Journal Reading

Diphtheria or Streptococcal Pharyngitis: A Case

Report Highlighting the Diagnostic Dilemma in
the Post-vaccination Era

Disusun oleh:
Farah Diba Sari Tanjung
Haja Mitari
Hapsah
Nita Lestari
Riefni Silara Dilara
Ulfa Husnul Khuluki

Pembimbing :
dr. Asmawati Adnan, Sp.THT-KL
dr. Ariman Syukri, Sp.THT-KL
dr. Harianto, Sp.THT-KL (K)
dr. Loriana Ulfa, Sp.THT-KL
dr. Ibrahim Irsan N, Sp.THT-KL (K)
dr. Yolazenia, M.Biomed, Sp.THT-KL

KEPANITERAAN KLINIK SENIOR BAGIAN THT-KL FAKULTAS

KEDOKTERAN UNIVERSITAS RIAU RUMAH SAKIT UMUM
DAERAH ARIFIN ACHMAD
PROVINSI RIAU
2022

Received 11/13/2019
Review began 11/15/2019
Review ended 11/17/2019
Published 11/18/2019
© Copyright 2019
Kandi et al. This is an open access article
distributed under the terms of the Creative
Commons Attribution License CC-BY 3.0.,
which permits unrestricted use, distribution,
and reproduction in any medium, provided
the original author and source are credited.
Open Access Case
Report DOI: 10.7759/cureus.6190
Diphtheria or Streptococcal Pharyngitis: A Case
Report Highlighting the Diagnostic Dilemma in
the Post-vaccination Era
Venkataramana Kandi 1 , Ritu Vaish 2
1. Clinical Microbiology, Prathima Institute of Medical Sciences, Karimnagar, IND 2. Microbiology, Prathima
Institute of Medical Sciences, Karimnagar, IND
Corresponding author: Venkataramana Kandi, ramana20021@gmail.com
Abstract
Diphtheria is an acute, highly infectious, toxigenic, and vaccine-preventable disease that commonly
affects children under 12 years of age. The incidences of diphtheria have significantly dropped due to
vaccination with diphtheria, pertussis, tetani (DPT). Recently, there is an increasing trend in reports of
diphtheria throughout the world and specifically from developing countries. According to a World Health
Organization (WHO) report, more than 80% of the global diphtheria cases in the post-vaccination era were
from India and Indonesia. This could probably be signaling its re-emergence, which may be attributed to
several factors that include incomplete immunization. Pharyngitis caused by group A Streptococcus is
most frequently seen in children and can be clinically similar in presentation to diphtheria. We share our
experience of managing a case of an eight-year-old child, who was clinically suspected to be suffering from
diphtheria.
Categories: Epidemiology/Public Health, Pediatrics, Infectious Disease
Keywords: diphtheria, tonsillitis, vaccine preventable disease, corynebacterium diphtheriae, children
Introduction
Diphtheria is a bacterial infection caused by Corynebacterium diphtheriae (C. diphtheriae). It is transmitted
among humans through the respiratory route (aerosols). Diphtheria is an acute, severely debilitating
illness, usually affecting children less than 12 years of age. In diphtheria, there is a formation of thick
pseudomembrane or a leathery sheet (diphtheros) on the posterior pharyngeal wall, formed by the
accumulation of bacterial cells, epithelial cells, and other inflammatory cells. This causes a mechanical
obstruction and results in difficulty in swallowing and, in some cases, dyspnoea (difficulty in breathing).
Since C. diphtheriae is a toxin-producing bacteria, the exo-toxin is released by the bacteria, which then
enters the blood/general circulation, resulting in several, other complications in the infected patients.
Clinically, diphtheria may present as faucial, laryngeal, cutaneous, and others. C. diphtheriae has been
noted to occur in three different strains/types depending on the intensity of the infection they cause, the
gravis type produces a severe infection, the intermedius type results in moderate infection, and the mitis
strain causes a mild type of diphtheria [1].
Clinical and laboratory diagnosis assumes great significance to efficiently manage the suspected cases of
diphtheria and minimize the resultant morbidity and mortality. Patients with diphtheria usually present
with sore throat and fever, which also is the presentation of patients suffering from infection with the
more common bacteria, Streptococcus pyogenes (beta-hemolytic streptococci/group A streptococci) and
other microbial infections [2]. In view of the fact that diphtheria, pertussis, and tetani (DPT) has been in
regular use as a vaccine against diphtheria for many years, the clinical cases of diphtheria have almost
been negligible. Most pediatricians are now in a dilemma regarding the prevalence of diphtheria and
probably misdiagnose the potential cases of diphtheria as a streptococcal sore throat. This type of
diagnosis and a delay in the appropriate management of cases of diphtheria may result in severe
complications among infected patients and could result in mortality.
Recently, there have been some reports of the re-emergence of diphtheria, which should be considered as
a cause of serious concern [3-5]. We report our experience of managing a clinically diagnosed case of
diphtheria and emphasize its significance in the era of vaccination.
How to cite this article
Kandi V, Vaish R (November 18, 2019) Diphtheria or Streptococcal Pharyngitis: A Case Report
Highlighting the Diagnostic Dilemma in the Post-vaccination Era. Cureus 11(11): e6190. DOI
10.7759/cureus.6190
 Case Presentation
An eight-year-old boy was brought to the casualty department attached to the Prathima Institute of
Medical Sciences with the chief complaints of fever, malaise, vomiting, and difficulty in swallowing. The
boy was admitted to the pediatric intensive care unit (PICU) for further evaluation. The boy’s parents
complained of acute onset of low-grade fever three days back. The boy was previously normal and was
going to school regularly. The fever episodes were not associated with any type of skin rash. Three to four
episodes of vomiting per day were noted along with the fever. The vomiting was non-projectile, non-
bilious, blood-tinged, and was stimulated by both solid and liquid food intake. The boy also complained of
pain in the throat and had difficulty swallowing. The patient had a loss of appetite, gave a history of high-
colored urine, and had generalized weakness.

No previous history of similar complaints in the patient, as well as his two other siblings, was reported.
There was no documented evidence/medical record that the patient was immunized with DPT although the
parents claimed that the patient was immunized according to the national immunization schedule.

On clinical examination, the patient’s vitals were all good. A noisy breath, probably due to the infection in
the throat, was noted, without any dyspnoea. Clinical examination of the pharynx showed grade IV
tonsillitis with a grayish-white membranous patch covering the tonsil, which was extending towards the
soft palate. The posterior pharyngeal wall revealed congestion, with both sides of the tonsil showing
enlargement. The uvula was central, oedematous, showed congestion, and was bleeding on touch.

General physical examination of the patient revealed sunken eyes, loss of the buccal pad of fat, a
prominent maxilla, and a scaphoid abdomen. The patient was noted to be underweight (20 kg) as against
the recommended weight at the same age (32 kg) and was 133 cm tall as against the recommended height
(140 cm) at a corresponding age.

The patient’s parents reported a low-calorie intake of 1200 KCal/day as against the recommended 1920
KCal/day. Also, the patient was only taking 24 g of protein against the daily recommended intake of 38.4
g/day. Considering this, the patient was diagnosed/categorized as suffering from protein-energy
malnutrition.

The complete blood picture showed neutrophilic leucocytosis, and borderline platelet counts (1.5 lakh
cells/mm3). The patient had raised C-reactive protein (CRP) (2.4 mg/dL) and erythrocyte sedimentation
rate (ESR) (40 mm).

A preliminary diagnosis of grade IV tonsillitis was made, and a throat swab was sent to the clinical
microbiology laboratory for a direct Gram's stain, culture, and sensitivity. On direct Gram’s stain of the
throat swab, plenty of Gram-positive bacilli were observed, with occasional Gram-positive cocci, as shown
in Figure 1.

2019 Kandi et al. Cureus 11(11): e6190. DOI 10.7759/cureus.6190 2 of 7

 FIGURE 1: Direct Gram’s stain of the throat swab showing plenty of
Gram-positive bacilli (white arrow) with occasional Gram-positive
cocci (black arrow)

Culture on blood agar showed 2-3 millimeter, small, round, white-cream-colored non-hemolytic colonies
along with 1-2-millimeter, pinpoint, translucent beta-hemolytic colonies, as shown in Figure 2.

FIGURE 2: Culture on blood agar showing opaque, non-hemolytic

colonies (white arrow) and translucent beta-hemolytic colonies (black
arrow)

Gram’s stain of the small and the pinpoint colonies revealed gram-positive bacilli and gram-positive cocci
in pairs respectively as shown in Figure 3.

FIGURE 3: Gram’s stain of the small colonies showing gram-positive

bacilli (A) and the pinpoint colonies showing gram-positive cocci (B)

The colonies on blood agar were non-hemolytic (C. diphtheriae forms hemolytic colonies), glossy (gravis
type is matt-like) in appearance, raised (intermedius are flat), and were glistening and butyrous (butter-
like) in texture, as shown in Figure 4.

2019 Kandi et al. Cureus 11(11): e6190. DOI 10.7759/cureus.6190 3 of 7

 FIGURE 4: White to cream-colored, raised, glossy, and butyrous
colonies (white arrow) of diphtheria like bacteria on blood agar

They were catalase-positive, non-motile, and non-fermenters on triple sugar iron agar (TSI). The Gram-
positive bacilli were identified as morphologically and biochemically resembling C. diphtheriae. The gram-
positive cocci were catalase-negative and were identified as Streptococcus species (Streptococcus Spp).

Both the gram-positive cocci and the bacilli showed varied sensitivity patterns using the Kirby-Bauer disk
diffusion method. The antimicrobial susceptibility pattern of gram-positive bacilli showed sensitivity to
vancomycin, linezolid, tetracycline, and ofloxacin. Resistance was observed against penicillin, oxacillin,
clindamycin, ciprofloxacin, cefotaxime, cefepime, cefoperazone, ceftriaxone, ceftazidime, amikacin,
gentamicin, and piperacillin-tazobactam, as shown in Figure 5.

FIGURE 5: Antimicrobial sensitivity pattern of diphtheria-like bacteria

by the Kirby-Bauer disk diffusion method

The Streptococcus spp. isolated was sensitive to amikacin, gentamicin, ciprofloxacin, ofloxacin,
trimethoprim-sulfamethoxazole, vancomycin, linezolid, tetracycline, and piperacillin-tazobactam.
Resistance was noted against penicillin, erythromycin, clindamycin, oxacillin, cefotaxime, cefepime,
cefoperazone, ceftriaxone, and ceftazidime, as shown in Figure 6.

2019 Kandi et al. Cureus 11(11): e6190. DOI 10.7759/cureus.6190 4 of 7

 FIGURE 6: Antimicrobial sensitivity pattern of Streptococcus species
by the Kirby-Bauer disk diffusion method

Considering the transmissibility of the infection, the patient was put under isolation. Treatment was
initiated with 80,000 units of diphtheria antitoxin through the intravenous route. Since the isolated
organisms were resistant both to penicillin and erythromycin, the drugs of choice in the case of suspected
diphtheria, and because the patient also had beta-hemolytic Streptococci, the patient was started on a
course of piperacillin-tazobactam and amikacin. The patient had a gradual and uneventful recovery.

The bacterium morphologically resembling C. diphtheriae was not confirmed using the standard anti-toxin
by the Elek’s gel precipitation test due to the unavailability of a suitable identification system. Also, the
close household contacts were neither screened nor administered prophylactic antibiotics as
suggested/recommended by the World Health Organization (WHO) because of the non-cooperation of the
patient's parents.

Discussion
Diphtheria is a highly infectious and reportable bacterial disease that is prevalent throughout the world.
The introduction and success of the DPT vaccination had been instrumental in the control of the disease,
which mostly affects children below 12 years of age, causing significant morbidity and mortality.
Streptococcal sore throat, caused by group A Streptococci is another upper respiratory tract infection
prevalent among children. The clinical presentation of both diphtheria and streptococcal pharyngitis
appears similar, and the clinical diagnosis becomes difficult. Assuming that the cases of diphtheria are
almost negligible due to DPT vaccine, and with limited knowledge of the prevalence of diphtheria in the
post-vaccination era, most physicians/pediatricians may misdiagnose the diphtheria cases as streptococcal
infections. Such diagnoses may result in the spread of diphtheria among the contacts and also delay
the initiation of treatment.

Global scenario of diphtheria

The re-emergence of diphtheria has been a point of discussion almost since the past decade. The
occurrence of diphtheria in the post-vaccination era was attributed to the discrepancies (incomplete
vaccination) in the immunization. Most infections in the post-vaccination era have been noted to emerge
from the developing nations, which include the incidences of outbreaks from Indonesia, Bangladesh, and
Yemen [6-9].

Isolated reports of outbreaks of diphtheria have also been reported from the developed nations, including
the United States of America (USA). Even such reports of outbreaks were attributed to low socioeconomic
conditions similar to those observed in the developing nations [10-12].

Indian scenario of diphtheria

Recent reports of outbreaks and isolated case reports from developing countries like India reassert the fact
that there is a possibility of the re-emergence of diphtheria in the post-vaccination era [13-15].
Also, reports of incidences of diphtheria from the combined state of Andhra Pradesh and the separated
state of Telangana (India) support the fact that the infection is prevalent and that the pediatricians need to
be cautious while diagnosing the suspected patients [16-17].

2019 Kandi et al. Cureus 11(11): e6190. DOI 10.7759/cureus.6190 5 of 7

 The epidemiological data of diphtheria in India appears to be inadequate. A recent article reported an
analysis of diphtheria in India over the past two decades (1996-2016) [18]. This report suggested that
diphtheria cases are frequent among school-going children and adolescents in India. The study had also
noted that there was an 80% coverage of the initial three doses of vaccine and that there is no reliable data
on the coverage of the booster dose. This report also observed that India accounts for more than half of the
diphtheria cases reported worldwide (2001-2015). It also confirms that most states in India had reported
outbreaks/cases of diphtheria, and amongst all, the combined Andhra Pradesh and Telangana reported an
increased frequency of diphtheria cases (>1000 cases/year between 2005 and 2014) [18].

There have been several recent reports of outbreaks and newspaper articles highlighting the seriousness of
the present situation, which emphasizes the role of the public, healthcare workers, and governments in
order to control and prevent the spread of diphtheria [19-20]. A local newspaper published (in the Telegu
language) a picture of parents and relatives carrying and transporting a pediatric patient to a better
medical facility whose condition worsened with suspected diphtheria, as shown in Figure 7.

FIGURE 7: A child possibly suffering from diphtheria is being carried to

a better medical facility by the relatives

Diphtheria has been controlled to a great extent with the introduction of DPT throughout the world. In
spite of the vaccination, several studies in the past have reported the incidences of diphtheria globally. The
condition in developing and financially constrained third-world countries appears to be worse due to
illiteracy, malnutrition, overcrowding, and inadequate immunization. Isolated clinical cases and frequent
reports of outbreaks of diphtheria-like infections should be adequately addressed in order to eliminate the
infection. The governments should, therefore, actively perform surveillance of immunization as well as
document the burden of morbidity and mortality associated with diphtheria.

Conclusions
The eight-year-old boy who presented with symptoms of fever, sore throat, and thickening of the posterior
pharyngeal wall was provisionally diagnosed as a possible case of diphtheria. The laboratory confirmation
of diphtheria was not possible because of inadequate facilities. The diagnosis was based on careful clinical
and laboratory observations. The patient was isolated from others to avoid contact infections and was
successfully treated with antibiotics and antidiphtheritic serum.

Additional Information
Disclosures
Human subjects: Consent was obtained by all participants in this study. Conflicts of interest: In

2019 Kandi et al. Cureus 11(11): e6190. DOI 10.7759/cureus.6190 6 of 7

 compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services
info: All authors have declared that no financial support was received from any organization for the
submitted work. Financial relationships: All authors have declared that they have no financial
relationships at present or within the previous three years with any organizations that might have an
interest in the submitted work. Other relationships: All authors have declared that there are no other
relationships or activities that could appear to have influenced the submitted work.

References
1. Corynebacterium diphtheriae (diphtheria) . (2017). Accessed: November 7, 2019:
http://www.antimicrobe.org/b99.asp.
2. Wolford RW, Schaefer TJ: Pharyngitis. Wolford RW, Schaefer TJ (ed): StatPearls Publishing, Treasure
Island (FL); 2019.
3. Dandinarasaiah M, Vikram BK, Krishnamurthy N, Chetan AC, Jain A: Diphtheria re-emergence: problems
faced by developing countries. Indian J Otolaryngol Head Neck Surg. 2013, 65:314-318. 10.1007/s12070-
012-0518-5
4. Diphtheria. A battle not yet won . (2017). Accessed: November 7, 2019:
https://www.icmr.nic.in/sites/default/files/policy_brief/ICMR_NITM_ROY_Policy_Brief_Diptheria_Final_2017
5. Review of the epidemiology of diphtheria - 2000-2016 . (2017). Accessed: November 7, 2019:
https://www.who.int/immunization/sage/meetings/2017/april/1_Final_report_Clarke_april3.pdf.
6. Immunization, vaccines and biologicals. (2016). Accessed: November 7, 2019:
http://www.who.int/immunization/monitoring_surveillance/data/en/.
7. Finger F, Funk S, White K, Siddiqui MR, Edmunds WJ, Kucharski AJ: Real-time analysis of the diphtheria
outbreak in forcibly displaced Myanmar nationals in Bangladesh. BMC Med. 2019, 17:58. 10.1186/s12916-
019-1288-7
8. Dureab F, Al-Sakkaf M, Ismail O, Kuunibe N, Krisam J, Müller O, Jahn A: Diphtheria outbreak in Yemen:
the impact of conflict on a fragile health system. Confl Health. 2019, 13:19. 10.1186/s13031-019-0204-2
9. Tosepu R, Gunawan J, Effendy DS, Ahmad LOAI, Farzan A: The outbreak of diphtheria in Indonesia. Pan
Afr Med J. 2018, 31:249. 10.11604/pamj.2018.31.249.16629
10. Zalma VM, Older JJ, Brooks GF: The Austin, Texas, diphtheria outbreak: clinical and epidemiological
aspects. JAMA. 1970, 211:2125-2129. 10.1001/jama.1970.03170130021004
11. Dixon JM: Diphtheria in North America . J Hyg (Lond). 1984, 93:2125-2129. 10.1017/s0022172400065013
12. Golaz A, Hardy IR, Strebel P, Bisgard KM, Vitek C, Popovic T, Wharton M: Epidemic diphtheria in the
newly independent states of the former Soviet Union: implications for diphtheria control in the United
States. J Infect Dis. 2000, 181:S237-243. 10.1086/315569
13. Krishnan S, Kizhakkekarammel P, George K, Johnson J, Kurukanari R, Raveendran G: Re-emergence of
diphtheria in Malappuram district, North Kerala, India. J Acad Clin Microbiol. 2018, 20:37-39.
10.4103/jacm.jacm_2_18
14. Mohanty A, Bhatia M, Gupta P, Varshney S, Malhotra M, Omar BJ: Diphtheria: the patch still remains—a
case report from the state of Uttarakhand. J Pharm Bioall Sci. 2019, 11:190-193. 10.4103/JPBS.JPBS_245_18
15. Nath B, Mahanta TG: Investigation of an outbreak of diphtheria in Borborooah block of Dibrugarh district,
Assam. Indian J Community Med. 2010, 35:436-438. 10.4103/0970-0218.69282
16. Meera M, Rajarao M: Diphtheria in Andhra Pradesh-a clinical-epidemiological study . Int J Infect Dis. 2014,
19:74-78. 10.1016/j.ijid.2013.10.017
17. Asma, Ivaturi PB: A study on clinical and epidemiological profile of patients admitted with white patch in
throat to Sir Ronald Ross Institute of Tropical and Communicable Diseases, Hyderabad, India. Int J
Community Med Public Health. 2018, 5:1984-1989. 10.18203/2394-6040.ijcmph20181710
18. Murhekar M: Epidemiology of diphtheria in India, 1996-2016: implications for prevention and control . Am
J Trop Med Hyg. 2017, 97:313-318. 10.4269/ajtmh.17-0047
19. Meshram RM, Patil A: Clinical profile and outcome of diphtheria in central India: a retrospective
observational study. Int J Contemp Pediatr. 2018, 5:1600-1605. 10.18203/2349-3291.ijcp20182572
20. Rahman MR, Islam K: Massive diphtheria outbreak among Rohingya refugees: lessons learnt. J Travel Med.
2019, 26:tay122. 10.1093/jtm/tay122

2019 Kandi et al. Cureus 11(11): e6190. DOI 10.7759/cureus.6190 7 of 7

Difteri atau Faringitis Streptococcal: Laporan
Kasus yang Menyoroti Dilema Diagnostik di Era
Pasca-vaksinasi
Venkataramana Kandi 1 , Ritu Vaish 2

1. Mikrobiologi Klinis, Institut Ilmu Kedokteran Prathima, Karimnagar, IND

2. Mikrobiologi, Institut Ilmu Kedokteran Prathima, Karimnagar, IND
- Penulis yang sesuai: Venkataramana Kandi, ramana20021@gmail.com

Abstrak
Difteri adalah penyakit akut, sangat menular, toksigenik, dan dapat
dicegah dengan vaksin yang umumnya menyerang anak-anak di bawah usia 12
tahun. Insiden difteri telah menurun secara signifikan karena vaksinasi dengan
difteri, pertusis, tetani (DPT). Baru-baru ini, ada tren peningkatan laporan
penyakit difteri di seluruh dunia dan khususnya dari negara berkembang. Menurut
laporan World Health Organization (WHO), lebih dari 80% kasus difteri global
pasca vaksinasi berasal dari India dan Indonesia. Hal ini mungkin menandakan
kemunculannya kembali, yang dikaitkan dengan beberapa faktor yang mencakup
imunisasi yang tidak lengkap. Faringitis yang disebabkan oleh grup A
Streptococcus paling sering terjadi pada anak-anak dan secara klinis mirip dengan
difteri.

Pengantar
Difteri adalah penyakit infeksi bakteri yang disebabkan oleh
Corynebacterium diphtheriae (C. difteri). Difteri ditularkan di antara manusia
melalui jalur pernapasan (aerosol). Difteri adalah penyakit akut yang sangat
melemahkan, biasanya menyerang anak-anak di bawah usia 12 tahun. Pada difteri,
terdapat pembentukan pseudomembran tebal atau lembaran kasar (diphtheros)
pada dinding posterior faring, yang dibentuk oleh akumulasi sel bakteri, sel epitel,
dan sel inflamasi lainnya. Hal ini menyebabkan obstruksi mekanis dan
mengakibatkan kesulitan menelan dan, dalam beberapa kasus, dyspnoea (kesulitan
bernapas). Corynebacterium diphtheriae adalah bakteri penghasil toksin, ekso-
toksin dilepaskan oleh bakteri, yang kemudian masuk ke dalam darah/ sirkulasi
umum, mengakibatkan beberapa komplikasi lain pada pasien yang terinfeksi.
Secara klinis, difteri dapat muncul sebagai faucial, laryngeal, cutaneous, dan lain-
lain. C. difteri telah dicatat terjadi pada tiga strain/ jenis yang berbeda tergantung
pada intensitas infeksi yang ditimbulkannya, jenis gravis menyebabkan infeksi
berat, jenis intermedius mengakibatkan infeksi sedang, dan jenis mitis
menyebabkan jenis difteri infeksi ringan.1

Diagnosis berdasarkan gejala klinis dan laboratorium sangat penting untuk

mengelola kasus dugaan difteri secara efisien dan meminimalkan morbiditas dan
mortalitas yang diakibatkannya. Pasien dengan difteri biasanya datang dengan
sakit tenggorokan dan demam, yang juga merupakan presentasi pasien yang
menderita infeksi bakteri yang lebih umum, Streptococcus pyogenes (streptokokus
beta-hemolitik/streptokokus grup A) dan infeksi mikroba lainnya.2 Mengingat
fakta bahwa difteri, pertusis, dan tetani (DPT) telah digunakan secara teratur
sebagai vaksin melawan difteri selama bertahun-tahun, kasus klinis difteri hampir
dapat diabaikan. Sebagian besar dokter anak sekarang berada dalam dilema
mengenai prevalensi difteri dan mungkin salah mendiagnosis kasus potensial
difteri sebagai sakit tenggorokan akibat streptokokus. Jenis diagnosis dan
keterlambatan dalam pengelolaan kasus difteri yang tepat dapat mengakibatkan
komplikasi parah pada pasien yang terinfeksi dan dapat mengakibatkan kematian.

Baru-baru ini, ada beberapa laporan tentang munculnya kembali difteri,

yang harus dianggap sebagai penyebab perhatian serius.3-5 Kami melaporkan
pengalaman kami dalam menangani kasus difteri yang didiagnosis secara klinis
dan menekankan pentingnya kasus tersebut di era vaksinasi.

Presentasi kasus

Seorang anak laki-laki berusia delapan tahun dibawa ke unit gawat darurat
Institut Ilmu Kedokteran Prathima dengan keluhan utama demam, malaise,
muntah, dan kesulitan menelan. Pasien kemudian dirawat di Unit Perawatan
Intensif Anak (PICU) untuk evaluasi lebih lanjut. Orangtuanya mengeluhkan
pasien demam sejak tiga hari yang lalu. Pasien sebelumnya baik-baik saja dan
pergi ke sekolah seperti biasa. Episode demam tidak terkait dengan semua jenis
ruam kulit. Muntah tiga sampai empat kali per hari bersamaan dengan demam.
Muntah tidak menyembur, tidak berwarna hijau, bercampur darah, dan
dirangsang oleh asupan makanan padat maupun cair. Pasien juga mengeluh sakit
di tenggorokan dan kesulitan menelan. Pasien mengalami penurunan nafsu
makan, urin berwarna kuning pekat dan seluruh tubuh terasa lemah.

Tidak ada riwayat keluhan yang sama sebelumnya pada pasien serta dua
saudara kandung lainnya. Tidak ada bukti/rekam medis yang menyatakan bahwa
pasien diimunisasi DPT meskipun orang tua menyatakan pasien diimunisasi
sesuai jadwal imunisasi nasional.

Pada pemeriksaan klinis, tanda-tanda vital pasien baik. Napas yang

berbunyi, mungkin dikarenakan infeksi di tenggorokan dan tanpa dispnea.
Pemeriksaan klinis faring menunjukkan tonsilitis grade IV dengan patch
membran berwarna putih keabu-abuan menutupi tonsil, yang meluas ke arah
palatum mole. Dinding posterior faring menunjukkan penyumbatan, dengan
kedua sisi tonsil menunjukkan pembesaran. Uvula berada di tengah, edema,
menyumbat, dan berdarah saat disentuh.

Pemeriksaan fisik umum pasien terdapat mata cekung, hilangnya bantalan

lemak bukal, rahang atas yang menonjol, dan perut skafoid (cekung). Berat badan
pasien kurang (20 kg) dibandingkan dengan berat badan yang direkomendasikan
pada usia yang sama (32 kg) dan tinggi 133 cm dibandingkan dengan tinggi yang
direkomendasikan (140 cm) pada usia yang sesuai.

Orang tua pasien mengatakan asupan kalori rendah 1200 KCal/hari

dibandingkan dengan 1920 KCal/hari yang dianjurkan. Selain itu, pasien hanya
mengonsumsi 24 g protein dibandingkan dengan asupan yang dianjurkan setiap
hari yaitu 38,4 g/hari. Dengan pertimbangan tersebut, pasien
didiagnosis/dikategorikan menderita malnutrisi energi protein.

Pemeriksaan darah lengkap menunjukkan leukositosis neutrofilik dan

penurunan jumlah trombosit (1,5 lakh sel/mm3). Pasien mengalami peningkatan
protein C-reaktif (CRP) (2,4 mg/dL) dan laju sedimentasi eritrosit (ESR) (40
mm).

Diagnosis awal tonsilitis derajat IV, dan usap tenggorokan dikirim ke

laboratorium mikrobiologi klinis untuk pewarnaan Gram langsung, kultur, dan
sensitivitas. Pada pewarnaan Gram langsung dari usap tenggorokan, banyak basil
Gram-positif yang didapatkan, dengan sesekali ditemukan kokus Gram-positif,
seperti yang ditunjukkan pada gambar 1.

Gambar 1: Pewarnaan Gram langsung pada usap tenggorokan menunjukkanbanyak

basil Gram-positif (panah putih) dengan kokus Gram-positif sesekali(panah hitam)

Kultur pada agar darah menunjukkan 2-3 milimeter, kecil, bulat, koloni
non-hemolitik berwarna putih krem bersama dengan 1-2 milimeter, pinpoint,
koloni beta-hemolitik yang transparan, seperti yang ditunjukkan pada Gambar 2.

Gambar 2: Kultur pada agar darah menunjukkan koloni non-hemolitik buram(panah

putih) dan koloni beta-hemolitik transparan (panah hitam)
 Pewarnaan Gram dari koloni kecil dan koloni tepat menunjukkan basil
gram positif dan kokus gram positif berpasangan masing-masing seperti yang
ditunjukkan pada gambar 3.

Gambar 3: Pewarnaan Gram pada koloni kecil yang menunjukkan basil grampositif (A)
dan koloni pinpoint yang menunjukkan kokus gram positif (B)

Koloni pada agar darah non-hemolitik (C.difteri membentuk koloni

hemolitik), tampak mengkilap (tipe gravis seperti matt), menonjol (intermedius
datar), dan teksturnya berkilau dan berbutir (seperti mentega), seperti yang
ditunjukkan pada gambar 4.

Gambar 4: Koloni bakteri difteri seperti difteri berwarna putih sampai krem,
menonjol, mengkilap, dan berbutir (panah putih) pada agar darah
 Koloni bakteri yang ditemukan yaitu katalase-positif, non-motil, dan non-
fermenter pada triple sugar iron agar (TSI). Basil Gram positif diidentifikasi
secara morfologi dan biokimia menyerupai C.difteri. Kokus gram positif adalah
katalase-negatif dan diidentifikasi sebagai Streptokokus species (Streptokokus
spp).

Baik kokus gram positif dan basil menunjukkan pola sensitivitas yang
bervariasi menggunakan metode difusi cakram Kirby-Bauer. Pola kerentanan
antimikroba basil gram positif menunjukkan sensitivitas terhadap vankomisin,
linezolid, tetrasiklin, dan ofloksasin. Resistensi diamati terhadap penisilin,
oksasilin, klindamisin, ciprofloxacin, cefotaxime, cefepime, cefoperazone,
ceftriaxone, ceftazidime, amikasin, gentamisin, dan piperacillin-tazobactam,
seperti yang ditunjukkan pada gambar 5.

Gambar 5: Pola sensitivitas antimikroba bakteri mirip difteri dengan metode difusi
cakram Kirby-Bauer

Streptokokus sp. diisolasi sensitif terhadap amikasin, gentamisin,

siprofloksasin, ofloksasin, trimetoprim-sulfametoksazol, vankomisin, linezolid,
tetrasiklin, dan piperasilin-tazobaktam. Resistensi tercatat terhadap penisilin,
eritromisin, klindamisin, oksasilin, sefotaksim, sefepim, sefoperazon, seftriakson,
dan seftazidim, seperti yang ditunjukkan pada gambar 6.

Gambar 6: Pola sensitivitas antimikroba spesies Streptococcus dengan metode difusi

cakram Kirby-Bauer
 Mengingat penularan infeksi, pasien ditempatkan di ruang isolasi.
Pengobatan dimulai dengan 80.000 unit antitoksin difteri melalui intravena.
Karena organisme yang diisolasi resisten baik terhadap penisilin dan eritromisin,
obat pilihan dalam kasus dugaan difteri, dan karena pasien juga menderita
Streptococci beta-hemolitik, pasien mulai menggunakan piperasilin-tazobactam
dan amikasin. Pasien mengalami pemulihan bertahap dan lancar.

Bakteri yang secara morfologis menyerupai C. difteri tidak dikonfirmasi

menggunakan anti-toksin standar dengan uji presipitasi Elek’s gel karena tidak
tersedianya sistem identifikasi yang sesuai. Juga, kontak dengan orang serumah
tidak diskrining atau diberikan antibiotik profilaksis seperti yang disarankan/
direkomendasikan oleh Organisasi Kesehatan Dunia (WHO) karena orang tua
pasien tidak mau bekerja sama.

Diskusi

Difteri adalah penyakit bakteri yang sangat menular dan sering dilaporkan
di seluruh dunia. Pengenalan dan keberhasilan vaksinasi DPT telah berperan
dalam pengendalian penyakit, yang sebagian besar menyerang anak-anak di
bawah usia 12 tahun ini, dan juga penyebab morbiditas dan mortalitas yang
signifikan. Infeksi saluran napas atas lain yang juga sering dilaporkan adalah
radang tenggorokan oleh bakteri Streptococcus A. Presentasi klinis faringitis
difteri dan streptokokus tampak serupa. Hal ini menyebabkan sulit membedakan
secara klinis. Asumsi bahwa kasus difteri bias sedikit diabaikan karena telah
mendapatkan vaksin DPT, dan dengan pengetahuan yang terbatas tentang
prevalensi difteri di era pasca-vaksinasi, sebagian besar dokter/dokter anak
mungkin salah mendiagnosis kasus difteri sebagai infeksi streptokokus.

Skenario Difteri Global

Kemunculan kembali penyakit difteri telah menjadi bahan diskusi hampir

sejak satu dekade terakhir. Terjadinya difteri pada era pasca vaksinasi disebabkan
oleh ketidaksesuaian (vaksinasi tidak lengkap) dalam pemberian imunisasi.
Sebagian besar infeksi di era pasca-vaksinasi tercatat muncul dari negara-negara
berkembang, termasuk peristiwa wabah dari Indonesia, Bangladesh, dan Yaman.6-
9

Laporan lain kejadian wabah difteri juga telah dilaporkan dari negara-
negara maju, termasuk Amerika Serikat (AS). Bahkan laporan wabah tersebut
dikaitkan dengan kondisi sosial ekonomi yang rendah seperti di negara
berkembang. 10-12

Skenario Difteri India

Laporan terbaru tentang wabah dan laporan kasus terisolasi dari negara
berkembang seperti India menegaskan kembali fakta bahwa ada kemungkinan
munculnya kembali difteri di era pasca-vaksinasi.13-15 Laporan insiden difteri dari
gabungan negara bagian Andhra Pradesh dan negara bagian Telangana (India)
yang terpisah juga mendukung fakta bahwa infeksi itu lazim dan dokter anak
perlu berhati-hati saat mendiagnosis pasien yang dicurigai difteri. 16-17

Data epidemiologi difteri di India tampaknya tidak memadai. Sebuah

artikel terbaru melaporkan analisis kejadia difteri di India selama dua dekade
terakhir (1996-2016).18 Laporan ini menunjukkan bahwa kasus difteri sering
terjadi pada anak-anak sekolah dan remaja di India. Studi tersebut juga mencatat
bahwa ada cakupan 80% dari tiga dosis awal vaksin dan tidak ada data yang dapat
diandalkan tentang cakupan dosis booster. Laporan ini juga menyatakan bahwa
India menyumbang lebih dari setengah kasus difteri yang dilaporkan di seluruh
dunia (2001-2015). Hal ini juga menegaskan bahwa sebagian besar negara bagian
di India telah melaporkan wabah/ kasus difteri. Di antara semuanya, gabungan
Andhra Pradesh dan Telangana melaporkan peningkatan frekuensi kasus difteri
hingga >1000 kasus/tahun antara 2005 dan 2014. 18

Beberapa laporan terkini tentang wabah dan artikel surat kabar menyoroti
keseriusan situasi saat ini, yang menekankan peran masyarakat, petugas
kesehatan, dan pemerintah dalam mengendalikan dan mencegah penyebaran
difteri. 19-20

Kesimpulan

Anak delapan tahun datang dengan gejala demam, sakit tenggorokan, dan
penebalan dinding faring posterior untuk sementara didiagnosis kemungkinan
kasus difteri. Konfirmasi laboratorium difteri tidak dapat dilakukan karena
fasilitas yang tidak memadai. Diagnosis didasarkan pada pengamatan klinis dan
laboratorium yang cermat. Pasien diisolasi dari orang lain untuk menghindari
infeksi kontak dan berhasil diobati dengan antibiotik dan serum antidifteri.

Informasi Tambahan
Pengungkapan

Subjek manusia: Persetujuan diperoleh oleh semua peserta dalam penelitian ini.
Konflik kepentingan: Di kepatuhan dengan formulir pengungkapan seragam
ICMJE, semua penulis menyatakan sebagai berikut: Info pembayaran/layanan:
Semua penulis telah menyatakan bahwa tidak ada dukungan keuangan yang
diterima dari organisasi mana pun untuk karya yang dikirimkan. Hubungan
keuangan: Semua penulis telah menyatakan bahwa mereka tidak memiliki
hubungan keuangan saat ini atau dalam tiga tahun sebelumnya dengan organisasi
mana pun yang mungkin berkepentingan dengan karya yang dikirimkan.
Hubungan lainnya: Semua penulis telah menyatakan bahwa tidak ada hubungan
atau aktivitas lain yang tampaknya dapat memengaruhi karya yang dikirimkan
 DAFTAR PUSTAKA

1. Corynebacterium diphtheriae (diphtheria). (2017). Accessed: November 7,

2019: http://www.antimicrobe.org/b99.asp.

2. Wolford RW, Schaefer TJ: Pharyngitis. Wolford RW, Schaefer TJ (ed):

StatPearls Publishing, Treasure Island (FL); 2019.

3. Dandinarasaiah M, Vikram BK, Krishnamurthy N, Chetan AC, Jain A:

Diphtheria re emergence: problems faced by developing countries. Indian J
Otolaryngol Head Neck Surg. 2013, 65:314-318. 10.1007/s12070-012-0518-5

4. Diphtheria. A battle not yet won. (2017). Accessed: November 7, 2019:

https://www.icmr.nic.in/sites/default/files/policy_brief/ICMR_NITM_ROY_P
olicy_Brief_Dipteria_Final_2017.pdf

5. Review of the epidemiology of diphtheria - 2000-2016 . (2017). Accessed:

November 7, 2019:
https://www.who.int/immunization/sage/meetings/2017/april/1_Final_report_
Clarke_april3.pdf.

6. Immunization, vaccines and biologicals. (2016). Accessed: November 7,

2019: http://www.who.int/immunization/monitoring_surveillance/data/en/.

7. Finger F, Funk S, White K, Siddiqui MR, Edmunds WJ, Kucharski AJ: Real-
time analysis of the diphtheria outbreak in forcibly displaced Myanmar
nationals in Bangladesh. BMC Med. 2019, 17:58. 10.1186/s12916-019-1288-7

8. Dureab F, Al-Sakkaf M, Ismail O, Kuunibe N, Krisam J, Müller O, Jahn A:

Diphtheria outbreak in Yemen: the impact of conflict on a fragile health
system. Confl Health. 2019, 13:19. 10.1186/s13031-019-0204-2

9. Tosepu R, Gunawan J, Effendy DS, Ahmad LOAI, Farzan A: The outbreak of

diphtheria in Indonesia. Pan Afr Med J. 2018, 31:249.
10.11604/pamj.2018.31.249.16629.
10. Zalma VM, Older JJ, Brooks GF: The Austin, Texas, diphtheria outbreak:
clinical and epidemiological aspects. JAMA. 1970, 211:2125-2129.
10.1001/jama.1970.03170130021004

11. Dixon JM: Diphtheria in North America . J Hyg (Lond). 1984, 93:2125-2129.
10.1017/s0022172400065013

12. Golaz A, Hardy IR, Strebel P, Bisgard KM, Vitek C, Popovic T, Wharton M:
Epidemic diphtheria in the newly independent states of the former Soviet
Union: implications for diphtheria control in the United States. J Infect Dis.
2000, 181:S237-243. 10.1086/315569

13. Krishnan S, Kizhakkekarammel P, George K, Johnson J, Kurukanari R,

Raveendran G: Re-emergence of diphtheria in Malappuram district, North
Kerala, India. J Acad Clin Microbiol. 2018, 20:37-39.
10.4103/jacm.jacm_2_18

14. Mohanty A, Bhatia M, Gupta P, Varshney S, Malhotra M, Omar BJ:

Diphtheria: the patch still remains—a case report from the state of
Uttarakhand. J Pharm Bioall Sci. 2019, 11:190-193.
10.4103/JPBS.JPBS_245_18

15. Nath B, Mahanta TG: Investigation of an outbreak of diphtheria in

Borborooah block of Dibrugarh district, Assam. Indian J Community Med.
2010, 35:436-438. 10.4103/0970-0218.69282

16. Meera M, Rajarao M: Diphtheria in Andhra Pradesh-a clinical-

epidemiological study. Int J Infect Dis. 2014, 19:74-78.
10.1016/j.ijid.2013.10.017

17. Asma, Ivaturi PB: A study on clinical and epidemiological profile of patients
admitted with white patch in throat to Sir Ronald Ross Institute of Tropical
and Communicable Diseases, Hyderabad, India. Int J Community Med Public
Health. 2018, 5:1984-1989. 10.18203/2394-6040.ijcmph20181710

18. Murhekar M: Epidemiology of diphtheria in India, 1996-2016: implications

for prevention and control. Am J Trop Med Hyg. 2017, 97:313-318.
10.4269/ajtmh.17-0047
19. Meshram RM, Patil A: Clinical profile and outcome of diphtheria in central
India: a retrospective observational study. Int J Contemp Pediatr. 2018,
5:1600-1605. 10.18203/2349 3291.ijcp20182572
20. Rahman MR, Islam K: Massive diphtheria outbreak among Rohingya
refugees: lessons learnt . J Travel Med. 2019, 26:tay122. 10.1093/jtm/tay122
2019