The bloodsucking arthropod bite as possible cofactor in the transmission of human herpesvirus-8 infection and in the expression of Kaposi’s sarcoma disease.

Based on a review of the literature on human herpesvirus-8 (HHV8) and Kaposi's sarcoma (KS) and on the distribution of KS in Italy (Veneto region particularly), we hypothesize that the bite of bloodsucking arthropods is a cofactor in the seroconversion to HHV8 positivity and probably in the pathogenesis of KS. The bloodsucking arthropod releases with saliva powerful antihaemostatics and immunomodulators which may favour the replication and the establishment of the pathogen. Transmission would depend on the close contact of the child with a seropositive mother (or relatives) whose infective saliva is used to relieve itching and scratching at the arthropod bite's sites. During any deregulation of the immune system (e.g. ageing), local immune responses to new insect bites may induce virus activation which could prelude KS insurgence. The pathogen is not directly transmitted by the arthropod which merely prepares the cutaneous microenvironment for the virus. We have therefore introduced a new category of medically important arthropods, "promoter arthropods", besides those already defined as biological or mechanical vectors. Promoter arthropods are species able to induce in the host long-lasting, immediate or delayed-type hypersensitivity responses as well as local immunosuppression due to substances injected with their saliva. The striking variability of ORF-K1 gene of HHV8 could be due to the adaptation of the virus to the specific microenvironments resulting from the immune response to the salivary antigens characteristic of the bloodsucking arthropod species prevalent in each geographical area. It is worth noting that other viruses (especially Hepatitis B Virus) may exploit the same non-sexual transmission route

Sistema informativo per le malattie professionali (ISOD): i dati di mortalit\ue0 della regione Liguria e Veneto.

Sistema informativo per le malattie professional

Bloodsucking arthropod bites as a possible cofactor in the transmission of HHV8 (uuman herpes virus 8) and in the expression of Kaposi's sarcoma

Based on a review of the literature on human herpesvirus 8 (HHV8) and Kaposi's sarcoma (KS) and on the distribution of KS in Italy (Veneto in particular), we hypothesize that the bite of bloodsucking arthropods is a cofactor in the seroconversion to HHV8 positivity and probably in the pathogenesis of KS. The essential issue is that HHV8 transmission is associated with the bite of a bloodsucking arthropod. Powerful immunomodulators, anticoagulants and vasodilators are released with arthropod saliva that are responsible for a local immunodepression and a cytokine-rich tissue microenvironment favouring virus replication. HHV8 eventually eludes host immune surveillance persisting in the infected organism. During any deregulation of the immune system (e.g. ageing), local immune responses to new insect bites may induce virus activation which could prelude KS insurgence. Although HHV8 seroconversion depends on the close contact of the child with seropositive parents or relatives, this condition alone seems not sufficient to explain the epidemiological patterns of KS distribution. The pathogen is not directly transmitted by the arthropod which merely prepares the skin microenvironment for the virus. The virus may be actually transmitted with the saliva of seropositive humans in view of frequent habits implying, for instance, sucking and licking at the child's itching and scratching sites. We therefore introduce a new category of medically important arthropods besides those already defined as biological or mechanical vectors that could be named the ≪promoter arthropods≫. The promoter arthropod would belong to species able to induce long-lasting, immediate or delayed-type hypersensitivity responses, due to substances injected with the arthropod's saliva. This type of inflammatory reaction is attributable to several bloodsucking arthropods not necessarily associated with humans, such as species of sandflies (Phlebotomus spp.), blackflies (Simulium spp.), biting midges (Culicoides spp., Leptoconops spp.) and culicine mosquitoes (i.e., Ochlerotatus, Coquilletidia, and Aedes). On the other hand, the available epidemiological data do not support the involvement of the common and ubiquitous domestic mosquito Culex pipiens nor of its tropical vicariant Cx quinquefasciatus, presumably because their bites seldom induce long-lasting inflammatory responses. It is also unlikely that the Afrotropical malaria vectors (Anopheles gambiae and An. Funestus), bedbugs, or lice play any role. The striking variability of orf-K1 gene of HHV8 could be due to the adaptation of the virus to the specific microenvironments resulting from the immune response to the salivary antigens characteristic of the bloodsucking arthropod species prevalent in each geographical area. The hypothesis of the promoter arthropod can be checked in animal models not too difficult to develop since some viral species closely related to HHV8 are present in chimpanzee and gorilla, as well as in macaqui and saimiri. Further information can be readily obtained from more detailed epidemiological surveys. Relevant data can also be obtained from children with seropositive parents and relatives comparing the seroconversion rates of those born and resident in Africa from those born and resident in Italy. Finally, the most convincing evidence may rely on field experiments in an area of high prevalence of HHV8 based on the recruitment of seronegative children born and cared by seropositive family members and on the monitoring of their seroconversion as randomly distributed in two groups: the first naturally exposed to bloodsucking arthropod bites and the other protected from bites by any available means (for example, insecticide impregnated bed nets, indoor insecticide spraying and repellents). This latter group could be further split in two subsamples one of which could be the target of an intervention whereby seropositive mothers and family members would be advised to avoid contact of their saliva with any cutaneous itching and scratching sites on the child. The possibility should be taken into account that other viruses (e.g., Hepatitis B Virus) exploit, more or less sporadically, the same non-sexual transmission route

La puntura di artropodi ematofagi quale possibile cofattore nella trasmissione dell’HHV8 e nell’espressione del sarcoma di Kaposi.

Bloodsucking arthropod bites as a possible cofactor in the transmission of HHV8 (Human Herpes Virus 8 ) and in the expression of Kaposi’s sarcoma. Based on a review of the literature on human herpesvirus 8 (HHV8) and Kaposi’s sarcoma (KS) and on the distribution of KS in Italy (Veneto in particular), we hypothesize that the bite of bloodsucking arthropods is a cofactor in the seroconversion to HHV8 positivity and probably in the pathogenesis of KS. The essential issue is that HHV8 transmission is associated with the bite of a bloodsucking arthropod. Powerful immunomodulators, anticoagulants and vasodilators are released with arthropod saliva that are responsible for a local immunodepression and a cytokine-rich tissue microenvironment favouring virus replication. HHV8 eventually eludes host immune surveillance persisting in the infected organism. During any deregulation of the immune system (e.g. ageing), local immune responses to new insect bites may induce virus activation which could prelude KS insurgence. Although HHV8 seroconversion depends on the close contact of the child with seropositive parents or relatives, this condition alone seems not sufficient to explain the epidemiological patterns of KS distribution. The pathogen is not directly transmitted by the arthropod which merely prepares the skin microenvironment for the virus. The virus may be actually transmitted with the saliva of seropositive humans in view of frequent habits implying, for instance, sucking and licking at the child’s itching and scratching sites. We therefore introduce a new category of medically important arthropods besides those already defined as biological or mechanical vectors that could be named the «promoter arthropod». The promoter arthropod would belong to species able to induce long-lasting, immediate or delayed-type hypersensitivity responses, due to substances injected with the arthropod’s saliva. This type of inflammatory reaction is attributable to several bloodsucking arthropods not necessarily associated with humans, such as species of sandflies (Phlebotomus spp.), blackflies (Simulium spp.), biting midges (Culicoides spp., Leptoconops spp.) and culicine mosquitoes (i.e., Ochlerotatus, Coquillettidia, and Aedes). On the other hand, the available epidemiological data do not support the involvement of the common and ubiquitous domestic mosquito Culex pipiens nor of its tropical vicariant Cx quinquefasciatus, presumably because their bites seldom induce long-lasting inflammatory responses. It is also unlikely that the Afrotropical malaria vectors (Anopheles gambiae and An. funestus), bedbugs, or lice play any role. The striking variability of orf -K1 gene of HHV8 could be due to the adaptation of the virus to the specific microenvironments resulting from the immune response to the salivary antigens characteristic of the bloodsucking arthropod species prevalent in each geographical area. The hypothesis of the promoter arthropod can be checked in animal models not too difficult to develop since some viral species closely related to HHV8 are present in chimpanzee and gorilla, as well as in macaqui and saimiri. Further information can be readily obtained from more detailed epidemiological surveys. Relevant data can also be obtained from children with seropositive parents and relatives comparing the seroconversion rates of those born and resident in Africa from those born and resident in Italy. Finally, the most convincing evidence may rely on field experiments in an area of high prevalence of HHV8 based on the recruitment of seronegative children born and cared by seropositive family members and on the monitoring of their seroconversion as randomly distributed in two groups: the first naturally exposed to bloodsucking arthropod bites and the other protected from bites by any available means (for example, insecticide impregnated bed nets, indoor insecticide spraying and repellents). This latter group could be further split in two subsamples one of which could be the target of an intervention whereby seropositive mothers and family members would be advised to avoid contact of their saliva with any cutaneous itching and scratching sites on the child. The possibility should be taken into account that other viruses (e.g., Hepatitis B Virus) exploit, more or less sporadically, the same non-sexual transmission route

Variability in the incidence of classic Kaposi's sarcoma in the Veneto region, Northern Italy.

The incidence of Kaposi's sarcoma was estimated in the Veneto Region, Italy (age > or = 50; 1990-96). Rates were higher in the coast and alpine valleys; in the latter there was an excess of cases for both sexes combined (SIR = 191.1; CI = 113.2-302.0). The hypothesis that birthplace/residency in areas abundant with bloodsucking insects may be a risk factor is discussed

La puntura di artropodi ematofagi quale possibile cofattore nella trasmissione dell’HHV8 e nell’espressione del sarcoma di Kaposi.

Sulla base di una revisione della letteratura su human herpesvirus 8 (HHV8) e sarcoma di Kaposi (KS) e sulla distribuzione del KS in Italia (in particolare in Veneto), ipotizziamo che la puntura di insetti ematofagi sia un cofattore nella sieroconversione per HHV8 e quindi nella trasmissione del virus e forse nella patogenesi del KS. Potenti sostanze con azione immunomodulante, anticoagulante e vasodilatante, rilasciate con la saliva degli artropodi, sono responsabili di un microambiente tessutale idoneo alla replicazione virale. HHV8 in seguito elude il sistema di immunosorveglianza dell’ospite persistendo in maniera latente nell’organismo infettato. Nell’eventualit`a di deregolazione del sistema immune (invecchiamento), la risposta locale a nuove punture d’insetti potrebbe indurre l’attivazione del virus e preludere all’insorgenza del KS. Sebbene la sieroconversione per HHV8 dipenda dall’intimo contatto tra bambino e genitori o familiari sieropositivi, questa condizione da sola non `e sufficiente a spiegare il pattern epidemiologico della distribuzione del KS. Il patogeno non verrebbe per`o trasmesso dall’artropode, il quale unicamente prepara il microambiente cutaneo per il virus. Il virus verrebbe trasmesso con la saliva dei soggetti sieropositivi, in considerazione della frequente abitudine di leccare e succhiare la cute del bambino in corrispondenza delle sedi del prurito e delle lesioni da grattamento dovute alle punture. Proponiamo quindi di introdurre una nuova categoria di artropode importante in medicina, oltre a quelle gi`a definite di vettore biologico e meccanico, che potrebbe essere denominata «artropode promotore». L’artropode promotore dovrebbe appartenere ad una specie capace di indurre una reazione di lunga durata di ipersensibilit`a immediata o ritardata, dovuta alle sostanze iniettate con la saliva. Questo tipo di reazione infiammatoria `e attribuibile a molti artropodi ematofagi, non necessariamente associati all’uomo, come specie di flebotomi (Phlebotomus spp.), simulidi (Simulium spp.), moscerini pungenti (Culicoides spp., Leptoconops spp.) e culicini (Ochlerotatus, Coquillettidia, e Aedes). D’altra parte, i dati epidemiologici non supportano il coinvolgimento della comune e ubiquitaria zanzara domestica Culex pipiens, n´e della vicaria tropicale Cx quinquefasciatus, verosimilmente perch´e le loro punture raramente inducono risposte infiammatorie di lunga durata. `E altres`ı improbabile che i vettori afrotropicali di malaria (Anopheles gambiae e An. funestus), le cimici, o i pidocchi svolgano alcun ruolo. La peculiare variabilit`a del gene di HHV8 orf -K1 potrebbe essere dovuta all’adattamento del virus allo specifico microambiente creato dalla risposta immune dell’ospite agli antigeni salivari delle specie di artropodi ematofagi prevalenti in una data area geografica. L’ipotesi dell’artropode promotore potrebbe essere testata in modelli animali dato che esistono virus filogeneticamente molto vicini ad HHV8 negli scimpanz`e, gorilla, macachi e saimiri. Ulteriori informazioni potrebbero essere ottenute da indagini epidemiologiche, ad esempio comparando la sieroconversione di bambini con genitori sieropositivi nati e residenti rispettivamente in Africa e in Italia e ipotizzando una minore frequenza di punture di artropodi nel secondo gruppo. La prova pi`u convincente potrebbe essere ottenuta da esperimenti sul campo in un’area ad alta prevalenza di HHV8 reclutando bambini sieronegativi nati e allevati da genitori o familiari sieropositivi, e monitorando la sieroconversione in due gruppi randomizzati: il primo naturalmente esposto alle punture di insetti e l’altro protetto dalle punture con ogni mezzo disponibile (zanzariere impregnate di insetticida, uso di insetticidi nelle abitazioni, e repellenti). Questo secondo gruppo potrebbe essere ulteriormente suddiviso in due sottogruppi uno dei quali dovrebbe essere oggetto di un intervento di educazione sanitaria esortando le madri e altri familiari ad evitare di contaminare con la loro saliva la cute dei figli. Si dovrebbe infine considerare la possibilit`a che altri virus possano utilizzare, pi`u o meno sporadicamente, questa stessa tipologia di trasmissione non sessuale (per esempio il virus dell’epatite B)

The bloodsucking arthropod bite as possible cofactor in the transmission of human herpesvirus-8 infection and in the expression of Kaposi's sarcoma disease

Based on a review of the literature on human herpesvirus-8 (HHV8) and Kaposi's sarcoma (KS) and on the distribution of KS in Italy (Veneto region particularly), we hypothesize that the bite of bloodsucking arthropods is a cofactor in the seroconversion to HHV8 positivity and probably in the pathogenesis of KS The bloodsucking arthropod releases with saliva powerful antihaemostatics and immunomodulators which may favour the replication and the establishment of the pathogen. Transmission would depend on the close contact of the child with a seropositive mother (or relatives) whose infective saliva is used to releave itching and scratching at the arthropod bite's sites. During any deregulation of the immune system (e g ageing), local immune responses to new insect bites may induce virus activation which could prelude KS insurgence. The pathogen is not directly transmitted by the arthropod which merely prepares the cutaneous microenvironment for the virus We have therefore introduced a new category of medically important arthropods, "promoter arthropods", besides those already defined as biological or mechanical vectors. Promoter arthropods are species able to induce in the host long-lasting, immediate or delayed-type hypersensitivity responses as well as local immunosuppression due to substances injected with their saliva The striking variability of ORF-K1 gene of HHV8 could be due to the adaptation of the virus to the specific microenvironments resulting from the immune response to the salivary antigens characteristic of the bloodsucking arthropod species prevalent in each geographical area. It is worth noting that other viruses (especially Hepatitis B Virus) may exploit the same non-sexual transmission route