Lecturer:

Tigran Ugujyan
Epidemiologist,
Master of Public
Health

Surface infections
TETANUS
An acute disease induced by the
exotoxin of Clostridium tetani and clinically
characterized by muscular rigidity which
persists throughout illness punctuated
by painful paroxysmal spasms of the
voluntary muscles, especially the
masseters (trismus or "lock-jaw"). the
facial muscles (risus sardonicus), the
muscles of the back and neck
(opisthotonos), and those of the lower
limbs and abdomen(1). The mortality
Problem statement
WORLD
Tetanus is now comparatively rare disease in the
developed countries. Neonatal tetanus (NT) is a killer
disease, second only to measles among the nine target
diseases of the EPI. In the absence of high quality treatment,
the case-fatality rate can be as high as 80- 90 per cent. It
tends to occur in areas with poor access to health care ,
hence it often remains hidden within the community.
Problem statement
Maternal and neonatal tetanus (MNT) is an important
preventable cause of neonatal and maternal mortality,
particularly in developing countries. Although easily
prevented by maternal immunization with tetanus toxoid
containing vaccines (TTCV) and aseptic obstetric and
postnatal umbilical cord care practices, both maternal and
neonatal tetanus persist as public health problems. Most
cases occur in poor, remote and isolated communities where
unhygienic obstetric and postnatal practices prevail along
with poor access to health services.
Problem statement
The spores of tetanus are very resistant and remain in the
environment in extremes of temperature for long periods.
Hence, technically it is not possible to eradicate tetanus,
including NT. However, MNT can be eliminated by reducing
the disease incidence to such low levels that it ceases to be a
public health problem.
Problem statement
The disease is easily preventable
through (2) :- (l) clean delivery and umbilical cord care
practices to ensure infection is not contracted by mother or
newborn during the delivery process; (2) delivery of
appropriate doses of TTCV to pregnant women through
antenatal care services and other routine contacts;
(3) vaccination campaigns with TTCV targeting all women of
reproductive age in high-risk areas; and (4) strengthening
surveillance to identify women at risk, reasons for the risk,
and potential clustering.
Problem statement
In the 1980s, over 1 million deaths every year were
attributable to tetanus, with an estimated 787,000 deaths in
1988 from NT alone. Recognizing, the substantial burden of
NT in developing countries, the 42nd World Health
Assembly adopted a resolution to eliminate NT by 1995,
through the increased availability of TTCV, clean deliveries
and improved surveillance. The elimination of NT was
defined as < 1 case per 1000 live births in every district.
Problem statement
In the early 1990s, it was estimated that maternal tetanus
accounted for about 5% of maternal mortality, or
15,000- 30,000 deaths every year. As a result, in 1999, the
elimination of maternal tetanus (MT) was added to the goals
of the elimination programme for neonatal tetanus, and the
programme title was changed to Maternal and Neonatal
Tetanus Elimination (MNTE). Since NT is linked to the
immunization status of mothers, elimination of NT has been
adopted as a proxy for the elimination of MT (2).
Problem statement
The implementation of various initiatives under the MNTE
programme led to a significant reduction in cases of
MNT. These initiatives included promotion of maternal
tetanus immunization along with safe delivery and avoidance
of unsafe abortion and umbilical cord care practices.
According to WHO estimates, substantial progress has been
made in the past decade in reducing neonatal incidence and
deaths from an estimated 787,000 deaths in 1988 to 34,000
in 2015, a reduction of about 96 per cent (3).
Maternal and Neonatal tetanus elimination
in
India (2)
A mix of strategies has been implemented in India to
facilitate clean deliveries by training auxiliary nurse,
midwives and other cadres of trained birth attendants who
work at the village level, in addition to increasing routine TT
protection. The Indian Ministry of Health & Family Welfare
in collaboration with WHO India, UNICEF and other
partners, designed and implemented the following strategies
to control neonatal tetanus:
Maternal and Neonatal tetanus elimination
in
India (2)
- acceleration of TT immunization coverage through the
WHO-recommended high risk approach, and
strengthening routine TT immunization of pregnant
women, and supplemental TT immunization activities
targeting women of child-bearing age in high-risk
districts;
- systematic vaccination of pregnant women attending
antenatal care (ANC) with TT vaccine;
Maternal and Neonatal tetanus elimination
in
India (2)
- promotion of institutional deliveries focusing on poor
pregnant women with an institutional stay for 48 hours,
through training of traditional birth attendants;
- intensive communication programme targeting
communities to reduce harmful cord care practices
(promotion of the 5 cleans - hand, delivery surfaces,
instruments for cutting the umbilical cord , cord tie and
caring of the umbilical cord); and
- distribution of disposable delivery kits to skilled birth
attendants for each pregnancy.
Maternal and Neonatal tetanus elimination
in
India (2)
The launch of the national rural health mission (NRHM)
in 2005 also helped to strengthen these initiatives. Strategies
to improve clean delivery included the innovative Janani
Suraksha Yojana (JSY), a conditional cash transfer scheme,
to encourage women to give birth in a health facility. Other
interventions to improve TT protection and reduce maternal
and neonatal mortality under the NRHM included:
Maternal and Neonatal tetanus elimination
in
India (2)
- Integrating and extending outreach services through
village health and nutrition days, including vaccination
of children, adolescents and pregnant women with TT
containing vaccines;
- Intense 3-week refresher training for all skilled birth
attendants;
- Operationalization of selected sub-centres and
community health centres to provide 24-hour services
7 days per week for obstetric and neonatal care;
Maternal and Neonatal tetanus elimination
in
India (2)
- Strengthening of facility-based neonatal care by setting
up newborn care corners in health facilities where
deliveries take place, special neonatal care units in
district hospitals and new born stabilization units in first
referral units for the care of sick neonates;
- Engagement of more than 896,411 accredited social
health activists (ASHA) to generate demand and
facilitate use of health-care services by communities and
poor women.
Maternal and Neonatal tetanus elimination
in
India (2)
As a result, safe deliveries rose from 52 per cent in 2007
to 76 per cent in 2009. Janani Shishu Suraksha Karyakram,
launched in 2011 also helped. India's successful
implementation of a mix of strategies, and experience and
knowledge gained from polio eradication efforts has led to a
substantial decline in the number of MNT cases in the
country. As of December 2014, 30 of the 36 states/UTs were
validated as having achieved MNT elimination and in May
2015, India was officially certified as achieving maternal and
neonatal elimination (4).
Epidemiological
determinants
Agent factors
(a) AGENT : Cl. tetani is a gram-positive, anaerobic, spore-bearing organism.
The spores are terminal and give the organism a drum-stick appearance. The
spores are highly resistant to a number of injurious agents, including
boiling, phenol, cresol and autoclaving for 15 minutes at 120 deg. Centigrade
(5). They germinate under anaerobic conditions and produce a potent
exotoxin ("tetanospasmin"). The spores are best destroyed by steam
under pressure at 120 deg. C for 20 minutes or by gamma
irradiation.
Agent factors
(b) RESERVOIR OF INFECTION : The natural
habitat of the organism is soil and dust. The bacilli are found
in the intestine of many herbivorous animals , e.g., cattle,
horses, goats and sheep and are excreted in their faeces.
The spores survive for years in nature. The bacilli may be
found frequently in the intestine of man without causing illeffects.
The spores are blown about in dust and may occur in
a wide variety of situations. including operation theatres.
Agent factors
(c) EXOTOXIN : Tetanus bacilli produce a solubl e exotoxin.
It has an astounding lethal toxicity, exceeded only by
botulinum toxin. The lethal dose for a 70 kg man is about
0.1 mg (6). The toxin acts on 4 areas of the nervous system :
(a) the motor end plates in skeletal system (b) the spinal
cord (c) the brain, and (d) the sympathetic system (5). Its
principal action is to block inhibition of spinal reflexes (7).
(d) PERIOD OF COMMUNICABILITY : None. Not
transmitted from person to person.
Host factors
(a) AGE : Commonly, tetanus is a disease of the active
age (5 to 40 years). This period predisposes to all kinds of
trauma and therefore, the risk of acquiring the disease is
pretty high. Tetanus occurring in the new-born is known as
"neonatal tetanus ". Infants typically contact the disease at
birth, when delivered in non-aseptic conditions - especially
when the umbilical cord is cut with unclean instruments or
when the umbilical stump is dressed with ashes, soil or
cowdung.
Host factors
(b) SEX: Although a higher incidence is found in
males, females are more exposed to the risk of tetanus,
especially during delivery or abortion leading to "puerperal
tetanus". Males appear to be more sensitive to tetanus toxin
than females (8). (c) OCCUPATION : Agricultural workers
are at special risk because of their contact with soil.
Host factors
(d) RURAL-URBAN DIFFERENCES : The incidence of
tetanus is much lower in urban than in rural areas. Within
the urban areas, there may be vast differences in the
incidence of tetanus. For example, it was observed in one
town that tetanus was more frequent on the outskirts where
floors were earthen and animals lived close to human
beings, than in the centre of the town where there were
paved and mosaic floors.
Host factors
(e) IMMUNITY: No age is immune
unless protected by previous immunization. The immunity
resulting from 2 injections of tetanus toxoid is highly
effective and lasts for several years. As a general rule,
patients who have recovered from tetanus must be actively
immunized, because the amounts of toxin responsible for
the disease in man do not stimulate protective immunity (7).
Host factors
Immunity lasting for a few weeks (less than 6 months) can be
transferred to the baby, if the mother is immunized during
pregnancy or if she already has a high level of immunity at
the time she becomes pregnant. Tetanus is one disease in
which herd immunity does not protect the individual.
Environmental and social factors
Tetanus is a positive environmental hazard (9). Its
occurrence depends upon man's physical and ecological
surroundings - the soil, agriculture, animal husbandry - and
not on the presence or absence of infection in the
population. The environmental factors are compounded by
social factors such as unhygienic customs and habits (e.g.,
application of dust or animal dung to wounds); unhygienic
delivery practices (e.g., using unsterilized instruments for
cutting the umbilical cord); ignorance of infection and lack
of primary health care services.
Environmental and social factors
In the developed countries,
urbanization , industrialization and mechanization of
agriculture have interfered with the normal process of
distribution of Cl. tetani and have reduced the morbidity
rate, as has occurred , for example in UK, USA and Germany
during the last 40 years (8).
Mode of transmission
Infection is acquired by contamination of wounds with
tetanus spores. The range of injuries and accidents which
may lead to tetanus - comprise a trivial pin prick, skin
abrasion, puncture wounds, burns, human bites, animal
bites and stings, unsterile surgery, intra-uterine death, bowel
surgery, dental extractions, injections, unsterile division of
umbilical cord, compound fractures, otitis media , chronic
skin ulcers, eye infections, and gangrenous limbs (7).
The sequence of events are : introduction of spores .
germination and elaboration of the exotoxin and binding to
the receptor.
Incubation period
The incubation period is usually 6 to 10 days. However, it
may be as short as one day or as long as several months (5) .
Long incubation is probably explained by the spores lying
dormant in the wounds. Incubation is also prolonged by
prophylaxis (7) .
Types of tetanus
(a) TRAUMATIC : Trauma -is a major and important cause
of tetanus. Sometimes tetanus may result from most trivial
or even unnoticed wounds. (b) PUERPERAL : Tetanus
follows abortion more frequently than a normal labour.
A post- abortal uterus is a favourable site for the germination
of tetanus spores. (c) OTOGENIC : Ear may be a rare portal
of entry. Foreign bodies such as infected pencils, matches,
and beads may introduce the infection. Otogenic tetanus is a
paediatric problem, but cases, may occur in adults also.
Types of tetanus
(d) IDIOPATHIC : In these cases there is no definite history
of sustaining an injury. Some consider it to be the result of
microscopic trauma . Others hold the view that it is due to
the absorption of tetanus toxin from the intestinal tract.
A third view is that the tetanus spores may be inhaled and
may start the infection.
Types of tetanus
(e) TETANUS NEONATORUM :
In many countries, neonatal tetanus kills about 85 per cent of
those afflicted. The common cause is infection of the
umbilical stump after birth , the first symptom being seen
about the 7th day. Therefore tetanus is known as " 8th day
disease " in Punjab (6). In any country where hygiene is
poor, neonatal tetanus may be common.
PREVENTION
1 . Active immunization (10, 11, 12)
Tetanus is best prevented by active immunization with
tetanus toxoid. It stimulates the production of the protective
antitoxin. The aim should be to vaccinate the entire
community and ensure a protective level of antitoxin
approximately 0.01 IU/ml serum throughout life. All persons
should be immunized regardless of age.
1 . Active immunization (10, 11, 12)
Two preparations are available for active immunization
a. Combined vaccine - DPT
b. Monovalent vaccines
i) Plain or fluid (formal) toxoid
ii) Tetanus vaccine. adsorbed (PTAP, APT)
a. COMBINED VACCINE
Tetanus vaccine is offered routinely to infants (Expanded
Immunization Programme) in combination with diphtheria
vaccine and killed B . pertussis organisms as DPT vaccine.
According to the National Immunization Schedule, the primary course
of immunization consists of 3 doses of DPT, at intervals of 4-8 weeks,
starting at 6 weeks of age,followed by a booster at 18 months of age,
and a second booster at 5- 6 years of age and a third booster (Only TT)
after 10 years of age.
a. COMBINED VACCINE
Pentavalent vaccine: At present pentavalent vaccine is
being given at 6th. 10th and 14th weeks of age instead of
DPT vaccine. The DPT vaccine is used for booster dose.
b. MONOVALENT VACCINES
Purified tetanus toxoid (adsorbed) has largely supplanted
plain toxoid because it stimulates a higher and longerlasting
immunity response than plain toxoid (13). However,
the latter may be employed for purposes of booster injection
when rapid protection is indicated.
A primary course of immunization consists of two doses
of tetanus toxoid adsorbed (each dose 0.5 ml, injected into
the arm) given at intervals of 1- 2 months.
b. MONOVALENT VACCINES
The longer the intervals between the two doses, the better Is the
immune response. The first booster dose (the third in order) should
be given a year after the initial two doses . The opinion was
expressed that no more than one additional booster dose
(a total of 4 doses altogether) given 5 years after the third
dose is required in adults (including pregnant women) in
developing countries (14) . Frequent boosters must be
avoided.
b. MONOVALENT VACCINES
Reactions following the injections of tetanus toxoid are
uncommon. They are less likely to occur with a refined and
adsorbed toxoid such as Purified Tetanus Toxoid
(Aluminium Phosphate Adsorbed) . However, in persons
giving history of allergy usual precautions should be
observed . Purified tetanus toxoid should be stored between
2 and 8 deg. C. It must not be allowed to freeze at any time.
2. Passive immunization (10, 11)
Temporary protection against tetanus can be provided by
an injection of human tetanus hyperimmunoglobulin (TIG) or
ATS . (I) HUMAN TETANUS HYPERIMMUNOGLOBULIN : It
is the best prophylactic to use . The dose for all ages is 250 IU .
It does not cause serum reactions. It gives a longer passive
protection upto 30 days or more compared with 7-10 days
for horse ATS. Human tetanus lg is now available in India - it
is produced by the Serum Institute of India, Pune.
2. Passive immunization (10, 11)
(II) ATS (EQUINE) : If human antitoxin is not available, equine
antitoxin (anti-tetanus serum or ATS) should be used. The
standard dose is 1500 IU, injected subcutaneously after
sensitivity testing. ATS gives passive protection for about
7- 10 days. Being a foreign protein, ATS is rapidly excreted
from the body and there may be very little antibody at the end
of 2 weeks. Because of this drawback, ATS may not cover the
tetanus incubation period in all cases.
2. Passive immunization (10, 11)
Horse ATS has other disadvantages too - (I) It causes sensitivity reaction in
many people because it contains foreign proteins. A person
receiving ATS for the first time may tolerate it well, but there
is a possibility that subsequent injections of horse serum may
lead to allergic reactions varying in severity from rash to
anaphylactic shock. It is estimated that the incidence of
serious systemic reactions to ATS is 5 to 10 per cent of the
persons who receive it. It is well to remember that local tests
for sensitivity are unreliable as to general sensitivity to horse
serum.
2. Passive immunization (10, 11)
(II) Another drawback of ATS is that it stimulates the
formation of antibodies to it and hence a person who has
once received ATS tends to rapidly eliminate subsequent
doses. As such the value of second and subsequent doses of
ATS becomes questionable. In practice , therefore, ATS
becomes less and less reliable as a prophylactic. These
drawbacks have been responsible for the growing
unpopularity of ATS as an agent for immediate protection
against tetanus.
3 . Active and passive immunization
Simultaneous active and passive immunization is widely
carried out in non-immune persons. The patient is given
1500 units of ATS or 250 units of Human lg in one arm, and
0.5 ml of adsorbed tetanus toxoid (PTAP or APT) into the
other arm or gluteal region. This should be followed 6 weeks
later by another dose of 0.5 ml of tetanus toxoid, and a third
dose one year later. The purpose of antitoxin is for
immediate temporary protection, and the purpose of toxoid
is for long-lasting protection.
4 . Antibiotics
Active immunization with tetanus toxoid is the ideal
method of tetanus prophylaxis, but it is of no immediate
avail to a person who is non-immune and has sustained
injury. ATS as an agent for immediate protection against
tetanus has its drawbacks. For these reasons, antibiotics are
indicated in the prophylaxis against tetanus.
4 . Antibiotics
A single intramuscular injection of 1.2 mega units of a long-acting
penicillin (e.g. , benzathine penicillin) will provide a
sustained concentration of the drug for 3 to 4 weeks, which
is sufficient to kill any vegetative forms of tetanus bacilli that
may emerge from the sporulating stage. Penicillin has no
effect on tetanus spores. For patients who are sensitive to
penicillin, a 7-day course of erythromycin estolate 500 mg
6-hourly by mouth will kill vegetative forms of
Cl. tetani but not spores.
4 . Antibiotics
Antibiotics should be given as soon
as possible after an injury, before a lethal dose of toxin is
produced in the wound, which may be as soon as 6 hours
after injury. Antibiotic prophylaxis should not be relied upon
for patients seen later than 6 hours after injury. Moreover, it
is not certain whether the antibiotic can reach the bacilli, if
there is dead tissue present in the wound. Therefore,
antibiotic alone is ineffective in the prevention of tetanus; it
is not a substitute to immunization.
Prevention of neonatal tetanus
Neonatal tetanus is well controlled in some industrialized
countries through clean delivery practices alone. Over the
last decade. most programmes in developing countries have
concentrated on training the traditional birth attendants,
providing home delivery kits and educating pregnant
women about the "five cleans" - clean hands, clean delivery
surface and clean cord care i.e .. clean blade for cutting the
cord, clean tie for the cord and no application on the cord
stump. Operational research has shown that training of birth
attendants alone can reduce death due to neonatal tetanus
by 90 per cent (15).
Prevention of neonatal tetanus
Tetanus toxoid will protect both the mother and her child. In
unimmunized pregnant women, two doses of tetanus toxoid
should be given, the first as early as possible during pregnancy
and the second at least a month later and at least
3 weeks before delivery. According to the National
Immunization Schedule, these doses may be
given between 16-36 weeks of pregnancy, allowing an interval
of 1-2 months between the 2 doses. In previously immunized
pregnant women, a booster dose is considered sufficient.
Prevention of neonatal tetanus
There is no need for a booster at every consecutive pregnancy,
because of the risk of hyper-immunization and side-effects.
In areas where the incidence of neonatal tetanus is high,
the primary 2- dose course can be extended to all women of
child-bearing age, particularly if the present coverage of
antenatal care is low.
Prevention of neonatal tetanus
In developing countries, the majority of pregnant women
are not seen antenatally. Since a pregnant woman coming
for an antenatal visit may in fact never return again,
immunization should be given regardless of the month of
pregnancy as there is no evidence to suggest that tetanus
toxoids are dangerous or harmful to the foetus. The golden
rule is that no pregnant mother should be denied even one
dose of tetanus toxoid if she is seen late In pregnancy.
Prevention of neonatal tetanus
The infants born to the mothers who have not previously
received 2-doses of tetanus toxoid are exposed to the risk of
neonatal tetanus. They can be protected by injection of
antitoxin (heterologous serum, 750 IU), if it is administered
within 6 hours of birth.
Prevention of tetanus after injury (12)
All wounds must be thoroughly cleaned soon after injury
- removal of foreign bodies, soil, dust, necrotic tissue. This
procedure will abolish anaerobic conditions which favour
germination of tetanus spores.
A useful scheme for the prevention of tetanus in the
wounded is given in Fig. 1.
Prevention of tetanus after injury (12)
When ATS is given, adrenaline solution 1 in 1000 for
intramuscular injection in the dosage of 0.5 to 1 ml and
hydrocortisone 100 mg for intravenous injection must be kept
available in case of a generalized anaphylactoid reaction (11).
A test dose of ATS (0.1 ml in a tuberculin syringe) should be
given subcutaneously (not intradermally) and the patient
observed carefully (not casually) at least for half an hour for
any evidence of general reaction (not only local reaction) ,
e.g. , alteration in pulse, fall in blood pressure, dyspnoea and
distress.
Prevention of tetanus after injury (12)
If there is reaction, the rest of the antitoxin should be
given in gradually increasing fractions after treatment with
adrenaline. In patients with history of allergy, e.g. , asthma,
eczema, food or drug idiosyncracy, the above test should be
preceded by a dose of 0.05 ml of 1 in 10 dilution of the ATS. If
there is reaction, ATS should be withheld.
Lastly, it should be pointed out that tetanus may
occasionally occur inspite of active or passive immunization
or both. Nevertheless, the aim is to provide as much
protection as possible in the light of our present scientific
knowledge.
References
1. WHO (1973), Council for International Organizations of Medical
Sciences (1973). Communicable Diseases, Provisional International
Nomenclature. c/o WHO, Geneva
2. WHO (2016), Weekly Epidemiological Record, No. 44, 30th Oct..
2016.
3. WHO (2018), Fact sheet Tetanus, 9th May, 2018.
4. Govt. of India (2016), Annual Report 2015-2016, Ministry of Health
and Family Welfare, New Delhi.
5. Weinstein, Louis (1973). N. Eng. J. Med., 289: 1293.
7. Warrel, David A ( 1981). Medicine International, 3: 118.
8. Bytchenko, B. (1966). Bull WHO, 34: 71.
References
9. Cvetanovic, B. et al (1978). Bui/ WHO, Supplement No.I to Vol 56, p.29.
6. Gordon. J.E. et al (1961). J. Indian M.A., 37 · 157.
10. Adams, E.B. et al (1969). Tetanus, Blackwell.
11 . Sen. B. (1972). J. Indian M.A., 59: 294.
12. Smith, J.W.G. et al (1975). Brit. Med. J. 3: 453- 455.
13. White, W.G. et al (1969). Lancet, 2: 94.
14. WHO (1982). Preuention of Neonatal Tetanus, SEARO Tech. Publ. No.3.
15. WHO (1992), World Health Statistics, Quarterly Report,
Communicable Disease, Vol. 45, No. 2/3.