Antidiphtheritic Serum Research Articles

Diphtheria Remains a Threat to the Health System Even in the Era of Vaccination: A Cross-sectional Observational Study from Karnataka, India

Introduction: Diphtheria is an infectious disease caused by a gram-positive facultatively anaerobic bacilli, Corynebacterium (C.) diphtheriae. The present health statistics and data from the few studies that have been carried out suggest that our war with this disease is still going on and is far from being over in spite of the vaccine that’s freely available. Aim: To study clinical profile, complications, and outcome of diphtheria in karnataka population and to correlate with immunisation status. Materials and Methods: This was a hospital-based prospective cross-sectional observational study done in the Department of Paediatrics, Karnataka Institute of Medical Sciences, Hubballi, Karnataka, India, from January 2018 to November 2018. Patients admitted with history suggestive of diphtheria were enrolled and categorised into probable and confirmed cases. The age, sex, area of residence, religion, immunisation status, mean time of presentation to hospital from onset of illness, use of inotropes and mechanical ventilation were recorded in a predesigned proforma. Throat swab smear for C.diphtheria and culture, complete blood count, Renal Function Tests (RFT) with serum electrolytes, chest radiograph, Electrocardiogram (ECG) and 2-Dimensional (2D) Echocardiogram (ECHO) were also recorded. Results: Out of total 28 cases, 18 fulfilled the inclusion criteria. Male to female ratio was 2:1 and the mean age of presentation was 9.7 years. Highest incidence (n=14, 77.8%) was seen in the age group of 09-11 years. Most common clinical presentation was fever and sore-throat present in all 18 (100%), neck swelling in 13 (72.2%), dysphagia in 05 (27.7%). Examination revealed tonsillar hypertrophy and pseudomembrane in 17 (94.4%) patients, whereas one patient had laryngeal diphtheria, which was diagnosed when swab was sent while intubating in view of membranous laryngitis. Mean time of presentation to hospital after the onset of symptoms was 5.65 days. All children received appropriate antibiotics and Antidiphtheritic Serum (ADS). Total of seven patients were ventilated, of which 5 (27.7%) succumbed, and two were extubated. Four (22.2%) patients developed myocarditis in the second week, and all succumbed to resistant arrhythmias. One patient developed sepsis with ventilator dependency, and succumbed to inotrope resistant septic shock. On follow-up, 5 (27.7%) developed palatal palsy among which three had associated polyneuropathy; all these children recovered with only supportive care. Conclusion: Diphtheria is down but not out, the present study unmasks the fact that the disease is equally prevalent in immunised and older children with the changing epidemiology of diphtheria in the era of vaccines.

Diphtheria: a re-emerging infectious disease

<p class="abstract"><strong>Background: </strong>Diphtheria is a fatal bacterial infection which affects the mucous membranes of oropharyngeal and nasal cavity, caused by aerobic gram-positive bacteria Corynebacterium diphtheriae. Clinical diphtheria is on the increase worldwide, mainly affecting developing countries and leading cause of morbidity and mortality. We sought to understand its presentation among patients and also early intervention of the disease. The objective of the study was to study the clinico-demographic profile of cases, the relationship between immunization status and clinical disease, the role of microbiological investigations and to identify complications in diphtheria cases.</p><p class="abstract"><strong>Methods:</strong> This study is a hospital based observational study from September 2019 - September 2020 at a tertiary care centre, S.Nijalingappa Medical College and HSK hospital, Bagalkot, Karnataka. The cases were analysed with respect to demographic details, clinical features, immunization status, microbiological confirmation and complications of diphtheria cases.</p><p class="abstract"><strong>Results: </strong>32 cases were suspected to have diphtheria on clinical examination. The mean age of presentation was 15 years. Fever, sore throat, difficulty in swallowing, neck swelling and pseudomembrane in oral cavity were the common signs and symptoms. Airway compromise, myocarditis and neurological complications were noted. Antidiphtheritic serum (ADS) was tried in all 32 cases and 8 cases had adverse reactions. Case fatality rate was 12.5%.</p><p class="abstract"><strong>Conclusions: </strong>Shifting of occurrence of diphtheria in the age group of >5 years suggest the need to improve and strengthen the immunization program specially the booster doses.</p>

Resurgence of diphtheria: clinical profile and outcome in a tertiary care hospital of South India

Background: Diphtheria is a potentially fatal acute disease caused by Corynebacterium diphtheria. It was one of the leading causes of mortality in the pre vaccination era. This study is an attempt to highlight the clinical profile, outcome and demographic characteristics, immunization status of pediatric diphtheria cases in South India. Objective of the study was to analyze the clinical profile, immunization status and outcome in children with diphtheria admitted to the PICU in a tertiary care hospital.Methods: This retrospective study was conducted in a tertiary care hospital in South India. The case records of all children admitted to the hospital between January 1st, 2014 to December 31st, 2018 with clinically suspected diphtheria were analyzed. The data was analyzed with respect to clinical features, demographic characteristics, immunization status, complications and outcome using appropriate statistical methods.Results: 18 cases were clinically suspected to have diphtheria. The average age of children presenting with diphtheria was 9 years. Out of the 18 cases, 11 were male, 7 were female. 16 out of 18 cases were from rural areas, whereas only 2 cases were from urban areas. Fever, sore throat and dysphagia were the presenting complaints in all cases. Neck swelling, white patch over tonsil and tender cervical lymphadenopathy were the other findings noted. Out of 18 cases, 7 were completely immunized, 8 were incompletely immunized and 3 were not immunized. Antidiphtheritic serum was given in 14 cases. Myocarditis, airway compromise and neurological deficits were the complications noted. Case fatality rate was 50%.Conclusions: Diphtheria still remains a major public health problem in developing countries like India. Mortality and morbidity due to diphtheria continues to be high despite ready availability of vaccines and antitoxin. Childhood immunization program, especially follow up and administration of booster doses must be prioritized.

The outcome of resurgence of diphtheria in older children in a tertiary care hospital

Background: Diphtheria is a fatal bacterial infection which affects the mucous membranes of oropharyngeal and nasal cavity, caused by aerobic gram-positive bacteria Corynebacterium diphtheriae. With the advent of universal immunization against diphtheria the incidence of this infectious disease has declined dramatically with few developed nations having eradicated the disease. No large outbreaks have been reported in India in recent times.Methods: In present study, authors reviewed an outbreak of diphtheria in Davangere between the months of June 2017 and July 2018. Case records of children suspected to have diphtheria, admitted to hospitals affiliated to JJM Medical College, Davangere were retrospectively analysed.Results: 15 cases were suspected to have diphtheria on clinical examination. The mean age of presentation was 7.5 years. Fever, sore throat, difficulty in swallowing, neck swelling and patch in oral cavity were the common signs and symptoms. Airway compromise, myocarditis and neurological complications were noted. Antidiphtheritic serum (ADS) was tried in all 15 cases. Case fatality rate was 40%.Conclusions: Diphtheria is a resurgent problem in India. Prompt identification and early appropriate treatment is essential to prevent morbidity and mortality. Strict adherence to the national immunisation schedule should also be emphasized.

Clinical profile and predictors of outcome of patients with diphtheria in tertiary care pediatric centre from Southern India

Background: Diphtheria is still a fatal infectious disease even in this era of universal immunization. The disease has been completely eradicated in most of the developed countries. On the contrary, in developing countries, although the incidence has drastically declined, still account for 80-90% of global burden. The objectives of this study is to study the clinical profile and predictors of outcome of patients with diphtheria.Methods: All children between the age group of 0 to 15 years admitted with signs and symptoms of diphtheria during January to August 2017 formed the study group. Throat swab for Albert’s stain and culture sensitivity were sent in all patients at the time of admission. All children were started on parenteral crystalline penicillin and Anti Diphtheritic Serum as recommended. All details that is demographic data, clinical features, immunization status, complications and outcome were entered in a proforma and analysed. Several variables were compared among the survivors and non-survivors to determine the predictors of outcome. Outcome is defined as either recovered or died.Results: A total of 42 patients were included in the study group. Among 42 patients, 21 (50 %) were between 5-10 years, 12 (28 %) were between 0-5 years and 9 patients (22 %) were more than 10 years. Most common symptoms were fever followed by throat pain, difficulty in swallowing and bull neck. Alberts stain was positive in 83% of cases and culture positivity in 30% of cases. Myocarditis (47%) was the most common complication followed by acute kidney injury (40%), airway compromise (59%) and thrombocytopenia (42%). A total number of 19 patients died.Conclusions: Diphtheria is highly fatal disease with increased mortality. Myocarditis was the commonest and most serious complication. Presence of myocarditis, AKI, thrombocytopenia, airway compromise and inadequate immunization are important predictors of outcome.

Re-emergence of diphtheria in Malappuram district, North Kerala, India

BACKGROUND AND OBJECTIVE: An outbreak of diphtheria was identified in Malappuram district, North Kerala, India, from July 2016 onwards as a sudden increase in the number of throat swabs with suspected diphtheria received in the Microbiology Lab of Government Medical College Manjeri, Malappuram district. The objective of this study was to confirm the outbreak and identify the organisms and their antibiotic sensitivity patterns.MATERIALS AND METHODS: A total of 554 throat swabs were received from July 2016 to June 2017 from neighbouring areas of Malappuram district for culture and sensitivity. Elek gel precipitation test and polymerase chain reaction of the isolates were performed at the State Public Health Lab, Thiruvananthapuram. All isolates of Corynebacterium diphtheriae possess diphtheria toxin gene. Antibiotic sensitivity tests were performed. Repeat swabs were not included in the study.RESULTS: Of the 29 (5.23%) confirmed cases, 18 (62%) were male and 11 (38%) were female. Fourteen (48.3%) cases were between 6 and 10 years of age with nine (64%) males and five (36%) females. Seven (24.2%) were between 11 and 15 years of age with four (57%) males and three (43%) females. Three (10.3%) were between 16 and 20 years of age (all males). Two (6.9%) cases from 26 to 30 years and one (3.4%) each from 21 to 25 years, 31–35 years and 36–40 years. All isolates were Penicillin sensitive.CONCLUSIONS AND DISCUSSION: Our study identified an upsurge of diphtheria in Malappuram district, North Kerala, among older children and adolescents. Most of them are partially immunised and immunity to diphtheria declines over time. Adults and adolescents thus become susceptible later in life. This emphasises the need for booster vaccination above five years in the endemic areas and making antidiphtheritic serum available in all major hospitals of these regions.

Resurgence of Diphtheria in Rural Areas of North Karnataka, India

Background: A diphtheria outbreak was identified from Vijayapura (formerly Bijapur) district in the South Indian state of Karnataka in 2011. There was a surge in the number of throat swab samples received under the Integrated Disease Surveillance Programme (IDSP) in North Karnataka since then. Objectives: A microbiological study was undertaken to generate information on the status of resurgence of the disease in the region. MaterialsandMethods: Throat swabs from 432 suspected cases of diphtheria during 2012–2015 were obtained from government hospitals and primary health centres of 8 districts in North Karnataka and were processed for the culture and identification of Corynebacterium diphtheriae. Polymerase chain reaction for the presence of toxin gene (toxA and toxB) was carried out on the isolates. Antibiotic sensitivity tests were performed on the isolates with a panel of 14 antibiotics. Results: Thirty-eight (8.79%) out of 432 samples yielded C. diphtheriae on culture. All isolates possessed the diphtheria toxin gene. Out of the 38 confirmed cases, whereas 21 (55.26%) were between 1 and 5 years of age, 14 (36.84%) were aged between 5 and 10 years. Male children were three times more than females in confirmed cases. No information was available on the immunisation status of the cases. Emergence of resistance to penicillin was found with minimum inhibitory concentration reaching up to 6.00 μg/ml. ConclusionandDiscussion: Our study identified an upsurge in cases of diphtheria in North Karnataka, particularly in Vijayapura District, and to the best of our knowledge, reports the emergence of penicillin resistance for the first time in India. The study calls for enhanced surveillance for the disease, making antidiphtheritic serum available in key hospitals in the region and serves to provide a baseline for future assessment of the impact of the recently launched ‘Mission Indradhanush’ programme in strengthening Universal Immunisation Programme (UIP).

Diphtheria Re-emergence: Problems Faced by Developing Countries

In the pre-vaccination era, diphtheria was a leading cause of childhood mortality. With the introduction of routine childhood immunization, paediatric care and improved hygiene status the disease has been almost completely eradicated in many developed countries. On the contrary developing countries, still account for 80-90% of the global burden. Retrospective analysis of 52 cases of diphtheria over a period of 12years at a tertiary referral hospital was carried out. They were analyzed for mortality and morbidity trends, immunization status, microbiological confirmation rates and antidiphtheritic serum (ADS) administration. Incidence in those over 5years was 59.61%. Only 11.54% cases were either partially or fully immunized. The case fatality rate was 36.53%. Culture was performed only in 17 cases whereas ADS was administered in only 16 cases. In conclusion, the occurrence of diphtheria even in those immunized highlights the flaws in the present immunization program. Poor immunization coverage, lack of ADS, antibiotic resistance are the main reasons for re-emergence of diphtheria.

Adolf Bingel's blinded, controlled comparison of different anti-diphtheritic sera in 1918

With the uptake of serum treatment for diphtheria from the end of the 19th century onwards, deaths from the disease fell dramatically,1 albeit, less dramatically in countries, such as the UK, in which serum treatment had not been adopted wholeheartedly.2 The development of serum therapy of humans – in a race between the Berlin Institute for Infectious Diseases and Emile Roux and his colleagues at the Pasteur Institute in Paris – led to the award of the first ever Nobel Prize in physiology or medicine, in 1901, to Emil Behring. This illustrated that there was wide acceptance that anti-diphtheritic serum was effective.

Danish contributions to the evaluation of serum therapy for diphtheria in the 1890s

Diphtheria's effects are caused by a toxin produced by the bacterium Corynebacterium diphtheriae. This toxin produces not only diphtheria's effects in the upper respiratory tract, but also later complications, including myocarditis and peripheral neuropathy. These complications, and superinfection with other bacterial pathogens (streptococci, in particular), contribute to the serious morbidity and mortality associated with the disease. In the early 1890s, in Berlin, Emil von Behring and Shibasabura Kitasato developed a serum from a hyper-immune horse, which seemed to confer passive immunity on patients with diphtheria. Experience with this serum was first reported in a paper published in 1893.1 The following year, Emile Roux, Louis Martin and Auguste Chaillou reported detailed information on 448 children admitted to the diphtheria service of the Hopital des Enfants-Malades in Paris. One hundred and nine of the 448 children admitted died – a fatality of 24.5%. This compared very favourably not only with a rate of about 50% in the same hospital during the four years 1891 to 1893, but also with a fatality of 60% in the Hopital Trousseau, where serum had not been used.2,3 The evidence from Paris and other evidence using historical controls did not convince everyone of the value of anti-diphtheritic serum, however. The debate was complicated both because the disease was undergoing spontaneous fluctuations with decreasing virulence and by claims that the success of serum treatment showed that laboratory research was a more promising approach to tackling diseases associated with poverty than the social reforms for which Virchow and others had been calling.4 Furthermore, deaths had been attributed to the antitoxin, some of which attracted wide publicity.4–6

Outcomes of respiratory diphtheria in a tertiary referral infectious disease hospital

Diphtheria is a fatal disease and may cause serious complications if not recognized early and treated properly. To study the epidemiology, clinical features, complications, and outcomes in respiratory diphtheria. Diphtheria cases admitted in the infectious disease hospital, Beliaghata, Kolkata, India between January 2009 to January 2011 were evaluated in respect to demographic profile, immunization status, clinical features, complications, and outcomes. 200 diphtheria cases were studied. 150 (75%) patients had history of an adequate immunization, and 100 (50%) patients were from lower socio-economic groups. Common clinical features observed were throat pain in 148 (74%) cases and fever in 112 (56%) cases. Complications observed were myocarditis in 136 (68%) cases, neuropathy in 30 (15%) cases, and respiratory compromise in 14 (7%) cases. Death occurred in 5 (2.5%) patients. diphtheria is still a public health problem in many developing countries. Strict public health measures like an increased immunization coverage, improvement of socio-economic status, easy availability of anti-diphtheritic serum (ADS), early recognition and effective treatment-all may reduce the incidence and mortality.

Upper respiratory tract and cutaneous diphtheria

With the global immunization programme of children there is a progressive decline in the number of diphtheria cases. It is a disease commonly affecting the children caused by Corynebacterium diphtheriae usually affecting the mucous membrane of the nose, pharynx or larynx. Cutaneous diphtheria is a rare entity. We present a rare case of cutaneous diphtheria in a 15-year-old boy with nasal pharyngeal and laryngeal involvement. The patient developed anaphylactic reaction to antidiphtheritic serum (ADS) during treatment, all of which were managed successfully.

Diphtheria—the patch remains

Background: Diphtheria, a leading cause of childhood mortality in the pre-vaccination era, has witnessed a resurgence in the last decade in the developing world and in parts of Europe. Faucial diphtheria can mimic acute tonsillitis and glandular fever, and a degree of clinical suspicion is required in order to diagnose and treat a potentially life-threatening condition. This assumes greater significance in today's world. Objective: To review the number of diphtheria cases admitted to Silchar Medical College and Hospital, a teaching hospital in the state of Assam in India over the last 5 years and to compare the profile of patients admitted here to cases reported elsewhere in the country and abroad. Methods: Details of patients were obtained from the hospital database. Comparisons were made with disease patterns reported elsewhere in the country and in parts of Europe in the late 1980s and 1990s. Results: A total of 101 patients were admitted with diphtheria over a period of 5 years (March 1997–March 2002). There were no peaks in the incident rate. About 82% of the patients admitted were below the age of 15. One adult with microbiologically confirmed diphtheria was seen. Immunisation status varied between no cover (70%), incomplete immunisation (20%), and full immunisation (10%). A majority of patients were from the rural environment and were economically disadvantaged. Treatment involved the administration of anti-diphtheritic serum (diphtheria antitoxin), IV Penicillin, and where indicated, tracheostomy. Conclusions: Results obtained show an endemic pattern of the disease in this part of the world. Persistence of the disease is due to poor immunisation coverage and problems such as poor hygiene associated with poverty. There is a rural preponderance of cases as opposed to the epidemics reported elsewhere in the country, the newly independent states of the former Soviet Union, and in parts of the USA. The case of the adult points to an interesting change in the normal age distribution of the disease.

Diphtheria: the patch remains.

This study analysed the number of patients admitted with diphtheria to a teaching hospital in the state of Assam in India over a period of five years and compared the disease characteristics and management with outcomes and incidences of diphtheria reported in the literature. It was a retrospective analysis of data elicited from clinical records of patients admitted to hospital. A total of 101 admissions were recorded during a five-year period between March 1997 to March 2002, mostly with pharyngeal diphtheria (90 per cent). The majority of patients had no history of immunization (70 per cent). Significant presenting features were a tonsillar patch, sore throat, respiratory distress and fever. All patients were treated with anti-diphtheritic serum and intravenous antibiotics. Steroids were given to 81 per cent of patients and tracheostomy was carried out in 10 per cent of cases. The mortality was 16 per cent. Diphtheria of the respiratory tract remains a potentially fatal disease commonly presenting with membranous pharyngitis. Early diagnosis and treatment with anti-diphtheritic serum and antibiotics remain the cornerstone of treatment. Inadequate immunization cover is deemed responsible for the continued menace of diphtheria.

Allergic shock following administration of anti-diphtheritic serum

Allergic shock following administration of anti-diphtheritic serum

ARTIFICIAL ANTIBODIES

In vitro synthesis of type specific antipneumococcus precipitins and agglutinins has been reported recently by Pauling and Campbell¹of the Department of Chemistry, California Institute of Technology. Substances simulating specific antibodies formed outside the animal body were demonstrated thirty years ago by Russian immunologists. Ostromyschlenski and Petroff,²for example, incubated a mixture of diphtheria toxin and normal horse serum and obtained an end product with all the therapeutic properties of diphtheria antitoxin. By incubating diphtheria toxin with different protein fractions of normal horse serum, Kryshanowski³prepared two artificial diphtheria antitoxins of different therapeutic value. By somewhat different technics, Sdrawosmisslow⁴and Kimmelstiel⁵incubated diphtheria toxin with commercial trypsin and reported the successful test tube synthesis of a "toxin trypsinate" with the therapeutic properties of an antidiphtheritic serum. In anticipation of future commercial value, artificial antitoxin made by incubating diphtheria toxin with normal serum plus pancreatin was

Value of Anti-Diphtheritic Serum Treatment

THE autumn issue of the Fight against Disease (22, No. 4), the quarterly journal of the Research Defence Society, contains an article by Sir Leonard Rogers showing the reduction in the suffering and the deaths of children from diphtheria during the last forty years consequent upon the use of anti-diphtheritic serum treatment. He points out that the case mortality, the most scientific test of the value of treatment, from diphtheria in the hospitals of the Metropolitan Asylums Board, has steadily fallen every year from a percentage of 30-4 in 1890-93 before serum was used, to 9-0 in 1905, 7-4 in 1910, and less than 4-0 in 1933, following the treatment of the disease with the serum. More striking still is the fall in mortality for laryngeal cases, from 62 per cent in 1894 to 11-7 in 1910. The value of the serum treatment is even more conclusively shown by its remarkable efficacy in the early stages of the disease, as compared with its comparative failure when given after the fourth day of the disease, when the toxaemia of the disease is fully developed, in accordance with what animal experiments had indicated would be the case. The case mortality per cent when treatment is commenced on the first day of the disease is only 1-6, on the second day it is 7-9, and on the third 17-2. As Sir Charles Martin has pointed out, “If the antitoxin (serum) were a remedy of no value, whether it was administered on the first or on the fifth day of the disease would be immaterial”. Clinical evidence is no less conclusive: many doctors still living can testify to the horrors of diphtheria in young children in the pre-serum days. This is now all changed, and the young diphtheria patient if treated early with serum will rarely succumb. Sir Leonard Rogers estimates that had the pre-serum mortality from diphtheria continued since 1911, there would have been 250,000 more deaths from diphtheria than were actually recorded.

PARIS

<h3>The Transmission of Poliomyelitis</h3> Levaditi, Kling and Lepine, who recently presented a report on the epidemic of poliomyelitis in Alsace, have now transmitted to the Academy of Medicine a contribution on the mode of transmission of the disease, which they suspected might be carried by water. They have discovered through research that domestic animals which have consumed food contaminated by the virus of poliomyelitis do not contract the disease but that the virus, after passing through the digestive tract, is found in their excrement, and thence passes into the water supplies of rural regions. Thus the transmission is brought about. During an epidemic, the virus can be eradicated by disinfecting the drinking water and that used for washing. The virus is likewise completely destroyed by small quantities of chlorine (0.0004 Gm. per liter). <h3>Intravenous Injections of Antidiphtheritic Serum</h3> The Société de pédiâtrie devoted recently a session to the study of

On Staphylococcal Precipitin Reactions in Cases of Acute and Chronic Infections and also in Serum Sickness

This work was undertaken for the purpose of determining the occurrence and specificity of bacterial precipitins in infections caused by the Staphylococcus aureus. The differences in antigenic properties of various strains of orange and white staphylococci employed in the preparation of the filtered antigens and the importance of the presence of peptone in this connection led to numerous experimental observations which had not been anticipated. The presence of strong S. aureus precipitins in the blood of an adult suffering from very acute serum sickness following an injection of anti-diphtheritic serum led to an investigation of the blood of patients suffering from serum sickness, the results of which are fully recorded here. The investigation of the blood of normal rabbits revealed the fact that in some of these animals staphylococcal precipitins were present, which led to unexpected difficulties in the study of precipitins in the actively immunised animal.

Non-Specific Therapy

IN inoculation against typhoid fever, dead typhoid bacilli are injected subcutaneously or into a muscle. Inoculation against plague consists in the injection of an emulsion of dead plague bacilli artificially grown in broth. These are prophylactic measures for the protection of persons who are likely to be exposed to infection. Hydrophobia vaccine, used in order to prevent the development of the disease in persons who have been bitten by a rabid animal, is prepared according to a definite system from the spinal cords of rabbits inoculated with the disease. Anti-diphtheritic serum, used in the treatment of patients actually suffering from diphtheria, is the blood-serum of a horse which has had diphtheria toxin (the broth in which diphtheria bacilli have been grown, and from which the bacilli have been filtered off) repeatedly injected into it.