International regulations and guidelines strongly suggest that the use of animal models in scientific research should be initiated only after the authority responsible for the review of animal studies has concluded a well-thought-out harm–benefit analysis (HBA) and deemed the project to be appropriate. Although the process for conducting HBAs may not be new, the relevant factors and algorithms used in conducting them during the review process are deemed to be poorly defined or lacking by committees in many institutions. This paper presents the current concept of HBAs based on a literature review. References on cost or risk benefit from clinical trials and other industries are also included. Several approaches to HBA have been discovered including algorithms, graphic presentations and generic processes. The aim of this study is to better aid and harmonize understanding of the concepts of ‘harm’, ‘benefit’ and ‘harm–benefit analysis’.

The etiological agent of epitheliocystis in lake trout Salvelinus namaycush at 2 hatcheries (A and B) in the United States was investigated utilizing light, immunofluorescence, and transmission electron microscopy. Branchial inclusions observed in fish at Hatchery A were dispersed at the base of, and randomly along, the secondary lamellae. They included epithelial hyperplasia and hypertrophy, and diffuse lamellar edema and fusion. In fish at Hatchery B the branchial inclusions were located predominantly on the primary lamellae. Pathological alterations were less severe, and were characterized primarily by focal lesions of epithelial hypertrophy. The epitheliocystis particles within the branchial inclusions of fish at both hatcheries exhibited typical chlamydia morphology, size, and developmental stages. A form uncharacteristic of chlamydia was also observed. In addition, a nonchlamydia-like agent was found in branchial tissue of fish at Hatchery B. Immunofluorescent staining of infected branchial tissue with a monoclonal antibody to an antigen specific for the chlamydia genus indicated that the agents lack the lipopolysaccharide common to all known Chlamydia species. Attempts to isolate the agents in McCoy and epithelioma papillosum cyprini (EPC) cell culture systems optirnized for chlamydial growth were unsuccessful, possibly due to the poor condition of tissue samples. Massive mortalities of lake trout observed at the 2 hatcheries were associated with the epitheliocystis infections. Investigations in other laboratories failed to reveal the presence of other agents (viruses, bacteria, fungi, ectoparasites) or suboptimal conditions in water quality that might account for the mortalities. The branchial and systemic lesions observed in fish during epizootics are consonant with findings for several epitheliocystis agents and for chlamydia-like agents in other fish species.

A Mycobacterium tuberculosis (H37Rv)-infected guinea pig model was used to screen for targeted delivery to the lungs by insufflation (with lactose excipient) or nebulization, of either rifampicin alone, rifampicin within poly(lactide-co-glycolide) microspheres (R-PLGA) or polymer microparticles alone (PLGA). Animals treated with single and double doses of R-PLGA microspheres exhibited significantly reduced numbers of viable bacteria, inflammation and lung damage compared with lactose-, PLGA- or rifampicin-treated animals 28 days post-infection (P < 0.05). Two doses of R-PLGA resulted in reduced splenic enlargement. These studies support the potential of R-PLGA delivered to the lung to treat pulmonary tuberculosis.

International regulations and guidelines strongly suggest that the use of animal models in scientific research should be initiated only after the authority responsible for the review of animal studies has concluded a well-thought-out harm–benefit analysis (HBA) and deemed the project to be appropriate. The AALAS–FELASA working group on HBA has performed a literature review and based on this review, proposed a method for HBA. Examples of the working group’s approach are included in this report.

These studies indicate the potential of R-PLGA, delivered by insufflation or nebulization directly to the lungs, to affect the early development of pulmonary TB.