Programmatic use of molecular xenomonitoring at the level of evaluation units to assess persistence of lymphatic filariasis in Sri Lanka

BACKGROUND:Sri Lanka's Anti Filariasis Campaign distributed 5 rounds of mass drug administration (MDA with DEC plus albendazole) to all endemic regions in the country from 2002-2006. Post-MDA surveillance results have generally been encouraging. However, recent studies have documented low level persistence of Wuchereria bancrofti in Galle district based on comprehensive surveys that include molecular xenomonitoring (MX, detection of filarial DNA in mosquitoes) results. The purposes of this study were to demonstrate the use of MX in large evaluation units (EUs) and to field test different mosquito sampling schemes. METHODOLOGY/PRINCIPAL FINDINGS:Galle district (population 1.1 million) was divided into two EUs. These included a coastal EU with known persistent LF and an inland EU with little persistent LF. Mosquitoes were systematically sampled from ~300 trap locations in 30 randomly selected clusters (health administrative units) per EU. Approximately 28,000 Culex quinquefasciatus were collected with gravid traps and tested for filarial DNA by qPCR. 92/625 pools (14.7%) from the coastal EU and 8/583 pools (1.4%) from the inland EU were positive for filarial DNA. Maximum likelihood estimates (MLE) for filarial DNA rates were essentially the same when the same number of mosquito pools were collected and tested from 75, 150, or 300 trap sites (range 0.61-0.78% for the coastal EU and 0.04-0.07% for the inland EU). The ability to use a smaller number of trap sites reduces the cost and time required for mosquito sampling. CONCLUSIONS/SIGNIFICANCE:These results suggest there is widespread persistence of W. bancrofti infection in the coastal Galle EU 8 years after the last round of MDA in 2006, and this is consistent with other data from the district. This study has shown that MX can be used by national programs to assess and map the persistence of W. bancrofti at the level of large EUs in areas with Culex transmission

Molecular heterogeneity and CXorf67 alterations in posterior fossa group A (PFA) ependymomas

Of nine ependymoma molecular groups detected by DNA methylation profiling, the posterior fossa type A (PFA) is most prevalent. We used DNA methylation profiling to look for further molecular heterogeneity among 675 PFA ependymomas. Two major subgroups, PFA-1 and PFA-2, and nine minor subtypes were discovered. Transcriptome profiling suggested a distinct histogenesis for PFA-1 and PFA-2, but their clinical parameters were similar. In contrast, PFA subtypes differed with respect to age at diagnosis, gender ratio, outcome, and frequencies of genetic alterations. One subtype, PFA-1c, was enriched for 1q gain and had a relatively poor outcome, while patients with PFA-2c ependymomas showed an overall survival at 5 years of > 90%. Unlike other ependymomas, PFA-2c tumors express high levels of OTX2, a potential biomarker for this ependymoma subtype with a good prognosis. We also discovered recurrent mutations among PFA ependymomas. H3 K27M mutations were present in 4.2%, occurring only in PFA-1 tumors, and missense mutations in an uncharacterized gene, CXorf67, were found in 9.4% of PFA ependymomas, but not in other groups. We detected high levels of wildtype or mutant CXorf67 expression in all PFA subtypes except PFA-1f, which is enriched for H3 K27M mutations. PFA ependymomas are characterized by lack of H3 K27 trimethylation (H3 K27-me3), and we tested the hypothesis that CXorf67 binds to PRC2 and can modulate levels of H3 K27-me3. Immunoprecipitation/mass spectrometry detected EZH2, SUZ12, and EED, core components of the PRC2 complex, bound to CXorf67 in the Daoy cell line, which shows high levels of CXorf67 and no expression of H3 K27-me3. Enforced reduction of CXorf67 in Daoy cells restored H3 K27-me3 levels, while enforced expression of CXorf67 in HEK293T and neural stem cells reduced H3 K27-me3 levels. Our data suggest that heterogeneity among PFA ependymomas could have clinicopathologic utility and that CXorf67 may have a functional role in these tumors

Beyond the walls: Outreach initiatives in Library, University of Moratuwa

Outreach librarianship – a concept which had a history of more than 40 years - has been diversely used in libraries all over the world as well as in Sri Lanka. Outreach Librarianship is aimed to reach out to traditional and non-traditional library users, extending beyond the walls of a physical library to serve underprivileged communities. Establishment of Outreach Services Division in Library, University of Moratuwa has fulfilled a long felt need to serve the community living in the vicinity of University of Moratuwa. “Child Development Programme” at Sumudu Preschool located in the University premises and “Reading Camp” at BodhirajaVidyalaya, Katubedda, Moratuwa are two outreach initiatives that the staff of Library, University of Moratuwa are currently engaged in. This paper describes the accomplishment of these two outreach initiatives through management of physical and human resources without an outreach budget

Picture Story A case of type I Waardenburg syndrome

A six year old boy presented with delay in acquiring language skills. Examination revealed heterochromia of both irides (Figure 1). Mother’s eyes were similar in appearance. An audiological evaluation revealed moderate to severe sensory neural hearing loss. Similar ocular changes with hearing loss had been noted in a maternal uncle. All other family members appeared normal. Figure 1 Discussion Waardenburg syndrome (WS) is named after a Dutch ophthalmologist, who first described a patient with hearing loss, dystopia canthorum (i.e. lateral displacement of inner canthi of eyes) and retinal pigmentary changes in 1947. Since then 4 types have been described. The prevalence of WS is estimated at 1 per 42,000 individuals 1. Types 1 and 2 are believed to be equally common. This syndrome is considered to be responsible for 2-3 % of cases of congenital deafness 2. Both types 1 and 2 are autosomal dominantly inherited conditions with marked interfamilial and intrafamilial variability 3. Both the auditory an

Case Reports A case of syringomyelia in a 12 year old child

Syringomyelia is defined as a chronic, progressive degenerative disorder of the spinal cord characterised by dissociated sensory loss and brachial amyotrophy with pathological evidence of central cor

Picture Story A case of cutis laxa

This one year and six months old girl was referred to our clinic for her abnormal appearance since birth. She was born at term to non-consanguineous parents by normal vaginal delivery. The birth weight was 2.8 kg. She was the only child in the family and there was no family history of a similar disorder. On examination, the most obvious findings were a prematurely aged appearance of the face and widespread lax skin with numerous skin folds resembling an ill-fitting suit. In addition she had other dysmorphic features such as large ears, hooked nose with everted nostrils, shaggy jaws, long upper lip and everted lower eyelids (Figures 1 & 2). Figure 1 and 2. Patient with Cutis laxa Her mental and physical development were normal. The joints were not hypermobile. There was no clinical evidence of cardiovascular complications such as peripheral pulmonary artery stenosis or aortic dilatation. So far she had not had any complications of the disease, such as pulmonary emphysema, bronchiectasis, pneumothorax, hernia or rectal prolapse. However, diverticula of the gastrointestinal and genitourinary tracts have not yet been excluded