120
MALARIA ATTACK RATES IN BRITISH RESIDENTS RETURNING FROM PRINCIPAL MALARIOUS COUNTRIES OF EAST AND WEST AFRICA, 1986-88
Trav travellers. RR = relative risk-attack rate 1988/attack rate 1986, shown with 95% confidence hmrts. Source travel statistics from OPCS and Department of Employment, malaria statistics from the Malaria Reference =
P falciparum from Ghana claiming to have taken chloroquine and proguanil has risen (from 2 to 21), as has the proportion of all cases (from 5% to 19%). This rise may be attributable to wider use of this chemoprophylactic combination. The number of cases taking no prophylaxis has also increased from 26 to 59, although the proportion of all cases fell from 60% to 45%. We cannot identify from the data the reason for the increasing frequency of infection in groups such as immigrants visiting relatives, who seldom take chemoprophylaxis. Has transmission of P falciparum increased in association with the spread of chloroquine resistance? Irrespective of the cause, these data strongly indicate that the risk of acquiring malaria in West Africa has increased greatly, and that this is likely to continue with the advancement of chloroquine-resistant P falciparum in West Africa. Travellers and their medical advisers should be aware of this. Hospital for Tropical Diseases, London NW1 OPE, UK
P. A. PHILLIPS-HOWARD J. PORTER R. H. BEHRENS
PHLS Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine, London WC1
D.
Travel Clinic,
J. BRADLEY
Phillips-Howard PA, Bradley DJ, Blaze M, Hurn M. Malaria in Britain, 1977-1986 Br Med J 1988; 296: 245-48. 2. Bradley DJ. Changing pattern of malaria in Britain JR Soc Med 1989; 82 (suppl): 1.
8-13. 3 Peters W.
Chemotherapy and drug resistance in malaria. London: Academic Press,
1987.
Phillips-Howard PA, Breeze E, Lakin C, Bradley DJ
Short term travel to malarious malaria risk in UK travellers. Trav Med Intern 1988; 6: 51-60. 5. Phillips-Howard PA, Radalowicz A, Mitchell J, Bradley DJ. The risk of malaria in British residents returning from malarious areas. Br Med J (in press) 6. Lobel HO, Phillips-Howard PA, Brandling-Bennett AD, et al Malaria incidence and prevention in European and North American travellers to Kenya. Bull WHO (in 4.
areas:
press). JS, Bernard KW. The spread of chloroquine-resistant malaria JAMA 1989; 262: 245-48
7. Moran
in
Africa
Mefloquine failure in child contracting falciparum malaria in West Africa SIR,-A 6-year-old boy from Paris travelled overland to Morocco, Senegal, and the Ivory Coast with his parents in June, 1988. Two weeks before leaving France he was started on mefloquine prophylaxis 100 mg per week (4-35 mg;kg) and he had been on continuous prophylaxis for 4 weeks before he reached the malaria
Laboratory.
endemic
area of Senegal. The family reached the Ivory Coast in where August, they stayed in small villages, and the boy was exposed to mosquitoes. On Aug 31 the family returned to France and mefloquine was continued for 4 more weeks, the last dose being on Sept 24. At the end of October the child had a fever with chills and headache, and was admitted to hospital in Paris, where uncomplicated Plasmodium falciparum malaria with high-grade parasitaemia was diagnosed. An adult dose of mefloquine was given (750 mg, 500 mg, and 250 mg doses 8 h apart from a total dose of 65 mg/kg instead of 25 mg/kg). The fever resolved and a smear was negative for parasites within 48 h. 3 weeks later (Nov 17) the patient again had fever with chills, sweating, severe headache, and drowsiness. He was admitted to 1’Hopital Pitié-Salpêtrière. Except for pallor, the physical and neurological findings were essentially normal. He had 07% P falciparum trophozoites on a thick smear; a normal blood count except for a slighly increased white cell count at 11 270/µl; and slightly increased total bilirubin (25 rnmol/1). The malaria immunofluorescent titre 1800 and was antibody immunoelectrophoresis was positive (two arcs). Blood and urine cultures and blood tests ruled out other medical conditions. The child was put on quinine by infusion (150 mg every 6 h for 5 days or 25 mg/kg daily). The fever resolved in 3 days; the parasite count fell in 2 days and was negative by the 4th day. He was then given oral quinine (’Quinimax’) at the same dose for 5 days. The patient had no side-effects from this treatment and his parasite count remained negative at follow-up. In-vitro drug sensitivity tests to chloroquine, quinine, and mefloquine were done but parasite growth was uninterpretable. His plasma level of mefloquine at admission was 328 ng/ml, which could explain the partial inhibition of parasite growth in the drug
sensitivity tests. Despite an adequate plasma drug level (328 ng/ml more than 2 weeks after the last therapeutic dose), prophylactic and, subsequently, therapeutic use of mefloquine failed in this child. To our knowledge, this is the first case of in-vivo type I mefloquine resistance in a child with recurrent P falciparium malaria acquired in West Africa. In adults one case of induced infection in a volunteer with the Vietnam Smith strainl and a case of mefloquine-resistant malaria acquired in Tanzania2 have been reported. Elimination of mefloquine is slow, with a half-life in healthy adults of about 3 weeks,3but it is more rapid in children with acute malaria .4 It was unexpected for mefloquine-resistant malaria to be contracted in Senegal or the Ivory Coast, areas with low levels or no resistance to
121
chloroquine and where mefloquine has not yet been used. Selection by drug pressure in the host may have happened during the prolonged prophylaxis (more than 3 months) and during treatment. However, even if selection of a resistant strain did take place by drug pressure under subtherapeutic doses, we cannot overlook another factor that could compound drug pressure-namely, selection by "therapeutic escape". This case raised questions about prolonged prophylaxis, or treatment with the same drug afterwards, especially in areas where mefloquine has been little used. Department of Parasitology, Tropical Medicine, and Public Health, INSERM Unit 313; and Paediatrics Service,
Groupe Hoapitalier Pitié- Salpêtrière, 75651 Paris, France, and Department of Pharmacology,
INSERM Unit 13,
Groupe Hospitalier
Bichat-Claude Bernard,
Paris
F. GAY M. H. BINET M. D. G. BUSTOS B. ROUVEIX M. DANIS C. ROY M. GENTILINI
1. Cosgriff TM, Pamplin CL, Craig CJ, Willet GP. Mefloquine failure in a case of falciparum malaria induced with a multidrug resistant isolate m a non-immune subject Am JTrop Med Hyg 1985; 34: 692-93. 2 Bygbjerg IC, Schaptra A, Flachs H, Gomme G, Jepsen S. Mefloquine resistance of falciparum malaria from Tanzania enhanced by treatment. Lancet 1983; i: 774-75. 3 Schwartz DE, Eckert G, Hartmann D, et al. Single dose kinetics of mefloquine in man. Chemotherapy 1982; 28: 70-84. 4. White NJ Drug treatment and prevention of malaria Eur J Clin Pharmacol 1988; 34: 1-14.
Diagnosis of malaria during chloroquine/proguanil prophylaxis SIR,-With the emergence of chloroquine-resistant Plasmodium falciparum malaria in Africa’ recommendations on the most effective chemoprophylaxis for long-term travellers to such areas have changed and nowadays include weekly chloroquine plus daily proguanip,3 We have experienced diagnostic difficulty in ten patients presenting with symptoms highly suggestive of malaria (fever, chills, fatigue, headache, arthralgia, muscle pain) while on regular chloroquine/proguanil prophylaxis at the appropriate dosage (table). A thin blood film (May-Griinwald-Giemsa stain) was negative in all patients. Thick blood films (Giemsa) contained parasites but they were hardly recognisable, being severely altered and atypical in shape and structure, with very irregular nuclei and vacuoles. Parasite counts calculated by a standard technique on 100 microscope fields’ were very low for all patients, ranging from 4 to 150/u) (table). All patients completely recovered after the institution of antimalarial therapy, usually quinine and/or pyrimethamine plus sulphadoxine (’Fansidar’). Our laboratory technicians had great difficulty in recognising parasites in blood and with low parasite counts. This could result in dangerous delays in diagnosis and treatment in less experienced centres, where the clinical picture might be incorrectly ascribed to other frequent infections. We are unaware of previous reports of severely altered P falciparum morphology and very low parasite counts
in
cases
of failed
be instituted without
delay in patients whose clinical picture is
compatible with malaria but whose blood films are "negative". Laboratory Division OCEAC, BP 288, Yaounde, Cameroon
CLAUDE HENGY
c/o Israel Embassy, Yaounde
DAVID GOZAL
1. Lobel HO, Campbell CC. Malaria prophylaxis and distribution of drug resistance. Clin Trop Med Commun Dis 1986; 1: 225-42. 2. Cook GC. Prevention and treatment of malaria. Lancet 1988; i: 32-36. 3. Anon. Vaccination certificate requirements and health advice for international travel. Geneva: World Health Organisation, 1987: 45. 4. Payne D. Use and limitations of light microscopy for diagnosing malaria at the primary health care level. Bull WHO 1988; 66: 621-26.
Oilseed rape
as a
potent antigen
SIR,-Oilseed rape pollen has been blamed for hayfever, asthma, and allergic dermatitis, but we can find no scientific evidence for this apart from a patient with contact dermatitis provoked by mustard seed (Brassica nigra) antigens who reacted on patch testing to oilseed rape (B napus) also.’ The availability of European Community subsidies has led to an increase in the amount of oilseed rape that is grown in the UK. In Scotland the amount of land under this crop increased from 1600 hectares in 1982 to about 42 000 hectares in 1988. On Tayside the increase has been from nil to 6000 hectares or so, and in the countryside it is difficult to avoid contact with the plant. Our serological investigation of sensitisation to oilseed rape shows that the pollen of this crop is one of the most potent antigens described to date. The sera tested had been sent to the allergy testing laboratories serving predominantly urban Glasgow and more rural Tayside for routine IgE antibody testing by radioallergosorbent test (RAST) to common allergens. No requests specifically mentioned oilseed rape allergy. Sera were stored at - 20°C. The "routine" antigens were mixed grasses, Dermatophagoides pteronyssinus, cat and dog dander, and mixed foods; tests for oilseed rape and mixed moulds (Penicillium notatum, Cladosporium herbarum, Aspergillus fumigatus, and Alternaria alternata) were done in Dundee on both sets of sera. We tested for mixed moulds, because rape, after flowering, is cut and left in the fields for several weeks before harvesting, during which time it often becomes mouldy. We used Thadebas’ RAST kits (Pharmacia) and recorded the results as 0 for no sensitisation and 1-4 for mild, moderate, high, or very high sensitisation. Total IgE levels were assayed by ’Phadezym’ kits (Pharmacia). In Dundee, 175 sera submitted between May and September, 1988, were tested and compared with 141 sera from Glasgow which had been collected during February, June, and July, 1988. (February and September both lie outside the flowering season of oilseed rape.) A further 82 Dundee sera from November and December, 1988, were also studied. ’
combined
chloroquine/proguanil
chemoprophylaxis. We suggest that empirical antimalarial therapy CLINICAL PICTURE AND PARASITE COUNT -
-
Seroprevalence of sensitisation to oilseed moulds in Tayside and Glasgow.
rape and mixed
Mixed mould results for Tayside in June and September, 1988, 96% and 129%, respectively
were
MALARIA ATTACK RATES IN BRITISH RESIDENTS RETURNING FROM PRINCIPAL MALARIOUS COUNTRIES OF EAST AND WEST AFRICA, 1986-88
Trav travellers. RR = relative risk-attack rate 1988/attack rate 1986, shown with 95% confidence hmrts. Source travel statistics from OPCS and Department of Employment, malaria statistics from the Malaria Reference =
P falciparum from Ghana claiming to have taken chloroquine and proguanil has risen (from 2 to 21), as has the proportion of all cases (from 5% to 19%). This rise may be attributable to wider use of this chemoprophylactic combination. The number of cases taking no prophylaxis has also increased from 26 to 59, although the proportion of all cases fell from 60% to 45%. We cannot identify from the data the reason for the increasing frequency of infection in groups such as immigrants visiting relatives, who seldom take chemoprophylaxis. Has transmission of P falciparum increased in association with the spread of chloroquine resistance? Irrespective of the cause, these data strongly indicate that the risk of acquiring malaria in West Africa has increased greatly, and that this is likely to continue with the advancement of chloroquine-resistant P falciparum in West Africa. Travellers and their medical advisers should be aware of this. Hospital for Tropical Diseases, London NW1 OPE, UK
P. A. PHILLIPS-HOWARD J. PORTER R. H. BEHRENS
PHLS Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine, London WC1
D.
Travel Clinic,
J. BRADLEY
Phillips-Howard PA, Bradley DJ, Blaze M, Hurn M. Malaria in Britain, 1977-1986 Br Med J 1988; 296: 245-48. 2. Bradley DJ. Changing pattern of malaria in Britain JR Soc Med 1989; 82 (suppl): 1.
8-13. 3 Peters W.
Chemotherapy and drug resistance in malaria. London: Academic Press,
1987.
Phillips-Howard PA, Breeze E, Lakin C, Bradley DJ
Short term travel to malarious malaria risk in UK travellers. Trav Med Intern 1988; 6: 51-60. 5. Phillips-Howard PA, Radalowicz A, Mitchell J, Bradley DJ. The risk of malaria in British residents returning from malarious areas. Br Med J (in press) 6. Lobel HO, Phillips-Howard PA, Brandling-Bennett AD, et al Malaria incidence and prevention in European and North American travellers to Kenya. Bull WHO (in 4.
areas:
press). JS, Bernard KW. The spread of chloroquine-resistant malaria JAMA 1989; 262: 245-48
7. Moran
in
Africa
Mefloquine failure in child contracting falciparum malaria in West Africa SIR,-A 6-year-old boy from Paris travelled overland to Morocco, Senegal, and the Ivory Coast with his parents in June, 1988. Two weeks before leaving France he was started on mefloquine prophylaxis 100 mg per week (4-35 mg;kg) and he had been on continuous prophylaxis for 4 weeks before he reached the malaria
Laboratory.
endemic
area of Senegal. The family reached the Ivory Coast in where August, they stayed in small villages, and the boy was exposed to mosquitoes. On Aug 31 the family returned to France and mefloquine was continued for 4 more weeks, the last dose being on Sept 24. At the end of October the child had a fever with chills and headache, and was admitted to hospital in Paris, where uncomplicated Plasmodium falciparum malaria with high-grade parasitaemia was diagnosed. An adult dose of mefloquine was given (750 mg, 500 mg, and 250 mg doses 8 h apart from a total dose of 65 mg/kg instead of 25 mg/kg). The fever resolved and a smear was negative for parasites within 48 h. 3 weeks later (Nov 17) the patient again had fever with chills, sweating, severe headache, and drowsiness. He was admitted to 1’Hopital Pitié-Salpêtrière. Except for pallor, the physical and neurological findings were essentially normal. He had 07% P falciparum trophozoites on a thick smear; a normal blood count except for a slighly increased white cell count at 11 270/µl; and slightly increased total bilirubin (25 rnmol/1). The malaria immunofluorescent titre 1800 and was antibody immunoelectrophoresis was positive (two arcs). Blood and urine cultures and blood tests ruled out other medical conditions. The child was put on quinine by infusion (150 mg every 6 h for 5 days or 25 mg/kg daily). The fever resolved in 3 days; the parasite count fell in 2 days and was negative by the 4th day. He was then given oral quinine (’Quinimax’) at the same dose for 5 days. The patient had no side-effects from this treatment and his parasite count remained negative at follow-up. In-vitro drug sensitivity tests to chloroquine, quinine, and mefloquine were done but parasite growth was uninterpretable. His plasma level of mefloquine at admission was 328 ng/ml, which could explain the partial inhibition of parasite growth in the drug
sensitivity tests. Despite an adequate plasma drug level (328 ng/ml more than 2 weeks after the last therapeutic dose), prophylactic and, subsequently, therapeutic use of mefloquine failed in this child. To our knowledge, this is the first case of in-vivo type I mefloquine resistance in a child with recurrent P falciparium malaria acquired in West Africa. In adults one case of induced infection in a volunteer with the Vietnam Smith strainl and a case of mefloquine-resistant malaria acquired in Tanzania2 have been reported. Elimination of mefloquine is slow, with a half-life in healthy adults of about 3 weeks,3but it is more rapid in children with acute malaria .4 It was unexpected for mefloquine-resistant malaria to be contracted in Senegal or the Ivory Coast, areas with low levels or no resistance to
121
chloroquine and where mefloquine has not yet been used. Selection by drug pressure in the host may have happened during the prolonged prophylaxis (more than 3 months) and during treatment. However, even if selection of a resistant strain did take place by drug pressure under subtherapeutic doses, we cannot overlook another factor that could compound drug pressure-namely, selection by "therapeutic escape". This case raised questions about prolonged prophylaxis, or treatment with the same drug afterwards, especially in areas where mefloquine has been little used. Department of Parasitology, Tropical Medicine, and Public Health, INSERM Unit 313; and Paediatrics Service,
Groupe Hoapitalier Pitié- Salpêtrière, 75651 Paris, France, and Department of Pharmacology,
INSERM Unit 13,
Groupe Hospitalier
Bichat-Claude Bernard,
Paris
F. GAY M. H. BINET M. D. G. BUSTOS B. ROUVEIX M. DANIS C. ROY M. GENTILINI
1. Cosgriff TM, Pamplin CL, Craig CJ, Willet GP. Mefloquine failure in a case of falciparum malaria induced with a multidrug resistant isolate m a non-immune subject Am JTrop Med Hyg 1985; 34: 692-93. 2 Bygbjerg IC, Schaptra A, Flachs H, Gomme G, Jepsen S. Mefloquine resistance of falciparum malaria from Tanzania enhanced by treatment. Lancet 1983; i: 774-75. 3 Schwartz DE, Eckert G, Hartmann D, et al. Single dose kinetics of mefloquine in man. Chemotherapy 1982; 28: 70-84. 4. White NJ Drug treatment and prevention of malaria Eur J Clin Pharmacol 1988; 34: 1-14.
Diagnosis of malaria during chloroquine/proguanil prophylaxis SIR,-With the emergence of chloroquine-resistant Plasmodium falciparum malaria in Africa’ recommendations on the most effective chemoprophylaxis for long-term travellers to such areas have changed and nowadays include weekly chloroquine plus daily proguanip,3 We have experienced diagnostic difficulty in ten patients presenting with symptoms highly suggestive of malaria (fever, chills, fatigue, headache, arthralgia, muscle pain) while on regular chloroquine/proguanil prophylaxis at the appropriate dosage (table). A thin blood film (May-Griinwald-Giemsa stain) was negative in all patients. Thick blood films (Giemsa) contained parasites but they were hardly recognisable, being severely altered and atypical in shape and structure, with very irregular nuclei and vacuoles. Parasite counts calculated by a standard technique on 100 microscope fields’ were very low for all patients, ranging from 4 to 150/u) (table). All patients completely recovered after the institution of antimalarial therapy, usually quinine and/or pyrimethamine plus sulphadoxine (’Fansidar’). Our laboratory technicians had great difficulty in recognising parasites in blood and with low parasite counts. This could result in dangerous delays in diagnosis and treatment in less experienced centres, where the clinical picture might be incorrectly ascribed to other frequent infections. We are unaware of previous reports of severely altered P falciparum morphology and very low parasite counts
in
cases
of failed
be instituted without
delay in patients whose clinical picture is
compatible with malaria but whose blood films are "negative". Laboratory Division OCEAC, BP 288, Yaounde, Cameroon
CLAUDE HENGY
c/o Israel Embassy, Yaounde
DAVID GOZAL
1. Lobel HO, Campbell CC. Malaria prophylaxis and distribution of drug resistance. Clin Trop Med Commun Dis 1986; 1: 225-42. 2. Cook GC. Prevention and treatment of malaria. Lancet 1988; i: 32-36. 3. Anon. Vaccination certificate requirements and health advice for international travel. Geneva: World Health Organisation, 1987: 45. 4. Payne D. Use and limitations of light microscopy for diagnosing malaria at the primary health care level. Bull WHO 1988; 66: 621-26.
Oilseed rape
as a
potent antigen
SIR,-Oilseed rape pollen has been blamed for hayfever, asthma, and allergic dermatitis, but we can find no scientific evidence for this apart from a patient with contact dermatitis provoked by mustard seed (Brassica nigra) antigens who reacted on patch testing to oilseed rape (B napus) also.’ The availability of European Community subsidies has led to an increase in the amount of oilseed rape that is grown in the UK. In Scotland the amount of land under this crop increased from 1600 hectares in 1982 to about 42 000 hectares in 1988. On Tayside the increase has been from nil to 6000 hectares or so, and in the countryside it is difficult to avoid contact with the plant. Our serological investigation of sensitisation to oilseed rape shows that the pollen of this crop is one of the most potent antigens described to date. The sera tested had been sent to the allergy testing laboratories serving predominantly urban Glasgow and more rural Tayside for routine IgE antibody testing by radioallergosorbent test (RAST) to common allergens. No requests specifically mentioned oilseed rape allergy. Sera were stored at - 20°C. The "routine" antigens were mixed grasses, Dermatophagoides pteronyssinus, cat and dog dander, and mixed foods; tests for oilseed rape and mixed moulds (Penicillium notatum, Cladosporium herbarum, Aspergillus fumigatus, and Alternaria alternata) were done in Dundee on both sets of sera. We tested for mixed moulds, because rape, after flowering, is cut and left in the fields for several weeks before harvesting, during which time it often becomes mouldy. We used Thadebas’ RAST kits (Pharmacia) and recorded the results as 0 for no sensitisation and 1-4 for mild, moderate, high, or very high sensitisation. Total IgE levels were assayed by ’Phadezym’ kits (Pharmacia). In Dundee, 175 sera submitted between May and September, 1988, were tested and compared with 141 sera from Glasgow which had been collected during February, June, and July, 1988. (February and September both lie outside the flowering season of oilseed rape.) A further 82 Dundee sera from November and December, 1988, were also studied. ’
combined
chloroquine/proguanil
chemoprophylaxis. We suggest that empirical antimalarial therapy CLINICAL PICTURE AND PARASITE COUNT -
-
Seroprevalence of sensitisation to oilseed moulds in Tayside and Glasgow.
rape and mixed
Mixed mould results for Tayside in June and September, 1988, 96% and 129%, respectively
were
