A crisis of global concern

New and reemerging infectious diseases pose an urgent threat to the health of world populations.

“We are standing on the brink of a global crisis in infectious diseases. No country is safe from them. No country can any longer afford to ignore their threat.” Dr. Hiroshi Nakajima, WHO World Health Report 1996

The spread of infectious diseases calls for international action, with premature deaths and human and socioeconomic impact as devastating consequences. And in this globalized and connected world, HIV and AIDS epidemics in Asia and Ebola outbreaks in West Africa are no longer only of local concern. They are a universal one.

A dark follower of mankind

Infectious diseases have haunted human kind since early civilization. When available supplies of game diminished early hunters migrated from tropical climates into temperate zones. According to historians, humans were relatively safe from infectious diseases during this period. However, as agriculture started to provide a considerable portion of the human diet populations were able to stabilize and grow, reaching a size that would support persistent person-to-person spread of infectious microorganisms. It did not take long before infectious diseases became widespread. The outbreaks were sudden and unpredictable and often of epidemic proportion. Some of the most well-known and most devastating epidemics in history are the Plague, or the Black Death, and the Spanish flu, which swept over Europe, leaving several millions of victims in its wake. Scientific advances in the late 19th and early 20th centuries resulted in the prevention and control of many infectious diseases, particularly in industrialized nations. But despite the improvements in health, infections in emerging and re-emerging forms continue to be a worldwide problem.

New era of epidemics

Over the past couple of decades at least 30 new infectious diseases have emerged, according to the World Health Organization (WHO), threating the health and lives of hundreds of millions. Some major diseases are making deadly comebacks, for example cholera, malaria and tuberculosis. At the same time the world is faced with new and highly infectious diseases, such as HIV/AIDS, a disease that 35 million people worldwide are currently living with, and Ebola, of which there was a major outbreak in West Africa during 2014. Infectious diseases such as HIV/AIDS, malaria, lower respiratory infections, diarrhea-related diseases and tuberculosis collectively account for almost one third of all deaths in developing countries, according to WHO. Mali, for example, one of the poorest countries in the world, is greatly burdened by infectious diseases that cause serious health problems. Its population of 15 million has a life expectancy of only 50 years, according to the World Bank (compare that to 82 in Sweden or 79 in the United States). One of the major concerns is malaria, the leading cause of death in Mali (followed by lower respiratory infections and diarrhea-related diseases). Other urgent, current situations such as global conflicts also bring about a risk of infections. The civil war that is raging in Syria as we speak, with one of the largest refugee crises since the Second World War, has introduced epidemics that are spreading through vulnerable populations in Syria and nearby countries.

Vast improvements with vaccines

Unlike diseases with genetic, physical or chemical sources, infectious diseases are caused by pathogenic organisms, such as viruses, bacteria, fungi or parasites. When it comes to treatment methods and prevention there have been some success stories throughout modern history. During the 20th century vast improvements were made, much thanks to vaccines and antibiotics. Some infectious diseases caused by viruses have been successfully treated with vaccines and mass vaccination programs, bringing down the mortality rate substantially, for example when it comes to deadly virus infections such as diphtheria, smallpox and measles. “About two million children died from measles each year before vaccination. That figure is down to around a hundred thousand now,” noted Professor of International Health, Hans Rosling, at the Swedish American Life Science Summit this August. The well-known professor and lecturer was invited to discuss infectious diseases together with other leading scientists and professors during the conference, to shine light on some of the current dilemmas and solutions.

Vaccines continue to be a very effective medical intervention and with “an explosion of new technologies making its way into new treatment methods; structural vaccinology, synthetic biology RNA vaccines, reverse vaccinology,” new treatment methods could be possible according to Rino Rappuoli, Chief Scientist at GSK Vaccines in Siena, Italy, who pointed this out during the SALSS 2015 conference. This year there have also been some major vaccine breakthroughs, noted Rappuoli. For example, the first malaria vaccine was licensed and an Ebola vaccine came through trials with a 100 percent efficacy.

According to Rappuoli, these advancements show how vital the vaccine system is. “The technology is there,” he said, “but the question is what we can do for our society.” Rappuoli suggests looking more into providing vaccines for specific groups in society, such as the elderly, pregnant women and adolescents who are at risk, but also the vulnerable populations of deprived countries. “What do people die of in poor countries? Infectious diseases. Vaccines can play a major role in closing the gap between rich and poor countries if the right resources are used,” says Rappuoli. The question is then, how does one develop vaccines for countries that cannot pay? Many developing countries in the world still don’t have access to antibiotics or vaccines. Rappuoli, like Rosling, pointed to the need for new business models and non-profit initiatives. Access must be secured for those in need. A key focus is thus to find clever business models that secure both financing and access, and that pushes innovation forward, concluded Rosling.

A super-wicked problem

Following the discovery of penicillin in 1928 several antibiotics have come a long way in the treatment of infectious diseases and more than 100 different kinds of antibiotics have been discovered to date. But antibiotics are rapidly losing their effectiveness, as bacteria and other microbes are developing resistance to them. And with 25,000 deaths annually in Europe, antibiotic resistance is starting to turn into a full-blown crisis, which was something that was  highlighted by Otto Cars, Professor at Uppsala University and a specialist in infectious diseases, at the SALSS 2015. The issue is a complex matter, where irrational use of antibiotics is the most important underlying factor, together with a drug development pipeline for antibiotics that has gone dry. “We are seeing very few big companies remaining in the business, and the innovative capacity is dangerously low. There aren’t just economic bottlenecks, but also scientific ones that are difficult to overcome,” Otto Cars says.

The message from Professor Cars is clear: this is a system failure where all parts of the chain need to be reviewed . “We need to look at innovation and define it in a much broader sense. Everything from behavior changes to prevention needs to be addressed. Antibiotic resistance is a collective action problem that has been below the radar screen for too long,” says Cars. His opinion is that new financial models for R&D, developing other alternatives, for example looking at natural resources, and speeding up the dialogue on a political level is needed in order to have a chance of overcoming this global issue. “Antibiotic resistance is a super-wicked problem. It cannot be solved by the present structure. We need to build new ones,” Cars concludes.

A new therapeutic strategy

Besides looking at possibilities for developing new type of vaccines, and getting to the core of antibiotic resistance, scientists are also discovering other fields in the fight against infectious diseases. Emmanuelle Charpentier, Professor at the Medical School of Hannover and a Guest Professor at the Laboratory for Molecular Infection Medicine Sweden (MIMS), at Umeå University, is recognized as a world-leading expert in regulatory mechanisms underlying the processes of infection and immunity in bacterial pathogens. Her recent groundbreaking findings in the field of RNA-mediated regulation based on the CRISPR-Cas9 system has laid a foundation for the development of a novel, versatile and specific genome editing tool, almost like a Swiss army knife. It has been described as revolutionizing life sciences research that could open up new opportunities in biomedical gene therapies. CRISPR-Cas9 helps scientists understand diseases at the fundamental level, Professor Charpentier explained during the SALSS 2015 conference.

At the beginning of 2009, Charpentier and her research group at MIMS, started learning more about the details around CRISPR and the other molecular components that are involved in the process. Together these components constitute a complex that can find and disarm the virus DNA by cutting it up. The scissors in this case are the protein Cas9. The small address tag, making sure that the complex can cut at the right place, is made of RNA. The bacteria can change this RNA depending on the need. That way it adapts its immunological defense to look for new viruses. Basically, CRISPR is about how bacteria defend themselves against intruders such as viruses by going towards the intruder’s genome. CRISPR can then affect the bacteria’s ability to cause a disease or withstand infections.

“CRISPR-Cas9 is really a tool that allows precise genome surgery to be performed in virtually any cell compartment or any organism,” says Charpentier.

CRISPR-Cas9 has now been established as a top research field within molecular biology. Scientists all over the world have started to use CRISPR-Cas9 for medical and biological research, especially to develop new treatments for various diseases, such as infectious diseases like HIV and malaria. For example, in March 2015 researchers at Virginia Tech revealed an improved way to study genes in mosquitoes using CRISPR-Cas9. Another article was published earlier this year in Nature Communications, where the system had been used as an intracellular defense against HIV-1 infection in human cells. As the authors noted, the results unveil the potential of the CRISPR-Cas9 system as a new therapeutic strategy against viral infections.

Life years lost

Each year more than 17 million people die from infectious diseases. The number of deaths is nevertheless “only” one side of the crisis. Even more people are actually living with an infectious disease, thus making the magnitude of the global suffering considerably larger. From the individual perspective that means people living with the horrors of a lethal disease on a daily basis, becoming forced to sell their property and livestock in order to afford treatments and sick children who can’t attend school. The case with infections is sadly also that they kill at a much younger age than non-communicable diseases. That’s why it is important to focus on life years lost, rather than death, something delicately put by Hans Rosling during his lecture at SALSS.

Another important factor that Rosling addressed during the conference was that the concept of rich and poor countries needs to be broadened. There is a huge group of countries that economically find themselves in the middle, where healthcare is poor and where children die of the diseases. This should be included in the equation when developing new business models to fight infectious diseases, as he stressed, “The world consists of three groups, not two. This is the way of thinking to find good business models.”

Distribution of malaria in the world. Brown: Elevated occurrence of chloroquine- or multi-resistant malaria. Red: Occurence of chloroquine-resistant malaria. Orange: No Plasmodium falciparum or chloriquine-resistance. Grey: No malaria

Image: US Centres for Disease Control and Prevention

What are infectious diseases?

Infectious diseases are caused by pathogenic organisms, such as viruses, bacteria, fungi or parasites. Diseases can be spread both indirectly or directly from one person to another. Infectious diseases kill more than 17 million people each year, that’s nearly 50,000 men, women and children every day. Among the most common infectious diseases are tuberculosis, sexually transmitted diseases (STIs), HIV/AIDS, diarrhea-related diseases, child illnesses (such as measles, polio, pertussis, diphtheria, tetanus), meningitis, hepatitis B and C, malaria, various tropical diseases, leprosy, dengue fever, Japanese encephalitis and respiratory tract infections.

Source: WHO, World Infection Fund

Facts and figures

• Pneumonia is still responsible for one-fifth of child deaths
• 35 million people worldwide are currently living with HIV/AIDS
• Almost 14 million people are infected with active, infectious tuberculosis
• Each year 247 million people are affected by malaria, with the heaviest mortality concentration in children under the age of 5 years
• 1.5 million children die each year from diseases that could be treated with vaccines

Source: WHO, Smart Global Health, Unicef

1 million people die every year due to malaria. Photo: Läkare utan gränser