Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus.

Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-κB and MAPK signaling pathways because either overexpression of a super-repressor form of IκBα or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-κB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs.

Evaluation of AFP surveillance indicators in polio-free Ghana, 2009-2013.

BACKGROUND: Ghana recorded the last case of indigenous wild poliovirus in 1999 but suffered two more outbreaks in 2003 and 2008. Following the World Health Organization (WHO) guidelines, transmission was interrupted through high routine immunisation coverage with live-attenuated oral polio vaccine (OPV), effective acute flaccid paralysis (AFP) surveillance and supplementary immunisation activities (SIA). This article describes the results of a five-year surveillance of AFP in polio-free Ghana, evaluate the surveillance indicators and identify areas that need improvement. METHODS: We investigated 1345 cases of AFP from children aged less than 15 years reported to the Disease Surveillance Department from January 2009 to December 2013. Data on demographic characteristics, vaccination history, clinical presentation and virological investigation on stool specimens collected during investigation were analysed. RESULTS: Of the specimens analysed, 56% were from males and 76.3% were from children less than 5 years of age. Twenty-four percent of the children received up to 3 doses of OPV, 57% received at least 4 doses while the status of 19% was unknown. Core AFP surveillance indicators were partly met for non-polio AFP rate while the WHO target for stool adequacy and timeliness was exceeded over the period of study. All the cases were classified virologically, however no wild polio was found. Sixty-day follow-up was conducted for 56.3% of cases and 8.6% cases classified as compactible with polio. CONCLUSION: Both laboratory and epidemiological surveillance for AFP were efficient and many WHO targets were met. However, due to the risk of poliovirus importation prior to global eradication, longterm surveillance is required to provide a high degree of confidence in prevention of poliovirus infection in Ghana. Thus, efforts should be made to strengthen regional performance and to follow-up on all AFP cases in order to establish proper diagnoses for the causes of the AFP leading to proper care.