Jayathunge, Parana Hewage Mangalasiri (2016) 'Straight cuts' and HIV prevention: translational research on conceptual, methodological and scientific challenges in Papua New Guinea. PhD thesis, James Cook University.

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Abstract

This thesis presents data on four separate areas related to male circumcision (MC) and preventing human immunodeficiency virus (HIV) in Papua New Guinea (PNG). First, this thesis examines the literature related to MC, with a specific focus on its protective mechanisms. This systematic review of MC's different proposed protective mechanisms indicated that several mechanisms are involved in explaining the total of 60% protection against HIV demonstrated by MC, as indicated by three large randomised clinical trials.

Second, this thesis measures the proportion of surface area of the foreskin on an erect status penis, and compares this with the total exposed surface area of the penis encountering sexual fluids during sexual intercourse. The results demonstrate that the exposed surface area of the foreskin represents only 48.4% (± 9.5) of the total exposed areas of the erect penis encountering sexual secretions. These results indicate the importance of factors other than loss of surface area of the foreskin in terms of the protection offered by MC. This provides room for theories on the potential protection provided by the 'straight cut' foreskin cuttings prevalent in PNG.

Third, this thesis assesses the reliability of self-reporting MC status among men in PNG. This is measured by comparing men's self-reported MC status and investigators' classification of MC status of the participants' genital photographs. Using a three-category classification, there was 90.6% (201/222) agreement between the self-reported MC status and investigator classification (κ value: 0.805). Given the great variety of foreskin cutting practices and appearances, feasible explanations could be suggested for the two-thirds (13/21) of the discordant results. Thus, this study demonstrates a high level of agreement between self-reporting and investigator assessment of MC status in PNG, which suggests that self-reporting of MC status is highly reliable among men in PNG.

Finally, Phase 1 of the study—titled '"Straight Cuts" and HIV Prevention: The Immunohistological Correlates of Dorsal Slit Foreskin Cuttings'—was completed at Pacific Adventist University of Papua New Guinea. Phase 1 focused on the feasibility of conducting a complex immunohistological study in resource-limited PNG. During this study, the conceptual, methodological and scientific challenges (and opportunities) of conducting such a study were successfully assessed. In addition to generating valuable data on changes in three histological features (the keratin layer, rete pegs and supra-papillary ridges) of dorsal slit (or 'straight cut') foreskins, this study proved that conducting such a study in PNG is feasible and effective.

The scientific findings of Phase 1 of the study, while not conclusive, indicated a positive relationship between 'straight cuts' and HIV prevention. The results for keratin thickness demonstrated that the outer foreskin is thicker than the inner foreskin, which aligns with the findings of other prominent studies. For the two other histological features—the rete peg length and supra-papillary length, which were tested for the first time ever for human foreskins during this study—the results revealed that supra-papillary ridges could be an important predictor in determining the level of protection provided by dorsal slit foreskins against HIV infection. However, rete peg length needs to be measured with an improved methodology during future studies because the measurements taken during this study did not reflect the accurate effect of the rete pegs in terms of a physical barrier against HIV invasion.

In conclusion, this thesis fills gaps in knowledge in three areas related to PNG's efforts to prevent heterosexual HIV transmission using MC. Epidemiological evidence is emerging to indicate a positive correlation between 'straight cuts' and HIV prevention. The findings of this study, alongside the results of Phase 2 of the study, will provide scientific evidence to determine the importance of dorsal slit foreskin cuttings in preventing heterosexual transmission of HIV to men.

Item ID:	46037
Item Type:	Thesis (PhD)
Keywords:	circumcision; foreskin; heterosexual HIV transmission; HIV infections; HIV prevention; HIV transmission; HIV; human immunodeficiency virus; immune cells; keratin layer; Papua New Guinea; preventative medicine; preventive medicine; virology
Related URLs:	http://researchonline.jcu.edu.au/26801/ http://researchonline.jcu.edu.au/39284/
Additional Information:	Publications arising from this thesis are available from the Related URLs field. The publications are: Chapter 3: Jayathunge, Parana H.M., McBride, William J.H., MacLaren, David, Kaldor, John, Vallely, Andrew, and Turville, Stuart (2014) Male circumcision and HIV transmission: what do we know? Open AIDS Journal, 8. pp. 31-44. Chapter 5: Jayathunge, Parana Hewage Mangalasiri, McBride, William John Hannan, MacLaren, David, and Browne, Kelwyn (2015) Men in Papua New Guinea accurately report their circumcision status. PLoS ONE, 10 (4). pp. 1-9.
Date Deposited:	13 Oct 2016 02:36
FoR Codes:	11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111716 Preventive Medicine @ 40% 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 30% 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110804 Medical Virology @ 30%
SEO Codes:	92 HEALTH > 9205 Specific Population Health (excl. Indigenous Health) > 920504 Occupational Health @ 40% 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 30% 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 30%
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