Rheumatic Heart Disease School Project
Condition: Rheumatic Heart Disease
MeSH terms: Rheumatic Heart Disease; Rheumatic Diseases; Heart Diseases
Study type: Interventional

Summary: 
      Acute rheumatic Fever (ARF) results from an autoimmune response due to molecular mimicry
      between the M-protein on the group A β-hemolytic streptococci (GABHS) cell membrane and
      cardiac myosin, and may lead through recurrent or sustained inflammation to Rheumatic Heart
      Disease (RHD). RHD remains a major contributor to morbidity and premature death in the
      working age population in Nepal. Secondary prevention with regular oral or intravenous
      administration of penicillin continued until early adulthood is recommended to prevent the
      progression of the development of endocarditis and subsequent valvular dysfunction.

      Screening for rheumatic heart disease using echocardiography has the potential to detect
      rheumatic valvular lesions at an earlier, clinically silent stage, as compared to clinical
      examination alone and might have a beneficial impact on long-term outcome of children with
      RHD. Schoolchildren aged 5-16 years from several public and private schools from rural and
      urban areas in Southeastern Nepal will be screened for RHD using portable echocardiography.

      Three main inter-related objectives will be pursued in three phases of the study: In a first
      phase using a cross sectional approach, the prevalence of clinical and subclinical RHD will
      be investigated among a representative sample of schoolchildren from public and private
      schools in urban and rural areas. In a second phase, using a cohort study approach among
      those children diagnosed at different stages of RHD, clinical outcomes with regular medical
      surveillance will be assessed (a), and clinical and social risk factors associated with
      prognosis of the disease after receiving medical care at various stages of disease at
      diagnosis will be determined (b). A third phase will integrate the prevalence rates from
      phase 1 and the clinical outcomes from phase 2 in a mathematical model to assess the impact
      of screening and RHD treatment on health resource utilization.
    

Detailed description: 
      Background

      Acute rheumatic Fever (ARF) results from an autoimmune response due to molecular mimicry
      between the M-protein on the group A β-hemolytic streptococci (GABHS) cell membrane and
      cardiac myosin, and may lead through recurrent or sustained inflammation to Rheumatic Heart
      Disease (RHD) (1). RHD is reported to affect over 15 million people worldwide and remains a
      major contributor to morbidity and premature death in the working age population in
      developing countries (2). Socioeconomic determinants such as poverty, overcrowding, and
      malnutrition have been related to RHD. The prevalence of ARF and RHD seems to be particularly
      high in Southeast Asia, the Western Pacific and Africa (3). Whereas heart murmurs detected on
      clinical examination may indicate clinically manifest RHD, echocardiographic screening
      revealed ten times higher prevalence rates of RHD among schoolchildren (4) and may help
      diagnose RHD at an earlier, "clinically silent" stage.

      Patients with a past medical history of ARF or RHD are recommended secondary prevention with
      regular oral or intravenous administration of penicillin continued until early adulthood.

      Even though preventive measures with penicillin are inexpensive and efficient, this strategy
      is difficult to effectuate in developing countries with limited access to health care
      resources.

      A recent study proved that enrolling patients with ARF and RHD in a registry with close
      follow-up increases compliance to treatment and thus helps in reducing the cardiovascular
      sequelae associated with disease progression (5).

      The prevalence of RHD among schoolchildren in urban and rural areas in Nepal is largely
      unknown, and risk factors associated with prognosis of the disease after receiving medical
      care at various stages of disease at diagnosis need to be determined. Moreover, the impact of
      screening using echocardiography, detecting RHD at an earlier, "clinically silent" stage of
      RHD on health resource utilization has to be determined.

      Objective

      Originally, three main inter-related objectives were to be pursued in three phases of the
      study: In the first phase using a cross sectional approach, the prevalence of clinical and
      subclinical RHD were to be investigated among a representative sample of schoolchildren from
      public and private schools in urban and rural areas. In the second phase, using a cohort
      study approach among those children diagnosed at different stages of RHD, clinical outcomes
      with regular medical surveillance were to be assessed (a), and clinical and social risk
      factors associated with prognosis of the disease after receiving medical care at various
      stages of disease at diagnosis were to be determined (b). A third phase was to integrate the
      prevalence rates from phase 1 and the clinical outcomes from phase 2 in a mathematical model
      to assess the impact of screening and RHD treatment on quality of life and health resource
      utilization.

      On August 14 2013, the Nepal Health Research Council required the introduction of a control
      group in the design of the Rheumatic Heart Disease (RHD) School Project. The original design
      included a random sampling stratified by urban versus rural location and public versus
      private status of schools, with a computer-generated random sequence used to determine which
      schools would be centrally selected during Phase 1 of the project to undergo screening for
      RHD. The original computer-generated random sequence was therefore used to determine which
      schools would be randomly selected as control schools which did not undergo the screening
      intervention during Phase 1, but would be selected for follow-up during Phase 2 of the
      project. This approach implicitly allowed for a cluster randomized comparison between
      intervention and control schools at follow-up in children aged 5 to 12 years at baseline,
      when phase 1 of the study took place.

      Methods

      The project will employ three types of study designs performed in sequential phases: a cross
      sectional study (part 1), a longitudinal cohort study (part 2) and an analysis of the impact
      of screening, secondary prevention and treatment on health resource utilization (part 3).

        1. Part 1: Cross-Sectional Survey Schoolchildren aged 5-16 years will be screened at
           selected schools in the Southeast area of Nepal. A follow-up examination will be
           performed in a subset of schools that underwent screening at baseline and in all control
           schools, allowing for a cluster randomized comparison at follow-up between schools that
           underwent screening at baseline and control schools in children aged 5 to 12 years at
           baseline.

        2. Part 2: Longitudinal Cohort Study Those children with documented history of ARF and/or
           RHD will be included into a prospective registry and receive secondary prevention will
           be followed on a regular basis.

        3. Part 3: Impact of Screening and Treatment of RHD The third phase will integrate the
           prevalence rates from phase 1 and the clinical outcomes from phase 2 in a mathematical
           model to assess the impact of screening and RHD treatment on health resource
           utilization.
    

Intervention name(s): Echocardiography
Intervention type(s): Diagnostic Test
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Screening
Keywords: Rheumatic Heart Disease