[Show abstract][Hide abstract] ABSTRACT: Post kala-azar dermal leishmaniasis (PKDL) is a neglected complication of visceral leishmaniasis (VL)[horizontal bar]a deadly, infectious disease that claims approximately 20,000 to 40,000 lives every year. PKDL is thought to be a reservoir for transmission of VL, thus, adequate control of PKDL plays a key role in the ongoing effort to eliminate VL. Over the past few years, several expert meetings have recommended that a greater focus on PKDL was needed, especially in South Asia. This report summarizes the Post Kala-Azar Dermal Leishmaniasis Consortium Meeting held in New Delhi, India, 27--29 June 2012. The PKDL Consortium is committed to promote and facilitate activities that lead to better understanding of all aspects of PKDL that are needed for improved clinical management and to achieve control of PKDL and VL. Fifty clinicians, scientists, policy makers, and advocates came together to discuss issues relating to PKDL epidemiology, diagnosis, pathogenesis, clinical presentation, treatment, and control. Colleagues who were unable to attend participated during drafting of the consortium meeting report.
[Show abstract][Hide abstract] ABSTRACT: As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 countries and three territories (see 'Leishmaniasis Country Profiles Text S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21, S22, S23, S24, S25, S26, S27, S28, S29, S30, S31, S32, S33, S34, S35, S36, S37, S38, S39, S40, S41, S42, S43, S44, S45, S46, S47, S48, S49, S50, S51, S52, S53, S54, S55, S56, S57, S58, S59, S60, S61, S62, S63, S64, S65, S66, S67, S68, S69, S70, S71, S72, S73, S74, S75, S76, S77, S78, S79, S80, S81, S82, S83, S84, S85, S86, S87, S88, S89, S90, S91, S92, S93, S94, S95, S96, S97, S98, S99, S100, S101'). Additional information was collated during meetings conducted at WHO regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence. Mortality data were extremely sparse and generally represent hospital-based deaths only. Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year. Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis. These data should help to define control strategies and reinforce leishmaniasis advocacy.
PLoS ONE 01/2012; 7(5):e35671. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Post-kala-azar dermal leishmaniasis (PKDL) is a cutaneous complication of visceral leishmaniasis (VL) which usually appears
after treatment of a VL episode. The incidence of PKDL varies across countries and no up-to-date global estimate is available.
Parasitological diagnostic tests show either low sensitivity or are difficult to decentralize in the field (e.g., polymerase
chain reaction). Available treatments are long, costly, and frequently toxic. It is believed that PKDL has a multi-factorial
and complex origin. It is widely accepted that persons with PKDL harbor Leishmania parasites in the skin and, therefore, act as reservoirs of infection in VL transmission, especially during interepidemic
periods. PKDL poses a serious threat to the success of the VL elimination program in South Asia, and requires an immediate
and focused strategy from the health authorities in charge of the national programs in India, Nepal, and Bangladesh. Control
and research efforts are urgently needed to improve PKDL surveillance and case management in order to reduce delays in diagnosis
and treatment and, hence, reduce morbidity and the risk of transmission.
KeywordsBangladesh-India-Kala-azar-Nepal-Post-kala-azar dermal leishmaniasis-Visceral leishmaniasis elimination program-Visceral leishmaniasis
[Show abstract][Hide abstract] ABSTRACT: The study presents the findings of a population-based survey of the annual incidence of visceral leishmaniasis (VL) in the rural areas of one VL-endemic district in Bihar, India. Stratified multi-stage sampling was applied in the selection of blocks, villages, hamlets, and households. We screened 15 178 households (91 000 individuals) in 80 villages in 7 of 27 administrative blocks of the district, East Champaran. We identified 227 VL cases that occurred in the past 12 months: 149 treated individuals who survived, 14 who died from VL, and 64 active cases. The high-incidence stratum had an estimated incidence of 35.6 cases per 10 000 persons per year (90% CI: 27.7-45.7). The annual incidence rate in the medium stratum areas was 16.8 cases per 10 000 (90% CI: 9.3-30.6). The combined annual incidence rate for the high and medium areas combined was 21.9 cases per 10 000 per year, (90% CI: 14.0-34.2). The Government of India's VL elimination goal is to reduce the VL incidence to one case per 10 000 at the sub-district level; thus, a 35-fold reduction will be required in those areas with the highest VL incidence.
Tropical Medicine & International Health 07/2010; 15 Suppl 2:4-11. · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To estimate the economic burden of visceral leishmaniasis (VL) on the rural population of one VL endemic district of Bihar, the state with 85% of India's cases.
Using a survey of a stratified multistage sampling of 15 178 households with 214 individuals with VL in the previous 12 months, the study provides data on VL treatment expenditures, financing and days of work lost in the context of overall household expenditures, income sources and assets.
Median household expenditures on VL treatment represent, on average, 11% of annual household expenditures and an estimated 7 months of an individual's income at the daily wage in rural Bihar. With 87% of households forced to take out loans to finance disease costs, VL can contribute to a spiral of increasing poverty. The current pattern of VL treatment, with multiple visits and treatments for a single episode of illness, significantly increases the economic burden on the household.
India's National Elimination Program to make effective treatments accessible to the rural poor, if combined with expanded efforts to improve timely access to diagnosis by conducting rapid diagnostic tests closer to the community (and mobilizing the rural population to seek effective treatment earlier), can reduce VL's economic burden on India's rural households.
Tropical Medicine & International Health 07/2010; 15 Suppl 2:42-9. · 2.94 Impact Factor
[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: Leishmania-HIV co-infection has been globally controlled in Southern Europe since 1997 because of highly active anti retroviral therapy (HAART), but it appears to be an increasing problem in other countries such as Ethopia, Sudan, Brazil or India where both infections are becoming more and more prevalent. Most of the scientific background on Leishmania/HIV co-infection has been dropped from the Mediterranean experience and although the situations among countries are not fully comparable, it is of high importance to take advantage of this knowledge. In this review several aspects of the Leishmania/HIV co-infection are emphasized viz., epidemiological features, new ways of transmission, pathogenesis, clinical outcome, diagnosis, treatment and secondary prohylaxis. An extensive review of the literature on Leishmania/HIV co-infection has allowed the inclusion of a comprehensive and updated list of bibliographical references.
The Indian Journal of Medical Research 04/2006; 123(3):357-88. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dengue, leishmaniasis, and African trypanosomiasis (sleeping sickness) are serious diseases that the World Health Organization (WHO) characterizes as lacking effective control measures. They are transmitted by insect vectors and can result in epidemic outbreaks. Specific treatment is unavailable for dengue, although good supportive treatment can drastically reduce mortality. For the leishmaniases and for sleeping sickness, treatment relies largely on antiquated drugs based on antimony and arsenic, respectively. Sustained control of the insect vectors is difficult for dengue and leishmaniasis because their high reproductive potential allows the vector populations to recover quickly after intervention wherever adequate breeding conditions exist. By contrast, tsetse flies, the vectors for sleeping sickness, have a much lower reproductive potential and could be eliminated over large areas, given adequate organization and surveillance. Through the African Union, African nations are developing a large-scale initiative for areawide elimination of tsetse flies, partly because of sleeping sickness, but also because of their importance as vectors of animal trypanosomiasis, which poses a serious constraint to livestock development and agriculture.
Disease Control Priorities in Developing Countries, 2nd edited by Dean T Jamison, Joel G Breman, Anthony R Measham, George Alleyne, Mariam Claeson, David B Evans, Prabhat Jha, Anne Mills, Philip Musgrove, 01/2006: chapter Chapter 23; World Bank., ISBN: 0821361791
[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