A prospective hospital-based surveillance of Rotaviral Disease in children at the Port Moresby General Hospital, Papua New Guinea. Dr.

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A prospective hospital-based surveillance of Rotaviral Disease in children at the Port Moresby General Hospital, Papua New Guinea. Dr. Fiona Kupe

Principle Investigator: Dr. Fiona Kupe 1 Co-Investigators: Dr. S. Siddhartta 2 Professor. N. Tefuarani 3 Professor. J. Vince 3 1. The Department of Paediatrics, Port Moresby General Hospital, Papua New Guinea 2. World Health Organization, Port Moresby, Papua New Guinea 3. Paediatric Division, School of Medicine & Health Sciences, University of Papua New Guinea

Introduction Acute Gastroenteritis one of the leading cause of illness and death in infancy & childhood worldwide. 1 Viral pathogens - ~70% cases; Rotavirus is the most common. 2 A double-stranded RNA virus; in the family Reoviridae. 2 Group A Rotavirus- most common; >90% of acute diarrhoeal disease in children. 2

Rotavirus Globally World wide ~40% of diarrhoeal hospitalizations in <5 yrs due to RV. (WHO Surveillance 2001-2008) 3 Estimated; > 2 million hospitalized annually; >500 000 die from the disease. 3 P[8]G1 strain most predominant worldwide 52.2% most countries. 4

Rotavirus in PNG Diarrhoeal disease accounts for 10% of admissions with case fatality rate 2.7% (PNG Department of Health child morbidity & mortality -2011) 5 Only limited studies (Goroka) have been conducted to determine the burden of Rotavirus in PNG RV detected 31.2% (n=254) with mortality rate of 2.4% (Horwood. P et al. 2012) 6 PMGH- Diarrhoeal disease 11.5% of OPD visits & hospitalizations. (PMGH COPD records-2012) Rotavirus is NOT diagnosed at PMGH & its burden UNKNOWN.

Data on disease burden will guide Vaccination considered most effective public health strategy prevent infection & reduce burden. Rotavirus vaccine efficacy (74%; 95% CI 35-90%) against severe RV infection. (systemic review 2010)

AIM: To estimate the burden of Rotavirus gastroenteritis at the Port Moresby General Hospital. OBJECTIVES: 1. What proportion of acute diarrhoeal cases are due to rotavirus at PMGH? 2. What are the genotypic patterns of Rotavirus at PMGH? 3. What s the contribution of rotavirus to deaths in children at PMGH?

METHODOLOGY STUDY DESIGN: Prospective hospital based surveillance from Sept 2011-Dec 2012

Study Participants INCLUSION: Children (age > 7 days; <5 yrs) with acute diarrhoea Verbal consent given No blood in stool EXCLUSION: Age range not met No verbal Consent Bloody diarrhoea

Data Collection & Sampling Strategy Following verbal consent- standard questionnaire used Hospitalized in-patients- additional information obtained from medical files. Specimens were collected at convenience 2 Fecal samples (4-5mls) were collected using a feeding tube passed PR

Stool Sample Handling & Lab Analysis Fecal samples collected within 48 hours Stored in an esky (4⁰C) prior to transfer to CPHL Analysis for Group A Rotavirus using ELISA test kit per manufacturers instruction. Stored at -20⁰C Genotyping RT-PCR - Melbourne

Statistical Analysis & Ethics All data entered onto Excel Spreadsheet & analysed using SPSS (version 19; SPSS Inc Chicago,IL USA) Statistical analysis of categorical variables was performed using x2 tests (p value <0.05) Ethical approval obtained from both UPNG SMHS research & ethical committee and PMGH Management.

RESULTS

Figure 1: Study Participants and Stool Sample Results. TOTAL ENROLLED - 267 12 EXCLUDED 10 samples misplaced CPHL 2 no stool samples recieved TOTAL ANALYSED - 255 ROTAVIRUS ELISA POSITIVE 120 (47.06%) ROTAVIRUS ELISA NEGATIVE 135 (52.94%) NO ENTEROPATHOGENS ISOLATED; NO OCP SEEN 120 (100%) ENTEROPATHOGENIC E.COLI ISOLATED 5 (3.7%) GENOTYPIC RESULTS 1 st 34 - all P[8]G3 Rest - pending NO ENTEROPATHOGENS ISOLATED; NO OCP SEEN - 130 (96.3%)

Figure 2: patients Age distribution of Rotaviral ELISA positive 16 P e r c e n t a g e 14 12 10 8 6 4 2 0 1 3 5 7 9 11 13 15 17 19 All RV ELISA Positive (n=120) Age (months) 35% (42) RV detected - <6 months age 88.3%(106) RV detected - <1 year age

Table 1: Demographical parameters Variables RV Positive (n=120) RV Negative (n=135) P value Gender F 48.3% 39.3% 0.92 M 51.7% 60.7% 0.72 Water Source Well/drum 3.2% 4.4% 0.39 Communal pipe 73% 66.7% 0.59 In-house 42% 28.9% 0.11 Toilet type Bush/sea 17.5% 20.7% 0.6 Pit 48.3% 50.4% 0.8 Flush 34.2% 28.9% 0.5 Feeding Practice Exclusive BF 20.8% 23% 0.73 Bottle 22.5% 21.5% 0.87 Mixed (Bot+BF) 5.8% 7.4% 0.65 Solids + BF 50.8% 48.1% 0.78

Table 2: Clinical Findings & Mx on Initial OPD presentation Nutritional Status RV ELISA Positive (n=120) RV ELISA Negative (n=135) P value Well nourished 88.3% 73.3% 0.23 Moderate Malnutrition 11.7% 23% 0.055 Hydration status Initial Therapy given Severe Malnutrition 0% 3.7% 0.054 Some dehydration 55% 60.7% 0.59 Severe; no shock 45% 39.3% 0.53 IV fluids (mainly HSD) 100% 100% 1 Additional meds given Ready- made ORS 0% 0% 1 None 11.7% 16.3% 0.38 Zinc 6.7% 3% 0.23 Antibiotics 30.8% 31.1% 0.97

Figure 3: Outcome of OPD Mx of Acute Gastroenteritis. Rotavirus ELISA POSITIVE (n=120) 10.8% Rotavirus ELISA NEGATIVE (n=135) 14.1 % 89.20% 85.90% Discharged Home Admitted to wards Discharged Home Admittedto wards

Figure 4: Main reason for Admission to wards 70.00% 60.00% 50.00% 40.00% 30.00% 30.80% 53.80% 63.20% 26.30% Rotavirus ELISA POSITIVE (n=13) Rotavirus ELISA NEGATIVE (n=19) 20.00% 10.00% 0.00% 10.50% 7.70% 0% 7.70%

Figure 5: Associated Co -morbidities 100.00% 90.00% 80.00% 70.00% 60.00% 50.00% 40.00% 30.00% 20.00% 10.00% 0.00% 92.30% 78.90% None 0% 21.10% Severe Malnutrition 7.70% 0% Others Rotavirus ELISA POSITIVE (n=13) Rotavirus ELISA NEGATIVE (n=19)

Figure 6: Complications Observed 80.00% 70.00% 60.00% 50.00% 40.00% 30.00% 20.00% 10.00% 0.00% 68.40% 61.50% 38.50% 31.60% 0% 0% 0% 0% 0% 0% Rotavirus ELISA POSITIVE (n=13) Rotavirus ELISA NEGATIVE (n=19)

Figure 7: O u t c o m e o f I n - p a t i e n t A d m i s s i o n s. 150% 100% 50% Rotavirus ELISA POSITIVE (n=13) Rotavirus ELISA NEGATIVE (n=19) 0% Discharged Died Others Figure 8: Length of Hospital Stay in RV ELISA Positive in-patients 40% 30% 20% 10% 0% 1 2 3 4 5 6 7 8 9 10 11 12 13 14+ (Number of days) RV ELISA Positive (n=13)

DISCUSSIONS Rotavirus detected 47.06% (n=255) & is similar to studies done in Goroka and within the Western Pacific Region. Pratt et al 1992 68% (n=30) Howard et al 2000 23% (n=1526) Fiji, Malaysia and Thailand; 39%, 38% & 39% respectively High proportion 88.3%(n=120) of RV hospitalization - first year of life (figure 2); Vaccine initiation in early infancy (age 2, 4 & 6 months) as shown in other countries will prevent RV infection prior to peak age group and hence reduce burden.

Preventative measures such as hygiene & sanitation have been shown to reduce the incidence of diarrhoea due to bacteria and parasites. This is not seen in Rotaviral diarrhoeal disease; global incidence in the developed and developing nations are still very much similar. In this study (Table 1) there was no statistical significance observed in the RV positive and negative groups residence, water & sanitation and feeding practices.

Main clinical management approach to diarrhoeal disease is addressing dehydration ORS, IV fluids & Zinc. In this study (table 2) <10% (n=255) were given Zinc No one was given ready- made ORS 100% (n=255) were given IV fluids for rehydration 30% - received antibiotics Huge economic burden placed on our health system; o Inconsistent supply of Zinc, o ORS not made readily available in COPD o IV fluids only for rehydration & routine use of antibiotics Vaccination may be the optimal option to reduce burden.

Further studies are required in different locations of PNG to characterize Rotavirus strains circulating within the country, prior to CONCLUSION This study has established that Rotavirus is an important cause of Morbidity in children under age 5 years at the PMGH. Vaccination is the way forward if we are to reduce the disease burden of Rotavirus

ACKNOWLEDGEMENT 1. Dr. Paulus Ripa for tremendous support with statistical analysis 2. Dr. E. Lavu, Janlyn Kumbu and CPHL team for doing all the Group A Rotaviral ELISA testing. 3. WHO & Dr. Siddharta Datta for the introduction and financial support of the project. 4. All patients who participated

REFERENCES 1. Widdownson MA; Steele D; Vojdani J; Wecker J; Parashar UD: Global Rotavirus Surveillance preparing for introduction of Rotavirus vaccines. J Infect Dis 2009, 200(suppl 1): 51-58. 2. Leung AK; Kellner JD; Davis HD: Rotavirus Gastroenteritis. Adv.Ther (2005), 22(5):476-87 3. WHO: Morbidity & Mortality Weekly Report. 2008;57(46):1255-1257 4. WHO: Global Rotavirus Information & Surveillance. Bulletine Report, Vol 2: July 2010 5. Papua New Guinea Department of Health: Childhood Mortality & Morbidity Report. 2011. 6. Horwood P et al: Surveillance & Molecular Characterization of Group A Rotavirus in Goroka, PNG. J. Trop. Med. Hyg., 87(6),2012, pp 1145-1148

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