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IVAC Blog

 

The news on the pre-qualification of Typhoid Conjugate Vaccine (TCV) by the World Health Organization on January 3rd, 2018 and endowment by Gavi have dawned a unique beginning for the entire field of public health. For the first time, a vaccine has been prequalified by WHO that is only needed in the routine immunization programs of of low and middle- income countries in South Asia and Africa.

My team and I have been working on meningitis and pneumonia for the last several decades to generate evidence and facilitate the introduction of vaccines against Haemophilus influence type b (Hib) and Streptococcus pneumoniae - two devastating organisms that affect children under 5 years of age in developing countries. When both vaccines were introduced in Bangladesh, we were proud but not satisfied. Much to our surprise, during all our surveillance studies, typhoid always emerged as the largest fraction of all invasive bacterial diseases, in spite of the fact that we were not even looking for it. Typhoid, then, was so neglected that it did not even make it to WHO’s list of neglected diseases. Quite rightly, John Maurice wrote in 2012 “Whoever invented the phrase ‘out of sight, out of mind’ must have been thinking of typhoid fever” (Lancet, 379(9817):699-700).

Historically, three countries of South Asia, Bangladesh, India and Pakistan, were assumed to bear the largest burden of typhoid. However, extended surveillance studies in recent years have elucidated its true burden in South Asia and several countries in Africa, which has changed the color of the world map on typhoid burden. Generation of such evidence incentivized overcoming the inertia and brought about the much needed momentum and energy to talking about typhoid.

Bangladesh scene

Photo credit: Sarah Lindsay, Sabin Vaccine Institute

There are a few ways of treating and preventing typhoid: through use of effective antibiotics, through improvement of water supply, sanitation and hygiene (WSH) systems and through vaccines. With rising antimicrobial resistance, antibiotics are becoming less effective; improvements in WSH worked well in developed countries, but comes with an exorbitant price tag in any low- and middle-income nations. It is expensive and challenging enough to provide every family with a constant water supply in a developing nation, and supplying water that is safe comes only after that. So, a vaccine is really the lowest hanging fruit. There have been vaccines for typhoid for decades in the market, but none of them elicit immunity in young children, and consequently, these vaccines did not gain popularity even in the pro-vaccine countries like Bangladesh. The delay in the initiative in investing on a conjugate vaccine was mainly due to a belief that typhoid is not very common among young children. However, there is substantial evidence now to contradict that claim. 

The decision of WHO for recommending the introduction of TCV in typhoid-endemic countries was a very pleasant surprise for all of us living the developing world with high prevalence of typhoid. We did not expect anyone to invest on typhoid as it is the “disease of the poor” and the associated possibility of market failure. Throughout my entire life working as a microbiologist, I observed that 3 out of 4 blood cultures isolates in the community was Salmonella Typhi, the causative organism of typhoid, and yet it went disregarded as a high burden infectious disease.

For introduction of any vaccine there is the need of collaboration between multiple groups, for example between donors, industries and the policy makers. Without their willingness and contribution, vaccines do not reach the population who needs them the most. I truly appreciate Bharat Biotech for taking up the initiative to invest on TCV even when the company was uncertain about the appetite for such a vaccine and a market that can pay for it! Now that it is pre-qualified by WHO, Gavi, without delay, declared a 85 million dollars funding for the availability of TCV for low middle-income countries.

Lest we forget, it is not a vaccine that prevents disease, it is vaccination that does; the journey has just begun and many obstacles are to be overcome. We have the data, we have an effective and safe vaccine pre-qualified by WHO and we have commitment of support from Gavi for its introduction. While the wheels have started rolling, it is now time for respective countries and policymakers to seize this opportunity, come together and play their roles to ensure that this vaccine reaches the children in need.  Researchers and scientists need to present their data convincingly and persuade the policymakers to institute the right combination of policy changes on the ground, accounting for limited resources and competing priorities.

Going forward, vaccination is not the end of the story either. We need to continue surveillance to measure the impact of TCV introduction on typhoid burden and the improvement of the overall health system. It will be vital to keep a closely monitor the behavior of the distant cousin of Salmonella Typhi, Salmonella Paratyphi, during the post TCV period. I urge that industries do not decelerate their effort on development of a bivalent vaccine that can prevent diseases by both these pathogens. Finally, I see one last but big challenge – the countries that need TCV the most, also has large birth cohorts and therefore will severely test the capability of only one industry to provide with uninterrupted supply of this vaccine to all countries in need. I hope, together we can encourage more industries to consolidate and produce more to ensure that countries in South Asia and Africa do not suffer from deficits, which can jeopardize the momentum of this whole campaign.

We, Bangladeshis, like any other low middle-income countries, usually receive a vaccine after 20-25 years of its introduction in the developed world - pneumococcal vaccines took 20 years and Hib vaccine took 25 years to travel here. This is the first time that a vaccine will be FIRST introduced in a country where it is needed the most. Its introduction will be a huge public health triumph. My heartfelt thanks to Bharat Biotech, WHO, Gavi and BMGF, for creating this opportunity. We are waiting keenly to watch the uptake of this vaccine and its impact on improvement of survival and wellbeing of children and getting one step closer to achieving Sustainable Development Goals.

Samir Saha Bio Photo

Samir Saha, MSc, PhD, Professor and Head of the Department of Microbiology, is also the Executive Director of the Child Health Research Foundation at Dhaka Shishu Hospital in Dhaka, Bangladesh.  Dr. Saha leads several infectious disease studies – with a focus on Hib and pneumococcus – which have contributed to a better understanding of the burden, drug resistance and epidemiology of major childhood diseases. He is a member of both the National Committee for Immunization Policies of the Government of Bangladesh and the World Health Organization’s Technical Working Group for Vaccine Preventable Diseases Surveillance Network. His passion has been working with limited resources and gradually building capacities, and as a tireless advocate for child health, he has leveraged the scientific knowledge he has helped to generate to buoy and sustain national political will around immunization in Bangladesh.

Young children and older adults are both at higher risk for potentially devastating and debilitating diseases, many of which are vaccine-preventable. Countries prioritize and routinely immunize infants, yet the same cannot be said for older adults, variably defined as 50, 60, 65, or 70+ years of age, with or without risk factors. There is no simple explanation of why countries looking at very similar data come to very different conclusions. Even experts and the global health community are divided on the role of adult immunization. As a result, a large portion of countries have failed to address vaccine-preventable diseases like influenza, pneumococcal disease, and herpes zoster (shingles),  which affect this fast-growing demographic.

Ageing population graphic

Why haven’t countries prioritized vaccinating adults?

Some reasons countries don’t prioritize vaccinating older adults include budgetary pressures and competing priorities. Vaccines also may be suboptimal for the elderly population. Countries may be unaware of the disease burden. As adults live longer and lead more productive lives, understanding opportunities for the prevention of premature death, disability, or serious economic consequences becomes increasingly important.

older man vaccination

Photo Courtesy of AMRO/PAHO

What is the state of adult immunization globally?

As a starting point, the International Vaccine Access Center (IVAC) was commissioned by the World Health Organization to conduct a preliminary literature review and qualitative interviews to characterize the state of adult immunization globally, including in low- and middle-income countries. The findings demonstrated a significant burden of disease and a need for a robust life course approach to be taken by both countries and the global community.

Although evidence gaps exist, there is a major opportunity to address vaccine-preventable disease—through immunization and other preventive measures—in the older population. However, there is a significant need for global technical consensus and more unified global guidance, as well as action at both the country and global level. The vaccine community can be alone in taking action: Diverse voices, representing the healthy aging community, must also be sitting at the table.

Photo by Gavi

Photo courtesy of Gavi

Reviewing policy across 30 countries to build a policy roadmap  

To build political priority, IVAC is first addressing basic criteria to develop a roadmap for policy decisions and increased uptake. This research, which includes both a desk review and in-country interviews, will contribute to:

  1. Establishing a summary resource of key data describing the state of adult vaccine policies and uptake around the world
  2. Highlighting key factors that influence and guide the introduction and use of adult vaccines
  3. Developing a framework to assess country archetypes for adult immunization that could help inform data needs or approaches that support policy making, access, and uptake.

A global platform is needed and IVAC’s adult immunization project is poised to fill this need. There are many ongoing individual and regional efforts to fill gaps, but there is no coordinated, global platform that promotes awareness, facilitates technical consensus, provides leadership, and collaborates and coordinates with other key stakeholders. In addition to the creation of a database and framework, IVAC is convening a group of independent experts with specialties in infectious disease, immunization, economics, and healthy aging to create the International Council on Adult Immunization. This council will review the research, determine a technical consensus, and lead international collaboration around adult immunization.

AMRO PAHO vaccination woman

Photo courtesy of AMRO/PAHO

For questions, please contact lprivor1@jhu.edu

Author Biographies

Lois Privor-Dumm, IMBA, is the Director, Policy, Advocacy & Communications (PAC) at the International Vaccine Access Center (IVAC) at Johns Hopkins Bloomberg School of Public Health.  She leads PAC team efforts on a variety of projects at country, regional, and global level, including advocacy and capacity building in low- and middle- income countries (with a strong focus on India), policy research and advocacy for adult vaccines, new vaccine introduction support for pneumococcal, rotavirus and HPV, advice and training on vaccine confidence, and communication of evidence to establish the broader value of vaccines through IVAC's new VoICE tool.

Nina Martin, PhD, is an expert in immunology and science communication at the International Vaccine Access Center (IVAC) at Johns Hopkins Bloomberg School of Public Health, where she also received a PhD in Molecular Microbiology and Immunology. At IVAC, Dr. Martin conducts research on how countries make decisions on adult vaccine recommendations, implementation and uptake and is leading a qualitative study on drivers of adult vaccination. She also supports activities and research for the International Council on Adult Immunization, a global group of diverse experts who will advocate for adult vaccine policies and help provide a roadmap for increasing action on prevention of adult infectious disease.

Prarthana Vasudevan, MS, MSPH,  is a public health professional, with a scientific background in microbiology & immunology and global disease epidemiology. Prar serves as a research lead for IVAC’s new project on adult vaccine use and policy. Under that project, she is leading a research team of five to develop a database that summarizes the current landscape and the factors that influence adult vaccine introduction decision-making, access, and uptake.

This blog was originally posted on March 6, 2018 in Pajhwok Afghan News.

By Lois Privor-Dumm and Dr. Ghulam Dastagir Nazary

Afghanistan is a country under siege, but one threat doesn’t make the news. The toll is felt among the most vulnerable in an already fragile country. Every year, nearly 5,000 children under five die of rotavirus, a fast-moving and severe form of diarrhea. Afghanistan’s rotavirus death rate is among the highest of any country in Asia.  

Fortunately, Afghanistan is among the frontrunners in Asia to introduce rotavirus vaccine for children to prevent this life-threatening disease. The vaccine, which will be available for free in health facilities throughout the country, is the 10th vaccine to be introduced in the national immunization schedule.

Click here to read more.

Afghanistan Immunization Poster UNICEF

Image courtesy of UNICEF

Cervical Cancer Campaign in Vietnam

Photo above: School girls at an HPV vaccination campaign event in Vietnam.
© 2007 Amynah Janmohamed, Courtesy of Photoshare

Despite effective vaccines, screening, and treatment, cervical cancer still kills hundreds of thousands of women, most outside rich countries. Experts call for scaling up proven solutions to prevent this.

Cervical health scares have reached mainstream awareness in pop culture, between Abbie in the film 20th Century Women, Hannah on HBO’s Girls, and Sharon on Channel 4’s Catastrophe.  

While a terrifying specter to these LA, New York, and London women, cervical cancer isn’t among the top 5 cancer killers in highly developed regions. Eight of every 10 cervical cancers occur in low- and middle-income countries. While this cancer is preventable, over 230,000 women globally die every year–most in low-resource countries, like those in Sub-Saharan Africa.

As the world observes World Cancer Day this year, we issue a challenge to all to remain focused on the continuing challenges preventing us from reaching more girls and women with effective primary and secondary cervical cancer prevention services in low- and middle-income countries. It’s time to take action, to take the tools we have and start building evidence-based programs, with communities, for the future.

cervical cancer

Photo: In Mozambique, nurse Celeste Machava and Cristina José discuss cervical cancer symptoms, screening and treatment during a medical consultation (Photo: Fernando Fidélis /Jhpiego).

Primary Prevention with HPV Vaccines

More than 3 out of 4 women globally will contract HPV, the primary cause of cervical cancer, within their lifetime. Three currently available HPV vaccines have close to 100% efficacy1 at preventing persistent infection and pre-cancerous disease caused by the two HPV types that cause 70% of the world’s cervical cancer, all with minimal and mild adverse reactions. The newest vaccine directly protects against 5 additional HPV types, which together account for another 20% of the world’s cervical cancer.

Vaccines are hailed as the best buy in public health: Compared to the considerable cost of treatment and lost productivity from cervical cancer, vaccinating girls against cervical cancer is usually a cost-effective investment2 for countries, particularly in a low-resource setting.

appointment

Photo: Education and counseling is a key component in cervical cancer screening. A health care provider in Abidjan, Cote d’Ivoire is using a job aid to explain the screening results.  (Photo courtesy of Ricky Lu)

What’s next in the vaccine landscape?

1. Taking steps to reduce vaccine price and ensure reliable supply. Currently licensed HPV vaccines are expensive compared to older, routine immunizations. A global HPV vaccine supply shortage over the past few years has also affected access for girls in the highest-burden, most price-sensitive countries.

But new vaccines must show equivalence against already-approved vaccines. To do this, companies need lab tests that allow direct comparison of molecular and immunology markers—tests that don’t yet exist. Looking to the future, the U.S. National Cancer Institute has launched a new initiative3 to develop and evaluate this type of lab test, opening the way for the development of new, potentially lower-cost HPV vaccines.

2. Reducing the number of doses. The World Health Organization (WHO) recommends two doses of HPV vaccine for girls aged 9-14, at least 6 months apart. Young people who are 15 years old and older, as well as people with a compromised immune system should get a third dose. Scientists are studying whether or not a single dose, or at least a much lengthier between-dose interval, might be as good as two doses. If the results are promising, this study could remove the logistical challenge of tracking down each girl to administer an additional dose for full coverage and reduce costs.

 

Informational poster

Photo: Poster announcing a screening campaign in San Juan De Lurigancho, in Peru. (Photo courtesy of Ricky Lu) 

Secondary Prevention: finding and treating pre-cancers

Tools for early detection and treatment of the precursors to cervical cancer build upon a solid basis of proven interventions. Yet to effectively prevent cervical cancer in low-resource settings, there are remaining challenges:

3. Scaling up the use of vinegar to identify abnormal cells. Cytology screening, wherein lab workers inspect cells from the cervix under the microscope for abnormalities, is relatively costly and requires access to a functioning and staffed laboratory system. Visual Inspection using Acetic Acid (VIA) technique, which has been used for over a decade, is a safe, effective alternative for onsite screening where there is no lab equipment or personnel. Most well trained health workers can perform this task—task shifting is an important cost savings technique. However, VIA requires robust quality assurance and a large pool of trained providers if it is to be delivered to women at scale. 

Vinegar

3. Reducing test prices. HPV DNA tests are quite accurate at flagging persistent and chronic infection with cancer causing human papilloma virus. Also, while cytology and VIA require pelvic examinations, women can collect HPV DNA tests at home or at a health facility. Facilities can process many tests together to maximize cost effectiveness. However, the tests require an initial start-up investment as well as continuing financing to purchase test kits and supplies. 

4. Expanding options for freezing therapies. Cryotherapy currently uses compressed nitrous oxide or carbon dioxide to freeze abnormal cells off the cervix so normal ones can grow back. Providers who aren’t physicians can be trained to provide the therapy, but machines require reliable gas supply as well as equipment maintenance and transport. Clinical trials are underway to develop new and more practical delivery approaches. Two promising developments are the gasless Cryopen and the dry-ice based CryoPop4. Both destroy the pre-cancerous lesion by freezing the offensive tissue.  

5. Heating to destroy precancerous cells. Thermal Coagulation, in which heat at 100-120 degree Celsius is applied to the cervix to destroy precancer lesions, is being clinically and programmatically evaluated to determine its effectiveness and safety by the International Agency for Research in Cancer.

cryotherapy orientation

Photo: An orientation on cryotherapy through clinical simulation for nurses and clinical officers in Nairobi, Kenya (Photo courtesy of Ricky Lu)

What lies ahead?

We have powerful tools: safe, effective vaccines, and many tested strategies to prevent cervical cancer. We welcome your ideas about additional opportunities to leap across barriers we’ve noted, as well as many others, and address this pervasive threat to women the world over.

Mary Carol Jennings, MD, MPH, is a public health physician and a scientist at the International Vaccine Access Center, in the Department of International Health at the Johns Hopkins Bloomberg School of Public Health. She serves as the IVAC HPV Technical Lead, and her research and work focus on innovative ways to ensure equitable vaccine delivery. Reach her at mcj@jhu.edu

Ricky Lu, MD, MPH is a public health physician and directs the FP/RH and Cervical Cancer Prevention unit at Jhpiego, an affiliate of the Johns Hopkins University and an implementing agency operating in over 40 countries globally.  He leads the Jhpiego cervical cancer prevention effort partnering with MOHs to strengthen their prevention and control program. Reach him at ricky.lu@jhpiego.org

References

1Chow EP, Danielewski JA, Fehler G, Tabrizi SN, Law MG, Bradshaw CS, Garland SM, Chen MY, Fairley CK. Human papillomavirus in young women with chlamydia trachomatis infection 7 years after the australian human papillomavirus vaccination programme: A cross-sectional study. The Lancet Infectious Diseases 2015;15(11):1314-23.

2Brisson M, Jit M, Boily M, Laprise J, Martin D, Drolet M, Alary M, Benard E. Modelling estimates of the incremental effectiveness & cost-effectiveness of HPV vaccination: Executive summary. ; 2016. Available from: http://www.who.int/immunization/sage/meetings/2016/october/07_Modelling_HPV_immunization_strategies.pdf?ua=1

3Cole M. New HPV Serology Laboratory Aims to Standardize Assays and Contribute to Vaccine Implementation and Access [Internet]National Cancer Institute: Frederick National Laboratory for Cancer Research; accessed Jan 21 2018, Available from: https://frederick.cancer.gov/news/new-hpv-serology-laboratory-aims-standardize-assays-and-contribute-vaccine-implementation-and

4Varady, M. et al. (2015) CryoPop: Merging design with demand to build a low-cost cervical cancer prevention toolAnnals of Global Health , Volume 81 , Issue 1 , 201. Retrieved from: http://dx.doi.org/10.1016/j.aogh.2015.02.963

This article was originally posted on the Impatient Optimists Blog on January 9, 2018.

45 million children have access today, millions more expected to gain access to vaccine in 2018

When I started my career in the 1970’s, I saw children die every day from severe diarrheal disease. Today, diarrhea is still responsible for half a million deaths in children under 5 worldwide. That is far too many—acute diarrhea is both preventable and treatable.

Many of these deaths occur because our prevention tools have yet to reach the world’s vulnerable children. The leading cause of severe diarrhea globally is rotavirus, which countries have taken steps to address. After one of the fastest global rollout campaigns in history, 93 countries (home to 1/3 of the world’s children) now include rotavirus vaccines in their national immunization programs.

Introducing vaccines will not completely solve the problem—vaccine coverage must be improved, as must coverage of oral rehydration therapy and zinc supplementation to further reduce the number of deaths and serious illness. Yet, the progress has been remarkable.

Here are 5 reasons we have made it here today:

1. Political leadership in South Asia has been critical

In 2016, India was the first South Asian country to introduce rotavirus vaccines into its public program, using a phased approach. A year later, Pakistan followed suit. Once these programs scale up, the vaccine should reach over 30 million children annually.  Keeping with this trend, Afghanistan, Bangladesh, and Nepal plan to use Gavi support to introduce the vaccine in 2018 and 2019.  

Pakistan Vaccine Poster

Vaccinator in South Asia

2. African countries were early adopters and have been at the vanguard 

African countries have been the vanguard of rotavirus vaccine introduction, which began when South Africa introduced in 2009. Since then, the WHO Regional Office for Africa has found that rotavirus-confirmed diarrhea hospitalizations in children under five has declined by one-third. 

The progress does not end there. 33 African countries have rotavirus in their national vaccine schedule, many having received support from Gavi, the Vaccine Alliance. Several large countries here plan to introduce rotavirus vaccines in the next few years. These include Nigeria and the Democratic Republic of Congo, where more than 40,000 children died from rotavirus in 2013. 

3. Manufacturing developments are expanding choice, potentially reducing prices 

Many new vaccines are in development or recently licensed in Asian countries. Notably, two newly licensed Indian vaccines are soon expected to be prequalified by the WHO: ROTAVAC, from Bharat Biotech, and ROTASIIL, from Serum Institute of India. Once prequalified, UNICEF can supply these new vaccines in Gavi-eligible countries. Expanding choices between vaccine products can drive down market prices and avoid supply constraints. You can read more about this here.

4. Scientists and communicators on the frontlines have enabled progress

Scientific leadership can drive political will to improve child health. Take Bangladesh as an example, which once struggled with extremely high child mortality. Widespread use and excellent coverage of new vaccines helped reverse this trend. Pivotal figures, including my colleagues Shams El Arifeen, K. Zaman, and Samir Saha, published evidence spanning three decades about the toll of rotavirus and diarrheal disease on Bangladeshi children and families.

Still, challenges exist. Bangladesh must double the country’s cold chain capacity and cope with an influx of over 600,000 Rohingya refugees. Beyond this, we recently found that thousands of children were turned away from a pediatric hospital due to a lack of beds. If these children had been vaccinated against rotavirus, the hospital may not have been overburdened in this way.

5. Middle-income countries face unique challenges 

For middle income countries like Thailand and the Philippines, it remains to be seen whether expanding supply choices will impact pricing and decision-making. The Philippines began a phased introduction in 2012 but has yet to scale up use. In Thailand, a pilot introduction showed that rotavirus vaccine would be efficacious and cost-effective. However, the scientists calculated based on current pricing that to purchase the vaccine for all children would be equal to 45% of the current budget for Thailand’s entire immunization program. Fortunately, the expansion in supply may change this calculus.

What Now?

Even with all this progress, can we feel hopeful that still 2 out of 3 children in the world don’t have access to vaccines that developed nations take for granted?

 I am an optimist and I have seen seemingly impossible journeys come to fruition. Achieving vaccine equity is a marathon, not a sprint, and the global community should applaud the many countries taking this important step toward ensuring a healthy start for all children.

More Resources

View-Hub Image of Rotavirus Coverage

This image is courtesy of View-Hub