Tetanus

Definition
• Tetanus is an acute disease of the nervous system, caused by
an exotoxin produced by the bacterium Clostridium tetani.
• clinical symptoms of tetanus is almost always associated with
working exotoxin (tetanospasmin) at the synapse connections
spinal ganglia, the neuromuscular junction (neuro muscular
junction) and nerve otonom.
Epidemiology
• Tetanus is a disease of the target of the World Health
Organization (WHO) Expanded Program on Immunization.
Overall, the annual incidence of tetanus is 0.5 to 1,000,000
• Tetanus is predominantly a disease of underdeveloped
countries, in countries without a comprehensive immunization
program. Tetanus mainly occurs in neonates and children.
• In the United States the majority of cases of tetanus occur due
to acute trauma, such as puncture wounds, lacerations or
abrasions.
Etiology
Port d'entre not always be known with certainty, but presumably
through:
• puncture wounds, fractures, complications accidents, animal
bites, extensive burns
• Surgical wounds, wounds that are not properly cleaned
(debridemant) with Otitis media, dental caries, chronic
wounds
• Cutting the umbilical cord is not sterile
patofisiologis
• This is a three-step process: binding to the presynaptic
membrane, translation of the toxin to the active site, and
induction of paralysis.
Presynaptic membrane
translation of the toxin to the
active site
induction of paralysis
 Clinical Manifestations
Generalized Tetanus
Symptoms of stiffness on all parts
such as
• trismus,
• risus sardonicus (forehead
wrinkle, eyes somewhat closed,
corners of the mouth are pulled
out and down),
• mouth pout,
• opistotonus (stiffness that
supports the body such as the
back muscles, neck muscles,
muscular body,
• trunk muscle), belly like a board.
Clinical Manifestation
local Tetanusis
• The initial symptoms are stiffness, spasms, and pain in the
muscles around the wound, followed by twitchings and brief
spasm of the muscles affected.
• most frequently in relation to wound the hand or forearm,
rarely in the stomach or paravertebral muscles.
Clinical manifestasi
• cephalic tetanusis a form of local tetanus in the wound to the
face and head. The incubation period is short, one or two
days. Muscles are affected (most often the face) become weak
or paralyzed. Cramps can occur face, tongue and throat, with
dysarthria, dysphonia and dysphagia.
Classification tetanus
• a. Grade 1 (mild): Trismus mild to moderate, common Stiffness: stiff
neck, opistotonus, abdominal board, not found or mild dysphagia, may
not find seizures, respiratory disorders not found
• b. Grade II (moderate): Trismus being, rigidity / stiffness may seem
obvious, a brief spasm of mild-to-moderate, moderate respiratory
distress with respiratory rate of more than 30 x / min mild dysphagia.
• c. Grade III (severe): Trismus severe generalized spasticity: spastic
muscle, spontaneous seizures, prolonged reflex spasm of respiratory
rate more than 40 times / minute, dysphagia severe apnea attacks and
tachycardia more than 120.
• d. Stage IV (very severe): stage III coupled with severe autonomic
disorders involving the cardiovascular system. Severe hypertension
with tachycardia occurs alternating with hypotension and bradycardia,
one of which can be settled.
Diagnosis
anamnesa
• Are found puncture wounds, accident or open fractures,
lukadengan pus or animal bites?
• Does it ever get out of pus from the ear?
• Whether you're suffering from tooth decay?
• Has it been immunized DT or TT, when did the last
immunization?
• The time interval between the onset of the first clinical
symptoms (trismus or local spasms) with seizure
 Diagnosis
Physical examination
• Trismus ie stiffness chewing muscles (masseter muscle) so difficult to open the mouth. In
neonates this rigidity causes mencucut mouth like the mouth of a fish, so that the baby
can not breastfeed. Clinically to assess the progress of healing, wide-open mouth was
measured every day.
• risus sardonicusoccur as a result of expression of muscle stiffness, so that it looks wrinkled
forehead, eyes slightly closed and the corners of the mouth drawn out and down
• Opistotonus is muscle stiffness that supports the body such as the back muscles, neck
muscles, muscular body and trunk muscle. Dapatmenyebabkan very severe stiffness of the
body curved like a bow
• belly board
• If rigidity is getting harder, there will be a generalized seizure that initially only occur after
stimulated, for example pinched, driven roughly or exposed to strong light. Gradually the
spasms shorter rest period so that the child fell in konvulsivus status.
• In tetanus severe respiratory problems will occur as a result of continuous seizures or by
laryngeal muscle stiffness that can lead to anoxia and death. Influence of the toxin on
autonomic nerves causing circulatory disorders and may also cause high body temperature
or sweating a lot. Sphincter muscle stiffness and other smooth muscle, causing retentio
Alvi, retentio urinae, or laryngospasm. Long bone fractures and spinal cord compression
 diagnosis
• Laboratory
• Results of laboratory tests for tetanus is not typical, namely:
• mild leukocytosis
• Platelets slightly increased
• Glucose and normal blood calcium
• Serum muscle enzymes may enhances
• But normal cerebrospinal fluid pressure may increases
•
• other supporting
• ECG and EEG normal
• Anaerobic culture and microscopic examination of pus taken from
the wound can help, but it is difficult to grow and Clostridium tetani
gram-positive rod-shaped stick drummer often can not be found.
 Procedures
• a. if possible ward / separate location to be designated for
tetanus patients. The patient should be placed in a shaded
area is quiet and protected from touch and auditory
stimulation as much as possible. All wounds should be
cleaned and debrided as ditunjukkan.7
• b. Immunotherapy: If available, provide a single dose of
3000-6000 IU TIHG with intramuscular or intravenous
injection (depending on the preparations available) as soon
as possible, 3-6 TIHG WHO recommends a single dose
administration intramuscularly at a dose of 500 IU.4-6
coupled with vaccine TT intramuscular injection of 0.5 cc.
Tetanus disease does not induce immunity, therefore
patients without a history of primary TT imuniasi should
receive a second dose 1-2 months after the first dose and the
third dose 6-12 months
• Doses of anti-tetanus serum (ATS), which is
100,000 IU recommended 50.000 IU and
50,000 IU intramuscularly administered
intravenously
 Treatment
• Antibiotic treatment:
• The first-line use of metronidazole 500 mg every six
hours intravenously or orally for 7-10 hari.2-6 In
children given an initial dose of 15 mg / kg IV / oral
dosage followed by a 30 mg / kg every six hours for 7 -
10 hari.1
• The second line is penicillin G 1.2 million units / day for
10 days. 5 (100,000-200,000 IU / kg / day intravenously,
given in 2-4 divided doses).
• Tetracycline 2 g / day, macrolides, clindamycin,
cephalosporins and chloramphenicol are also effective
 treatment
• Control convulsions: benzodiazepines are
preferred. For adults, intravenous diazepam
may be given in stages of 5 mg or 2 mg
lorazepam on the rise, titration to achieve
seizure control without excessive sedation and
hypoventilation (for children, starting with a
dose of 0.1-0.2 mg / kg every 2-6 hours,
titration up required). large amounts may be
required (up to 600 mg / day).
• Autonomic dysfunction control: magnesium sulphate as
above; or morphine. Note: β-blockers such as propranolol
used in the past but may cause hypotension and sudden
death; only this time esmalol
•
• Respiratory control: drugs used to control seizures and
provide sedation can result in respiratory depression. If
mechanical ventilation is provided, this is less of a problem;
if not, the patient should be carefully monitored and drug
dosage adjusted. Autonomic dysfunction control while
avoiding respiratory failure. mechanical ventilation is
recommended whenever possible. tracheostomy to
prevent apnea
 treatment
• Adequate fluid and nutrition should be
provided, such as tetanus spasms result in
high metabolic demands and a catabolic state.
nutritional support will improve the chances
of survival.
 Prevention
• Injury cure. Wound care should be done primarily in puncture
wounds, wounds allegedly dirty or contaminated with tetanus
spores. Especially wound care in order to prevent anaerobic
network.
• The provision of ATS and tetanus toxoid to the wound. Prophylaxis
with pemberianATS effective only on fresh wounds (less than 6
hours) and should segeradilanjutkan with active immunization.
• Active immunization. Active Imuniasi given that DPT, DT, or
tetanustoksoid. Imuniasi types depending on age group and
gender. VaksinDPT administered as primary immunization 3 times,
DPT IV at the age of 18 months and DPT V at the age of 5 years
and at the age of 12 years is given DT. Tetanustoksoid given to
women of childbearing age, women aged 12 years and ibuhamil.
DPT or DT given after the patient recovered and continued given
as scheduled,
 Complications
• sepsis,
• bronchopneumonia due to secondary
bacterial infection,
• laryngeal muscle stiffness and muscle of the
airway,
• aspiration of mucus / food / beverage,
• vertebral fractures (compression fracture)
 prognosis
• On this scale, 1 point is given for each as follows .:
• • shorter incubation period of 7 days
• • The period of onset less than 48 hours
• • Tetanus is obtained from burns, surgical wounds,
compound fractures, septic abortion, cutting the
umbilical cord, or intramuscular injection
• • drug users
• • Generalized tetanus
• • Temperatures higher than 104 ° F (40 ° C)
• • Tachycardia more than 120 beats / min (150 beats
/ min in neonates)
• • 0 or 1 - Mild tetanus; deaths down 10%
• • 2 or 3 - Moderate tetanus; 10-20% mortality
• • 4 - Severe tetanus; mortality of 20-40%
• • 5 or 6 - Very severe tetanus; mortality above
50%
• • cephalic tetanus always severe or very severe.
• • Neonatal tetanus is always very parah
Critical of Journal
• Title : “Prevalence of protective tetanus antibodies and
immunological response following tetanus toxoid vaccination
among men seeking medical circumcision services in Ugand”

• Date : 2018

• Author : Fredrick Makumbi, John Byabagambi, Richard

Muwanika, Godfrey Kigozi, Ronald Gray, Moses Galukande,
Bernard Bagaya, Darix Ssebagala, Esther Karamagi, Mirwais
Rahimzai, Mugagga Kaggwa, Stephen Watya, Anthony K.
Mbonye, Jane Ruth Aceng, Joshua Musinguzi, Valerian
Kiggundu, Emmanuel Njeuhmeli, Barbara Nanteza
introduction
• Uganda adopted a Safe Male Circumcision (SMC) policy in
2010, following three randomized clinical trials showing
efficacy for HIV prevention in men [1–3]. The prevalence of
HIV among adults aged 15 to 64 in Uganda remains high at
6.2%: 7.6% among females and 4.7% among males, and 0.4%
among 0–14 years
• Lack of tetanus vaccination policy for males may compromise
the quality of circumcision services, increase the risk of
infection, and impact service uptake. Therefore, in 2015 WHO
identified areas for which evidence was needed to make
recommendations on improved SMC safety, including antibody
titres prior to TT vaccination, antibody response to tetanus
toxoidcontaining vaccines (TTCV), and the correlation between
antibody titres and prior tetanus vaccination
Material and method
Study area
• Thirteen SMC sites in five regions of the Uganda were
selected to participate in the study: Rakai Health Science
Program and Nkozi Hospital in Central Region; Mukono
Hospital, Kojja Health Center (HC) IV, and Kayunga Hospital in
Central-1 Region; Kabwohe HC IV, Munobwa Tea Estate Clinic,
and Mbarara and Fort Portal Regional Referral Hospitals in
Western Region; Busesa HC IV and Masfau and Princess Diana
Hospitals in Eastern Region; and Gulu Regional Referral
Hospital in Northern Region.
Meterial and methods
Recruitment of participants
• All males aged 10 years or older seeking SMC services who
were eligible for SMC were invited to participate in the study.
Written informed consent for study participation was obtained
from men aged 18 years and older and from parents or
guardians of minors (aged 10 to 17 years). Minors also
provided written informed assent in addition to
parental/guardian consent. The study informed
consents/assents were in addition to the routine
consent/assent administered in the SMC progra
Material and method
Sample size
• The sample size estimates for the prevalence of protective
tetanus antitoxin antibodies was 769 participants based on
the following assumptions; 5% type-I error, 5% precision, 50%
prevalence of protective antibodies and a design effect of 2.0.
• For this analysis, a total of 620 men with complete data on
questionnaires and blood sample draw are presented, where
247 men have data on at least one follow-up. .
Material and method
Laboratory testing
• Anti-tetanus toxoid IgG antibody levels were determined using
a commercially available indirect ELISA kit (EuroImmun AG, EI
2060–9601 G, Lubeck, Germany). Results were qualitatively
interpreted as per kit insert using the categories: i) Insufficient
immunity (<0.1 IU/mL) ii) Need Booster (0.1–0.5 IU/mL), iii)
Booster needed 2–5 years (>0.5–1.1 IU/mL), iv) Booster
needed 5–10 years (>1.1–5.0 IU/mL) or v) Booster needed 10
years (>5.0 IU/mL).
Data management and statistical analysis
• The data management team at the Rakai Health Sciences
Program (RHSP) generated the computer identifications for
samples and questionnaires
• The tetanus antibody concentrations (IU/mL) ranging from 0
to 5.1+ were analyzed using descriptive statistics (means, SD;
median, IQR) and presented graphically using Spaghetti plots.
In order to determine the rate of immunological response of
clients following TTCV at days 0 and 28, a mixed effects model
was used to estimate the rates of change in levels of antibody
concentrations, with corresponding 95% confidence interval
result
• A total of 620 clients had both questionnaire and laboratory
data. The mean age of participants was 21.4 (SD 7.6) years,
and nearly half (49.7%) had post-primary education. Sexual
debut was reported by 53.4%, wherein 17.4% were currently
married and 38.8% reported non-marital relationships. About
two thirds (65.2%) responded affirmatively about knowledge
of tetanus infection, and just over a half (56.6%) knew how
tetanus was contracted. Self-reported receipt of tetanus
toxoid-containing vaccine (TTCV) was low (22.8%). However,
willingness to receive tetanus vaccination prior to circumcision
was high (99.6%)
Result
• For the follow-up component, 256 randomly selected
participants consented. The followup rate was high, with
blood draws obtained from 237 (92.5%) on day 14, 213
(83.2%) on day 28, and 147 (57.4%) on day 42.
Result
Discussion
• The study found that 57% of men attending SMC services had
insufficient immunity to tetanus. The prevalence of protective
tetanus toxoid antibodies increased rapidly following TTCV by
day 14. The finding of sero-prevalence of protective tetanus
antibody levels of 43% is consistent with DPT3 coverage in
Uganda of 50% prior to 2000, although the latter increased to
85% in 2007. Moreover, sero-prevalence at enrollment was
similar across all ages. This finding suggests that DPT3
coverage has not significantly improved over time, especially
in the rural settings where most of the circumcision clients
reside
Discussion
• Tetanus infection in Uganda is still common with a two fold
increase in the number of female cases aged 5 or more old
were observed from 755 in 2011 to 1665 in 2014; similarly the
number of males aged 5 years or older increased from 1007 to
1311 in the same period [11], and wounds due to trauma have
been reported, especially among farmers [14]. Road traffic
injuries are also common [15–16], as are Jigger infestations
(Tungiasis) [17]. Therefore, the risk of current or recently
healed wounds and jigger infestations among SMC clients
remains a public health challenge which needs to be
addressed with better tetanus toxoid vaccination coverage
and wound care to minimize the risk of tetanus
• The study was conducted within routine SMC services, and
findings are likely to be generalizable to other circumcision
programs. However, the study population of clients seeking
circumcision services is likely to be self-selected, in good
health, and may not be representative of the general male
population
conclusion
• There remains a significant risk of tetanus among men seeking
circumcision in Uganda due to insufficient immunity against
tetanus infection (57%). Tetanus toxoid immunization results
in a rapid immunological response, providing almost universal
protection by day 14 after immunization
CRITICAL APPRAISSAL
• PICO
• Patient/Problem : men who medical circumcision
• Intervention : vaccination tetanus
• Comparison :-
• Outcome : safely men with medical circumcision
for tetanus infection
 Yes/No/Can’t Statement
tell

Title and abstract Yes “Prevalence of protective tetanus antibodies and

immunological response following tetanus toxoid
vaccination among men seeking medical circumcision
services in Uganda”

Introduction

Background/rationale/ Yes “Tetanus infection associated with men who had male
Objectives circumcision has been reported in East Africa, suggesting a
need for tetanus toxoid-containing vaccines (TTCV)”
“Lack of tetanus vaccination policy for males may
compromise the quality of circumcision services, increase
the risk of infection, and impact service uptake. Therefore,
in 2015 WHO identified areas for which evidence was
needed to make recommendations on improved SMC
safety, including antibody titres prior to TT vaccination,
antibody response to tetanus toxoidcontaining vaccines
(TTCV), and the correlation between antibody titres and
prior tetanus vaccination”

Methods

Study design Yes “On each follow-up visit after receipt of the TTCV, client’s
identity was verified, and confirmed their willingness to continue
participation in the study”

Setting Yes “Thirteen SMC sites in five regions of the Uganda. All the sites
provided SMC services through implementing partners working
with the Ministry of Health”

Participants Yes “All males aged 10 years or older seeking SMC services who
were eligible for SMC were invited to participate in the study.
Written informed consent for study participation was obtained
from men aged 18 years and older and from parents or guardians
of minors (aged 10 to 17 years).”
Variables Yes “Participants completed an interview on social-demographic
characteristics, knowledge of tetanus infection and its causes, and
prior receipt of tetanus vaccination”

Data sources/ Yes “On each follow-up visit after receipt of the TTCV, client’s
measurement identity was verified, and confirmed their willingness to continue
participation in the study. Blood sample collection and
processing used standard operating procedures. All samples were
labeled with a pre-printed, computer-generated study identifier
and visit number.”

Bias Yes “All sites received tetanus toxoid vaccines from the district health
office following the UNEPI guidelines”

Study size Yes “For this analysis, a total of 620 men with complete data on
questionnaires and blood sample draw are presented, where 247
men have data on at least one follow-up.”

Quantitative variables Yes “The sample size estimates for the prevalence of protective
tetanus antitoxin antibodies was 769 participants based on the
following assumptions; 5% type-I error, 5% precision, 50%
prevalence of protective antibodies and a design effect of 2.0. A
total of 256 participants were estimated for the assessment of
immunological response assuming 95% of TTCV-naïve clients
would achieve a protective antitoxin concentration compared to
100% of those receiving a booster, over three follow-up visits,
adjusting for individual correlation of 0.5 due to repeated
observations and a loss to follow-up of 20%”

Statistical methods yes “The data management team at the Rakai Health Sciences
Program (RHSP) generated the computer identifications for
samples and questionnaires. Data management teams at the
RHSP, at the USAID ASSIST Project office in Kampala, and at
the Makerere University School of Public Health captured
questionnaire data electronically. All the questionnaire data were
double entered using FoxPro version 9.0 (at the RHSP) and
CSPro, cleaned and appended to form one dataset. Data were
transferred into Stata version 14 for statistical analyses”

“The tetanus antibody concentrations (IU/mL) ranging from 0 to

5.1+ were analyzed using descriptive statistics (means, SD;
median, IQR) and presented graphically using Spaghetti plots. In
order to determine the rate of immunological response of clients
following TTCV at days 0 and 28, a mixed effects model was
Results

Participants Yes “A total of 620 clients had both questionnaire and laboratory
data. The mean age of participants was 21.4 (SD 7.6) years, and
nearly half (49.7%) had post-primary education. Sexual debut
was reported by 53.4%, wherein 17.4% were currently married
and 38.8% reported non-marital relationships. About two thirds
(65.2%) responded affirmatively about knowledge of tetanus
infection, and just over a half (56.6%) knew how tetanus was
contracted. Self-reported receipt of tetanus toxoid-containing
vaccine (TTCV) was low (22.8%). However, willingness to
receive tetanus vaccination prior to circumcision was high
(99.6%).”

Descriptive data Yes “A total of 620 clients had both questionnaire and laboratory
data. The mean age of participants was 21.4 (SD 7.6) years, and
nearly half (49.7%) had post-primary education. Sexual debut
was reported by 53.4%, wherein 17.4% were currently married
and 38.8% reported non-marital relationships. About two thirds
(65.2%) responded affirmatively about knowledge of tetanus
infection, and just over a half (56.6%) knew how tetanus was
contracted. Self-reported receipt of tetanus toxoid-containing
vaccine (TTCV) was low (22.8%). However, willingness to
receive tetanus vaccination prior to circumcision was high
(99.6%).”

(b) Indicate number of participants with missing data for each

variable of interest

Outcome data Yes “For the follow-up component, 256 randomly selected
participants consented. The followup rate was high, with blood
draws obtained from 237 (92.5%) on day 14, 213 (83.2%) on day
28, and 147 (57.4%) on day 42.”

Main results Yes “The coefficient for days since vaccination, a measure of rate of
change, was 0.27 (95% CI: 0.25, 0.29), and the quadratic term for
days since vaccination was -0.004 (95% CI: -0.0047, -0.0038);
both were statistically significant, p<0.001.”
Other analyses Yes “A total of 247 HIV-negative clients had at least one follow-up
study visit, where 49.4% (122/ 247) had all the four visits and
26.7% (66/247) and 23.9% (59/247) had three and two visits,
respectively. interactions, and sensitivity analyses”

Discussion

Key results Yes “This study suggests a rapid immunological response within the
first 14 days following TTCV when the majority of clients
attained protective antibody levels. Previous studies have only
provided data at day 28 as the first follow-up visit, and so it was
not empirically possible to know how much earlier the
immunological response occurs”

Limitations Yes “Baseline protective antitoxin levels depend on the coverage of

prior vaccination programs, which may vary across different
regions, but the study was not powered to detect regional
differences.”

Interpretation Yes “These findings suggest the importance of HIV testing and
counseling for clients seeking circumcision”

Generalisability Yes “Circumcision may be conducted 14 days following TTCV, and

clients should be encouraged to return for a second immunization
after their last post-operative visit. However, screening for HIV
and older age is needed since there is a slow or delayed response
to TTCV. In the long-term, mass tetanus vaccination campaigns
should be conducted, and men should be offered a TTCV booster
at time of first contact for SMC if documentation of participation
in mass vaccination is available.”

Other information

Funding Yes “We acknowledge the assistance of Heather Scobie for guidance
on laboratory tests for tetanus toxoid and the support of Sheila
Kyobutungi (USAID, Uganda) and Ibrahim Lutalo (METS
Project, Makerere University School of Public Health) for their
support during study implementation.”