-World Population

-How many in developing countries?

-How many die each year?

-6.5 billion

-5.5 billion

-60 million

Cardiovascular

Cancer

HIV

Lower resp tract infect

Diarrhoeal dx

Malaria

Measles

Variola virus

Transmitted by close personal contact (droplets)

Variola major (most common); 30% mortality

Variola minor (less common); 1% mortality

Smallpox:

• Incubation period
• Symptoms
• Can lead to more serious complication such as:

• ~2 weeks
• Fever, aches, vomiting, rash (with scaring)
• Pneumonia and encephalitis

• Particles that infect cells of biological organisms
• Cannot reproduce on their own and therefore hijack cellular mechanisms of the host to reproduce
• Consist of a genome (RNA or DNA) and a protective coat (capsid)

10 diseases spread through droplet

(cough/sneeze)

1. Bacterial meningitis
2. Chickenpox/shingles: VZV/HHV3
3. Common col (rhinovirus/coronavirus/picornavirus)
4. Influenza
5. Mumps
6. Streptococcal throat
7. TB
8. Measles (paramyxovirus)
9. Rubella
10. Whooping cough

1. Cholera
2. Hep A
3. Polio
4. Rotavirus
5. Salmonella

1. HIV
2. Chlamydia
3. Genital warts
4. Gonorrhoea
5. Hep B
6. Syphilis

1. Athletes foot
2. Impetigo (Staph. aureus)

1. HIV
2. Syphilis
3. Hep B

Kaposi Sarcoma cause

Retrovirus

Reverse Transcriptase

• TB
• Certain fungal infections (eg, severe candida, PCP)
• Certain viral infections (eg, CMV, herpes simplex)
• Toxoplasma (a parasite)
• Certain cancers, which are themselves caused by other underlying infection

1. Avoid high risk sexual behaviour
2. Make testing more available
3. Condoms
4. Vaginal microbicides
5. Management of STDs
6. Circumcision

1. Introduction of blood donor and product screening
2. Promotion and distribution of condoms at affordable prices
3. Peer education for high risk groups (eg, sex workers)
4. Promotion of safer sexual behaviour at the population level
5. Diagnosis and tx of STDs
6. HIV voluntary counselling and testing

1. Home-based care for people with AIDS
2. Opportunistic infection prophylaxis (eg, Cotrimoxazole) or TB prophylaxis
3. Prevention of mother-to-child HIV txmission
4. ART tx for immunocompromised adults (CD4<200) and children

ART during pregnancy

Delivery by C-section

Formula feeding (where possible)

Screening of blood banks

Needle exchange

Post-exposure prophylaxis

• Economics: healthcare dollars per annum per capita
• Priorities: Academic analyses of cost-effectiveness may not reflect developing world realities
• Setting: Political openness towards HIV (good in Uganda and Senegal)

1. Prevention of new infections is the key to long term control of the pandemic 
2. Tx of people w/AIDS and low CD4 counts also prevents some new cases
3. Development of prophylactic vaccines & vaginal microbicides

1. HIV-1 is a retrovirus with inherent error-prone transcription; ie, very high mutation rates and multiple immune escape mechanisms; large amount of sub-types and recombinants
2. Although a small number of monoclonal antibodies exhibiting broad cross-clade neutralisation have been described, no immunogens have been able to induce such neutralising antibodies
3. For vaccine to be effective against HIV-1, it would need to induce neutralising antibodies, as well as CD8 and CD4-T cells responses

1. Condoms prevent HIV, but are under the control of men
2. For many women, esp. in the developing world, current prevention options offer little control or protection
3. A new female-controlled effective HIV prevention method would be invaluable

• How do microbicides work?
• Requirements for microbicide (3)
• Delivery options for microbicides

• Act by blocking the mechanism of cellular infection or by killing the virus pre-infection
• Must be safe; absorption should be minimal; amount of drug needed to kill or block virus must be less than that which kills/inflames body cells
• Gels, films, pessaries, rings

1. Anti-retroviral drugs
2. Combination of drugs that inhibit the action of reverse transcriptase
3. Reduce viral replication and viral load, thereby reducing infectivity

1. Must be acceptable, locale specific, and sustainable
2. Quality assured HIV testing, CD4 count enumeration, and ART, as well as healthcare infrastructure and continuous drug supplies need to be permanently established

• Based on analysis of 1300 chimpanzee faecal samples, infection is likely to have originated in wild chimps in SE Cameroon (Sanga river)
• Based on fixed mutation rates of the virus, the jump to humans probably happened between 1920-1950, via butchering and consumption of bushmeat

• Epidemic is still spreading
• Drug resistance is a growing problem
• No vaccine is available
• Control programmes are patchy

1. Africa still struggles against debt, trade restrictions, and inadequate aid provision, with little G8 alleviation
2. 3 by 5 missed its target, ~1.2 million of tx by end of 2005, the big players (SA, India, etc) are not delivering, but the principle is established
3. The Global Fund is under-resourced, with estimated funding gaps of $900 million for 2006 rising to $2.1 billion by end-2007
4. Long term commitments to AIDS funding by G8 would be ideal solution

• Providing ART to those who need it is necessary now and will continue to be so for the forseeable future as the millions of prevalent infections progress to clinical dx.  However, such ART will bring its own complications including drug side-effects and the generation and onward txmission of drug resistant strains
• We must, therefore, continue to work ceaslessly on vaccines, microbicides, and other new preventative technologies

• TB known as:
• Lymphatic spread
• Skin lesions
• Abdominal spread
• Spine
• Joints
• Disseminated

• Consumption and Phthisis
• Scrofula
• Lupus vulagaris
• Tabes mesenterica
• Pott's dx
• Gibbus
• Military TB

• Mycobacterium tuberculosis
• In immunosuppressed people:
• M. bovis
• M. africanum
• M. microti

Transmission of TB

• Spread how
• Can infect how many people a year
• At risk populations?

• Spread in droplets (cough, sneeze, speak, kiss, spit)
• Someone with chronic active TB may infect 10-15 people per year
• "At risk" populations include those from areas where TB is common, health-care workers, drug users, and immunosuppressed people

1. Mycobacterium reaches pulmonary alveoli
2. Replicates within alveolar macrophages
3. Bacteria enters dendritic cells (not replicating) and travels to lymph nodes
4. Enters bld and spread to organs of the body
5. Infected macrophages become surrounded by T & B lymphocytes and fibroblasts (forming a "granuloma," limiting dissemination)
6. Granulomas can become necrotic in the centre 

__/__ world population has been exposed to TB

1 new infection per ___ worldwide

Most infections are _____

__/__ progress to active TB

Of those, __% die (_____ people annually)

1/3 (~2 billion people)

Second

latent (non-infectious

1/10

50 (1.6-2 million people)

• In 2004, there were ___ cases chronic-active TB
• ___ new cases
• ___ deaths
• __% resistant to 1st-line tx
• __% resistant to 2nd-line tx
• Highest incidence in ___
• Largest number of cases in ____

• 14.6 million
• 9 million
• 1.6 million
• 20%
• 2%
• 780 cases per 100k people
• 1.8 million

In 2004, UK TB incidence ranged from __ to ___

5/100k in rural areas

40/100k in London

1. HIV/immunosuppression
2. Smoking (4-fold excess risk)
3. Diabetes

• Bacteria is slow, therefore difficult to diagnose by culturing infected samples
• Active lung infection can be diagnosed by staining bacteria in sputum sample
• Latent infection diagnosed in a non-immunised person with skin test leading to hypersensitivity to TB-derived proteins (NO USE IF VACCINATED)

• 4 antibiotics for 2 months (Isoniazid, rifampicin, pyrazinamide, and ethambutol) then
• 2 antibiotics for 4 months (Isoniazid and rifampicin)

MDR-TB

• Highest rates in:
• Associated with:
• Can develop during ___ due to___

• Baltic states, Argentina, India, and China
• Associated with poor or failing TB control programmes (also seen in NY in the '90s)
• Can develop during the tx of sensitive TB due to non-compliance

XDR-TB

• Epidemic in ___
• First report
• How many cases/year estimated in 2008
• Most frequent where
• In US, __% of MDR met criteria for XDR
• In Latvia, __% of MDR met criteria...

• KwaZulu-Natal in South Africa recently
• First report of 52/53 cases, all died within 16 days of sputum collection; all in previously untreated people; most were HIV infected as well
• 40,000 cases (WHO)
• Former Soviet Union and parts of Asia; found in all regions of the world
• 4%
• 19%

BCG vaccine trial in UK

• __% effective
• First trial
• 1966 US trial in Alabama showed __% efficacy
• 1979 trial in South India showed __ effect
• Duration of protection?
• Most effective in preventing ___

• 60-80% effective; elsewhere-no effect
• First trial was conducted in 1956-1963 in school children (84% efficacy after 5 years)
• 16%
• no effect
• Unclear
• Military TB or TB meningitis (especially in infants); effect on pulmonary TB less clear

1. Background prevalence of TB
2. Background prevalence of non-tuberculous mycobacterium
3. Interference of other parasites
4. Genetic variation (host or bacterial)

Worldwide BCG vaccine programmes

• US
• UK
• India

• None
• Universal vaccination 1953-2005
• Universal vaccination since 1948

Derived from the Greek

Pan = all

demos = people

1. Emergence of new (or variant dx)
2. The dx is infectious to humans and causes severe illness
3. The agent spreads easily and sustainably in human population

Typhus caused by

Where is this endemic?  How spreads to humans

Rickettsia

Mice and rats; spread to humans via mites, fleas, and lice

Typhus has a ___ vector

Dx also known as 

Arthropod vector that flourishes in unhygienic conditions

"Camp fever" or "Jail fever"

Typhus symptoms

Treatable with

Vaccine available?

Typhus controls what populations?

High fever and delirium

Antibiotics

Vaccine available

Controls rats and mice populations

Antonine Plague

• Historical accounts written by ___
• Probably describing 

• Greek physician Galen in 165-180
• Smallpox or measles
• He describes the plague as "great" and of long duration and mentions fever, diarrhea, and inflammation of the pharynx, as well as a skin eruption, sometimes dry and sometimes pustular, appearing on the ninth day of the illness. 

Plague of Justinian

• Named after whom
• Spreads from __ to __ then __
• Cut the european population by ___
• Probably ___

• Byzantine emperor Justinian I
• Spread from Egypt to Constantinople and then in waves across Europe
• 50%
• Bubonic Plague

• 430 BC - Peloponnesian War (Typhoid fever killing 1/4 of Athenians)
• 165-180 Antonine Plague (Smallpox? Killed >5million)
• 541-570 Plague of Justinian (Bubonic plague)

Vibrio Cholera

• Type of bacteria
• Secretes __
• Causes __
• Fatality?
• Patients require what
• Spread via __
• Easily controlled by __ and __
• Most recent outbreaks in __

• Gram negative
• Enterotoxin
• Extreme diarrhoea
• Rapidly fata - can cause hypotension within 1 hour of symptom onset and death within 3 hours (more usually, death occurs in 18-20 hrs)
• Urgent rehydration
• Contaminated water
• Good sanitation and water tx
• Afghanistan, Iraq, Zimbabwe

• Sodium 75 mmol/L
• Glucose 75 mmol/L
• Potassium 20 mmol/L
• Chloride 65 mmol/L
• Citrate 10 mmol/L

• CAFFEINE: diuretic effect
• HIGH SUGAR DRINKS: hypertonicity has a diuretic effect

Buboes (necrotic lymph nodes), purpura (subepidermal haemorrhages), and acral necrosis (gangrene of the extremities)

Can turn to pneumonic plague

Total number of deaths from bubonic plague

Deaths in europe

How many separate epidemics?

75 million

20-30 million (1/3 to 2/3 of the population)

At least 100

Yersinia pestis

• Bacteria description
• Normally a disease of
• Human infecction occurs
• Human infection takes the form of (3)
• Treated how
• Vaccine?

• Gram negative, anaerobic bacterium
• Dx of rodents and fleas
• When bitten by an infected flea (that was carried by an infected rat)
• Pneumonia, septicemia, bubonic plagues
• Combination of antibiotics
• Vaccine of limited use was withdrawn by FDA due to side-effect profile

Xenopsylla cheopis

• How bacteria works

• Bacteria multiplies in the flea, forming a plug blocking the stomach
• It starts to starve, and so bites voraciously
• After feeding, it vomits bacteria into the wound, infecting the rat
• Rodent deaths often precede a human epidemic
• if an infected flea bites a human, it can cause infection

Xenopsylla Cheopis

• Pathology

• Infection travels from the wound to lymph nodes
• Causes haemorrhagic inflammation of lymph nodes (causing a 'bubo')
• Can lead to septicaemia (if untreated, always fatal)
• If the lungs are infected, it can cause "pneumonic plague" (with this comes the possibility of human-to-human txmission)
• Bacteria secretes several toxins, including one that causes beta-andrenergic blockage

SARS

• Caused by
• Caused "near pandemic" when
• How many cases identified
• How many died
• Symptoms (what are they) occur when

• Corona virus (RNA virus)
• 2003-4
• 8096
• 774 (~10%)
• SOB (eventually resp. dx), malaise, myalgia, and fever occur 3 days post-infection

• Probably started in Guangdon Province, China in Nov. 2002
• Picked up by the "Global Public Health Intelligence Network" (WHO)
• Became prominent when an American became sick on a flight from China (died)
• Cases occured in Toronto, Vancouver, SF, Ulan Bator, Maila, Singapore, Hanoi, Taiwan, HK, and several other Chinese provinces

Influenza

• Caused by
• Transmitted by
• Kills how many?
• Mini-epidemics occur ___ and affect ___

• Virus
• Droplets; very infectious
• 250k-500k people annually
• Every year, 5-15% of the pop.

Influenza virus

• Virus description
• Causes what
• People are infectious ___ before symptoms
• Txmission via ____
• Annual epidemics arise because ___

• RNA virus
• Generalised illness and pneumonia
• 1-2 weeks p/infection a/symptoms
• Droplets
• virus constantly changes so that the immune system is faced w/a slightly new version every year

Cause of Malaria

Transmitted how?

• protozoan parasite
• Txmitted by female Anopheles mosquito

Vaccine for malaria?

Treatment?

• No vaccine available
• Can be treated with derivatives of quinine or artemisinin

• First effective tx was the bark of the cinchona tree (contains quinine)
• Used by locals to control malaria
• Jesuits introduced it to Europe in the 1640s

• Bld stage of malaria was recognised in the 19th and early 20th century
• Latent form of the dx (in the liver) was recognised in the 1980s
• Explained why "cured" people could have recurrent episodes years later, in the absence of new exposure

Epidemiology of malaria

• Cases of fever/year
• Affects __ per year
• Kills __ per year
• Most death occur in ___ where
• One death every ___
• __% of world population "at risk"

MOST CASES RURAL

• 400-900 million cases of fever annually
• 515 million people/year
• 1-3 million/year (85-90% in s-Saharan Africa)
• Most deaths occur in children <5 in sub-Saharan Africa (preggers also vulnerable)
• 30 seconds
• 40%

• Fever, shivering, arthralgia, vomiting, anaemia
• If severe: convulsions, coma, and death; cerebral ischaemia, hepatomegaly, and renal failure
• Cyclical coldness, followed by rigor, then fever
• Splenomegaly
• Children can display neurological symptoms
• Symptoms occur 6-14 days p//infection
• Long term can cause cognitive impairment in children

(P.=plasmodium)

P. falciparum

P. malariae

P. ovale

P. vivax

• Female Anopheles mosquitoes (only female feeds on bld)
• Inject parasite from infected human blood whilst feeding
• Carry sporozoites in salivary gland

Because it hides in rbcs or in the liver. 

Circulating rbcs can be destroyed in the spleen

Parasite infected cells stick to the bld vessel wall (to avoid spleen) - can cause strokes in cerebral malaria.

• Most reliable and cheap method of dx-ing involves microscopy of a blood specimen
• Thick film - very sensitive at detecting malaria (lrg vol of blood)
• Thin film allows for species identification
• Antigen detection in bld is also used (but expensive)
• Dx is often made based on symptoms

• Emergency and requires hospitalisation
• Can be cured using drugs
• Most drugs are based on quinine or artemisin (derived from the plant Artemisia annua)
• Many drugs can be used for prophylaxis and at higher doses for tx
• Resistance is a problem (as is counterfeit drugs)

1. Prophylatic drugs
2. Mosquito eradication
3. Prevention of mosquito bites

1. Drainage of standing water (but ag. irrigation is becoming more common)
2. Widespread use of pesticides (DDT was the most effective)
3. Local use of insecticides in the home

1. Appropriate clothing
2. Insect repellent
3. Bed nets (most bites occur at dusk and through the night; nets more effective if treated with insecticide)

• In hyperendemic areas, dx found in Black, Asian, and European children and less commonly in children with Sickle dx
• Not at altitudes >300 mils 1000 miles south of the equator nor at altitudes >5000 at the equator
• Not when average temp <60F
• Not when annual precipitation <20 inches
• Most where faliciparum malaria is holoendemic
• Not in malarious areas when anti-malarial interventions in place

• Herpes-like virus first seen within lymphoid cells from Uganda children
• 9% of malignant BL tumours in tropical regions since shown to contain EBV
• EBV virus also found in pts with non-malignant dx (glandular fever) in the west
• In temperate zones: EBV in adolesence
• In Africa: EBV very early in life, often before one year old

• Use of insecticides in the home
• Use of bed nets (80% reduction in risk)

1. Identification of cases
2. Isolation
3. Treatment
4. Understand transmission and intervene in the lifecycle of the pathogen
5. Vaccination (primary prevention)

Sabin - live, attenuated virus, oral

Salk - inactivated virus, injected

Since 1979, there have been 8 cases/year contracted b/c of the vaccine.  Salk vaccine has thus been reintroduced, even though it's harder to use

1. Most vaccines elicit formation of neutralising antibodies rather than provoking cell-mediated immunity
2. This is fine for diseases caused by toxins, extracellular bacteria, and viruses that pass through blood to reach the tissue or origin (polio, rabies)
3. Many infections, including parasites, are intracellular and so out of reach of antibodies (malaria)

1. Immunisation slips leading to explosive epidemics (e.g., 1996 polio epidemics in Greece and Albania)
2. Air travel and immigration facilitate txport of infections from one continent to another
3. Increased drug resistance
4. Emergence of new pathogens

1. HIV
2. Pneumonia
3. TB
4. Diarrhoeal dxs
5. Malaria
6. Measles

Pneumonia

• Killer of children?
• __% of deaths occur in developing countries
• Who is effected most?

• Kills more children than any other infectious dx
• 99% of the deaths from pneumonia occur in developing countries
• Affects children of low birth weights or those with immune systems damaged by malnutrition or other conditions

Diarrhoea

• More than ___ deaths annually
• Dx leads to __
• __ bouts of illness a year in children alone
• Burden is highest in areas ___
• What affects both adults and children; which affect mainly children

• More than 2 million deaths annually
• Leads to rapid fluid loss and death
• 1.5 billion bouts of illness a year in children alone
• Burden is highest in areas with poor sanitation
• Cholera and dysentery affects both adults and children; typhoid and rotavirus mainly affect children

Malaria

• Kills __ annually
• Over __ cases globally each year
• __/__ of all childhood deaths in sub-Saharan Africa
• Symptoms
• Detail economic cost

• Kills 1-2 million people annually
• Over 275 million cases globally each year
• 1/5 of all childhood deaths in sub-Saharan Africa
• High fever, convulsions, breathing difficulties, and death
• In Nigeria, amongst subsistence farmers, 1/3 of all income is used to pay for malaria tx

Measles

• Contagious?
• How many deaths in 1998
• Responsible for child deaths? 
• Dx effects if not death

• Most contagious human dx
• 900,000 deaths in 1998
• Responsible for more child deaths than any other microbe
• Also causes blindness, deafness, brain/lung damage, and stunted growth and development

Lymphatic filariasis

• Cause of long-term disability?
• What causes
• Affects how many people; how many are at risk; how many are severely disabled
• Causes what

• Second only to mental illness as the leading cause of long-term disability
• Mosquito-borne parasitic worm
• Affects about 120 million people; a billion are at risk; >40 million are severely disabled
• Causes gross enlargement of the limbs and genitals in addition to damage to internal organs

Schistosomiasis

• What causes
• Causes what
• __ people infected; ___x that at risk
• Spread by what

• Schistomoa (parasitic worm)
• Causes chronic UT dx and can lead to cirrhosis of the liver and cancer
• 200 million people infected; 3x that at risk
• Spread by water snails

• ·      Fresh water becomes contaminated by Schistosoma eggs when infected people urinate or defecate in the water; the eggs hatch if certain types of snails are present in the water; these parasites grow/develop in the snail; after the parasite leaves, it can survive for about 48 hours; can enter the skin of people wading, swimming, bathing, etc in contaminated water