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Drug Discovery and Development in Addressing Public Health Threats and…
Drug Discovery and Development in Addressing Public Health Threats and Targets
Neglected Tropical Diseases (NTDs)
Group of diseases that occur under tropical and subtropical climate conditions and are intimately linked to poverty
Affect some of the world's poorest and marginalized communities, predominantly in Africa, Asia and the Americas
NTDs cause important local burdens of disease, but individually none of them represents a global priority in terms of numbers of people affected or DALYs lost
Control Principles and Methods
Control can be directed to any part of the communicable disease framework and is sometimes necessary to use several control strategies
Control vs Eradication
Vaccination
Artificial infection to administer antigenic substances produced by the disease organisms in a vaccine without the host developing the disease
Does not always result to immunity due to
Poor administration
No longer potent
Host did not develop an immune response
Vaccination ~/ immunization
WHO vaccine trial tracker
environmental control
many diseases result from contamination of the environment by fecal matter with transmission by the direct rout or via food
personal and domestic hygiene
proper food preparation, cooking and storage
use of water supply
proper disposal of excreta and waste
Personal and Domestic Hygiene
Personal hygiene is closely related to the availability of water in sufficient quantity
Washing is improved by using warm water and soap (reduces and surface tension and emulsifies oils allowing bacteria to be more easily removed)
Protection of Foods
Food-transmitted infections can spread either through contamination or by specific intermediate host
Protection of food we eat can be by the following
Inspection of raw produce
Packaging and avoiding contamination
Suitable storage conditions and time-limits
Washing and correct preparation
Adequate and even cooking
Preventing contamination of cooked foods
Eating cooked foods immediately
Water Supply
Water is important in diseases for poor hygiene as a medium for intermediate hosts and as a breeding place for vectors of disease
Four aspects (or process) of water supply
Improve water quantity
Improve water quality
Reduce water contact by bringing water to site of use
Prevent spillage by proper maintenance of supplies and drainage
Sanitation
To reduce the source of contamination
Provision: water supply not qual to sanitary defecation practice
Contamination: pit latrines
Wash
Wash, Sanitation and Hygiene services
Over 700 children under age 5 die every day of diarrheal diseases due to lack of appropriate WASH services
In 2018, nearly 90 million people in the WPRO did not use a basic drinking-water facility and more than 400 million did not use a basic sanitation facility
Vector Control
Vectors are viral parts of parasite development, it cannot continue growth if the vector is destroyed or reduced to sufficiently low numbers
Examples of vector control methods
Gene drive
Wolbachia
Spatial repellents
Treatment and Mass Drug Administration
Treatment reduces the length of illness and period of communicability of disease, thus aiding in population control
Rapid diagnosis and diagnosis are important to control infection and reduce incidence of mortality
Development of single-dose therapies aid in medication adherence
Mass drug administration can be used for prevention (e.g., doxycycline in rainy season)
London Declaration on NTDs
Pharmaceutical companies, donors, endemic countries and NGOs signed the London Declaration on Neglected Tropical Disease
Committed to control,, eliminate or eradicate 10 diseases by 2020 and improve the lives of over a billion people
Objectives
To eradicate, eliminate or control 10 NTDs by 2020
Eradicating Guinea worm disease by 2020
Eliminating lymphatic filariases, leprosy, sleeping sickness (human African trypanosomiasis) and blinding trachoma by 2020
Controlling schistosomiasis, soil-transmitted helminths, Chagas disease, visceral leishmaniasis, and river blindness (onchocerciasis) by 2020
NTDs SDG
Successful interventions against NTDs can contribute to various other SDGs besides good health and well-being
1 No poverty
2 Zero Hunger
4 Quality Education
5 Gender Equality
8 Decent work and economic growth
10 Reduced inequalities
3 Good health and well-beign
Progress on other SDGs can help achieve the NTD goals
6 Clean water and sanitation
9 Industry, Innovation and Infrastructure
11 Sustainable cities and communities
13 Climate Action
3 Good Health and Well-being
SDGs require strong global partnership
17 Partnership for the goals
3 Good health and well-being
Commitment to Support Fight Against NTDs
Delivery of Interventions and Impact
Strengthening NTD structures and cross-sectoral collaboration
Extension of overall scope and support for NTDs
Creation of strategies, guidelines and resolutions
New interventions, tools and diagnostics
Increase in country ownership and commitment
Viral infections
dengue
dracunculiasis
human african trypanomaniasis
leishmaniasis (visceral)
leprosy
lymphatic filariasis
onchocerciasis
rabies
schistosomanias
soil-transmitted helminthiases
trachoma
Yaws
Problems in Drug Innovation
USD 307 million per million DALYs is used worldwide for non-infectious respiratory diseases, while only USD 3 million per million DALYs was for NTDs in 1999
Between 2000 to 2013, there were three new approvals for NTD drugs, and five products targeting NTDs wre in phase III clinical trials including one for Dengue fever, three for onchocerciasis/schistosomiasis and one for diseases (leishmaniasis, chagas disease and african sleeping sickness)
AMR
a natural phenomenon of pathogen resistance to medicines that is accelerated by the misuse and overuse of existing antimicrobials in humans, animal and plants
There is no direct connection between AMR and virulence
resistant bacteria have increased opportunity to produce disease bu the disease itself is the same
MRSA - mutation in virulence genes, plasmids
Development of new antibacterial treatments is inadequate to address the mounting threat of antimicrobial resistance
Approaches to Drug Innovation
Process
Pull (Currting the cost of R&D
Push Increasing market attractiveness
Neglected NTDs
Tuberculosis
number 1 global infectious
patients with mdr need complex and prolonged multidrug trreatment with costly, highly toxic and much line medicines -> limited
Malaria
in 2017, the WHO estimated that there were 219 million malaria worldwide, an increase of 2 million from the previous year, and as a result the 435k deaths or 1190 per day, mostly young children
Treatment include the use of quinine, chloroquine, primaquine, artemether, lumefantrin, doxycycline, mefloquine and chloroquine
The malaria box (2015) has assembled by MMV in a bid to catalyse malaria and neglected disease drug discovery and research. All of the compounds have confirmed activity against the blood-stage of P. falciparum and are commercially available. It includes:
200 diverse drug-like compounds as starting points for oral drug discovery and development
200 diverse probe-like commpounds for use as biological tools in malaria research
The global pipeline of new medicines for the control and elimination of malaria