Olivier Petitat^a, Matthias Berger^b, Eugénie Colin-Benoit^c, Charles Béguelin^d, Bernard Flückiger^e, Bettina Hurni^f, Massimo Ruffo^f, Alexandra Röllin^g, Gisela Etter^h, Martina Heimⁱ, Katia Boggian^j, Philip Tarr^a

Im Alter sind gewisse Infektionskrankheiten und schwere Verläufe häufiger und das Ansprechen auf Impfungen weniger gut. Dies wegen Komorbiditäten, funktioneller Einschränkungen und altersbedingter (Immunseneszenz) oder anderer Abwehrschwäche. Infektionen können sich mit wenig fokalen (organbezogenen) Symptomen präsentieren; Fieber und Symptome können fehlen. Dies kann die Infektionsdiagnose erschweren.

Einleitung

Gemäss Weltgesundheitsorganisation (WHO) gelten Menschen >65 Jahre als «alt» [1]. Hausärztinnen sehen zunehmend alte Menschen, und Infektionen sind im Alter häufig. Wegen steigender Lebenserwartung leben mehr alte Personen mit kognitiven und anderen funktionellen Einschränkungen, Komorbiditäten und Polypharmazie. Von eben diesen Faktoren, vom sozialen Umfeld [2] – und spannenderweise weniger vom Alter selbst – hängen die Häufigkeit und Prognose von Infektionskrankheiten ab. Gute Übersichtsartikel sind zu Immunologie [3, 4], Infektionskrankheiten [5, 6] und Impfungen [7, 8] im Alter erhältlich. Hier möchten wir die für die Praxis relevanten Konzepte zusammenzufassen.

Das Immunsystem bei älteren Menschen

«Älter werden heisst besser werden» (Jack Nicholson) – Gilt das auch für unser Immunsystem?

Leider nicht. Parallel zur Abnahme der Funktion der Organe [9–12] nehmen im Alter auch viele Funktionen des Immunsystems ab, was man «Immunseneszenz» nennt [7, 13, 14]. Diese geht mit erhöhter Infektions-Anfälligkeit [15] und vermindertem Ansprechen auf Impfungen [16] einher [14, 17–19].

Geht es mit dem Immunsystem im Alter nur in eine Richtung, nämlich abwärts?

Im Alter kommt es sogar noch zu einer zweiten ominösen Entwicklung, dem «Inflammaging» [20, 21]. Diese chronische, subklinische Aktivierung des Immunsystems geschieht auch bei vielen gesunden älteren Personen [22–24]. Die Plasmakonzentration von Entzündungsmediatoren nimmt dabei oft um einen Faktor 2–4 zu [20, 22, 25].

Ist Inflammaging die Folge des Alters? Oder beschleunigt Inflammaging den Alterungsprozess?

Vermutlich beides: Entzündungsprozesse begünstigen altersassoziierte Krankheiten wie Atherosklerose und Diabetes [22, 26–43]. Ältere Personen mit diesen Komorbiditäten tendieren umgekehrt auch zu einem ungünstigeren Verlauf von Infektionen [28] und schlechterem Ansprechen auf Impfungen [44, 45]. Personen mit chronischen Infektionen wie Cytomegalovirus oder HIV (v.a. solange unbehandelt) könnten erhöhte Entzündungsaktivität im Blut [46] und erhöhtes kardiovaskuläres Risiko haben [47, 48] – daher die Hypothese des «akzelerierten» Alterns bei HIV [49, 50].

Bestimmt das Immunsystem, wie lange wir leben?

Ein komplexes Thema. Etwa 1 von 5000 Personen wird heute 100-jährig, und dies ist eines der am schnellsten wachsenden Bevölkerungssegmente (1990 wurde erst 1 von 10 000 Personen 100-jährig [51]). Untersuchungen bei >90-Jährigen zeigen: Erfolgreiches Altern ist teils genetisch bedingt [52] und teils via Biomarker wie Telomerlänge [53–55] oder DNA-Methylierung («epigenetische Uhren») [56–59] voraussagbar. Genetische Faktoren [60] und die Zusammensetzung des intestinalen Mikrobioms [61]) beeinflussen auch die Funktion des Immunsystems. Kürzlich bestimmten Forscher bei 135 Personen Tausende von Immunmarkern und ermittelten damit ein sogenanntes Immun-Alter [62]. Dieses verbesserte die Prädiktion der Lebensdauer [62]. Kurz, wir alle altern chronologisch gleich schnell, aber unser biologisches, epigenetisches oder Immun-Alter ist sehr unterschiedlich.

Können wir das Immunsystem vor dem Älterwerden schützen?

Klar ist: Regelmässige Bewegung hat einen positiven Einfluss auf die Immunseneszenz [63, 64]. Das Interesse an einem gesunden Immunsystem ist hoch. Die prophylaktische Einnahme von immunstimulierenden Substanzen wie Vitamin D und Echinacea kann vor Erkältungen und Influenza schützen [65–69]. Zahlreiche andere Substanzen zeigen keinen definitiven günstigen Einfluss auf die Immunseneszenz im Tiermodell [70–84]. Vitamin C [85, 86]), Zink [85, 87, 88], Omega-3-Fettsäuren [89] und Probiotika [90] beeinflussen zwar gewisse Immunmarker günstig, aber die Evidenz für einen klinischen Nutzen ist schwach.

Infektionen bei älteren Menschen

Wir gehen hier auf Pneumonie, Harnwegsinfekt und Erysipel ein. Zu Divertikulitis und Zoster berichten wir separat.

Sterben wir in der Schweiz noch an Infektionskrankheiten?

Anfang des 20. Jahrhunderts starben etwa 20% der Bevölkerung an Infektionskrankheiten, davon 3/4 an Tuberkulose. Ab 1940 sank die infektionsbedingte Mortalität deutlich – aufgrund der neu entdeckten Antibiotika [91–95], Impfungen [96–99], aber v.a. aufgrund sozioökonomischer und hygienischer Verbesserungen [100]. In der Schweiz ist heute nur noch ca. 1% der Todesfälle auf Infektionskrankheiten zurückzuführen, v.a. die Pneumonie. Die Mortalität für Infektionskrankheiten steigt allerdings ab ca. dem 70. Altersjahr stark an [101, 102]. Bei COVID-19 besteht eine ausgeprägte altersbedingte Zunahme von Hospitalisationen und Mortalität, auch bei der weniger virulenten Omikron-Variante (Kasten 1).

Sind chronische Krankheiten durch Infektionen bedingt?

Nein, diese werden gemäss heutigem Wissen fast ausschliesslich zu den nicht-infektiösen, «nicht übertragbaren» Krankheiten gezählt [129].

Welche Infektionen sind bei älteren Menschen in der Praxis am häufigsten?

Respiratorische Infektionen, Harnwegsinfekte, Haut-, Weichteil- und Wundinfektionen, Divertikulitis und Zoster [6, 130]. Die winterliche Influenza-Inzidenz ist übrigens bei Kindern/Jugendlichen und Erwachsenen <65 Jahren etwa 3–4-mal bzw. 2-mal höher als bei den über 65-Jährigen [131]. Grippebedingte Hospitalisationen hingegen sind bei der Altersklasse Ü65 viel häufiger.

Gibt es Infektionen, die im Alter seltener sind als bei jungen Menschen?

Werden Infektionen beim alten Menschen oft verpasst?

Die Infektdiagnose kann erschwert sein, denn ältere Personen haben häufiger atypische Präsentationen mit weniger fokalen (organbezogenen) Symptomen (Kasten 2) [140]:

Impfungen bei älteren Menschen

Gegen häufige Infektionen wie HWI, Sepsis und Erysipele ist keine Impfung verfügbar, und die Impfungen gegen Pneumokokken und Influenza sind nur beschränkt wirksam [157–160]. Die FSME-Impfung nicht vergessen: V.a. frisch Pensionierte verbringen vielleicht mehr Zeit im Freien [161]. Über die neue Zoster-Impfung Shingrix werden wir separat berichten.

Wie wirksam ist die Pneumokokken-Impfung bei >65-Jährigen?

Nicht besonders, siehe Studienresultate [162–164] und unsere PHC-Artikel [159, 160]. Es müssten 234–1000 Personen >65 geimpft werden, um eine Pneumokokken-Pneumonie zu verhindern [164–169]. Daher wird die Pneumokokken-Impfung im Alter in den USA seit 2019 nur noch als fakultativ gewertet [170]. Das BAG empfiehlt seit 2014 nur noch Prevenar 13 [171] (neu auch Vaxneuvance und bald Prevenar 20 [172]), und zwar allen Personen ab 65 Jahren mit Risikofaktoren wie COPD, Nieren- oder Herzinsuffizienz und Immunsuppression [173]. Die OKP-Kostenübernahme ist neu seit 1.3.2023 gewährleistet.

Sollen wir Kinder mit Prevenar 13 impfen, damit alte Menschen weniger Pneumokokken-Pneumonie kriegen?

Die Impfung der Säuglinge ist wirksamer als die Impfung der >65-Jährigen, um die Pneumonieinzidenz im Alter zu senken [174–177] – und die geimpften Kinder haben einen persönlichen Nutzen: weniger Mittelohr- und Lungenentzündungen [168, 178, 179]. Daher wird seit dem Impfplan 2019 Prevenar 13 neu den 2-, 4- und 12-monatigen Säuglingen als Basisimpfung empfohlen [164, 180, 181].

Wie wirksam ist die Grippeimpfung bei >65-Jährigen?

Die Datenlage ist erstaunlich schwach: Wir haben in PHC 02/2021 und 03/2022 dazu berichtet [157, 159]. Die Grippeimpfung ist deutlich weniger wirksam, als oft angegeben wird [182, 182–186]. Ja, die vorliegenden Daten erlauben gemäss Cochrane-Gruppe bei Personen >65 Jahre gar keine klare Impfempfehlung [187]. Es müssten gemäss sehr optimistischem Szenario (59% Impfwirksamkeit) 30 Personen >65 geimpft werden, um einen Influenzafall zu verhindern [187].

Sollen wir Kinder impfen, damit alte Leute weniger Grippe oder COVID-19 kriegen?

Weil durch die Grippeimpfung der Kinder indirekt das Ansteckungsrisiko der über 65-Jährigen gesenkt werden kann, wird in den USA die Grippeimpfung allen Kindern ab 6 Monaten empfohlen [188]. In der Schweiz nicht [189], denn Kinder sollen bei Impfungen in erster Linie einen persönlichen Nutzen haben. Die allermeisten Kinder mit Influenza haben aber ein sehr geringes Komplikations- und Hospitalisationsrisiko.

Wie können wir die Impfwirksamkeit bei älteren Menschen verbessern [190–192]?

Verschiedene Konzepte sind in Erprobung: Mit einer höheren Dosis des Grippeimpfstoffs [193–195] und mit immunologischen Verstärkern (Adjuvanzien) [196] wurden bisher leicht bessere Antikörpertiter erzielt, ohne klare Senkung der Influenza-Häufigkeit. Erste Resultate von mRNA-Impfstoffen gegen Influenza werden noch 2023 erwartet [197–199].

Korrespondenzadresse

Prof. Dr. med. Philip Tarr

Medizinische Universitätsklinik

Kantonsspital Baselland

CH-4101 Bruderholz

philip.tarr[at]unibas.ch

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