African isolates show a high proportion of multiple copies of the Plasmodium falciparum plasmepsin-2 gene, a piperaquine resistance marker

Background: Today, the development of new and well-tolerated anti-malarial drugs is strongly justifed by the emer‑ gence of Plasmodium falciparum resistance. In 2014–2015, a phase 2b clinical study was conducted to evaluate the efcacy of a single oral dose of Artefenomel (OZ439)–piperaquine (PPQ) in Asian and African patients presenting with uncomplicated falciparum malaria. Methods: Blood samples collected before treatment ofered the opportunity to investigate the proportion of mul‑ tidrug resistant parasite genotypes, including P. falciparum kelch13 mutations and copy number variation of both P. falciparum plasmepsin 2 (Pfpm2) and P. falciparum multidrug resistance 1 (Pfmdr1) genes. Results: Validated kelch13 resistance mutations including C580Y, I543T, P553L and V568G were only detected in parasites from Vietnamese patients. In Africa, isolates with multiple copies of the Pfmdr1 gene were shown to be more frequent than previously reported (21.1%, range from 12.4% in Burkina Faso to 27.4% in Uganda). More strikingly, high proportions of isolates with multiple copies of the Pfpm2 gene, associated with piperaquine (PPQ) resistance, were frequently observed in the African sites, especially in Burkina Faso and Uganda (>30%). Conclusions: These fndings were considered to sharply contrast with the recent description of increased sensitivity to PPQ of Ugandan parasite isolates. This emphasizes the necessity to investigate in vitro susceptibility profles to PPQ of African isolates with multiple copies of the Pfpm2 gene and estimate the risk of development of PPQ resistance in Africa

¿No es la misma de siempre esta mujer? Género, raza y poesía cubana de los ochenta en la obra poética de Soleida Ríos

Este artículo se propone determinar cuán revolucionarias fueron las construcciones poético discursivas de las categorías identitarias de raza y género, según las imágenes poéticas creadas por la escritora afrodescendiente cubana Soleida Ríos (Santiago de Cuba, 1950), en la década de los ochenta. Es decir, cómo la poeta se vio a sí misma como mujer negra, dentro de un contexto cuya retórica de igualdad se contradecía con su praxis diferenciadora. Me interesa la evolución de la mujer negra cubana a casi treinta años de iniciado el proyecto revolucionario del “hombre nuevo”. Analizo el diálogo del discurso poético con el discurso dominante (el político), para distinguir cuán considerable fue la participación de este último en la redefinición de las categorías género y raza, teniendo en cuenta que tales conceptos de identidad no son construcciones exclusivamente culturales, sino también políticas, camufladas estratégicamente detrás de lo cultural, tradicional e histórico

A randomised, double-blind clinical phase II trial of the efficacy, safety, tolerability and pharmacokinetics of a single dose combination treatment with artefenomel and piperaquine in adults and children with uncomplicated Plasmodium falciparum malaria

BACKGROUND: The clinical development of a single encounter treatment for uncomplicated malaria has the potential to significantly improve the effectiveness of antimalarials. Exploratory data suggested that the combination of artefenomel and piperaquine phosphate (PQP) has the potential to achieve satisfactory cure rates as a single dose therapy. The primary objective of the study was to determine whether a single dose of artefenomel (800 mg) plus PQP in ascending doses is an efficacious treatment for uncomplicated Plasmodium falciparum malaria in the 'target' population of children ≤ 5 years of age in Africa as well as Asian patients of all ages. METHODS: Patients in six African countries and in Vietnam were randomised to treatment with follow-up for 42-63 days. Efficacy, tolerability, safety and pharmacokinetics were assessed. Additional key objectives were to characterise the exposure-response relationship for polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response at day 28 post-dose (ACPR28) and to further investigate Kelch13 mutations. Patients in Africa (n = 355) and Vietnam (n = 82) were included, with 85% of the total population being children < 5 years of age. RESULTS: ACPR28 in the per protocol population (95% confidence interval) was 70.8% (61.13-79.19), 68.4% (59.13-76.66) and 78.6% (70.09-85.67) for doses of 800 mg artefenomel with 640 mg, 960 mg and 1440 mg of PQP respectively. ACPR28 was lower in Vietnamese than in African patients (66.2%; 54.55-76.62 and 74.5%; 68.81-79.68) respectively. Within the African population, efficacy was lowest in the youngest age group of ≥ 0.5 to ≤ 2 years, 52.7% (38.80-66.35). Initial parasite clearance was twice as long in Vietnam than in Africa. Within Vietnam, the frequency of the Kelch13 mutation was 70.1% and was clearly associated with parasite clearance half-life (PCt1/2). The most significant tolerability finding was vomiting (28.8%). CONCLUSIONS: In this first clinical trial evaluating a single encounter antimalarial therapy, none of the treatment arms reached the target efficacy of > 95% PCR-adjusted ACPR at day 28. Achieving very high efficacy following single dose treatment is challenging, since > 95% of the population must have sufficient concentrations to achieve cure across a range of parasite sensitivities and baseline parasitaemia levels. While challenging, the development of tools suitable for deployment as single encounter curative treatments for adults and children in Africa and to support elimination strategies remains a key development goal