HPV Vaccination in the Japanese MSM Community: A Call to Action

~Written by David Boedeker (Contact: dhboedeker@gmail.com; Twitter: @dhboedeker)

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Source: cancerfrontline.org

HPV vaccination has faced pushback from communities since its introduction in 2006. Perhaps the most shocking story comes from Japan. In 2010, the Japanese government began to give girls ages 12 to 16 the vaccine for free. The government recommended girls receive the vaccine[1], and vaccination rates climbed. However, all of that changed in 2013 when an anti-HPV vaccination movement successfully advocated that the government withdraw its recommendation. The aftermath has been dramatic: vaccination rates dropped from roughly 70% to 1%, leaving millions of adolescents unprotected from HPV-related cancers. Interestingly, this decision coincided with the United States moving to ramp up vaccination efforts. Moreover, the scientific data that prompted the Japanese government to withdraw its recommendation is based in theories that are not biologically possible, as one critic noted[2].

In response, many researchers and physicians are advocating for increased vaccination campaigns in Japan. Historically, these initiatives have focused on females since it has been established that HPV vaccination is important to prevent cervical cancer and other HPV-related cancers. However, it is increasingly recognized that HPV vaccination for males is also critical, especially to prevent throat cancers, which are expected to surpass cervical cancers as the most common HPV-related cancer by 2020.

HPV infection is not only related to throat and cervical cancers; it also increases the risk of developing mouth, tongue, and anal cancers. These are all cancers men can develop, and these are all cancers that Japanese men are currently at risk of developing because they are not vaccinated. Physicians, researchers, and government officials in Japan must expand vaccination efforts to include males, particularly the men who have sex with men (MSM).

MSMs are especially susceptible to anal cancer, a rare cancer, but one that disproportionately affects the LGBTQ+ community. Gay men are 20 times more likely to develop anal cancer compared to the general population, and HIV positive gay and bisexual men are 40 times more likely than the general population to develop this cancer[3].

Why must the Japanese government in particular take action? In Japan, same-sex behavior is stigmatized, which makes the LGBTQ+ community a hard-to-reach population [4] that may face challenges [5] when seeking healthcare services. These challenges may negatively impact the likelihood that they will receive the HPV vaccine. Also, the oncogenic (cancer-causing) HPV infection rate in the Japanese MSM community is 75.9%. Among MSMs who are HIV positive, the oncogenic HPV infection rate is 66% [6]. Most of these infections would have been preventable with administration of the HPV vaccine.

So, what can these government officials do? A driving force behind HPV vaccination is provider recommendation. Many patients state the reason they ultimately received the HPV vaccine is because their provider recommended it to them[7]. Some Japanese OB/GYNs are currently advocating that the government reinstate its HPV vaccination recommendation. A reinstatement might encourage more Japanese physicians to recommend the HPV vaccine, increasing the country’s vaccination rate and protecting its currently vulnerable population. However, it is important for these providers to advocate that the government not only recommend the vaccine to females, but to males as well. Moreover, this policy may benefit the MSM community by improving healthcare access and decreasing oncogenic HPV infection rates.

References:

[1] Hanley SJB, Yoshioka E, Ito Y, Kishi R. HPV vaccination crisis in Japan. The Lancet. 2015 June 27; 385(9987): 2571. DOI: http://dx.doi.org/10.1016/S0140-6736(15)61152-7

[2] The Public Hearing on Adverse Events following HPV vaccine in Japan [Internet]. Japan: Ministry of Health, Labour and Welfare; 2014 Feb [cited 2016 Sep 10]. Available from: http://www.mhlw.go.jp/stf/shingi/0000048229.html

[3] Margolies L, Goeren B. Anal cancer, HIV, and gay/bisexual men [Internet]. New York: Gay Men's Health Crisis; 2009 Sep [cited 2016 Sep 10]. Available from: http://www.gmhc.org/files/editor/file/ti_0909.pdf

[4] Nomura Y, Poudel KC, Jimba M. Hard-to-reach populations in Japan. Southeast Asian J Trop Med Public Health. 2007 Mar;38(2):325-7.

[5] Hidaka Y, Operario D, Tsuji H, et al. Prevalence of Sexual Victimization and Correlates of Forced Sex in Japanese Men Who Have Sex with Men. Stephenson R, ed. PLoS ONE. 2014;9(5):e95675. doi:10.1371/journal.pone.0095675.

[6] Nagata N, Watanabe K, Nishijima T, Tadokoro K, Watanabe K, Shimbo T, Niikura R, Sekine K, Akiyama J, Teruya K, Gatanaga H, Kikuchi Y, Uemura N, Oka S. Prevalence of Anal Human Papillomavirus Infection and Risk Factors among HIV-positive Patients in Tokyo, Japan. PLoS One. 2015;10(9):e0137434. doi: 10.1371/journal.pone.0137434. PMID: 26368294, PMCID: PMC4569050

[7] Hanley SJ, Yoshioka E, Ito Y, Konno R, Hayashi Y, et al. Acceptance of and attitudes towards human papillomavirus vaccination in Japanese mothers of adolescent girls. Vaccine. 2012 Aug 24;30(39):5740-7. PubMed PMID: 22796375.

Lessons Learned from Ebola

~Written by Kelly Ann Hanzlik (Contact: kelly_hanzlik@hotmail.com)

According to the World Health Organization, 28,616 people contracted Ebola and 11,310 lives were lost during the Ebola epidemic. After so many lives lost and the hopeful, but understandably tentative countdown of Ebola free days continues once again in West Africa, it is imperative that we take a moment to consider what we learned from the devastating and tragic epidemic.

I spoke with Dr. Ali S. Khan, former senior administrator for the Centers for Disease Control and Prevention, former Assistant Surgeon General, and current Dean of the University Of Nebraska College Of Public Health. He noted initially, that there is always the risk of importation of cases; that is how it started he reminds us. He elaborated further that the epidemic “changed the response from the WHO and caused a change in political focus by the nations involved that will affect future outbreaks and ensure native capabilities, as well as link them to the global response.” He also noted that new medical counter measures, such as vaccines and related therapeutics, were also the result of the Ebola impact. When asked about what we learned, he did not hesitate. “The first thing was a new vaccine that permits a novel prevention strategy using ring vaccination to prevent spread and new cases. The second is the new monoclonals and antivirals for treatment.” He also noted the better understanding of the viral progression and clinical diseases that will influence options for acute treatment and follow up of convalescents.

Ebola has provided us with a virtual plethora of opportunities to learn about the disease, its treatment and control, as well as the control of other infectious illnesses through our attempts to prevent its spread as well as through our failures, and successes. We gained valuable treatment modalities and tactics that will likely be used in future outbreaks of Ebola, as well as many other infectious diseases.

Ebola taught us other things too. It has been some time since global health has taken center stage. Ebola changed that. During the epidemic, one could not watch the news or go through a day without hearing an update on the latest development in the Ebola crisis. Although other infectious diseases like Plague, Polio, AIDS, SARS, H1N1, Cholera, and now Zika have captured the world’s attention, few diseases have made such an intense impact, nor caused the uproar and fervor that Ebola elicited. Ebola reminded us that global health is public health and affects us all, and as such, deserves to be a priority for national and international focus and funding for everything from vaccine development and research, to capacity for response locally, nationally, and internationally. Global health has teetered on the edge of public awareness, and remained a quiet player in the competition of priorities in national budgets. Today, it is abundantly clear how vital this sector is to each nation’s, as well as the world’s health, safety, success and even its survival.

Another effect from the Ebola crisis was the opportunity to educate people about public health and the transmission of infectious disease. Through education, public health officials were able to promote behaviors that ensured the safety and health of the public. It is stunning that in this day and age, we persist in so many behaviors that put us and those we interact with at risk. The discrepancy in what we say we will do, and what we are actually willing to commit to and take action on, looms large. Persisting low vaccination rates and the prevalence of infectious diseases such as sexually transmitted diseases, measles, pertussis and influenza show this. Ebola offers yet another opportunity to demonstrate the connection between our behaviors and our risks and disease.

Ebola also showed us that many nations continue to lack sufficient financing, infrastructure, facilities, support and medical staff to treat their own populations. Endemic conditions like malaria, and neglected tropical diseases like Guinea worm disease, Yaws, Leishmaniasis, Filariasis, and Helminths, as well as other conditions continue to affect millions globally.  Maternal and childhood morbidity and mortality rates remain deplorable as well. And millions of children around the world continue to suffer and die of malnutrition and disease before they reach the age of five. This is unacceptable, especially because proper treatment and cures for these conditions exist. Ebola also highlighted the need for treatments for chronic non-infectious conditions as well.

Moreover, Ebola clearly demonstrated the enormous need that remains for sufficiently trained medical professionals and healthcare staff to provide adequate care for many populations throughout the world. The loss of so many extraordinary and heroic staff that dedicated their lives to helping others in need under the most daunting and challenging of circumstances was devastating to those whom they served, and must not be in vain.

Additionally, Ebola provided us with yet another chance to relearn lessons about the role of safety in giving aid to others in need. We learned that we cannot just rush in with aid, but must recall the basics that every first responder and medical student must learn:  Ensure scene safety before giving care, and first do no harm. Ebola showed us the necessity to strategize and prepare to give care by utilizing personal protective equipment. It also reminded us very quickly that we could indeed do harm, and worsen the epidemic when we acted without first assessing the situation and ensuring proper protection and preparation.

So, it remains to be seen just how much we will learn from Ebola. Will we learn from our mistakes? Will we take the global view in the future, or the narrow one? Will we truly live by the motto of the Three Musketeers and be "one for all and all for one", or persist in "it's all about me"? Only time will tell. 

Is Measles Eradication Possible when the World is Still Trying to Eradicate Polio?

~Written by Theresa Majeski (Contact: theresa.majeski@gmail.com)

Also published on Global Contagions

Humanity has only truly conquered one human infectious disease, smallpox. Smallpox was successfully eradicated in 1977 after causing between 100 and 300 million deaths in the 20th century. Strides are being made to make polio the second eradicated infectious disease. Polio eradication efforts have been ongoing for almost 30 years, costing nearly 11 billion dollars. The World Health Organization (WHO) set a goal for polio eradication by 2000 but, 16 years later, that goal has yet to be achieved for reasons such as oral polio vaccine (OPV) effectiveness, armed conflict, and myths about vaccine dangers. The global public health community has been “burned” by the polio eradication campaign and may not have the money or energy for another global eradication campaign, especially since the polio campaign is still ongoing. Even if the global health community is burnt out on polio eradication efforts, is it time to turn our attention toward measles eradication?

Measles, along with smallpox and polio, is one of the very few diseases that meets the criteria necessary for eradication. Measles cases can be easily diagnosed due to the characteristic rash, the vaccine is incredibly effective, and there is no animal host where the virus can hide. Perhaps most importantly, measles transmission has been eliminated in large geographic areas, demonstrating that eradication may be feasible.

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Number of reported measles cases from April 2015 to September 2015 (6 months); Photo Credit: World Health Organization

Measles is a deadly disease. In 2013, measles killed an estimated 145,000 people, mostly children in Africa, while leaving countless others deaf, blind, or otherwise disabled. To prevent measles individuals need to receive two vaccinations, which are 99% effective at preventing measles. While the number of children receiving measles vaccinations has risen over the past decade, there are still a handful of countries where children aren’t receiving vaccines (Democratic Republic of Congo, Ethiopia, Nigeria, India, Pakistan). Even places like the United States and some countries in Europe, which have eliminated measles locally, are seeing outbreaks due to imported cases. Until measles is eradicated, imported cases will continue to pop-up in countries without local transmission.

While measles meets the criteria for eradication efforts, there are still challenges to achieving that goal. One major challenge is that measles is incredibly contagious; infectious droplets can linger in the air for up to two hours, infecting unsuspecting people. To interrupt measles transmission, over 95% of the population needs to be vaccinated, compared to only 80% for smallpox and polio. The measles vaccine is also harder to deliver than the OPV, which is administered via a few drops in a child’s mouth. The measles vaccine must be given via injection, thus trained staff is necessary, and the vaccine has to be reconstituted in the field (liquid added to the powder vaccine to make the complete vaccine). Once reconstituted, the vaccine is only viable for six hours, which isn’t much of an issue for large vaccination campaigns but becomes problematic when only one or two children need to be vaccinated.

As with many global public health campaigns, governments and non-governmental organizations donate money to help high-risk countries control the spread of measles. In 2009, the global recession hit and measles eradication efforts lost significant funding. Mass vaccination campaigns were canceled or reduced and routine vaccination programs suffered. Following the reduction in vaccinations the number of measles cases exploded in southern African countries, going from 170,000 in 2008 to 200,000 in 2011. Added to these challenges is the perception of measles in high-income countries. Even though measles is a deadly disease, many in high income countries view measles as a minor illness with  a rash and fever; certainly not something worth spending billions of dollars on over the course of many years.

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Source: Butler D (2015). Measles by the numbers: A race to eradication. Nature 518 (7538): 148-149. doi: 10.1038/518148a.

Measles eradication is feasible. Measles meets the criteria necessary for eradication; it is easily diagnosed, it has an effective vaccine, and humans are the only host. It has been successfully eliminated in large areas of the world (for example, all 35 countries of the Americas eliminated measles in 2002), demonstrating that it is possible to at least end local transmission. However, significant challenges do exist. While the global health world may be hesitant to embark on another “eradication” campaign after the continued struggle with eradicating polio, perhaps it’s best to start eradicating measles without labeling it an “eradication” campaign. Avoiding the “eradication” label may help prevent critics who are hesitant about taking on another potentially long and expensive eradication campaign, especially as the polio eradication campaign is still ongoing. Regardless of the use of the word “eradication” in the efforts to rid the world of measles, without measles in the world, lives will be saved. Let’s ensure measles is added to the very short list of human diseases we’ve eradicated.

Defeating Tuberculosis: A Possibility?

~Written by Sarah Khalid Khan (Contact: sk_scarab@yahoo.com)

Disease has always played a part in reforming community and geographical distribution of people through the ages. The bubonic plague, the Spanish flu, cholera and tuberculosis (TB), are some of the illnesses that have altered human history. Interestingly, TB has been glorified in literature more than others. The characters, Mimi in La boheme, Fantine in Les Miserables and Satine in Moulin Rouge all met with a similar fate at the hands of this disease.

According to the Global Tuberculosis Report 2015, the year 2015 is considered a turning point for TB as the global community progressed from Millennium Development Goals (MDGs) to Sustainable Development Goals (SDGs). TB mortality has decreased by 47% since 1990. Between 1990 and 2014, as a result of correct and timely diagnosis, 43 million lives were saved. We have made progress by moving from the “Stop TB Strategy” to the “End TB Strategy”. According to the latter, the targets for 2030 are to reduce the number of TB deaths by 90% and incidence by 80% (1).

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Source: TBAlert.org

These statistics give us hope for a world without TB. But, having worked in a tertiary hospital in a low middle-income country, I have my doubts. Although the statistics reported by the World Health Organization (WHO) are the best available at the moment, these are estimates with very wide confidence intervals and may not provide a precise idea of the current situation in low and low middle income countries (LIC and LMICs).

In the surgical ward where I worked, one-third of the abdominal procedures were for perforation due to abdominal TB. To my knowledge, patient records were maintained through an electronic health system on the hospital server. Hard copies of the records were kept in nurses’ offices or junior doctors; duty rooms. These were put in storage, usually available for 4 to 5 years. The conditions of the storage area were extremely shabby and damp, where paper records could hardly survive. Electronic records, however, were said to be available in perpetuity. No one knew if these records were ever shared with the WHO to help with estimates. Popular opinion was that if the world knew the actual incidence and prevalence of diseases like TB in countries like ours it would be an embarrassment. Regardless, it is essential to have as accurate as possible estimates to converge efforts towards a TB free world.

Despite the best intentions and apparently achievable goals, the situation remains grim. According to the WHO, TB still imposes a great burden on the world. In 2014, 9.6 million new cases of TB were diagnosed while 1.5 million people died as a result of TB (2). Despite the history of this disease, research for newer TB drugs has been limited (3). In 2012, a new drug for multidrug resistant TB was introduced after a drought of 50 years (4). In addition, though BCG vaccines are part of immunization programs in countries where the disease is endemic, the current vaccine was developed in 1921 and is not entirely effective (5). A systemic review and meta-analysis that included articles from 1950 to 2013 reported 19% efficacy against TB in vaccinated children compared to non-vaccinated children (6). Although current research is encouraging there are questions of affordability of newer drugs for low resource countries where TB is more prevalent. Furthermore, five percent of the global burden of TB is due to multidrug resistant strains (7). The research required for averting these cases poses additional problems of affordability, availability and accessibility in LICs and LMICs.

Children present another area of grave concern. It is estimated that 550,000 children are infected with TB each year. The condition is frequently overlooked in children, often due to delayed and inefficient diagnosis (8). Adoption of the latest recommended diagnostic tools by the WHO is a challenge in itself because accessibility, affordability and availability again come into play in LICs and LMICs. Since TB flourishes in poor living conditions, the current global refugee and migrant situation has increased concerns about TB exposure, infection and transmission (9).

It is time that LICs and LMICs focus on establishing the true burden of major diseases like TB, and work towards adopting recommended diagnostic tools and treatment for all forms of TB. Unless the state actors and international community work together, the policies and aid provided will continue to fall short and the target to end TB will remain out of reach.

References:

1. World Health Organization. Global Tuberculosis Report 2015. 2015.

2. World Health Organization. Research for Tuberculosis Elimination. 2014.

3. Frick M. 2014. Report on Tuberculosis Research Funding Trends, 2005-2013. [Internet]. Treatment Action Group. 2015. Available from: http://www.treatmentactiongroup.org/sites/tagone.drupalgardens.com/files/tbrd2012 final.pdf

4. Médecins Sans Frontières, International Union Against Tuberculosis and Lung Disease. DR-TB Drugs Under the Microscope. Sources and prices for drug-resistant tuberculosis medicines. 2nd edition. 2013.

5. World Health Organization. Tuberculosis vaccine development [Internet]. World Health Organization; 2015 [cited 2016 Mar 19]. Available from: http://www.who.int/immunization/research/development/tuberculosis/en/

6. A Roy et al. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systemic review and meta-analysis.  BMJ 2014; 349:g4643

7. World Health Organization. Multidrug Resistant Tuberculosis (MDR-TB). 2015.

8. World Health Organization. Combating Tuberculosis in Children. 2015.

9. World Health Organization. Tuberculosis prevention and care for migrants. 2014.

Battling Cancer across Different Income Settings

~Written by Sarah Khalid Khan (Contact: sk_scarab@yahoo.com)

David Bowie, Alan Rickman and Rene Angelil, are a few of the well-known people that the world lost to cancer in the year 2015. My familiarity with cancer comes not just from losing my favourite celebrities to cancer, or dealing with patients in a tertiary care hospital in Lahore, but also from losing a few people very dear to me in my family. Every case of cancer is a battle for the person, their families, friends and doctors, as well as the healthcare system.

Cancer forms a major proportion of non-communicable diseases today. There were an estimated 14.1 million new diagnosed cases of cancer with an estimated 8.2 million deaths in 2012 (1). The most common sites of cancer have been recognized to be lung, colon, breast, liver, stomach and the cervix while the majority of cancer-related deaths are due to lung, stomach and esophageal cancer (2). Previously, cancer remained a low priority for low income (LICs) and low middle income countries (LMICs), as well as for donors (3). In 2008 72% of deaths due to cancer occurred in LICs and LMICs (4).  This may be a consequence of not only longer life spans and the majority of the world’s population being in the LIC and LMIC countries but also a lack of accessible and affordable treatment in these parts of the world.

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Estimated global numbers of new cases and deaths with proportaions by major world  regions, for all malignant cancers (excluding non-melanoma skin cancer) in both sexes combined, 2012. Source: The Cancer Atlas

While higher income countries have progressed from chemotherapy and radiotherapy to gene therapy, LMICs continue to focus on finding ways for uneducated or less educated to identify cancerous conditions in order to seek medical help before it is too late, for instance promoting breast self-examination. The increasing prevalence of cancer in LMICs exasperates the health sector with an already increasing burden of infectious diseases like tuberculosis, malaria and diarrhea. In these contexts cancer contributes to altering the epidemiology of these countries adding to the burden of non-communicable diseases which in turn worsens the double burden of disease. This creates considerable strain on the healthcare system due to increasing needs of diagnostic and treatment modalities besides the already unmet needs concerning infectious diseases.

There is an immense need for healthcare systems in resource poor settings to focus more on prevention rather than cure. Health professionals working in LMICs need to place greater emphasis on informing and educating people about warning signs of cancer as many resource poor settings have technology constraints and limited means of gaining health information. There are no quick fixes and circumstances are never as simple as they seem. Campaigns against smoking to prevent lung cancer have been addressed by discussions advocating for the rights of the poor who own tobacco farms as their only source of income (5). Modification of social behaviours for instance, requires extensive out-reach programmes by medical professionals but also bring into question the financial constraints of the country in order to pay for the services of these local healthcare workers.

In summary, LICs and LMICs have a longer way to go to provide sufficient healthcare for cancer patients. While high income countries are more likely to make medical advances for cancer treatment, resource poor countries can make strides through preventive measures like vaccination, behaviour modification and self-examination.

References :

1. Cancer. WHO Media Centre. World Health Organization; 2016 [cited 2016 Feb 14]. Available from: http://www.who.int/mediacentre/factsheets/fs297/en
2. World Cancer Report published by the International Agency for Cancer Research, WHO
3. Scaling up cancer diagnosis and treatment in developing countries: what can we learn from the HIV/AIDS epidemic? Can Treat International. Ann Oncol [Internet]. 2010;21(4):680–2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20338877
4. Cancer in Developing Countries International Network for Cancer Treatment and Research. INCTR. 2016 [cited 2016 Feb 14]. Available from: http://www.inctr.org/about-inctr/cancer-in-developing-countries/
5. Tobacco Company Strategies to Undermine Tobacco Control Activities at the World Health Organization. Committee of Experts on Tobacco Industry Documents. World Health Organization. 2000.
   
6. International Women ’ s Day 2014 : women ’ s health equity is progress for all. Ginsburg O. 2014.

Recent Therapeutic Advancements in Combating Dengue and Glioma

~Written by Kate Lee, MPH (Contact: kate@recombine.com)

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Sanofi-Pasteur's Dengvaxia has been approved for the prevention of the four subtypes of dengue in children over 9 years old and adults under 45 years old. Photo Credit: European Pharmaceutical Review

Infectious and chronic diseases are some of the top priorities in global health. Abundant funding, both from the government and private sector, is poured into therapeutics research to help decrease morbidity and mortality from both types of diseases. For example, recent news has highlighted two promising therapies with the potential to alleviate the global burden of two diseases: dengue fever, an infectious disease, and glioblastoma, a chronic disease.

After 20 years of research, Sanofi, a French pharmaceutical company, developed Dengvaxia, a vaccine to prevent dengue. Mexico is the first country to approve the vaccine for use in children over the age of nine and adults under the age of 45. A clinical trial last year found the vaccine to have an effectiveness of 60.8% against four strains of the virus[1]. Sanofi bypassed European and US regulations and sought regulatory approval for Dengvaxia in dengue-endemic countries. According to their press release, the vaccine, “will be priced at a fair, affordable, equitable, and sustainable price... and may be distributed for free in certain countries”[2].

Dengue is a febrile viral illness that is spread via the bite of an infected mosquito, and is endemic to tropical and sub-tropical climates. According to the World Health Organization (WHO), about 400 million people globally are infected with the dengue virus each year. Prevention has been limited to effective mosquito control and appropriate medical care[3]. These measures are often either ineffectively implemented, or there are limited, or no available medical resources in the community. Dengvaxia has the potential to reduce the burden of dengue, especially in developing countries that are particularly hard-hit with the disease. Future research could be directed towards making the vaccine more effective in children, as severe forms of dengue are the leading cause of illness and death in children in Asian and Latin American countries[3].

As one tropical virus is being prevented, another virus is being used to combat brain cancer. Researchers at Harvard and Yale have teamed up to use vesicular stomatitis virus (VSV) and Lassa virus, to search for and destroy cancer cells in mice[4]. Lassa is a febrile illness, usually transmitted by rodents, and is endemic to tropical and subtropical regions of the world[5]. VSV has been studied for many years and is generally effective in killing cancer cells; it becomes deadly to the patient when it reaches the brain[4,6]. Interestingly, including Lassa virus appears to make VSV safe for cancer therapy in the brain.

Researchers created a Lassa-VSV chimera, an organism that includes the genetic codes of two different organisms, to target glioma, one of the deadliest forms of brain cancer, which accounts for more than 80% of primary malignant brain tumors[7]. Glioblastoma is the most common form of glioma and is associated with poor survival, making this chimeric treatment a potential life saver for many patients. The next step in the treatment development process is primate research to evaluate safety. This is still a long way from the initiation of human trials, and eventual market, but promising nevertheless, for the millions of people globally who are affected by brain cancer.

Dengvaxia and the Lassa-VSV chimera represent recent advancements in therapeutics with potentially significant global impact for brain cancer and dengue respectively - diseases that affect populations in many nations.

References:

1.     Sanofi's Dengvaxia, World's First Dengue Vaccine, Approved For Use In Mexico. International Business Times. http://www.ibtimes.com/sanofis-dengvaxia-worlds-first-dengue-vaccine-approved-use-mexico-2219515. Published December 10, 2015. Accessed December 20, 2015.

2.     World’s First Dengue Vaccine Approved After 20 Years of Research. Bloomberg Business. http://www.bloomberg.com/news/articles/2015-12-09/world-s-first-dengue-vaccine-approved-after-20-years-of-research. Published December 9, 2015. Accessed December 20, 2015.

3.     Dengue and severe dengue. World Health Organization. http://www.who.int/mediacentre/factsheets/fs117/en/. Updated May 2015. Accessed December 20, 2015.

4.     Using a deadly virus to kill cancer: Scientists experiment with new treatment. The Washington Post. https://www.washingtonpost.com/national/health-science/using-a-deadly-virus-to-kill-cancer-scientists-experiment-with-new-treatment/2015/12/07/7d30bc5a-9785-11e5-8917-653b65c809eb_story.html. Published December 7, 2015. Accessed December 20, 2015.

5.     Lassa fever. World Health Organization. http://www.who.int/mediacentre/factsheets/fs179/en/. Updated March 13, 2015. Accessed December 20, 2015.

6.     Viral Therapy in Treating Patient with Liver Cancer. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01628640. Updated July 2015. Accessed December 20, 2015.

7.     Schwartzbaum J A, Fisher J L, Aldape K D, Wrensch M. Epidemiology and molecular pathology of glioma. Nature Clinical Practice Neurology (2006) 2, 494-503. doi:10.1038/ncpneuro0289

Will We Witness the End of HIV in Our Lifetime?

~Written by Theresa Majeski (Contact: theresa.majeski@gmail.com; Twitter: @theresamajeski)

December 1st of every year is designated as World AIDS Day, a day devoted to increasing knowledge and awareness about the impact of HIV/AIDS around the world. This year is no different, and over the last few months and years some exciting things have been happening regarding HIV/AIDS.

The year 2013 has become known as the “turning point” or “tipping point” in the HIV/AIDS epidemic. This describes the fact that 2.3 million people began anti-retroviral medication in 2013 while only 2.1 million new infections were diagnosed. In other words, more people are receiving treatment and fewer people are becoming infected than ever before. If we keep this accelerating HIV scale-up through 2020, UNAIDS predicts we could see the end of HIV/AIDS by 2030

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Figure 1. WHO infograph detailing the impact of expanding ART (antiretroviral therapy)

In the United States there has been a lot of media coverage, over the last year or two, surrounding pre-exposure prophylaxis (PrEP) for use by HIV-negative people to prevent HIV infection. PrEP is daily medication regimen utilizing an HIV drug called Truvada. Studies have shown that people who take PrEP as directed were 92% less likely to contract HIV. However, although it is increasing, PrEp usage remains lower than anticipated. Some barriers include a lack of PrEP awareness in people who are most at risk for HIV, some medical provider resistance to prescribing PrEP and some inconsistent insurance coverage. Additionally, PrEP continues to suffer from an image problem. When PrEP first became available, many critics were skeptical of its effectiveness in real-world settings and thought that it would undo years of work to educate folks about the dangers of HIV/AIDS. Critics also thought that being able to take a daily drug to prevent HIV would promote promiscuity and unsafe sex. A recent study in JAMA Internal Medicine proves the critics wrong on some of their fears.

An HIV/AIDS vaccine has been on the horizon ever since the epidemic was discovered. However, as we learned more about HIV, it became apparent that developing a vaccine was going to be a challenging effort. While there continue to be many HIV vaccines at various stages of development, scientists are excited about one being developed by one of the scientists who identified HIV as the cause of AIDS, Dr. Robert Gallo. His team at the University of Maryland School of Medicine’s Institute of Human Virology is beginning human trials on a potentially groundbreaking HIV vaccine. Instead of targeting different HIV viral markers to help the immune system recognize and eliminate HIV-infected cells, Dr. Gallo and his team’s vaccine targets HIV when it enters the body to prevent it from infecting cells.

All of these promising developments relating to HIV/AIDS should not overshadow the challenges that still lie ahead. Many people do not know they have HIV because they’ve never been tested. The Berkshire town of Reading in the UK is expanding its HIV testing program by offering free tests because it has more than double the UK average of HIV-positive people. The number of HIV-positive people in Russia continues to increase and has reached almost 1 million people. Some countries are passing anti-gay legislation and there is a direct link between criminalizing laws and increased rates of HIV. These are the challenges some parts of the world face in the efforts to end the HIV/AIDS epidemic.

World AIDS Day provides a way for everyone to get involved in the fight against HIV/AIDS. It’s an annual day to think about the people who’ve lost their lives to AIDS-related illnesses and to champion efforts to prevent more people from losing their lives due to HIV/AIDS related causes. This December 1st do a little research, learn about the burden of HIV/AIDS in your community, and decide how to get involved. Together we can end HIV/AIDS in our lifetime.

We Can End Rabies Together

~Written by Theresa Majeski (Contact: theresa.majeski@gmail.com; Twitter: @theresamajeski)

Rabies is a neglected viral disease that is found on all continents except Antarctica and is endemic in 150 countries and territories. While rabies can be found almost everywhere, 95% of cases occur in Africa and Asia. Rabies is almost always fatal following the onset of symptoms. However, rabies is vaccine-preventable and can be eliminated. The World Health Organization (WHO) in conjunction with the Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health (OIE), and the Global Alliance for Rabies Control is raising awareness about rabies. September 28th is World Rabies Day and this year’s theme is “End Rabies Together”.

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Figure 1. Worldwide map of rabies indicating level of risk by country, 2011. Courtesy of the World Health Organization. http://www.who.int/rabies/Global_distribution_risk_humans_contracting_rabies_2011.png?ua=1

Rabies is usually transmitted to humans from the deep bite or scratch of an infected animal. Domestic dogs are responsible for more than 99% of human rabies cases throughout the world. According to the WHO, “while infected domestic dogs cause human rabies deaths in Africa and Asia; in the Americas, Australia and Europe, bats are the primary source of human rabies infections.” Children are disproportionately affected by rabies. Forty percent of people who are bitten by suspected rabid animals are children under 15 years of age.

No tests are available to determine if a person is infected with rabies before they show clinical symptoms. Once a person begins to show clinical symptoms of rabies, the disease is almost always fatal. There have been a few cases of people developing rabies symptoms and surviving, with the use of the Milwaukee Protocol. In 2004, a Wisconsin teenager was bitten by an infected bat. She did not seek medical treatment and did not receive PEP. Dr. Willoughby, an infectious disease specialist at the Children’s Hospital of Wisconsin near Milwaukee, tried an experimental treatment that included an induced coma and antiviral medication. The teen survived with few lasting complications. However, many experts caution that the Milwaukee Protocol is not the cure for rabies, at least not yet. The first 43 human rabies cases where doctors attempted to replicate the Milwaukee Protocol resulted in only five survivors. Admittedly, five survivors are pretty good for a nearly always fatal disease, but not enough to say that the Milwaukee Protocol is a cure for human rabies.

Vaccinating dogs is the most cost effective way to prevent human rabies deaths because it results in a decrease in the global deaths attributable to rabies and a decrease in the need for post-exposure prophylaxis (PEP). Post-exposure prophylaxis is the administration of rabies immunoglobulin and rabies vaccine to an exposed person immediately after exposure, in order to prevent infection. Timely PEP can prevent the onset of rabies symptoms and death. However, PEP is expensive and not widely available in many of the resource poor settings with high rabies burden. Eighty percent of dog-mediated rabies deaths occur in rural areas that lack awareness about, and access to, PEP.

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Figure 2. The 2015 World Rabies Day logo. Courtesy of the Global Alliance for Rabies Control. http://logos.rabiesalliance.org.s3-website-us-east-1.amazonaws.com/englishweb.jp

Rabies elimination is achievable for many of the countries with a high burden of dog-mediated rabies cases. Achieving a dog vaccination rate of at least 70% is accepted as the most effective way to prevent human rabies deaths. Rabies transmitted by dogs has been eliminated in many Latin American countries including Chile, Costa Rica, Panama, Uruguay, most of Argentina, the states of Sao Paulo and Rio de Janeiro in Brazil, and large parts of Mexico and Brazil. A Bill and Melinda Gates Foundation project, led by WHO, has made great strides against human rabies cases in the Philippines, South Africa and Tanzania. Furthermore, many countries in WHO South-East Asia Region have begun elimination campaigns with the goal of meeting the 2020 target for regional rabies elimination. Bangladesh, for example, launched an elimination program in 2010 and has seen human rabies deaths decrease by 50% during 2010-2013.

While there are still challenges in achieving a high vaccination rate in some areas of the world, such as vaccine availability and community support, some countries have been able to achieve rabies elimination. Events like World Rabies Day help draw attention to the high burden of rabies in resource poor settings and help to highlight the work being done to eliminate rabies.

Life after Polio: Towards Improving the Situation of Polio Survivors

~Written by Hussain Zandam (Contact: huzandam@gmail.com, twitter: @zandamatique)

A woman paralyzed by polio, Rotary International (2010)

here is a surge of excitement among international development communities and global health partners as the World Health Organization announced that the battle against polio is gradually coming to an end (WHO, 2013). The Global Polio Eradication Initiative (GPEI) has set out a new strategy (Eradication and Endgame Strategic Plan), which hopefully will be the final onslaught that will result in a global certificate eradication of the disease by 2018 (GPEI, 2013). The eradication will be a significant victory for the global population, as future generations will also be saved from polio's devastating toll of death, morbidity, and disability.

Map of the world comparing countries with polio cases in 1988 and 2014. Centers for Disease Control and Prevention, CDC (2014).

While a vast amount of resources has been disbursed to prevent polio since 1952, inadequate attention has been devoted to understanding the devastations left behind in the lives and households of polio survivors. The damage is more severe in those permanently disabled by the disease and those recently identified with post-polio syndrome (PPS). Post-polio syndrome is characterized by a renewal or new experience of polio symptoms including disability and functional deterioration after years of recovery and functional stability. PPS usually occurs 30-40 years after original infection and affects about 40% of polio survivors including those who developed permanent disability and those who recover from initial affectation with no or few symptoms (Lin and Lim, 2005). 

Although the situation of polio survivors in high-income countries is relatively well documented, there is a dearth of information in low and middle-income countries. This has profound political, economic and social implications for local, national and international policy-making. While the number of individuals disabled by polio will begin to disappear in the next few decades in the developed world, those in the developing world will continue to be a major concern for at least another generation (Gonzalez et al., 2010). And as the population of younger polio survivors reaches middle and old age, a new wave of individuals with PPS will begin to make additional demands on developing countries’ health systems.

Generally, individuals disabled through polio confront not only a range of physical disabilities but also significant social, financial and human rights barriers hindering integration and participation in families and communities. These barriers in turn, lead to chronic ill-health, social marginalization, limited access to education and employment, and high rates of poverty (Groce et al, 2011). Women are impacted disproportionately, as are individuals from poorer households, minority communities and from rural and urban slum areas (WHO/World Bank, 2011). 

To design effective programs and policies that improve life course outcomes for polio survivors, more research is essential. To begin, more accurate estimates of regional prevalence of polio survivors and the degree of residual disability sustained will be useful for efficient planning and appropriate resource allocation. In particular, addressing the stigma and prejudice encountered by persons disabled by polio must be part of long-term strategies to address the needs of people living with PPS and must be linked to broader efforts to confront disability and stigma faced by all people with disabilities. Ratification by countries of the Convention on the Rights of Persons with Disabilities (CRPD) and progressive national legislation are not enough - inclusion of polio survivors in community awareness campaigns and increased support by DPOs is also needed. And given the disproportionate impact of polio on women, DPOs must pay particular attention to gender sensitive research.

References:

Global Polio Eradication Initiative, 2013. Polio Eradication and Endgame Strategic Plan: 2013e2018.

Groce, N., Kett, M., Lang, R., Trani, J.F., 2011. Disability and poverty: the need for a more nuanced understanding of implications for development policy and practice. Third World Quarterly 32 (8), 1493e1513.

Gonzalez, H., Olsson, T., Borg, K., 2010. Management of postpolio syndrome. The Lancet Neurology 9 (6), 634e642.

Lin, K.H., Lim, Y.W., 2005. Post-poliomyelitis syndrome: case report and review of the literature. Annals-academy of MEDICINE SINGAPORE 34 (7), 447

WHO, 2013. Poliomyelitis. Fact Sheet No. 114. WHO, Geneva. http://www.who.int/ mediacentre/factsheets/fs114/en/index.html (accessed 11.08.15.).

WHO/World Bank, 2011. World Report on Disability. WHO, Geneva. http://www. who.int/disabilities/world_report/2011/en/index.html (accessed 12.08.15.).

Polio Eradication: How Close are We?

~Written by Theresa Majeski (Contact: theresa.majeski@gmail.com, twitter: @theresamajeski)

Polio may become the second viral human disease (following smallpox) ever eradicated from this planet. Like smallpox, polio can be prevented with vaccination and, perhaps most importantly, polio relies solely on person-to-person transmission for survival. This means that polio does not require any vectors like mosquitos or snails for its life cycle, so humans are the only ones infected by poliovirus. Polio is usually spread through a fecal-oral route, meaning that the virus is in the stool of an infected person and could come in contact with the mouth of an uninfected person through contaminated foods, hands, utensils, etc. If we can interrupt transmission through vaccination, poliovirus will be unable to find someone unimmunized to infect and will be eradicated.

Polio has a long history within the human population. Only sixty years ago, polio was a feared disease in the United States. Summer time brought with it polio season and public facilities such as swimming pools were shut down. This reaction was not unwarranted. In 1952 almost 600,000 children were infected with the virus. More than 3,000 died and thousands were paralyzed. Iron lungs were used to keep children alive as the paralysis left them unable to breathe on their own.

Photo of children in iron lungs. Photo courtesy of the National Museum of Health and Medicine. 

President Franklin D. Roosevelt contracted polio as an adult, years before taking office. He made fighting polio a national priority and established the March of Dimes to encourage everyday citizens to fund polio research. Jonas Salk created the first polio vaccine, approved in 1955; Alfred Sabin created a second polio vaccine, approved in 1963. Through the use of these two vaccines, the United States was able to eradicate polio by 1979.

Despite this, it wasn’t until the 1970’s that polio was recognized as a serious problem in developing countries. Once polio was identified as being prevalent in developing countries, routine immunization campaigns were implemented worldwide which helped bring polio under control in many countries. In 1988, when the Global Polio Eradication Initiative began, more than 1000 children worldwide were paralyzed by polio every day. Since then, the global incidence of polio has decreased by 99 percent.

Countries that have achieved elimination have not done so without challenges. The two polio vaccines have benefits and drawbacks. The Salk vaccine, also called the inactivated polio vaccine (IPV), contains chemically inactivated polio virus. It stimulates a strong systemic immune response but because it is an injection, it does not cause a strong mucosal immunity. Without a strong mucosal immune response poliovirus can replicate in the intestines of immunized people without causing symptoms and can then be contagious. On the other hand, the Sabin vaccine, also called the oral polio vaccine (OPV), is a live-attenuated vaccine. This means that the vaccine contains live, weakened poliovirus. The Sabin vaccine is given orally so it stimulates mucosal immunity and systemic immunity. However, because it is a live vaccine, it can revert to a virulent form and cause vaccine-derived polio infection. The Sabin vaccine is easier to administer because it doesn’t require syringes, and it provides longer immunity than the Salk vaccine, however, it requires strict transport conditions because it is live. The World Health Organization is advocating for countries to move towards the IPV and phase out use of the OPV, to help prevent vaccine-derived polio cases. The Global Alliance for Vaccines (GAVI) recently announced that they will be helping Pakistan introduce the IPV as part of the Polio Eradication and Endgame Strategic Plan 2013-2018.

Currently, polio is endemic in only three countries: Nigeria, Pakistan and Afghanistan. In order for a country to be declared free of polio, three years must pass without a case of endemic (wild type) polio. Nigeria achieved one year without an endemic polio case on 24 July 2015. This means that only two more years remain before the African continent may be declared polio-free. India was removed from the list of polio-endemic countries in 2012, and in 2014 India achieved polio-free status. India, long considered the country facing the greatest challenges to eradication, demonstrates that global eradication is possible. However, some countries that had achieved elimination are experiencing outbreaks of polio, partly due to political instability, which has impacted vaccination rates. For example, Syria was polio free from 1999 to October 2013 when imported cases of polio closely related to strains circulating in Pakistan were confirmed in Deir ex-Zor and Aleppo. This demonstrates the importance of maintaining a high vaccination rate in every country until the disease is eradicated. 

Current polio distribution around the world. Graphic courtesy of Global Polio Eradication Initiative. 

Achieving eradication through eliminating polio in the last few countries will not be easy. The areas with endemic polio transmission face several challenges including conflict and political instability, hard-to-reach populations, and poor infrastructure. Furthermore, community workers trying to administer polio vaccine are being attacked by groups who oppose polio vaccination. The CIA providing vaccinations as a cover for searching for Osama bin Laden certainly eroded trust between health workers administering vaccines and community members, making poliovirus vaccination campaigns that much harder. However, focusing on strengthening all routine immunization delivery, helping locals take ownership of polio eradication in their communities, working directly with community members and leaders, and building trust by keeping a lower profile on international deadlines may help overcome the remaining challenges.

Humanity is on the cusp of another great infectious disease achievement, eradicating polio by 2018. Polio eradication is achievable; however continued focus and resources are required to interrupt transmission in the hardest to reach places. Eradicating polio will save many lives and prevent countless children from paralysis; a goal that can be achieved in our lifetime.