'Relief of oppression': An organizing principle for researchers' obligations to participants in observational studies in the developing world

<p>Abstract</p> <p>Background</p> <p>A central question in the debate about exploitation in international research is whether investigators and sponsors from high-income countries (HIC) have obligations to address background conditions of injustice in the communities in which they conduct their research, beyond the healthcare and other research-related needs of participants, to aspects of their basic life circumstances.</p> <p>Discussion</p> <p>In this paper, we describe <b>t</b>he Majengo sexually transmitted disease (STD) Cohort study, a long-term prospective, observational cohort of sex workers in Nairobi, Kenya. Despite important scientific contributions and a wide range of benefits to the women of the cohort, most of the women have remained in the sex trade during their long-standing participation in the cohort, prompting allegations of exploitation. The Majengo STD cohort case extends the debate about justice in international research ethics beyond clinical trials into long-term observational research. We sketch the basic features of a new approach to understanding and operationalizing obligations of observational researchers, which we call 'relief of oppression'. 'Relief of oppression' is an organizing principle, analogous to the principle of harm reduction that is now widely applied in public health practice. Relief of oppression aims to help observational researchers working in conditions of injustice and deprivation to clarify their ethical obligations to participants. It aims to bridge the gap between a narrow, transaction-oriented account of avoiding exploitation and a broad account emphasizing obligations of reparation for historic injustices. We propose that relief of oppression might focus researchers' consideration of benefits on those that have some relevance to background conditions of injustice, and so elevate the priority of these benefits, in relation to others that might be considered and negotiated with participants, according to the degree to which the participating communities are constrained in their realization of fundamental freedoms.</p> <p>Summary</p> <p>The over-arching aim of relief of oppression is that, within the range of benefits negotiated over time with the local communities and organizations, an increasing proportion reflects a shared interest in improving participants' fundamental freedoms. We describe how harm reduction serves as a useful analogy for how we envision relief of oppression functioning in international research.</p

Growth patterns of the pearl oyster Pinctada margaritifera L. in Gazi Bay, Kenya

Culture of pearl oysters is rapidly increasing worldwide, including the western Indian Ocean. The oyster Pinctada margaritifera L., which produces the most highly valued black pearls, occurs in East Africa, and has been exploited there for the shell for many decades. The growth patterns of P. margaritifera from a natural population in the sheltered back-reef, and from oysters translocated to a tidal current-swept site, both sites within Gazi Bay, Kenya, are described. The growth rate in the natural population ranged from 31.3mm year–1 (60–65mm size-class) to 7.6mm year–1 (105–110mm sizeclass). The von Bertalanffy growth calculated with a fixed L&#8734 of 127.2mm, was 0.30 for the natural population and 0.38 for the translocated oysters. The mean growth rate during the north-east monsoon season was approximately double that for during the south-east monsoon season. The daily rate of nacre deposition ranged from 1.3µm to 5.9µm (mean 3.45µm); it declined with the size of oysters and was marginally higher at the high-energy current site. At that rate, it would take approximately two years to produce a marketable cultured half pearl with a 2.5mm layer of nacre. The results of the study are relevant to the understanding of the influence of the environment on growth, and are applicable to the optimisation of growth rate of pearl oysters in the inshore region along the east coast of Africa. Keywords: growth rate, Kenya, monsoon seasons, nacre deposition, Pinctada margaritifera, tidal currentsAfrican Journal of Marine Science 2005, 27(3): 567–57

CD4+ T cell responses to the Plasmodium falciparum erythrocyte membrane protein 1 in children with mild malaria.

The immune response against the variant surface Ag Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a key component of clinical immunity against malaria. We have investigated the development and maintenance of CD4(+) T cell responses to a small semiconserved area of the Duffy binding-like domain (DBL)α-domain of PfEMP1, the DBLα-tag. Young children were followed up longitudinally, and parasites and PBMCs were isolated from 35 patients presenting with an acute case of uncomplicated malaria. The DBLα-tag from the PfEMP1 dominantly expressed by the homologous parasite isolate was cloned and expressed as recombinant protein. The recombinant DBLα-tag was used to activate PBMCs collected from each acute episode and from an annual cross-sectional survey performed after the acute malaria episode. In this article, we report that CD4(+) T cell responses to the homologous DBLα-tag were induced in 75% of the children at the time of the acute episode and in 62% of the children at the following cross-sectional survey on average 235 d later. Furthermore, children who had induced DBLα-tag-specific CD4(+)IL-4(+) T cells at the acute episode remained episode free for longer than children who induced other types of CD4(+) T cell responses. These results suggest that a wide range of DBLα-tag-specific CD4(+) T cell responses were induced in children with mild malaria and, in the case of CD4(+)IL-4(+) T cell responses, were associated with protection from clinical episodes

Monthly antibiotic chemoprophylaxis and incidence of sexually transmitted infections and HIV-1 infection in Kenyan sex workers: A randomized controlled trial

Context Sexually transmitted infections (STIs) are common in female sex workers (FSWs) and may enhance susceptibility to infection with human immunodeficiency virus type 1 (HIV-1). Objective To examine regular antibiotic prophylaxis in FSWs as a strategy for reducing the incidence of bacterial STIs and HIV-1. Design, Setting, and Participants Randomized, double-blind, placebo-controlled trial conducted between 1998-2002 among FSWs in an urban slum area of Nairobi, Kenya. Of 890 FSWs screened, 466 who were seronegative for HIV-1 infection were enrolled and randomly assigned to receive azithromycin (n = 230) or placebo (n = 236). Groups were well matched at baseline for sexual risk taking and STI rates. Intervention Monthly oral administration of 1 g of azithromycin or identical placebo, as directly observed therapy. All participants were provided with free condoms, risk-reduction counseling, and STI case management. Main Outcome Measures The primary study end point was incidence of HIV-1 infection. Secondary end points were the incidence of STIs due to Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Treponema pallidum, and Haemophilus ducreyi, as well as bacterial vaginosis. Analysis of herpes simplex virus type 2 (HSV-2) infection was performed post hoc. Results Seventy-three percent of participants (n = 341) were followed up for 2 or more years or until they reached an administrative trial end point. Incidence of HIV-1 did not differ between treatment and placebo groups (4% [19 cases per 473 person-years of follow-up] vs 3.2% [16 cases per 495 person-years of follow-up] rate ratio [RR], 1.2; 95% CI, 0.6-2.5). Incident HIV-1 infection was associated with preceding infection with N gonorrhoeae (rate ratio [RR], 4.9; 95% CI, 1.7-14.3) or C trachomatis (RR, 3.0; 95% CI, 1.1-8.9). There was a reduced incidence in the treatment group of infection with N gonorrhoeae (RR, 0.46; 95% CI, 0.31-0.68), C trachomatis (RR, 0.38; 95% CI, 0.26-0.57), and T vaginalis (RR, 0.56; 95% CI, 0.40-0.78). The seroprevalence of HSV-2 infection at enrollment was 72.7%, and HSV-2 infection at baseline was independently associated with HIV-1 acquisition (RR, 6.3; 95% CI, 1.5-27.1). Conclusions Despite an association between bacterial STIs and acquisition of HIV-1 infection, the addition of monthly azithromycin prophylaxis to established HIV-1 risk reduction strategies substantially reduced the incidence of STIs but did not reduce the incidence of HIV-1. Prevalent HSV-2 infection may have been an important cofactor in acquisition of HIV-1. Sexually transmitted infections (STIs) are important cofactors in the human immunodeficiency virus type 1 (HIV-1)/AIDS pandemic. In HIV-infected individuals, not only may symptomatic and asymptomatic STIs enhance sexual transmission of HIV-1 by increasing virus shedding from the genital tract,1-3 but at the same time HIV-1 infection itself increases susceptibility to STIs.4 There is also considerable evidence that STIs may increase HIV-1 susceptibility in uninfected individuals,5,6 although differentiating cause from effect is more difficult in this situation.7 Prevention or control of STIs as a strategy for preventing HIV-1 transmission has met with mixed success. Improved syndromic management of STIs reduced HIV-1 incidence in communities in Mwanza, Tanzania,8 but in Uganda neither a similar strategy nor antibiotic mass-treatment of whole communities had an impact on HIV-1 incidence.9,10 Factors contributing to the lack of efficacy in the Uganda trials may have included the greater effectiveness of continuously available STI treatment services11 and the reduction in spread of HIV-1 during primary infection due to counseling given at the time of STI therapy.12 Another important factor may be that the Tanzanian study was performed early in the epidemic, when community prevalence of HIV-1 was below 5%. The Ugandan studies, by contrast, were performed later, in communities with much higher prevalences of HIV-1 (range, 10%-16%).11,13 Curable STIs may play a lesser role in HIV-1 transmission in the context of a mature epidemic, because most transmission occurs in the context of stable partnerships, reducing the potential impact of STI prevention and treatment.14 Interventions based on prevention or control of STIs may therefore be more effective in communities in the early stages of an epidemic13 or in subgroups at high risk of STIs.3 Female sex workers (FSWs) constitute an important vulnerable group in the acquisition and transmission of both HIV-1 infection and STIs15 but may be excluded from household-based community studies of STI control.16 It has therefore been suggested that interventions for control of STIs should target these women specifically.17 Studies in Kenya have shown that certain FSW cohorts have an annual HIV incidence of 16% to 50%18,19 and a high incidence of cervicitis due to infection with Neisseria gonorrhoeae and Chlamydia trachomatis.18 This may be partly attributed to low levels of condom use and poor access to STI counseling and treatment services.20 We hypothesized that these high rates of bacterial STI and HIV-1 infection would make FSWs an ideal population in which to test antibiotic prophylaxis of common genital tract infections as an HIV-1 prevention strategy. Since the use of prophylactic antibiotics by FSWs has been associated with increased sexual risk taking,21 we elected to test this intervention in a blinded fashion

A randomized, placebo-controlled trial of monthly azithromycin prophylaxis to prevent sexually transmitted infections and HIV-1 in Kenyan sex workers: study design and baseline findings.

Our objectives were to describe the baseline findings of a trial of antibiotic prophylaxis to prevent sexually transmitted infections (STIs) and HIV-1 in a cohort of Nairobi female sex workers (FSWs). A questionnaire was administered and a medical examination was performed. HIV-negative women were randomly assigned to either one gram azithromycin or placebo monthly. Mean age of the 318 women was 32 years, mean duration of sex work 7 years and mean number of clients was 4 per day. High-risk behaviour was frequent: 14% practised anal intercourse, 23% sex during menses, and 3% used intravenous drugs. While 20% reported condom use with all clients, 37% never use condoms. However, STI prevalence was relatively low: HIV-1 27%, bacterial vaginosis 46%, Trichomonas vaginalis 13%, Neisseria gonorrhoeae 8%, Chlamydia trachomatis 7%, syphilis 6% and cervical intraepithelial neoplasia (CIN) 3%. It appears feasible to access a population of high-risk FSWs in Nairobi with prevention programmes, including a proposed trial of HIV prevention through STI chemoprophylaxis

Comparing drug regimens for clearance of malaria parasites in asymptomatic adults using PCR in Kilifi County, Kenya: an open-label randomised controlled clinical trial (MalPaC)

Background: To restrict trial endpoints to infections acquired after vaccination in Phase IIb trials of candidate malaria vaccines, participants are treated with anti-malarial drugs to clear existing infections. Anti-malarial drugs with a long half-life may inhibit the acquisition of new infections. This study evaluated the effects of three anti-malarial drug regimens on the clearance of existing infections and acquisition of new infections. Methods: An open-label randomised controlled trial (MalPaC) was conducted between November 2013 and February 2014. Ninety adults were randomised 1:1:1 to receive one of three treatments: atovaquone/proguanil and artesunate (AP+AS); artesunate (AS); or sulphadoxine-pyrimethamine, artesunate, and primaquine (SP+AS+PQ). Parasite monitoring was determined over 84-day follow-up by assessing Plasmodium falciparum positivity by 18s qPCR, live and sexual stage parasites by RT-PCR, and recrudescence of infections by msp2 genotyping. Results: At enrolment, parasite prevalence by qPCR was 44% (40/90, day 0), which fell to 10% (9/90, day 16), then rose to almost the initial rates by day 84 (39%, 35/90). Individuals treated with AS and SP+AS+PQ were more likely to have higher qPCR positive rates compared to participants treated with AP+AS in the immediate post-treatment phase (days 16-28) (OR=7.7 [95%CI 4.6-12.8] p Conclusion: Falciparum DNA remained detectable by PCR post-treatment with incomplete parasite clearance regardless of drug regimen. Though AP+AS drug regimen may also have partially suppressed the acquisition of new infections during post-treatment follow-up. Trial registration: Pan African Clinical Trials Registry, 22nd of August 2013, PACTR201309000625311.</p