The 12th Awards Term
The topics of the 12th term, 2021-2022 were selected to be for Grand Hamdan International Award - Infectious Diseases, and for Hamdan Award for Medical Research Excellence - Prevention, Immunity, Therapy.


Infectious Diseases

In the nineteenth century, nearly half of all deaths were from infectious diseases. During the period 1848 and 1872, the leading cause of death in Britain was tuberculosis (causing 15.0 percent of all deaths). Bronchitis was responsible for 6.7 percent of all deaths, followed by scarlet fever and diphtheria (accounting for 5.7 percent), and diarrhoea and enteritis (4.4 percent of deaths). In contrast, heart disease, strokes, etc., accounted for only 5.8 percent and cancer for a mere 1.7 percent of recorded causes of death.


Humans successively defeated the first pathogen, Plague or the Black Death (Yersinia pestis, a bacterial infection, now treatable with antibiotics), in Europe. For centuries, Europe suffered from the Plague of Justinian in 541–542 AD and had recurrences down to the mid-eighth century. It is believed to have killed between one and two-thirds of Europe’s population between 1347 and 1352. Plague, a vastly more lethal pathogen than Covid-19 with fatality rates that may have amounted to 60 and 90 percent, was probably defeated by the development of relatively simple but stringent surveillance and quarantine measures. Systematic quarantine, cordons Sanitaire, and public health measures, including contact tracing, were first developed in the Renaissance.


Many great scientists played a huge part in our understanding of diseases. Girolamo Fracastoro (c.1476-1553), an Italian physician, poet, and natural philosopher named the then-new disease ‘syphilis’ in a poem of 1530. His work on contagion (1546), with its notion of ‘seeds of disease’, is sometimes seen as a forerunner of modern germ theory. Louis Pasteur's (1822-1895) studies of yeast, bacteria, and viruses had a big impact on wine-making, milk safety (‘Pasteurisation’) and medicine. This was the first thorough notion of a germ theory of disease. Joseph Lister (1827-1912) was inspired by Pasteur’s research to use carbolic acid dressings to disinfect surgical wounds (1867). Joseph Lister also did original research on bacteria, and his system was developed into an ‘aseptic’ surgical practice. Robert Koch (1843-1910) elucidated the life cycle of the anthrax bacillus. This led the German bacteriologist to a research post in Berlin where he discovered the causative organisms of tuberculosis and cholera, for which, he won the 1905 Nobel Prize for Medicine.


Studies by Dutch botanist and microbiologist Martinus Beijerinck (1851-1931) on the tobacco mosaic virus (TMV) in the 1890s led to a better understanding of the nature of viruses and their relationship to the cells of the organism they invade. Paul Ehrlich (1854-1915) influenced microscopy, tissue staining, embryology, chemotherapy, and immunology. His theory of the chemical nature of antigens and antibodies, with a “lock and key mechanism of action”, was key to understanding infection. The American virologist Albert Sabin (1906-1993) developed a polio vaccine that used an attenuated strain of the virus. It could be given orally (the transmission route of the disease) and from the 1960s became the vaccine of choice in the worldwide campaign against the disease. French virologist Françoise Barré-Sinoussi (b. 1947) shared the 2008 Nobel Prize in physiology or medicine for her work on retroviruses, of which HIV is the most significant. Retroviruses use their RNA in the host cell to make DNA (the reverse of the usual pattern of DNA used as a template for RNA).


In our present society, WHO has warned that infectious diseases are spreading more rapidly than ever before.Vaccine-preventable infectious diseases like meningococcal disease, yellow fever, and cholera have had devastating effects in areas with limited health infrastructure and resources and where timely detection and response are difficult. Scientists are discovering new pathogens at a higher rate than at any time in history. In the past few years, the WHO identified over 1000 epidemics of infectious diseases such as avian flu, swine flu, polio, and cholera, which might have severe global consequences like pandemics owing to the rapid and unexpected nature of the spread of some pathogens.


Despite substantial advances in research and management of diseases in the 20th century and the successful fight against many infections by using vaccines, antivirals, antifungal drugs, and antibiotics, the control and extermination of these diseases face substantial difficulties. These difficulties result from the many factors including the revival of some old infections, the growing resistance to medications, the new emerging diseases such as HIV/AIDS and Severe Acute Respiratory Syndrome, the human impact and interaction with the environment, and the rising rate of international traveling. All of these factors have led to a higher risk for potential pandemics like the current COVID-19 caused by the novel coronavirus SARS-CoV-2.


The Prophet Muhammad, peace be upon him, had put some sanitary measures for his followers; he referred to purity as half of faith. Purity is half of faith, and the praise of Allah fills the scale (Sahih Muslim). Similarly, the Quran states: Truly, God loves those who turn unto Him in repentance and loves those who purify themselves (Quran 2:222). While this purity involves a spiritual aspect, it also includes physical cleanliness. The Prophet, peace be upon him, taught that blessings are found when one washes their hands before eating. He said: “Blessing in food lies with washing the hand before and after eating” (Tirmidhi). He instructed Muslims to cover their faces when sneezing, and said: “If you hear that there is a plague in a land, do not enter it; and if it (plague) visits a land while you are therein, do not go out of it” (Sahih Bukhari). The Prophet, peace be upon him, was essentially instituting strategies that are implemented in modern times by public health organizations.


In Islamic history, the importance of public health was very well realized. Several hospitals were built to prevent the spread of illnesses. For example, in 706 AD the Umayyad caliph Al-Walid built the first hospital in Damascus and issued an order to isolate those infected with leprosy from other patients in the hospital. This practice continued for more than a thousand years. During the Middle Ages, many Muslim scientists built on this notion. For instance, the book "The Canon of Medicine" by Ibn Sina in the 10th-11th century described the transmitting nature of diseases such as tuberculosis and introduced quarantine as a way of preventing its transmission. Ibn al-Khatib referred to the Black Death that ravished Europe at the time during the 14th century in his book ‘On the Plague.’ At the beginning of the thirteenth century, the Muslim-Arab physician Alaa Al-Din Ali Ibn Abi Al-Hazm Al-Qurashi Al-Demashki Al-Masri, better known as Ibn An-Nafis, spent the first half of his life in Damascus where he studied medicine. He then settled in Cairo, where he practiced at its largest hospital, Al-Bimaristan Al-Nasiri. His most influential work was in the field of medicine and discovery of the pulmonary blood circulation. He is also credited with early work in cardiology. However, his interests extended beyond medicine and included epidemiology, nutrition, Islamic religion, and philosophy as evidenced by at least 24 books authored by him.


In healthcare settings, Infection Prevention and Control (IPC) is essential for healthcare services, as defective IPC makes it impossible to achieve quality healthcare and patient safety. Healthcare-associated infections (HAIs) are a persistent worldwide problem. They represent the fourth-largest cause of death in the United States, with two million patients acquiring infections from health care visits every year. The health authorities’ interventions endorsed by evidence-based knowledge play a crucial role in controlling avoidable infections. This could be accomplished through monitoring infection occurrences, developing and implementing policies and procedures, and educating stakeholders. Safety programs such as hand hygiene, blood-borne pathogen prevention, surgical site infections, antimicrobial resistance monitoring, compliance with regulatory requirements, are elements of concern that should be addressed. We all realized how the orderly vaccination programs of health care workers and general public can make a difference in the prevention and control of infections.


Humanity has to consider the importance of scientific contribution to endorse decisions. Interaction and collaboration among universities, governments, corporations, and civil society are effective tools to minimize the impacts of future challenges, guaranteeing better management of infection risks and adaptation of potential solutions.


The concept of immunity dates back at least to Greece in the 5th century BC. Thucydides wrote of individuals who recovered from the plague, which was raging in Athens at the time. These individuals, who had already contracted the disease, recovered and became “immune” or “exempt.” However, the earliest recognized attempt to intentionally induce immunity to an infectious disease was in the 10th century in China, where smallpox was endemic. The process of “variolation” involved exposing healthy people to material from the lesions caused by the disease, either by putting it under the skin or, more often, inserting powdered scabs from smallpox pustules into the nose. Variolation was known and practiced frequently in the Ottoman Empire, introduced by Circassian traders around 1670. Unfortunately, because there was no standardization of the inoculum, the variolation occasionally resulted in death or disfigurement from smallpox, thus limiting its acceptance.


Many scientists had contributed to our understanding to infection and human immunity. Metchnikoff was the first to recognize the contribution of phagocytosis to the generation of immunity. In Italy, while studying the origin of digestive organs in starfish larvae, he observed that some cells unconnected with digestion surrounded and engulfed carmine dye particles and splinters that he had introduced into the bodies of the larvae. He called these cells phagocytes (from Greek words meaning “devouring cells”). Working first at the Bacteriological Institute in Odessa (1886-87) and later at the Pasteur Institute in Paris, Metchnikoff established that the phagocyte is the first line of defence against infection.


The first Nobel Prize in Physiology or Medicine was awarded to von Behring “for his work on serum therapy, especially its application against diphtheria, by which he has opened a new road in the domain of medical science and thereby placed in the hands of the physician a victorious weapon against illness and deaths”. Metchnikoff and Ehrlich shared the Nobel Prize in 1908 “in recognition of their work on immunity.”


Building upon the demonstration by Von Behring and Kitasato of the transfer of immunity against Diphtheria by a soluble “anti-toxin” in the blood, Paul Ehrlich predicted the existence of immune bodies (antibodies) and side-chains from which they arise (receptors). Ehrlich suggested that antigens interact with receptors borne by cells, resulting in the secretion of excess receptors (antibodies). Ehrlich surmised that erythrocytes would not have this capacity and speculated that this immune function might be a specialized characteristic or “haemopoietic tissue”


There have been many seminal contributions to immunology that received the Nobel Prize. In 1960, along with Peter Medawar, McFarlane Burnet was awarded the Nobel Prize for "the discovery of acquired immunological tolerance rather than the clonal selection theory". Neils Jerne would later win the Nobel Prize in 1984 for "theories concerning the specificity in development and control of the immune system"


In the near future, further advances in the cell biology of the immune system will no doubt occur, leading to the development of novel vaccines. New receptor or cytokine-modifying therapeutics will be developed based on insights obtained from experimental immunology. The application of the human genome project to diseased populations will identify new drug targets, and high-throughput screens and combinatorial chemistry will accelerate the pace of drug discovery. Gene and protein microarray techniques and proteomics will reveal new components of immunity that will expand our knowledge of how the immune system works.


In the late 20th century, infectious diseases have resurfaced as a significant public health problem worldwide. Nowadays, the management is often addressed in the context of poverty, mental illness, addiction, and discrimination management, and not only the medical approach. 


The development of antibiotics during the early and mid-twentieth century has been highly acknowledged, resulting in hundreds of different kinds of antibiotics following the discovery of penicillin in 1928. Antimicrobials, including antibiotics, antivirals, antifungals, and anti-parasitic, are used to manage infections, allowing the body’s natural defences to eradicate the pathogens. In addition to treating community-acquired (CA) and hospital-acquired infections (HAIs), antibiotics are used to prevent infections in immunosuppressed patients, cancer patients with suppressed immune systems, as well as surgical procedures. This flexible usage resulted in the decline of infection-related mortality in the first half of the 20th century. However, the available medications are not adequate to combat drug-resistant microbes or protect us against new microbes for which therapy is not available or ineffective.


For example, the development of antimicrobial resistance by the microbes known as superbugs has posed new challenges due to the rise in the related mortality rate. HAIs are more likely to be caused by bacteria resistant to antibiotics and result in greater mortality than CA infections and constitute a significant clinical and economic burden worldwide. An estimated 5–10% of all hospitalizations acquire infections each year in the USA alone. The WHO has warned that infectious diseases might become non-treatable owing to high levels of multiple drug resistance. The condition might be attributed to the overuse and misuse of antibiotics, high human mobility across the globe, and evolutionary selection of pre-existing species and variation through mutation or DNA transfer.


Modern medical practice is in need of new approaches to treat infectious diseases and to improve the efficacy of therapies against emerging epidemics. The pipeline of new drugs is limited and the process is very slow as major pharmaceutical companies have limited interest in the antibiotics market because these are not as profitable, the research and development are expensive, risky, and time-consuming considering that resistance to antibiotics develops over time, eventually making them less effective.


The search for substitutes for antibiotics has thus become essential. The effect of some of these alternatives are known in vitro, but they have not been explored for their pharmaceutical properties. Exploration of alternative therapies like Phage therapy, which was recognized in the early 20th century but overshadowed by the discovery of antibiotics, is still experimental and not yet approved. Bacteriophages are viruses that infect and then kill specific bacteria and not human cells and could be an option to treat bacterial infection. On the other hand, bacteriocines are limited to food preservation though their indirect application in the form of probiotics is broadly recognized. The emergent understanding of host-microbe interaction allowed for the design of immune-based therapeutic modalities. Immune therapy, which encompasses pathogen-specific and non-pathogen-specific modalities designed to enhance host immunity is expected to play a part in modern anti-infective treatments.


Unlike antibacterial drugs, which may ensure a wide spectrum of pathogens, antiviral medications are used to treat a narrower range of organisms. Besides, it is typically limited to the viral phase of infection and not to the later inflammatory phase, in which it is ineffective.  Scientists have two paths to develop new therapeutics, either to repurpose existing drugs or discover novel ones. Unfortunately, new antiviral drugs are in short supply as they are much harder to develop than antibacterial drugs because they can damage host cells where the viruses exist. At present, novel drugs are enormously needed to combat viral infections, such as influenza and hepatitis B and C, and to counterweight the developing resistance of viruses, fungi, and parasites to antimicrobials. For example, HIV develops resistance to treatment so patients always take more than one type of antiviral medication to reduce such resistance. Candida auris is a pathogenic fungus that can be resistant to all antifungal medications. Malaria is an example of a parasite that has developed resistance to many anti- parasitic medications, limiting public health efforts to control it.


It is observed that Vaccines also have the potential to be used to treat diseases, rather than prevent them. Such therapeutic vaccines are being targeted at persistent infections, such as shingles and human papilloma virus. They are also being targeted at non-infectious conditions, including autoimmune disorders, tumours, allergies, and drug addiction. Another potential importance of using existing vaccines and developing new ones will manifest itself in the reduction of the infection spread and so will be the antibiotics use and resistance. For example, if every child in the world received a vaccine for an infection with Streptococcus pneumoniae bacteria (which can cause pneumonia, meningitis and middle ear infections), this would prevent an estimated 11 million days of antibiotic use each year.


The COVID-19 pandemic has clearly proved the need to anticipate and prepare, rather than merely react to emerging pathogens. New therapeutics and vaccines need proactive drug development strategy to shorten the time before treatments are accessible.