Rheumatic Fever and Rheumatic Heart Disease among Children Presenting at

two Central Hospitals In Harare Zimbabwe

Report of a dissertation done as part fulfilment of the requirements of a Masters in Medicine (Paediatrics) 2013

Dr P Gapu

Co-authors:Bwakura-Dangarembizi MF, Kandawasvika G, Kao D, Bannerman C, Hakim J, Matenga J

Acknowledgements• The children who participated in this study, and

their caregivers• The co-authors • Prof K Nathoo• The Department of Paediatrics and Child Health• Professors James Hakim and Ed Havranek and the

CHRIS/NECTAR program of the University of Zimbabwe, University of Colorado, Denver and partner Universities.

• Statisticians MR V Chikwasha and Mr M P Mapingure of the University of Zimbabwe

Outline

• Background• Methods• Results and discussion• Conclusions and recommendations

Background• Due to improved standards of living and antibiotic

use, ARF is no longer a significant problem in most of the developed world– Except for certain ethnic groups such as indigenous

populations of Australia and New Zealand• However this is still a significant cause of acquired

heart disease in resource limited settings– RHD is the progressive and permanent cardiac valve

damage which usually follow from recurrent ARF

Carapetis J R. NEJM 2007Sliwa K . Lancet 2008Steer A C. J Paediatr Child Health 2002Carapetis JR . Lancet Inf Dis 2005

Background• Estimates from 2005 showed – 15-19 million people living with RHD worldwide • 79% in resource limited settings• 2.4 million children 5 – 14 years

– 471 000 new cases of ARF per year• 95% in resource limited settings

– ~233 000 people dying annually from RHD

Carapetis JR Lancet Inf Dis 2005

Global Burden of Rheumatic Heart Disease

Carapetis JR Lancet InfectDis 2005

Screening for RHD• Recent estimates based on echocardiographic

screening show a much higher burden of disease– A study from Mozambique showed a prevalence of RHD

of 30.4/1000 among school children • Hospital-based estimates have also shown RHD to

be a significant cause of disease among African children – 6.6 – 34% of patients hospitalized with heart disease or

seen in echocardiographic clinics have RHD.

Marijon E NEJM 2007Zühlke L. Heart 2013

Justification• In Zimbabwe a large number of patients with chronic

RHD are still being seen. • Poverty remains an important issue with overcrowding,

malnutrition and poor access to medical services. • The epidemiology of RHD in Zimbabwe remain largely

unknown– the burden of ARF among children, the clinical and

demographic characteristics of these patients, and adequacy of treatment practices have not been systematically documented.

• Such information may help identify opportunities for improving the care of these patients

Objectives

• To document the cases of ARF and RHD among children presenting at two referral hospitals in

Harare • Determine their clinical and echocardiographic

features, and the complications present• Determine the status of secondary antibiotic

prophylaxis at presentation• Identify opportunities for improving care of these

patients in Zimbabwe.

Methodology • Study design –A descriptive cross-sectional survey carried out

from 01 July 2012 to 31 May 2013• Study Setting–Harare Children’s Hospital and Parirenyatwa

Hospital–Patients were identified from the paediatric

medical inpatient and outpatient units

Sampling

• Inclusion criteria–Children aged up to 12 years with evidence of

cardiac failure, cardiac murmur, chorea, or arthritis and satisfied the 2002-3 WHO modified Jones criteria for ARF/RHD–Caregiver consent and assent from the child

according to local IRB guidelines• Exclusion criteria–Children less than 1 year

WHO Technical Report Series 2004

Data Collection• Patients were identified from admission records and

hand-held outpatient notes at the time of hospitalization or presentation to the clinic

• Data was extracted through interviewing the caregiver/child and from case notes and results of selected laboratory investigations

• Hospitalised patients were followed up to discharge or death during the initial presentation

Study Variables• Demographic and clinical features• Select laboratory results (CRP, ESR, WCC, ASOT)• A 12 lead ECG and rhythm strip • CXR was reviewed were available• Echocardiography was done using a Sonosite M-

turbo USS SN NG020N portable echocardiography machine, Sonosite Inc (Bothell USA), according to the guidelines of the American Society of Echocardiography.

• All images were recorded and subsequently reviewed with a paediatric cardiologistLai WW et al. J Am Echo. 2006

Statistical Analysis

• Data was collected, verified and checked for completeness and then entered on REDCap for storage

• Data was analysed using Stata, version 10.1 • Descriptive statistics between patient groups were

compared using the chi-squared test.– A p-value of < 0.05 was considered significant

Harris P A, Taylor R et al. J Biomed Inform. 2009 Apr;42(2):377-81

Results

Total

hospitalized children

2601

2499 did not meet

inclusion criteria

102 (3.9%) children had cardiac

failure/murmur, chorea, or arthritis

31 children had ARF

and/or RHD

CHD (18) CMP (16)

Cor pulmonale (12)

Severe anemia (11)

TB pericarditis (8)

Septic arthritis (1)

JIA (3)Choreoathetoid

CP (1)Denied consent

(1)

Total OPD visits 1026

19 children had chronic RHD

50 children with ARF and/or RHD

Age Distribution of cases of ARF/RHD

• 32 (64%) patients were female, female:male ratio = 1.8• Median age 9.5yrs (IQR 7.5 – 10.5, range 4 – 12yrs)

< 5 yrs 5 - 10 yrs > 10 yrsAge in years

0

5

10

15

20

25

30

35

40

2

36

12Num

ber

Genetic Association with ARF

• Family history of RHD was present in 3/50 children (6%)– Positive family history has been documented in 2

– 14% of cases

de Carvallo SM Rev Bras Rheumatol 2012Ravisha MS Arch of Medical Res 2003

ARF and RHD among hospitalised Children

• Of the 2 601 children ages 1 – 12 years admitted over 10 months, 733 (28.2%) children were aged 5 – 12 yrs– 31 had ARF and/or RHD

• Case rate = 11.9/1000 children 1 – 12yrs

– 22 children with chronic RHD (all aged 5 – 12yrs of age)• Case rate = 40/1000 hospitalised children 1 – 12yrs

– 85 children hospitalised with cardiovascular-related conditions• 25.9% had RHD(6-6 – 34% patients hospitalized or seen in echo clinics with CVS disease in Africa have RHD)

– Only 2 (4%) children < 5 years, both with ARF only (5% in the USA) Zühlke L Heart 2013

Tani LY Pediatrics 2003

Disease status at presentation

Inpatient (n = 31)

Outpatient (n = 19)

Total(n = 50)

ARF only 9 0 9

ARF with RHD

De-novo presentation

5 0 5

Previously diagnosed

2 0 2

RHD only De-novo presentation

9 1 10

Previously diagnosed

6 18 24

Late Presentation • Many children presenting with established RHD de-

novo without prior history of ARF – 36.6% (15/41) of all the patients seen with RHD– 63.6% (14/22) of those hospitalised with RHD– More than the rate of 8.6% found in South Africa (adult

series), but similar to a rate of 38% in Fiji (children and adults)

• Recurrence rate of 43.8% (7/16 chn with ARF), very high compared to other regions, 8.1% - 23%

Ravisha MS Arch of Med Res 2003Orun UA Eur J Ped 2012Smith MT J Ped and Child Health 2011Sliwa K Eur Heart J 2010Steer AC MJA 2009

Clinical Features Present in Children Hospitalized With ARF (n = 16)

Clinical feature ARF without RHD (n= 9)

ARF with RHD (n= 7)

Total n/%

Review of 164 articles on ARFSeckeler MD. Clin Epid 2011

Arthritis 4 1 5/31.25 59.3

Carditis 4 6 10/62.5 59.5

Chorea 3 2 5/31.25 12.9

Subcutaneous nodules 0 1 1/6.25 3.7

Erythema marginatum 0 0 0 5.9

Fever 6 5 11/68.75 65.6

Arthralgia 3 3 6/37.5 40.7

Elevated acute phase reactants 8 5 13/81.25 81.4(ESR)

Elevated ASOT 7 5 12/75.0 75.3

Clinical Features in Children with RHDHospitalized patients

• Congestive cardiac failure was present in all the 22 children with RHD, and all had a cardiac murmur (of AR and/or MR)

• Pericarditis was present in 4 (18.2%) children

• CXR was available in 17 children, all of whom had cardiomegaly

• 16 children had clinical pulmonary HTN

Outpatients

• Chronic cardiac failure was present in 15/19 (78.9%) children

• 18/19 still had a cardiac murmur

• CXR was available in 6 children, all of whom had cardiomegaly

• 9 (47.4%) children had clinical pulmonary HTN

Echocardiographic features in patients with ARF and RHD (n=49)

Valve lesion ARF only (n=9)

ARF with RHD (n=7)

RHD only (n=33) Total(n=49)

Inpatients (n=15)

Outpatients (n=18)

MR 4 (44.4%) 7 (100%) 15 (100%) 18 (100%) 44 (89.8%)

MR + MS 0 1 (14.3%) 1 (6.7%) 0 2 (4.1%)

MR + AR 0 2 (28.6%) 9 (60%) 5 (27.8%) 16 (32.7%)

Pulmonary hypertension

1 (11.1%) 1 (14.3%) 11 (73.3%) 4 (22.2%) 17 (34.7%)

Complications of RHD

• Common complications – Acute and chronic CCF in 90.2% of children with RHD• 32% in Fijian study• 36.5% in an Indian study

– Clinical pulmonary hypertension in 50%• CVA and infective endocarditis were present in 1

child • CFR among hospitalised children = 6.5%

Steer AC MJA 2009Ravisha MS Arch of Med Res2003

Management of ARF/RHD

• Medical therapy for complications was the main form of treatment available with no open heart surgical facilities for valve repair/replacement

• Only one patient had surgical MV replacement at a time she was living in another country

Penicillin prophylaxis

• 26 known cases of ARF and/or RHD• 25 (96.2%) on penicillin prophylaxis• 18/25 (72%) were on oral penicillin• Self-reported good adherence in 68% – Completion of adherence found to be 63.2% in a previous WHO study

between 1986 - 1990 WHO Bulletin OMS 1992;70:218

70%

26%4%

oral penicillin injectable penicillinnot on penicillin prophylaxis

Penicillin prophylaxis

• 72% of the patients were on oral penicillin • Injectable penicillin has been found to be

more efficacious than oral penicillin in preventing RF recurrences and progression to RHD

Essop M R Circulation 2005Carapetis J R Lancet 2005Geber M A et al. Circulation 2009;119(11)1541-51Manyemba J and Mayosi B M. SAMJ 2003WHO Technical Report Series 2004

Study Limitations• Small number of patients limit the conclusions that

can be made from the study• Hospitalised children tend to reflect severe cases

and with these coming from disparate communities, conclusions from this study may not be directly inferable to the community

• Unreliable hospital records, minimised by one of the investigators visiting the wards on a daily basis to screen all hospitalised children

• Some variables such as adherence to penicillin prophylaxis based on history only therefore subject to recall bias

Conclusions• ARF remains a significant problem and cause of

acquired heart disease among children presenting at tertiary hospitals in Zimbabwe

• There was a pattern of late presentation with many patients presenting de-novo with established RHD

• Clinical and echocardiographic features were comparable to what has been found in similar settings

• Secondary prophylaxis was suboptimal, with a large number of patients on the less efficacious oral penicillin

Recommendations• It is important to raise awareness among

patients, the community, health care workers and policy makers on the disease presentation and best treatment practices to enable more optimal utilization of available resources

• Given the high burden of rheumatic valve disease with complications, cardiac surgical services may be an important addition to the management of RHD in Zimbabwe

The End