These questions have kindly been answered by Dr Michael Loubser, (ML), Professor David Beatty (DB) and Natal Bioproducts Institute (NBI). If you have additional comment, you are invited to do so either by mailing the webmaster (jgrosario@mweb.co.za) or by going to the guest book page.
1. Primary Immune Deficiency is a chronic condition. Has the State set in place or intends setting in place, the infrastructure for home therapy e.g. home nurses, like what is done in other countries.
(ML) NO, IN GENERAL WE ARE NOT SOPHISTICATED ENOUGH TO ENCOURAGE HOME THERAPY IN ANY BUT A VERY SELECT ONE OR TWO PATIENTS.
(DB) NO, NOT FOR THE FORESEEABLE FUTURE.
2. How safe is the local immunoglobulin therapy in terms of transfer of infections e.g. Hepatitis and AIDS?
(ML) TO THE BEST OF MY KNOWLEDGE, HIV HAS NEVER BEEN TRANSMITTED BY IVIG ANYWHERE, THE SCIENTIFIC PEOPLE ASSURE US THAT, ALTHOUGH THE PRODUCT IS NOT SUBJECT TO A SOLVENT DETERGENT PROCESS, A NUMBER OF STEPS ARE TAKEN TO ENSURE INACTIVATION OF "ALL KNOWN VIRUSES". THE SHORT ANSWER IS THAT IT IS SAFE FOR INFECTIOUS AGENTS THAT WE KNOW ABOUT TODAY.
(DB) THE SAFETY OF OUR LOCALLY PRODUCED IMMUNOGLOBULIN THERAPY IS AS GOOD OR BETTER THAN PRODUCTS FROM ELSEWHERE (EUROPE AND NORTH AMERICA). THE PURIFICATION PROCESS EFFECTIVELY ELIMINATES AND INACTIVATES KNOWN PATHOGENS.
(NBI) Polygam is manufactured from plasma, which is collected from healthy, voluntary, non-remunerated blood donors. Each unit of plasma has been individually tested and found non-reactive for hepatitis B surface antigen, antibodies to the hepatitis C virus and antibodies to the human immunodeficiency viruses, HIV-1 and HIV-2, using approved methods. In order to decrease the viral load, hepatitis C nucleic acid amplification (NAT) testing was introduced in March 1999 for all plasma pools, while NAT for HIV was introduced in April 2001. All plasma for fractionation complies with the European Pharmacopoeia monograph on "Plasma for Fractionation". Polygam is prepared by cold ethanol fractionation, to further reduce the risk of viral transmission. It is also prepared by a pH4 treatment, which has a good safety record with no published viral transmissions. The viral validation work done by NBI supports the findings of textbook viral validations, which have shown good, log kills with low pH for hepatitis C and HIV.
3. How safe is the long term use of immunoglobulin therapy?
(ML) ASSUMING THE LOCAL PRODUCTS HAVE THE SAME SAFETY PROFILE AS OTHER COMMERCIALLY PRODUCES IVIGS, THEY ARE SAFE. MANY PATIENTS HAVE RECEIVED IVIG FOR 10-15 YEARS WITHOUT ANY OBVIOUS PROBLEMS. TO ADD A SENSE OF BALANCE, AN ANTIBODY DEFICIENT PATIENT LEFT UNTREATED WILL DIE FROM INFECTION/CHRONIC LUNG DISEASE WHEREAS THEY ARE OFFERED AN ALMOST NORMAL LIFE ON THE TREATMENT.
(DB) AS FOR 2.
(NBI) All our products are registered with the Medicines Control Council in terms of their safety, efficacy and quality. There has been no documentation of residual effects with long-term use of intravenous immunoglobulins. Since they provide passive immunisation their protective effect against infections is short-lived. However, this must be balanced against the beneficial effects of IVIG in PID i.e. improved quality of life, fewer infections and the resultant lung damage. There have been some retrospective studies that followed up patients in terms of clinical efficacy while receiving IVIG. The documented adverse effects in these studies are similar to those published in the PI for Polygam.
4. Are there any other side effects other than those specified in the brochures?
(ML) NOT THAT WE KNOW ABOUT. PRODUCT INSERTS TEND TO LIST EVERY POSSIBLE SIDE EFFECT, EVEN IF IT ONLY HAPPENED ONCE.
(DB) NO.
(NBI) All side effects that are known to us are listed in the approved package insert. NBI has it’s an in-house pharmacovigilance programme that collects information on reported adverse events and determines their impact on the safety profile of the product. This surveillance system, which is a regulatory requirement, allows us to make amendments to the package insert as and when necessary.
5. How close are we to a cure of primary immune deficiency through gene therapy?
(ML) TOO BROAD A QUESTION. THE TERM PRIMARY IMMUNE DEFICIENCY ENCOMPASSES OVER EIGHTY DIFFERENT DISEASES. SOME OF THE VARIETIES OF SCID (X-SCID AND RAG-SCID) ARE ON THE VERGE OF CURE BY GENE THERAPY. AT THE OTHER EXTREME WE REALLY DO NOT HAVE A GOOD IDEA OF THE CAUSE OF CVID.
(DB) REALISTICALLY, PROBABLY QUITE A WHILE i.e. MORE THAN TEN TO FIFTEEN YEARS.
6. Are vaccinations dangerous for immune deficient children and adults?
(ML) LIVE VACCINES ARE CONTRAINDICATED IN ALL IMMUNODEFICIENT PATIENTS. PATIENTS WITH DEFECTS IN THEIR T-CELL OR B-CELL MEDIATED IMMUNITY ARE UNABLE TO MAKE ANTIBODY RESPONSES TO VACCINES - THAT IS THE REASON THEY RECEIVE IVIG. VACCINATION IN THIS GROUP OF PATIENTS DOES NOT WORK. MOST IMPORTANTLY, BECAUSE THEY HAVE DEFECTIVE IMMUNITY, THEY ARE PRONE TO INFECTIONS EVEN BY THE MOST ATTENUATED ORGANISMS, HENCE LIVE VACCINES (BCG, MEASLES, MUMPS, RUBELLA, POLIO, CHICKENPOX ETC.) POSE A SIGNIFICANT INFECTION RISK TO THESE PATIENTS AND ARE CONTRAINDICATED. EVEN PEOPLE LIVING IN THE SAME HOUSEHOLD AS AN IMMUNODEFICIENT PATIENT SHOULD NOT RECEIVE THE LIVE POLIO VACCINE (POLIO DROPS). PATIENTS WITH PHAGOCYTE AND COMPLEMENT DEFICIENCIES CAN BE VACCINATED SAFELY BUT ONLY WITH INACTIVATED VACCINES - ONCE AGAIN LIVE VACCINES ARE CONTRAINDICATED.
(DB) ALL LIVE VACCINES ARE POTENTIALLY DANGEROUS AND THEREFORE SHOULD NOT BE GIVEN TO INDIVIDUALS WITH IMMUNODEFICIENCY (IN SOUTH AFRICA THIS INCLUDES BCG, POLIO, MUMPS, MEASLES AND RUBELLA).
7. Can PID people take medication e.g. malaria pills, without fear?
(ML) YES.
(DB) YES.
8. What tests should be administered to people receiving immunoglobulin therapy on a regular basis and who should prompt these tests being performed?
(ML) I BELIEVE THAT A BASIC SET OF TESTS PRIOR TO EVERY INFUSION SHOULD INCLUDE FBC AND DIFFERENTIAL, IGG, IGA, IGM ANS AST, ALT. THIS REFLECTS MY PERSONAL PREFERENCE AND IS A PRACTICE THAT I HAVE FOUND HELPFUL IN THE PAST. THE RATIONALE BEHIND THESE INVESTIGATIONS IS BEYOND THE SCOPE OF THIS Q/A SECTION, BUT I WOULD BE HAPPY TO EXPAND ON IT ELSEWHERE. NOTE: PERFORMANCE OF THESE INVESTIGATIONS IS NOT LAID DOWN BY ANY GROUP OR ASSOCIATION - IT REFLECTS MY PERSONAL PRACTICE.
(DB) THE ANSWER RANGES FROM NO TESTS TO HUNDREDS OF TESTS WHICH MIGHT PICK UP EARLY SIGNS OF TRANSMITTED INFECTION E.G. LIVER FUNCTION TESTS. THE PROMPTING COULD BE BY EITHER PARTY (I.E. PATIENT AND DOCTOR) AND SHOULD INCLUDE AN UNDERSTANDING OF THE VALUE OF SUCH TESTS.
9. According to clinical management norms in the UK, PCR testing for liver function should be performed every three months on anyone receiving immune therapy. Is the test available, how much is it and if not available/too expensive how can patients go about lobbying for it?
(ML) YOU NEED TO CLARIFY WHAT ORGANISM THE PCR IS DESIGNED TO LOOK FOR. I DON'T THINK PCR FOR VIRUSES IS PART OF ANY GLOBALLY RECOGNISED AND ACCEPTED PROTOCOL.
(DB) PCR IS USED FOR DETECTING VIRAL ANTIGENS AND COULD INCLUDE A LONG LIST OF VIRUS THAT COULD BE POSSIBLY TRANSMITTED BY IV GAMMAGLOBULIN. THEY CAN BE DONE IN SOUTH AFRICA BUT AS WITH ANYWHERE IN THE WORLD, THEY ARE VERY EXPENSIVE.
10. Some patients feel that the insurance industry discriminates against people with primary immune deficiency despite the fact that PID is recognised by the World Health Organisation as a legitimate illness. How can 'we', the patients, lobby for a turnaround in attitude?
(DB) (Answer for 10 and 11) PRIMARY IMMUNODEFICIENCY IS A CHRONIC DISORDER REQUIRING LONG-TERM TREATMENT AND CAN COMPARED TO DIABETES, ASTHMA, RHEUMATOID ARTHRITIS AND HAEMOPHILIA. MEDICAL AIDS CAN ONLY BE CONVINCED OF THIS THROUGH GROUP PRESSURE - HENCE THE VALUE OF PiNSA.
11. Although there are new laws in South Africa regarding access to medical aid by chronically ill people, some PID patients feel discriminated in terms of treatment. How can 'we', the patients, lobby for a turnaround in attitude.?
(ML) I AM NOT AWARE OF THIS. AS A DOCTOR, MY APPROACH TO THE INSURANCE INDUSTRY IS TO WRITE AND EXPLAIN WHY I AM ORDERING THE TREATMENT, DETAIL THE LITERATURE SUPPORTING THE DECISION AND PROVIDE LITERATURE OUTLINING THE CONSEQUENCES OF WITH HOLDING THERAPY (INCLUDING THE CERTAINTY OF AN EARLY DEATH). I THEN LAY THE RESPONSIBILITY FOR THIS POTENTIAL CONSEQUENCE AT THEIR FEET SHOULD THEY REFUSE TO APPROVE THERAPY. SO FAR I HAVEN'T HAD A PROBLEM.
12. Is there current research being done in gene therapy for Hyper IgM and if so where and when is it expected to be a safe treatment?
(ML) I CANNOT SAY WITH CERTAINTY. TO THE BEST OF MY KNOWLEDGE THERE ARE NO HIGM GENE THERAPY PROTOCOLS TO DATE. REMEMBER TO DIFFERENTIATE BETWEEN HIGM-1, 2 AND 3.HIGM-1 WILL PROBABLY BE THE FIRST FOR GENE THERAPY (THERE ARE JUST MORE PATIENTS).
(DB) I DON'T KNOW.
13. There have been incidents of encephalomyelitis in primary hypogammaglobulinaemia (Brain 1996). Is this problem being tracked and if so by whom as the report is not particularly new.
(ML) AS YOU KNOW A REGISTRY HAS BEEN ESTABLISHED.
(DB) I READ THIS ARTICLE AND THE ENCEPHALOMYELITIS DESCRIBED OCCURRED IN PATIENTS PRIOR TO INTRODUCTION OF APPROPRIATE DOSE INTRAVENOUS IMMUNOGLOBULIN. THE PROBLEM HAS SUBSEQUENTLY DISAPPEARED (TO MY KNOWLEDGE) PROVIDED PATIENTS GET APPROPRIATE IV TREATMENT.
14. In terms of the genetic basis of anyone with PID in South Africa, where can the family be tested to find out if the problem is hereditary?
(ML) I HAVE MANY CONTACTS OVERSEAS AND HAVE FOUND THIS TO BE THE BEST OPTION. PROF BEATTY AND DR ELEY ARE DOING SOME RESEARCH.
(DB) GENETIC DIAGNOSIS MAY BE POSSIBLE IN SOME CONDITIONS AND FAMILIES. UNIVERSITY OF CAPE TOWN (DEPARTMENT OF PAEDIATRICS) CAN ADVISE ON WHAT IS AVAILABLE HERE AND LIAISE WITH UNITS IN THE UNITED KINGDOM ABOUT ADDITIONAL STUDIES. TRANSPORTING DNA FOR TESTING IS EASY.
15. What is the general opinion of PID patients being on, as a matter of course, a good prophylaxis antibiotic? What of the long term effect?
(ML) IT DEPENDS ON THE DISEASE AND AGAINST WHAT ORGANISMS ONE WANTS TO PROPHYLAX. PATIENTS WITH T-CELL DISORDERS REQUIRE BACTRIM FOR PCP PROPHYLAXIS (VERY EFFECTIVE). PATIENTS WITH CGD ABSOLUTELY REQUIRE BACTRIM AND ITRACONIZOLE. IN THE GREY AREA, SOME ANTIBODY DEFICIENT PATIENTS SEEM TO DO BETTER WHEN BACTRIM IS USED IN ADDITION TO ADEQUATE DOSES OF IVIG, SOME AUTHORS ADVOCATE THE USE OF CRYPTOSPORIDIAL PROPHYLAXIS IN HIGM-1. SO THE SHORT ANSWER IS THAT IT DEPENDS ON THE DISEASE AND THE PATIENT.
(DB) PROPHYLACTIC ANTIBIOTICS ARE INDICATED IN SOME PRIMARY IMMUNE DEFICIENCIES WHEN THERE IS NO OTHER EFFECTIVE TREATMENT. THE BENEFITS OUTWEIGH ANY LONG-TERM ADVERSE EFFECTS, WHICH IN THEORY AND PRACTICE ARE INFREQUENT AND MINOR.
16. Would/could the medical fraternity advise a standard procedure in terms of clinical management of anyone with PID, obviously tailored to the need of the individual. Could this be made available on the website or in the brochure going to the doctors?
(ML) PID IS TOO BROAD A TERM. DIFFERENT DISEASES HAVE DIFFERENT MANAGEMENT REQUIREMENTS.
(DB) YES.
17. Bearing in mind patient confidentiality, is there a national registry of patients with PID (as they have in other countries) and if not, would the medical profession like one developed?
(ML) NO, THERE IS NO SUCH REGISTRY. I THINK ENTRY INTO SUCH A REGISTRY MUST BE VOLUNTARY AND FOR A REASON. I WOULD LIKE TO KNOW WHO ALL OF THE PATIENTS ARE SIMPLY TO MAKE SURE THEIR TREATMENT IS OPTIMAL - SINCE IN REALITY THERE ARE FEW DOCTORS IN THE COUNTRY WHO HAVE AN INTEREST AND THE SKILLS TO MANAGE THESE PATIENTS. THE PATIENTS WOULD BENEFIT IF THOSE DOCTORS KNEW WHO THE PATIENTS WERE. I WONDER ABOUT THE PRACTICALITY THOUGH, WOULD THE INSURANCE INDUSTRY INSIST THAT ANY PATIENT BEING GIVEN IVIG FOR IMMUNE DEFICIENCY BE EVALUATED BY ONE OF THE PHYSICIANS FIRST?
(DB) THERE IS NO NATIONAL REGISTRY AND IT WOULD BENEFIT EVERYONE TO HAVE ONE - INCLUDING THE MEDICAL PROFESSION.
18. Is the product for subcut therapy available in South Africa and if not, when will it be available?
(ML) NBI HAS A PRODUCT USED FOR INTRAMUSCULAR ADMINISTRATION.
(DB) I DON'T THINK SPECIFIC SUBCUT IMMUNOGLOBULIN IS AVAILABLE - WILL HAVE TO ENQUIRE.
(NBI) There is no product which is specifically registered for subcutaneous therapy worldwide. However, most of the products used in published studies or in clinical practice are normal immunoglobulins for intramuscular administration. NBI’s intramuscular product, Intragam is not registered for this route of administration.
19. The pumps necessary for subcut therapy are very expensive, would the state hospitals consider investing in these or assist in making them available?
(ML) UNLIKELY.
(DB) STATE HOSPITALS WOULD NOT LOAN OUT ANY SYRINGE PUMPS. THE ACADEMIC HOSPITALS DO HAVE THEM FOR INPATIENT USE.
20. Moducare is evidently an excellent product for anyone with PID, would the medical profession support it being available to them on prescription or at least at a lowered price?
(ML) NO - THERE IS NO REAL EVIDENCE AS TO THIS PRODUCTS EFFICACY.
(DB) I DO NOT HAVE ANY KNOWLEDGE OF MODUCARE.
21. Given the fact that newly diagnosed patients rarely have insight into the disease, if you had a child diagnosed with PID what would be the first question you would ask?
(DB) WHY AND WHAT IS THE PROGNOSIS?
