Correspondence
with high intracranial pressure, epileptic seizures disappeared in 86 of 93 patients (92%) who used to have epileptic seizures after treatment with 20 mg/kg albendazole daily for 12 days followed by 15 mg/kg praziquantel daily for 12 days. CT follow-up showed 36% of patients returned to having no seizures and 61% only having some separated calcified foci, whereas 3% still had some low-density, calcified foci, but the focus areas shortened.3 In China, a consensus virtually exists that the combination of albendazole and praziquantel increases the therapeutic efficacy for cerebral cysticercosis.4 Additionally, the study by Garcia and colleagues 1 has a limitation that treatment-associated adverse effects are not described in detail. To our knowledge, very severe adverse events can develop after praziquantel treatment, notably in large doses or at the early stage of the first course of treatment. 87% of the 450 patients with cerebral cysticercosis had adverse reactions during the first course of treatment with praziquantel, including 9% with epileptic seizures, 18% with high intracranial pressure, 3% with mental symptoms, 2% with coma, and 1% with cerebral hernia.5 Because praziquantel treatment causes more adverse events than does albendazole, Chinese clinicians recommend administration of albendazole first, followed by praziquantel with simultaneous administration of steroids for treat ment of neuro cysticercosis, notably in the first course of treatment.4 Further large-scale, multicentre, randomised, controlled trials with rigorous design might be needed to validate the efficacy of the albendazole–praziquantel combination regimen for neurocysticercosis. This study was supported by the Natural Science Foundation of Jiangsu Province (BK20141105). We declare no competing interests.
Wei Wang [email protected] Jiangsu Institute of Parasitic Diseases, 117 Yangxiang, Meiyuan, Wuxi City, Jiangsu Province, 214064, China; and Key Laboratory on Technology for Parasitic Disease Prevention and
266
Control, National Health and Family Planning Commission, and Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Yangxiang, Meiyuan, Wuxi City, Jiangsu Province, China 1
2
3
4
5
Garcia HH, Gonzales I, Lescano AG, et al, for the Cysticercosis Working Group in Peru. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis 2014; 14: 687–95. Xu HX, Zhang QZ, Liu YL, Mao DH, Shi SJ, Xu J. Effect of praziquantel alone or albendazole alone or combination of two drugs in treatment of cysticercosis. J Qiqihar Med College 2001; 22: 999–1000 (in Chinese). Yue JE, Li H, Wu XY, Huo HY, Yang SF. Clinical study on treatment of cysticercosis patients with high cranial pressure. Chin Trop Med 2005; 5: 43–44 (in Chinese). Wu W, Jia F, Wang W, Huang Y, Huang Y. Antiparasitic treatment of cerebral cysticercosis: lessons and experiences from China. Parasitol Res 2013; 112: 2879–90. Ma YX, Zhu JH, Liu ZS, et al. A clinical study on the treatment of cerebral cysticercosis with praziquantel. Chin Med J 1984; 64: 79–83 (in Chinese).
Authors’ reply We thank Aba Mahamat and colleagues for their comments on our Article1 and patient data illustrating a difficult case successfully treated with combined albendazole and praziquantel. We do not deem use of the combination a “shift”, rather a refinement in use of antiparasitic treatment to destroy viable brain parasites, which has been in use for more than 25 years. We certainly agree that antiparasitic treatment in neurocysticercosis should be individualised and not used as a blanket recipe. Arturo Carpio and Matthew Romo bring up several points, including whether seizures in patients with cerebral cysticercal lesions are actually due to these lesions, previous evidence that complete cyst resolution leads to fewer seizure relapses than without resolution, and whether combined treatment really affects seizure recurrence. We concur that in a few cases, seizures might just coexist with brain cysticerci by simple chance. To assume that chance is the usual explanation seems quite far-fetched. Clinicians treating cysticercosis in endemic regions have, since the introduction of antiparasitic treatment,
been aware that destruction of cysts with either albendazole or praziquantel leads to better seizure control and long-term prognosis than if cysts are not destroyed. Our study1 is one of a few masked randomised trials providing type I evidence to support this claim. In our study, combined antiparasitic treatment led to much higher cyst clearance in patients with multiple cysts than did singledrug treatment, and seizures were significantly less common in patients who cleared all their cysts after antiparasitic treatment than in those with remnant live cysts. These results, together with the data suggesting that cyst clearance is predictive of low seizure recurrence2 cited in Carpio and Romo’s letter, leads to the conclusion that antiparasitic treatment results in fewer seizures in the follow-up of treated patients than of untreated patients. Even if we oversimplify this outcome to whether treated patients had at least one further seizure in the follow up, 41% fewer cases occurred in patients who were free of cysts than in those with remnant live cysts (11 [18%] of 60 patients vs 15 [26%] of 58 patients), although this difference was not statistically significant (p=0·324). Seizures in patients free of viable cysts might still occur in relation to their residual calcified scars. An ideal treatment will destroy the cysts, avoiding residual calcium deposit in resolved lesions. In relation to Carpio and Romo’s claim that antiparasitic treatment does not help to resolve extraparenchymal cysts, we do not endorse or suggest this concept at all (and we clearly disagree with it). Finally, Wei Wang adds information on the use of combined albendazole plus praziquantel in a clinical trial3 published in a Chinese journal to which we had had no access, and bring up their own conclusion that praziquantel causes more adverse events than does albendazole. To extract information from this publication is very difficult without knowing the characteristics of neurocysticercosis in www.thelancet.com/infection Vol 15 March 2015
Correspondence
the included patients or the regimens of concomitant steroids that were used during antiparasitic treatment. In our trial1 and the previous phase 2 trial,4 adverse events were very carefully assessed and reported, and no differences between treatment groups were noted. Caution is certainly welcomed until more experience with use of the combination develops worldwide. Our study treated patients with fewer than 20 viable brain cysts, no large cyst masses, no extraparenchymal lesions, and no intracranial hypertension. Treatment of patients with these or other disease characteristics that could be associated with an increased risk of side-effects should be done with extreme caution. HHG reports grants from the National Institute of Neurological Disorders and Stroke, the Fogarty International Center, and the Wellcome Trust. All other authors declare no competing interests.
*Hector H Garcia, Isidro Gonzales, Javier A Bustos, Herbert Saavedra, Martin Gavidia, Lourdes Rodriguez, Enrique Najar, Hugo Umeres, E Javier Pretell [email protected] Cysticercosis Unit, Instituto Nacional de Ciencias Neurológicas, Barrios Altos, Lima 1, Peru (HHG, IG, HS); Department of Microbiology (HHG, JAB), and Center for Global Health - Tumbes (HHG), Universidad Peruana Cayetano Heredia, Lima, Perú; Hospital Nacional Edgardo Rebagliatti, ESSALUD, Lima, Perú (MG); Hospital Nacional Guillermo Almenara, ESSALUD, Lima, Perú (LR); Hospital Nacional Cayetano Heredia, Ministerio de Salud, Lima, Perú (EN, HU); and Hospital Nacional Alberto Sabogal, ESSALUD, Callao, Perú (EJP) 1
2
3
4
Garcia HH, Gonzales I, Lescano AG, et al, for the Cysticercosis Working Group in Peru. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis 2014; 14: 687–95. Carpio A, Hauser WA. Prognosis for seizure recurrence in patients with newly diagnosed neurocysticercosis. Neurology 2002; 59: 1730–34. Xu HX, Zhang QZ, Liu YL, Mao DH, Shi SJ, Xu J. Effect of praziquantel alone or albendazole alone or combination of two drugs in treatment of cysticercosis. J Qiqihar Med College 2001; 22: 999–1000 (in Chinese). Garcia HH, Lescano AG, Lanchote VL, et al, for the Cysticercosis Working Group in Peru. Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis. Br J Clin Pharmacol 2011; 72: 77–84.
www.thelancet.com/infection Vol 15 March 2015
Influenza vaccine for Hajj and Umrah pilgrims In their Series paper, Brian McCloskey and colleagues1 point out that access to influenza vaccine is a key element in the global strategy to minimise risk of pandemic influenza. 1 The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia has prompted worldwide preparedness and a responsive attitude in many countries for surveillance and detection of cases in individuals returning from the Arabian Peninsula. The virology laboratory of the Public Hospital system of Marseille has received 33 samples from patients classified as having suspect or probable MERS-CoV cases on the basis of national criteria from August, 2013, to April, 2014. Most of the samples were from patients who had returned from Saudi Arabia after participating to the Umrah and Hajj pilgrimages. None of these patients was infected with MERS-CoV; however, 17 (52%) were infected with respiratory viruses. 13 of these virus-positive samples contained influenza virus RNA (seven contained influenza A subtype H3N2, four contained pandemic influenza A subtype H1N1 2009, and two contained influenza B); of the remaining positive samples, two contained CoV-229E, one contained human metapneumovirus, and one contained rhinovirus. In summary, 75% of viruses detected in patients returning from the Arabian Peninsula with clinical features compatible with a MERS-CoV were influenza viruses for which a vaccine is theoretically available. The Saudi Ministry of Health recom mends seasonal influenza vaccine for all international pilgrims.2 In France, influenza vaccine is accessible to individuals and the public health-care system only during a specific period (eg, Oct 11, 2013, to Feb 28, 2014, for the 2013–14
season), which corresponds to the epidemic influenza season in the northern hemisphere. 30 (91%) of the 33 pilgrims that we assessed did not have the opportunity to get immunised against influenza because the vaccine was not available in the period before they travelled. Another study that systematically screened a cohort of returned French Hajj pilgrims in 2013 showed that eight (6%) of 129 acquired influenza virus during the pilgrimage. None was vaccinated against influenza in 2013.3 Accordingly, a substantial proportion of individuals crossing hemispheres, or participating in mass gathering events grouping people from both hemispheres, clearly have no access to vaccine-based prevention of influenza because of regulations. Seasonal availability of influenza vaccine in a globally mobile world is an insufficient way to prevent a disease that is notoriously transmitted from person to person irrespective of their location on the planet. We believe that influenza vaccine should be made available at any time to overcome this contradictory situation. We declare no competing interests.
*Remi N Charrel, Antoine Nougairede, Philippe Brouqui, Didier Raoult, Philippe Gautret [email protected] Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR_D 190 “Emergence des Pathologies Virales”, Marseille 13385, France (RNC, AN); Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France (RNC, AN, PB, DR, PG); and Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France (PB, DR, PG) 1
2
3
McCloskey B, Dar O, Zumla A, Heymann DL. Emerging infectious diseases and pandemic potential: status quo and reducing risk of global spread. Lancet Infect Dis 2014; 14: 1001–10. Memish ZA, Al Rabeeah AA. Health conditions for travellers to Saudi Arabia for the Umra and pilgrimage to Mecca (Hajj)—2014. J Epidemiol Glob Health 2014; 4: 73–75. Gautret P, Charrel R, Benkouiten S, et al. Lack of MERS coronavirus but prevalence of influenza virus in French pilgrims after 2013 Hajj. Emerg Infect Dis 2014; 20: 728–30.
267
with high intracranial pressure, epileptic seizures disappeared in 86 of 93 patients (92%) who used to have epileptic seizures after treatment with 20 mg/kg albendazole daily for 12 days followed by 15 mg/kg praziquantel daily for 12 days. CT follow-up showed 36% of patients returned to having no seizures and 61% only having some separated calcified foci, whereas 3% still had some low-density, calcified foci, but the focus areas shortened.3 In China, a consensus virtually exists that the combination of albendazole and praziquantel increases the therapeutic efficacy for cerebral cysticercosis.4 Additionally, the study by Garcia and colleagues 1 has a limitation that treatment-associated adverse effects are not described in detail. To our knowledge, very severe adverse events can develop after praziquantel treatment, notably in large doses or at the early stage of the first course of treatment. 87% of the 450 patients with cerebral cysticercosis had adverse reactions during the first course of treatment with praziquantel, including 9% with epileptic seizures, 18% with high intracranial pressure, 3% with mental symptoms, 2% with coma, and 1% with cerebral hernia.5 Because praziquantel treatment causes more adverse events than does albendazole, Chinese clinicians recommend administration of albendazole first, followed by praziquantel with simultaneous administration of steroids for treat ment of neuro cysticercosis, notably in the first course of treatment.4 Further large-scale, multicentre, randomised, controlled trials with rigorous design might be needed to validate the efficacy of the albendazole–praziquantel combination regimen for neurocysticercosis. This study was supported by the Natural Science Foundation of Jiangsu Province (BK20141105). We declare no competing interests.
Wei Wang [email protected] Jiangsu Institute of Parasitic Diseases, 117 Yangxiang, Meiyuan, Wuxi City, Jiangsu Province, 214064, China; and Key Laboratory on Technology for Parasitic Disease Prevention and
266
Control, National Health and Family Planning Commission, and Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Yangxiang, Meiyuan, Wuxi City, Jiangsu Province, China 1
2
3
4
5
Garcia HH, Gonzales I, Lescano AG, et al, for the Cysticercosis Working Group in Peru. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis 2014; 14: 687–95. Xu HX, Zhang QZ, Liu YL, Mao DH, Shi SJ, Xu J. Effect of praziquantel alone or albendazole alone or combination of two drugs in treatment of cysticercosis. J Qiqihar Med College 2001; 22: 999–1000 (in Chinese). Yue JE, Li H, Wu XY, Huo HY, Yang SF. Clinical study on treatment of cysticercosis patients with high cranial pressure. Chin Trop Med 2005; 5: 43–44 (in Chinese). Wu W, Jia F, Wang W, Huang Y, Huang Y. Antiparasitic treatment of cerebral cysticercosis: lessons and experiences from China. Parasitol Res 2013; 112: 2879–90. Ma YX, Zhu JH, Liu ZS, et al. A clinical study on the treatment of cerebral cysticercosis with praziquantel. Chin Med J 1984; 64: 79–83 (in Chinese).
Authors’ reply We thank Aba Mahamat and colleagues for their comments on our Article1 and patient data illustrating a difficult case successfully treated with combined albendazole and praziquantel. We do not deem use of the combination a “shift”, rather a refinement in use of antiparasitic treatment to destroy viable brain parasites, which has been in use for more than 25 years. We certainly agree that antiparasitic treatment in neurocysticercosis should be individualised and not used as a blanket recipe. Arturo Carpio and Matthew Romo bring up several points, including whether seizures in patients with cerebral cysticercal lesions are actually due to these lesions, previous evidence that complete cyst resolution leads to fewer seizure relapses than without resolution, and whether combined treatment really affects seizure recurrence. We concur that in a few cases, seizures might just coexist with brain cysticerci by simple chance. To assume that chance is the usual explanation seems quite far-fetched. Clinicians treating cysticercosis in endemic regions have, since the introduction of antiparasitic treatment,
been aware that destruction of cysts with either albendazole or praziquantel leads to better seizure control and long-term prognosis than if cysts are not destroyed. Our study1 is one of a few masked randomised trials providing type I evidence to support this claim. In our study, combined antiparasitic treatment led to much higher cyst clearance in patients with multiple cysts than did singledrug treatment, and seizures were significantly less common in patients who cleared all their cysts after antiparasitic treatment than in those with remnant live cysts. These results, together with the data suggesting that cyst clearance is predictive of low seizure recurrence2 cited in Carpio and Romo’s letter, leads to the conclusion that antiparasitic treatment results in fewer seizures in the follow-up of treated patients than of untreated patients. Even if we oversimplify this outcome to whether treated patients had at least one further seizure in the follow up, 41% fewer cases occurred in patients who were free of cysts than in those with remnant live cysts (11 [18%] of 60 patients vs 15 [26%] of 58 patients), although this difference was not statistically significant (p=0·324). Seizures in patients free of viable cysts might still occur in relation to their residual calcified scars. An ideal treatment will destroy the cysts, avoiding residual calcium deposit in resolved lesions. In relation to Carpio and Romo’s claim that antiparasitic treatment does not help to resolve extraparenchymal cysts, we do not endorse or suggest this concept at all (and we clearly disagree with it). Finally, Wei Wang adds information on the use of combined albendazole plus praziquantel in a clinical trial3 published in a Chinese journal to which we had had no access, and bring up their own conclusion that praziquantel causes more adverse events than does albendazole. To extract information from this publication is very difficult without knowing the characteristics of neurocysticercosis in www.thelancet.com/infection Vol 15 March 2015
Correspondence
the included patients or the regimens of concomitant steroids that were used during antiparasitic treatment. In our trial1 and the previous phase 2 trial,4 adverse events were very carefully assessed and reported, and no differences between treatment groups were noted. Caution is certainly welcomed until more experience with use of the combination develops worldwide. Our study treated patients with fewer than 20 viable brain cysts, no large cyst masses, no extraparenchymal lesions, and no intracranial hypertension. Treatment of patients with these or other disease characteristics that could be associated with an increased risk of side-effects should be done with extreme caution. HHG reports grants from the National Institute of Neurological Disorders and Stroke, the Fogarty International Center, and the Wellcome Trust. All other authors declare no competing interests.
*Hector H Garcia, Isidro Gonzales, Javier A Bustos, Herbert Saavedra, Martin Gavidia, Lourdes Rodriguez, Enrique Najar, Hugo Umeres, E Javier Pretell [email protected] Cysticercosis Unit, Instituto Nacional de Ciencias Neurológicas, Barrios Altos, Lima 1, Peru (HHG, IG, HS); Department of Microbiology (HHG, JAB), and Center for Global Health - Tumbes (HHG), Universidad Peruana Cayetano Heredia, Lima, Perú; Hospital Nacional Edgardo Rebagliatti, ESSALUD, Lima, Perú (MG); Hospital Nacional Guillermo Almenara, ESSALUD, Lima, Perú (LR); Hospital Nacional Cayetano Heredia, Ministerio de Salud, Lima, Perú (EN, HU); and Hospital Nacional Alberto Sabogal, ESSALUD, Callao, Perú (EJP) 1
2
3
4
Garcia HH, Gonzales I, Lescano AG, et al, for the Cysticercosis Working Group in Peru. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis 2014; 14: 687–95. Carpio A, Hauser WA. Prognosis for seizure recurrence in patients with newly diagnosed neurocysticercosis. Neurology 2002; 59: 1730–34. Xu HX, Zhang QZ, Liu YL, Mao DH, Shi SJ, Xu J. Effect of praziquantel alone or albendazole alone or combination of two drugs in treatment of cysticercosis. J Qiqihar Med College 2001; 22: 999–1000 (in Chinese). Garcia HH, Lescano AG, Lanchote VL, et al, for the Cysticercosis Working Group in Peru. Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis. Br J Clin Pharmacol 2011; 72: 77–84.
www.thelancet.com/infection Vol 15 March 2015
Influenza vaccine for Hajj and Umrah pilgrims In their Series paper, Brian McCloskey and colleagues1 point out that access to influenza vaccine is a key element in the global strategy to minimise risk of pandemic influenza. 1 The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia has prompted worldwide preparedness and a responsive attitude in many countries for surveillance and detection of cases in individuals returning from the Arabian Peninsula. The virology laboratory of the Public Hospital system of Marseille has received 33 samples from patients classified as having suspect or probable MERS-CoV cases on the basis of national criteria from August, 2013, to April, 2014. Most of the samples were from patients who had returned from Saudi Arabia after participating to the Umrah and Hajj pilgrimages. None of these patients was infected with MERS-CoV; however, 17 (52%) were infected with respiratory viruses. 13 of these virus-positive samples contained influenza virus RNA (seven contained influenza A subtype H3N2, four contained pandemic influenza A subtype H1N1 2009, and two contained influenza B); of the remaining positive samples, two contained CoV-229E, one contained human metapneumovirus, and one contained rhinovirus. In summary, 75% of viruses detected in patients returning from the Arabian Peninsula with clinical features compatible with a MERS-CoV were influenza viruses for which a vaccine is theoretically available. The Saudi Ministry of Health recom mends seasonal influenza vaccine for all international pilgrims.2 In France, influenza vaccine is accessible to individuals and the public health-care system only during a specific period (eg, Oct 11, 2013, to Feb 28, 2014, for the 2013–14
season), which corresponds to the epidemic influenza season in the northern hemisphere. 30 (91%) of the 33 pilgrims that we assessed did not have the opportunity to get immunised against influenza because the vaccine was not available in the period before they travelled. Another study that systematically screened a cohort of returned French Hajj pilgrims in 2013 showed that eight (6%) of 129 acquired influenza virus during the pilgrimage. None was vaccinated against influenza in 2013.3 Accordingly, a substantial proportion of individuals crossing hemispheres, or participating in mass gathering events grouping people from both hemispheres, clearly have no access to vaccine-based prevention of influenza because of regulations. Seasonal availability of influenza vaccine in a globally mobile world is an insufficient way to prevent a disease that is notoriously transmitted from person to person irrespective of their location on the planet. We believe that influenza vaccine should be made available at any time to overcome this contradictory situation. We declare no competing interests.
*Remi N Charrel, Antoine Nougairede, Philippe Brouqui, Didier Raoult, Philippe Gautret [email protected] Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR_D 190 “Emergence des Pathologies Virales”, Marseille 13385, France (RNC, AN); Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France (RNC, AN, PB, DR, PG); and Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France (PB, DR, PG) 1
2
3
McCloskey B, Dar O, Zumla A, Heymann DL. Emerging infectious diseases and pandemic potential: status quo and reducing risk of global spread. Lancet Infect Dis 2014; 14: 1001–10. Memish ZA, Al Rabeeah AA. Health conditions for travellers to Saudi Arabia for the Umra and pilgrimage to Mecca (Hajj)—2014. J Epidemiol Glob Health 2014; 4: 73–75. Gautret P, Charrel R, Benkouiten S, et al. Lack of MERS coronavirus but prevalence of influenza virus in French pilgrims after 2013 Hajj. Emerg Infect Dis 2014; 20: 728–30.
267
