IMMUNIZE AND PROTECT YOUR FAMILY In this issue:

1 Americas Successfully Complete Phase 1 of Polio Containment 1 Pandemic Influenza (H1N1) 2009 and Vaccine Safety 3 ProVac: Cost-effectiveness Analysis of Rotavirus Vaccines 6 8th Vaccination Week in the Americas 7 How to Perform the Shake Test

Volume XXXII, Number 2 April 2010

Poliovirus Containment: The American Region Pandemic Influenza has Successfully Completed Phase I (H1N1) 2009 and Vaccine Safety Introduction Although the current influenza The American Regional Commission for Certification of Poliovirus Laboratory Containment and Verification (H1N1) 2009 pandemic is consid- of Polio-free Status (AMR RCC) held its 5th meeting in Buenos Aires, Argentina, from 4-5 March 2010. The ered moderate in severity, the pan- AMR RCC was established by the Director of the Pan American Health Organization (PAHO) in February 2004 demic influenza virus has caused an to independently document that the Phase I requirements for wild poliovirus (WPV) laboratory containment average of 6-14 deaths per 1 million had been fulfilled and to verify that the polio-free status of the Region remained unchanged. The purpose of population. In the Americas, as of 16 this 5th meeting was to review the final report from Brazil and report update from Canada, and to verify the April 2010, there have been at least completeness and quality of Phase I activities of all Member States of the Region. 8,309 deaths from confirmed cases reported in 28 countries of the Re- Current Status gion. From September 2009 to 16 April 2010, over 350 million doses Phase I laboratory containment for infectious and potentially infectious (WPV) materials requires each Mem- of the vaccine against pandemic in- ber State to conduct a nation-wide survey of biomedical facilities and compile an inventory of all facilities fluenza (H1N1) were administered holding infectious WPV materials. Phase I provides the facility database for all subsequent steps towards around the world to health work- global poliovirus containment. At its previous meeting in Punta del Este, Uruguay, the RCC concluded that the ers, high-risk groups, and the gen- American Region was nearing completion of Phase I. It requested Canada to present an updated report and eral population. In the Americas, as Brazil to present a final report at this current 5th Meeting in Buenos Aires. of 16 April 2010, 49.4 million doses As of March 2010, a total of 82,678 laboratories/institutions were identified in the Region of the Americas. Of had been administered in 22 coun- these, 59,618 (72.1%) were selected for the survey in accordance with the Phase I global guidelines. All labo- tries of the Region: Anguilla, Argen- ratories/institutions were classified into tina, Bahamas, Barbados, Belize, three risk categories (high, medium, low). Bermuda, Brazil, Cayman Islands, American Regional Commission for Certification of Poliovirus Laboratory Colombia, Costa Rica, Ecuador, El Sal- Containment and Verification of Polio-free status Eighty-six percent of low-risk laboratories/ Buenos Aires, Argentina institutions and 100% of high- and medi- vador, Guatemala, Honduras, Mexico, um-risk laboratories/institutions were in- Montserrat, Nicaragua, Panama, Peru, 4-5 March 2010 cluded in the survey. While most countries Suriname, Trinidad and Tobago, and

Hereby, the American Regional Commission for Certification of Poliovirus Laboratory surveyed all low-risk laboratories/institu- Uruguay. Containment and Verification of Polio-free status (AMR RCC) concludes and declares at their 5th meeting held in Buenos Aires, Argentina, 4-5 March 2010, that the WHO Region of the tions, eight countries surveyed representa- Americas has successfully completed phase I of poliovirus containment. tive samples of 13-59% of laboratories/in- Criteria for the Definition of stitutions to validate their classification as the Influenza (H1N1) 2009 Signatures of AMR RCC members low-risk. Responses were obtained from Pandemic all laboratories/institutions included in the survey. The influenza (H1N1) 2009 pan- Dr. Carlyle Guerra de Macedo Dr. Walter Dowdle demic is a scientifically documented President Rapporteur The surveys identified 215 laboratories/ institutions with infectious or potentially event in which a new influenza virus infectious WPV materials in nine countries. caused unusual disease patterns Dr. Claudette Harry Dr. Elsa Margarita Moreno Thirty-three countries and territories re- worldwide, predominantly impacting Member Member ported no laboratories with infectious or young people. potentially infectious WPV materials, and In 2005, the World Health Organiza- three (Colombia, Cuba, and Panama), de- tion (WHO) published a global plan Dr. Jesús Querales Castillo Member stroyed all WPV materials identified during the survey process. The countries retain- See H1N1 page 3 2 IMMUNIZATION NEWSLETTER Volume XXXII, Number 2 April 2010 PAN AMERICAN HEALTH ORGANIZATION ing infectious and/or potentially infectious WPV process. Canada’s successful application of the to initiate efforts in collaboration with WHO/ materials are Argentina, Brazil, Canada, Chile, Act for control and tracking of polioviruses and Geneva, to develop guidelines and plans to as- Costa Rica, Guatemala, Mexico, Trinidad & To- other infectious agents in institutions validates sist Member States in developing legislative or bago, and the United States. the advanced Canadian system as a potential regulatory text consistent with global policy on The AMR RCC also reviewed evidence presented model for other countries, both within the Re- post-eradication destruction or containment of by PAHO on vaccination coverage and acute flac- gion and globally. WPV materials. cid paralysis (AFP) surveillance, confirming the The RCC congratulated all PAHO Member States The RCC notes that after 19 years of not having Region’s uninterrupted polio-free status. The last and their National Committees for the submis- detected WPV with similar or better surveillance case of poliomyelitis due to a WPV was reported sion of final country reports. The RCC was im- than was present in 1991, the evidence that the in 1991, and the American Region was certified pressed with the quality and completeness of American Region remains polio-free is at least as free of endemic WPV circulation in 1994. the reports and the enormity of the effort put as strong, if not stronger, as it was at the time forth by all countries to meet Phase I goals and of certification in 1994. However, the RCC has AMR RCC Conclusions objectives. The RCC was appreciative of Mem- identified some countries in the Region that do ber States’ efforts to address recommendations not meet the required AFP surveillance stan- The RCC commended Brazil for its excellent re- made at previous meetings of the Commission. dards and high polio immunization coverage port and presentation and concludes that Brazil The RCC was confident that the reports and and may constitute a risk for WPV circulation in has successfully completed Phase I containment presentations from every country of the Region the event of importation, or for the emergence activities. The RCC was pleased with Brazil’s demonstrate that all facilities with infectious or of circulating vaccine-derived poliovirus. The comprehensive approach to national implemen- potentially infectious WPV materials have been RCC reaffirms its terms of reference “to evaluate tation of Phase I activities and that Brazil had identified. annual PAHO and requested National Contain- taken full advantage of the opportunity to estab- ment Commissions reports on polio immuniza- The RCC will provide a report on the finalization lish a database of laboratories with application tion, surveillance, and laboratory performance of Phase I to the Global Certification Commission far beyond the goal of poliovirus containment. in accord with GCC criteria”. (GCC) by the end of May 2010. The RCC notes The RCC also commended Canada for its pre- the lack of activity of the GCC and expresses its Finally, the American Regional Commission con- sentation comparing the list of laboratories concerns on this respect. cluded that the American Region had success- registered as a result of the Human Pathogens fully completed phase I of poliovirus contain- Recognizing the current progress in global polio and Toxins Act (2009) to the list of laboratories ment. identified and surveyed during the 2002-2004 eradication, the RCC encourages the Secretariat

Fifth Meeting of the AMR RCC: Recommendations

Phase 1 reports from countries of the Ameri- be submitted to PAHO on an annual basis. vention. can Region demonstrate the completeness and 2. Member States should ensure that the na- 6. The Secretariat, in collaboration with WHO/ quality of the national survey and inventory tional committee and a designated respon- Geneva, should report to the RCC at their activities, and provide critical documentation sible government official is continued as long next meeting on progress towards guidelines for the eventual Global Certification of the as required by the GCC. The name of the re- and plans to assist Member States in devel- Eradication of Poliomyelitis. The Regional and sponsible official should be communicated to oping legislative or regulatory text consistent national infrastructures that have been created PAHO annually. with global policy on post-eradication de- and the information gained through this signifi- 3. Member States with facilities listed on the struction or containment of WPV materials. cant achievement are valuable assets that must national WPV inventory should encourage Maintenance of polio-free status be maintained as polio eradication nears, full destruction of unneeded infectious and po- WPV containment is implemented, and global tentially infectious materials and submit docu- 7. The Secretariat should provide the RCC at certification is eventually declared. To ensure mented evidence of destruction to its National their next meeting with a detailed overview Member States remain alert and prepared to Containment Commission and PAHO. of AFP surveillance and polio immunization meet subsequent poliovirus requirements, the 4. PAHO Headquarters should ensure that the activities in countries of the Region, with spe- RCC recommends the following: Regional Report, which includes documenta- cific attention to Member States with sub-op- tion (both paper and electronic) submitted timal performance. The information should Containment from Member States, is securely maintained include a detailed analysis of data at national 1. Member States should ensure the national for future reference. and first sub-national levels. inventory of WPV-holding facilities is main- 5. The process and achievement of Phase I 8. PAHO should ensure a designated staff mem- tained and updated annually along with completion in the American Region should ber continues to be responsible for oversight maintenance of the Phase I report, support- be documented and published in the Weekly of polio activities, including containment, AFP ing documentation (both paper and elec- Epidemiological Report (WER) of the World surveillance, polio immunization, and secu- tronic), and the national laboratory data- Health Organization (WHO) and the MMWR of rity and maintenance of documents, as long base. An updated national inventory should the U.S. Centers for Disease Control and Pre- as is needed to complete Global Certification. PAN AMERICAN HEALTH ORGANIZATION IMMUNIZATION NEWSLETTER Volume XXXII, Number 2 April 2010 3 tance of the methodology and assumptions of ProVac: Essential Components of a Cost- the model. • Participants acknowledged the positive impact effectiveness Analysis for Rotavirus Vaccine of the incorporation of requested changes from the Paraguay workshop (otitis media, Introduction Methodology herd immunity, flexible schedules). • The model is more user-friendly than previous The fourth Regional ProVac meeting was con- The methodology used for the workshop was a versions, participants understood the Excel vened in Managua, Nicaragua, from 2-3 March combination of plenary sessions and practical background and found it more useful than the 2010. The ProVac initiative seeks to enhance exercises performed by the country teams. Ple- Visual Basic interface presented in Paraguay. national capacity to make evidence-based deci- nary sessions covered all components of a cost- • Participants who had attended the Paraguay effectiveness analysis, which included disease sions regarding new vaccine introduction. The workshop perceived progress from the Para- burden, vaccine efficacy and coverage, vaccina- objective of the workshop was for participants guay workshop’s approach of “playing with a tion program cost, health service utilization and to understand the main components of a cost- model” to the current approach of discussing costs prevented, as well as results and scenarios. effectiveness analysis and discuss possible data possible national and international data sourc- The country teams performed exercises to ad- es to perform a country-level analysis. sources, using rotavirus vaccine as an example. dress each of the model components in greater Even though some of the countries attending • Participants acknowledged a very good level details. Each country team was provided with a of oral presentations. the workshop had already introduced the rota- computer loaded with the model and internet virus vaccine, this vaccine was chosen because a • The ProVac Centers of Excellence have the access to the ProVac e-Support Center (www. right profile for a balanced approach that concrete vaccine example was needed, rotavirus paho.org/provac). To the extent possible, these vaccine is an expensive vaccine, and there are couples scientific rigor with a practical meth- country teams exercised populating the model odology to be implemented in countries of the still many countries interested in evaluating its with their national data. Participants were asked Region. introduction. to think of possible local data sources for each • The training on the utilization of scientific tools Ninety participants from 19 Latin American and model component. They were also challenged by EPI managers was considered a success. Caribbean countries attended the workshop. The to consider the quality of different data sources. • Promoting the formation of working teams in members of each multidisciplinary country team The final session focused on country experiences each country was considered very important. using the ProVac cost-effectiveness model, chal- were the PAHO focal point in that country, the lenges, and lessons learned. At the end of the The following are suggestions received for future EPI manager, a health economist, and the sur- workshop, forms were distributed to the partici- workshops: veillance manager for new vaccines. pants to collect feedback that would allow for fu- • Oral presentations should be integrated with Representatives from the following organizations ture model and workshop improvements. the practical exercises. also participated in the workshop: Ministries of • Some exercises should be conducted in gen- Health, the Center for Disease Control and Pre- Conclusions and Recommendations eral sessions using one single data set. • Sharing the model and exercises with the par- vention (CDC), Canadian Public Health Associa- The following comments were received as feed- ticipants in advance of the workshop. tion (CPHA), SIVAC Initiative, Harvard University, back regarding the model and the methodology • Considering a virtual introductory presenta- the London School of Hygiene and Tropical Med- of the workshop: icine (LSHTM), and the University of Medicine tion prior to the workshop to expose partici- • Participants gave very positive feedback about and Dentistry of New Jersey (UMDNJ). pants to the model and the terms and defini- the model itself, and there was general accep- tions of each variable to be discussed.

H1N1 from page 1 plan, which retains the six-phase structure of Director-General on an appropriate response. the response but regroups and redefines the In the emergency committee’s second meeting defining six phases of a pandemic in order to phases to more accurately reflect the pandemic on 27 April 2009, the decision was made that the identify increasing levels of risk. The document, risk based on observable phenomena. (Figure 1, epidemiological data from Canada, Mexico, and which provided recommendations to guide na- page 4) the USA showing person-to-person transmission tional authorities in pandemic planning, was the was sufficient to recommend that the Director- result of a December 2004 WHO advisory meet- Chronology of the Declaration of General raise the Phase from 3 to 4. On 29 April, ing to recommend national and international the Pandemic based on evidence of sustained transmission in steps to take before and during pandemics. In North America and the emergency committee’s the plan, pandemics are defined not in terms of Pursuant to the procedures established in the recommendations, the Director-General raised their severity, but of the transmission of a new International Health Regulations (IHR-2005) the Phase from 4 to 5. On 11 June, when the subtype of influenza virus with broader and sus- and adopted by WHO Member States in 2005, pandemic virus had already shown sustained tained transmission throughout the community. WHO Director-General Dr. Margaret Chan called circulation in more than one WHO Region, the After consultations in 2008, in April 2009 WHO a meeting of the emergency committee on 25 Director-General declared Phase 6 of the pan- published an updated version of the 2005 global April 2009 to assess the situation and advise the demic. 4 IMMUNIZATION NEWSLETTER Volume XXXII, Number 2 April 2010 PAN AMERICAN HEALTH ORGANIZATION

influenza (H1N1) 2009 differs from that of seasonal influenza, since pandemic influenza Definition of a pandemic predominantly affects young people, who get A pandemic is defined as the emergence of a new influenza virus that has caused sustained com- infected more often, end up hospitalized, re- munity outbreaks in two or more countries in a WHO Region and sustained community outbreaks quire intensive care, and die. WHO continues in at least in one other country in a different WHO Region. The criteria for the definition of a pan- in the view that the pandemic influenza has demic remain geographical dispersion and viral transmission. The clinical severity of the disease is had a moderate impact. Most likely, it will be an important consideration but differs from geographical dispersion, and is not currently included impossible to calculate the precise number of in the definition of a pandemic. WHO is working in substantial and measurable ways to incorpo- deaths and mortality rates until a year or two rate definitions of clinical severity in the general definition of a pandemic.* after the pandemic has peaked, and that cal- culation will be based on methods similar to * World Health Organization. Current phases of alert of the pandemic according to WHO (Internet); accessed on 19 those used to calculate excess mortality dur- April 2010 at: http://www.who.int/csr/disease/influenza/pandemic/en/index.html. ing seasonal influenza epidemics.

Severity of the Pandemic numbers do not reflect the actual mortality Safety of the Pandemic Influenza rate during the pandemic, which is undoubt- (H1N1) 2009 Vaccine 1. Estimates of mortality from seasonal in- edly higher than the laboratory-confirmed fluenza: During the annual peak of seasonal cases indicate. Since the signs and symptoms The safety profile of the pandemic influenza influenza, some 90% of deaths occur in indi- of pandemic influenza are similar to those of (H1N1) 2009 vaccine is quite similar to that of viduals aged >65 years who often already have many common infectious diseases, physicians the seasonal influenza vaccine. Since vaccination underlying illness. Although influenza can ex- often do not suspect infection due to the pan- activities began, no event has occurred that acerbate these preexisting conditions, diagnos- demic influenza (H1N1) 2009 and thus do not puts into question the safety of the pandemic tic tests for influenza are usually not conduct- order diagnostic tests. It is especially frequent influenza vaccine: ed, and the deaths are often attributed to the for cases to go undiagnosed in developing • No increase has been observed in the rate of underlying condition. Deaths from seasonal countries, where deaths from respiratory dis- abortion or intrauterine fetal death in preg- influenza are estimated using mathematical eases (especially pneumonia) are common. nant women who received the pandemic in- models to determine the excess deaths caused Even when tests confirm infection with the fluenza (H1N1) vaccine, compared with preg- by influenza. pandemic influenza (H1N1) 2009 virus in pa- nant women who have not been vaccinated. 2. Deaths from pandemic influenza: The num- tients with some underlying illness, many phy- • The reported rate of anaphylaxis continues ber of deaths from the pandemic influenza sicians attribute the death to the latter and not to oscillate in the expected range (0.1-1.0 (H1N1) 2009 reported by national authori- to influenza; therefore, these deaths do not cases/100,000 doses). Special emphasis ties and compiled by WHO are laboratory- appear in the official statistics. has been placed on the detection, accurate confirmed cases and not estimates. These The impact of mortality from the pandemic diagnosis, and treatment of anaphylaxis in

Figure 1. Pandemic Influenza Phases, 2009

PHASE 5-6/ PANDEMIC

PHASE 4 POST PEAK POST PHASE 1-3 PANDEMIC

TIME

PREDOMINATELY SUSTAINED WIDESPREAD POSSIBILITY DISEASE ACTIVITY ANIMAL INFECTIONS; HUMAN TO HUMAN OF RECURRENT AT SEASONAL FEW HUMAN HUMAN INFECTION EVENTS LEVELS INFECTIONS TRANSMISSION

Source: World Health Organization (http://www.who.int/csr/disease/avian_influenza/phase/en/). PAN AMERICAN HEALTH ORGANIZATION IMMUNIZATION NEWSLETTER Volume XXXII, Number 2 April 2010 5

the causality between the event and the vaccina- Vaccine Production: Types of Vaccine and Efficacy tion. Once the investigation has concluded, the case can be classified as coincidental (without The process for producing the pandemic influenza (H1N1) 2009 vaccine has been the same used a causal relationship), a program error (related to produce seasonal influenza vaccines. Because of the urgency to rapidly produce the pandemic to an operational aspect of the vaccination), or vaccine, some production phases were accelerated. However, vaccine production quality stan- a vaccine-associated event (causal relationship dards have been maintained, which can be confirmed by the constant drug surveillance estab- with one or more components of the vaccine). lished by the manufacturing laboratories themselves and by quality controls established by the As of 19 April 2010, 1,198 ESAVIs have been re- countries. ported in the Americas. Of these, 113 were clas- The pandemic vaccine used in the countries of the Region is inactivated, with and without adju- sified as serious.1 However, a thorough investi- vant. There is also a trivalent vaccine, which includes the pandemic strain (H1N1) and seasonal gation will help countries classify serious events (H3N2) and Brisbane strains. This formulation is similar in the Northern and Southern Hemi- as coincidental, programmatic errors, vaccine- spheres. Some countries in the Region have procured the trivalent vaccine through PAHO’s Re- related, or inconclusive. volving Fund. This formulation was recommended by WHO for the 2010-2011 period. The sensitivity of the surveillance systems in Current data show that the pandemic influenza (H1N1) 2009 vaccine is immunogenic. A single Northern Hemisphere countries such as Cana- dose is recommended for adults to obtain high immunity and two doses for children aged <9 da, China, European countries, and the United years. States (the first to administer the vaccine), was stepped up substantially in order to capture any order to avoid fatal outcomes. To this end, ty. Steps have, therefore, been taken to improve ESAVI from the pandemic influenza (H1N1) vac- the Brighton Collaboration Group developed ESAVI monitoring. Surveillance begins with the cine, which was being administered on a large definitions and degrees of diagnostic cer- report of an ESAVI. An ESAVI consists of clini- scale. These countries are now analyzing the tainty that were included in the Pan American cal symptoms occurring after an individual has compiled data so that they can provide sound Health Organization’s field guide Surveillance received a vaccine that raise concerns and are and consistent evidence on the vaccine’s safety. of Events Supposedly Attributable to Vaccina- supposedly attributable to the vaccination. It is Updates on the adverse events reported are no tion or Immunization (ESAVIs) Linked to the important to stress that although denoting a as- Pandemic Influenza (H1N1) 2009 Vaccine sociation in time, an ESAVI does not necessarily 1 An event is serious if it leads to death, hospitalization, pro- longed hospitalization, persistent disability and/or consti- and Crisis Prevention. imply a cause-and-effect relationship. Subse- tutes a threat to life. Serious is not a synonym of severe • Only two deaths associated with program er- quent investigations of the case will determine (intensity/severity). rors have been reported (in Canada and the Netherlands). In the case in Canada, timely adequate medical treatment was not given H1N1 Pandemic Vaccine Safety: Results from Clinical Trials to the person, who developed anaphylaxis, Results on the H1N1 pandemic vaccine safety are available from three recent clinical trials in which triggered death. In the case in the Neth- China1 (12,691 people aged 3-87 years/different formulations of the vaccine), the United States2 erlands, insulin was administered instead of (children and adults/vaccine without adjuvant) and Hungary3 (355 people aged 18-60+/vaccine the vaccine. without adjuvant). The following are the main conclusions of the studies: • The regulatory authorities in several coun- • The adverse events reported were moderate and limited; the most commonly reported ESAVIs tries around the world have jointly examined were pain at the injection site, cough, rhinorrhea, and nasal congestion. The most common the adverse effects of the vaccine that were severe event was fever. identified in clinical trials and compared these • The incidence of systemic reactions was similar in all age groups in China’s multicenter, ran- results with those for seasonal influenza. The domized, double-blind, placebo-controlled trial. On increasing the amount of antigen (7.5-30 conclusion reached was that the safety pro- µg), the number of adverse events increased as well. On the other hand, with increasing age, files of the two vaccines coincide; that is, the the number of adverse events decreased. adverse effects of the pandemic vaccine ob- • The incidence of local reactions ranged from 12-50%, while systemic reactions ranged from served in clinical trials are similar to those of 16-49% in all age groups (study in the United States). The most common systemic reactions the seasonal influenza vaccine. reported in adults were headache, myalgia, and discomfort. Most common in children were • After analysis of the data reported by the frequent crying, irritability, loss of appetite, and insomnia. VAERS system (U.S. Vaccine Adverse Event • The number of events increased when the pandemic vaccine without adjuvant was adminis- Reporting System) from October-November tered at the same time as the seasonal influenza vaccine (from 10-18%). This difference is due 2009, it was concluded that the pandemic in- to moderate soreness at the injection site reported by individuals who received the two vaccines fluenza (H1N1) vaccine continues to be safe, (study in Hungary). since there was no increase in ESAVIs report- ed compared with the frequency of ESAVIs 1 X-F Liang, H-Q Wang, J-Z Wang et al.. Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: a multicentre, double-blind, randomized, placebo-controlled trial. Lancet 2009. Published online December 16. reported with the seasonal influenza vaccine. DOI: 10.1016/S0140-6736(09)62003-1. 2 E Plennevaux, E Sheldon, M Blatter, M-K Reeves-Hoché, M Denis. Immune response after a single vaccination against ESAVI Monitoring 2009 influenza A H1N1 in USA: a preliminary report of two randomized controlled phase 2 trials. Lancet 2009. Pub- lished online December 16. DOI 10.1016/S0140-6736(09)62026-2 One of the countries’ concerns—among the au- 3 Z Vajo, F Tamas, L Sinka, I Jankovics. Safety and immunogenicity of a 2009 pandemic influenza A H1N1 vaccine when thorities and general public alike—is vaccine safe- administered alone or simultaneously with the seasonal influenza vaccine for the 2009–10 influenza season: a multi- centre, randomized controlled trial. Lancet 2009. Published online December 16. DOI 10.1016/S0140-6736(09)620:39-0. 6 IMMUNIZATION NEWSLETTER Volume XXXII, Number 2 April 2010 PAN AMERICAN HEALTH ORGANIZATION longer issued as often as they were at the begin- miscarriages that could occur as a result of the many estimates, the number of doses distrib- ning of vaccination (daily or weekly reports vs. vaccination. The comparison between what is uted, not the number of doses administered. monthly or quarterly). anticipated and what is observed serves as one As a result, due to the uncertainty in estimat- Some studies have been published estimating more element for assessing the causal relation- ing reliable base rates for some diseases, cau- the rate of adverse events that could occur in ship between vaccination and the ESAVIs identi- tion should be used in interpreting these data, mass immunization campaigns against influ- fied. bearing in mind the assumptions used when the enza (H1N1) 2009. For example, in 2009, Steven Without denying the usefulness of predicting es- estimates were calculated since they could raise Black et al. published an article in the The Lan- timates prior to vaccination activities—since they false alarms or lead to counterproductive infor- cet stating that in a six-week period, for every 10 help assess the vaccine’s safety—it is important mation on the safety of the vaccine. million people vaccinated, 22 cases of Guillain- to note the following: Some countries have been able to closely moni- Barré Syndrome (GBS) would occur in the United • Identifying reliable base rates for any disease tor adverse events associated with the influenza Kingdom, 83 cases of optic neuritis in the United is difficult, due to the lack of systematic re- (H1N1) 2009 vaccine during mass vaccination. States, and 397 miscarriages the day following porting of diseases, underreporting, lack of The health authorities of Taiwan, for example, vaccination for every 1 million pregnant women standardized case definitions, different meth- estimated that 27 GBS cases would occur dur- vaccinated. odologies for identifying cases, etc. ing the six weeks following vaccination, after 15 It is important to note that these are the number • The denominator used is also an estimate and million doses had been administered. However, of cases expected for each of these pathologies is often unknown (for example, the number of by 16 March 2010, 5.66 million people had been vaccinated and only four GBS cases had been for a population of 10 million in a six-week pe- individuals vaccinated), and it is critical infor- confirmed during the following six weeks. riod. However, these estimates do not indicate mation in determining whether the number of the number of cases of GBS, optic neuritis, or events observed is greater than expected. In See H1N1 page 8

th launch of WHO/AFRO’s first vaccination week in 8 Vaccination Week in the Americas 2011. Dr. Mihigo participated in the VWA launch- ing events in Haiti and the Dominican Republic, The 8th annual Vaccination Week in the Ameri- ditional information on VWA 2010 can be found and both delegates spent two days in Washing- cas (VWA) was celebrated throughout the Region online at www.paho.org/vwa. ton after VWA had concluded to meet with Pan of the Americas from 24 April to 1 May 2010. Un- This year, PAHO also hosted two delegates from American Health Organization staff involved in der the slogan of “Reaching everyone,” countries the African Region of the World Health Organiza- the initiative. The Americas look forward to sup- and territories realized a wide variety of vacci- tion (WHO), Drs. Levon Arevshatian and Richard porting Africa in the organization of their vac- nation and social communication activities and Mihigo, to learn more about the organization and cination week and to continue working towards some also took advantage of VWA to integrate implementation of VWA, in preparation for the the goal of a Global Vaccination Week. other preventative interventions with vaccina- tion. Prior to the initiative, countries and territo- ries had planned to vaccinate approximately 42 million people, including 27 million individuals against influenza. Final activity reports from the countries are expected to arrive shortly for con- solidation into the final VWA 2010 report. Regional VWA launching events took place in Ni- caragua, on the United States/Mexico border (in conjunction with National Infant Immunization Week in the U.S.), in Haiti and the Dominican Re- public, and on the border between French Gui- ana and Suriname. The latter can be considered as the first ever bi-regional launch (Americas- Europe), as French Guiana is a French overseas department and, therefore, part of the European Union. All VWA regional launching events count- ed on the participation of high level authorities, including political and religious leaders, heads of international organizations and community leaders. Smaller scale, tri-national, bi-national, and national launching events also occurred in the majority of other countries in the Region. Ad- PAHO Director, Dr. Mirta Roses, vaccinating a child in Jimaní, Dominican Republic, during the 2010 VWA. PAN AMERICAN HEALTH ORGANIZATION IMMUNIZATION NEWSLETTER Volume XXXII, Number 2 April 2010 7 How to perform the “Shake Test” The “shake test” was designed to detect freeze damage in aluminum-based, adsorbed, freeze 10:25 a.m. sensitive vaccines such as DTP, DT, Td, TT, ty- phoid, and hepatitis B. These vaccines must nev- er be frozen as this reduces their immunogenic- ity. When these vaccines freeze, the alum content gets loose, tends to agglomerate, and sediments SUSPECT (Test Vial) faster than vaccines that have not suffered freeze damage. If you suspect that a vaccine has been frozen (e.g., thermometer marks temperature <0oC), conduct a “Shake test”: FROZEN (Control Vial) Minutes after placing the vials on the table. Step 1. Freeze a vial until it is solid; this will be your con- trol vial – call it “FROZEN”. 10:28 a.m. Step 2. Allow FROZEN vial to thaw completely. Step 3. Select one sample of each vaccine you suspect has been frozen – call it “SUSPECT”. Step 4. Shake FROZEN and SUSPECT vials. Step 5. Observe FROZEN and SUSPECT vials side-by- 10:31 a.m. side to compare how they sediment (5-15 minutes).

IF SUSPECT vial sediments slower than FRO- ZEN vial USE (see Figures at left).

IF SUSPECT vial sediments at the same rate as or faster than FROZEN vial DO NOT USE.

A Shake Test must be performed for each separate batch of vaccine.

10:33 a.m. Further information: • To see a step-by-step video on the Shake Test, go to http://vimeo.com/8389435. • To download a WHO learning guide on how to use the shake test, go to https://apps.who. int/vaccines-access/vacman/temperature/ shake_test_learning_guide.htm. Sedimentation in test vial is slower • PATH Poster: Has your vaccine been dam- than the frozen control vial. aged by freezing? Available at: http://www. Test vial has not been damaged and path.org/files/TS_cc_shake_test.pdf. can be used. 8 IMMUNIZATION NEWSLETTER Volume XXXII, Number 2 April 2010 PAN AMERICAN HEALTH ORGANIZATION

H1N1 from page 6 Region through PAHO’s Revolving Fund come infections and deaths from this disease. It is im- In general, a misinterpretation of estimated from laboratories that have been prequalified portant that the population be properly informed base-rate and/or the results of ESAVIs could not by WHO. As is known, the world’s principal ref- about the benefits of vaccination and the safety of only damage pandemic influenza (H1N1) vacci- erence on vaccines for public health is WHO, the vaccine. Its use should be promoted and reli- nation activities but also contribute to a loss of which monitors and certifies the quality and able technical and scientific information provided. public confidence in the vaccine and undermine good practices of the manufacturing laborato- the credibility of the health services. ries. Pandemic vaccine purchase for countries of Assessment the Americas was made through the Revolving An external assessment of the global response to Communication in Risk Situations Fund; a few countries also opted to purchase the influenza pandemic has begun. The purpose Faulty communication strategies and uncertainty directly from the manufacturing laboratories; about the vaccine’s safety may have caused the and others received donations from WHO and/ of the assessment is to identify ways to improve news media to report on pandemic vaccination or industrialized countries. the international community’s response to public in a way that contributed to lower coverage. Im- health emergencies in order to protect the public. Regarding donations from industrialized coun- PAHO/WHO welcomes with satisfaction the op- munization remains the cornerstone of a pan- tries to developing countries, it is untrue that portunity to learn from this exercise and expects demic response. the reason for these donations is that the vac- the assessment committee to provide clear, criti- Public health officials and the news media should cine is ineffective or that the donor countries’ cal, transparent, reliable, and independent feed- know how to respond jointly and appropriately own populations have refused vaccination. De- back to reinforce successful activities and rethink to any misunderstanding or inaccuracy about veloped countries prioritized the vaccination of the less successful ones, facilitating a more effec- the safety of the vaccine that could trigger panic up to 50% of their population and, as a result, in the population. A joint health/news effort calls purchased large amounts of vaccine. As the pan- tive response to the next health emergency. for partnerships with the media, as well as the demic evolved, these countries adjusted their This article is adapted from Facts About the Definition of implementation of a plan for crisis and risk com- vaccination plans, putting the emphasis on the the Pandemic Influenza (H1N1) 2009 and Vaccine Safety. munication. three main risk groups, which account for ap- The full version of the document (with a complete list of ref- proximately 20% of the total population. The erences) is available at: www.paho.org/PandemicH1N1_Vac- Procurement of the Pandemic Vac- result was a vaccine surplus. cineSafety. cine in the Americas The use of the pandemic influenza (H1N1) 2009 All vaccines procured by the countries of the vaccine is a great opportunity for preventing

The Immunization Newsletter is published every two months, in English, Spanish, and French by the Immunization Unit of the Pan American Health Organization (PAHO), Regional Office for the Americas of the World Health Organization (WHO). The purpose of the Immunization Newsletter is to facilitate the exchange of ideas and information concerning immunization programs in the Region, in order to promote greater knowledge of the problems faced and possible solutions to those problems.

References to commercial products and the publication 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 XXXII, Number 2 • April 2010

Editor: Jon Andrus Associate Editors: Béatrice Carpano and Carolina Danovaro

Immunization Unit 525 Twenty-third Street, N.W. Washington, D.C. 20037 U.S.A. http://www.paho.org/immunization