You are about to leave the website of the Global Health Institute of Merck KGaA, Darmstadt, Germany

Infectious Diseases

Drug pressure and climate change at the heart of the re-emergence of infectious disease threats

Although the worldwide spread of non-communicable diseases (e.g. cancer, diabetes...) receives incremental attention, the spread of communicable or “infectious” diseases remains a major global health issue. Historical lack of investment in infectious diseases that were no longer considered important has made the current situation critical. Neglected tropical diseases such as Schistosomiasis tend to appear in places where they were not observed previously and continue to seriously impact economies of endemic countries.

image-1

For other tropical diseases such as malaria, the continuous emergence of resistance to antimalarials is significantly postponing the overall goal to eliminate this disease within a reasonable time frame. Bacterial infections are becoming increasingly severe and the wide spread antimicrobial resistance observed on most antibiotics has finally triggered a global reaction within the international community to address this emergency.

Malaria

Despite major efforts and significant progress over the last decade, malaria remains a major health problem with a third of the world’s population being at risk of contracting it, and provoking half a million deaths every year, mainly within children in Africa. The Institute’s antimalarial strategic intent is to develop and to market innovative drug products and tools supporting elimination.

image-1

Our research efforts are focused on developing new affordable tools to prevent infection, to test and to treat patients and to block malaria transmission from and to the mosquito. Access path is defined through discussions with key organizations involved in public procurement as well as through elaboration of innovative procurement and distribution mechanisms for the private sector.

Treatment 

Anti-parasitic resistance to currently existing drugs against malaria is a major concern and may lead to a rebound of the disease and reappearance of malaria in historical regions, consequently of climate change.

The Institute is developing a small targeted portfolio of drugs and research platforms to address unmet medical needs such as new treatment approaches against resistant plasmodium strains, new prophylaxis approaches, and new ways to help block transmission from human to mosquitoes.

Detection 

In malaria endemic areas, where people are infected frequently, most infections are controlled by acquired immunity at low parasite densities causing little or no symptoms. Infection can persist for weeks or months and constitute a parasite reservoir contributing to maintaining a high prevalence of the disease.  To achieve elimination and eradication of malaria, highly sensitive, easy-to-use and reliable methods of detection need to be developed so that all parasite carriers can be actively identified and treated.

The strategic positioning of the Institute is to build a portfolio of highly sensitive diagnostic tools to foster the use of more efficient anti-malarials, thus fighting resistance and supporting elimination. Leveraging technologies of the Life Science business sector of Merck KGaA, Darmstadt, Germany, we have developed a diagnostic platform that aims to increase the sensitivity of detection as compared to current devices. This platform is to simplify and standardize the malaria detection procedure allowing any Health Care facility to perform highly reliable diagnostics.

We are also co-developing a new user-friendly technology to test validity of drugs to prevent the issue of counterfeited medicines and the challenge of increasing resistance.

Transmission control 

Malaria is transmitted through mosquito bites, usually occurring between dawn and sunrise. Today, massive distribution of impregnated bed nets and awareness campaigns contributed to major improvements in controlling the transmission of malaria in endemic populations. Despite their successes, bed nets do not protect from mosquito bites for the most at-risk population, including pregnant women and children usually infected just before bedtime.  In partnership with Performance Material business sector, the Institute is completing the registration of IR3535, a powerful and safe insect repellent, for the protection against malaria. IR3535 could significantly synergize the impact of impregnated bed nets on children and pregnant women if deployed in a conjunct campaign.

Health system strengthening and access to innovation

To ensure access to drugs and affordability, the Institute is exploring innovative business models and partnerships to minimize its development and manufacturing costs through partnerships with other players, and through lean and shared distribution paths and innovative sales models.

A key element of the success to implement our innovation is to contribute to the building of a sustainable ecosystem in the countries and to involve very early on the local stakeholders. Partnerships with institutions in endemic countries are allowing us to identify specific needs, tailor our product profiles to real-life conditions and to build strong relationships with ministries and regulatory bodies in the countries.

Schistosomiasis

Schistosomiasis is a water and vector-borne neglected tropical disease. The parasitic blood flukes, known as schistosomes, multiply in freshwater snails and spread through the water. Infection is acquired when people come into contact with fresh water infested with the larval forms of the schistosomes. A lack of awareness and understanding of this disease is massively undermining the efforts to control, and ultimately to eliminate the disease.

image-1

According to recent figures from WHO, Schistosomiasis affects at least 206 million people worldwide. It is endemic in 78 developing countries. An estimated 90% of schistosomiasis cases are found in sub-Saharan Africa. It is the most important cause of parasite morbidity and mortality in Africa after malaria.

Treatment 

Praziquantel (PZQ) is the recommended treatment against schistosomiasis; PZQ is included in the WHO list of essential
medicines
.
 Although 500 mg and 600 mg PZQ tablets are able to treat adults and school-age children, there is an urgent need for a suitable pediatric formulation to treat the pre-school aged children (PSAC), a high-risk group for schistosome infections accounting for 20-25 million of the global prevalence.

The Institute leading the Pediatric Praziquantel Consortium which is currently developing a suitable orally disintegrating tablet (ODT) formulation of PZQ for PSAC, thus supporting the 2020 WHO NTD Roadmap targets for control and elimination of schistosomiasis in multiple countries in Sub-Saharan Africa.

Besides the need for a pediatric PZQ formulation, a potential risk of resistance to PZQ exists, should the drug pressure increase in the communities. Also, new drugs that could meet the elimination agenda should be developed. The Institute aims at generating a small and focused pipeline of new chemical entities with differentiated target product profiles, i.e. active on multiple stages of the schistosome’s lifecycle across species. Also, the management of schistosoma-induced complications, such as female genital schistosomiasis, is a priority.

Detection

Schistosoma infections are diagnosed by counting the parasite eggs in the stools or by filtration of the urine using methods such as the Kato-Katz technique. However, the lack of sensitivity of such methods in mid-to-low infectious settings poses problem to reliably identify infected populations. The Institute is focusing its efforts to develop the next generation of diagnostic tools including new biomarkers of infection, and identification of suitable technologies that would provide reliable, simple and standardized diagnostic methods that can be easily used by health workers.

Transmission control

The transmission of schistosomiasis to human occurs when larval forms of the parasite – released by freshwater snails – penetrate the skin during contact with infested water.

The control of the transmission could be addressed either by controlling the snails’ population or by avoiding contamination of the water by freshly released parasite eggs from human urine or feces.

Snails’ control can be achieved by using molluscicides and environmental or biological measures. The Institute is contributing to the transmission control agenda by supporting a postdoctoral program exploring ways to eliminate the infectivity of snails through gene editing, using technologies and strategies already successful in the control of malaria and dengue fever.

The Institute is also closely collaborating with WASH programs and is leveraging internally-developed technologies for the control of the quality of the water.

Health system strengthening

The involvement of stakeholders in endemic countries is a key factor of success for the programs of the Institute.

The development of the pediatric praziquantel formulation has led the Consortium to strengthen the infrastructure of the health research facility in the rural village of Man (Ivory Coast) by building an annex research facility, a new waiting area protected by a roof, and by providing the necessary equipment needed for the conduct of the Phase II clinical trial. The unit has now the capacity to become a sustainable research center for several infectious diseases.

Key collaborations have also been established with researchers in Kenya, South Africa and Cameroon to perform early research projects that will improve our understanding of the disease and the consequences of the infection, and that will shape our mid-term strategy.

Bacterial Infection and AntiMicrobial Resistance

Over-use of antibiotics has led to increased bacterial resistance. While resistant infections developed primarily in hospitals or healthcare settings, this has now spread to wider communities. According to the Centers for Disease Control and Prevention, it is estimated that in the USA only, more than 2 million infections per year are caused by resistant bacteria, which leads to over 20 000 deaths.

image-1

The economical toll is important with over 20 billion USD in costs per year. The toll is even bigger in developing economies where antibiotic stewardship, access and care are still crucially needed.

Detection & Technologies

Most antibiotics are prescribed or used without any proper diagnostics. Current methods of bacterial infection identification require dedicated equipment, training, and are not rapid enough to guide the treatment decision. Therefore, there is a major need to develop new technological platforms to speed up the assessment of the type of infection to significantly decrease the unnecessary use of antibiotics or other antimicrobials such as anti-malarials.    

We are also co-developing a new user-friendly technology to test validity of drugs to prevent the issue of counterfeited medicines and the challenge of increasing resistance.

Health system strengthening

Surveillance and awareness of the consequences of antibiotic misuse need to be strengthened. Developing laboratory capacities as well as educational programs of local healthcare providers are part of the Institute’s deliverables within the next years.