Emerging Approaches to Tackle Neglected Diseases: From Molecule to End Product

Neglected tropical diseases (NTDs) are a widespread category of communicable illnesses that thrive in tropical and subtropical environments. More than a billion people are affected by these illnesses, which annually drain billions of dollars from developing nations' economies. The most severely impacted populations are those who lack access to basic sanitation, live in poverty, and are in close proximity to disease vectors, domestic animals, and livestock. The World Health Organization (WHO) is a United Nations department focusing on public health issues. NTDs pose a significant threat to public health both globally and in India. Lymphatic filariasis (LF), Visceral Leishmaniasis (VL), Rabies, Soil-Transmitted Helminthic Infections (STH), and Dengue are the principal parasitic and associated infections that the World Health Organization (WHO) has designated as neglected tropical diseases (NTDs). These neglected diseases represent a concern to millions of underprivileged Indians who live in deplorable conditions. The current chapter examines the common NTDs in India, their prevalence, the state of control strategies, and obstacles and prospects for NTD eradication. 

Neglected tropical diseases (NTDs) are highly prevalent in Sub-Saharan Africa. In the World Bank's definition of poverty, nearly all people suffer from at least one NTD. Among the most widespread NTDs are malaria, HIV, and soil-transmitted helminths like lymphatic filariasis, schistosomiasis, trachoma, and onchocerciasis. A recent study suggests that NTDs may influence the evolution of HIV and AIDS, malaria, and tuberculosis. These interactions may be influenced by epidemiological, immunological, and clinical factors, which may impair the prognosis for those with HIV/AIDS, TB, or malaria. World Health Organization (WHO) suggests five main strategies for preventing and controlling NTDs for public health-intensified case management, vector control, preventive chemotherapy, sanitation, the provision of safe water, veterinary public health, and hygiene. Despite only using one method and doing it locally, to control, and eliminate the NTDs, these methods can be used as a mark for achieving the Sustainable Development Goals as they are mainly found in disadvantaged regions and environments. The development of pilot projects and initiatives can help achieve the Millennium Development Goals. The poor and marginalised could gain from innovative treatments for neglected diseases (particularly parasite infections) based on sustainability concepts and knowledge of key factors affecting health.

The chronic infectious condition known as leprosy is brought on by the bacteria Mycobacterium leprae. Peripheral nerves and the skin are frequently attacked, which can result in impairments. The incidence of M. leprae infection has decreased in endemic countries as a result of the WHO's multidrug therapy (MDT) program for leprosy treatment, but there is still active transmission as evidenced by the high rate of newly reported cases. It is critical to diagnose leprosy as early as possible, hence clinical examination and research are required. Leprosy has six subgroups, according to the Ridley-Jopling classification: Tuberculoid (TT), Borderline Tuberculoid (BT), Borderline-borderline Mid-borderline (BB), Borderline-lepromatous (BL), Subpolar Lepromatous (LLs), and Polar Lepromatous (LLp). Based on the type of therapy, leprosy is categorised into paucibacillary (PB) and multibacillary subtypes (MB). Skin scraping smears are still the preferred laboratory test for leprosy diagnosis. Depending on the type of leprosy, whether it belongs to the PB or MB group, the course of treatment with Multi-Drug Therapy (MDT) is modified. Rifampicin and dapsone are the recommended regimens for the treatment of PB type, whereas rifampicin, dapsone, and clofazimine are recommended for MB-type patients. To identify an efficient MDT treatment and stop the spread of the illness, a correct leprosy diagnosis must be made by both a physical examination and a laboratory analysis. 

There are over 60 countries where dengue fever is endemic, and 2.5 billion people could get sick from it. An RNA virus belonging to the Flaviviridae family that causes acute viral disease dengue is transmitted by Aedes mosquitoes. The presenting signs may be asymptomatic fever with severe implications such as hemorrhagic fever and shock. The most common symptoms are acute-onset high fever, cutaneous rash, hemorrhagic episodes, myalgia and circulatory shock. Although oral symptoms are seldom the primary presenting sign of dengue infection, they may occur in certain cases. Early and precise diagnosis is necessary for lowering mortality. Dengue virus infections are typically self-limiting, but in tropical and subtropical countries, dengue infection has become a public health threat. A detailed explanation of dengue virus infections, clinical symptoms, diagnostic techniques, and preventative measures are all included in this book chapter.

In poor nations, helminthic illnesses are a major source of social, economic, and medical problems. These parasite illnesses affect a large number of people, and there are not enough effective treatments available. It is necessary to step up research on novel medications and treatments to address this pressing need. The lymphatic system is hampered by lymphatic filariasis, which can result in aberrant body part growth and cause discomfort, severe disability, and social stigma. As of 2018, there were 51 million cases, a 74% decrease from the 2000 commencement of the WHO's Global Programme to Eradicate Lymphatic Filariasis. With 27 cases documented in 2020, the devastating parasite disease dracunculiasis is almost completely eradicated. The transmission cycle takes between 10 and 14 months to complete after infection. The aim of the book chapter is to focus on pathogenesis, diagnosis, available treatment, and measures to eradicate these infections caused by helminthic parasites, which have been declared as neglected diseases by the World Health Organization.

Soil-transmitted helminths [STH] are described as neglected tropical disorders (NTDS) since these impose terrific distress and disability, nevertheless, they can be eradicated or controlled. The pervasiveness of STH is more usual in rustic/bucolic areas than in city areas. STH signifies the worms present in the intestine provoking infection in humans and are transmitted/ conveyed via unhygienic/ dirty soil. “Helminth” denotes a parasitic worm and the causative agents/ chief species that can harm humans are the hookworms (Ancylostomaduodenale and Necatoramericanus), whipworms (Trichuristrichiura) and roundworms (Ascarislumbricoides). Various features namely, Hypersensitivity reaction (Type -1), the response of defective Th2, mucosal inflammation, volvulus, obstruction of small bowel and intussusception, blood loss in the mucosa, anaemia, etc. are involved in the pathophysiology of STH. To control mortality and morbidity, WHO has recommended population-based, specific, and target-based approaches. The medications recommended by WHO are Albendazole, Levamisole, Mebendazole, and Pyrantelpamoate as a single dose. Preclinical studies are being carried out on the ayurvedic and herbal treatments employing medicinal plants for STH infections as these are compatible with the body and have fewer side effects. The infection is now considered a major public health issue; the major role played by poor sanitation and hygiene in addition to this is certain environmental conditions. Thus, soil-conveyed helminth infections have a primary influence on socio-economic progress and advancement of society where occurrence rates are higher as such acquired infections influence the performance of adults to do work properly and provoke absenteeism amongst school-going children.

The most prevalent parasite condition affecting the brain, neurocysticercosis (NCC), is a well-known contributor to new seizures all over the world including India. The only prevalent cause of acquired epileptic seizures in underdeveloped nations, whereas active epilepsy is a common cause in affluent nations, that is cysticercosis, a parasitic ailment of the neurological structure in humans initiated by the larval stage of the tapeworm Taenia solium. The location of the cysticercus affects the pathogenesis, natural history, clinical symptoms, and therapy. For instance, the primary clinical signs and symptoms differ depending on the type of disease. Seizures or headaches are generally the first symptoms of parenchymal NCC. Leishmaniasis is brought on by parasites of the genus Leishmania in the Trypanosomatidae family which is among the most neglected tropical infectious diseases. Over 20 different Leishmania protozoa types can cause the complex vector-borne disorder leishmaniasis, which has a variety of clinical presentations ranging from localised skin ulcers (cutaneous leishmaniasis) to a systemic illness that can be fatal if left untreated (visceral leishmaniasis). There is not a single effective Leishmaniasis treatment available now for all species and symptoms. Furthermore, the present therapeutic approaches frequently do not lead to a parasitological cure and recurrence in the context of immunodeficiency (i.e., HIV) is an emerging area that needs further research. So, this review is a discussion of a combination of all aspects related to Leishmaniasis, and how to use old treatment methods such as monotherapy along with modern strategies to combat this major health issue all over the world.

The skin is a multifaceted organ with varied functions, but its exposure to various environmental conditions, including exposure to ultraviolet light, trauma, and infections, makes it more prone to ulcers. Ageing, poor lifestyle, and certain diseases, like obesity, hypertension, diabetes, etc., further exaggerate the cause. Skin ulcers are wounds (sores) often caused by reduced blood flow leading to absolute loss of the epidermal layer along with parts of the dermis or subcutaneous fat, and thus have tremendously slow healing affinity. Buruli ulcer (BU), or Bairnsdale is a type of necrotizing skin ulcer mainly caused by the bacterium, Mycobacterium ulcerans, and characterized initially by the formation of papules or nodules (edematous lesions), which further progresses to chronic skin ulceration as a result of epidermal hyperplasia, collagen destruction, and vascular damage in the underlying dermis and subcutis. It is considered one of the 20 neglected diseases of the skin by the World Health Organization (WHO). Although scattered in more than 33 countries, its prevalence is the highest in West Africa and this incidence has risen manifold during the last few years, which might be due to deforestation, artificial topographic alterations, and increased manual agriculture. Mycolactone, a polyketide-based immunosuppressive macrolide, is considered the major factor responsible for the pathogenesis of the disease. Its high toxicity dampens the immune system, causing extensive tissue destruction mainly in skin cells and minute blood vessels, leading to ulceration and skin loss. Generally, a combination of rifampicin with streptomycin, amikacin, clarithromycin, or ciprofloxacin along with oral prednisolone for eight weeks is specified as a first-line treatment. Surgery to remove necrotic tissue, BCG vaccination for short-term protection, and physiotherapy to promote healing are also found beneficial. To combat this deadly disease, enhanced public education and awareness through outreach initiatives is a must as prevention is always considered better than cure. Further studies in this area may be helpful in investigating more treatment regimens along with various ways by which the occurrence of Buruli ulcer can be avoided. The present study is therefore designed to compile all relevant literature, which can serve as an important lead for further investigations in this area of research.

As a result of persistent follicular conjunctivitis brought on by Chlamydia trachomatis and consequent corneal scarring, about 6 million people have irreparable blindness. Chlamydia trachomatis is a bacterium that causes trachoma, an eye infection. Early signs include eyelid itchiness and irritation, whereas advanced signs include swollen eyelids, pus oozing from the eyes, photophobia (light sensitivity), discomfort in the eye, and vision issues. Using the SAFE strategy, the WHO is driving an international campaign to eradicate Blinding Trachoma. Trichiasis surgery, antibiotic treatment for infection, hygiene promotion on the face, and environmental changes to improve air quality are all part of this. The best antibacterial medication for widespread distribution is oral azithromycin.

Food-borne trematodiases are among the neglected tropical diseases caused due to liver flukes (Clonorchissinensis, Fasciolagigantica, Opisthorchis vivernii), lung flukes (Paragonimus spp.) and intestinal parasitic flukes (Echinostoma spp.) infections and is an emerging public health problem. They are mostly found in developing countries and in areas where they are present, they aggravate poverty. However, they are no longer being neglected because of their broad geographical distribution, a wide range of infected people, and measures available to control several neglected tropical diseases. WHO estimates that every year two million people are suffering from disability and death due to these neglected diseases. The treatment of food-borne trematodiases, a neglected disease, is important for preventing the progression of clinical diseases and reducing the associated morbidity. In the present chapter, we will discuss the food-borne trematodes’ life cycle, associated symptoms, diagnosis and various strategies used in treating food-borne trematodiases. Currently used chemotherapeutic drugs, their safety, therapeutic profile, and resistance developed are summarized here. Furthermore, emphasis is given to developing a broad-spectrum trematocidal drug with high safety and efficacy.