Book: pathogens Flashcards
What is the type of microorganism causing Trachoma?
Bacteria. Chlamydia trachomatis, a microorganism that has features of both a
bacterium and a virus.
What is the organism causing poliomyelitis (polio)?
Poliovirus (Enterovirus) types 1, 2 and 3 cause poliomyelitis (polio)
What are the clinical features of poliomyelitis (polio)?
The clinical features of poliomyelitis (polio):
Infection commences with fever, general malaise and headache, the majority of cases resolving after these mild symptoms, but approximately 1% proceed to paralytic disease.
The virus has a predilection for nerve cells, especially those with a motor function (the anterior horn cells of the spinal cord and the motor nuclei of the cranial nerves). These cells are destroyed and a flaccid paralysis results.
In general, the paralysis is more common in the lower part of the body, becoming less common the higher up it affects. Unilateral lameness is commoner than bilateral lameness. The severe form of bulbar poliomyelitis is generally fatal in poor countries where respirators and intensive nursing care are not available. The site of paralysis is associated with injections or operations and such procedures should be avoided if there is any suggestion of poliomyelitis.
How is poliomyelitis (polio) diagnosed?
Diagnosis of polio(-myelitis) of the disabled case is made on clinical grounds, differentiating from
the spastic paralysis of birth injury with which it is commonly confused. In polio, there will be a history of normal birth with commencement of walking, followed by a feverish illness and the development of flaccid paralysis. The paralysis is limited to well-demarcated muscle groups and there is no sensory loss.
A similar history may be given for meningitis, but the damage will be central with accompanying mental deficiency. Virus may be recovered from
throat swabs in the early stages of the illness or from rectal swabs or faeces later on. A rise in the antibody level of serological tests is not diagnostic due to the widespread use of polio vaccine.
How is polio/poliomyelitis transmitted?
Transmission is generally via the faecal–oral route, although the virus initially multiplies in the oropharynx so airborne transmission can also occur.
The virus then invades the gastrointestinal tract, where it is excreted for several weeks. A disease of low hygiene, young children (4–5 months) meet the virus with only a small proportion showing overt disease; 80–90% have an inapparent subclinical disease, 5–10% suffer from fever, headache and minor clinical signs,
with 1% only going on to paralysis. Paralysis is more common with older age, so a non-immune person going into an endemic environment is at far greater danger of developing paralytic poliomyelitis. Raising standards of hygiene will also have the same effect because it spares people from meeting the virus as young children and allows a pool of susceptibles to develop. In time, the number of non-immunes will be sufficient for an epidemic to take place. There will also be a higher proportion of paralysed cases (peak age 5–9 years), and many deaths. So, sadly, the raising of living standards will change polio from an endemic disease with a few paralysed cases to an epidemic disease of increased severity.
In epidemic poliomyelitis, where sanitation is good, pharyngeal spread becomes a more important method of transmission.
Poliovirus strains vary in their neurovirulence, with the more virulent strains having a greater tendency to spread. This could be due to a lower infective dose of the virulent virus being required to produce disease.
What is the occurrence and distribution of polio/poliomyelitis?
Poliomyelitis formerly occurred throughout the world, and was endemic in the poorer regions and epidemic in those with good sanitation, but this has changed considerably with the WHO programme of eradicating polio from the world.
The Americas, Europe, South-east Asia and Western Pacific are now free of infection. Only three countries are now endemic with polio – Nigeria, Pakistan and Afghanistan – but outbreaks occur in countries previously free of infection, such as China, resulting from these endemic sources. The fatwa declared by Islamic fundamentalists against vaccination in northern Nigeria has resulted in several outbreaks.
What are the methods of control and prevention of polio/poliomyelitis?
The main method of prevention and control is with polio vaccine. Two types of vaccine are available: the inactivated polio vaccine (IPV) (Salk) and the attenuated live vaccine (Sabin).
The Salk vaccine is given by intramuscular injection, inducing a high level of immunity that is not antagonized by inhibitory factors in the gut, but is expensive to produce because it contains many organisms. The Sabin vaccine is administered orally (oral polio vaccine, OPV), making it easier and cheaper, as well as producing intestinal immunity which can block infection with wild strains of poliovirus.
Multiplication of the OPV virus in the intestine makes it very useful in preventing epidemics and allows it to spread to non-vaccinated persons in conditions of poor hygiene, so protecting them as well.
Unfortunately, the inhibiting action of antibodies in breast milk and colonization of the gut by other enteroviruses can reduce its effectiveness. Increasing the dosage and telling mothers not to breastfeed for at least an hour after administration can help.
Because there are three strains of the poliovirus, the vaccine should be given on three separate occasions, separated by periods of at least 1 month, to ensure that immunity develops to each of the strains. Polio vaccine is conveniently administered at the same time as diphtheria, tetanus and pertussis (DTP). Where there is a high risk of poliovirus and importation or the transmission potential is high, then a first dose should be given soon after birth.
In countries nearing eradication, a monovalent polio vaccine has been found to be more effective than the trivalent one, with type 3 virus predominating in the Indian subcontinent and type 1 in the remaining endemic parts of the world.
A bivalent oral polio vaccine (bOPV) containing just type 1 and 3 viruses gives a higher rate of protection and is easier to administer. Unfortunately, the use of monovalent and bivalent vaccines has led to the development of vaccine-derived poliovirus (VDPV) outbreaks, mainly in Africa and the Indian subcontinent. This has been a particular problem in the immunodeficient, leading to the risk that they will develop paralytic disease, while also being reservoirs for the spread of poliovirus. Where incomplete vaccination programmes are occurring, then the full triple vaccine should be used. VDPV can also develop after prolonged replication of OPV, reacquiring neurovirulence and transmissible characteristics of wild poliovirus (WPV). This is associated with low vaccine coverage and particularly Sabin 2 vaccine. IPV can be used to prevent this happening, but it is less effective at producing intestinal mucosal immunity. Both vaccines can be used together, especially where the incidence of paralytic polio has remained high.
WHO now recommends that one dose of IPV should be added to the routine three-dose OPV schedule, to be given from 14 weeks of age. WHO is in the process of moving to a strategy of bivalent rather than trivalent OPV with the addition of IPV.
Many countries where polio has been eradicated now use IPV in their routine vaccination programmes. A high level of vaccination must be maintained to produce ‘herd immunity’ as there is still a risk of introduced cases from parts of the world where wild virus is still circulating.
Schoolchildren and adults who have received a full course of childhood vaccinations should have booster doses every 10 years. Maintenance of vaccination coverage should continue even in countries now free of infection and is essential for travellers going to parts of the world where polio has not yet been eradicated.
The long-term aim of prevention should be to raise standards of hygiene with the provision of water supplies and sanitation, but this must proceed at the same time as an adequate vaccination programme.
What is the treatment of polio/poliomyelitis?
There is no specific treatment for the acute stage, but rest and the avoidance of physical activity are beneficial. Specific supportive measures can
be given to those with disabilities.
What is the surveillance in place for polio/poliomyelitis?
Surveillance developed for poliomyelitis eradication looks for cases of acute flaccid paralysis (AFP) in children under 15 years of age. These are investigated by stool examination, inquiry and search for other cases in the area. Remedial measures are carried out around the case, vaccinating all contacts.
What are the clinical features of trachoma?
Clinical features. Commencing as a keratoconjunctivitis, the first sign is red eye. There may be irritation and discharge but this is passed off as a self-limiting infection. A follicular infiltration of the conjunctiva then takes place, particularly in the upper lid. Blood vessels grow into the periphery of the eye, forming pannus.
However, it is at the late stages of the disease, when it is non-infectious, that scarring, particularly of the upper eyelid, turns the eyelashes inwards to rub on the eye, a condition called trichiasis.
This constant rubbing of the eyeball, aided by the dryness of the conjunctiva, damages the cornea, leading to scarring and finally blindness. Trachoma is often further complicated by secondary infection.
How is trachoma diagnosed?
Diagnosis of trachoma is usually made on clinical grounds, but can be confirmed by finding the characteristic inclusion bodies in scrapings taken from the conjunctiva.
How is trachoma transmitted?
Trachoma is a disease of poor sanitary conditions where a combination of close contact and dirty conditions encourages transmission.
Within the family unit, transmission is from child to child or by flies (mainly M. sorbens) that are attracted to the discharges around the eyes. Cycles of reinfection and recrudescence continue to damage the eye and lead to blindness at school age. The usual method of wiping away secretions with hands, towels or clothing, which is then used by the adult on other children or themselves, is a typical pattern of transmission.
What is the occurrence and distribution of trachoma?
Trachoma is found mainly in the dry regions of the world, especially Africa, South America and the extensive semidesert regions of Asia. A disease of antiquity, it was first described by the
ancient Egyptians.
In endemic areas, 80–90% of children are infected by the age of 3 years. In conditions of improved sanitation, there is a natural cycle lasting until 11 years of age, with little residual damage. Females develop trachoma and blindness as adults more commonly than males, because they are directly concerned with looking after children. The chance of acquiring infection is increased by large families with short birth intervals, as there are more children of a young age living in close proximity.
Since the introduction of the WHO elimination programme, there has been a reduction of trachoma cases from an estimated 360 million in 1985 to 41 million in 2009. Half the global burden of active trachoma is concentrated in Ethiopia, Guinea, India, Nigeria and South Sudan. It is hoped that active trachoma can be eliminated by 2020.
What is done for the control and prevention of trachoma?
The use of water to wash away secretions, the wearing of clean clothes and keeping the surroundings clean are the most effective methods. Face washing has been shown to reduce the risk of developing trachoma, so regular daily face washing should be encouraged. Long-term preventive measures are to improve sanitation and provide water supplies.
Flies proliferate in rubbish and excrement, reaching their maximum numbers during the dry sunny period of the year. The damp, moist conditions in open pit latrines may be more important in encouraging fly breeding than non use of latrines. Any flushing mechanism or improved latrine will discourage flies.
A strategy for a control programme is as follows:
• Conduct a survey to find the worst affected areas.
• Give mass treatment.
• Conduct health education through schools, stressing regular face washing.
• Provide back-up services.
WHO has launched a programme for the global elimination of trachoma by 2020 and given it the acronym of SAFE. This stands for: Surgery for trichiasis Antibiotics Facial cleanliness Environmental improvement.
What is the treatment for trachoma?
Mass treatment is preferable, as the majority of the population in an infected area will have trachoma. This is given easily in schools, but is better done in the home, where the main transmission takes place. A single dose of azithromycin (20 mg/kg) is better than topical tetracycline, and one dose a year may be sufficient to eliminate the blinding propensity of trachoma. Mothers can be taught to treat all children in the household regularly.
Preventing blindness once scarring and trichiasis have developed is very easily done by a simple operation that a medical assistant can be trained to do. This involves cutting through the scarred conjunctiva of the upper lid and everting it so that the eyelashes no longer rub on the cornea.
What kind of surveillance is done for trachoma?
After the initial survey, follow-up surveys should be conducted at
regular intervals. This is most easily done in primary schools.
What microorganism causes gastroenteritis?
Strains of enterotoxigenic, enteropathogenic and enteroaggregative Escherichia coli, as well as enteric viruses, are the main organisms. Rotavirus and Campylobacter are major causes. Norovirus is a common cause of epidemics.
What are the clinical features of gastroenteritis?
Profuse, watery diarrhoea with occasional vomiting, but despite the fluid nature of the stools, faecal material is always present. There is never the rice-water stool characteristic of cholera.
Water and electrolytes are lost which, in the young child, may be sufficient to cause dehydration and ionic imbalance, leading to death. Normally, a self-limiting condition but in unhygienic surroundings, or where babies’ bottles are used, repeated infections occur, leading to chronic loss of nutrients and subsequent malnutrition. A serious infection in neonates, mortality decreases with age until in adults it is just a passing inconvenience (travellers’ diarrhoea).
How is the diagnosis of gastroenteritis made?
Diagnosis of gastroenteritis is made on clinical criteria unless laboratory facilities sufficient to
identify viral infections are available. Specific DNA probes are likely to be the
most appropriate method of identifying causative organisms in developing
countries if they can be made cheap enough
How is gastroenteritis transmitted?
Epidemics of gastroenteritis occur in families or groups of children sharing similar
surroundings. Infection is often seasonal, the beginning of the rains heralding an
outbreak. This would suggest transmission by water, and simple control
measures such as boiling of water can stop the epidemic. Improperly sterilized
babies’ bottles or their contents are a common method of infecting the neonate.
What is the occurence and distribution of gastroenteritis?
Gastroenteritis is found throughout the world,
especially in developing countries and in conditions of poor hygiene. It is
particularly common where bottle-feeding has been recently introduced, such as
by unscrupulous infant-feed companies. A seasonal distribution suggests
contamination of the water supply.
What are methods of control and prevention of gastroenteritis?
Control and prevention of gastroenteritis are by the following:
• promotion of breastfeeding;
• use of oral rehydration solution (ORS) in the community;
• improvement in water supply and sanitation;
• promoting personal and domestic hygiene;
• vaccination (rotavirus and other vaccines, e.g. measles); and
• fly control (Box 7.1).
Breastfeeding not only provides a sterile milk formula in the correct
proportions (in contrast to the often-contaminated bottle) but also promotes
lactobacilli and contains lactoferrins and lysozymes. Promoting breastfeeding
and the administration of ORS solution in the community are the main control
strategies. Improvement in water supplies and sanitation, with the promotion of
personal hygiene, are long-term measures.
Rotavirus vaccination should now become part of the routine childhood
vaccination programme (see Section 8.2). The oral cholera vaccine WC/rBS has
been shown to be about 60% effective against enterotoxigenic E. coli so might
have some place in control, although its protective effect in infants is
considerably less than in adults. Preventing other childhood infections by
vaccination, especially those associated with gastrointestinal disease, such as
polio and measles, can reduce the severity of gastroenteritis.
What is the treatment of gastroenteritis?
Treatment of gastroenteritis is by the replacement of fluid and electrolytes using oral rehydration solution in the
moderately dehydrated and intravenous replacement in the severely dehydrated. A naturally available rehydration solution is the fluid from a green coconut.
A 7-month-old coconut has been found to be the most suitable. Rice water made
from a handful of rice boiled in a saucepan of water until it dissolves, plus the
appropriate amount of salt for the volume of water, makes a simple rehydration
solution. Carrot water can also be used.
If mothers are taught how to make up these solutions, then they can treat
their own children as soon as they start to get diarrhoea. The mother should use a
cup and a spoon and sit with her child, giving small quantities of fluid at
frequent intervals. Severe dehydration can usually be prevented by primary care
from the mother.
There is no need to use an antibiotic or an antispasmodic, both of which are
contraindicated. Lactobacilli, which inhibit E. coli, colonize the gut in the
breastfed infant. Live yoghurt (curd) contains lactobacilli and can be quite
effective, especially in adults, in reducing the severity and duration of diarrhoea.
What is done in terms of surveillance for gastroenteritis?
In countries with a seasonal rainfall pattern, gastroenteritis
outbreaks often start with the beginning of the rains, so monitoring the weather
can provide early warning of an impending outbreak.
Which microorganism causes cholera?
Vibrio cholerae. Classical cholera is caused by V. cholerae 01, while
most of the recent epidemics have been due to the El Tor biotype. Two variant
strains of the El Tor biotype have developed, 0139 Bengal, restricted to Asia,
and an El Tor producing toxin of the classical strain (ETEC).
What are the clinical features of cholera?
A profound diarrhoea of rapid onset that leads to dehydration,
and death should be considered as a case of cholera until proved otherwise. The diarrhoea contains no faecal particles but is watery and flecked with mucus (not
cells), the so-called rice-water stools. The passage of large quantities of fluid and
electrolytes leads to rapid and extreme dehydration, which can be fatal. Vomiting
can also be present in the early stages. Blood group O is associated with more
severe cholera.
How is the diagnosis of cholera made?
V. cholerae can be identified from the diarrhoeal discharge, vomitus
or by rectal swab. Its characteristic mobility (it vibrates, hence being called a
vibrio) can be seen by dark ground or phase contrast microscopy and is inhibited
by specific antiserum. Confirmation of the diagnosis is made by culture on
TCBS (thiosulfate-citrate-bile salts-sucrose) agar. A suitable transport medium is
Carey Blair, or alternatively 1% alkaline (pH 8.5) peptone water, which can also
be used for water samples. A dipstick rapid diagnostic test is available.
How is cholera transmitted?
Classical cholera is a disease of water transmission, whereas
transmission of El Tor is by both water and food. Generally, epidemic cholera is
transmitted by water, and endemic cholera by food. It may appear in a seasonal
pattern, often in association with other causes of diarrhoea (Fig. 8.2). It is the
endemic nature of El Tor and its persistence in the environment that has been
responsible for its prodigious spread.
For every clinical case of El Tor cholera there can be as many as 100
asymptomatic cases, explaining how epidemics spread from one region to
another, but not how infection remains in the environment. One method may be
the persistence of infection in the human population due to continuous personto-person transmission in a subclinical asymptomatic cycle. When a susceptible
person enters the cycle, or there is an environmental or climatic change, a fresh
epidemic starts.
A natural cycle has now been established in an aquatic environment, with V.
cholerae living in copepods, or in other zooplankton, as found in algal blooms.
Vibrios are easily destroyed by sunlight, chemical action or competing bacteria;
however, where these elements are not present, they can survive in fresh water
for some time and in saline for at least a week. The level of salinity needs to be
between 0.01 and 0.1%, as is found in estuarine or lagoon water. V. cholerae in
this saline environment can be taken up by shellfish or fish, which then form an
alternative method of infection when eaten uncooked. Rising sea levels and
increase in water temperature due to climate change make cholera outbreaks
developing from an estuarine environment more likely.
The isolation of V. cholerae from river water has been an enigma because
epidemiological investigations show this source of infection to be important, but
bacteriologists have not isolated organisms in sufficient numbers. One possible
explanation is the presence of non-agglutinable vibrios (alternatively known as
non-cholera vibrios), which are closely related to V. cholerae, except that they do
not agglutinate antisera. However if they are infected with a phage virus, this
transfers a toxin gene, which if in sufficient numbers leads to an outbreak. It is
this multiplication of vibrios during the wet season, many of which contain the
toxigenic phage, that leads to an epidemic.
V. cholerae has been found to remain viable in crude sewage for over a
month and in sewage-contaminated soil for up to 10 days, thereby providing a
possible source of infection to rivers or wells. It has been isolated from a number
of foodstuffs, especially those with a pH of between 6 and 8, such as milk
produce (e.g. ice cream), sugar solutions, meat extracts or articles of food
preserved by salt. Uncooked fish and vegetables that have been washed or
irrigated by sewage effluent have been responsible for outbreaks.
Direct person-to-person spread, or via fomites such as utensils or drinking
straws (in home-brewed alcohol parties), do not appear to be as important as
expected. Even in persons attending the death of a cholera case, it is more likely
that infection will result from drinking water or consuming food that has been
prepared for the mourning ceremony, rather than from the dead person or their
shrouds.
A case of cholera can excrete between 10
7 and 10
9 V. cholerae/ml of
diarrhoeal discharge, and as the volume of this discharge may be in excess of 20
l/day, the potential for contamination of the environment is enormous. Clearly
though, the severe case is unlikely to be anything but a transitory source; it is the
asymptomatic case passing 10
2–10
5 organisms/g of stool in a spasmodic manner
that poses the greatest hazard.
A high dose of V. cholerae is required to infect the healthy subject. Some
10
6–10
8 organisms are needed, but if the person has a decreased gastric acidity,
then 10
3 organisms may be sufficient. Lowered gastric acidity is found more
commonly than expected and may be related to malnutrition or diet. Cannabis
smoking is also known to depress gastric acidity.
How are carriers involved in the spread of cholera?
Carriers are of short duration. Seventy per cent of cholera cases are free of
vibrios at the end of the first week and 98% by the end of the third. Long-term
carriers are rare and of no epidemiological importance.
What is the occurrence and distribution of cholera?
Humans are the only known reservoir, but the
persistence of the organism in the environment, in association with a toxigenic
phage, as discussed above, may be another source. In endemic areas cholera is a
disease of children (adults having developed immunity in childhood), whereas in
its epidemic form adults are the more usual victims. The disease is associated
with poverty and poor hygienic practices.
Classical cholera is restricted to South Asia and caused by V. cholerae 01.
The El Tor biotype has infected Asia, Africa, Europe, Pacific Islands and South
America, while the majority of cases are now found in Africa (Fig. 8.3). First
isolated from pilgrims to Mecca in the quarantine station of El Tor in West Sinai
(now Egypt) in 1906, it differs from the classical variety by producing a soluble
haemolysin. It is classified as either Ogawa, Inaba or Hikojima of the classical
serotypes. The importance of the El Tor biotype is that it can survive longer in
water, is more infectious, can cause mild infections and more frequently
produces the carrier state. These characteristics have all assisted in the extensive
spread of this organism. The more virulent El Tor V. cholerae 0139 has been
responsible for epidemics in India, Bangladesh, Myanmar, Thailand and
Malaysia, but is fortunately now on the decline. In 1992, a variant of the El Tor
biotype but with toxigenic effects similar to those of classical cholera (ETEC)
appeared in Asia and has now replaced the original El Tor strain in many parts of
Asia and Africa. Antibiotic-resistant strains are appearing but proper
management of cases should not require the use of antibiotics.
What is done in terms of control and prevention for cholera?
Control is aimed at the cause. All too often a panic
situation develops, foods are banned, vaccination given and quarantine
instigated. If cholera is epidemic and preliminary investigations indicate that
water is the vehicle of transmission, then the supply should be sterilized by
super-chlorination (adding two to three times the calculated amount of chlorine
required for the volume of water) or everybody told to boil their water. Boiling
water is unpopular as it uses vital firewood and monopolizes scarce cooking
pots, and the water has a flat taste. However, there is no reason why water cannot
be boiled at the same time as the meal is cooked and simple clay pots used
instead of metal ones. Boiled water can be re-aerated by shaking it up. A not so
safe, but easier, method is to leave water to stand and then decant off the
supernatant. A simple way of doing this is the three-pot system (Fig. 3.6). The
SODIS method using polythene bottles of water heated by the sun can also be
used. Chlorine can be added to a well or communal water supply, but any
vegetable matter in the water will inactivate chlorine, and several times the
amount calculated may be required.
The banning or restriction of food should only be made on good
epidemiological evidence. If fish are properly cooked before being eaten, then
they are unlikely to be a source. Disruption of a fish-eating practice may have
dire consequences on other aspects of people’s health. It is more often the
fisherman rather than the fish, or the farmers rather than their produce, that are
the purveyors of cholera.
Quarantine is rarely effective, as bribery or evasion of the barricades by the
few who might be carrying the infection negates the hardships borne by the
many who are not. Giving tetracycline to immediate contacts of cases will
reduce the number of asymptomatic carriers, but the widespread distribution of
the drug will encourage tetracycline resistance.
The original inactivated V. cholerae vaccination gives about 50% protection
and only lasts for 6 months. It does not prevent the asymptomatic disease state
and can actively encourage the spread of infection, so is not recommended as a
method of control.
Dukoral (WC/rBS) cholera vaccine consists of killed whole V. cholerae 01 in
combination with a recombinant B subunit of cholera toxin. It confers protection
of up to 90% for 6 months and has been found to be effective in preventing
cholera in high-risk areas such as refugee camps and urban slums. Protection has
been found to remain at about 60% for at least 2 years in adults and older
children but declines rapidly in young children after 6 months. The vaccine is
administered to adults and children over 6 years in two oral doses given 7 days
apart. Children aged 2–5 years should have three doses, each given 7 days apart.
A booster dose to adults and children over 6 years can be given after 2 years.
The vaccine has been found to be safe when given to pregnant women and those
with HIV infection.
Dukoral can be used pre-emptively in high-risk areas, in epidemic situations
and to protect travellers entering areas of high endemicity. Several mass
vaccination campaigns have demonstrated its value in protecting populations at
risk in an ongoing epidemic and in crisis situations where an outbreak of cholera
has a high likelihood of occurring. It has also been found effective against
ETEC.
Two other vaccines, Shanchol and mORCVAX, are based on serogroups 01
and 0139, but do not contain bacterial toxin B subunits so are not effective
against ETEC. Shancol is produced in India for internal and international use,
while mORCVAX is used only in Vietnam. Shancol can be given to those over 1
year old and is administered in two oral doses given 14 days apart. These
vaccines have been found to be as effective as Dukoral where ETEC cholera is
not involved, providing longer-term protection to children under 5 years of age,
as well as being cheaper.
All these vaccines provide herd immunity, which is especially valuable in
protecting young children. In high-risk areas, children as young as 1 year old
should be targeted with Shancol or mORCVAX and 2 years olds with Dukoral,
in periodic mass vaccination campaigns. Follow-up should be provided to give
the second dose (and third with Dukoral) at 6 months. Booster doses should be
given every 2 years. Pregnant women and HIV-positive persons should also be
vaccinated.
In epidemic situations, oral cholera vaccines can be administered to
populations in high-risk areas, but this is only a short-term option. Reliance
should not be placed on vaccination to control an epidemic, but other methods of
control such as sterilizing water supplies should mainly be used.
Persons dying from cholera should be buried promptly and the ceremony
kept to a minimum. Disinfectants and hand-washing facilities should be
provided at treatment centres and when bodies are prepared for burial. Flies
should be controlled by disposing of or covering all faecal discharges, although
they have not been shown to play a significant role in transmission
How is cholera treated?
The vibrio binds to the cells and produces an enterotoxin, which
activates adenyl cyclase, an intracellular enzyme that initiates a system of fluid
and ion transport from the plasma to the intestinal lumen. This strategy is used
by the vibrio to flush out other bacteria that normally live in the intestine and
compete with it. There is no mucosal damage and increased permeability is
unlikely, which explains why glucose and electrolytes can still be absorbed by
the mucosa. This allows large quantities of low-protein fluid, bicarbonate and
potassium to escape through an essentially undamaged intestine. Management is
to correct dehydration in this otherwise self-limiting disease.
Fluid replacement must be rapid and adequate, the most easily available
being the first choice. If rehydration can be started as soon as cholera symptoms
begin, then oral rehydration will be all that is required. ORS can either be
prepared from ready-mixed packets of salts (Section 8.1) or by making a sugar
and salt solution (Fig. 8.1). Unfortunately, most cases have already lost a
considerable quantity of body fluid on presentation, which means that they will
require intravenous infusion. If available, Ringer-lactate solution (Hartmann’s)
contains the nearest approximation of electrolytes to that being passed in the
diarrhoeal fluid. As a second best, a mixture of two units of normal saline and
one of sodium bicarbonate can be used. The patient should be rehydrated
intravenously as rapidly as possible, then oral rehydration solution substituted
once the patient can swallow. This allows the body mechanisms to regulate
electrolytes, as ionic imbalance can rapidly occur with intravenous infusion –
from which many patients succumb. The body fluid deficit should be restored,
followed by maintenance of one and a half times the equivalent amount of bowel
loss. Fluid loss can be measured into a bucket under the bed. A bed or cholera
cot is not essential though, and the patient can be nursed on a plastic sheet laid
on the ground with the earth hollowed out under the pelvis to take a receptacle to
collect the outpouring fluid.
Tetracycline is not essential in treatment, but shortens the duration of the illness
and quantity of fluid replacement required. Tetracycline is given in a dose of 500
mg 6 hourly for 3 days, or doxycycline in a single dose of 300 mg. Sensitivity
must be monitored as the development of tetracycline resistance will necessitate
changing to another antibiotic.
The management of a cholera epidemic requires speed and good
organization. Essentially, treatment is taken to the people by setting up treatment
centres at strategic places in the vicinity of the epidemic. These can be
dispensaries, schools, church halls or even tents that are supplied with staff and
fluids. Cholera patients do not need to be treated in hospital.
What is done for cholera in terms of surveillance?
Surveillance for cholera is both national and international. Under the
International Health Regulations (2005) any outbreak is a health event of
international concern so should be reported to the World Health Organization
(WHO). This will provide an advance warning system to other countries, but
neighbouring countries should be notified directly. Cases should be reported
using the WHO case definition and not just laboratory-confirmed cases.
Nationally, a warning system can be implemented for diarrhoeal diseases where
an increase in numbers, or in persons dying from diarrhoea, may indicate an
underlying outbreak of cholera (Fig. 8.2). There is considerable concern that V.
cholerae 0139 has the potential to cause a pandemic, so this serogroup should be
tested for. Where cholera exhibits a seasonal pattern, then the population and
health staff can be placed on the alert when the next season starts.
What microorganism causes hepatitis A?
Infectious hepatitis is a viral infection caused by hepatitis A virus
(HAV).
What are the clinical features of hepatitis A?
The main pathology is inflammation, infiltration and necrosis
of the liver, resulting in biliary stasis and jaundice. The infection generally starts
insidiously; the person feels lethargic, anorexic and depressed. Fever, vomiting,
diarrhoea and abdominal discomfort ensue, with the passing of pale-coloured
stools, before the appearance of jaundice reveals the diagnosis. Once jaundice
appears, the person generally starts to feel better. Hepatitis A is a mild disease
leading to spontaneous cure in the large majority, with only a few cases
developing acute fulminant hepatitis and, even more rarely, severe chronic liver
damage. There is an increase in symptomatic and severe cases with increasing
age, while children may be virtually asymptomatic
How is hepatitis A diagnosed?
Diagnosis is made on clinical grounds and by the demonstration of IgM
antibodies to HAV (IgM anti-HAV) in serum. When the symptoms are jaundice, the disease is determined by looking at clinical indicators (fever, lethargy, abdominal discomfort for hepA) and occurrence (worldwide, epidemic in institutions for hepA)
How is hepatitis A transmitted?
The early case is highly infectious, contaminating food and water.
Infection can also be transmitted directly from poor personal hygiene, such as by
handshaking. Intrafamilial transmission is the commonest pattern, generally due
to contamination of food and utensils by a food handler, but large epidemics can
occur where a person in the early stages of the illness prepares communal food.
Because of its insidious nature, the disease is not generally recognized until
jaundice appears, by which time infection may have been widely transmitted.
Hepatitis is mainly a disease of poor sanitation, with water and food as the
principal vehicles of transmission, but it can also occur when sanitation is good.
Salads, cold meats and raw seafood are common vehicles of transmission.
The carrier state is not important, but a large number of asymptomatic cases
are produced. Epidemics occur when sewage contaminates water supplies,
producing infection in people who have previously acquired some immunity,
suggesting that the disease may be dose dependent. Where there is a large
infecting inoculum, then infection can occur despite previous experience of the
disease. Chimpanzees and other animals have been found infected, but probably
have no epidemiological significance.
What is the occurrence and distribution of hepatitis A?
Hepatitis is endemic in most tropical countries,
children coming into contact with it early in life and developing a degree of
immunity. Non-immune persons, such as those from an area of good sanitation,
coming into this environment are likely to develop the disease. Epidemics occur
in developed countries, especially in institutions such as schools and prisons,
owing to poor food hygiene.
What is done in regard to control and prevention for hepatitis A?
During an outbreak of hepatitis A, extra effort should
be made to encourage scrupulous personal hygiene with hand washing. Anybody
who starts to feel unwell should be temporarily relieved of preparing food. In an
epidemic situation, a search should be made for the origin of the outbreak and
preventive measures taken. In the long term, water supplies and sanitation
should be upgraded.
Hepatitis A vaccine protects the individual at risk, and should be mandatory
for those going from an area of good sanitation to one of poor sanitation, such as
tourists and expatriates. Two doses are required given 6–18 months apart,
although one dose still gives high levels of immunity. Immunity from a two-dose
regime may be lifelong, but a booster at 10 years is currently recommended. As
most of the population in an endemic area will have met the infection as children
and either had no symptoms or just a mild infection, there is no case for mass
vaccination, except for high-risk groups. Some countries in the Americas now
include hepatitis A in the routine childhood vaccination programme.
How is hepatits A treated?
There is no specific treatment for hepA and supportive measures should be
undertaken. Fatty foods should be avoided and a good fluid intake maintained.
What is done in regard for surveillance for hepatitis A?
Once hepatitis (A) has been detected, health authorities should notify central authorities and surrounding areas.
What microorganism are the beef and pork tapeworms?
Parasites. Taenia saginata, the beef tapeworm, and Taenia solium, the pork tapeworm.
What are clinical features caused by beef and pork tapeworms?
The adult worm of both species can live in the intestines,
producing little pathology, being diagnosed often by accident. It does, however,
share the food supply of its host so that debility can occur. The serious problems
are due to the Cysticercus cellulosae (from T. solium). The cysticerci die and
calcify, those in the brain being a common cause of epilepsy or mental disorder.
Gastric disturbances can occur, often with mild pain, or the patient may
notice the proglottids being discharged. If people are unfortunate enough to be
infected with cysticercosis, they may suffer from convulsions, intracranial
hypertension (vomiting, violent headaches and visual disturbances) or
psychiatric disorders (confusion, apathy or dementia), there being a 50%
mortality in untreated cases.
How are beef and pork tapeworms diagnosed?
Diagnosis of beef and pork tapeworms is made by finding the proglottids in the faeces, with patients often
making their own diagnosis. It is very important to distinguish between T.
saginata and T. solium in view of the danger of inducing cysticercosis: T.
saginata has 18–30 compound branches of the uterus on each side, whereas T.
solium has only 8–12 (Fig. 9.6).
How are beef and pork tapeworms transmitted?
The adult worm lives in the small intestine of humans and as it
matures gravid segments break off and are passed in the faeces. Cattle or pigs
inadvertently eat the proglottids (the mature segments), or the discharged eggs
contaminate the pasture. Alternatively, the animal can become infected by
drinking water polluted by sewage. It has also been found that birds feeding on
sewage can carry eggs long distances and then deposit them on pastureland.
Flies might have a place in transmission as well. The eggs develop into
cysticerci in the muscles, favouring the jaw, heart, diaphragm, shoulder and
oesophagus. Humans acquire the disease by eating improperly cooked beef or
pork containing the cysticercus.
The beef tapeworm (T. saginata) and the pork tapeworm (T. solium) have the
same life cycle except that the intermediate stage, the cysticercus of T. solium,
can also occur in humans. This happens by swallowing eggs directly, either by
autoinfection from eggs in food or water, or through sewage contamination.
Also, any gastric disturbance that might cause the regurgitation of proglottids
into the stomach (including improper treatment) can lead to the liberation of vast
quantities of eggs, with the result that cysticerci are produced anywhere in the
body, including the brain, orbit and muscle.
What is the occurrence and distribution for beef and pork tapeworms?
Beef and tapeworms are the commonest and most cosmopolitan
of all the tapeworms, with a worldwide distribution in beef- and pork-eating
areas, especially in the tropical belt and Eastern Europe. Over 60 million people
are thought to be infected.
In such areas of beef and pork eating, there is a ready transmission cycle in
operation. Finding the worm in humans means that transmission is probably
reasonably common in that area, whereas in other places where beef and pork
eating are just as much part of the usual diet, but food hygiene is adequate, they
are not found. T. saginata is increasing in Europe, probably because of human
sewage contamination of animal drinking water. T. solium is common in Mexico,
Chile, Africa, India, Indonesia and Russia.
What is done in regards to control and prevention for beef and pork tapeworms?
The main means of controlling beef and pork tapeworms is the proper cooking of
meat. The underdone steak or joint of meat where internal temperatures are not
high enough to kill the cysticercus are common ways in which transmission can
still take place, despite cooking. Proper control of slaughtering in official
abattoirs, with meat inspection, can prevent the dissemination of infected meat.
Condemned carcasses must be burnt
What is the treatment for beef and pork tapeworms?
The treatment for both beef and pork tapeworms is with niclosamide 2 g as a single dose.
Alternatively, praziquantel as a single dose of 5–10 mg/kg can be given.
Praziquantel at a dose of 50 mg/kg for 15 days can be used for cerebral
cysticercosis in conjunction with corticosteroids, as an inpatient.
What is done in regards to surveillance for beef and pork tapeworms?
Where a localized cycle of infection of beef and/or pork tapeworms is occurring, investigation
may reveal a sewage leak or other source of contamination that could easily be
rectified.
What microorganisms are hookworms?
Parasites. Ancylostoma duodenale and Necator americanus cause the two
common hookworm infections of humans.
What are the clinical features of hookworms?
The infective (filariform) larvae directly penetrate the skin and
migrate to a blood or lymphatic vessel, where they are carried in the circulation
to the lungs. Here they break out of the alveoli, find their way up the trachea and
enter the gastrointestinal tract. The adult stage is finally reached in the
duodenum or jejunum, where the male and female worms mate and produce
eggs.
Despite its extensive journey through the human body, like Ascaris, the
hookworms are very well adapted to their host and only produce symptoms
when heavy infections occur. The passage through the skin can result in a
transient urticaria (ground itch), while that through the lungs can cause
pneumonitis and haemoptysis. Occasionally, the haemoptysis can be sufficient to
suggest a diagnosis of tuberculosis. The main effect results from the adult worms
attaching to the intestinal wall, where they invaginate a piece of mucosa and
extract blood and nutrients. Anaemia results from continued blood loss and
depletion of iron reserves. The degree of anaemia produced depends on the
worm load, and one estimate calculates that 60–120 worms (measured by 30
worms excreting 1000 eggs/g faeces) will result in slight anaemia, whereas over
300 worms (10,000 eggs/g faeces) will cause severe anaemia. The newly
established worm may produce several bleeding points, and if the sexes are
unbalanced the search for a mate can result in increased activity. These effects
will naturally be most profound in the growing child and the pregnant woman. It
is the combination of malaria, malnutrition and other intercurrent infections with
hookworms that accentuates the seriousness of this infection.
On the plus side, recent research suggests that low-level infections may have a
protective effect from the child developing asthma, inflammatory bowel
disorders and even diabetes type 1. So long has the parasite been in association
with humans that the anti-inflammatory substances secreted by the worms are
used to desensitize the body. So a few worms may be an advantage.
How are hookworms diagnosed?
Hookworm eggs are found in faecal examination. They are oval and have
colourless thin walls that differentiate them from Ascaris, which has a thick
brown exterior. The eggs of the two hookworm species are identical
and only the adults can be differentiated, mainly from their characteristic
mouthparts. A polymerase chain reaction (PCR) method of
identification can be a useful additional aid.
How are hookworms transmitted?
The eggs are passed in the faeces and hatch within 24–48 h to
liberate an intermediate (rhabditiform) larva. After some days, it moults to
produce the infective filariform larva. In suitable conditions of moist, warm but
shaded soil (30°C for N. americanus and 25°C for A. duodenale), this stage of
the larva can live for several months, awaiting the opportunity to penetrate
through the skin of a new host. (The ingested third-stage larvae of Ancylostoma
can also produce infection.) The larva commonly penetrates the foot of the
unshod person and intense infection can occur where areas of beach or bush are
demarcated for defecation purposes. Non-human hookworms can also penetrate
the skin and produce cutaneous larva migrans.
Young infants can have very high infections due to larvae in the mothers’ breast
milk. Hormonal change during pregnancy causes a migration of dormant
hookworms, many of which reach the mammary glands.
What is the occurrence and distribution of hookworms?
N. americanus, despite its name, is the more
widely distributed, being found extensively throughout the tropical belt and well
north of the tropic of Cancer in America and the Far East. A. duodenale is found
in the Far East, the Mediterranean and the Andean part of South America (Fig.
10.3). It has been suggested that N. americanus was carried from Africa to the
Americas as a result of the slave trade. Altogether, some 740 million of the
world population have hookworms.
What methods of control and preventions for hookworms?
Control and prevention is of hookworms by use of pit latrines or other methods of sanitation.
The wearing of footwear effectively prevents penetration by the larvae. The open sandal type of footwear often worn (thongs, flip-flops) is not effective and
infection can readily occur. Mass treatment can be given to reduce the parasite load, but without health education and the proper use of latrines this will only
produce a temporary improvement.
How are hookworms treated?
A number of drugs are effective in treatment of hookworms: albendazole 400 mg
single dose, mebendazole 500 mg single dose or 100 mg twice a day for 3 days;
levamisole 2.5 mg/kg daily for 3 days; oxantel 10 mg/kg daily for 3 days; or
pyrantel pamoate 10 mg/kg daily for 3 days. The treatment should be repeated
12 weeks after the original course of treatment. There is concern that resistance
could develop, as has happened in veterinary practice, so combinations such as
mebendazole plus levamisole or pyrantel plus oxantel have been advocated. In
the debilitated child, supportive therapy will need to accompany deworming.
Iron supplementation, or in the severe case blood transfusion, will be required to
treat the anaemia.
In the treatment of filariasis and onchocerciasis, a combination of albendazole
plus ivermectin or albendazole plus diethylcarbamazine are used (see Sections
15.7 and 15.8), so treatment of helminths often occurs as an extra benefit. The
albendazole plus ivermectin combination is more effective for Ascaris and
Trichuris.
What is done for surveillance for hookworms?
When mass treatment is planned, an initial survey will delineate
the size of the problem. Follow-up spot checks of individual stool specimens can
be made to assess progress.
What are the microorganisms causing schistosomiasis?
The main parasites are Schistosoma haematobium, S. mansoni and S.
japonicum. Other species, such as S. intercalatum and S. mekongi, do occur, but
they are only important in well-defined areas and their epidemiology and control
are similar to those of one of the three main types.
What are the clinical features of schistosomiasis?
Infection normally starts in childhood, often with very few
signs of the disease until adulthood. Passing blood in the urine is one of the first
signs of S. haematobium disease, but because it is so common in the local area it
is generally ignored; boys thinking it quite normal that they should have period
bleeding like girls do. Infection and egg output increases up to about 15 years of
age and then declines; individuals vary in their response, some persons acquiring
heavy infections and developing severe pathological changes, while others have
only minor symptoms. The more serious manifestations are liver fibrosis, portal
hypertension and obstructive urinary problems, the pathology depending upon
the species of parasite and the number of eggs deposited in the tissues; S.
mansoni and S. japonicum infections lead to intestinal and liver damage, while S.
haematobium infection leads to bladder complications, including bladder cancer.
How is schistosomiasis diagnosed?
Diagnosis of schistosomiasis is made by finding the characteristic eggs (Fig. 9.1), in S.
haematobium in the urine, and in S. mansoni and S. japonicum in the faeces or
from a rectal snip. Urine samples are best collected between 11.00 and 15.00 h,
when egg output is at a maximum. Leaving the urine to stand, centrifuging it, or
passing it through a filter increases the chance of finding eggs. While qualitative
diagnosis is required in the individual case, quantitative estimates are more
valuable in epidemiological investigations. In S. haematobium, the simplest
method is to pass 10 ml of urine through a filter in a Millipore holder. The paper
or membrane is taken out, dried and stained with ninhydrin and the eggs counted
directly. Immunological methods, immunofluorescence antibody test (IFAT) and
enzyme-linked immunosorbent assay (ELISA), have also been developed for
schistosomiasis, but they only indicate recent or past infection, so eggs must be
looked for to confirm the diagnosis. However, these tests are useful in
epidemiological surveys for rapidly defining the extent of the infected area.
Pathology is related to the number of worms, which can be measured by the
number of eggs produced. In S. haematobium, the production of 50 eggs/ml of
urine or above is regarded as the level of severe pathology and much of presentday control strategy is aimed at reducing the egg count to below this level.
How is schistosomiasis transmitted?
Infection results from cercariae directly piercing the skin of a
person when they go into the water. On penetrating the subcutaneous layer of the
host, the cercaria becomes a schistosomule, migrates to the lungs and finally
develops into an adult in the portal vessels of the liver. Both male and female
worms are required, so pairing takes place prior to migration to the final
destination in the mesenteric or vesical plexus. Adult worms can live 20–30
years, but are active egg producers for 3–8 years, although some have produced
viable eggs for over 30 years. The egg output/day in S. haematobium is some
20–250, in S. mansoni 100–300 and in S. japonicum 1500–3500. It is this
massive output of eggs in S. japonicum that leads to the more rapidly developing
and severe pathology of infection with this parasite.
Less than 50% of eggs manage to pass through the bladder or intestinal wall
to develop further, the remainder being trapped in the tissue. On reaching water,
a temperature of 10–30°C and the presence of light induce hatching. Miracidia
actively search out a snail using geotactic and phototactic behaviour, homing in
on a chemical substance ‘miraxone’, inadvertently liberated by the snail. The
miracidium must penetrate a snail within 8–12 h, their chance of success
decreasing with age. Some 40% of snails are infected at a distance of 5 m in still
water, but where the water is moving, similar infection rates can occur at a far
greater distance. Normally, infection occurs in water flowing at 10 cm/s or less.
Even after the rigours of the journey, when miracidia have entered the correct
species of snail, many are inactivated and only a small proportion develop into
sporocysts. This is determined by the part of the snail entered and immunity to
reinfection developed by the snail.
Cercariae are stimulated by light to emerge from the snail when the ambient
temperature is between 10 and 30°C. Cercarial emergence increases as daylight
penetrates the watery environment, producing a peak for S. mansoni at 12 noon
and for S. haematobium in the mid-to-late afternoon. With S. japonicum, the
stimulus produced by light is delayed and maximal cercarial liberation occurs at
23.00 h. The number of cercariae issuing from a snail can be immense, in the
order of 1000–3000/day, but this depends upon the species and relative size of
the snail. Where more than one miracidium has penetrated a snail, there is
depression of cercarial production; this may also occur if the snail is host to
other trematode infections. Cercarial output is greatest in S. mansoni, less in S.
haematobium and least of all in S. japonicum. Cercariae survive for 24 h, but
their greatest chance of penetrating the host is when they are young. When
cercariae enter within 2 h of release, only 30% die, but this rises to 50% at 8 h
and 85% at 24 h.
The snail intermediate hosts are species specific, Bulinus spp. in S.
haematobium, Biomphalaria spp. in S. mansoni and Oncomelania spp. in S.
japonicum. They are illustrated in Fig. 11.1. They can adapt to a wide range of
habitats, from natural waterways to temporary ponds and cultivated rice fields.
Whenever there is sufficient organic matter on which to feed, snails will be
found. Within a body of water, distribution may be quite irregular, with dense
colonies in some places and complete absence in others. Various factors which
may influence snail colonization, are:
• Electrolyte concentration. Snails demand a minimum calcium concentration,
and cannot tolerate high salt content or a low pH.
• Light is not required by the snail, and they can often survive in near total
darkness.
• Rainfall may herald the end of the dry season and provide water in which snail
populations can increase, but if the rainfall is too heavy it may flush out the
snails, resulting in a subsequent decrease. Snail populations may therefore
follow a seasonal pattern.
• Temperature rise encourages expansion of the population up to a maximum of
approximately 30°C.
• Density is a limiting factor and results in reduced growth.
• Aestivation or the ability of snails to survive out of the water for weeks or
months allows populations of snails to continue from one season to another,
possibly also transferring immature infections of S. haematobium and S.
mansoni. The snail host of S. japonicum can survive conditions of desiccation
best of all.
Snails are capable of self-fertilization, although cross-fertilization is more
common. Their reproductive capacity is phenomenal and a single snail can
produce a colony within 40 days and be infective in 60. When conditions are
optimal, many species of snails will double their population in 2–3 weeks. In
measuring the age of snail populations, size of snails is a useful indicator. A
large number of small samples from several different areas are preferable to a
few large samples in estimating the numbers and density in watercourses.
Infection rates in snails are generally low, only some 1–2% of the colony being
infective, but even so, this level is sufficient to account for high prevalence rates
in the human population.
Humans contaminate water either by urinating or defecating into or near
watercourses. Egg output is variable between individuals and at different times
in their lives; a few individuals have heavy infections and egg outputs, while the
majority have light infections. In areas of high endemicity, children between 5
and 14 years are responsible for over 50% of the contamination. As the infection
rate declines, then older age groups become more important.
People are infected by collecting water, washing (both clothes and the
person), in their occupations (such as fishing) or during recreation. Children are
most commonly infected when they play in the water, while in adults it is when
they carry out their domestic duties or occupations. Infection is generally due to
repeated water contact over a long period, but can occur from a single immersion
if it coincides with a large number of cercariae in the water.
Animals such as water buffalo, cattle, pigs, dogs, cats and horses can also
serve as reservoirs of S. japonicum, but they are less important than humans as
sources of infection.
What is the occurrence and distribution of schistosomiasis?
S. haematobium and S. mansoni were originally
diseases of Africa, where they were widely distributed, but with the massive
exodus of slaves that took place in the 17th and 18th centuries this legacy was
carried with them. The East African slave trade carried S. mansoni to the
Arabian peninsula, and S. haematobium to the Yemen and Iraq. The Western
trade was solely in S. mansoni, which found a suitable snail host in South
America and the Caribbean. S. japonicum probably originated in China, where it
has been discovered in mummified bodies, but is also found in the Philippines,
Taiwan and Sulawesi in Indonesia (Fig. 11.2). No cases have been found in
Japan since 1978. A separate species, S. intercalatum, pathogenically similar to
S. mansoni, is found in the Congo, Cameroon, Central African Republic (CAR),
Chad, Gabon and São Tomé. S. mekongi is restricted to the Mekong River basin
in Laos, Thailand and Cambodia. Other localized species are Schistosoma
malayensis in Peninsular Malaysia and Schistosoma mattheei in southern Africa.
Climate change is likely to reduce the areas where S. mansoni is prevalent
due to it becoming too hot for the snail host to breed. However, in areas where
the snail is reduced by a cooler temperature, such as in southern Africa,
increased warming could increase its endemicity.
What is done for control prevention and treatment for schistosomiasis?
Control, prevention and treatment. There are two approaches to the control of
schistosomiasis:
• Reduce the transmission of the parasite.
• Reduce the level of infection in individuals.
The first attempts to control the parasite, while the second aims at minimizing
the pathological effects. The various methods of control are:
Reduce contamination of the environment. Humans pollute the
environment by urinating or defecating into bodies of water. This can be
minimized by encouraging the use of latrines. Unfortunately, it is very difficult
to get everybody in a family or community to always use a latrine and the few
non-users will be sufficient to maintain a level of pollution (see Section 2.4.2).
There is also the longevity of the adult worms, meaning that prevalence rates
will remain static in the community for a considerable length of time.
Reduction of the snail intermediate host. The snail is a vulnerable link in
the life cycle of the parasite and can be attacked in an effort to break
transmission. The various methods that can be used are:
• predators;
• biological control;
• water management and engineering; and
• molluscicides.
Various kinds of fish (Tilapia and Gambusia particularly) are natural
predators, but they will only reduce snails to a certain level unless they have an
additional source of food when there are few snails left. Snails, especially of the
Marisa and Helisoma genera, compete for food supplies and Marisa will even
prey on eggs and juveniles of Biomphalaria. Another approach to biological
control is the sterile male technique, but as many snails are hermaphrodite, this
is only suitable with Oncomelania.
Where foci of infection consist of small and temporary ponds, these can be
drained or filled (by controlled tipping of household refuse). Where canals and
irrigation systems are responsible, then a concrete lining, increasing the rate of
flow and any method to reduce vegetation can discourage snail habitation.
Unfortunately, these methods are rarely effective on their own and need to be
combined with a molluscicide, niclosamide (Bayluscide), which can be
administered as a liquid, which is suitable for treating moving water, or as
granules in lakes and ponds. Continuous application is required to have a
sustained effect on the snail population. This method has the disadvantage of
killing fish and is expensive. Cheaper preparations, such as copper sulfate, are
still in limited use and naturally occurring plant preparations such as Endod
(Phytolacca dodecandra) have shown promise. However, the remarkable
recovery of snail populations once control methods are removed, and the cost of
molluscicides, make snail reduction a less effective approach to schistosomiasis
control.
Reduction of water contact. Preventing water contact can be highly effective
in the individual. Various ways of encouraging this are:
• Health education, especially in schoolchildren, but this is often ineffective
unless an alternative, e.g. swimming pool, is provided.
• Providing places to wash has been disappointingly ineffective for the cost
involved.
• Where areas of absent or minimal transmission occur in occupational or
recreational bodies of water, people can be encouraged to use these, rather
than the heavily infected parts.
• Wearing rubber boots when wading through water, or if accidental exposure
occurs, then rubbing vigorously with a towel and applying 70% alcohol.
• Drinking water can be treated with iodine or chlorine, or if left to stand for at
least 48 h, cercarial die-off will be complete.
Reduction of human infection by mass chemotherapy. Praziquantel single
dose mass drug administration at 40 mg/kg is now the method of choice. A
suitable target population is schoolchildren between 5 and 15 years of age, where
mass therapy is used. Alternatively, only the positive cases, or those with heavy
infections, are treated following a simple diagnostic procedure. Individual
treatment, based on worm-load estimation, aims at disease control by reducing
morbidity. It permits limited resources to be more widely spread and attempts the
less ambitious target of disease reduction rather than transmission reduction.
The antimalarial drug artemethur is also valuable in the control of
schistosomiasis and could be used in areas where there is no malaria, such as
China, southern Brazil and South-west Asia. It can be used in combination with
praziquantel.
Reduction of the animal reservoir. Animal reservoirs are responsible for
maintaining S. japonicum. In order of importance, these are dogs, cows, pigs,
rats and water buffalo. As most of these are domestic animals, proper animal
management can reduce contamination of the environment. Vaccination of
domestic animals could be used. Baboons and monkeys have been shown to be
reservoirs of S. mansoni and could play a part in maintaining infection. There is
little prospect of controlling these animals.
Vaccination. There are difficulties in preparing a vaccine because the
schistosome is able to absorb host antigen and mask its presence, but several
vaccines are under trial. A 28 kD S. haematobium GST (glutathione Stransferase) vaccine is showing some promise, while S. mansoni antigens have
also been tried, but no vaccine has shown more than partial protection. Another
approach is to reduce egg production in female worms, with which some success
has been achieved in S. japonicum.
Strategies for schistosomiasis control. Various different approaches to the
control of schistosomiasis have been tried depending on the resources and nature
of the disease, as follows:
• The raising of economic standards by the provision of water supplies,
sanitation, environmental engineering and water management has been shown
to be effective on a long-term basis in countries such as Japan and China.
• In well-controlled irrigation schemes, mollusciciding on its own may be
effective. Where discipline and motivation of the population are less certain,
then a double approach of mass chemotherapy and reduction of water contact
is more effective.
• When resources are meagre and the greatest benefit for limited finance is
required, then treatment of high worm load cases is the method of choice.
What is done for surveillance for schistosomiasis
Effectiveness of control strategies can be measured by:
• change in incidence rate;
• a shift in peak prevalence to an older age group;
• reduction in geometric mean egg output; and
• greater awareness of socio-economic values, e.g. the use of water supplies and
sanitation facilities.
Which microorganism causes measles?
Measles virus is a member of the Paramyxoviridae family of viruses.
What are the clinical features of measles?
Measles normally commences with a prodromal fever, cough,
conjunctivitis and small spots (Koplik’s spots) most easily seen inside the mouth.
The characteristic blotchy rash begins on the third to seventh day of the illness,
generally on the face, but soon spreads to the whole body.
In developing countries, measles is a serious disease and accounts for a
considerable amount of mortality and morbidity in the childhood population. It
has a particularly severe effect on the nutritional status of the child, so the
healthy child will lose weight and the malnourished child will become critically
ill. The peak of infection is between 1 and 2 years of age, at the very time when
breast milk alone is an inadequate source of food and weaning foods may not yet
have been introduced. The association of nutritional change and measles can be,
and often is, a lethal combination.
There are a number of reasons for the nutritional depletion produced by
measles. Any disease process puts extra demands on the body, increasing
catabolism. Fever and the desquamation of all epithelial surfaces demands
protein replacement, which is handicapped by a sore mouth, often secondarily
infected by Candida, preventing the child from sucking properly, so that even
breast milk is not taken. Then from the other end, diarrhoea, which is such a
common feature of measles in developing countries, discharges further the body
reserves. But perhaps the greatest weight loss is due to immunosuppression,
much of this taking place after the child has recovered from the acute attack.
The disease process attacks all epithelial surfaces, producing most of its
complications in the respiratory tract. Pneumonia is the commonest
complication, while laryngotracheobronchitis is serious, with a high mortality.
Acute respiratory infections (ARIs, see Section 13.2) are one of the leading
causes of childhood ill health, and the sequelae of measles responsible for a large
component of this problem. If the acute pneumonia does not kill, the damage
done makes the child more susceptible to further attacks of respiratory infection
when the measles has long gone.
The effects on the eye can cause blindness. Corneal lesions result from
epithelial damage, which can lead to ulceration, secondary infection and
scarring. In severe cases, perforation or total disorganization of the eye can
occur. These severe effects only result if there is concomitant Vitamin A
deficiency, so giving Vitamin A to all measles cases is effective. Measles, by its
nutritional and direct effects, has been regarded as the most important cause of
blindness in a number of tropical countries.
Measles is an important cause of otitis media. It can also result in
encephalitis, either the acute form or a late slow-onset sclerosing
panencephalitis, which is always fatal.
How is measles diagnosed?
Measles is diagnosed on clinical criteria, but measles IgM can be found in the saliva with
immunological tests.
How is measles transmitted?
Although the main feature of measles is the skin rash, it is
transmitted by the airborne route, from nasal and pharyngeal secretions. This can
be by articles contaminated with secretions, such as cloth or clothing used to
wipe a running nose, as well as by respiratory droplets produced in a coughing
bout. Virus can remain active in droplets in the air or on surfaces for up to 2 h.
Measles is the most contagious of all infectious diseases and no age is
spared. In the Fijian outbreak in the 1870s, adults as well as children succumbed,
so that whole families were affected at the same time, deprivation and starvation
resulting in a high death rate. Now that adults have experienced measles as
children, the age of infection is getting younger. This is explained by greater
contact of communities due to improvement of communication, while the
intense social contact at a very young age (babies carried on their mothers’
backs) gives maximum opportunity for early transmissions.
What is the occurrence and distribution of measles?
Measles has been a severe infection in Western
countries for a considerable period, producing mortality in poor and slum
populations similar to that now seen in developing countries. Introduced with
European exploration, it caused devastating epidemics, particularly in island
communities, some of which never recovered their former population numbers.
However, in many developing countries, in which it is a major problem, there is
evidence that measles has been present for several 100 years, the pattern having
changed from sporadic epidemics with all ages involved to one of endemicity in which the under 5 year olds are predominantly affected.
What is done for the control and prevention of measles?
Control and Prevention of measles is by vaccination. As measles is such an
infectious disease, it can be reckoned that every child will develop it. Some 10%
will either have such a mild infection or be partially protected by maternal
antibodies as to appear not to have been infected. A further 10–20% will not
have measles until the following year owing to the epidemic effect, so the
expected number of cases of measles can be calculated from the birth rate minus
25%. If the birth rate in a developing country is 50/1000, then 75% of this means
that 37.5 cases of measles/1000 can be expected each year, which represents
37,500 cases in an administrative unit of a million people. Calculations like these
can be used to estimate the number of children to be vaccinated and hence the
vaccine requirements.
At least 80% of susceptibles will need to be vaccinated to produce control of
the disease, but a lower target may be acceptable in more isolated communities.
This target will need to be achieved every year in rural areas, but as much as
every 6 months in urban areas. Measles vaccine is 90% effective if the cold
chain is not broken.
Maternal antibodies protect the newborn infant for the first 6 months of life,
but thereafter the child becomes readily susceptible to infection, with a peak
around 1 year. The seroconversion rate is some 76% at age 6 months, 88% at 9
months and 100% at 12 months. Giving measles vaccination at 1 year would
produce the best conversion, but by that time in developing countries some 50%
will already have had the disease. Giving it at 6 months will be before all but a
few have had the disease, but the seroconversion rate is so poor that not many
will be protected. The best compromise is a first vaccination at 9 months, with a
second vaccination at 12–18 months. In conditions of high infectivity, such as
during an epidemic, admission to hospital or in a refugee camp, or in areas of
high HIV prevalence (or if the infant has HIV), then reducing the age of
vaccination to 6 months is justified. In this case, two further vaccinations should
be given, the second between 12 and 15 months.
In developed countries, vaccination is given at 12–13 months so the time
taken to reduce the incidence in the population will be less, as shown in Fig.
12.1. The greater the coverage, the more rapidly this is achieved. For example,
60% coverage will theoretically take 12 years to reduce the incidence to zero if
vaccination is given at 12 months, but will never be achieved with vaccination at
9 months. However, 70% coverage will achieve zero incidence with vaccination
given at 9 months; this is being achieved by an increasing number of developing
countries.
Effective measles vaccination coverage will not only reduce the number of
children developing the disease in an epidemic, but will have the secondary
benefit of raising the age of developing the disease, as can be seen in Fig. 12.2.
Epidemics had occurred in the Namanyere area of Tanzania regularly every
second year until 1978, when there was only a minor increase, the main
epidemic being delayed until 1979. This meant that children born in 1977 who
could have expected to become infected in their second year of life (1978) had
their measles put off until 1979, when they were beyond the age of maximum
mortality.
The chances of a susceptible child developing measles when admitted to
hospital are very high as he or she is already sick with another complaint. It is
fortunate that measles vaccine can produce protective immunity quicker than the
wild virus (about 8 days for the vaccine and 10 for the disease), so as long as the
child is vaccinated within 48 h of admission, he or she will be protected.
Because of the severity of disease in the debilitated child, there are very few
contraindications and the malnourished and those with minor infections should
all be vaccinated. HIV infection is not a contraindication as the child is more
likely to die from measles than from any complications of receiving a live
vaccine.
As vaccination coverage is increasing, a potential problem could arise
because less maternal antibody is produced by mothers who have acquired their
immunity from vaccination rather than by having measles. This means that
infants of a younger age will become susceptible, so vaccination may need to be
given earlier if coverage is not complete.
Measles vaccine is conveniently combined with rubella (MR) or with both
rubella and mumps (MMR) in countries intending to vaccinate against these
diseases. Despite adverse publicity given to the MMR vaccine, no complications
have been confirmed and the vaccine should continue to be used. However,
MMR or MR should only be used in countries with a high vaccination coverage
(over 80%) or else there is a danger of shifting the age of developing rubella, and
hence congenital rubella syndrome (CRS), to women of childbearing age (see
Section 12.3).
Because of the effectiveness of measles vaccination, there is the very real
hope that measles can be eliminated as a public health problem. A measles
elimination programme has therefore been launched by WHO. On 29 April
2015, the WHO Region of the Americas was certified as having eradicated
measles. This has been an incredible achievement and gives hope that similar
action can eliminate this disease from other parts of the world.
What is the treatment for measles?
There is no specific treatment for measles, but supportive therapy with fluids and
easily digested foods needs to be given. Vitamin A supplementation should be
given to all children with measles. Complications may require additional
treatment, such as antibiotics for bacterial chest infections.
What is done for measles surveillance?
All cases of measles should be recorded and monthly totals
charted to indicate epidemics and estimate when new epidemics will occur (Fig.
12.2). Measles has a seasonal pattern, which can vary markedly from country to
country (Fig. 1.9), so this needs to be determined to work out the best time to
supplement routine vaccination programmes. If measles cases are focal, then this
may indicate gaps in vaccination coverage. As all children should be
vaccinated, an estimate of vaccine coverage can be made by comparing the number of new vaccinations with the number of children born.
What microorganism causes leprosy?
Mycobacterium leprae
What are the clinical features of leprosy?
Leprosy more dramatically than any other disease illustrates
the conflict between the infecting organism and the host. M. leprae is
widespread in the environment, yet only a small proportion of people ever show
clinical symptoms of the disease, and the few that contact the disease respond in
different ways to the challenge.
The generation time from inoculation to multiplication of a stable number of
M. leprae is only 18–24 days, but the development of the disease will take
anything from 7 months to in excess of 7 years (mean 3–6 years). The first lesion
is described as indeterminate (Fig. 12.3), because at this early stage it is
impossible to decide to which place in the spectrum of disease it will develop.
There is either a single, ill-defined, slightly hypopigmented macule, commonly
seen on the face, trunk or exterior surfaces, or there may be a small anaesthetic
patch. The lesion will then develop into a lepromatous or tuberculoid type, or
oscillate in the transitional state of borderline leprosy between these two
extremes.
Lepromatous leprosy (LL) reflects the complete breakdown of the host’s
immune responses and the maximum infection with M. leprae. In the early
stages, signs of disease may be very few, but a skin smear will reveal large
numbers of mycobacteria (multi-bacillary). Early signs that have been described
but rarely observed are oedema of the legs and nasal symptoms of stuffiness,
crust formation and bloodstained discharge. These are unlikely to be recognized
as leprosy and it is generally not until the more obvious skin lesions become
apparent that the diagnosis is made.
Leprosy lesions favour the cooler parts of the body, so the buttocks, trunk,
exposed limbs and face are the more likely sites. Lesions may be macules,
papules or nodules, with or without a colour change, and often show lack of
sweating when the patient becomes hot. The signs of nerve damage do not
appear until much later in lepromatous leprosy, with a concurrent thickening of
the skin of the forehead, loss of eyebrows and damage to the cartilage of the
nose. The eyes are also attacked with an infiltrative keratitis, iritis and eventually
blindness.
Tuberculoid leprosy (TT) is at the opposite end of the spectrum, showing the
full response of cell-mediated immunity to the attacking organism (Fig. 12.3). M.
leprae has a predilection for nervous tissue and it is within this nervous tissue
that the cell-mediated response takes place, causing early damage to the nerves.
The tuberculoid patient therefore tends to present early with signs of weakness
or loss of sensation. Palpation of the nerves will often demonstrate a thickening
with loss of sensation or motor power in the distribution of the affected nerve.
The ulnar nerve as it bends over the medial epicondyle at the elbow or the lateral
popliteal nerve where it curves round the neck of the fibula are good places to
palpate nerves for thickening. Dermal lesions are not raised, often appearing as
apparently normal areas of skin, but lacking sensation or sweating when the
patient exercises. Occasionally though, lesions are well defined and scaly with
raised edges, but quite different from the succulent macules and papules of
lepromatous leprosy. Loss of sensation should be demonstrated with a pin as
well as with light touch. A skin smear in tuberculoid leprosy is nearly always
free of bacilli (pauci-bacillary), so the diagnosis depends upon the detection of
nerve damage.
Borderline leprosy, as its name suggests, is on the border between the two
extremes of lepromatous and tuberculoid leprosy. True borderline (BB) leprosy
is uncommon, with the disease tending to progress to either the lepromatous
(BL) or tuberculoid (BT) part of the spectrum. Signs therefore vary between the
two extremes with features of each, but predominating in the features of one or
the other. Borderline leprosy is common, but its instability leads to reaction and
nerve damage, which can often be severe.
Where the host response is adequate and cell-mediated immunity high, the
disease tends towards the tuberculoid end of the spectrum; where response is
low, the disease tends to lepromatous leprosy. Simultaneous HIV infection will
shift the host response from tuberculoid towards lepromatous. Otherwise, the
host response can vary over the course of the illness, producing reactions, which
can either be upgrading (towards tuberculoid leprosy) or downgrading (towards
the lepromatous). These are type 1 reactions. The nearer the case is to the centre
of the spectrum, the more severe the reaction. Type 1 reactions may affect all
tissues, or skin and nerves only, or produce a generalized systemic reaction.
A different type of reaction (type 2) is found in lepromatous and borderline
lepromatous cases and is associated with massive destruction of bacilli. Immune
complexes are formed in the tissues and these lead to an increased reaction in
existing lesions. The characteristic finding is erythema nodosum leprosum,
which appears on the skin as painful red nodules, commonly on the face and
exterior surfaces.
How is leprosy diagnosed?
A skin smear is made from every suspected case of leprosy,
collecting dermal tissue without drawing blood. A negative smear does not mean
that a case is not leprosy, as tuberculoid cases rarely have mycobacteria. Smears
are stained with Ziehl–Neelsen stain and the number of mycobacteria counted to
give the bacillary index.
6+ Over 1000 bacilli in an average field
5+ 100–1000 bacilli in an average field
4+ 10–100 bacilli in an average field
3+ 1–10 bacilli in an average field
2+ 1–10 bacilli in 10 fields
1+ 1–10 bacilli in 100 fields
Mycobacteria can also be obtained from nasal scrapings of the inferior
turbinate. A skin biopsy is taken from tuberculoid and borderline patients, or a
nerve biopsy where there is no skin lesion.
How is leprosy transmitted?
After a long period of uncertainty it has finally been shown that
leprosy is transmitted via droplets from the nose and mouth during close and
frequent contact. Large numbers of bacilli are found in the nasal discharges of
lepromatous cases, and these are able to survive for 2–7 days outside the body.
Individuals vary in their susceptibility and it is possible that repeated doses of
bacilli, or a large infective dose, are required to produce disease.
What is the occurrence and distribution of leprosy?
Leprosy is found mainly in the tropical regions of
the world, with poor socio-economic conditions probably a major factor.
Lepromatous leprosy is more common in Asia and tuberculoid in Africa. This
differing susceptibility might help to explain the response to BCG (Bacillus
Calmette–Guérin) vaccination (see Section 13.1) in these two peoples. BCG
given at birth can produce a hypersensitivity and change the cell-mediated
immunity from negative to positive, but some people appear to have no natural
immunity and remain always susceptible to the lepromatous form of the disease.
BCG protected over 80% of schoolchildren in Uganda, but only 40% of children
under 5 years of age in Myanmar.
Leprosy can occur in an epidemic as well as an endemic pattern, but owing
to the incredibly protracted life history of the disease, the epidemic form is rarely
seen. Between 1921 and 1925 there was an epidemic on the Pacific island of
Nauru; 30% of the population was infected and the disease was notably nonfocal. All ages were susceptible, with most people developing tuberculoid (BT–
TT) leprosy, which healed spontaneously.
It has been estimated that up to 5% of people are susceptible to lepromatous
leprosy and contact with a lepromatous case increases the risk of infection.
Children and young adults are more commonly affected, but the children of
leprosy patients do not develop lepromatous leprosy any more frequently than
the general population. It would seem that leprosy is very similar to tuberculosis
(TB) in that the organism is more common than realized, asymptomatic
infections may occur, but only those that are susceptible will develop the disease.
Due to active control measures and multidrug therapy, there has been a
marked reduction of leprosy in the world, with 180,000 new cases detected in
2012. Foci of high endemicity remain in Angola, Brazil, Central African
Republic (CAR), Democratic Republic of Congo (DRC), India, Indonesia,
Madagascar, Mozambique, Nepal and Tanzania.
How is leprosy being controlled and prevented?
The immediate control is a reduction of the leprosy
reservoir by case finding, treatment and follow-up, especially of those with the
lepromatous form of the disease. A small proportion of cases will present
themselves, but an active search must be made for others, concentrating on
selective groups. Schoolchildren should receive priority, as they are likely to
contain a quarter of all cases and a higher proportion of new ones. Also, contacts
of any case should be examined at frequent intervals, as leprosy is more common
in those people that have prolonged contact with a leprosy case. All new cases
are treated by multidrug therapy (see below).
BCG vaccination induces hypersensitivity and increased resistance to
developing leprosy in some ethnic groups, so is valuable in the prevention of
leprosy as well as TB (Section 13.1). M. leprae-based vaccines are under trial in
several countries, with promising results. The long-term reduction of disease will
require an improvement in general hygiene, better housing and less
overcrowding.
How is leprosy treated?
Treatment is determined by the bacillary index of the case.
1. High risk (multi-bacillary) LL and BL cases: a three-drug regime consisting of
rifampicin 600 mg once a month supervised, dapsone 100 mg daily selfadministered, clofazamine 300 mg once a month supervised, then 50 mg daily
self-administered. Treatment should be continued for a minimum of 12 months.
2. Non-bacillary cases, BT or TT: rifampicin 600 mg once a month supervised,
plus dapsone 100 mg daily self-administered, for 6 months or six monthly doses
within a 9 month period.
3. Non-bacillary single skin lesion: single dose of rifampicin 600 mg, ofloxacin
400 mg and minocycline 100 mg.
All patients with positive skin smears at the start of treatment should have
repeat skin smears at 6 and 12 months. Clofazamine has the advantage of being
anti-inflammatory as well as bacteriostatic, so can be used in the treatment of
reactions at a dose of 100 mg three times a week. Steroids and thalidomide are
useful in the treatment of reactions.
Part of any leprosy programme is the development of a rehabilitation
service. This not only encourages leprosy patients to present themselves for
treatment, but also helps to return them as participating members of the
community. Much can be done from limited resources, such as making sandals
out of old tyres and pieces of wood. The elements of rehabilitation are to protect
anaesthetic limbs, actively treat sores and ulcers, and provide support (including
surgery) to restore function. The eyes are also damaged in leprosy and
supportive treatment can do much to prevent blindness from developing.
What is done for surveillance for leprosy?
. Dedicated leprosy fieldworkers have been found to be of
considerable value in detecting new cases and following up cases under
treatment, otherwise a system within the existing health service should be
developed. Combining leprosy and TB surveillance is a useful economy.
Initially, whole populations should be screened in areas of high endemicity,
then concentration should be on examining schoolchildren and all contacts of
cases. All cases should be registered, often managed as a combined programme
with TB. Section 13.1 on TB follow-up and registration is equally applicable to
both diseases.
What is the microorganism causing tuberculosis?
Mycobacterium tuberculosis, but infection can also be caused by
Mycobacterium bovis (from cattle) or Mycobacterium africanum. There are
many mycobacteria occurring naturally in nature, including Mycobacterium
avium, Mycobacterium intracellulare and Mycobacterium scrofulaceum, that can
sensitize the individual and interfere with the BCG (Bacillus Calmette–Guérin)
vaccination against TB. In endemic countries, M. tuberculosis is widespread, and
a quarter to a third of people in developing countries will develop the disease.
What are the clinical features of tuberculosis?
A productive cough with weight loss, fever and anaemia are
the most important signs of TB. Any chronic cough persisting for 3 weeks or
more, especially if there is also weight loss and anaemia, should be regarded as a
possible case of TB, and sputum smears taken. Haemoptysis is an important
diagnostic sign; there may be streaking of the sputum with blood or coughing up
of fresh blood. A difficulty arises with the HIV-positive person as in this case a
chronic cough is not a good indicator of TB; rather, night sweats lasting for more
than 3 weeks, combined with a cough or fever of any duration, should be used
instead.
TB infects people over a spectrum of severity depending on the host
response, the dose of organisms and the length of time. The first sign of infection
is the primary complex in which the organism is localized to an area of the lung,
with a corresponding enlargement of the hilar lymph nodes. In the majority of
people, this heals completely or with a residual scar, and the person develops
immunity to further challenge. If healing does not occur, then the focus extends
to cause glandular enlargement, pleural effusion or cavity formation. The third
phase of the disease results from complications of the regional nodes. These may
be obstructive, leading to collapse and consolidation, cause erosion and
bronchial destruction or spread locally. The final stage is one of bloodstream
spread, disseminating bacilli to all parts of the body, where they may produce
tuberculous meningitis or miliary infection. Longer-term complications are those
of bones, joints, the renal tract, skin and many other rare sites.
The risk of developing local and disseminated lesions decreases over a
period of 2 years. In the majority of cases, if the disease is going to progress, it
will do so within 12 months of infection or 6 months from the development of
the primary complex. By the end of 2 years, 90% of complications will have
occurred. Bone and other late complications make up a very small proportion
beyond this time.
How is tuberculosis diagnosed?
TB is spread by droplet infection, so sputum-positive cases transmit
the disease much more efficiently than those whose sputum is negative on
microscopy. The risk to the community is therefore from pulmonary TB and the
emphasis should be on finding these cases by taking a sputum smear, ideally
confirmed by culture. The comparative costs of diagnostic techniques are:
Smear 0.02
Culture 0.20
Sensitivity 0.40
Full plate X-ray 1.00
Fifty sputum smears can be made for the equivalent cost of one X-ray, and
this comparative cost should be considered when diagnosing cases in the
community. Anybody presenting to the health services with a cough for 3 weeks
or more should be asked to produce some sputum and a smear made; this is dried
and treated with Ziehl–Neelsen stain for acid-fast bacilli. X-ray examination has
a high sensitivity so is of more value in countries with a low incidence of TB and
plentiful resources, but sputum microbiology is still necessary to confirm the
diagnosis and provide cultures for drug-susceptibility testing.
A fully automated DNA test, such as Xpert MTB/RIF, which simultaneously
detects positive cases and rifampicin drug resistance, is set to revolutionize the
diagnosis of TB. It is more sensitive than ordinary sputum smears, which depend
upon the accuracy of the microscopist, and gives results within 10 min, so
suspected cases can be diagnosed and started on treatment much more rapidly.
The test is particularly useful for detecting TB in the person with HIV, as well as
the multidrug-resistant case.
When a new case is diagnosed, a simpler form of search is made in the house
and surrounding households. Any contacts of the case, such as family or friends,
are examined to see if anybody has a productive cough or clinical signs, and a
smear made. Contacts should be given BCG. Chemoprophylaxis is given to
children under 6 years old and to contacts positive for HIV, and followed up at
regular intervals. Follow-up information can all be included in the national
registration system.
How is tuberculosis transmitted?
Transmission of tuberculosis is by the airborne route, with coughing and spitting the main
methods of disseminating the organism. Many people meet the tubercle bacillus
in early life, acquire resistance and are quite unaware of ever having come into
contact with it. A proportion, approximately 5%, will manifest the disease in
varying levels of severity. This might be nothing more than an enlargement of
the primary focus with a few systemic effects, and resolve spontaneously, while
other cases may have respiratory symptoms or progress rapidly to bloodstream
spread, presenting as a case of miliary infection or tuberculous meningitis. The
type and severity of the disease is determined by the host response, but why one
person should develop TB and another not cannot generally be determined.
There is some evidence that susceptibility may be genetically determined, as
people who have suffered from TB, even if adequately cured, are more likely to
develop a new infection a second time. Some families are particularly
susceptible, as with the famous literary family the Brontës, in which first the
mother died from TB, followed by nearly all the children, yet the father never
succumbed to the disease. The dose of bacilli might also be important because
young children in close contact with an active case more commonly develop
severe TB (miliary or meningitis). Factors that are known to reduce resistance
are:
• young age, especially the first year of life;
• pregnancy;
• malnutrition;
• intercurrent infections such as measles, whooping cough and streptococcal
infection;
• HIV infection; and
• occupations or environments that damage the lung (mining, dust, smoke).
As well as variation among individuals, there are also considerable
differences in the susceptibility of populations. This can be measured by the
annual TB infection rate, which compares the tuberculin reaction of nonvaccinated subjects of the same age every 5 years. With BCG vaccination at
birth, this can no longer be done, but data obtained before this became a
universal policy are still valid. Another method of estimating incidence is from
TB notifications. Environmental factors are also significant in infection, and the population
density is as important as its susceptibility. The dose of bacilli that the individual
will meet is increased by continued contact over time. This dose/time factor is
more likely to be found in conditions of poverty and overcrowding. If the dose is
sufficiently large and maintained for long enough, even the defences of the
immunologically competent individual may be broken down.
The risk of infection is greatest in the young and rises again in the old, so
overcrowding increases the opportunity for infection to be acquired at a younger
age. As the young mix extensively, they will also have a greater opportunity to
pass on the infection. At the other end of life, the elderly often form persistent
foci in a community – a potent source of infection to the young.
HIV infection has changed the epidemiology and presentation of TB,
especially in Africa, leading to more lower lobe and extrapulmonary disease.
(There are estimated to be more than 20 million persons worldwide with dual TB
and HIV, the majority of these in Africa.) Reduced host response has increased
susceptibility and allowed reactivation or reinfection to take place, as well as
increasing the likelihood of new infection from a contact or case. However, there
is evidence to suggest that HIV/TB patients are less infectious than those with
just TB. Conversely, TB patients are more likely to rapidly progress to fullblown acquired immunodeficiency syndrome (AIDS) when infected with the
HIV virus. Initially, HIV-infected TB patients commonly present with pulmonary
infection similar to the HIV-negative case, but as the disease progresses
extrapulmonary TB predominates and other manifestations of HIV disease such
as chronic diarrhoea, generalized lymphadenopathy, oral thrush and Kaposi’s
sarcoma become more common. All HIV-positive cases should therefore be
investigated for TB and all TB cases tested for HIV. Despite the increase in
extrapulmonary TB, it is still the sputum-positive case that is responsible for
transmission of infection, and this must remain the priority in searching for
cases.
Consumption of unpasteurized milk may result in bovine TB in humans
where the disease is present in the animal population. This presents with
enlargement and suppuration of the cervical lymph nodes rather than pulmonary
disease. It is now less common than formerly with the testing of cattle and
pasteurization of milk, but in developing countries where cattle and their
produce are an important part of the diet, such as in Central and South America,
bovine TB is still found.
What is the occurrence and distribution of tuberculosis?
TB may well be one of the most ancient of human
diseases, having been detected in bones submerged off the coast of Israel dating
to 9000 years ago. It is found worldwide at various levels of severity.
In 2013 there were an estimated 9 million new cases, 1.1 million of these being
HIV positive; 1.5 million died, of which 360,000 were HIV positive. Fifty-six
per cent of cases were in the South-East Asia and Western Pacific regions of the
World Health Organization (WHO), with 24% of all cases in India and 11% in
China. Twenty-five per cent of all cases were in Africa. Between 1990 and 2013,
prevalence rates fell by 41% and continued to decrease slowly each year.
Countries of low TB prevalence are defined as those where less than 10% of
children under 15 have a positive tuberculin test. These are largely the countries
of Western Europe and North America. TB is, however, increasing in Eastern
Europe and the former USSR. Nearly the whole of the tropical world has a high
prevalence rate, with some countries experiencing over 50% of the under 15 year
olds tuberculin positive. Also, urban areas have higher rates than rural areas.
There are high rates in Africa and parts of South America. Asia, India,
Myanmar, Thailand and Indonesia all have high tuberculin-positive rates too. In
the Americas, the indigenous peoples have a much higher TB rate than the nonindigenous. There is a high susceptibility in the Pacific Islands, in which TB was
an unknown disease until the arrival of explorers, who introduced the disease.
What is done for the control and prevention of tuberculosis?
There are four main strategies for the control and
prevention of TB, in the following order of priority:
• search and contact tracing for new cases;
• adequate treatment of all cases, especially the sputum positive;
• improvement of social and living conditions; and
• BCG vaccination.
Vaccination by BCG induces cell-mediated immunity to the mycobacteria
but does not generate humoral immunity, as do other vaccines. BCG vaccination
therefore alerts the body’s defences rather than inducing antibody formation.
After a BCG vaccination, a primary infection will still take place, but the
progressive or disseminated infection will be reduced. BCG protects against
miliary and meningitis infection, the worst kinds of childhood TB, but does not
have much effect on adult cases, which are generally the source of infection.
The effectiveness of BCG varies considerably in different countries. In
Europe there is a good response, while in India it is marginal. This is thought to
be due to atypical mycobacteria circulating in the environment, so BCG should
be given in developing countries at birth or as soon after as possible. In
developed countries, BCG is given selectively to high-risk groups, such as
immigrants. BCG should not be given to children who are known to be HIV
positive, even if they are asymptomatic, nor to pregnant women.
BCG is a freeze-dried vaccine given intradermally. Other methods, such as
multiple puncture, jet injection or scarification have been found to be not so
satisfactory. The vaccine is sensitive to heat and light, so must be carefully
protected.
Sputum smear examination is a very simple technique for screening
populations, especially where there has recently been a case of TB. All contacts
of a case should have several sputum smears taken, concentrating on the young
and elderly.
TB is particularly a disease of poor social conditions and overcrowding, as
shown by the remarkable decline of the infection in industrialized countries prior
to the advent of chemotherapy. The disease was as bad, if not worse, in Europe
at the turn of the century than in many developing countries now, but showed a
progressive and continuous reduction of cases as living conditions improved. As
standards increased, there was a demand for improved housing with fewer
people sharing the same room, so that overcrowding declined. Personal hygiene
improved and practices such as spitting disappeared almost completely.
What is done for the treatment and prophylaxis of tuberculosis?
The functions of chemotherapy can be summarized
as follows:
• Treat individual cases to reduce morbidity and mortality.
• Reduce the number and period of infectious cases.
• Provide a method of disease reduction in developing countries where the
raising of social standards would take some time to achieve.
• Prevent the emergence of resistant strains.
A newly diagnosed case of TB should be treated with a four-drug regime for
2 months, consisting of:
Isoniazid 300 mg daily
Rifampicin 10 mg/kg up to 600 mg daily
Pyrazinamide 35 mg/kg up to 2 g daily
Ethambutol 25 mg/kg daily
After the 2-month period, isoniazid and rifampicin only are taken daily for a
further 4 months. In areas of known isoniazid resistance, then a three-drug
regime of isoniazid, rifampicin and ethambutol is taken for the 4-month period.
In cases of miliary or meningitis TB or bone/joint disease, treatment should
continue for 9–12 months.
In a case where retreatment is required or drug resistance is suspected, then
streptomycin at 15 mg/kg daily is added to the four-drug regime for 2 months,
then the four-drug regime is continued for a further month, and isoniazid,
rifampicin and ethambutol for 5 months. Once the drug susceptibility test (DST)
result is known, the regime can be modified accordingly.
Early and adequate treatment is essential if drug resistance is not to develop.
Sadly, there are now many cases of multidrug-resistant TB (MDR-TB), resistant
to both isoniazid and rifampicin. A link with HIV infection has shown the
development of MDR-TB to occur twice as often in patients with both TB and
HIV. These cases will need to be put on MDR regimes, which include more
drugs, are expensive and need to be taken for a longer period.
Very welcome progress has been made in the treatment of TB by the
introduction of several new drugs: bedaquiline, delamanid, linezolid, rifapentine
and terizidone. WHO has drawn up guidelines for their introduction and
monitoring to decide on the best combinations. Delamid has been used in
combination to treat MDR-TB cases.
A more serious problem has been the development of extensively drugresistant TB (XDR-TB), a virtually untreatable form of TB. This is particularly
prevalent in Eastern Europe, Russia and Central Asia. Considerable expenditure
and strict control will be required to contain this problem.
Prophylaxis with daily isoniazid (300 mg) for 6 months can be given to close
contacts under 35 years of age and people with HIV, and to babies (5 mg/kg)
born to mothers who develop TB shortly before or after delivery.
The WHO’s Stop-TB strategy (also known by the ‘brand name’ DOTS –
Directly Observed Therapy, Short-course) includes political and financial
commitment, standardized diagnosis, treatment and adherence support, and
monitoring. Until recently, this strategy recommended that all cases should have
directly observed therapy (DOT) to ensure adherence. However, evidence from
randomized trials has shown that DOT (as opposed to self-administration) does
not improve cure rates. For all patients, WHO recommends good education on
the diagnosis of TB and importance of treatment adherence. Patients should
choose a treatment supporter, who is someone who is accessible, concerned and
reliable, such as a family member or community health worker/volunteer. The
treatment supporter encourages the patient when they are feeling demotivated,
and to keep follow-up appointments and take the right tablets for the full course
of treatment, until cured.
What is done for surveillance of tuberculosis?
A system to follow up all diagnosed cases of TB discharged from a
hospital or health centre is required on the following lines:
• Register the case with a central registry on diagnosis.
• When the patient is discharged, inform the registry, the nearest clinic to the
person’s home and the supervising doctor.
• The clinic ensures the patient receives regular follow-up treatment or goes and
finds them if they default.
• The supervising doctor visits on a regular basis to check the clinic records and
make sure that the registered patients are receiving treatment.
• When the full course of treatment is completed and the doctor is satisfied that
the patient is cured, the central registry is notified.
Reminders and double checks can be built into the system, such as the
central registry sending out quarterly checks on each patient.
The sophistication of the system depends on the resources of the country, but
lack of resources is never an excuse not to have a system at all. To not follow up
a partially treated patient is a waste of expensive hospital treatment, encourages
the development of resistant organisms and increases the risk to the community.
Follow-up is always cheaper than re-diagnosis and treatment.
Evaluation of TB control programmes is by measuring the proportion of new
smear-positive cases that are cured or are certified to have completed treatment.
The WHO target is 85%. Other useful indicators are:
• annual rate of new TB cases diagnosed;
• rate of sputum-positive cases diagnosed;
• proportion of children under 5 years of age diagnosed;
• proportion of miliary and meningeal TB;
• rate of sputum smears examined;
• rate of BCG scars, on survey;
• relapse rate; and
• rate lost to follow up.
A decrease in the proportion of children under 5 years of age diagnosed and
of those with miliary and meningeal TB will indicate improvement; however,
this will need to be confirmed by a sputum smear survey. Nursing staff should be
taught to always give the BCG vaccination in the same place, normally the
deltoid area of the left arm, so that touring staff, schoolteachers, etc. can rapidly
examine a group of children.
Not only is the standard treatment regime for TB likely to use newly
introduced drugs, but new diagnostic techniques are also likely to be introduced
over the next few years. In order to facilitate these changes, WHO has
established a Stop TB Partnership to prepare countries for the introduction of
these new tools in order to minimize the delay between licensure, availability
and adoption.
Which microorganisms cause acute respiratory infections?
A number of different organisms produce infection, including
Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae,
influenza, rhinoviruses, adenoviruses, metapneumovirus and respiratory
syncytial virus (RSV). The most important of these are S. pneumoniae or the
pneumococcus, H. influenzae bacteria, and RSV and parainfluenza viruses. As
well as there being a wide range of viruses, each species may have a number of
serotypes, with new ones appearing from time to time. Hosts defend themselves
by producing an appropriate immune response, but because of the large number
of serotypes this is a continuous process. Infection will cause illness in some
people but not in others who have developed an immune response either to the
specific organism or to an antigenically similar serotype. New antigenic
mutations, as occur in influenza, can cause epidemic or pandemic spread
because no prior contact with the new variant has been made.
What are the clinical features of acute respiratory infections?
ARIs are divided into upper respiratory and lower respiratory,
the former producing a runny nose, sneezing and headache, while the main
symptoms of lower respiratory infection are a cough, shortness of breath and
inward drawing of the bony structure of the lower chest wall during inspiration,
which is called chest indrawing. Both are generally accompanied by fever. The
main pathological feature is pneumonia, which can either be lobar or bronchial.
In lobar pneumonia, one or more well-defined lobes of the lung are involved,
whereas in bronchial pneumonia the condition is widespread.
How are acute respiratory infections diagnosed?
Identifying the organism by culture of the sputum can be attempted
where facilities permit, but in most developing countries ARI will be diagnosed
on clinical criteria.
How are acute respiratory infections transmitted?
Acute respiratory infections are transmitted by coughing out a large number of organisms in an aerosol of
droplets, which are either breathed in, enter via the conjunctiva, or land on
surfaces and subsequently enter mucous membranes from fingers. (See further
under influenza, Section 13.3.) Susceptibility and response is determined by host
factors, some of which are:
• Age. Young children develop obstructive diseases such as croup
(laryngotracheobronchitis) and bronchiolitis. Tonsillitis is commonest at
school age, whereas influenza and pneumonia are important causes of death in
the elderly. In young children, mortality is inversely related to age.
• Portal of entry. Volunteers have been more easily infected by some organisms
applied to the conjunctiva than through the nasopharynx.
• Nutrition. Low birth weight and malnourished children have a higher morbidity
and mortality. Certain nutritional deficiencies, such as lack of Vitamin A and
zinc, contribute to the development of a more severe disease and higher death
rate. Breastfeeding appears to have a protective effect.
• Socio-economic. ARI is a disease of poverty with higher incidence in lower
socio-economic groups and those that live in urban slums. Higher rates of
lower respiratory disease have been found with increasing family size. Much
of the reason for this increase appears to be due to increased contact and
agglomeration, as shown in children attending day-care facilities or school,
where infection occurs irrespective of social class.
• Air pollution. A correlation with domestic air pollution has been shown in
South Africa and Nepal. Passive smoking may affect pulmonary function and
make the child more susceptible to infection as well as influence the child to
become a smoker.
• Climate. More respiratory infections are found in the cooler parts of the world
or in the higher altitude regions of the tropics. There is a distinct seasonal
effect in many countries, with more respiratory infections in the winter.
However, cold alone is not a causative factor. The ‘cold’ derives its name from
the belief that becoming chilled or standing in a draught is responsible, but
when volunteers are subjected to these stresses and inoculated with
rhinoviruses, they develop no more ‘colds’ than controls. In the tropics,
respiratory infections occur more commonly with the rains.
• Other infections. Any infection that causes damage to the respiratory mucosa
will allow a mild infecting organism to progress to more serious
consequences. The most important of these diseases is measles, post-measles
pneumonia being particularly common.
What is the occurrence and distribution of acute respiratory infections?
Worldwide, the most important cause of death in
children in developing countries.
How are acute respiratory infections treated?
The first line of action is to assess the severity of illness and give
treatment. This is supportive therapy for mild infections and the active
administration of antibiotics to the severe case. The mild infection is best treated
at home and kept away from sources of other infection, which may cause more
serious disease, while the severe case requires early treatment to prevent
complications and death. In children, the respiratory rate and chest indrawing are
used to decide management:
• Mild cases with a respiratory rate of less than 40 breaths/min in children 2–12
months old, and 50 breaths/min in children 1–5 years old, are treated at home
with supportive therapy. The mother should be encouraged to nurse her child,
giving him or her plenty of fluids (breastfeeding or from a cup), regular
feeding, cleaning the nose, maintaining the child at a comfortable temperature
and avoiding contact with others.
• Moderate cases with a respiratory rate over 40 breaths/min in under 1 year olds
and 50 breaths/min in children 1–5 years old, but with no chest indrawing,
should be given antibiotics (oral co-trimoxazole (4 mg/kg twice daily); oral
amoxycillin (15 mg/kg three times a day); or intramuscular penicillin G) and
nursed at home.
• Severe cases with chest indrawing, cyanosis or cases too sick to feed must be
admitted as inpatients and given active support as well as treatment with
antibiotics.
