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MICR3001

Microbes and Human Health

 

1997 Exam

 

(In 1997 this was called MY364 Microbes in Medicine and Public Health)

 

1.      Write about the mechanisms by which TWO (2) of the following bacteria exert their pathogenic effect AND discuss the implications for vaccination.

(a)     Haemophilus influenzae

(b)     Vibrio cholerae

(c)     Mycobacterium tuberculosis

 


(a)     Pathogenesis of Haemophilus influenzae:

Gram-negative rods/coccobacillus.

Common secondary invader in lower respiratory tract.

6 types of Haemophilus influenzae, a – f.

H. influenzae is distinguished by its capsule polysaccharides.

Unencapsulated strains of H. influenzae are common in the throat of most healthy people.

Capsulated type B is a common inhabitant of the respiratory tract of infants and young children.

Type B is most frequently found.

Occasionally it invades the blood and reaches the meninges.

Maternal antibodies protect the child for 3-4 weeks.

As the maternal antibodies wane, there is a window of susceptibility until the child produces their own antibody at about 2-3 years of age.

Anticapsular antibodies of H. influenzae are good opsonins which allow the bacteria to be phagocytosed and killed.

There is an effective Hib vaccine suitable for children under 6 months.

Close contacts of patients are given rifampicin prophylaxis.

The polysaccharide capsule of Hib is an established example of a subcellular fraction vaccine.  It is important to remove all live infectious material to ensure the safety of the vaccine.

Diseases H. influenzae causes are:

meningitis          }

all more common in young children

osteomyelitis     }

epiglottitis         }

otitis                 }

Non-capsulate strains cause acute exacerbations of chronic bronchitis.

Transmitted from person to person via airborne route.

No known exotoxin.

Outer membrane and endotoxin may play a part.

Polysaccharide capsule is the important virulence factor.

 


(b)     Pathogenesis of Vibrio cholerae

Curved gram-negative rod

Disease: cholera.

V. parahaemolytica causes diarrhoea, and other species cause wound infection.

Transmission

Human pathogen with no animal reservoir.

‘El Tor’ biotype survives better in inanimate environment than classical V. cholerae.

Infection usually from contaminated water and sometimes from contaminated food.

Pathogenesis

V. cholerae has several virulence factors:

motility

mucinase

adherins

and ENTEROTOXIN

 

Chromosomally encoded subunit toxin produced after V. cholerae binds to the enterocytes.

Toxin enters enterocytes and binds to ganglioside receptors.

Activates adenylyl cyclase, causes fluid loss and massive watery diarrhoea.

Treatment

Fluid and electrolyte replacement (oral rehydration therapy).

Tetracycline shortens symptoms and carrier time.

Prevention depends on clean chlorinated water supply and adequate sewage disposal.

A whole-cell vaccine is available for V. cholerae but is of limited use.  New vaccines are under development.

 


(c)     Mycobacterium tuberculosis

Rods, gram positive cell wall structure but stain with difficulty because of long chain fatty acids in cell wall (mycolic acids).  Acid-fast.  Ziehl-Nielsen stain.

Disease: M. tuberculosis causes tuberculosis in humans and animals.

Range of conditions, usually in immunocompromised hosts.

M. avium - intracellular – important association with AIDS patients.

M. tuberculosis transmission:

Droplet spread

Aided by ability to survive in the environment.

Transmission to humans from cattle via milk was common.

Social and environmental factors and genetic disposition all have a role.

Pathogenesis

Intracellular parasites living within macrophages.

Slowly developing chronic condition.

Much pathology is attributable to the host’s immune response rather than to the bacterial toxicity.

Treatment

Prolonged treatment with combinations of antimycobacterial drugs.

Prevention

BCG vaccination valuable for prevention in people who are not environmentally exposed to heavy loads of mycobacteria early in life.

Isoniazid prophylaxis for contacts of TB cases.

Pasteurisation of mild and improved living conditions important in prevention.

 


2.      Answer TWO (2) of the following questions:

(a)     Discuss the molecular basis of antigenic shift and drift in influenza viruses.  How do these impact on the pattern of infection in both local and global communities?  What vaccination strategies can be employed to address the resulting antigenic variation?

(b)     The pathogenic consequences of a viral infection may be the result of either direct or indirect damage to cellular and/or tissue function.  Within this framework, and using specific examples, discuss the different mechanisms known to contribute to disease outcome.

(c)     Latency is a feature of herpes virus infections.  What do you understand by the term latency and what are its consequences?  Discuss the distinguishing features of the latent state amongst the different herpes viruses.

 


(a)     Influenza virus – orthomyxovirus, ss RNA.

Antigenic shift

Occurs less commonly and only with Influenza A.

It means that there is recombination between different virus strains infecting the same cell.

It results in a major shift change in the antigenicity of the H or N antigens.

Pattern of the infection

The change means that the new strain can spread through populations that were immune to pre-existing strains, and possibly cause a pandemic.

-        there are 13 types of H and 9 types of N, mostly occurring in birds, makes 117 possible strains.

-        71 combinations have been found so far, in birds, especially ducks, chickens and turkeys.

-        3 only so far in humans.  Only some of the combinations are successful in humans: A, B and C.

The internal ribonucleoprotein (RNP) is a group-specific antigen that distinguishes Influenza A, B and C.

Influenza A viruses: causes epidemics and pandemics in humans.  Also occurs in animals: birds, pigs, dogs, seals, other mammals.

Influenza B viruses: only cause epidemics in humans.  Does not occur in animals.

Influenza C viruses: do not cause epidemics, only minor respiratory illnesses.

Antigenic drift

is where there are relatively minor changes in the antigenic structure of a virus strain, probably resulting from natural selection of virus variants circulating among an immune or partly immune population.

Small mutations affecting the H and N antigens occur constantly with all types of influenza.

Sometimes these changes enable the virus to multiply significantly in individuals with immunity to9 preceding strains so that the new subtype can reinfect the community.

The influenza virus has no defined shape and is polymorphic as it buds from a cell.

Spikes on the outside of its envelope interact with the host cell surface.

One spike is haemagglutinin – it agglutinates red blood cells, because they have sialic acid on their membrane surface, the same as the mucous membranes of the respiratory tract which the virus targets.

Vaccines: antibodies against haemagglutinin – neutralise the virus.

The second spike is neuraminidase.

Pattern of infection:

SHIFT – got Influenza A from animals to humans.

DRIFT – got A →B→C, each successively better adapted to its human host.

Vaccines

Influenza does not induce good long-lasting immunity even after healthy people recover from infection.  This is because of shift and drift, but also responses to different strains are dominated by the antibody against the strain first encountered.

A range of only partially-effective vaccines are in use because of the high mortality rate pending the development of something better.

Most widely used are: killed viral vaccines, including 2 subtypes of A and one of B, and containing the H and N prevalent or anticipated.  These are for high risk groups and are 70% effective at reducing severity and 30% effective at prevention.

Revaccination in subsequent years is required to maintain antibody levels.

A recombinant virus with portions of RNA coding for H and N antigens would be an advantage because it would induce cytotoxic T-cell memory, which doesn’t happen with killed viruses.  Viral antigens trapped in ISCOMs can also induce good cytotoxic T-cell responses.

 


(b)

Hepatitis

The virus is spread via the blood, eg contaminated needles by sexual routes from mother to child.

It spreads via blood to the liver and replicates in hepatocytes.

Indirect:

The immune complex formation can cause the initial rash and arthritis.

Hepatitis is largely due to immune destruction of infected liver cells.

Persistent infection is common and blood can remain infectious for life.

Massive doses of alpha and beta interferon can terminate carrier status.

Chronic hepatitis can lead to cirrhosis and liver cancer.

 

Rabies

Transmitted by bite of infected animal.  Not usually transmitted human to human but may be present in saliva.

Direct:

Virus replicates at site of bite, and ascends axons to CNS, where it spreads.

It descends peripheral nerves to skin and salivary glands.

 

Post-exposure prophylaxis by washing wound and giving vaccine, but there are neurological sequelae.

 

(c)     Latency is a quiescent period which follows an active period in an infectious disease, where the pathogen remains dormant for a variable length of time before again initiating signs of active disease.  There are no symptoms.

The genetic material of the virus may:

i)       exist in the host cytoplasm (herpes viruses)

ii)      be incorporated into the genome (retroviruses)

Replication does not take place until some signal triggers a release from latency.

Consequences

Host defences are designed to control microbial growth and spread and to eliminate the microbe from the body.

Persistent infections can be regarded as  failure of host defences.

Cells may continue to release virus particles at a slow rate and the infected person may act as a carrier.

Different types of herpes viruses

HSV-1: causes cold sores.  Latency sites in sensory ganglia.  Reactivation causes cold sores.  Axonal travel to latency sites.

HSV-2: causes genital herpes.  Same as above.

HHV-3: VZV. Latency sites in sensory ganglia.  Reactivation causes shingles (zoster).  Axonal travel to latency sites.

HHV-4: EBV.  Latency in B cells.  Subclinical reactivation.

HHV-5: CMV. Latency in mononuclear cells.  Reactivation.

HHV-6}: Mild febrile illness.

HHV-7}

HHV-8: Kaposi’s sarcoma.

 


3.      Describe and discuss:

(a)     the environmental factors which pertain to epidemic activity of mosquito-borne arboviruses.

 


Arboviruses:

·              toga         -           alphaviruses

                                    flaviviruses

         bunya      -           mosquitos, ticks or s’flies.

Cause encephalitis.

Eastern equine encephalitis

Alphavirus.

Aedes spp.  mosquito.

USA (Atlantic Gulf states).

Wild birds, horses, dead-end hosts.

50% fatal.

Western equine encephalitis

Alphavirus.

Culex spp. mosquito.

USA (west of Mississippi).

Wild birds, horses, dead-end hosts.

2% fatal.

St Louis encephalitis

Flavivirus.

Culex spp. mosquito.

USA (Southern, Central, Western states).

Wild birds.

10% fatal.

Californian encephalitis

Bunyavirus.

Aedes spp. mosquito.

USA (Northern and Central).

Small mammals.

Fatalities rare.

Japanese encephalitis

Flavivirus.

Culex spp. mosquito.

Far East and South East Asia.

Birds and pigs.

8% fatal.

Murray Valley encephalitis.

Flavivirus.

Culex spp.

Australian birds.

70% fatal.

Venezuelan encephalitis

Alphavirus.

Mosquito.

Southern USA, Central and South America.

Rodents.

Rare, but 70% fatal.

 

Arboviruses are major causes of fever in endemic areas of the world.

 

Cause fevers and haemorrhagic disease

Yellow fever

(Alphavirus)

Africa, Central and South America.

Aedes spp.

Dengue

(Flavivirus)

India, SEA, Pacific, S. America, Caribbean.

Mosquito.

Ross River virus

(Alphavirus)

Australia, Pacific Islands.

Mosquito.

Rift Valley fever

(Bunyavirus)

Africa.

Mosquito.

La Crosse fever

(Bunyavirus)

USA.

Mosquito.

 

Arthropods: includes -  6-legged insects

                                    8-legged arachnids

 

Environmental factors

In sparsely populated areas, transmission by insects is an effective means of spread.

The parasite has to be present in the right place at the right time (eg, some insects only bite at night).

 

The conditions found in the vector are likely to be very different from the conditions found in the host, and the parasite may have to make a transition in a short time.

Some insect vectors have lifespans hardly longer than their parasite.

A difference of a few days in a mosquito’s lifespan can make an enormous difference in the effectiveness of malaria transmission.

This explains the endemic infection in Africa and the sporadic epidemics in India.

The disease may be controlled by controlling the vector.

Trying to eradicate malaria by DDT spraying of breeding areas led to the mosquitoes developing resistance and more damage was done to the environment than to the insects.

Vector control is highly desirable and is the only reason malaria is not endemic in Northern Europe.

Control of arthropod vectors (insecticides and attention to breeding sites) and reduced exposure (insect repellent, mosquito nets) are important.

Control of malaria is best effected by eliminating Anopheles.  2 approaches:

i)       elimination of habitat.  Drainages of swamps and breeding areas.

ii)      elimination of mosquito by insecticides and treating patients with Primaquine to break life cycle.

 


(b)     The role of rodents in viral diseases

 


The ability of arthropods to transmit infections acquired from animals poses a constant threat of zoonoses to humans.

Arboviruses → dengue

                        yellow fever

                        encephali tides

                        haemorrhagic fevers

 

With regard to arboviruses that can cause encephalitis, rodents do not act as the vector for human infection, but as the vertebrate reservoir for:

Venezuelan encephalitis (human vector is mosquito)

Powassan                     (human vector is tick).

 

In the case of arboviruses than can cause fevers and haemorrhagic diseases, rodents do not act as the vector, but are the animal reservoir for:

Kyasanur forest virus    (vector is tick)

Congo-Crimean haemorrhagic fever (vector is tick)

Colorado tick fever       (vector is tick)

La Cross                      (vector is mosquito).

 


(c)     The transmission and control of viral diseases in developing countries.

 


Sexually transmitted diseases which produce long-lasting infections are ideally suited to persisting in low-density human communities.

In developing countries, the average age at infection is typically much lower than in the UK or USA.

The fraction of the total population susceptible to infection is:

 

         L – M     =          (Life expectancy)                      – (Average duration of maternal antibody derived protection)

         A – M                 (Average age at infection)         – (Average duration of maternal antibody derived protection)

 

For an infection (except an STD) to take hold, the density of susceptible people must exceed a critical value.

In  mass vaccination programs, to eradicate the infection, the density of susceptibles must be reduced below:

   1    =                        1                      x Average duration of infection.

BD                   transmission coefficient

 

In a directly transmitted respiratory infection,

Ro                                =          β                                  x          D

The rate of infection                  transmission coefficient              average duration of infectiousness

 

For the infection to take hold,

Ro                                          1

The rate of infection

 

Density of susceptible people    >          XT

                                                >          1/βD

 

Behavioural factors are of particular importance for STDs like gonorrhoea and AIDS.

Those who have many sexual partners are more likely to acquire and transmit infection and are important in the persistence of infections.

Different patterns of population mixing are important in designing policies to control infection: spatial, behavioural or demographic studies.

Developed countries

High rates of transmission among children at primary and secondary schools who seed infection by family contacts.

High levels of vaccination coverage in developed countries but still pockets of infection in poor communities in major urban centres with low rates of vaccine uptake.

Effective target:             - children before primary school.

                                    - young children in poor urban centres.

Average age at vaccination must be less than average age of infection for eradication.

 

Developing countries

2-stage vaccination program can be effective.   Infants around 1 year (to reduce transmission efficacy) and young children at 2 or 3 (to block transmission).

 

Vaccination success is influenced by population density particularly in developing countries.

Small villages in rural areas, population density and assoc. net birth rate too low for endemic maintenance of infections.

At risk of contact from large urban centres.

 

If urban centres have mass vaccination, this can block transmission since they are the reservoir of infection for low density rural regions.

Average incubation of HIV/AIDS may be less in developing countries where continuous exposure to a wider range of infections may speed the development of a severe immunodeficiency.

 


4.      Answer, with examples where necessary, TWO (2) of the following:

(a)     Cholera has scourged mankind for centuries yet is included in the current list of “emerging infectious diseases”.  Discuss briefly the reasons for the recent upsurge and changing epidemiological patterns of this disease.

 


Vibrio cholerae, Gram-negative rod.

See Mims pp260-262, 522.

V. cholerae is a human pathogen with no known animal reservoir.

An emerging infection is an infectious disease whose incidence has increased in the past 20 years, or whose incidence threatens to increase in the near future.  An emerging infection is a disease that suddenly becomes prevalent.  It is not limited to ‘new’ diseases.

A re-emergent infection is an infectious disease thought to be under control that produces a new epidemic, eg when antibiotics become less effective or public health systems fail.

Cholera is a human pathogen with no known animal reservoir (although “El Tor” biotype survives better in the inanimate environment than classical V. cholerae.

 

How

Infection is transmitted through contaminated water (usually) or sometimes fish.

What

Several virulence factors:

-           motility

-           mucinase

-           adhesins

-           enterotoxin

Vibrio cholerae binds to enterocytes, binds to ganglioside receptors.  Activates adenylyl cyclase, causes fluid loss.

 

The number of Vibrio cholerae necessary to produce infection is greater if individual is malnourished, or if Vibrio cholerae is ingested with food, because the food neutralises the stomach acid that would otherwise destroy the pathogen.

 

Recent upsurge of cholera due to breakdown in public health measures.

Cholera can be adequately controlled, even in endemic areas, by proper sanitation, especially for water sources.

Outbreak in Peru 1991, 4000 dead.

 

 Cholera is eliminated from sewage during proper sewage treatment but is now endemic on the Gulf Coast of the USA although with low incidence.

 


4. (b) Salmonellosis is a major cause of foodborne disease which remains uncontrolled in industrial countries.

.        Draw a diagram showing the major reservoirs of salmonellae and the routes of transmission of the bacterium from the farm to the consumer.

.        Make a list of the major reasons why salmonellosis remains uncontrolled.

 


Salmonella – Gram negative rod.

Salmonella typhi – humans only.

All other Salmonellae in animals.

 

Infection acquired:

-        by ingestion of contaminated food: poultry, eggs, meat, milk, cream;

-        or by faecal-oral route.

S. typhi by contaminated water or food.  Carriers important source.

Salmonellae are the most common cause of food-associated diarrhoea in developed countries (in some places Salmonellae are second to Campylobacter).

Animal feed

 

 


Wild animals                                                     Domestic food animals              Human food                 Man

 

 


                                                                                    Effluent                         Sewage

 

 

Salmonella        stomach            small intestine                Peyer’s patches in jejunum or distal ileum          intestinal lymph nodes

            macrophages.

Transported to mesenteric lymph nodes             thoracic duct        bloodstream.

Circulate and seed many organs: spleen, liver, kidney, gallbladder, bone marrow.

 

Why is it difficult to control?

-        People can carry the infection for months or years and provide a continuing source from which others are infected.

-        It survives and multiplies in macrophages.

-        Resistant to bile so survives in gallbladder and biliary tract.

-        Many antibiotics are successful in vitro but not in vivo because they do not reach the bacteria in their intracellular location.

 

Good personal hygiene, adequate sewage disposal and a clean water supply important.

Antibiotic resistance more important in many countries with implications for travellers.

 


4. (c) Describe the prevention and control measures which can be applied in reducing the incidence of Leptospirosis and Q fever within industry and the community.

 


Leptospirosis

Rodents are the natural hosts of most leptospiras – the disease is a zoonosis.

Dogs and pigs are carriers of some strains.

Weil’s disease is a severe form of leptospirosis.

Infection is via infected urine – through abraded skin and conjunctiva.

Contact is often through occupation (sewer workers, farmers, abattoir workers) or recreation (canoeing and windsurfing).

 

Proper urine disposal important.

Therapy requires extended courses to eliminate leptospira from the kidney.

Vaccinate domestic animals eg dogs with a killed virulent strain (distemper-leptospira-hepatis vaccine).

Elimination of disease from animals is the main human prevention.

*          Rodent control

*          Protective clothing

*          Prophylactic penicillin after cuts and abrasions for sewer and abattoir workers.

 

Q fever

Coxiella burnetii

Q fever is caused by rickettsias.

Can be detected by ELISAs.

Pneumonia-like infection.

Obligate intracellular parasite.

Not transmitted directly by insect bite - the agent is transmitted to animals by insect bites.

Arthropods are reservoirs of infection.

Domestic animals with inapparent infections can shed large quantities in urine, faeces, milk and body fluids.

Control – tetracycline in suspected human cases to prevent heart damage from endocarditis; erythromycin.

            - insect repellent

            - ethanol to remove ticks better.

            - pasteurise milk.

Animals involved can include sheep, goats, cattle.  There is no arthropod vector.

 

Coxiella burnetii is resistant to desiccation, heat and sunlight.

Stable enough to be acquired by the airborne route.

The lung is the main site so there is usually no rash.

Vets can catch it as well as farmers and abattoir workers.

Mims pp 357, 370-371.

 

 


4. (d) Discuss the continuing evolution of the worldwide HIV pandemic and give at least 5 examples of the changing nature of the pandemic.

 


Continuing evolution

Many drugs lose antiviral potency with time due to emergence of drug-resistant viruses.

Because of pre-existing host damage and destruction of CD4-T-lymphocytes, AIDS patients cannot mount resistance to infections, and acquire opportunistic pathogens, eg. Kaposi’s sarcoma (HHV-8).

There is loss of humoral and cellular immunity.

Public education and avoidance of high risk behaviour are the major tools.

 

Changing nature

1.      HIV-2 is a related virus to HIV-1 that causes a very mild form of AIDS with a very long latent period.  The virus is adapting better to its new host.

2.      The risk of contracting HIV from contaminated blood or blood products is now very low.

         Sexual promiscuity and group intravenous drug use are the major routes of infection today.

3.      1970s – HIV spread rapidly following socioeconomic upheavals and migrations from Central to East Africa.  Female prostitutes and mobile male soldiers.

         Spread to Haiti, USA, Europe and Australasia.

         1980s – explosive spread of HIV from heterosexual transmission.  High infection rates in female sexworkers and intravenous drug users.

4.      Next stop China.

5.      Incidence of new infections in females now equals males.

         9 of 25 million infected so far are female.

         5-10 million children will be orphaned.