Pleuromutilins are a group of antibiotics derived from the naturally occurring compound. The recent approval of lefamulin for both intravenous and oral doses in humans to treat community-acquired bacterial pneumonia has prompted investigations in modifying the structure to broaden the antibacterial spectrum, enhance the activity, and improve the pharmacokinetic properties. AN11251 is a C(14)-functionalized pleuromutilin with a boron-containing heterocycle substructure. It was demonstrated to be an anti-Wolbachia agent with therapeutic potential for Onchocerciasis and lymphatic filariasis. Here, the in vitro and in vivo PK parameters of AN11251 were measured including PPB, intrinsic clearance, half-life, systemic clearance, and volume of distribution. The results indicate that the benzoxaborole-modified pleuromutilin possesses good ADME and PK properties. AN11251 has potent activities against the Gram-positive bacterial pathogens tested, including various drug-resistant strains, and against the slow-growing mycobacterial species. Finally, we employed PK/PD modeling to predict the human dose for treatment of disease caused by Wolbachia, Gram-positive bacteria, or Mycobacterium tuberculosis, which might facilitate the further development of AN11251.

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.

暂无摘要。

Onchocerciasis in camels is caused by adult Onchocerca spp. and results in great economic losses to the camel industry. However, only a few studies on Onchocerca have been conducted, especially regarding the intermediate host and vector(s). In the present study, 192 camels were examined from December and January during 2013 and 2016, and the filarial larvae suspected to be Onchocerca spp. were further identified. Furthermore, aquatic dipteran insects in the living environment of camels were collected from May to September between 2013 and 2017 and dissected. Eventually, onchocercal lesions were observed in 95 of 192 (49%) camels and the captured insects were classified into 49 species from 42 genera in 21 families, among which 18 species were newly recorded in Inner Mongolia and 14 were haematophagous species. The filarial larvae were found in Culicoides puncticollis and identified as Onchocerca fasciata, indicating that C. puncticollis is the vector of O. fasciata in Inner Mongolia. These findings provide an estimate of onchocerciasis infection in camels and an alternative method of identifying insects and screening vectors using molecular methods. Important data are also provided for the diagnosis and control of onchocerciasis, thereby further filling the gap in knowledge regarding transmission vectors in China.

暂无摘要。

The goal of this study was to provide insight into the pathogenicity of Onchocerca fasciata in Camelus bactrianus to help control onchocerciasis. From November 2015 to January 2016, the prevalence and severity of onchocerciasis were recorded in 152 camels. Nodules containing Onchocerca were collected and observed. Adult parasites were extracted from the nodules and identified via light microscopy as well as by partial sequencing of the cytochrome oxidase subunit I (COI) gene. The sequences were examined and compared to similar sequences from other Onchocerca species. In total, 80.3% of camels were parasitized. The severity of infection varied, as camels harboured between one and fifteen nodules. The morphology and the cuticle differed in both sexes and displayed considerable variation in the thickness and structure of different body parts. Identification was further confirmed using molecular biology methods. This study provides a comprehensive morphological description of Onchocerca fasciata isolated from camels. The prevalence and intensity of infection (assessed via nodules) varied in the Bactrian camels. The structure of the cuticle was an important morphological feature for species differentiation in Onchocerca. Based on our data, the morphological assessment of O. fasciata represents a reliable method to characterize other Onchocerca species.

Development times of eggs, larvae and pupae of vectors of onchocerciasis (Simulium spp.) and of Onchocerca volvulus larvae within the adult females of the vectors decrease with increasing temperature. At and above 25°C, the parasite could reach its infective stage in less than 7 days when vectors could transmit after only two gonotrophic cycles. After incorporating exponential functions for vector development into a novel blackfly population model, it was predicted that fly numbers in Liberia and Ghana would peak at air temperatures of 29°C and 34°C, about 3°C and 7°C above current monthly averages, respectively; parous rates of forest flies (Liberia) would peak at 29°C and of savannah flies (Ghana) at 30°C. Small temperature increases (less than 2°C) might lead to changes in geographical distributions of different vector taxa. When the new model was linked to an existing framework for the population dynamics of onchocerciasis in humans and vectors, transmission rates and worm loads were projected to increase with temperature to at least 33°C. By contrast, analyses of field data on forest flies in Liberia and savannah flies in Ghana, in relation to regional climate change predictions, suggested, on the basis of simple regressions, that 13-41% decreases in fly numbers would be expected between the present and before 2040. Further research is needed to reconcile these conflicting conclusions.

OBJECTIVE: To investigate the progress and challenges of the implementation of the global programme in Taraba State, Nigeria.
METHODS: The African Programme for Onchocerciasis Control (APOC) as the first neglected tropical diseases (NTD) control initiative in Africa had been introduced to Nigeria since 1997. Community-directed distributors of community-directed treatment with ivermectin had been adopted as its main strategy. As a qualitative study, in-depth interview and focus group discussion were used as data collection methods. The thematic framework method was used as a data analysis method.
RESULTS: The community reported that they had benefited from the programme. The study findings showed that the health education on NTDs remained very poor, and the community had not fully realized its responsibility for the drug distribution and NTDs control, and the community drug distributor (CDDs) had not been developed as a substantial team working for other projects.
CONCLUSIONS: The goals of community-directed treatment with ivermectin (CDTI) only have been achieved partly. China should learn from the experience.