island will likely remain vulnerable to following areas: for cholera outbreak response, namely on repeated epidemics, even with a large-scale • a) OCV introduction as part of the routine treatment to prevent deaths and traditional cholera vaccination program in place. national schedule for children aged one year linked to the delivery of the MR vaccine, preventative actions to halt transmission (i.e. • TAG recommends that OCV be used in Hai- b) in the metropolitan area, supplemental delivery of safe potable water, provision of ti, leveraging its delivery to strengthen the immunization activities (SIA) targeting in- supplies for hand washing and other hygienic provision of other cholera prevention meas- ures (i.e., social mobilization and active ternally displaced people residing in camps measures, sanitation, and proper waste dis- (i.e., a group with low immunity likely case-finding) and national immunization posal). An expert consultation convened by transitioning to higher risk circumstances) services. To reach this objective, incremen- PAHO in December 2010 recommended that and/or larger populations residing in shanty tal advances are needed in the integration of the limited vaccine supply be used for dem- towns (a group with current moderate to onstration projects and that efforts be initi- OCV use with Water, Sanitation, and Hy- high immunity, but ongoing high risk cir- ated to increase OCV availability. giene (WASH) development plans, in assur- cumstances), and c) in rural areas, through ing sufficient OCV availability and financial SIA targeting the population who have diffi- At least four elements warrant a reconsidera- sustainability of its purchase and delivery, tion of OCV deployment in the Island of His- cult access to health care. Vaccination in ru- and in developing operational and monitor- ral areas will most likely require additional paniola: the ongoing occurrence of cholera ing immunization capacities. These advanc- prioritization based on geospatial analyses now almost two years after the epidemic be- es need to build national and local capacity of a defined set of criteria defined a priori. gan; the WHO-prequalification in September of immunization programs and the health Regardless of the time and eventual scope 2011 of a second OCV (Shanchol) that eases system as a whole. The timeframe during of a cholera vaccination program, additional some operational challenges; the immedi- which vaccination will be needed depends resources and funds will be needed for the ate availability in principle of up to 600,000 on the advances in access to potable water program to be successful, and without ongo- OCV doses; and the demonstration that, with and provision of sanitation and on the evo- ing attention to strengthening water, sanita- substantial planning and logistic resources, lution of natural and vaccine immunities at tion, and hygiene, OCV use will not prevent OCV deployment is feasible on the Island1. population level. Contingent on firm orders, long-term risk of disease outbreaks and re- global production capacity could be scaled Most important, interventions to decrease surgence. cholera transmission through improvements in water and sanitation, as well as the pro- vision of clean water and sanitation to every household will take years to accomplish and Oral inactivated vaccines * will require the mobilization of billions of dollars, while immunization against cholera Whole-cell V. cholerae O1 in Matlab, offers immediate short-term benefits to sup- w/ cholera toxin B subunit Bangladesh, 1985 port the long-term vision. (WC-BS) Recommendations: • TAG commends the work of PAHO and partners for establishing and recently ex- Whole-cell V. cholerae O1 Whole-cell V. cholerae O1 and O139 panding the Regional Coalition on Water w/ recombinant cholera (WC) and Sanitation for the Elimination of Chol- toxin B subunit (WC-rBS) era in the Island of Hispaniola. mORCVAX™ • Advocated by this Coalition, the elimination Licensed in 1997 in Vietnam of cholera transmission in the Island of His- Produced for local use only paniola, defined as cholera no longer being a public health burden, will only be achieved Dukoral™ (Crucell) Shanchol™ (Shanta Biotech) in the long run through considerable invest- Licensed in 1991 in Sweden, Licensed in 2009 in India ments towards significant and sustained im- since then in >60 countries Intended for global market provements in access to potable water and Primarily as travelers’ vaccine sanitation. To achieve the overarching goal

1 Immunization Newsletter, February 2011, Vol. * Formalin- and heat-inactivated whole cell vaccines that require 2–3 XXXIII, No. 1: Cholera Outbreak in Haiti. Available doses in primary immunization series. at: http://paho.org/inb/. 6 Immunization Newsletter Volume XXXIV Number 5 October 2012 Pan American Health Organization Thimerosal-Containing Vaccines Continue to be Safe

At its twentieth meeting held in October meet all the requirements of the regulatory 2012, the Technical Advisory Group (TAG) authorities for its substitution. This could Absence of Scientific Evidence on Vaccine-preventable Diseases recom- require a new license request, including on Harm—Conclusions of the mended continuing the use of ethylmercury performing new pre-clinical and clinical (thimerosal)-containing vaccines, following studies. This process is slow and expen- GACVS current vaccination schedules for children. In sive and could lead to an increase in the In 2000, WHO asked the Global Advisory this way, the TAG revisits the recommendation cost of the vaccine and even disrupt the Committee on Vaccine Safety (GACVS) of the Strategic Advisory Group of Experts on global supply of vaccines. Furthermore, to investigate safety concerns related to Immunization (SAGE) of the World Health WHO does not currently have a program the use of thimerosal. From 2002 to 2008, Organization (WHO), which recognized that to evaluate alternative preservatives to the members of the GACVS reviewed sev- thimerosal-containing vaccines are safe and thimerosal, given the lack of scientific eral pharmacokinetic and epidemiological that replacing this compound with an alterna- evidence to suggest that its replacement is studies on thimerosal. According to the tive preservative could affect the quality, safe- required. results of the pharmacokinetic studies con- ty and effectiveness of vaccines. 2. The replacement of vaccines from multi- ducted in children, including premature The SAGE also established that the informa- dose to single-dose vials: Currently, there and low birthweight babies, the half-life tion available justifies the recommendation not is not enough capacity for the production of ethylmercury was 3-5 days; ethylmer- to change WHO policy on immunization with of single-dose vials for the more than 325 cury is excreted efficiently in the stool; and respect to thimerosal-containing vaccines. million doses that are produced today; it there is no long-term accumulation in the Other expert groups (the Institute of Medicine would have important implications on blood or tissues, as ethylmercury levels re- of the United States, the American Academy the cold chain, storage, and final disposal turned to average values less than 30 days of Pediatrics, the United Kingdom’s Commit- and as a result, increasing the operational after vaccination [4]. tee on Safety of Medicines, and the European costs of immunization programs. At its most recent meeting, the members Agency for the Evaluation of Medicinal Prod- According to an analysis conducted by the of the GACVS examined the results of 28 ucts) have reached similar conclusions. Pan American Health Organization’s (PAHO) published studies (from 2008 to the pre- For over 10 years, through its Global Advi- Revolving Fund on the impact of removing sent) that measured short- and long-term sory Committee on Vaccine Safety (GACVS), thimerosal from vaccines, the cost of pur- blood mercury levels following vaccina- WHO has closely followed scientific evidence chasing vaccines in the Americas would in- tion, and epidemiological studies that ex- pertaining to the use of thimerosal as a vaccine crease from $97 million to $770 million (7.9 amined the relationship between thimero- preservative. Following the examination of times more). Furthermore, it would require sal and different health problems. Three available epidemiological information and the more resources to guarantee adequate stor- ecological studies that suggested a causal pharmacokinetic profile of this compound, it age and transport of vaccines. A single-dose relationship between neurodevelopmental concluded that there was no evidence of mer- vial (1 dose) occupies, in terms of space, 19.2 disorders and thimerosal were discounted cury toxicity in infants, children or adults ex- cm3/dose while a multi-dose vial (10 doses) due to methodological errors. In addition, posed to from vaccines. Therefore, occupies 4.4cm3/dose. Lastly, the volume of the steady increase in the number of au- there is no safety-related reason to change cur- annual vial waste would increase 4.2 times tism cases diagnosed in the United States, rent vaccination practices involving vaccines more, from 18.6 million vials to 70.3 million. despite the elimination of thimerosal from containing this preservative. most vaccines administered in the country, As a result, either of the two alternatives could was a convincing argument against any In response to the United Nations Environ- endanger the success of the routine immuni- causal relationship. In the other epide- ment Program’s (UNEP) proposal to approve zation programs as well as the vaccination miological studies reviewed, which were a world treaty to prohibit the use of mercury in campaigns with a predictable and significant conducted in different countries, no asso- increase in both morbidity and mortality along every product or process, which would entail ciation with neurodevelopmental disorders with very limited benefits for the environment. 1) replacing thiomersal in vaccines or 2) pro- could be identified. ducing vaccines in single-dose vials without Finally, both the SAGE and TAG encouraged preservatives. In response to these two propos- continuing the ongoing dialogue between the As a result, GACVS concludes that the als, SAGE and TAG members reaffirmed that health and environmental sectors in the country evidence available to date firmly supports thimerosal-containing vaccines are safe and in order to facilitate a common understanding the use of thimerosal as a preservative in irreplaceable components of immunization of the important role of thimerosal-containing inactivated vaccines. Research to gather programs, especially in developing countries, vaccines in the health of the population. new evidence of a causal relationship based on the following arguments: with thimerosal for scientific considera- On Thimerosal and Vaccines tion should be conducted using the highest 1. The substitution of the preservative. The Mercury exists in different forms and com- standards for causal inference in epidemio- available alternative preservatives cur- pounds that can be found in the environment. logical studies. Thimerosal gives millions rently interact unpredictably with existing Major sources of exposure include an accu- of people around the world access to safe vaccines and there is no consensus for the mulation of methylmercury within the food vaccines, and to date, there is no safe and use of these preservatives in the medium chain and through fish consumption. Meth- effective alternative. or long-term. Likewise, it would need to Immunization Newsletter Volume XXXIV Number 5 October 2012 Pan American Health Organization 7 ylmercury is a neurotoxic of major public leading causes of death: diphtheria, tetanus, Recommendations: health concern, with a half-life of approxi- , and Haemophilus influen- • Continue using ethylmercury (thiomersal)- mately 50 days. Thiomersal, which is also zae type b. They have also been used in both containing vaccines, following current vac- known as thimerosal, mercuriothiolate and the industrialized and developing countries cination schedules for children. sodium 2-ethylmercuriothio-benzoate, is a to protect their populations against • PAHO should mount an aggressive strat- compound that contains ethylmercury, and influenza [3]. egy and plan to effectively communicate not methylmercury. It is used to prevent the The Source of the Concern and educate health care workers, as well as proliferation of bacteria and fungus during ministries of health and environment, par- storage and, above all, during the use of open Since 1999, concerns have been raised about liamentarians, and other decision-makers, multi-dose vials of certain vaccines. Ethyl- the possibility of adverse effects, autism in and the media on the safety of thiomersal- mercury has a very short life with a half-life particular, following the use of thimerosal- containing vaccines. of roughly a week; it is quickly excreted, and containing vaccines. That year, the U.S. therefore does not accumulate in the human Food and Drug Administration (FDA) said References 1. WHO Meeting Report; Informal Consultation (April 3-4 body. that children who were vaccinated according 2012) to Develop Further Guidance on Vaccines for UNEP- convened Intergovernmental Negotiating Committee Meet- Some vaccines may contain trace amounts of to the immunization schedule for their age could be exposed to 187.5 µg of mercury, an ing 4 http://www.who.int/biologicals/Report_THIOMER- thimerosal even if it is not part of the final SAL_WHO_Mtg_3-4_April_2012.pdf formulation of the product, because it may amount that would exceed allowable methyl- 2. UNEP United Nations Environment Programme Nairobi, mercury exposure levels. Kenya, 31 October–4 November 2011. Addressing health in have been used in the production chain. This the mercury instrument. http://www.unep.org/hazardoussub- is true of inactivated vaccines to which this As stated previously, thimerosal consists of stances/Portals/9/Mercury/Documents/INC3/3_6_health_ad- vance.pdf compound is added to maintain sterility dur- ethylmercury, which is very different from 3. WHO Weekly Epidemiological Record, no. 30, 27 July ing production. Thimerosal has been used the neurotoxic methylmercury. It is the meth- 2012 Global Advisory Committee on Vaccine Safety, June since the 1930s in the manufacture of some ylmercury, not the ethylmercury, that causes 2012 thiomersal in vaccines. http://www.who.int/wer/2012/ wer8730.pdf vaccines and other medical products, and not histopathological brain lesions, and these are 4. WHO thiomersal and vaccines: questions and answers. http:// only in pentavalent vaccines (DPT-Hib-HB). different from the ones found in autistic chil- www.who.int/vaccine_safety/committee/topics/thiomersal/ dren. questions/en/ Currently, thimerosal-containing vaccines 5. Immunization Newsletter, October 2005, Vol. XXVII, No. 5: are used in more than 120 countries to im- It is important to clarify that the measles, Update on Thimerosal and Autism. Available at: http://new. paho.org/inb/. munize at least 64% of the annual world birth mumps, and rubella (MMR) vaccine does not cohort. These vaccines protect against four contain thimerosal.

The PAHO Revolving Fund and the Current Global Vaccine Market

For over three decades, as part of the Region- Other important international actors related • PAHO should maintain its commitment to al Expanded Program on Immunization (EPI) to vaccine procurement include UNICEF, strengthen operating and financial manage- established in 1977, PAHO has managed the GAVI Alliance, Bill and Melinda Gates ment of the Fund in order to provide in- Revolving Fund (RF) for the procurement of Foundation (BMGF) and Doctors without creasingly better service and greater credit vaccines and vaccination supplies on behalf Borders (Médecins Sans Frontières or MSF). capacity to participating countries and ter- of Member States. These organizations were convened to the ritories. TAG meeting, highlighting the importance of • In light of current challenges, PAHO should Although the RF has gained relevant strengths having all of the key stakeholders involved in continue building its knowledge of global and made significant contributions, it also vaccine procurement and deployment strate- markets and strive for continuous commu- faces considerable challenges including an gies at the table for this discussion. nication and coordination with its major insufficient supply of vaccines such as yel- Recommendations: partners in the global immunization field, to low fever vaccine, a reduction of the global • TAG congratulates PAHO’s EPI Revolving maintain updated information on the mar- supply of trivalent oral polio vaccine, a lim- kets where it participates, for the develop- ited supply base of one or two laboratories Fund for vaccine procurement and reaffirms its support to the Fund as a key pillar of im- ment of its procurement strategies. for new vaccines and the existence of other munization programs in the Americas. • TAG recommends that all those agencies stakeholders whose plans have an impact on • TAG recommends that Member States con- that deal with vaccine forecasting, procure- the world vaccine market, specifically dose tinue to participate in the Revolving Fund to ment and distribution meet periodically to availability and prices of some vaccines for continue obtaining the benefits of a strong exchange information on their activities and the Region. economy of scale in the procurement of vac- strategies to identify those areas in which The RF continuously seeks to address these cines, syringes and supplies. closer collaboration could facilitate the challenges, while preserving its principles of • The Revolving Fund should continue im- availability of vaccines, enhance security of supply, and encourage high quality at af- Pan-Americanism, equity, universal access proving vaccine forecasting, including new- fordable prices. and quality. ly available vaccines. The Immunization Newsletter is published every two months, in English, Spanish, and French by the Comprehensive Family Immunization Project of the Pan American Health Organization (PAHO), Re- gional Office for the Americas of the World Health Organization (WHO). The purpose of the Immuniza- tion Newsletter is to facilitate the exchange of ideas Comprehensive Family Immunization Project and information concerning immunization programs 525 Twenty-third Street, N.W. in the Region, in order to promote greater knowledge Washington, D.C. 20037 U.S.A. of the problems faced and possible solutions to those http://www.paho.org/immunization problems. An electronic compilation of the Newsletter, “Thirty years of Immunization Newsletter: the History of the EPI in the Americas”, is now available at: www. paho.org/inb. References to commercial products and the pub- lication of signed articles in this Newsletter do not constitute endorsement by PAHO/WHO, nor do they necessarily represent the policy of the Organization.

ISSN 1814-6244 Volume XXXIV, Number 5 • October 2012

Editor: Carolina Danovaro Associate Editors: Nabely Castillo and Cuauhtémoc Ruiz Matus © Pan-American Health Organization, 2012. All rights reserved.

Immunization Newsletter Volume XXXIV Number 5 October 2012 Pan American Health Organization 8

Improving Regional Vaccine Production Capacity to Meet the WANTED: Needs of the Americas Members of Trinidad and Tobago’s East Leo Club that collected money for PAHO’s Revolv- The Region of the Americas has proven experience in vaccine develop- ing Fund for vaccine procurement in 1982 ment and production. Also, in LAC there are national regulatory au- thorities (NRAs) with improved capacity for monitoring vaccine qual- In 1982, Trinidad and Tobago’s East Leo Club, formed of ity, safety and effectiveness during the pre and post-marketing phases. sons and daughters of Lions’ Club members, collected mon- ey to contribute to capitalizing the Pan American Health Or- Vaccine production in the public, as well as the private field, has served ganization’s (PAHO) Revolving Fund for vaccine procure- to meet a significant portion of the demand from NIPs. Despite this fact, ment. Through a variety of initiatives, which included car installed capacity has not necessarily been sufficient to cover growing washes and other community activities, the children’s club regional demand, since in many cases the production volume is only collected $1,500 for the Fund. geared toward fulfilling domestic needs, with little possibility ofex- porting vaccines. The establishment of technology transfer agreements Now that 30 years have passed and the RF manages a capital between the transnational pharmaceutical industry and regional produc- fund of $100 million and a purchase value of approximately ers has not yet led to improvements in local capacity to produce new $500 million, and buys about 60 different products for its vaccines; therefore, a more thorough analysis of the role regional pro- participating countries, PAHO is looking for those people, ducers can play in meeting the needs of countries in the Region for safe, then entrepreneur children, to better document that interest- effective and high quality vaccines is needed. ing experience. If you know any of these people, or were Recommendation: one of those children, we urge you to contact PAHO’s im- munization program at [email protected] PAHO should convene a task group with representatives from vaccine manufactures from Latin America and the Caribbean (LAC) to identify Reference common areas of work and brainstorm a LAC regional strategy for vac- 1. EPI Newsletter, February 1982, Vol. IV, No. 1: Donations to EPI Revolving cine research, development and production. PAHO should then report Fund. Available at: http://paho.org/inb/. back to TAG on this topic.