Comment
that their child might miss out on various physical and team-based activities such as swimming or gymnastics for a long time until all lesions are healed. I believe that active treatment of lesions is often preferable.7 It might be necessary to assuage fears of transmission and autoinoculation, improve cosmetic appearance, reduce the social stigma associated with visible lesions, or alleviate discomfort.7 I agree with Olsen and colleagues that treatment should be considered, especially in children with many lesions and those with severe reduction in quality of life. The preference of the child or parents should be taken into consideration in the decision process. As such, the present study provides crucial information about the expected natural history of molluscum contagiosum that can better inform the decision-making process.
P Marazzi/Science Photo Library
13 children with molluscum contagiosum in Alaska and noted that the duration of lesions ranged from 2 weeks to 18 months.3 Takemura and colleagues4 reported that the mean duration of spontaneous resolution was 6·5 months in 205 of 217 Japanese children with molluscum contagiosum. The study by Olsen and colleagues is the largest reported prospective cohort of children with molluscum contagiosum up to now and provides invaluable information about the natural history of the disorder. The study would have been strengthened had every case been confirmed by a clinician and, when relevant, reporting of comorbidities because the natural history of molluscum contagiosum in healthy children is probably different from those with risk factors such as immunodeficiency and extensive atopic dermatitis. Most researchers believe that molluscum contagiosum lesions persist in immunocompromised hosts.6 As such, it would be informative to analyse children with risk factors separately. The time of resolution of individual lesions is much shorter than what is commonly believed. Autoinoculation and so-called ping-pong infection from affected family members might prolong the time taken to achieve complete clinical resolution because new lesions can appear as old ones resolve. Hopefully, future large, well-designed, prospective studies can shed light on the natural history of individual lesions. In this regard, timely treatment of initial lesions might prevent the occurrence of new lesions.6,7 Because molluscum contagiosum is benign and self-limiting, some researchers suggest conservative, supportive management while awaiting spontaneous resolution.8 One major concern expressed by parents is
Alexander K C Leung University of Calgary, Alberta Children’s Hospital, Alberta T2M 0H5, Canada [email protected] I declare no competing interests. 1
2 3 4 5
6 7 8
Kyriakis KP, Palamaras I, Alexoudi I, Vrani F. Molluscum contagiosum detection rates among Greek dermatology outpatients. Scand J Infect Dis 2010; 42: 719–20. Hawley TG. The natural history of molluscum contagiosum in Fijian children. J Hyg 1970; 68: 631–32. Overfield TM, Brody JA. An epidemiologic study of molluscum contagiosum in Anchorage, Alaska. J Pediatr 1970; 69: 640–42. Takemura T, Ohkuma K, Ngai H, Saito T. The natural history of molluscum contagiosum. 1983; 5: 667–70 (in Japanese). Olsen JR, Gallacher J, Finlay AY, Piguet V, Francis NA. Time to resolution and effect on quality of life of molluscum contagiosum in children in the UK: a prospective community cohort study. 2014; published online Dec 23. http://dx.doi.org/10.1016/S1473-3099(14)71061-8. Leung AK, Davies HD. Molluscum contagiosum: an overview. Curr Pediatr Rev 2012; 8: 346–49. Silverberg NB. Warts and molluscum in children. Adv Dermatol 2004; 20: 23–73. Brown J, Janniger CK, Schwartz RA, Silverberg NB. Childhood molluscum contagiosum. Int J Dermatol 2006; 45: 93–99.
Babesiosis in China, an emerging threat In The Lancet Infectious Diseases, Jia-Fu Jiang and colleagues report 48 cases of “Babesia venatorum” infection in a northeastern forested province of China between 2011 and 2014.1 This case series is the largest ever reported for “B venatorum” and the first description of a “B venatorum” endemic area. The investigators also detected “B venatorum” in Ixodes persulcatus ticks, suggesting that this tick species is the local vector for the parasite. Zoonotic transmission of “B venatorum” is not restricted to the www.thelancet.com/infection Vol 15 February 2015
northeast, as shown by a recent case of “B venatorum” infection in a semiarid northwestern province.2 Because Babesia microti and Babesia divergens have caused disease in western and southeastern mainland China, the health burden imposed by babesiosis in this country of 1·3 billion people could be substantial (figure).1–5 Cases were identified by use of molecular screening with nested PCR to amplify a 373 base-pair fragment of the babesia 18S rRNA gene.1 These short amplicons
Published Online December 22, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)71062-X See Articles page 196
137
Comment
“B venatorum” (n=1)
Heilongjiang
Jilin
Inner Mongolia
Xinjiang
Liaoning Gansu
Shanxi
Ningxia
Qinghai
Beijing Tianjin Hebei
B divergens (n=2)
Shandong
Uncharacterised (n=9)
Shaanxi Henan
Xizang Sichuan
Hubei
Jiangsu
Anhui
Chongqing
Shanghai
Zhejiang
Jiangxi Guizhou
B microti (n=11) Uncharacterised (n=1)
Forest types Coniferous Broad leaved Mixed coniferous and broad leaved
B microti (n=1)
Hunan Fujian
B microti (n=1)
Yunnan
Uncharacterised (n=2)
*”B venatorum” (n=48)
Guangxi
Taiwan
Guangdong Hong Kong
B microti (n=1)
Hainan
Figure: Babesiosis cases reported in mainland China and Taiwan The number of cases are shown in parentheses. B=Babesia. *Cases reported by Jiang and colleagues.
were identical in all 48 cases and consistent with “B venatorum”. A longer fragment of the 18S rRNA gene was amplified from blood samples from four patients and differed by only two base pairs from those obtained in European patients with “B venatorum”, thereby showing a striking similarity in the isolates collected in very different ecosystems.1,3,6 Additional evidence of active babesia infection were obtained from a subset of cases by use of standard microscopy and fluorescence in-situ hybridisation of blood smears and by inoculation of patient blood into mice with severe combined immunodeficiency (SCID). 32 of 48 cases met the US Centers for Disease Control and Prevention (CDC) case definition of confirmed babesiosis that includes both clinical and laboratory criteria.7 16 cases were described as probable, although none had the objective or subjective clinical criteria to meet the CDC probable case definition. 138
Human babesiosis is a worldwide emerging infectious disease caused by intraerythrocytic parasites of the genus Babesia that infect a wide array of wild and domestic vertebrate reservoirs.3 Most human cases have been described in the USA and are due to B microti, a parasite transmitted by Ixodes scapularis ticks and less commonly by blood transfusion and transplacentally.3,8 These different modes of transmission have not been shown for “B venatorum”. All five previous cases of “B venatorum” were admitted to hospital, of which four individuals had had their spleens removed.3,6,9 Jiang and colleagues now report a broad range of “B venatorum” disease severity in apparently immune-intact individuals.1 A third of cases were asymptomatic, the proportion reported for B microti infection.10 Symptoms of “B venatorum” illness were also like those of B microti, but fever and chills were less common.1,3,11 Although the hospital admission rate was www.thelancet.com/infection Vol 15 February 2015
Comment
similar to the rates reported for B microti infection, there were no acute complications and no deaths.1,10 These data suggest that “B venatorum” disease is milder than B microti disease in immunocompetent individuals. Reasons for milder disease might include lower microbial virulence, as suggested by low “B venatorum” parasitemia in SCID mice, and a younger patient population because two-thirds of the confirmed cases were younger than 50 years. Circulating concentrations of several proinflammatory cytokines (tumour necrosis factor α, interferon γ, and interleukin 6) and one adhesion molecule (vascular cell adhesion molecule 1) were increased in confirmed cases, lending support to the idea that excessive production of proinflammatory cytokines and activated vascular endothelium contribute to the pathogenesis of the disease. Cure of “B venatorum” infection previously was achieved with quinine plus clindamycin or atovaquone plus azithromycin.2,6,9 In the current case series, none of the seven patients admitted to hospital received standard regimens; four were given clindamycin without quinine. All patients recovered, however, follow-up to detect possible sequelae was not done. Cases of babesiosis have been reported in mainland China and Taiwan for more than three decades, but there is still much to be learned.4 Co-infections with B microti and Plasmodium falciparum have been reported in areas of Yunnan province that border Burma.12 B microti, B divergens, and “B venatorum” can all infect I persulcatus and human co-infection with several of these pathogens is an intriguing possibility.13 As cases continue to emerge in mainland China and elsewhere in Asia, it is imperative that we improve our understanding of the health burden of human babesiosis in this densely
populated region of the globe. This report should provide further impetus and direction toward that goal. Edouard Vannier, *Peter J Krause Department of Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, MA (EV); and Department of Epidemiology of Microbial Diseases, Yale School of Public Health and Departments of Medicine and Pediatrics, Yale School of Medicine, 60 College Street, New Haven, CT 06520, USA (PJK) [email protected] We declare no competing interests. EV and PJK were supported by the Gordon and Llura Gund Foundation, EV by the National Research Fund for Tick-Borne Diseases, and PJK by the National Institutes of Health (R21 AI09486). 1
2 3 4 5
6 7 8
9 10 11 12
13
Jiang JF, Zheng YC, Jiang RR, et al. Epidemiological, clinical, and laboratory characteristics of 48 cases with “Babesia venatorum” infection in China: a descriptive study. Lancet Infect Dis 2014; published Dec 22. http://dx.doi. org/10.1016/S1473-3099(14)71046-1. Sun YS, Li SG, Jiang JF, et al. Babesia venatorum infection in child, China. Emerg Infect Dis 2014; 20: 896–97. Vannier E, Krause PJ. Human babesiosis. N Engl J Med 2012; 366: 2397–407. Zhou X, Li S, Wang J, et al. Human babesiosis, an emerging tick-borne disease in the People’s Republic of China. Parasit Vectors 2014; 7: 509. Qi C, Zhou D, Liu J, et al. Detection of Babesia divergens using molecular methods in anemic patients in Shandong Province, China. Parasitol Res 2011; 109: 241–45. Hunfeld KP, Hildebrandt A, Gray JS. Babesiosis: recent insights into an ancient disease. Int J Parasitol 2008; 38: 1219–37. Prevention CDC. Babesiosis surveillance—18 states, 2011. Morb Mortal Wkly Rep 2012; 61: 505–09. Herwaldt BL, Linden JV, Bosserman E, et al. Transfusion-associated babesiosis in the United States: a description of cases. Ann Intern Med 2011; 155: 509–19. Blum S, Gattringer R, Haschke E, et al. The case: hemolysis and acute renal failure. Kidney Int 2011; 80: 681–83. Krause PJ, McKay K, Gadbaw J, et al. Increasing health burden of human babesiosis in endemic sites. Am J Trop Med Hyg 2003; 68: 431–06. Joseph JT, Roy SS, Shams N, et al. Babesiosis in Lower Hudson Valley, New York, USA. Emerg Infect Dis 2011; 17: 843–47. Zhou X, Li S, Chen S, et al. Co-infections with Babesia microti and plasmodium parasites along the China—Myanmar border. Infect Dis Poverty 2013; 2: 24. Rar VA, Epikhina TI, Livanova NN et al. Genetic diversity of babesia in Ixodes persulcatus and small mammals from North Ural and West Siberia, Russia. Parasitol 2011; 138: 175–82.
Controlling Ebola: key role of Ebola treatment centres What initially was perceived to be a self-limited outbreak of Ebola virus disease in a forested area of Guinea has become an unprecedented epidemic of international concern that continues to spread unabated in parts of west Africa.1,2 A lack of public health infrastructure together with delays in virus detection and implementation of control interventions have contributed to the widespread transmission of Ebola virus disease in a region inexperienced with this disease.3 As in previous international health crises, such as www.thelancet.com/infection Vol 15 February 2015
the severe acute respiratory syndrome epidemic and the 2009 influenza pandemic, mathematical models are proving instrumental to guide the public health response against Ebola virus disease and monitor the effectiveness of control interventions.4,5 Whereas earlier modelling efforts have relied on compartmental homogeneous-mixing models,6–8 the study by Stefano Merler and colleagues,9 reported in The Lancet Infectious Diseases, uses a microsimulation model to capture spatial heterogeneity in the transmission dynamics of
Published Online January 7, 2015 http://dx.doi.org/10.1016/ S1473-3099(14)71086-2 See Articles page 204
139
that their child might miss out on various physical and team-based activities such as swimming or gymnastics for a long time until all lesions are healed. I believe that active treatment of lesions is often preferable.7 It might be necessary to assuage fears of transmission and autoinoculation, improve cosmetic appearance, reduce the social stigma associated with visible lesions, or alleviate discomfort.7 I agree with Olsen and colleagues that treatment should be considered, especially in children with many lesions and those with severe reduction in quality of life. The preference of the child or parents should be taken into consideration in the decision process. As such, the present study provides crucial information about the expected natural history of molluscum contagiosum that can better inform the decision-making process.
P Marazzi/Science Photo Library
13 children with molluscum contagiosum in Alaska and noted that the duration of lesions ranged from 2 weeks to 18 months.3 Takemura and colleagues4 reported that the mean duration of spontaneous resolution was 6·5 months in 205 of 217 Japanese children with molluscum contagiosum. The study by Olsen and colleagues is the largest reported prospective cohort of children with molluscum contagiosum up to now and provides invaluable information about the natural history of the disorder. The study would have been strengthened had every case been confirmed by a clinician and, when relevant, reporting of comorbidities because the natural history of molluscum contagiosum in healthy children is probably different from those with risk factors such as immunodeficiency and extensive atopic dermatitis. Most researchers believe that molluscum contagiosum lesions persist in immunocompromised hosts.6 As such, it would be informative to analyse children with risk factors separately. The time of resolution of individual lesions is much shorter than what is commonly believed. Autoinoculation and so-called ping-pong infection from affected family members might prolong the time taken to achieve complete clinical resolution because new lesions can appear as old ones resolve. Hopefully, future large, well-designed, prospective studies can shed light on the natural history of individual lesions. In this regard, timely treatment of initial lesions might prevent the occurrence of new lesions.6,7 Because molluscum contagiosum is benign and self-limiting, some researchers suggest conservative, supportive management while awaiting spontaneous resolution.8 One major concern expressed by parents is
Alexander K C Leung University of Calgary, Alberta Children’s Hospital, Alberta T2M 0H5, Canada [email protected] I declare no competing interests. 1
2 3 4 5
6 7 8
Kyriakis KP, Palamaras I, Alexoudi I, Vrani F. Molluscum contagiosum detection rates among Greek dermatology outpatients. Scand J Infect Dis 2010; 42: 719–20. Hawley TG. The natural history of molluscum contagiosum in Fijian children. J Hyg 1970; 68: 631–32. Overfield TM, Brody JA. An epidemiologic study of molluscum contagiosum in Anchorage, Alaska. J Pediatr 1970; 69: 640–42. Takemura T, Ohkuma K, Ngai H, Saito T. The natural history of molluscum contagiosum. 1983; 5: 667–70 (in Japanese). Olsen JR, Gallacher J, Finlay AY, Piguet V, Francis NA. Time to resolution and effect on quality of life of molluscum contagiosum in children in the UK: a prospective community cohort study. 2014; published online Dec 23. http://dx.doi.org/10.1016/S1473-3099(14)71061-8. Leung AK, Davies HD. Molluscum contagiosum: an overview. Curr Pediatr Rev 2012; 8: 346–49. Silverberg NB. Warts and molluscum in children. Adv Dermatol 2004; 20: 23–73. Brown J, Janniger CK, Schwartz RA, Silverberg NB. Childhood molluscum contagiosum. Int J Dermatol 2006; 45: 93–99.
Babesiosis in China, an emerging threat In The Lancet Infectious Diseases, Jia-Fu Jiang and colleagues report 48 cases of “Babesia venatorum” infection in a northeastern forested province of China between 2011 and 2014.1 This case series is the largest ever reported for “B venatorum” and the first description of a “B venatorum” endemic area. The investigators also detected “B venatorum” in Ixodes persulcatus ticks, suggesting that this tick species is the local vector for the parasite. Zoonotic transmission of “B venatorum” is not restricted to the www.thelancet.com/infection Vol 15 February 2015
northeast, as shown by a recent case of “B venatorum” infection in a semiarid northwestern province.2 Because Babesia microti and Babesia divergens have caused disease in western and southeastern mainland China, the health burden imposed by babesiosis in this country of 1·3 billion people could be substantial (figure).1–5 Cases were identified by use of molecular screening with nested PCR to amplify a 373 base-pair fragment of the babesia 18S rRNA gene.1 These short amplicons
Published Online December 22, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)71062-X See Articles page 196
137
Comment
“B venatorum” (n=1)
Heilongjiang
Jilin
Inner Mongolia
Xinjiang
Liaoning Gansu
Shanxi
Ningxia
Qinghai
Beijing Tianjin Hebei
B divergens (n=2)
Shandong
Uncharacterised (n=9)
Shaanxi Henan
Xizang Sichuan
Hubei
Jiangsu
Anhui
Chongqing
Shanghai
Zhejiang
Jiangxi Guizhou
B microti (n=11) Uncharacterised (n=1)
Forest types Coniferous Broad leaved Mixed coniferous and broad leaved
B microti (n=1)
Hunan Fujian
B microti (n=1)
Yunnan
Uncharacterised (n=2)
*”B venatorum” (n=48)
Guangxi
Taiwan
Guangdong Hong Kong
B microti (n=1)
Hainan
Figure: Babesiosis cases reported in mainland China and Taiwan The number of cases are shown in parentheses. B=Babesia. *Cases reported by Jiang and colleagues.
were identical in all 48 cases and consistent with “B venatorum”. A longer fragment of the 18S rRNA gene was amplified from blood samples from four patients and differed by only two base pairs from those obtained in European patients with “B venatorum”, thereby showing a striking similarity in the isolates collected in very different ecosystems.1,3,6 Additional evidence of active babesia infection were obtained from a subset of cases by use of standard microscopy and fluorescence in-situ hybridisation of blood smears and by inoculation of patient blood into mice with severe combined immunodeficiency (SCID). 32 of 48 cases met the US Centers for Disease Control and Prevention (CDC) case definition of confirmed babesiosis that includes both clinical and laboratory criteria.7 16 cases were described as probable, although none had the objective or subjective clinical criteria to meet the CDC probable case definition. 138
Human babesiosis is a worldwide emerging infectious disease caused by intraerythrocytic parasites of the genus Babesia that infect a wide array of wild and domestic vertebrate reservoirs.3 Most human cases have been described in the USA and are due to B microti, a parasite transmitted by Ixodes scapularis ticks and less commonly by blood transfusion and transplacentally.3,8 These different modes of transmission have not been shown for “B venatorum”. All five previous cases of “B venatorum” were admitted to hospital, of which four individuals had had their spleens removed.3,6,9 Jiang and colleagues now report a broad range of “B venatorum” disease severity in apparently immune-intact individuals.1 A third of cases were asymptomatic, the proportion reported for B microti infection.10 Symptoms of “B venatorum” illness were also like those of B microti, but fever and chills were less common.1,3,11 Although the hospital admission rate was www.thelancet.com/infection Vol 15 February 2015
Comment
similar to the rates reported for B microti infection, there were no acute complications and no deaths.1,10 These data suggest that “B venatorum” disease is milder than B microti disease in immunocompetent individuals. Reasons for milder disease might include lower microbial virulence, as suggested by low “B venatorum” parasitemia in SCID mice, and a younger patient population because two-thirds of the confirmed cases were younger than 50 years. Circulating concentrations of several proinflammatory cytokines (tumour necrosis factor α, interferon γ, and interleukin 6) and one adhesion molecule (vascular cell adhesion molecule 1) were increased in confirmed cases, lending support to the idea that excessive production of proinflammatory cytokines and activated vascular endothelium contribute to the pathogenesis of the disease. Cure of “B venatorum” infection previously was achieved with quinine plus clindamycin or atovaquone plus azithromycin.2,6,9 In the current case series, none of the seven patients admitted to hospital received standard regimens; four were given clindamycin without quinine. All patients recovered, however, follow-up to detect possible sequelae was not done. Cases of babesiosis have been reported in mainland China and Taiwan for more than three decades, but there is still much to be learned.4 Co-infections with B microti and Plasmodium falciparum have been reported in areas of Yunnan province that border Burma.12 B microti, B divergens, and “B venatorum” can all infect I persulcatus and human co-infection with several of these pathogens is an intriguing possibility.13 As cases continue to emerge in mainland China and elsewhere in Asia, it is imperative that we improve our understanding of the health burden of human babesiosis in this densely
populated region of the globe. This report should provide further impetus and direction toward that goal. Edouard Vannier, *Peter J Krause Department of Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, MA (EV); and Department of Epidemiology of Microbial Diseases, Yale School of Public Health and Departments of Medicine and Pediatrics, Yale School of Medicine, 60 College Street, New Haven, CT 06520, USA (PJK) [email protected] We declare no competing interests. EV and PJK were supported by the Gordon and Llura Gund Foundation, EV by the National Research Fund for Tick-Borne Diseases, and PJK by the National Institutes of Health (R21 AI09486). 1
2 3 4 5
6 7 8
9 10 11 12
13
Jiang JF, Zheng YC, Jiang RR, et al. Epidemiological, clinical, and laboratory characteristics of 48 cases with “Babesia venatorum” infection in China: a descriptive study. Lancet Infect Dis 2014; published Dec 22. http://dx.doi. org/10.1016/S1473-3099(14)71046-1. Sun YS, Li SG, Jiang JF, et al. Babesia venatorum infection in child, China. Emerg Infect Dis 2014; 20: 896–97. Vannier E, Krause PJ. Human babesiosis. N Engl J Med 2012; 366: 2397–407. Zhou X, Li S, Wang J, et al. Human babesiosis, an emerging tick-borne disease in the People’s Republic of China. Parasit Vectors 2014; 7: 509. Qi C, Zhou D, Liu J, et al. Detection of Babesia divergens using molecular methods in anemic patients in Shandong Province, China. Parasitol Res 2011; 109: 241–45. Hunfeld KP, Hildebrandt A, Gray JS. Babesiosis: recent insights into an ancient disease. Int J Parasitol 2008; 38: 1219–37. Prevention CDC. Babesiosis surveillance—18 states, 2011. Morb Mortal Wkly Rep 2012; 61: 505–09. Herwaldt BL, Linden JV, Bosserman E, et al. Transfusion-associated babesiosis in the United States: a description of cases. Ann Intern Med 2011; 155: 509–19. Blum S, Gattringer R, Haschke E, et al. The case: hemolysis and acute renal failure. Kidney Int 2011; 80: 681–83. Krause PJ, McKay K, Gadbaw J, et al. Increasing health burden of human babesiosis in endemic sites. Am J Trop Med Hyg 2003; 68: 431–06. Joseph JT, Roy SS, Shams N, et al. Babesiosis in Lower Hudson Valley, New York, USA. Emerg Infect Dis 2011; 17: 843–47. Zhou X, Li S, Chen S, et al. Co-infections with Babesia microti and plasmodium parasites along the China—Myanmar border. Infect Dis Poverty 2013; 2: 24. Rar VA, Epikhina TI, Livanova NN et al. Genetic diversity of babesia in Ixodes persulcatus and small mammals from North Ural and West Siberia, Russia. Parasitol 2011; 138: 175–82.
Controlling Ebola: key role of Ebola treatment centres What initially was perceived to be a self-limited outbreak of Ebola virus disease in a forested area of Guinea has become an unprecedented epidemic of international concern that continues to spread unabated in parts of west Africa.1,2 A lack of public health infrastructure together with delays in virus detection and implementation of control interventions have contributed to the widespread transmission of Ebola virus disease in a region inexperienced with this disease.3 As in previous international health crises, such as www.thelancet.com/infection Vol 15 February 2015
the severe acute respiratory syndrome epidemic and the 2009 influenza pandemic, mathematical models are proving instrumental to guide the public health response against Ebola virus disease and monitor the effectiveness of control interventions.4,5 Whereas earlier modelling efforts have relied on compartmental homogeneous-mixing models,6–8 the study by Stefano Merler and colleagues,9 reported in The Lancet Infectious Diseases, uses a microsimulation model to capture spatial heterogeneity in the transmission dynamics of
Published Online January 7, 2015 http://dx.doi.org/10.1016/ S1473-3099(14)71086-2 See Articles page 204
139
