Community Mobilization and Empowerment of Female Sex Workers in Karnataka State,South India: Associations With HIV and Sexually Transmitted Infection Risk

Objectives. We examined the impact of community mobilization (CM) on the empowerment, risk behaviors, and prevalence of HIV and sexually transmitted infection in female sex workers (FSWs) in Karnataka, India.Methods. We conducted behavioral–biological surveys in 2008 and 2011 in 4 districts of Karnataka, India. We defined exposure to CM as low, medium (attended nongovernmental organization meeting or drop-in centre), or high (member of collective or peer group). We used regression analyses to explore whether exposure to CM was associated with the preceding outcomes. Pathway analyses explored the degree to which effects could be attributable to CM.Results. By the final survey, FSWs with high CM exposure were more likely to have been tested for HIV (adjusted odd ratio [AOR] = 25.13; 95% confidence interval [CI] = 13.07, 48.34) and to have used a condom at last sex with occasional clients (AOR = 4.74; 95% CI =  2.17, 10.37), repeat clients (AOR = 4.29; 95% CI = 2.24, 8.20), and regular partners (AOR = 2.80; 95% CI = 1.43, 5.45) than FSWs with low CM exposure. They were also less likely to be infected with gonorrhea or chlamydia (AOR = 0.53; 95% CI = 0.31, 0.87). Pathway analyses suggested CM acted above and beyond peer education; reduction in gonorrhea or chlamydia was attributable to CM.Conclusions. CM is a central part of HIV prevention programming among FSWs, empowering them to better negotiate condom use and access services, as well as address other concerns in their lives.HIV prevention strategies with female sex workers (FSWs) have traditionally relied on individual behavior change, involving peer educators, condom promotion, and provision of sexual health services.1,2 Over the past decade, there has been a growing recognition that HIV epidemics are “socially and culturally produced,”3 and that psychosocial and community-level processes underlie an individual’s ability to adopt safer sexual behaviors. This has influenced approaches to HIV prevention, with more attention being paid to structural and social factors (such as violence, stigma, and poverty) that shape individual-level risk behaviors (e.g., condom use) and interventions that are targeted toward contextual factors in the HIV risk environment.4–8Among FSW populations, community mobilization (CM) has been endorsed as one of the structural interventions that improve the risk environment, with it''s effectiveness in addressing health and social issues of poor and marginalized populations largely explained through “empowerment.”9–12 Such programs have been recognized in the Joint United Nations Programme on HIV/AIDS investment framework, which includes CM as a critical enabler to core programs.13 In contrast to peer education, which usually involves peers meeting FSWs in the field, talking to them about the program, about difficulties they are facing in their lives, about the importance of condom use, and about the clinics and drop-in centers and other program activities, CM involves bringing together FSWs of various typologies who are scattered and hidden across rural areas and towns through mobilization, participation, and empowerment processes, to provide them with the space and the opportunity to act together, to fight injustices against them, and to campaign for their rights. Thus, whereas peer education can be a fairly “top down” approach, CM is designed to be an inclusive process that is initiated and sustained by the community to bring about the changes they desire (e.g., reduction in violence) through the process of empowerment. Empowerment can be defined as “the processes by which those who have been denied the ability to make choices (disempowered) acquire such an ability.”14^(p437) Most empowerment approaches recognize a dynamic interplay between gaining internal skills and overcoming external barriers, often drawing upon a conceptual framework that distinguishes “power within” (for example, self-confidence or critical thinking skills that contribute to individual agency), “power to” (for example, the ability to make individual decisions that determine and demonstrate such agency), and “power with” (communal decisions, such as group solidarity or collective action, which acknowledge that positive change may often be effected by individuals working together, rather than alone).9,15,16 In the context of sex work, the principles of social solidarity and CM seek to shift the burden of safer sex negotiation from being solely that of an individual FSW to a concept that is collectively shared and owned by the SW community, by acknowledging the dynamics and inequalities between a FSW and her client and the owners, pimps, and madams of sex establishments where sex workers work.17The Sonagachi program in Kolkata in east India provided one of the first examples of a rights-based HIV prevention program for FSWs, focusing on the mobilization and empowerment of brothel-based sex workers, as well as engagement with power structures,12,18–20 with data suggesting that HIV prevalence remained much lower in this setting compared with FSWs elsewhere in India.19 More recently, a growing body of evidence has suggested that organizing FSWs into support groups and community-based organizations can help the community to collectively challenge factors contributing to their vulnerability, such as stigma, discrimination, poverty, housing instability, violence, and harassment.21–31 However, although studies have reported strong associations between CM and collective power, uptake of sexually transmitted infection (STI) services, and consistent condom use with clients,11,17,32–35 there remains a paucity of data examining the impact of CM on biological (HIV or STI) outcomes.India has an estimated 2.4 million people living with HIV.36 Karnataka state in south India has the fourth highest HIV prevalence in the country. HIV is predominantly transmitted heterosexually, with the prevalence of HIV previously exceeding 1% in the general population, and a prevalence of more than 30% among FSWs in some districts.37,38 Before 2003, there was little HIV prevention programming in Karnataka. The Karnataka Health Promotion Trust was established in 2003 as part of the India Avahan initiative, funded by the Bill & Melinda Gates foundation.39,40 The program aimed to slow the HIV epidemic by rapidly scaling up targeted HIV prevention programs, reaching more than 60 000 FSWs and 20 000 men who have sex with men and transgenders in 20 of the 30 districts in the state.Community mobilization and the empowerment of FSWs formed a core part of HIV prevention programming in Karnataka (Figure 1).21,29–31 The process of mobilization and empowerment was gradual, with later phases of the program building on previous phases, and each activity contributing to the mobilization of SWs. For example, in the early phase of the project, peer educators were recruited from the FSW community. FSWs were brought together, and safe drop-in centers were created to respond to FSWs’ need for somewhere safe to rest, dress up, and meet friends. The program organized events and meetings for FSWs together with clinical services in these drop-in centers. These services included the provision of the “gray pack,” which was supplied every 3 to 6 months for the periodic presumptive treatment of gonorrhea and Chlamydia (containing 1 g azithromycin and 400 mg cefixime). These drop-in centers, in turn, helped attract more SWs, which resulted in the centers becoming a space where FSWs could meet each other and share their experiences, which helped create a sense of solidarity. The program then worked to support and develop critical thinking among the FSW community, providing a forum where FSWs could discuss the difficulties in their lives and reflect on how they could work together to address the challenges they faced.Open in a separate windowFIGURE 1—Community mobilization activities of Karnataka Health Promotion Trust: Karnataka, India, 2003–2014.Note. DIC = drop-in center; FSW = female sex worker; STI = sexually transmitted infection.In the intensive phases of the program (2006–2008), FSWs built on their sense of solidarity and started to undertake collective action, working with policymakers, the police, government officials, human rights lawyers, and the media to address issues of stigma, discrimination, violence, and social inequity.21,31 This, in turn, gave birth to collectivization and the formation of community-based institutions, such as peer groups or collectives. In the maintenance phase (2008–2013), FSW community-based organizations were formed to enable the process of handing over ownership of the Avahan program to FSWs and to the state government by 2013, which is now complete.41A detailed analysis of the impact of Avahan on HIV and risk behavior has been conducted, and suggests that the combination HIV program had a significant impact on HIV prevalence in Karnataka.42 However, a key policy debate, especially given current resource constraints, has been whether it is necessary to include CM, collectivization, and empowerment components in FSW HIV prevention programming, which can be costly and time-consuming. Therefore, we examined the impact of CM on HIV and STI prevalence, HIV risk behaviors, and collective and individual power among FSWs in Karnataka, using secondary analyses of data from 2 rounds of behavioral–biological surveys conducted with FSWs in 2008 and 2011.     

Characterization and Epitope Mapping of the Polyclonal Antibody Repertoire Elicited by Ricin Holotoxin-Based Vaccination

Ricin, one of the most potent and lethal toxins known, is classified by the Centers for Disease Control and Prevention (CDC) as a select agent. Currently, there is no available antidote against ricin exposure, and the most promising therapy is based on neutralizing antibodies elicited by active vaccination or that are given passively. The aim of this study was to characterize the repertoire of anti-ricin antibodies generated in rabbits immunized with ricin toxoid. These anti-ricin antibodies exhibit an exceptionally high avidity (thiocyanate-based avidity index, 9 M) toward ricin and an apparent affinity of 1 nM. Utilizing a novel tissue culture-based assay that enables the determination of ricin activity within a short time period, we found that the anti-ricin antibodies also possess a very high neutralizing titer. In line with these findings, these antibodies conferred mice with full protection against pulmonary ricinosis when administered as a passive vaccination. Epitope mapping analysis using phage display random peptide libraries revealed that the polyclonal serum contains four immunodominant epitopes, three of which are located on the A subunit and one on the B subunit of ricin. Only two of the four epitopes were found to have a significant role in ricin neutralization. To the best of our knowledge, this is the first work that characterizes these immunological aspects of the polyclonal response to ricin holotoxin-based vaccination. These findings provide useful information and a possible strategy for the development and design of an improved ricin holotoxin-based vaccine.     

A novel multimodal nanoplatform for targeting tumor necrosis

Peri-necrotic tumor regions have been found to be a source of cancer stem cells (CSC), important in tumor recurrence. Necrotic and peri-necrotic tumor zones have poor vascular supply, limiting effective exposure to systemically administered therapeutics. Therefore, there is a critical need to develop agents that can effectively target these relatively protected tumor areas. We have developed a multi-property nanoplatform with necrosis avidity, fluorescence imaging and X-ray tracking capabilities to evaluate its feasibility for therapeutic drug delivery. The developed nanoparticle consists of three elements: poly(ethylene glycol)-block-poly(ε-caprolactone) as the biodegradable carrier; hypericin as a natural compound with fluorescence and necrosis avidity; and gold nanoparticles for X-ray tracking. This reproducible nanoparticle has a hydrodynamic size of 103.9 ± 1.7 nm with a uniform spherical morphology (polydispersity index = 0.12). The nanoparticle shows safety with systemic administration and a stable 30 day profile. Intravenous nanoparticle injection into a subcutaneous tumor-bearing mouse and intra-arterial nanoparticle injection into rabbits bearing VX2 orthotopic liver tumors resulted in fluorescence and X-ray attenuation within the tumors. In addition, ex vivo and histological analysis confirmed the accumulation of hypericin and gold in areas of necrosis and peri-necrosis. This nanoplatform, therefore, has the potential to enhance putative therapeutic drug delivery to necrotic and peri-necrotic areas, and may also have an application for monitoring early response to anti-tumor therapies.

Au-Hyp-NP developed by encapsulation of gold and hypericin into PEG-PCL nanoplatform for fluorescence and X-ray tracking with tumor necrosis targeting.     

Immunology in Africa

Africa is a continent with a large burden of both infectious and non‐communicable diseases. If we are to move forward as a continent, we need to equip our growing cadre of exceptional young scientists with the skills needed to tackle the diseases endemic to this continent. For this, immunology is among the key disciplines. Africans should be empowered to study and understand the diseases that affect them, and to perform their cutting‐edge research in their country of origin. This requires a multifaceted approach, with buy‐in from funders, overseas partners and perhaps, most important of all, African governments themselves.     

The anti-leukaemic activity of novel synthetic naphthoquinones against acute myeloid leukaemia: induction of cell death via the triggering of multiple signalling pathways

Naphthoquinones, such as menadione, display lower toxicity than anthracyclins used in cancer chemotherapy. Novel anti-leukaemic compounds comprised of chloro-amino-phenyl naphthoquinones with substitutions on the benzoic ring were developed. Structure–activity relationship studies indicated that the analogue with both methyl and amine substitutions (named TW-92) was the most efficient in killing leukaemic cells. Treatment of U-937 promonocytic cells with TW-92 induced apoptotic or necrotic cell death, dependent on incubation and dose conditions. TW-92 induced rapid phosphorylation of p38 mitogen-activated protein kinase (p38^MAPK) and of extracellular signal-regulated protein kinases (ERK1/2). The generation of apoptosis was preceded by intracellular H₂O₂ accumulation accompanied by glutathione depletion, the former inhibited by di-phenyl-iodonium (DPI), an inhibitor of NADPH oxidase. TW-92 induced swelling of isolated rat liver mitochondria, indicative of a direct effect on mitochondria. Apoptosis in intact cells was accompanied by a decrease in mitochondrial membrane potential, cytochrome c release and caspase activation. In addition, the level of Mcl-1, an anti-apoptotic regulatory protein, was down-regulated, whereas the expression of the pro-apoptotic BAX was elevated. Finally, TW-92 exerted strong pro-apoptotic and necrotic effects in primary acute myeloid leukaemia samples when given in submicromolar concentrations. Together, these findings demonstrate that TW-92 may provide an effective anti-leukaemic strategy.