Pathogenesis of lymphatic disease in bancroftian filariasis: a clinical perspective

The pathogenesis of lymphatic filariasis has been a matter of debate for many decades. Here, Gerusa Dreyer and colleagues propose a dynamic model of bancroftian filariasis, integrating clinical, parasitological, surgical, therapeutic, ultrasonographic and histopathological data. This model has profound implications for filariasis control programs and the management of the individual patient.     

Screening the elderly in the community: controlled trial of dependency surveillance using a questionnaire administered by volunteers.

OBJECTIVE--To test the benefits of regular surveillance of the elderly at home using an activities of daily living questionnaire administered by volunteers. DESIGN--Randomised controlled study. PATIENTS--539 Subjects aged 75 and over from two general practices. INTERVENTION--All subjects were visited at the beginning and end of the study by volunteers, who completed a scored activity of daily living questionnaire. The study group were revisited at regular intervals. Individuals with an increase in score greater than 5 were referred to their general practitioners. All interactions with social services and health authorities were recorded for both groups. MAIN OUTCOME MEASURES--Mortality, activity of daily living score, total number of days in institutions, geriatric and psychogeriatric service contacts, primary health care team contacts, use of community support services. RESULTS--The study group were admitted to hospital more often than the controls (335 occasions v 252), but the control group spent 33% more days in institutions, mainly in long term admissions to residential accommodation. The number of falls reported in the control group doubled (from 17 before the first interview to 36 before the last) and in the study group remained unchanged (12 before both interviews). The study group received community support services sooner than the control group. There was no difference between the groups in mortality or activity of daily living score. CONCLUSION--Regular visiting of old people at home by non-professional volunteers using a simple activity of daily living questionnaire is a practical way of identifying problems and initiating action for this group.     

Recombinant antigen-based antibody assays for the diagnosis and surveillance of lymphatic filariasis - a multicenter trial

The development of antifilarial antibody responses is a characteristic feature of infection with filarial parasites. It should be possible to exploit this fact to develop tools to monitor the progress of the global program to eliminate lymphatic filariasis (LF); however, assays based on parasite extracts suffer from a number of limitations, including the paucity of parasite material, the difficulty of assay standardization and problems with assay specificity. In principle, assays based on recombinant filarial antigens should address these limitations and provide useful tools for diagnosis and surveillance of LF. The present multicenter study was designed to compare the performance of antibody assays for filariasis based on recombinant antigens Bm14, WbSXP, and BmR1. Coded serum specimens were distributed to five participating laboratories where assays for each antigen were conducted in parallel. Assays based on Bm14, WbSXP, or BmR1 demonstrated good sensitivity (>90%) for field use and none of the assays demonstrated reactivity with specimens from persons with non-filarial helminth infections. Limitations of the assays are discussed. Well-designed field studies are now needed to assess sampling methodology and the application of antibody testing to the monitoring and surveillance of LF elimination programs.     

Albendazole sulphoxide concentrations in plasma of endemic normals from a lymphatic filariasis endemic region using liquid chromatography

A simple and sensitive reversed-phase isocratic HPLC method for the determination of albendazole and its metabolites has been developed. The mobile phase consisting of acetonitrile-water-perchloric acid (70%) (30:110:0.06 (v/v/v)) was pumped at a flow rate of 0.80 ml/min on a 5 microm, reverse phase, Discovery RPamide C16 column with UV detection at 290 nm. The calibration graphs were linear in the range of 0.05- 1 microg/ml for albendazole, albendazole sulphoxide and albendazole sulphone. The limit of quantification was 50 ng/ml for albendazole, 25 ng/ml for albendazole sulphoxide and 30 ng/ml for albendazole sulphone. The within-day and day-to-day coefficient of variation averaged 4.98 and 6.95% for albendazole, 3.83 and 6.83% for albendazole sulphoxide and 3.44 and 5.51% for albendazole sulphone, respectively. The mean extraction recoveries of albendazole, albendazole sulphoxide and albendazole sulphone were 79.25, 93.03 and 88.78%, respectively. The method was applied to determine the plasma levels of albendazole sulphoxide in endemic normals administered with albendazole during pharmacokinetic studies.     

Advances and challenges in predicting the impact of lymphatic filariasis elimination programmes by mathematical modelling

Background

Infection with the filarial nematode Onchocerca volvulus can lead to severe dermatitis, visual impairment, and ultimately blindness. Since the currently used drug, ivermectin does not have macrofilaricidal or strong permanent sterilising effects on the adult worm, more effective drugs are needed to complement the use of ivermectin alone. Wolbachia endosymbiotic bacteria in filariae have emerged as a new target for treatment with antibiotics which can lead to long -term sterilization of the adult female filariae.

Methods

In the Central Region of Ghana, 60 patients were recruited, allocated into four groups and treated with 200 mg doxycycline per day for 2 weeks, 4 weeks, 6 weeks respectively. Untreated patients served as controls. Some of the treated patients and the untreated controls were given 150 μg/kg ivermectin 8 months after the start of doxycycline treatment.

Results

A follow up study 18 months post treatment showed that when using doxycycline alone there was a significant reduction of microfilarial (mf) loads in patients treated for either 4 or 6 weeks. However, there was no significant difference between the untreated controls and those given the 2 weeks regimen. Although no significant difference was demonstrated between the 4 and 6 weeks regimens, there was a trend observed, in that, microfilarial reduction appeared to have been greater following the 6 weeks regimen. Twelve months after ivermectin (i.e. 20 months after doxycycline) treatment, 8 out of 11 ivermectin-alone treated patients were mf-positive. In contrast, 1 out of the 7 patients treated for 4 weeks with doxycycline and none of the 4 patients treated for 6 weeks doxycycline (who were available for re-examination) were mf-positive after the combined treatment of doxycycline plus ivermectin treatment.

Conclusion

Treatment of onchocerciasis with doxycycline for 4 weeks is effective. Nonetheless, mf reduction appeared to be greater in the 6 weeks regimen. It is recommended that until further studies are carried out i.e. 4 weeks treatment with doxycycline is proven equivalent to the 6 weeks, selected groups of onchocerciasis patients should be treated for 6 weeks with doxycycline. As discussed earlier, this treatment should be accompanied by two doses of ivermectin.     

Predicting the current and future potential distributions of lymphatic filariasis in Africa using maximum entropy ecological niche modelling

Modelling the spatial distributions of human parasite species is crucial to understanding the environmental determinants of infection as well as for guiding the planning of control programmes. Here, we use ecological niche modelling to map the current potential distribution of the macroparasitic disease, lymphatic filariasis (LF), in Africa, and to estimate how future changes in climate and population could affect its spread and burden across the continent. We used 508 community-specific infection presence data collated from the published literature in conjunction with five predictive environmental/climatic and demographic variables, and a maximum entropy niche modelling method to construct the first ecological niche maps describing potential distribution and burden of LF in Africa. We also ran the best-fit model against climate projections made by the HADCM3 and CCCMA models for 2050 under A2a and B2a scenarios to simulate the likely distribution of LF under future climate and population changes. We predict a broad geographic distribution of LF in Africa extending from the west to the east across the middle region of the continent, with high probabilities of occurrence in the Western Africa compared to large areas of medium probability interspersed with smaller areas of high probability in Central and Eastern Africa and in Madagascar. We uncovered complex relationships between predictor ecological niche variables and the probability of LF occurrence. We show for the first time that predicted climate change and population growth will expand both the range and risk of LF infection (and ultimately disease) in an endemic region. We estimate that populations at risk to LF may range from 543 and 804 million currently, and that this could rise to between 1.65 to 1.86 billion in the future depending on the climate scenario used and thresholds applied to signify infection presence.     

Diminished expression and function of TLR in lymphatic filariasis: a novel mechanism of immune dysregulation

Lymphatic filariasis is a disease characterized by immune dysregulation involving APC and T cell populations. To assess the contribution of TLR in mediating this dysregulation, we examined the expression of TLR1, TLR2, TLR4, and TLR9 on B cells and monocytes of filaria-infected and uninfected individuals. Baseline expression of TLR was significantly lower in B cells but not in monocytes of the filaria-infected group compared with the uninfected group. Upon stimulation with filarial Ag, a diminished up-regulation of TLR was observed in both B cells and monocytes of infected individuals. Finally, stimulation of B cells and monocytes with TLR ligands resulted in decreased B cell and monocyte activation/cytokine production, indicating a state of immune tolerance. This dysregulation is associated with diminished CD4(+) T cell production of IFN-gamma and IL-5. The diminished expression and function of TLR is thus a likely consequence of chronic Ag stimulation and could serve as a novel mechanism underlying the dysfunctional immune response in filariasis.     

The use of a mobile laboratory unit in support of patient management and epidemiological surveillance during the 2005 Marburg Outbreak in Angola

Background

Marburg virus (MARV), a zoonotic pathogen causing severe hemorrhagic fever in man, has emerged in Angola resulting in the largest outbreak of Marburg hemorrhagic fever (MHF) with the highest case fatality rate to date.

Methodology/Principal Findings

A mobile laboratory unit (MLU) was deployed as part of the World Health Organization outbreak response. Utilizing quantitative real-time PCR assays, this laboratory provided specific MARV diagnostics in Uige, the epicentre of the outbreak. The MLU operated over a period of 88 days and tested 620 specimens from 388 individuals. Specimens included mainly oral swabs and EDTA blood. Following establishing on site, the MLU operation allowed a diagnostic response in <4 hours from sample receiving. Most cases were found among females in the child-bearing age and in children less than five years of age. The outbreak had a high number of paediatric cases and breastfeeding may have been a factor in MARV transmission as indicated by the epidemiology and MARV positive breast milk specimens. Oral swabs were a useful alternative specimen source to whole blood/serum allowing testing of patients in circumstances of resistance to invasive procedures but limited diagnostic testing to molecular approaches. There was a high concordance in test results between the MLU and the reference laboratory in Luanda operated by the US Centers for Disease Control and Prevention.

Conclusions/Significance

The MLU was an important outbreak response asset providing support in patient management and epidemiological surveillance. Field laboratory capacity should be expanded and made an essential part of any future outbreak investigation.     

Impact on the quality of life of lymphoedema patients following introduction of a hygiene and skin care regimen in a Guyanese community endemic for lymphatic filariasis: A preliminary clinical intervention study

BACKGROUND: Hygiene and skin care are effective and important interventions in the management of lymphoedema secondary to lymphatic filariasis. We analyzed the impact on the quality of life that education and introduction of a designated nurse had on lymphoedema patients in a community that was endemic for lymphatic filariasis. METHODS: Patients' life quality was assessed using a Dermatology Life Quality Index (DLQI) questionnaire. At the same time they received education on appropriate hygiene, skin care techniques and simple exercises that encourage lymph drainage. A designated nurse was provided with educational materials and treatments. The DLQI life quality measure was repeated one year later. RESULTS: The DLQI improved for all patients and reported acute attacks were reduced. A paired t-test showed the improvement in DLQI to be highly significant (P = < 0.0001). CONCLUSIONS: A nurse-led service combined with patient education in communities endemic for lymphatic filariasis is an effective intervention in improving the quality of life of patients with lymphoedema.     

Improved malaria case management through the implementation of a health facility-based sentinel site surveillance system in Uganda

Background

Heath facility-based sentinel site surveillance has been proposed as a means of monitoring trends in malaria morbidity but may also provide an opportunity to improve malaria case management. Here we described the impact of a sentinel site malaria surveillance system on promoting laboratory testing and rational antimalarial drug use.

Methodology/Principal Findings

Sentinel site malaria surveillance was established at six health facilities in Uganda between September 2006 and January 2007. Data were collected from all patients presenting to the outpatient departments including demographics, laboratory results, diagnoses, and treatments prescribed. Between the start of surveillance and March 2010, a total 424,701 patients were seen of which 229,375 (54%) were suspected of having malaria. Comparing the first three months with the last three months of surveillance, the proportion of patients with suspected malaria who underwent diagnostic testing increased from 39% to 97% (p<0.001). The proportion of patients with an appropriate decision to prescribe antimalarial therapy (positive test result prescribed, negative test result not prescribed) increased from 64% to 95% (p<0.001). The proportion of patients appropriately prescribed antimalarial therapy who were prescribed the recommended first-line regimen artemether-lumefantrine increased from 48% to 69% (p<0.001).

Conclusions/Significance

The establishment of a sentinel site malaria surveillance system in Uganda achieved almost universal utilization of diagnostic testing in patients with suspected malaria and appropriate decisions to prescribed antimalarial based on test results. Less success was achieved in promoting prescribing practice for the recommended first-line therapy. This system could provide a model for improving malaria case management in other health facilities in Africa.     

Proteomic surveillance of autoantigens in patients with Behcet's disease by a proteomic approach

To promote an understanding of autoimmunity in BD, we surveyed autoAgs in patients with BD and investigated the prevalence and clinical significance of the identified autoAbs. Specifically, proteins, extracted from peripheral blood mononuclear cells and separated by 2DE, were subjected to WB, using five serum samples from patients with BD. The detected candidate autoAgs were identified by mass spectrometry. As a result, 17 autoantigenic spots were detected by the 2DE‐WB, out of which eight spots were identified. They are enolase‐1, cofilin‐1, vimentin, Rho‐GDI β protein, tubulin‐like protein, and actin‐like proteins. The autoAbs to one of the identified proteins, cofilin‐1, were investigated by WB using a recombinant protein in 30 patients with BD, 35 patients with RA, 32 patients with SLE, and 16 patients with PM/DM. The autoAbs to cofilin‐1 were detected by WB in four (13.3%) of the 30 patients with BD, five (14.3%) of the 35 patients with RA, two (6.3%) of the 32 patients with SLE, and eight (24.2%) of the 33 patients with PM/DM. Our data indicate that the generation of autoAbs to cofilin‐1 may reflect common immunological disorders in BD, RA, and PM/DM. Our data would help understanding of the immunopathology of BD. In addition, the proteomic approach would be a useful way to investigate autoAgs.     

The amount and value of work time of community medicine distributors in community case management of malaria among children under five years in the Ejisu-Juaben District of Ghana

ABSTRACT: BACKGROUND: The contribution of community medicine distributors (CMD) to prompt health service delivery in areas described as "hard-to-reach" is important but the value of their work time remains unknown and thus makes it difficult to design appropriate regular financial incentives to motivate them. This makes CMDs feel their efforts are not recognized. An attempt to estimate the value of 54 CMDs work time involved in community case management of malaria (CCMm) in a rural district in Ghana is presented. METHODS: Time spent by CMDs on CCMm activities were recorded for a period of 12 months to determine the work-time value. Cost analysis was performed in Microsoft Excel with data from CMD records and at 2007 market price in Ghana. RESULTS: A CMD spent 4.8 hours, [95% CI: 3.9; 5.3] on all CCMm-related activities per day. The time value of CMD work ranged from GHc 2.04 (US$ 2.24) to GHc 4.1 [US$ 4.6] per week and GHc 19.2 - 86.4 (US$ 21.10-94.95) per month. The gross wage outside CCMm as reported by CMD was GHc 58.4 [US$ 64.69] and value of foregone income of GHc 86.40 (US$94.95) per month, about 14-times higher than the monthly incentives of GHc 6.0 given by the CCMm programme. CONCLUSION: The value of work time and the foregone income of CMDs in CCMm are high and yet there are no regular and sustainable incentives provided for them. The results are significant to policy in designing incentives to motivate CMDs in large-scale implementation of CCMm.     

Simultaneous measurements of auto-immune and infectious disease specific antibodies using a high throughput multiplexing tool

Considering importance of ganglioside antibodies as biomarkers in various immune-mediated neuropathies and neurological disorders, we developed a high throughput multiplexing tool for the assessment of gangliosides-specific antibodies based on Biolpex/Luminex platform. In this report, we demonstrate that the ganglioside high throughput multiplexing tool is robust, highly specific and demonstrating ～100-fold higher concentration sensitivity for IgG detection than ELISA. In addition to the ganglioside-coated array, the high throughput multiplexing tool contains beads coated with influenza hemagglutinins derived from H1N1 A/Brisbane/59/07 and H1N1 A/California/07/09 strains. Influenza beads provided an added advantage of simultaneous detection of ganglioside- and influenza-specific antibodies, a capacity important for the assay of both infectious antigen-specific and autoimmune antibodies following vaccination or disease. Taken together, these results support the potential adoption of the ganglioside high throughput multiplexing tool for measuring ganglioside antibodies in various neuropathic and neurological disorders.     

Prospective validation of American Diabetes Association risk tool for predicting pre-diabetes and diabetes in Taiwan-Taichung community health study

Background

A simple diabetes risk tool that does not require laboratory tests would be beneficial in screening individuals at higher risk. Few studies have evaluated the ability of these tools to identify new cases of pre-diabetes. This study aimed to assess the ability of the American Diabetes Association Risk Tool (ADART) to predict the 3-year incidence of pre-diabetes and diabetes in Taiwanese.

Methods

This was a 3-year prospective study of 1021 residents with normoglycemia at baseline, gathered from a random sample of residents aged 40–88 years in a metropolitan city in Taiwan. The areas under the curve (AUCs) of three models were compared: ADART only, ADART plus lifestyle behaviors at baseline, and ADART plus lifestyle behaviors and biomarkers at baseline. The performance of ADART was compared with that of 16 tools that had been reported in the literature.

Results

The AUCs and their 95% confidence intervals (CIs) were 0.60 (0.54–0.66) for men and 0.72 (0.66–0.77) for women in model 1; 0.62 (0.56–0.68) for men and 0.74 (0.68–0.80) for women in model 2; and 0.64 (0.58–0.71) for men and 0.75 (0.69–0.80) for women in model 3. The AUCs of these three models were all above 0.7 in women, but not in men. No significant difference in either women or men (p = 0.268 and 0.156, respectively) was observed in the AUC of these three models. Compared to 16 tools published in the literature, ADART had the second largest AUC in both men and women.

Conclusions

ADART is a good screening tool for predicting the three-year incidence of pre-diabetes and diabetes in females of a Taiwanese population. The performance of ADART in men was similar to the results with other tools published in the literature. Its performance was one of the best among the tools reported in the literature.     

A multifaceted strategy using mobile technology to assist rural primary healthcare doctors and frontline health workers in cardiovascular disease risk management: protocol for the SMARTHealth India cluster randomised controlled trial

Background

Blood Pressure related disease affected 118 million people in India in the year 2000; this figure will double by 2025. Around one in four adults in rural India have hypertension, and of those, only a minority are accessing appropriate care. Health systems in India face substantial challenges to meet these gaps in care, and innovative solutions are needed.

Methods

We hypothesise that a multifaceted intervention involving capacity strengthening of primary healthcare doctors and non-physician healthcare workers through use of a mobile device-based clinical decision support system will result in improved blood pressure control for individuals at high risk of a cardiovascular disease event when compared with usual healthcare. This intervention will be implemented as a stepped wedge, cluster randomised controlled trial in 18 primary health centres and 54 villages in rural Andhra Pradesh involving adults aged ≥40 years at high cardiovascular disease event risk (approximately 15,000 people). Cardiovascular disease event risk will be calculated based on World Health Organisation/International Society of Hypertension’s region-specific risk charts. Cluster randomisation will occur at the level of the primary health centres. Outcome analyses will be conducted blinded to intervention allocation.

Expected outcomes

The primary study outcome is the difference in the proportion of people meeting guideline-recommended blood pressure targets in the intervention period vs. the control period. Secondary outcomes include mean reduction in blood pressure levels; change in other cardiovascular disease risk factors, including body mass index, current smoking, reported healthy eating habits, and reported physical activity levels; self-reported use of blood pressure and other cardiovascular medicines; quality of life (using the EQ-5D); and cardiovascular disease events (using hospitalisation data). Trial outcomes will be accompanied by detailed process and economic evaluations.

Significance

The findings are likely to inform policy on a scalable strategy to overcome entrenched inequities in access to effective healthcare for under-served populations in low and middle income country settings.

Trial registration

Clinical Trial Registry India CTRI/2013/06/003753.

     

Changes in liana community structure and functional traits along a chronosequence of selective logging in a moist semi-deciduous forest in Ghana

ABSTRACT

Background: Lianas are an important component of tropical forests that respond to logging disturbance. Determining liana response to selective logging chronosequence is important for understanding long-term logging effects on lianas and tropical forests.

Aims: Our objective was to quantify the response of liana communities to selective logging chronosequence in a moist semi-deciduous forest in Ghana.

Methods: Liana community characteristics were determined in ten 40 m × 40 m plots randomly and homogenously distributed in each of four selectively logged forest stands that had been logged 2, 14, 40 and 68 years before the surveys and in an old-growth forest stand (ca. >200 years).

Results: Liana species composition differed significantly among the forest stands, as a function of logging time span, while species richness fluctuated along the chronosequence. The abundance of liana communities and of reproductive and climbing guilds was lower in the logged forests than in the old-growth forest. The ratio of liana abundance and basal area to those of trees was similar in the logged forests, but significantly lower than those in the old-growth forest.

Conclusions: Logging impacts on liana community structure and functional traits were largely evident, though no clear chronosequence trends were recorded, except for species composition.