KUALA LUMPUR, Jan 15 – The country’s literal handful of clinical immunologists have recommended recognition as subspecialists to manage primary immunodeficiencies (PIDs), a group of nearly 500 genetic disorders.
According to Prof Dr Amir Hamzah Abdul Latiff, a clinical immunologist and allergist in Pantai Hospital Kuala Lumpur, Malaysia only has two clinicians wholly trained in clinical immunology for both adults and children, both of whom are in the private sector, while another five are paediatric immunologists by training who are based in university hospitals by Universiti Kebangsaan Malaysia (UKM), Universiti Sains Malaysia (USM), and Universiti Putra Malaysia (UPM).
In total, there are only seven clinicians with training in clinical immunology in Malaysia (six of whom are located in the Klang Valley, with the other in Penang) to treat an estimated 26,000 people with PIDs.
This figure – provided by Prof Dr Lokman Mohd Noh, a former honorary consultant paediatrician (Immunology) at Tunku Azizah Women & Children Hospital Kuala Lumpur and who previously served as professor of paediatric immunologist at UKMMC Cheras KL – is an extrapolation to the Malaysian population from the incidence of one PID case per 1,200 people in the United States.
However, the Malaysian PID Network (MyPIN) registry recorded only 294 cases of PID between 1986 and 2017, as reported in the APSID-MSAI Conference 2022, which the clinical immunologists consider to be under-reporting.
Dr Lokman said at least two clinical immunologists per million population are needed, compared to the current seven in the country that includes both him and Dr Amir Hamzah.
PIDs weaken the immune system, making individuals prone to infections like recurrent flu, fever, and diarrhoea.
Often misdiagnosed due to their deceptive symptoms, PID patients are usually given temporary relief through antibiotics, which fails to address the underlying immune disorders. Mismanagement can lead to severe health complications, including permanent impairments and a significant decrease in life quality, affecting their education, careers, and social lives.
Dr Lokman said not recognising clinical immunology as a subspecialty weakens advocacy for improvement of patient care.
“In Malaysia, recognition is paramount, without which the role of the clinical immunologist to undertake is ineffectual,” Dr Lokman told CodeBlue.
“Creating awareness and recommendations for better diagnostics and treatment are less heeded. Registries developed by universities showing morbidity and high mortality are often ignored. Preventive measures may be trivialised.
“Requests for including the development of newer laboratory tests and to provide current therapy are often not taken seriously. Plans for expansion of service will be sluggish.”
Dr Lokman pointed out that there are no clinical immunologists in public hospitals for adult PID patients, citing as an example some PIDs, especially antibody deficiency, require immunoglobulin administration to adhere closely to a standard protocol at recommended dosage and regular intervals.
“Non-clinical immunologist physicians find it hard to adhere to the requirements of the regime – correct dose, intervals etc – with associated mismanagement and complications,” he said.
“General specialists (as an area of interest only) having no official training in immunology may not observe the preferred treatment.”
The clinical immunologists expressed lack of confidence in democratising immunology services outside Kuala Lumpur and Penang, as long as clinical immunology is not recognised as a subspecialty.
Why Clinical Immunology Isn’t Recognised As A Subspecialty Despite Application Since 2007
The Ministry of Health’s (MOH) stance is that immune-mediated diseases should be managed by general specialists, considering it an “area of interest only”.
Efforts to establish clinical immunology as a subspecialty in Malaysia by the seven clinical immunologists in Malaysia have faced challenges over the years since an application nearly 17 years ago in 2007, as related by Dr Lokman to CodeBlue.
In 2008, the MOH and the Malaysian Medical Council (MMC) cited the limited demand for clinical immunology services, an already high number of paediatric subspecialties, and the belief that paediatric infectious disease consultants and pulmonologists could manage primary immunodeficiencies and allergies, respectively, as reasons clinical immunology is not required as a subspecialty.
The clinical immunologists’ team rebutted by highlighting increased research in the field and the presence of trained clinical immunologists in Malaysia that have added newer inputs to improve diagnosis and management of immune-mediated disease.
What is more relevant is the aforementioned unrelated professionals would be more conversant in their chosen field [viz pulmonology or paediatric infectious diseases], much less in clinical immunology. The number of subspecialities in existence in the National Specialist Register (NSR) is immaterial.
In 2011, the MOH deemed clinical immunology as more research-oriented and not suitable as a standalone subspecialty. But clinical immunologists argued that this view overlooked the need for specialised care in PIDs and complex allergy cases that are the fruit of research.
Clinical immunologists are in a better position to optimise research findings for patient care of immune-mediated diseases, as clinical care and research are inseparable.
By 2019, another added delay was attributed to an absence of standard accreditation criteria protocol that was being developed by the MMC-NSR, a rationale that the team found inconsistent, given the 11-year wait for patients.
During the Covid-19 pandemic, a meeting with then-Health Minister Khairy Jamaluddin was held on December 2, 2021, in Putrajaya. According to them, Khairy acknowledged the importance of clinical immunology as a subspecialty, in light of the pandemic, and instructed an application to the MMC-NSR to be made again. A follow-up meeting to finalise the application was made on February 15, 2022.
Unfortunately, after much delay in processing and discussing the application a couple of times, the MMC stated that the scope of clinical immunology was so broad that it overlaps with other specialties, such as internal medicine, paediatrics, public health, and pathology, and thus an overlap in practice, that MMC could not recognise clinical immunology as a subspecialty.
The clinical immunologists’ team countered by emphasising that clinical immunology could be categorised under the parent specialties as indicated as in other developed countries, suggesting a similar approach for Malaysia.
They noted that in Australia, clinical immunology is practised under a parent specialty separately as paediatrics, adult medicine, or immunopathology (pathology), arguing there is no overlap.
Efforts were subsequently made by the clinical immunologists to this end, and there was a unanimous agreement by the parent specialty of paediatrics for the subspecialty of clinical immunology to exist under them, but this was overlooked by the MMC.
Regarding the concern on definitions on how a patient is to be categorised according to age, Dr Lokman said: “As a clinical discipline, if it is under 18 years, it is under paediatrics. For those above 18 years old, it is under adult medicine. However, Malaysia may need adolescent paediatrics for 15 to 18-year-olds to manage the transition of care.”
He that two clinical immunologists in their group fit the role needed for adult medicine.
What Is Immunology And What Do Clinical Immunologists Do?
Dr Amir Hamzah explained that immunology is a discipline focused on diagnosing and managing immune system disorders, emphasising the critical role of allergies within this specialty. It merges the study of allergies with immune responses, forming a key part of both treatment and prevention strategies.
“Most immunologists have a dual role as both a pathologist in the laboratory and a clinician. Some work primarily as academics pursuing research careers, while others may be scientists who do not see patients directly,” Dr Amir Hamzah told CodeBlue.
“Taking an example from the NHS services in UK, the responsibilities of laboratory leadership and direction, supervision, quality management, clinical interpretation and clinical liaison rest with the clinical immunologist.”
A key area within immunology is the study of PIDs, now increasingly known as inborn errors of immunity (IEI). These are not just singular disorders but encompass a vast array of nearly 500 different conditions.
“PIDs or now more appropriately known as IEI are a growing group of nearly 500 different disorders caused by ineffective, absent or an increasing number of gain of function (GOF) mutations in immune components, mainly cells and proteins,” Dr Amir Hamzah said.
“Thus, IEI manifest themselves as infections, autoimmunity, autoinflammatory, malignancy or allergy (primary atopic disorders).”
Economic Impact Of Undiagnosed PID Estimated US$2.7 Billion Annually
A presentation by the clinical immunologists in July 2022 to YB Khairy stated that each undiagnosed PID case costs an average of US$102,736 annually.
Given the estimated prevalence of PID in Malaysia at around 27,000 cases (1 per 1,200 population), the total annual cost of all undiagnosed PID cases could reach approximately US$2.7 billion (around RM10 billion).
In contrast, if all these PIDs were diagnosed, the cost per case would significantly reduce to about US$22,096. Consequently, diagnosing all 27,000 estimated PIDs in Malaysia could lower the total cost to around US$540 million annually.
This represents a potential saving of approximately US$2 billion a year, said the clinical immunologists, highlighting the immense economic benefit of effective diagnosis and management of PID.
Inadequate Information, Wrong Treatment Recommended
Bruce Lim Wee Diong, president of the Malaysian Patients Organization for Primary Immunodeficiencies (MyPOPI) and a father of a child with PID, explained that while PIDs differ, they share one common feature: the disruption of the body’s immune system.
Anyone, regardless of age, gender, or race, can get these diseases because of hereditary genetic flaws, he said.
“Because the most important function of the immune system is to protect against infection, people with PID commonly experience increased susceptibility to infection,” Lim told CodeBlue.
“The infections may be in the skin, sinuses, throat, ears, lungs, brain, or spinal cord, or in the urinary or intestinal tracts. Increased susceptibility to infection may show up as repeated infections, infections that won’t clear up, or unusually severe infections.”
MyPOPI membership has been growing annually, with more than 110 patients currently.
He stressed the urgent need for recognising clinical immunology as a subspecialty in Malaysia.
“If clinical immunologist is not recognised as a subspecialty, it will deter specialist doctors (paediatrician, physician, surgeon) to take up the subspecialty. Hence, there will not be sufficient clinical immunologists to treat and care for inborn error of immunity (IEI) and immunological patients in Malaysia for both paediatric and adults.”
Lim said currently, many PID patients in public hospitals are treated by non-clinical immunological doctors, who do not fully understand the complexity of diagnosis and treating a PID patient. Hence, PID patients may develop a lot of other complications or even succumb to their disease.
A 2017 White Paper by MyPOPI on PID in Malaysia highlighted Lim’s anecdote on how his son, Caleb, was always sick and had a history of recurrent pneumonia and bronchitis after turning one. When Caleb was five years old, he was diagnosed with X-Linked agammaglobulinaemia (XLA) at Universiti Malaya Medical Centre (UMMC) but did not get referred to a clinical immunologist.
Caleb’s parents, Lim and Karen Koh Yah Hui, chose to seek a second opinion after a hepatologist at UMMC recommended a bone marrow transplant for Caleb to undergo as soon as possible.
“We were not given adequate information about the disease when we were informed about Caleb’s diagnosis at UMMC,” Lim and Koh wrote in the White Paper.
“To make matters worse, we were recommended the wrong treatment. We were really lost and didn’t know who to turn to (UMMC did not refer us to any clinical immunologist) or where we could get more information about XLA.”
In the end, Caleb’s parents managed to get their son treated by a clinical immunologist in Singapore in 2008. Since August 2015, Caleb has been undergoing subcutaneous IG (IGSC) therapy at HUKM in Malaysia under Dr Lokman’s supervision.
MyPOPI said in its White Paper that awareness of PID in Malaysia is still low.
“The primary concern is that individuals who may have the disease but have no knowledge about it are not being diagnosed and treated. For the medical community, lack of awareness will result in incorrect or delayed diagnoses and consequently patients may not get the treatment they need,” said the PID patient group.
“Therefore, it is imperative that not only efforts to raise awareness on PID are ongoing but also that it is recognised and supported by the Ministry of Health.
“We caution on the wisdom of the tenacity of opposition by the MMC to include clinical immunology into the NSR and hence, recognising the lead role this subspecialty holds in management of immune-mediated diseases, especially PID and complex allergy cases, besides providing advocacy towards optimum patient care.
“To deny this will signal the slow death of this potential growing area of medicine for Malaysia. The current mood in the country is to consider what is new and beneficial to the nation.”
