Attitudes toward home-based malaria testing in rural and urban Sierra Leone.

BACKGROUND: The purpose of this study was to examine malaria testing practices and preferences in Bo, Sierra Leone, and to ascertain interest in and willingness to take a home-based rapid diagnostic test administered by a community health volunteer (CHV) or a trained family member rather than travelling to a clinical facility for laboratory-based testing. METHODS: A population-based, cross-sectional survey of 667 randomly-sampled rural households and 157 urban households was conducted in December 2013 and January 2014. RESULTS: Among rural residents, 69% preferred a self/family- or CHV-conducted home-based malaria test and 20% preferred a laboratory-based test (with others indicating no preference). Among urban residents, these numbers were 38% and 44%, respectively. If offered a home-based test, 28% of rural residents would prefer a self/family-conducted test and 68% would prefer a CHV-assisted test. For urban residents, these numbers were 21% and 77%. In total, 36% of rural and 63% of urban residents reported usually taking a diagnostic test to confirm suspected malaria. The most common reasons for not seeking malaria testing were the cost of testing, waiting to see if the fever resolved on its own, and not wanting to travel to a clinical facility for a test. In total, 32% of rural and 27% of urban participants were very confident they could perform a malaria test on themselves or a family member without assistance, 50% of rural and 62% of urban participants were very confident they could perform a test after training, and 56% of rural and 33% of urban participants said they would pay more for a home-based test than a laboratory-based test. CONCLUSION: Expanding community case management of malaria to include home testing by CHVs and family members may increase the proportion of individuals with febrile illnesses who confirm a positive diagnosis prior to initiating treatment.

A novel mouse model of rhabdomyosarcoma underscores the dichotomy of MDM2-ALT1 function in vivo.

Alternative splicing of the oncogene murine double minute 2 (MDM2) is induced in response to genotoxic stress. MDM2-ALT1, the major splice variant generated, is known to activate the p53 pathway and impede full-length MDM2's negative regulation of p53. Despite this perceptible tumor-suppressive role, MDM2-ALT1 is also associated with several cancers. Furthermore, expression of MDM2-ALT1 has been observed in aggressive metastatic disease in pediatric rhabdomyosarcoma (RMS), irrespective of histological subtype. Therefore, we generated a transgenic MDM2-ALT1 mouse model that would allow us to investigate the effects of this splice variant on the progression of tumorigenesis. Here we show that when MDM2-ALT1 is ubiquitously expressed in p53 null mice it leads to increased incidence of spindle cell sarcomas, including RMS. Our data provide evidence that constitutive MDM2-ALT1 expression is itself an oncogenic lesion that aggravates the tumorigenesis induced by p53 loss. On the contrary, when MDM2-ALT1 is expressed solely in B-cells in the presence of homozygous wild-type p53 it leads to significantly increased lymphomagenesis (56%) when compared with control mice (27%). However, this phenotype is observable only at later stages in life (⩾18 months). Moreover, flow cytometric analyses for B-cell markers revealed an MDM2-ALT1-associated decrease in the B-cell population of the spleens of these animals. Our data suggest that the B-cell loss is p53 dependent and is a response mounted to persistent MDM2-ALT1 expression in a wild-type p53 background. Overall, our findings highlight the importance of an MDM2 splice variant as a critical modifier of both p53-dependent and -independent tumorigenesis, underscoring the complexity of MDM2 posttranscriptional regulation in cancer. Furthermore, MDM2-ALT1-expressing p53 null mice represent a novel mouse model of fusion-negative RMS.

Intensified tuberculosis case finding amongst vulnerable communities in southern India.

India mainly uses passive case finding to detect tuberculosis (TB) patients through the Revised National Tuberculosis Control Programme (RNTCP). An intensified case finding (ICF) intervention was conducted among vulnerable communities in two districts of Karnataka during July-December 2013; 658 sputum smear-positive TB cases were detected. The number of smear-positive cases detected increased by 8.8% relative to the pre-intervention period (July-December 2012) in intervention communities as compared to an 8.6% decrease in communities without the ICF intervention. ICF activities brought TB services closer to vulnerable communities, moderately increasing TB case detection rates.

L'Inde recourt en majorité à la détection passive des cas de patients avec la tuberculose (TB) à travers le Programme national révisé de Lutte contre la Tuberculose. Une intervention de recherche intensifiée de cas (ICF) a été réalisée au sein de communautés vulnérables dans deux districts de Karnataka entre juillet et décembre 2013 ; 658 cas de TB à frottis positif ont été détectés. Le nombre de cas à frottis positif a augmenté de 8,8% par comparaison à la période précédant l'intervention (juillet­décembre 2012) dans les communautés bénéficiaires comparées aux 8,6% de diminution dans les communautés témoins. Des activités de recherche de cas intensifiées ont amené les services de TB plus près des communautés vulnérables, ce qui a accru modérément le taux de détection des cas de TB.

En la India se da preferencia a la estrategia de búsqueda pasiva con el fin de detectar los casos de tuberculosis (TB) en el marco del Programa Nacional Revisado. Se llevó a cabo una intervención de búsqueda intensificada de casos en las comunidades vulnerables de dos distritos de Karnataka de julio a diciembre del 2013 y se detectaron 658 casos de TB con baciloscopia positiva. El número de casos con baciloscopia positiva aumentó un 8,8% con respecto al período anterior a la intervención (de julio a diciembre del 2012) en las comunidades de la intervención, en comparación con una disminución de 8,6% en las comunidades que no recibieron la intervención. Las actividades de intensificación de la búsqueda de casos llevaron los servicios de atención de la TB a las comunidades vulnerables y aumentaron de manera moderada las tasas de detección de la enfermedad.

Herbs and herbal combinations used to treat suspected malaria in Bo, Sierra Leone.

ETHNOPHARMACOLOGICAL RELEVANCE: Most adults in West Africa treat acute febrile illnesses with local herbs, but the patterns of herbs used for malaria have not been recently described in Sierra Leone. MATERIALS AND METHODS: We used a population-based cross-sectional approach to interview 810 randomly-sampled rural and urban adult residents of Bo, Sierra Leone, in December 2013 and January 2014 about their use of herbal remedies when they suspect they have malaria. RESULTS: In total, 55% of the participants reported taking one or more of seven herbs to treat symptoms of malaria. Among herb users, the most commonly used anti-malarial herbs were Moringa oleifera (moringa, 52%) and Sarcocephalus latifolius (yumbuyambay, 50%). The other herbs used included Senna siamea (shekutoure, 18%), Cassia sieberiana (gbangba, 18%), Uvaria afzelii (gone-botai, 14%), Morinda chrysorhiza (njasui, 14%), and Craterispermum laurinum (nyelleh, 7%). Combination herbal therapy was common, with 37% of herb users taking two or more herbs together when ill with suspected malaria. CONCLUSIONS: Indigenous medical knowledge about herbal remedies and combinations of local herbs remains an integral part of malaria case management in Sierra Leone.

Klippel-Trénaunay syndrome: spectrum and management.

OBJECTIVE: To describe a series of 252 patients with Klippel-Trénaunay syndrome (KTS), a rare congenital malformation characterized by the triad of capillary malformations, atypical varicosities or venous malformations, and bony or soft tissue hypertrophy usually affecting one extremity. MATERIAL AND METHODS: We reviewed the clinical characteristics and findings in 136 female and 116 male patients with KTS who underwent assessment at Mayo Clinic Rochester between January 1956 and January 1995. In addition, management options are discussed. RESULTS: Capillary malformations (port-wine stains) were found in 246 patients (98%), varicosities or venous malformations in 182 (72%), and limb hypertrophy in 170 (67%). All three features of KTS were present in 159 patients (63%), and 93 (37%) had two of the three features. Atypical veins, including lateral veins and persistent sciatic vein, occurred in 182 patients (72%). Operations performed in 145 patients with KTS included epiphysiodesis, stripping of varicose veins or venous malformations, excision of vascular malformations, amputations, and debulking procedures. CONCLUSION: Most patients with KTS should be managed conservatively. The clearest indication for operation is a leg length discrepancy projected to exceed 2.0 cm at skeletal maturity, which can be treated with epiphysiodesis in the growing child. If a functioning deep vein system is present, removal of symptomatic varicosities or localized superficial venous malformations in selected patients can yield good results.

Advances in pediatric rhabdomyosarcoma characterization and disease model development.

Rhabdomyosarcoma (RMS), a form of soft tissue sarcoma, is one of the most common pediatric malignancies. A complex disease with at least three different subtypes, it is characterized by perturbations in a number of signaling pathways and genetic abnormalities. Extensive clinical studies have helped classify these tumors into high and low risk groups to facilitate different treatment regimens. Research into the etiology of the disease has helped uncover numerous potential therapeutic intervention points which can be tested on various animal models of RMS; both genetically modified models and tumor xenograft models. Taken together, there has been a marked increase in the survival rate of RMS patients but the highly invasive, metastatic forms of the disease continue to baffle researchers. This review aims to highlight and summarize some of the most important developments in characterization and in vivo model generation for RMS research, in the last few decades.