An Observational Study on Association of Clinical Outcome of Diphtheria Cases with Immunization Status: A Tertiary Care Hospital, Jaipur

Abstract

Background. Diphtheria is an important vaccine preventable disease with varied outcome from mild to death. It was observed that the outcome also gets affected with status of immunization. The outcome is relatively milder in immunized children. Objective. To find out the clinical presentation and outcome of diphtheria cases and its association with the immunization status. Methods. A descriptive analysis of 64 diphtheria cases admitted from January 2019 to May 2020 at SMS hospital, a tertiary care referral hospital in Jaipur. Results. Half of (51.56%, 33/60) patients were in the age group of 6–10 years. The peak load (48.44%) of diphtheria cases was seen in the monsoon season. Around 60% of the patients were fully immunized and around 10% partially immunized, every third case was un-immunized. The most common complication was neurological in 13 cases (20.31%), followed by cardiac complications in 11 cases (17.19%), and respiratory (7.81%). The proportion of complication was much lower (26.3%) in immunized cases as compare to partially immunized and un immunized. The proportion of myocarditis was significantly higher in un immunized cases (40%) than partially immunized (16.7%) and filly immunized group (5.3%). Similarly, Bronchopneumonia was also significantly higher (20%) in unimmunized. Conclusion. Our study depicted that there has been a shift of age above 5 years for diphtheria which suggests the need for the booster dose. Also high chances of complications are seen in unimmunized and partially immunized calling for public awareness regarding complete immunization.

Introduction

Twenty thousand cases of diphtheria were reported by the World Health Organization during 2007–2011, of which 17,926 cases (89.6%) were from India and this was more than all other highest reporting countries [1]. Poor immunization coverage is found to be the main factor responsible for the persistence of diphtheria. This disease mostly occurs in children under 5 years of age, but may also occur in children over 5 years (5–19 years) and in adults [2]. Several studies have shown that low vaccination coverage, crowding, migration, or a combination of host, agent, and environmental factors, can influence the incidence of diphtheria [3, 4] in addition to nutritional status, parental behavior, and personal hygiene of children [5]. Earlier, the most common age group during pre-vaccination era was under 5 years due to natural boost to the development and maintenance of immunity in adolescence and adults. Recently there has been shift of age for the occurrence of disease in older children and adults because of widespread immunization in children, waning immunity lack of or inadequate booster doses in children and adult and decrease incidence of cutaneous diphtheria.

Diphtheria, taken from the Greek, “diphthera” which means leather hide, was first identified by Hippocrates [6]. Diphtheria is an acute infectious upper respiratory tract disease caused by toxigenic strains of Corynebacterium diphtheriae. It is a major preventable disease of childhood with a high morbidity and mortality. The organism is locally invasive and secretes exotoxins,

which can lead to life threatening consequences mainly involving the heart muscle and nervous system. If diagnosed early, it responds to antitoxin therapy and appropriate antibiotics [7].

Diphtheria vaccine is a bacterial toxoid, i.e. a toxin whose toxicity has been inactivated. The vaccine is normally given in combination with other vaccines as DTwP/DTaP vaccine or.

pentavalent vaccine. For adolescents and adults, the diphtheria toxoid is frequently combined with tetanus toxoid in lower concentration (Td vaccine).

WHO recommends a 3-dose primary vaccination series with diphtheria containing vaccine followed by 3 booster doses. The primary series should begin as early as 6-week of age with subsequent doses given with a minimum interval of 4 weeks between doses. The 3 booster doses should preferably be given during the second year of life (12–23 months), at 4–7 years and at 9–15 years of age. Ideally, there should be at least 4 years between booster doses [8].

In India according to National Immunization schedule, pentavalent vaccine (diphtheria, pertussis, tetanus, hepatitis B and Hemophilus influenza type b) is administered at 6 weeks, 10 weeks and 14 weeks (can be given till one year of age). DPT booster dose 1st is given at 16–24 months and 2nd one at 5–6 years of age.

Hence, the aim of our study was to study the clinical presentation and outcome of diphtheria cases and its association with the immunization status.

Material and Methods

This hospital based, observational, prospective study was conducted in the Department of Otorhinolaryngology and Head Neck Surgery at S.M.S. Hospital, Jaipur from January 2019 to May 2020 after clearance from the ethical committee. Total 64 patients presented in ENT OPD of age 3–18 years, with membranous tonsillitis who were diagnosed on the basis of throat swab.

Cases of membranous tonsillitis with negative throat swab and patients presenting with neurological symptoms but without any membrane upon examination of oral cavity were excluded from the study.

The management of a patient with suspected diphtheria includes administration of antidiphtheritic serum (ADS) after hypersensitivity test with horse serum comes negative, administration of antibiotics and securing airway.

After obtaining written consent from parents of all patients, cases were evaluated with respect to demographic details, immunization status, clinical features and complications. The immunization status was documented as per the information given by the parents/guardians. Patients were divided on the basis of immunization into the three groups i.e. unimmunized, partially immunized and fully immunized.

Those who had received three primary doses at 4–6 weeks interval starting at 6 weeks of age, followed by booster doses at 18 months and 5 years were recorded as “Fully Immunized”. Those who had not received any doses were considered as “Unimmunized”/“Unknown status”. Patients who had missed one or more of the three primary doses or booster doses were included as “Partially immunized”. Throat swab for Albert’s stain and culture were done and diphtheria was confirmed in all the cases.

Observation and Results

Out of 64 patients, half of patients 33(51.56%) were of age group 6–10 years, followed by 19(29.69%) patients of less than 5 years age, followed by 10(15.63%) who were between 11 and 15 years age and the least 2(3.13%) patients of 16–20 years age group. (Table 1) Around 62.5% of cases were male whereas the rest of 37.5% were females. (Table 2).

Table 1.

Age distribution of diphtheria cases

Age(yrs)	No. of cases (n)	Percentage (%)
0–5	19	29.69
6–10	33	51.56
11–15	10	15.63
16–20	2	3.13
Total	64	100.00

Table 2.

Gender distribution of diphtheria cases

Gender	No. of cases (n)	Percentage (%)
Male	40	62.50
Female	24	37.50
Total	64	100.00

A total of 16 cases out of 64 (25%) were reported from Jaipur district, followed by Sawai Madhopur (12 cases, 18.75%), Alwar (10 cases, 15.62%) forming the major hotspots of the disease supplemented by nearby districts and states such as Uttar Pradesh and Haryana. Half of the cases (48.44%) presented to ENT OPD during monsoon season. (Table 3) Around 60% of the patients were fully immunized and around 10% partially immunized, every third case was un-immunized (Fig. 1).

Table 3.

Distribution of anatomical areal involved

Anatomical areas involved by membrane	No. of patients	Percentage
Tonsils	64	100
Posterior pharyngeal wall	60	93.75
Uvula	32	50
Total	64	100

Fig. 1.

Immunization status of cases

During clinical examination of all the cases, it was observed that bilateral tonsils were most frequently involved subsite (100%) followed by posterior pharyngeal wall (93.75%), uvula in 50% of cases while only one patient had mild involvement of a single tonsil. (Table 3).

All 64 cases presented with fever and throat pain (100%) followed by cough in 36 patients (56.25%) and bull neck swelling in 34 patients (53.12%). (Table 4).

Table 4.

Distribution of clinical presentation

Clinical presentation	Number of patients (%)
Fever	64 (100%)
Throat pain	64 (100%)
Cough	36 (56.25%)
Bull neck swelling	34 (53.12%)
Dysphagia	22 (34.3%)
Epistaxis	2 (3.12%)

The most common complication overall in our study observed was neurological accounting for 13(20.31%) cases which included soft palate paralysis, weakness of posterior pharyngeal, laryngeal and facial nerves causing a nasal twang in voice, difficulty in swallowing and aspiration, and proximal muscular weakness.

Out of 13 cases, 8 cases (61.53%) had palatal palsy, 3 cases (23.07%) had lower limb ascending type of LMN palsy, associated with hypotonia and hyporeflexia, 1 case (7.6%) had bilateral abductor palsy with facial nerve palsy and remaining 1 (7.6%) had paralytic ileus.

The onset of neurological complications in this study varied from 10 to 36 days. Similarly, the recovery pattern varied highly from 60 days for palatal palsy to even 240 days required for complete recovery of lower limb LMN palsy and paralytic ileus. The second most common complication turned out to be myocarditis in 11 cases (17.19%). The ECG changes observed were sinus tachycardia, arrhythmia, abnormal Q waves, ST segment elevation, T-wave inversion, atrioventricular block, bundle branch block, and complete heart block. Bronchopneumonia was seen in 5 cases (7.81%) (Fig. 2).

Fig. 2.

Distribution of complications among cases

The proportion of complication was much lower (26.3%) in immunized cases as compare to partially immunized and un immunized. The proportion of myocarditis was significantly higher in un immunized cases (40%) than partially immunized (16.7%) and filly immunized group (5.3%). Similarly, Bronchopneumonia was also significantly higher (20%) in unimmunized. However, there is no significant difference in neurological complication in cases with different immunization status. Association of immunization with complications is statistically significant (p < 0.05).(Table 5) (Fig. 3).

Table 5.

Association between immunization status and complications

Complications	Unimmunized	Partially immunized	Fully immunized	Total
Myocarditis	8(40)	1(16.7)	2(5.3)	11(17.2)
Bronchopneumonia	4(20)	0(0)	1(2.6)	5(7.8)
Neurological	5(25)	1(16.7)	7(18.4)	13(20.3)
None	3(15)	4(66.7)	28(73.7)	35(54.7)
Total	20(100)	6(100)	38(100)	64(100)

X² = 23.525, df = 6, p value = 0.01

Fig. 3.

Association between immunization status and complications

Discussion

Globally, diphtheria has been showing declining trend due to effective immunization programs. Diphtheria is fatal in 5–10% of cases, with a higher mortality rate in young children [8]. However, there has been a shift of patients affected with diphtheria from under 5 years age group to adolescent and adults due to unimmunization or partial immunization. In outbreaks also, more adolescents and adults were found to have diphtheria. This shifting of age occurrence in diphtheria has been observed in recent years especially in developed countries and developing countries including India [9].

Hence, our study was conducted to study the clinic-demographic presentation and outcome of diphtheria cases and its association with the immunization status.

In present study 51.56% patients were more than 5 years of age similar to Meshram et al. (55.32%), Suligavi1 et al. (93.8%). Basavaraja et al. (74.1%), Bandichhode et al. (66.66%) have reported resurgence of disease in children of more than 5 years of age. [10–13]. In our study ratio of male: female is 1.6. Mehariya et al., Jain et al. and Arya et al. observed male predominance below 10 years of age and few studies noted predominantly female involvement, this can be due to geographical variations. [14–16]

Cases of diphtheria were most commonly seen in monsoon in our study (48.44%) similar to Suligavi1et al [13]. Some authors reported peak during the winter season and some in rainy season. [12, 17]

Our study was more focused on pharyngeal diphtheria and hence the most common anatomical site encountered by us to be involved were the tonsils (100%) in all cases similar to Arya et al. (100%). [15]

The most common complication in diphtheria cases was neurological in which palatal palsy was most common presentation, followed by motor weakness and an unusual case of paralytic ileus and bilateral abductor palsy with facial nerve palsy. Palatal palsy was characterized by a nasal quality of voice, nasal regurgitation commonly occurring in second and third week and was the earliest neurological complication which may occur alone or in association with other types of paralysis. The exact mention of paralytic ileus was not found in literature but can be attributed to the fact that the parasympathetic fibers to bowel and bladder are located more medially in the spinal cord and hence, are last to be affected by the pathological process.

The second most common complication occurring in diphtheria is myocarditis. Myocarditis occurs due to bacterial exotoxin which causes DNA fragmentation and cytolysis by inhibiting elongation factor-2 activity in protein synthesis in addition to damage to conduction tissue. It has been proven to be associated with highest rate of mortality [18, 19].

Present immunization coverage in India is around 61%, with geographical, religion, rural, urban and gender variation. [20] Minimum immunization coverage of 90% in children and 75% in adult is required to prevent spread of diphtheria.

Out of 64 patients, 38 cases (59.37%) were found to be fully immunised,6 cases (9.38%) were partially immunized, while rest of the 20 cases (31.25%) had no history of immunization, Jain et al. (17) reported 54% population of unimmunized cases in their study.

Our study depicted that 85% cases among un immunized, 33.33% among partially immunized and 26.31% among fully immunized cases developed complications, there is statistically significant association between complication and immunization status (p value < 0.05).

The occurrence of disease among immunized and partially immunized can be due to interruption of cold chain, waning of immunity in children and adolescents, poor immunization coverage, decreased compliance on behalf of the people for complete vaccination as per National Immunization Schedule.

Thus our study concludes that vaccination schedules should include boosters, based on accurate surveillance, to reach high vaccination coverage in order to prevent diphtheria outbreaks and control the disease.

Conclusion

Diphtheria is a vaccine preventable disease, continued occurrence of it emphasizes on the need for public health measures such as strengthening of routine immunization along with, emphasis on booster vaccination at school entry, and tetanus toxoid and low dose diphtheria toxoid vaccine/tetanus toxoid, low dose diphtheria toxoid and acellular pertussis vaccine booster at regular intervals of 10 years. Vaccinations and prophylactic antibiotics administration to susceptible contacts should also be a priority.

Funding

No financial funding received. Patients were treated free of cost under ‘MNDY (Mukhyamantri Nishulk Dava Yojana) scheme’ sponsored by Government of Rajasthan.

Data availability

Pro-forma of the data taken is filled for every patient and is available with the first author for review.

Declarations

Conflict of interest

Authors declare no conflict of interest.

Consent for publication

Written Informed Consent was taken.

Ethical approval

“All procedures performed in the presented study involving human participants were in accordance with the ethical standards of the institutional ethical committee of SMS Medical College Jaipur and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.”

Informed consent

Written informed consent was obtained from all individual participants included in the study in native language.