Cost and Cost-Effectiveness of a Demand Creation Intervention to Increase Uptake of Voluntary Medical Male Circumcision in Tanzania: Spending More to Spend Less.

BACKGROUND: Although voluntary medical male circumcision (VMMC) reduces the risk of HIV acquisition, demand for services is lower among men in most at-risk age groups (ages 20-34 years). A randomized controlled trial was conducted to assess the effectiveness of locally-tailored demand creation activities (including mass media, community mobilization, and targeted service delivery) in increasing uptake of campaign-delivered VMMC among men aged 20-34 years. We conducted an economic evaluation to understand the intervention's cost and cost-effectiveness. SETTING: Tanzania (Njombe and Tabora regions). METHODS: Cost data were collected on surgery, demand creation activities, and monitoring and supervision related to VMMC implementation across clusters in both trial arms, as well as start-up activities for the intervention arms. The Decision Makers' Program Planning Tool was used to estimate the number of HIV infections averted and related cost savings, given the total VMMCs per cluster. Disability-adjusted life years were calculated and used to estimate incremental cost-effectiveness ratios. RESULTS: Client load was higher in the intervention arms than in the control arms: 4394 vs. 2901 in Tabora and 1797 vs. 1025 in Njombe, respectively. Despite additional costs of tailored demand creation, demand increased more than proportionally: mean costs per VMMC in the intervention arms were $62 in Tabora and $130 in Njombe, and in the control arms $70 and $191, respectively. More infections were averted in the intervention arm than in the control arm in Tabora (123 vs. 67, respectively) and in Njombe (164 vs. 102, respectively). The intervention dominated the control because it was both less costly and more effective. Cost savings were observed in both regions stemming from the antiretroviral treatment costs averted as a result of the VMMCs performed. CONCLUSIONS: Spending more to address local preferences as a way to increase uptake of VMMC can be cost-saving.

Prospective Study of the Diagnostic Accuracy of the In Vivo Laser Scanning Confocal Microscope for Severe Microbial Keratitis.

PURPOSE: To determine the diagnostic accuracy of in vivo confocal microscopy (IVCM) for moderate to severe microbial keratitis (MK). DESIGN: Double-masked prospective cohort study. PARTICIPANTS: Consecutive patients presenting to Aravind Eye Hospital, Madurai, India, between February 2012 and February 2013 with MK (diameter ≥3 mm, excluding descemetocele, perforation, or herpetic keratitis). METHODS: Following examination, the corneal ulcer was scanned by IVCM (HRT3/RCM, Heidelberg Engineering, Heidelberg, Germany). Images were graded for the presence or absence of fungal hyphae or Acanthamoeba cysts by the confocal microscopist who performed the scan (masked to microbial diagnosis) and 4 other experienced confocal graders (masked to clinical features and microbiology). The regrading of the shuffled image set was performed by 3 graders, 3 weeks later. Corneal-scrape samples were collected for microscopy and culture. MAIN OUTCOME MEASURES: The main outcome measures were sensitivity, specificity, and positive and negative predictive values of IVCM compared with those of a reference standard of positive culture or light microscopy. Sensitivities and specificities for multiple graders were pooled and 95% confidence intervals calculated using a bivariate random-effects regression model. RESULTS: The study enrolled 239 patients with MK. Fungal infection was detected in 176 (74%) and Acanthamoeba in 17 (7%) by microbiological methods. IVCM had an overall pooled (5 graders) sensitivity of 85.7% (95% confidence interval [CI]: 82.2%-88.6%) and pooled specificity of 81.4% (95% CI: 76.0%-85.9%) for fungal filament detection. For Acanthamoeba, the pooled sensitivity was 88.2% (95% CI: 76.2%-94.6%) and pooled specificity was 98.2% (95% CI: 94.9%-99.3%). Intergrader agreement was good: κ was 0.88 for definite fungus; κ was 0.72 for definite Acanthamoeba. Intragrader repeatability was high for both definite fungus (κ: 0.88-0.95) and definite Acanthamoeba classification (κ: 0.63-0.90). IVCM images from 11 patients were considered by all 5 graders to have a specific organism present (10 fungus, 1 Acanthamoeba) but had negative results via culture and light microscopy. CONCLUSIONS: Laser scanning IVCM performed with experienced confocal graders has high sensitivity, specificity, and test reproducibility for detecting fungal filaments and Acanthamoeba cysts in moderate to large corneal ulcers in India. This imaging modality was particularly useful for detecting organisms in deep ulcers in which culture and light microscopy results were negative.

Human papillomavirus infection and increased risk of HIV acquisition. A systematic review and meta-analysis.

OBJECTIVES: Human papillomavirus (HPV), one of the commonest sexually transmitted infections, may be a cofactor in HIV acquisition. We systematically reviewed the evidence for an association of HPV infection with HIV acquisition in women, heterosexual men and men who have sex with men (MSM). DESIGN: : Systematic review and meta-analysis. METHODS: Studies meeting inclusion criteria in Pubmed, Embase and conference abstracts up to 29 July 2011 were identified. Random effects meta-analyses were performed to calculate summary hazard ratios (HR). Publication bias and statistical heterogeneity were evaluated and population attributable fractions (PAFs) calculated. RESULTS: Eight articles were included, with previously unpublished data from five authors. Seven studies found an association between prevalent HPV and HIV acquisition. Risk of HIV acquisition in women doubled with prevalent HPV infection with any genotype [HR = 2.06 (95% CI = 1.44-2.94), I = 0%], although adjustment for confounders was often inadequate. The effect was similar for high-risk [HR = 1.99 (95% CI = 1.54-2.56), I = 8.4%] and low-risk [HR = 2.01 (95% CI = 1.27-3.20), I = 0%] HPV genotypes with weak evidence of publication bias (P = 0.06). Two studies in men were identified: both showed an association between HPV infection and HIV acquisition. Unpublished data from one of two studies in women indicated an association between genotypes targeted by HPV vaccines and HIV acquisition. PAFs for HIV attributable to infection with any HPV genotype ranged between 21 and 37%. CONCLUSION: If further studies validate the association between HPV infection and HIV acquisition, HPV vaccines may reduce HIV incidence in high HPV prevalence populations, in addition to preventing cervical cancer. HIV surveillance studies during implementation of HPV vaccine programmes are warranted.

Male circumcision and human papillomavirus infection in men: a systematic review and meta-analysis.

BACKGROUND: We systematically reviewed the evidence for an association between male circumcision and Human Papillomavirus (HPV) infection and genital warts in men. METHODS: PubMed and Embase were searched to 15 September 2010. The measure of effect was the adjusted odds ratio (OR) or rate ratio (RR) when present and the crude estimate otherwise. Random effects meta-analyses were used to calculate summary measures of effect. RESULTS: We identified 23 papers about the association between circumcision and HPV DNA. Circumcised men were less likely to have prevalent genital HPV infection than uncircumcised men (summary OR, 0.57, 95% confidence interval [CI], 0.45-0.71) with between-study heterogeneity (P-heterogeneity = 0.006; I(2) = 50.5%; 19 studies). Similar summary associations were seen in clinical and methodological subgroups. The effect of circumcision was stronger at the glans/corona (OR, 0.47; 95% CI, 0.37-0.60) and urethra (OR, 0.35; 95% CI, 0.12-1.05) compared with sites more distal to the foreskin. There was weak evidence that circumcision was associated with decreased HPV incidence (summary RR, 0.75, 95% CI, 0.57-0.99; 3 studies) and increased HPV clearance (summary RR, 1.33; 95% CI, 0.89-1.98; 3 studies) but no evidence of an association with prevalent genital warts (OR, 0.93, 95% CI, 0.65-1.33; 15 studies). CONCLUSIONS: Several countries are expanding access to voluntary medical male circumcision to reduce HIV prevalence. This could provide additional benefit in reducing HPV prevalence.

Male circumcision and penile cancer: a systematic review and meta-analysis.

OBJECTIVE: We systematically reviewed the evidence of an association between male circumcision and penile cancer. METHODS: Databases were searched using keywords and text terms for the epidemiology of penile cancer. Random effects meta-analyses were used to calculate summary odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: We identified eight papers which evaluated the association of circumcision with penile cancer, of which seven were case-control studies. There was a strong protective effect of childhood/adolescent circumcision on invasive penile cancer (OR = 0.33; 95% CI 0.13-0.83; 3 studies). In two studies, the protective effect of childhood/adolescent circumcision on invasive cancer no longer persisted when analyses were restricted to boys with no history of phimosis. In contrast, there was some evidence that circumcision in adulthood was associated with an increased risk of invasive penile cancer (summary OR = 2.71; 95% CI 0.93-7.94; 3 studies). There was little evidence for an association of penile intra-epithelial neoplasia and in situ penile cancer with circumcision performed at any age. CONCLUSIONS: Men circumcised in childhood/adolescence are at substantially reduced risk of invasive penile cancer, and this effect could be mediated partly through an effect on phimosis. Expansion of circumcision services in sub-Saharan Africa as an HIV prevention strategy may additionally reduce penile cancer risk.

Male circumcision, HIV and sexually transmitted infections: a review.

Three randomized controlled trials in sub-Saharan Africa have shown that circumcision reduces the risk of acquiring HIV infection in men by approximately 60%. In this paper, we review the evidence that male circumcision protects against infection with HIV and other sexually transmitted infections (STIs) in men and their female partners. Data from the clinical trials indicate that circumcision may be protective against genital ulcer disease, Herpes simplex type 2, Trichomonas vaginalis and human papillomavirus infection in men. No evidence exists of a protective effect against Chlamydia trachomatis or Neisseria gonorrhea. There is weak evidence that circumcision has a direct protective effect on HIV infection in women, although there is likely to be an indirect benefit, since HIV prevalence is likely to be lower in circumcised male partners. Although there is little evidence from the trials of serious adverse events from the procedure and of behavioural risk compensation among circumcised men, essential operational research is being conducted to evaluate these key issues outside the trial setting as circumcision services are expanded. Following the publication of the clinical trial results in early 2007, the World Health Organization/UNAIDS has advised that promotion of male circumcision should be included as an additional HIV strategy for the prevention of heterosexually acquired HIV infection in men in areas of high HIV prevalence. As circumcision services are expanded in settings where resources are limited, non-physician providers including nurses will play an important role in the provision of services.

The genome of the African trypanosome Trypanosoma brucei.

African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.

Genome of the host-cell transforming parasite Theileria annulata compared with T. parva.

Theileria annulata and T. parva are closely related protozoan parasites that cause lymphoproliferative diseases of cattle. We sequenced the genome of T. annulata and compared it with that of T. parva to understand the mechanisms underlying transformation and tropism. Despite high conservation of gene sequences and synteny, the analysis reveals unequally expanded gene families and species-specific genes. We also identify divergent families of putative secreted polypeptides that may reduce immune recognition, candidate regulators of host-cell transformation, and a Theileria-specific protein domain [frequently associated in Theileria (FAINT)] present in a large number of secreted proteins.