Targeting the gut microbiota by Asian and Western dietary constituents: a new avenue for diabetes.

Increasing numerous diabetes annually is a great concern in public health globally. Gut microbiota recently has been suggested to be an emerging organ acting as a critical regulator in diabetes. Notably, gut microbiota is closely affected through an individual's nutrient intake and dietary pattern. Moreover, the metabolites of diets through gut microbiota are closely associated with the development of diabetes. Increasing evidence has established the association of different dietary pattern with alterations of the gut microbiota profile, in particular, the Asian diet and Western diet are typically as essential components linked to the interactions between gut microbiota and induction of obesity which is a significant risk factor for diabetes. In addition, some bacteria-related therapeutic methods including probiotics, dietary short-chain fatty acids immunotherapy, and gut microbiome transfer would be applied in the clinical prevention and control diabetes. Taken together, based on current published observations, the gut microbiota may serve as regulator or targets by the Asian diet and Western diet, contributing to the prevention or induction of diabetes eventually. In general, in the upcoming future, one of the emerging strategies for the prevention and control of diabetes may modulate gut microbiota through precise dietary strategies.

Progress on elimination of lymphatic filariasis in Sierra Leone.

BACKGROUND: A baseline survey in 2007-2008 found lymphatic filariasis (LF) to be endemic in Sierra Leone in all 14 districts and co-endemic with onchocerciasis in 12 districts. Mass drug administration (MDA) with ivermectin started in 2006 for onchocerciasis and was modified to add albendazole in 2008 to include LF treatment. In 2011, after three effective MDAs, a significant reduction in microfilaraemia (mf) prevalence and density was reported at the midterm assessment. After five MDAs, in 2013, mf prevalence and density were again measured as part of a pre-transmission assessment survey (pre-TAS) conducted per WHO guidelines. METHODS: For the pre-TAS survey, districts were paired to represent populations of one million for impact assessment. One sentinel site selected from baseline and one spot check site purposefully selected based upon local knowledge of patients with LF were surveyed per pair (two districts). At each site, 300 people over five years of age provided mid-night blood samples and mf prevalence and density were determined using thick blood film microscopy. Results are compared with baseline and midterm data. RESULTS: At pre-TAS the overall mf prevalence was 0.54% (95% CI: 0.36-0.81%), compared to 0.30% (95% CI: 0.19-0.47) at midterm and 2.6% (95% CI: 2.3-3.0%) at baseline. There was a higher, but non-significant, mf prevalence among males vs females. Eight districts (four pairs) had a prevalence of mf < 1% at all sites. Two pairs (four districts) had a prevalence of mf > 1% at one of the two sites: Koinadugu 0.98% (95% CI: 0.34-2.85%) and Bombali 2.67% (95% CI: 1.41-5.00%), and Kailahun 1.56% (95% CI: 0.72-3.36%) and Kenema 0% (95% CI: 0.00-1.21%). CONCLUSIONS: Compared to baseline, there was a significant reduction of LF mf prevalence and density in the 12 districts co-endemic for LF and onchocerciasis after five annual LF MDAs. No statistically significant difference was seen in either measure compared to midterm. Eight of the 12 districts qualified for TAS. The other four districts that failed to qualify for TAS had historically high LF baseline prevalence and density and had regular cross-border movement of populations. These four districts needed to conduct two additional rounds of LF MDA before repeating the pre-TAS. The results showed that Sierra Leone continued to make progress towards the elimination of LF as a public health problem.

Impact of five annual rounds of mass drug administration with ivermectin on onchocerciasis in Sierra Leone.

BACKGROUND: Onchocerciasis is endemic in 12 of the 14 health districts of Sierra Leone. Good treatment coverage of community-directed treatment with ivermectin was achieved between 2005 and 2009 after the 11-year civil conflict. Sentinel site surveys were conducted in 2010 to evaluate the impact of five annual rounds of ivermectin distribution. METHODS: In total, 39 sentinel villages from hyper- and meso-endemic areas across the 12 endemic districts were surveyed using skin snips in 2010. Results were analyzed and compared with the baseline data from the same 39 villages. RESULTS: The average microfilaridermia (MF) prevalence across 39 sentinel villages was 53.10% at baseline. The MF prevalence was higher in older age groups, with the lowest in the age group of 1-9 years (11.00%) and the highest in the age group of 40-49 years (82.31%). Overall mean MF density among the positives was 28.87 microfilariae (mf)/snip, increasing with age with the lowest in the age group of 1-9 years and the highest in the age group of 40-49 years. Males had higher MF prevalence and density than females. In 2010 after five rounds of mass drug administration, the overall MF prevalence decreased by 60.26% from 53.10% to 21.10%; the overall mean MF density among the positives decreased by 71.29% from 28.87 mf/snip to 8.29 mf/snip; and the overall mean MF density among all persons examined decreased by 88.58% from 15.33 mf/snip to 1.75 mf/snip. Ten of 12 endemic districts had > 50% reduction in MF prevalence. Eleven of 12 districts had ≥50% reduction in mean MF density among the positives. CONCLUSIONS: A significant reduction of onchocerciasis MF prevalence and mean density was recorded in all 12 districts of Sierra Leone after five annual MDAs with effective treatment coverage. The results suggested that the onchocerciasis elimination programme in Sierra Leone was on course to reach the objective of eliminating onchocerciasis in the country by the year 2025. Annual MDA with ivermectin should continue in all 12 districts and further evaluations are needed across the country to assist the NTDP with programme decision making.

The Sierra Leone Ultrasound Rainbow4Africa Project (SLURP): an observational study of ultrasound effectiveness in developing countries.

BACKGROUND: Diagnostic tools available in low-income countries are often really basic even if patients can be as sick as those of the richer countries. Point-of-care ultrasound could be a solution for this problem. We studied the impact of ultrasound at the Holy Spirit Hospital, Makeni, Sierra Leone. METHODS: This is a prospective, observational study on outpatients presenting at the HSH. We enrolled continually for 1 month 105 patients asked for ultrasound examination by the caring physician that had to indicate the differential diagnosis hypothesized, the confidence degree about these on a 5-point Likert scale, and the therapy before and after the US. The primary outcome was to measure the difference in the number of differential diagnoses. Secondary outcomes were the rate of new diagnoses, the confidence changes of the visiting physician, and the changes in prescribed therapy or management. Categorical variables were compared using the Chi-square test, and continuous ones using two-tailed Student's test and Likert with the Wilcoxon rank-sum test. RESULTS: 194 differential diagnoses were formulated, with a mean of 1.85 (DS 0.87) diagnoses per patient. 89 (46%) were excluded on the basis of US, reducing the mean of differential diagnosis per patient to 1, 0 (p < 0.001). US also introduced 53 new diagnoses in 42 patients (mean 1.26; SD 0.54), raising the final differential diagnosis from 105 to 158 (+50.5%) that is 1.51 (DS 0.79) per patient. There is a statistically significant reduction (18.6%) in diagnoses per patient after having performed the ultrasound (p < 0.001). The certainty level increased (Wilcoxon rank-sum test: p < 0.001). We did not reach the statistical significance studying the changes in therapy and management because the subgroups for analysis were too small. Nonetheless, we saw interesting changes in drug prescription and referral rate before and after the US. CONCLUSION: Ultrasound is feasible in low-income countries; with it diagnostic hypotheses were reduced and new unexpected diagnoses were introduced. Further studies are needed to explore other strong outcomes like mortality, length of stay in hospital, and money saved with the use of ultrasound in developing countries.

High coverage of mass drug administration for lymphatic filariasis in rural and non-rural settings in the Western Area, Sierra Leone.

BACKGROUND: Lymphatic filariasis elimination programs are based upon preventative chemotherapy annually in populations with prevalence more than or equal to 1%. The goal is to treat 80% of the eligible, at risk population yearly, for at least 5 years, in order to interrupt transmission and prevent children from becoming infected. This level of coverage has been a challenge in urban settings. Assessing the coverage in a rapidly growing urban/non-rural setting with inadequate population data is also problematic. In Sierra Leone, a 5-day preventative chemotherapy campaign was carried out in the Western Area including the capital: Freetown. An intensive, social mobilization strategy combined traditional and modern communication channels. To aid dissemination of appropriate information Frequently Asked Questions were developed and widely circulated. The population of the Western Area has grown faster than projected by the 2004 National Census due to the post-war settlement of internally displaced persons. As a reliable denominator was not available, independent monitoring was adapted and performed "in process" to aid program performance and "end process" to assess final coverage. RESULTS: In 5 days 1,104,407 eligible persons were treated. Using the projected population from the 2004 census this figure represented coverage of 116% in the Urban Western Area and 129% in the Rural Western Area. Independent monitors interviewed a total of 9,253 persons during the 2 End Process days representing 1% of the projected population. Of these, 85.8% recalled taking both ivermectin and albendazole (Urban: 85.2%, Rural: 87.1%). No serious adverse drug reactions were reported. CONCLUSION: The paper presents the key elements of success of the social mobilization and implementation strategy and describes the independent monitoring used to estimate final coverage in this urban/non-rural setting where the current population size is uncertain. This implementation strategy and Independent Monitoring tool could be useful in similar, rapidly growing cities implementing lymphatic filariasis elimination programs.

Cyanide trapping of iminium ion reactive intermediates followed by detection and structure identification using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Secondary and tertiary alicyclic amines are widely found in pharmaceuticals and environmental compounds. The formation of iminium ions as reactive intermediates in the metabolic activation of alicyclic amines has previously been investigated in radiometric assays where radiolabeled cyanide is typically employed. In this paper, we report a relatively high throughput LC-MS/MS method for the detection of the nonradiolabeled cyanide adduct formed in rat or human liver microsomal incubations via constant neutral loss scan followed by structural characterization using product ion scan on a triple quadrupole mass spectrometer. A total of 14 alicyclic amine compounds were investigated with the cyanide trapping LC-MS/MS screen and also with the glutathione (GSH) trapping screen, a well-established and commonly employed technique for reactive metabolite screening. Our results are found to be in general agreement with the previous metabolism reports for these compounds, demonstrating the effectiveness, speed, and simplicity of the cyanide trapping LC-MS/MS method to study the iminium ion intermediates from alicyclic amines and its complementarities to GSH trapping method for reactive metabolite screenings.