Clinical guidelines /

Chapter 7: Bacterial diseases

Tetanus

Clinical feat ures

Children and adult s
Neonat es
Treat ment
General measures
Neut ralisat ion of toxin
Inhibit ion of toxin product ion
Cont rol of rigidit y and spasms, and sedat ion of t he pat ient
Treat ment of pain
Treat ment of t he ent ry point and associat ed infect ions
Tet anus vaccinat ion
Prevent ion
1) Post -exposure prophylaxis
2) Rout ine vaccinat ion (pre-exposure prophylaxis)

– Tet anus is a severe infect ion due to t he bacillus  Clostridium tetani, found in soil, and human and
animal wast e. T he infect ion is noncont agious.

– Clostridium tetani is int roduced into t he body t hrough a wound and produces a toxin whose act ion
on t he cent ral nervous syst em is responsible for t he symptoms of t et anus.

– Tet anus is ent irely prevent able by vaccinat ion. It occurs in people who have not been fully
vaccinat ed before exposure or have not received adequat e post -exposure prophylaxis. In t hese
individuals, most breaks in t he skin or mucous membranes carry a risk of t et anus, but t he wounds
wit h t he great est risk are: t he st ump of t he umbilical cord in neonat es, punct ure wounds, wounds
wit h t issue loss or cont aminat ion wit h foreign mat erial or soil, avulsion and crush injuries, sit es of
non-st erile inject ions, chronic wounds (e.g. lower ext remit y ulcers), burns and bit es. Surgical or
obst et rical procedures performed under non-st erile condit ions also carry a risk of t et anus.

Clinical features
Generalised t et anus is t he most frequent and severe form of t he infect ion. It present s as muscular
rigidit y, which progresses rapidly to involve t he ent ire body, and muscle spasms, which are very
painful. Level of consciousness is not alt ered.

Children and adults

– Average t ime from exposure to onset of symptoms is 7 days (3 to 21 days).

– Muscular rigidit y begins in t he jaw muscles (difficult y wit h t hen inabilit y to open mout h [t rismus]
prevent ing t he pat ient from speaking, eat ing), spreading to t he face (fixed smile), neck (difficult y
wit h swallowing), to t he t runk (rest rict ion of respiratory muscles; hyperext ension of spine
[opist hotonus]), to t he abdomen (guarding) and to t he limbs (flexion of t he upper limbs and
ext ension of t he lower limbs).
– Muscle spasms, which are very painful, appear at t he onset or when muscular rigidit y becomes
generalised. T hey are t riggered by st imuli (noise, light , touch) or arise spont aneously. Spasms of t he
t horacic and laryngeal muscles may cause respiratory dist ress or aspirat ion.

Neonates
– In 90% of cases, init ial symptoms appear wit hin 3 to 14 days of birt h.

– T he first signs are significant irrit abilit y and difficult y sucking (rigidit y of t he lips, t rismus) t hen
rigidit y becomes generalised, as in adult s. Any neonat e, who init ially sucked and cried normally,
present ing wit h irrit abilit y and difficult y sucking 3 to 28 days aft er birt h and demonst rat ing rigidit y
and muscle spasms should be assumed to have neonat al t et anus.

Treatment
Hospit alisat ion is needed and usually last s 3 to 4 weeks. Correct management can reduce mort alit y
even in hospit als wit h limit ed resources.

General measures
– Ensure int ensive nursing care.

– T he pat ient should be in a dark, quiet room. Blindfold neonat es wit h a clot h bandage.

– Handle t he pat ient carefully, while sedat ed and as lit t le as possible; change posit ion every 3 to 4
hours to avoid bedsores.

– Teach family t he danger signs and inst ruct t hem to call t he nurse for t he slight est respiratory
symptom (cough, difficult y breat hing, apnoea, excessive secret ions, cyanosis, et c.).

– Est ablish IV access for hydrat ion, IV inject ions.

– Gent le suct ion of secret ions (mout h, oropharynx).

– Insert a nasogast ric t ube for hydrat ion, feeding and administ rat ion of oral medicat ions.

– Provide hydrat ion and nut rit ion in feeds divided over 24 hours. In neonat es, give expressed breast
milk every 3 hours (risk of hypoglycaemia).

Neutralisation of toxin
human t et anus immunoglobulin IM
Neonat es, children and adult s: 500 IU single dose, inject ed into 2 separat e sit es

Inhibition of toxin production

met ronidazole 1
 IV infusion (30 minut es; 60 minut es in neonat es) for 7 days

Neonat es:
• 0 to 7 days: 15 mg/kg on D1 t hen, aft er 24 hours, 7.5 mg/kg every 12 hours

• 8 days to < 1 mont h (< 2 kg): same doses

• 8 days to < 1 mont h (≥ 2 kg): 15 mg/kg every 12 hours

Children 1 mont h and over: 10 mg/kg every 8 hours (max. 1500 mg daily)

Adult s: 500 mg every 8 hours

Control of rigidity and spasms, and sedation of the patient

Diazepam should decrease t he frequency and int ensit y of spams wit hout causing respiratory
depression. T he dose and frequency of administ rat ion depend on t he pat ient ’s clinical response and
tolerance.

– T here is a high risk of respiratory depression and hypot ension when using diazepam,
especially in children and elderly pat ient s. Const ant and close monitoring of t he pat ient ‘s respiratory
rat e (RR) and oxygen sat urat ion (SpO2 ) is essent ial, wit h immediat e availabilit y of equipment for
manual vent ilat ion (Ambu bag, face mask) and int ubat ion, suct ion (elect ric if possible) and Ringer
lact at e.
– A cont inuous IV infusion of diazepam requires t he use of a dedicat ed vein (no ot her
infusion/inject ion in t his vein); avoid t he ant ecubit al fossa if possible.

– Do not stop t reat ment abrupt ly; an abrupt stop can cause spasms.

Neonat es diazepam emulsion for inject ion (10 mg ampoule, 5 mg/ml, 2 ml)

• 0.1 to 0.3 mg/kg by slow IV inject ion (3 to 5 minut es) every 1 to 4 hours depending
on t he severit y and t he persist ence of t he spasms as long as t he RR is ≥ 30.

• If despit e hourly diazepam t he spasms persist , st art a cont inuous infusion of

diazepam wit h an elect ric syringe: 0.1 to 0.5 mg/kg/hour (2.4 to 12 mg/kg every 24
hours). St art wit h 0.1 mg/kg/hour and if symptoms persist , increase by 0.1
mg/kg/hour as long as RR is ≥ 30.

• If in spit e of 0.5 mg/kg/hour symptoms persist , t he dose can be increased up to

0.8 mg/kg/hour as long as t he RR ≥ 30.

• Dilut ed diazepam emulsion does not keep for more t han 6 hours.

Example:

Neonate weighing 3 kg (administration by electric syringe)

0.1 mg/kg/hour x 3 kg = 0.3 mg/hour

Dilute one 10 mg ampoule of diazepam emulsion for injection in 50 ml of 10% glucose

to obtain a solution containing 0.2 mg of diazepam per ml.

Administer 1.5 ml/hour [dose (in mg/hour) ÷ dilution (in mg/ml) = dose in ml/hour i.e.
0.3 (mg/hour) ÷ 0.2 (mg/ml) = 1.5 ml/hour].

If an elect ric syringe is not available, dilut ing t he diazepam emulsion in an infusion
bag for cont inuous infusion may be considered. Weigh t he risks associat ed wit h
t his mode of administ rat ion (accident al bolus or insufficient dose). T he infusion
should be monitored closely to avoid any change, however small, of t he prescribed
rat e.

Children
Same doses and protocol as in neonat es but :

>1 • Use diazepam solut ion for inject ion 5 mg/ml: (10 mg ampoule, 5 mg/ml, 2 ml) 2
.

mont h • T hese doses can be administ ered as long as t he RR is:

and ≥ 30 in children under 1 year

adult s ≥ 25 in children 1 to 4 years

≥ 20 in children 5 to 12 years

≥ 14 in children over 12 years

≥ 12 in adult s

Examples:

• Child weighing 6 kg (continuous IV infusion using a pediatric infusion set; 1 ml = 60

drops)

0.1 mg/kg/hour x 6 kg = 0.6 mg/hour

Dilute one 10 mg ampoule of diazepam solution for injection in 50 ml of 5% glucose

(10% glucose if child < 3 months) to obtain a solution containing 0.2 mg of diazepam
per ml.

Administer 3 ml/hour [dose (in mg/hour) ÷ dilution (in mg/ml) = dose in ml/hour i.e.
 0.6 (mg/hour) ÷ 0.2 (mg/ml) = 3 ml/hour] or 3 drops/minute (in a paediatric infusion
set ml/hour = drops/minute).

• Adult weighing 60 kg (standard adult infusion set, 1 ml = 20 drops)

0.1 mg/kg/hour x 60 kg = 6 mg/hour

Dilute 5 ampoules of 10 mg of diazepam solution (50 mg) in 250 ml of 0.9% sodium

chloride or 5% glucose to obtain a solution containing 0.2 mg of diazepam per ml.

Administer 30 ml/hour [dose (in mg/hour) ÷ dilution (in mg/ml) = dose in ml/hour e.g.
6 (mg/hour) ÷ 0.5 (mg/ml) = 30 ml/hour] or 10 drops/minute.

Count t he volume of t he infusion of diazepam as part of t he pat ient ’s daily fluid int ake.

When t he frequency and severit y of t he spasms have decreased, st art weaning t he diazepam
(gradually decrease t he rat e of infusion):

– Calculat e t he tot al daily dose of IV diazepam and administ er it orally in 4 divided doses, 6 hours
apart , via nasogast ric (NG) 3
t ube.

– Give first NG dose and decrease rat e of IV infusion by 50%.

– Give second NG dose and stop IV diazepam infusion.

– If wit hdrawal signs 4

appear, wean more slowly.

– Once on diazepam PO, wean by 10 to 20% of t he original dose daily, unt il at a dose of 0.05 mg/kg
every 6 hours.

– T hen increase t he int erval from every 6 hours to every 8 hours for 24 hours as tolerat ed (wean
more slowly if wit hdrawal signs appear).

– Cont inue to increase t he int erval bet ween t he doses from every 8 hours to every 12 hours and t hen
to every 24 hours before stopping t he diazepam.

– Each st ep should be for 24 hours or more if wit hdrawal signs appear.

Notes:

– It is oft en at t hese smaller doses t hat it is difficult to wean diazepam. If t his is t he case, slow t he
wean furt her: dropping t he % wean (e.g. 5% wean every 24 hours inst ead of 10% wean) or increasing
t he int erval bet ween weans (e.g. going from every 24 hours to every 48 hours).

– If t he pat ient is also receiving morphine, wean diazepam first t hen, wean morphine.

– Non-pharmacological measures to reduce wit hdrawal: reduce environment al st imuli; swaddle

infant s, frequent feedings.

– Infant s who have had t et anus remain hypertonic, even when t hey are no longer having spams.

Treatment of pain
morphine PO (via nasogast ric t ube) if necessary (see Pain, Chapt er 1).

When morphine is administ ered wit h diazepam t he risk of respiratory depression is increased, t hus
closer monitoring is required. When morphine is no longer required, wean t he same way as diazepam.

Treatment of the entry point and associated infections

– Search syst emat ically t he ent ry wound. Provide local t reat ment under sedat ion: cleansing and for
deep wounds, irrigat ion and debridement .
– Cord infect ion: do not excise or debride; t reat bact erial omphalit is and sepsis, add to
met ronidazole IV: cloxacillin IV + cefot axime IV or cloxacillin IV + gent amicin IV (for doses,
see Bact erial meningit is).
Tetanus vaccination
As t et anus does not confer immunit y, vaccinat ion against t et anus must be administ ered once t he
pat ient has recovered.

In case of neonat al t et anus, init iat e t he vaccinat ion of t he mot her.

Prevention
Of crit ical import ance, given t he difficult y of t reat ing t et anus once est ablished.

1) Post-exposure prophylaxis
– In all cases:
• Cleansing and disinfect ion of t he wound, and removal of any foreign body.

• Ant ibiot ics are not prescribed rout inely for prophylaxis. T he decision to administ er an ant ibiot ic
(met ronidazole or penicillin) is made on a case-by-case basis, according to t he pat ient ’s clinical
st at us.

– Depending on pre-exposure vaccinat ion st at us:

Tet anus vaccine (T V) 5

 and immunoglobulin: see indicat ions below.

Type of Complet e vaccinat ion (3 or more Incomplet e vaccinat ion (less t han 3
wound
doses)
doses)
T ime since administ rat ion of last dose: or no vaccinat ion

or unknown st at us
<5 5-10 years > 10 years
years

Minor, clean None None T V

Init iat e or complet e T V
1 boost er
dose

Ot her None T V
T V
Init iat e or complet e T V

1 boost er 1 boost er and administ er t et anus

dose dose immunoglobulin

t et anus vaccine IM

Children and adult s: 0.5 ml per dose

If no vaccinat ion or unknown vaccinat ion st at us: administ er at least 2 doses at an int erval of 4
weeks.
If incomplet e vaccinat ion: administ er one dose.

T hen, to ensure long-last ing prot ect ion, administ er addit ional doses to complet e a tot al of 5 doses,
as indicat ed in t he t able below.

human ant i-t et anus immunoglobulin IM

Children and adult s: 250 IU single dose; 500 IU for wounds more t han 24 hours old.

Inject t he vaccine and t he immunoglobulin in 2 different sit es, using a separat e syringe for each.

2) Routine vaccination (pre-exposure prophylaxis)

– Children: 6 doses in tot al: a first series of 3 doses of DT P or DT P + HepB or DT P + HepB + Hib before
t he age of 1 year, administ ered at an int erval of 1 mont h (e.g. at t he age of 6, 10 and 14 weeks), t hen
a dose of a vaccine cont aining t et anus toxoid bet ween t he age of 12 and 23 mont hs, a dose
bet ween t he age of 4 to 7 years, t hen a dose bet ween t he age of 12 and 15 years.

– Women of childbearing age: 5 doses during t he reproduct ive years: a series of 3 doses of Td or
T T 6
 wit h an int erval of at least one mont h bet ween t he first  and second dose and an int erval of at
least 6 mont hs bet ween t he second and t hird dose, t hen t wo ot her doses, each at minimum int erval
of one year, e.g. during pregnancies (see t able below).

– Pregnant women: if a woman has never been vaccinat ed or if her vaccinat ion st at us is unknown: 2
doses of Td or T T 6
during t he pregnancy to reduce t he risk of t et anus in mot her and  neonat e: t he
first as soon as possible during t he pregnancy and t he second at least 4 weeks lat er and at least 2
weeks before delivery. T his vaccinat ion schedule prot ect s more t han 80% of neonat es from
t et anus. A single dose offers no prot ect ion

Dose Vaccinat ion schedule in adult s Degree and durat ion of prot ect ion

T V1 On first cont act wit h t he healt h care syst em

No prot ect ion
or as soon as possible during pregnancy

T V2 At least 4 weeks aft er T V1 80%

1 to 3 years

T V3 6 mont hs to 1 year aft er T V2

95%

or during t he following pregnancy 5 years

T V4 1 to 5 years aft er T V3
99%

or during t he following pregnancy 10 years

T V5 1 to 10 years aft er T V4
99%

or during t he following pregnancy T hroughout t he reproduct ive years

1
Clindamycin IV for 7 days is an alt ernat ive (for doses, see Periorbit al and orbit al cellulit is, Chapt er
5).
2
Administ er t he first dose rect ally if an IV cannot be placed immediat ely.
3 Administ rat ion of oral diazepam t ablet s to infant s: calculat e t he exact dose of diazepam, e.g. to
obt ain 0.5 mg of diazepam, cut a scored diazepam 2 mg t ablet in half along scoring t hen split in
half again. Crush quart er t ablet and dissolve in expressed breast milk or infant formula.
4
Wit hdrawal signs: excessive irrit abilit y, t remors, increased muscle tone, frequent yawning, poor
feeding, wat ery stools and sweat ing.
5 Tet anus-cont aining vaccine, such as Td or T T or DT P or DT P + HepB or DT P + HepB + Hib
according to availabilit y and pat ient ’s age.
6 Use preferably Td vaccine (t et anus toxoid-dipht heria) or, if not available, T T vaccine (t et anus
toxoid). [ a b ]