Detection of Diphtheritic Polyneuropathy by Acute Flaccid Paralysis Surveillance, India

Farrah J. Mateen¹

, Sunil Bahl, Ajay Khera, and Roland W. Sutter

Author affiliations: Johns Hopkins University, Baltimore, Maryland, USA (F.J. Mateen); World Health Organization, Geneva, Switzerland (F.J. Mateen, R.W. Sutter); World Health Organization National Polio Surveillance Project, New Delhi, India (S. Bahl); Ministry of Health and Family Welfare, New Delhi (A. Khera)

Abstract

Diphtheritic polyneuropathy is a vaccine-preventable illness caused by exotoxin-producing strains of Corynebacterium diphtheriae. We present a retrospective convenience case series of 15 children (6 girls) < 15 years of age (mean age 5.2 years, case-fatality rate 53%, and 1 additional case-patient who was ventilator dependent at the time of last follow-up; median follow-up period 60 days) with signs and symptoms suggestive of diphtheritic polyneuropathy. All cases were identified through national acute flaccid paralysis surveillance, which was designed to detect poliomyelitis in India during 2002–2008. We also report data on detection of diphtheritic polyneuropathy compared with other causes of acute flaccid paralysis identified by this surveillance system.

Diphtheria is caused by toxin-producing strains of the bacterium Corynebacterium diphtheriae and is spread by human-to-human contact (respiratory secretions and cutaneous lesions). Before the advent of vaccination with diphtheria toxoid in the 1940s, ≈1 in 20 persons in temperate zones had diphtheria in their lifetime and 5%–10% of cases led to death (1). The last case of diphtheria in the United States was in 2003 in a traveler who returned from Haiti (2). However, diphtheria remains a health concern among immigrants, travelers, and those with incomplete immunity and vaccination coverage in many regions. Adults may also be increasingly at risk for diphtheria because of waning immunity or incomplete immunization, especially in outbreak situations (3).
Although diphtheria is preventable by vaccination, only 24% of countries worldwide reached the targeted > 80% routine coverage of all districts for diphtheria-tetanus-pertussis (DTP3) vaccine in 2011 (4). In 2004, the World Health Organization (WHO) reported 5,000 deaths caused by diphtheria, all of which were in children < 5 years of age (5). However, reporting of diphtheria is variable, and some countries report cases inconsistently because of limited recognition among health care workers and no dedicated surveillance systems (5). It is likely that many cases are not reported. Diphtheria is clinically considered to be a biphasic illness with initial symptoms of low-grade fever, sore throat, neck swelling, nasal twang, and usually ipsilateral palatal paralysis. The time between the first symptoms of diphtheria and the onset of polyneuropathy is deemed the latency period. Diphtheritic polyneuropathy occurs in ≈20% of patients with diphtheria. It is considered more likely with higher release of exotoxin (6,7) The classic features of diphtheritic polyneuropathy include sensory and motor signs and symptoms, most notably acute flaccid paralysis (AFP) with reduced or absent deep tendon reflexes. Limb paralysis from a segmental demyelinating process occurs with temporal regularity, with onset and resolution 35–140 days after the onset of bulbar signs and symptoms (6,7). Although serious, diphtheritic polyneuropathy is not consistently fatal and may resolve. Death from diphtheria occurs by parasympathetic dysfunction of the vagal nerve with cardiac arrhythmias, myocarditis, or from respiratory paralysis caused by laryngeal involvement (2).We report a case series of diphtheritic polyneuropathy in children in India identified by routine screening for AFP, which was performed to achieve eradication of poliomyelitis in India. The clinical characteristics of diphtheritic polyneuropathy are presented in detail to remind clinicians of the key diagnostic features of this major cause of neuropathy and the value of a throat examination in persons with AFP.
Cases of diphtheria with associated flaccid paralysis are reported to the polio eradication program in India as part of routine surveillance of AFP in children ≤15 years of age. All children with new-onset weakness in ≥1 limbs or facial weakness are reported by a network of health facilities that have been established in all districts of India for AFP reporting. Cases are reviewed for poliomyelitis; this review includes results of fecal testing for poliovirus serotyping. Case-patients, or primary providers for young or severely ill children, are interviewed. All case-patients with AFP are examined in detail by district medical officers trained by government/WHO surveillance officers.
On the basis of results of fecal testing, preliminary clinical findings, and course of the illness, a final diagnosis is established by the district government/WHO medical officers in tandem with local physicians. For patients from whom fecal samples are not collected in time to diagnose poliomyelitis (cases with inadequate samples or inadequate signs and symptoms), the final diagnosis is made by an expert review committee of neurologists, virologists, pediatricians, and epidemiologists convened by the WHO–India National Polio Surveillance Unit in New Delhi, India (8,9). This committee comprises a minimum of 3 senior experts, usually professors of major academic centers in India, to determine the final diagnosis of children with AFP and inadequate fecal specimens. The committee uses no specific algorithm or diagnostic criteria for every case but comes to a consensus on the most likely diagnosis on the basis of clinical, laboratory, and epidemiologic data.
All cases in this series were given a final clinical diagnosis of diphtheritic neuropathy. The European Union case definition (2002) for the National Diphtheria Surveillance category of probable diphtheria was used to look for diphtheria: “a clinically compatible case that is not laboratory confirmed and does not have an epidemiological link to a laboratory case.” Diphtheria is clinically defined “as an upper respiratory tract illness characterized by sore throat, low grade fever, and an adherent membrane of the tonsils, pharynx or nose or non-respiratory diphtheria; cutaneous, conjunctival, otic, and genital lesions” (10). The cases reported represent a convenience sample of cases suggestive of diphtheritic polyneuropathy during 2002–2008 in which Guillain-Barré syndrome or poliomyelitis was first suspected. For many case-patients, details of antecedent sore throat, adherent membrane, and respiratory and systemic features were not available because the investigation began only after reporting of AFP and surveillance dedication to poliomyelitis. All cases were diagnosed as diphtheria clinically by at least the treating physicians and the expert review committee in New Delhi.
The cases reported were included because of chart accessibility at the National Polio Surveillance Unit and accessibility of paper files from large storage containers in off-site warehouses. All cases were classified as cases having inadequate fecal specimens for poliovirus testing.
Clinical features were extracted from information obtained by medical officers at the time of clinical presentation. Preselected clinical history, physical examination, baseline demographics, and laboratory findings were obtained from standardized reporting forms. All surviving case-patients were evaluated and caregivers were interviewed at a follow-up visit 60 days after diagnosis per usual protocols during AFP surveillance in India. Death information was also ascertained at 60 days. A neurologist (F.J.M.) extracted all relevant and available clinical information from the medical and surveillance records and retrospectively assigned a Guillain-Barré syndrome disability outcome score (11).