Skip to main content
Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases 5/2014

01.05.2014 | Article

Comparison of the Kato-Katz method and ether-concentration technique for the diagnosis of soil-transmitted helminth infections in the framework of a randomised controlled trial

verfasst von: B. Speich, J. Utzinger, H. Marti, S. M. Ame, S. M. Ali, M. Albonico, J. Keiser

Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases | Ausgabe 5/2014

Einloggen, um Zugang zu erhalten

Abstract

Soil-transmitted helminth infections are a major public health problem. An accurate diagnosis is important in order to identify individuals and communities in need of intervention, and for monitoring drug efficacy and potential emergence of resistance. We compared the accuracy of the Kato-Katz method and ether-concentration technique for the diagnosis of soil-transmitted helminth infections within a randomised controlled trial. Quadruplicate Kato-Katz thick smears (duplicate Kato-Katz from two stool samples each) were examined before (baseline) and 3 weeks after treatment (follow-up). Additionally, at baseline and follow-up, the first stool sample was subjected to an ether-concentration method. We determined the prevalence, sensitivity, negative predictive value, diagnostic agreement and cure rates for single and duplicate Kato-Katz thick smears from the first stool sample, quadruplicate Kato-Katz thick smears produced from two stool samples and single ether-concentration as compared to our ‘gold’ standard (i.e. quadruplicate Kato-Katz plus ether-concentration). Quadruplicate Kato-Katz revealed a higher sensitivity than single ether-concentration for Trichuris trichiura at baseline (94.3 % vs. 88.5 %, p = 0.002) and follow-up (93.8 % vs. 83.5 %, p < 0.001). In contrary, at follow-up, ether-concentration showed a higher sensitivity than quadruplicate Kato-Katz for Ascaris lumbricoides diagnosis (86.7 % vs. 46.7 %, p = 0.012). The ether-concentration method showed similar or slightly higher sensitivity than the Kato-Katz technique based on a single stool sample for all soil-transmitted helminth infections. The estimated cure rates were heavily dependent on the diagnostic technique and sampling effort. In conclusion, data on the prevalence of soil-transmitted helminth infections and the efficacy of anthelminthics are greatly influenced by the diagnostic method and sampling effort. The ether-concentration technique is a valuable alternative to the Kato-Katz method for helminth diagnosis.
Literatur
1.
Zurück zum Zitat Murray CJL, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C et al (2012) Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2197–2223PubMedCrossRef Murray CJL, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C et al (2012) Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2197–2223PubMedCrossRef
2.
Zurück zum Zitat World Health Organization (2006) Preventive chemotherapy in human helminthiasis. Coordinated use of anthelminthic drugs in control interventions: a manual for health professionals and programme managers. WHO, Geneva, pp 1–62 World Health Organization (2006) Preventive chemotherapy in human helminthiasis. Coordinated use of anthelminthic drugs in control interventions: a manual for health professionals and programme managers. WHO, Geneva, pp 1–62
3.
Zurück zum Zitat Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Ehrlich Sachs S, Sachs JD et al (2007) Control of neglected tropical diseases. N Engl J Med 357:1018–1027 Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Ehrlich Sachs S, Sachs JD et al (2007) Control of neglected tropical diseases. N Engl J Med 357:1018–1027
4.
Zurück zum Zitat World Health Organization (2013) Sustaining the drive to overcome the global impact of neglected tropical diseases. Second WHO report on neglected tropical diseases. WHO, Geneva, pp 1–139 World Health Organization (2013) Sustaining the drive to overcome the global impact of neglected tropical diseases. Second WHO report on neglected tropical diseases. WHO, Geneva, pp 1–139
5.
Zurück zum Zitat Bergquist R, Johansen MV, Utzinger J (2009) Diagnostic dilemmas in helminthology: what tools to use and when? Trends Parasitol 25:151–156PubMedCrossRef Bergquist R, Johansen MV, Utzinger J (2009) Diagnostic dilemmas in helminthology: what tools to use and when? Trends Parasitol 25:151–156PubMedCrossRef
6.
Zurück zum Zitat McCarthy JS, Lustigman S, Yang GJ, Barakat RM, García HH, Sripa B et al (2012) A research agenda for helminth diseases of humans: diagnostics for control and elimination programmes. PLoS Negl Trop Dis 6:e1601PubMedCentralPubMedCrossRef McCarthy JS, Lustigman S, Yang GJ, Barakat RM, García HH, Sripa B et al (2012) A research agenda for helminth diseases of humans: diagnostics for control and elimination programmes. PLoS Negl Trop Dis 6:e1601PubMedCentralPubMedCrossRef
7.
Zurück zum Zitat Katz N, Chaves A, Pellegrino J (1972) A simple device for quantitative stool thick-smear technique in schistosomiasis mansoni. Rev Inst Med Trop São Paulo 14:397–400 Katz N, Chaves A, Pellegrino J (1972) A simple device for quantitative stool thick-smear technique in schistosomiasis mansoni. Rev Inst Med Trop São Paulo 14:397–400
8.
Zurück zum Zitat Booth M, Vounatsou P, N’Goran EK, Tanner M, Utzinger J (2003) The influence of sampling effort and the performance of the Kato-Katz technique in diagnosing Schistosoma mansoni and hookworm co-infections in rural Côte d’Ivoire. Parasitology 127:525–531PubMedCrossRef Booth M, Vounatsou P, N’Goran EK, Tanner M, Utzinger J (2003) The influence of sampling effort and the performance of the Kato-Katz technique in diagnosing Schistosoma mansoni and hookworm co-infections in rural Côte d’Ivoire. Parasitology 127:525–531PubMedCrossRef
9.
Zurück zum Zitat Lin D-D, Liu J-X, Liu Y-M, Hu F, Zhang Y-Y, Xu J-M et al (2008) Routine Kato-Katz technique underestimates the prevalence of Schistosoma japonicum: a case study in an endemic area of the People’s Republic of China. Parasitol Int 57:281–286PubMedCrossRef Lin D-D, Liu J-X, Liu Y-M, Hu F, Zhang Y-Y, Xu J-M et al (2008) Routine Kato-Katz technique underestimates the prevalence of Schistosoma japonicum: a case study in an endemic area of the People’s Republic of China. Parasitol Int 57:281–286PubMedCrossRef
10.
Zurück zum Zitat Speich B, Knopp S, Mohammed KA, Khamis IS, Rinaldi L, Cringoli G et al (2010) Comparative cost assessment of the Kato-Katz and FLOTAC techniques for soil-transmitted helminth diagnosis in epidemiological surveys. Parasit Vectors 3:71PubMedCentralPubMedCrossRef Speich B, Knopp S, Mohammed KA, Khamis IS, Rinaldi L, Cringoli G et al (2010) Comparative cost assessment of the Kato-Katz and FLOTAC techniques for soil-transmitted helminth diagnosis in epidemiological surveys. Parasit Vectors 3:71PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat Lovis L, Mak TK, Phongluxa K, Ayé Soukhathammavong P, Vonghachack Y, Keiser J et al (2012) Efficacy of praziquantel against Schistosoma mekongi and Opisthorchis viverrini: a randomized, single-blinded dose-comparison trial. PLoS Negl Trop Dis 6:e1726 Lovis L, Mak TK, Phongluxa K, Ayé Soukhathammavong P, Vonghachack Y, Keiser J et al (2012) Efficacy of praziquantel against Schistosoma mekongi and Opisthorchis viverrini: a randomized, single-blinded dose-comparison trial. PLoS Negl Trop Dis 6:e1726
12.
Zurück zum Zitat Ebrahim A, El-Morshedy H, Omer E, El-Daly S, Barakat R (1997) Evaluation of the Kato-Katz thick smear and formol ether sedimentation techniques for quantitative diagnosis of Schistosoma mansoni infection. Am J Trop Med Hyg 57:706–708PubMed Ebrahim A, El-Morshedy H, Omer E, El-Daly S, Barakat R (1997) Evaluation of the Kato-Katz thick smear and formol ether sedimentation techniques for quantitative diagnosis of Schistosoma mansoni infection. Am J Trop Med Hyg 57:706–708PubMed
13.
Zurück zum Zitat Utzinger J, Booth M, N’Goran EK, Müller I, Tanner M, Lengeler C (2001) Relative contribution of day-to-day and intra-specimen variation in faecal egg counts of Schistosoma mansoni before and after treatment with praziquantel. Parasitology 122:537–544PubMedCrossRef Utzinger J, Booth M, N’Goran EK, Müller I, Tanner M, Lengeler C (2001) Relative contribution of day-to-day and intra-specimen variation in faecal egg counts of Schistosoma mansoni before and after treatment with praziquantel. Parasitology 122:537–544PubMedCrossRef
14.
Zurück zum Zitat Steinmann P, Du ZW, Wang LB, Wang XZ, Jiang JY, Li LH et al (2008) Extensive multiparasitism in a village of Yunnan province, People’s Republic of China, revealed by a suite of diagnostic methods. Am J Trop Med Hyg 78:760–769PubMed Steinmann P, Du ZW, Wang LB, Wang XZ, Jiang JY, Li LH et al (2008) Extensive multiparasitism in a village of Yunnan province, People’s Republic of China, revealed by a suite of diagnostic methods. Am J Trop Med Hyg 78:760–769PubMed
15.
Zurück zum Zitat Knopp S, Rinaldi L, Khamis IS, Stothard JR, Rollinson D, Maurelli MP et al (2009) A single FLOTAC is more sensitive than triplicate Kato-Katz for the diagnosis of low-intensity soil-transmitted helminth infections. Trans R Soc Trop Med Hyg 103:347–354PubMedCrossRef Knopp S, Rinaldi L, Khamis IS, Stothard JR, Rollinson D, Maurelli MP et al (2009) A single FLOTAC is more sensitive than triplicate Kato-Katz for the diagnosis of low-intensity soil-transmitted helminth infections. Trans R Soc Trop Med Hyg 103:347–354PubMedCrossRef
16.
Zurück zum Zitat Glinz D, Silué KD, Knopp S, Lohourignon LK, Yao KP, Steinmann P et al (2010) Comparing diagnostic accuracy of Kato-Katz, Koga agar plate, ether-concentration, and FLOTAC for Schistosoma mansoni and soil-transmitted helminths. PLoS Negl Trop Dis 4:e754PubMedCentralPubMedCrossRef Glinz D, Silué KD, Knopp S, Lohourignon LK, Yao KP, Steinmann P et al (2010) Comparing diagnostic accuracy of Kato-Katz, Koga agar plate, ether-concentration, and FLOTAC for Schistosoma mansoni and soil-transmitted helminths. PLoS Negl Trop Dis 4:e754PubMedCentralPubMedCrossRef
17.
Zurück zum Zitat Levallois P, Chevalier P, Gingras S, Déry P, Payment P, Michel P et al (2013) Risk of infectious gastroenteritis in young children living in Québec rural areas with intensive animal farming: results of a case–control study (2004–2007). Zoonoses Public Health. doi:10.1111/zph.12039 Levallois P, Chevalier P, Gingras S, Déry P, Payment P, Michel P et al (2013) Risk of infectious gastroenteritis in young children living in Québec rural areas with intensive animal farming: results of a case–control study (2004–2007). Zoonoses Public Health. doi:10.​1111/​zph.​12039
18.
Zurück zum Zitat World Health Organization (2008) Action against worms. February 2008, Issue 11 World Health Organization (2008) Action against worms. February 2008, Issue 11
19.
20.
Zurück zum Zitat Speich B, Ame SM, Ali SM, Alles R, Hattendorf J, Utzinger J et al (2012) Efficacy and safety of nitazoxanide, albendazole, and nitazoxanide–albendazole against Trichuris trichiura infection: a randomized controlled trial. PLoS Negl Trop Dis 6:e1685PubMedCentralPubMedCrossRef Speich B, Ame SM, Ali SM, Alles R, Hattendorf J, Utzinger J et al (2012) Efficacy and safety of nitazoxanide, albendazole, and nitazoxanide–albendazole against Trichuris trichiura infection: a randomized controlled trial. PLoS Negl Trop Dis 6:e1685PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Marti H, Escher E (1990) SAF—an alternative fixation solution for parasitological stool specimens. Schweiz Med Wochenschr 120:1473–1476PubMed Marti H, Escher E (1990) SAF—an alternative fixation solution for parasitological stool specimens. Schweiz Med Wochenschr 120:1473–1476PubMed
22.
Zurück zum Zitat Utzinger J, Botero-Kleiven S, Castelli F, Chiodini PL, Edwards H, Köhler N et al (2010) Microscopic diagnosis of sodium acetate-acetic acid-formalin-fixed stool samples for helminths and intestinal protozoa: a comparison among European reference laboratories. Clin Microbiol Infect 16:267–273PubMedCrossRef Utzinger J, Botero-Kleiven S, Castelli F, Chiodini PL, Edwards H, Köhler N et al (2010) Microscopic diagnosis of sodium acetate-acetic acid-formalin-fixed stool samples for helminths and intestinal protozoa: a comparison among European reference laboratories. Clin Microbiol Infect 16:267–273PubMedCrossRef
23.
Zurück zum Zitat Speich B, Marti H, Ame SM, Ali SM, Bogoch II, Utzinger J et al (2013) Prevalence of intestinal protozoa infection among school-aged children on Pemba Island, Tanzania, and effect of single-dose albendazole, nitazoxanide and albendazole–nitazoxanide. Parasit Vectors 6:3PubMedCentralPubMedCrossRef Speich B, Marti H, Ame SM, Ali SM, Bogoch II, Utzinger J et al (2013) Prevalence of intestinal protozoa infection among school-aged children on Pemba Island, Tanzania, and effect of single-dose albendazole, nitazoxanide and albendazole–nitazoxanide. Parasit Vectors 6:3PubMedCentralPubMedCrossRef
24.
Zurück zum Zitat Cohen J (1960) A coefficient of agreement for nominal scales. Educ Psychol Meas 20:37–46CrossRef Cohen J (1960) A coefficient of agreement for nominal scales. Educ Psychol Meas 20:37–46CrossRef
25.
Zurück zum Zitat Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33:159–174PubMedCrossRef Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33:159–174PubMedCrossRef
26.
Zurück zum Zitat Hawass NE (1997) Comparing the sensitivities and specificities of two diagnostic procedures performed on the same group of patients. Br J Radiol 70:360–366PubMed Hawass NE (1997) Comparing the sensitivities and specificities of two diagnostic procedures performed on the same group of patients. Br J Radiol 70:360–366PubMed
27.
Zurück zum Zitat Albonico M, Engels D, Savioli L (2004) Monitoring drug efficacy and early detection of drug resistance in human soil-transmitted nematodes: a pressing public health agenda for helminth control. Int J Parasitol 34:1205–1210PubMedCrossRef Albonico M, Engels D, Savioli L (2004) Monitoring drug efficacy and early detection of drug resistance in human soil-transmitted nematodes: a pressing public health agenda for helminth control. Int J Parasitol 34:1205–1210PubMedCrossRef
28.
Zurück zum Zitat Cringoli G, Rinaldi L, Maurelli MP, Utzinger J (2010) FLOTAC: new multivalent techniques for qualitative and quantitative copromicroscopic diagnosis of parasites in animals and humans. Nat Protoc 5:503–515PubMedCrossRef Cringoli G, Rinaldi L, Maurelli MP, Utzinger J (2010) FLOTAC: new multivalent techniques for qualitative and quantitative copromicroscopic diagnosis of parasites in animals and humans. Nat Protoc 5:503–515PubMedCrossRef
29.
Zurück zum Zitat King JD, Endeshaw T, Escher E, Alemtaye G, Melaku S, Gelaye W et al (2013) Intestinal parasite prevalence in an area of Ethiopia after implementing the SAFE strategy, enhanced outreach services, and health extension program. PLoS Negl Trop Dis 7:e2223PubMedCentralPubMedCrossRef King JD, Endeshaw T, Escher E, Alemtaye G, Melaku S, Gelaye W et al (2013) Intestinal parasite prevalence in an area of Ethiopia after implementing the SAFE strategy, enhanced outreach services, and health extension program. PLoS Negl Trop Dis 7:e2223PubMedCentralPubMedCrossRef
30.
Zurück zum Zitat Bogoch II, Andrews JR, Speich B, Utzinger J, Ame SM, Ali SM et al (2013) Mobile phone microscopy for the diagnosis of soil-transmitted helminth infections: a proof-of-concept study. Am J Trop Med Hyg 88:626–629PubMedCentralPubMedCrossRef Bogoch II, Andrews JR, Speich B, Utzinger J, Ame SM, Ali SM et al (2013) Mobile phone microscopy for the diagnosis of soil-transmitted helminth infections: a proof-of-concept study. Am J Trop Med Hyg 88:626–629PubMedCentralPubMedCrossRef
31.
Zurück zum Zitat Khieu V, Schär F, Marti H, Sayasone S, Duong S, Muth S et al (2013) Diagnosis, treatment and risk factors of Strongyloides stercoralis in schoolchildren in Cambodia. PLoS Negl Trop Dis 7:e2035PubMedCentralPubMedCrossRef Khieu V, Schär F, Marti H, Sayasone S, Duong S, Muth S et al (2013) Diagnosis, treatment and risk factors of Strongyloides stercoralis in schoolchildren in Cambodia. PLoS Negl Trop Dis 7:e2035PubMedCentralPubMedCrossRef
32.
Zurück zum Zitat Jeandron A, Abdyldaieva G, Usubalieva J, Ensink JH, Cox J, Matthys B et al (2010) Accuracy of the Kato-Katz, adhesive tape and FLOTAC techniques for helminth diagnosis among children in Kyrgyzstan. Acta Trop 116:185–192PubMedCrossRef Jeandron A, Abdyldaieva G, Usubalieva J, Ensink JH, Cox J, Matthys B et al (2010) Accuracy of the Kato-Katz, adhesive tape and FLOTAC techniques for helminth diagnosis among children in Kyrgyzstan. Acta Trop 116:185–192PubMedCrossRef
33.
Zurück zum Zitat Knopp S, Mgeni AF, Khamis IS, Steinmann P, Stothard JR, Rollinson D et al (2008) Diagnosis of soil-transmitted helminths in the era of preventive chemotherapy: effect of multiple stool sampling and use of different diagnostic techniques. PLoS Negl Trop Dis 2:e331PubMedCentralPubMedCrossRef Knopp S, Mgeni AF, Khamis IS, Steinmann P, Stothard JR, Rollinson D et al (2008) Diagnosis of soil-transmitted helminths in the era of preventive chemotherapy: effect of multiple stool sampling and use of different diagnostic techniques. PLoS Negl Trop Dis 2:e331PubMedCentralPubMedCrossRef
34.
Zurück zum Zitat Utzinger J, Rinaldi L, Lohourignon LK, Rohner F, Zimmermann MB, Tschannen AB et al (2008) FLOTAC: a new sensitive technique for the diagnosis of hookworm infections in humans. Trans R Soc Trop Med Hyg 102:84–90PubMedCrossRef Utzinger J, Rinaldi L, Lohourignon LK, Rohner F, Zimmermann MB, Tschannen AB et al (2008) FLOTAC: a new sensitive technique for the diagnosis of hookworm infections in humans. Trans R Soc Trop Med Hyg 102:84–90PubMedCrossRef
35.
Zurück zum Zitat Habtamu K, Degarege A, Ye-Ebiyo Y, Erko B (2011) Comparison of the Kato-Katz and FLOTAC techniques for the diagnosis of soil-transmitted helminth infections. Parasitol Int 60:398–402PubMedCrossRef Habtamu K, Degarege A, Ye-Ebiyo Y, Erko B (2011) Comparison of the Kato-Katz and FLOTAC techniques for the diagnosis of soil-transmitted helminth infections. Parasitol Int 60:398–402PubMedCrossRef
36.
Zurück zum Zitat Knopp S, Speich B, Hattendorf J, Rinaldi L, Mohammed KA, Khamis IS et al (2011) Diagnostic accuracy of Kato-Katz and FLOTAC for assessing anthelmintic drug efficacy. PLoS Negl Trop Dis 5:e1036PubMedCentralPubMedCrossRef Knopp S, Speich B, Hattendorf J, Rinaldi L, Mohammed KA, Khamis IS et al (2011) Diagnostic accuracy of Kato-Katz and FLOTAC for assessing anthelmintic drug efficacy. PLoS Negl Trop Dis 5:e1036PubMedCentralPubMedCrossRef
37.
Zurück zum Zitat World Health Organization (2008) Working group on soil-transmitted helminthiasis. Monitoring anthelmintic efficacy for soil transmitted helminths (STH) World Health Organization (2008) Working group on soil-transmitted helminthiasis. Monitoring anthelmintic efficacy for soil transmitted helminths (STH)
38.
Zurück zum Zitat Bogoch II, Raso G, N’Goran EK, Marti HP, Utzinger J (2006) Differences in microscopic diagnosis of helminths and intestinal protozoa among diagnostic centres. Eur J Clin Microbiol Infect Dis 25:344–347PubMedCrossRef Bogoch II, Raso G, N’Goran EK, Marti HP, Utzinger J (2006) Differences in microscopic diagnosis of helminths and intestinal protozoa among diagnostic centres. Eur J Clin Microbiol Infect Dis 25:344–347PubMedCrossRef
Metadaten
Titel
Comparison of the Kato-Katz method and ether-concentration technique for the diagnosis of soil-transmitted helminth infections in the framework of a randomised controlled trial
verfasst von
B. Speich
J. Utzinger
H. Marti
S. M. Ame
S. M. Ali
M. Albonico
J. Keiser
Publikationsdatum
01.05.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Clinical Microbiology & Infectious Diseases / Ausgabe 5/2014
Print ISSN: 0934-9723
Elektronische ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-013-2019-1

Weitere Artikel der Ausgabe 5/2014

European Journal of Clinical Microbiology & Infectious Diseases 5/2014 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Semaglutid bei Herzinsuffizienz: Wie erklärt sich die Wirksamkeit?

17.05.2024 Herzinsuffizienz Nachrichten

Bei adipösen Patienten mit Herzinsuffizienz des HFpEF-Phänotyps ist Semaglutid von symptomatischem Nutzen. Resultiert dieser Benefit allein aus der Gewichtsreduktion oder auch aus spezifischen Effekten auf die Herzinsuffizienz-Pathogenese? Eine neue Analyse gibt Aufschluss.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.