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Molecular studies on the tissue-specific gene expression in the salivary glands of Anopheles gambiae may provide useful tools for the development of new strategies for the control of the most efficient malaria vector in the sub-Saharan Africa. We summarize here the results of a recent investigation focused on the isolation of secreted factors and putative receptors from the salivary glands of An. gambiae. Using the Signal Sequence Trap technique we have identified the first cDNAs specifically expressed in the An. gambiae salivary glands. Among these, four are exclusively expressed in female glands and encode factors presumably involved in blood-feeding, whereas two other cDNAs seem to be expressed both in male and in female glands and are likely implicated in sugar-feeding. Homologues of genes previously identified in the yellow fever mosquito Aedes aegypti, like the apyrase and D7, as well as novel salivary gland-specific cDNAs, were identified. The isolation and characterization of promoter sequences from the corresponding genes may prove useful for the expression of anti parasitic agents in the salivary glands of transgenic mosquitoes.

The text summarizes the principal current fields of investigation and the recent achievements of the research groups presently contributing to the Molecular Entomology Cluster of the Italian Malaria Network. Particular emphasis is given to the researches with a more direct impact on the fight against malaria vectors.

The gallstone ileus is a rare complication of cholelithiasis and it represents the 1-4% of small intestinal mechanical obstruction. Gallstone is generally wedged in the terminal ileum, even if unusual locations have been described. The literature reports a very high morbidity and mortality, often because misdiagnosis or delayed diagnosis. There is no unique opinion in literature about the choice between one-stage and two-stage surgery. We report a clinical case that summarizes the diagnostic and therapeutic difficulties of gallstone ileus.

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.

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.

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