Journal Article > ResearchFull Text
Am J Trop Med Hyg. 7 October 2019; Volume 101 (Issue 6); DOI:10.4269/ajtmh.19-0430
Kamink SS, Abdi AM, Kamau C, Ashraf S, Ansari MA, et al.
Am J Trop Med Hyg. 7 October 2019; Volume 101 (Issue 6); DOI:10.4269/ajtmh.19-0430
Cutaneous leishmaniasis (CL), a neglected parasitic skin disease, is endemic in Pakistan, where Leishmania tropica and Leishmania major are the causative protozoan species. Standard treatment with antimonial injections is long, painful, and costly; has toxic side effects; and is not always available in public hospitals. Small pilot studies have previously evaluated a low-cost and noninvasive hand-held exothermic crystallization thermotherapy (HECT-CL) device. We aimed to further establish the effectiveness, safety, and feasibility of HECT-CL in L. tropica. In a prospective observational study, patients with parasitological confirmation of CL were treated using the HECT-CL heat pack for 3 minutes with an initial temperature of 52-53°C for 7 consecutive days. Dried blood spot samples were taken for species identification by PCR. Effectiveness was assessed by using medical photographs and measurements of the lesion size at baseline and subsequent follow-up visits, for up to 180 days. We intended to enroll 317 patients. The HECT-CL treatment was easy to apply and well tolerated. Species identification demonstrated the presence of L. tropica. Interim analysis of 56 patients showed a failure rate of 91% at follow-up (median 45 days after treatment, interquartile range 30-60 days). Enrollment of patients was prematurely suspended because of futility. This study showed a high failure rate for HECT-CL thermotherapy in this setting. Leishmania tropica is known to be less sensitive to antileishmanial drugs, more temperature-resistant, and spontaneous healing is slower than that in L. major. More research is needed to identify low-cost, effective, and more patient-friendly treatment for L. tropica.
Journal Article > ReviewFull Text
PLOS One. 25 May 2016; Volume 11 (Issue 5); e0155968.; DOI:10.1371/journal.pone.0155968
Mitnick CD, Rodriguez CA, Hatton ML, Brigden G, Cobelens F, et al.
PLOS One. 25 May 2016; Volume 11 (Issue 5); e0155968.; DOI:10.1371/journal.pone.0155968
INTRODUCTION
There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey.
METHODS
Publications citing the 2008 research agenda and normative documents were reviewed for evidence gaps. Gaps were formulated into questions and grouped as in the 2008 research agenda: Laboratory Support, Treatment Strategy, Programmatically Relevant Research, Epidemiology, and Management of Contacts. A survey was distributed through snowball sampling to identify research priorities. Respondent priority rankings were scored and summarized by mean. Sensitivity analyses explored weighting and handling of missing rankings.
RESULTS
Thirty normative documents and publications were reviewed for stated research needs; these were collapsed into 56 research questions across 5 categories. Of more than 500 survey recipients, 133 ranked priorities within at least one category. Priorities within categories included new diagnostics and their effect on improving treatment outcomes, improved diagnosis of paucibacillary and extra pulmonary TB, and development of shorter, effective regimens. Interruption of nosocomial transmission and treatment for latent TB infection in contacts of known MDR−TB patients were also top priorities in their respective categories. Results were internally consistent and robust.
DISCUSSION
Priorities retained from the 2008 research agenda include shorter MDR-TB regimens and averting transmission. Limitations of recent advances were implied in the continued quest for: shorter regimens containing new drugs, rapid diagnostics that improve treatment outcomes, and improved methods of estimating burden without representative data.
CONCLUSION
There is continuity around the priorities for research in PMDT. Coordinated efforts to address questions regarding shorter treatment regimens, knowledge of disease burden without representative data, and treatment for LTBI in contacts of known DR-TB patients are essential to stem the epidemic of TB, including DR-TB.
There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey.
METHODS
Publications citing the 2008 research agenda and normative documents were reviewed for evidence gaps. Gaps were formulated into questions and grouped as in the 2008 research agenda: Laboratory Support, Treatment Strategy, Programmatically Relevant Research, Epidemiology, and Management of Contacts. A survey was distributed through snowball sampling to identify research priorities. Respondent priority rankings were scored and summarized by mean. Sensitivity analyses explored weighting and handling of missing rankings.
RESULTS
Thirty normative documents and publications were reviewed for stated research needs; these were collapsed into 56 research questions across 5 categories. Of more than 500 survey recipients, 133 ranked priorities within at least one category. Priorities within categories included new diagnostics and their effect on improving treatment outcomes, improved diagnosis of paucibacillary and extra pulmonary TB, and development of shorter, effective regimens. Interruption of nosocomial transmission and treatment for latent TB infection in contacts of known MDR−TB patients were also top priorities in their respective categories. Results were internally consistent and robust.
DISCUSSION
Priorities retained from the 2008 research agenda include shorter MDR-TB regimens and averting transmission. Limitations of recent advances were implied in the continued quest for: shorter regimens containing new drugs, rapid diagnostics that improve treatment outcomes, and improved methods of estimating burden without representative data.
CONCLUSION
There is continuity around the priorities for research in PMDT. Coordinated efforts to address questions regarding shorter treatment regimens, knowledge of disease burden without representative data, and treatment for LTBI in contacts of known DR-TB patients are essential to stem the epidemic of TB, including DR-TB.
Journal Article > ReviewAbstract
Travel Med Infect Dis. 21 November 2020; Volume 39; DOI:10.1016/j.tmaid.2020.101924
Belard S, Stratta S, Zhao A, Ritmeijer KKD, Moreto-Planas L, et al.
Travel Med Infect Dis. 21 November 2020; Volume 39; DOI:10.1016/j.tmaid.2020.101924
Background
Visceral leishmaniasis (VL) is predominantly a neglected tropical parasitic disease but may also be acquired by travellers. We aimed at summarizing knowledge on sonographic presentation of VL to better understand sonographic features of VL.
Methods
PubMed was searched for studies and case reports presenting original data on sonographic findings of VL, published before August 13th, 2019. Demographic, clinical, and sonographic data were extracted and summarized in a qualitative approach.
Results
A total of 36 publications were included in this review; 27 of these were case reports and the remainder were prospective or retrospective studies. No study reported systematic cross-sectional comparative imaging. Overall, publications reported on 512 patients with VL of whom 12 were reported HIV-infected. Spleno- and hepatomegaly were the most frequently reported findings. Further relevant and repeatedly reported findings were splenic and hepatic lesions, abdominal lymphadenopathy, pleural and pericardial effusion and ascites. Reported focal splenic lesions were heterogeneous in size, shape, and echogenicity. Several publications reported gradual diminution and resolution of sonographic findings with VL treatment.
Conclusion
Available literature on sonographic findings of VL is limited. Available reports indicate that spleno- and hepatomegaly, free fluid, abdominal lymphadenopathy, and focal splenic lesions may be common sonographic features in patients with VL. Because of the apparent overlap of sonographic features of VL, extrapulmonary tuberculosis and other conditions, interpretation of sonographic findings needs to be made with particular caution.
Visceral leishmaniasis (VL) is predominantly a neglected tropical parasitic disease but may also be acquired by travellers. We aimed at summarizing knowledge on sonographic presentation of VL to better understand sonographic features of VL.
Methods
PubMed was searched for studies and case reports presenting original data on sonographic findings of VL, published before August 13th, 2019. Demographic, clinical, and sonographic data were extracted and summarized in a qualitative approach.
Results
A total of 36 publications were included in this review; 27 of these were case reports and the remainder were prospective or retrospective studies. No study reported systematic cross-sectional comparative imaging. Overall, publications reported on 512 patients with VL of whom 12 were reported HIV-infected. Spleno- and hepatomegaly were the most frequently reported findings. Further relevant and repeatedly reported findings were splenic and hepatic lesions, abdominal lymphadenopathy, pleural and pericardial effusion and ascites. Reported focal splenic lesions were heterogeneous in size, shape, and echogenicity. Several publications reported gradual diminution and resolution of sonographic findings with VL treatment.
Conclusion
Available literature on sonographic findings of VL is limited. Available reports indicate that spleno- and hepatomegaly, free fluid, abdominal lymphadenopathy, and focal splenic lesions may be common sonographic features in patients with VL. Because of the apparent overlap of sonographic features of VL, extrapulmonary tuberculosis and other conditions, interpretation of sonographic findings needs to be made with particular caution.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 1 March 2016; Volume 20 (Issue 3); 290-294.; DOI:10.5588/ijtld.15.0490
Furin J, Alirol E, Allen E, Fielding K, Merle CS, et al.
Int J Tuberc Lung Dis. 1 March 2016; Volume 20 (Issue 3); 290-294.; DOI:10.5588/ijtld.15.0490
Drug-resistant tuberculosis (DR-TB) is a growing public health problem, and for the first time in decades, new drugs for the treatment of this disease have been developed. These new drugs have prompted strengthened efforts in DR-TB clinical trials research, and there are now multiple ongoing and planned DR-TB clinical trials. To facilitate comparability and maximise policy impact, a common set of core research definitions is needed, and this paper presents a core set of efficacy and safety definitions as well as other important considerations in DR-TB clinical trials work. To elaborate these definitions, a search of clinical trials registries, published manuscripts and conference proceedings was undertaken to identify groups conducting trials of new regimens for the treatment of DR-TB. Individuals from these groups developed the core set of definitions presented here. Further work is needed to validate and assess the utility of these definitions but they represent an important first step to ensure there is comparability in clinical trials on multidrug-resistant TB.
Conference Material > Poster
Kamink SS, Masih B, Saleem A, Khan J, Masih S, et al.
MSF Scientific Days International 2021: Research. 18 May 2021
Journal Article > ReviewAbstract
J Infect Dis. 3 April 2012; Volume 205 (Issue suppl_2); DOI:10.1093/infdis/jir858
Zumla A, Abubakar I, Raviglione M, Hoelscher M, Ditui L, et al.
J Infect Dis. 3 April 2012; Volume 205 (Issue suppl_2); DOI:10.1093/infdis/jir858
Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis-specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR tuberculosis are discussed.
Journal Article > ResearchFull Text
Parasitol Res. 28 April 2005; Volume 96 (Issue 3); 162-165.; DOI:10.1007/s00436-005-1325-7
Graupner J, Göbels K, Grobusch MP, Lund A, Richter J, et al.
Parasitol Res. 28 April 2005; Volume 96 (Issue 3); 162-165.; DOI:10.1007/s00436-005-1325-7
Falciparum malaria is hyperendemic in southern Nigeria and chloroquine resistance is an increasing problem. Therefore, the parasitological and haematological response to treatment with amodiaquine was studied in children under 5 years during a 14-day follow-up. Of 105 children who accomplished the study (out of 114 who were enrolled), 95.3% were parasite-negative on thick blood film on day 7, which decreased to 89.5% on day 14. The haemoglobin levels increased on average by 1.3% on day 14 (+/-1.9) and more pronounced in children with anaemia<10 g/dl on enrollment. The number of patients with adverse events (mainly pruritus and nausea) was few. This study shows that amodiaquine is effective, safe and affordable in an area with high resistance to chloroquine.
Journal Article > ReviewAbstract
J Infect Dis. 10 April 2012; Volume 205 (Issue suppl_2); DOI:10.1093/infdis/jir860
McNerney R, Maeurer M, Abubakar I, Marais BJ, McHugh TD, et al.
J Infect Dis. 10 April 2012; Volume 205 (Issue suppl_2); DOI:10.1093/infdis/jir860
Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics.
Journal Article > ResearchFull Text
PLOS Med. 14 April 2009; Volume 6 (Issue 4); DOI:10.1371/journal.pmed.1000055
Pearce RJ, Pota H, Evehe M-SB, Ba EH, Mombo-Ngoma G, et al.
PLOS Med. 14 April 2009; Volume 6 (Issue 4); DOI:10.1371/journal.pmed.1000055
BACKGROUND: Although the molecular basis of resistance to a number of common antimalarial drugs is well known, a geographic description of the emergence and dispersal of resistance mutations across Africa has not been attempted. To that end we have characterised the evolutionary origins of antifolate resistance mutations in the dihydropteroate synthase (dhps) gene and mapped their contemporary distribution. METHODS AND FINDINGS: We used microsatellite polymorphism flanking the dhps gene to determine which resistance alleles shared common ancestry and found five major lineages each of which had a unique geographical distribution. The extent to which allelic lineages were shared among 20 African Plasmodium falciparum populations revealed five major geographical groupings. Resistance lineages were common to all sites within these regions. The most marked differentiation was between east and west African P. falciparum, in which resistance alleles were not only of different ancestry but also carried different resistance mutations. CONCLUSIONS: Resistant dhps has emerged independently in multiple sites in Africa during the past 10-20 years. Our data show the molecular basis of resistance differs between east and west Africa, which is likely to translate into differing antifolate sensitivity. We have also demonstrated that the dispersal patterns of resistance lineages give unique insights into recent parasite migration patterns.
Journal Article > CommentaryFull Text
Nat Rev Drug Discov. 17 July 2015; Volume 14 (Issue 8); DOI:10.1038/nrd4696
Zumla A, Chakaya JM, Hoelscher M, Ntoumi F, Rustomjee R, et al.
Nat Rev Drug Discov. 17 July 2015; Volume 14 (Issue 8); DOI:10.1038/nrd4696