By Dr. Anne von Gottberg, Respiratory and Meningeal Pathogens Research Unit, National Institute for Communicable Diseases
This article was originally published on www.vaccineswork.org and is cross-posted here with permission.
If you had looked at South Africa’s invasive pneumococcal disease (IPD) surveillance data before 2002, you would have never guessed that one day that data would land on the pages of the New England Journal of Medicine.
Even I thought such a feat was impossible. Surveillance for IPD was passive and patchy – certainly not the kind of data you could use to examine trends or measure impact. In 2002, experts in pneumonia and respiratory disease suggested that we completely revamp the system: start measuring antimicrobial resistance and serotypes, obtain clinical data from cases to explore risk factors for resistance. Although this was long before the pneumococcal conjugate vaccine (PCV) was introduced, we knew any investments we made in the surveillance system now would pay huge dividends later, and possibly allow us to measure the impact of PCV introduction.
An example of disease surveillance activities. Here, Noluthando Duma works in the lab. Photo: NICD.
Revamping a national surveillance system was not an easy task. Our institute managed the process - from employing surveillance staff throughout the country to collecting data - and we had many, many challenges. This project seemed so unusual, so impossible, that it was difficult to convince anyone to join us. We would interview surveillance officers at remote regional sites who wondered how they could report to a central office in Johannesburg, given that they had never even been there; they couldn’t imagine how such a big, unwieldy national program could ever work. We would answer their questions with what I hoped sounded like confidence, but the truth was that we were figuring out the answers as we went along.
Despite these human resource challenges, we charged ahead, but it was a slow-and-steady race. At our national surveillance officer and principle investigator meetings, we had to bring together key stakeholders to discuss the surveillance network. We had to get buy-in on the methods, the case definitions, the flow of data, and sharing of information, and then we had to hire staff to operationalize our ambitious plans. Many new hires had never been on an airplane before, and some had never seen the ocean – the surveillance network really made South Africa smaller, bringing people together in the “new South Africa” in ways that I could not have predicted. So we anxiously booked window seats, made time for quick excursions to the beach, and hoped for the best. And although we had our fair share of hiccups along the way, our small team continued to grow, the years passed, and we kept on finding ways to silence the naysayers!
Meanwhile, things did not stay still around us. The South African government suddenly found the political will to tackle the HIV/AIDS epidemic, and with a tremendous effort, the government and civil society rapidly improved care of HIV-infected pregnant women, HIV-infected children, and adults in general. With these sudden improvements in healthcare, IPD also changed, making it more difficult to attribute any declines to the vaccine, even with the new surveillance system. But through a series of discussions with local and international colleagues and friends, countless conference calls, and careful review of the data, it finally became possible to tell the story that was in the data, collected for so many years by our dedicated surveillance teams.
Colleague Kedibone Ndlangisa conducting lab work. Photo: NICD
Last week, as experts and decision makers gathered in Kenya to discuss the results of various PCV impact studies from across Africa – all showing significant reductions in pneumococcal disease after the introduction of the vaccine – I was reminded of how far we had come on our journey and the many lessons learned on our path.
By maintaining our slow-and-steady approach remembering to “ask a friend” when we were stumped, and above all continuing to plow on in the face of challenges, we were able to turn data that at first glance may have looked like a mess into a meaningful and robust assessment of the impact of PCV.
This study is part of the the Vaccine Implementation Technical Assistance Consortium (VITAC) - a collaboration of PATH, CDC, and IVAC - supports the achievement of the mission to save lives, prevent disease, and promote health through timely and equitable access to new and underused vaccines. VITAC is focused on accelerating the introduction and sustained use of vaccines by creating the evidence base, advocating for evidence-driven decision making, and establishing a platform for countries to assess the resources needed for sustained and optimal use of vaccines.
This post originally appeared on the VaccinesWork blog and is cross-posted here with permission.
By Huma Khawar
In 2012, Pakistan was the first South Asian country to introduce the pneumococcal vaccine with Gavi support. Provided free of charge to children under the age of five, the vaccine protects against a major cause of pneumonia, a disease that is a major killer of children worldwide. But in order for any vaccine programme to be successful, information and support are essential. And where do many people get their information? The media.
The question and answer session in action. Photo: Huma Khawar
Dr Taimoor Shah, Deputy Director Khyber Pakhtunkhaw province’s Expanded Programme on Immunization (EPI), knows this well. On World Pneumonia Day last November, he took the opportunity to gather a room full of journalists of all backgrounds at the Press Club in Peshawar, to talk specifically about the pneumococcal vaccine and to answer their questions.
The result was a discussion that sounded more like a medical classroom than a group of reporters. How many vaccines are included in a child’s immunisation programme? What are the diseases that can be prevented through immunisation? How expensive is the pneumonia injection? It was difficult to decide whether to feel surprise at the lack of awareness among the media about vaccine preventable diseases or to be happy at the eagerness and genuine interest expressed in the reasons for Pakistan’s high rates of child mortality.
The session was both informal and interactive. Journalists from different organisations suggested ways to educate people on vaccination and eradication of fatal diseases through media messages. They concluded that it was the common duty of parents, government health institutions, media and civil society to take steps for overcoming health issues through vaccination and timely treatment.
One journalist confessed that although he knew all about how and when to give the different vaccinations, he didn’t know the importance of each. ”It will be easier, he said, to convince mothers on the importance of getting their babies immunised.”
The session also gave the health journalists an opportunity to express their own opinions and share insights. They talked openly about how, over the years, with so much money and emphasis directed towards polio eradication, routine immunisation had taken a backseat.
By the end of the session, some 30 plus media personnel had learned much more about vaccines and routine immunisation. One digital reporter admitted that this type of question and answer sessions was essential as a vast majority of journalists have limited knowledge of vaccines and their potential.
“A lot of mothers get their information from newspapers. Media should be up to date. If their knowledge is suspect, they will pass on wrong information to parents. This can be very dangerous,” he said.
And in a country where each year one in twelve children born die before reaching the age of five, many of them due to vaccine-preventable diseases, spreading this newfound knowledge can only be a good thing.
Photo: Humar Khawar
Huma Khawar is a freelance journalist and IVAC communications consultant who works in Pakistan.
Huma Khawar is a freelance journalist and IVAC communications consultant who works in Pakistan.
This post originally appeared on the VaccinesWork blog and is cross-posted here with permission.
Vaccine implementation requires policy and community-level approaches to ensure on the one hand that vaccines are available and on the other hand that parents bring their children to be immunized. Two events held in Pakistan this year on World Pneumonia Day illustrate the importance of these approaches.
On the eve of World Pneumonia Day, as a joint initiative of the communications team at the Federal Expanded Program on Immunization (EPI), which includes Pakistan’s EPI and partners from Gavi, UNICEF, and Japan’s International Cooperation Agency, a meeting with members of Provincial Assembly of Sindh was held to discuss immunization, not just for pneumonia but the entire routine immunization program and polio, which is of course a top priority for the country.
More than 70 members of the Sindh Assembly attended. Deputy Speaker Syeda Shehla Raza opened the meeting, followed by remarks by Ms. Ayesha Raza Farooq, Coordinator Prime Minister’s Polio Cell, who spoke about the role of the Federal government in routine immunization and the Prime Minister’s commitment to the cause. Ms. Shahnaz Wazir Ali, Provincial Coordinator for public and primary health care programme, spoke about the current status of polio and routine immunization in Sindh, where vaccine coverage levels are very low. Members expressed their concern about the overall 29% coverage of routine immunization in the province and recommended legislation on compulsory immunization to improve the current state of the coverage. The meeting concluded with a declaration presented by Syeda Shehla Raza on behalf of all members in support of Immunization and Polio Eradication Program.
The next day, in Islamabad, the capital city of Pakistan, civil society organizations working with Expanded Programme on Immunization and Civil Society Human and institutional Development Program held an awareness raising event in a minority slum community. More than 120 children and their mothers participated. The event included a puppet show that gave the children information about immunization, followed by a quiz with prizes awarded. The children also enjoyed face painting and games while an EPI vaccinator administered PCV 10 to children who had previously been missed in the community.
Many other organizations across Pakistan took advantage of the day to draw attention to pneumonia, which kills more than 100,000 children in Pakistan each year and sickens many more.
Above: the one day event for under privileged children in Islamabad, Pakistan. Messages on pneumonia and other preventable diseases were given by doctors to children and their mothers. A quiz competition on vaccine preventable diseases and a puppet show was also part of the event.
Photo: Huma Khawar
Daniel Feikin, MD, MSPH
Special thanks to Daniel Feikin, MD, MSPH, for sharing his insight on his team’s latest publication. Dr. Feikin has been with the U.S. Centers for Disease Control and Prevention (CDC) for 15 years, where he spent 6 years with the Respiratory Diseases Branch and also served as the Epidemiology Section Chief for the International Emerging Infections Program in Kenya. Dr. Feikin has worked on a number of projects including surveillance establishing the burden and epidemiology of respiratory and diarrheal illness. Since 2010, Dr. Feikin has served as the Director of the Epidemiology team at the International Vaccine Access Center (IVAC).
Published in the September issue of PLOS Medicine, Serotype-Specific Changes in Invasive Pneumococcal Disease after Pneumococcal Conjugate Vaccine Introduction: A Pooled Analysis of Multiple Surveillance Sites analyzes the rates of invasive pneumococcal disease after the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7). Dr. Feikin and colleagues from IVAC and CDC conducted this meta-analysis which showed that a reduction in all-cause and vaccine-type invasive pneumococcal disease happened rather quickly and was sustained for seven years after the introduction of PCV across the study sites. In the following interview, Dr. Feikin shares his insight on the issue of serotype replacement and how this it relates to decision making regarding PCV use.
What is serotype replacement (SR) and why is it an issue?
We have a unique situation with pneumococcus and pneumococcal vaccines with respect to serotype replacement. With pneumococcus, serotypes are defined by the kind of sugar capsule that surrounds the bacterium, and 90 different types have been defined. This creates a challenge for vaccines, which are based on specific serotypes. The first iteration of this conjugate vaccine could only fit in seven serotypes. They put the seven most common serotypes that you’d find in the US and Europe into the vaccine – that covered about 85% of the disease in the U.S.
First, SR was observed in the nose, which is where pneumococcus resides. Most of the time, the bacteria doesn’t cause disease, it just lives there in back of the nose (the nasopharynx) and a small percentage of the time, the bacteria in the nose will go on to cause an infection. When you get vaccinated, you get rid of the seven pneumococcal serotypes contained in the vaccine from the nose – quite effectively and quite rapidly. But what we also saw was that the seven serotypes that were wiped out by the vaccine were replaced by other serotypes of pneumococcus. That phenomenon – when you get rid of [serotypes] and they are replaced by others – is dubbed SR. The concern was: this is what happens to the bacteria living in the nose; does the same thing happen with disease caused by those bacteria? Are you just getting rid of the disease caused by the seven serotypes in the vaccine and having it be replaced by pneumococcal disease (PD) from the other serotypes? If that were to happen, you have the paradoxical situation of a vaccine that works against the seven serotypes you want it to work against, but your overall disease rates might not change in the long run because of SR. It was a really important question about whether this vaccine had an overall impact on disease – we needed to clarify whether SR exists and how much it exists.
What type of study did you choose to look at this issue and why did you feel it was the best way to research this question?
We conducted a meta-analysis, using 21 databases that were identified, to look at IPD rates after PCV7 introduction. When you are considering PD, you have to think about several different types of disease. The first type of disease is called invasive pneumococcal disease (IPD). IPD is the most straightforward because it means bacteria have invaded a normally sterile site – usually the cerebrospinal fluid, (the fluid surrounding the meninges) or the blood – and you can grow the bacteria from this fluid so it can be detected and positively identified. But the much bigger burden of PD is pneumonia, and most of the time when you have pneumococcal pneumonia you’re not going to isolate the bacteria since you can’t get a sample from the lung to grow and it normally isn’t a sterile site. So, when you want to look at SR, you are limited to looking at IPD – where you are able to culture the pneumococcus. That’s why the study focuses on IPD.
The second thing to understand is that there have been lots of individual studies from different countries, or different sites from the same country, that have looked at the issue of SR. There were many reports that came out after vaccine introduction and they were variable. There were some sites that showed very little SR and big impact of the vaccine. Then, there were other studies that showed up to full SR, meaning that you get rid of the vaccine serotype [with] full replacement by non-vaccine serotype (NVT), so in those sites there were no changes in overall disease rates.
This led to a lot of confusion. As countries in Africa and Asia were thinking about introducing PCV, they were concerned and somewhat confused about this issue of SR and wanted to know if PCV was worth their investment. That was the impetus in doing the study and it’s unclear why there were different results in different places. Some of it might have been that there truly was more SR in some sites, but it also could have been methodological differences or that some sites had very small samples sizes. One outlier site was potentially getting a lot of attention and people were looking at that saying there was complete SR, whereas another site was not showing that. So the idea behind the study was to put all the sites together, weigh all the studies according to their size and findings, and see if we could come up with some sort of summary of SR.
In the course of this analysis, was there anything that was surprising to you?
I have two answers for that. First, although a lot of countries had introduced PCV7, there weren’t many sites that had done the type of surveillance that we felt would be appropriate for this type of analysis. There were sites that were doing surveillance, but when you boiled it down to who met stringent criteria for being able to evaluate SR, there weren’t as many as I thought. That was a lesson because people are out there publishing studies and making conclusions about SR with limitations in their surveillance, which we felt would affect their interpretation of SR, so we did not include those types of studies. We were fairly rigorous in our inclusion and exclusion criteria, so we only ended up including 21 studies.
The second thing that was somewhat surprising to me in the results was that when we looked at children, and when we looked at the overall impact of this vaccine on children, there was about a 50% reduction in overall IPD. So, overall IPD decreased by half. We saw that decrease happen by the first year after the vaccine was introduced and it stayed at roughly 50% reduction all the way out to about seven years. I thought that initially there would be a growing reduction in overall PD over time. The drop in the first year was greater than I thought – suggesting that this vaccine had a pretty fast impact on pneumococcal epidemiology in children – and it didn’t change a lot after that first year. Now, there was a lot going on with each progressive year, so vaccine types started to go down and they continued to go down out to seven years until they were virtually gone. You were getting a lot of change in the different serotypes starting in the first year after vaccine introduction and continuing out, but changes in the vaccine types and changes in the NVTs balanced each other out, so this overall 50% reduction remained fairly consistent over the seven years.
How could this study contribute to policy making?
I think that for policy makers (people that don’t think about PD everyday), I think their take-home point is that there’s about a 50% reduction in IPD in children and it lasts all the way out to seven years. There is SR; it exists. It’s a real phenomenon, but the proportion of disease caused by vaccine serotypes is greater than non-vaccine serotypes, so the vaccines do have an overall impact on disease in children. I think that’s the first message.
The second is that you do see a herd effect in adults. There is a decrease in overall IPD in adults. It’s not as great as what is seen in children and it’s a bit delayed, but at least in the countries that introduced PCV, there was herd protection among adults – which could potentially have a big impact for countries, especially low-income countries, that have a lot of PD in adults. For a decision maker, hopefully that’s the message they get from this.
Are there any plans that you know of to build on the evidence provided by this study, and investigate SR in higher valency PCV?
There are some clear limitations to this study. The first limitation is that this study looked at the impact of the 7-valent PCV. That vaccine is no longer made. Countries are introducing either 10-valent vaccine or 13-valent vaccine. Much of the SR that we saw occurring came from the six extra serotypes that were not in the 7-valent vaccine but are now in the higher valency vaccines, so we suspect that these higher valency vaccines would take care of a good deal of the SR that we saw.
What we don’t know is: Are there other serotypes that are waiting in the wing that will cause SR in the same way? It would be important to follow countries as they introduce the higher valency vaccines and do a similar type of analysis several years out after the vaccine has been introduced. The problem is: we showed that you really need to go out to five or more years after vaccine introduction to see what exactly is going to happen to this dynamic process overtime. You can’t do the studies yet because the vaccines have just been introduced in the last couple of years so we need to wait, particularly for developing countries because they are just introducing.
The second major limitation is that the studies we looked at in our analysis were mostly from developed countries (North America, Europe, and Australia). There were a few indigenous populations in our data set – the Navajo and the Australian indigenous – which might be more like the low-income country populations, but not exactly the same. So, it is possible that in Africa and South Asia, where the epidemiology of PD is different, the results of the vaccine could potentially be different as well. It would be important to do a similar type of analysis in those countries. I think this type of analysis needs to be repeated in a few years, and it needs to be repeated in low-income settings that have the higher valency vaccines.
Do you have any other thoughts that you want to convey that we have not covered?
I think there is one thing, not based on the data itself, but just a comment. One of the things this study showed is the power of collaboration. Any single site would not be able to do this type of analysis, but they showed data from their own site and they made conclusions for their own site. But in order to understand an epidemiologic concept in a broader way that may vary site by site, you really need to have data from different places. The willingness of investigators to collaborate on this project, to lend their data to be looked at, to work together to make some sort of conclusion that was bigger than their own data was a really valuable exercise. This type of collaboration between sites is becoming more and more important, and we’re seeing more of it happening in the field of epidemiology. So, the example of doing a multi-site analysis, where sites give their data and they participate in the interpretation, was a valuable lesson and exercise.
By Dr. Samba Sow
Dr. Samba Sow is Director General of the Center for Vaccine Development – Mali (CVD Mali) and a Professor of Medicine at the University of Maryland School of Medicine. This blog is cross-posted from Lancet Global Health.
Scientific research, by definition, is about process. Scientists must follow carefully developed guidelines and established protocols to make sure research is conducted validly, accurately, and ethically. As any field researcher knows, meticulous attention to detail is challenging at the best of times, when obstacles like staff turnover, equipment shortages or delays, power outages, strikes, security concerns, and disruptive rumours are not out of the ordinary. But these “everyday” logistical challenges of doing research are further compounded when political instability surrounds your research site.
In the past year, my colleagues and I at Center for Vaccine Development (CVD) Mali faced immeasurable challenges in keeping research efforts going when the insurgency that has afflicted our country for decades began moving southward and threatening the capital city of Bamako, where our research centre is located. Read the full blog at the Lancet Global Health.