Lecture 22 2024 PDF

Key Questions What is smallpox? ▪ How were/are vaccine development strategies developed? How was the virus eradicated? ▪ How did smallpox eradication shape Global Health perspectives? Eradication is Permanent Rinderpest (animal viral infection; eradicated through improved hygiene, quarantine, slaugh...

Key Questions What is smallpox? ▪ How were/are vaccine development strategies developed? How was the virus eradicated? ▪ How did smallpox eradication shape Global Health perspectives? Eradication is Permanent Rinderpest (animal viral infection; eradicated through improved hygiene, quarantine, slaughter, and vaccination) Smallpox (only eradicated human disease): - Serious, contagious, and sometimes fatal infectious disease - Transmission occurs through airborne respiratory droplet secretions or direct contact with lesions Smallpox Symptoms Starts with unspecific symptoms (like common cold), but within a few days a widespread rash would develop ▪ After a few weeks pustules would form over body (including inside mouth), eventually crusting over and falling off (scars would remain for life, could also cause blindness) ▪ Mortality rate of ~30% for more virulent disease strain, no effective treatment Smallpox Disease which virtually everyone eventually acquired ▪ Around for ~3000 years; eradicated by 1980 ▪ Edward Jenner created the the smallpox vaccine in 1796, and was the first successful vaccine to be developed ▪ One of the most “notable and profound public health successes in history” (WHO Historically endemic in Africa, Europe, and Asia; brought to the Americas by colonists (with devastating effects) ▪ Estimated to have killed hundreds of millions of people (at least) in course of human history Historic Smallpox Distribution ▪ The origin of smallpox is unknown ▪ Smallpox-like rashes on Egyptian mummies suggests existence for at least 3,000 years ▪ Earliest written description of a disease like smallpox appeared in China in 4th century CE (Common Era), in India in the 7th century, & in Asia Minor in the 10th century (present day Turkey) What is a Vaccine? Substance used to stimulate the production of antibodies and provide immunity against one or several diseases ▪ Prepared from the causative agent of a disease, its products, or a synthetic substitute ▪ Acts as an antigen without inducing the disease Vaccines Take advantage of the immune system’s ability to recognize and remember pathogens (adaptive immunity) ▪ Basic idea: introduce a safe version of the pathogen (or a piece of the pathogen) to teach the immune system how to recognize it in the future ▪ This ensures that future exposure to the pathogen results in a rapid and effective immune response, protects from developing the full-blown disease Trial and Error First contemporary vaccine attributed to Edward Jenner in 1796 for smallpox Observed milkmaids less likely to get smallpox, hypothesized because exposed to cowpox Injected James Phipps with cowpox pus, waited for him to become infected, then injected him with smallpox (very unethical)… no disease Making Vaccines Then and Now Historically, vaccine testing continued to be very unethical (often administered to institutionalized, vulnerable individuals) Today (ethical regulations and consent): ▪ Discovery phase ▪ Pre-clinical phase – tested on animals ▪ Clinical trials –people enroll in https://www.who.int/news-room/spotlight/history-of-vaccination/a-briefhistory-of-vaccination Vaccine Limitations Hard to develop vaccines for: ▪ Diseases that don’t affect high-income countries or many people ▪ Pathogens that mutate rapidly ▪ Large, complex pathogens (e.g., multicellular parasites) ▪ Pathogens with multiple life stages and hosts (e.g., malaria) ▪ Novel or poorly studied pathogens (don’t know what to target Factors Facilitating Smallpox Eradication 1) The virus is human-specific, no non-human reservoirs 2) Disease symptoms (e.g., rash and pustules) clearly visible and recognizable (no need for a lab test) 3) Effective vaccine available (heat stable and offered protection for 5-10 years) 4) Other regions had successfully eliminated the virus, demonstrating that it was possible 5) Also, there was political will and financial backing to support eradication efforts WHO Eradication Campaign ▪ Thought to be impossible given the number of people infected, limited vaccine supply, and difficulty of reaching remote populations ▪ Involved high levels of international cooperation: ▪ Hundreds of individuals… from WHO leadership, to young health workers willing travel to millions of household bringing vaccines, to community partners ▪ Also important: bifurcated needle (required less vaccine and was simpler to use) Basic Eradication Process In each affected country: 1) Vaccinate at least 80% of the population (in hopes of achieving herd immunity) 2) Establish effective surveillance network, to quickly identify novel smallpox cases and contain disease spread (e.g., ring vaccination) - “vaccinates the contacts of confirmed smallpox patients…vaccinates people who are in close contact with those contacts. This way, everyone who has been, or could have been, exposed to a patient with smallpox receives the vaccine” (CDC) 3) Regularly distribute surveillance reports, tracking progress and novel containment strategies Last Smallpox Cases 1975: Last known case of more virulent viral strain (3-year- old in Bangladesh; isolated until no longer infectious) ▪ 1977: Last known case of less virulent strain (Ali Maow Maalin, a hospital worker in Somalia who guided two young smallpox patients and their families to the hospital)… he made a full recovery, last known person naturally infected with smallpox ▪ 1978: English medical photographer exposed to smallpox as a result of exposure to lab specimens in the hospital where she worked, she sadly died (last known person to have died from the virus) ▪ After additional surveillance, the WHO declared smallpox to be eradicated in 1980 Does Smallpox Still Exist? ▪ There are currently two WHO-designated labs with stocks of variola virus: the CDC in the US and the Russian State Centre for Research on Virology and Biotechnology ▪ Fear that specimens (or other undocumented samples) could somehow be used in future bioterrorism, since people aren’t routinely vaccinated for smallpox anymore ▪ Researchers argue smallpox research is needed to find better ways to treat the disease, make safer vaccines, and improve diagnostic tests