Comparative assessment of a DNA and protein Leishmania donovani gamma glutamyl cysteine synthetase vaccine to cross-protect against murine cutaneous leishmaniasis caused by L. major or L. mexicana infection.

Leishmaniasis is a major health problem and it is estimated that 12 million people are currently infected. A vaccine which could cross-protect people against different Leishmania spp. would facilitate control of this disease as more than one species of Leishmania may be present. In this study the ability of a DNA vaccine, using the full gene sequence for L. donovani gamma glutamyl cysteine synthetase (γGCS) incorporated in the pVAX vector (pVAXγGCS), and a protein vaccine, using the corresponding recombinant L. donovani γGCS protein (LdγGCS), to protect against L. major or L. mexicana infection was evaluated. DNA vaccination gave transient protection against L. major and no protection against L. mexicana despite significantly enhancing specific antibody titres in vaccinated infected mice compared to infected controls. Vaccination with the LdγGCS protected against both species but only if the protein was incorporated into non-ionic surfactant vesicles for L. mexicana. The results of this study indicate that a L. donovani γGCS vaccine could be used to vaccinate against more than one Leishmania species but only if the recombinant protein is used.

An essential role for IL-13 in maintaining a non-healing response following Leishmania mexicana infection.

A comparison of the growth of Leishmania mexicana in IL-4(-/-), IL-4Ralpha(-/-) and wild-type BALB/c mice demonstrated a disease exacerbative role for IL-13 as well as IL-4. Thus, while both IL-4(-/-) and IL-4Ralpha(-/-) mice were more resistant than wild-type controls to infection with L. mexicana, IL-4Ralpha(-/-) mice, which are unresponsive to IL-13 as well as IL-4, were significantly more resistant to parasite growth than their IL-4(-/-) counterparts. Cytokine and antibody analysis revealed a Th1-biased specific response in both infected IL-4(-/-) and IL-4Ralpha(-/-) mice compared with wild-type animals. Reconstituting SCID mice with IL-4(-/-), IL-4Ralpha(-/-) or wild-type splenocytes prior to infection demonstrated that the early onset of lesion growth was dependent on the presence of lymphocytes responding to IL-4 and/or IL-13, as lesions failed to develop in only the SCID IL-4Ralpha(-/-) reconstituted mice. An independent role for IL-13 in L. mexicana infection was demonstrated by comparing disease progression in IL-13(-/-), IL-4(-/-)/IL-13(-/-) and wild-type B6/129 mice. In contrast to IL-4(-/-)/IL-13(-/-) mice, which were resistant, IL-13(-/-) mice developed lesions similar in size to wild-type animals up to week 8 post-infection. However, in contrast to wild-type mice in which disease continued to progress, lesions eventually healed in IL-13(-/-) mice, in association with the development of a Th1 response. Collectively our results suggest that IL-4 plays a critical role in early lesion development, and that IL-13 plays a crucial part in maintaining a chronic non-healing infection.

HIV risk perception, risk behavior, and seroprevalence among female commercial sex workers in Georgetown, Guyana.

A study of 108 female sex workers engaged in prostitution in Georgetown, Guyana, was made in April 1993. Based on interviews and procurement of blood samples, the study investigated relationships between HIV seroprevalences and AIDS knowledge, risk behaviors, client characteristics, and condom use. Street-walkers-as distinct from sex workers in bars, hotels, and Port Georgetown-tended to charge less, be worse off socioeconomically, and have clients who were similarly disadvantaged; they were therefore classified as belonging to a "lower" socio-economic stratum, while the other workers were classified as belonging to a "higher" stratum. The overall HIV seroprevalence found among the sex workers was 25% (95% CI: 17%-33%). But the 50 subjects in the lower stratum had a relatively high seroprevalence (42%, as compared to 10% among those in the higher stratum), accounting for 21 of the 27 HIV-seropositive subjects. Reported patterns of client origins (Guyanese or foreign), worker willingness to have sex without a condom, and condom use by clients differed by stratum. Participants in the higher stratum were more disposed to having sex without a condom. The workers' knowledge of what causes AIDS and how HIV is transmitted was low in both strata; substantial numbers of workers said they had contracted a sexually transmitted disease within the past two years or were users of illicit drugs. Condom use is reportedly less common among Guyanese than foreign clients, suggesting a greater risk of contracting HIV from Guyanese clients or infecting Guyanese clients with it. The HIV seroprevalence among workers who said they had only Guyanese clients was statistically greater than the rate among those who said they had only foreign clients. The HIV seroprevalence among those reporting more than five clients per week was statistically greater than among those reporting fewer. HIV seropositivity was relatively high among the 12 workers who said they used cocaine. Overall, the findings supported the view that interventions targeted at female sex workers and their clients should be strengthened-more specifically, that concerted efforts should be made to intensity condom promotion, distribution, and social marketing; to improve STD services that provide treatment and counseling for female sex workers; and to increase educational activities among the workers' Guyanese clients.