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1.
Sakib Burza Prabhat Kumar Sinha Raman Mahajan Marta González Sanz María Angeles Lima Gaurab Mitra Neena Verma Pradeep Das 《PLoS neglected tropical diseases》2014,8(1)
Background
The skin disorder Post Kala-Azar Dermal Leishmaniasis (PKDL) occurs in up to 10% of patients treated for visceral leishmaniasis (VL) in India. The pathogenesis of PKDL is not yet fully understood. Cases have been reported in India following therapy with most available treatments, but rarely in those treated with liposomal amphotericin B (Ambisome). Between July 2007 and August 2012 with the support of the Rajendra Memorial Research Institute (RMRI), Médecins Sans Frontières (MSF) supported a VL treatment programme in Bihar, India—an area highly endemic for Leishmania donovani—in which 8749 patients received 20 mg/kg intravenous Ambisome as first-line treatment. This study describes the characteristics of patients who returned to the MSF supported treatment programme with PKDL.Methods and Principal Findings
Over a 5-year period, Ambisome was administered to 8749 patients with laboratory-confirmed VL (clinical signs, rK39 positive, with/without parasite confirmation) in four intravenous doses of 5 mg/kg to a total of 20 mg/kg, with a high initial-cure rate (99.3%) and low default rate (0.3%). All patients received health education highlighting the possibility and symptoms of developing PKDL, and advice to return to the MSF programme if these symptoms developed. This is an observational retrospective cohort study of the programme outcomes. Of the 8311 patients completing treatment for their first episode of VL, 24 (0.3%) returned passively to the programme complaining of symptoms subsequently confirmed as PKDL, diagnosed from clinical history, appearance consistent with PKDL, and slit-skin smear examination. Of the 24 patients, 89% had macular lesions, with a median time (interquartile range) to development of 1.2 (0.8–2.2) years following treatment. Comparison of the demographic and clinical characteristics of the VL patients treated with Ambisome who later developed PKDL, with those of the remaining cohort did not identify any significant risk factors for PKDL. However, the time to developing PKDL was significantly shorter with Ambisome than in a subset of patients presenting to the programme with PKDL following previous sodium stibogluconate treatment for VL.Conclusions
In this large cohort of patients with VL in Bihar who were treated with 20 mg/kg Ambisome, PKDL following treatment appears to be infrequent with no predictive risk factors. The shorter median time to developing symptoms of PKDL compared with that after conventional VL treatments should be taken into account when counseling patients treated with regimens including Ambisome. 相似文献2.
Sakib Burza Prabhat K. Sinha Raman Mahajan María Angeles Lima Gaurab Mitra Neena Verma Manica Balsegaram Pradeep Das 《PLoS neglected tropical diseases》2014,8(1)
Background
A proportion of all immunocompetent patients treated for visceral leishmaniasis (VL) are known to relapse; however, the risk factors for relapse are not well understood. With the support of the Rajendra Memorial Research Institute (RMRI), Médecins Sans Frontières (MSF) implemented a program in Bihar, India, using intravenous liposomal amphotericin B (Ambisome) as a first-line treatment for VL. The aim of this study was to identify risk factors for VL relapse by examining the characteristics of immunocompetent patients who relapsed following this regimen.Methods and Principal Findings
This is an observational retrospective cohort study of all VL patients treated by the MSF program from July 2007 to August 2012. Intravenous Ambisome was administered to 8749 patients with VL in four doses of 5 mg/kg (for a total dose of 20 mg/kg) over 4–10 days, depending on the severity of disease. Out of 8588 patients not known to be HIV-positive, 8537 (99.4%) were discharged as initial cures, 24 (0.3%) defaulted, and 27 (0.3%) died during or immediately after treatment. In total, 1.4% (n = 119) of the initial cured patients re-attended the programme with parasitologically confirmed VL relapse, with a median time to relapse of 10.1 months. Male sex, age <5 years and ≥45 years, a decrease in spleen size at time of discharge of ≤0.5 cm/day, and a shorter duration of symptoms prior to seeking treatment were significantly associated with relapse. Spleen size at admission, hemoglobin level, nutritional status, and previous history of relapse were not associated with relapse.Conclusions
This is the largest cohort of VL patients treated with Ambisome worldwide. The risk factors for relapse included male sex, age <5 and ≥45 years, a smaller decrease in splenomegaly at discharge, and a shorter duration of symptoms prior to seeking treatment. The majority of relapses in this cohort occurred 6–12 months following treatment, suggesting that a 1-year follow-up is appropriate in future studies. 相似文献3.
Sakib Burza Raman Mahajan Prabhat K. Sinha Johan van Griensven Krishna Pandey María Angeles Lima Marta Gonzalez Sanz Temmy Sunyoto Sunil Kumar Gaurab Mitra Ranjeet Kumar Neena Verma Pradeep Das 《PLoS neglected tropical diseases》2014,8(8)
Background
Visceral Leishmaniasis (VL; also known as kala-azar) is an ultimately fatal disease endemic in the Indian state of Bihar, while HIV/AIDS is an emerging disease in this region. A 2011 observational cohort study conducted in Bihar involving 55 VL/HIV co-infected patients treated with 20–25 mg/kg intravenous liposomal amphotericin B (AmBisome) estimated an 85.5% probability of survival and a 26.5% probability of VL relapse within 2 years. Here we report the long-term field outcomes of a larger cohort of co-infected patients treated with this regimen between 2007 and 2012.Methods and Principal Findings
Intravenous AmBisome (20–25 mg/kg) was administered to 159 VL/HIV co-infected patients (both primary infections and relapses) in four or five doses of 5 mg/kg over 4–10 days. Initial cure of VL at discharge was defined as improved symptoms, cessation of fever, improvement of appetite and recession of spleen enlargement. Test of cure was not routinely performed. Antiretroviral treatment (ART) was initiated in 23 (14.5%), 39 (24.5%) and 61 (38.4%) before, during and after admission respectively. Initial cure was achieved in all discharged patients. A total of 36 patients died during follow-up, including six who died shortly after admission. Death occurred at a median of 11 weeks (IQR 4–51) after starting VL treatment. Estimated mortality risk was 14.3% at six months, 22.4% at two years and 29.7% at four years after treatment. Among the 153 patients discharged from the hospital, 26 cases of VL relapse were diagnosed during follow-up, occurring at a median of 10 months (IQR 7–14) after discharge. After accounting for competing risks, the estimated risk of relapse was 16.1% at one year, 20.4% at two years and 25.9% at four years. Low hemoglobin level and concurrent infection with tuberculosis were independent risk factors for mortality, while ART initiated shortly after admission for VL treatment was associated with a 64–66% reduced risk of mortality and 75% reduced risk of relapse.Significance
This is the largest cohort of HIV-VL co-infected patients reported from the Indian subcontinent. Even after initial cure following treatment with AmBisome, these patients appear to have much higher rates of VL relapse and mortality than patients not known to be HIV-positive, although relapse rates appear to stabilize after 2 years. These results extend the earlier findings that co-infected patients are at increased risk of death and require a multidisciplinary approach for long-term management. 相似文献4.
Eltahir A. G. Khalil Teklu Weldegebreal Brima M. Younis Raymond Omollo Ahmed M. Musa Workagegnehu Hailu Abuzaid A. Abuzaid Thomas P. C. Dorlo Zewdu Hurissa Sisay Yifru William Haleke Peter G. Smith Sally Ellis Manica Balasegaram Ahmed M. EL-Hassan Gerard J. Schoone Monique Wasunna Robert Kimutai Tansy Edwards Asrat Hailu 《PLoS neglected tropical diseases》2014,8(1)
5.
Emiliano Lucero Simon M. Collin Sujit Gomes Fatima Akter Asaduzzam Asad Asish Kumar Das Koert Ritmeijer 《PLoS neglected tropical diseases》2015,9(4)
Background
Bangladesh is one of the endemic countries for Visceral Leishmaniasis (VL). Médecins Sans Frontières (MSF) ran a VL treatment clinic in the most endemic district (Fulbaria) between 2010 and 2013 using a semi-ambulatory regimen for primary VL of 15mg/kg Liposomal Amphotericin-B (AmBisome) in three equal doses of 5mg/kg. The main objective of this study was to analyze the effectiveness and safety of this regimen after a 12 month follow-up period by retrospective analysis of routinely collected program data. A secondary objective was to explore risk factors for relapse.Methods and Principal Findings
Our analysis included 1521 patients who were initially cured, of whom 1278 (84%) and 1179 (77.5%) were followed-up at 6 and 12 months, respectively. Cure rates at 6 and 12 months were 98.7% (1262/1278) and 96.4% (1137/1179), respectively. Most relapses (26/39) occurred between 6 and 12 months after treatment. Serious adverse events (SAE) were recorded for 7 patients (0.5%). Odds of relapse at 12 months were highest in the youngest and oldest age groups. There was some evidence that spleen size measured on discharge (one month after initiation of treatment) was associated with risk of relapse: OR=1.25 (95% CI 1.01 to 1.55) per cm below lower costal margin (P=0.04).Conclusions
Our study demonstrates that 15mg/kg AmBisome in three doses of 5mg/kg is an effective (>95% cure rate) and safe (<1% SAE) treatment for primary VL in Bangladesh. The majority of relapses occurred between 6 and 12 months, justifying the use of a longer follow-up period when feasible. Assessment of risk of relapse based on easily measured clinical parameters such as spleen size could be incorporated in VL treatment protocols in resource-poor settings where test-of-cure is not always feasible. 相似文献6.
Shyam Sundar Krishna Pandey Chandreshwar Prasad Thakur Tara Kant Jha Vidya Nand Ravi Das Neena Verma Chandra Shekhar Lal Deepak Verma Shahnawaz Alam Pradeep Das 《PLoS neglected tropical diseases》2014,8(9)
Background
India is home to 60% of the total global visceral leishmaniasis (VL) population. Use of long-term oral (e.g. miltefosine) and parenteral drugs, considered the mainstay for treatment of VL, is now faced with increased resistance, decreased efficacy, low compliance and safety issues. The authors evaluated the efficacy and safety of an alternate treatment option, i.e. single infusion of preformed amphotericin B (AmB) lipid emulsion (ABLE) in comparison with that of liposomal formulation (LAmB).Methods
In this multicentric, open-label study, 500 patients with VL were randomly assigned in a 3∶1 ratio to receive 15 mg/kg single infusion of either ABLE (N = 376) or LAmB (N = 124). Initial cure (Day 30/45), clinical improvement (Day 30) and long term definitive cure (Day 180) were assessed.Findings
A total of 326 (86.7%) patients in the ABLE group and 122 (98.4%) patients in the LAmB group completed the study. Initial cure was achieved by 95.9% of patients in the ABLE group compared to 100% in the LAmB group (p = 0.028; 95% CI: −0.0663, −0.0150). Clinical improvement was comparable between treatments (ABLE: 98.9% vs. LAmB: 98.4%). Definitive cure was achieved in 85.9% with ABLE compared to 98.4% with LAmB. Infusion-related pyrexia (37.2% vs. 32.3%) and chills (18.4% vs. 18.5%) were comparable between ABLE and LAmB, respectively. Treatment-related serious adverse events were fewer in ABLE (0.3%) compared to LAmB (1.6%). Two deaths occurred in the ABLE group, of which one was probably related to the study drug. Nephrotoxicity and hepatotoxicity was not observed in either group.Conclusions
ABLE 15 mg/kg single infusion had favorable efficacy and was well tolerated. Considering the demographic profile of the population in this region, a single dose treatment offers advantages in terms of compliance, cost and applicability.Trial Registration
www.clinicaltrials.gov NCT00876824相似文献7.
Stanislaw Gorski Simon M. Collin Koert Ritmeijer Kees Keus Francis Gatluak Marius Mueller Robert N. Davidson 《PLoS neglected tropical diseases》2010,4(6)
Background
Risk factors associated with L. donovani visceral leishmaniasis (VL; kala azar) relapse are poorly characterized.Methods
We investigated patient characteristics and drug regimens associated with VL relapse using data from Médecins Sans Frontières - Holland (MSF) treatment centres in Southern Sudan. We used MSF operational data to investigate trends in VL relapse and associated risk factors.Results
We obtained data for 8,800 primary VL and 621 relapse VL patients treated between 1999 and 2007. Records of previous treatment for 166 VL relapse patients (26.7%) were compared with 7,924 primary VL patients who had no record of subsequent relapse. Primary VL patients who relapsed had larger spleens on admission (Hackett grade ≥3 vs0, odds ratio (OR) for relapse = 3.62 (95% CI 1.08, 12.12)) and on discharge (Hackett grade ≥3 vs 0, OR = 5.50 (1.84, 16.49)). Age, sex, malnutrition, mobility, and complications of treatment were not associated with risk of relapse, nor was there any trend over time. Treatment with 17-day sodium stibogluconate/paromomycin (SSG/PM) combination therapy vs 30-day SSG monotherapy was associated with increased risk of relapse (OR = 2.08 (1.21, 3.58)) but reduced risk of death (OR = 0.27 (0.20, 0.37)), although these estimates are likely to be residually confounded. MSF operational data showed a crude upward trend in the proportion of VL relapse patients (annual percentage change (APC) = 11.4% (−3.4%, 28.5%)) and a downward trend in deaths (APC = −18.1% (−22.5%, −13.4%)).Conclusions
Splenomegaly and 17-day SSG/PM vs 30-day SSG were associated with increased risk of VL relapse. The crude upward trend in VL relapses in Southern Sudan may be attributable to improved access to treatment and reduced mortality due to SSG/PM combination therapy. 相似文献8.
Ermias Diro Lutgarde Lynen Rezika Mohammed Marleen Boelaert Asrat Hailu Johan van Griensven 《PLoS neglected tropical diseases》2014,8(5)
Background
Antimonials are still being used for visceral leishmaniasis (VL) treatment among HIV co-infected patients in East-Africa due to the shortage of alternative safer drugs like liposomal amphotericin B. Besides tolerability, emergence of resistance to antimonials is a major concern.Objectives
This study was aimed at assessing the clinical outcome of VL-HIV co-infected patients when treated with sodium stibogluconate (SSG).Methods
Retrospective patient record analysis of VL-HIV co-infected patients treated at a clinical trial site in north-west Ethiopia was done. Patients with parasitologically confirmed VL and HIV co-infection treated with SSG were included. The dose of SSG used was 20 mg Sb5 (pentavalent antimony)/kg and maximum of 850 mg Sb5 for 30 days. The clinical outcomes were defined based on the tissue aspiration results as cure or failure, and additionally the safety and mortality rates were computed.Results
The study included 57 patients treated with SSG and by the end of treatment only 43.9% of patients were cured. The parasitological treatment failure and the case fatality rate were 31.6% and 14.0% respectively. SSG was discontinued temporarily or permanently for 12 (21.1%) cases due to safety issues. High baseline parasite load (graded more than 4+) was significantly associated with treatment failure (odds ratio = 8.9, 95% confidence interval = .5-51.7).Conclusion
SSG is not only unsafe, but also has low effectiveness for VL-HIV patients. Safe and effective alternative medications are very urgently needed. Drug sensitivity surveillance should be introduced in the region. 相似文献9.
Zehava Grossman Jonathan M. Schapiro Itzchak Levy Daniel Elbirt Michal Chowers Klaris Riesenberg Karen Olstein-Pops Eduardo Shahar Valery Istomin Ilan Asher Bat-Sheva Gottessman Yonat Shemer Hila Elinav Gamal Hassoun Shira Rosenberg Diana Averbuch Keren Machleb-Guri Zipi Kra-Oz Sara Radian-Sade Hagit Rudich Daniela Ram Shlomo Maayan Nancy Agmon-Levin Zev Sthoeger 《PloS one》2014,9(1)
Background
Analysis of potentially different impact of Lopinavir/Ritonavir (LPV/r) on non-B subtypes is confounded by dissimilarities in the conditions existing in different countries. We retrospectively compared its impact on populations infected with subtypes B and C in Israel, where patients infected with different subtypes receive the same treatment.Methods
Clinical and demographic data were reported by physicians. Resistance was tested after treatment failure. Statistical analyses were conducted using SPSS.Results
607 LPV/r treated patients (365 male) were included. 139 had HIV subtype B, 391 C, and 77 other subtypes. At study end 429 (71%) were receiving LPV/r. No significant differences in PI treatment history and in median viral-load (VL) at treatment initiation and termination existed between subtypes. MSM discontinued LPV/r more often than others even when the virologic outcome was good (p = 0.001). VL was below detection level in 81% of patients for whom LPV/r was first PI and in 67% when it was second (P = 0.001). Median VL decrease from baseline was 1.9±0.1 logs and was not significantly associated with subtype. Median CD4 increase was: 162 and 92cells/µl, respectively, for patients receiving LPV/r as first and second PI (P = 0.001), and 175 and 98, respectively, for subtypes B and C (P<0.001). Only 52 (22%) of 237 patients genotyped while under LPV/r were fully resistant to the drug; 12(5%) were partially resistant. In48%, population sequencing did not reveal resistance to any drug notwithstanding the virologic failure. No difference was found in the rates of resistance development between B and C (p = 0.16).Conclusions
Treatment with LPV/r appeared efficient and tolerable in both subtypes, B and C, but CD4 recovery was significantly better in virologically suppressed subtype-B patients. In both subtypes, LPV/r was more beneficial when given as first PI. Mostly, reasons other than resistance development caused discontinuation of treatment. 相似文献10.
11.
Raida Petrela Loreta Kuneshka Eli Foto Ferit Zavalani Luigi Gradoni 《PLoS neglected tropical diseases》2010,4(9)
Background
Little information is available about infantile visceral leishmaniasis (VL) in Albania as regards incidence, diagnosis and management of the disease.Methodology/Principal Findings
Demographic data, clinical and laboratory features and therapeutic findings were considered in children admitted to University Hospital of Tirana from 1995 to 2009, and diagnosed as having VL. The diagnosis was based on bone-marrow microscopy/culture in 77.5% of patients, serology in 16.1%, and ex juvantibus in 6.4%. A total of 1,210 children were considered, of whom 74% came from urbanized areas. All patients were in the age range 0–14 years, with a median of 4 years. Hepatosplenomegaly was recorded in 100%, fever in 95.4% and moderate to severe anemia in 88% of cases. Concomitant conditions were frequent: 84% had bronchopneumonia; diarrhea was present in 27%, with acute manifestations in 5%; 3% had salmonellosis. First-line therapy was meglumine antimoniate for all patients, given at the standard Sbv dosage of 20 mg/kg/day for 21 to 28 days. Two children died under treatment, one of sepsis, the other of acute renal impairment. There were no cases of primary unresponsiveness to treatment, and only 8 (0.67%) relapsed within 6–12 months after therapy. These patients have been re-treated with liposomal amphotericin B, with successful cure.Conclusions
Visceral leishmaniasis in pediatric age is relatively frequent in Albania; therefore an improvement is warranted of a disease-specific surveillance system in this country, especially as regards diagnosis. Despite recent reports on decreased responses to antimonial drugs of patients with Mediterranean VL, meglumine antimoniate treatment appears to be still highly effective in Albania. 相似文献12.
Tapan Bhattacharyya Armon Ayandeh Andrew K. Falconar Shyam Sundar Sayda El-Safi Marissa A. Gripenberg Duncan E. Bowes Caroline Thunissen Om Prakash Singh Rajiv Kumar Osman Ahmed Osama Eisa Alfarazdeg Saad Sara Silva Pereira Marleen Boelaert Pascal Mertens Michael A. Miles 《PLoS neglected tropical diseases》2014,8(10)
Background
Visceral leishmaniasis (VL), caused by protozoa of the Leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic VL is usually fatal. Distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hampered by the lack of prognostic biomarkers for use at point of care.Methodology/Principal Findings
All IgG subclass and IgG isotype antibody levels were determined using unpaired serum samples from Indian and Sudanese patients with differing clinical status of VL, which included pre-treatment active VL, post-treatment cured, post-treatment relapsed, and post kala-azar dermal leishmaniasis (PKDL), as well as seropositive (DAT and/or rK39) endemic healthy controls (EHCs) and seronegative EHCs. L. donovani antigen-specific IgG1 levels were significantly elevated in relapsed versus cured VL patients (p<0.0001). Using paired Indian VL sera, consistent with the known IgG1 half-life, IgG1 levels had not decreased significantly at day 30 after the start of treatment (p = 0.8304), but were dramatically decreased by 6 months compared to day 0 (p = 0.0032) or day 15 (p<0.0001) after start of treatment. Similarly, Sudanese sera taken soon after treatment did not show a significant change in the IgG1 levels (p = 0.3939). Two prototype lateral flow immunochromatographic rapid diagnostic tests (RDTs) were developed to detect IgG1 levels following VL treatment: more than 80% of the relapsed VL patients were IgG1 positive; at least 80% of the cured VL patients were IgG1 negative (p<0.0001).Conclusions/Significance
Six months after treatment of active VL, elevated levels of specific IgG1 were associated with treatment failure and relapse, whereas no IgG1 or low levels were detected in cured VL patients. A lateral flow RDT was successfully developed to detect anti-Leishmania IgG1 as a potential biomarker of post-chemotherapeutic relapse. 相似文献13.
Jennifer Keiser Kigbafori D. Silué Lukas K. Adiossan Nicaise A. N'Guessan N'Chou Monsan Jürg Utzinger Eliézer K. N'Goran 《PLoS neglected tropical diseases》2014,8(7)
Background
Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against schistosomiasis. The antimalarial drug mefloquine shows antischistosomal activity in animal models and clinical trials, which calls for further investigations.Methodology
We comparatively assessed the efficacy and tolerability of the following treatments against Schistosoma haematobium in school-aged children in Côte d''Ivoire: (i) praziquantel (40 mg/kg; standard treatment); (ii) mefloquine (25 mg/kg) combined with praziquantel (40 mg/kg); and (iii) mefloquine-artesunate (3× (100 mg artesunate +250 mg mefloquine)) combined with praziquantel (40 mg/kg) (treatments administered on subsequent days). Two urine samples were collected before, and on days 21–22 and 78–79 after the first dosing.Principal Findings
Sixty-one children were present on all examination time points and had complete datasets. No difference in efficacy was observed between the three treatment groups on either follow-up. On the 21–22 day posttreatment follow-up, based on available case analysis, cure rates of 33% (95% confidence interval (CI) 11–55%), 29% (95% CI 8–50%), and 26% (95% CI 5–48%) were observed for praziquantel, mefloquine-artesunate-praziquantel, and mefloquine-praziquantel, respectively. The corresponding egg reduction rates were 94% and above. On the second follow-up, observed cure rates ranged from 19% (praziquantel) to 33% (mefloquine-artesunate-praziquantel), and egg reduction rates were above 90%. Praziquantel monotherapy was the best tolerated treatment. In the mefloquine-artesunate-praziquantel group, adverse events were reported by 91% of the participants, and in the mefloquine-praziquantel group, 95% experienced adverse events. With the exception of abdominal pain at moderate severity, adverse events were mild.Conclusions/Significance
The addition of mefloquine or mefloquine-artesunate does not increase the efficacy of praziquantel against chronic S. haematobium infection. Additional studies are necessary to elucidate the effect of the combinations against acute schistosomiasis. 相似文献14.
Keiser J Sayed H el-Ghanam M Sabry H Anani S el-Wakeel A Hatz C Utzinger J el-Din SS el-Maadawy W Botros S 《PLoS neglected tropical diseases》2011,5(9):e1285
Background
Fascioliasis is an emerging zoonotic disease of considerable veterinary and public health importance. Triclabendazole is the only available drug for treatment. Laboratory studies have documented promising fasciocidal properties of the artemisinins (e.g., artemether).Methodology
We carried out two exploratory phase-2 trials to assess the efficacy and safety of oral artemether administered at (i) 6×80 mg over 3 consecutive days, and (ii) 3×200 mg within 24 h in 36 Fasciola-infected individuals in Egypt. Efficacy was determined by cure rate (CR) and egg reduction rate (ERR) based on multiple Kato-Katz thick smears before and after drug administration. Patients who remained Fasciola-positive following artemether dosing were treated with single 10 mg/kg oral triclabendazole. In case of treatment failure, triclabendazole was re-administered at 20 mg/kg in two divided doses.Principal Findings
CRs achieved with 6×80 mg and 3×200 mg artemether were 35% and 6%, respectively. The corresponding ERRs were 63% and nil, respectively. Artemether was well tolerated. A high efficacy was observed with triclabendazole administered at 10 mg/kg (16 patients; CR: 67%, ERR: 94%) and 20 mg/kg (4 patients; CR: 75%, ERR: 96%).Conclusions/Significance
Artemether, administered at malaria treatment regimens, shows no or only little effect against fascioliasis, and hence does not represent an alternative to triclabendazole. The role of artemether and other artemisinin derivatives as partner drug in combination chemotherapy remains to be elucidated. 相似文献15.
Jane Mbui Monique Wasunna Manica Balasegaram Adrian Laussermayer Rashid Juma Simon Njoroge Njenga George Kirigi Mark Riongoita Roberto de la Tour Joke van Peteghem Raymond Omollo Fran?ois Chappuis 《PLoS neglected tropical diseases》2013,7(9)
Background
Visceral leishmaniasis (VL) is a systemic parasitic disease that is fatal unless treated. In Kenya, national VL guidelines rely on microscopic examination of spleen aspirate to confirm diagnosis. As this procedure is invasive, it cannot be safely implemented in peripheral health structures, where non-invasive, accurate, easy to use diagnostic tests are needed.Methodology
We evaluated the sensitivity, specificity and predictive values of two rapid diagnostic tests (RDT), DiaMed IT LEISH and Signal-KA, among consecutive patients with clinical suspicion of VL in two treatment centres located in Baringo and North Pokot District, Rift Valley province, Kenya. Microscopic examination of spleen aspirate was the reference diagnostic standard. Patients were prospectively recruited between May 2010 and July 2011.Principal Findings
Of 251 eligible patients, 219 patients were analyzed, including 131 VL and 88 non-VL patients. The median age of VL patients was 16 years with predominance of males (66%). None of the tested VL patients were co-infected with HIV. Sensitivity and specificity of the DiaMed IT LEISH were 89.3% (95%CI: 82.7–94%) and 89.8% (95%CI: 81.5–95.2%), respectively. The Signal KA showed trends towards lower sensitivity (77.1%; 95%CI: 68.9–84%) and higher specificity (95.5%; 95%CI: 88.7–98.7%). Combining the tests did not improve the overall diagnostic performance, as all patients with a positive Signal KA were also positive with the DiaMed IT LEISH.Conclusion/Significance
The DiaMed IT LEISH can be used to diagnose VL in Kenyan peripheral health facilities where microscopic examination of spleen aspirate or sophisticated serological techniques are not feasible. There is a crucial need for an improved RDT for VL diagnosis in East Africa. 相似文献16.
Vincenzo Ravo Immacolata Marrone Anna Morra Roberto Manzo Paola Murino Fabrizio Cammarota Paolo Muto 《Reports of Practical Oncology and Radiotherapy》2010,15(5):119-124
Background
Adjuvant radiotherapy (RTE) still has a fundamental role as a post-operative treatment of locally advanced soft tissues sarcomas of the extremities. Moreover the employment of combined modalities in locally advanced soft tissues sarcomas of the extremities allow to maximize the chance of local cure even in difficult presentation cases, and possibly improve survival, especially in high-risk disease patients. In patients with sarcomas of the extremities in which definitive surgery has not been radical (with positive or “close” margins) radiotherapy can improve the results in terms of Disease Free Survival (DFS) and, together with chemotherapy, of Overall Survival (OS). We recommend radiotherapy in case of deep tumor location, inadequate surgical margins and grade 3 tumour; for positive or “marginal (or close)” excision (that means inadequate surgery) or in selected patients with a bad prognosis, we believe that a multidisciplinary approach can be preferable.Introduction
Adjuvant radiotherapy (RTE) still has a fundamental role as a post-operative treatment. In patients with sarcomas of the extremities in whom definitive surgery has been or not radical (positive or “close” margins), radiotherapy with chemotherapy can improve the results in terms of Disease Free Survival (DFS) and Overall Survival (OS), while RTE alone seems to improve local control.Materials and methods
From 1/2000 to 12/2005 we treated 34 patients affected by locally advanced sarcomas of the upper or lower extremities with radiotherapy (doses ranging from 54 to 66 Gy) and chemotherapy in 18/34 with an adjuvant scheme that consisted in Epirubicine (120 mg/m2) plus Ifosfamide (7000–9000 mg/m2).Results
Disease Free Survival (DFS) and the Overall Survival (OS) rates were 76% and 82%, respectively. Eighteen patients developed one or more long-term side effects. Most of these complications were mild: all patients experienced only erithema, edema, local sclerosis or moderate pain.Conclusion
Radiotherapy has an important role as a post-operative treatment also when surgery was non-radical. It improves local control more in patients with high-grade sarcomas of the extremity with positive or close margins. It is still difficult to assess the role of adjuvant chemotherapy. 相似文献17.
Ermias Diro Koert Ritmeijer Marleen Boelaert Fabiana Alves Rezika Mohammed Charles Abongomera Raffaella Ravinetto Maaike De Crop Helina Fikre Cherinet Adera Robert Colebunders Harry van Loen Joris Menten Lutgarde Lynen Asrat Hailu Johan van Griensven 《PLoS neglected tropical diseases》2015,9(10)
Background
Visceral leishmaniasis (VL) has become an important opportunistic infection in persons with HIV-infection in VL-endemic areas. The co-infection leads to profound immunosuppression and high rate of annual VL recurrence. This study assessed the effectiveness, safety and feasibility of monthly pentamidine infusions to prevent recurrence of VL in HIV co-infected patients.Methods
A single-arm, open-label trial was conducted at two leishmaniasis treatment centers in northwest Ethiopia. HIV-infected patients with a VL episode were included after parasitological cure. Monthly infusions of 4mg/kg pentamidine-isethionate diluted in normal-saline were started for 12months. All received antiretroviral therapy (ART). Time-to-relapse or death was the primary end point.Results
Seventy-four patients were included. The probability of relapse-free survival at 6months and at 12 months was 79% and 71% respectively. Renal failure, a possible drug-related serious adverse event, occurred in two patients with severe pneumonia. Forty-one patients completed the regimen taking at least 11 of the 12 doses. Main reasons to discontinue were: 15 relapsed, five died and seven became lost to follow-up. More patients failed among those with a CD4+cell count ≤ 50cells/μl, 5/7 (71.4%) than those with counts above 200 cells/μl, 2/12 (16.7%), (p = 0.005).Conclusion
Pentamidine secondary prophylaxis led to a 29% failure rate within one year, much lower than reported in historical controls (50%-100%). Patients with low CD4+cell counts are at increased risk of relapse despite effective initial VL treatment, ART and secondary prophylaxis. VL should be detected and treated early enough in patients with HIV infection before profound immune deficiency installs. 相似文献18.
Yolanda Kathrin Mueller Fabienne Nackers Khalid A. Ahmed Marleen Boelaert Jean-Claude Djoumessi Rahma Eltigani Himida Ali Gorashi Omer Hammam Koert Ritmeijer Niven Salih Dagemlidet Worku Jean-Fran?ois Etard Fran?ois Chappuis 《PLoS neglected tropical diseases》2012,6(11)
Background
Since December 2009, Médecins Sans Frontières has diagnosed and treated patients with visceral leishmaniasis (VL) in Tabarak Allah Hospital, eastern Gedaref State, one of the main endemic foci of VL in Sudan. A survey was conducted to estimate the VL incidence in villages around Tabarak Allah.Methods
Between the 5th of May and the 17th of June 2011, we conducted an exhaustive door-to-door survey in 45 villages of Al-Gureisha locality. Deaths were investigated by verbal autopsies. All individuals with (i) fever of at least two weeks, (ii) VL diagnosed and treated in the previous year, and (iii) clinical suspicion of post-kala-azar dermal leishmaniasis (PKDL) were referred to medical teams for case ascertainment. A new case of VL was a clinical suspect with a positive rk39 rapid test or direct agglutination test (DAT).Results
In the 45 villages screened, 17,702 households were interviewed, for a population of 94,369 inhabitants. The crude mortality rate over the mean recall period of 409 days was 0.13/10''000 people per day. VL was a possible or probable cause for 19% of all deaths. The VL-specific mortality rate was estimated at 0.9/1000 per year.The medical teams examined 551 individuals referred for a history of fever of at least two weeks. Out of these, 16 were diagnosed with primary VL. The overall incidence of VL over the past year was 7.0/1000 persons per year, or 7.9/1000 per year when deaths possibly or probably due to VL were included. Overall, 12.5% (11,943/95,609) of the population reported a past VL treatment episode.Discussion and Conclusion
VL represents a significant health burden in eastern Gedaref State. Active VL case detection had a very low yield in this specific setting with adequate access to care and may not be the priority intervention to enhance control in similar contexts. 相似文献19.
Cecilia Ferreyra Oliver Yun Nell Eisenberg Elena Alonso Ashimosi S. Khamadi Matilu Mwau Martha Kihara Mugendi Ana Alvarez Elena Velilla Laurence Flevaud Mireia Arnedo David Dalmau Paul Roddy Andrea Bernasconi Pedro Pablo Palma 《PloS one》2012,7(11)
Background
In resource-limited settings where viral load (VL) monitoring is scarce or unavailable, clinicians must use immunological and clinical criteria to define HIV virological treatment failure. This study examined the performance of World Health Organization (WHO) clinical and immunological failure criteria in predicting virological failure in HIV patients receiving antiretroviral therapy (ART).Methods
In a HIV/AIDS program in Busia District Hospital, Kenya, a retrospective, cross-sectional cohort analysis was performed in April 2008 for all adult patients (>18 years old) on ART for ≥12 months, treatment-naive at ART start, attending the clinic at least once in last 6 months, and who had given informed consent. Treatment failure was assessed per WHO clinical (disease stage 3 or 4) and immunological (CD4 cell count) criteria, and compared with virological failure (VL >5,000 copies/mL).Results
Of 926 patients, 123 (13.3%) had clinically defined treatment failure, 53 (5.7%) immunologically defined failure, and 55 (6.0%) virological failure. Sensitivity, specificity, positive predictive value, and negative predictive value of both clinical and immunological criteria (combined) in predicting virological failure were 36.4%, 83.5%, 12.3%, and 95.4%, respectively.Conclusions
In this analysis, clinical and immunological criteria were found to perform relatively poorly in predicting virological failure of ART. VL monitoring and new algorithms for assessing clinical or immunological treatment failure, as well as improved adherence strategies, are required in ART programs in resource-limited settings. 相似文献20.
Simnikiwe H. Mayaphi Marieke Brauer Daniel M. Morobadi Ahmad H. Mazanderani Rendani T. Mafuyeka Steve A. S. Olorunju Gregory R. Tintinger Anton Stoltz 《PloS one》2014,9(4)