Dominant transmission of multiple uterine and cutaneous smooth-muscle tumors is seen in the disorder multiple leiomyomatosis (ML). We undertook a genomewide screen of 11 families segregating ML and found evidence for linkage to chromosome 1q42.3-q43 (maximum multipoint LOD score 5.40). Haplotype construction and analysis of recombinations permitted the minimal interval containing the locus, which we have designated "MCUL1," to be refined to an approximately 14-cM region flanked by markers D1S517 and D1S2842. Allelic-loss studies of tumors indicated that MCUL1 may act as a tumor suppressor. Identification of MCUL1 should have wide interest, since this gene may harbor low-penetrance variants predisposing to the common form of uterine fibroids and/or may undergo somatic mutation in sporadic leiomyomata.
This first multi-country report of the long-term impact of CDTI reveals a substantial reduction in itching and OSD. APOC operations are having a major effect in improving skin health in poor rural populations in Africa.
IntroductionOnchocerciasis is targeted for elimination mainly with annual community-directed treatment with ivermectin (CDTI). High infection levels have been reported in South-West Cameroon, despite ≥15 years of CDTI. The aim of this study was to assess factors associated with continued onchocerciasis transmission and skin disease.MethodsA large-scale cross-sectional study was conducted in 2017 in 20 communities in a loiasis-risk area in South-West Cameroon. A mixed-methods approach was used. Associations between infection levels, skin disease and adherence to CDTI were assessed using mixed regression modelling. Different community members’ perception and acceptability of the CDTI strategy was explored using semi-structured interviews.ResultsOnchocerciasis prevalence was 44.4% among 9456 participants. 17.5% of adults were systematic non-adherers and 5.9% participated in ≥75% of CDTI rounds. Skin disease affected 1/10 participants, including children. Increasing self-reported adherence to CDTI was associated with lower infection levels in participants aged ≥15 years but not in children. Adherence to CDTI was positively influenced by perceived health benefits, and negatively influenced by fear of adverse events linked with economic loss. Concern of lethal adverse events was a common reason for systematic non-adherence.ConclusionCDTI alone is unlikely to achieve elimination in those high transmission areas where low participation is commonly associated with the fear of adverse events, despite the current quasi absence of high-risk levels of loiasis. Such persisting historical memories and fear of ivermectin might impact adherence to CDTI also in areas with historical presence but current absence of loiasis. Because such issues are unlikely to be tackled by CDTI adaptive measures, alternative strategies are needed for onchocerciasis elimination where negative perception of ivermectin is an entrenched barrier to community participation in programmes.
A community-directed treatment with ivermectin (CDTI) for fighting onchocerciasis was started in 2003 in the hyperendemic province of Bandundu, Democratic Republic of Congo (DRC); such initiative was supported by the African Programme for Onchocerciasis Control (APOC). As the APOC stopped at the end of 2015, there was an urgent need to assess the sustainability of an ivermectin treatment. A cross-sectional survey of knowledge, attitude and perception was conducted to determine the awareness level of local population regarding the disease. A multi-stage random sampling technique allowed the selection of 450 heads of households. Most respondents (96.9%) knew about onchocerciasis as a disease. The black-fly was viewed as the causing agent of onchocerciasis by 49.9% of respondents. The most commonly cited clinical manifestations were nodules (34.4%) and pruritus (31.1%), while blindness was the most frequently reported complication (90.7%). Approximately 55.1% of respondents had a good knowledge of onchocerciasis and CDTI. Overall, only 37% of participants had a favourable attitude and 46% a positive perception. Good knowledge was associated with school attendance (adjusted OR=1.9, 95%CI: 1.3-2.8, p=0.001), while education and continuation of treatment were related with good attitude (adjusted OR=9.7, 95%CI:4.8-19.5 and adjusted OR=19.8, 95%CI: 9.7-40.6, respectively, both with p<0.001). Good perception was associated with being at least 46 years old, non-Catholic and continuing the treatment (adjusted OR=3.2, 95%CI:1.2-9.1; adjusted OR=29.6, 95%CI:14.1-62.2 and adjusted OR=5.1, 95%CI:1.6-16.0 respectively, all with p<0.001). A good level of knowledge, attitude and perception is needed for a massive adherence of population to onchocerciasis control programmes. In the area of study (Moanza, DRC), good attitude and perception motivated the continuation of treatment in the population. In the future, different plans should focus on educational strategies to maintain a massive adherence and reduce onchocerciasis prevalence.
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