Rare disease surveillance: An international perspective

Abstract

BACKGROUND:

The International Network of Paediatric Surveillance Units (INoPSU) was established in 1998 and met formally for the first time in Ottawa, Ontario in June 2000.

OBJECTIVES:

To document the methodology and activities of existing national paediatric surveillance units; the formation of INoPSU; the diseases studied by INoPSU members; and the impact of such studies on education, public health and paediatric practice.

METHODS:

Directors of paediatric surveillance units in Australia, Britain, Canada, Germany, the Netherlands, Latvia, Malaysia, Papua New Guinea, New Zealand and Switzerland were asked to provide information on each unit’s affiliations, funding and staffing; the method of case ascertainment, the mailing list and response rates; and diseases studied. Original articles that reported data derived from units were identified by a search of an electronic database (MEDLINE), and additional information was obtained from units’ annual reports.

RESULTS:

Worldwide, 10 units (established from 1986 to 1997), use active national surveillance of more than 8500 clinicians each month to identify cases of rare or uncommon diseases in a childhood population (younger than 15 years of age) of over 47 million (monthly response rate 73% to 98%). By January 1999, units had initiated 147 studies on 103 different conditions, and 63 studies were completed.

CONCLUSION:

INoPSU enhances collaboration among units from four continents, providing a unique opportunity for simultaneous cross-sectional studies of rare diseases in populations with diverse geographical and ethnic characteristics. It facilitates the sharing of ideas regarding current methodology, ethics, the most appropriate means of evaluating units and their potential application.

BACKGROUND

Rare disease surveillance

Rare and uncommon diseases number in the thousands, and contribute significantly to morbidity and mortality in childhood (1). Such diseases are demanding of health care resources, and have a large financial and emotional impact on families of affected children and communities. The low frequency of individual diseases may result in a delay in their recognition and diagnosis, increasing the risk of preventable complications or death. For many rare and uncommon conditions, little is known about their etiology, clinical spectrum, sequelae and management. However, to generate a sufficient number of cases to derive meaningful data, the study of rare and uncommon diseases requires data collection from large and, often, geographically diverse populations (1,2). In most countries, no mechanism has been available to enable the prospective collection of national epidemiological data on these diseases. Thus, management and resource decisions have relied on data contained in anecdotal or retrospective reports, often from a selected and potentially biased population.

In 1986, the British Paediatric Surveillance Unit (BPSU) was established to redress this deficiency (3). A joint initiative of the British Paediatric Association (now the Royal College of Paediatrics and Child Health), the Public Health Laboratory Service and the Institute of Child Health, the BPSU was based on a simple but novel concept. Each month, all paediatricians in Britain were sent a report card listing a number of rare conditions and were asked to indicate whether during that month they had seen any children who were newly diagnosed with any of the conditions listed. In 1992, Australia (2), the Netherlands (4) and Germany (5) established similar units. Malaysia followed in 1994; Switzerland (6), Canada (7), Papua New Guinea and Latvia in 1996; and New Zealand in 1997 (8). Units are currently being set up in Spain and the Republic of Ireland. In 1994 and 1998, Wales and the Republic of Ireland, respectively, established units that survey more common disorders on a regional basis. In Britain, subspecialty units conduct surveillance through the participation of gastroenterologists and opthalmologists using the methodology initially developed in Britain. The present paper represents the first collation of activities of paediatric surveillance units worldwide. MEDLINE was searched using Ovid and the terms ‘paediatric surveillance’ and ‘surveillance unit’, and additional details about publications were obtained from unit directors.

Establishment of an International Network of Paediatric Surveillance Units

European units have met informally since 1992 to discuss research protocols and funding issues. BPSU has had close ties with the Australian Paediatric Surveillance Unit (APSU) and the Canadian Paediatric Surveillance Program. The APSU advised units in Malaysia, Papua New Guinea and New Zealand during their development. The Australian and New Zealand units have representation on each other’s administrative committees, while Britain is represented on that of the Canadian unit. In 1996, units accepted the need for an International Network of Paediatric Surveillance Units (INoPSU) to formalize links among units. A proposal for INoPSU was ratified at the 22nd International Congress of Paediatrics held in Amsterdam, the Netherlands in August 1998.

The first INoPSU symposium, sponsored by Health Canada, was held in Ottawa, Canada in June 2000 in conjunction with Beyond 2000: Healthy Tomorrows for Children and Youth, a joint meeting of the Canadian Paediatric Society, the Canadian Institute of Child Health and the Canadian Academy of Child Psychiatry. INoPSU’s business meeting was attended by 12 representatives from eight countries. The increasingly important issues of privacy and confidentiality of health data were discussed, and INoPSU proposed a set of ethical guidelines for surveillance programs. A symposium on Methodological issues in paediatric surveillance included presentations on methodology, application and practical difficulties associated with surveillance, mother-child transmission of the human immunodeficiency virus (HIV), surveillance for perinatal exposure to HIV, Canada’s Immunization Monitoring Program ACTive and ethics. A keynote speaker gave the address Surveillance in children: Is there strength in numbers?

Mission and aims of INoPSU

The mission of INoPSU is “the advancement of knowledge about rare and uncommon childhood infections and disorders through the participation of paediatricians in surveillance on a national and international basis”. INoPSU’s primary aim is to facilitate communication and co-operation among national paediatric surveillance units (and researchers who use these units), and to assist in the development of new and existing units. INoPSU’s aims are detailed in Table 1. Communication is enhanced by the establishment of the INoPSU Web site <http//:www.inopsu.com> that links the Web sites of individual units and various national paediatric bodies to facilitate the sharing of information on methodology, evaluation and ethical issues, and data derived from studies. The simultaneous collection of identical data in different countries also allows comparisons to be made of disease incidence, management and outcome among geographic regions. INoPSU also aims to develop uniform diagnostic criteria, disseminate new knowledge and enhance the ability to mount international surveillance of emerging disorders rapidly.

TABLE 1:

Mission and aims of the International Network of Paediatric Surveillance Units

Mission

The advancement of knowledge about uncommon childhood infections and disorders through the participation of paediatricians in surveillance on a national and international basis

Aims

To encourage and facilitate

communication and co-operation among existing units

the development of new and existing units

information sharing about the surveillance process and methods such as study selection, data validation, statistical techniques,

surveillance methodology and evaluation, including development of an International Network of Paediatric Surveillance Units Web site

peer review and evaluation of ethics and confidentiality issues

simultaneous or sequential collection of comparable epidemiological and clinical data in two or more nations

national comparisons of incidence estimates for selected rare disorders of childhood

dissemination of information to national and international health authorities to raise awareness and encourage early diagnosis and management of rare conditions

identification of emerging disorders

establishment of international cohorts that could potentially support future research

development and clarification of internationally recognized diagnostic criteria

dissemination of new knowledge to the general public and others (eg, parent support groups)

prompt response to international emergencies relating to emerging rare childhood conditions

INoPSU structure

Founding members of the INoPSU network are listed in Table 2. An elected secretariat oversees INoPSU, undertaking regular consultation with units and seeking funding, as necessary. An ‘international link person’ has been nominated from each unit. INoPSU functions primarily as an electronic network via its Web site. BPSU acts as the INoPSU secretariat, and APSU administers INoPSU’s Web site.

Table 2:

Founding members of the International Network of Paediatric Surveillance Units

Founding member	Year established	Affiliations	Staffing (salaried FTE)
Australian Paediatric Surveillance Unit	1992	Division of Paediatrics, Royal Australasian College of Physicians	1.8
		Centre for Disease Control, Department of Health & Aged Care
British Paediatric Surveillance Unit	1986	Scottish Centre for Infectious and Environmental Health	1.4
		Faculty of Paediatrics, Royal College of Physicians (Ireland)
		Public Health Laboratory Service
		Royal College of Paediatrics and Child Health
		Institute of Child Health
Canadian Paediatric Surveillance Program	1996	Canadian Paediatric Society	1.0
		Centre for Infectious Disease Prevention and Control, Health Canada
German Paediatric Surveillance Unit	1992	German Paediatric Association	1.0
Latvian Paediatric Surveillance Unit	1996	Latvian Paediatric Association	1.0
Malaysian Paediatric Surveillance Unit	1993	Malaysian Paediatric Association	1.0
Netherlands Paediatric Surveillance Unit	1992	Dutch Paediatric Association	0.6
New Zealand Paediatric Surveillance Unit	1997	New Zealand Paediatric Society	0.5
		New Zealand Ministry for Health
Papua New Guinea Paediatric Surveillance Unit	1996	Paediatric Society for Papua New Guinea	0
		HOPE worldwide (Papua New Guinea branch)
Swiss Paediatric Surveillance Unit	1995	Swiss Federation of Public Health	0.3
		Swiss Paediatric Society

FTE Full time equivalent

Most national units are affiliated with their country’s professional paediatric organization, and a variety of other organizations concerned with child and public health are frequently represented on the units’ administrative boards. Staffing levels vary (Table 2).

Conditions studied and selection of studies

Paediatric surveillance units provide a mechanism for active case finding for individuals or organizations wishing to study rare or uncommon conditions in childhood. Units encourage or facilitate studies but do not generally undertake research. Units simultaneously collect monthly data on eight or more conditions. Conditions studied include infections, infection-related conditions, vaccine-preventable diseases, congenital and inherited diseases, unusual injuries or therapies, and rare complications of common diseases. Current and completed studies and conditions approved for future study are shown in Tables 3 and 4; they indicate a considerable overlap among units. By the start of 1999, the 10 units had initiated 147 studies on 103 different conditions. At this time, 63 of these studies had been completed and a further 12 applications had been approved for new studies. Eight collaborative studies have been undertaken among units. Some studies also incorporate the collection of biological specimens from notified cases (Table 3).

Table 3:

Conditions currently under surveillance by national paediatric surveillance units and studies that requested biological specimens at January 1999

Condition	Unit performing surveillance
	Current studies	Specimens requested
Acute flaccid paralysis	APSU, CPSP, NSCK, NZPSU, PNGPSU, SPSU	APSU, CPSP, NZPSU, PNGPSU, SPSU
Aseptic meningitis following measles, mumps, rubella vaccine	ESPED
Chronic inflammatory bowel disease*	BPSU
Celiac disease	LPSU, NSCK	LPSU
Congenital adrenal hyperplasia	NSCK
Congenital brachial palsy	BPSU
Congenital heart disease	MPSU
Congenital hypothyroidism	PNGPSU
Congenital rubella	APSU, BPSU, CPSP, NZPSU, SPSU	CPSP, SPSU
Cystic fibrosis	LPSU
Duchenne muscular dystrophy	MPSU
Encephalitis in children three to 36 months of age	BPSU	BPSU
Fatal or near fatal asthma	MPSU
Group B streptoccal infection	NSCK
Hemolytic uremic syndrome	APSU, BPSU†, ESPED, NZPSU, SPSU	APSU, BPSU, NZPSU
Vitamin K deficiency bleeding (including hemorrhagic disease of the newborn)	APSU, CPSP, ESPED, NZPSU, SPSU	CPSP, SPSU
Hirschsprung disease	APSU
HIV/AIDS with or without perinatal exposure to HIV	APSU, BPSU, LPSU, MPSU, NSCK, NZPSU, PNGPSU	BPSU, LPSU
Hospitalized pertussis	ESPED, NSCK
Idiopathic thrombocytopenia	ESPED
Insulin-dependent diabetes mellitus	ESPED, LPSU, NSCK, PNGPSU, NZPSU	LPSU
Invasive Haemophilus influenzae infection	APSU, BPSU, ESPED	APSU, BPSU
Ischemic stroke in infants	ESPED
Leukemia	LPSU	LPSU
Lues congenita	LPSU	LPSU
Multiple sclerosis in infants	ESPED
Neonatal fungal septicemia	ESPED
Neonatal herpes simplex virus infection	APSU, NZPSU
Neonatal meningitis	MPSU
Neural tube defects	NSCK
Neurological endemic cretinism	PNGPSU
Organocidopathia and fatty acid oxidation defects	ESPED
Paediatric malignancies‡	PNGPSU
Pneumoccoccal sepsis and/or meningitis	ESPED	ESPED
Prader-Willi syndrome	APSU
Primary immunodeficiency disorders§	APSU
Progredient subacute neurological diseases	LPSU	LPSU
Progressive intellectual and neurological deterioration (including Creutzfeld-Jakob disease)	BPSU, CPSP	CPSP
Renal tubular acidosis	PNGPSU
Retinopathy of prematurity (stage III and beyond)	NZPSU
Reye syndrome	BPSU
Rotavirus infection	NSCK
Severe combined immunodeficiency	APSU
Subacute sclerosing panencephalitis	APSU, BPSU, CPSP, PNGPSU	CPSP, PNGPSU
Subdural hematoma or effusion (in children younger than two years of age)	BPSU, NZPSU
Transient myeloproliferative syndrome in newborns with Down syndrome	ESPED
Venous thromboembolic complaints	NSCK

^*Ulcerative colitis, Crohn’s disease and intermediate colitis;

^†Previously studied by the British Paediatric Surveillance Unit (BPSU) from 1986 to 1989;

^‡Wilms tumour, Burkitt lymphoma, leukemia, neuroblastoma, lymphoma (non-Burkitt), other;

^§Predominantly antibody defects (eg, X-linked agammaglobulinemia, immunogloblulin A deficiency, immunogloblulin G subclass deficiency), combined immunodeficiencies (eg, severe combined immunodeficiency, common variable immunodeficiency), immunodeficiencies with other major defects (eg, Wiscott-Aldrich syndrome, Di George syndrome, ataxia telangiectasia), complement deficiencies, including C1 esterase inhibitor deficiency (eg, hereditary angioneurotic edema), defects of phagocytic function (eg, chronic granulomatous disease, leukocyte-adhesion deficiency, Schwachman syndrome) and other. AIDS Acquired immunodeficiency syndrome; APSU Australian Paediatric Surveillance Unit; CPSP Canadian Paediatric Surveillance Program; ESPED Erhebungseinheit fur Seltene Padiatrische Erkrankungen in Deutschland; HIV Human immunodeficiency virus; LPSU Latvian Paediatric Surveillance Unit; MPSU Malaysian Paediatric Surveillance Unit; NSCK Nederlands Signalerings-Centrum Kindergeneeskunde; NZPSU New Zealand Paediatric Surveillance Unit; PNGPSU Papua New Guinea Paediatric Surveillance Unit; SPSU Swiss Paediatric Surveillance Unit

Table 4:

Conditions for which studies were completed by national paediatric surveillance units at January 1999, and approvals for future studies

Condition	Unit performing surveillance
	Completed studies	Approved studies
Acute flaccid paralysis	BPSU
Acute liver failure	MPSU
AIDS in childhood	BPSU
Anaphylaxis		CPSP
Androgen insensitivity syndrome	BPSU
Autoimmune hepatitis	ESPED
Arthrogryposis multiplex congenita	APSU
Cerebral edema in diabetic ketoacidosis		CPSP
CHARGE association		APSU
Chemistry set poisoning	BPSU
Childhood dementia	APSU
Congenital adrenal hyperplasia	APSU
Congenital cytomegalovirus infection		APSU
Congenital cataracts	BPSU
Congenital dislocation of the hip	BPSU
Congenital and neonatal varicella	APSU
Congenital rubella	NSCK
Congenital syphilis	BPSU
Congenital toxoplasmosis	BPSU, SPSU
Cystic periventricular leukomalacia	SPSU
Drowning or near-drowning	APSU, BPSU
Extrahepatic biliary atresia	APSU, BPSU
Fatal or near fatal asthma	ESPED
Galactosemia	BPSU
Group B streptoccal infection	CPSP
Hemophagocytic lymphohistiocytosis	BPSU
Hemolytic uremic syndrome	BPSU (study recommenced in 1997)	SPSU
Hemorrhagic disease of the newborn (includes vitamin K deficiency bleeding)	NSCK	BPSU
Herpes 6/7 virus infection		BPSU
High order births	BPSU
Hemorrhagic shock encephalopathy syndrome	BPSU, ESPED
Idiopathic interstitial lung disease		CPSP
Idiopathic thrombocytopenia	ESPED
Insulin-dependent diabetes mellitus	BPSU
Invasive Haemophilus influenzae infection	ESPED, NSCK	APSU
Irregular blood group reactions (non-D, non-ABO)	NSCK
Juvenile dermatomyositis	BPSU
Kawasaki disease	APSU, BPSU, ESPED	LPSU, MPSU
Long term total parenteral nutrition	BPSU
Lowe syndrome	BPSU
Medium chain acyl CoA dehydrogenase deficiency	BPSU
Measles-mumps-rubella vaccine-associated meningoencephilitis	BPSU
Munchausen syndrome by proxy and/or nonaccidental poisoning and suffocation	BPSU	APSU
Nephrotic syndrome (congenital and idiopathic)		APSU
Neonatal thrombosis	ESPED
Neonatal meningitis	BPSU
Neonatal necrotising enterocolitis	BPSU
Neural tube defects	CPSP
Ondine’s curse	ESPED
Perinatal hemocromatosis		CPSP
Postneonatal mortality in premature babies	NSCK
Pyridoxine-dependent status epilepticus	BPSU	CPSP
Rett syndrome	APSU, BPSU	Repeat study APSU
Reye syndrome	ESPED
Rheumatic fever	BPSU, NSCK
Rickets		CPSP
Sickle cell disease	NSCK
Thalassemia major	NSCK, PNGPSU
Tic-borne encephalitis	ESPED
Transient and permanent neonatal diabetes mellitus	BPSU
Visual impairment and blindness		BPSU
Water births	BPSU
X-linked anhydrotic ectodermal dysplasia	BPSU

AIDS Acquired immunodeficiency syndrome; APSU Australian Paediatric Surveillance Unit; BPSU British Paediatric Surveillance Unit; CHARGE Coloboma, heart defects, atresia choanae, retardation of growth and development and/or central nervous system anomalies, genital anomalies and/or hypogonadism, and ear anomalies and/or hearing loss; CPSP Canadian Paediatric Surveillance Program; ESPED Erhebungseinheit fur Seltene Padiatrische Erkrankungen in Deutschland; LPSU Latvian Paediatric Surveillance Unit; MPSU Malaysian Paediatric Surveillance Unit; NSCK Nederlands Signalerings-Centrum Kindergeneeskunde; NZPSU New Zealand Paediatric Surveillance Unit; PNGPSU Papua New Guinea Paediatric Surveillance Unit; SPSU Swiss Paediatric Surveillance Unit

Applications to conduct a study are considered by a scientific panel with epidemiological and public health expertise, and may also be reviewed externally by experts in the field. To be approved for study, conditions must fulfill certain criteria. They must be sufficiently uncommon so that they do not overload the system, although short-duration studies of relatively common conditions may be studied. Research questions must be important and, ideally, all patients should be seen by clinicians whose names are on the mailing list. Similar data should not be readily available through an existing source, although when alternative sources are available, their use is encouraged, particularly when the study aims require complete or near complete case ascertainment. Studies must conform to international ethical guidelines (International Ethical Guidelines for Biomedical Research Involving Human Subjects [9] prepared by the Council for International Organizations of Medical Sciences and the World Health Organization in 1993).

Studies judged to be feasible and to have sufficient resources are monitored for one to three years initially. Studies may be extended if the condition is of particular public health significance (eg, HIV and AIDS) or the paediatric surveillance unit is the optimal mechanism for gathering routine surveillance data. A protocol sheet outlining study aims, case definition and reporting instructions is distributed to the mailing list before the commencement of a new study.

METHODS

Data collection

According to the principle of ‘active’ surveillance, initiation for notification comes from the unit rather than the clinician. Active surveillance results in considerably higher case ascertainment than passive surveillance, and minimizes recall bias (2). The methodology varies slightly among units to suit local conditions. In principle, the surveillance unit sends a monthly report card to a ‘mailing list’ of paediatricians and asks paediatricians simply to indicate whether they have ‘nothing to report’, or to mark the number of new cases of each condition listed that they saw during the previous month. Cards are returned to the unit. The individual or organization responsible for a study (the ‘investigator’) is notified about positive case reports and given the contact details for the reporting clinician. The investigator is then responsible for obtaining clinical and epidemiological data from reporting doctors by postal questionnaire, and for the collation, analysis, presentation and publication of data and feedback to the unit’s secretariat. Alternative data sources may be used to validate ascertainment. In most countries, data collection is anonymous; investigators use a patient code and have no direct access to information that would allow them to identify or contact patients, or their families (Table 5).

Table 5:

Reporting mechanisms used by member countries of the International Network of Paediatric Surveillance Units

Country	Reply-paid cards	Report cards (% returned)	Other forms of reporting (conditions reported)	Questionnaire (% returned)
Australia	Yes	93	Telephone (AFP)	66 to 97
			E-mail (all conditions)
Britain	No	94	Telephone (AFP, IILH, Hib, HUS, encephalitis)	85 to 98
Canada	Yes	86	None	90 to 100
Germany	No	95	None	47 to 100
Latvia	No	Not known	Telephone (all conditions)	Not known
			E-mail (all conditions)
Malaysia	Yes	75	None	Not known
Netherlands	Yes	92	Telephone (Pertussis)	93
New Zealand	Yes	94	Telephone (AFP, HUS)	Not known
			Fax (AFP, HUS)
			E-mail (AFP/HUS)
Papua New Guinea	Yes	72.7	None	Not known
Switzerland	Yes	98	None	96 to 100

^*129 (14%) of 928 clinicians reported to the Australian Paediatric Surveillance Unit by e-mail in 1998, and over 30% used e-mail reporting in 1999. AFP Acute flaccid paralysis; IILH Idiopathic interstitial lung disease; Hib Haemophilus influenzae type b; HUS Hemolytic uremic syndrome

Some units use a reply-paid report card, and e-mail reporting was introduced in Australia in 1997 (Table 5). Telephone and facsimile reporting is requested for some studies when a timely report is required (eg, to facilitate obtaining biological specimens). On receipt of a case notification, two units (the Canadian Paediatric Surveillance Program and the New Zealand Paediatric Surveillance Unit) send study questionnaires directly to the notifying clinician rather than sending the notifying doctor’s details to the investigator in an attempt to make the receipt of questionnaires more timely (8). In 1998, the return rate of monthly cards to units ranged from 73% to 98%, and that of questionnaires ranged from 47% to 100% (Table 5). The proportion of clinicians who report by e-mail to APSU increased from 14% in 1997 to over 30% in 1999, with a 99% response rate (Table 5). The workload for most clinicians who participate in national surveillance of rare diseases is low. In any single year, a large proportion of clinicians on mailing lists do not report a single case and, hence, are not required to complete a questionnaire requesting further details (10,11).

Mailing lists

In 1998, mailing lists ranged in size from seven to 2125 individuals (Table 6), and included general and specialist paediatricians and nonpaediatric specialists (eg, paediatric surgeons and dermatologists). In Switzerland, Germany and Latvia, department heads rather than individual clinicians report on behalf of their colleagues. Surveillance covers the national population younger than 15 years of age, which ranges from 0.5 million individuals in Latvia to approximately 13 million patients in the British Isles (Table 6). Currently, over 8500 paediatricians worldwide contribute monthly to the reporting of uncommon diseases in a population of over 47.6 million.

Table 6:

Mailing lists used by member countries of the International Network of Paediatric Surveillance Units

Country	Population younger than 15 years of age (millions)	Number of clinicians on mailing list
Australia	2	928
Britain	12.8	1925
Canada	6	2125
Germany	12	496*
Latvia	0.5	7*
Malaysia	7.6	340
Netherlands	2.8	416
New Zealand	0.8	163
Papua New Guinea	1.8	40
Switzerland	1.3	41†

^*Reporting by heads of hospital paediatric units;

^†Reporting by heads of paediatric centres on behalf of 500 respondents

Funding sources

Units represent ‘value for money’ because they conduct up to 15 research studies simultaneously; however, fixed costs include postage and salaries. Most units are funded by a variety of government, charitable and commercial sources. The national health department is the predominant funding source in New Zealand, Switzerland and Britain, and a major funder in Australia and Canada. In some countries, an investigator fee contributes towards infrastructure costs and ranges from EURO€111 to EURO€5555 per year.

RESULTS

Evaluation

The Australian unit has undergone formal evaluation (12), and some of its findings are applicable to other units. The evaluation showed that clinicians perceived this method of surveillance to be simple and useful. The high return rate of monthly cards and questionnaires indicates acceptability by clinicians on the mailing list. The sensitivity of case ascertainment was acceptable for most APSU studies, and the positive predictive value was over 70% for most notifications.

Although desirable, full case ascertainment is not always achieved (1,12–14). Indeed, complete case ascertainment is not always required to fulfill the aims of some studies, especially when the system aims to identify cohorts that are later invited to enter randomized control trials or clinical surveys. However, it is important that mailing lists are as inclusive (hence as representative) as possible, to maximize ascertainment. A comparison of the BPSU mailing list with the 1996 national paediatric manpower census identified the involvement of 96% of all paediatricians who are most likely to see cases (15). Where full ascertainment is desired, alternative sources of data are used to supplement surveillance unit data. These sources include birth defect registers, death registers, parent support groups and laboratory surveillance programs (1,16). When used in conjunction with other data sources, this methodology results in levels of case ascertainment between 70% and 95% (15,17–19).

The APSU evaluation concluded that the support of professional paediatric bodies, the simplicity of the reporting scheme, the low workload for clinicians, and the educational value and relevance for clinical practice accounted for the high compliance within these schemes (12).

Impact

The effectiveness of units is measured by their impact on education and public health. Educational impact is achieved by the dissemination of information via newsletters, annual reports, presentations to scientific meetings and publication in the scientific literature. In the APSU evaluation, the majority of clinicians reported that the provision of diagnostic criteria and information derived from studies was educationally useful, and 33% of respondents reported said that such information had informed or changed their clinical practice (12). The increase in reports of Kawasaki disease in the British Isles during 1986/87 was attributed not to a true increase in incidence but to the newly established active reporting system of the BPSU, which increased clinicians’ awareness of the diagnostic criteria for this condition (20). A similar phenomenon occurred in Australia when congenital and neonatal varicella became notifiable to the APSU (21).

Many units have affected public health by monitoring outcomes of national vaccination programs, the late sequelae of vaccination or the incidence of vaccine-preventable conditions before the availability of vaccination. These monitoring effects include surveys of congenital rubella (21,22), subacute sclerosing panencephalitis (23), meningoencephalitis after measles-mumps-rubella vaccination (24), acute flaccid paralysis (25,26) and Haemophilus influenzae type b vaccine failures (14,27), with the latter being a part of a collaborative Dutch and British surveillance.

Units also have the ability to respond rapidly to public health emergencies. Several units have assessed the impact of changing the route of administration of vitamin K prophylaxis on the incidence of vitamin K deficiency bleeding in the newborn (28–33). Other units are monitoring the association between hemolytic uremic syndrome and Shiga toxin-producing Escherichia coli (34,35). The recent identification of new variant Creutzfeld-Jakob disease in Britain (36) has led to the monitoring of the incidence and etiology of progressive intellectual and neurological degeneration in childhood (37). Studies have also provided information that has influenced public health policy development as follows.

Studies of HIV/AIDS and perinatal exposure to HIV provided information on perinatal transmission of HIV (38), and the role of screening and treatment in pregnancy (17,39).

Studies on toxoplasmosis and neonatal herpes simplex virus infection concluded that universal screening in pregnancy was not warranted due to insufficient case frequency (40,41).

Repeated warnings about the danger of using acetylsalicylic acid in childhood were issued after the BPSU study on Reye syndrome described the continued association between acetylsalicylic acid use in children and this disorder (42,43).

The APSU study on hemolytic uremic syndrome provided data to the National Food Authority to support a change in the Food Standards Code relating to the safety of fermented meat small goods products (34,44).

Studies allowed the evaluation of prevention strategies such as pool fencing (45).

Studies identified potential risk factors, for example epilepsy for drowning (45), or being the child of an immigrant parent not vaccinated for congenital rubella (46).

The BPSU study on chemistry set poisoning supported data that led to changes in European Union law regarding the packaging of children’s toys (47).

Some studies, for example, on Rett Syndrome (48–50), provided insight into disease etiology and identified cohorts for future research, including randomized clinical trials of treatment (51). Studies also provided information on current management strategies, such as the use of immunoglobulin in Kawasaki disease (20,52), and the usefulness of a pilot neonatal screening program for congenital adrenal hyperplasia (53). Data from studies also allowed the validation of diagnostic criteria (52), documentation of short term outcomes (26,45) and the description of the clinical spectrum of disease (54). Dutch, British and German units collaborated on surveillance of insulin-dependent diabetes mellitus in children younger than five years of age (18), while Dutch and British units collaborated on a study on H influenzae type b vaccine failures (27). The use of several Australian study protocols (hemolytic uremic syndrome, congenital rubella, acute flaccid paralysis, HIV/AIDS, neonatal herpes simplex virus infection and vitamin K deficiency bleeding) by New Zealand researchers will allow international comparison of data. The exciting potential for the simultaneous study of a single condition by all INoPSU member countries also exists.

CONCLUSIONS

In formalizing established links among 10 existing national paediatric surveillance units, INoPSU provides a unique mechanism for the development of international collaborations. INoPSU allows the collection of information from member nations with diverse geographical locations and population characteristics, the development of uniform diagnostic criteria and the dissemination of new knowledge that will benefit paediatric care. A crucial role of INoPSU will be to ensure the ongoing evaluation of the methodology used by units and the quality of data collected.