[show abstract][hide abstract] ABSTRACT: Three diagnostic tests for visceral leishmaniasis (VL), the freeze-dried direct agglutination test (FD-DAT), the rK39 dipstick and a urine latex antigen test (KAtex), were evaluated for use in primary care in East Africa and the Indian subcontinent. Clinical suspects were prospectively recruited and tissue, blood and urine samples were taken. Direct microscopic examination of tissue smear, and FD-DAT, rK39 and KAtex were performed. Sensitivity and specificity with 95% credible intervals were estimated using Bayesian latent class analysis. On the Indian subcontinent both the FD-DAT and the rK39 strip test exceeded the 95% sensitivity and 90% specificity target, but not so in East Africa. Sensitivity of the FD-DAT was high in Ethiopia and Kenya but lower in Sudan, while its specificity was below 90% in Kenya. Sensitivity of the rK39 was below 80% in the three countries, and its specificity was only 70% in Ethiopia. KAtex showed moderate to very low sensitivity in all countries. FD-DAT and rK39 can be recommended for clinical practice on the Indian subcontinent. In East Africa, their clinical use should be carefully monitored. More work is needed to improve existing formats, and to develop better VL diagnostics.
Transactions of the Royal Society of Tropical Medicine and Hygiene 02/2008; 102(1):32-40. · 1.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: Three novel diagnostic tests for visceral leishmaniasis (VL), namely FD-DAT, rK39 dipstick and KATEX, were evaluated under field conditions using 101 clinical cases suspected of having VL enrolled in a trial either by active (63 patients) or passive (38 patients) surveillance. VL was confirmed in 49 patients: 35 by both aspirate smear microscopy and NNN culture, 10 by NNN culture alone and 4 by aspirate smear microscopy alone. Based on tests performed in the field, sensitivity for FD-DAT, rK39 dipstick and KATEX was determined to be 95.3% (95% CI 82.9-99.2%), 71.7% (95% CI 56.3-83.5%) and 57.4% (95% CI 42.3-71.4%), respectively. Similarly, the specificity was determined to be 62.7% (95% CI 48.1-75.5%), 82.4% (95% CI 68.6-91.1%) and 84.3% (95% CI 70.9-92.5%), respectively. A higher sensitivity of KATEX (73.9% vs. 41.7%) and higher specificity of FD-DAT (100.0% vs. 48.6%) were demonstrated under passive case detection compared with active case detection. FD-DAT is recommended for confirmation of VL diagnosis in hospital settings, whereas its use in the field will be limited to exclude VL in clinical suspects. The sensitivity of KATEX and rK39 dipstick tests needs to be improved to promote their use as first-line diagnostic tests in the field setting of northwestern Ethiopia.
Transactions of the Royal Society of Tropical Medicine and Hygiene 10/2007; 101(9):908-14. · 1.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: Human cutaneous leishmaniasis (CL) and mucous leishmaniasis (ML) are highly endemic in Isiboro Secure Park, which lies in the Bolivian department of Cochabamba--an area where branded meglumine antimoniate (Glucantime) is expensive and poorly distributed. The safety and efficacy of generic sodium stibogluconate (SSG), from Albert David Ltd, was therefore explored, in CL and ML cases from the park, who were treated with 20 mg/kg.day for 20 and 30 days, respectively. A questionnaire recording adverse effects was completed by a physician in each treatment centre. Efficacy of treatment was assessed at the end of treatment and at follow-ups 1 month and 3, 6 and 12 months later. Overall, 146 patients completed treatment with SSG in 2003-2004. No fatalities or severe adverse effects were reported but mild to moderate adverse effects were noted in 41 (28%) of the patients. The incidence of adverse effects was significantly higher among the cases of ML than among the cases of CL. Of the 86 patients with CL who completed 6 months of follow-up, 81 (94.2%) were considered to have been clinically cured; a comparable cohort of 69 CL cases who had been treated with Glucantime in 2001-2002 showed a similar frequency of clinical cure (90%). Generic SSG was shown to be safe and efficacious for the treatment of tegumentary leishmaniasis in Bolivia. Being several times cheaper than Glucantime, it could contribute to improving the access of CL and ML patients to treatment, not only in Bolivia but also in other countries of Latin America.
Annals of Tropical Medicine and Parasitology 11/2006; 100(7):591-600. · 1.31 Impact Factor
[show abstract][hide abstract] ABSTRACT: In Bihar, India, where visceral leishmaniasis (VL) is hyperendemic and refractory to antimony, amphotericin B is the most effective option for the treatment of VL. Lipid formulations of amphotericin B are able to circumvent the toxic effect of conventional amphotericin B, and the total dose of these formulations can be administered over a short duration. However, cost is a major constraint in the use of lipid formulations of amphotericin B. Amphotericin B colloidal dispersion (ABCD), which is a less expensive lipid formulation, has not been tested for the treatment of VL in India.
In an open-label, randomized clinical trial, we evaluated the efficacy and safety of a 6-day course of ABCD administered to 3 different dose groups (total dose: 7.5 mg/kg [group A], 10 mg/kg [group B], and 15 mg/kg [group C]), each of which included a cohort of 135 patients.
Although infusion-related fever and chills occurred in 56%-68% of patients in the 3 different dose groups, 401 of 405 patients completed the treatment. All 135 patients in group A completed treatment, and the final cure rate for this group was 97%. In the group that received the highest dose of ABCD (group C), severe backache, an unusual side effect, was observed in 8 patients (5.92%). Serious adverse effects led to the withdrawal of 2 patients (1.48%) each from group B and group C.
Although the cost of ABCD is prohibitive, the high level of efficacy associated with short-term treatment with low-dose ABCD provides another alternative for the treatment of VL, especially in regions where VL is antimony refractory.
[show abstract][hide abstract] ABSTRACT: The definitive version is available at www3.interscience.wiley.com OBJECTIVES: To assess the field accuracy, reproducibility and feasibility of the formol gel test (FGT), the urine latex agglutination test (KAtex) and a rK39 antigen-based dipstick for the diagnosis of visceral leishmaniasis (VL) in rural Nepal. METHOD: Patients with clinical suspicion of VL were recruited at Rangeli District Hospital (DH), a 15-bed government hospital located in south-eastern Nepal. FGT, KAtex and rK39 dipstick tests were performed on site and later repeated at a reference kala-azar diagnostic laboratory to assess reproducibility. Diagnosis of VL was confirmed by either a positive bone marrow aspirate examination or a positive direct agglutination test (DAT titre > or = 1:3200) in patients who later responded to anti-leishmanial therapy. RESULTS: Of 155 patients initially recruited, 142 (85 with VL and 57 with another diagnosis) were included in the study. The sensitivity of the rK39 dipstick [89%; 95% confidence interval (CI): 81-94] was significantly higher than that of the KAtex (57%; 95% CI: 46-67) and the FGT (52%; 95% CI: 41-62). All three tests had a specificity of at least 90%. Agreement was higher for the rK39 dipstick (kappa = 0.87) than for the FGT (0.68) and the KAtex (0.43). All tests required < or = 20 min of actual work and < or = 40 min to obtain the results. CONCLUSION: The rK39 dipstick was easy to do, more accurate and reproducible than other rapid diagnostic tests for VL in a DH of rural Nepal. It should be integrated into the field diagnostic algorithm of VL in this region and mechanisms to secure its availability should be found.
Tropical Medicine & International Health 01/2006; · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. Visceral leishmaniasis (VL) is of higher priority than cutaneous leishmaniasis (CL) as it is a fatal disease in the absence of treatment. Anthroponotic VL foci are of special concern as they are at the origin of frequent and deathly epidemics (e.g. Sudan). Leishmaniasis burden remains important: 88 countries, 350 million people at risk, 500,000 new cases of VL per year, 1-1.5 million for CL and DALYs: 2.4 millions. Most of the burden is concentrated on few countries which allows clear geographic priorities. Leishmaniasis is still an important public health problem due to not only environmental risk factors such as massive migrations, urbanisation, deforestation, new irrigation schemes, but also to individual risk factors: HIV, malnutrition, genetic, etc em leader Leishmaniasis is part of those diseases which still requires improved control tools. Consequently WHO/TDR research for leishmaniasis has been more and more focusing on the development of new tools such as diagnostic tests, drugs and vaccines. The ongoing effort has already produced significant results. The newly available control tools should allow a scaling up of control activities in priority areas. In anthroponotic foci, the feasibility of getting a strong impact on mortality, morbidity and transmission, is high.
[show abstract][hide abstract] ABSTRACT: We evaluated the diagnostic accuracy as well as the reproducibility of the urine latex agglutination test 'KAtex' in the diagnosis of kala-azar in patients recruited at a tertiary care centre in Dharan, Nepal, between November 2000 and January 2002.
All patients presenting with fever of 2 weeks or more and splenomegaly were consecutively enrolled. Bone marrow and--if negative--spleen aspirates were examined for Leishmania donovani. Serum and urine samples were taken in duplicate for the Direct Agglutination Test (DAT) and KAtex. The reference laboratory determined sensitivity and specificity of KAtex. Reproducibility between both laboratories was assessed.
KAtex was performed on urine from 155 parasitologically confirmed kala-azar and 77 non-kala-azar cases (parasitology and DAT-negative). KAtex showed a sensitivity of 47.7% (74/155, 95% CI: 39.7-55.9) and a specificity of 98.7% (76/77, 95% CI: 93.0-100.0). Reproducibility of KAtex showed a kappa of 0.684 (P < 0.001, n = 232).
KAtex evaluation showed high specificity, low sensitivity and moderate reproducibility. A urine test for kala-azar could become a real breakthrough in kala-azar management if its reproducibility and sensitivity could be further improved.
Tropical Medicine & International Health 06/2004; 9(6):724-9. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: We compared the validity of pancytopenia, the formol-gel test (FGT), the indirect fluorescence antibody test (IFAT), the direct agglutination test (DAT), and the rK39 dipstick test as diagnostic criteria for visceral leishmaniasis (VL) in Nepal. Between September 2000 and January 2002, 310 clinical suspects had a bone marrow aspirate, and if negative, a spleen aspirate smear examined for Leishmania donovani. Sensitivity and specificity of all tests were determined compared with parasitology and by latent class analysis (LCA). Compared with parasitology, the sensitivities of the other tests were as follows: pancytopenia = 16.3% (95% confidence interval [CI] = 11.3-22.5%), FGT = 39.9% (95% CI = 32.7-47.4%), IFAT = 28.4% (95% CI = 22.0-35.5%), DAT = 95.1% (95% CI = 90.8-97.7%), and the rK39 dipstick test = 87.4% (95% CI = 81.7-91.9%). Sensitivity estimates obtained by LCA were similar, but specificity estimates were substantially higher (DAT = 93.7% versus 77.8%; rK39 dipstick test = 93.1% versus 77.0%). The DAT or the rK39 dipstick test can replace parasitology as the basis of a decision to treat VL in Nepalese peripheral health services.
The American journal of tropical medicine and hygiene 02/2004; 70(1):72-7. · 2.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: As the AIDS pandemic spreads to rural areas and human visceral leishmaniasis (VL) becomes more common in suburban areas, there is an ever greater degree of overlap between the geographical distributions of the two diseases and, in consequence, an increasing incidence of Leishmania/HIV co-infection. Cases of the co-infection have been reported from 35 countries around the world but most have been recorded in south-western Europe. There has been a total of 1911 cases detected in Spain, France, Italy and Portugal. The incidence of Leishmania/HIV co-infection is expected to continue increasing in eastern Africa but to fall in south-western Europe as increasing numbers of HIV-positives in the latter region are given the new, highly active, antiretroviral therapy (HAART). In 1998, a world-wide network of surveillance for the co-infection, which now includes 28 member institutions, was established by the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS). In south-western Europe, the surveillance system is based on 16 institutions and is already well established. The systematic use of standardized and recently computerized case-report forms, a central international registry at the WHO's headquarters in Geneva, and the use of a geographical information system (GIS) for mapping and monitoring the co-infections have together improved the overall quality of the epidemiological data-gathering. All member institutions of the global network report to the WHO on an annual basis. The data collected are then analysed and periodically disseminated through international publications. The GIS allows the relevant epidemiological and demographic data-sets to be integrated and permits all detected cases of co-infection to be mapped down to locality level. The system also allows the spatial distribution of cases to be visualised and analysed and the geographical spread of the co-infection to be monitored over time. The risk posed by co-infected patients, as a source of Leishmania infection for the sandflies feeding on them, has recently been confirmed. The parasites and HIV may also be transmitted as the result of needle-sharing among intravenous-drug users.
Annals of Tropical Medicine and Parasitology 11/2003; 97 Suppl 1:3-15. · 1.31 Impact Factor
[show abstract][hide abstract] ABSTRACT: The diagnosis of visceral leishmaniasis (kala-azar) remains difficult in rural endemic areas and practical and reliable tests are badly needed. Two serological tests, the Direct Agglutination Test (DAT) and an rK39-antigen-based dipstick test, were compared to parasitological diagnosis in a group of 184 patients presenting at a tertiary care centre in south-eastern Nepal with a history of fever > or = 14 days and splenomegaly; 139 patients had a parasitologically proven kala-azar and 45 patients had a negative parasitological work-up. The rK39 dipstick showed a sensitivity of 97% and a specificity of 71%. The DAT was up to 99% sensitive with a low cut-off titre (1:400) but its specificity did not exceed 82% even with a high cut-off titre (1:51 200). Both tests could be used for screening suspect patients in endemic areas. However, their use as confirmatory tests should be restricted to situations where the proportion of kala-azar among clinical suspect patients is high. The rK39 dipstick is cheaper and easier to use than the DAT and could be used widely provided that both its performance and production remain stable.
Tropical Medicine & International Health 03/2003; 8(3):277-85. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Sodium stibogluconate (SSG) is the first-line therapy for visceral leishmaniasis (VL) in south-eastern Nepal. Recent studies from the neighbouring state of Bihar, India, have shown a dramatic fall in cure rates with treatment failure occurring in up to 65% of VL patients treated with SSG. A prospective study was conducted at a tertiary-level hospital located in south-eastern Nepal from July 1999 to January 2001. Parasitologically proven kala-azar patients with no previous history of treatment for VL were treated with SSG 20 mg/kg/d for 30 d which was extended to 40 d in those with persistent positive parasitology. Of the 110 patients who completed SSG therapy and were assessed at 1 and 6 months, definite cure was achieved in 99 patients (90%) and SSG failure occurred in 11 patients (10%). Except for the presence of hepatomegaly and a lower platelet count there was no clinical or laboratory baseline characteristic associated with treatment failure. A significantly lower cure rate (76%, P = 0.03) was observed in patients from the district of Saptari, which borders the antimony-resistant VL areas of Bihar. The efficacy of SSG as a first-line treatment for VL in south-eastern Nepal was still satisfactory, except for the patients living closer to the antimony-resistant VL areas of India. These findings indicate that the spread of resistance to antimonials is already taking place in Nepal and that a policy to control further spread should be urgently implemented.
Transactions of the Royal Society of Tropical Medicine and Hygiene 01/2003; 97(3):350-4. · 1.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: Visceral leishmaniasis is common in less developed countries, with an estimated 500000 new cases each year. Because of the diversity of epidemiological situations, no single diagnosis, treatment, or control will be suitable for all. Control measures through case finding, treatment, and vector control are seldom used, even where they could be useful. There is a place for a vaccine, and new imaginative approaches are needed. HIV co-infection is changing the epidemiology and presents problems for diagnosis and case management. Field diagnosis is difficult; simpler, less invasive tests are needed. Current treatments require long courses and parenteral administration, and most are expensive. Resistance is making the mainstay of treatment, agents based on pentavalent antimony, useless in northeastern India, where disease incidence is highest. Second-line drugs (pentamidine and amphotericin B) are limited by toxicity and availability, and newer formulations of amphotericin B are not affordable. The first effective oral drug, miltefosine, has been licensed in India, but the development of other drugs in clinical phases (paromomycin and sitamaquine) is slow. No novel compound is in the pipeline. Drug combinations must be developed to prevent drug resistance. Despite these urgent needs, research and development has been neglected, because a disease that mainly affects the poor ranks as a low priority in the private sector, and the public sector currently struggles to undertake the development of drugs and diagnostics in the absence of adequate funds and infrastructure. This article reviews the current situation and perspectives for diagnosis, treatment, and control of visceral leishmaniasis, and lists some priorities for research and development.
The Lancet Infectious Diseases 09/2002; 2(8):494-501. · 19.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: Predictions that deforestation would reduce American cutaneous leishmaniasis incidence have proved incorrect. Presentations at a recent international workshop, instead, demonstrated frequent domestication of transmission throughout Latin America. While posing new threats, this process also increases the effectiveness of vector control in and around houses. New approaches for sand fly control and effective targeting of resources are reviewed.
Memórias do Instituto Oswaldo Cruz 03/2001; 96(2):159-62. · 1.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Reported are the results of a formal decision analysis which facilitated the choice of the most appropriate test-treatment strategy for visceral leishmaniasis in areas where the disease is endemic. The following strategies were compared: treatment of all suspects (strategy A); testing by means of parasitological investigation followed by treatment of positives (strategy B); two-step testing by means of the direct agglutination test (DAT) followed by treatment of patients with high titres as well as those with parasitologically confirmed borderline titres (strategy C); and DAT followed by treatment of positives (strategy D). The results for each strategy were expressed as costs in US$ per death averted. The effectiveness of strategies C and D was close to that of strategy A and far better than that of strategy B. The cost-effectiveness ratio for strategies C and D (US$ 465 per death averted) was not substantially higher than that of testing by means of parasitological investigation followed by treatment of positives (strategy B), which was the most cost-effective strategy at US$448 per death averted. At current prices of antimonial drugs, the cost of test-treatment strategies depends more on the cost of treatment than on that of testing. The use of a sensitive serological test such as the DAT is recommended as the basis of test-treatment strategies for visceral leishmaniasis in areas where the disease is endemic.
Bulletin of the World Health Organisation 02/1999; 77(8):667-74. · 5.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: Up-to-date information is given on the epidemiological situation of zoonotic visceral leishmaniasis (ZVL) in nine Mediterranean countries, and on drug regimens adopted in the management of ZVL patients in each country. Results of experimental and clinical trials on the efficacy and tolerability of liposomal amphotericin B in laboratory animals and in patients with ZVL are presented, as well as conclusions and recommendations on drug regimens to be used in the treatment of ZVL.
Bulletin of the World Health Organisation 02/1995; 73(2):191-7. · 5.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: We examined the expression and the antigenicity of the major surface polypeptides of Leishmania braziliensis braziliensis and Leishmania donovani chagasi, parasites which commonly coexist in the same endemic areas of Bolivia. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profiles from surface-iodinated promastigotes showed the presence of a unique iodinatable polypeptide of 72 kDa on the L. b. braziliensis surface and of two major components of 65 and 50 kDa exposed at the surface of L. d. chagasi. Comparison of the peptide digestion profiles of the major iodinated polypeptides of both strains showed no similarity between the maps of the 72- and the 65-kDa polypeptides of L. b. braziliensis and L. d. chagasi, respectively. Immunoprecipitation of surface-labeled L. b. braziliensis Nonidet P-40 extracts with 35 serum specimens obtained from Bolivian patients with cutaneous and mucocutaneous leishmaniasis showed that all serum specimens recognized predominantly the 72-kDa antigen and high-molecular-mass proteins in some cases. The recognition patterns were independent of the geographical origin of the patient, the type of lesion, and the serum antibody titer. Serum specimens from children with visceral leishmaniasis did not precipitate the L. b. braziliensis 72-kDa antigen. Hamster hyperimmune serum against L. b. braziliensis also recognized the 72-kDa surface antigen. However, this recognition was inhibited in the presence of the homologous nonlabeled antigen but not in the presence of heterologous (L. d. chagasi and Trypanosoma cruzi) antigens. The specific recognition of 72-kDa surface antigen in both natural and experimental L. b. braziliensis infections suggests that this antigen could be a good candidate for use in the differential immunodiagnosis and prognosis of the disease.
Journal of Clinical Microbiology 04/1991; 29(3):595-9. · 4.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Description de deux nouvelles espèces de Phlébotomes de région subandine de Bolivie (alt. : 900-2700 m). #Lutzomyia torresi$ n.sp. est très proche de #L. boliviana$ qui n'a jusqu'à maintenant été rattachée à aucun groupe ou série; elle est cavernicole ou péridomestique et se nourrit sur chauves-souris et poulets. #L. mollinedoi$ n.sp. est une espèce proche de #L. oliveirae$, #L. brisolai$ et #L. waltoni$; elle n'a été trouvée que dans des grottes où elle se nourrit sur les vampires (#Desmodus rotundus$). (Résumé d'auteur)
[show abstract][hide abstract] ABSTRACT: Specimens of two species of sandfly, Psychodopygus carrerai carrerai and P. yucumensis, vectors of Leishmania braziliensis braziliensis in the subandean lowlands of Bolivia, were subjected to cuticular hydrocarbon analysis to ascertain if the technique could separate the females. A high degree of separation (87%) was obtained based on significant differences in the cuticular hydrocarbon composition of these two species. Statistical treatment of the data shows that these species, initially identified by the colour of the mesonotum, can also be distinguished by their hydrocarbons.