Abstract
Summary
A retrospective study was done on 48 consecutive patients with clinical diagnosis of postdiphtheritic neuropathy admitted to the paediatric intensive care unit of tertiary care hospital in North India between January 2008 and December 2010 to study the clinical profile of post-diphtheritic neuropathy in children. The case records were reviewed and information regarding personal details, clinical features, recovery parameters and outcome was recorded using a predesigned proforma. Median age was 4.25 years. All cases were unimmunized. Median latency period was 15 days. Of the children, 52% had palatal palsy whereas 48% had limb weakness initially. Median duration of progression of weakness was five days. Limb muscle weakness was present in 94%. Respiratory muscles were involved in 85.4% cases and 60.4% required mechanical ventilation, while 14.6% had fatal outcome and 10.4% had hypoxic neurological injury. Boys were affected more. Median duration of latency was shorter; muscle weakness, progression and recovery were faster as compared with observational studies in adults.
Introduction
Diphtheria is still a cause of concern in many developing countries in spite of national programmes of vaccination with diptheria-pertusis-tetanus (DPT) in children. In India, diphtheria is still endemic and resurgence has been noted recently. 1 India reported 3529 and 3123 cases to the World Health Organization (WHO) in 2009 and 2010, respectively, which accounted for nearly 74% of the total burden of the disease in the world. 2
Post-diphtheritic polyneuropathy is a major complication of diphtheria and its incidence is directly proportional to the severity of diphtheria. It is reported to occur in up to 15% of diphtheritic patients. 3 There have been many studies on diphtheria and its complication from India, but none has reported on post-diphtheritic polyneuropathy and its implications for intensive care requirements of affected children. We report the clinical profile of post-diphtheritic neuropathy and their outcome in North Indian children.
Materials and Methods
This is a descriptive retrospective study conducted on 48 consecutive patients with the clinical diagnosis of postdiphtheritic polyneuropathy who were admitted to the paediatric intensive care unit (PICU) of a tertiary level hospital in New Delhi from January 2008 to December 2010. These children are referred from different parts of North India for mechanical ventilation or PICU care. Post-diphtheritic neuropathy was defined as signs and symptoms suggestive of various cranial nerve involvement and/or limb neuropathy within six weeks of compatible clinical illness suggestive of diphtheria. 4 All cases were evaluated as for acute flaccid paralysis (AFP), Guillain–Barre syndrome and poliomyelitis were excluded. 5 Throat swab for staining and culture for Corynebacterium diptheriae was done in all cases. Case records of all patients were retrieved and detailed clinical characteristics of the patients were recorded in a predesigned proforma. Time period between appearance of first symptom of diphtheria and development of diphtheritic neuropathy was termed latency. 6 Clinical outcome was classified as discharge and death. Limb, palatal and respiratory muscle weakness and recovery time were calculated from the records. Incidence of complications in children ≤5 years of age and >5 years of age were compared using SPSS version 16.0 (SPSS Inc., Chicago, IL, USA) and P value <0.05 was considered significant. Group comparison was done using Chi-square test for categorical data and Student's t-test or Mann Whitney test for parametric or non-parametric continuous data respectively.
Results
A total of 48 patients of post-diphtheritic neuropathy were admitted to PICU during the three-year period. Boys were three-fourths of total admissions. All of the patients belonged to Delhi and neighbouring states. Detailed demographic and clinical features of patients are presented in Table 1. Median age of patients was 4.25 years. Immunization profile showed that 15 children were unimmunized, 32 had incomplete primary vaccination series and one child had received complete primary series but did not receive DPT booster. All children had compatible clinical manifestations of diphtheria: neck swelling with a throat membrane. Only two had confirmed reports of C. diphtheria isolated on culture. Neck swelling persisted for 3–10 days in most of the patients. Median latency period was 15 days (5–45 days). A total of 52% children presented with initial symptom of palatal palsy, while 48% had limb weakness initially. Median duration of progression of weakness was five days. Cranial nerves were involved in 91.5% of cases, IX/X nerve in 75%, III 4.1% VI in 6.2% and VII in 6.2%. Limb muscle weakness was noted in 94% during the clinical course. Respiratory muscles were involved in 85.4% of cases. Intercostals muscles were involved in 6.3%, diaphragm in 14.6% and both in 64.6%. A total of 60.4% required mechanical ventilation whereas the rest required monitoring and supportive therapy. Median duration of mechanical ventilation was 13 days. Nerve conduction velocity (NCV) was performed in 12 children and revealed decreased amplitude in three, decreased conduction velocity in four or both in five children. Post-diphtheritic myocarditis was observed in 41.7% of children; 25% had cardiogenic shock and 10.4% had rhythm disturbances. Median duration of hospital stay was 18 days and 20.8% patients stayed for more than one month. A full 85.4% of children were discharged and 14.6% died. Respiratory muscle function was first to recover with median duration of 14 (5–62) days, followed by palatal recovery 16 (7–50) days and limb muscle power ≥3/5 18 (8–48) days. Neurological sequelae (hypoxic brain injury) were seen in 10.4% of patients.
Demographic and clinical profile of patients
Discussion
The endemicity of diphtheria has decreased in developed countries through sustained high immunization coverage, but a resurgence was noted in former Soviet republics, largely due to waning vaccine immunity among adults. The epidemiological situation in India is different and complex as diphtheria is still endemic here, because not only of poor immunization coverage with DPT primary series but also of booster vaccination. According to the National Family Health Survey-3 (NFHS-3) only 55.3% children below five years of age are immunized with three doses of DPT. 7 Decreased coverage with DPT booster and decreasing immunity is probably responsible for the upward shift in the age of diphtheria noted in various studies from India.1,8 Age group of more than 15 years was the most commonly affected in a recent diphtheria outbreak in the state of Assam. 9 In our study 40% of total cases were children more than five years of age. Thus, disease in India is affecting young children as well as young adults pointing, to low childhood immunization coverage and continued transmission of C. diphtheriae.
No recent literature is available on the clinical profile of diphtheritic polyneuropathy in children. However, few studies from Soviet republics on clinical profile of postdiphtheritic neuropathy in adults are available.3,6,10 The latency period is longer in adults as compared to children.3,6 Palatal palsy has higher incidence and follows a biphasic pattern among adults. Motor weakness significantly persists for longer duration; autonomic and sensory symptoms are more commonly seen in adults than in children. 6 More respiratory weakness is noted in children and higher proportion required mechanical ventilation. Cranial nerves (II, V, XI and XII) involvement and cardiovascular complications are more common in adults.6,10 Respiratory muscles were first to recover in our study, followed by palatal and limb muscles. This is in contrast to observations of Piradov et al. who reported cranial nerves (especially IX and X) to affect as well as recover first. 6 We found no significant difference in the progression of the disease, complication rate or recovery in children less than five years and greater than five years of age.
Despite PICU care for polyneuropathy, 15% cases died and 10.4% had long-term morbidity in the form of hypoxic brain injury. Most patients required prolonged PICU stay and required therapy in the form of mechanical ventilation care, oxygen therapy, intravenous fluids and antibiotics. All of this added to the cost burden of this vaccine-preventable disease. Vaccination is the only practical and cost-effective method available to prevent diphtheria and its complications like polyneuropathy. Hence, the primary and booster DPT vaccination programme should be strengthened in the Universal Immunization programme. Simultaneously, surveillance system should be setup for all infectious diseases including diphtheria.
Footnotes
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