A perpetual source of DNA or something really different: ethical issues in the creation of cell lines for African genomics research

Background: The rise of genomic studies in Africa – not least due to projects funded under H3Africa – is associated with the development of a small number of biorepositories across Africa. For the ultimate success of these biorepositories, the creation of cell lines including those from selected H3Africa samples would be beneficial. In this paper, we map ethical challenges in the creation of cell lines. Discussion: The first challenge we identified relates to the moral status of cells living in culture. There is no doubt that cells in culture are alive, and the question is how this characteristic is relevant to ethical decision-making. The second challenge relates to the fact that cells in culture are a source of cell products and mitochondrial DNA. In combination with other technologies, cells in culture could also be used to grow human tissue. Whilst on the one hand, this feature increases the potential utility of the sample and promotes science, on the other it also enables further scientific work that may not have been specifically consented to or approved. The third challenge relates to ownership over samples, particularly in cases where cell lines are created by a biobank, and in a different country than where samples were collected. Relevant questions here concern the export of samples, approval of secondary use and the acceptability of commercialisation. A fourth challenge relates to perceptions of blood and bodily integrity, which may be particularly relevant for African research participants from certain cultures or backgrounds. Finally, we discuss challenges around informed consent and ethical review. Summary: In this paper, we sought to map the myriad of ethical challenges that need to be considered prior to making cell line creation a reality in the H3Africa project. Considering the relative novelty of this practice in Africa, such challenges will need to be considered, discussed and potentially be resolved before cell line creation in Africa becomes financially feasible and sustainable. We suggest that discussions need to be undertaken between stakeholders internationally, considering the international character of the H3Africa project. We also map out avenues for empirical research

Prevalence of Blood-Borne Infectious Diseases in Blood Donors in Ghana

Transfusion-transmissible infections among 808 blood donors in Ghana were investigated in 1999. Antibody seroprevalences of 3.8, 0.7, 8.4, and 13.5%, respectively, for human immunodeficiency virus, human T-cell lymphotrophic virus type 1, hepatitis C virus (HCV), and Treponema pallidum were obtained. The seroprevalence of HCV infection was confirmed to be 0.9% after supplementary testing, and the transfusion risk potential of these pathogens was demonstrated

HIV-1 drug-resistance surveillance among treatment-experienced and -naïve patients after the implementation of antiretroviral therapy in Ghana.

BACKGROUND: Limited HIV-1 drug-resistance surveillance has been carried out in Ghana since the implementation of antiretroviral therapy (ART). This study sought to provide data on the profile of HIV-1 drug resistance in ART-experienced and newly diagnosed individuals in Ghana. METHODS: Samples were collected from 101 HIV-1-infected patients (32 ART-experienced cases with virological failure and 69 newly diagnosed ART-naïve cases, including 11 children), in Koforidua, Eastern region of Ghana, from February 2009 to January 2010. The pol gene sequences were analyzed by in-house HIV-1 drug-resistance testing. RESULTS: The most prevalent HIV-1 subtype was CRF02_AG (66.3%, 67/101) followed by unique recombinant forms (25.7%, 26/101). Among 31 ART-experienced adults, 22 (71.0%) possessed at least one drug-resistance mutation, and 14 (45.2%) had two-class-resistance to nucleoside and non-nucleoside reverse-transcriptase inhibitors used in their first ART regimen. Importantly, the number of accumulated mutations clearly correlated with the duration of ART. The most prevalent mutation was lamivudine-resistance M184V (n = 12, 38.7%) followed by efavirenz/nevirapine-resistance K103N (n = 9, 29.0%), and zidovudine/stavudine-resistance T215Y/F (n = 6, 19.4%). Within the viral protease, the major nelfinavir-resistance mutation L90M was found in one case. No transmitted HIV-1 drug-resistance mutation was found in 59 ART-naïve adults, but K103N and G190S mutations were observed in one ART-naïve child. CONCLUSIONS: Despite expanding accessibility to ART in Eastern Ghana, the prevalence of transmitted HIV-1 drug resistance presently appears to be low. As ART provision with limited options is scaled up nationwide in Ghana, careful monitoring of transmitted HIV-1 drug resistance is necessary

ガーナ ホクブ ノ エイズ チリョウ セイジン カンジャ ニ オケル HIV-1 クミカエ ト ヤクザイ タイセイ

熊本大

Frequency of HIV-1 drug-resistance mutations in ART-experienced and -naïve adult patients (≧15 years old) (<i>n</i> = 90)^a.

<p>ART, antiretroviral therapy; NNRTI, non-nucleoside reverse-transcriptase inhibitor; NRTI, nucleoside reverse-transcriptase inhibitor; PI, protease inhibitor; and TAMs, thymidine analog-associated mutations.</p>a<p>HIV-1 drug-resistance mutations were detected according to the latest definition of the International AIDS Society-USA panel <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071972#pone.0071972-Johnson1" target="_blank">[10]</a>. For ART-naïve patients, transmitted drug resistance was defined according to the latest definition of the WHO drug-resistance surveillance <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071972#pone.0071972-Bennett1" target="_blank">[11]</a>.</p

Demographic and clinical characteristics of HIV-1-infected patients <15 years old (<i>n</i> = 11)^a.

<p>ART, antiretroviral therapy; CRF, circulating recombinant form; d4T, stavudine; EFV, efavirenz; IQR, interquartile range; 3TC, lamivudine; and URF, unique recombinant form.</p>a<p>All were HIV-1 seropositive alone, and their risk factor for infection was mother-to-child transmission.</p>b<p>Only one case had been on treatment for 9.6 months.</p

Molecular epidemiology of HIV-1 infections in Koforidua, Ghana.

<p>HIV-1 subtypes of 101 isolates were determined through the construction of phylogenetic trees, similarity plotting, and boot-scanning analyses. (A) Phylogenetic tree containing our 75 isolates classified into known subtypes and CRFs. (B) Phylogenetic tree containing our 26 URF isolates identified with unknown mosaic patterns of the <i>pol</i> gene. Two clusters of URF isolates are represented by #1 and #2. (C) Summary on the chimeric patterns of 26 URF isolates. The trees were constructed by the neighbor-joining method. Bootstrap values were calculated from 1,000 analyses, and values greater than 70% are shown at tree nodes. Our isolates are represented by colored circles, and subtype reference isolates are represented by their subtype and name. Scale bar represents nucleotide substitutions per site. HIV-1 group O isolate, ANT70, was used as the outgroup. CRF, circulating recombinant form; PR, protease; RT, reverse transcriptase; and URF, unique recombinant form.</p

Demographic and clinical characteristics of ART-experienced and -naïve HIV-1-infected patients ≧15 years old (<i>n</i> = 90).

<p>ART, antiretroviral therapy; AZT, zidovudine; CRF, circulating recombinant form; d4T, stavudine; EFV, efavirenz; IQR, interquartile range; NFV, nelfinavir; NVP, nevirapine; 3TC, lamivudine; and URF, unique recombinant form.</p>a<p>HIV serology was determined using New LAV Blot I and II (Bio-Rad Laboratories, Marnes-la-Coquette, France).</p>b<p>Good, 100% pills taken; Satisfactory, ≧95%, but <100% pills taken; Poor, <95% pills taken.</p

List of primers used in HIV-1 genotypic drug-resistance testing.

<p>bp, base pairs; PCR, polymerase chain reaction; and RT-PCR, reverse transcription and polymerase chain reaction.</p>a<p>Amplicon positions in the reference HIV-1 HXB2 sequence are represented.</p