2. Toxic reactions to dapsone and the incidence of cancer among male veterans

19 Pages·2013·4.38 MB·English

Contents
This book is dedicated to:
Frank Benfield
Wayne Brown MM Acknowledgements 5
John Irvine Foreword 7
Robert Keates
Introduction 11
Trevor Luke
John Moller (NZ) 1 Up, up and away- to war 14
Peter Moore 2 A Deadly Mix 20
Mike Schar
Roy Sprake 3 The Greatest Fraud This Century 30
And all who suffered during and after 4 The Fittest and the Healthiest... 36
Australian and New Zealand participation
5 For All My Sons 46
in the undeclared Vietnam War
1962-1975 6 Hands Across the Tasman 60
The later date is due to evidence that four 7 The Dapsone Paper Chase 66
RAAF Australian defence guards narrowly 8 Lest We Forget ... the DVA 100
escaped with their lives from Tan Son
Nhut airfield on 25/4/75. I) Medley of Chemicals 119
10 Motor Neurone Disease 132
jJ Can of Worms 160
12 VungTau 174
13 Chemical Warfare -perversion of science 187
THE DEVIL'S RAINBOW-Conscripts, Chemicals, Catastrophe
14 Menzies, McMahon & Co .... the road to hell 206
© 1998 Jean Williams
15 Poetry of War 230
Published by 257
Appendices
Homecoming Publications
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111e Devirs Rainbow A Deadly Mix
ORGANS AND TISSUES THAT MAY BE AFFECTED BY
PARTICULAR CHEMICAlS AND PF.STICIDES.
Chapter Two GRAIN
(..?~lead, mt:rt-IAry,
cadrnium and their
C.O>ttf'OLIM,;:js, c.arbDr!
monoxide, sol"er~ts,
pe<iticidll$.
A Deadly Mix
In the early 1960's American scientists felt that not enough
was known about the effects of massive herbicide applications
on health and the environment to permit their use in military
operations in Vietnam.
In the Bulletin of the atomic scientists' Vol38 May 1982, mt:n:.«ry} cadmiu~t~ al"'d
their c.ompt>w1ds,
an article on the 500 page history of the US Air Force -
pNa.qut~t, dllorin.:~ted
'Operation Ranch Hand: The Air Force and Herbicides in hy.i,-oc:arl:ror1!>.
Southeast Asia 1961-71' written by Major William A.
EMBBYq/FETU? REPBOPUCTIVE OR(?ANS
Buckingham sent shockwaves throughout America. The Jea,;J, merc.ury, (in women a>ld me..)
National Veterans Law Center in Washington DC obtained cadmium t~nd tkel r I~ .al"d its compou11ds,
comrourlds, solvents, forrnaldehydt, ~lvtnts,
copies after a prolonged lawsuit under the Freedom of virty <!hloride: l'll0110tl11!(, orqanocltlorines (oc,),
or!Jtll10dll()(it1&.; {OCs), dapsone, poly vi11yl·
Information Act.
onprtophosphtttes (OP~), chlorid~(PVC),
It was encyclopaedic in scope (with almost 500 c.arl1.ort1dt!:>S) hydr"ocarlnn1S·
formaldehyde,
references, many of which are formerly top secret messages
car!>on mo11oxide:.
between Presidents and Cabinet members) and, the article ·111uc.ury, c.admiurn
states, is required reading for all historians of the Vietnam SKIN ..::~nd 1helr compourtd>,
deterqents,all pGS'Iicide> Or<Ja11ophospliate~
war. indudirtq linda11e, (OPs), e<~rPe:~mates,
******* c.hlorinare.d hydrocar/:lons, solvents.
Jul>ricatirtg mineral oils, @ONE MARRON
After a meeting of the National Security Council on 11 May rninu.::~l e::~c.ids. ~en :zen e.
1961, President John Kennedy set out military objectives in
South Vietnam. In order to implement these actions a team of
experts went to Vietnam with the mission 'to acquire directly,
develop, and/ or test novel and improved military hardware
for employment in the Indo Chinese environment subject to
political-psychological restrictions.'
Courtesy o,j'Total Environment Centre, Sydney, NSW
20 21
The Devil's Rainbow Chemical Warfare-perversion ofs cience
CHEMICAL WARFARE- a Perversion of Science
THEW~ PosT
AFTEREFFECTS OF VIETNAM By Dr. J. K. Pollak
Senior Lecturer in Histology and Embryology,
The Departmtnl of Veterans Affairs recoGnizes n i nP (q) condi · University of Sydney
t ~ o:~s . that entitle affected Vietnam veterans to compensation
and Dr. G. M. H. Waites
for their exposure to Agent Orang<. an herbicide used to defoliate the
Associate Professor of Physiology,
jungles of Vietnam.
Symptoms of possli.W> University of Sydney
nine diseases officially linked
contamination
to Agent Orange
<1 ) ..... Soft tissue sarcoma
Rare cancer affecting Depression, sleep
On 17th June, 1925, 42 nations. agreed never to use gas in warfare
muscle or internal disorders
again. The horrors of the gas-warfare of World War I were then apparent
connective tissue.
. , Impaired sight to everyone and the League of Nations wanted to legislate for a saner
< 2) ..... Non-Hodgkin s or hearing and better future.
lymphoma
Cancer affecting Skin conditions Now, nearly 50 years later, the arsenals of the nations, big and
lymph nodes, small, are again swollen with gas and aerosol canisters. Tear gases and
spleen and liver. riot control gases, which in small doses harass and temporarily incapacitate,
< 3) ...,..._.. C'o"1 l on<:ne - • .•• Cdiasrodridoevrass cular are commonly used to quell civil disturbances, and the use of such gases
Severe skJn is proposed as not only militarily desirable, but also as the preferred
disease similar to ·· -· Respiratory problems weapon on humanitarian grounds. It is argued that the enemy could be
teenage acne but temporarily disabled with gas, and battles could be won without severe
may involve cysts
casualties.
and rashes. >-----'•- Acute abdominal pain
Nothing could be further from the truth. Firstly, .it has become
obvious that even the so-called harassing or incapacitating gases have
(4) -~~,~yria cutanea temporary effects only when used under strictly specified conditions. When
· ·..r.-.'1:-" ·:··. .·· . .··>·:!\- ·~":"" -11. c 11. ver Urinary tract disorders euvseedn etihtehseer ihna rcaosnsfiinnge d asnpda ceins coapr aocnit atthine gv egrays eyso ucnagu, seth es eovledr eo ra tnhde ilnafsitrimng,
9!!!>....:" :·=---:--.:·::.:-, respiratory disorders and also death.
(5) IJ>.: i,t······· 4·· -· ··· __ ~)), Weakness of However, such gases make up only a small proportion of those
to-extremities being accumulated for future gas warfare. Gases which are being produced
in vast amounts belong to the so-called lethal gases and also nerve gases,
the latter being lethal in even smaller quantities than the former. The
so-called nerve gases seem to act by inhibiting cholinesterase, the enzyme
participating in events taking place at neuro-muscular junctions, and thus
cause continued muscular contractions eventually leading to death by
Numbness In asphyxiation.
fingefS and toes
( 6) Respiratory Even the least lethal of the nerve gases, such as tabun and sarin,
cancers are about 30 times more lethal than phosgene, the most deadly of all gases
(7) Prostate cancer
used in the first world war. Only recently it was demonstrated how
( 8) Multiple myeloma SOURCE: KRT GraphiCS
(9) Peripheral Neuropathy "effective" gas warfare can be, when U.N. observers reported that nearly
(Acute & S~bacute) all the population of a village in the Yemen was killed by what almost
certainly was an attack with mustard gas by the United Arab Republic.
203
202
The Dev11's Rainbow Collected Poems
I knew that it was called
How they grei ved about the
defoliation,
Miscarriages, one, two. three
that the spray would destroy even seven.
the hiding places of snipers
Their pain, their helplessness,
and ambushing guerrillas.
their rage when Marianne
I did not ask:
died of leukemia at 2,
at what price?
and Michelle died of cancer at 2
Every evening and a half. Their fear of what might happen
the sunset choppers arrived
I knew more
filled with soldiers burning
when I watched my parents
from jungle fevers:;
celebrate their fortieth
malaria, dengue, dysentery.
wedding anniversary,
We took them directly
four children, three grandchildren
to the cooling showers, sitting in the pews.
stripped their wet
I knew what I would never know,
dirt encrusted uniforms
what the poisons and my fears
as we lowered their temperatures
have removed forever from my knowing.
and prepared them for bed.
The conceiving, the carrying of a child,
I did not ask them where they
the stretching of my womb, my breasts
had been caught in the mist,
The pain of labor.
whether defoliation had saved
The bringing forth from my body a new life.
their lives
I choose not to know
I did not know to ask.
if my eggs are
I knew part of the price misshapen and withered
when nine other women as trees along the river.
who watched the helicopters If snipers are hidden
and seen the mist in the coils of my DNA.
talked of their children:
Marilyn McMahon-
Jason's heart defects, and
Amy's and Rachel's and Timothy's. Navy Nurse Corps, Da Nang
Mary's eye problems. Naval Hospital1969-70
The multiple operations to make (written 1988)
and repair digestive organs for VISIONS OF WAR/ DREAMS OF PEACE WrHings of
John and Kathleen and little John women in the Vietnam 1i0Jr
How lucky they felt when one
child was born healthy whole.
236
237
The Devjj's Rainbow
Appendix4
2. Toxic reactions to dapsone and the
incidence of cancer among male
veterans .
./-L-lf~
8+!' 4l Af~~l
Summary
Ten cases of possible adverse reactions to dapsone administered in Vietnam have been
identified. Case histories are presented. One of the possible cases was fatal; the remaining
nine veterans are all living and none has developed cancer. Speculation that those who
suffered toxic reactions may have been liable to later development of cancer has not been
borne out.
Background
This study is the third of a series commissioned by the Department of Veterans' Affairs.
In 1985 the Royal Commission into the Use and Effects of Chemical Agents on Australian
Personnel in Vietnam recommended studies be undertaken of the carcinogenicity of
dapsone. In 1987 the Government agreed to establish an epidemiological study into possible
cancers arising from the use of dapsone.
Subsequently, the Department of Veterans' Affairs (OVA) commissioned the Australian
Institute of Health, now the Australian Institute of Health and Welfare (AIHW) to undertake
the study. After exploratory work in 1989 and 1990, the Institute carried out a study of the
relation between use of dapsone and cancer in male veterans. The report of that study,
containing more background information than given here, has been published (AIHW 1992).
Aim
The aim of this study was to document the cancer history of individuals who may have
suffered toxic reactions to dapsone while they were taking the drug either in Vietnam or as
they returned to Australia.
The rationale for the study derives from evidence to the Royal Commission on the Use and
Effects of Chemical Agents on Australian Personnel in Vietnam relating to the
carcinogenicity of dapsone, and its recommendations for further study. It was speculated
that those who suffered toxic reactions may have been tmusually liable to later development
of cancer. There is no scientific literature relating to this speculation.
Methods
illnesses that may have been toxic reactions to dapsone were identified by examination of the
following Army records:
• 2 Field Ambulance Admission and Discharge Books, 1 June 1966 to 27 April1967;
• 8 Field Ambulance Admission and Discharge Books, 1 January 1967 to 22 February 1972;
• 1 Australian Field Hospital Admission and Discharge Books, 1 April 1968 to 9 July 1970;
• Admission and Discharge Books for Australian personnel admitted to US Forces hospitals
in Vietnam, 30 May 1965 to 13 July 1970;
5
275
The Devil~· Rainbow Appendix 4
• Monthly medical reports of the Australian Force Vietnam (AFV), May 1965 to February history, as found in Army and Department of Veterans' Affairs records. Dates have been
suppressed for reasons of confidentiality; day 1 is the day of first admission to hospital.
1972;
• Reports of AFV physicians, January 1968 to November 1971; Case 1
A 21-year-old man was admitted to 1AF H, diagnosed as suffering from falciparum malaria.
• Reports of AFV pathologists, January 1968 to November 1971; and
He had not taken any dapsone for malaria prophylaxis. Treatment was commenced on day 4
• miscellaneous Army reports and other documents dealing with medical matters in with quinine, pyrimethamine and dapsone, the last at a dosage of 25 mg per day.
Vietnam. The patient developed pains in the Joins and, on day 12, haemolysis. The treating physician
Admission and Discharge Books for 1 Australian Field Hospital (1AFH) from 10 July 1970 to considered that the haemolysis had been caused by dapsone rather than rupture of red blood
15 November 1971 could not be found. However several of the other sources listed above cells infected by the malaria parasite. Dapsone and pyrimethamine were withdrawn on day
cover this period and, because medical officers in Vietnam were by this time concerned over 14. On day 15, the patient was jaundiced. Quinine administration was suspended on that
toxic reactions to dapsone, it is likely that any cases admitted to 1AFH would have been day, as it appeared to aggravate the haemolysis.
mentioned in one of the surviving sources. Blood examination also now revealed the presence of macrocytes in the blood. This was
These records were examined for mention of the following conditions recognised as adverse interpreted as evidence of a megaloblastic anaemia, arising as a consequence of the
reactions to dapsone: haemolytic anaemia. Because of the macrocytosis, folic acid in a dosage of 5 mg three times
per day was given from day 22. The patient was medically evacuated to Australia on day 35.
• agranulocytosis;
The total dose of dapsone consumed by this man was 250 mg.
• granulocytopenia, neutropenia, leucopenia or synonyms;
• aplastic anaemia; Case 2
A soldier aged 21 was admitted to 1AFH and transferred the same day to the US Army's 36
• haemolytic anaemia or haematuria;
Evacuation Hospital. He was diagnosed as having mixed falciparum and vivax malaria. He
• skin reactions associated with dapsone; and had not taken dapsone for malaria prophylaxis.
• dapsone or sulphone sensitivity. Treatment was commenced on day 2 with the standard therapeutic regimen of quinine,
pyrimethamine and dapsone. After 15 days of the 30-day course of treatment with dapsone,
Methaemoglobinaemia, which resolves on cessation of exposure to dapsone, and does not
the patient's haematocrit was found to have fallen to 19% (normal: 42-52%) and his
cause any long-term adverse effects, was not included in this list.
haemoglobin level to 6 g per 100 ml (normal: 14-18). His reticulocyte count was 5% (normal:
Details of each case identified were obtained from the Army medical records. Records held 0.5-2.5%), indicating increased production of red blood cells. A Coombs' test for antibodies
by the Department of Veterans' Affairs were also examined. to red blood cells was negative. The white blood cell count was normal. On the basis of these
Checks were made in the National Cancer Statistics Clearing House in December 1993 for the tests the physician at the hospital concluded that the patient was suffering from a haemolytic
subsequent occurrence of any cancers in those veterans. At this time, the Clearing House anaemia which had been induced by dapsone. Administration of the drug was immediately
included records for all cases of cancer reported to cancer registries in Australia as diagnosed stopped and primaquine substituted.
from 1982 to 1988 (or 1991 in SA). A search was also made for current electoral enrolment in Following the withdrawal of dapsone, the haematocrit gradually rose to 28%. The patient
the State of residence of each veteran, as known to the Department of Veterans' Affairs. was transferred back to 1AFH on day 32 and medically evacuated from Vietnam on day 38.
Searches were to be made for death registrations where the veterans could not be Later tests showed that the man was not deficient in the blood enzyme, glucose-6-phosphate
demonstrated to be alive. dehydrogenase.
Reports of adverse reactions to dapsone that had been notified to the precursor of the In reviewing the case shortly afterwards, the Army's Consultant Pathologist thought that the
Adverse Drug Reactions Advisory Committee in the Vietnam war era were provided by the haemolysis was simply due to parasitisation of the red blood cells.
Committee. Although these reports Jacked names of patients, they did include sex, age,
This case was reported as a suspected toxic reaction to dapsone.
reason for use, and date of reporting. It was thus not difficult to identify reports that might
have related to Vietnam service. Case 3
Three of the cases described below have already been reported in the scientific literature A 21-year-old serviceman was admitted to 1AFH. He was diagnosed as suffering from
(Stickland and Hurdle 1970; Smithurst eta!. 1971). falciparum malaria. He had not taken any dapsone for malaria prophylaxis. Treatment was
commenced with quinine, pyrimethamine and dapsone. The usual daily prophylactic dose of
paludrine was also maintained during treatment.
Results
On day 9, the patient became febrile again, had rigors and complained of pain in the back.
Case reports Quinine was withdrawn on suspicion that the patient had developed cinchonism. The fever
The following case reports consist of a summary of the suspected toxic reaction episode, continued, however, and from day 10 to day 12, the patient's haemoglobin dropped from 12
including evidence for and against the identification of dapsone as the cause. Where it is g to 9 g per 100 ml. At the same time, heavy concentrations of urobilinogen appeared in the
available, the case reports also include a brief account of each subject's subsequent medical patient's urine.
7
6
277
276
The Devits Rainbow
The physician diagnosed haemolytic anaemia induced by dapsone. Administration of the After three more days, he had developed jaundice and felt anorexic. On admission to 1AFH,
drug was immediately stopped and the symptoms 'promptly' subsided. The patient received his bilirubin level was found to be 4.7 direct (normal: 0.1--{).3 mg/100 ml) and 4.0 indirect
a blood transfusion of 2500 ml to which the physician reported he responded 'satisfactorily'. (normal: 0.2-0.7 mg/100 ml), a sign of increased haemolysis of red blood cells. His
Recovery was thereafter said to have been uneventful. A test for glucose-6-phosphate reticulocyte count was 3.7%, but he was not anaemic. There was no evidence of infective
dehydrogenase deficiency was negative. He was medically evacuated from Vietnam to hepatitis.
Australia and remained in hospital for a total of 12 weeks. The physician treating him had 'no doubt' that the jaundice was haemolytic in origin and
Ten months later, the man was again admitted to hospital in Australia, diagnosed on clinical considered that the combination of dapsone and primaquine had caused it.
grounds as suffering from malaria. He underwent a course of treatment with chloroquine The total consumption of dapsone was approximately 550 mg.
and primaquine. A bone marrow biopsy was performed at this time. Peripheral blood films
This man's haemolysis had become evident only after he had commenced taking
showed a mild lymphocytosis with occasional atypical forms. The pathologist commented
primaquine, suggesting a prime causative role for this drug. Later investigations revealed
that this was consistent with a reaction to viral infection or possibly drug therapy.
that he suffered from a deficiency of glucose-6-phosphate dehydrogenase and hence was
One month later he was readmitted to hospital, again diagnosed on clinical grounds as susceptible to acute haemolytic episodes precipitated by such drugs as primaquine.
suffering from malaria. He was treated with chloroquine and primaquine and possibly-the
This case was reported as a suspected toxic reaction to dapsone and primaquine in
records are contradictory-with dapsone.
combination.
The total consumption of dapsone by this man while in Vietnam was 375 mg.
CaseS
The Army's Consultant Pathologist at the time challenged the original diagnosis of dapsone
A 23-year-old man developed an itchy hive-like rash of the body two weeks after he
induced haemolytic anaemia in this case. The pathologist thought that 'there [was] nothing commenced taking dapsone at a dose of 25 mg per day for malaria prophylaxis. The rash
to indicate that the haemolysis was in any way related to anything but having malaria, or seemed to settle quickly without treatment, but two days later he developed giant urticaria
that drugs were necessarily the cause'. In other words, the haemolysis could have been with oedema of the face and eyelids. He was then admitted to 8 Field Ambulance. On day 3,
caused by the parasitisation of red blood cells. he was transferred to 1AFH.
This case was reported as a toxic reaction to dapsone. Treatment with prednisone was commenced on day 5 and continued through to day 15. The
rash returned on cessation of the drug and another course of prednisone was started.
Case4
'Further enquiry' now revealed that the patient had an allergy to sulphonamides. It was then
A 24-year-old serviceman was admitted to 1AFH complaining of a severely itchy widespread
considered that dapsone, which is chemically related to the sulphonamides, was the likely
rash. He also complained of feeling cold and shivery. He had commenced taking dapsone for
cause of the condition.
malaria prophylaxis three days previously. He had suffered from similar episodes of rashes
after taking primaquine and chloroquine in Borneo and New Guinea. On day 18, both dapsone and paludrine were stopped. For the next three days the patient
experienced a few episodes of acute urticaria. These were treated successfully with
On examination, he was found to have a macular rash especially affecting his arms and adrenaline. From day 21, his skin was completely normal and the patient felt 'very well'. He
trunk, and faint peripheral cyanosis. Medical officers concluded that the patient had a was discharged from hospital on day 30. It was considered that the resolution of the skin
sensitivity to certain antimalarial drugs and that the current episode was precipitated by condition on cessation of dapsone strongly supported the diagnosis of sui phone sensitivity.
consumption of dapsone. The drug was discontinued after day 1 and treatment with The patient's medical records were marked 'never to receive Sulphonamides or Dapsone'.
antihistamines initiated. These measures were followed by the virtual clearance of the rash His total consumption of dapsone was 800 mg.
within 24 hours.
Since his Vietnam service, this man has experienced a series of skin problems, none of which
Despite the evidence of his sensitivity to antimalarial drugs, this serviceman was again given appear relevant to dapsone.
primaquine and chloroquine in Vietnam five months later. Again he experienced a skin
reaction, described as generalised erythema. The episode provided additional evidence of his Case7
sensitivity to some antimalarial drugs. A report on this case was published by Stickland and Hurdle in 1970. Much of the summary
below is based on their report.
In 1981, this man was referred to a dermatologist for examination. The reason for the referral
was 'a heaped up ulcer' on his chest wall since 1973. The lesion was found to be a basal cell A 21-year-old man arrived in Vietnam and commenced taking dapsone for malaria
carcinoma. The surgeon noted that the man had multiple degenerative skin lesions, prophylaxis at a dosage of 25 mg per day. Six weeks later, he cut his left thumb. The wound
especially on his hands, eyes and anus. appeared to heal normally. 'Three days later, he developed a fever with rigors and a sore
throat, and the next day he was given codeine compound tablets by an orderly.'
The total amount of dapsone consumed by the man in the initial illness was 75 mg.
On the following day (day 1), he was admitted to 8 Field Ambulance where he was
Cases diagnosed as having an acute upper respiratory tract infection and given an injection of
A24-year-old man commenced taking routine antimalarial drugs, paludrine and dapsone, penicillin. On day 2, he was still febrile, his pharynx had become ulcerated and his left thumb
the latter at a dosage of 25 mg per day. Two weeks later he commenced his 'Return-to acutely infected. Erythromycin was given. Blood examination revealed a profound
Australia' course of chloroquine and primaquine; he continued to take paludrine and neutropenia, with 1,000 white cells per mm3 (normal: 4,300--10,000) and 60 neutrophils per
3
dapsone. mm (normal: 1,200--8,150). Wound and blood cultures on day 3 both grew Pseudomonas
8 9
278 279
The Devirs Rainbow Appendix 4
pyocyanea (contemporary nomenclature). On day 4, his bone marrow showed Case 10
granulopoietic hypoplasia with maturation arrest at the myelocytic stage. A man, who had served in Vietnam for 12 months, took 25 mg of dapsone daily for the last
three months of his tour, adding to a total of 1,825 mg of the drug.
With continuing antibiotic therapy, the patient's temperature at first fell and his white blood
cell count started to rise. However, despite the continuing treatment with antibiotics, the At his final medical board in Australia prior to discharge from the Army, he was referred for
white cell count again fell on day 10 and, on day 13, the patient's temperature rose once admission and investigation to 1 Military Hospital in Brisbane.
more. He was admitted to hospital in Australia on day 17. A blood examination at this time On admission (day 1), two months after return to Australia, it was observed that he was very
revealed a white cell count of 1,000 per mm3. He was diagnosed as having agranulocytosis pale and had multiple spontaneous bruises, which he said he had first noticed six months
and, on the basis of the earlier blood culture, septicaemia. previously in Vietnam. He had no history of any serious illness or disability prior to his
The thumb wound healed. By day 26 the white cell count was 20,000 per mm3, and an Vietnam service. There was no family history of bruising or other blood dyscrasia. In
eosinophilia became apparent by day 28. Bone marrow aspirate on that day was normal, Vietnam, he had suffered a mild attack of tonsillitis which had been treated with aspirin. He
except for an increase in eosinophil precursors. Ova of Necator american us were found in the may have suffered a second attack of tonsillitis, accompanied by mouth ulcers one month
faeces; two courses of thiabendazole were administered. The patient was discharged from later, two months before his return. He considered that he had first become vaguely aware at
hospital on day 44. this time of general weakness, lethargy and dyspnoea on exertion. Apart from this and a
circumcision operation, he had been well in Vietnam, except that his vision had been 'playing
lt was considered that dapsone was by far the most likely cause of the agranulocytosis, up'. The only medication he had taken in Vietnam, other than dapsone, consisted of
although phenacetin, contained in the codeine tablets the man had taken, could not be paludrine at a dosage of 200 mg per day, some aspirin and the 'Return-to-Australia' course of
entirely ruled out. chloroquine and primaquine.
The man's total consumption of dapsone was approximately 1,375 mg. Blood tests were carried out on day 1. These revealed a white blood cell count of 5,400 per
3
mm (normal: 4,300-10,000), a haematocrit of 20% (normal: 42-52%) and a haemoglobin level
CaseS
of 6.7 g per 100 rnl (normal: 14-18). A platelet count on day 2 was 8,000 (normal: 140,000-
A report on this case, and on Case 9 (below), was published by Smithurst et al. in 1971. 440,000). By day 5, his white blood cell count had dropped to 2,600 per mm3 and his
A 21-year-old man commenced taking 25 mg of dapsone per day for malaria prophylaxis haemoglobin to 6.3 g. The blood tests indicated a marked deficiency of both red and white
four days after arrival in Vietnam. blood cells and of platelets. A bone marrow biopsy on day 13 showed that both the
erythropoietic and granulopoietic tissue were almost acellular. As a result of these tests and
Six weeks later (day 1), he was admitted to 8 Field Ambulance with an acutely sore throat clinical observations, the man was provisionally diagnosed as suffering from idiopathic
due to acute pharyngitis and a temperature of 37.8°C. Despite treatment, his condition aplastic anaemia. All other tests and investigations over the ensuing months confirmed this
deteriorated and he was admitted to 1AFH on day 3. Blood examination showed a white diagnosis.
blood cell count of 200 per mm3.
Treatment initially comprised top-up blood transfusions for anaemia and antibiotics to
The man was diagnosed as having probable drug-induced agranulocytosis complicated by prevent or control infections. He was also treated with courses of prednisone, oxymethalone,
Gram-negative septicaemia. The only two drugs he had taken in the previous 12 months thyroxine and vitamin injections in combination. These produced no clinical improvement,
were dapsone and paludrine. Of the two, only dapsone had been associated with and the man's condition gradually deteriorated. Four months after admission, mini exchange
agranulocytosis and it was therefore regarded as the likely cause. The amount of dapsone transfusions of fresh whole blood or platelet-rich concentrate were commenced, initially at a
consumed was 1,275 mg. rate of twice a week. However, the man produced antibodies to transfused platelets very
The following year, the man saw a dermatologist about his hair falling out. The quickly, and two months later it was estimated that the life of transfused platelets was less
than 24 hours.
dermatologist considered that the condition was drug induced, presumably by dapsone, and
prescribed no treatment. The outcome of this episode is not recorded. He developed multiple skin, oral and pharyngeal infections and had episodes of bleeding
into gut, joints, urinary tract, brain and lungs. Six months after admission, he developed a
Case 9 severe chest infection which could not be controlled with antibiotics in large doses. His
A 26-year-old man commenced taking 25 mg of dapsone per day for malaria prophylaxis condition deteriorated over the following weeks, with the episodes of bleeding continuing.
immediately on arrival in Vietnam. Six weeks later (day 1), he presented to 8 Field Daily mini exchange transfusions provided only temporary alleviation. His condition
Ambulance, complaining of a sore throat. A blood examination revealed a white blood cell deteriorated rapidly and he died after a massive mediastinal haemorrhage.
count of 1,800 per mm3 (normal: 4,300-10,000), with 10% neutrophils (normal: 25-83%). The Autopsy confirmed bronchopneumonia of the left lung. Examination of the bone marrow
proportion of neutrophils continued to fall until day 3, when it reached nil. From this time showed that it was almost completely aplastic and was being replaced by adipose tissue.
until day 14, peripheral blood examinations showed no cells of the myeloid series. The only
The specific cause of the man's aplastic anaemia was never identified. Nevertheless, there
drugs the man had taken in the previous 12 months were dapsone, paludrine and an
was a suspicion that dapsone was a contributing factor.
occasional aspirin. It was considered that his agranulocytosis had been caused by dapsone.
His consumption of dapsone amounted to 1,225 mg. Possible other cases
Examination of his service medical records to 1990 revealed that this man had suffered no Two other unnamed soldiers with 'significant haemolytic anaemia' were seen by the
occurrences of cancer or any other long-term effects of his toxic reaction episode. Consultant Physician sometime in the period 4 December 1968 to 26 February 1969, almost
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The De vii's Rainbow Appendix 4
certainly in December. His interpretation of these cases was that 'There was no evidence to Message PA 13800, Austforce Vietnam to List C, 29 Dec 1968, 1ATF 515/1/3, AWM.
suggest that the anaemia resulted from heavy parasitaemia with malaria. There was a
Minute, Col DC Cowling to Brig AP Hanway, 'Haemolytic Anaemia', 30 Jan 1969, 1AFH
possibility that the haemolysis resulted from the potentiation of primaquine's haemolytic R523/7 /1, AWM.
tendency by regular dapsone'.
'Worksheet No. 206: All Notifiable Casualties in Australia and Overseas from 1200 hrs
The Consultant Pathologist challenged this interpretation of the cases of haemolytic anaemia:
5 Jun 70 to 1200 hrs 12 Jun 70', p.3, DAHS 4057/13.
'The case reports in the memo ... give no indication of the degree of persistence of
parasitisation of red cells, and there is nothing to indicate that the haemolysis was in any way Minute, Gp Capt HJ Hardy to DGMS RAAF, 10 Jan 1969, Dept Air 652/14/4 pt 2; 'Sun
related to anything but having malaria, or that drugs were necessarily the cause'. Herald', 22 Dec 1968; minute, DPA to Branch Secretary, Clipping from 'Sun Herald' of 22 Dec
68; 23 Dec 1968; minute, PLO to file, 'Press Item Malaria 'Sun Herald' of 22 Dec 68, 27 Dec
Other follow-up 1968, Dept Army 515/R4/8, DAHS.
None of the nine surviving servicemen was recorded in the National Cancer Statistics Minute, Lt Col WJ Watson to DGMS, 'Haemolytic Anaemia', 27 Dec 1968, 1AFH R523/7 /1,
Clearing House in December 1993. All were then on the latest publicly available electoral AWM.
rolls for the last State or Territory of residence known to the Department of Veterans' Affairs.
Col RD Rothfield, 'Pathology Department 1 Aust Fd Hosp Report for period Dec 70-Feb 71
inc!', 1 Mar 1971, p.2 and Annex A, Dept Army 526/M1/12, DAHS.
Discussion
Message, Aust Arm Singapore to Aust Force Vietnam, 20 Apr 1968, HQ AFV R515/1/1,
Because of the very small number of cases, statistical power is very low and no statistical AWM.
analysis has been attempted. However, no cases of cancer were identified in those who had
adverse reactions. The thoroughness of the search for possible cases of toxic reactions to
dapsone in Australian service personnel makes it likely that all such reactions, other than
methaemoglobinaemia, have been included. Some of those included (for example case 5)
have revealed other explanations for the illnesses and are unlikely to be adverse reactions to
dapsone.
References
Australian Institute of Health and Welfare. Dapsone exposure, Vietnam service, and cancer
incidence. Canberra: AIHW, 1992.
Smithurst BA, Robertson I, Naughton MA. Dapsone-induced agranulocytosis complicated
by Gram-negative septicaemia. Med J Aust 1971; 1: 537.
Stickland JF, Hurdle ADF. Agranulocytosis probably due to Dapsone in an infantry soldier.
Med J Aust 1970; 1: 959.
Other reference material examined
(In this list the details identifying cases have been suppressed.)
Lt Col RJ Kennedy, 'Aplastic Anaemia: case 10' February 1970, ADMS HQ AFV 515/1/15
(med), DAHS.
Report, Maj Dowling to DGMS, 'Agranulocytosis Survey: case 9' 9 Apr 1970, ADMS HQ AFV
515/1/15 (med), DAHS; 1AFH R515/1/4, AWM.
Signal, Army Melbourne to Austforce Vietnam, 11 Feb 1970, ADMS HQ AFV 515/1/8 (med),
DAHS.
Maj Gen CM Gumer, 'Notification of Diseases', 12 Sep 1969, ADMS HQ AFV 515/1/8 (med),
DAHS.
Minute, Maj B Daniel to Lt Col RN Hurley,' Case 4', 21 Nov 1968, HQ AFV R515/1/9 vol. 1,
AWM.
Minute, Lt Col A Kerr Grant to Lt Col RN Hurley, 'Haemolytic Anaemia patients in 1 Aust Fd
Hosp', 12 Dec 1968, 1AFH R523/7 /1, AWM.
Lt Col A Kerr Grant, 'Physicians Report Dec 68-Mar 69', 28 Feb 1969, p.2, Dept Army 723/4/
2,DAHS.
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