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Mosquitos breed in standing water

By Dagna Constenla, Gatien de Broucker and Jorge Martin del Campo

This article was originally published in the Dengue Vaccine Initiative newsletter on March 7, 2016, available publicly here.  It is cross-posted here with permission. IVAC is a member of the Dengue Vaccine Initiative (DVI).

A public health emergency of international concern

It’s summer in Brazil now and the sweltering heat of the Northeast Atlantic coast of the country drives many people outdoors where they come into contact with the Zika virus. In Recife, the capital of the state of Pernambuco where a third of the 4,000 reported cases of microcephaly in Brazil have been reported since early 2015, many people cannot afford to buy insect repellent in their local pharmacies. Most families in this part of the country live in impoverished areas with no running water and near open drums that serve as breeding grounds for the mosquito vector. Air conditioning and window screens that could help keep the mosquitoes out are prohibitively expensive.

Today, 24 of 26 states in Brazil are grappling with the rapid spread of the virus. This outbreak, driven by the global trends of population growth, urbanization, globalization expansion of mosquito vectors and the effects of El Niño, shows no signs of abating this year. Every day up to five new microcephaly cases are diagnosed, creating chaos and a break down in primary health care as hospitals and clinics become overburdened with mothers whose babies are waiting to be seen by pediatric neurologists and other specialists.

While the link between Zika virus infection and microcephaly in babies is still under investigation, the sudden exponential rise of cases, following closely the rise of Zika cases is unnerving. This situation has forced the World Health Organization to declare the epidemic of microcephaly cases in regions affected by Zika virus a matter of public health emergency of international concern. If the link between Zika and microcephaly is proven biologically, and evidence are cumulating in support of this relationship, the impact of the mounting epidemic will be far-reaching for Brazil and countries and territories with active Zika virus transmission.

People in Brazil are concerned about the uncertainty and risk of this outbreak and the lack of information regarding the virus. The concern is even greater among pregnant women who don’t understand the long-term implications of the Zika virus on their baby’s life: will their baby’s head fully grow? Will their baby be able to talk and walk? Will they be able to hear? Will they be able to attend school?

The prognosis for children born with microcephaly varies, according to the National Institute of Neurological Disorders, depending on the severity of the symptoms, ranging from impaired cognitive development to delayed motor functions and speech. Brazil’s Health Minister and health care officials in Colombia, El Salvador and the remaining 21 countries and territories of the Americas with Zika outbreaks have advised women of reproductive age to delay pregnancy.

While the Zika virus is new to Brazil and other countries of the region, Aedes Aegypti, the mosquito that spreads the disease, is well known for causing other emerging infectious diseases like dengue, Chikungunya and yellow fever.

Macroeconomic impact of the Zika virus

Beyond the silent suffering among those directly affected by the Zika virus, state officials have raised concerns about the negative impact that the Zika outbreak will have on the economy of Brazil and beyond. One concern is the potential negative impact of the Zika virus on the tourism industry last month (February), just when the Carnival season begins, and during the Olympic Games scheduled for August 2016 in Rio de Janeiro. Though currently there are no travel restrictions imposed by the World Health Organization (WHO), there have been anecdotal reports about international airlines already cancelling or rescheduling flights for passengers that are traveling to the region that are pregnant or may become pregnant. Moreover, evidence is emerging on the impact that Aedes Aegypti diseases have on tourism revenues. In their 2009 report, Mavalankar and colleagues quantified the impact of Chikungunya and dengue on tourism revenues of three Asian economies: the state of Gujarat in India, Malaysia and Thailand. They reported a substantial loss of tourism revenues: an estimated 4% decline, which represents at least US$ 8 million for Gujarat, US$ 65 million for Malaysia and US$ 363 million for Thailand.  

Added to the potential significant losses associated with tourism, the possible decline on foreign direct investment due to the Zika outbreak is a major concern. During the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak, mainland China reported a decline of US$ 2.7 billion and Hong Kong foreign direct investment inflows fell 62% in one quarter. When the outbreak ended, this decline in foreign direct investment inflows was reversed.

Investments in outbreak control and surveillance infrastructure may also be impacted by the recent Zika outbreak. Recently, Brazilian authorities invested considerable resources to prevent the growth and spread of dengue. Funding for dengue outbreak prevention registered an increase of 32% over the last four years, from BRL $ 947.7 million in 2012 to $ 1.25 billion, in 2015. This funding was invested in supporting surveillance and preventive measures as well as in studying dengue. These investments are expected to increase with the rapid spread of the Zika virus. As the government of Brazil continues to make investments on preventive and control measures of Aedes Aegypti diseases, the government will continue to make debt repayments in the absence of significant financial inflows to finance outbreak control and surveillance infrastructure.

The loss of productivity due to the Zika outbreak is an even greater concern. Children with microcephaly may not have the ability to achieve their full cognitive potential because they are generally born with impaired cognitive and physical development. Moreover, children who are physically and cognitively disadvantaged are less likely to attend school, resulting in lower educational achievement.

At a macro level, the Zika outbreak could have other long-term repercussions. The government in Brazil and other countries in the region are already advising women of reproductive age to postpone pregnancies anywhere from six months to two years. If women in the region observe these warnings for a significant period of time, there may be a decrease in pregnancies that will ultimately result in a decrease in population growth. This could negatively impact the continued productivity associated with the sizable workforce in Brazil and the region as a whole.

What can we expect?

In terms of opportunities in containing the spread of the virus, recent advances in dengue research have resulted in development of new tools that show promise for use in prevention and control of other Aedes Aegypti diseases. These include vaccines*, antiviral drugs, therapeutic antibodies, biomarkers for severe disease, and mosquito-control methods that are biological, genetic and insecticidal in nature. Many of these new tools will not become available for use for another three to five years. The full potential of these tools, in terms of decreased transmission and prevention of major epidemics of dengue and other Aedes transmitted viruses, will be realized if used together instead of independently.

There are several challenges that Brazil and other Zika-affected countries in the Americas face to contain the spread of the virus. Currently, an overall strategy is lacking to effectively use these new tools and to educate the affected communities. Funding for research in this area and operational program implementation are fragmented and often uncoordinated. However, Brazil’s institutional capacity to manage outbreaks shows promise. The Oswaldo Cruz Foundation is one of many credible, government-funded institutions working to characterize Aedes transmitted viruses, like Zika, and its epidemiology. Moreover, a strong community of health networks across all states in Brazil is helping to promote positive behavioral changes that can temper the spread of Zika at the community and household levels so, next year, when those sweltering in the heat of the Northeastern Atlantic coast of Recife come into contact with Zika, they may be at a lower risk of contracting the virus.

* Denvaxia® has recently become available for the prevention of dengue. There are many other dengue vaccine candidates in the pipeline. No vaccines are currently available to target the Zika virus.

This article was originally published on the Dengue Vaccine Initiative website and is cross-posted here with permission. IVAC is a member of the Dengue Vaccine Initiative (DVI). 

On December 9 2015, Mexico approved Sanofi Pasteur’s dengue vaccine marking the first time a dengue vaccine has been licensed for use in a country. Called Dengvaxia® and developed by the French pharmaceutical company, Sanofi Pasteur, the vaccine was approved for people aged 9 to 45 years in areas that are highly endemic, with a dengue seroprevalence of more than 60 percent.

The Dengue Vaccine Initiative (DVI) views Mexico’s licensure of Dengvaxia® as an important milestone in the fight against dengue. Recent studies have demonstrated that in children and adolescents aged 9 years and above, Dengvaxia® reduces dengue cases overall by approximately 65 percent; dengue cases requiring hospitalization by 81 percent; and severe dengue cases by 93 percent. The vaccine’s efficacy was most apparent in individuals with evidence of prior dengue virus exposure. In children below the age of 9 years and in those with no evidence of prior dengue, the vaccine’s efficacy was substantially lower. There was also an increased risk of cases requiring hospitalization during the third year after vaccine initiation in children under 9.

These results suggest that Dengvaxia® may have significant public health impact in reducing dengue disease burden for people 9 years of age and older, especially in areas with existing high infection rates of dengue. Questions remain regarding Dengvaxia®, including duration of protection, price, and impact on overall dengue virus transmission given that the youngest age groups will not be vaccinated. These and other issues will have to be closely followed in order to ascertain the ultimate impact of this vaccine.

Dengue, also known as “breakbone fever,” is caused by a virus transmitted by Aedes mosquitoes, the same mosquitoes that can transmit chikungunya and Zika virus. Dengue virus causes approximately 400 million infections globally each year. In the Americas alone, dengue’s economic burden has been estimated to cost $2.1 billion dollars a year.

DVI believes that this first vaccine licensure in a dengue-endemic country may pave the way for other countries considering new technologies to fight dengue, but stresses that the decision to introduce a dengue vaccine should follow scientific evidence. Following registration, ministries of health will still face important decisions about whether and how to introduce the vaccine into national programs. These decisions may vary according to the specific demographic characteristics, dengue epidemiology and the capacity of public health systems of each country. Therefore, DVI continues to strongly support increasing efforts to improve endemic countries’ access to the evidence needed to inform vaccine introduction decisions.

DVI also welcomes the decision by Mexico as an opportunity to increase our understanding of the questions raised above, as well as the effectiveness of the vaccine in field conditions. DVI recognizes the importance of effective integration of dengue prevention and control strategies, notably vaccination and vector-control approaches, to comprehensively reduce dengue. DVI also encourages the global health community to facilitate and support mechanisms for regional knowledge transfers and information sharing among endemic countries to collectively fight dengue and other vector-borne diseases that are also on the rise. We hope this development spurs other vaccine candidates currently in clinical development to continue to progress in the pipeline.

About the Dengue Vaccine Initiative
The Dengue Vaccine Initiative is an international consortium of the International Vaccine Institute, the World Health Organization Initiative for Vaccine Research, the International Vaccine Access Center at the Johns Hopkins University Bloomberg School of Public Health and the Sabin Vaccine Institute that specializes in research, health economics, policy and advocacy to equip countries with objective information and scientific evidence to fight dengue fever. The Initiative is supported by the Bill & Melinda Gates Foundation.

By Rose Weeks

This article was originally published on Next Billion and is cross-posted here with permission. 

FOUR REASONS TO STEP UP PROGRESS ON REDUCING DIARRHEAL DISEASE

When my 6-week-old son got his first rotavirus vaccine dose last year, my husband and I were up what seemed like all night as he fussed and spat up. But even in my sleep-deprived state, I felt relieved to know that he would be protected from this life-threatening diarrheal disease.

Before the rotavirus vaccine was introduced in 2006, hundreds of children died from diarrheal disease in the United States. It was a devastating and preventable loss of life, but a tiny fraction of the 600,000 children estimated to die globally from diarrheal disease annually.

The just-published Pneumonia & Diarrhea Progress Report states that countries with the largest number of deaths from these diseases have not yet fully scaled up the use of available solutions to prevent and treat diarrhea, like rotavirus vaccine, oral rehydration solution (ORS) and breastfeeding.

Diarrhea still kills 1,000 per day: “It’s better, but it’s still horrific,” said Dr. Richard Guerrant, the director of the University of Virginia’s Center for Global Health, at last month’s annual meeting of the American Society of Tropical Medicine & Hygiene, a convening of thousands of public health scientists.

Beyond the death toll, incidence has barely waned at all. Children in low- and middle-income countries continue to experience about three episodes of diarrhea each year. Repeated cases of severe diarrhea, especially during important development stages in a child’s life, can have a lasting impact on physical and cognitive growth. Diarrhea can also make children more susceptible to death from other causes like pneumonia.

THE UNFINISHED AGENDA


ORS only reaches 1 of 3 children in need.
Children sick with severe diarrhea can be fully rehydrated with ORS – an inexpensive mixture of sugar, salt and safe water – within a few hours. ORS has saved an estimated 50 million lives worldwide. However, only one-third of children in low- and middle-income countries who need ORS get it.

Dr. Christopher Duggan, a professor in the Harvard School of Public Health who has studied ORS since the 1980s, spoke at the TropMed annual meeting about how social marketing is a critical tool to expand access. In Bangladesh, Social Marketing Company, an offshoot of PSI, has invested millions in marketing the use of ORS. Today, Bangladesh’s coverage for ORS is 77 percent, the best of the high-burden countries. Bangladesh also packages zinc supplements – another proven way to reduce the duration and severity of diarrheal episodes – with ORS. As a result, the country has attained higher coverage of zinc use than any other country surveyed.

Even when not fatal, diarrheal infections stunt children’s growth and cognitive development.
Malnutrition weakens immune systems, making children more vulnerable to infections like diarrhea. Diarrhea, in turn, prevents children from absorbing nutrients, contributing to malnutrition. This creates a viscous cycle. Children with a typical number of diarrhea cases per year suffer an average of 8-centimeter growth loss and a 10-point IQ loss, said Guerrant.

Making the situation worse, many caregivers withhold food from children and babies when they are suffering from diarrhea. It is very important to continue feeding children appropriate food during an episode of diarrhea, said Duggan.

Innovative market-based approaches to improving nutrition include mobile clinics, training community health workers and door-to-door sales of Sprinkles (sachets containing micronutrients). Some m-health programs like Totohealth in Kenya use SMS to monitor child development.

Vaccines against rotavirus, which causes 2 in 5 diarrheal deaths, are not reaching more than 90 million children or 70 percent of all infants worldwide. And not all children in the U.S. are vaccinated.
Rotavirus causes 40 percent of diarrhea hospitalizations and 200,000 deaths in children younger than 5 each year. Unlike other forms of diarrhea, rotavirus infections cannot be controlled by hygiene and sanitation alone.

Two rotavirus vaccines have been internationally licensed since 2006 and are used routinely in nearly 80 countries. Despite this, only 15 percent of the children in countries eligible for vaccine support from Gavi, the Vaccine Alliance – the world’s poorest – have access to rotavirus vaccines.

Dr. Umesh Parashar, who leads the Centers for Disease Control and Prevention’s Enteric Viruses Epidemiology Team, said that the use of rotavirus vaccines in the U.S. has led to a striking decline in rotavirus-related hospitalizations. In some years, there are few cases observed. Yet, because coverage is still not routinely high, varying geographically from 59-88 percent, the accumulation of unvaccinated infants periodically leads to outbreaks.

Public health impact has been dramatic in low- and middle-income countries where rotavirus vaccines have been introduced. In Mexico, the vaccine led to a 50 percent decrease in diarrheal deaths in children younger than 5.

New rotavirus vaccines are being developed in emerging economies to expand supply and lower price, but may need more help to be available for other countries.
Dr. Duncan Steele of the Bill & Melinda Gates Foundation – now making headline-worthy investments in accelerating the introduction of rotavirus vaccine in low- and middle-income countries – discussed one bright spot on the horizon.

Companies in China, India, Indonesia and Vietnam are developing new vaccines with prices as low as U.S. $1 per dose for governments (such as Bharat Biotech’s ROTAVAC, which India is soon rolling out in four states). But there are not yet enough doses of these new vaccines to cover all children in the countries where they are being produced, much less the millions of children around the world who are in need of this vaccine.

THE TIME TO ACT IS NOW

“The main message is – we are not winning this fight,” Steele summarized, pointing to the need for greater advocacy to mobilize support for proven, low-cost diarrheal disease solutions such as ORS, zinc and dysentery treatment.

“The time to act is now,” urged Mathu Santosham, chair for the Rotavirus Organization of Technical Allies Council.

Fourteen of the 15 countries with the most deaths due to pneumonia and diarrhea are currently eligible for new vaccine support from Gavi, but five won’t be eligible for long and some have only months to seek funding for rotavirus vaccines. Most poor countries have yet to approach global targets for ORS and zinc use.

Regardless of their birthplace, all children should be protected from suffering, stunting and the risk of death from diarrheal disease.

Rose Weeks is the director of communications for the Center for American Indian Health at Johns Hopkins Bloomberg School of Public Health and secunded to the International Vaccine Access Center to support the ROTA Council project.

By Dr. Mathuram Santosham, Chair for the Rotavirus Organization of Technical Allies (ROTA) Council, Director of the Johns Hopkins Center for American Indian Health, and Senior Advisor for the International Vaccine Access Center (IVAC) at the Johns Hopkins University, where he is also a Professor of International Health and Pediatrics.

This article was originally published on Impatient Optimists and is cross-posted here with permission. 

In 1980, the first summer I worked on the White Mountain Apache reservation, a community of fewer than 10,000 people in Arizona, so many babies were dying of diarrhea that we buried one every week.

To combat this major problem, we trained community outreach workers to give oral rehydration solution (ORS)—a mixture of sugar, salt and safe water—to babies and young children sick with severe, dehydrating diarrhea. Over time the practice spread and diarrhea deaths in the community dropped to nearly zero.

Proven solutions like ORS, vaccines and better sanitation and hygiene have dramatically reduced childhood diarrhea deaths around the world—from 5 million deaths in 1980 to 600,000 today.

But it’s not just deaths we have to worry about. Illnesses are a major issue too. As the rate of diarrhea deaths have dramatically come down, incidence has barely decreased at all. Children continue to experience an average of three episodes of diarrhea each year. A case of severe diarrhea, especially during important development stages in a child’s life, can have a lasting impact on physical and cognitive growth. Diarrhea can also make children more susceptible to death from other causes like pneumonia.

Recently, at TropMed in Philadelphia, recent progress in global efforts to protect children from diarrhea was hailed and the unfinished agenda highlighted.

Here are four critical things we need to do to protect children from diarrhea:

1. Expand access to ORS.

Children sick with severe diarrhea can be fully rehydrated within a few hours when provided with ORS. However, only one-third of children in low- and middle-income countries who need ORS get it. 

2. Improve nutrition and be sure to feed children suffering from diarrhea to stop the vicious cycle of malnutrition and diarrhea.

Malnutrition weakens immune systems, making children more vulnerable to infections like diarrhea. Diarrhea, in turn, prevents children from absorbing nutrients, contributing to malnutrition. This creates a vicious cycle. Because of malnutrition, one in five children worldwide is moderately to severely stunted. Children with two to three diarrheal disease infections a year suffer an average of 8 cm growth loss and a 10 IQ point loss.

Making the situation worse, many caregivers withhold food from children and babies when they are suffering from diarrhea. It is very important to continue feeding children appropriate food during an episode of diarrhea.  

3. Vaccinate all children against rotavirus, the leading cause of severe and deadly diarrhea.

Rotavirus causes 40% of diarrhea hospitalizations—and 200,000 deaths in children under 5 each year. Unlike other forms of diarrhea, rotavirus infections cannot be controlled by hygiene and sanitation alone. Vaccines are essential to prevention.

Two rotavirus vaccines are available and have been internationally licensed since 2006. These vaccines are currently used in the national immunization programs of nearly 80 countries. Despite this, only 15 % of the children in Gavi countries—the world’s poorest—have access to this life saving vaccine. Even in countries where rotavirus vaccines are used, the poorest children often do not get vaccinated.         

In the US, use of rotavirus vaccines led to a striking decline in rotavirus-related hospitalizations. In some years, there are almost no cases observed. Yet because coverage is still not routinely high (it’s varies geographically from 59-88% now), the accumulation of unvaccinated infants periodically leads to outbreaks. In the US, rotavirus vaccine coverage must be improved.

Worldwide, more than 90 million children still don’t have access to rotavirus vaccines. In countries where the most diarrhea deaths occur, almost none have introduced the rotavirus vaccine, despite considerable evidence of its public health impact, cost saving potential and the prospect of introduction support from Gavi, the Vaccine Alliance

Public health impact has been dramatic in low- and middle-income countries where rotavirus vaccines have been introduced. In Mexico, the vaccine led to a decrease by 50% in diarrheal deaths in children under 5.

Countries that do not already include the rotavirus vaccine in their national immunization program should consider the striking public health and economic benefits and take steps to introduce it as soon as possible. Countries that do, should work to ensure good coverage.  

4. Develop new, low-cost rotavirus vaccines to help reach all children. 

New rotavirus vaccines are in the pipeline and could help to accelerate coverage. Companies in China, India, Indonesia and Vietnam are developing new vaccines with prices as low as US$1.00 per dose for governments (such as Bharat Biotech’s ROTAVAC, which India is rolling out soon in four states). There are not yet enough doses of these new vaccines to cover all children in the countries where they are being produced, much less the millions of children around the world who are in need of this vaccine. Yet with new product licensures expected as soon as 2017, the product landscape could be quite different very soon. 

One thousand children per day still die from diarrhea—a preventable tragedy. We’ve made progress, but we can do much better.

As Nobel Laurate Gabriela Mistral said:

"We are guilty of many errors and many faults, but our worst crime is abandoning the children, neglecting the fountain of life. Many of the things we need can wait. The child cannot. Right now is the time his bones are being formed, his blood is being made, and his senses are being developed. To him we cannot answer ‘Tomorrow,’ his name is today.”

The Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhea goal is to reduce mortality from diarrhea in children under 5 to fewer than 1 per 1,000 live births. This is a very ambitious goal but we know it is possible as long as the public health community can work together and garner political support. We need to make it happen.

To learn more about how you can get involved, visit this page.

By Huma Khawar, freelance journalist and consultant for Vaccine Implementation Technical Advisory Consortium (VITAC).

This article was originally published on the VaccinesWork blog and is cross-posted here with permission.

Girl with vaccine card

A little girl with her vaccination card. Photo: Gavi/Doune Porter

Doctors from across Pakistan gathered in Islamabad last Thursday to fight a disease that’s threatening children across the country. This time it wasn’t polio they were working against, but pneumonia, which kills as many as 71,000 children every year in Pakistan.

The event, held to mark World Pneumonia Day, aimed to empower key influencers to better advocate to stop pneumonia and discuss challenges to its prevention. It took place at the Children’s Hospital, Pakistan Institute of Medical Sciences (PIMS), which itself sees many cases of the disease with a daily turnover of over 500 children in its outpatient department from in and around Islamabad.

WPD Seminar Event

The entrance to the seminar. Photo: Huma Khawar.

The pneumococcal vaccine was rolled out in Pakistan in 2012 as part of the routine immunization schedule, when it had already helped children in many other countries avoid pneumonia. It is also proving effective in Pakistan, as Dr. Asad Ali, from Aga Khan University Karachi, demonstrated by sharing preliminary findings from the vaccine impact assessment in Sindh. He explained that even one dose of pneumococcal vaccine is highly effective against the main germs that cause pneumonia (pneumococcus and Hib).

However, pneumonia is still one of the major killers of children under five years old in Pakistan.  A major reason is limited routine immunization coverage – a little more than 50% of children are covered by a basic set of vaccines nationally, and the numbers of children immunized has even been declining in Balochistan. As a result, pneumococcal vaccine faces challenges reaching children across the whole country through this system, and so its population-level effects cannot yet be expected to be significant.

Doctors estimated that this underperformance is fuelled by caregivers’ lack of awareness. Too few parents know that the vaccine is necessary for child health, free-of-cost and available at immunization centers nationally. Yet improving vaccine coverage is crucial, as once infected, access to treatment options for infants remain limited especially in Pakistan’s rural, impoverished regions. Dr. Syed Saqlain Ahmad Gillani, National Immunization Program Manager, concluded the session by voicing support for a public-private health sector partnership to increase routine immunization coverage in the country.

Presentation at Pakistan Event

One presentation from the day. Photo: Huma Khawar.

Facing such a challenge, medical professionals are not the only ones who need to advocate for vaccination against pneumonia. Following the conclusion of the main session, an advocacy session tailored for teachers and headmistresses of public schools was initiated during which they were informed of the need to prevent pneumonia through other proven, low-cost techniques such as immunization, sound hygienic practices and balanced diets for infants and exclusive breast feeding for six months, ensuring good nutrition.

The teachers also shared various risk factors which make children more prone to pneumonia. Poor parental healthcare seeking was one: when children with severe pneumonia often undergo of trial and error at the field levels, before they actually reach the health facility for the right treatment in time.

Exposure to indoor smoke, which in rural Pakistan is an issue for more than 60% of families, is also damaging beyond imagination. There, an average household size is seven, which makes overcrowding (i.e the number of people sharing same room where children sleep) is another important factor contributing to pneumonia.

The teachers agreed that, more than ever before, we know how to protect and prevent children from catching pneumonia, and how to treat those suffering with this illness. They returned home to spread the message. 

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