Globally visceral leishmaniasis (VL) causes thousands of human deaths every year. In South America, the etiologic agent, Leishmania infantum, is transmitted from an infected canine reservoir to human hosts by the blood-feeding activity of the sand fly vector, predominantly, Lutzomyia longipalpis. Previous evidence from model rodent systems have suggested that the odour of infected hosts is altered by the parasite making them more attractive to the vector leading to an increased biting rate and improved transmission prospects for the pathogen. However, the effect of Le. infantum infection on the attractiveness of naturally infected dogs which are integral to human infection, has not been assessed.Hair collected from infected and uninfected dogs residing in a VL endemic city in Brazil. was entrained to collect the volatile chemical odours present in the headspace. Female and male Lu. longipalpis sand flies were offered a choice of infected or uninfected odour in a series of behavioural experiments. Control experiments established that female and male Lu. longipalpis were equally attracted to uninfected dog odour, female Lu. longipalpis were significantly more attracted to infected dog odour than uninfected dog odour in all 15 experimental replicates (average 45.7±0.87 females attracted to infected odour; 23.9±0.82 to uninfected odour; paired T-test, P=0.000). Male Lu. longipalpis did not significantly prefer either infected or uninfected odour (average 36.1±0.4 males to infected odour; 35.7±0.6 to uninfected odour; paired T-test, P=0.722). A significantly greater proportion of females chose the infected dog odour compared to the males (paired T-test, P=0.000).The results show that dogs infected with Le. infantum are significantly more attractive to blood-feeding female than male sand flies. This is strong evidence for parasite manipulation of the host odour in a natural transmission system and indicates that infected dogs may have a disproportionate significance in maintaining infection in canine and human infection.Author SummaryVisceral leishmaniasis (VL) is a disease caused by the Protist parasite Leishmania infantum. In Brazil and other South and Central American countries, the parasite is transmitted by the blood-feeding activity of infected female Lutzomyia longipalpis sand flies. The disease leads to thousands of human cases and deaths every year. Domestic dogs are the reservoir of infection for humans therefore understanding the effect of infection on dogs is important in developing an understanding of the epidemiology of the disease. Although previous studies on rodent models of Le. infantum infection have shown that infected Golden Hamsters are more attractive to Lu. longipalpis the attractiveness of naturally infected dogs to the insect vector has not been previously been investigated. In this study we showed that the odour of infected dogs is significantly more attractive to female sand flies which can transmit the pathogen than to male sand flies which do not. This clear-cut difference in attraction of female and males suggests that the females are preferentially attracted by parasite infected hosts and may lead to enhanced infection and transmission opportunities for the parasite.