Clinical profile and risk factors for mortality in children admitted with diphtheria: an observational study.

BACKGROUND: There is an ongoing resurgence of diphtheria infection worldwide despite a vaccine being available to prevent it for more than four decades. OBJECTIVES: To study the clinical characteristics and risk factors for mortality of diphtheria cases among children 1-12 years of age treated in our hospital from 1 April 2014 to 31 March 2021. METHODOLOGY: The data of hospitalised cases of childhood diphtheria from 1 April 2014 to 31 March 2019 were retrospectively analysed from the medical records department of our hospital. All hospitalised children with diphtheria from 1 April 2019 to 31 March 2021, were prospectively studied. All categorical variables were expressed as proportion/percentage and all continuous variables were expressed as median with interquartile range (IQR). Risk factors for morbidity and mortality were analysed and tested for significance. Unadjusted odds ratio (OR) was calculated and significant variables were subjected to multivariate logistic regression. RESULTS: Of the 58 children with diphtheria, 62% were lab-confirmed, most cases (45%) were between 5 and 9 years of age. Majority (57%) were completely immunised as per the national immunisation schedule. Fever (97%) was the most predominant clinical symptom. The classical diphtheria pseudo membrane was identified in all. Respiratory failure was the most predominant complication, followed by myocarditis and acute kidney injury. The case fatality rate was 8.6%. CONCLUSION: Diphtheria cases were seen among children 5-9 years of age more commonly. Infection requiring hospitalisation was seen in vaccinated children too. No atypical manifestations were observed. Complications of the disease adversely affected the overall survival.

Diphtheritic myocarditis: a case report, with toxinmediated complications and multi-organ involvement.

The re-emergence of diphtheria in South Africa in recent years warns of incomplete vaccination coverage. Recent outbreaks have been associated with a high mortality rate, due to late presentation, limited access to antitoxin and the occurrence of serious systemic complications. Death due to diphtheria is most commonly associated with diphtheritic myocarditis, which presents with heart failure, cardiogenic shock and conduction abnormalities. This case highlights the key clinical features and systemic complications, and examines the reasons for the return of diphtheria in our community.

Diphtheria outbreak in Jakarta and Tangerang, Indonesia: Epidemiological and clinical predictor factors for death.

BACKGROUND: In 2017, a diphtheria outbreak occurred in several provinces in Indonesia. The aim of this study was to identify predictors of mortality outcome of pediatric patients with clinical diphtheria. METHODS: A retrospective cohort study was conducted using patient medical records at five referral hospitals in the Province of Jakarta and one in Tangerang District, Banten Province during January 2017 to 31 August 2018. All children in the age group of 1-18 years old discharged with diagnosis of clinical diphtheria formed the study group. All anonymized patient data were evaluated for demographic issues, clinical features, immunization status, complication, laboratory profiles and outcome. RESULTS: A total of 283 patients with clinical diphtheria were included in the study group with case fatality rate of 3.5%. All mortal patients had the complication of myocarditis. Regression analyses revealed factors for predicting mortality. Incomplete primary diphtheria toxoid immunization, stridor, bull neck, leukocytosis ≥15 x109 cells/L and thrombocytopenia ≤150 x109 cells/L in each combination for 2 predictors modeling were correlated with death. CONCLUSIONS: We report key predictors of mortality in pediatric patients with clinical diphtheria. The presence of these features when admitted to the hospital must be taken into account, because they can lead to fatal outcome.

A hyperalgesic ulcer on return from Senegal.

Diphtheria is an infectious disease transmitted by air or by contact. There are three main species of corynebacterium: diphtheriae, ulcerans, and pseudotuberculosis. They may or may not secrete a toxin responsible for serious cardiac or neurological complications. The frequent clinical presentations are diphtheria angina and cutaneous diphtheria. When it is suspected, it is urgent to send cutaneous or pharyngeal samples to the National Reference Center. If toxin is present, serotherapy should be instituted and the case should be reported. Antibiotic therapy with amoxicillin or azithromycin is the standard treatment. Vaccine prevention begun in the middle of the 20th century has helped to slow epidemics.

Clinico-epidemiological profile and predictors of outcome in children with diphtheria: a study from northern India.

Diphtheria, a vaccine preventable disease in children, is still being reported from India. Details of 99 children with a clinical diagnosis of diphtheria admitted to a paediatric tertiary care teaching and referral hospital between January 2008 and December 2015 were collected retrospectively and analysed. The median (interquartile range [IQR]) age of the study group was 7.0 years (IQR = 5.0-8.0 years). Nearly two-thirds were unimmunised. Clinical features included fever (97%), dysphagia (82%), sore throat (67%), bull neck (54%), stridor (40%), neuropathy (27%) and nasal discharge (14%). Throat swab for Albert stain was positive in only 21% of cases and C. diphtheriae was isolated in only 28%. Complications included airway compromise (61.7%) followed by myocarditis (35.4%), acute kidney injury (22.3%), thrombocytopenia (25.3%) and neuropathy (27.3%). In all, 66% survived, 23% died and 11% opted for discontinuity of care owing to unfavourable prognoses. On multivariable logistic regression analysis, shorter duration of symptoms before presentation to our hospital was an independent predictor of unfavourable outcome (adjusted odds ratio = 0.88, 95% confidence interval = 0.79-0.99, P = 0.03).

Cardiotoxicity Associated with Midazolam in a Patient with Diphtheria.

BACKGROUND: Adverse cardiorespiratory events are associated with midazolam continuous IV infusion, used for sedation. HISTORY: Here we are reporting a case of 5 year old male child suffering from diphtheria induced airway obstruction, and myocarditis, who received midazolam in the form of IV infusion for sedation while undergoing mechanical ventilation for respiratory failure. Adverse Event: Six hours after starting midazolam infusion he started developing pulsus bigeminus and bradycardia and eventual death after two hours. CONCLUSION: Midazolam, although considered one of the safest drugs, need to be used cautiously in a child with myocarditis, because of the possible cardiotoxic effect in an already affected heart.

Severe diphtheria with neurologic and myocardial involvement in a Swedish patient: a case report.

BACKGROUND: Diphtheria is caused by Corynebacterium diphtheriae. Although waning in incidence diphtheria can cause severe disease as in this rare Swedish case with several complications. CASE PRESENTATION: A 55-year old male presented to the emergency room with severe respiratory symptoms and greyish membranes in the airways, which turned positive for C. diphtheriae. He was put on ventilator support and remained hospitalized for three months. During care he developed myocarditis and severe neurological disease and he was also co-infected with tuberculosis. The patient was discharged with a favorable outcome. CONCLUSIONS: Diphtheria should be suspected in patients with life-threatening pneumonia especially if the patient has a history of travelling. Our patient was not treated with diphtheria anti-toxin (DAT) which may have contributed to the severity of the disease.

Cardiac complications in diphtheria and predictors of outcomes.

OBJECTIVE: To study the cardiac complications in diphtheria patients and to study the predictors of outcomes. STUDY DESIGN: Single centre prospective analysis of cardiac complications in diphtheria patients. RESULTS: In this study, there were 60 patients diagnosed with diphtheria with ECG changes. The ECG changes seen were sinus tachycardia (68.3%), T wave inversion (20%), ST segment depression (13.3%), right bundle branch block (5%), multiple atrial ectopics (3.3%). The case fatality rate in our study was 25% (15 patients). High CPK-MB, myoglobulin and cardiac troponin levels were associated with cardiac mortality. In our study, cardiac troponin T had the highest sensitivity (80%) and CK-MB had the highest specificity (95.56%). CONCLUSION: Cardiac involvement is a common complication of infection with C. diphtheria and is associated with high mortality. As diphtheria can be prevented by adequate vaccination, efforts should be maximized for high vaccine coverage with booster doses.

Fatal diphtheria myocarditis in a 3-year-old girl-related to late availability and administration of antitoxin?

Sporadic cases of diphtheria are very rare throughout Europe. A 3-year-old incompletely vaccinated girl was admitted with pharyngotonsillitis caused by diphtheria. On day 9 of her illness, renal and cardiac failure with a third-degree AV-block occurred. Unfortunately, she died within 36 h of admission to intensive care, despite pacemaker placement, the administration of antibiotics and diphtheria antitoxin. The delayed antitoxin administration 7 days after admission to hospital was related to a lack of availability and knowledge of its availability in Europe and this is likely to have contributed to the unfavourable outcome.

Diphtheric encephalitis and brain neuroimaging features.

We report a rare case of paediatric diphtheria complicated with encephalitis. A 6-year-old boy who did not receive his scheduled diptheria-tetanus-pertusis vaccination presented with one episode of generalised convulsive seizure. His illness was preceded by a 3day history of fever associated with enlarged exudative tonsils with a pseudomembrane. He was commenced on intravenous penicillin and oral erythromycin. However, he developed progressive encephalopathy with focal neurological deficit which required intubation on day 5 of illness. Throat swab polymerase chain reaction for diphtheria toxin A and B were positive and diphtheria antitoxin was given. Magnetic resonance imaging (MRI) of brain showed T2-weighted hyperintensities over the anterior cingulate gyri, insular cortex and cerebellum. This is the first reported MRI finding of diphtheric encephalitis. Our report highlights the importance of neuroimaging in diagnosing diphtheric encephalitis particularly in cases with unremarkable cerebrospinal findings.

Late Presentation of Post Diphtheritic Myocarditis in a 15-year Male.

A 15-year old male patient presented to us with dyspnoea for four days. He had a history of fever, pseudo-membranous tonsillitis and cervical adenopathy twenty-five days prior to the presentation. On examination and laboratory investigations, he had features suggestive of myocarditis with biventricular failure. There was no reliable history of immunisation and he had a positive history of contact. He was planned for anti-diphtheria toxin but before the anti-toxin could be initiated, the patient succumbed to refractory cardiogenic shock. This was a rare case of late onset diphtheritic myocarditis in an unimmunised adult. With the advent of universal immunisation, there has been a significant decline in the incidence but there is still some road to cover.

Diphtheria: It is still prevalent!!!

BACKGROUND: Diphtheria is a respiratory infectious disease of childhood. It is a fatal disease and may cause complications if not recognized early and treated properly. Despite availability of effective vaccination it continues to be reported from many parts of the world particularly developing countries. OBJECTIVE: To assess the demographic and clinical characteristics of diphtheria patients, and the predictors of outcomes of respiratory diphtheria. METHODS: A prospective analysis of 180 patients with a clinical diagnosis of respiratory diphtheria admitted from 2011 to 2014 at a tertiary referral hospital. They were evaluated with respect to demographic details, immunization status, clinical features, complications and outcomes. RESULTS: Most common age group affected was children less than 5 years of age (87 cases, 48.33%). The peak incidence of diphtheria was seen in the months of September and October (111 cases, 62%). Majority of the patients were unimmunized (54%), followed by partially immunized (21%). The most common complication was respiratory in 80 cases (44%), followed by cardiac complications in 54 cases (30%), and renal (16%) and neurological complications (10%). Cardiac complications were associated with the highest mortality rate (63%). The presence of bull neck and pseudomembrane score >2 was associated with a high mortality. CONCLUSION: Diphtheria is still a preventable public health problem in many developing countries. Improved vaccination coverage, including booster dosage, coupled with early detection and effective treatment, may all reduce incidence and mortality.

Potency of a human monoclonal antibody to diphtheria toxin relative to equine diphtheria anti-toxin in a guinea pig intoxication model.

Prompt administration of anti-toxin reduces mortality following Corynebacterium diphtheriae infection. Current treatment relies upon equine diphtheria anti-toxin (DAT), with a 10% risk of serum sickness and rarely anaphylaxis. The global DAT supply is extremely limited; most manufacturers have ceased production. S315 is a neutralizing human IgG1 monoclonal antibody to diphtheria toxin that may provide a safe and effective alternative to equine DAT and address critical supply issues. To guide dose selection for IND-enabling pharmacology and toxicology studies, we dose-ranged S315 and DAT in a guinea pig model of diphtheria intoxication based on the NIH Minimum Requirements potency assay. Animals received a single injection of antibody premixed with toxin, were monitored for 30 days, and assigned a numeric score for clinical signs of disease. Animals receiving ≥ 27.5 µg of S315 or ≥ 1.75 IU of DAT survived whereas animals receiving ≤ 22.5 µg of S315 or ≤ 1.25 IU of DAT died, yielding a potency estimate of 17 µg S315/IU DAT (95% CI 16-21) for an endpoint of survival. Because some surviving animals exhibited transient limb weakness, likely a systemic sign of toxicity, DAT and S315 doses required to prevent hind limb paralysis were also determined, yielding a relative potency of 48 µg/IU (95% CI 38-59) for this alternate endpoint. To support advancement of S315 into clinical trials, potency estimates will be used to evaluate the efficacy of S315 versus DAT in an animal model with antibody administration after toxin exposure, more closely modeling anti-toxin therapy in humans.

A 9-year-old boy with severe diphtherial infection and cardiac complications.

The incidence of diphtheria has decreased since the introduction of an effective vaccine. However, in countries with low vaccination rates it has now become a re-emerging disease. Complications from diphtheria commonly include upper airway obstruction and cardiac complications. We present a 9-year-old boy who was diagnosed with diphtheria. He presented with fever, tonsilar plaques, respiratory failure and an incomplete vaccination history. He was endotracheal intubated and received diphtheria antitoxin and penicillin on the first day of hospitalisation. He developed progressive arrhythmias and fulminant myocarditis despite early identification and treatment with equine antitoxin and antibiotics. After a temporary transvenous pacemaker insertion due to third-degree atrioventricular block and hypotension for 1 week, he developed myocardial perforation from the pacemaker tip resulting in pericardial effusion. The treatment included emergency pericardiocentesis and pacemaker removal. His electrocardiogram showed a junctional rhythm with occasional premature ventricular complexes. He then developed ventricular tachycardia and cardiac arrest and finally died.