Ricardo Sorensen M.D.,1 Amos Etzioni, M.D.,2 Ahmed Aziz Bousfiha , M.D.,3 John B. Zeiger, M.D.4
1. Department of Paediatrics Children's Hospital, 200 Henry Clay Ave. New Orleans, LA, USA
2. Meyer Children's Hospital, Haifa, Israel
3. Clinical Immunology Unit, King Hassan II University, Averroes Hospital, Casablanca, Morocco
4. Sydney Children’s Hospital, Randwick, New South Wales, Australia
Introduction
World Primary Immunodeficiency
Week (WPIW) 2013 runs from 22–29th April (www.worldpiweek.org). As this celebration and
awareness campaign approaches, it is time to reflect on progress made and the
challenges that remain for the primary immunodeficiency diseases (PID)
community. In this article, representatives from leading PID societies evaluate
the situation and plans for further progress in their respective areas of the
world. It is hoped that this situation analysis will prompt further focus and
enhanced collaboration on the gaps that remain in the pursuit of promoting
early diagnosis and treatment of PIDs.
Europe
The European Society for Primary
Immunodeficiency (ESID) is the oldest and largest professional organization
focused on PIDs. Currently ESID has 800 members and almost 2000 individuals
attended its last biennial meeting (Florence, October 2012).
ESID developed the first
clinical database for PIDs. Containing data from over 10,000 patients, this
large registry has been used for many important projects and published studies
(1-3). Furthermore, in 2012, ESID members collaborated in the publication of an
updated PID diagnostic protocol for non-immunologists. This protocol
incorporates newly defined PIDs and is designed to assist physicians caring for
adults and children to promptly and cost-effectively screen and diagnose PIDs
based on the clinical presentation and laboratory tests, with definitive tests
subsequently performed in partnership with specialist immunologists (4).
Aside from organizing the
biennial meeting, ESID is involved in many other educational activities, such
as a summer school for PID. A major objective of the organization is to
increase awareness of PID through a new website and meetings with patient
organizations. ESID also supports the wonderful ‘J project’, conducted by Prof.
László Maródi (Hungary), which aims to develop PID awareness and expertise in
eastern and central European countries (5).
In the upcoming year, ESID will
focus on two main points for Europe:
*
Implementation of neonatal screening for severe combined immunodeficiency
(SCID). After the success of the program in several states in the USA, ESID
will push for SCID screening to be established soon in many European countries.
* Provision of adequate treatment
of the various PIDs across Europe. Unfortunately, in many countries the supply
of intravenous immunoglobulin (IVIG) is inadequate and haematopoietic stem cell
transplantation (HSCT) centres have yet to be developed in some countries,
mainly in eastern Europe.
Although much has been achieved,
there is still a long way to go in providing the early and precise diagnosis of
PID, together with the appropriate treatment, to the many thousands of patients
all over Europe and the world.
Latin America
Organised efforts towards
improving the diagnosis and management of patients with PIDs in Latin America
started in 1993 when a small group of immunologists from Argentina, Brazil,
Chile and Colombia teamed up with Ricardo Sorensen, M.D., in the USA to create
a joint patient reporting form under the auspices of an informal group called
the Latin American Group for Primary Immunodeficiencies (LAGID). The goals of
this organization were to include other Latin American countries and to create
registries of patients with PIDs in each participating country. The group grew
from the initial four to a total of 14 countries with a wide population range.
Many of the objectives set forth
by LAGID have been accomplished, including: the development of patient and
parent support groups in most participating countries; the creation of a
website for members; the organization of 12 yearly scientific meetings held
from 1995 to 2007; educational programmes and the education of paediatricians
and general practitioners; and extensive collaborative efforts between member
countries and between Latin American immunologists and their colleagues in
Europe and the US. These efforts led to the creation of the first joint PID
registry published by eight countries in 1998 (6). A second report was published in 2007 (7)
A second official electronic
registry, following the model of the ESID registry, was established for all of
Latin America in Sao Paulo, Brazil, with the assistance of ESID. Other actions
have contributed to advancing the care of patients with PIDs in Latin America
and have brought a new dynamic to diagnosis, treatment and research in the
region (8,9). These
actions include the sponsored fellowship programme led by the Latin American
Society for Immunodeficiencies (LASID), founded in 2009, which has assisted
young immunologist in five countries to specialise in the diagnosis and care of
PIDs, and the establishment of a network of Jeffrey Modell Diagnostic and
Research Centers in Sao Paulo, Mexico City, Medellin, Chile and Buenos Aires.
Created by the Jeffrey Modell Foundation, these centres offer enhanced
diagnostic and treatment capabilities for PID across the world, including now
in Latin America. Health authorities in several countries, including Mexico,
Colombia, Argentina, Brazil and Chile, have now recognised PIDs as a special
group of diseases and facilitated access to treatment.
The present day challenges of
PID in Latin America are two-fold: to continue to expand awareness and
diagnosis and treatment possibilities to more areas in Latin America where
there has been little or no progress, and to satisfy the desire of young Latin
American immunologists to bring state-of-the-art advances in diagnosis and
treatment to their patients. The encouraging experience gained from years of
successful collaborative efforts allows LASID to look with great optimism to
its future.
Africa and Middle East
PID diagnosis and care in Africa
and the Middle East has developed tremendously over the past 2 years, but major
efforts are still needed, especially in Sub-Saharan Africa.
Indeed, we have witnessed the
creation of PID networks and the release of multicentre studies on these
conditions. In particular, two workshops bringing together experts from the
North Africa and Middle East were held in Athens in 2012 and in Dubai in 2013.
These led to the sharing of solutions between experts and to the building of
cooperative bridges in training and research. In 2011, Ridha Barbouche and
colleagues published a profile of PIDs in North Africa (Morocco, Tunisia and
Egypt), (10) while Saleh Al Muhsen and colleagues published on the
epidemiology of PID in the Middle East (11).
Both regions are characterised
by high rates of in-breeding (20–60%) and they have a comparable distribution
of PID causes, with a high incidence of SCID and founder mutations. Teams in
the Middle East, including Saudi Arabia, have published excellent results on
HSCT and have contributed to internationals research on PID specific cases
(12). PID treatment has been slower to develop in North Africa,
with difficulties existing in IVIG access and HSCT being introduced only
timidly.
These advances allow high hopes
for patients with PIDs in the aforementioned regions. However, with the
exception of South Africa — where the situation is comparable to that in North
Africa — progress is lagging in the rest of the African countries. Indeed,
there seems to be little or no activity in the PID field in over 40 of the 54
countries of this continent. To address this issue, the African Society for
Immunodeficiencies (ASID), created in Casablanca in 2008, opted for regional
actions to educate paediatricians and other healthcare professionals and to
promote cross-country initiatives to allow the exchange of expert experience
and education. ASID’s achievements are already palpable: Africa has a
spokesperson for PID scientific and social societies, and schools to provide
education about PIDs have involved a dozen countries in each region of Africa.
However, challenges remain in
Africa, whose population has this year exceeded 1 billion citizens, and urgent
international actions are necessary in this continent. These should aim not
only to increase awareness of PIDs among physicians, nurses and other
healthcare professionals, but in particular to bring the attention of the
authorities and the general public to this large group of rare diseases and
their significant effect on infant mortality. Indeed, PIDs are more common than
is generally thought. It is estimated that up to 900,000 people in Africa may
have a PID, whereas only around 1000 cases are currently registered (13).
The two regions of North Africa
and the Middle East have rightly decided to work together to improve PID
diagnosis and care. Corresponding joint efforts are also needed in the rest of
Africa to enable the work of patient groups, doctors and nurses to bring a
positive change for PID patients.
Australia
There is an active
immunodeficiency community in Australia, with many of the major interactions
revolving around the PID Committee of the Australasian Society of Clinical
Immunology and Allergy (ASCIA) and the now well-established triennial Asia
Pacific Primary Immune Deficiency (APPID) Summer School. While geographical
constraints make large PID centres difficult to envisage, there are a number of
major centres seeing patients with complex immunodeficiency disorders and the
first Australian Jeffrey Modell Foundation Center will soon open at Sydney
Children's Hospital, Randwick. The outcomes amongst the five centres currently
performing HSCT for PIDs in Australia compare favourably to those from other
parts of the world (14).
From a research perspective
there has been an effort to form collaborative research partnerships across the
country, initially through the Australian PID registry (15) and more
recently through the antibody deficiency orientated Australia and New Zealand
Antibody Deficiency Allele (ANZADA) study, which has now being joined by the
more paediatric-orientated CIRCA group.
As in other (but not all)
countries with similar economies, IVIG use is increasing by more than 10% per
annum. In Australia most IVIG use is funded by the federal government (16) and
distributed through the Red Cross Blood Service. A study in New South Wales is
interrogating the Red Cross database to improve our understanding of the
factors driving these changes. Subcutaneous immunoglobulin (SCIG) is becoming
increasing popular among PID patients. SCIG appears to require lower overall
immunoglobulin doses and some centres report that more patients are now using
SCIG rather than IVIG. Although three products have been approved by regulatory
authorities for SCIG use, and SCIG has been endorsed in the Australian criteria
for the clinical use of immunglobulin (http://www.nba.gov.au/ivig/index.html),
national funding of SCIG use is still awaited.
Conclusion
The last 10 years has seen an
unprecedented improvement in PID care in many areas of the world, including
some areas where provision was seriously lacking. These improvements have
resulted from collaborative efforts involving immunologists, non-specialist
physicians, nurses’ associations, health providers, policymakers, and patient
organisations. Such collaborations offer a model for further efforts to promote
early diagnosis and therapy in order to extend and improve the lives of people
with PIDs, especially in areas of greatest need.
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