Human brucellosis still presents scientists and clinicians with several challenges, such as the understanding of pathogenic mechanisms of Brucella spp, the identification of markers for disease severity, progression, and treatment response, and the development of improved treatment regimens. Molecular studies have shed new light on the pathogenesis of Brucella spp, and new technologies have permitted the development of diagnostic tools that will be useful in developing countries, where brucellosis is still a very common but often neglected disease. However, further studies are needed to establish optimum treatment regimens and local and international control programmes. This Review summarises current knowledge of the pathogenic mechanisms, new diagnostic advances, therapeutic options, and the situation of developing countries in regard to human brucellosis.

Cytotoxic T lymphocyte (CTL) peptide epitopes can be used for immunization of mice against lethal virus infection. To study whether this approach can be successful against virus-induced tumors we generated a B6 (H-2b) tumorigenic cell line transformed by human papillomavirus (HPV). This virus is detected in over 90% of all human cervical cancers. To identify vaccine candidates, we generated a set of 240 overlapping peptides derived from the HPV type 16 (HPV16) oncogenes E6 and E7. These peptides were tested for their ability to bind H-2Kb and H-2Db MHC class I molecules. Binding peptides were compared with the presently known peptide-binding motifs for H-2Kb and H-2Db and the predictive value of these motifs is shortly discussed. The high-affinity H-2Db-binding peptide and putative CTL epitope E7 49-57 (RAHYNIVTF) was used in vaccination studies against HPV 16-transformed tumor cells. Immunization with peptide E7 49-57 rendered mice insensitive to a subsequent challenge with HPV 16-transformed tumor cells in vivo, and induced a CTL response which lysed the tumor cells in vitro.

The epidermodysplasia verruciformis (EV)-associated human papillomaviruses (HPVs) constitute a group of HPV genotypes isolated mostly from the cutaneous lesions of patients with the genetic disorder of EV. Broad-spectrum detection of EV HPVs in cutaneous lesions of non-EV patients was previously difficult because no EV HPV consensus PCR was available. We describe a nested PCR that enables the detection of all known EV HPV types at relatively low-copy-number levels. The deduced sequences of a 92-amino-acid stretch of the L1 open reading frames of all types are shown for convenient typing. The technique proved very valuable in viral studies of skin cancers from renal transplant recipients. A high prevalence (81%) of EV HPV types was found in skin cancer biopsies. A wide spectrum of EV HPV types that differed from HPV-5 and-8 was found to be involved. The technique also proved useful in detecting potentially novel EV HPV types in skin cancers. The relationship of these new types to known HPV types is demonstrated by phylogenetic tree analysis.

The interruption of leprosy transmission is one of the main challenges for leprosy control programs since no consistent evidence exists that transmission has been reduced after the introduction of multidrug therapy. Leprosy, a disease caused by Mycobacterium leprae, particularly affects the less privileged parts of the population in countries where the disease is endemic. This intracellular bacillus is assumed not to be very pathogenic, most infections do not result in chronic disease but in skin lesions that heal spontaneously (13).

Based on immunologic and epidemiologic data, it is plausible that skin cancer in renal transplant recipients is associated with human papillomaviruses (HPV). At present, conflicting evidence exists concerning the presence of HPV DNA in these cancers. We recently described a nested polymerase chain reaction method that enables the detection of all previously isolated epidermodysplasia verruciformis (EV)-associated HPVs. We now describe the detection of EV-associated HPV DNA in 49 (80%) of 61 biopsies from squamous cell carcinomas, in four (50%) of eight basal cell carcinomas, in 14 (93%) of 15 actinic keratoses, in two (40%) of five cases of Bowen's disease, and in four (57%) of seven keratoacanthomas. HPV DNA typing revealed that all detected HPV types belonged to the EV-associated HPV types. A wide spectrum of EV-associated HPVs was found, including six putative new HPV types. In a high percentage of the lesions more than one HPV type was detected. We often found the same HPV types in different skin biopsies from both malignant and premalignant lesions from the same patient. The high frequency of detection of EV-associated HPV types in biopsies from malignant and premalignant lesions is in agreement with the hypothesis that EV-associated HPVs are involved in the pathogenesis of skin cancer in renal transplant recipients.