Saliva and the transmission of human herpesvirus 8: potential role of promoter-arthropod bites.

To the Editor—The study by Mbulaiteye et al. [1] examines the distribution of human herpesvirus 8 (HHV-8) seropositivity within families in rural Tanzania, to determine routes of the infection’s spread. Their findings agree with those from epidemiological surveys of other endemic areas; such surveys show that there are significant nonsexual associations within families, with high seroprevalence in young children. Although Mbulaiteye et al. recognize that it is not clear what the routes of HHV-8 transmission are, they propose that young children may become infected with this virus “through exposure to HHV-8–infected saliva, mainly from family members” (p. 1783); concerning the mechanisms of exposure to saliva, Mbulaiteye et al. suggest that it “may occur when mothers premasticate food for infants or clean children’s faces with saliva” (p. 1783). Nonetheless, these cultural practices can only partially explain the seroprevalence of HHV-8 in younger children. A more general explanation is provided by Coluzzi et al. [2] and is reinforced by Coluzzi et al. [3], who have suggested that blood-feeding arthropods (e.g., mosquitoes) play a role in the epidemiology of HHV-8 infection. According to this hypothesis, the conditions for HHV-8 transmission are met when (1) a child shows a response to the bites of blood-feeding arthropods and (2) an HHV-8–seropositive mother (or other relative), attempting to cleanse the spots and to relieve the child’s itching and reduce scratching, applies her infective saliva to the bite sites, either by licking or by using her fingers. The habitual use of saliva as first-aid medication is typical in poor villages, such as those in Mbulaiteye et al.’s area of study in Tanzania, but becomes rarer with economic development and progressive improvement in hygiene. Infection may be promoted by a child’s scratching the sites of insect bites, and virus replication may be facilitated both by the local down-regulation of immunity and by the recruitment of inflammatory cells induced by arthropod saliva [4–6]. However, we do not suggest that arthropods are directly involved in the transmission of HHV-8; to distinguish between this mode of infection and mechanical or biological vectors, Coluzzi et al. [2] proposed the term “promoter arthropod,” to stress the role played in the stimulation of the use of saliva and, possibly, in the facilitation of HHV-8’s entry—and subsequent replication—in humans. The promoter-arthropod hypothesis fits well with various and sometimes puzzling epidemiological phenomena—for example, the increase in HHV-8 infection in children 12 years old, who are unlikely to require premasticated food, and the association between HHV-8 and hepatitis B virus [7]. In Mbulaiteye et al.’s study of HHV-8 infection in rural Tanzania [1], the promoter-arthropod hypothesis could explain the higher HHV-8 seroprevalence observed in residents of “low-lying villages” near Lake Victoria, compared with that in residents of “high-elevation villages” (60.1% and 49.7%, respectively; ); P p . 04 residents of villages nearer the lake would inevitably suffer higher frequencies of bites from hematophagous arthropods (mostly culicine mosquitoes and ceratopogonid midges [8]) than would the residents of villages on the hills. It follows logically from the promoter-arthropod hypothesis that a more-intense circulation of HHV8 would be expected in low-lying villages, and it should be feasible to find evidence for such a relationship. After the moreaggressive arthropods are identified (because they are more likely to be the promoter arthropods), villages should be ranked both with regard to the frequency of bites by these arthropods and with regard to the seroprevalence of HHV-8, allowing correlationanalysis between the 2 data sets. Further evidence may be obtained via socioanthropological surveys involving questionnaires (administered to children as well as to adults), to evaluate the frequency of the use of saliva therapy. The results could provide baseline data to be used in an attempt to reduce HHV-8 seroprevalence via behavioral change (i.e., discontinuation of saliva therapy in favor of other treatments for bites) resulting from health-education campaigns in multiple villages; the same health-education campaigns could be conducted in matched control villages, except that they would address various other suitable behavioral changes while carefully avoiding any influence on the use of traditional saliva therapy. The monitoring of seroconversion rates in the 2 groups of villages might demonstrate the validity of the promoter-arthropod hypothesis. Additional, simultaneous serosurveys of infection with hepatitis B and C viruses could provide parallel information on the epidemiologies of these viruses in relation to the use of saliva therapy.