Anticandidal Therapeutics: Discovery and Development

By Awanish Kumar and Anubhuti Jha

Developments of antifungal agents have declined as compared to other antibiotics that have displayed a potent development with time. There is an urgent need for both prophylactic and therapeutic treatments worldwide to control the severity of infections caused by Candida. Anticandidal Therapeutics: Discovery and Development provides the readers with a compiled knowledge of the fungal human infection Candida and the development of anticandidal drugs. Anticandidal Therapeutics helps researchers form the basis for the discovery and development of novel anticandidal therapies. In 14 chapters this book provides collective information on anticandidal agents and their discovery and development with respect to major drug transporter families, different stages of anticandidal agent development, recent trends and progress in antifungal translational research, clinical studies status of anticandidal therapeutic agents, and drug repurposing for development of novel anticandidal agents.

• Highlights the mechanistic actions of some therapeutic agents against Candida
• Focuses on anticandidal agents rather than general antifungal agents
• Discusses the stage of development of new antifungal drugs, the repositioning of drugs, and how this could help in treatment

• Language: English
• Publisher: Academic Press
• Release date: Jan 20, 2023
• ISBN: 9780443187452

Awanish Kumar

Dr. Awanish Kumar is currently an Associate Professor in the Department of Biotechnology at the National Institute of Technology, Raipur (CG), India. He has more than 13 years of research experience. He received his PhD in Molecular Parasitology from the CSIR-Central Drug Research Institute, Lucknow, India, and Jawaharlal Nehru University, Delhi, India, and completed his postdoctoral studies at McGill University, Montreal, Canada. His research interests are infection biology, drug targeting, and drug discovery. Dr. Kumar has served on various national and international organizations in different academic and research capacities. He has also served on many national committees, scientific society, and advisory panels, as a member of many international professional research societies, and as a reviewer and editorial board member of reputed and refereed journals. He has authored or edited several monographs, books, and book chapters.

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Chapter 1: History of infection

Abstract

Throughout history, communicable diseases have harmed humans; but, as society transitioned to agrarian life around 10,000 years ago, these diseases became more dangerous. Infectious diseases had more opportunities to spread as a result of the emergence of more tightly connected populations. Flu, smallpox, leprosy, malaria, and tuberculosis are just a few of the diseases that have thrived since the transition. Pandemics have become more likely as human civilization has progressed and communities have gotten more connected. In this chapter, we look at the history of infectious diseases and how they have affected our lives today. In this chapter we take a look at the course of these pandemics with respect to initiation, spread, and persistence of each infection.

Keywords

Bacterial; Fungal; Pandemic; Various infections

Introduction

Introduction to plague

Types of plague

14th century plagues

Plague of Athens

Second plague pandemic

Black Death

Third plague pandemic

Smallpox

Tuberculosis

Spanish flu

HIV/AIDS

Swine flu

COVID-19 (current pandemic)

A note on the future

References

Introduction

According to the Spanish philosopher George Santayana, Those who don't know history are destined to repeat it. One should never forget where they came from. The history of infectious diseases warns us of the same notion more starkly—sometimes trying to make us aware beforehand, other times, making us afraid so much that we tend to be visibly scared every time we breathe, but most importantly, it guides and prepares us for a future full of uncertainties, vulnerabilities, and also, possibilities. Without a thorough understanding of how infectious diseases came to be, survived to thrive, ruled to abolish, and remained deadly to create havoc beyond one's imagination, it is futile to discuss how they can be tackled, managed, and dealt with effectively. Since the beginning of humanity on Earth, infectious diseases have affected the way humans have interacted with each other and nature. To understand and tackle this issue, it becomes crucial to comprehend the origin, spread, function and casualty these diseases created. In order to deal with the disease effectively, we must inspect the cause and effect deeper and with precision. Studying the history of infectious diseases can be the first step toward a long journey. The historical knowledge has been retrieved thanks to the historical information and vivid description of the infectious diseases individual historians who witnessed the brutality of the disease themselves have documented. Many of these historians' accuracy has been confirmed by modern researchers with empirical data and excavations. A majority of plagues seem to receive a perfect ground to grow and expand near ports with heavy human activity, poor hygiene, and close proximity. These epidemics are also notorious for returning with much force and increased infections, as the interval between one outbreak and another does not provide enough time for recovery and proper medical preparation.

With each infectious disease, people started discovering more advanced methods to prevent and diagnose them. This led to an advancement in public health and hygiene culture. Microbiologists started to understand the functionalities of bacteria, virus, fungi, protozoa, and parasites better. Working on the pathogens, the advancement on the treatment, prevention, and control have been immense. One of the profound impacts infectious diseases had on the human population was mass migration. Civilization after civilizations have been destroyed and rebuilt due to the death toll and economic burden a pandemic puts on the human population. The idea that infectious disease history has everything to do with human history, impacting it more profoundly and severely than world wars, should not be surprising [1].

Advancement in traveling led to advancement in the spread of infectious diseases. For example, European travelers between 1518 and 1568 introduced smallpox, measles, and typhus to the Central and Latin American native population. Smallpox alone was responsible for wiping out 17 million of the population in Mexico, making the population to be just under 3 million [2].

Introduction to plague

Plague is caused by a zoonotic bacteria, Yersinia pestis, found in small mammals and their fleas. The patients of plague start to develop symptoms in 1–7days of getting infected [3]. It can spread directly when the infected tissue is in contact, by the bite of an infection-carrying flea, being in contact with contaminated material, and by inhaling the infected droplets. The bacteria can be easily destroyed when exposed to sunlight but it can still survive for up to 1h in favorable conditions. When left untreated, the plague can prove to be fatal with a fatality rate of 30%–60% and in some cases death being the only option. With the help of antibiotics, the patients can be treated after an early diagnosis. In medieval times, plague occurred pretty frequently because of poor hygiene and lack of proper treatment. Modern treatments have given us a ground to have a chance to treat the patient but that does not mean that we have completely eliminated the plague-causing bacteria itself. With time, the pathogen evolves too with far greater capabilities to survive in the host for a considerable period of time, so much that it can affect the daily functioning of the patient and can infect the people surrounding them. According to the World Health Organization (WHO), during the period of 2010–2015, 3248 cases of plague were reported, resulting in 584 deaths [4].

Types of plague

1. Bubonic plague: It is the most common form of plague, caused by Y. pestis when an infected flea bites a person. Reaching inside the skin, the bacteria replicates in the lymph node and causes headache, fever, weakness, and chills in the patient. An inflamed lymph node, also known as bubo, at an advanced stage, can become an open sore and release pus. It is a rarity for this infection to transmit from human to human directly. Once it reaches the lungs, the disease displays its severity.

2. Pneumonic plague: It is the most severe and virulent of all the types of plague with an incubation period as short as 24h. Not only does it cause grave discomfort in breathing, but it also spreads from person to person through the air. An infected droplet when inhaled can infect a healthy person when there is proximity with the patients. Untreated bubonic plague can also turn into pneumonic plague when the bacteria enter the lungs. If diagnosed within 24h of the symptom, recovery rate increases.

3. Septicemic plague: When the bacteria start multiplying in the blood, without showing any open sore, this plague occurs. All the other symptoms are the same as bubonic plague. It does not spread from person to person.

To address the present problems, one must study and analyze the historical data, their shortcomings, and progression.

14th century plagues

There are some speculations about the origin and spread of the epidemic. According to a modern theory about the spread of the disease, the climate change in the Asia region led the rodents to shift from grasslands to more populated areas. Y. pestis is commonly present in fleas carried by ground rodents. Discovered in 1894 in Hong Kong by Alexandre Yersin, it was suggested that rodents can be the carrier of the plague. 4 years later, Paul-Louis Simond found that fleas were also involved in the transmission as the bacteria replicated itself in their midgut, blocking it, leading the fleas to starve. This starvation leads to an aggressive food consumption behavior, but due to the blockage, the bacteria are thrown to the feeding ground by a process called regurgitation. This results in multiple numbers of bacteria infecting the