Scientists that pursue a cure for neglected tropical conditions are now using their experience to combat COVID-19.
The Kilimani neighbourhood, in Nairobi, capital of Kenya, used to be a residential area for British colonists. Today, shopping malls and offices are widespread, such as those rented in the Tetezi Towers, a modern steel and glass facade multi-story building that does not go unnoticed in the still unpaved streets. What no one can imagine is that inside that building some of the most promising medical innovations are being developed: we are referring to the regional office for Africa of the Drugs for Neglected Diseases Initiative (DNDi), a non-profit global organization that supports research of new treatments for these conditions. The organization is managed by Dr Borna Nyaoke, who is regarded as one of the Top 40 under 40 Woman in Kenya. And now she has more work than ever.
At a time when COVID-19 is wreaking havoc worldwide, Dr Nyaoke, specialist in Public Health trained in Harvard, Liverpool and Nairobi, has two open fronts: on the one hand, closely monitoring progress in the six currently ongoing clinical trials for three of the neglected tropical diseases (NTDs): leishmaniasis, mycetoma and paediatric HIV. NTDs are so called because, although they affect some 1,700 million people, they do not attract sufficient interest; indeed, since NTDs affect mainly impoverished populations that cannot afford a treatment, funding or time attributed to research to find a cure is not enough. Buruli ulcer, Chagas disease, leishmaniasis, river blindness, sleeping sickness…
Those working in countries with constrained resources to stop NTDs are looking at COVID-19 world spread with great concern: if pandemic has supposedly crippled health systems in wealthy countries, in less resourceful countries, it may mean a disaster.
To get ready, in April 2020 DNDi launched the COVID-19 Clinical Research Coalition, a consortium of more than one hundred physicians, researchers, pharmaceuticals, funders and legislators from 30 different countries, with the aim of accelerating research about prevention, diagnosis and management of cases at sites where the virus might wreak more havoc. In an e-mail message, Dr Nyaoke explained that “In resource-poor contexts, very few clinical trials of COVID-19 are being conducted; our African researchers contribute only 1% of the medical clinical publications worldwide”. Indeed, in a few months, abundant scientific literature has been generated: today, there are 1976 studies on the disease caused by SARS-CoV-2 recorded at the WHO database. “Africa shows an unbelievable amount of genetic diversity and, therefore, the results of the numerous studies of coronavirus that are being conducted in the world may not be relevant for people in the African continent, unless the studies are conducted at the local level.”
Dr Nyaoke is embarked on this new undertaking, since, as usually said, experience is a great teacher. “Our research on NTDs has entailed working in some of the hardest and resource-limited settings in the region, as well as on diseases for which no previous clinical trials have been made, such as mycetoma”, Dr Nyaoke said, and added how specialists like her have developed the capacity to conduct quality clinical trials in adverse contexts and to encourage key partners and collaborators to speed up research. “We have also had dialogues with political actors to promote the access to treatments once clinical trials are completed”, Nyaoke said.
Thus, as the new coronavirus became stronger in the world, more and more physicians, scientists and researchers like those headed by Dr Nyaoke decided to devote their efforts to contributing to the pursuit of treatment or a vaccine that helps to eliminate the disease.
Chagas disease, an NTD caused by the parasite Trypanosoma cruzi, affects more than seven million people worldwide, and can be lethal. Research done on this NTD has provided insight that could help find a cure for COVID-19. Silvia Gold, president of Mundo Sano, explains some ongoing advances. This is the only Spanish-American organization included in the Uniting to Combat NTD program, and one of its main achievements is the inclusion of Chagas disease in the London Declaration (the greatest global alliance to combat NTDs) and the creation of a public-private partnership to manufacture and distribute benznidazole, the main drug used to treat this disease.
Gold highlights the use of ivermectin, an antiparasitic drug used to treat some NTDs, such as river blindness and lymphatic filariaisis, which has been shown to be very safe. In Mundo Sano Foundation, ivermectin was considered the second treatment of Chagas disease. “We are very interested in it as an antiparasitic drug; it has a lot more to offer and we are working in different formulations”, Dr Gold explained. In April 2020, Australian scientists demonstrated that the drug acts against SARS-CoV-2 in vitro; further research is being conducted based on that result. To date, there are up to 32 ideas underway. One of them is in Argentina. “We are conducting a trial in Buenos Aires, in which we measure if ivermectin administration lowers the viral load in 45 patients. We still do not have results, but if it works well, we will conduct a large trial with clinical indicators”, she said.
Another example from Spain is the project coordinated by the Barcelona Institute for Global Health (ISGlobal), and the University of Navarra. It is the Saint Project, a trial involving 24 patients, which is planned to end in late August and whose goal is the same: to confirm whether this drug reduces the viral load.
“Another very attractive project that has been widely disseminated in the media involves horse serum: horses are great producers of antibodies”, Gold explained about another line of research that has been opened to cure COVID-19. The human clinical trial stage of the study started this July, and consists of producing sera from blood plasma of horses to stop the disease at the earliest stages, since it has been shown to block the virus entry to the cells and, therefore, the virus cannot reproduce; thus, the serum behaves as the antivenom against spider and scorpion venoms, among others. “The equine serum plasma has already been extracted and measured in three different reference laboratories: Barcelona, Buenos Aires and Córdoba province in Argentina. These antibodies allow us to generate a more easily manufactured and scalable product, since the amount of serum obtained from convalescent human plasma depends on the supply, but this is a product that can be scaled up and manufactured”, Gold said.
In this case, advantage is being taken from the technique used in the search of a medicine to treat hemolytic-uremic syndrome; there was an outbreak in 2011 in Germany, which triggered the so called “cucumber crisis” because it was believed that cucumbers imported from Spain were the cause of the outbreak. “COVID-19 has caught us with an already prepared platform”, Mundo Sano founder added.
Another technique well known by Dr Gold and her team is the so called testing pools, an intervention model for group detection of the virus designed to test more people using fewer kits, a usually scarce resource, and therefore, to lower the costs. The technique consists of taking a sample with a swab introduced in a tube containing a liquid that preserves the virus. This part of the technique is similar to that used in individual tests. The difference lies in that in the laboratory, the swabs are not processed individually in the machine where the PCR tests are performed to detect the presence of COVID-19; rather, the liquid of several tubes is put together for analysis all at once. If the result is negative, it means that none of the persons are infected. If it is positive, then an individual test is made to each person. “The pool allows us to make more tests, but it has the limitation of the test sensitivity”, Gold warned about a technique that was previously used to detect dengue. “We make pools of four samples; that is the limit that we consider reliable for not missing a positive case.”
Obtaining a vaccine against a disease is simpler if all the parts of the causing virus or bacterium are correctly identified. A group of physicians and biologists at the Hospital Clínic of Barcelona is working under this premise. María Jesús Picazo, senior specialist of the International Health Service of the Hospital Clínic and researcher at ISGlobal, described: “We seek for peptides or fractions of proteins that may serve as the basis to design a vaccine against COVID-19 based on the extraction of extracellular vesicles”. In simple words, what they do is analyse all the virus parts that generate or not the presence of symptoms and that make these symptoms more or less severe.
“If we recognize which parts of the virus we should work on, we will be able to lay down the principle of a vaccine”, Picazo said; her team used to do the same before COVID-19, but with other purpose: treatment of Chagas disease. According to Picazo, they are different diseases that require different responses, but the techniques and hypotheses are similar. They are still at a preliminary phase of research, but the earliest results show what has been already detected clinically: “There is great heterogeneity among the peptides that are being found in SARS-CoV-2; it is a multi-faceted virus: in several patients it is not evident, whereas in others it manifests in a very severe way and affecting not only the respiratory system. Biologically, this is translated into something, but we still do not know what. ”
Azithromycin is an effective, cheap and easy to administer antibiotic that in 2012 acquired importance when doctors Oriol Mitjà and Quique Bassat from ISGlobal demonstrated that a single dose was enough to cure a person with yaws, another neglected disease similar to syphilis but that is not sexually transmitted, and that affects especially children. This finding paved the way for WHO to consider its eradication for 2020, after 60 years with no significant progress.
Now, azithromycin can be another tool to face this new coronavirus, as indicated in a study by the University of Oxford, United Kingdom, which intends to confirm if the use of this antibiotic may prevent COVID-19 patients from becoming sicker. Among other factors, this could reduce the number of admissions to hospitals and avoid the subsequent collapse of the health system. For the preliminary phase of the investigation, 800 patients will be recruited and azithromycin will be administered to half of them for 14 days. After one month, the severity of symptoms will be evaluated in patients from both groups.
Planeta Futuro – El País – Full article