- Email: [email protected]
CHLOROQUINE-RESISTANT PLASMODIUM FALCIPARUM IN AFRICA
1374 SERUM-IMMUNOGLOBULINS IN CHILD ADMITTED WITH INTRACTABLE DIARRHEA CONTRACTED ON VISIT TO
..=not
PUNJAB
detectable.
maternal IgG had waned. If his deficiency is acquired, is it possible that his traveller’s diarrhoea, associated with severe smallintestinal enteropathy, has permanently affected his humoral immunity? If so, this would have considerable implication for the cycle of chronic diarrhoea and malnutrition in the developing world. Although the number of children is small, they were all well in Britain and rapidly became severely ill on travelling to their ancestral homeland. The risks of such travel for children, particularly for infants, should be carefully considered by parents when they plan such a journey. Careful investigation of such children may give us useful insights into the interrelationship between chronic diarrhoea and malnutrition of relevance to the developing world. PAUL HUTCHINS PRAVIN HINDOCHA ALAN PHILLIPS Elizabeth for Children, Hospital Queen JOHN WALKER-SMITH London E2 8PS
vomited bright red blood before reaching hospital. The child had laboured breathing. The respiratory rate was 35/min but there was no cyanosis or anaemia. He was afebrile. Throat examination did not reveal any abnormality except that the mucosa was coated with blood, but no active bleeding site was visible. The child was coughing and retching and vomited blood with clots three times after admission. Systemic examination was non-contributory. The speech was normal and the child denied inhaling a foreign body. About 6 h after admission, he had a severe bout of retching and vomited out the 6-7 cm headless body of a leech engorged with blood. The child became comfortable and no further bleeding occurred after expulsion of the leech. The head of the leech could not be identified in the throat or larynx on re-examination. The family came from Pule Khumri, a village about 100 km north of Kabul. The boy’s father told us that the source of water in the village is a pond which is heavily infested with leeches. Leech infestation is rampant in the Badghis Province of north-west Afghanistan, and medical problems with live foreign bodies are not uncommon. In Afghanistan water is often drunk straight from ponds and wayside drainage nallahs which are loaded with visible and invisible hazards to human
health. Institute of Child Health,
Kabul, Afghanistan
MEHARBAN SINGH AHMAD FARID NAIM
Nations agencies have made clean water supplies <’priority United programme for the 1980s.-ED. L.
a
CHLOROQUINE-RESISTANT PLASMODIUM FALCIPARUM IN AFRICA
CHEMICAL PERITONITIS AFTER CETRIMIDE WASHOUT IN HYDATID-CYST SURGERY
°
SiR,—Ihave come across a problem with the use of cetrimide 5% injection of cysts, with 0.5% as a peritoneal washout, during surgery on hydatid cysts. I have been working for the African Medical and Research Foundation’s Hydatid Project for 4 iyears and do an average of 80 laparotomies for hydatid cysts each year. 5% cetrimide is used, calculated as a dilution in the cysts, which often measure 3 litres, and in one case measured 9 litres. On three occasions sterile chemical peritonitis with massive adhesions and obstruction have developed postoperatively. One young child twice required surgery for small-bowel obstruction; the adhesions affected practically all the small and large bowel. No deaths resulted. However, follow-up of patients in the vast areas inhabited by nomadic peoples makes scolicidal cetrimide a questionable technique since the longterm effects cannot be known. The use of scolicidal fluids seem to be more problematic than effective as judged from recurrence rates. The proper surgical treatment of hydatidosis will need to include an oral medication rather than one of the many scolicidal fluids that have been tried and found insufficient or dangerous. Mebendazole is certainly scolicidal and is a promising agent, provided it is safe. East African Flying Doctor Services, African Medical Research Foundation, Wilson Airport, PO Box 30125, Nairobi, Kenya
DONALD S. GILCHRIST
RESPIRATORY OBSTRUCTION AND HÆMATEMESIS DUE TO LEECH
SiR,-—A 3-year-old boy was brought to the emergency department of the Institute of Child Health, Kabul, with cough, dyspnoea, and haematemesis of 6 h duration. The symptoms developed suddenly in this previously healthy child who
SIR,-The paper by Dr Campbell and colleagues (Dec. 1, p. 1115) is the first fully substantiated report on the presence in Africa of strains of Plasmodium falciparum resistant to chloroquine. As Campbell et al. point out none of the previous similar observations has been confirmed in the same way, by clinical follow-up, induced infection of Aotus monkeys, and testing of the in-vitro culture. This study commands much attention, since it endorses our oft-expressed fear that resistance to 4-aminoquinolines, hitherto the most reliable compounds, may sooner or later appear in Africa. Despite the chilling implications of this report one should perhaps keep a sense of proportion about the present practice of prevention and treatment of malaria not only in Africa but also of cases imported into Europe and other parts of the temperate world.
The patient infected in Tanzania took no preventive antimalarials during his stay there; not surprisingly the disease developed on his return to the U.S.A. One might argue that even if he had been on a proper prophylactic regimen during his visit to Africa and for one month afterwards, the infection by the resistant strain would have still "broken through" the drug cover. This may be so but remains to be proven. The presence of this indicator case of chloroquine resistance does not mean that such strains are prevalent in many parts of Africa. On the contrary, there is good evidence that the two 4-aminoquinolines (chloroquine and amodiaquine) are still excellent suppressive and therapeutic compounds over vast areas of the African continent. It would be tragic to see a panicky stampede away from these drugs in favour of many other compounds to which resistance of P. falciparum exists, although its degree and distribution are little known because of the absence of detailed surveys and lack of suitable testing methods. No other drug generally available can compete with chloroquine’s suppressive and therapeutic effects against all species of plasmodia. Proguanil and pyrimethamine or a combination of sulfone with pyrimethamine, while useful prophylactics in some areas, are not suitable for treatment. Other drug combinations, such as sulfadoxine with pyrimethamine, while ac-
1375 of chloroquine-resistant falciparum inyet proved to be suitable for long-term prophylaxis and are of limited value for prevention and treatment of vivax malaria. There is no ideal antimalarial drug for all areas and all circumstances. Nevertheless, several current drugs may give a reasonable degree of protection and a good chance of rapid and complete cure of malaria. Together with quinine-"the old faithful" drug of renewed therapeutic usefulness-chloroquine has proved its great value. The appearance in Africa of a strain of falciparum malaria with a degree of resistance to this compound must not be interpreted as an excuse for its
ceptable for fections,
treatment
are
not
rejection. Wellcome Museum of Medical 183 Euston Road, London NW1 2BP
Science, L.
London School of Hygiene and Tropical Medicine, London WC1
J. BRUCE-CHWATT
WALLACE PETERS
DIATOMS IN LUNG TISSUE
SIR,-Dr Watson and Dr Oliver (Oct. 27,
p. 913) describe technique for isolating diatoms from lung tissue. However, drowning as a cause of death cannot be proved by the demonstration of unicellular algse (diatoms) in the lungs. Diatomaceous earth or kieselguhr deposits are formed by the sedimentation of dead diatoms from water. Large deposits have been found in Europe, the U.S.A., and Australia. Diatomaceous earth consists mainly of amorphous silica, which has high chemical and thermal resistance, properties which have led to widespread use of this product for insulation, as an absorbent for chemicals, as a carrier of catalysts, in filters, and as an additive to cement, paints, paper, asphalt, rubber, and other products. People will be exposed through mining, production, and application of diatomaceous earth, and particles (algae fragments) may be deposited in the lungs. These small respirable particles could penetrate into the lung alveoli where phagocytosis occurs. Moreover, the general population will also be exposed as consumer products are eroded or broken up. Water drinking may be another route of exposure, and transportation of particles through the lymphatic vessels may occur. Analysis of inorganic particles in lung tissue’ can be performed by low-temperature plasma ashing for degradation of dried tissue, and the ash can be analysed by scanning electronmicroscopy and energy dispersive X-ray spectrometry. When analysing lung tissue from occupationally exposed and non-exposed persons, we have often found diatomaceous earth fragments. a new
B. GYLSETH G. MOWÉ
Institute of Occupational Health, P.O. Box 8149, Oslo 1, Norway
** This letter has been shown lows.-ED. L.
to Dr
Watson, whose reply fol-
SIR,-During the past few years several methods of diagnosing death from drowning have been elaborated but the efficacy of any method depends largely on the interval between death and necropsy; if the body has been in the water for a long time such methods become unreliable. Where decomposition is advanced the diatom test can help considerably with the diagnosis. The principle is simple; diatoms are carried by the water into the alveoli of the lungs and in the living person travel to various organs and tissues. There are two major criticisms of the diatom test, and these are fully recognised by all workers in forensic pathology. First, in some fatal drownings no diatoms are found in any organ 1.
or
tissue. One wonders whether the
cause
of death
was
Gylseth B, Ophus EM, Mowé G. Determination of inorganic fibre density in human lung tissue by scanning electron microscopy after low temperature ashing. Scand J Work Environ Health 1979; 5: 151-57.
due to reflex cardiac arrest on immersion in water. Frequently the time of the year when the tests were done is not given, and there are periods when the population of diatoms is decreased and water may be almost devoid of them. Also, the amount of water inhaled is often insufficient to provide the evidence. Clearly there is a relationship between the volume of water inhaled and the concentration of the diatoms. This is an area that requires further research. The second criticism is that diatoms have been found in organs of persons who have died from causes other than drowning.’ There are three explanations for this. First, a large number of diatoms are ingested with unprepared foods, especially raw foods and shellfish. Some diatoms could leave the gut and enter the body. A second reason is, as suggested by the Oslo workers, that an increasing amount of diatomaceous earth has been imported and used, for example, for lagging pipes, furnaces, and refrigerators or for soundproofing telephone booths. A third source is a diatom-containing dusting powder. It would therefore not be surprising to find diatoms in several of the organs of the body. The diatom test is only valid if it can be shown that the species recovered from the drowned person is also present in the water in which the drowning took place and that diatoms in . the water are present in reasonable numbers. Where possible samples of water and samples from the lungs should be matched. All species of diatoms in the pathological specimen other than those seen at the site where the drowning took place should be ignored; when this is done the diatom test will be on a firm scientific basis and can face the criticisms such as those suggested by the Oslo workers. Department of Forensic and Science, University of Glasgow, Glasgow G12 8QQ
Medicine
ALAN A. WATSON
WHY BLAME CHOLESTEROL?
SIR,-Sir John McMichael (Dec.1,
p. 1182), in his latest articleto reference the following statement: "the elevated cholesterol levels of myxaedema and nephrosis are not associated with increased coronary disease, even when the nephrosis becomes complicated by hypertension at a later stage". I hope that his other attributions are more accurate, for what our study undoubtedly showed was that, in relation to other causes of death (in particular renal failure), ischsemic heart-disease is a trivial risk in patients with the nephrotic syndrome. We did not find any difference in IHD mortality rates between the patients and the general population, but could not definitely exclude the possibility of differences given the numbers studied-the nephrotic syndrome is not common. Furthermore the duration of observation was limited. As for Sir John’s confident statement about myxoedema, an association with atherosclerosis was noted as long ago as 19243 and has been confirmed.4 Furthermore, a prospective study has demonstrated that, in men, thyroid autoantibodies indicate an increased risk of coronary heart disease.5 The mechanisms may be disputed, but the link with thyroid disease is clear.
essay in
cholesterophilia,
uses our
Department of Community Medicine, Guy’s Hospital Medical School,
R.
London SE1 9RT
1.
Hendry
NI. The
diagnostic
value of diatoms in
cases
of
J. JARRETT
drowning.
Med Sci
Law
1973; 13: 23-34. 2. Wass VJ, Jarrett RJ, Chilvers C, Cameron JS. Does the nephrotic syndrome increase the risk of cardiovascular disease? Lancet 1979; ii: 664-67. 3. Fishberg AM. Arteriosclerosis in thyroid deficiency. JAMA 1924; 82: 463-65. 4. Vanhaelst L, Neve P, Chailly P, Bastenie PA. Coronary artery disease in hypothyroidism. Lancet 1967; ii: 800-02. 5. Bastenie PA, Vanhaelst L, Golstein J, Smets P, Keys A, Karvonen MJ, Punsar S. Asymptomatic auto-immune thyroiditis and coronary heart disease. Lancet 1977; ii: 155-58.
..=not
PUNJAB
detectable.
maternal IgG had waned. If his deficiency is acquired, is it possible that his traveller’s diarrhoea, associated with severe smallintestinal enteropathy, has permanently affected his humoral immunity? If so, this would have considerable implication for the cycle of chronic diarrhoea and malnutrition in the developing world. Although the number of children is small, they were all well in Britain and rapidly became severely ill on travelling to their ancestral homeland. The risks of such travel for children, particularly for infants, should be carefully considered by parents when they plan such a journey. Careful investigation of such children may give us useful insights into the interrelationship between chronic diarrhoea and malnutrition of relevance to the developing world. PAUL HUTCHINS PRAVIN HINDOCHA ALAN PHILLIPS Elizabeth for Children, Hospital Queen JOHN WALKER-SMITH London E2 8PS
vomited bright red blood before reaching hospital. The child had laboured breathing. The respiratory rate was 35/min but there was no cyanosis or anaemia. He was afebrile. Throat examination did not reveal any abnormality except that the mucosa was coated with blood, but no active bleeding site was visible. The child was coughing and retching and vomited blood with clots three times after admission. Systemic examination was non-contributory. The speech was normal and the child denied inhaling a foreign body. About 6 h after admission, he had a severe bout of retching and vomited out the 6-7 cm headless body of a leech engorged with blood. The child became comfortable and no further bleeding occurred after expulsion of the leech. The head of the leech could not be identified in the throat or larynx on re-examination. The family came from Pule Khumri, a village about 100 km north of Kabul. The boy’s father told us that the source of water in the village is a pond which is heavily infested with leeches. Leech infestation is rampant in the Badghis Province of north-west Afghanistan, and medical problems with live foreign bodies are not uncommon. In Afghanistan water is often drunk straight from ponds and wayside drainage nallahs which are loaded with visible and invisible hazards to human
health. Institute of Child Health,
Kabul, Afghanistan
MEHARBAN SINGH AHMAD FARID NAIM
Nations agencies have made clean water supplies <’priority United programme for the 1980s.-ED. L.
a
CHLOROQUINE-RESISTANT PLASMODIUM FALCIPARUM IN AFRICA
CHEMICAL PERITONITIS AFTER CETRIMIDE WASHOUT IN HYDATID-CYST SURGERY
°
SiR,—Ihave come across a problem with the use of cetrimide 5% injection of cysts, with 0.5% as a peritoneal washout, during surgery on hydatid cysts. I have been working for the African Medical and Research Foundation’s Hydatid Project for 4 iyears and do an average of 80 laparotomies for hydatid cysts each year. 5% cetrimide is used, calculated as a dilution in the cysts, which often measure 3 litres, and in one case measured 9 litres. On three occasions sterile chemical peritonitis with massive adhesions and obstruction have developed postoperatively. One young child twice required surgery for small-bowel obstruction; the adhesions affected practically all the small and large bowel. No deaths resulted. However, follow-up of patients in the vast areas inhabited by nomadic peoples makes scolicidal cetrimide a questionable technique since the longterm effects cannot be known. The use of scolicidal fluids seem to be more problematic than effective as judged from recurrence rates. The proper surgical treatment of hydatidosis will need to include an oral medication rather than one of the many scolicidal fluids that have been tried and found insufficient or dangerous. Mebendazole is certainly scolicidal and is a promising agent, provided it is safe. East African Flying Doctor Services, African Medical Research Foundation, Wilson Airport, PO Box 30125, Nairobi, Kenya
DONALD S. GILCHRIST
RESPIRATORY OBSTRUCTION AND HÆMATEMESIS DUE TO LEECH
SiR,-—A 3-year-old boy was brought to the emergency department of the Institute of Child Health, Kabul, with cough, dyspnoea, and haematemesis of 6 h duration. The symptoms developed suddenly in this previously healthy child who
SIR,-The paper by Dr Campbell and colleagues (Dec. 1, p. 1115) is the first fully substantiated report on the presence in Africa of strains of Plasmodium falciparum resistant to chloroquine. As Campbell et al. point out none of the previous similar observations has been confirmed in the same way, by clinical follow-up, induced infection of Aotus monkeys, and testing of the in-vitro culture. This study commands much attention, since it endorses our oft-expressed fear that resistance to 4-aminoquinolines, hitherto the most reliable compounds, may sooner or later appear in Africa. Despite the chilling implications of this report one should perhaps keep a sense of proportion about the present practice of prevention and treatment of malaria not only in Africa but also of cases imported into Europe and other parts of the temperate world.
The patient infected in Tanzania took no preventive antimalarials during his stay there; not surprisingly the disease developed on his return to the U.S.A. One might argue that even if he had been on a proper prophylactic regimen during his visit to Africa and for one month afterwards, the infection by the resistant strain would have still "broken through" the drug cover. This may be so but remains to be proven. The presence of this indicator case of chloroquine resistance does not mean that such strains are prevalent in many parts of Africa. On the contrary, there is good evidence that the two 4-aminoquinolines (chloroquine and amodiaquine) are still excellent suppressive and therapeutic compounds over vast areas of the African continent. It would be tragic to see a panicky stampede away from these drugs in favour of many other compounds to which resistance of P. falciparum exists, although its degree and distribution are little known because of the absence of detailed surveys and lack of suitable testing methods. No other drug generally available can compete with chloroquine’s suppressive and therapeutic effects against all species of plasmodia. Proguanil and pyrimethamine or a combination of sulfone with pyrimethamine, while useful prophylactics in some areas, are not suitable for treatment. Other drug combinations, such as sulfadoxine with pyrimethamine, while ac-
1375 of chloroquine-resistant falciparum inyet proved to be suitable for long-term prophylaxis and are of limited value for prevention and treatment of vivax malaria. There is no ideal antimalarial drug for all areas and all circumstances. Nevertheless, several current drugs may give a reasonable degree of protection and a good chance of rapid and complete cure of malaria. Together with quinine-"the old faithful" drug of renewed therapeutic usefulness-chloroquine has proved its great value. The appearance in Africa of a strain of falciparum malaria with a degree of resistance to this compound must not be interpreted as an excuse for its
ceptable for fections,
treatment
are
not
rejection. Wellcome Museum of Medical 183 Euston Road, London NW1 2BP
Science, L.
London School of Hygiene and Tropical Medicine, London WC1
J. BRUCE-CHWATT
WALLACE PETERS
DIATOMS IN LUNG TISSUE
SIR,-Dr Watson and Dr Oliver (Oct. 27,
p. 913) describe technique for isolating diatoms from lung tissue. However, drowning as a cause of death cannot be proved by the demonstration of unicellular algse (diatoms) in the lungs. Diatomaceous earth or kieselguhr deposits are formed by the sedimentation of dead diatoms from water. Large deposits have been found in Europe, the U.S.A., and Australia. Diatomaceous earth consists mainly of amorphous silica, which has high chemical and thermal resistance, properties which have led to widespread use of this product for insulation, as an absorbent for chemicals, as a carrier of catalysts, in filters, and as an additive to cement, paints, paper, asphalt, rubber, and other products. People will be exposed through mining, production, and application of diatomaceous earth, and particles (algae fragments) may be deposited in the lungs. These small respirable particles could penetrate into the lung alveoli where phagocytosis occurs. Moreover, the general population will also be exposed as consumer products are eroded or broken up. Water drinking may be another route of exposure, and transportation of particles through the lymphatic vessels may occur. Analysis of inorganic particles in lung tissue’ can be performed by low-temperature plasma ashing for degradation of dried tissue, and the ash can be analysed by scanning electronmicroscopy and energy dispersive X-ray spectrometry. When analysing lung tissue from occupationally exposed and non-exposed persons, we have often found diatomaceous earth fragments. a new
B. GYLSETH G. MOWÉ
Institute of Occupational Health, P.O. Box 8149, Oslo 1, Norway
** This letter has been shown lows.-ED. L.
to Dr
Watson, whose reply fol-
SIR,-During the past few years several methods of diagnosing death from drowning have been elaborated but the efficacy of any method depends largely on the interval between death and necropsy; if the body has been in the water for a long time such methods become unreliable. Where decomposition is advanced the diatom test can help considerably with the diagnosis. The principle is simple; diatoms are carried by the water into the alveoli of the lungs and in the living person travel to various organs and tissues. There are two major criticisms of the diatom test, and these are fully recognised by all workers in forensic pathology. First, in some fatal drownings no diatoms are found in any organ 1.
or
tissue. One wonders whether the
cause
of death
was
Gylseth B, Ophus EM, Mowé G. Determination of inorganic fibre density in human lung tissue by scanning electron microscopy after low temperature ashing. Scand J Work Environ Health 1979; 5: 151-57.
due to reflex cardiac arrest on immersion in water. Frequently the time of the year when the tests were done is not given, and there are periods when the population of diatoms is decreased and water may be almost devoid of them. Also, the amount of water inhaled is often insufficient to provide the evidence. Clearly there is a relationship between the volume of water inhaled and the concentration of the diatoms. This is an area that requires further research. The second criticism is that diatoms have been found in organs of persons who have died from causes other than drowning.’ There are three explanations for this. First, a large number of diatoms are ingested with unprepared foods, especially raw foods and shellfish. Some diatoms could leave the gut and enter the body. A second reason is, as suggested by the Oslo workers, that an increasing amount of diatomaceous earth has been imported and used, for example, for lagging pipes, furnaces, and refrigerators or for soundproofing telephone booths. A third source is a diatom-containing dusting powder. It would therefore not be surprising to find diatoms in several of the organs of the body. The diatom test is only valid if it can be shown that the species recovered from the drowned person is also present in the water in which the drowning took place and that diatoms in . the water are present in reasonable numbers. Where possible samples of water and samples from the lungs should be matched. All species of diatoms in the pathological specimen other than those seen at the site where the drowning took place should be ignored; when this is done the diatom test will be on a firm scientific basis and can face the criticisms such as those suggested by the Oslo workers. Department of Forensic and Science, University of Glasgow, Glasgow G12 8QQ
Medicine
ALAN A. WATSON
WHY BLAME CHOLESTEROL?
SIR,-Sir John McMichael (Dec.1,
p. 1182), in his latest articleto reference the following statement: "the elevated cholesterol levels of myxaedema and nephrosis are not associated with increased coronary disease, even when the nephrosis becomes complicated by hypertension at a later stage". I hope that his other attributions are more accurate, for what our study undoubtedly showed was that, in relation to other causes of death (in particular renal failure), ischsemic heart-disease is a trivial risk in patients with the nephrotic syndrome. We did not find any difference in IHD mortality rates between the patients and the general population, but could not definitely exclude the possibility of differences given the numbers studied-the nephrotic syndrome is not common. Furthermore the duration of observation was limited. As for Sir John’s confident statement about myxoedema, an association with atherosclerosis was noted as long ago as 19243 and has been confirmed.4 Furthermore, a prospective study has demonstrated that, in men, thyroid autoantibodies indicate an increased risk of coronary heart disease.5 The mechanisms may be disputed, but the link with thyroid disease is clear.
essay in
cholesterophilia,
uses our
Department of Community Medicine, Guy’s Hospital Medical School,
R.
London SE1 9RT
1.
Hendry
NI. The
diagnostic
value of diatoms in
cases
of
J. JARRETT
drowning.
Med Sci
Law
1973; 13: 23-34. 2. Wass VJ, Jarrett RJ, Chilvers C, Cameron JS. Does the nephrotic syndrome increase the risk of cardiovascular disease? Lancet 1979; ii: 664-67. 3. Fishberg AM. Arteriosclerosis in thyroid deficiency. JAMA 1924; 82: 463-65. 4. Vanhaelst L, Neve P, Chailly P, Bastenie PA. Coronary artery disease in hypothyroidism. Lancet 1967; ii: 800-02. 5. Bastenie PA, Vanhaelst L, Golstein J, Smets P, Keys A, Karvonen MJ, Punsar S. Asymptomatic auto-immune thyroiditis and coronary heart disease. Lancet 1977; ii: 155-58.