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Vaccine 27S (2009) F108–F111

Contents lists available at ScienceDirect

Vaccine

journa l homepage: www.e lsev ier .com/ locate /vacc ine

he burden of hospitalised rotavirus infections in Fiji

dam Jenneya,∗, Lisi Tikoduaduab, Eka Buadromob, Graeme Barnesc,d, Carl D. Kirkwoodc,d,aren Bonifacec,d, Julie Binesc,d, Kim Mulhollanda,e, Fiona Russell a

Centre for International Child Health, Department of Paediatrics, University of Melbourne, Parkville, Victoria 3051, AustraliaColonial War Memorial Hospital, Ministry of Health, Suva, FijiMurdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Victoria 3052, AustraliaDepartment of Paediatrics, University of Melbourne, Parkville, Victoria 3052, AustraliaInfectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom

r t i c l e i n f o

eywords:

a b s t r a c t

otavirusurveillanceaccine

Rotavirus is the most common cause of acute severe dehydrating diarrhoea in young children worldwide.We describe the burden of rotavirus disease and the rotavirus types causing it in the largest city in Fiji.During 2006 and 2007, 592 children under 5 years of age were admitted to hospital in Suva, Fiji with acutediarrhoea. Of the 454 children for whom a stool specimen was tested, 39% were positive for rotavirus andthe predominant strain found was the serotype G3[P8]. There is a significant burden of disease due torotavirus in Fiji and the introduction of rotavirus vaccines into the national immunization schedule may

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drastically reduce inpatie

. Introduction

Rotavirus is the commonest cause of severe acute gastroenteri-is in children under 5 years of age in both the developed and theeveloping world. Globally, rotavirus is responsible for enormousorbidity and is estimated to cause 114 million episodes of diar-

hoea per year [1]. While the proportion of these infections thatesult in death is relatively small, the high number of cases meanshere are estimated to be over half a million deaths among infantsnd children worldwide per annum due to rotavirus [2].

In the last few years, rotavirus vaccines have been licensed inore than 100 countries but are only available in the national

mmunization schedules of about eleven predominantly highnd middle-income countries. These vaccines can prevent severeotavirus disease and thereby have the potential to markedlyeduce this morbidity. In 2006, the GAVI Alliance indicated thathey would support the introduction of rotavirus vaccine in eligibleountries in regions where vaccine efficacy had been demonstrated.

owever, these vaccines are expensive and widespread introduc-

ion into a non-GAVI eligible developing country like Fiji couldverstretch an already overburdened health budget. Although mostovernments are very keen to introduce measures to relieve their

Abbreviations: CWMH, Colonial War Memorial Hospital; EIA, enzymemmunoassay; MAb, monoclonal antibody; RT-PCR, reverse transcription/olymerase chain reaction.∗ Corresponding author. Tel.: +61 3 9345 4098; fax: +61 3 9345 6667.

E-mail address: jenneya@unimelb.edu.au (A. Jenney).

264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved.oi:10.1016/j.vaccine.2009.08.071

arrhoeal disease.© 2009 Elsevier Ltd. All rights reserved.

population of medical disease, rotavirus vaccine introduction maybe prevented by lack of funds. Nonetheless, if a vaccine can beshown to be safe, reliable and cost effective by reducing the finan-cial burden that comes with reducing the medical and social costs ofinfection, then this may make the prospect of its introduction morefeasible. In this study we aimed to describe the burden of rotavirusdiarrhoeal disease requiring admission among children under 5years of age in the largest hospital in Fiji, particularly regardingthe demographics of those affected and to record the serotypesresponsible for the disease.

2. Methods

2.1. Setting

The Republic of the Fiji Islands comprises more than 330 islandsin the tropical Western Pacific. In 2007, the total national popula-tion was 860,743 comprising mainly two racial groups: IndigenousFijians (56%) and Indo-Fijians (36%) (Fiji Islands Bureau of Statistics,2007) [3]. Of the total population, 83,437 were under 5 years of ageat the time of the census. Fiji is ranked 93 out of 177 nations onthe 2007 United Nations Development Programme Human Devel-opment Index [4]. Fiji has a Gross Domestic Product per capita ofUS$6049 and approximately half of the population live in rural

areas. The infant mortality rate was 16.8 per 1000 in 2003 [3]. TheColonial War Memorial Hospital (CWMH) is the nation’s largesthospital and principal referral centre for the eastern region of Fiji’slargest and most populous island, Viti Levu. This region is called theCentral Division and contains approximately one-third of the total

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Fig. 1. Admissions for diarrhoea to Colonial War Memorial Hospital, Suva for 2006and 2007 in children under 5 years of age indicating monthly proportions tested

A. Jenney et al. / Vacci

opulation of Fiji. Children with diarrhoeal disease are admittedo district hospitals throughout the Division so CWMH admits onlyhose from the city of Suva and some surrounding villages. The esti-

ated population of children under 5 years of age in the Greateruva area is 23,660.

.2. Study participants

Children less than 60 months old who were admitted to theWMH with a gastroenteritis illness, including diarrhoea (i.e., 3r more looser than normal stools [without blood] within 24 h ofdmission) had a stool sample collected and tested for rotavirusntigen. Children with diarrhoea were identified by daily checkingf the written and computerised admission data and by daily visitso the children’s wards. If rotavirus was identified in a child’s stoolample the parents or guardians were approached and informedbout the study. If informed consent for participation was obtained,questionnaire and the medical record were employed to recordemographic and clinical information. Children in the Suva areaequiring inpatient treatment for gastroenteritis are admitted toWMH as there are no other appropriate facilities available.

.3. Materials and methods

Faecal specimens were collected and tested for rotavirus usinghe Rotavirus IDEIA (Oxoid, Basingstoke, Hampshire, UK). Rotavirusositive specimens were frozen at −70 ◦C and transported onry ice to the WHO Collaborating Centre for Research on Humanotaviruses, Murdoch Children’s Research Institute, Parkville, Aus-ralia. Rotavirus positive specimens were then typed for G and

genotype. G type was determined using an in-house mono-lonal antibody (MAb) based serotyping enzyme immunoassayEIA) [5]. The EIA employed a panel of MAbs specific for the majorlycoprotein VP7 of the outer capsid of the five major group Auman rotavirus serotypes (G1, G2, G3, G4 and G9). Strains whichould not be assigned a G serotype by EIA were genotyped bysing a hemi-nested multiplex reverse transcription/polymerasehain reaction (RT-PCR). P genotypes were determined by usinghemi-nested multiplex RT-PCR assay [6,7]. Electrolyte abnor-alities were recorded when values for a child were outside the

ormal range for the CWMH laboratory (normal range for sodium35–145 mmol/L and for potassium 3.5–5.0 mmol/L).

.4. Statistical analysis

Data were analysed using STATA, version 9.1 (StataCorp LP,ollege Station, TX, USA) to calculate Chi square statistics whenomparing groups from a cross-sectional survey and the Poissonistribution for calculating confidence intervals of the incidenceates.

.5. Ethical approval

Ethical approval for this study was obtained from the Universityf Melbourne Human Research Ethics Committee and from the Fijiational Research Ethics Review Committee.

. Results

During the 24 months of the study, 592 children under 5 yearsf age were admitted for diarrhoeal disease to the CWMH. This rep-

esents an annual incidence of 1251 per 100,000 (95% confidencenterval 1113–1402) among the under 5-year-old population in thereater Suva area. Of the total number of children admitted withiarrhoea 178 (30%) were confirmed to have rotavirus. Howeverhis is likely to under-represent the burden of disease as there were

for rotavirus and confirmed positive for rotavirus. In a total of 395 admissions forthe year 2006, 324 were tested for rotavirus and 167 were positive. In a total of 197admissions for the year 2007, 130 were tested for rotavirus and 11 were positive.

only 454 stool specimens available for testing, thus making the pro-portion of tested stool that was positive for rotavirus 39% (178/454).In the first 12 months of the study, 167 of the 324 (52%) diarrhoeaadmissions that had stool tested were found to be rotavirus pos-itive making an annual incidence of admissions due to rotavirusof 866 per 100,000 under 5 years of age in the Greater Suva area(95% CI 752–994). However, in the second year there were only 197diarrhoea admissions in total and, of the 130 that were tested forrotavirus, only 11 (8.5%) were positive resulting in an annual inci-dence of 72 per 100,000 under 5 years of age (95% CI 42–115). Theproportion of diarrhoea due to rotavirus was significantly smaller in2007 compared with 2006 (p < 0.0001). Over the 2 years, the annualincidence of admissions due to rotavirus in children under 5 yearsof age was 486 per 100,000 (95% CI 401–583).

The monthly admissions for 2006 and 2007 demonstrated a peakin the cooler months of 2006 (June to August), a pattern that was notrepeated in 2007 (Fig. 1). Approximately half (51%) of the diarrhoeaadmissions occurred in the 6–17-month age group. However, thisage group included 63% (112 of 178) of all rotavirus cases. Compar-ing this age group (6–17 months) to both the younger age group(0–5 months) and the older children (18–59 months), the propor-tion of diarrhoea due to rotavirus was significantly greater in the6–17 months group (p < 0.001 for both) (Table 1).

Demographic and clinical data were recorded for 150 childrenwith confirmed rotavirus infection. Among these 150, there were95 (64%) boys and 55 girls. The majority (74%) were Fijian while anadditional 20% were Indo-Fijian and 6% represented other ethnicgroups (i.e., Chinese and Polynesian). Even while allowing for thedifferences in the general population between ethnic groups, therewere significantly fewer Indo-Fijian, compared with Fijian, childrenwith rotavirus admitted to hospital (p < 0.001).

The median length of hospital stay was 2 days (the mean was 3.7days, and the range of stay was 1–37 days). When a child remainedan inpatient for longer than 1 week, the prolonged duration of hos-pitalisation was invariably due to illness other than rotavirus. All

F110 A. Jenney et al. / Vaccine 27S (2009) F108–F111

Table 1Age distribution of cases of diarrhoea admitted to Colonial War Memorial Hospital, Suva, Fiji during the 2-year period January 2006 to December 2007.

Age (months) Cases ofdiarrhoea (n)

Cases of provenrotavirus infection (n)

Proportion of all cases ofdiarrhoea due to rotavirus (%)

Number of specimenstested for rotavirus

Proportion of all tested specimensthat were positive for rotavirus (%)

0–2 37 8 22 25 323–5 59 13 22 44 306–8 90 37 41 79 479–11 98 29 29 82 3512–17 111 46 41 83 5518–23 62 16 26 49 3224–35 70 19 27 47 40

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36–47 38 5 1348–59 27 5 19

Total 592 178 30

50 children had diarrhoea although in 3 children it developedoon after arrival to hospital (Table 2). On presentation at CWMHhose with diarrhoea (147 children) showed a median duration ofdays (range 1–56) with a median of 3 bowel actions in the pre-

ious 24 h (range 1–24). Vomiting was recorded in 137 childrenrior to admission, with a median of 4 episodes in the 24 h leadingp to admission. Dehydration was a major reason given for admis-ion and reported in 138 (92%) children. According to the admittingoctor, sunken eyes and lethargy were seen in 88% and 66%, respec-ively, with 31% of the children noted to have difficulty drinkinguids. Five children were considered malnourished. On arrival toWMH, 45 (30%) children were febrile with a temperature ≥38 ◦C.neumonia was the most common serious co-morbidity diagnosedn 17 (11%) of the children.

Of the 150 cases of rotavirus described, three children died.otavirus was considered the primary cause of death in only onehild. The other two deaths were associated with bacterial sep-is and complications of congenital heart disease with pulmonaryypertension. Eighty-four (56%) children had at least one manifes-ation of electrolyte disturbance recorded: 22% had hypernatremia,

5% hyponatremia (usually mild where the Na ≥130 mmol/L);1% had hyperkalemia; and 23% hypokalemia. Two children wereiagnosed with metabolic acidosis by their treating paediatrician.wenty-eight children were admitted to the intensive care unit fortotal of 97 days and three children were ventilated for a total of

able 2linical manifestations, complications and therapy for 150 children under 5 years ofge treated as inpatients at the Colonial War Memorial Hospital, Suva with rotavirusiarrhoea during the 2-year period January 2006 to December 2007.

Characteristic Number (n) Percentage (%)

On admissionDiarrhoea 147a 98Vomiting 137 91Fever ≥38 ◦C 45 30Lethargy 100 66Sunken eyes 132 88

Severity of dehydrationSevere 132 88Mild 18 12

Complications during admissionHypo- or hypernatremia 56 37Hypo- or hyperkalemia 64 43ICU admission 28 19Intubation and ventilation 3 2

TherapyIV fluids 132 88ORS 133 89

Median RangeLength of stay (days) 2 1–20

CU: intensive care unit; ORS: oral rehydration solution.a All 150 children had community-acquired rotavirus infection but in three the

iarrhoea was first recorded in the first day after admission.

27 1918 28

454 39

27 days. The need for invasive respiratory support was due to co-morbidities rather than rotavirus per se (i.e., the children who diedfrom sepsis and a congenital cardiac problem and a third child withconcurrent meningitis).

The use of intravenous fluids was recorded in 132 of the 150children (88%) and ORS was used in 133 (89%) with the majorityreceiving both means of rehydration. One child received neitherORS nor intravenous fluid (according to the medical record) butwas treated with oral fluids other than the ‘ORS’. There were 59children (39%) who were given antibiotics, although the two mostcommonly prescribed agents were penicillin and flucloxacillin thatwere usually given for chest or skin infections rather than for diar-rhoea. Thirty-six children (23%) were treated using agents withactivity against bacterial gut pathogens.

Rotavirus antigen was detected in 178 stool samples and, ofthese, 116 samples were available for G and P type analysis(Table 3). G3P[8] was the dominant type detected, being identi-fied in 85% of samples. Single G1P[8], G3P[8], G3P[6] and G4P[6]strains were identified during the study period. No mixed G or Ptypes were identified. A G or P genotype could not be identified in5.2% of the samples.

4. Discussion

Rotavirus is a very important cause of hospitalised diarrhoea inchildren under 5 years of age in Fiji. The epidemiology of rotavirusinfection during the 2-year study did not show a consistent annualseasonal pattern. In the first year, rotavirus accounted for 52% ofdiarrhoea that was serious enough to warrant admission to hos-

pital and underwent testing for rotavirus antigen. In the coolermonths of 2006, rotavirus was responsible for more than 60% ofthe diarrhoea admissions. While the second year’s figures weremuch reduced and failed to demonstrate seasonal variation, theoverall rotavirus positive rate of 39% (i.e., 178 rotavirus positive

Table 3G and P typing results for the 116 rotavirus positive stool specimens available fortesting collected from children under 5 years of age admitted to Colonial War Memo-rial Hospital, Suva during the 2-year period January 2006 to December 2007.

G and P typing Number %

G1[P8] 1 0.9G3[P8] 98 85G3[P6] 1 0.9G4[P6] 1 0.9G9[P8] 1 0.9G1[P nontypable] 1 0.9G3 [P nontypable] 1 0.9G9 [P nontypable] 1 0.9G nontypable [P8] 4 3.4G nontypable [P6] 1 0.9G and P nontypable 6 5.2

Total 116

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pecimens from 454 faecal samples tested over the 2 years) showsotavirus to be an important cause of severe diarrhoea in younghildren. It is not clear why the two individual years were so differ-nt in their seasonal distribution of rotavirus infections. However,he phenomenon has been described before and attributed to herdmmunity effects. Thus, when there is a large number of infectionsuring one season, an increased proportion of the under 5-year-oldopulation will have protective antibodies in the following seasonnd, therefore, the total number of infections will be lower (i.e., the–4-year olds affected in the first year will be the protected 2–5-ear olds of the next year) [8]. It is known that previous rotavirusnfection in a child can lead to a reduction in future risk from the dis-ase [9] and so the cohort infected in 2006 may have been protectedrom rotavirus infection in 2007.

We are confident that the discrepancy between the 2 years iseal as very few cases of diarrhoea admitted to CWMH would haveeen missed by the week-day rounds to the admitting wards andhe monthly review of the hospital’s discharge records. This dif-erence between the 2 years was reflected throughout the countrys, for under 5-year olds, the number of admissions for diarrhoeaationally was 1076 for 2006 and this fell to just 403 in 2007. Itas expected that the seasonal winter peak of rotavirus infection

hat is seen in more temperate populations [10] might not haveccurred in a tropical island where the extremes of temperaturesre less profound. Nonetheless there was such a peak in the cooleronths of 2006, as has been seen in other tropical island surveys

.g. in Madagascar [11] and Jamaica [12]. This is the first study tonvestigate rotavirus disease in Fiji. Indeed, there have been fewtudies anywhere in the South Pacific [13]. Nonetheless rotavirusnfection has been documented in Papua New Guinea [14], Vanuatu15] and on the Island of Truk [16].

The peak of disease occurred in the 6–17-month age group andith most of the isolates tested being genotype G3[P8], an infant

accination schedule in the first 6 months of life using currentlyvailable vaccines would be anticipated to prevent the majorityf rotavirus infections requiring hospital admission. In a review ofrevious epidemiological studies from Australia/Oceania, G1[P8]ccounted for more than 80% of the strains, though these studiesredominantly report data from Australia [17]. However, G3P[8]trains were recently found to be emerging as a significant causef acute diarrhoea in several settings, including China, Japan andustralia since 2000 [18–20].

While mortality from rotavirus was low, this study shows thathere is a significant burden of rotavirus disease in Fiji with signif-cant morbidity as reflected by the high number of children withlectrolyte abnormalities, requirement for intravenous fluids (88%)nd intensive care admission (20%). Eighty-eight percent of the chil-ren had clinical signs of severe dehydration. This degree of severityight reflect late presentation to hospital and indicate the greaterorbidity from rotavirus disease seen in developing, comparedith developed, countries. This study was limited to inpatients

nd does not include the very many outpatient cases that certainlyccur. It has been estimated that for every child with rotavirusdmitted to hospital there are possibly 40 cases not admitted [21].nother potential problem with the study is that the mortality due

o rotavirus infection is likely to have been underestimated as its probable that some children living in rural areas may not haveeen able to travel to the capital for treatment due to poor transportacilities. There is also reluctance for many who live in the coun-ry to go to hospital even when their child is very sick due to highransport costs.

It would be of great value to conduct a prospective study of diar-hoea in children under 5 years of age in Fiji to examine rotavirusn both outpatient and inpatient settings. Such surveillance wouldllow a more accurate estimation of the burden of rotavirus diar-hoea and its financial cost and enable a more complete appraisal

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of the potential benefits of introducing rotavirus vaccines into thispopulation.

Acknowledgements

The authors would like to thank Priya Francis, Agnes Rounds,Tania Ah Kee, Anna Seduadua, Reginald Chandra, Meredani Guni-valu, Simione Sokiqele, Robert Cabemaiwesa, Kathryn Bright, SusanDonath, Suzanna Vidmar, Trevor Duke, Andrew Steer, the staff ofthe Centre for International Child Health and the children, parentsand staff of CWMH and the CWMH microbiology laboratory.

Conflict of interest statement

None declared.

Funding

This project was generously funded by the World Health Organ-isation (Registry File No. V27-181-188).

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