Gregory Petrossian

B.S. BioResource Research and

B.A. International Studies

Internship Abroad in India 2009

Analyze the differences in infectious disease burden between developed and developing world

Highlight the burden of Neglected Tropical Diseases (NTDs)

Examine ways to spur drug development for NTDs

Compare strategies of disease elimination between developed and developing worlds

“It is time to close the book on

infectious diseases and pay more

attention to chronic ailments such as

cancer and heart disease” - Surgeon General William H. Stewart,

late 1960s

• In response to smallpox, polio, and rheumatic

fever tamed by vaccines or antibiotics

The epidemiological transition • Progress in healthcare between 19th and 20th century

• Significant advances leading to dramatic declines in

death rates due to infectious diseases Sanitation & hygiene

Immunizations

Antibiotics

• Vaccines had greatest impact 1977 after a decade-long campaign involving 13 countries

which lead to the eradication of smallpox from the world

Today, pertussis (whooping cough) has made resurgence due to populations choosing NOT to immunize their children due to misinformed stigma

Not as successful as developed world in implementing control strategies • World Health Organization (WHO) describes

immunization coverage as “challenging due to high population growth rates, limited infrastructure and resources, and fluctuating demand for services”.

Estimated mortality from infectious diseases accounts for >25% of deaths worldwide and over 40% of deaths in developing countries

Slower progress in life expectancy and

control of infectious disease

• Socioeconomic discrepancy of population growth

and limited resources

Estimated if “under the age of five” mortality rate in

poorest 80% of the population of the developing world

was reduced to that of the richest 20%

= global mortality would be reduced by 40%

theoretically

WHO describes three confounding factors to progress • 1) failure to use existing tools effectively Lack of education, incomplete treatment regimens, broad

spectrum antibiotics, and repeated trial-and-error prescriptions

• 2) inadequate or non-existent diagnostic tools Diagnoses primarily made without diagnostics to save time

and money

• 3) insufficient knowledge of diseases Little to no attention to disease awareness programs

Subset of infectious diseases called Neglected Tropical Diseases (NTDs) plague developing world • 1-3) helminth infections (ascariasis, hookworm, and whipworm) • 4) lymphatic filariasis (elephantiasis)

• 5) onchocerciasis (river blindness) • 6) dracunculiasis (guinea worm disease) • 7) schistosomiasis (gut parasite from snail - Trematodes)

• 8) Chagas disease (parasite from bite of insect - Trypanosoma cruzi) • 9) human African trypanosomiasis (sleeping sickness)

• 10) leishmaniasis • 11) Buruli ulcer • 12) leprosy

• 13) trachoma (bacterial infection of eye)

“Neglected” = lack of attention to diseases of the developing world due to the focus on tackling HIV/AIDS, tuberculosis, and malaria

Top ten leading causes of healthy life lost to long-term disability and premature deaths worldwide are due to NTDs

Sub-Saharan Africa bears the largest burden of many NTDs with over 90% of the world’s burden

NTDs have severe consequences on population • long-term illness, disfigurement, social stigma, immuno-

suppresion, and decreased productivity • Leprosy = stigma and disfigurement • Leishmaniasis and Tuberculosis = long-term illness even

with treatment

• affect worker productivity households and firms must adapt their productive activities in

response

• coping strategies can lead to low savings and investment, lost capital and purchasing power, and inefficient labor substitution

Treatments lacking for NTDs because they do not offer sufficient financial returns for the pharmaceutical industry to engage in R&D

NTDs represent 11.4% global burden • Only 1% of the 1393 new chemical entities marked

between 1975 and 1999 were registered for these diseases

Innovation gap for novel antibiotics is evident in the dramatically reduced number of new antibiotic approvals by the United States Federal Drug Administration (FDA) over the past two decades • Termed “antibiotic drought”

New paradigm for drug development • Public-private partnerships (PPPs) attempt to

meet the needs of developing countries

through establishing public-private

collaborations, networks, and partnerships

• intricately structured to shift the industrial

strategy from maximizing profits to

establishing equitable pricing policy

worldwide

Maintaining low cost for NTD control imperative

Low cost determined by 4 factors: • Commitment of pharmaceutical companies to

provide subsidized medicines

• Scale of the programs

• Potential for synergizing delivery methods

• Volunteer contribution of communities for distribution

Highest burden of three major NTDs • Leprosy, lymphatic filariasis, and leishmaniasis

• Several factors make eliminating these NTDs an

attainable goal by the WHO

• WHO working with partners such as The World

Bank and Special Programme for Research and

Training in Tropical Diseases

Observational medical internship for 10 weeks

visiting 6 different cities in Northern India

Focused on communicable diseases

Also observed traditional medicine

Saw first hand the devastation caused by NTDs

Immersed in the culture

Leprosy

• Caused by bacterium Mycobacterium leprae • Not very contagious with long incubation time • Symptoms: skin sores, nerve damage, and muscle

weakness

• Control • 67% of cases detected globally in 2008 in this region

• Multidrug therapy to treat and cure reservoir

• Free global supply provided by partnership with Novartis

• Cured 12.8 million cases of 15 million reported in 2010

Leishmaniasis • Parasitic disease spread by bite of female sandfly • Symptoms include: skin sores, breathing difficulty, ulcers, and

erosion in mouth, tongue, gums, lips, and inner nose • Death happens within two years

Control • Use of rapid dipstick diagnostic screening rK39

• Drugs available (antimony-containing compounds)

• Sandfly vector control by indoor residual spraying

• Pilot exercises in 11 districts of India expanded to all 52 endemic districts by 2010

H1N1 pandemic response by United States

First emerged in Mexico in April 2009 and rapidly spread in following months

Mass vaccination most effective and utilized method • Quaranting and antiviral agents slow spread

Currently, more than 20 manufacturers in various

stages of vaccine • Effective vaccine was ready by September 2009

U.S., surveillance at federal and state level

• U.S. departments CDC, NTSB, NIH • Swift response and control

Developing World

• Requires partnerships

and outside funding

• Distribution relies on

volunteer work

• Countries must work

with limited

infrastructure

• Slow response,

delayed control

Developed World

• Funding within

privatized

pharmaceutical

industry

• Distribution centers

and hospitals

• Advanced surveillance

infrastructure

• Fast response,

effective control

Shifted focus from infectious diseases in the developed world may allow vulnerabilities for emerging infectious diseases due to globalization promoted by ease of travel and climate change

Necessity for new drug development targets and new strategies for equitable pharmaceutical distribution on a world-wide scale

Fostering the same progress previously experienced by the developed world in the developing world could relegate the overwhelming burden of infectious diseases to something of the past

Subsurface Biosphere Initiative (SBI) summer undergraduate internship

Intervet/Schering Plough Animal Health

Dr. Kerry McPhail

Nick Fleury

Dr. Mark Zabriskie

OREGON STATE UNIVERSITY