The impact of ivermectin on onchocerciasis in villages co-endemic for lymphatic filariasis in an area of onchocerciasis recrudescence in Burkina Faso

In Burkina Faso, onchocerciasis was no longer a public health problem when the WHO Onchocerciasis Control Programme in West Africa closed at the end in 2002. However, epidemiological surveillance carried out from November 2010 to February of 2011, showed a recrudescence of infection in the Cascades Region. This finding was made at a time when ivermectin, a drug recommended for the treatment of both onchocerciasis and lymphatic filariasis, had been distributed in this area since 2004 for the elimination of lymphatic filariasis. It was surprising that ivermectin distributed for treating lymphatic filariasis had not prevented the recrudescence of onchocerciasis. Faced with this situation, the aim of our study was to evaluate the effectiveness of ivermectin on the onchocerciasis parasite. The percentage reduction in microfilarial load after treatment with ivermectin was used as a proxy measure for assessing possible resistance. A cohort study was carried out with 130 individuals who had tested positive for microfilariae of Onchocerca volvulus in 2010 using microscopic examination of skin-snip biopsies from five endemic villages. Subjects were followed from July 2011 to June 2012. The microfilarial load of each individual was enumerated by skin-snip biopsy in 2010, prior to the first ivermectin treatment against onchocerciasis under community guidelines. All individuals received two ivermectin treatments six months apart. In 2012, the microfilarial loads were determined again, six months after the second round of ivermectin and the reductions in parasite loads were calculated to measure the impact of the drug. The percentage reduction of the microfilarial loads ranged from 87% to 98% in the villages. In all villages, there was a statistically significant difference between the average microfilarial loads in 2010 and 2012. The level of reduction of microfilarial loads suggests that ivermectin is effective against the recrudescent population of O. volvulus in Cascades Region of Burkina Faso. Further investigations would be necessary to determine the causes of the recrudescence of onchocerciasis. (For French language abstract, see S1 Alternative Language Abstract—Translation of the Abstract into French by the authors.)     

Tectonic vicariance versus Messinian dispersal in western Mediterranean ground beetles

The complex geological history of the western Mediterranean region conceals the interpretation of the evolutionary history of its current fauna, as similar distribution patterns may have very different temporal and geographic origins. Particularly intriguing are some subterranean species in islands, which origin is usually difficult to interpret as their strongly modified morphologies obscure their relationships. We studied subterranean taxa and their likely relatives of two groups of ground beetles in the western Mediterranean: the Duvalius lineage (“isotopic” Trechini) and Molopina (Pterostichini). We included specimens from the islands of Mallorca, Sardinia and Sicily, plus mainland Europe and North Africa. Phylogenetic relationships were reconstructed with a combination of mitochondrial and nuclear data, and divergence dates were estimated with Bayesian methods using the same a priori molecular evolutionary rates for the same gene fragments in the two groups. In the Duvalius lineage, the subgenus Trechopsis, including all the highly modified cave or nivicolous species, was found to be polyphyletic: the species from Mallorca was found to be of Pleistocene origin and sister to the less modified species of subgenus Duvalius from the same island, whereas the Algerian species of Trechopsis were, on the contrary, related to the Sicilian Duvalius, indicating a northern colonisation route during the late Pliocene. Molopina was divided into three main lineages: the genera Abax, Percus, and the Molops groups of genera. The basal diversification of the latter was dated within a temporal window (35–25 Ma) fully congruent with the tectonic opening of the western Mediterranean basin and included six main lineages with uncertain relationships among them: the epigean genera (a) Molops and (b) Tanythrix; and the subterranean (c) Typhlochoromus (Eastern Alps), (d) Speomolops (Sardinia), (e) Henrotius (Mallorca) and (f) a strongly supported clade including the Pyrenean genera Zariquieya, Oscadytes and Molopidius. Despite the similar distribution of some of their subterranean taxa, the two studied groups show a strongly contrasting origin and mode of diversification. While the Duvalius lineage had a recent origin, with complex colonisation patterns and widespread morphological convergence among the subterranean species, the subterranean Molopina had an ancient vicariant origin resulting from the tectonic opening of the western Mediterranean basin.     

Homologous Recombination Offers Advantages over Transposition-Based Systems to Generate Recombinant Baculovirus for Adeno-Associated Viral Vector Production

Viral vectors have a great potential for gene delivery, but manufacturing is a big challenge for the industry. The baculovirus-insect cell is one of the most scalable platforms to produce recombinant adeno-associated virus (rAAV) vectors. The standard procedure to generate recombinant baculovirus is based on Tn7 transposition which is time-consuming and suffers technical constraints. Moreover, baculoviral sequences adjacent to the AAV ITRs are preferentially encapsidated into the rAAV vector particles. This observation raises concerns about safety due to the presence of bacterial and antibiotic resistance coding sequences with a Tn7-mediated system for the construction of baculoviruses reagents. Here, a faster and safer method based on homologous recombination (HR) is investigated. First, the functionality of the inserted cassette and the absence of undesirable genes into HR-derived baculoviral genomes are confirmed. Strikingly, it is found that the exogenous cassette showed increased stability over passages when using the HR system. Finally, both materials generated high rAAV vector genome titers, with the advantage of the HR system being exempted from undesirable bacterial genes which provides an additional level of safety for its manufacturing. Overall, this study highlights the importance of the upstream process and starting biologic materials to generate safer rAAV biotherapeutic products.