Genome Wide Linkage Study,Using a 250K SNP Map,of Plasmodium falciparum Infection and Mild Malaria Attack in a Senegalese Population

Multiple factors are involved in the variability of host''s response to P. falciparum infection, like the intensity and seasonality of malaria transmission, the virulence of parasite and host characteristics like age or genetic make-up. Although admitted nowadays, the involvement of host genetic factors remains unclear. Discordant results exist, even concerning the best-known malaria resistance genes that determine the structure or function of red blood cells. Here we report on a genome-wide linkage and association study for P. falciparum infection intensity and mild malaria attack among a Senegalese population of children and young adults from 2 to 18 years old. A high density single nucleotide polymorphisms (SNP) genome scan (Affimetrix GeneChip Human Mapping 250K-nsp) was performed for 626 individuals: i.e. 249 parents and 377 children out of the 504 ones included in the follow-up. The population belongs to a unique ethnic group and was closely followed-up during 3 years. Genome-wide linkage analyses were performed on four clinical and parasitological phenotypes and association analyses using the family based association tests (FBAT) method were carried out in regions previously linked to malaria phenotypes in literature and in the regions for which we identified a linkage peak. Analyses revealed three strongly suggestive evidences for linkage: between mild malaria attack and both the 6p25.1 and the 12q22 regions (empirical p-value = 5×10⁻⁵ and 9×10⁻⁵ respectively), and between the 20p11q11 region and the prevalence of parasite density in asymptomatic children (empirical p-value = 1.5×10⁻⁴). Family based association analysis pointed out one significant association between the intensity of plasmodial infection and a polymorphism located in ARHGAP26 gene in the 5q31–q33 region (p-value = 3.7×10⁻⁵). This study identified three candidate regions, two of them containing genes that could point out new pathways implicated in the response to malaria infection. Furthermore, we detected one gene associated with malaria infection in the 5q31–q33 region.     

Mesenchymal Stem Cell Therapy Regenerates the Native Bone-Tendon Junction after Surgical Repair in a Degenerative Rat Model

Background

The enthesis, which attaches the tendon to the bone, naturally disappears with aging, thus limiting joint mobility. Surgery is frequently needed but the clinical outcome is often poor due to the decreased natural healing capacity of the elderly. This study explored the benefits of a treatment based on injecting chondrocyte and mesenchymal stem cells (MSC) in a new rat model of degenerative enthesis repair.

Methodology

The Achilles'' tendon was cut and the enthesis destroyed. The damage was repaired by classical surgery without cell injection (group G1, n = 52) and with chondrocyte (group G2, n = 51) or MSC injection (group G3, n = 39). The healing rate was determined macroscopically 15, 30 and 45 days later. The production and organization of a new enthesis was assessed by histological scoring of collagen II immunostaining, glycoaminoglycan production and the presence of columnar chondrocytes. The biomechanical load required to rupture the bone-tendon junction was determined.

Principal Findings

The spontaneous healing rate in the G1 control group was 40%, close to those observed in humans. Cell injection significantly improved healing (69%, p = 0.0028 for G2 and p = 0.006 for G3) and the load-to-failure after 45 days (p<0.05) over controls. A new enthesis was clearly produced in cell-injected G2 and G3 rats, but not in the controls. Only the MSC-injected G3 rats had an organized enthesis with columnar chondrocytes as in a native enthesis 45 days after surgery.

Conclusions

Cell therapy is an efficient procedure for reconstructing degenerative entheses. MSC treatment produced better organ regeneration than chondrocyte treatment. The morphological and biomechanical properties were similar to those of a native enthesis.     

Genetic diversity in Bambara groundnut (Vigna subterranea L.) germplasm revealed by RAPD markers.

Random amplified polymorphic DNA (RAPD) markers were used to assess genetic diversity in Bambara groundnut (Vigna subterranea L.) germplasm using 25 African accessions from the collection in the International Institute for Tropical Agriculture, Ibadan, Nigeria. Fifty random decamer primers were screened to assess their ability to detect polymorphism in bambara; 17 of them were selected for this study. Considerable genetic diversity was found among the V. subterranea accessions studied. The relationships among the 25 accessions were studied by cluster analysis. The dendrograms showed two main groups of accessions mainly along the lines of their geographic origin. It is concluded that RAPD can be used for germplasm classification in bambara groundnut and hence for improving this crop.     

Implementation of mass drug administration for neglected tropical diseases in Guinea during the COVID-19 pandemic

BackgroundGuinea reported its first case of COVID-19 on March 12, 2020. Soon thereafter, a national state of emergency was declared, all land borders were closed, schools were shut down, and public gatherings were limited. Many health activities, including field-based activities targeting neglected tropical diseases (NTDs), were paused. The World Health Organization (WHO) issued updated guidance on the resumption of NTD field-based activities on July 27, 2020. In response, the Guinea Ministry of Health (MoH) and its partners planned and resumed mass drug administration (MDA) in mid-August to September 2020 in 19 health districts.Methodology/principal findingsA risk-benefit assessment was conducted to identify potential risks associated with the MDA in the COVID-19 context. Following this assessment, a risk mitigation plan with barrier measures was developed to guide MDA implementation. These measures included COVID-19 testing for all national staff leaving Conakry, mask wearing, social distancing of two meters, and hand washing/sanitizing. A checklist was developed and used to monitor compliance to risk mitigation measures. Data on adherence to risk mitigation measures were collected electronically during the MDA. A total of 120 checklists, representing 120 community drug distributor (CDD) teams (two CDDs per team) and 120 households, were completed. Results indicated that washing or disinfecting hands was practiced by 68.3% of CDD teams, compared to 45.0% among households. Face masks to cover the mouth and nose were worn by 79.2% of CDD teams, while this was low among households (23.3%). In 87.5% of households, participants did not touch the dose pole and in 88.3% of CDD teams, CDDs did not touch the hands of the participants while giving the drugs. A large majority of CDD teams (94.2%) and household members (94.2%) were willing to participate in the MDA despite the pandemic. The epidemiological coverage was ≥65% for lymphatic filariasis, onchocerciasis and soil-transmitted helminths in 10 out of 19 HDs and ≥75% for schistosomiasis for school-aged children in 7 out of 11 HDs.Conclusions/significanceGuinea was one of the first countries in Africa to resume MDA activities during the COVID-19 pandemic without causing an observed increase of transmission. The development of a risk mitigation plan and a method to monitor adherence to barrier measures was critical to this unprecedented effort. The rapid incorporation of COVID-19 barrier measures and their acceptance by CDDs and household members demonstrated both the adaptability of the National NTD Program to respond to emerging issues and the commitment of the MoH to implement NTD programs.     

Genome-Scale Phylogenetic Analyses of Chikungunya Virus Reveal Independent Emergences of Recent Epidemics and Various Evolutionary Rates

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has traditionally circulated in Africa and Asia, causing human febrile illness accompanied by severe, chronic joint pain. In Africa, epidemic emergence of CHIKV involves the transition from an enzootic, sylvatic cycle involving arboreal mosquito vectors and nonhuman primates, into an urban cycle where peridomestic mosquitoes transmit among humans. In Asia, however, CHIKV appears to circulate only in the endemic, urban cycle. Recently, CHIKV emerged into the Indian Ocean and the Indian subcontinent to cause major epidemics. To examine patterns of CHIKV evolution and the origins of these outbreaks, as well as to examine whether evolutionary rates that vary between enzootic and epidemic transmission, we sequenced the genomes of 40 CHIKV strains and performed a phylogenetic analysis representing the most comprehensive study of its kind to date. We inferred that extant CHIKV strains evolved from an ancestor that existed within the last 500 years and that some geographic overlap exists between two main enzootic lineages previously thought to be geographically separated within Africa. We estimated that CHIKV was introduced from Africa into Asia 70 to 90 years ago. The recent Indian Ocean and Indian subcontinent epidemics appear to have emerged independently from the mainland of East Africa. This finding underscores the importance of surveillance to rapidly detect and control African outbreaks before exportation can occur. Significantly higher rates of nucleotide substitution appear to occur during urban than during enzootic transmission. These results suggest fundamental differences in transmission modes and/or dynamics in these two transmission cycles.Chikungunya virus (CHIKV; Togaviridae: Alphavirus) is an arbovirus (arthropod-borne virus) vectored by Aedes mosquitoes to humans in tropical and subtropical regions of Africa and Asia (Fig. ​(Fig.1;1; reviewed in references 26 and 46). CHIKV has a single-stranded, positive-sense RNA genome of ∼12 kb and causes chikungunya fever (CHIK), a febrile illness associated with severe arthralgia and rash (2, 15, 31, 35); the name is derived from a Bantu language word describing the severe arthritic signs (32), which can persist for years. Thus, CHIK has enormous economic costs in addition to its public health impact (9). Because the signs and symptoms of CHIK overlap with those of dengue and because CHIKV is transmitted sympatrically in urban areas by the same mosquito vectors, it is grossly underreported in the absence of laboratory diagnostics (10, 37).Open in a separate windowFIG. 1.Distribution of the CHIKV strains used in this study. The map, based on a world map template from http://www.presentationmagazine.com, was edited with permission.CHIKV was first isolated during a 1953 outbreak in present-day Tanzania by Ross (48, 49). Since then, outbreaks have been documented in Africa and Asia, including the Indian subcontinent (Fig. ​(Fig.1)1) (1, 4). In 2005, CHIKV emerged from East Africa to cause an explosive urban epidemic in popular tourist island destinations in the Indian Ocean (Fig. ​(Fig.1;1; reviewed in reference 31). In late 2005, CHIKV spread into the Indian subcontinent, where millions of people have been affected (5). However, the geographic source of spread into India, from the mainland of Africa or from the Indian Ocean Islands, has not been delineated. India had seen large epidemics of CHIK in the past (reviewed in reference 30), but CHIKV apparently disappeared during the 1970s (5). Since 2006, CHIKV has been imported into Europe and the western hemisphere (including the United States) via many viremic travelers, and an epidemic was initiated in Italy by a traveler from India (4, 11, 47). The dramatic spread since 1980 of dengue viruses (DENV) throughout tropical America, via the same vectors, portends the severity of the public health problem if CHIKV becomes established in the western hemisphere.The first phylogenetic analysis of CHIKV (45) identified three geographically associated genotypes: the West African (WAf), East/Central/South African (ECSA), and Asian genotypes. More recent analyses indicate that the recent Indian Ocean and Indian strains form a monophyletic group within the ECSA lineage (5, 12, 14, 27, 40, 51, 52). However, most CHIKV phylogenetic studies (1, 14, 28, 29, 38, 40, 41, 47, 52) have utilized only partial sequences from the envelope glycoprotein E1 gene, preventing a robust assessment of some of the relationships among strains and of their evolutionary dynamics.The CHIKV strains represented in different geographic lineages apparently circulate in different ecological cycles. In Asia, CHIKV appears to circulate primarily in an urban transmission cycle involving the peridomestic mosquitoes Aedes aegypti and A. albopictus, as well as humans (25, 45). Asian epidemics typically infect thousands-to-millions of people over the course of several years (46). In contrast, African CHIKV circulates primarily in a sylvatic/enzootic cycle, transmitted by arboreal primatophilic Aedes mosquitoes (e.g., A. furcifer and A. africanus) and probably relies on nonhuman primates as reservoir hosts (reviewed in reference 16). Epidemics in rural Africa usually occur on a much smaller scale than in Asia, likely a result of the lower human population densities, and possibly more stable herd immunity. Although the assignments of “urban” and “sylvatic/enzootic” are based on the most common mode of transmission, CHIKV strains of African origin are capable of urban transmission by A. aegypti and A. albopictus, as evidenced by outbreaks in the Democratic Republic of the Congo (41), Nigeria (36), Kenya (27), and Gabon (42). The ecological differences between the sylvatic/enzootic (henceforth called enzootic) and urban/endemic/epidemic transmission cycles (henceforth called epidemic) such as seasonality of vector larval habitats, vertebrate host abundance and herd immunity, and vector host preferences, prompted us to hypothesize that the evolutionary dynamics of CHIKV may differ between the two transmission cycles. To test this hypothesis, to provide more robust estimates of the evolutionary relationships among the CHIKV strains including the sources of the recent epidemics, and to elucidate the temporal and spatial history of CHIKV evolution, we performed an extensive, genome-scale phylogenetic analysis, utilizing complete open reading frame (ORF) sequences of a large collection of 80 isolates with broad temporal, spatial, and host coverage.     

Profil spermiologique des hommes infertiles au Mali

Infertility remains a major sociocultural problem in view of the fact that in Africa, in general, and in Mali, in particular, the main purpose of marriage remains procreation. The birth of a child is a source of joy and contributes to maintenance of a certain harmony in the home. In Africa, infertility is a dramatic problem that is difficult to bear for the couple. It is the leading cause of marital discord or divorce. It is considered to be due to fate, or a curse inflicted on the couple. For the woman, it represents a divine punishment, as it is usually the woman who is blamed for the problem male responsibility is only discovered during assessment of the couple’s infertility. Sperm count and sperm cytology are the basic examinations performed on semen. These examinations constitute key elements to evaluate the quality of semen. In Mali, the Cytogenetics and Reproduction Biology laboratory performs the greatest number of semen examinations in the country. The purpose of this study was to present the sperm profile of infertile men in Mali based on a 5-year retrospective study. Male infertility is a public health problem in Mali. The age-group most frequently affected is between 30 and 39 years. Primary sterility was the predominant form, observed in 70% of the subjects studied. Schistosomiasis plays a predominant role in the infectious history. The sperm count results show that cases of oligoasthenozoospermia and azoospermia represent 49.5% and 23.7% of the study population, respectively.