London Cholera Outbreak & Disease Investigation

• The study notes cover the London Cholera Outbreak, infectious agents, outbreak investigations, West Nile virus, globalization, vector-borne diseases, food and waterborne illnesses, influenza, tuberculosis, SARS, vaccine-preventable diseases, polio, measles, and historical outbreaks.

Cholera & Investigation of John Snow

• The 19th-century London Cholera Outbreak involves key figures like William Farr, who quantified mortality data and collected water source data, initially a miasmatist but later convinced of cholera's cause.
• John Snow conducted a grand experiment in 1853 involving the Lambeth waterworks company and the Southwark and Vauxhall water company, which caused cholera outbreaks.
• Snow counted cholera deaths per house in relation to the water company used.
• In the 1854 Soho London Outbreak, the Broad Street pump was central, its removal led to a case decline, possibly due to the disease already declining.
• Henry Whitehead's investigations led to an index case at 40 Broad Street, initially believing in miasma before accepting Snow's theory.
• Vibrio cholerae is the source of cholera, cholera toxin is coded by bacteriophage and infected drinking water sources, with dumping sewers into the Thames River identified as a risk.
• Initially, cholera was believed to be transmitted through miasma until John Snow proved it spread via contaminated water.
• Cholera is now caused by ingesting water or food contaminated with Vibrio cholerae, often from human feces.
• John Snow mapped cholera cases around the Broad Street pump, revealing clusters, and statistically analyzed cholera rates among people using different water sources, proving higher infection rates from the Broad Street pump.
• Removing the Broad Street pump handle ended the outbreak, supporting Snow's hypothesis.
• The dominant 19th-century theory was miasma, cholera spread by "bad air" from decomposing matter.
• Cholera is primarily transmitted through contaminated water or food.

Biology & Epidemiology of Infectious Agents

• Viruses cannot reproduce outside a host cell and a virion refers infectious viral particle.
• A virion consists of a core with a genome and proteins, a capsid that protects its contents, and sometimes a lipid membrane.
• Viruses undergo mutation, RNA mutates faster than DNA, creating quasispecies, and viral replication includes attachment, entry, uncoating, replication, assembly, and release.
• Tropism is where the initial infection site may not be the final site of pathogenic damage, being either localized (rhinoviruses) or systemic (varicella, measles, polio).
• Bacteria contain cytoplasm, ribosomes, a nucleoid, a plasma membrane, and a cell wall but gram-negative bacteria have lipopolysaccharide producing endotoxin during cell lysis which causes fever, changes in WBC count, hypotension, and shock.
• Exotoxin is secreted by bacteria, damaging the host through disrupted cell metabolism, exemplified by cholera toxin.
• Bacteria can develop antibiotic resistance through mutations or horizontal gene transfer, conjugation which transfers a plasmid, transformation uptakes free DNA, and transduction mediates transfer of DNA.
• Plasmids provide an ecological advantage and examples of bacterial infections include tetanus, diphtheria, cholera, and scarlet fever.
• Parasites live on or in a host and protozoa are unicellular while metazoa are multicellular organisms.
• Endoparasites live within another organism, ectoparasites live on another organism.
• A host is an organism in which a parasite lives, definitive hosts harbor adult parasites, and intermediate hosts harbor parasites in the larval stage.
• Obligatory describes the paratenic host that provides temporary refuge.
• Natural hosts and accidental hosts do not get infected with the parasite.
• Stopping any stages of the life cycle stops the spread of the parasite.
• Vertical transmission modes include via the placenta (HIV, rubella, HBV) and neonatally (HIV, HSV, HBV), as well as postnatally (HIV, HBV).
• Horizontal transmission modes include direct physical or sexual contact as well as through indirect contact via vectors, vehicles (food, water, fomites, iatrogenic), or airborne droplets.
• Respiratory transmission affects viruses (measles, flu, varicella), bacteria (TB, meningitis), and fungi (aspergillus).
• Common vehicle spread from fecal-oral routes includes viruses (Hep-A, polio), bacteria (cholera, E. coli), and protozoa (giardia lamblia) or through biological products like blood or zoonoses.
• Zoonoses (diseases spread from animal to human) happens through animal bites, blood-borne transmission and vector-borne transmissions.
• Vector-borne transmission include mosquitoes (zika, malaria, fever), flies (African sleeping sickness), fleas (plague) and ticks Lyme's disease.
• Reservoirs are living organisms that carry the pathogen, harboring it chronically with little to no illness.
• Human reservoirs include Hep B and C, typhoid, polio, and HIV
• Animal reservoirs include Flu, plague, rabies and E. coli.
• Environmental reservoirs (plants, soil, and water) include histoplasmosis or legionnaire's disease.
• The SIR model of infectious disease transmission includes susceptibles, infectives, and removals.
• An epidemic starts if an infective enters a susceptible population only if susceptible density exceeds a threshold.
• Epidemics end when population density is below a threshold and the population consists of susceptibles w/o disease and removals that are immune.
• Herd immunity involves reducing a certain amount of susceptibles through mass vaccination.
• A disease can be unlikely to spread through an immune population.
• The basic reproduction number measures the number of secondary cases a single individual causes in a fully susceptible population.
• Ro>1 causes a disease and can be epidemic, Ro<1 causes a disease and can die out and Ro=1 means the disease will continue to persist endemically.
• Effective Reproduction Number (Rt) is the actual rate, and the critical vaccination threshold is the population proportion needing vaccination to induce herd immunity.

Steps of Outbreak Investigations Surveillance

• An outbreak investigation requires establishing the outbreak's existence while verifying its cause.
• Steps include forming case definitions, finding cases systematically, taking immediate control measures, developing hypotheses, comparing lab studies, implementing control measures, initiating surveillance, and communicating findings.
• Epidemic curves graphically show outbreak cases by illness onset date, illustrating spread patterns and incubation periods.
• Common source outbreaks are due to intermittent (irregular peaks from exposure), continuous (gradual rise in cases), or point source exposures from a relatively brief exposure period.
• Propagated outbreaks spread person to person and last longer.
• Syndromic surveillance finds cases based on clinical signs and symptom groups rather than lab testing, which may be non-specific but timely.
• Passive surveillance relies on healthcare providers or labs reporting diseases, active surveillance involves health departments requesting information, and indicator-based surveillance targets specific diseases or risk exposures.
• Investigating the 1999 West Nile Outbreak from NY city required reporting cases to NYCDOH and constructing working case definitions including fever, altered mental status, and muscle weakness.
• Hospitals were asked to report cases passively via fax while active case finding included weekly phone calls to obtain CS and serum samples.
• A press conference was held about spray and protective measures, a live action drill was canceled and testing was done to confirm the hypothesis, but labs could not identify WNV.
• Findings showed WNV to be like SLE, with new surveillance based on diagnosis and communication to report the WNV outbreak in NYC.
• West Nile virus is transmitted through mosquito vectors from horses (dead-end hosts), birds (amplifier hosts), and humans (dead-end hosts) and can be prevented through measures such as insect repellent, long clothing, limiting outdoor time, screens, eliminating standing water, and mosquito control programs.

Globalization and Infectious Diseases

• Globalization involves trades, transactions, capital movements, migration and knowledge spread and deforestation can change the land and increase malaria cases.
• Urbanization causes cholera outbreaks, agricultural intensification causes Nipah virus, irrigation and water can cause cholera, and increased travel can cause SARS or plague which is the Silk Road.
• Higher CO2 can increase Hantavirus, war and disasters disrupt transportation, increasing infectious disease outbreaks through contaminated resources or contact with disease vectors.
• Deforestation increased chances of contact with vectors, leading to mosquito-borne cases.
• Climate change affects vector activity.
• Plague is caused by Yersinia pestis is zoonotic spreads from rodents to humans by flea bites.
• Bubonic plague causes fever, headache, chills, swollen lymph nodes which leads to a 50% fatality.
• Septicemic plague causes bacteria in the bloodstream causes fever, headache, chills, weakness 100% fatality.
• Pneumonic plague causes pneumonia, respiratory failure 100% fatality.
• Plague is disseminated via the Silk Road historically.
• Nipah outbreaks are patterns similar to historical ones, originated in Malaysia due to the high intensity of agricultural areas because it transforms agricultural systems from low energy ones to higher energy ones and land sparing.
• Intensive argirculture comes with cons such as water and environmental stresses, and mixing habitants.
• mixing habitats intorduces reservoirs of disease to new hosts because bats carry the virus and infect pigs.
• symptoms such as headache, fever, drowsiness, and death occurred in farmers and people who worked with slaughtering pigs because there was an overlap of mango production and where pigs were raised.
• Hanta virus is an agent → Deer Mouse (vector) → Human (Host) & Environment.
• Climate change and rainfall led to an increase of deer mice that spread the disease.
• Cholera was due to a natural disaster and earthquake in Haiti because of sanitation problems and the Haiti outbreak in 2010 was traced to the UN.
• Urbanization leads to several overcrowded slums with poor building quality, poor roads, sanitation and access to water.
• A group of individuals living under the same roof in an urban area lack one or more of the following durable housing, sufficient living space, easy access to water, adequate sanitation, and security for tenants.
• More density leads to outbreaks of diseases such as mosquitoes that spread Zika and dengue.

HIV

• HIV-1 biology affects the disease's epidemiology, it targets CD4+ T lymphocytes, monocytes/macrophages, and dendritic cells, integrating into the host genome.
• HIV-1 mutates rapidly creating diversity complicating vaccine development and influencing the copies of a virus affecting an area.
• HIV-1 originated from SIV in chimpanzees in southeast Cameroon leading to a spillover in 1884-1924, and urbanization, trade colonial trade routes and unsafe practices caused the spread.
• In the US, AIDS came from the gay community and in Africa, it became widespread because heterosexuals were spreading it.
• The first cases in the US was identified to be from Dr. Michael Gottlieb when five gay men showed signs of PCP.
• The first cases in Africa were found in Kinshasa.
• In Malawi, a strain was spread from a person from outside who had infected three people at Karonga.
• A major reason that HIV exploded in sub-Saharan Africa was because early deaths meant other disease-related factors were low for concern.
• Short-sighted laws such as banning needle exchanges let to to increase of HIV amongst IV users.

Vector-borne Diseases

• Malaria is transmitted through the bite of Anopheles mosquitoes and parasites including Plasmodium falciparum, P. vivax, P. malariae, and P. ovale.

• Malaria symptoms include headache, fever, fatigue, pain, spleen enlargement, chills, dry cough, and vomiting, and impairs cognitive function.

• Severe malaria can cause anemia or cerebral malaria.

• Yellow fever is transmitted by Aedes aegypti which causes flu-like symptoms, and serious disease with jaundice, hemorrhagic symptoms and is dangerous.

• Dengue is transmitted via infected mosquitoes, infections include DENV 1 - 4.

• There re outbreaks every year in areas such as Mexico. South America, Africa, India, SE Asia, W Pacific and the US.

• Current malaria rank in 2019 include 19th deaths and 11 in DALYs were caused.

• Malaria prevention includes repellent, standing water elimination and insecticide.

• Early yellow fever breakouts occurred in Philadelphia

Hemorrhagic Fever Diseases

• Lassa Agent is spread through Arenaviruses zoonic and is a person-to-person transmission because it can be contracted from excretion of infected bodily fluids.
• Marburg is agent is Filoviruses and transmission is from animals, including cave-dwelling ones.
• Ebola Agent is Filoviruses and transmission is zoonic through bats.
• West Africa had an outbreak of Lassa where the nurse from Nigeria initially contracted it in 1968.
• In 1967, there was a large outbreak of Marburg in Marburg, Germany.
• First Ebola outbreaks were in 1976 in Zaire and Sudan using syringes in the Yambuku Hospital causing mass infection.

Vaccine Preventable Diseases

• The immune system provides general resistance through skin, mucous, tears, and gastric acid, while immunity involves specific antibody reactions and vaccines.
• Active immunity happens when the body produces its own resistance, either naturally or artificially acquired, while passive immunity involves receiving antibodies from another person or animal, either naturally or artificially.
• Adaptive immune responses target specific antigens, providing protection with memory.
• Lymphocytes, including B cells for antibody-mediated immunity and T cells for cell-mediated immunity, play a role in the process.
• Live attenuated vaccines provide protective immunity with less adjuvant but there is a higher chance of infection when the vaccine is made.
• Inactive vaccines provide protection and there is less risk of infection from the shot.
• An infectious disease with specific traits are needed to eradicate the disease.
• Extinction is when a disease agent is eradicated.
• Smallpox attempts protect had been recorded as early at 7-17 days.
• Boston in 1721 had a deadly outbreak of an illness coming from England.
• Edward Jenner in 1719 first used smallpox fluid pustule to inoculate a young boy and in the modern age, cases are surveyed with a goal of total eradication.
• Measles have great chance of being eradicated because they only infect humans but it is deadly without precautions and it is prevalent in other world countries increasing chances of spread.
• Polio was around as early as 1403 BC, however, it was not until 1954 that a solution was around the corner but there are still outbreaks to this day and it is hard to to implement a full cure because of a bad vaccine in circulation.