Category: Perspectives

Show Me The Money – Childhood Diarrhea and The Politics of Vaccines

Vaccines in the News…Again

The start of the year has been dominated by news headlines of ongoing measles outbreaks in the United States and Europe. Antivaxxers seem to be winning the messaging on vaccination by convincing a growing number of parents to decline vaccinating their children. This is very concerning to public health experts who worry about more frequent outbreaks and deaths from preventable childhood diseases.

Wealthy countries, fortunately do not have to contend with the additional issues around sustained supply and access to life-saving vaccines for those who actually want them. In less privileged countries, the main barrier to vaccination remains the lack of continued access and stable supplies, a constant challenge for health authorities .

In November 2018, the pharmaceutical company Merck announced it was pulling out from its agreement with GAVI – the vaccine alliance, to supply its rotavirus vaccine Rotateq® to four low income countries in West Africa. This announcement at face value sounds like another boring headline. It however has implications that run deep, but hardly created a ripple in the constant stream of news. 

More Than Just Diarrhea 

The WHO estimates that worldwide there are 1.7 billion cases every year of diarrheal illnesses in children under 5. That’s a lot of poo, but more importantly these diseases kill half a million children every year. For those who survive through childhood, there is significant morbidity including malnutrition, growth retardation, recurrent infections and impaired cognitive development. A large proportion of affected children live in low- and middle-income countries, with obvious implications for the economic development and population growth of these regions. Rota virus infection is the leading cause of diarrhea-illness in early childhood and kills about 215,000 children under the age of 5 every year. 

Rota virions

The development of two effective rotavirus vaccines administered orally has been a saving grace for many children in developing countries especially in Africa. Following successful clinical trials demonstrating their efficacy in poor and high mortality settings, the WHO recommended the inclusion of these vaccines in the national immunization programs of all countries.  

A Worthy Investment?

Oral Rotavirus Vaccine

Rolling out Rotavirus vaccination in high mortality regions has been challenging but is a worthy investment with indisputable positive outcomes. Since its introduction in Ethiopia in 2013, Rotavirus vaccination has saved an estimated 3700 childhood lives and 800,000$ in household expenditures every year. Even more striking is the projection that expanding its use to all eligible countries could prevent an estimated 180,000 deaths and avert 6 million hospital and clinic visits, saving 68 million dollars in annual costs. With numbers like these, funding this vaccine should be a no brainer and a guaranteed win for all parties involved.

https://www.gavi.org/library/audio-visual/galleries/accelerating-africa-s-access-to-rotavirus-vaccine/

There are two main licensed Rotavirus vaccines on the global market today, Rotarix® manufactured by GlaxoSmithKline and Rotateq® manufactured by Merck and Co. A lot of the countries in sub-Saharan Africa have only been able to afford these vaccines with the support of the GAVI. In 2011, Merck agreed to sell Rotateq® to GAVI at a discounted price of 3.50$ per dose. Through this agreement over the past 6 years, 30 million doses of the vaccine have been delivered to four countries in West Africa – Burkina Faso, Ivory Coast, Mali and Sao Tome and Principe. GSK also sells its Rotavirus vaccine Rotarix, to GAVI at a reduced cost of 2.25$ per dose and has so far delivered 220 million doses to 42 countries around the world through this agreement. 

A Change of Heart with Serious Implications 

All seemed to be going well until the end of 2018 when Merck informed GAVI it was backing out of the agreement and will not deliver a third of vaccine doses needed for 2018 and 2019. They also plan to cease all rotavirus vaccine deliveries to these countries by 2020. This casual change of heart by Merck, in reality leaves 2.5 million vulnerable children without an alternative Rota virus vaccine source in just three years. 

Merck has cited “country-specific requirements, unanticipated manufacturing issues and packaging challenges that put greater stress on our already strained packaging capacity” as the main reason for pulling out of the supply agreement. Simultaneously, however it is moving to start supplying the same vaccine to China at a higher price of 40$ a dose. The higher profit margin, promised by the more lucrative Chinese markets sticks out like a sore thumb and makes Merck’s supply chain excuse a little less plausible.

Too hard to resist – The lure of the Chinese vaccine market 

China’s vaccine market is sizable but also notoriously difficult to break into for multinational BigPharma companies. Until very recently, the Chinese government required that all vaccines be tested in clinical trials conducted within the country, prior to their introduction. As a result, a lot of the vaccines used in the country are manufactured by local Chinese pharmaceutical companies. Recent scandals around the distribution of faulty vaccines by major Chinese pharmaceutical companies has created vaccine shortages and a loss of trust in locally manufactured vaccines. This has led to the relaxation of some of the regulations around vaccine supplies and opened a window for foreign pharmaceutical companies to come in. 

Syringe on a twenty dollar bills background

With an estimated 17 million births every year, gaining authorization to sell vaccines on the Chinese market can mean a significant profit boon for any pharmaceutical company. When GSK gained approval for its HPV vaccine to be sold in China, this boosted global sales by approximately 60 percent to $185 million, a windfall of profit for the company. Merck has also had success on the Chinese markets with their own HPV vaccine. They saw a 24% boost in sales, an estimated $660million in the first quarter of 2018 following its introduction in China.

Rotavirus infection remains a big problem in China where it kills an estimated 3000 children every year and causes 30-40 percent of hospitalizations and doctor visits. Although no one can predict how well Merck’s Rotateq® will compete with the locally manufactured Rotavirus vaccine currently available in China, the potential for the company to make a larger profit margin in the Chinese market is undeniable and certainly worth the effort. Sadly, this likely means diverting supply chain resources from the commitments made to four West African countries in the pursuit of these bigger profits.

Protecting all children – Beyond Profits 

One could argue that the four African countries left in limbo by Merck, could simply switch to the GSK Rotarix® vaccine as an alternative. In reality, the logistics around switching a vaccine supplier in developing countries, requires several years of pre-planning and costs agreements which are challenging to put in place given the timeframe.

Furthermore, GSK does not plan to expand its supply agreements for its Rota vaccine beyond the countries it currently covers. Two new Rotavirus vaccines produced by Indian, pharmaceutical companies have been recently pre-qualified by the WHO to be sold at affordable costs to GAVI. Rolling them out on a large scale could take several years and will not reliably close the supply gap that Merck leaves behind in the short term. 

A hand protecting children

All children need reliable access to life saving vaccines. No monetary value can be substituted for a life saved by effective vaccination, be it that of a Chinese child or an African child. Merck’s decision on discontinuing their supply of rotavirus vaccines to four West African countries, sets a dangerous precedent. It also highlights the precarity that many developing countries continue to face when it comes to the supply of life saving vaccines and medicines.

Beyond profits and lucrative markets, the focus should be on every s child having access to vaccines regardless of whether they come from a poor or a wealthy country. Even a year’s lapse in supply puts millions of innocent babies at risk of death – an unjustifiable failure, which places an entire generation in peril.

Written by Boghuma K Titanji

In the Shadows: “Neglected” but Not Forgotten

Down memory lane …

My earliest excursions into the world of “neglected” tropical diseases takes me back to mass distributions of Albendazole in my public primary school. At the age of 8 it seemed like any other curious and exciting experience. Getting in line with my school mates and being handed two flavored pink pills to take – for the worms! At that time, I did not realize that I was actively taking part in a huge public health campaign, aimed at reducing the burden of helminthic diseases in school age children.

A health worker gives Praziquantel and Albendazole deworming tablets to a child at a school-based mass drug administration day://www.schisto.org/

Though simple at face value, this intervention kept me and my peers on the growth curve, prevented us from getting anemia and gave us a shot at growing into healthy adults in an environment where the odds are often stacked against you.  Similar campaigns continue to this day and are pivotal in reducing the negative effects these diseases place on developing world populations. 

While simple interventions have proven invaluable in select cases, the vast majority of these diseases remain in the shadows, infrequently talked about and far removed from the consciousness of those not affected by them. Yet they continue to place an undue burden on the world’s poorest and most vulnerable populations. Having practiced medicine in sub-Saharan Africa, I know too well the realities of dealing first hand with the irreversible blindness caused by untreated onchocerciasis or the disfiguring and life-altering effects of filarial elephantiasis, just to name a few. 

Man Blind as a result of Onchocerciasis -https://www.flickr.com/photos/communityeyehealth/

Out of Sight and Out of Mind – A luxury not afforded to all 

I grew up knowing and fearing these diseases with strange names and devastating consequences, first as a child then later as a healthcare provider with limited treatment options for my patients. To me and many others these weren’t “neglected diseases” but real-life threats with potentially nefarious consequences. I currently live and practice medicine in a western country and now fully realize just how easily one becomes removed and unconcerned by issues that do not directly affect your daily life. Therein lies the central thesis of the “neglected” tropical disease – out of sight really is out of mind!  

By current World Health Organization data, 1 billion people in 149 countries suffer from one or more “neglected” tropical diseases which claim half a million lives every year. These diseases disproportionately affect the world’s poorest and most vulnerable communities and remain at the bottom of the priority list for new drugs and vaccines research.

The Curious Case of Sleeping Sickness

Trypanosoma brucei parasites- courtesy cdc.gov

One of the most refreshing news headlines of 2018, was the rapid approval of a new and simple oral treatment for sleeping sickness. Sleeping sickness refers to Human African Trypansosomiasis (HAT), a parasitic infection caused by Trypanosoma gambiense and Trypanosoma rhodesiense, parasites transmitted by Tsetse flies.  An estimated 57 million people are at risk from this disease with 100,000 contracting it every year. Although sporadic cases do occur in tourists infected through Tsetse fly bites while on Safari, those most directly affected are the populations living in areas where the transmission of the parasite is endemic.

Tsetse fly vector of Human African Trypanosomiasis- Courtesy Science Photo Library

Sleeping sickness has severe consequences for those who contract the disease with symptoms ranging from fever, headache and joint pain in the early stages to behavioral changes and neuro-psychiatric manifestations in its later stages. Those affected undergo a horrific transformation and become aggressive, delusional and unrecognizable to their family members, before ultimately succumbing to death in a few months usually through coma.

Natascha, 11, passed away as a result of Sleeping Sickness. Image: MSF

For the longest time, the only available treatment options were severely toxic and difficult to administer regimens, which themselves could be fatal for the patient. The main drug used for treatment was Eflornithine which though freely supplied by its manufacturer Sanofi, required 4 infusions daily for a 14-day period. It is usually delivered in combination with an oral drug Nifurtimox. Administering this type of treatment in rural parts of Africa can be especially challenging. Hospital wards are often rudimentary rows of iron beds, severely understaffed and poorly equipped and most of the patient care is provided by relatives sleeping on floors next to their loved ones. Monitoring and safely delivering this type of treatment under such circumstances is hazardous at best and near impossible at worst.

Overcrowded hospital ward in sub-saharan Africa – https://www.tcsnetwork.co.uk/wp-content/uploads/2018/01/african-hospital-1200×675.jpg

In 2012 the world health organization created a road map with the goal of eradicating the disease by 2020. This galvanized international funding to pursue development of oral treatment candidates for the disease. The efforts have been fruitful with the approval of Fexinidazole, an oral drug that cures all stages of the disease within 10 days. Fexinidazole was developed by a German pharmaceutical company Hoechst in the 1980s but its development was halted when the company abandoned its tropical diseases program. It took almost 30 years to reignite the desire to see this drug through clinical trials leading to its approval for the treatment of sleeping sickness in 2018. 

Card Agglutination Test for HAT Screening performed by mobile health worker in DRC – courtesy https://www.theguardian.com/world/2018/nov/16/congo-drc-sleeping-sickness-upside-tropical-disease-ntd

This triumph is a real game changer in the treatment of the disease but is slightly tainted by the cost in human life and time it took to arrive at this point. The drive for the approval of Fexinidazole is the result of a 10-year partnership between the Drugs for Neglected Diseases initiative (DNDi), Sanofi and African Partners and cost an estimated 63 million dollars. This cost is dwarfed in comparison to the cumulative direct and indirect costs of the disease on affected populations through the years when treatment options were complex and limited.  More importantly it provides the proof of concept that setting clear goals and igniting global commitment in the fight against neglected tropical diseases can lead to concrete results and raise real hope to eradicate some of these diseases.

One Down, Nineteen to go 

Neglected Diseases of the World

As I reflect on the success story of sleeping sickness, I can’t help but wonder how many drug candidates for the other 19 neglected tropical diseases remain suspended in the research pipelines of pharmaceutical companies around the globe. These drugs likely will never see the light of day due to a lack of incentive to take them through expensive drug development processes. The reality is the 1 billion people who directly suffer the brunt of “neglected” tropical diseases are poor and represent the least profitable markets for pharmaceutical companies.

Global trends in distribution of “Neglected” Diseases – https://adc.bmj.com/content/archdischild/98/8/635/F1.large.jpg

Eflornithine which has been until recently the mainstay of treatment for sleeping sickness, saw its supply threatened severely in the early 2000s. The patent holder for the drug abandoned production due to its failure to live up to its potential as a drug for cancer, a far more lucrative target. This left only a few thousand doses of the life-saving medication available to the thousands of invisible patients tucked away in remote parts of the African continent. The clock was ticking down with many fearing the worst.

Eflornithine hydrochloride – Intravenous infusion for treatment of HAT

The saving grace for this drug came through an alternative profitable cosmetic use being identified for the molecule. Eflornithine was found to be effective for facial hair removal in women, leading to a revival of the patent and ensuring its continued production and supply for the treatment of sleeping sickness.  In this particular instance, a happy compromise was made after intense international pressure. The pharmaceutical companies could continue to reap profits through sales of a lucrative facial hair removal cream and in exchange sustain production of the less profitable intravenous formulation of the drug needed to treat sleeping sickness. 

Eflornithine cream formulation for removal of facial hair, the same drug formulated as an infusion has been the mainstay for Treatment of HAT

Sadly, the world of big pharma is still largely commanded by the ability of new drugs to generate huge profits. As a result, most “neglected” diseases will not have a romantic ending like that of sleeping sickness and will remain in the shadows. Sanofi, through the role it has played in the development and approval of Fexinidazole has proven that the conversation does not always have to be solely based around profits. It can be a more human conversation that focuses on the real human lives at stake and finds the balance between profitable vanity projects and drug development for less profitable targets.

Until that time comes, in my little bubble of comfort I live in hope that a molecule in my daily facial cream is somehow sustaining the production or development of a drug that treats a “neglected” tropical disease somewhere far away. A highly improbable thought which makes me feel slightly better about my neglect of diseases which are way too real for millions of others with less fortunate circumstances.

Written by Boghuma. K. Titanji

To support the fight against neglected diseases consider donating to Drugs for Neglected Diseases initiative and Doctors without borders by following the links below:

https://www.doctorswithoutborders.org/what-we-do/medical-issues/sleeping-sicknesshuman-african-trypanosomiasis

https://www.dndi.org/donate/

America’s Dark Secret – The HIV Epidemic of the South

Good morning I’ll be your doctor today …

These simple words mark the beginning of my relationship with Jay, as I usher him through the doors of my office. Jay is a black gay man in his twenties, living in Atlanta and newly diagnosed with HIV. He tested positive for HIV infection during an emergency room visit for a fever, three weeks ago.

As he settles into his seat his demeanor appears timid and withdrawn and he answers my initial questions mostly in brief monosyllables, barely making eye contact. The first visit is always the hardest both for the healthcare provider and for the patient. I feel the pressure of getting it right and gaining this patient’s trust as I am sure he in turn feels the unease of divulging to a complete stranger the most intimate details of his life.

As the encounter progresses Jay relaxes a little, he is still struggling to come to terms with his diagnosis and what it means for his life moving forward. He shares an apartment with two roommates and works at a fast food restaurant in the city. He admits to having some friends living with HIV, but he never thought he would be faced with the same diagnosis. I provide reassurance but mostly a listening ear which I feel is what he needs most at this time. I ask if he has a support network, someone he can talk to about his diagnosis and the adjustments of living with HIV. While he has family in nearby Alabama, he is estranged from his parents who do not know he is gay and he feels they would not approve of his “lifestyle choices”.

He wishes to keep his diagnosis to himself for now and reassures me he is a fighter and will pull through. We discuss treatment options and clinic resources available to support him. He leaves the office with his first prescription of antiretroviral treatment, marking the start of a challenging new chapter of his life: living with HIV as a black gay male in the South of the United States.

Jay, unfortunately, will not be the only new patient diagnosis of HIV infection I see in the clinic this month. In reality there will be multiple, mostly young, gay/bisexual, male and black making it impossible to ignore the epidemic unfolding in real time. I will go over the same scenario again and again, hoping to gauge every initial clinical encounter right and lay a foundation of trust in the healthcare system which will ensure long-term engagement with HIV care.

Some of the of the less fortunate ones, I will only see as hospitalized patients, battling for survival as opportunistic infections ravage their immunocompromised bodies, sometimes well past the point where their lives can be saved. The deaths are the hardest to deal with, especially knowing that it doesn’t have to be this way in 2018.

Against terrible odds

Worldwide, the incredible advances in treatment and prevention over the past 37 years, have transformed the face of HIV completely. What was once a death sentence is now a chronic and manageable infection with effective and simplified treatment options.

In cities like New York and San Francisco, once among the hardest hit by the epidemic in the early 1980s, infection rates continue to decline and HIV-infected individuals are retained in care at high rates.

Sadly, the same cannot be said for the epidemic of HIV in the South of the US where the virus continues to plough through the black gay/bisexual/trans community at an alarming pace. In 2016, the Centers for Disease Control and Prevention estimated that one in two African-American gay/bisexual males (men who have sex with other men-MSM) will become infected with HIV over the course of their lifetime, a staggering statistic when compared to the 1 in 99 lifetime risk of HIV infection for all Americans and the 1 in 11 lifetime risk of infection for white gay/bisexual men.

These rates are among the highest rates of HIV infection in the world! The Southern States represent about 37% percent of the US population, yet per recent public health estimates account for just over half of the new HIV diagnoses nationwide, with most of these being in gay/bisexual black males. The odds are incredibly harsh for patients like Jay for whom a diagnosis of HIV at some point in their lives almost seems to be an inevitable outcome. The reasons behind this raging epidemic are multifaceted and extremely complex rooted in a history of racial discrimination, homophobia, economic and social disparities. These elements have come together to create a perfect storm and continue to feed an epidemic which is proving challenging to contain.

The deadly trifecta – Racial discrimination, Homophobia and Stigma

During the very early years of the HIV epidemic in the 1980s, white gay men very quickly became the face of the epidemic due to the sheer numbers of them who were infected and dying from AIDS. This led to a galvanization of public health efforts aimed at prevention, education and treatment resulting in a sharp decline of new infections as awareness of the problem grew. As the years went by and new effective treatments for HIV were developed, the focus and funding began to shift to other areas like marriage equality, with many considering HIV an issue that was largely under control.

In reality, the legacy of the focus on the white gay/bisexual male HIV epidemic in the US was a silent epidemic allowed to take root in the black gay community, where being identified as a gay/bisexual male was shrouded with taboo and stigma. The complacency could not have come at a worse time, laying the foundation for an epidemic at its peak today. The advent of the HIV epidemic in the black MSM community, joined the ranks of existing healthcare disparities which disproportionately affect minorities in the United States and the extensive stigma and discrimination associated with being black and MSM.

All of these factors are amplified several fold in the Southern States of the United States where deeply held Christian religious views promote and sustain homophobia and stigma. I continue to be surprised at the number of MSM patients I see in clinic who live a life of secrecy to preserve family ties and relationships with loved ones they feel may not be accepting of the sexual orientation. In many ways Atlanta is a safe haven and an oasis of acceptance for black MSM much like San Francisco for white MSM in the 1980s and 1990s but this virtue also makes it one of the epicenters of the Southern Epidemic.

The concentration of black MSM in the city has also increased the risks of HIV transmission. Sexual networks and the pool of potential partners tend to be closed within the black community with black MSM having sex with other black MSM. When infections do occur, access to healthcare services is hindered by a lack of education on available options for prevention, testing and treatment, homelessness and poverty, substance abuse issues and the stigma of being labelled as infected with HIV. It is estimated that 45% of MSM in the United States have never tested for HIV infection and about 40% of new infections are transmitted by people living with undiagnosed HIV.

The low rates of testing and diagnosis mean that we are seeing far too many people diagnosed with advanced disease and serious opportunistic infections which can have serious life changing consequences or result in death. In 2016, there were and estimated 1513 new diagnoses of HIV infection in the city of Atlanta, a number which has held steady since 2012. Out of these, 360 deaths of people diagnosed with HIV were recorded in the city. The numbers are stark and the picture, though somber, shows the true face of the HIV epidemic in the black MSM community, highlighting the need to do more if we hope to win this fight.

Winning the fight against HIV- Leave no one behind

As we mark yet again another world AIDS day this December 1st, there are many reasons to feel hopeful about how far we have come since the beginning of the HIV/AIDS epidemic. We have effective treatments that allow people infected with HIV to live normal lives and have essentially the same life expectancy as uninfected individuals. Also, there is effective pre-exposure prophylaxes which prevents infection from happening in high risk individuals. These advances are real triumphs considering where we were almost 40 years ago but also the reason why it is unconscionable that we leave anyone behind.

In 2015, it was estimated that in the United States about 49% of people infected with HIV were on treatment and about half of that number have effectively suppressed their virus. These estimates were even lower in the subgroup of black MSM, the group hardest hit by the current epidemic. We have incredible tools to curb the spread of HIV in our arsenal but we seem not to be getting them to where they are most needed. We cannot allow complacency to set in when the fight is far from won.

A copy and paste model from the early days of the epidemic has clearly not been effective in stemming the tide of the epidemic in black MSM. We must rethink our approaches to engaging the community, fighting stigma, social and economic inequalities. In my opinion this will only be effective through giving the community a voice and a seat at the table in developing innovative strategies for raising awareness on treatment, prevention and HIV care in general.

 

 

I am hopeful that Jay will return for subsequent treatment visits and will become one of the many success stories in the clinic. In a fight that’s far from over every little step forward counts and sustains the hope that we can beat this once and for all. No one will be left behind this time.

 

Written by Boghuma K. Titanji 

( Names and timing of events have been modified to preserve patient anonymity)

A Rising Tide – Africa’s Not So Silent Opioid Crisis

From Guangzhou and Mumbai with love?

The sights and sounds of a busy African city are something when once experienced are never forgotten. Rowdy traders haggling prices with their customers, street food vendors assembling delicious meals at the roadside and motorcycle taxis zooming through, transporting people to their various destinations.  Everyone is in a hurry and everyone is busy trying to survive and make it through another day.

The imagery though chaotic, is a fond one for many who have experienced it first hand either through tourism or by growing up in Africa.  Buried amidst the chaos is the ever-present street “pharmacist”. Usually, a small makeshift stand or sometimes just a carton box packed with contraband medicines for all ailments. The stand is typically manned by an ordinary looking person everyone calls “docta”. Projecting an air of confidence on all things health-related next to signs displaying his or her areas of specialty. People stop by for consultations and prescriptions, a quick exchange of cash is made and they walk away with a supply of pills for whatever illnesses they seek to address.

The combination of poverty, high unemployment rates and lack of access to healthcare means that street medications are for many the only affordable option for healthcare, despite the associated risks. This is  fertile ground for the never-ending stream of counterfeit medicines, which pour unto Africa’s streets from China and India. The demand feeding this multibillion-dollar industry is driven by factors too daunting for corrupt governments with little will to effectively address. Crackdowns when they do happen, are mostly for show than a real attempt at effective regulation.

For many years the focus has been on the risk of sub-standard antibiotics driving antimicrobial resistance and ineffective fake treatments and toxic drugs killing thousands in these parts of the world.  While these issues continue to prevail, the last five years have seen a rise in contraband opioids, take the illicit medication market in Africa’s major cities by storm. This newcomer adds another crisis to the ever-growing list, one that the region is wholly unprepared for, with sinister implications for gains made in other areas of public health.

 Meet Tramadol – Africa’s Choice Opioid

Healthcare providers in developed countries have access to a wide array of opioid medications to treat their patients. 4 countries – the US, Canada, the UK and Australia consume a remarkable 68% of the opioids produced by pharmaceutical companies worldwide. This privilege, abused by some healthcare providers through overprescribing, has been the biggest segue way to the serious opioid crisis now facing the US. In staggering contrast over 150 countries have little or no access to these medications, which when used and prescribed appropriately are essential to address pain in patients with cancer and other chronic pain syndromes.

The main reason behind this inequality in distribution is a system for international drug control, led by the United Nations Office on Drugs and Crime (UNODC) and the International Narcotics Control Board (INCB). These organizations were created to regulate licit use of opioids for medical purposes. Unfortunately, in the process they have created rules of surveillance and accountability that are almost impossible for poor countries to comply with. This has led to severe access issues and very limited options to treat pain syndromes in patients living in developing countries.

Enter Tramadol, a weak synthetic opioid that unlike its much stronger cousins Fentanyl and Methadone is not on the list of medicines regulated by the INCB. For this same reason it very quickly became a favorite on the prescription lists in poor countries. It is frequently the only option to help patients deal with post-surgical pain, cancer pain and other chronic pain issues.Depending on the dosing, Tramadol can have a sedating or a stimulant effect and produce a high like that caused by heroin. The news of these “desirable” effects has quickly filtered unto the streets and docta’s medicine cabinet, driving the non-medical use of Tramadol through Africa’s major cities to new highs.

Young people doing physically demanding work to earn a living are seeking out the drug for its stimulant effects, to allow them to work longer hours only to quickly become trapped in the vicious cycle of addiction. It has also gained popularity in high school and university campuses as a sex enhancing party drug. Tramadol at the right dosing antagonizes serotonin receptors and as a result can delay ejaculation. 

The drug is very cheap costing only a few pennies to score a dozen 50mg tablets, and is readily available on any street corner. The illicit drug market responded to the growing numbers of Tramadol users, by smuggling millions of tablets from India and China into major African cities. The fact that this drug is synthetic implies that there is no limitation to its production by the suppliers in Guangzhou and Mumbai.

In December 2017, Italian authorities intercepted a 50 million dollar shipment of Tramadol pills destined for Libya and in 2016, the US State Department declared Benin, a small West African country of 11 million people, the world’s second largest destination for Indian counterfeit Tramadol. Even more worrisome is the fact that producers have now increased the dosing strength of the pills being sold on the contraband medicine market. A drug usually prescribed in doses of 50mg and 100mg, you now find pills of 120mg, 225mg and 250mg being sold on the street. At higher doses, the nefarious effects of the drug are also increased. More instances of overdose and death as well as higher rates of aggressive and criminal behavior are being reported in recent months.

The agricultural industry has not been spared by the widespread abuse of Tramadol and it has filtered its way even into farming communities. Farmers in West and Central Africa have used the drug to enhance cattle feed, so the farm animals can plough for longer hours. This curious discovery was made when, researchers in Cameroon thought they had identified a medicinal plant source for Tramadol. They realized upon further inquiry that this was the result of direct human contamination from farmers feeding this medication to cattle.  

Several countries in the region have stepped up to try and fight the growing scourge of Tramadol addiction, though many others seem oblivious to the issue growing in plain sight. Egypt is now strictly regulating Tramadol use and cracking down on illicit shipments of the drug, after a study led by the Ministry of Health showed that  a staggering 70% of people seeking addiction treatment in the country were victims of Tramadol abuse.

Out of Sight is Out of Mind

Hardly a day goes by without a headline or an article on the opioid crisis that’s sweeping across the US, now considered to be one of the biggest public health crises facing the country. The United States, is one of the wealthiest and most powerful countries in the world, yet has struggled with effectively containing the ravages of the opioid crisis happening within its borders. Africa’s opioid crisis on the other hand is steadily growing and claiming more victims by the day with little attention paid to it both at the local level and at an international level.

The main reason behind this is the epidemic is affecting the poorest and most vulnerable groups in the society who mostly have no one to advocate for them at the national level. The thousands of addicted youth dying from overdose, or suffering the crippling effects of addiction are at the very bottom of the social strata. They rely on the stimulant effects of Tramadol to continue to do the kinds of physically demanding jobs, which allow them to make a living.  A lot of them are porters, motorbike taxi riders, manual laborers on construction sites in big cities etc.

Those of them who want to seek help for their addiction find that these services are not readily available or affordable for them. Centers for the treatment of addiction are few and far between and barely equipped to serve the growing numbers of victims of addiction in need of assistance. One can easily imagine the far-reaching effects of this growing epidemic extending to other areas of public health. Africa is a region that continues to bear a considerable burden of infectious diseases and mental health issues. The emergence of an opioid crisis would certainly erode the gains made in controlling these public health issues.

Is Tighter Regulation the Answer?

At the end of 2017, the UNOCD issued a statement raising the alarm on the increased trafficking and consumption of Tramadol and its health and security implications for the region. This has led to increased interceptions and seizures of Tramadol across W. Africa by government authorities. Despite these crackdowns, there has barely been  a dent in the supply chain of the drug, given the porous nature of borders connecting countries in the region.

The WHO has been shy in voicing its endorsement for a tighter regulation of Tramadol, a move that could essentially mean adding this medication to the list of internationally controlled opioids. While this may possibly decrease the illicit use of the drug by tightly regulating its importation and use, it will also penalize millions of patients with chronic pain who are for most part  sub-optimally treated and die in agony. Many also argue that a tighter regulation of Tramadol will simply open the way for other opioids to become the drug of choice on the illicit drug market.

These conflicting factors mean that there isn’t a straightforward answer to addressing the problem.  If governments in the regions hope to swing the tide toward winning the fight against the opioid crisis in Africa, they will have to take on the issue as seriously as any of the other major public health issues affecting the region.  This will require concerted collaborative efforts between countries in the region to target trafficking networks within and between  borders. Also more effective reporting systems will need to be put in place to capture the scale of the problem. Most importantly treatment facilities will have to be made available and affordable for persons struggling will issues related to addiction in order to break the cycle. Implementing these measures is certainly not easy in a region with a lot on its public health priority list.

A good place start is acknowledging that there is indeed an issue and raising awareness about it. Africa has a growing opioid problem and its not going away, the time to wake up and face it head on is now.

 

Written by : Boghuma K. Titanji 

To Vaxx or not to Vaxx – That is not the question!

 

Measles, Measles everywhere…

The first six months of this year marked a record high number of measles cases across Europe, exceeding the 12-month totals of any year in the past decade. According to the WHO 41,000 people have so far been infected with measles in the region in 2018. This is not the health record I was hoping to see broken this summer considering the strides we have made in preventing infectious disease in the past century. 37 deaths were recorded of those infected, fatalities that were completely avoidable given that measles is a vaccine preventable infection. These measles outbreaks have been directly linked to sub-optimal vaccination coverage, a growing and increasingly worrisome trend in developed countries.

As an infectious disease professional I especially struggle with understanding this regression, which goes against the overwhelming evidence demonstrating the benefits of vaccination and vaccines. How did we arrive here and where did we go wrong?  Conversations around vaccines and vaccination have become highly contentious and deeply polarizing, splitting people into vaxxer and anti-vaxxer camps.  A debate that often misses the point and does a huge disservice to the vulnerable groups vaccines most seek to protect.  Maybe it’s time to rethink the messaging around vaccines and vaccination if we hope to reverse this trend.

How vaccines have literally saved the world – Lest we forget

A good starting point is reminding ourselves exactly how far we have come thanks to vaccines. A fact that gets lost in the discourse as many take for granted these valuable disease-preventing tools that were not always available to humanity. Edward Jenner first used material from cowpox lesions to create immunity to smallpox in 1796. Over the 200 years that followed, his innovation underwent medical and technological changes eventually resulting in the eradication of smallpox eradication in 1977, saving over 5 million lives a year. Over that same time period, vaccines were developed to protect from most of the deadliest childhood diseases and effectively raised the average life expectancy by 30 years over the past century. The numbers are compelling and vaccination remains one of the greatest medical triumphs of our generation.

The message certainly seems to have resonated at least on a certain level and global vaccination coverage remains at a steady 85% over recent years without significant changes. While this is reassuring to a certain degree, the recent outbreaks of vaccine preventable diseases and the noted decline in vaccine uptake marks a chink in the armour and should be a warning against complacency. My greatest fear is, if the reasons behind declining vaccination uptake are not addressed, we risk losing the hard earned gains we’ve made in global vaccination coverage, a setback we cannot afford

The rise of Anti-Vaxxers – It’s not the full story

People who oppose vaccination, often referred to as “anti-vaxxers”, bear the brunt of the blame for low vaccine uptake, a lazy mistake that I’ve been guilty of making in the past. In reality, anti-vaxxers are a small minority with estimates of these groups in Europe and the United States hovering around only 2-3% of the population. While there is a lot of fear that anti-vaxxers may influence the public view on vaccination and drive the decrease in vaccination uptake, a closer look reveals the problem to be way more complex.  The anti-vaxxer movement has always co-existed with the vaccine revolution but gained steam in the late 1990s. In 1998, a fraudulent study published in the Lancet, which is now widely disproved, suggested a link between the Measles, Mumps and Rubella vaccine (MMR) and autism, giving fuel to the movement. Despite the researcher and study losing all scientific credibility, some people continue to hold the view that the connection still exist. With that being said, it is very difficult to find an anti-vaxxer group that has consistently impacted on the uptake of vaccines to fully explain the sharp declines that we are now seeing. The coverage and attention given to anti-vaxxers is disproportionate to the impact that they have and in essence diverts attention away from more concerning drivers of vaccination decline.

 

The hidden issues – Poverty , Inequality and Lack of Information

With the media being mostly pro-vaccination, targeting anti-vaxxers makes for a good story and enables avoidance of less popular issues. Poverty and exclusion, as well and inadequate supply and access to vaccination services locally and globally, are still the main reason why vaccination rates are declining.

In the US, children from families living in poverty tend not to have a regular relationship with a pediatrician, as a result they miss out or are late to vaccinations despite federal programs providing vaccines at no cost. Furthermore, across Europe and the US, advice on child health and vaccination services is not usually readily available in economically deprived areas. These areas disproportionately represent newly arrived migrant settlements and other vulnerable minority groups. We cannot also ignore the growing proportion of parents who, though not against vaccination in general, may delay or pick and choose which vaccines their children receive based on preconceived erroneous ideas on the adverse effects of vaccines. The common theme connecting these issues is access- to information, healthcare, and to the appropriate messaging.

Winter is coming… and so is flu season

Ironically I routinely have patients in my clinic asking about vaccine availability to emerging infectious disease threats such as Zika and Ebola yet at the same time declining my offer to get a flu shot.  This attitude highlights the false perception that somehow, vaccination against common infections is less important and can be overlooked, as opposed to the latest infection grabbing the headlines.  This is the dangerous complacency that puts us all at risk of large outbreaks and losing the ground that we have made with the vaccine revolution. Last year’s flu season, by CDC estimates, was the worst in almost a decade, breaking records just like this year’s measles crisis across Europe. Ultimately we have come too far and should know better than to ignore our most potent tools to fight infection. This message may sound trite but is still as valuable and important today as it was 50 years ago, vaccines prevent disease and save lives. Ignoring that simple fact makes us all less safe!

Written by Boghuma Titanji 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A Gathering Storm – The Superbugs are here and the world is not ready!

The Rise of Superbugs

“Doc, I think I have a bad sinus infection, I was hoping you could prescribe some antibiotics to help clear it”.  Sounds familiar?  It is always a bad clinic day for any healthcare provider, when the first patient on the schedule is requesting antibiotics they probably do not need.  After talking to my patient about his symptoms and performing a thorough physical exam, I carefully explain why his symptoms do not warrant a course of antibiotics. He reluctantly agrees to my plan for symptomatic management but his demeanor clearly shows disappointment at leaving my office without a prescription.

This scenario plays over multiple times in doctors’ offices around the globe and most times the ending is quite different. The patient gets to leave with an unnecessary prescription for antibiotics and the provider is guaranteed excellent patient satisfaction scores. In many parts of the world, the healthcare provider as a gatekeeper is nonexistent with patients easily self-prescribing over the counter antibiotics for a variety of ailments. The gross overuse of antibiotics is one of the main drivers for the explosive rise of pathogens with wide ranging resistance to available antibiotics – Superbugs.

The advent of drug resistant pathogens is considered to be one of the most threatening emerging global health issues affecting our generation.  The current estimates are staggering, with drug resistant pathogens claiming 700,000 lives every year. This number is projected to increase to 10 million by 2050 (that’s one death every 3 seconds!), surpassing deaths from cancer.  Superbugs are here to stay and we are simply not ready for them.

The Golden age of Penicillin and the Antibiotic Boom is gone

This year marked the 90thanniversary of the discovery of Penicillin by Sir Alexander Fleming, a forever milestone in antimicrobial therapy.  In the 50 years that followed this discovery about 270 antibiotics were developed and approved, revolutionizing the practice of medicine and patient survival from infections. Beyond saving lives, the antibiotic age played a critical role in significant advances in the fields of medicine and surgery. Without antibiotics a majority of the surgical procedures that are performed today would not be possible or survivable due to the risk of post-surgical infections. Also the availability of effective antibiotics to prevent and treat infections has enabled the use of potent chemotherapies for cancer treatment and immunosuppressive therapies needed to preserve transplanted organs.

The boom of the antibiotic era came with a heavy cost in pervasive unregulated use and food chain contamination with the use of antibiotics in agriculture and animal farming.  This era has now given way to a new age of antibiotic drug resistance and Superbugs and at the same time the development of new antibiotics is stalling.  In recent years pharmaceutical companies have shifted their research priorities to more lucrative horizons, and the timing could not be much worse.

Superbugs and Big Pharma – A marriage without benefits

Given the burden of disease and mortality from Superbugs, one would think that there would be a rush by Big Pharma to develop new drugs and cash in on a problem that is affecting millions. In reality this is not happening and the past two years have been one of the worse periods for the development of new antibiotics. This summer, Novartis ended its antibacterial and antiviral research programs in order to “prioritize resources”. This followed other pharmaceutical giants like Sanofi, Astra Zeneca and Allergan who have also shifted priorities away from developing new antibiotics in recent years, shutting down their antibiotic development programs.

All of this is happening despite grave warnings by the WHO and public health specialists that “the pipeline of new antimicrobial therapies is grossly insufficient to mitigate the threat posed by drug resistant pathogens ”.  A quick Google search on incurable infections reveals several alarming headlines from, “Super gonorrhea in the UK ” to   “Woman dies from Superbug that resisted 26 antibiotics”. It is tempting to brush off these sensational headlines as click bait but these stories are reported with increasing frequency in the news, and should sound the alarm that Superbugs have won the last several rounds in this fight.

How did we get here?

The main reason though unpalatable, is quite simple – developing new antibiotics is not good for business. A study by the health policy center at Duke University in 2017 showed that only 5 of the 16 newly FDA approved antimicrobials between 2000-2017 were able to generate more than 100 million in sales annually.  This is a huge loss for the pharmaceutical companies, which invest billions of dollars to get a new drug on the market but in the real world make no return on investment. These dismal sales are a pittance in comparison to the larger profits generated by sales of new chemotherapy or a heart failure drugs. Drugs for cancer and chronic conditions like cardiovascular diseases, diabetes and rheumatologic conditions are generally administered to patients for several months or years compared to shorter antibiotic courses of a few days to weeks. Furthermore new antibiotics hitting the market are not widely distributed to the “consumer” but instead are held in reserve for use when resistance develops to older antibiotics.

Taking these factors into consideration, it is very hard to make a convincing business case for developing new antibiotics. Simply put, a patient with an infection that is curable with the right antibiotic does not make a lucrative long-term investment for the drug developer. Some may reason that Big Pharma companies could show more altruism by putting human lives above profits. Unfortunately in an industry in which survival is driven by sales and profits, this rose-tinted view is not an argument that helps to move the conversation forward or generate meaningful solutions.

Besides the challenges we are facing with developing new antibiotics, patient attitudes and healthcare practices are also contributing significantly to the overuse of the antibiotics that we have available to fight disease.  Several studies have clearly demonstrated that patient expectations drive inappropriate prescription of antibiotics even if they have a condition like the common cold for which antibiotic therapy may not be needed. From a healthcare provider’s perspective, it is more time consuming to explain to a patient that an antibiotic is not needed, than to write a prescription.  Another study, showed that even when healthcare providers know that antibiotics will not improve or change patient outcomes for conditions like bronchitis and common colds, the fear of jeopardizing good relationships with patients often still leads to poor antibiotic stewardship practices and overprescribing. In an industry in which patient satisfaction makes a difference with the competition, doing the right thing may be harder if the consequence you face is losing your patients to other providers.

We are all a part of the problem, which now threatens a lot of the advances made in medicine over the past half-century. Making significant gains against this global health threat will require a concerted collaborative effort of all players involved including Big Pharma, governments, healthcare providers and patients.

Winning “the fight for our lives”

An exhibition at London’s Science Museum in 2017 on Superbugs, appropriately dubbed the issue “the fight for our lives”. This is a very apt description of what the rise and spread of superbugs and antibiotic drug resistance means for our generation. We have lost several battles in recent years but not the war, and starting now we still have the opportunity to turn things around.

For this to happen Big Pharma must be brought back to the table. With the currently flawed business model, governments will have to provide more incentives to pharmaceutical companies to help offset the costs of developing new antimicrobial agents. While awareness of the problem is increasing and discussions are happening between the main players to this end, a compromise is yet to be reached which will draw drug companies back into the business of developing new antibiotics. From the healthcare provider side of things, the growth and expansion of antibiotics stewardship programs in recent years is helping curb antibiotics overuse and guiding appropriate antibiotic selection in hospitals. Turning patient attitudes away from viewing antibiotics as the remedy for minor ailments is a lot more challenging and will take time. Healthcare providers will have to invest time in raising awareness on antibiotic resistance in their practices, but also be ready to limit overprescribing even at the cost of compromising patient satisfaction. The Superbugs are here to stay, it is up to us to heed the warning signs and fight back. Playing catch-up on this issue will not be fun and is a situation we must avoid at all cost.

Written by Boghuma. K. Titanji

Facing Ebola Outbreaks – Beyond Compassionate Vaccines

 

Another summer, another Ebola outbreak …

On August 1st, 2018 the Ministry of Health in the Democratic Republic of Congo (DRC) reported an outbreak of Ebola virus disease (EVD) in its’ North Kivu province. It is the second outbreak reported in the country this year. Both outbreaks are unrelated and occurred barely two months apart. The response this time has been prompt with the deployment of an experimental vaccine on the ground. A sign that we have learned some tough lessons from the deadly EVD outbreak in W. Africa, which claimed over 11,000 lives.

A chequered journey to success
The current response is laudable but there is a long way to go before we can declare victory. The cost in human life of the EVD outbreak in W. Africa captured global attention and is fresh in our memories. The scale of devastation led to a push for drug and vaccine research against EVD. Reminding us of the pervasive inequities in research funding for diseases that affect the world’s poorest and most vulnerable.

Canadian scientists designed the experimental EVD vaccine rVSV-ZEBOV in 2003. It was shown to be 100% protective in primate models shortly after, in 2005.  Funding for clinical trials however stalled for another decade, with the vaccine effectively left on the shelves before moving into human trials in 2014. In hindsight we could have had a tool to prevent what happened in W. Africa, but developing it was not a global health priority until the broader global health community felt threatened by EVD.

The vaccine now produced by MERCK, was used effectively at the end of West Africa’s EVD outbreak in 2016. Over 5000 individuals received the vaccine and none of them developed EVD compared to 23 people in the control group of similar size. These compelling results were too late to change the course of the W. African outbreak. However it provided hope that a future EVD outbreak could be contained in its early stages by timely vaccination.

Following the declaration of the first outbreak in the DRC’s North West city of Mbandaka earlier this year, the government quickly authorized the use of rVSV-EBOV on compassionate grounds. The WHO was greatly criticized for its lack of leadership and sluggish response to the W. African outbreak from 2013-2017. This time it sprung into action partnering with the Global Alliance for Vaccines and Immunization (GAVI) and local health authorities to deliver over 7000 stockpiled doses of the vaccine in a ring vaccination model. Immunizing the immediate contacts — friends, family, housemates, and neighbours — of infected people, to create a protective ring around them and stop transmission.

Effectively implementing the vaccination strategy on the ground is no small feat. The terrain is incredibly difficult with limited transport networks, lack of basic infrastructure to maintain a cold chain, and inherent cultural and linguistic barriers to properly consent the target population. Despite these challenges, 7 weeks after the first case, the outbreak in Mbandaka is effectively contained. This clearly demonstrates that a quick response with the right tools makes a tremendous difference in stopping an outbreak in its tracks. Although this is encouraging, what it means for response preparedness in future outbreaks is more nuanced.

One size does not fit all

Every outbreak is its own separate beast and although we now have a vaccine to combat EVD, its effective use hinges on the unique challenges of where an outbreak occurs. The West Africa outbreak of EVD has been described as the “perfect storm” alluding to the unique challenges in the region that coalesced to create the worst Ebola outbreak in history.  In Guinea, Liberia and Sierra Leone, years of civil wars, dysfunctional health care systems, mistrust of the government and western medicine and the ease of movement of populations across porous borders contributed to the devastation of the outbreak. These conditions are similar to those encountered in other countries in the region, also at risk for EVD and other emerging infections.

The DRC knows Ebola too well, a virus named after one of the country’s rivers. The country is on its tenth outbreak in recorded history, most of which have been relatively quickly contained. Previous outbreaks have mostly occurred in remote, inaccessible and rural parts of the country, which helped to limit spread to densely populated major cities.  The latest outbreak affecting the North Kivu province is especially scary. North Kivu is at the epicentre of a deadly and protracted civil war and one of the most dangerous parts of the DRC. It is also densely populated with over 8 million inhabitants and shares borders with neighbouring Uganda and Rwanda. There are on-going daily clashes between rival rebel groups, thousands of displaced refugees and near absence of a functional healthcare system.

Even with a vaccine available, we are facing a novel challenge – containing a deadly outbreak of Ebola, where there is war. The coming weeks will be critical as the WHO and the local government grapple with the security concerns for frontline responders, in a race to prevent another humanitarian disaster. With the proximity to international borders, the spectre of the outbreak spreading to other countries in the region is real and should concern us all.

Compassionate preparedness, the way forward


The current scenario in the DRC is not surprising, as interactions between humans and the viral reservoir in endemic regions is a primer for future EVD outbreaks. It was only a matter of time before we saw an outbreak,  intersecting with the country’s civil war. The situation the DRC is facing, should send a strong signal that there needs be a more sustained effort to help address systemic issues that make the country and others in the region a especially vulnerable.

We know from previous Ebola outbreaks that it is much more cost-effective for the global community to invest in preparedness than to spend in response. Yet once an outbreak ends the promises for strengthening healthcare systems, improving surveillance and continuing clinical trials for new therapies quickly fade with it. As  populations continue to grow and humans encroach on the habitat of zoonotic virus reservoirs, more outbreaks of emerging infections will occur.  This year so far Ebola, Human Monkey pox, Lassa and Nipah virus outbreaks have been reported and are on going in parts of  Africa and Asia.

Compassionate vaccines and therapies to accelerate response to outbreaks when they occur are welcome but can only be used to their full potential if there are structures and systems in place to deploy them safely. I have no doubt that the DRC will overcome its latest challenge but there will be consequences and a heavy toll to pay if the global community does not rally in support. This support will need to be sustained beyond the present, so we can be truly ready to use the tools we now have, in the future.

Written by Boghuma. K. Titanji