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Lenacapavir: A Game Changer in HIV Prevention with New Hurdles to Overcome

A new long-acting option for HIV PrEP

On Thursday, June 20, 2024, Gilead released the highly anticipated topline results of the PURPOSE-1 trial. This phase three randomized controlled trial demonstrated that a twice-yearly subcutaneous injection of the antiretroviral drug Lenacapavir was 100% effective in preventing HIV infection. This is in compared to the once-daily oral pill of Descovy (which contains tenofovir alafenamide and emtricitabine) or Truvada (tenofovir disoproxil fumarate and emtricitabine). Although these results have not yet been peer-reviewed, they are truly groundbreaking and mark a pivotal moment in HIV prevention.

The study, conducted in Uganda and South Africa, included 5,300 cisgender women and adolescent girls aged 16-25. It is the first-time initial results for a novel agent for HIV pre-exposure prophylaxis (PrEP) comes from a study including cisgender women. Historically, available options for HIV PrEP were initially studied among men who have sex with men (MSM), with studies in cisgender women, particularly in Africa, lagging several years behind.

The trial Results:

Lenacapavir Group: Among 2,134 women receiving lenacapavir, there were zero incident cases of HIV infection, yielding an incidence rate of 0.00 per 100 person-years.Truvada Group: In the group of 1,068 women taking Truvada, there were 16 incident cases of HIV, resulting in an incidence rate of 1.69 per 100 person-years. Descovy Group: Among 2,136 women, there were 39 incident cases of HIV, resulting in an incidence rate of 2.02 per 100 person-years. This rate was numerically similar to that of the Truvada group and not statistically superior to background HIV incidence.

Despite a decade of PrEP, barriers to access persist

It has been 12 years since the Food and Drug Administration approved the first combination drug, Truvada, for use as PrEP (pre-exposure prophylaxis). In the absence of an HIV vaccine, PrEP has been transformative in the fight against the HIV epidemic, offering people the option to live and love without the fear of acquiring HIV. However, despite its promise, oral PrEP which now includes Truvada and Descovy, has not fully lived up to its fullest potential. Many populations that could benefit from it continue to struggle with awareness about the intervention and ways to access it.

For example, in the United States, Black women accounted for 54% of new HIV infections in women in 2021, yet only 2% of the estimated 468,000 Black women who could benefit from PrEP receive a prescription for it. This disparity is partly due to a lack of awareness about the benefits of HIV PrEP, the prohibitive cost of accessing the intervention in some States, and the absence of messaging that addresses the unique needs of this group. Stark disparities also exist across racial groups. The CDC estimates that while 94% of White people who could benefit from PrEP have been prescribed the intervention, only 13% of Black and 24% of Hispanic/Latino people who could benefit have been prescribed PrEP.

In Africa, home to 70% of the 38 million people living with HIV globally and 50% of new infections reported in 2023—most of which occur among young women and adolescent girls—the struggle to access PrEP is an ongoing challenge. Real-world implementation has been hampered by challenges such as sustainable funding for national PrEP programs, retention in care, stigma, and a lack of awareness. Despite these challenges to the broad-scale implementation of PrEP globally, this intervention, which is highly effective when available, has prevented hundreds of thousands of new HIV infections since it first emerged.

A new era of long acting injectable PrEP

In 2021, the FDA approved Cabotegravir as the first long-acting injectable antiretroviral drug for PrEP. Administered intramuscularly every eight weeks, Cabotegravir has been shown in randomized controlled clinical trials to be superior to oral Truvada for PrEP in both cisgender MSM and cisgender women for preventing HIV infection. The results of the PURPOSE-1 trial bring with them the promise of a second long-acting injectable option for HIV prevention. These injectable options are not only highly effective but also offer the unique benefits of flexibility and discrete use, which are essential for overcoming some of the most significant barriers to real-world implementation.

However, like with oral PrEP, the challenges of cost and equitable access for those who need these interventions the most, must be addressed if they are to achieve their full potential. In the United States, accessing long-acting Cabotegravir comes at a staggering cost of $23,000 per year, compared to the more reasonably priced $300 per year for oral PrEP options, which now have generic forms. As a result, many individuals who wish to use injectable PrEP find that their health insurance is not always willing to cover the added cost.

In South Africa it’s taken the sustained advocacy of tireless activists to make the cost of Cabotegravir for PrEP more affordable for African countries and importantly, accessible to African women. ViiV, the company that manufactures Cabotegravir, has renewed its commitment to “non-profit” pricing for the drug and is providing doses to support the PEPFAR initiative to expand PrEP access in Africa in 2025. It is worth noting that this compromise “non-profit” pricing although a great starting point, will need to come down significantly for broad scale access and implementation to be feasible across the African continent. PrEP is undoubtedly highly effective, but it only works if people take it. Having options ensures that there is a PrEP solution that fits the unique needs of each person. In rural communities in Africa, for example, people often have to travel long distances to access health services, making regular trips to a health center for medication refills and monitoring challenging. Women and adolescent girls disproportionately affected by new HIV infections do not always have autonomy and control over their sexual and reproductive health and having choices is even more crucial for this group. Long-acting options hold the promise of circumventing some of these barriers.

Cautious optimism amidst uncertainties for the future

As the HIV community embraces the exciting news about Lenacapavir for PrEP, many questions around pricing for African countries and the availability of generic formulations remain unanswered. The current cost of HIV treatment with Lenacapavir in the United States is estimated at $42,250 per year, a similar pricing for PrEP will make accessing the drug a challenge even for individuals living in the wealthiest countries. The history of the HIV epidemic has been marred by the constant tussle between innovation and equitable access to the newest tools to fight the spread of HIV and reduce its negative impact of communities around the world. One of the darkest moments of this checkered past is the 10-year delay it took for African countries to gain access to life-saving antiretroviral therapies after these drugs first became available in Europe and North America in the mid-nineties. This delay was largely attributed to the cost of these medications and patents that limited the manufacturing of generic formulations and led to millions of avoidable deaths from complications of HIV.

Some skeptics may argue that the urgency of providing HIV prevention tools and a variety of options is secondary to ensuring access to treatment. Or that highly effective oral PrEP options are sufficient and we should focus of expanding access to these instead of funding more expensive injectable drugs. In reality, giving equal priority to all the strategies we have for both prevention and treatment is essential to ending the HIV epidemic. Antiretroviral therapy (ART) reduces HIV levels in the blood of those living with the virus to undetectable levels, making it impossible for them to transmit the virus to others. Additionally, pre-exposure prophylaxis (PrEP) with a daily oral pill or with long acting injectable drugs is 98-100% effective in preventing HIV acquisition and, adherence is most optimal when people have the freedom of choice. With these tools, we now have the capability to significantly interrupt HIV transmission and drive new infections globally toward zero. But promise alone is not enough and the last 12 years of PrEP existing have taught us that even our sharpest tools can’t accomplish much if they remain locked in the toolbox.

Only time will tell how well we have learned the lessons of the past and how strong our resolve is to end this epidemic once and for all. For now, I celebrate this important milestone and eagerly anticipate the publication of the PURPOSE-1 study details. I also hold on to the dream of a future where every new HIV transmission is easily prevented, regardless of whether someone is a 30-year-old MSM person living in San Francisco or an 18-year-old young woman in a country in Africa. This dream is closer to becoming a reality but only if we are intentional in ensuring that those most likely to benefit from these new drugs have access to them without further delay.

Written by BK. Titanji

Previously published on substack: https://bktitanji.substack.com/p/lenacapavir-a-game-changer-in-hiv

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Malaria’s Big Year: New Horizons for Vaccines and Prophylaxis

A great year of Malaria research has been overshadowed by the global pandemic of COVID-19. Headlines on promising new vaccines and prevention strategies barely survive the 24-hour news cycle, quickly superseded by the latest COVID-19 related research. Malaria remains a leading cause of death in children under the age of 5 who account for 57% of the > 400,000 deaths/ year from Malaria. With global deaths on this scale, Malaria still very much qualifies as a pandemic but doesn’t get the attention it deserves. Sub-Saharan Africa carries 94% of the burden of disease, a major reason why Malaria has become the neglected pandemic of the poor. The positive results on new vaccines and novel approaches for prevention (monoclonal antibodies) bring much needed hope for eradicating this disease.

A slow ROAD to PROGRESS

It took a year to develop over ten effective vaccines to prevent COVID-19, a disease that did not exist before the end of 2019. Progress on developing a vaccine for Malaria, which has been around for decades, has been very slow. So far Malaria vaccine research have yielded only one partially effective Malaria vaccine (RTS,S or Mosquirix). This vaccine offers a modest 56% protection against Malaria in the first year and effectiveness drops to 36% over 4 years.

Despite its modest effectiveness, Mosquirix has been rolled out as part of ongoing studies in thousands of children in Malawi, Kenya and Ghana. Modeling studies indicate that if Mosquirix use is targeted to areas with the highest malaria burden, it could prevent thousands of childhood deaths. The slow process of developing effective Malaria vaccines is due in part to insufficient funding for Malaria research but also the complex life-cycle of the causal parasite (Plasmodium spp), which is versatile and difficult to target.

New Vaccines, New Hope

This summer a new Malaria vaccine candidate showed promising results in a study in children ages 5-17months. The new vaccine R21 is an updated/modified version of Mosquirix which uses a new adjuvant and generates a stronger immune response. In the phase 2 clinical trial of 450 children in Burkina-Faso, R21 effectively prevented Malaria by up to 77% over a one year period. This level of efficacy meets the preset target of 75% set by the World Health Organization (WHO). A large phase 3 trial will include 4800 children with the hope of confirming these exciting results. The new vaccine is manufactured by the Serum Institute of India, which has pledged to produce 200 million doses of the vaccine every year if it gains approval.

Source: https://www.bbc.com/news/health-56858158

new innovations,NeW CHALLENGES

Another clinical study published this summer used a novel approach , combined a live-parasite vaccine with antimalarial drugs. In this study which included 42 volunteers, the investigators injected participants with sporozoites (the stage of the malaria parasite that is transmitted from the mosquito to humans). They also treated the vaccinated individuals with antimalarial drugs to kill the parasites if they reached the liver or bloodstream so as to prevent the infection of red blood cells and symptomatic malaria. How does this work?- Exposing volunteers to live sporozoites stimulates a protective immune response against future malaria challenge while the antimalarial drug given at the time of vaccination prevents symptomatic malaria from occurring as a result of vaccination.

Malaria sporozoites, the infectious form of the malaria parasite that is injected into people by mosquitoes – image source NIAID

The volunteers who received the vaccine were infected with malaria 3 months after vaccination to assess the efficacy of the vaccine. 87.5% of those who received the vaccine were protected from Malaria after being exposed to the same malaria strain as the one used in the vaccine. While 77.8% of those infected with a different strain of the parasite were protected. The study is proof of concept that high levels of vaccine efficacy can be achieved with a live-parasite vaccine. It also advances our understanding of what it takes to develop protective immunity to the parasite.

This approach however presents many challenges. Malaria sporozoites cannot be grown in batches in a laboratory for large scale vaccine production and only multiply in the salivary glands of mosquitos. Making enough live-parasite vaccine for larger clinical trials requires isolating sporozoites from millions of mosquitos (through dissection). Also storage of the isolated parasites requires ultra-cold temperatures, which has implications for the vaccine cold chain. These hurdles will increase manufacturing and distribution costs of any potential approved vaccine based on this approach. In addition, the need for combining antimalarial drugs with vaccination could drive development of drug resistance to effective antimalarial drugs. These factors need careful consideration in moving this vaccine forward through larger clinical studies.

Monoclonal Antibodies take on Malaria

Current prophylaxis against Malaria relies almost completely on the use of antimalarial drugs. In a new clinical study led by the National Institutes of Health in the USA, a neutralizing monoclonal antibody (nMAb) was effective in preventing Malaria for up to 9 months in healthy volunteers. nMAbs are laboratory-made proteins, that can attach to harmful pathogens like bacteria, viruses and parasites and target them for destruction by the immune system.

In this study a nMAb called CIS43L3 derived from a naturally occurring neutralizing antibody called CIS43, was delivered through intravenous (IV) infusion or subcutaneous injection to 21 healthy volunteers who had never had Malaria before. CIS43 is an antibody that attaches to a unique site (crucial for facilitating infection), found on all species of malaria sporozoites worldwide. The volunteers were followed for 6 months to assess the safety and tolerability of the intervention and to determine how long CIS43L3 persisted in the blood. The IV infusions and subcutaneous injections of CIS43L3 were safe and well tolerated during the study period with minimal adverse effects.

Colorized electron micrograph showing malaria parasite (right, blue) attaching to a human red blood cell. The inset shows a detail of the attachment point at higher magnification. NIAID

In the second part of the study, 9 participants who received the nMAb (CIS43L3) treatment and 6 controls (individuals who did not receive nMAbs) were voluntarily exposed to Malaria infection in a controlled setting and closely monitored for symptoms for 21 days. None of the participants treated with nMAbs developed Malaria meanwhile 5/6 individuals in the control group did.

This successful phase I study, supports the viability of monoclonal antibodies for Malaria prevention in travelers visiting endemic regions. It also opens a range of possibilities nMAbs as a prevention tool for controlling seasonal Malaria in Africa and for future elimination campaigns. Ongoing clinical studies will help to better define the role of this exciting new strategy.

Combining old strategies with new ones

Reaching the goal of eliminating Malaria needs more than one intervention. A recent clinical study including 6861 children, showed that combining the Mosquirix vaccine with antimalarial drugs for preventing Malaria provided 72.9% protective efficacy against severe disease and death. The effect of combining two interventions was superior to either intervention alone. Seasonal prevention of Malaria through monthly doses of antimalarial drugs is highly effective in preventing Malaria during high transmission seasons. However, this intervention has been insufficient to reduce the burden of Malaria in the most affected areas. Combining novel vaccines with older interventions could maximize benefits for preventing severe disease and improve on existing interventions for Malaria control.

Breaking the plateau – the final push to eliminating Malaria

In recent years the push to eliminate Malaria hit what felt like an unsurmountable plateau. Effective strategies including; vector control, mosquito nets and chemoprophylaxis prevented millions of deaths but have seen their sustained efficacy wane. Resistance to antimalarial drugs and insecticides is on the rise and population growth in endemic areas has led to more cases. Complacency in the lack of progress means accepting 400,000 plus deaths from Malaria every year, mainly in children. That is what makes the new promising avenues of Malaria research so exciting. Renewed enthusiasm for re-igniting a final push towards eliminating a neglected pandemic and saving lives. At a time when a new pandemic is causing much sadness, I am hopeful for a future without malaria and that is worth celebrating.

Image Source: https://www.health.harvard.edu/blog/

Written by Dr. Boghuma K. Titanji

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COVID19 Vaccines – Not For Wealthy Countries Only

New Year, Same Pandemic

The turn of the year has come and gone but a lot of the news feels the same in year two of the COVID19 pandemic. Many countries are experiencing severe 2^nd and 3^rd waves of infection. Highly transmissible new variants of the virus cast a cloud on the excitement and hope brought by effective new vaccines. COVID19 has become a part of daily life as a mask weary society trudges along, numb to the rising global death count.

Road ahead — Source https://www.statnews.com/feature/coronavirus/the-road-ahead-the-next-12-months-and-beyond/

When does it end? How does in end? When can we get back to life as we once knew it? I get these questions often and wish I had good answers. Effective vaccines are a light at the end of the tunnel but in an unequal world, how close that light feels and how brightly it shines depends on where you find yourself. As a frontline health worker in the United States, I was privileged to be among the first to receive the Pfizer mRNA vaccine. My absolute joy and relief at being immunized are tempered by the uncertainty that surrounds when my parents, will be able to access these live-saving vaccines. Like many others living in resource poor countries, for my parents the projections for access to COVID19 vaccines are bleak. It is estimated that at least 85 poor countries will not have widespread access to COVID19 vaccination before 2023, year 4 of the pandemic !!!

Source : https://www.economist.com/leaders/2020/11/14/the-promise-of-the-new-covid-19-vaccine-is-immense

Effective Vaccines, Amplified Inequity

It is a feat of science that in just over a year since SARSCoV2 was identified, we now have 10 effective vaccines being deployed around the globe. Inequity has sadly been a central feature of this pandemic affecting access to protective equipment, diagnostics and treatment and now vaccines. At the current global vaccination rate of 4,607,324 doses a day it would take an estimated 6.8 years to vaccinate 75% of the world’s population. The world’s poorest and most vulnerable find themselves at the tail end of the global queue for COVID19 vaccination. 124 million vaccine doses have been delivered in 73 countries of which 4,935,611 doses (4%) in South America and a paltry 446,904 doses (0.37%) in Africa. The 20 wealthiest countries have the lion’s share representing 80% of the vaccine doses delivered so far.

Source: Bloomberg COVID19 vaccine tracker

COVAX – Bringing the World Together

The COVAX initiative co-led by WHO, GAVI and CEPI provides a risk-sharing mechanism for pooling resources to procure and equitably distribute COVID19 vaccines to countries regardless of wealth. It aims to deliver enough vaccine doses to allow participating countries to immunize 20% of their populations by the end of 2021. This goal is ambitious but the urgency of the moment demands it. To achieve this target, COVAX will have to raise an additional $6.8 billion in 2021 – $800 million for research and development, $4.6 billion for acquiring doses and $1.4 billion for delivery support. Its success largely depends on effective fundraising and donors making good on their pledges. The recent news that COVAX will ship 90 million doses of vaccine to Africa starting in February of 2021 is a welcome start. Put in perspective, these doses will cover about 3% of the continent’s 1.3 billion strong population. COVAX is doing a lot but it cannot do it all alone. Important regional and national efforts to bolster vaccine access for poor countries have to contend with a tense and competitive vaccine market as well as vaccine nationalism.

Image result for vaccine nationalism — Source: Getty Images

Vaccine Nationalism – An Existential Threat

So far in the pandemic, countries have prioritized their own populations instead of a more concerted global effort working together to defeat the virus. This has been reflected in international trade restrictions which in the early days of the pandemic severely hampered the ability of poorer countries to respond effectively. The ongoing dispute on vaccine access and rollout between the EU and the UK is just the latest illustration of this. With many vaccine manufacturers experiencing delays in production and failing to meet delivery targets, the shortfall led the EU to impose export restrictions on COVID19 vaccines produced within the bloc. Although the EU has since backtracked on the widely condemned decision, the words of the EU commission

“The protection and safety of our citizens is a priority and the challenges we now face left us with no choice but to act,”

raise alarm bells that more countries will impose vaccine export bans to protect their own supplies. Poorer countries already struggling for access to vaccines will bear the brunt of the fall out.

Similar scenarios have played out in very recent history. In 2009 during the H1N1 influenza outbreak which killed 284,000 people globally, a vaccine was developed in just 7 months. However almost all of the vaccine supplies were hoarded by wealthy countries leaving others with nothing. The same can be said about eradication programs for smallpox and polio, for which vaccines only became widely available to the world’s poorest when these diseases had been largely eradicated from richer parts of the world.

Data as of Nov. 30. Potential dose purchases include deals that are under negotiation and options for additional doses as part of existing confirmed deals.
Source: Launch and Scale Speedometer, Duke Global Health Innovation Center
Credit: Connie Hanzhang Jin/NPR

The Case for Acting Now and Acting Fast

The cost of inaction on global vaccine inequity is the risk of seeing COVID19 become just another in a long list of diseases which primarily affect the poor. Unlike Malaria, Tuberculosis and HIV, the world will not be able to “move on” if the problem is not confronted simultaneously on all fronts. The estimated monthly financial cost of the pandemic to the global economy is a staggering $375 billion. Besides the moral imperative to act, the financial arguments are equally compelling.

VAXXING TO SAVE Economies

A recent study commissioned by the international chamber of commerce projects that in a worse case scenario in which wealthiest countries are fully vaccinated by the middle of this year and poor countries are completely left out, the global economy could see losses exceeding $9 trillion! In the more likely scenario in which most wealthy countries could vaccinate 70-80% of their populations by the end of the 2021, the projected losses will still fall in the $1.8-$3.8trillion range. A significant proportion of these losses will be borne by wealthy countries, especially those heavily reliant on trade. In an interconnected world with global supply chains, sharing vaccines is more than just charity. In essence, the economic recovery of the strongest and the weakest economies are intimately connected to controlling the spread of the virus globally.

Image result for saving economies — Source: Franesco Ciccolella

Emerging variants and the race to vaccinate

Emerging variants of SARSCoV2 present a new challenge and have brought a sense of enhanced urgency to accelerate the distribution of vaccines. Some of the more concerning variants have accumulated changes in the genome of the virus which make them more transmissible and easier to spread. In addition there is growing evidence that some of the changes in the virus genome could compromise the efficacy of first generation vaccines and antibody-based therapies. Many countries in sub-saharan Africa are seeing a surge of cases and deaths fueled by the spread of these new variants. Between December 29th 2020 and January 25th, 2021, new infections on the continent rose by 50% when compared to the preceding four weeks. The region had successfully weathered relatively milder first waves of the pandemic compared to other regions, by relying mainly on rigorous public health mitigation.

The collision of COVID19 fatigue, substantial economic losses from lockdowns and more transmissible variants creates a perfect storm. Severe subsequent waves of the virus could quickly overwhelm fragile health systems and be the deadliest yet. South Africa, where the 501Y-V2 variant of the virus was first identified, is experiencing its worse pandemic surge with massive case spikes, overwhelmed hospitals and a rising death toll. For weak healthcare systems with limited human and material resources, providing vaccination to frontline workers at the minimum is vital to preserving a functioning healthcare system. This is especially important in lower income countries where the pandemic has already severely impacted gains in other priority areas of global health including; access to HIV treatment, Polio eradication, Tuberculosis Control and Malaria prevention.

COVID DENIALISM AND Vaccine hesitancy – The ElephantS in the room

Vaccine hesitancy and COVID19 denialism are important and concerning threats which must be confronted and addressed in tandem with ensuring access to vaccines for all. Effective vaccines will only help if these can be delivered to those who need them the most. The current situation in Tanzania, has garnered international attention with its government openly shunning mask mandates and lockdowns and now rejecting COVID19 vaccines. Burundi, has also opted out, stating its intention to focus efforts more towards mitigation than mass immunization. Brazil which has experienced one of the worse outbreaks of COVID19 was largely crippled in its response by leadership which also shunned containment measures and vaccination. Even in countries willing to accept vaccine doses, there is considerable hesitancy within the populations which could significantly compromise vaccine distribution. The same fervor that is being applied to sourcing vaccines, must also be directed at increasing uptake. Aggressive information and education campaigns as well as incentives which have proven useful for other epidemics must serve as lessons. Confronting government sponsored vaccine denialism is more challenging because every country has the autonomy to define its internal health policy, even if these policies are harmful to its own citizens.

Where DO We GO FROM HERE?

Despite the isolation of the pandemic, the world strangely feels more connected through our shared trauma from the losses we have experienced and the changes in our daily lives. Effective vaccines provide hope for better days ahead and our collective humanity demands that we ensure this hope is felt by all. No country is an island in a global pandemic and making it out together also means bringing along those who need a little extra help on the road.

Written by Boghuma. K. Titanji

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Will We See Wide Spread of COVID19 in Africa?

Pandemic and Pandemonium

Image result for pandemic — Countries with COVID19 cases around the globe

It’s only March and 2020 already feels like a really long year. Like many around the world, every waking moment is filled with news of COVID19. As the SARS-CoV2 virus steadily continues its march across countries and continents with no respect for borders, it leaves panic and fear in its wake. As an infectious disease physician and a virologist, I try to be the voice of calm, holding on to the science of what we know about epidemics and this pandemic so far – “this too shall pass” has become a mantra I repeat to myself and loved ones seeking reassurance. As a human with parents in the most vulnerable age bracket being rational is much harder.

Mama Said Not to Worry

You see my parents are not only over age 60, they also reside in sub-Saharan Africa which is home to the world’s most vulnerable health systems. I called my mother earlier this week to check in and reinforce the messaging on infection prevention strategies and social distancing. It is the peak of the dry season in Cameroon, and like in many parts of the continent this means sweltering heat and scorching temperatures through the day. My mother knows my choice of specialty has me at the frontlines of this pandemic in the USA where I work. She tries to be reassuring “Don’t worry about us Bo, we are being safe, I don’t think the virus can even survive this horrible heat” she says. We both laugh nervously at this and chat about how so far, Africa seems to be relatively spared from a severe outbreak. I tell her to continue being safe and promise to check in again later in the week.

Hoping for the best

Image result for COVID19 in AFRICA — Traveller getting temperature checked at major African airport

Africa so far has been relatively spared a severe outbreak on the scale of which we have seen in parts of Asia and now in parts of Europe and the United States. As of March 13^th,there were 147 confirmed cases of COVID19 in 15 African countries (most of these imported from Europe and Asia) with 4 deaths and very limited evidence of widespread community dissemination. Many have pondered the reasons behind this. I do believe that there is some merit to what I am calling “Mama’s dry season theory” but I think this only partially explains why Africa hopefully might actually sit this one out (i.e. be spared a catastrophic outbreak).

Climate Matters

Image result for climate — Will the climate play a role in curbing this pandemic?

Many have expressed the hope that as the temperatures rise in temperate regions this could actually limit the spread of the virus and eventually lead to a sharp decline in cases. The evidence from other respiratory viruses like influenza which peak in the winter and decline in summer suggest that this may actually hold true to a certain degree. With hotter temperatures infectious droplets which transport the virus particles are likely to dry up more quickly and not travel as far. Ultraviolet rays from more sunshine in spring and summer months will make it more difficult for the virus to survive for extended times in the environment. Also, people will spend more time outdoors thus limiting indoor crowding.

The influenza surveillance data for countries in sub-Saharan Africa, albeit limited, consistently show lower detection of circulating Influenza A and B. This may be in part be due to the fact that the climate is less favorable to the sustained transmission and persistence of viruses which predominantly spread through droplets. Other human coronaviruses have behaved similarly, showing seasonality and a predominance in the winter months but only time will tell whether SARS-CoV will follow this pattern.

Age Really Matters

So far what we have seen in the COVID19 pandemic are very high rates of severe illness and death in patients older than 60 years and with underlying chronic medical conditions. The young and healthy have generally done well, with zero deaths in the 0-10-year age group and < 2% of deaths in people under the age of 30. Africa is the second largest and second most populated continent on the planet after Asia. Its population as a whole is very young with 60% of the entire continent aged below 25! This makes it by far the youngest continent in the world. In Italy which has the worst COVID19 outbreak outside of Asia, the median age is 47.3 years. Compare this to the 17.9 median age of Africa’s most populated nation Nigeria and the difference is striking.

If and when community spread becomes established in sub-Saharan Africa, I believe that herd immunity will accumulate quickly in a youthful population which is more likely to have mild disease and a higher rates of recovery and survival. This will be crucial in providing some degree of protection to continent’s elderly (> 60 years old), who represent 35% of the population . Another factor worth mentioning is that many of the Africa’s elderly live out their latter years within the family unit and nursing homes for the elderly are not the norm as in most developed countries. This limits the threat of high lethality outbreaks in settings with concentrations of vulnerable persons.

Limited Mobility… A Saving Grace?

The African continent by its sheer size and limited access to good road and rail networks is not as well connected as Europe, the United States and or Asia. Air travel is only marginally better with very few flight options between countries and associated significant cost of air travel as a result. Even within the borders of individual countries, travel between regions in a country is often limited by challenging terrains and unsafe roads. These logistical challenges which severely limit movement within the continent, may in the face of this pandemic be a positive factor for slowing the spread of COVID19 between countries. Whether this will have a significant role in how widely the virus will spread within the continent is something that cannot be predicted at this time and only time will tell.

What about Immunity?

Another question which has frequently come up in conversations with friends and family is whether being black and of African descent is protective against infection with SARS-CoV2. The simple answer is no, it is not. While we have fewer cases in Africa so far due to the reasons detailed above there is no evidence at this time to suggest that race or ethnicity confers a special protective benefit against COVID19. With that being said, the high burden of parasitic infections in sub-Saharan Africa has been suggested as protective in reducing the severity of some viral infections.

Good examples of this phenomenon are reduced severity of diarrhea from rotavirus infections in children who also concomitantly have infection with the intestinal parasite Giardia lamblia. A similar effect of decreased severity of Chikungunya virus infections has been noted with concomitant plasmodium infection. The immune mechanisms which explain these observations are complex and incompletely understood and also well beyond the scope of our current discussion (further reading in this link). Whether the phenomenon of parasitic antagonism will have an impact on severity COVID19 in Africa remains to be determined, but is certainly an interesting thought.

Coronaviruses are widespread among mammals and birds and cause a variety of diseases. Human coronaviruses are major causes of the “common cold” and generally cause mild infections. Occasionally, animal coronaviruses successfully emerge and adapt to infect humans as we have seen with SARS, MERS and now SARS-CoV2. Whether frequent exposure to animal coronaviruses through manipulation for food or close contact with animals and birds will confer any meaningful cross-protection against COVID19 in Africa is unlikely, as this has not been observed in other parts of the world. Data from patients who survive infection with SARS-CoV and MERS-CoV suggest that those who recover from these infections develop some degree of humoral immunity which can last for 2-6 years and we hope this will be similar for SARS-CoV2.

Getting better but not there yet

Image result for intensive care in africa ebola

Earlier this week I took care of my first patient with confirmed COVID19. I know there will be many more in coming days and weeks. Things now feel very real with China and Italy clearly illustrating how much pressure a flood of cases can inflict and even break the most robust healthcare systems. The fragile healthcare systems in Africa do not stand a a fighting chance to cope with the clinical care of a large volume of patients. The lack of ventilators, limited numbers of ICU beds, and severe short-staffing in medical personnel are not challenges which can be overcome overnight. This makes aggressive public health measures to prevent community spread from establishing itself absolutely key. Basic hygiene remains a big challenge in many parts of the continent where access to soap and clean water are not always a given.

The continent may draw some level of comfort from the points I have discussed above. However, we cannot afford to be complacent. Following common sense public health measures of social distancing and effective hand hygiene remain crucial in slowing/delaying community spread. Local governments will need to double their efforts to ensure that when they call for more hand washing and social distancing, they are also putting their populations in the position to adhere to these measures.

One of the positives that emerged from the Ebola outbreak in W. Africa in 2016, is countries stepping up their public health response preparedness by improving laboratory capacity, strengthening public health institutions and increasing outbreak surveillance systems. There’s still a lot that needs to be done but these changes represent the first steps in the right direction. As we nervously continue to watch the numbers of COVID19 cases, we can only hope that Africa will be spared the worst. This year, the continent has already dealt with several outbreaks including measles, cholera, monkey pox, Lassa fever and Ebola with several still ongoing.

#ThisTooShallPass

The current pandemic of COVID19 illustrates more than ever before, the need to respond and prepare for outbreaks as a global collective. We have to do better at ensuring that the weakest links in the chain can respond and stop any outbreak from becoming a pandemic. This will not happen if every country continues to only look within its borders and we wait for pandemics to happen before we react. The reactionary response is much more costly than planning ahead and hopefully the lessons will stick this time. Three and a half months ago Wuhan and Hubei provinces in China seemed like very far off places. I occasionally spared a thought for medical colleagues at the frontlines there fighting the spread of the virus and wondered what it was like to be in their shoes.

Today alongside valiant co-workers, I find myself on America’s frontline while worrying about my parents in Cameroon. Things now feel uncomfortably close to home on all fronts. Mama’s always right they say and I sure hope her “dry season theory” holds true . While we await the warmer temperatures let’s remember to be kind to one another, provide a word of encouragement if you see someone who is struggling at this time. We will need each other more than ever in the coming months but I promise you we will get through this. #ThisTooShallPass.

Written by : Boghuma . K. Titanji

*For reliable information on what to do to protect yourself and those around you at this time the IDSA website offers excellent resources.

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Ebola Marches on in the DRC – “Not a Public Health Emergency of International Concern”?

Nine months and counting …

Image result for zaire ebola virus map — The Ebola outbreak in East Kivu, DRC

It has been almost a year since the beginning of the ongoing Ebola outbreak in the Democratic Republic of Congo( DRC). Since it started in August of 2018, it has infected an estimated 1206 people and killed 764 as of last week. The numbers continue to rise daily with record breaking new infections recorded this week. Despite the high hopes many placed on the experimental vaccine deployed in this outbreak, it has failed to be the magic bullet to stop the outbreak in its tracks.

Not an International Public Health Emergency

Image result for crisis — No crisis global just yet!

Following a meeting of its International Health Emergency Regulatory Committee (IHR), the WHO declared on Friday that the outbreak in the DRC did not constitute a public health emergency of international concern (PHEIC). This may come as a surprise to many, given the sense of fear and panic that deadly diseases like Ebola engender. However, within the confines of strict WHO definitions, the outbreak simple does not check the boxes required for it to be labelled an International Public Health Emergency at this time. If the outbreak remains confined within a country it simply is not considered an issue of international concern.

This conclusion by the WHO and its position to stick to a strict definition gives me pause and raises the question of whether now is really the time to be conservative in using all available resources to fight an outbreak that is proving tough to control. Since global health emergency responses were first enacted in 2007, the WHO has only made 4 such declarations; in 2009 with the H1N1 influenza outbreak, May 2014 during an increase in numbers of polio cases which threatened eradication efforts, August 2014 during the Ebola outbreak in West Africa and most recently in 2016 during the outbreak of Zika in South and Central America.

Health Emergency Declarations have Consequences

Image result for domino effect — Declaring a Global Health emergency can have a domino effect

Declaring a PHEIC is a powerful tool which brings international focus and attention to a public health concern and galvanizes a robust response in addressing it. The WHO tries to use this tool judiciously so as to preserve its significance and avoid the label of “boy who cried wolf”. Many still criticize the organization’s slow response in triggering the alert during Ebola in W. Africa which led to a severely delayed response and deadliest Ebola outbreak in history.

That being said labelling a disease outbreak a PHEIC doesn’t come without consequences for the countries and regions involved. Public health emergency declarations have significant economic costs to the targeted countries, frequently leading to travel restrictions which impact on trade and the local economy.

Take the example of the Zika outbreak in Latin America and the Caribbean, which led to a social and economic costs estimated between 7-18 billion from 2015-2017. Most of these losses stemmed from the effects of a decline in tourism on the GDP of countries in this region.

As someone who travels with a W. African passport, I remember too well the stigma of being subjected to extra scrutiny by immigration officers at international airports while traveling during the Ebola outbreak in West Africa between 2014-2016. My country, Cameroon was not implicated in the W. African outbreak but being a traveler with a passport from that part of the world quickly became a stigmatizing red-flag. This to show that the economic and social impact of public health emergency declarations usually extend beyond the areas of the outbreak and cannot be ignored.

Where does the outbreak go from here?

The ongoing outbreak in the DRC is the tenth in the country’s history but also its deadliest and hardest to control by far. For the first time the response is having to deal with deploying interventions in an area of active conflict. The fear and mistrust of the local populations compounded by health systems weakened by decades of civil unrest present unique challenges. This is very much uncharted territory and makes the outbreak not only dangerous but also completely unpredictable.

The impact of an Ebola vaccine

Image result for ebola vaccine — A healthcare worker holds a vial of the Ebola vaccine

There is no doubt that the experimental Ebola vaccine (rVSV-ZEBOV), has had a huge impact in limiting the spread of the current outbreak. The experimental vaccine is 97.5% effective according to new data released by the WHO. It has been delivered to over 90,000 people in the DRC and some neighboring countries since the start of the outbreak in August of 2018. Of the people vaccinated only 71 went on to develop Ebola and none of these died from the infection. The vaccine appears not only to protect vaccinated individuals from infection but also provides immunity which allows those who acquire the infection despite being vaccinated, to not succumb to it. This is fantastic news, again affirming the powerful tool of vaccination in the control of infectious diseases outbreaks.

A coalition of fear, mistrust and high stakes

Image result for DRC conflict — Armed Militia in the DRC

The unsung heroes of the current outbreak of Ebola in the DRC are the frontline health workers involved in contact tracing, vaccination and educating the populations at risk. Last month, several media outlets reported attacks on Ebola treatment centers in the Eastern city of Butembo by armed men. These attacks left several health workers wounded and one dead. The insecurity that permeates the North Eastern region of the DRC highlights the explosive consequences conflict intersecting with health.

We now have powerful tools in the way of a vaccine and experimental antiviral therapies to combat the threat of Ebola. These tools can be rendered moot when deploying them comes at the risk of death for frontline workers. Some aid organizations have had to suspend response efforts in some parts of the region due the pervasive dangers. If any good has come out of this, it is bringing the spotlight on a civil war that has lasted over two decades and is in itself a humanitarian crisis often forgotten by the rest of the world.

The North Eastern region of the DRC has not dealt with Ebola outbreaks before, as previous outbreaks that have occurred in this vast country have been in other regions. The population that lives under the threatening presence of violent militia factions , is deeply mistrustful of a government. They feel they have been down through the decades of conflict as warring factions fight to control the lucrative mines in the region. The current outbreak in the DRC cannot be effectively addressed in isolation without taking into account the underlying conflict impeding its control. It is becoming increasingly clear that there is a real risk of Ebola becoming endemic in the North Eastern region of the DRC if things remain as they are.

Felix Tshisekedi holds the constitution after being sworn as president of the Democratic Republic of the Congo

January 24th 2019, saw the swearing in of Felix Tshisikedi as the new head of State of the DRC . The peaceful transition of power through a democratic process sparked a new hope for peace and reconciliation and the end of the civil war. The task of the new leader to reconcile the warring factions in his country is not easy. Doing it while fighting an outbreak of a deadly disease , makes it even harder.

The Fight Continues

Image result for the fight against Ebola

The WHO and the Ministry of Health in the DRC bear the brunt of the ongoing response to the Ebola outbreak. Their efforts have been significant but, have not been successful in ending the outbreak which is edging close to its one-year anniversary. New cases and new deaths are recorded daily.

The fact remains, that though contained within the borders of a single country, Ebola in the DRC is an emergency and an ongoing threat to the global community. Adhering to strict definitions in the face of a crisis comes with the risk of underestimating the scale of the problem and delaying the best possible response. Every outbreak is different and one size does not fit all in these scenarios. For now we wait and trust the guidance of the world’s leading health organization while hoping for the best outcome – an end to Ebola in the DRC.

Written by Boghuma. K Titanji

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