- Email: [email protected]
Efficacy of low-dose halofantrine for second treatment of uncomplicated falciparum malaria
THE LANCET
leptospirosis that occurred in Nicaragua in November, 1995, was associated with uncommon bleeding complications. Fatal pulmonary haemorrhage occurred in at least 40 patients among the about 2000 who contracted the disease. Dengue and dengue haemorrhagic fever were initially suspected as the cause of the outbreak, until Leptospira were detected in patient tissues by immunohistochemistry. Isolation was not accomplished until about 6–8 weeks after initial outbreak.2 Dengue was also considered in another selflimited, not haemorrhagic outbreak of L interrogans in Columbia in 1995.3 Distinguishing the haemorrhagic diathesis of leptospirosis, which has been attributed to vasculitis,4,5 from other haemorrhagic fevers may be difficult because thrombocytopenia can be seen in patients with leptospirosis. Also, many patients with viral haemorrhagic fevers do not have coagulation abnormalities early in the course of the disease. An antibiotic regimen whose spectrum includes activity against Leptospira should be considered in association with isolation in travellers with unexplained haemorrhagic fever, until the results of serological examinations and viral cultures become available. 1 2
3 4 5
Van Crevel R, Speelman P, Gravekamp C, Terpstra WJ. Leptospirosis in travelers. Clin Infect Dis 1994; 19: 132–34. Zaki SR, Shieh WJ, et al. Leptospirosis associated with outbreak of acute febrile illness and pulmonary haemorrhage, Nicaragua, 1995. Lancet 1996; 347: 535–36. Epstein PR, Calix Pena O, Recedo JB. Climate and disease in Columbia. Lancet 1995; 346: 1243–44. Farr RW. Leptospirosis. Clin Infect Dis 1996; 21: 1–8. Kreisberg RA. An abundance of options. N Engl J Med 1993; 329: 413–16.
Service de Médecine Interne, Hôpital Paul Brousse, 12, avenue Paul Vaillant Couturier, F 94804 Villejuif, France (J J Monsuez); Centre National de Référence, pour les fièvres hémorragiques virales,Institut Pasteur, Paris, France; and Centre National de Référence des Leptospires, Institut Pasteur, Paris
Patients
C-KS (n=18) T-KS (n=2) AIDS-KS (n=7) Healthy blood donors (n=14) Chronic dermatitis (n=20)
M C Sirianni, S Uccini, A Angeloni, A Faggioni, F Cottoni, B Ensoli
Circulating Kaposi’s sarcoma (KS)-like spindle cells have been isolated and cultured from patients with AIDS-KS or at risk of AIDS-KS.1 These cells are adherent and possess markers of macrophages and endothelial cells as well as functional activities similar to lesional spindle cells.1 A new human herpesvirus, HHV-8, has been identified in lesions and peripheral blood mononuclear cells (PBMC) of all forms of KS.2–5 We looked for HHV-8 in cultures of KS-like spindle cells from the blood of 18 patients with classic KS (C-KS 14 men and four women mean age 67 years), two who developed KS after transplantation (T-KS), and seven male homosexuals with AIDS-KS. 34 healthy blood donors and patients with cutaneous disease other than KS were controls. PBMC were cultured as described, in the presence or absence of conditioned medium from activated T cells (TCM).1 KS-like cells were cultured from PBMCs of 83% (15/18) of patients with C-KS and from all patients with T-KS and AIDS-KS, irrespective of addition of TCM (table). Of the three C-KS patients who did not develop these cells, one was having intravenous bleomycin at the time of testing; 1 month after treatment KS-like cells were found. Circulating spindle cells were also cultured from about 50% of normal donors and patients with chronic skin disorders, but in much lower numbers, as evaluated by double staining of cell
Vol 349 • January 25, 1997
83 100 100 57 50
% KS-like cells (SD) +TCM
–TCM
45 (10)* 40 (9)* 41 (4)* 40 (2)* 42 (9)* 53 (10)* 3 (1) 2·8 (0·9) 4 (1·6)
HHV-8-positive (%) 11/14 (78%) 2/2 (100%) 3/3 (100%) 0/14 (0%)
3 (0·9)
0/20 (0%)
% KS-like cells refers to the number of spindle cells defined according to the co-expression of the endothelial cell marker VE-cadherin and the macrophage marker PAM-1. *: results statistically (p<0·001) different from normal donors and chronic dermatitis. HHV-8 positivity refers to the positive cases (%) detected by Southern blot hybridisation of nested PCR products.
cultures with the endothelial cell marker VE-cadherin and the tissue-macrophage marker PAM-1 (40–60% in KS patients and 0·5–6% in controls) (table). 4 weeks later, culture were examined for HHV-8 DNA sequences by nested PCR.4 None of the control cultures was positive, whereas HHV-8 was detected in all T-KS and AIDS-KS cases and in 11/14 cultures derived from patients with C-KS (table). HHV-8 was also detected in the patient with C-KS after bleomycin therapy. Our results indicate that an expansion of circulating KS-like cells or their progenitors is present in all forms of KS; KS-derived cultures are infected by HHV-8; and the presence of HHV-8 in these cells correlates with KS. Since these cells are capable of chemotaxis and can induce KS-like lesion formation in nude mice,1 our data suggest that they may localise into tissues, transmit HHV-8 infection to neighbour cells, and participate in the formation of KS lesions. 1
2
3
Circulating spindle cells: correlation with human herpesvirus-8 (HHV-8) infection and Kaposi’s sarcoma
With KS-like cells (%)
4
5
Browning PJ, Sechler MG, Kaplan M, et al. Identification and culture of Kaposi’s sarcoma-like spindle cells from the peripheral blood of human immunodeficiency virus-1-infected individuals and normal controls. Blood 1994; 84: 2711–20. Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesviruslike DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 1994; 266: 1865–68. Boshoff C, Whitby D, Hatziioannou T, et al. Kaposi’s sarcomaassociated herpesvirus in HIV-negative Kaposi’s sarcoma. Lancet 1995; 345: 1043–44. Whitby D, Howard MR, Tenant-Flowers M, et al. Detection of Kaposi’s sarcoma associated herpesvirus in peripheral blood of HIVinfected individuals and progression to Kaposi’s sarcoma. Lancet 1995; 346: 799–802. Ambroziak JA, Blackbourn DJ, Herndier BG, et al. Herpes-like sequences in HIV-infected and uninfected Kaposi’s sarcoma patients. Science 1995; 268: 582–83.
Departments of Clinical Medicine, Experimental Medicine, and Pathology, University of Rome “La Sapienza”, Rome; Department of Dermatology, University of Sassari, Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy (B Ensoli)
Efficacy of low-dose halofantrine for second treatment of uncomplicated falciparum malaria J E Touze, J L Perret, X Nicolas, L Fourcade, J Bernard, A Keundjian, J M Soares, J C Doury
Halofantrine at a dose of 24 mg/kg is a currently recommended treatment for uncomplicated falciparum malaria in non-immune patients. To prevent recurrence, a second treatment is recommended 7 days later.1 Several reports have described cardiac changes after halofantrine therapy.2,3 These changes are more common after the second treatment4 and appear to be dose dependent.5 This study was undertaken to investigate the efficacy of low-dose second treatment. 54 French servicemen stationed in Libreville, Gabon, were enrolled after informed consent (mean age: 26 years, mean
255
THE LANCET
weight 73·3 kg). All had uncomplicated falciparum malaria. 14 were diagnosed within 3 weeks of their return to France. All were still taking chemoprophylaxis with chloroquine (100 mg) and proguanil (200 mg) at the time of diagnosis. All received halofantrine in two 1-day courses 7 days apart. The first treatment was 1500 mg in three doses 2 h after meals; the second a single 250 mg tablets at 09.00 h. Clinical status and parasite counts were ascertained every 12 h until two consecutive thick blood smears were negative. Follow-up examinations including physical examination, complete blood count, thick blood smears, and parasite identification and count were done weekly for 4 weeks. Plasma concentrations of halofantrine and N-desbutyl halofantrine (DBHal) were determined by high performance liquid chromatography in 14 patients. Sampling was done immediately before treatment and at 6, 12, 24, 48, and 72 h after intake. Symptoms disappeared within 5 days after the first treatment in all patients. (Fever clearance time: 51·5 [SD 27·2] h ; parasite clearance time: 56·7 [26·4] h). 28 days after the second treatment, 53 patients had no symptoms and no identifiable parasites. One patient who remained in Gabon for 1 month after the second treatment relapsed at day 27. Maximum plasma concentration of halofantrine was 709·4 (581) ng/mL 12 h after the first of treatment and 395·28 (220·7) ng/mL 6 h after the second treatment (p<0·01). Maximum plasma concentration of DBHal was 280·3 (170·2) ng/mL 24 h after the first treatment and 122·4 (62·8) ng/mL 12 h after the second (p<0·01). Our results show that second treatment at a dose of 250 mg is effective for mild to moderate acute falciparum malaria in non-immune people. Clinical recovery and parasite clearance was observed within 5 days in all patients. Only one patient relapsed at day 27. Since this patient remained in Gabon, reinfection cannot be ruled out. A low-dose second treatment at 250 mg appears to be effective in preventing recurrence and could reduce the risk of cardiac complications, given the low plasma concentrations of halofantrine and DBHal during the second treatment. 1
2 3
4
5
Coulaud JP, Le Bras J, Matheron S, et al. Treatment of imported cases of falciparum malaria in France with halofantrine. Trans R Soc Trop Med Hyg 1986; 80: 615–16. Nosten F, Ter Kuile FO, Luxemburger C, et al. Cardiac effects of antimalarial treatment with halofantrine. Lancet 1993; 341: 1054–56. Matson PA, Luby SP, Redd SC, Rolka HR, Meriwether RA. Cardiac effects of standard-dose halofantrine therapy. Am J Trop Med Hyg 1996; 54: 229–31. Touze JE, Bernard J, Keundjian A, et al. Electrocardiographic changes and halofantrine plasma level during acute falciparum malaria. Am J Trop Med Hyg 1996; 54: 225–28. Karbwang J, Milton KA, Bangchang K, Ward SA, Edwards G, Bunnag D. Pharmacokinetics of halofantrine in Thai patients with acute uncomplicated falciparum malaria. Br J Clin Pharmacol 1991; 31: 484–87.
Tropical Medical Institute for French Army, Le Pharo, Marseille-13998, France (J E Touze); Larrey’s Hospital, Toulouse, France
a) Eggs of Capillaria sp with shells ornamented by a network resembling a more or less fine mesh varying in aspect from structured to random (70 µm⫻31·5 µm).
b) Eggs of Capillaria sp with mammillated shells endowed with rounded protuberances that lend them dictyospored appearance (62 µm⫻35 µm).
(C hepatica), and intestinal (C philippensis) forms. Species determination of Capillaria eggs remains hypothetical. They are separated into two groups: eggs with shells ornamented by a network, and eggs with mammillated shells (figure). The first group contains C hepatica and C aerophilus, parasites of wild (Apodemus sp, Microtus sp) and habitationassociated rodents (Mus sp, Rattus sp), and also some insectivores (Sorex sp). Human infection is rare, with only a dozen or so cases of hepatic capillariosis recorded in Western Europe. Common present-day habitation-associated rodents, mice and rats, had not been introduced into Europe in the neolithic period. The source of capillarioses may have been animals such as Meles sp, Mustela sp, or Erinaceus sp, which were known to be present then.2 In Moravec’s classification of the Capillaria,3 eggs in the second group mostly belong to species that parasitise fish. Eggs in the coprolites could be C brevispicula, C petruschewkii, or C salvelini, and the fish parasitised Salmo trutta, Lota lota, and Perca fluviatilis, species known from their remains at Chalain. These Capillaria might have had a biological cycle similar to that of C philippensis, endemic today in Eastern Asia, the larvae of which infect fish and reach their maturity in aquatic birds or in human beings.4 There remains a slight possibility that the eggs belong to Eustrongylides sp, which rarely causes disease in human beings today.5 From the evidence available, it is not possible to tell if the infected neolithic people were definitive, intermediary, paratenic, or transitory hosts. Paleoparasitological studies should shed new light on the prevalence of parasitoses in neolithic times. I thank P Pétrequin (University CNRS, UMR 9946) for the material from Chalain, and W Berry for translation. 1
Intestinal capillariasis in neolithic inhabitants of Chalain (Jura, France)
2
Françoise Bouchet
3
23 coprolites of human origin from samples taken from shoreline habitation sites of the neolithic Chalain Lake settlement (3200–2980 BC) were rehydrated, suspended, and separated by flotation and sedimentation.1 21 contained eggs of Capillaria sp (Trichiuriodae). Today, three human capillarioses are known: pulmonary (C aerophilus), hepatic
4 5
256
Bouchet F, Paicheler JC. Palaeoparasitology: presumption of Bilharziose on an archaeological site from XV° century in Montbeliard (Doubs, France). Comptes Rendus Acad Sci Paris 1995; 318: 811–14. Arbogast AJG, Pétrequin AM, Pétrequin P. Le fonctionnement de la cellule domestique d’apres l’etude des restes osseux d’animaux: le cas d’un village néolithique du lac de Chalain (Jura, France). Anthropozoologica 1995; 21: 131–46. Moravec F. Revision of Nematodes of the genus Capillaria from european freshwater fishes. Folia parasitologia 1980; 27: 309–24. Cross JH. Intestinal capillariasis. Parasitol Today 1990; 6: 26–28. Eberhard ML, Hurwitz H, Sun AM, Coletta D. Intestinal perforation caused by larval Eustrongylides (Nematoda: Dioctophymatoidae) in New-Jersey. Am J Trop Med Hyg 1989; 40: 648–50.
Université de Reims, Laboratoire de Paléoparasitologie CNRS-URA 1415, 51096 Reims, France
Vol 349 • January 25, 1997
leptospirosis that occurred in Nicaragua in November, 1995, was associated with uncommon bleeding complications. Fatal pulmonary haemorrhage occurred in at least 40 patients among the about 2000 who contracted the disease. Dengue and dengue haemorrhagic fever were initially suspected as the cause of the outbreak, until Leptospira were detected in patient tissues by immunohistochemistry. Isolation was not accomplished until about 6–8 weeks after initial outbreak.2 Dengue was also considered in another selflimited, not haemorrhagic outbreak of L interrogans in Columbia in 1995.3 Distinguishing the haemorrhagic diathesis of leptospirosis, which has been attributed to vasculitis,4,5 from other haemorrhagic fevers may be difficult because thrombocytopenia can be seen in patients with leptospirosis. Also, many patients with viral haemorrhagic fevers do not have coagulation abnormalities early in the course of the disease. An antibiotic regimen whose spectrum includes activity against Leptospira should be considered in association with isolation in travellers with unexplained haemorrhagic fever, until the results of serological examinations and viral cultures become available. 1 2
3 4 5
Van Crevel R, Speelman P, Gravekamp C, Terpstra WJ. Leptospirosis in travelers. Clin Infect Dis 1994; 19: 132–34. Zaki SR, Shieh WJ, et al. Leptospirosis associated with outbreak of acute febrile illness and pulmonary haemorrhage, Nicaragua, 1995. Lancet 1996; 347: 535–36. Epstein PR, Calix Pena O, Recedo JB. Climate and disease in Columbia. Lancet 1995; 346: 1243–44. Farr RW. Leptospirosis. Clin Infect Dis 1996; 21: 1–8. Kreisberg RA. An abundance of options. N Engl J Med 1993; 329: 413–16.
Service de Médecine Interne, Hôpital Paul Brousse, 12, avenue Paul Vaillant Couturier, F 94804 Villejuif, France (J J Monsuez); Centre National de Référence, pour les fièvres hémorragiques virales,Institut Pasteur, Paris, France; and Centre National de Référence des Leptospires, Institut Pasteur, Paris
Patients
C-KS (n=18) T-KS (n=2) AIDS-KS (n=7) Healthy blood donors (n=14) Chronic dermatitis (n=20)
M C Sirianni, S Uccini, A Angeloni, A Faggioni, F Cottoni, B Ensoli
Circulating Kaposi’s sarcoma (KS)-like spindle cells have been isolated and cultured from patients with AIDS-KS or at risk of AIDS-KS.1 These cells are adherent and possess markers of macrophages and endothelial cells as well as functional activities similar to lesional spindle cells.1 A new human herpesvirus, HHV-8, has been identified in lesions and peripheral blood mononuclear cells (PBMC) of all forms of KS.2–5 We looked for HHV-8 in cultures of KS-like spindle cells from the blood of 18 patients with classic KS (C-KS 14 men and four women mean age 67 years), two who developed KS after transplantation (T-KS), and seven male homosexuals with AIDS-KS. 34 healthy blood donors and patients with cutaneous disease other than KS were controls. PBMC were cultured as described, in the presence or absence of conditioned medium from activated T cells (TCM).1 KS-like cells were cultured from PBMCs of 83% (15/18) of patients with C-KS and from all patients with T-KS and AIDS-KS, irrespective of addition of TCM (table). Of the three C-KS patients who did not develop these cells, one was having intravenous bleomycin at the time of testing; 1 month after treatment KS-like cells were found. Circulating spindle cells were also cultured from about 50% of normal donors and patients with chronic skin disorders, but in much lower numbers, as evaluated by double staining of cell
Vol 349 • January 25, 1997
83 100 100 57 50
% KS-like cells (SD) +TCM
–TCM
45 (10)* 40 (9)* 41 (4)* 40 (2)* 42 (9)* 53 (10)* 3 (1) 2·8 (0·9) 4 (1·6)
HHV-8-positive (%) 11/14 (78%) 2/2 (100%) 3/3 (100%) 0/14 (0%)
3 (0·9)
0/20 (0%)
% KS-like cells refers to the number of spindle cells defined according to the co-expression of the endothelial cell marker VE-cadherin and the macrophage marker PAM-1. *: results statistically (p<0·001) different from normal donors and chronic dermatitis. HHV-8 positivity refers to the positive cases (%) detected by Southern blot hybridisation of nested PCR products.
cultures with the endothelial cell marker VE-cadherin and the tissue-macrophage marker PAM-1 (40–60% in KS patients and 0·5–6% in controls) (table). 4 weeks later, culture were examined for HHV-8 DNA sequences by nested PCR.4 None of the control cultures was positive, whereas HHV-8 was detected in all T-KS and AIDS-KS cases and in 11/14 cultures derived from patients with C-KS (table). HHV-8 was also detected in the patient with C-KS after bleomycin therapy. Our results indicate that an expansion of circulating KS-like cells or their progenitors is present in all forms of KS; KS-derived cultures are infected by HHV-8; and the presence of HHV-8 in these cells correlates with KS. Since these cells are capable of chemotaxis and can induce KS-like lesion formation in nude mice,1 our data suggest that they may localise into tissues, transmit HHV-8 infection to neighbour cells, and participate in the formation of KS lesions. 1
2
3
Circulating spindle cells: correlation with human herpesvirus-8 (HHV-8) infection and Kaposi’s sarcoma
With KS-like cells (%)
4
5
Browning PJ, Sechler MG, Kaplan M, et al. Identification and culture of Kaposi’s sarcoma-like spindle cells from the peripheral blood of human immunodeficiency virus-1-infected individuals and normal controls. Blood 1994; 84: 2711–20. Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesviruslike DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 1994; 266: 1865–68. Boshoff C, Whitby D, Hatziioannou T, et al. Kaposi’s sarcomaassociated herpesvirus in HIV-negative Kaposi’s sarcoma. Lancet 1995; 345: 1043–44. Whitby D, Howard MR, Tenant-Flowers M, et al. Detection of Kaposi’s sarcoma associated herpesvirus in peripheral blood of HIVinfected individuals and progression to Kaposi’s sarcoma. Lancet 1995; 346: 799–802. Ambroziak JA, Blackbourn DJ, Herndier BG, et al. Herpes-like sequences in HIV-infected and uninfected Kaposi’s sarcoma patients. Science 1995; 268: 582–83.
Departments of Clinical Medicine, Experimental Medicine, and Pathology, University of Rome “La Sapienza”, Rome; Department of Dermatology, University of Sassari, Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy (B Ensoli)
Efficacy of low-dose halofantrine for second treatment of uncomplicated falciparum malaria J E Touze, J L Perret, X Nicolas, L Fourcade, J Bernard, A Keundjian, J M Soares, J C Doury
Halofantrine at a dose of 24 mg/kg is a currently recommended treatment for uncomplicated falciparum malaria in non-immune patients. To prevent recurrence, a second treatment is recommended 7 days later.1 Several reports have described cardiac changes after halofantrine therapy.2,3 These changes are more common after the second treatment4 and appear to be dose dependent.5 This study was undertaken to investigate the efficacy of low-dose second treatment. 54 French servicemen stationed in Libreville, Gabon, were enrolled after informed consent (mean age: 26 years, mean
255
THE LANCET
weight 73·3 kg). All had uncomplicated falciparum malaria. 14 were diagnosed within 3 weeks of their return to France. All were still taking chemoprophylaxis with chloroquine (100 mg) and proguanil (200 mg) at the time of diagnosis. All received halofantrine in two 1-day courses 7 days apart. The first treatment was 1500 mg in three doses 2 h after meals; the second a single 250 mg tablets at 09.00 h. Clinical status and parasite counts were ascertained every 12 h until two consecutive thick blood smears were negative. Follow-up examinations including physical examination, complete blood count, thick blood smears, and parasite identification and count were done weekly for 4 weeks. Plasma concentrations of halofantrine and N-desbutyl halofantrine (DBHal) were determined by high performance liquid chromatography in 14 patients. Sampling was done immediately before treatment and at 6, 12, 24, 48, and 72 h after intake. Symptoms disappeared within 5 days after the first treatment in all patients. (Fever clearance time: 51·5 [SD 27·2] h ; parasite clearance time: 56·7 [26·4] h). 28 days after the second treatment, 53 patients had no symptoms and no identifiable parasites. One patient who remained in Gabon for 1 month after the second treatment relapsed at day 27. Maximum plasma concentration of halofantrine was 709·4 (581) ng/mL 12 h after the first of treatment and 395·28 (220·7) ng/mL 6 h after the second treatment (p<0·01). Maximum plasma concentration of DBHal was 280·3 (170·2) ng/mL 24 h after the first treatment and 122·4 (62·8) ng/mL 12 h after the second (p<0·01). Our results show that second treatment at a dose of 250 mg is effective for mild to moderate acute falciparum malaria in non-immune people. Clinical recovery and parasite clearance was observed within 5 days in all patients. Only one patient relapsed at day 27. Since this patient remained in Gabon, reinfection cannot be ruled out. A low-dose second treatment at 250 mg appears to be effective in preventing recurrence and could reduce the risk of cardiac complications, given the low plasma concentrations of halofantrine and DBHal during the second treatment. 1
2 3
4
5
Coulaud JP, Le Bras J, Matheron S, et al. Treatment of imported cases of falciparum malaria in France with halofantrine. Trans R Soc Trop Med Hyg 1986; 80: 615–16. Nosten F, Ter Kuile FO, Luxemburger C, et al. Cardiac effects of antimalarial treatment with halofantrine. Lancet 1993; 341: 1054–56. Matson PA, Luby SP, Redd SC, Rolka HR, Meriwether RA. Cardiac effects of standard-dose halofantrine therapy. Am J Trop Med Hyg 1996; 54: 229–31. Touze JE, Bernard J, Keundjian A, et al. Electrocardiographic changes and halofantrine plasma level during acute falciparum malaria. Am J Trop Med Hyg 1996; 54: 225–28. Karbwang J, Milton KA, Bangchang K, Ward SA, Edwards G, Bunnag D. Pharmacokinetics of halofantrine in Thai patients with acute uncomplicated falciparum malaria. Br J Clin Pharmacol 1991; 31: 484–87.
Tropical Medical Institute for French Army, Le Pharo, Marseille-13998, France (J E Touze); Larrey’s Hospital, Toulouse, France
a) Eggs of Capillaria sp with shells ornamented by a network resembling a more or less fine mesh varying in aspect from structured to random (70 µm⫻31·5 µm).
b) Eggs of Capillaria sp with mammillated shells endowed with rounded protuberances that lend them dictyospored appearance (62 µm⫻35 µm).
(C hepatica), and intestinal (C philippensis) forms. Species determination of Capillaria eggs remains hypothetical. They are separated into two groups: eggs with shells ornamented by a network, and eggs with mammillated shells (figure). The first group contains C hepatica and C aerophilus, parasites of wild (Apodemus sp, Microtus sp) and habitationassociated rodents (Mus sp, Rattus sp), and also some insectivores (Sorex sp). Human infection is rare, with only a dozen or so cases of hepatic capillariosis recorded in Western Europe. Common present-day habitation-associated rodents, mice and rats, had not been introduced into Europe in the neolithic period. The source of capillarioses may have been animals such as Meles sp, Mustela sp, or Erinaceus sp, which were known to be present then.2 In Moravec’s classification of the Capillaria,3 eggs in the second group mostly belong to species that parasitise fish. Eggs in the coprolites could be C brevispicula, C petruschewkii, or C salvelini, and the fish parasitised Salmo trutta, Lota lota, and Perca fluviatilis, species known from their remains at Chalain. These Capillaria might have had a biological cycle similar to that of C philippensis, endemic today in Eastern Asia, the larvae of which infect fish and reach their maturity in aquatic birds or in human beings.4 There remains a slight possibility that the eggs belong to Eustrongylides sp, which rarely causes disease in human beings today.5 From the evidence available, it is not possible to tell if the infected neolithic people were definitive, intermediary, paratenic, or transitory hosts. Paleoparasitological studies should shed new light on the prevalence of parasitoses in neolithic times. I thank P Pétrequin (University CNRS, UMR 9946) for the material from Chalain, and W Berry for translation. 1
Intestinal capillariasis in neolithic inhabitants of Chalain (Jura, France)
2
Françoise Bouchet
3
23 coprolites of human origin from samples taken from shoreline habitation sites of the neolithic Chalain Lake settlement (3200–2980 BC) were rehydrated, suspended, and separated by flotation and sedimentation.1 21 contained eggs of Capillaria sp (Trichiuriodae). Today, three human capillarioses are known: pulmonary (C aerophilus), hepatic
4 5
256
Bouchet F, Paicheler JC. Palaeoparasitology: presumption of Bilharziose on an archaeological site from XV° century in Montbeliard (Doubs, France). Comptes Rendus Acad Sci Paris 1995; 318: 811–14. Arbogast AJG, Pétrequin AM, Pétrequin P. Le fonctionnement de la cellule domestique d’apres l’etude des restes osseux d’animaux: le cas d’un village néolithique du lac de Chalain (Jura, France). Anthropozoologica 1995; 21: 131–46. Moravec F. Revision of Nematodes of the genus Capillaria from european freshwater fishes. Folia parasitologia 1980; 27: 309–24. Cross JH. Intestinal capillariasis. Parasitol Today 1990; 6: 26–28. Eberhard ML, Hurwitz H, Sun AM, Coletta D. Intestinal perforation caused by larval Eustrongylides (Nematoda: Dioctophymatoidae) in New-Jersey. Am J Trop Med Hyg 1989; 40: 648–50.
Université de Reims, Laboratoire de Paléoparasitologie CNRS-URA 1415, 51096 Reims, France
Vol 349 • January 25, 1997