Field evaluation of the CATT/Trypanosoma brucei gambiense on blood-impregnated filter papers for diagnosis of human African trypanosomiasis in southern Sudan.

Most Human African Trypanosomiasis (HAT) control programmes in areas endemic for Trypanosoma brucei gambiense rely on a strategy of active mass screening with the Card Agglutination Test for Trypanosomiasis (CATT)/T. b. gambiense. We evaluated the performance, stability and reproducibility of the CATT/T. b. gambiense on blood-impregnated filter papers (CATT-FP) in Kajo-Keji County, South-Sudan, where some areas are inaccessible to mobile teams. The CATT-FP was performed with a group of 100 people with a positive CATT on whole blood including 17 confirmed HAT patients and the results were compared with the CATT on plasma (CATT-P). The CATT-FP was repeated on impregnated filter papers stored at ambient and refrigerated temperature for 1, 3, 7 and 14 days. Another 82 patients with HAT, including 78 with a positive parasitology, were tested with the CATT-FP and duplicate filter paper samples were sent to a reference laboratory to assess reproducibility. The CATT-FP was positive in 90 of 99 patients with HAT (sensitivity: 91%). It was less sensitive than the CATT-P (mean dilution difference: -2.5). There was no significant loss of sensitivity after storage for up to 14 days both at ambient and cool temperature. Reproducibility of the CATT-FP was found to be excellent (kappa: 0.84). The CATT-FP can therefore be recommended as a screening test for HAT in areas where the use of CATT-P is not possible. Further studies on larger population samples in different endemic foci are still needed before the CATT-FP can be recommended for universal use

Rapid Diagnostic Tests for Non-Malarial Febrile Illness in the Tropics

The recent roll-out of rapid diagnostic tests (RDTs) for malaria has highlighted the decreasing proportion of malaria-attributable illness in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low resource settings. This review summarizes the current state of RDT development for several key infections, including dengue fever, enteric fever, leptospirosis, brucellosis, visceral leishmaniasis and human African trypanosomiasis, and highlights many remaining gaps. Most RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent. The sensitivity and specificity of host-antibody detection tests are both inherently limited. Moreover, prolonged antibody responses to many infections preclude the use of most serological RDTs for monitoring response to treatment and/or for diagnosing relapse. Considering these limitations, there is a pressing need for sensitive pathogen-detection-based RDTs, as have been successfully developed for malaria and dengue. Ultimately, integration of RDTs into a validated syndromic approach to tropical fevers is urgently needed. Related research priorities are to define the evolving epidemiology of fever in the tropics, and to determine how combinations of RDTs could be best used to improve the management of severe and treatable infections requiring specific therapy

Thermic effect of glucose in obese subjects studied by direct and indirect calorimetry

1. The thermic effect of a glucose load (50 g) was studied in ten control and eleven obese female subjects, using both direct and indirect calorimetry simultaneously. Experiments were done under conditions of thermal equilibrium (28° and 30% relative humidity).. 2. Thermal balance (heat production measured by indirect calorimetry minus heat losses measured directly) was negative in the control group during the fasting period (heat deficit - 14.2 ± 5.0 kJ/m2 per h), whereas that of the obese group was in equilibrium (+ 1.4 ± 4.8 kJ/m2 per h).. 3. After the glucose load, metabolic rate increased 13.0 ± 1.5 and 5.2 ± 1.3% in the control and obese groups respectively.. 4. In contrast to the metabolic rate, total heat losses were not significantly altered in either group after the glucose load. Total heat losses of the obese group were significantly lower than those of the control group throughout the experimental period.. 5. During the experiments the amount of heat stored was increased in both groups. Thermal balance in the control group became positive while that of the obese group remained positive.. 6. During the fasting period, the control subjects oxidized more carbohydrates (90.4 mg/min) than lipids (68.8 mg/min), whereas obese subjects oxidized more lipids (103.7 mg/min) than carbohydrates (50.2 mg/min). After the glucose load, the oxidation rate of carbohydrates was increased in both groups to 158.1 mg/min in control subjects and 95.6 mg/min in obese subjects.. 7. The mean skin temperature of the control subjects was significantly higher than that of the obese subjects and remained higher throughout the postprandial period.. 8. These results indicate that: (a) during the fasting period, the energy sources utilized and the thermal balance of the two groups were different; (b) the thermic effect of glucose was less in the obese subjects and, therefore, might be a factor contributing to their low energy expenditur

Effectiveness of melarsoprol and eflornithine as first-line regimens for gambiense sleeping sickness in nine Médecins Sans Frontières programmes.

This paper describes the effectiveness of first-line regimens for stage 2 human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense infection in nine Médecins Sans Frontières HAT treatment programmes in Angola, Republic of Congo, Sudan and Uganda. Regimens included eflornithine and standard- and short-course melarsoprol. Outcomes for 10461 naïve stage 2 patients fitting a standardised case definition and allocated to one of the above regimens were analysed by intention-to-treat analysis. Effectiveness was quantified by the case fatality rate (CFR) during treatment, the proportion probably and definitely cured and the Kaplan-Meier probability of relapse-free survival at 12 months and 24 months post admission. The CFR was similar for the standard- and short-course melarsoprol regimens (4.9% and 4.2%, respectively). The CFR for eflornithine was 1.2%. Kaplan-Meier survival probabilities varied from 71.4-91.8% at 1 year and 56.5-87.9% at 2 years for standard-course melarsoprol, to 73.0-91.1% at 1 year for short-course melarsoprol, and 79.9-97.4% at 1 year and 68.6-93.7% at 2 years for eflornithine. With the exception of one programme, survival at 12 months was >90% for eflornithine, whilst for melarsoprol it was <90% except in two sites. Eflornithine is recommended where feasible, especially in areas with low melarsoprol effectiveness

Arsenic exposure and outcomes of antimonial treatment in visceral leishmaniasis patients in bihar, India:a retrospective cohort study

Funding: This work was supported by a Clinical PhD Fellowship to MRP (090665) and a Principal Research Fellowship to AHF (079838) from the Wellcome Trust (http://www.wellcome.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Identification of sVSG117 as an immunodiagnostic antigen and evaluation of a dual-antigen lateral flow test for the diagnosis of human african trypanosomiasis

The diagnosis of human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense relies mainly on the Card Agglutination Test for Trypanosomiasis (CATT). There is no immunodiagnostic for HAT caused by T. b. rhodesiense. Our principle aim was to develop a prototype lateral flow test that might be an improvement on CATT.Pools of infection and control sera were screened against four different soluble form variant surface glycoproteins (sVSGs) by ELISA and one, sVSG117, showed particularly strong immunoreactivity to pooled infection sera. Using individual sera, sVSG117 was shown to be able to discriminate between T. b. gambiense infection and control sera by both ELISA and lateral flow test. The sVSG117 antigen was subsequently used with a previously described recombinant diagnostic antigen, rISG65, to create a dual-antigen lateral flow test prototype. The latter was used blind in a virtual field trial of 431 randomized infection and control sera from the WHO HAT Specimen Biobank.In the virtual field trial, using two positive antigen bands as the criterion for infection, the sVSG117 and rISG65 dual-antigen lateral flow test prototype showed a sensitivity of 97.3% (95% CI: 93.3 to 99.2) and a specificity of 83.3% (95% CI: 76.4 to 88.9) for the detection of T. b. gambiense infections. The device was not as good for detecting T. b. rhodesiense infections using two positive antigen bands as the criterion for infection, with a sensitivity of 58.9% (95% CI: 44.9 to 71.9) and specificity of 97.3% (95% CI: 90.7 to 99.7). However, using one or both positive antigen band(s) as the criterion for T. b. rhodesiense infection improved the sensitivity to 83.9% (95% CI: 71.7 to 92.4) with a specificity of 85.3% (95% CI: 75.3 to 92.4). These results encourage further development of the dual-antigen device for clinical use

Growth in densely populated Asia: implications for primary product exporters

Economic growth and integration in Asia is rapidly increasing the global economic importance of the region. To the extent that this growth continues and is strongest in natural resource-poor Asian economies, it will add to global demand for imports of primary products, to the benefit of (especially nearby) resource-abundant countries. How will global production, consumption and trade patterns change by 2030 in the course of such economic developments and structural changes? We address this question using the GTAP model and Version 8.1 of the 2007 GTAP database, together with supplementary data from a range of sources, to support projections of the global economy from 2007 to 2030 under various scenarios. Factor endowments and real gross domestic product are assumed to grow at exogenous rates, and trade-related policies are kept unchanged to generate a core baseline, which is compared with an alternative slower growth scenario. We also consider the impact of several policy changes aimed at increasing China's agricultural self-sufficiency relative to the 2030 baseline. Policy implications for countries of the Asia-Pacific region are drawn out in the final section

Impact of a positive family history on diagnosis, management, and survival of breast cancer: different effects across socio-economic groups

Background: This study aims to investigate whether increased awareness of breast cancer, due to a positive family history (FH), reduces diagnostic, therapeutic, and survival differences between women of low versus high socio-economic status (SES). Methods: All breast cancer patients registered between 1990 and 2005 at the population-based Geneva Cancer Registry were included. With multivariate logistic and Cox regression analysis, we estimated the impact of SES and FH on method of detection, treatment, and mortality from breast cancer. Results: SES discrepancies in method of detection and suboptimal treatment, as seen among women without a FH, disappeared in the presence of a positive FH. SES differences in stage and survival remained regardless of the presence of a positive FH. Overall, positive FH was associated with better survival. This effect was the strongest in women of high SES (age-adjusted Hazard Ratio [HRageadj] 0.54 [0.3-1.0]) but less pronounced in women of middle (0.77 [0.6-1.0]), and absent in women of low SES (0.80 [0.5-1.2]). Conclusion: A positive FH of breast cancer may reduce SES differences in access to screening and optimal treatment. However, even with better access to early detection and optimal treatment, women of low SES have higher risks of death from their disease than those of high SE

Accuracy of five algorithms to diagnose gambiense human African trypanosomiasis.

Algorithms to diagnose gambiense human African trypanosomiasis (HAT, sleeping sickness) are often complex due to the unsatisfactory sensitivity and/or specificity of available tests, and typically include a screening (serological), confirmation (parasitological) and staging component. There is insufficient evidence on the relative accuracy of these algorithms. This paper presents estimates of the accuracy of five algorithms used by past Médecins Sans Frontières programmes in the Republic of Congo, Southern Sudan and Uganda

Hormonal therapy for oestrogen receptor-negative breast cancer is associated with higher disease-specific mortality

Background: Tamoxifen has a remarkable impact on the outcome of oestrogen receptor (ER)-positive breast cancer. Without proven benefits, tamoxifen is occasionally prescribed for women with ER-negative disease. This population-based study aims to estimate the impact of tamoxifen on the outcome of ER-negative disease. Methods: We identified all women (n = 528) diagnosed with ER-negative invasive breast cancer between 1995 and 2005. With Cox regression analysis, we calculated breast cancer mortality risks of patients treated with tamoxifen compared with those treated without tamoxifen. We adjusted these risks for the individual probabilities (propensity scores) of having received tamoxifen. Results: Sixty-nine patients (13%) with ER-negative disease were treated with tamoxifen. Five-year disease-specific survival for women treated with versus without tamoxifen were 62% [95% confidence interval (CI) 48% to 76%] and 79% (95% CI 75% to 83%), respectively (PLog-rank < 0.001). For ER-negative patients, risk of death from breast cancer was significantly increased in those treated with tamoxifen compared with patients treated without tamoxifen (adjusted hazard ratio = 1.7, 95% CI 1.1-2.9, P = 0.031). Conclusion: Our results show that patients with ER-negative breast cancer treated with tamoxifen have an increased risk of death from their disease. Tamoxifen use should be avoided for these patient