- Email: [email protected]
Sandflies and leishmaniasis
Science Photo Library
Correspondence
Rights were not granted to include this image in electronic media. Please refer to the printed journal
hypoglycaemia (six fatal cases out of 19; p=0·4) whereas in the artesunate group, mortality was higher in those with late hypoglycaemia (four of six; p=0·005). This suggests that it is malaria-associated rather than quinine-induced hypoglycaemia that is associated with mortality. Additionally, in our subgroup analysis, hyperparasitaemia was associated with the most striking mortality benefit of artesunate compared with quinine, as would be expected if the treatment effect is due to the superior antiparasitic effect of artesunate rather than an adverse effect of quinine. There was no association between hyperparasitaemia and late hypoglycaemia. Stephen Toovey’s view that antimalarial treatment with artemisinin derivatives causes neurotoxicity is well known, but few agree with him. After animal studies indicated that intramuscular artemether and artemotil could produce an unusual selective and largely irreversible pattern of neuronal damage in some brainstem nuclei, particularly those involved in hearing and balance, there have been extensive studies (clinical, audiometric, auditory evoked potential, and neuropathological assessments) to determine whether this damage occurs in human beings treated with artemether and artemotil for malaria. All were negative2 except for Toovey’s own retrospective case-control audiometric assessment of oral artemetherlumefantrine.3,4 Now he postulates that an undefined but rapidly reversible anaesthetic neurotoxic process delayed coma recovery in artesunate recipients. There is no correlate for this in the animal studies. Furthermore a difference in coma recovery time would not necessarily be expected because the action of quinine and artemisinin derivatives on the parasites already sequestered in the brain venules and capillaries (which cause cerebral malaria) is similar.5 The main difference between the two drugs is in the prevention of sequestration. We declare that we have no conflict of interest.
112
*N J White, A M Dondorp, F Nosten, N P J Day, on behalf of the SEAQUAMAT study group [email protected] Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand 1
2 3
4
5
White NJ, Warrell DA, Chanthavanich P, et al. Severe hypoglycemia and hyperinsulinemia in falciparum malaria. N Engl J Med 1983; 309: 61-66. Taylor WR, White NJ. Antimalarial drug toxicity: a review. Drug Safety 2004; 27: 25–61. Toovey S, Jamieson A. Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether. Trans R Soc Trop Med Hyg 2004; 98: 261–67. Mehta U, Barnes KI, Kathard H, Vugt M, Durrheim D. Comment on: audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether. Trans R Soc Trop Med Hyg 2005; 99: 313–14. Gravenor MB, van Hensbroek MB, Kwiatkowski D. Estimating sequestered parasite population dynamics in cerebral malaria. Proc Natl Acad Sci USA 1998; 95: 7620–24.
Sandflies and leishmaniasis As noted by Henry Murray and colleagues (Oct 29, p 1561),1 in the absence of an effective vaccine against leishmaniasis, the first line of defence is to avoid sandfly bites. However, phlebotomine sandflies that are infected with leishmania differ in their hostseeking behaviour from healthy sandflies.2 This difference has important implications for bite avoidance strategies and must be taken into account when advising travellers and when designing local leishmaniasis prevention programmes. A phlebotomine sandfly heavily infected with leishmania probes much more frequently than an uninfected fly.2 Each individual probe might last only a few seconds, but all probes are likely to inoculate promastigotes into the host. This frenetic vector behaviour probably explains the multiple lesions seen in some patients, especially those with L major infections.2 It might also account for the fact that insecticides that repel healthy sandflies under laboratory conditions are not always effective in the field. Contrary to expectations, a randomised trial of per-
methrin-impregnated uniforms versus untreated uniforms in 324 Iranian soldiers showed no significant difference at 9 months in cutaneous leishmaniasis acquisition between the intervention and the control groups (p0·05).3 Some plant-based repellents, such as lemon essential oil, have been found more effective in repelling healthy sandflies than broad-spectrum chemical repellents such as DEET (diethyl toluamide).4 The results of such studies need to be assessed with caution, since in most cases the primary endpoint of the study was a simple bite count, whereas a more appropriate endpoint would have been laboratory-confirmed episodes of clinical leishmaniasis. In one area alone there is little doubt. Sandflies are poor flyers, and can move vertically only in short hops of about 1 m. Substantial protection can be gained from sleeping in the upper stories of available accommodation. A survey of 613 residents of high-rise apartment blocks in Kabul found that active cutaneous leishmaniasis lesions were up to 84% fewer (p=0·008) in residents who slept on floors three to five of the blocks, compared with those who slept on the ground or first floors.5 To avoid being bitten during the night by sandflies, infected or uninfected, your hammock or camp bed should be at least 1 m above the ground. We declare that we have no conflict of interest.
*A M Croft, N A Taylor, K E Rodenhurst [email protected] Medical Branch, Headquarters Fifth Division, Copthorne Barracks, Shrewsbury SY3 8LZ, UK 1 2
3
4
5
Murray HW, Berman JD, Saravia NG. Advances in leishmaniasis. Lancet 2005; 366: 1561–77. Lane RP. Phlebotomine sandflies. In: Cook GC, Zumla A, eds. Manson’s tropical diseases, 21st edn. London: WB Saunders, 2002. Asilian A, Sadeghinia A, Shariati F, Jome MI, Ghoddusi A. Efficacy of permethrinimpregnated uniforms in the prevention of cutaneous leishmaniasis in Iranian soldiers. J Clin Pharm Ther 2003; 28: 175–78. Rojas E, Scorza JV. The use of lemon essential oil as a sandfly repellent. Trans R Soc Trop Med Hyg 1991; 85: 803. Hewitt S, Reyburn H, Ashford R, Rowland M. Anthroponotic cutaneous leishmaniasis in Kabul, Afghanistan: vertical distribution of cases in apartment blocks. Trans R Soc Trop Med Hyg 1998; 92: 273–74.
www.thelancet.com Vol 367 January 14, 2006
Correspondence
Rights were not granted to include this image in electronic media. Please refer to the printed journal
hypoglycaemia (six fatal cases out of 19; p=0·4) whereas in the artesunate group, mortality was higher in those with late hypoglycaemia (four of six; p=0·005). This suggests that it is malaria-associated rather than quinine-induced hypoglycaemia that is associated with mortality. Additionally, in our subgroup analysis, hyperparasitaemia was associated with the most striking mortality benefit of artesunate compared with quinine, as would be expected if the treatment effect is due to the superior antiparasitic effect of artesunate rather than an adverse effect of quinine. There was no association between hyperparasitaemia and late hypoglycaemia. Stephen Toovey’s view that antimalarial treatment with artemisinin derivatives causes neurotoxicity is well known, but few agree with him. After animal studies indicated that intramuscular artemether and artemotil could produce an unusual selective and largely irreversible pattern of neuronal damage in some brainstem nuclei, particularly those involved in hearing and balance, there have been extensive studies (clinical, audiometric, auditory evoked potential, and neuropathological assessments) to determine whether this damage occurs in human beings treated with artemether and artemotil for malaria. All were negative2 except for Toovey’s own retrospective case-control audiometric assessment of oral artemetherlumefantrine.3,4 Now he postulates that an undefined but rapidly reversible anaesthetic neurotoxic process delayed coma recovery in artesunate recipients. There is no correlate for this in the animal studies. Furthermore a difference in coma recovery time would not necessarily be expected because the action of quinine and artemisinin derivatives on the parasites already sequestered in the brain venules and capillaries (which cause cerebral malaria) is similar.5 The main difference between the two drugs is in the prevention of sequestration. We declare that we have no conflict of interest.
112
*N J White, A M Dondorp, F Nosten, N P J Day, on behalf of the SEAQUAMAT study group [email protected] Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand 1
2 3
4
5
White NJ, Warrell DA, Chanthavanich P, et al. Severe hypoglycemia and hyperinsulinemia in falciparum malaria. N Engl J Med 1983; 309: 61-66. Taylor WR, White NJ. Antimalarial drug toxicity: a review. Drug Safety 2004; 27: 25–61. Toovey S, Jamieson A. Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether. Trans R Soc Trop Med Hyg 2004; 98: 261–67. Mehta U, Barnes KI, Kathard H, Vugt M, Durrheim D. Comment on: audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether. Trans R Soc Trop Med Hyg 2005; 99: 313–14. Gravenor MB, van Hensbroek MB, Kwiatkowski D. Estimating sequestered parasite population dynamics in cerebral malaria. Proc Natl Acad Sci USA 1998; 95: 7620–24.
Sandflies and leishmaniasis As noted by Henry Murray and colleagues (Oct 29, p 1561),1 in the absence of an effective vaccine against leishmaniasis, the first line of defence is to avoid sandfly bites. However, phlebotomine sandflies that are infected with leishmania differ in their hostseeking behaviour from healthy sandflies.2 This difference has important implications for bite avoidance strategies and must be taken into account when advising travellers and when designing local leishmaniasis prevention programmes. A phlebotomine sandfly heavily infected with leishmania probes much more frequently than an uninfected fly.2 Each individual probe might last only a few seconds, but all probes are likely to inoculate promastigotes into the host. This frenetic vector behaviour probably explains the multiple lesions seen in some patients, especially those with L major infections.2 It might also account for the fact that insecticides that repel healthy sandflies under laboratory conditions are not always effective in the field. Contrary to expectations, a randomised trial of per-
methrin-impregnated uniforms versus untreated uniforms in 324 Iranian soldiers showed no significant difference at 9 months in cutaneous leishmaniasis acquisition between the intervention and the control groups (p0·05).3 Some plant-based repellents, such as lemon essential oil, have been found more effective in repelling healthy sandflies than broad-spectrum chemical repellents such as DEET (diethyl toluamide).4 The results of such studies need to be assessed with caution, since in most cases the primary endpoint of the study was a simple bite count, whereas a more appropriate endpoint would have been laboratory-confirmed episodes of clinical leishmaniasis. In one area alone there is little doubt. Sandflies are poor flyers, and can move vertically only in short hops of about 1 m. Substantial protection can be gained from sleeping in the upper stories of available accommodation. A survey of 613 residents of high-rise apartment blocks in Kabul found that active cutaneous leishmaniasis lesions were up to 84% fewer (p=0·008) in residents who slept on floors three to five of the blocks, compared with those who slept on the ground or first floors.5 To avoid being bitten during the night by sandflies, infected or uninfected, your hammock or camp bed should be at least 1 m above the ground. We declare that we have no conflict of interest.
*A M Croft, N A Taylor, K E Rodenhurst [email protected] Medical Branch, Headquarters Fifth Division, Copthorne Barracks, Shrewsbury SY3 8LZ, UK 1 2
3
4
5
Murray HW, Berman JD, Saravia NG. Advances in leishmaniasis. Lancet 2005; 366: 1561–77. Lane RP. Phlebotomine sandflies. In: Cook GC, Zumla A, eds. Manson’s tropical diseases, 21st edn. London: WB Saunders, 2002. Asilian A, Sadeghinia A, Shariati F, Jome MI, Ghoddusi A. Efficacy of permethrinimpregnated uniforms in the prevention of cutaneous leishmaniasis in Iranian soldiers. J Clin Pharm Ther 2003; 28: 175–78. Rojas E, Scorza JV. The use of lemon essential oil as a sandfly repellent. Trans R Soc Trop Med Hyg 1991; 85: 803. Hewitt S, Reyburn H, Ashford R, Rowland M. Anthroponotic cutaneous leishmaniasis in Kabul, Afghanistan: vertical distribution of cases in apartment blocks. Trans R Soc Trop Med Hyg 1998; 92: 273–74.
www.thelancet.com Vol 367 January 14, 2006