Tonsilopharyngitis Diphtheriae Complicated With......

Journal of Clinical Microbiology & Infectious Disease
JCMID. Volume 1, Number 1, January-April 2014: 6-16

Print-ISSN: 2355-1909, E-ISSN: 2355-1984.
TONSILOPHARYNGITIS DIPHTHERIAE COMPLICATED WITH

DIPHTHERITIC MYOCARDITIS IN 13 YEARS OLD GIRL AT
DR. KARIADI HOSPITAL SEMARANG-INDONESIA
1Nursyamsi-Agustina,
N., 2Wahyutomo, R., 1Hapsari, MMDEAH., and 2Wahjono, H.
1Department
of Pediatric, Faculty of Medicine Diponegoro University/

Dr. Kariadi Hospital Semarang-Indonesia
2Department of Clinical Microbiology, Faculty of Medicine Diponegoro University/
Dr. Kariadi Hospital Semarang-Indonesia
ABSTRACT
Background: Diphtheria is a frequent upper respiratory tract illness caused by Coryne-bacterium
diphtheriae characterized by sore throat, low fever, malaise, anorexia and pseudo-membrane on the
tonsils, pharynx, larynx and nasal cavity. Case description: It was reported that 13 years old girl
from Kudus referred to Dr. Kariadi Hospital with sore throat, low fever, hoarseness, cough,
anorexia and malaise. Patient has history of immunization completely. Physical examination
indicates enlarged tonsil grade II and pseudo-membranous in the area of the tonsils, uvula, and
pharynx. There was no bull neck. Results: The result of throat swab culture and Neisser staining
were positive, Blood agar, and Telurit agar culture lead to the performance Coryne-bacterium
diphtherias colonies. From the result of the ECG, CK-MB and Troponin I show myocarditiss sign.
Patient should be in strict isolation room until 3 times of cultures show negative results. The
theraphy was ADS 80,000 unit i. v. (DAT treatment), penicillin procaine 50000-100000 IU/kg/day
intramuscularly for 10 days and was given prednisone for reducing inflammatory reaction that can
lead to airway obstruction. Examination of serial ECG is important to look at the complications of
myocarditis. Having obtained the results of 3 times negative cultures, and/or at least 24 hours
after completing treatment and show an improvement of symptoms, finally the patient was getting
improvement clinically and then transferred to the inpatient ward. Conclusion: Early detection
and good blood telurit culture result is important to confirm the diagnostic of diphtheria and very
useful for the clinicians to do the right clinical management for tonsilopharyngitis diphtheria in
children. Subsequently, the role of clinical microbiologist in this case not only to support the
clinical diagnostic but also the epidemiology in term of spreading of Corynebacterium diphtheriae
among their family and neighbours in the community.
Keyword : Corynebacterium diphtheriae, tonsilopharyngitis diphteriae, myocarditis,
INTRODUCTION
Diphtheria is an acute, communicable
disease
caused
by
exotoxin
producing
Corynebacterium diphtheriae. Review of pathology
in archived cases and the literature shows that
C.diphtheriae usually localizes in the upper
respiratory tract, ulcerates the mucosa, and
induces the formation of an inflammatory
pseudomembrane.
The exceedingly potent toxin is absorbed into

the circulation and damages remote organs,
potentially resulting in death. Although primary
infection can occur at sites other than the
pharyngeal mucosa, lesions usually occur as local
pseudo-membranous inflammation on mucosal
surfaces of the upper respiratory tract and
systemic lesions of the heart and (to a lesser
extent) nerves.1,2
Corresponding Author:
N. Nursyamsi Agustina
Department of Pediatric, Faculty of Medicine
Diponegoro University/Dr. Kariadi Hospital
Semarang-Indonesia
E mail: agustina@gmail.com
MATERIALS AND METHODS

Case report
The case reported 13-year 8-month old girl
hospitalized since January 31th 2013 until
February 18th 2013. Her main complaint was sore
throat (referred from Kudus Hospital with
www.jcmid.com

Print-ISSN: 2355-1909, E-ISSN: 2355-1984.
membranous tonsillitis suspected diphtheria).

Since 4 days before hospitalization, the girl
suffered from fever, low-grade fever, no seizure,
no shivering, cough (+), disphagia (-), no
discharge from ears, no nose bleeding, no gums
bleeding, no ptechie, no nausea, no vomite, no
gastrointestinal and urinary tract complaints. She
was got to physician and given some medicine.
Three days before hospitalization, the girl was
still fever, sore throat, disphagia, hoarseness, but
no difficulty in breathing. The parents took her to
physician again and she was diagnosed tonsillitis.
The doctor suggested to bring her to ENT
specialist. Two days later, the girl suffered from
difficulty in speaking and sore throat increased.
The parents took her to Kudus Hospital and she
was hospitalized during 1 day in ward. She
received tosmicyl
injection 2x1 gr
iv,
metronidazol injection 3x500 mg iv, ketorolac
injection 3x1amp iv, methyl prednisolon injection
2x1 amp, vitamin C injection 1x1 amp iv. In the
course of hospitalization, the girl was dispneu
then she was referred to Kariadi Hospital. From
physical examination in emergency room, there
were tonsil enlargement grade II and grayish
patch pseudo-membranous in the area of the
tonsils, uvula, and pharynx. There was no bull
neck. The result of throat swab culture and
Neisser staining were positive. Blood agar and
Telurit agar culture lead to the performance
Corynebacterium diphtherias colonies. She was
hospitalized in isolation room in C1L2 ward and
transferred to PINERE on January 31th 2013.
Patient should be in strict isolation room until 3
times of cultures showed negative results.
She lived in Islamic Education Center. Her
friends in this place suffered from sore throat and
cough but there were no data about source of
transmission of diphtheria.
She was born from G2P2A0 mother, 27 years
old, aterm. Her mother got medical check up to
midwife more than 4 times during pregnancy
regularly
and
received
vitamin,
iron
supplementation, and TT injection for twice.
There was no history of illness during pregnancy.
Basic immunization was complete. She received
booster when she was in 1st class elementary
school and no booster when she was sixth class.
Her father is a mechanic with average
income is of IDR. 1.000.000,-/month and her
mother is a housewife. Health cost was covered
by Locally State Health Insurance.
Social
economic impression is poor. From physical
examination, a 13-year 8-month old girl, with
weight was 39 kg and height was 148 cm. General
conditions
were
conscious,
spontaneous
breathing, and no retraction. Heart rate was 98
www.jcmid.com
beats/minute and regular with good pulse.

Respiratory rate was 28 times/minutes. Body
temperature was 36,70C and blood pressure was
100/65 mmHg. Head was mesocephal, eyes were
no conjunctival anemic, no icteric. Nasal flare was
negative, no nasal discharge, mouth was no
cyanotic with tonsil enlargement T2-2, hyperemis,
grayish pseudomembrane in tonsils, uvula, and
pharynx, no lymph neck enlargement, no
bullneck, tenderness (+). Chest: symmetrical, no
suprasternal and epigastrial retraction, no distant
regular heart sound, and no gallop. Lungs breath
sound were regular, normal and no crackles.
Abdomen was flat, no enlargement of liver and
spleen. All extremities were not cyanotic,
capillary refill <2. Anthropometry examination
was HAZ: -1.61 SD; BMI: -0.67 SD.
Laboratory examinations on January 31th
2013 were Hb 10.5 g/%l, Ht 35.2%, leucocytes
20.200/mmk,
erythrocyte
3.97million/mmk,
thrombocyte 119.000/mmk, MCV 88.8 fl, MCH
26.30 pg, MCHC 29.70 gr/dl, cells count
E0/B0/Bt0/Li77/Mo16, CKMB 35 U/l.
ECG showed sinus arithymia. Chest X-ray
showed
normal.
Results
of
cardiology
consultation were sinus arythmia with suggestion
for checking CKMB, troponin T, ECG monitoring,
and bed rest.
In isolation room the patient received nasal
oxygen 2 l/minute, infused 2A1/2N 1440/60/15
drops/minute, Peniciline procain injection 2
million unit (right and left buttom) for 10 days,
DAT 80.000 unit, ketorolac injection 3x30 mg. Peroral: paracetamol 4-6x500 mg (if T>380C),
prednisone 40 mg daily (3-3-2 tablets) for
reducing inflammatory reaction that can lead to
airway obstruction, and diet 6x300 cc liquid diet I.
Result of clinical nutrition consultation, the
patient was given diet via NGT with the need of
energy was 1900 kcal per day, 285 grams
carbohydrates, 60 grams protein, and 58 grams
lipid.
The patient was given 6x300 cc liquid diet I.
On 2nd day, the patients were still dispneu, sore
throat (+). She was stridor and supraclavicular
retraction on physical examination, T2-2,
hyperemic, and pseudo-membrane (+). On the 3rd
day, the patient was still dispneu, sore throat (+).
Laboratory results were Hb 12.7 g/%, Ht 41.2%,
leucocytes
27.600/mmk,
erythrocyte
4.65
million/mmk, thrombocyte 97.400/ mmk, MCH
27.4 pg, MCV 88.6 fL, MCHC 30.9 g/dL, ureum 45
mg/dL, creatinin 0.36 mg/dL, SGOT 46 U/l,
SGPT 72 U/l, CKMB 27 U/l, Troponin I <0.01
g/L. Urine analysis was normal. Swab culture
was positive for Corynebacterium diphtheria.

Print-ISSN: 2355-1909, E-ISSN: 2355-1984.
On the 5th day, the patient was still dispneu,

sore throat, and hoarseness. She looked ill
appearance. Pseudo-membrane was still positive
in uvula, bleeding (+), but showed improvement.
Tonsil was T2-2, hiperemis (+). Throat swab
culture was still positive for Corynebacterium
diphtheria.
On the 7th days, the patient was still sore
throat, dispneu, but had no fever. General
condition: conscious, spontaneous breathing, and
ill appearance. Her heart rate was 90 beats /
minute and regular, good pulse, respiratory rate
was 30 times/minutes, body temperature was
37,20C. Physical examination of tonsil showed T2T2 hyperemic, pseudo-membrane was still
positive in uvula but showed improvement.
Suggestion swab and culture daily until 3 times
examination showed negative. There was no
Corynebacterium diphtheriae colonization in both of
throat swab and culture. Prednisone began to be
tapering off 2-2-1 tablets (25 mg).
On the 8th days, sore throat decreased and
dispneu (-). Tonsil was still T2-T2 hyperemic but
pseudo-membrane (-). Second throat swab and
culture showed no Corynebacterium diphtheriae
colonization. Nasogastric tube was off and tried to
oral diet gradually.
On the 9th days, sore throat decreased and
patient got liquid diet II. Tonsil was still T2-T2
hiperemis but pseudo-membrane was negative.
Third throat swab and culture showed no
Corynebacterium diphtheriae colonization.
On the 10th day, sore throat decreased and
the patient could eat, cough (+), dispneu (-).
Tonsil was T1-1 and was not hiperemis. Procaine
penicillin injection was stopped after 10 days
administration. Ketorolac injection was stopped
and prednisone was 1-0-1 tablets (10 mg). The
patient was transferred to C1L2 ward and the
disease gradually got improvement.
On the 12th day, sore throat was
improvement but she was still cough. There were
crackles on chest auscultation. Laboratory results
were Hb 10.7 g/%, Ht 34.8%, leucocyte
15.700/mmk, erythrocyte 3.89millions/mmk,
thrombocyte 648.000/mmk, MCH 27.5 pg, MCV
89.6 fl, MCHC 3.,7 g/dL, ureum 33 mg/dL,
creatinine 0.91 mg/dl, SGOT 95 U/l, SGPT 256
U/l, CKMB 35.6 U/l.
On 13th day, the patient complained about
hoarseness. Antibiotic have been switched to
erythromycin oral 3x500 mg. She was
programmed to indirect laryngoscope and
consulted to pediatric cardiology. She was
assessed myocarditis diphtheria and received
prednisone 6-5-5 tablets. On the 15th day, the
patient was still hoarseness. The result of indirect
www.jcmid.com
laryngoscopy showed laryngitis. On the 16th day,

laboratory result of CKMB showed 23 U/l.
Electrocardiography showed sinus rhythm,
normoaxis deviation, T-inverted in lead II, III, V3V6 and depression of ST segment in lead II, V4V6.
On the 17th day, the patient had no
complaint. Electrocardiography showed sinus
rhythm, normoaxis deviation, T inverted in lead
II, III, AVF, V1-V6, and depression of ST segment
in lead II.
On the 19th day, electrocardiography showed
sinus rhythm, normoaxis deviation, T inverted in
lead II, III, V3-V6 and depression of ST segment in
lead II. The patient got improvement and had no
complaint. So she discharged from hospital and
had to control to policlinic.
RESULTS AND DISCUSSIONS
In this case, swab staining and culture were
positive for Corynebacterium diphtheria and the
patient was diagnosed with tonsilopharyngitis
diphtheria.
Pathology of Diphtheria
C. diphtheria is usually transmitted by direct
contact or by sneezing or coughing. In
populations with a high rate of immunization,
improved coverage in children has shifted the age
distribution of those afflicted to unimmunized or
poorly immunized adults. Furthermore, relatively
increased isolation of nontoxigenic strains of C.
diphtheria versus toxigenic strains is noted when
immunization rates are improved.1
Diphtheria commonly affects the tonsils,
pharynx, and larynx. The C. diphtheria remains in
the superficial mucosa or skin and elaborates its
exotoxin. The diphtheria exotoxin, a potent 62 kd
polypeptide inhibits protein synthesis leading to
local tissue necrosis.2,4 The exotoxin is absorbed
into the mucous membranes and causes
destruction of epithelium and a superficial
inflammatory response.15 The necrotic epithelium
becomes embedded in exuding fibrin and red and
white cells, resulting in a dense necrotic coagulum
of organisms, epithelial cells, fibrin, leukocytes,
and erythrocytes.4,15 This advances commonly
over the tonsils, pharynx, or larynx, and becomes
a gray-brown, leather-like adherent pseudomembrane. With increase in the concentration of
toxin, it is spread to other tissues through
haematogenous dissemination.4
Diphtheriae toxin, which is secreted by
toxigenic strains of C. diphtheriae, is a single
polypeptide of mol weight 58,342. Toxigenic
strains of C. diphtheria carry the tox structural gene
found in lysogenic corynebacteriophages b tox1, g
8

Print-ISSN: 2355-1909, E-ISSN: 2355-1984.
tox1, and q tox1. Highly toxic strains have two or

three tox1 genes inserted into the genome.
Expression of the gene is regulated by the
bacterial host and is iron dependent. In the
presence of low concentrations of iron, the gene
regulator is inhibited, resulting in increased toxin
production. Toxin is excreted from the bacterial
cell and undergoes cleavage to form two chains, A
and B, which are held together by an inter chain
disulfide bond between cysteine residues at
positions 186 and 201. As toxin concentrations
increase, the toxic effects extend beyond the local
area due to distribution of the toxin by the
circulation.3 Diphtheria toxin does not have a
specific target organ, but myocardium and
peripheral nerves are most affected.1,7,16
Human diphtheria infection may terminate
with acute cardiac failure or may prove fatal
weeks later during convalescence. Examination of
heart tissues after death demonstrates cardiac
damage in many cases, although the pathologic
lesions are varied and inconsistent, perhaps
representing a spectrum of changes related to
cumulative exposure to toxin. When toxin
concentrations are low, the heart chambers may
be dilated with no effusion or malformation. The
valves, coronary vessels, epicardium, and
endocardium are normal. The myocardium
appears pale brown and soft. The myocardium
appears distorted by widely distributed areas of
granular degeneration and loss of cross striations.
Neutral fat droplets occur in 50% of fatal cases of
diphtheria. The fat droplets appear as beaded
configurations in the sarcoplasm of muscle cells
with oil Red O stains. Nuclei may form caterpillar
chromatin configurations. Some nuclei are
pyknotic. Caterpillar cells are histiocytes.
Neutrophilsin the sarcoplasm of degenerating
myocardial cells are except in areas of maximal
degeneration, where they are associated with
slight hemorrhage. No other inflammatory cells
are observed. Conduction tissue lesions are not
extensive. Abnormalities of coronary vessels,
endocardium, or epicardium are not seen.5
Clinical Presentation
Classic diphtheria is an upper-respiratory
tract illness characterized by sore throat, lowgrade fever, and an adherent pseudo-membrane
of the tonsil(s), pharynx, and/or nose. The disease
can involve almost any mucous membrane.17 The
characteristic lesion, caused by liberation of a
specific cytotoxin, is marked by a patch or patches
of an adherent grayish-white membrane with
surrounding inflammation. The infection most
often manifests as membranous naso-pharyngitis
or obstructive laryngotracheitis.
www.jcmid.com
The toxin produced by some strains can

cause severe damage to the throat or other tissues.
Occasionally, C. diphtheria disseminates from the
skin or respiratory tract and causes invasive
systemic
infections
including
bacteremia,
endocarditis and arthritis.18
In this case, the girl suffered from low grade
fever, sore throat, cough, disphagia, hoarseness,
difficult in speaking and in the course of disease,
the girl was dispneu. From physical examination,
there were stridor, tonsil enlargement T2-2,
hyperemic, and an adherent grayish-white
pseudo-membranous in the area of the tonsils,
uvula, and pharynx. These clinical manifestations
were
corresponded
to
tonsilopharyngitis
diphtheria. This is the most common site of
infection and is associated with the absorption of
toxin. The onset is insidious. Early symptoms
include malaise, sore throat, anorexia and lowgrade fever. Two to three days later the
membrane appears in the pharyngeal/tonsillar
area. The membrane initially appears white and
glossy, but evolves into a dirty gray color with
patches of green or black necrosis. The extent of
the membrane correlates with the severity of
symptoms (i.e. with posterior pharynx, soft palate
and periglottal area involvement, profound
malaise and obstructed breathing may occur). In
cases of severe disease the individual may also
develop edema of the submandibular areas and
the anterior neck, along with lymphadenopathy,
giving the characteristic bullneck appearance.
The individual may recover or, depending on the
amount of toxin absorbed, develop severe illness,
pallor, rapid pulse, stupor and coma with death
occurring in six to 10 days.17,18 In this patient,
there wasnt bullneck.
On the 13th day, the patient complained
about hoarseness. Then she was programmed to
indirect laryngoscope. The result of indirect
laryngoscope showed laryngitis.This may be
either an extension of the pharyngeal form or be
the only site involved. Symptoms include fever,
hoarseness and a barking cough. Development of
the membrane may lead to airway obstruction,
coma, and death.17,18
Diagnosis of Diphtheria
Diagnosis is usually made based on history,
clinical presentation, and swab staining and
culture as it is essential to begin therapy as soon
as possible. Diphtheria should be suspected based
on the following clinical clues:18
mildly painful tonsillitis and/or pharyngitis
with associated membrane, especially if the
membrane extends to the uvula and soft
palate;
9

Print-ISSN: 2355-1909, E-ISSN: 2355-1984.
adenopathy and cervical swelling, especially

if associated with the membranous
pharyngitis and signs of systemic toxicity;
hoarseness and stridor; palatal paralysis;
serosanguinous
nasal
discharge
with
associated
mucosal
membrane;
and
temperature elevation rarely in excess of
39.4C (103F).
mechanism for these delayed features of

diphtheria (level of evidence 3).15
The role of the clinical microbiology in the
diagnosis of diphtheria is to assist the clinicians in
confirming their clinical diagnosis. Diagnosis is
confirmed by bacteriologic examination of
specimens. Cultures of lesions, if present and the
nasopharynx are done to confirm the diagnosis.
Swab(s) from the nasopharynx, especially the
membrane, is essential. Isolates should be tested
for toxigenicity. Toxigenicity tests require an
additional 48 to 72 hours (level of evidence 3).15
Centre for Disease Control and Prevention
(CDC 2010) defines diphtheria as:1,12
Probable: In the absence of a more likely
diagnosis, an upper respiratory tract illness
with an adherent membrane of the nose,
pharynx, tonsils, or larynx; and absence of
laboratory confirmation;
and
lack of
epidemiologic linkage to a laboratory
confirmed case of diphtheria.
Confirmed: An upper respiratory tract illness
with an adherent membrane of the nose,
pharynx, tonsils, or larynx; and any of the
following:
isolation
of
Corynebacterium
diphtheriae from the nose or throat; or
histopathologic diagnosis of diphtheria; or
epidemiologic linkage to a laboratory
confirmed case of diphtheria.
Figure 1
Diphtheria at first presentation
Laryngeal involvement, which may occur on
its own or as a result of membrane extension from
the nasopharynx, presents as hoarseness, stridor,
croupy cough and dyspnea. These patients are at
significant risk for suffocation because of local
soft tissue edema and airway obstruction by the
diphtheritic membrane.15 (level of evidence 3)
There may be toxin-mediated paralysis of
soft
palate,
posterior
oropharynx
and
hypopharynx. Although the toxin has no target
organs the myocardium and peripheral nerves are
most affected.Other toxin mediated complications
of diphtheria are toxic cardiomyopathy which
occurs in 1025% of patients with respiratory
diphtheria and is responsible for 5060% of
deaths. Neurotoxicity and renal damage can also
occur. Some of these features may present up to
six weeks after the onset of the illness suggesting
an immunological basis for the pathophysiologic
www.jcmid.com
Figure 2
Algorithm for laboratory diagnosis of diphtheria19
Source: Efstratiou A, Engler KH, Mazurova IK,
Glushkevich T, Vuopio-Varkila J, Popovic T.
Current Approaches to the Laboratory Diagnosis
of Diphtheria.
10

Print-ISSN: 2355-1909, E-ISSN: 2355-1984.
In this case, based on history of illness, the

patient suffered from low-grade fever and cough
(+) since 4 days before hospitalization . One day
later, she was sore throat, disphagia, and
hoarseness. The parents take her to physician
again and she was diagnosed tonsillitis. Two days
later, the girl suffered from difficulty in speaking
and sore throat increased. The parents took her to
Kudus Hospital and she was hospitalized during
1 day in ward. From her past history, she lived in
Islamic Education Center. Her friends in her place
suffered from sore throat and cough.
From physical examination result, there were
tonsil enlargement grade II and an adherent
grayish-white pseudo-membranous in the area of
the tonsils, uvula, and pharynx. The result of
indirect laryngoscope showed laryngitis. This
may occur on its own or as a result of membrane
extension from the nasopharynx. The result of
throat swab culture and Neisser staining were
positive, Blood Telurit agar culture lead to the
performance Corynebacterium diphtherias colonies.
According to CDC classification, the patient was
categorized to confirmed diphtheria because there
were upper respiratory tract illness with an
adherent membrane of the nose, pharynx, tonsils,
or larynx with positive culture for Corynebacterium
diphtherias colonies (level of evidence 1).12
Figure 3
Blood agar culture of Corynebacterium diphtheria
Figure 4
Blood Telurit agar culture of Corynebacterium
diphtheria
www.jcmid.com
Treatment
The treatment of diphtheria is divided into
general and specific treatment. The general
treatments includes: 1) isolation, 2) bed rest at
least 2-3 weeks, 3) soft or liquid food depending
on the state of the patient, 4) cleanliness of
respiratory track and liquid absorption, and 5)
electrocardiography control 2-3 times a week for
4-6 weeks to detect myocarditis earlier. The
specific treatment aims to neutralize toxin
produces by diphtheria bacilli and kill diphtheria
bacilli producing toxin (level of evidence 3).7
In this case, the decision to treat not only
based on clinical manifestation but also from
microbiology examination on the first admission
in emergency unit. Rapid detection by means of
neisser staining is important for diphtheria.
Furthermore, swab of pseudo-membranous area
were taken to confirm for diphtheriae cultures
too. The patient received general and specific
treatment. She was placed in isolation room in
PINERE until having obtained the results of 3
times negative cultures and took bed rest in
hospital. For nutritional support, the patient
received 6x300 cc liquid diet I via NGT with the
need of energy was 1900 kcal per day, 285 grams
of carbohydrates, 60 grams of protein, and 58
grams of lipid. For specific treatment, the patient
received procaine penicillin injection of 2 million
unit (right and left buttom) for 10 days, DAT
80.000 unit, ketorolac injection 3x30 mg. Per-oral :
paracetamol 4-6x500 mg (if T>38oC), prednisone
40 mg daily (3-3-2 tablets) for reducing
inflammatory reaction that can lead to airway
obstruction.
The most effective treatment for diphtheria is
early administration of diphtheria antitoxin
(DAT), along with appropriate antimicrobial
therapy to eliminate the corynebacteria from the
site of infection thus stopping ongoing toxinproduction (level of evidence 3).20 Kneen et al
showed that penicillin and erythromycin are both
effective for the treatment of diphtheria (level of
evidence 2).21
Having obtained the results of 3 times
negative cultures, and/or at least 24 hours after
completing treatment and show an improvement
of symptoms, finally the patient was getting
improvement clinically and then transferred to
the inpatient ward. Finally there is no growth in
culture and Neisser staining result during the
fourth until sixth day hospitalization.
Complication
Toxin mediated complications of diphtheria
are toxic cardio-myopathy which occurs in 10
25% of patients with respiratory diphtheria and is
11

Print-ISSN: 2355-1909, E-ISSN: 2355-1984.
Table 1
DAT treatment for cases18
Type of Diphtheria
Nasal
Tonsillar
Pharyngeal or laryngeal
Cutaneous
Combined types or delayed diagnosis (or
nasopharyngeal with membrane present)
Extensive disease of > 3 days duration and/or severe
swelling of neck (bullneck)
Dose
(units)
10.000-20.000
15.000-25.000
20.000-40.000
20.000-40.000
40.000-60.000
Route
(one time dose*)
IM
IM or slow IV
IM or slow IV
IV
IV
80.000-120.000
IV
*Additional doses may be warranted based on the persons symptoms and response
IM = intra muscular, IV = intra vena
Source: Alberta Health and Wellness. Public Health Notifiable Disease Management Guidelines
Table 2
Antibiotic treatment for case18
Age/Weight
< 9 kg (20 lbs)
> 9 kg (20 lbs)
Agent
Procaine Pen G
Pen G
Dose
300.000 U BID
600.000 U BID
When patient can swallow comfortably:

Child2/Adult
Penicillin V
125-250 mg QID
OR
OR
Erythromycin
125-500 mg QID
Duration
Route
14 days1
14 days1
IM
IM
14 days1
PO
14 days1
PO
1 Total
treatment time is 14 days (i.e. if taking IM antibiotic for 10 days would complete treatment with
4 additional adays of PO antibiotic
2 Use a lower Dose in children < 6 years of age
Source : Alberta Health and Wellness. Public Health Notifiable Disease Management Guidelines
Table 3
Antibiotic prophylaxis for contacts and treatment for carriers of diphtheria 18
Age
Agent
Dose
Route
Duration
< 6 years old
Penicillin G benzathine
OR
Erythromycin
600.000 units
IM
One time dose
40 mg/kg in 4 divided doses
PO
days
Penicillin G benzathine
OR
Erythromycin
1.2 million units
IM
One time dose
g/day in 4 divided doses
PO
7-10 days
> 6 years old
Source : Alberta Health and Wellness. Public Health Notifiable Disease Management Guidelines
responsible for 5060% of deaths. Neurotoxicity
and renal damage can also occur. Some of these
features may present up to six weeks after the
onset of the illness suggesting an immunological
www.jcmid.com
basis for the pathophysiologic mechanism for

these delayed features of diphtheria.4 Acute
mortality is due to toxin-mediated diphtheritic
cardio-myopathy, suffocation by the pseudo12

Print-ISSN: 2355-1909, E-ISSN: 2355-1984.
membrane,
disseminated
intravascular
coagulation, and renal failure. The risk of cardiac
involvement is higher in patients presenting with
fever, toxic disease, and membranous disease
(level of evidence 3).22
In the course of the disease, the patient
suffered from diphtheritic myocarditis. CKMB
was 35,6 U/l. Electrocardiography showed sinus
rhythm, normoaxis deviation, T inverted in lead
II, III, V3-V6 and depression of ST segment in lead
II, V4-V6. Then she was treated for diphtheritic
myocarditis and monitored for ECG. She was not
complicated by both neurological and renal
disorder. Myocarditis was reported to cause high
mortality.16,22,23 Clinical signs of diphtheritic
cardio-myopathy become apparent by the end of
week 2 of infection but, in severe cases, may be a
presenting feature (level of evidence 3).22
Diphtheritic myocarditis is frequently
complicated by arrhythmias that can cause
sudden death if not managed properly. The
patients with cardiac involvement may be
asymptomatic (ECG change and/or raised SGOT)
or symptomatic (features of heart failure). The
ECG changes of myocarditis may be sickle-like
sagging of the ST segment (specific for
diphtheritic
myocarditis),
arrhythmias
(supraventricular or ventricular), abnormal Q
waves, repolarization abnormalities, ST-segment
elevation > 1 mm in at least two chest leads or one
limb lead, T-wave inversion (except in leads V1
and aVR), iso-electric T waves and QTc interval >
0.39 s for men and > 0.41 s for women,
atrioventricular block, bundle branch block,
hemiblock, etc (level of evidence 3).16
Myocarditis was the most common
complication observed in less than 10 years of age
group, whereas neurological complication was
mainly seen in adults. Majority of the patients
with myocarditis were asymptomatic, had only
ECG changes, SGOT elevation, and had a
favorable outcomes. Another observation was
that almost all patients developed cardiac
involvement within first week of onset of
respiratory symptoms and patients who had bull
neck and extensive faucial patches had more
incidence of cardiac involvement (level of
evidence 3).22
Although the presence of bull neck in
diphtheria patient is associated with development
of myocarditis according to references, but in this
patient was not like that. There was no bullneck in
clinical presentation.
Kole et al reported that the most common
complication was myocarditis (68%), mostly were
asymptomatic (64%) and recovered
with
www.jcmid.com
normalization of ECG changes within 4-6 weeks

of presentation. Symptomatic patients who had
myocarditis recovered all, except one succumbed
to refractory heart failure due to late presentation.
Other important observations were early cardiac
involvement (within 3-4 days) and development
of myocarditis in all patients with bull neck. All
patient with cranial mononeuropathy recovered
within 6-10 weeks of presentations, but patients
with polyneuropathy required an intensive care
(level of evidence 3).24 Kneen et al reported that
clinical features at presentation provided useful
indicators of how patients will fare. The
combination of the presence of a bull neck and a
pseudomembrane score of 12 was the best
predictor that patients would develop diphtheritic
cardiomyopathy, whereas the combination of
diphtheritic
cardiomyopathy
at
hospital
admission and a pseudomembrane score of 12
was the best predictor of a fatal outcome (level of
evidence 3).25
Prognosis
Diphtheria is associated with high mortality.
For those in whom the disease is recognized on
the first day and appropriate treatment instituted
mortality is 1% but those in whom such treatment
is delayed till the fourth day mortality rises to
20% (level of evidence 3).4
In this case, the patient had good outcome
and prognosis was good with no mortality. Its
due to an early recognition, prompt ADS
administration, better care, and monitoring. The
patient should be monitored closely for
complications and checked for routine blood
biochemistry
including
CPK-MB,
SGOT,
Troponin-T, and ECG monitoring (level of
evidence 3).24 Jayashree et al investigated the
outcome and predictors of mortality of diphtheria
in children receiving intensive care. They reported
that the immediate cause of death was
myocarditis (85%), airway compromise (11.1%)
and septic shock due to nosocomial sepsis.
Inadequate immunization, hypotension at
admission and presence of any complication like
airway compromise, myocarditis and renal failure
had a significant adverse effect on outcome (P
<0.05)
and
multiple
regression
analysis
ascertained that development of myocarditis was
the only independent predictor of death (level of
evidence 3).22
Findings that indicate a worse prognosis for
heart disease in diphtheria are ventricular ectopy
on presentation, aspartate trans-aminase levels
exceeding 80 U/L, white blood cell count
exceeding 25,000 cells/L, and membrane
extending to at least 2 anatomic sites (level of
13

Print-ISSN: 2355-1909, E-ISSN: 2355-1984.
evidence 3).23 Kole et al had been observed that

outcomes of diphtheria were good with fewer
complications in those who were adequately

immunized than unimmunized patients.
Table 4
Predictors for development of diphtheritic cardiomyopathy after hospital admission among 141 children
with diphtheria22
Source: Jayashree M, Shruthi N, Singhi S. Predictors of outcome in patients with diphtheria receiving
intensive care. Indian Pediatr. 2006; 43: 155-60.
They reported that increase immunization
coverage, improvement of socio-economic status,
easy availability of anti-diphtheritic serum (ADS),
early recognition and effective treatment may
reduce the incidence and mortality of
diphtheria.24 (level of evidence 3).24 Vaccinated
people may become infected or become carriers
but have less morbidity and mortality.
In this case, the patient completed basic
immunization. She received booster when she
was in 1st class elementary school and no booster
when she was sixth class. Although she was
completely immunization, the patient still
suffered from diphtheria. It may be caused by
having no booster when she was sixth class. The
DT booster dose which is given at the school entry
age is highly immunogenic and raises both
vaccine efficacy and antibody titer. The significant
difference in both efficacy and antibody titer in
both diphtheria and tetanus before and after the
reinforcing dose emphasizes the need for such a
booster (level of evidence 3).26 Al Aswad reported
that overall 87.8% of children below 12 years old
were well immunized against diphtheria and had
a protective level of diphtheria antibody ( 0.1
IU/mL). There was also a significant difference of
protection against diphtheria after the DT booster
dose given at 6 years old (P = 0.040) (level of
evidence 3).26 Ren, et al reported that maintenance
of the cold chain during transportation and
storage is needed to guarantee the effectiveness of
vaccination in remote areas. Vaccines are
temperature-sensitive
biological
products.
Exposure to heat shortens a vaccine's shelf life,
while freezing vaccines that should not be frozen
causes irreversible loss of potency. Therefore,
maintaining vaccines inside the cold chain (ICC)
www.jcmid.com
is an essential part of a successful immunization

program (level of evidence 3).27
Figure 6
Improvement of Diphtheria
CONCLUSION
Early detection and good blood telurit
culture result is important to confirm the
diagnostic of diphtheria and very useful for the
clinicians to do the right clinical management for
tonsilopharyngitis
diphtheria
in
children.
Subsequently, the role of clinical microbiologist in
this case not only to support the clinical
diagnostic but also the epidemiology in term of
spreading of Corynebacterium diphtheriae among
their family and neighbors in the community.
REFFERENCES
1. Kumar R, Kumar P, Prajapati NC, Kumar D,
Goyal A, Abbas J, Vijayran M. Diphtheria: Is it
2. really out? Journal of Pediatric Sciences.
2013;5:e188.
14

Print-ISSN: 2355-1909, E-ISSN: 2355-1984.
3. Demirci CS. Pediatric Diphtheria. 2011 [cited

2013 August 25]. Available from:
http://emedicine.medscape.com/article/9633
34-overview.
4. Hadfield TL, McEvoy P, Polotsky Y,
Tzinserling VA, Yakovlev AA. The Pathology
of Diphtheria. JID 2000;181:116-120.
5. Sadoh AE, Sadoh WE. Diphtheria mortality in
Nigeria: the need to stock diphtheria antitoxin.
AFR. J. CLN. EXPER. MICROBIOL. 2011; 12(2):
82- 85.
6. Mattos AL, Moreira LO, Damasco PV, Junior
RH. Diphtheria remains a threat to health in
the developing world- an overview.
MemInstOswaldo Cruz, Rio de Janeiro. 2003;
98 (8): 987-93.
7. Kurugol Z, Midyat L, Turkoglu E, Isler A.
Immunity against diphtheria among children
and adults in Izmir, Turkey. Vaccine 29 (2011)
43414344.
8. Arfijanto MV, Mashitah SI, Widiyanti P,
Bramantono. A patient with suspected
diphtheria. Indonesian journal of tropical and
infectious disease. 2010; 1(2): 69-75.
9. Wharton M, Vitek CR. Diphtheria toxoid. In:
Plotkin SA, Orenstein WA, editors. Vaccines.
4th ed. Philadelphia: W.B. Saunders Co.; 2004.
p. 21128.
10. Dinas Kesehatan Jatim. Penyakit Difteri dan
situasi di Jatim [internet]. 2012 [cited 2013
August 24]. Available from :
http://www.jatimprov.go.id.
11. Kementrian Kesehatan Republik Indonesia.
Profil kesehatan Indonesia 2012 [internet]. 2013
[cited 2014 September 28]. Available from:
http://www.depkes.go.id.
12. Lai S, Efstratiou A. Report on the Sixth
International Meeting of the European
Laboratory Working Group on Diphtheria,
Brussels, Belgium. Eurosurveillance. 2002; 7
(1): 350.
13. Centers for disease control and prevention.
Diphtheria [cited 2013 August 24). Available at
http://www. cdc.gov
/diphtheria/surveillance.html .
14. Volzke H, Warnke C, Dorr M, Kramer A,
Guertier L, Hoffman, et al. Association
between cardiac disorders and decadesprevious history of diphtheria. Eur J
ClinMicrobiol Infect Dis. 2006; 25: 651-5.
15. Soedarmo SSP, Garna H, Hadinegoro SRS,
Satari HI. Difteria.In : Buku Ajar Infeksi &
Pediatri Tropis.Jakarta: Badan Penerbit IDAI;
2010. 312-21
www.jcmid.com
16. Long SS. Diphtheria (Corynebacterium

diphtheria). In: Behrman RE, Kliegman RM,
Jensen HB, editors. Nelson textbook of
Pediatrics. Philadelphia: WB Saunders
company; 2000. 817-20.
17. Kole AK, Roy R, Kar SS. Cardiac involvement
in diphtheria: Study from a tertiary referral
infectious disease hospital. Ann Trop Med
Public Health 2012;5:302-6.
18. Washington State Departement of Health.
Diphtheria [internet]. 2011 [cited 2013 August
24]. Available from:
http://www.doh.wa.gov/Portals/1/.../420052-Guideline-Diphtheria.pdf.
19. Alberta Health and Wellness. Public Health
Notifiable Disease Management Guidelines.
Diphtheria [internet]. 2011 [cited 2013 August
24]. Available
from:http://www.health.alberta.ca/document
s/Guidelines-Diphtheria-2011.pdf.
20. Efstratiou A, Engler KH, Mazurova IK,
Glushkevich T, Vuopio-Varkila J, Popovic T.
Current Approaches to the Laboratory
Diagnosis of Diphtheria. The Journal of
Infectious Diseases 2000;181(Suppl 1):S13845.
21. Wagner KS, Stickings P, White JM, Neal S,
Crowcroft NS, Sesardic D, Efstratiou A. A
review of the international issues surrounding
the availability and demand for diphtheria
antitoxin for therapeutic use. Vaccine. 2010;28 :
1420.
22. Kneen R, Giao PN, Solomon T, Van TTM, Hoa
NTT, Long TB, et al. Penicillin vs.
erythromycin in the treatment of diphtheria.
Clinical Infectious Diseases 1998;27:84550.
23. Jayashree M, Shruthi N, Singhi S. Predictors of
outcome in patients with diphtheria receiving
intensive care. Indian Pediatr. 2006;43:155-60..
24. Nalmas S, Nagarakanti R, Slim J, Abter E,
Bishburg E. Electrocardiographic changes in
infectious disease. Hospital Physician.2007; 9:
15-27.
25. Kole AK, Roy R, Kar SS, Chanda D. Outcomes
of respiratory diphtheria in a tertiary referral
infectious disease hospital. Indian Journal of
Medical Sciences. 2010; 64 (8): 1-5.
26. Kneen R, DungNM, Solomon T, Giao PN,
Parry CM, Hoa NTT, et al. Clinical Features
and Predictors of Diphtheritic
Cardiomyopathy in Vietnamese Children.
Clinical Infectious Diseases. 2004; 39:15918.
27. Al Aswad IH, Shubair ME. Efficacy of
diphtheria and tetanus vaccination in Gaza,
Palestina. Eastern Mediterranean Health
Journal. 2009; 15 (2) : 285-95.
15

Print-ISSN: 2355-1909, E-ISSN: 2355-1984.
28. Ren Q, Xiong H, Li Y, Xu R, Zhu C. Evaluation

of an Outside-the-Cold-Chain Vaccine
Delivery Strategy in Remote Regions of
Western China. Public Health Rep . 2009;
124(5): 74550
www.jcmid.com
This work is licensed under

a Creative Commons Attribution
16

Tonsilopharyngitis Diphtheriae Complicated With......

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Tonsilopharyngitis Diphtheriae Complicated With......

Uploaded by

Copyright:

Available Formats

Journal of Clinical Microbiology & Infectious Disease

JCMID. Volume 1, Number 1, January-April 2014: 6-16