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Urinary tract infections (UTIs)
The urinary tract is one of the most common sites of bacterial infection, particularly in
females
...
Severe infections result in a loss of renal
function
...
UTIs may be community acquired or
nosocomially acquired due to catheterization
...
Citrobacter, Klebsiella, Enterobacter, Proteus and
Pseudomonas aeruginosa, are frequently found in hospital acquired UTIs as their resistance
to antibiotics favours their selection in hospital patients
...

Viral causes of UTI appear to be rare, although there are associations with hemorrhagic
cystitis and other renal syndromes
...
the human polyomaviruses JC and BK
...

Very few parasites cause UTIs
...
And
Histoplasma capsulatum, the protozoan Trichomonas vaginales, and infections with
schistosoma haematobium
...
The shorter female urethra is a less
effective deterrent to infection than the male urethra
...
UTIs are common in uncircumcised male infants
...
increased volumes if post-void
residual urine are associated with a greater likelihood of infection
...
Catheterization is a major
predisposing factor for UTI
...
The duration of catheterization is directly associated with increased
probability of infection, due in part to the formation of biofilms
...
Uropathogenic E
...
fimbriae
(pyelonephritis-associated pili), which allows uropathogenic E
...

Clinical features
Acute lower UTIs case dysuria, urgency and frequency
...
The urine is cloudy owing to the
presence of pus cells (pyuria) and bacteria (bacteriuria), and may contain blood
(haematuria)
...
Recurrent infections of the lower UT occur in a significant number of patients
...
Acute bacterial prostatitis causes systemic symptoms (fever) and local symptoms
(perineal and low back pain, dysuria, and frequency)
...
Staphylococci are a common cause and renal abscesses are present
...
Pyuria in the absence of positive urine cultures can
be due to chlamydia or tuberculosis
...

Laboratory diagnosis
Infection can be distinguished from contamination by quantitative culture methods
...
Urine specimens may
become contaminated with periurethral flora during collection
...
Infected urine usually contains a single predominant bacterial
species
...
In urine collected from catheters any number of organisms may be
significant because the specimen is not contaminated by periurethral flora
...
An MSU sample should be
collected into a sterile wide-mouthed container after careful cleansing of the labia or glans,
and after allowing the first part of the urine stream to be voided, as this helps to wash out
contaminants in the lower urethra
...
For
patients with a catheter, a catheter specimen of urine is used for microbiological
examination
...
tuberculosis and schistosoma
haematobium
...
tuberculosis,
the last few milliliters should be collected early afternoon after exercise for detection of
S
...
Microscopic examination of urine allows a rapid preliminary report
...
However, they
are not necessarily indicative of infection, but may indicate that the specimen has been
poorly collected or left at room temperature
...
hematuria may be present in
association with; infection of the UT and elsewhere, renal trauma, calculi, UT carcinomas,
clotting disorders, or thrombocytopenia
...
A laboratory diagnosis of significant bacteriuria requires quantification of
the bacteria
...
Direct
antibiotic susceptibility tests may be initiated upon detection of abnormal numbers of white
blood cells or bacteria on microscopy, so that both culture and susceptibility results are
available within 24h
...
These factors relate to; collection- specimen collection must be
carried out correctly, storage- the urine must be cultured within 1h of collection or held at 4
degrees celsius for no more than 18h before culture, antibiotic treatment- in s patient

receiving antibiotics smaller numbers of organisms may be significant and may represent an
emerging resistant population, fluid intake- the patient may be taking more or less fluid than
usual and this will influence the quantitative result, and the specimen- the quantitative
guidelines are valid for MSU specimens
...

Nitrofurantoin a urinary antiseptic
...
Initial treatment of
complicated UTI (pyelonephritis) usually involved a systemic antibacterial agent
...
the prophylactic use of
antibiotics may also prevent recurrent infections
...

Antibiotic resistance
A resistant organism is one that will not be inhibited or killed by an antibacterial agent at
concentrations of the drug achievable in the body after normal dosage
...
However, within
species that are innately susceptible, there are also strains that develop or acquire
resistance
...
Resistance may arise from; a single chromosomal mutation in one bacterial cell
resulting in the synthesis of n altered protein eg
...
changes in
penicillin binding proteins in penicillin-resistant pneumococci
...
Chromosomal mutations are relatively rare events and generally
provide resistance to a single class of antimicrobials
...
Bacteria are able to acquire resistance genes on transmissible
plasmids, such plasmids often code for resistance determinants to several unrelated families
of antibacterial agents
...
Some plasmids are promiscuous, crossing species barrier and the same
resistance gene is therefore found in widely different species, eg
...
coli and

other enterobacterial and also accounts for penicillin resistance in Neisseria gonorrhoeae
and ampicillin resistance in H
...

Resistance may be acquired from transposons and other mobile elements
...

Multiple resistance genes may be organized into genetic elements called integrons
...
A strong integron
promoter controls transcription of the inserted genes
...
With their ability to capture, organize and rearrange different
antibiotic-resistance genes, integrons represent an important mechanism for the spread of
multiple antibiotic resistance in clinically important microorganisms
...
SCCmec inserts into a unique target site on the staphylococcal chromosome
...
transposons and plasmids
...
alternatively , an additional (more
resistant) target (eg
...

Access to the target site may be altered, decreasing the amount of drug that reaches the
target, either by; altering entry eg
...

Enzymes that modify or destroy the antibacterial agent may be produced-drug inactivation,
eg
...

Use and misuse of antimicrobial agents
Antimicrobial agents should only be used appropriately for prophylaxis or treatment
...

Antibiotic susceptibility tests
Disk diffusion tests involve seeding the organism on an agar plate and applying filter paper
disks containing antibiotics
...
The size of the inhibition zone is an indicator of
susceptibility of the isolate
...

A dilution test provides a quantitative estimate of susceptibility to an antibiotic
...
a test to find the lowest concentration that will inhibit visible growth of
the bacterial oslate in vitro)
...
After overnight incubation,
the MIC is recorded as the highest dilution in which there is no macroscopic growth
...
The concentration on the strip
at which growth is inhibited indicates the MIC
...
An advantage of an MIC test is that it can be extended to
determine the MBC (minimum bacterial concentration), which is the lowest concentration of
an antibiotic required to kill the organism
...
The antibacterial agent is
considered to be bactericidal if the MBC is equal to or not greater than fourfold higher than
the MIC
...
One disadvantage of
MIC and MBC tests is that the result is read at only one point in time
...
Killing curves are more time consuming and expensive than disk
diffusion methods
...
turbidity, electrical impedance) in the presence of an antibacterial their indicator
system
...

Combining antibacterial agents can lead to synergism, their activity is greater than the sum
of the individual activities, or antagonism, the activity of one drug os compromised in the
presence of the other
...

Antimicrobial agents
Antimicrobials are chemicals used to inhibit the growth of or kill a specific microorganism or
group of organisms
...
Antibacterial agents derived from natural sources, eg
...
semi-synthetic, to improve their
antibacterial or pharmacological properties
...

sulphonamides or quinolones
...
This is more
achievable in microorganisms that are prokaryotes than in those that are eukaryotes, as

prokaryotes are structurally more distinct from the host cells
...
Some antibacterial agents are bactericidal (kill
bacteria), others are bacteriostatic (inhibit growth of bacteria)
...
In immunocompromised patients,
bacteriostatic drugs may be less efficacious
...
folic acid metabolism), and cell membrane function
...

Antibacterial agents
Penicillin
Peptidoglycan is a vital component of the bacterial cell wall and is a compound unique to
bacteria, therefore representing s target for selective toxicity
...
Penicillins have a five membered beta-lactam ring
...
carboxypeptidases, transglycosylases and
transpeptidases, capable of binding to penicillin and are responsible for the final stages of
cross-linking of the bacterial cell wall structure
...
Penicillins are active against gram-positive organisms
...
Benzylpenicillin
is excreted rapidly in urine and hence requires frequent doses
...
A common side effect of ampicillin treatment is a mild idiopathic reaction, usually
in the form of a rash
...
Carbenicillin can cause platelet dysfunction and sodium
overload (because it is given as a sodium salt), especially in patients with liver failure, renal
failure, and congestive heart failure
...
Penicillins may be administered
intramuscularly, intravenously or orally
...
Members of the family differ more in their pharmacological properties than in
their spectrum of activity
...
Tetracyclines inhibit
protein synthesis by binding to the small ribosomal subunit in a manner that prevents
aminoacyl transfer RNA from entering the acceptor sites in the ribosome
...
Tetracyclines are administered
orally
...
Tetracyclines are excreted in bile and urine
...
Tetracycline use is restricted
due to widespread resistance
...
staph
...
candida)
...
Example of tetracyclines include; tetracycline, doxycycline, demeclocycline,
minocycline, and tigecycline
...
Trimethoprim prevents THFA
synthesis by inhibiting dihydrofolate reduction
...
Sulfonamides are bacteriostatic compounds
that are structural analogues of and act in competition with para-aminobenzoic acid (PABA),
for the active site of dihydropteroate synthase, an enzyme that catalyses an essential
reaction in the synthetic pathway of tetrahydrofolic acid (THFA), which is required for the
synthesis of purines and pyrimidines and therefore nucleic acid synthesis
...
Trimethoprim Is often given in
combination with sulfamethoxazole as co-trimethoxazole
...
double mutation), and the fact that the two agents act
synergistically against some bacteria
...
Co-trimoxazole
is active against a wide range of urinary tract pathogens and against s
...
Co-trimoxazole
is used in the treatment of pneumonia caused by the fungus pneumocystis jiroveci
...
Co-trimoxazole teearment can
cause neutropenia, nausea and vomiting
...
The problem in developing
new antivirals has been due to the difficulty of interfering with viral activity in the cell without
adversely affecting the host
...

Aciclovir
Acyclovir is used in the treatment of HSV and Varicella-zoster virus (VZV) infections
...
Aciclovir is inactive
until phosphorylated by the herpes simplex virus thymidine kinase to acyclovir
monophosphate, which is then converted by cellular kinases to acyclovir triphosphate, which
inhibits the herpesvirus DNA polymerase
...
The drug is also incorporated into viral
DNA, resulting in chain termination
...
Otherwise,
aciclovir has an excellent safety profile
...
As the oral bioavailability is only 15-20%, aciclovir is given
intravenously
...
AZT is an analogue of the nucleoside thymidine in
which the hydroxyl group on the ribose is replaced by an azido group
...
The azido group prevents the formation of
phosphodiester linkages
...
AZT is given orally
...
AZT is used in the
treatment of HIV
...
Selective toxicity is more difficult to
achieve in the eukaryotic fungal cells than in the prokaryotic bacteria
...

Antifungal resistance is increasing
...
Thus the development of antifungals is a priority
...
The exceptions are
flucytosine and griseofulvin which interfere with DNA synthesis, and caspofungin which
inhibits cell wall formation
...

Azole compounds
Azole antifungals act by inhibiting lanosterol C14-demethylase, an important enzyme in
sterol biosynthesis
...

Itraconazole and fluconazole are used in treatment of a variety of serious fungal infections
...
Newer azole
compounds include posaconazole, which is used in aspergillosis unresponsive to
amphotericin B, and itraconazole, which is used in the treatment of invasive mucormycosis
...
Amphotericin B and nystatin act by binding to
sterols in cell membranes, resulting in leakage of cellular contents and cell death
...

Amphotericin is used in the treatment of serious fungal infections
...
Nystatin is used in topical
formulations
...
Drug resistance is an increasing problem
...

Chloroquine is administered orally and is used in the treatment of P
...
Quinine is administered orally or intravenously and is used as the treatment
against drug resistant p
...
As red blood cells break down they release the haem
group which is toxic
...
Quinine and its derivatives inhibit the parasite haem polymerase
enzyme
...
Quinine is used to treat
severe malaria if artesunate, the drug of choice, is not available, though quinine requires
careful monitoring during treatment to avoid toxicity
...
falciparum to chloroquine and mefloquine
...
PZQ targets intracellular calcium
levels, thus disrupting the outer coat of helminth cells exposing helminth antigens to the host
immune system, additionally the structure of the worm is altered and as calcium levels are
affected so is muscle contraction and so the worm cannot attach to host gut wall and is thus
excreted
...

Malaria is initiated by the bite of an infected female anopheline mosquito
...
falciparum, P
...
ovale, P
...
T
​ he life
cycle of malaria in humans and mosquitoes; in the symptomless pre-erythrocytic stage,
sporozoites from the saliva of an infected anopheles mosquito are injected into the human
bloodstream, when the mosquito bites, they then enter the parenchymal cells of the liver
where they mature in approximately 2 weeks into pre-erythrocytic schizonts, finally rupturing
to produce 10 000 - 40 000 merozoites, these circulate in the blood for a few minutes before
entering the red blood cells to intiate the asexula blood stage, for ​P vivax a
​ nd ​P
...

Trypanosoma spp
...
brucie i​ s transmitted by the tsetse fly and causes human african trypanosomiasis (HAT) or
sleeping sickness
...

T
...
​T
...
Chagas disease has
serious long term effects which include fatal heart disease
...

Borrelia spp
...
C
​ auses lyme disease and is transmitted by ixodes ticks
...
Lyme disease commonly causes additional disease 1
week to 2 years after the initial illness
...

Culex spp
...
C
​ auses west nile encephalitis
...
The vector for human infection is the ​culex spp
...
The
vertebrate reservoir for west nile virus is birds
...

Blood borne infections
Viruses may be transmitted via blood and body fluids
...
Blood borne
viruses may be transmitted through blood transfusions, as such donated blood is screened
for many microorganisms including; herpes B virus, herpes C virus, and CMV
...

Hepatitis B
HBV is a hepadna virus, hepadnavirus are also found in woodchucks, ground squirrels and
peking duck
...
HBV baltimore
classification: group VII
...
Infection with a given strain of HBV confers
resistance to all strains, but antigenic variation occurs
...
HBV type can influence the clinical outcome of infection in response to
antiviral treatment, and are useful in epidemiological studies
...

HBV infection may be asymptomatic or symptomatic with malaise, anorexia, nausea,
abdominal pain and jaundice
...

HBV can be transmitted; via sexual intercourse; vertically from mother to child due to fluid
transmission during birth, blood products and blood contaminated needles, and in healthcare
settings
...
The
prevalence of HBV varies; <2% in western europe and north america, 2-8% in southern
europe and esatern europe, middle east, central and south america, >8% in south-east asia
and sub-saharan africa
...
people with a more
vigorous immune response to infection clear the virus more rapidly, but tend to suffer a more
severe illness
...
Immunodeficient patients males and infants, who are infected are all more
likely to become carriers
...
HBV carriers are managed using oral antib=viral therapy,
including; lamivudine, adefovir, entecavir, emtricitabine, and tenofovir
...
The current vaccine is genetically
engineered
...
Three injections of the vaccine
are given over a six month period
...
HBV vaccination is being introduced into childhood
vaccination programs
...

Human immunodeficiency virus
Acquired immune deficiency syndrome (AIDS) was first recognized in 1981 in the USA
...
HIV infection started in Africa between 1910-1930
...
Any one patient
contains many variants of HIV, and drug-resistant and immune resistant HIV mutants
emerge
...
The CD4 molecule acts as a high affinity
binding site for the viral genome gp120 envelope glycoprotein
...
Productive replication and cell destruction does not occur until the Th cell is
activated
...
The CCR5 beta -chemokine receptor is
important in establishing the infection, as is the CXCR4 alpha- chemokine receptor
...
One
inside the cell, viral reverse transcriptase copies single stranded DNA from viral RNA
genome
...
During the first few months virus-specific
CD8 positive T cells are formed and reduce the viraemia, the HIV load
...

The HIV transmission route involves mucosal surfaces, in particular cervicovaginal, penile
and rectal
...
I'm resource
rich
...
this is due to the higher risk of transmission by
receptive anal intercourse, sex networks, and risk taking increasing due to effective
antiretroviral treatment (ART)
...
HIV is sexually transmitted
...

Primary HIV infection may be accompanied by a mold mononucleosis type illness signs and
symptoms of the mild mononucleosis type illness associated with HIV infection include fever
...
The acute infection and rapid,
widespread viral dissemination is followed by a chronic asymptomatic stage
...
Further viral replication takes place until finally, years after initial
infection, full blown AIDS develops
...
These cells
express the CD4 antigen, and infected monocytes carry the virus into the brain
...
such opportunistic
infections include; disseminated CMV HSV JC virus, EBVm HHV-8, mycobacteria,
salmonella septicaemia, toxoplasma gondii, histoplasmosis, coccidioides, wasting disease,
and HIV encephalopathy
...
In addition, initially, an HIV-1 and -2 antibody/antigen combination assay which
includes antibody and p24 antigen is carried out
...
Part of monitoring HIV-1
infected individuals on or off antiretroviral therapy involves measuring the plasma HIV-1 RNA
load using assays based on reverse transcription polymerase chain reaction, branched DNA
signal amplification, and RNA transcription isothermal amplification
...
Monitoring of HIV infected patients involves measurement of p24 antigen levels
and CD4+ cell count
...
Antiretroviral
therapies include nucleoside reverse transcriptase inhibitors, non-nucleoside reverse
transcriptase inhibitors, protease inhibitors, fusion inhibitors, integrase inhibitors, and
chemokine receptor antagonists
...
As a result of improved diagnosis, surveillance, prevention, and antiretroviral
treatment, the number of AIDSrelated deaths among children and adults worldwide has
fallen
...
Some drug resistance mutations confer resistance to
more than one drug of the same class, whereas others appear unique to specific drugs
...
Drug resistance mutations per
sample tested has fallen from antiretroviral therapy naive adults infected with HIV in the UK
...

There are a number of preventative measures to reduce the spread of HIV
...
Prevention of mother-to-child HIV transmission involved the use of
antiretroviral treatment started after the first trimester of pregnancy
...

There are a number of challenges in developing a successful vaccine against HIV infection,
including viral antigenic variation, sequence diversity, slow neutralizing antibody response to
HIV infection, viral evasion of immune responses, and establishment of latent viral
reservoirs
...
Consequently they are much more liable to suffer from severe
and life threatening infections
...
Primary immunodeficiency is inherited or occurs by exposure in utero to
environmental factors or by other mechanisms
...

Secondary immunodeficiency or acquired immunodeficiency is due to an underlying disease
state or occurs as a result of treatment for a disease
...
Primary
adaptive immune deficiencies result from defects in primary differentiation environment or in
cell differentiation
...


Fungal infections in compromised hosts
Candida is the most common fungal pathogen in compromised patients
...
Candida causes; vaginal and oral thrush, skin infections, and
endocarditis
...
Chronic mucocutaneous
candidiasis requires repeated or long term treatment with azole antifungal drugs
...
Oropharyngeal and esophageal
candidiasis is seen in a variety of compromised individuals, including HIV-infected
individuals and people with ill fitting dentures, diabetes mellitus, or on antibiotics or
corticosteroids
...
nystatin)
...

Esophageal candidiasis requires systemic therapy
...
The organism can pass through the intestinal wall and spread from a
gastrointestinal focus
...
If there is dissemination from the gut, blood cultures may
become positive and candida antigens may be detectable in serum
...
Disseminated candidiasis can be acquired either via the gastrointestinal tract, or
from acterter related infections
...
Blood borne infections spread to almost any organ can
occur
...

Aspergillus spp
...
Aspergilli are found in soil,
but have a worldwide distribution
...
Dissemination to other sites, particularly the CNS
and heart, occurs in compromised individuals with lung infection
...
Invasive aspergillosis has a high mortality rate in the compromised patient
...
Prophylactic antifungal agents such as caspofungin, posaconazole, and
voriconazole, early diagnosis and institution of treatment using intravenous lipid formulation
of amphotericin B known as liposomal amphotericin B complexes or AmBisome, together
with reduction in corticosteroid and cytotoxic therapy, improve prognosis
...
with advanced HIV infection
...
Paromycin reduces oocyst output but dies not clear infection
...

Cystiospora bellu is another protozoan parasite that produces severe diarrhoea in people
with AIDS
...
Infections with microsporidia also
cause diarrhea in people with AIDS and other immunocompromised patients
...
Albendazole treatment is effective against encephalitozoon intestinalis but not
Enterocytozoon bieneusi
...

Microorganism toxins
Chain of infection
-reservoir, where an infectious agent normally lives, grows and multiplies, reservoirs include
humans, animals and the environment
- portal of exit, is the path by which the pathogen leaves its host
- modes of transmission, describe the way in which an infectious agent is transmitted from its
natural reservoir ro a susceptible host, transmission occurs by many routes and can be
direct or indirect
- portal of entry, the way in which a pathogen enters a susceptible host, the portal of entry
must provide access to tissues in which the pathogen can multiply or a toxin can act
-host, susceptibility of a host depends on genetic or constitutional factors, specific immunity
and nonspecific factors that affect an individual's ability to resist infection
Microorganism toxins
The pathogen may actively secrete exotoxins which aid in pathogen entry, spread, or
defense against the host
...

Exotoxins consist of a functional and a binding domain
...
Microbes that multiply in cells cannot afford to cause
serious damage at too early a stage, and such toxins therefore tend to be less prominent in
intracellular infections
...

Bacteria may produce enzymes to promote their survival or spread, eg
...

Toxins may damage or destroy cells and are then known as hemolysins
...

Toxins may enter cells and actively alter metabolic machinery
...
When the binding B subunit binds to receptors on the cell
membrane, the functional A subunit, or the whole toxin-receptor complex, is taken into the
cell by endocytosis and the A subunit is activated
...
by formaldehyde) without altering their antigenicity, and the
resulting toxoids are among the most successful vaccines
...
For example, the

plant toxin ricin, the A subunit can be attached to a monoclonal antibody to make it a specific
poison for tumour cells
...

Spores of ​C
...

When foods are canned or preserved without adequate sterilization (often at home),
contaminating spores survive and can germinate in the anaerobic environment leading to the
formation of toxin
...
While not destroyed by digestive enzymes
the toxins are inactivated after 30 minutes at 80 degrees celsius
...

Botulinum toxins have a characteristic two subunit structure, a functional A domain and a
binding B domain
...
The toxin affects peripheral nerve endings at the neuromuscular
junction, blocking presynaptic release of acetylcholine
...

Botulinum toxins are extremely potent and active at low doses
...
Then respiratory and cardiac muscles are
affected
...

There are three forms of botulism; food-bourne botulism, infant botulism, and wound
botulism
...
In infant botulism the organisms are ingested and multiply and
elboarte toxin in vivo
...
botulinum ​spores
...
Laboratory diagnosis involves demonstrating the presence of toxin in clinical
specimens or food or culturing the bacteria
...
Culture of faces or wound exudate for ​C
...

Since the specific ​C
...
Supportive therapy may include mechanical ventilation, due
to difficulty in breathing, and intravenous and nasogastric nutritional support, due to
dysphagia
...

Tetanus
Tetanus is caused by the bacteria ​clostridium tetani
...
tetani ​ produce endospores within
their cells, enabling them to survive in adverse conditions
...
when environmental conditions change or when nutrients are
exhausted
...

Tetanus spores are widespread in soil and originate from the faeces of domestic animals
...
Tetanus toxins are
extremely potent and active at low doses
...
The B subunit binds to ganglioside receptors on nerve cells
...
This allows the excitatry transmitter
to continuoulsy stimluate the mototr neurons, causing spastic paralysis
...

The diagnosis if tetanus is clinical
...
The wound should be excused if necessary
...
Muscle relaxants are used
...
Tetanus is a vaccine preventable disease
...
cholerae
...
The disease remains endemic in South-East
Asia, parts of Africa, and South America
...
cholerae ​ is a free-living inhabitant in fresh
water, and only causes infection in humans
...
The disease is spread via contaminated food
...
​V
...

Only O1 and O139 serogroups cause epidemic cholera
...
E1 Tor differs from classical ​V
...
The O139 strain

infects O1-immune individuals
...
cholerae ​O139 originated from E1 To O1 biotype and then
acquired a new capsular O antigen by horizontal gene transfer from a non O1-strain, but is
otherwise identical to O1 E1 Tor
...

The symptoms of cholera are due to the production of an enterotoxin in the gastrointestinal
tract
...
The A subunit
activates adenylate cyclase causing intracellular cAMP to rise, resulting in chloride secretion
and secretory diarrhoea
...
​V
...

After an incubation period of 2-3 days, ​V
...
The severe watery non-bloody diarrhea is known as rice
water stool because of its appearance and can result in the loss of 1 litre of fluid every hour
...

Culture is necessary to diagnose sporadic or imported cases of cholera and carriers
...
ETEC infection
is a possible differential diagnosis
...
Antibiotics reduce the duration of excretion of ​V
...

Clean drinking water and adequate sewage disposal are fundamental to the prevention of
cholera
...

Shigellosis
Shigellosis is a gram-negative rod
...
The main route of transmission of shigella
pathogens is the fecal-oral route
...

There are four subgroups of shigella; ​Shigella sonnei w
​ hich causes mild infection, ​S
...
boydii, a
​ nd ​S
...
Shigella has a large
virulence plasmid that encodes secreted proteins acting on colonic epithelial cells that
damage the epithelial lining as well as acting on the host immune response
...
​S
...
After an incubation period of 1-4 days, shigellosis presents
clinically with severe lower abdominal cramps and fever
...
The disease is usually self-limiting, but dehydration can
occur in the young and the elderly
...
coli​
...

Shigellosis is treated through rehydration
...

Staphylococcus aureus
Enterotoxigenic strains of ​S
...
The classic
serotypes are enterotoxins A-E, with A being the most commonly associated with
food-bourne intoxication
...
​S
...
Their effect on the central nervous
system results in severe vomiting within 3-6 hours of consumption
...

Recovery within 24 hours is usual
...

Food may be contaminated with enterotoxins by human carriers
...
The bacteria grow at room
temperature and release toxin
...

Enterotoxin have been detected by a latex agglutination test, but immunoassays are more
sensitive
...
epidemiology is concerned with populations rather than individuals
...

Prevalence is the number of people in the population who have the disease at a specified
point in time
...
Incidence and prevalence are typically expressed as a proportion of 100 000/ case
fatality rate is the ratio of deaths from a certain disease to the total number of people
diagnosed with this disease for a certain period of time
...
A disease may have a
high case fatality rate but a low mortality rate
...
Coronavirus is an
example of an emerging infectious disease
...
Measles is an example of an
re-emerging infectious disease
...

Case
Sets of criteria are used to define someone as definitely having a specified disease
...
A case is typically laboratory
defined
...
The index case is the first
person to be identified as having the disease through the set criteria
...
The index and the primary case
aren't necessarily the same
...

Notifiable diseases
Notifiable diseases are rare fatal infectious diseases, or vaccine preventable diseases in
which case notifying the proper authorities enables surveillance of a vaccine program
...
Examples of notifiable
diseases include; measles, mumps, rubella, whooping cough, anthrax, rabies, tuberculosis,
and viral haemorrhagic fever
...
There are
infectious diseases in animals which are also notifiable for reasons of animal welfare and
due to risk of zoonotic transmission
...
The attack rate is calculated as
the number if people who became ill divided by the number of people at risk for the illness
...

The basic reproduction number (R0) is the average number of infected cases produced by
each infectious case in a totally susceptible population
...
The basic
reproduction number depends on the duration of infectiousness of the case (D), the number
of contacts per unit time (K), and the transmission probability (B): R0=D*K*B
...
Different diseases have different
reproductive rates
...
More commonly, a
population consists of susceptible and immune individuals
...
The net reproduction number depends on the basic reproduction and the
proportion of susceptible individuals (x): R=R0*x
...
Thus, if the proportion of susceptibles (x) is small
enough, R will be less than 1 and the disease can be eradicated
...
The herd immunity
threshold is the proportion of the population that needs to be immune in order for a disease
to eventually die out (R<1): HI=R0-1/R0
...
The basic reproduction number allows us to
estimate the vaccination coverage which needs to be achieved in order to control an
infectious disease
...
B is determined by susceptibility of people in
the population to that disease
...
However, where case fatality is high to where the
carrier state is likely to develop with long term consequences, public health organisations will
consider interventions to change B
...
In the
UK, HBV vaccines are included in routine childhood immunisation schemes
...
Vaccination lowers the B value for HBV
...
The variola virus is a large, double-stranded DNA
virus, belonging to the family : poxviridae
...
Clinical symptoms
include; flu-like symptoms, flu-like symptoms resolve in 2-3 days and then a vesicular rash
appears initially on the face and limbs and then spreads to the trunk
...
There are two strains of the virus; variola major which is
responsible for 50% of cases and has a case fatality rate of 50%, and variola minor which
accounts for the pther 50% of cases and which has a case fatality rate of 1%
...
Smallpox remains the only
human infectious disease to be eradicated through the use of a vaccine
...
In 1967 the World
Health Organisation (WHO) started a campaign to eradicate smallpox from the world,
focusing on South AMerica, Africa, India, and Indonesia, making use of vaccination,
surveillance, and containment of cases
...
The last case was recorded in
Somalia in October 1977
...
Global eradication of smallpox was possible for a variety of
reasons; there were no subclinical infections so cases could be readily identified, the virus
was eliminated from the body on reviery with no carriers, humans were the only host there
was no animal reservoirs, and an effective vaccine was available
...
Stocks of live vaccinia
virus are kept for use in the development of diagnostic tests and new treatments
...
Poliovirus is a single stranded positive sense RNA
virus
...

Poliovirus is an enterovirus and belongs to the family: picornaviridae
...
There are
three strains of poliovirus, type 1-3, of which type 1 is the most virulent
...
Poliovirus is spread by the faecal-oral route
...
Polio virus is a strictly human pathogen
with no animal reservoir
...
Poliovirus replicates in lymphoid tissue in the pharynx and thus enters the
systemic bloodstream
...
The poliovirus confers life long
immunity to the infected individual
...
When present, symptoms include; fever, lethargy, sore throat, and malaise,
such cases are termed abortive polio
...

In such cases the virus infects the central nervous system, after an initial 104 days of fever,
sore throat, and malaise, meningeal signs and symptoms appear, followed by involvement of
motor neurons and paralysis
...
The first polio vaccine was a
killed vaccine (inactivated polio vaccine, IPV) developed by Salk
...
Advantages of the IPV include; safety as the virus is
inactivated, suitable for use in immunocompromised individuals as the virus does not
undergo its typical life cycle and thus does not elicit as strong an immune response, it can be
kept at room temperature which is an advantage in tropical countries and it elicits a rapid
immune response providing immediate immunity
...
A live polio vaccine (oral polio vaccine,
OPV) was developed by Sabin
...
Disadvantages of OPV include; requirement to keep cold, lacks genetic stability
and so virus can revert back to wild type, it can cause vaccine associated paralytic polio
(VAPP), OPV is transmissible from vaccines to their close contacts, and it can persist in the
community as VAPP
...
By 2016, 80% of the
global population lived in regions where polio had been eradicated
...
Cases of VAPP have
been reported from several African countries
...
wild type poliovirus type 2 confirmed as

eradicated in 2015
...
Complete
eradication of polio has not been achieved as; the majority of individuals infected with the
wild type virus are asymptomatic and thus continue transmission, and live attenuated
vaccine strains can revert to a wild type strain but the vaccine remains asymptomatic but still
transmits the virulent virus, and eradication depends upon strong infrastructure which is not
always available particularly in developing countries
...

Measles
...
Rubella virus
infection causes a multisystem infection but its main impact is on the fetus, congenital
rubella
...
If the fetus survives, it
may show characteristic abnormalities such as; patent ductus arteriosus, patent
interventricular septum, mental retardation, cataracts, microphthalmia, and hearing defects
...
Virus can be isolated from infants throat and urine
...
Vaccination with live
attenuated rubella virus is given during childhood, before girls become sexually active to
reduce the risk of congenital rubella
...

Mumps is caused by the paramyxovirus
...
The
mumps virus is spread by air-bourne droplets and infects the salivary glands
...
Laboratory
diagnosis is made; by detecting viral RNA in throat swabs, cerebrospinal fluid, or urine, by
isolating the virus in cell culture, or by detecting mumps specific IgM antibody
...
Mumps is prevented by
using the live attenuated vaccine, which is safe and effective
...
Measles is transmitted by respiratory droplets
...

The disease is so characteristic that a clinical diagnosis can be made without laboratory
tests
...
There is only one
antigenic strain of measles virus
...

Measles is highly infectious, and nearly all susceptible children contract the disease on
exposure
...
Complications of
measles, due to the loss of memory B and T cells and a resulting generalized immune
suppression, include; opportunistic bacterial superinfections, which are common, especially
otitis media and pneumoniae, as a result of virus damage to respiratory surfaces; a primary
measles virus pneumoniae (giant cell pneumoniae) which is seen in patients with serious
cell-mediated immune response defects; post-infectious encephalitis which occurs in 1 in
1000 patients; and very rarely, subacute sclerosing panencephalitis, this develop 1-10 years
after apparent recovery from acute infection
...
Complicated measles infection can be treated with ribavirin
...

The measles, mumps and rubella (MMR) vaccine combines the live attenuated vaccines for
measles, mumps and rubella in one vaccination
...
All children were immunised at 18 months of
age
...

Between 2000-2015, there was an estimated 79% drop in measles deaths worldwide, with
an estimated 20 million deaths from measles prevented by vaccination
...
Cases of measles increased in the UK after 2001
...
This resulted from the suggestion that the MMR vaccine caused autism, as there
was an apparent rise in autism in both California and the UK that seemed to coincide with
the introduction of the vaccine
...


Rotavirus vaccine
Rotavirus causes the most serious gastrointestinal disease in infants
...

Two new live oral vaccines are now in use: the RV5 vaccine (RotaTep) contains five
restaurant rotavirus developed from human and bovine parent strains, while the RV1 vaccine
(Rotarix) contains one live attenuated rotavirus strain
...

Studies from a number of countries have demonstrated marked reductions in
hospitalizations and in GP visits for all cause acute gastroenteritis in children after rotavirus
vaccine was introduced
...

Mycobacterium tuberculosis causes tuberculosis (TB), which is one of the top 10 causes of
death globally
...
TB is primarily a disease of
the lungs, but may spread to other sites or proceed to a generalized infection, miliary TB
...
tuberculosis in aerosols and dust
...

Pathogenesis
In primary infection the organisms are engulfed by the alveolar macrophages, in which they
can both survive and multiply
...
In the lymph
nodes, the immune response, predominantly a cell mediated immune response, is

stimulated
...
tuberculosis organisms may have escaped the immune response and
set up foci of infection in other body sites
...
The body
reacts to contain the organisms within ‘tubercles’, which are small granulomas consisting of
epithelioid cells and giant cells
...
After a time, the material within the granulomas becomes necrotic
and caseous or cheesy in appearance
...

However, in a small percentage of people with primary infection, and particularly in the
immunocompromised, the mycobacteria are not contained within the tuberculosis, but invade
the bloodstream and cause disseminated disease, military tuberculosis
...
AIDS,
chemotherapy for treatment of malignancy, or corticosteroids for the treatment of
inflammatory diseases
...
The immune response controls infection and, when it is inadequate, the infection
disseminates or reactivates
...
tuberculosis causes little or no direct toxin-mediated damage
...

Clinical features
The onset of TB is insidious
...
However, clinical disease develops in a minority of cases
...
The clinical
manifestations are variable and may include; fatigue, weight loss, weakness, and fever
...
Necrosis may erode blood vessels, which can
rupture and cause death through haemorrhage
...

Alternatively, spread may be by extension to a neighbouring part of the lung, for instance
when a tubercule erodes into a bronchus and discharges its contents, or into the pleural
cavity, resulting in a pleural effusion
...
tuberculosis into the skin to assess whether someone is sensitive to
tuberculin protein
...
However, as for the other commercial interferon-gamma test for TB, a positive
response could mean that the person has been infected previously, has latent TB infection
or has an active TB infection
...
Tubercles are visible on a chest

radiograph as radio-opaque nodules
...
These tests are confirmed by microscopic demonstration
of acid-fast rods and culture of M
...
Microscopic examination of a smear of
sputum stained by Ziehl-Neelsen’s method or by auramine often reveals acid fast rods
...
This is
important because M
...
Rapid non-culture tests to detect M
...
Further tests are required to identify the mycobacterial species and to establish
susceptibility to antituberculosis drugs
...
Treatment includes combination therapy, usually
consisting of four drugs such as isoniazid, rifampicin, ethambutol and pyrazinamide, to
prevent emergence of resistance
...
The
number of strains resistant to the first line antituberculosis drugs has increased as these
antibiotics have been used for decades and may appear if there are compliance problems
due to the number of drugs and lengthy treatment period
...
Treatment of monitored carefully with
directly observed treatment and shorter courses
...
Extremely drug resistant TB
does not respond to the second line drugs
...
however, there has been an
increase in the number of cases associated with AIDS, particularly in resource poor
countries
...
immunization , which confers positive
skin test reactivity, does not prevent infection, but it does allow the body to react quickly to
limit proliferation of the organisms
...
In the UK, prophylaxis with
rifampin and isoniazid for 3 months is recommended for people who have had close contact
with a case of TB

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