Searching for solutions to deaths and hospitalization from serious childhood diseases like Rotavirus diarrhea

Rotavirus is one of the several viruses known to cause a self-limited gastroenteritis, better known as diarrhea. Fluid stool losses may be dramatic, and death from dehydration is not uncommon, particularly in developing countries like Bangladesh. More than 80 percent of children infected by 5 years of age. Around 40 percent of the diarrheas in the world are due to rotavirus. In 2013, rotavirus killed 215,000 young children worldwide.

There are dramatic reductions of diarrhoeal deaths among children under five, through providing oral rehydration solution (ORS), increasing access to clinical facilities, and improving water and sanitation programmes. However, too many children still suffer growth and cognitive impairments from serious and repeated diarrhoeal disease illnesses.

The health and economic consequences of rotavirus ripple across families, communities, and countries. In Bangladesh, a recent study showed that a single episode of rotavirus costs the average Bangladeshi family US$ 84, or nearly 85 percent of the average Bangladeshi family’s monthly income. Moreover, the total cost of rotavirus hospitalizations to the country is an estimated US$66.8 million (about 500 crore Taka) each year, resulting in major economic strain.

More emphasis needs to be given on preventive measures, particularly vaccine, and implementation of hygienic practices and sanitation facilities. Vaccines are the best way to prevent severe rotavirus infections and the deadly, dehydrating diarrhea they can cause.

Rotavirus vaccines are improving health, reducing health care costs, and saving lives today in countries where they are in use. To make the case in point, introducing rotavirus vaccine in Bangladesh could prevent an estimated 135,000 hospitalizations yearly and protect thousands of children from sickness, malnourishment, and death.

Dr. K Zaman

Dr. K Zaman, Senior Scientist and Epidemiologist at icddr,b in Bangladesh

Bangladesh is a pioneer in inventing the life-saving oral rehydration saline (ORS) and many research on rotavirus diarrhea have been conducted here. One of the eminent scientists in this sector is Dr. K. Zaman. He is a Senior Scientist and Epidemiologist at the International Centre for Diarrhoeal Disease Research (icddr,b) in Bangladesh.

In the last 33 years, Dr. Zaman has worked extensively on vaccines and infectious diseases. He has been involved with clinical studies on ORS, drug trial, vaccine studies, vitamin A supplementation and hospital surveillance. Dr. Zaman also has experience in community-based research on diarrhoeal and respiratory diseases, as well as other public health problems in Bangladesh.

He is also the Principal Investigator leading several rotavirus, influenza, pneumococcal, Hepatitis E, polio and Japanese encephalitis (JE) vaccine studies as well as epidemiological studies on tuberculosis in icddr,b. He has 145 publications in international journals and more than 120 presentations in scientific conferences. Dr. Zaman also serves as Section Editor of the Journal of “Health, Population and Nutrition” and is a reviewer for more than 20 international journals.

Today, we will learn from Dr. Zaman about his works searching for solutions to deaths and hospitalization from serious childhood diseases like Rotavirus diarrhea.

 

Question: What brought you to work on the subject of vaccines? Has there been any inspiring incident which motivated you to work on the subject?

Answer: As a medical doctor it was my dream underprivileged and distressed population in Bangladesh and icddr,b gave me the platform to be directly connected with rural people in Matlab where I have worked for 19 years at the beginning of my research career. At that time I found thousands of children suffered from diarrhea and many died from the diarrheal illness that might be due to various infectious agents including rotavirus. It grows my interest to prevent diarrhoeal diseases and their risk factors. Interestingly I found rotaviral diarrhea cannot be prevented only by safe water and sanitation – the vaccine is the most cost-effective preventive strategy as there was no antiviral drug was available to treat rota illness. And I started to work with the vaccine.

Question: Are there any cases or certain vignettes that you remember from your career which motivate you to push further in the field of innovations for child health?

Answer: I always remember one incident from my personal life that one night my only little daughter started loose stool with severe vomiting and fever which I tried to manage at home with ORS but failed. Then I started treating her with intravenous fluid. We spent the sleepless night beside her bed. Even being a doctor I felt helpless as I could not able to reduce her sufferings except fluid management. Ultimately she suffered for a few days and was diagnosed with rotaviral diarrhea which could be prevented by vaccine if it was available.

Question: Do you recall the story of any particular family, whom you had met personally, affected by rotavirus/diarrheal disease? If yes, can you tell us more about the case? What was it like for the parents and the child? How did it affect the family?

Answer: I worked as a medical officer at the Matlab hospital. I see thousands of diarrhea cases. I have seen their worries and sufferings. Hospitalization of their children is a great economic loss to their families.

Question: What is the one advice you give to parents who bring their children for immunization?

Answer: Please give your child all vaccines on time and protect them from dreadful diseases.

Question: If you had the power to change one thing in the landscape of medical innovations and technology, what would that be?

Answer: I will find a combined, safe, effective and affordable vaccine to all that could prevent many illness and death, ensure a healthy life.

Question: What are the innovations in child health that you are currently excited about?

Answer: I have shown for the first time that by giving influenza vaccine to pregnant women, it protects from respiratory infections to both mother and children. Further, it increased the birth weight of the infant. Based on our findings WHO has recommended influenza vaccine among pregnant mothers. I am very excited that Rota vaccine is going to be introduced into the routine EPI programme in Bangladesh. Our researches on rota vaccine and also from Africa facilitated WHO on the global recommendation of rotavirus vaccine. Bangladesh has been declared Polio Free. Due to a shortage of inactivated polio vaccine, a small volume of the vaccine is now used. We conducted this research which helped with this recommendation. As a member of WHO polio SAGE committee, I am actively involved in polio endgame strategy.

Question: What has your journey working on vaccines in Bangladesh been like?

Answer: I have been working for the last 35 years in clinical trials and vaccines which has been very extensive and eventful. Till now I conducted more than 50 vaccine studies and continuing with different vaccines like Rota, Polio, Influenza, JE, RSV, measles, Typhoid, Hepatitis E etc. Many of my research results have been implemented in policy level by immunization policymakers.

Question: In your opinion, how did Bangladesh, a developing nation, improve many of its health indicators over the last decade? What are the major developments which contributed to this improvement?

Answer: The big indicator for improved health in Bangladesh is a remarkable reduction of child death rate. This has been possible due to a strong Government commitment, strong health care system, successful implementation of EPI vaccine, improving nutritional status, and improvement of safe water supply and sanitation with health awareness initiative. Overall life expectancy has been improved from 58.2 years in 1990 to 73.4 years in 2017.

Question: Going forward, are there any milestones which you wish to see Bangladesh achieve in its fight against vaccine-preventable diseases such as rotavirus?

Answer: As introduced recently of Pneumonia and Inactivated polio vaccine I wish Rotavirus vaccine will be introduced in Bangladesh EPI Program by 2018 so then we can avoid at least 3,000 diarrhoeal death in each year.

Question: What is the extent of rotavirus diarrhea in Bangladesh?

Answer: Almost 50% of children under 2 years of age are hospitalized due to rotavirus diarrhea. It is estimated that about 24 lac children under the age of 5 get rotavirus diarrhea each year. Among them, 300,000 children get admitted with severe diarrheal episodes. Ten years ago, the death due to rotavirus diarrhea was 20,000. Right now, the figure is about 3,000 in Bangladesh. Globally it claims the lives of about 200,000 children. The reason behind this sharp decline of death due to rotavirus diarrhea is mainly contributed by oral rehydration solution, improvement in the healthcare system, water sanitation. That means, over the period of time, the mortality has been decreased, but the morbidity has not yet. And, this is not only the scenario of Bangladesh – it is a global scenario.

Question: In spite of the fatality, why the disease has not yet attracted enough attention from the stakeholders?

Answer: In fact, unlike the severe cases of pneumonia, people take diarrhea for granted. They think that the disease will be recovered by the natural course of time and people hardly can differentiate between ordinary diarrhea and rotavirus diarrhea. So, lack of attention is given at the community level. People think that the disease is mainly contributed by the poor quality of water, sanitation and hygiene – which are not only the reasons in fact. Other factors are needed to combat rotavirus diarrhea adequately.

Question: What is causing the delay to introduce rotavirus vaccine in the national immunization program in Bangladesh whereas the vaccine is in the market for quite a long time?

Answer: The research for rotavirus vaccine started back in 1988. Two vaccines are available in the market since 2006. One is Rotarix, manufactured by GlaxoSmithKline (GSK), and another is RotaTeq, manufactured by Merck. Rotavirus vaccine is licensed in more than 130 countries and got introduced into the EPI schedule in 90 countries. Unfortunately, most of the Asian countries don’t have it in the EPI schedule.

Question: Why it’s not getting included in the EPL schedule in countries like Bangladesh?

Answer: Bangladesh applied to Gavi, the Vaccine Alliance to include rotavirus vaccine in routine EPI in the country in 2016. You know this is a costly vaccine. A single dose costs for $50 in developed countries. It is also available in the clinics at the private setup in Bangladesh, and it costs about $17 – that means Tk. 1,200 per dose. Rotarix requires 2 doses and RotaTeq requires 3 doses. People in Bangladesh hardly can afford this costly vaccine. To introduce the vaccine in the EPI program in the whole country, it requires a huge amount of vaccine doses which is not possible to supply buying the whole lot. It also requires proper cold chain throughout the country. For a birth cohort of 300,000 children, it requires 2-3 times of vaccine doses a year which is really difficult for the government to procure at its own cost. That is why, we applied to Gavi for the funding In September 2016, and eventually it got approved in the following November. Bangladesh has recently introduced pneumococcal conjugate vaccine and Inactivated Polio Vaccine (IPV). Now the country is getting prepared for the cold chain for rotavirus vaccine. It is hoped that the vaccine will be available for everyone by the end of 2018.

Question: What is the prevalence of rotavirus diarrhea in Bangladesh in comparison to the neighboring countries in the region? Is it the same or higher in numbers?

Answer: The prevalence of rotavirus diarrhea is similar in all the developing countries. Almost all children under the age of 5 get infected by rotavirus diarrhea at least once in their life cycle. We can just prevent the mortality by providing good quality of treatment like oral rehydration solution, liquid intake, electrolytes etc. In case of severe diarrhea, only oral saline does not work – it requires intravenous administration of electrolytes. But it will not prevent the disease completely. The vaccine is the ultimate preventive tool for rotavirus diarrhea.

Question: What is the difference between normal diarrhea and rotaviral diarrhea?

Answer: Any type of loose motion is generally called diarrhea. It may be caused by a variety of reasons. But if it is caused by rotavirus, then it is called rotaviral diarrhea. It mostly affects children under the age of 2. Mostly it happens in the winter season. There are more episodes of watery diarrhea of yellowish color. Dehydration develops very fast in case of rotavirus diarrhea. It is usually accompanied by fever.

Question: Our neighboring country India has developed rotavirus vaccine by their local pharmaceutical companies. Can we use those types of vaccine which could reduce the cost?

Answer: There are many pharmaceutical companies in our country, but very few of them manufacture vaccines. The reason is – it needs to be prequalified by the World Health Organization (WHO), otherwise, it will not be sold out. From manufacturing to marketing a vaccine, it requires a huge amount of financial investment. That is a real challenge. Very few companies can afford this.

Question: Can we produce own vaccine if we know the formulation? Is there any bar for producing vaccines or any conflict related to the original patent?

Answer: In fact, there are many issues involved. First of all, it requires to be WHO prequalified. Moreover, the drug administration in Bangladesh which certifies products of the local pharmaceutical companies needs to be WHO prequalified. It is a long way to achieve this prequalification status, as there are many steps to overcome which is also a time-consuming process.

Question: The pneumococcal vaccine has a number of variations to cover all the serotypes of the causing bacteria. This is why a single vaccine may not be simultaneously effective in two different geographical locations in the world. Is there similar kind of phenomena in rotavirus vaccine?

Answer: There are also different strains in rotavirus, but the vaccine has got an advantage that a single vaccine can provide cross-protection to defend strains of the virus; which is not the case for pneumonia.

Question: Is rotavirus diarrhea more prevalent in developing countries than that of the developed ones?

Answer: The difference is not very huge in two worlds. But it is true that the disease is obviously better managed in developed countries. For example, the death rate due to rotavirus diarrhea in the USA is about 15, whereas it is about 3,000 in Bangladesh.

Question: Are there any recent successes with rotavirus vaccine in South East Asia that Bangladesh can learn from?

Answer: India has already launched Rotavirus vaccine on March 9, 2015, and already has been using and more than 130 countries rotavirus vaccine has been licensed and 90 countries introduced in their national EPI programme. As a native country, Bangladesh can learn the recent experience from India how they are gradually incorporating this vaccine in different states in the EPI Programme.

Question: Are we in the back foot introducing the rotavirus vaccine?

Answer: I would like to say ‘no’. If all the logistic arrangements go into place, we can introduce this vaccine by the end of 2018. Most of the Asian countries have not yet introduced it. There is the introduction of the vaccines in some parts (in some provinces) of the countries like India, Philippines – not in the whole country – due to their logistic limitation.

Question: Can you share some of your experiences wherein regional cooperation has helped Bangladesh in raising awareness? Would you like to cite any remarkable contribution made by ROTA Council in the region?

Answer: I am a member of Rota Council. The council is responsible for creating awareness in different countries to introduce the vaccine. They do advocacy and try to sensitize the government, policymakers and other stakeholders. They also conducted several meetings in Bangladesh with different stakeholders at the ministry, Director General of Health Services (DGHS), and EPI level. We have shown that the vaccine could help the country’s economy at scale.

Question: In a resource-poor country like Bangladesh, what is the current priority?

Answer: Right now, rotavirus vaccine is at the top of the priorities. The HPV vaccine is next in the pipeline.

Question: How long the Gavi will support for rotavirus vaccine?

Answer: Currently, the Gavi is to provide support up to the next 5 years. Then the government will have to chalk out a sustainability plan.

Question: What is the post-vaccine surveillance plan in Bangladesh following the introduction at scale?

Answer: We have conducted trials of the vaccine efficacy at different levels of all the vaccine in Bangladesh at different capacities and I was involved at all levels of these trials. We will conduct the post-introduction trial for sure.

Question: What else do we need to do following the introduction of the vaccine?

Answer: There is no less significance of breastfeeding, improved WaSH, ORS to prevent the disease. Introduction of vaccine does not rule them out at all.

Question: What is the coverage of rotavirus vaccine?

Answer: The first episode of rotavirus vaccine is more severe. So, the plan is to combat the first episode. If you can win the battle of the first episode, then you can easily prevent many deaths due to this disease. The vaccine is not likely to provide 100% protection since there are other contributing factors like malnutrition, bacteria, environmental condition and so on. We expect about 45-50% protection by the vaccine.

Question: What else is needed to push the government to expedite the introduction of rotavirus vaccine?

Answer:  In September 2016, Bangladesh applied to GAVI, the Vaccine Alliance, to seek support to include rotavirus immunization as part of our EPI. In November 2016 the application was approved. Currently, the biggest limitation to widespread rotavirus immunization is the limited cold chain facilities- as these vaccines use a live virus, they are not stable at room temperature. The government of Bangladesh is expanding cold chain capacity and plans to fully introduce routine rotavirus immunization by 2018.

Question: What the government needs to do now? How positive is the Government of Bangladesh to introduce the rotavirus vaccine in comparison to other neighboring countries?

Answer: For any vaccine introduction, the government has a very big role to play. They definitely need the political commitment. And we are fortunate enough that the current government of Bangladesh has that commitment. They are very positive for the introduction of Rotavirus vaccine in EPI Programme and plan for introduction by end of 2018. Then it requires the logistic arrangements that are ongoing right now.

Question: Advise how other countries can benefit from Bangladesh experience and data.

Answer: Bangladesh can be a role model for other Asian and Africa countries as we have very successful EPI programme with vaccine coverage about 93%. This includes vaccine supply and storage, maintenance of proper cold chain and building awareness, among communities including hard to reach area, proper recordings, media and NGO’s engagement etc.

Dr. Tareq Salahuddin is an award-winning journalist and a Special Correspondent of News Hour. He is a Public Health Professional working in the development sector. Dr. Tareq, a medical graduate, is a member of Public Health Association of Bangladesh and a former member of the Governing Council and Policy Committee of the World Federation of Public Health Associations (WFPHA), a J2J Fellow on HIV/AIDS and a member of the International AIDS Society. To know more about Dr. Tareq, please visit his personal website (www.tareqsalahuddin.net) or simply Google his name.
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