Clinico-Epidemiological Study of Acute Flaccid Paralysis at a Tertiary Centre

Objectives: To study the clinico-epidemiological profile of different causes of Acute Flaccid Paralysis (AFP) including Acute Encephalitis Syndrome (AES) and their associated co-morbidities. Methodology : A prospective hospital-based study was carried out including all cases fulfilling AFP case definition. History, clinical examination, necessary investigations were performed and required treatment given. Regular follow-ups were done and final classification made alongwith AFP surveillance team. Results : Out of 43 children included in the study, 18 expired and 25 completed follow-up. Final classification showed 53.5% AES, 9.3% Guillain Barre Syndrome (GBS), 9.3% dyselectrolytemia, 9.3%, peripheral neuritis, 7% Non-Polio Entero Virus (NPEV) and 11.6% others. Fever, altered sensorium and convulsions were present in 79.1%, 65.1% and 58.1% respectively. Eighty-four percent had asymmetrical paralysis with quadriparesis in 72%. Cerebrospinal fluid was abnormal in 34.9%. Japanese encephalitis serology was positive in 4.7%.  The mean GCS was 9.53±4.27 with a significant difference between survivors and non-survivors (p=0.02). Almost half (52.2%) required ICU care, of which 14 expired (p=0.005). Seventeen children needed mechanical ventilation, of which 13 died (p<0.001). Requirement of inotropes and complications like respiratory failure and autonomic failure were significantly related to death. Conclusion: AES, being one of the commonest causes of AFP, should be included in AFP surveillance. Poor GCS, requirement of inotropes, complications like respiratory failure and autonomic failure are related with poor prognosis. This study also helped in national surveillance of AFP cases in the eastern region and the target to achieve polio eradication in our country. doi: http://dx.doi.org/10.3126/jnps.v34i2.9794 J Nepal Paediatr Soc 2014;34(2):104-110


Introduction
A cute fl accid paralysis (AFP), as defi ned by World Health Organiza on (WHO), is sudden onset of weakness and fl oppiness in any part of the body in a child less than 15 years age or if a clinician suspects polio in any person of any age (excluding adults, spas c paralysis, old cases or cases with obvious causes like trauma 1,2 . There are many condi ons leading to AFP, poliomyeli s being one of the most important diff eren al diagnoses.The diagnoses most o en confused with polio are Guillain-Barre syndrome (GBS), transverse myeli s, trauma c paralysis and some mes other neurotropic viruses like Rabies, Japanese encephali s.Similarly, cri cal illnesses like polyneuropathy, metabolic disorder like hypokalemic periodic paralysis, polymyosi s, neuropathies, neuromuscular junc on disorders and tumours should also be considered in evalua on of AFP 3 .
The possibility of polio should be considered in any case of AFP 4 .Polio eradica on is based on WHO's four-pronged eradica on strategy: 1) rou ne immuniza on with oral polio vaccine (OPV); 2) supplementary, addi onal doses of OPV countrywide during Na onal Immuniza on Days (NIDs); 3) moppingup immuniza on ac vi es to catch any below fi ve children who may have been missed during stages one and two; and 4) enhanced surveillance for all cases of AFP and wild poliovirus 3 .WHO has established standards to check the effi cacy of surveillance systems in each country, polio-endemic or not, should be able to detect at least two cases of AFP not caused by polio every 100,000 children under age 15 3 .
Globally, polio cases have decreased by over 99% since 1988, the year Global Polio Eradica on Ini a ve was launched (~350 000 cases; >125 endemic countries) to 2009 (1604 reported cases) 4,5 .In 2010, only parts of 4 countries -Pakistan, Afghanistan, Nigeria and India remained endemic for polio 4 .But in 2009-2010, 23 previously polio-free countries were reinfected due to imports of virus.The year 2011 saw a signifi cant decline in the total number of polio cases world-wide.A er having zero cases of wild poliovirus for a year, India is no more in the list of polio-endemic countries since January 13, 2011.
Despite the overall decline, there has been a steep increase in polio cases in 2011 in the other three polio-endemic countries 4 .The increase in cases in key endemic areas cons tutes an incontrover ble risk to global polio eradica on.As long as a single child remains infected; children in all countries remain at risk of contrac ng polio 4 .Frequently, a child with acute encephali s syndrome may have acute fl accid paralysis which also should be inves gated and not a single case of AFP should go unevaluated.Acute Encephali s Syndrome (AES) surveillance has also been integrated with AFP surveillance since 2004 6,7 .
The AFP surveillance in Nepal was ini ated in 1995 with passive repor ng of AFP cases through the Early Warning and Repor ng System (EWARS), a sen nel system for surveillance of six priority infec ous diseases 3,4,5   .Nepal has been free of indigenous poliovirus since 2000.However, due to its proximity to India and sociocultural rela ons, it has been subjected to repeated polio importa ons, in par cular from Bihar 3 .A er having zero case record for four years from 2001 to 2004; it faced resurgence of polio in 2005 when four cases of wild polio were detected in the terai region.According to the AFP surveillance record, there were 451 cases in 2009, 564 in 2010 and 567 in 2011amongst which, there were no cases of polio in 2009, 6 polio cases in 2010 5 and none detected since 2011.Nepal will con nue to be at par cular risk of re-infec on un l all endemic polio transmission in neighbouring countries has been successfully interrupted.
According to B P Koirala Ins tute of Health Sciences (BPKIHS) hospital sta s cs, there were a very few cases of AFP reported from 2008 to 2010, with no cases of wild polio, and the majority being Guillain Barre Syndrome.
As Nepal faced re-emergence of polio in the last six years period, and BPKIHS being referral as well as focal centre of EWARS in Eastern region, we felt the need to take up this study.This study not only helped in fi nding out the clinico-epidemiological pa ern of AFP in the Eastern Nepal but also supported in the polio surveillance in-depth as no case would go unreported when we involved all the diff eren al diagnoses including AES.

Materials and Methods
It was a prospec ve hospital-based study done over one year period in 2011 in the Department of Paediatrics and Adolescent Medicine, BPKIHS, Dharan, Nepal.

Inclusion Criteria: Any child of age ≤15 years presen ng with Acute Flaccid Paralysis (AFP) in any form including acute encephalopathies or Acute Encephali s Syndrome (AES) as defi ned by WHO.
Exclusion Criteria: Age >15yrs, spas c paralysis, old cases or cases with obvious causes like trauma, obvious congenital anomalies or birth defects, AES without acute fl accid paralysis.
Sample size: All cases fulfi lling the inclusion criteria during the study period were included in the study.
A er taking consent from the parent/guardian, all children fulfi lling inclusion criteria were enrolled and detail history with clinical examina on were recorded in a pre-designed pro forma.The relevant laboratory and/or radiological inves ga ons were carried out like complete blood counts; electrolytes, blood cultures; rapid diagnos c test for malaria screening.Cerebrospinal Fluid (CSF) was collected and sent for cytology, biochemistry, microscopy and culture for bacteriology.Test for an body to JE virus in CSF and serum was done by IgM capture ELISA at JE laboratory, BPKIHS.Stool samples were sent for examina on as per AFP surveillance guidelines and sent to the IPD fi eld offi ce and then to the WHO-accredited Poliovirus Laboratory in Bangkok, Thailand.
Based on detail clinical evalua on, relevant inves ga ons and WHO case defi ni ons, diagnoses were made and treatment ins tuted.Pa ents were observed for any complica ons or sequelae.Regular follow-ups were done a er discharge at 15 days/30 days/60 days alongwith the surveillance team and fi nal classifi ca on made.
The acquired data were entered in SPSS Sta s cs so ware version 14. Diff erences between clinical groups (survivors and non-survivors) were compared using Student independent samples t-tests (for normally distributed data), Mann-Whitney U-tests (for non-normally distributed data) and Fisher Exact tests (for categorical data/propor ons).Sta s cal signifi cance was set at the conven onal 5% level for all analyses and fi nal inferences made.

Results
Out of the 3432 children admi ed in paediatric wards during the one-year study period, 43 (1.25%) children were diagnosed to have AFP.The fi nal classifi ca on showed Acute Encephali s Syndrome (AES) in 23 (53.5%) children.Guillain Barre Syndrome (GBS), Dyselectrolytemia and Peripheral neuri s in 4 (9.3%)childreneach; Non-Polio Enterovirus in 3 (7%) children and other causes of AFP like TB cervical spine, Neurocys cercosis (NCC), Inborn Error of Metabolism (IEM),etc.in 5 (11.6%) children.Maximum (37.2%) children fell in the age group 1-5 yrs with a mean age of 5.6 ± 4.1 years.Most of them were male (58.1%) and mostly (88.4%)Hindus.Majority came from the Eastern part of Nepal along with a few cases from Bihar, India.The dura on of illness prior to hospital admission ranged from <1 to >15 days with mean dura on of illness being 6.79±6.68days.
On clinical examina on, the Glasgow Coma Scale (GCS) was found to be 3-8 in majority of the children (44.2%).The mean GCS was 9.53±4.27.Thirty-four (79.1%) children had fever, out of which 20.6% had high grade temperature >101˚F.There was associated undernutri on and pallor in 62.8% and 27.9% children respec vely.
On neurological examina on, mental status was found to be abnormal in 28 (65%) children with altered sensorium in 46% and unconsciousness in 19% children.Deep Tendon Refl exes(DTR) were absent in 46.5%, sluggish in 41.9% and normal in 11.6% children with AES.The signs of meningeal irrita on were found in 9.3% children.Majority, i.e. 31 children with AFP (72%) had quadriparesis, 7 paraparesis, 2 hemiparesis and 3 monoparesis.Cranial nerve involvement was seen in 7% children, all having bilateral involvement and mostly sixth nerve involvement.
One child with AES presen ng with AFP was clinically diagnosed to have cerebral malaria.
There was dyselectrolytemia in the form of hypokalemia in 9.3% children with AFP.Out of the 31 children who underwent lumbar puncture, 48.4% had abnormal fi ndings.There were 2 children with posi ve test for JE virus in CSF and serum (4.7%).CT scan-head was done in 13 children, out of which 18.6% children had abnormal fi ndings of temporal lobe cerebral abscess, thalamic infarct with frontal lobe calcifi ca on, neurocys cercosis, etc.
Stool examina on was done as per AFP surveillance criteria.In 8 (18.6%) children who expired, stool could not be collected due to very poor GCS.Among the rest 35 pa ents, 7% had Non-Polio Enterovirus(NPEV) while no virus was isolated in 74.4%.Twenty-two (51.2%) children required ICU care, out of which 39.5% received mechanical ven la on.An bio cs were used in almost all cases-95.3%.Inotropes were required in 67.4% of the sick children, an convulsants in 60.5%, osmo c diure c in 39.5% and steroids in 25.6%.
Diff erences between clinical groups (survivors and non-survivors) were compared using Student independent samples t-tests (for normally distributed data), Mann-Whitney U-tests (for non-normally distributed data) and Fisher Exact tests (for categorical data/propor ons).On comparing the children with AFP in terms of mortality, various clinical parameters were found to be related to poor prognosis as shown in table 1.The categorical data being binomial with small sample size were compared using Fisher Exact tests.The numerical data with Gaussian distribu on were compared by Student independent samples t-tests and non-parametric data by Mann-Whitney U-tests as the two groups (survivors and non-survivors) were unpaired.The treatment details and outcome of children with AFP are tabulated in table 2.

Discussion
In this prospec ve hospital-based study done at BPKIHS, AES was the most common cause of AFP in children.This is in contrast to most of the previous studies where GBS was the most common cause of AFP.2011) showed GBS as the major leading cause of AFP in children 8,12,13,14 .In this study, we had a total of only 4(9.3%) children with GBS while in a similar clinico-epidemiological study done at BPKIHS by Sharma KS et al, 90% were GBS 14 .Studies by McKhann GM et al and Morris M et al also had GBS as the most common cause 12,15 .The obvious reasons for this could be 1) inclusion of AES and hence 2) increased no. of cases and 3) decreased percentage of GBS.

Studies of AFP by
Among the children with AES with AFP, fever and weakness were associated with altered mental status (87%), convulsions (73.9%) and loss of consciousness (34.8%) which is similar to studies by Singh RR et al. 16 and Rayamajhi A et al. 17 .Similar to our study, viral encephali s was the most common cause (46%) of acute febrile encephalopathy in the study by Singh RR et al. 16 .Our study had smaller propor on of children (4.7%) with Japanese encephali s as compared to studies by Singh RR et al.(40%) 16 , Rayamajhi A et al.(61.7%) 17and Khinchi Y R et al.(18%) 18 .This could be due to the fact that they included all AES and not just AES with AFP.With the inclusion of JE vaccine in EPI schedule of Nepal as a part of rou ne immuniza on, the overall cases of JE have also decreased drama cally.In our study, only 1 (4.3%) child had cerebral malaria with posi ve screening test in contrast to studies by Singh RR et al. and Kumar et al. 16,20 .Thus, it was an uncommon cause of fever presen ng with encephalopathy in the present study area.
No virus was isolated from stool of the 20 children of AES with AFP and thus this strengthened the AFP surveillance.There are no published data of studies from Nepal for AES with inclusion of stool examina on as per AFP surveillance guidelines ll now.Inclusion of AES in AFP surveillance has been ini ated in Nepal since 2004 so as not to miss any case of AFP.
In our study, Non-Polio Enterovirus (NPEV) was isolated in 4.3% children, of which all had complete recovery which is also similar to study in Pakistan by Saeed M et al 30 .
The most common electrolyte disturbance seen in our study was hypokalemia in 6.9% children, which is similar to study by Narang et al. 10 and Sharma PP et al. 29 , where there were six malnourished children presen ng with AFP due to hypokalaemia who were successfully treated with potassium supplementa on emphasizing the need to consider hypokalaemia in the diff eren al diagnosis of AFP in malnourished children.
In our study, 37.2% of cases were between one to fi ve years with the mean age of 5.6 ± 4.1 years, which is similar to previous studies of Jalal et al, Bassey et al and Narang et al 8,9,10 .In our study, the male:female ra o was 1.39:1 which is also in accordance with the observa ons of other workers like Karmarkar SA et al. 11 and Narang et al. 10 which may be due to the fact that more male sick children are brought to hospitals in our country.
Among the children with GBS, preceeding viral illness was found in 75% children in form of diarrhea and respiratory tract infec on similar to the study of Sharma KS et al. 14 and other studies from Italy 24 , Sweden 25 , Srilanka 26 , Netherlands 27 .Complica ons of GBS were no ced in 50% children in the form of respiratory failure (50%) and autonomic failure (25%) with improvement seen in 25%, which is comparable to studies by Sharma KS et al. 14 , Chang Q et al 25 , Narang et al 10 , Koul et al 28 and Morris et al 13 .
The mean Glasgow Coma Scale in our study was 9.53±4.27.There was signifi cant diff erence in the mean GCS of survivor and non-survivor groups (p=0.02).More than half (65.2%) of the children with AES with AFP had GCS in the range of 3-8.Our fi nding is similar to the study by Singh RR et al, G Anga et al, CR Kennedy et al and Rayamajhi A et al 16,21,22,23 .
Overall, in our study, we found diff erent causes with various clinico-epidemiological features for children presen ng with AFP.AES was the major diff eren al diagnosis, besides the known diff eren al of Guillain Barre Syndrome and other causes.Various parameters like low GCS, high temperature, low respiratory rate, need for endotracheal intuba on/ mechanical ven la on/ICU care, requirement of inotropes and complica ons like respiratory failure and autonomic failure were found to be signifi cantly related to poor prognosis.

Conclusion
In our study, AES was one of the common causes of AFP and it could be the most common diff eren al diagnosis, when all AES presen ng with AFP were included.The diff eren al diagnoses of AFP were found to be AES, GBS, dyselectrolytemia, peripheral neuri s, Non-polio Enterovirus and others like Neurocys cercosis, temporal lobe abscess,etc.Apart from fl oppiness/ weakness, the other associated presen ng features of the typical disease supported to clinch the diagnosis.Low GCS, high temperature, low respiratory rate, need for endotracheal intuba on/ mechanical ven la on/ICU care, requirement of inotropes and complica ons like respiratory failure and autonomic failure were associated with signifi cant morbidity and mortality.

Objec ves: 1 )
To study the clinico-epidemiological profi le of the diff eren al diagnoses of Acute Flaccid Paralysis (AFP) including AES with fl accid paralysis, 2) To study the associated co-morbidi es in children with AFP.

Table 1 :
Comparison of clinical examina on details in children with AFP

Table 2 :
Treatment details and outcome of pa ents with AFP in BPKIHS