High tuberculosis (TB) prevalence in Papua New Guinea (PNG) is a serious public health concern. The epidemic in this region is exacerbated by the presence of drug-resistant TB strains as well as HIV infection. This presents a public health threat not only locally but also to Australia due to the high potential for cross-border transmission between PNG’s Western Province and the Australian Torres Strait Islands. We present two mathematical models of TB in the Western Province: a simple model of the underlying TB dynamics, and a detailed model which accounts for the additional effects of HIV and drug resistance. The detailed model is used to make quantitative predictions about the impact of expanding the TB case detection rate under the Directly Observed Treatment, Short-course treatment regimen. This paper provides a framework for future investigation into the economic costs and public health benefits of potential TB interventions in this region, with the eventual aim of providing recommendations to guide policy makers in both PNG and Australia.

Host immunity will result in increased homozygosity at immunogenic loci if they encode products that elicit allele-specific immune responses. This increased homozygosity can be detected by comparison to ‘neutral’ (i. e. unselected) loci in the same genome which act as controls for the various epidemiological factors, such as biting rate, which affect homozygosity. Numerical results suggest that homozygosity should be 20 to 500 % higher at immunogenic loci, a result which is robust to changes in host death rate and the degree of linkage between the immunogenic and neutral loci. The same logic applies to loci which encode drug resistance: treated individuals with resistant infections will transmit zygotes homozygous for the resistance allele. It is argued that this increased homozygosity at putative immunogenic loci can act as a diagnostic feature to test using field data. The method also serves as a potentially very powerful method of identifying immunogenic and drug-resistant loci in laboratory studies of species such as the murine malaria Plasmodium chabaudi.

The monomer–dimer equilibrium for the human immunodeficiency virus type 1 (HIV-1) protease has been investigated under physiological conditions. Dimer dissociation at pH 7.0 was correlated with a loss in β-sheet structure and a lower degree of ANS binding. An autolysis-resistant mutant, Q7K/L33I/L63I, was used to facilitate sedimentation equilibrium studies at neutral pH where the wild-type enzyme is typically unstable in the absence of bound inhibitor. The dimer dissociation constant (KD) of the triple mutant was 5.8 μM at pH 7.0 and was below the limit of measurement (∼100 nM) at pH 4.5. Similar studies using the catalytically inactive D25N mutant yielded a KD value of 1.0 μM at pH 7.0. These values differ significantly from a previously reported value of 23 nM obtained indirectly from inhibitor binding measurements (Darke et al., 1994). We show that the discrepancy may result from the thermodynamic linkage between the monomer–dimer and inhibitor binding equilibria. Under conditions where a significant degree of monomer is present, both substrates and competitive inhibitors will shift the equilibrium toward the dimer, resulting in apparent increases in dimer stability and decreases in ligand binding affinity. Sedimentation equilibrium studies were also carried out on several drug-resistant HIV-1 protease mutants: V82F, V82F/I84V, V82T/I84V, and L90M. All four mutants exhibited reduced dimer stability relative to the autolysis-resistant mutant at pH 7.0. Our results indicate that reductions in drug affinity may be due to the combined effects of mutations on both dimer stability and inhibitor binding.