Advertisement
  • Loading metrics

Complexities of Assessing the Disease Burden Attributable to Leishmaniasis

  • Caryn Bern ,

    CBern@cdc.gov

    Affiliation Division of Parasitic Diseases, National Center for Zoonotic, Vector-Borne and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

  • James H. Maguire,

    Affiliation Harvard Medical School and Division of Infectious Disease, Brigham and Women's Hospital, Boston, Massachusetts, United States of America

  • Jorge Alvar

    Affiliation Department for the Control of Neglected Tropical Diseases (HTM/NTD/IDM), Leishmaniasis Control Program, World Health Organization, Geneva, Switzerland

Complexities of Assessing the Disease Burden Attributable to Leishmaniasis

  • Caryn Bern, 
  • James H. Maguire, 
  • Jorge Alvar
PLOS
x

Abstract

Among parasitic diseases, morbidity and mortality caused by leishmaniasis are surpassed only by malaria and lymphatic filariasis. However, estimation of the leishmaniasis disease burden is challenging, due to clinical and epidemiological diversity, marked geographic clustering, and lack of reliable data on incidence, duration, and impact of the various disease syndromes. Non-health effects such as impoverishment, disfigurement, and stigma add to the burden, and introduce further complexities. Leishmaniasis occurs globally, but has disproportionate impact in the Horn of Africa, South Asia and Brazil (for visceral leishmaniasis), and Latin America, Central Asia, and southwestern Asia (for cutaneous leishmaniasis). Disease characteristics and challenges for control are reviewed for each of these foci. We recommend review of reliable secondary data sources and collection of baseline active survey data to improve current disease burden estimates, plus the improvement or establishment of effective surveillance systems to monitor the impact of control efforts.

Introduction

Leishmaniasis comprises a complex of vector-borne diseases, caused by more than 20 species of the protozoan genus Leishmania, and ranging from localized skin ulcers to lethal systemic disease [1],[2]. Leishmaniasis is classified as one of the “most neglected diseases” [3], based on the limited resources invested in diagnosis, treatment, and control, and its strong association with poverty [4]. Published disease burden estimates place leishmaniasis second in mortality and fourth in morbidity among all tropical diseases [5].

The tools exist to achieve much better control of leishmaniasis. Research efforts over the past decade have augmented the range of field-applicable diagnostic tools and effective antileishmanial drugs available, especially for visceral leishmaniasis [6]. Appropriate use of vector control interventions, such as insecticide-treated nets and indoor residual spraying, would greatly reduce incidence [7][10]. Nevertheless, leishmaniasis control efforts have been impeded by the lack of a simple strategy, such as a vaccine. With the impetus of a “rapid impact package” for the small group of neglected diseases amenable to control through mass drug administration [11], leishmaniasis is in danger of becoming an even more neglected disease.

The characteristics that complicate large-scale interventions against leishmaniasis also present a challenge to preparing realistic disease burden estimates. Leishmaniasis incidence is geographically heterogeneous: while the rate across a region may appear low, focal areas are intensely affected [9],[12]. Leishmaniasis causes highly varied clinical syndromes, each presenting distinct diagnostic challenges, most requiring prolonged, expensive drug therapy, and each contributing differently to disease burden. Interactions with malnutrition and HIV alter the clinical course, and complicate therapeutic strategies [13],[14]. Epidemiologic features and the choice of appropriate control measures vary with parasite species and geographic area, depending on reservoir hosts and biological aspects of the vectors [2]. Finally, the impact on patients and their families does not end with health effects, but includes the social and psychological stigma of visible lesions and disfigurement, and significant economic losses [4]. This article reviews the major clinical features and epidemiology of leishmaniasis, and describes aspects of the disease burden in the most important foci.

Clinical Features

The most common syndrome is localized cutaneous leishmaniasis (CL), most frequently caused by Leishmania major and L. tropica in the Old World, and L. braziliensis, L. mexicana, and related species in the New World [1],[15]. Spontaneous healing is the rule, but requires months to years, and varies by species [15]. Mucosal leishmaniasis (ML) usually occurs months or years after healing of primary CL, most commonly due to L. braziliensis, and can cause destruction of the nasal septum, palate, and other mucosal structures, leading to devastating facial mutilation and, rarely, death from airway involvement [16]. Other complicated forms include disseminated cutaneous leishmaniasis (DCL), diffuse nodular non-ulcerating disease, and leishmaniasis recidivans, localized slowly progressive non-healing lesions. Both are rare, difficult to treat, and can be severe.

Visceral leishmaniasis (VL) is usually caused by L. donovani and L. infantum, and is characterized by progressive fever, weight loss, splenomegaly, hepatomegaly, hypergammaglobulinemia, and pancytopenia [1]. Complications include immunosuppression and secondary bacterial infections, hemorrhage, anemia, and, when kala-azar occurs during pregnancy, fetal wastage or congenital leishmaniasis [17]. Kala-azar is lethal in nearly all untreated cases [18],[19]. Even in treated patients, case-fatality rates are often 10% or higher; jaundice, wasting, severe anemia, and HIV co-infection are associated with increased risk of mortality [9],[20],[21].

Post-kala-azar dermal leishmaniasis (PKDL) is a chronic rash seen in apparently cured kala-azar patients in South Asia and the Horn of Africa [22],[23]. PKDL patients present with erythematous or hypopigmented macules, sometimes progressing to plaques or nodules. In Sudan, PKDL is reported to resolve without treatment in most mild cases, while the condition is said to require universal treatment in South Asia [23]. However, recent data from Bangladesh suggest that a proportion of PKDL cases self-resolve in South Asia as well [24]. Up to 60% of kala-azar patients develop PKDL in Sudan [23]; in South Asia, prospective data are lacking, but the cumulative incidence is currently thought to be in the range of 10%–20% [22],[24].

HIV–leishmaniasis co-infection poses a growing problem in developing countries [13]. In HIV-infected individuals without severe immunosuppression, manifestations are similar to those in immunocompetent persons. Among those with CD4+ T lymphocyte counts <200 cells/µL, manifestations of leishmaniasis may be more severe or affect unusual sites such as the gastrointestinal tract [25]. In the absence of highly active antiretroviral therapy (HAART), the relapse rate after treatment approaches 100% [13].

Epidemiology and Ecology

The leishmaniases are transmitted to humans in sylvatic, domestic, and peridomestic cycles ranging from cities to deserts and rain forests on every continent except Australia and Antarctica (Table 1). Nevertheless, the human disease burden is relatively concentrated; 90% of VL cases occur in India, Bangladesh, Nepal, Sudan, Ethiopia, and Brazil, while 90% of CL occurs in Afghanistan, Algeria, Iran, Saudi Arabia, Syria, Brazil, Colombia, Peru, and Bolivia [26],[27]. The distribution is dynamic: Colombia and Ethiopia have recently joined this list, and Pakistan currently faces a large epidemic of CL in Baluchistan and Sindh (World Health Organization [WHO], unpublished data). Climate change and other environmental changes have the potential to expand the geographic range of the vectors and leishmaniasis transmission in the future [28].

thumbnail
Table 1. Characteristics of the major geographic foci of leishmaniasis.

https://doi.org/10.1371/journal.pntd.0000313.t001

In sylvatic cycles, such as those in New World rain forests and the deserts of Central Asia, animal reservoir hosts can maintain enzootic transmission indefinitely without human disease. Sporadic or epidemic leishmaniasis occurs when humans enter the sylvatic habitat for economic or military purposes, or when human habitation encroaches on the sylvatic setting. In domestic cycles, humans or dogs form the predominant or sole infection reservoir. The foci that account for the largest number of human cases, for example, VL in South Asia and CL in Afghanistan, usually reflect anthroponotic transmission [1],[29]. In anthroponotic VL foci, the reservoir includes humans with untreated kala-azar [9], but PKDL patients may maintain the infection between kala-azar epidemics [30]. Up to half the population in highly affected foci may have asymptomatic leishmanial infection; the contribution of such individuals to transmission is presumed to be less than for active kala-azar, but has never been quantified [31],[32].

Disease Burden Estimates

The most objective measures of disease burden are incidence, prevalence, and mortality. Several derived measures incorporate indicators of disease severity, disability, and/or quality of life into composite outcomes that can be compared across diseases [33]. Currently, the most widely used measure is “disability-adjusted life years lost” (DALY) [5],[33]. Leishmaniasis DALY estimates are based on (1) figures assumed for regional incidence and prevalence, (2) assumed case-fatality rates, and (3) assigned disability weights for CL and VL [33]. For leishmaniasis, there are major uncertainties and sparse documentation for the assumptions underlying all three of these components. The empirical basis and derivation of global and regional leishmaniasis incidence and prevalence figures have not been documented since 1991 [34],[35]. Passive surveillance is generally given as their basis, but leishmaniasis is notifiable in only 33 of 88 endemic countries [26]. Substantial underreporting is widely acknowledged [26], but its magnitude has rarely been measured, and in studies, has varied from 2-fold to 40-fold [36][38]. In many countries, the majority of leishmaniasis cases are treated by non-governmental organizations or in the private sector, but these cases are not usually included in surveillance data, exacerbating underreporting. Underreporting is likely to vary greatly, not only among countries and depending on the clinical syndrome, but even between localities in the same district, based on distance to health care, availability of private providers and of antileishmanial drugs, the presence of research groups, and local awareness of the disease. Differential underreporting is labor-intensive to document, and precludes valid generalization of incidence and reporting rates presented in research studies. Underreporting of deaths is even more pronounced. One study from Sudan estimates that 91% of all kala-azar deaths went unrecognized [39], while data from a village-based study in India suggest that as many as 20% of VL patients, disproportionately poor and female, died before their disease was recognized [40]. The origin and derivation of the disability weights assigned for VL and CL are not documented [33]. In the absence of data to address these shortcomings, this article will describe the characteristics of leishmaniasis that contribute to the disease burden in the most important foci, and aspects that should be taken into account in future attempts to quantify its impact and monitor control programs.

Horn of Africa

In global estimates, the Horn of Africa (Sudan, Ethiopia, Kenya, Somalia) accounts for the second largest number of annual VL cases, after South Asia [41]. Transmission dynamics are complex, involving parasites identified by standard laboratory techniques as both L. donovani and L. infantum [42],[43], and two distinct ecological settings, semi-arid regions in the north where Phlebotomus orientalis is the major vector, and the savanna and forest areas in the south where P. martini and P. celiae are found in association with Macrotermes termite mounds [44],[45]. Investigators have suggested that VL originated in the Sudan, based on the ancestral position of the circulating parasites in genetic analyses [46],[47]. While sporadic sylvatic VL transmission is well recognized [48], sustained peridomestic and domestic cycles in villages, and explosive epidemics affecting populations displaced in recent wars, account for the bulk of human cases [42],[43],[49]. In zoonotic foci, both sylvatic rodents [50] and domestic dogs [51] may act as infection reservoirs, but large outbreaks are usually thought to involve anthroponotic transmission.

The association of leishmaniasis epidemics with war, ecological disasters, famine, and forced migration is most marked in the Horn of Africa. During the long civil war in Sudan, hundreds of thousands of VL cases occurred, causing the deaths of 30%–60% of the population in many communities [49]. The high attack rates among all ages and very high mortality rates were due to the confluence of displaced populations with no immunity, high rates of malnutrition, and lack of treatment access [20],[49],[52],[53]. Malnutrition is a major determinant of both progression to and severity of clinically manifest VL [14],[54],[55], and greatly increases the case-fatality rate [20]. Poverty, poor housing, crowded conditions, lack of personal protective modalities such as bed nets, environmental degradation, and collapse of health care systems intensify the spread and impact of VL in these settings. Seasonal labor movements may also spread the disease: introduction of the parasite by returning migrant farm workers is thought to have initiated an outbreak of VL in north central Ethiopia, an area not previously endemic [42]. VL epidemics with similar underlying causes have occurred recently in Somalia [56],[57] and Kenya [58],[59]. Cutaneous leishmaniasis may also accompany population displacements, for example, in Kurdish refugee camps in north Syria, Sudanese refugee camps in Chad, and among returned refugees in Afghanistan [60][62] (and WHO, unpublished data).

HIV–VL co-infection further complicates the picture by accelerating the progression of both diseases and making VL virtually untreatable in the absence of HAART [13],[63]. The Tigray region, bordering Eritrea and Sudan, has high rates of both HIV and VL among the many soldiers and seasonal workers; seasonal workers often sleep under Acacia trees where sand flies rest, increasing risk of VL [44]. In recent studies in Tigray, 20%–30% of VL patients were co-infected with HIV; co-infection was associated with a 5-fold increase in mortality within 6 months, lower clinical cure rates with frequent relapses, and increased side effects from antimonial drugs [64],[65]. HIV–VL co-infected patients are highly infectious to sand flies [66], and have the potential to spread resistant parasite clones, posing an additional threat to control programs.

South Asia (India, Nepal, and Bangladesh)

If Sudan is the original home of VL, South Asia is its domestic heartland. In the 19th century, devastating outbreaks of a chronic progressive febrile illness with cachexia, hepatosplenomegaly, and high fatality rates were reported in Bengal and Assam, and retrospectively thought to be the first recorded VL epidemics [19]. In 1903, Leishman and Donovan first described the organism that now bears their names in patients infected in India [67],[68]. Today, South Asia is estimated to account for 60% of the global VL disease burden [41], with a sustained endemic focus stretching from Bihar and Bengal in northeastern India, across the border into southeastern Nepal, and to the east into central and western Bangladesh. The parasite in South Asia is transmitted by Phlebotomus argentipes, an endophilic vector that rests in human and animal dwellings in densely populated agricultural villages. Kala-azar incidence fell substantially during the indoor residual insecticide spray campaigns of the malaria eradication effort of the 1950s and 1960s, but the disease returned in the 1970s and transmission has been sustained since then [69],[70].

Superimposed on this poorly controlled endemic picture, India has experienced recurrent epidemics in the 1970s and early 1990s, and Bangladesh has seen a progressive increase in VL incidence from the mid-1990s to the present that shows no signs of abating [12],[69],[70]. In most areas, there is a fairly stable incidence of two to three kala-azar cases per 1,000 population per year [36], but with localized foci of intense transmission and 10-fold higher annual incidence rates [71]. Transmission hot spots may be sustained for several years, but then appear to burn out, limited by saturation of the susceptible population [9]; increases in incidence are then seen in neighboring areas. Several years after peaks in kala-azar incidence, the same communities may see large numbers of PKDL cases, in an echo of the original kala-azar outbreak [24]. PKDL patients remain infectious for years to decades [30], and require prolonged antileishmanial treatment, up to 120 days [72], representing a significant challenge to health care systems in which kala-azar patients experience difficulty obtaining much shorter treatment courses [73].

Facility-based studies from South Asia often report higher kala-azar incidence in males than females [74]; community-based data suggest that there is little difference in incidence by sex, but substantial differences in care-seeking behavior [40],[71]. In South Asia, the mean duration of kala-azar illness before treatment is 3–5 months; on average, women are ill longer than men, and are more likely to die from the disease [8],[40],[71],[75],[76]. In one highly affected village in Bangladesh, reproductive-age women were three times as likely to die from kala-azar compared to men or children; kala-azar accounted for 23% of all deaths, and 80% of those in adult women [71],[73]. Qualitative data from the same village suggest that women experience higher barriers to seeking care [71],[75]; poorer baseline iron, zinc, and vitamin A status may also play a role in higher morbidity and mortality among women [31].

Although the morbidity and mortality caused by kala-azar and PKDL are substantial, the impact on affected individuals and their families is compounded by the expense and time involved in gaining access to appropriate diagnosis and treatment. The cost of caring for a patient with kala-azar in South Asia (US$80–US$120) approaches or surpasses the annual per capita income, and substantial additional income is lost by patients and family members unable to work [73], [77][79]. In Bihar and southern Nepal, costs have been multiplied many-fold by resistance to antimonial drugs and the imperative to use more expensive alternatives [6],[80],[81]. The upsurge in PKDL cases now seen in Bangladesh will also increase difficulties for patients and their families; even if the drug is supplied gratis, the 120-day parenteral treatment course entails many other costs, such as payments for daily injections and transport to the health care facility, and is associated with much lost work time. Anecdotally, a number of PKDL patients died suddenly during treatment, consistent with antimonial cardiotoxicity [24].

Visceral Leishmaniasis in Brazil and Other Parts of Latin America

From Mexico to Argentina, L. infantum (synonym L. chagasi) is transmitted from dogs to humans primarily by Lutzomyia longipalpis, a vector well adapted to the domestic and peridomestic environment. Brazil accounts for 90% of reported VL cases in the Americas, and is the third most important VL focus globally [82]; unlike other major VL foci, case reporting is mandatory in Brazil, and surveillance data are more complete. However, American VL is in the midst of dramatic changes in transmission patterns and a marked geographic expansion, superseding previous estimates of disease burden.

VL traditionally occurred in poor rural areas in dry northeast Brazil. In the early 1980s, the first of a series of urban epidemics occurred in Teresina [83], followed by outbreaks in São Luis, Natal, Fortaleza, and elsewhere [84]. Periurban VL outbreaks followed the massive migration of rural populations to the periphery of large cities because of drought, loss of farmland, and poverty [85]. In rapidly growing, densely settled favelas, environmental degradation, precarious living conditions, inadequate sewage and garbage disposal, and close contact with dogs and other domestic animals promote vector proliferation and disease transmission [86],[87]. The reported VL incidence in Brazil doubled from a mean of 1,500 cases per year in the 1980s to more than 3,000 per year from 2000 to 2005; the disease now occurs in urban, periurban, and rural areas as far south as the states of São Paulo and Mato Grosso do Sul, in addition to the traditionally endemic northeast [82]. Children, particularly those with malnutrition, have the highest risk for kala-azar [14],[55]; the case-fatality rate approaches 10% in some centers, despite good availability of treatment [88]. Although the geographic ranges of HIV infection and VL overlap and continue to expand, the number of reported cases of VL with AIDS (176 from 2001–2005) has been fewer than expected, perhaps because of free, universal distribution of antiretroviral drugs by the Brazilian government, and some degree of underrecognition by clinicians [89]. An additional 315 cases of VL–HIV co-infection without AIDS are estimated to have occurred during that period [90].

Control of zoonotic VL has proved difficult. From 1999–2005, human VL incidence remained high despite aggressive control efforts centered on culling of infected dogs and insecticide application [91]. The failure of the previous control strategy [92], and demonstration of canine infections and subclinical human infections in areas not previously endemic [93], have led to a revised national strategy that includes surveillance and preventive measures in areas considered at risk for infection, even in the absence of clinical cases [82].

Cutaneous Leishmaniasis in the Americas

At least 12 different Leishmania species cause American CL, and the disease occurs in every country from the United States to Argentina, except Uruguay and Chile. Until recently, Brazil and Peru reported the first and second highest incidence in the Americas [15],[26]. However, with more than 15,000 reported cases in 2005 and 2006, Colombia now ranks second after Brazil (>30,000 per year); thousands of cases occur in Peru (∼6,500 per year) and elsewhere in Latin America as well [15],[89],[94],[95]. The epidemiology of CL in the Americas is complex, with intra- and inter-specific variation in transmission cycles, reservoir hosts, sand fly vectors, clinical manifestations, and response to therapy [96]. Studies often demonstrate five or more species causing lesions in the same area [97][99].

There has been an expansion both in the geographic range and risk factors for CL transmission. In the past, American CL was predominantly an occupational disease, related to activities in forests and other enzootic areas. Occupational exposures remain important, as demonstrated by 3,163 reported CL cases among Colombian soldiers infected during patrols in forested areas held by insurgents in 2004 [60]. However, widespread deforestation has led to a rapid increase in cases, rather than a decrease as once predicted, and to peridomestic, periurban, and even urban transmission [100]. For example, from 1980 to 2001, there was a 10-fold increase in CL incidence and spread to all of the states of Brazil [63],[101]. Outbreaks in newly arrived, immunologically naive immigrants have occurred in new settlements in previously forested areas [102] and among economic migrants in the lowlands of Bolivia [103]. A contrasting report documents new occurrence of L. amazonensis infection in a settled population in a sub-Andean region of Bolivia at 1,450–2,100 meters above sea level, presumably reflecting spread from its traditional lowland focus [104].

CL patients face social stigma and isolation [27]. A study from Colombia reported that cutaneous ulcers in a woman can be the pretext for spousal abandonment [105]. Among Ecuadorian villagers, almost 70% of persons believed that CL interfered with the capacity to work, while 82% stated that the presence of an ulcer or scar diminished self-esteem [106]. Participants mentioned over 150 different treatments for CL, including potentially harmful application of acids, gasoline, and lighted matches [106]. Disfiguring, mutilating, and occasionally life-threatening lesions of ML have been reported in 25%, 14%, 2%, and 0.3% of persons with L. braziliensis infections in Bolivia, Peru, Colombia, and Venezuela, respectively [107]. Diffuse cutaneous leishmaniasis, like ML, does not heal spontaneously and is difficult to treat; although rare, this syndrome can occur in persons with L. amazonensis or L. mexicana infections, or co-infection with HIV and other species of Leishmania [101]. The nodular lesions resemble those of lepromatous leprosy, and persons with DCL can suffer stigma similar to that associated with leprosy.

CL in the Americas is a disease of the poor; in many countries, patients and their families shoulder the high cost of treatment, and suffer substantial lost income. For example, in Guatemala, the cost of treatment is about US$250, beyond the means of most rural inhabitants [27]. The disease also causes a major financial burden on public health systems. Treatment is provided free of charge by the governments of Colombia, where the cost of pentavalent antimony is approximately US$345 per person cured [108], and in Brazil, which has spent the equivalent of US$2.5 million to treat 35,000 persons with antimonial drugs, and an additional US$500,000 to treat 95 persons with liposomal amphotericin [27].

Anthroponotic CL in Afghanistan and Southwestern Asia

Of the major forms of leishmaniasis, the only historically urbanized form is anthroponotic CL due to L. tropica, as illustrated by its vernacular names, “Baghdad boil”, “Aleppo boil”, “Balkh sore”, and others [46]. Although infections in dogs and other animals have been documented, the disease is characterized by large outbreaks in densely populated cities, especially in the setting of war and large-scale population migration. In Syria, especially the traditional focus in the city of Aleppo, a marked increase to more than 15,000 cases per year was documented during the 1990s, with only a temporary decline when insecticide spray programs were instituted in 1991 [109]. A huge CL epidemic has occurred in Afghanistan since 1992, with estimates of 200,000 cases in Kabul alone [110]. The annual CL incidence in Kabul peaked at 12% in 1996, and averaged 3% per year from 1992 to 2002 [29],[62]. The association between migration and CL transmission may be more complex than originally postulated: while migrants within Kabul were at the highest risk of CL, possibly because of economic disadvantage, immigrants from outside Kabul were at no higher risk, but appeared to fuel local transmission by adding to the pool of susceptible residents [62]. Transmission occurred within the household, even up to second floor apartments [111], and often resulted in facial lesions, especially in women and children [62]. Women with lesions were considered unfit to marry, have children, or breastfeed, and children with lesions were sometimes ostracized by playmates [112].

Conclusions and Recommendations

Current methods of assessing disease burden fail to take into account the clinical and epidemiological diversity of leishmaniasis, and the intense medical, social, and economic impact within highly affected foci. Furthermore, existing passive surveillance data are grossly inadequate to be used to make reliable estimates. Active, rigorous assessments of the true incidence, morbidity, mortality, current transmission patterns, and non-health effects of leishmaniasis are urgently needed. The following steps are recommended to achieve better estimates of current disease burden, and establish systems to monitor the impact of control measures:

  1. Assessment of the critical needs for data by geographic focus, and development of focus-specific strategies for filling in the many data gaps. Leishmaniasis foci targeted for elimination or intensified control should be given highest priority. In areas without reliable data, on-the-ground rapid epidemiologic assessments may be necessary to develop an appropriate plan for data collection. Strategies include reviews of existing data, baseline field surveys, and establishment of surveillance systems. More than one technique may be needed in a single focus.
  2. Reviews of reported incidence and mortality data. Potential data sources include existing surveillance systems, hospital and specialized treatment facility records, and past surveys. Data analysis should be preceded by a critical assessment of data sources, quality, and potential biases.
  3. Where indicated, baseline surveys to collect empirical incidence and prevalence data, with the focus on the most affected regions, and those with planned elimination or intensified control programs. Appropriate case definitions and techniques to capture illness onset, severity, and duration should be developed and tested before deployment. Surveys must be carefully designed to avoid biases due to disease clustering, employ valid statistical methods, ensure adequate sample size, and, if possible, employ new mapping technologies. Specialized sampling and analysis methods, such as adaptive sampling [113], may be necessary to address the clustered transmission pattern of leishmaniasis. Wherever practical, risk factor assessments should be incorporated into baseline surveys in order to guide control efforts and make the best use of limited resources.
  4. The data collected in rapid assessments and baseline surveys should be used to evaluate and improve existing leishmaniasis surveillance and reporting systems. In areas without existing surveillance, systems should be established. Where complete coverage is not feasible, sentinel surveillance based on carefully selected, sustainable sites with known catchment populations may be the best option to provide data to evaluate trends over time [114]. Systems should be tailored to local conditions, but should be subject to ongoing evaluation to ensure reliability and appropriateness to monitor the impact of control programs.
  5. Studies and/or surveillance system components should be designed to provide measures of disease impact, severity, and duration that realistically reflect the heterogeneity of leishmaniasis. This effort should incorporate new thinking on disease burden assessment [115], for example, including the impact of non-health outcomes, such as economic costs, and interaction with malnutrition or other conditions.
  6. The data resulting from the above efforts should be incorporated into a more precise assessment of disease burden, including periodic reassessments as conditions change and new assessment tools become available.

Acknowledgments

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

References

  1. 1. Jeronimo SMB, de Queiroz Sousa A, Pearson RD (2006) Leishmaniasis. In: Guerrant RL, Walker DH, Weller PF, editors. Tropical infectious diseases: principles, pathogens and practice. Edinburgh, Scotland: Churchill Livingstone Elsevier. pp. 1095–1113.SMB JeronimoA. de Queiroz SousaRD Pearson2006Leishmaniasis.RL GuerrantDH WalkerPF WellerTropical infectious diseases: principles, pathogens and practiceEdinburgh, ScotlandChurchill Livingstone Elsevier10951113
  2. 2. World Health Organization (1990) Control of the leishmaniases. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser 793: 1–158.World Health Organization1990Control of the leishmaniases. Report of a WHO Expert Committee.World Health Organ Tech Rep Ser7931158
  3. 3. Yamey G, Torreele E (2002) The world's most neglected diseases [editorial]. British Medical Journal 325: 176–177.G. YameyE. Torreele2002The world's most neglected diseases [editorial].British Medical Journal325176177
  4. 4. Alvar J, Yactayo S, Bern C (2006) Leishmaniasis and poverty. Trends Parasitol 22: 552–557.J. AlvarS. YactayoC. Bern2006Leishmaniasis and poverty.Trends Parasitol22552557
  5. 5. Mathers CD, Ezzati M, Lopez AD (2007) Measuring the burden of neglected tropical diseases: the global burden of disease framework. PLoS Negl Trop Dis 1: e114.CD MathersM. EzzatiAD Lopez2007Measuring the burden of neglected tropical diseases: the global burden of disease framework.PLoS Negl Trop Dis1e114
  6. 6. Murray HW (2004) Treatment of visceral leishmaniasis in 2004. Am J Trop Med Hyg 71: 787–794.HW Murray2004Treatment of visceral leishmaniasis in 2004.Am J Trop Med Hyg71787794
  7. 7. Reyburn H, Ashford R, Mohsen M, Hewitt S, Rowland M (2000) A randomized controlled trial of insecticide-treated bednets and chaddars or top sheets, and residual spraying of interior rooms for the prevention of cutaneous leishmaniasis in Kabul, Afghanistan. Trans R Soc Trop Med Hyg 94: 361–366.H. ReyburnR. AshfordM. MohsenS. HewittM. Rowland2000A randomized controlled trial of insecticide-treated bednets and chaddars or top sheets, and residual spraying of interior rooms for the prevention of cutaneous leishmaniasis in Kabul, Afghanistan.Trans R Soc Trop Med Hyg94361366
  8. 8. Bern C, Joshi AB, Jha SN, Das ML, Hightower A, et al. (2000) Factors associated with visceral leishmaniasis in Nepal: bed-net use is strongly protective. American Journal of Tropical Medicine and Hygiene 63: 184–188.C. BernAB JoshiSN JhaML DasA. Hightower2000Factors associated with visceral leishmaniasis in Nepal: bed-net use is strongly protective.American Journal of Tropical Medicine and Hygiene63184188
  9. 9. Bern C, Hightower AW, Chowdhury R, Ali M, Amann J, et al. (2005) Risk factors for kala-azar in Bangladesh. Emerging Infectious Diseases 11: 655–662.C. BernAW HightowerR. ChowdhuryM. AliJ. Amann2005Risk factors for kala-azar in Bangladesh.Emerging Infectious Diseases11655662
  10. 10. Ritmeijer K, Davies C, van Zorge R, Wang SJ, Schorscher J, et al. (2007) Evaluation of a mass distribution programme for fine-mesh impregnated bednets against visceral leishmaniasis in eastern Sudan. Trop Med Int Health 12: 404–414.K. RitmeijerC. DaviesR. van ZorgeSJ WangJ. Schorscher2007Evaluation of a mass distribution programme for fine-mesh impregnated bednets against visceral leishmaniasis in eastern Sudan.Trop Med Int Health12404414
  11. 11. Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, et al. (2006) Incorporating a Rapid-Impact Package for Neglected Tropical Diseases with Programs for HIV/AIDS, Tuberculosis, and Malaria. PLoS Med 3: e102.PJ HotezDH MolyneuxA. FenwickE. OttesenS. Ehrlich Sachs2006Incorporating a Rapid-Impact Package for Neglected Tropical Diseases with Programs for HIV/AIDS, Tuberculosis, and Malaria.PLoS Med3e102
  12. 12. Bern C, Chowdhury R (2006) The epidemiology of visceral leishmaniasis in Bangladesh: prospects for improved control. Indian J Med Res 123: 275–288.C. BernR. Chowdhury2006The epidemiology of visceral leishmaniasis in Bangladesh: prospects for improved control.Indian J Med Res123275288
  13. 13. Alvar J, Aparicio P, Aseffa A, den Boer M, Cañavate C, et al. (2008) The Relationship between Leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev 21: 334–359.J. AlvarP. AparicioA. AseffaM. den BoerC. Cañavate2008The Relationship between Leishmaniasis and AIDS: the second 10 years.Clin Microbiol Rev21334359
  14. 14. Cerf BJ, Jones TC, Badaro R, Sampaio D, Teixeira R, et al. (1987) Malnutrition as a risk factor for severe visceral leishmaniasis. Journal of Infectious Diseases 156: 1030–1033.BJ CerfTC JonesR. BadaroD. SampaioR. Teixeira1987Malnutrition as a risk factor for severe visceral leishmaniasis.Journal of Infectious Diseases15610301033
  15. 15. Reithinger R, Dujardin JC, Louzir H, Pirmez C, Alexander B, et al. (2007) Cutaneous leishmaniasis. Lancet Infect Dis 7: 581–596.R. ReithingerJC DujardinH. LouzirC. PirmezB. Alexander2007Cutaneous leishmaniasis.Lancet Infect Dis7581596
  16. 16. Marsden PD (1986) Mucosal leishmaniasis (“espundia” Escomel, 1911). Trans R Soc Trop Med Hyg 80: 859–876.PD Marsden1986Mucosal leishmaniasis (“espundia” Escomel, 1911).Trans R Soc Trop Med Hyg80859876
  17. 17. Pagliano P, Carannante N, Rossi M, Gramiccia M, Gradoni L, et al. (2005) Visceral leishmaniasis in pregnancy: a case series and a systematic review of the literature. J Antimicrob Chemother 55: 229–233.P. PaglianoN. CarannanteM. RossiM. GramicciaL. Gradoni2005Visceral leishmaniasis in pregnancy: a case series and a systematic review of the literature.J Antimicrob Chemother55229233
  18. 18. Desjeux P (1996) Leishmaniasis. Public health aspects and control. Clin Dermatol 14: 417–423.P. Desjeux1996Leishmaniasis. Public health aspects and control.Clin Dermatol14417423
  19. 19. Sengupta PC (1947) History of kala-azar in India. Indian Medical Gazette 82: 281–286.PC Sengupta1947History of kala-azar in India.Indian Medical Gazette82281286
  20. 20. Collin S, Davidson R, Ritmeijer K, Keus K, Melaku Y, et al. (2004) Conflict and kala-azar: determinants of adverse outcomes of kala-azar among patients in southern Sudan. Clin Infect Dis 38: 612–619.S. CollinR. DavidsonK. RitmeijerK. KeusY. Melaku2004Conflict and kala-azar: determinants of adverse outcomes of kala-azar among patients in southern Sudan.Clin Infect Dis38612619
  21. 21. Rey LC, Martins CV, Ribeiro HB, Lima AA (2005) American visceral leishmaniasis (kala-azar) in hospitalized children from an endemic area. J Pediatr (Rio J) 81: 73–78.LC ReyCV MartinsHB RibeiroAA Lima2005American visceral leishmaniasis (kala-azar) in hospitalized children from an endemic area.J Pediatr (Rio J)817378
  22. 22. Ramesh V (1995) Post-kala-azar dermal leishmaniasis. International Journal of Dermatology 34: 85–91.V. Ramesh1995Post-kala-azar dermal leishmaniasis.International Journal of Dermatology348591
  23. 23. Zijlstra EE, Musa AM, Khalil EA, el-Hassan IM, el-Hassan AM (2003) Post-kala-azar dermal leishmaniasis. Lancet Infect Dis 3: 87–98.EE ZijlstraAM MusaEA KhalilIM el-HassanAM el-Hassan2003Post-kala-azar dermal leishmaniasis.Lancet Infect Dis38798
  24. 24. ICDDRB (2007) Post kala-azar dermal leishmaniasis: New observations challenge previous assumptions. Health and Science Bulletin 5: 6–12.ICDDRB2007Post kala-azar dermal leishmaniasis: New observations challenge previous assumptions.Health and Science Bulletin5612
  25. 25. Alvar J, Canavate C, Gutierrez-Solar B, Jimenez M, Laguna F, et al. (1997) Leishmania and human immunodeficiency virus coinfection: the first 10 years. Clin Microbiol Rev 10: 298–319.J. AlvarC. CanavateB. Gutierrez-SolarM. JimenezF. Laguna1997Leishmania and human immunodeficiency virus coinfection: the first 10 years.Clin Microbiol Rev10298319
  26. 26. Desjeux P (2004) Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis 27: 305–318.P. Desjeux2004Leishmaniasis: current situation and new perspectives.Comp Immunol Microbiol Infect Dis27305318
  27. 27. Modabber F, Buffet PA, Torreele E, Milon G, Croft SL (2007) Consultative meeting to develop a strategy for treatment of cutaneous leishmaniasis. Institute Pasteur, Paris. 13–15 June, 2006. Kinetoplastid Biol Dis 6: 3.F. ModabberPA BuffetE. TorreeleG. MilonSL Croft2007Consultative meeting to develop a strategy for treatment of cutaneous leishmaniasis. Institute Pasteur, Paris. 13–15 June, 2006.Kinetoplastid Biol Dis63
  28. 28. Patz JA, Graczyk TK, Geller N, Vittor AY (2000) Effects of environmental change on emerging parasitic diseases. Int J Parasitol 30: 1395–1405.JA PatzTK GraczykN. GellerAY Vittor2000Effects of environmental change on emerging parasitic diseases.Int J Parasitol3013951405
  29. 29. Reithinger R, Mohsen M, Aadil K, Sidiqi M, Erasmus P, et al. (2003) Anthroponotic cutaneous leishmaniasis, Kabul, Afghanistan. Emerg Infect Dis 9: 727–729.R. ReithingerM. MohsenK. AadilM. SidiqiP. Erasmus2003Anthroponotic cutaneous leishmaniasis, Kabul, Afghanistan.Emerg Infect Dis9727729
  30. 30. Addy M, Nandy A (1992) Ten years of kala-azar in west Bengal, Part I. Did post-kala-azar dermal leishmaniasis initiate the outbreak in 24-Parganas? Bull World Health Organ 70: 341–346.M. AddyA. Nandy1992Ten years of kala-azar in west Bengal, Part I. Did post-kala-azar dermal leishmaniasis initiate the outbreak in 24-Parganas?Bull World Health Organ70341346
  31. 31. Bern C, Haque R, Chowdhury R, Ali M, Kurkjian KM, et al. (2007) The epidemiology of visceral leishmaniasis and asymptomatic leishmanial infection in a highly endemic Bangladeshi village. Am J Trop Med Hyg 76: 909–914.C. BernR. HaqueR. ChowdhuryM. AliKM Kurkjian2007The epidemiology of visceral leishmaniasis and asymptomatic leishmanial infection in a highly endemic Bangladeshi village.Am J Trop Med Hyg76909914
  32. 32. Costa CH, Stewart JM, Gomes RB, Garcez LM, Ramos PK, et al. (2002) Asymptomatic human carriers of Leishmania chagasi. Am J Trop Med Hyg 66: 334–337.CH CostaJM StewartRB GomesLM GarcezPK Ramos2002Asymptomatic human carriers of Leishmania chagasi.Am J Trop Med Hyg66334337
  33. 33. Murray C, Lopez A, editors. (1996) Global Burden of Disease: A comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Cambridge, MA: Harvard University Press. C. MurrayA. Lopez1996Global Burden of Disease: A comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020Cambridge, MAHarvard University Press
  34. 34. Ashford RW, Desjeux P, deRaadt P (1992) Estimation of population at risk of infection and number of cases of leishmaniasis. Parasitology Today 8: 104–105.RW AshfordP. DesjeuxP. deRaadt1992Estimation of population at risk of infection and number of cases of leishmaniasis.Parasitology Today8104105
  35. 35. Desjeux P (1991) Information on the epidemiology and control of the leishmaniases by country or territory. Geneva: World Health Organization. pp. 1–47.P. Desjeux1991Information on the epidemiology and control of the leishmaniases by country or territoryGenevaWorld Health Organization147
  36. 36. Singh SP, Reddy DC, Rai M, Sundar S (2006) Serious underreporting of visceral leishmaniasis through passive case reporting in Bihar, India. Trop Med Int Health 11: 899–905.SP SinghDC ReddyM. RaiS. Sundar2006Serious underreporting of visceral leishmaniasis through passive case reporting in Bihar, India.Trop Med Int Health11899905
  37. 37. Copeland HW, Arana BA, Navin TR (1990) Comparison of active and passive case detection of cutaneous leishmaniasis in Guatemala. Am J Trop Med Hyg 43: 257–259.HW CopelandBA AranaTR Navin1990Comparison of active and passive case detection of cutaneous leishmaniasis in Guatemala.Am J Trop Med Hyg43257259
  38. 38. Bora D, Singh J, Bhattacharjee J, Kureel VR, Singh S, et al. (1994) An estimate of kala azar in 1991 in district Vaishali and Bihar. J Commun Dis 26: 120–122.D. BoraJ. SinghJ. BhattacharjeeVR KureelS. Singh1994An estimate of kala azar in 1991 in district Vaishali and Bihar.J Commun Dis26120122
  39. 39. Collin SM, Coleman PG, Ritmeijer K, Davidson RN (2006) Unseen Kala-azar deaths in south Sudan (1999–2002). Trop Med Int Health 11: 509–512.SM CollinPG ColemanK. RitmeijerRN Davidson2006Unseen Kala-azar deaths in south Sudan (1999–2002).Trop Med Int Health11509512
  40. 40. Barnett P, Singh SP, Bern C, Hightower AW, Sundar S (2005) Virgin soil: the spread of visceral leishmaniasis into Uttar Pradesh, India. American Journal of Tropical Medicine and Hygiene 73: 720–725.P. BarnettSP SinghC. BernAW HightowerS. Sundar2005Virgin soil: the spread of visceral leishmaniasis into Uttar Pradesh, India.American Journal of Tropical Medicine and Hygiene73720725
  41. 41. World Health Organization (2002) Global Burden of Disease Estimates. Geneva: WHO. World Health Organization2002Global Burden of Disease EstimatesGenevaWHO
  42. 42. Alvar J, Bashaye S, Argaw D, Cruz I, Aparicio P, et al. (2007) Kala-azar outbreak in Libo Kemkem, Ethiopia: epidemiologic and parasitologic assessment. Am J Trop Med Hyg 77: 275–282.J. AlvarS. BashayeD. ArgawI. CruzP. Aparicio2007Kala-azar outbreak in Libo Kemkem, Ethiopia: epidemiologic and parasitologic assessment.Am J Trop Med Hyg77275282
  43. 43. Bucheton B, Kheir MM, El-Safi SH, Hammad A, Mergani A, et al. (2002) The interplay between environmental and host factors during an outbreak of visceral leishmaniasis in eastern Sudan. Microbes Infect 4: 1449–1457.B. BuchetonMM KheirSH El-SafiA. HammadA. Mergani2002The interplay between environmental and host factors during an outbreak of visceral leishmaniasis in eastern Sudan.Microbes Infect414491457
  44. 44. Elnaiem DA, Connor SJ, Thomson MC, Hassan MM, Hassan HK, et al. (1998) Environmental determinants of the distribution of Phlebotomus orientalis in Sudan. Ann Trop Med Parasitol 92: 877–887.DA ElnaiemSJ ConnorMC ThomsonMM HassanHK Hassan1998Environmental determinants of the distribution of Phlebotomus orientalis in Sudan.Ann Trop Med Parasitol92877887
  45. 45. Gebre-Michael T, Lane RP (1996) The roles of Phlebotomus martini and P.celiae (Diptera: Phlebotominae) as vectors of visceral leishmaniasis in the Aba Roba focus, southern Ethiopia. Med Vet Entomol 10: 53–62.T. Gebre-MichaelRP Lane1996The roles of Phlebotomus martini and P.celiae (Diptera: Phlebotominae) as vectors of visceral leishmaniasis in the Aba Roba focus, southern Ethiopia.Med Vet Entomol105362
  46. 46. Ashford RW (2000) The leishmaniases as emerging and reemerging zoonoses. Int J Parasitol 30: 1269–1281.RW Ashford2000The leishmaniases as emerging and reemerging zoonoses.Int J Parasitol3012691281
  47. 47. Pratlong F, Dereure J, Bucheton B, El-Saf S, Dessein A, et al. (2001) Sudan: the possible original focus of visceral leishmaniasis. Parasitology 122: 599–605.F. PratlongJ. DereureB. BuchetonS. El-SafA. Dessein2001Sudan: the possible original focus of visceral leishmaniasis.Parasitology122599605
  48. 48. Elnaiem DA, Hassan HK, Ward RD (1997) Phlebotomine sandflies in a focus of visceral leishmaniasis in a border area of eastern Sudan. Ann Trop Med Parasitol 91: 307–318.DA ElnaiemHK HassanRD Ward1997Phlebotomine sandflies in a focus of visceral leishmaniasis in a border area of eastern Sudan.Ann Trop Med Parasitol91307318
  49. 49. Seaman J, Mercer AJ, Sondorp E (1996) The epidemic of visceral leishmaniasis in western Upper Nile, southern Sudan: course and impact from 1984 to 1994. Int J Epidemiol 25: 862–871.J. SeamanAJ MercerE. Sondorp1996The epidemic of visceral leishmaniasis in western Upper Nile, southern Sudan: course and impact from 1984 to 1994.Int J Epidemiol25862871
  50. 50. Elnaiem DA, Hassan MM, Maingon R, Nureldin GH, Mekawi AM, et al. (2001) The Egyptian mongoose, Herpestes ichneumon, is a possible reservoir host of visceral leishmaniasis in eastern Sudan. Parasitology 122: 531–536.DA ElnaiemMM HassanR. MaingonGH NureldinAM Mekawi2001The Egyptian mongoose, Herpestes ichneumon, is a possible reservoir host of visceral leishmaniasis in eastern Sudan.Parasitology122531536
  51. 51. Dereure J, El-Safi SH, Bucheton B, Boni M, Kheir MM, et al. (2003) Visceral leishmaniasis in eastern Sudan: parasite identification in humans and dogs; host-parasite relationships. Microbes Infect 5: 1103–1108.J. DereureSH El-SafiB. BuchetonM. BoniMM Kheir2003Visceral leishmaniasis in eastern Sudan: parasite identification in humans and dogs; host-parasite relationships.Microbes Infect511031108
  52. 52. Desjeux P (2001) The increase in risk factors for leishmaniasis worldwide. Trans R Soc Trop Med Hyg 95: 239–243.P. Desjeux2001The increase in risk factors for leishmaniasis worldwide.Trans R Soc Trop Med Hyg95239243
  53. 53. Zijlstra EE, Ali MS, el-Hassan AM, el-Toum IA, Satti M, et al. (1991) Kala-azar in displaced people from southern Sudan: epidemiological, clinical and therapeutic findings. Trans R Soc Trop Med Hyg 85: 365–369.EE ZijlstraMS AliAM el-HassanIA el-ToumM. Satti1991Kala-azar in displaced people from southern Sudan: epidemiological, clinical and therapeutic findings.Trans R Soc Trop Med Hyg85365369
  54. 54. Anstead GM, Chandrasekar B, Zhao W, Yang J, Perez LE, et al. (2001) Malnutrition alters the innate immune response and increases early visceralization following Leishmania donovani infection. Infect Immun 69: 4709–4718.GM AnsteadB. ChandrasekarW. ZhaoJ. YangLE Perez2001Malnutrition alters the innate immune response and increases early visceralization following Leishmania donovani infection.Infect Immun6947094718
  55. 55. Badaro R, Jones TC, Lorenco R, Cerf BJ, Sampaio D, et al. (1986) A prospective study of visceral leishmaniasis in an endemic area of Brazil. J Infect Dis 154: 639–649.R. BadaroTC JonesR. LorencoBJ CerfD. Sampaio1986A prospective study of visceral leishmaniasis in an endemic area of Brazil.J Infect Dis154639649
  56. 56. Marlet MV, Wuillaume F, Jacquet D, Quispe KW, Dujardin JC, et al. (2003) A neglected disease of humans: a new focus of visceral leishmaniasis in Bakool, Somalia. Trans R Soc Trop Med Hyg 97: 667–671.MV MarletF. WuillaumeD. JacquetKW QuispeJC Dujardin2003A neglected disease of humans: a new focus of visceral leishmaniasis in Bakool, Somalia.Trans R Soc Trop Med Hyg97667671
  57. 57. Raguenaud ME, Jansson A, Vanlerberghe V, Van der Auwera G, Deborggraeve S, et al. (2007) Epidemiology and Clinical Features of Patients with Visceral Leishmaniasis Treated by an MSF Clinic in Bakool Region, Somalia, 2004–2006. PLoS Negl Trop Dis 1: e85.ME RaguenaudA. JanssonV. VanlerbergheG. Van der AuweraS. Deborggraeve2007Epidemiology and Clinical Features of Patients with Visceral Leishmaniasis Treated by an MSF Clinic in Bakool Region, Somalia, 2004–2006.PLoS Negl Trop Dis1e85
  58. 58. Boussery G, Boelaert M, van Peteghem J, Ejikon P, Henckaerts K (2001) Visceral leishmaniasis (kala-azar) outbreak in Somali refugees and Kenyan shepherds, Kenya. Emerg Infect Dis 7: 603–604.G. BousseryM. BoelaertJ. van PeteghemP. EjikonK. Henckaerts2001Visceral leishmaniasis (kala-azar) outbreak in Somali refugees and Kenyan shepherds, Kenya.Emerg Infect Dis7603604
  59. 59. Marlet MV, Sang DK, Ritmeijer K, Muga RO, Onsongo J, et al. (2003) Emergence or re-emergence of visceral leishmaniasis in areas of Somalia, north-eastern Kenya, and south-eastern Ethiopia in 2000–01. Trans R Soc Trop Med Hyg 97: 515–518.MV MarletDK SangK. RitmeijerRO MugaJ. Onsongo2003Emergence or re-emergence of visceral leishmaniasis in areas of Somalia, north-eastern Kenya, and south-eastern Ethiopia in 2000–01.Trans R Soc Trop Med Hyg97515518
  60. 60. Beyrer C, Villar JC, Suwanvanichkij V, Singh S, Baral SD, et al. (2007) Neglected diseases, civil conflicts, and the right to health. Lancet 370: 619–627.C. BeyrerJC VillarV. SuwanvanichkijS. SinghSD Baral2007Neglected diseases, civil conflicts, and the right to health.Lancet370619627
  61. 61. Reithinger R, Coleman PG (2007) Treating cutaneous leishmaniasis patients in Kabul, Afghanistan: cost-effectiveness of an operational program in a complex emergency setting. BMC Infect Dis 7: 3.R. ReithingerPG Coleman2007Treating cutaneous leishmaniasis patients in Kabul, Afghanistan: cost-effectiveness of an operational program in a complex emergency setting.BMC Infect Dis73
  62. 62. Reyburn H, Rowland M, Mohsen M, Khan B, Davies C (2003) The prolonged epidemic of anthroponotic cutaneous leishmaniasis in Kabul, Afghanistan: 'bringing down the neighbourhood'. Trans R Soc Trop Med Hyg 97: 170–176.H. ReyburnM. RowlandM. MohsenB. KhanC. Davies2003The prolonged epidemic of anthroponotic cutaneous leishmaniasis in Kabul, Afghanistan: 'bringing down the neighbourhood'.Trans R Soc Trop Med Hyg97170176
  63. 63. World Health OrganizationWorld Health OrganizationReport of the 5th Consultative Meeting on Leishmania/HIV Coinfection. WHO Technical Report Series WHO/CDS/NTD/IDM/2007.5.; 2007 20–22 March 2007; Addis Ababa, Ethiopia. Report of the 5th Consultative Meeting on Leishmania/HIV Coinfection. WHO Technical Report Series WHO/CDS/NTD/IDM/2007.5.; 2007 20–22 March 2007; Addis Ababa, Ethiopia.
  64. 64. Lyons S, Veeken H, Long J (2003) Visceral leishmaniasis and HIV in Tigray, Ethiopia. Trop Med Int Health 8: 733–739.S. LyonsH. VeekenJ. Long2003Visceral leishmaniasis and HIV in Tigray, Ethiopia.Trop Med Int Health8733739
  65. 65. Ritmeijer K, Dejenie A, Assefa Y, Hundie TB, Mesure J, et al. (2006) A comparison of miltefosine and sodium stibogluconate for treatment of visceral leishmaniasis in an Ethiopian population with high prevalence of HIV infection. Clin Infect Dis 43: 357–364.K. RitmeijerA. DejenieY. AssefaTB HundieJ. Mesure2006A comparison of miltefosine and sodium stibogluconate for treatment of visceral leishmaniasis in an Ethiopian population with high prevalence of HIV infection.Clin Infect Dis43357364
  66. 66. Molina R, Lohse JM, Pulido F, Laguna F, Lopez-Velez R, et al. (1999) Infection of sand flies by humans coinfected with Leishmania infantum and human immunodeficiency virus. Am J Trop Med Hyg 60: 51–53.R. MolinaJM LohseF. PulidoF. LagunaR. Lopez-Velez1999Infection of sand flies by humans coinfected with Leishmania infantum and human immunodeficiency virus.Am J Trop Med Hyg605153
  67. 67. Leishman W (1903) On the possibility of the occurrence of trypanosomiasis in India. British Medical Journal 1: 1252–1254.W. Leishman1903On the possibility of the occurrence of trypanosomiasis in India.British Medical Journal112521254
  68. 68. Donovan C (1903) The etiology of heterogeneous fevers in India. Lancet 2: 1401.C. Donovan1903The etiology of heterogeneous fevers in India.Lancet21401
  69. 69. Bora D (1999) Epidemiology of visceral leishmaniasis in India. Natl Med J India 12: 62–68.D. Bora1999Epidemiology of visceral leishmaniasis in India.Natl Med J India126268
  70. 70. Sanyal RK (1985) Leishmaniasis in the Indian sub-continent. In: Chang KP, Bray RS, editors. Leishmaniasis. Amsterdam: Elsevier Science Publishers, B.V. pp. 443–467.RK Sanyal1985Leishmaniasis in the Indian sub-continent.KP ChangRS BrayLeishmaniasisAmsterdamElsevier Science Publishers, B.V443467
  71. 71. Ahluwalia IB, Bern C, Costa C, Akter T, Chowdhury R, et al. (2003) Visceral leishmaniasis: consequences of a neglected disease in a Bangladeshi community. American Journal of Tropical Medicine and Hygiene 69: 624–628.IB AhluwaliaC. BernC. CostaT. AkterR. Chowdhury2003Visceral leishmaniasis: consequences of a neglected disease in a Bangladeshi community.American Journal of Tropical Medicine and Hygiene69624628
  72. 72. Thakur CP, Kumar K, Sinha PK, Mishra BN, Pandey AK (1987) Treatment of post-kala-azar dermal leishmaniasis with sodium stibogluconate. Br Med J (Clin Res Ed) 295: 886–887.CP ThakurK. KumarPK SinhaBN MishraAK Pandey1987Treatment of post-kala-azar dermal leishmaniasis with sodium stibogluconate.Br Med J (Clin Res Ed)295886887
  73. 73. Sharma DA, Bern C, Varghese B, Chowdhury R, Haque R, et al. (2006) The economic impact of visceral leishmaniasis on households in Bangladesh. Trop Med Int Health 11: 757–764.DA SharmaC. BernB. VargheseR. ChowdhuryR. Haque2006The economic impact of visceral leishmaniasis on households in Bangladesh.Trop Med Int Health11757764
  74. 74. Thakur CP (1984) Epidemiological, clinical and therapeutic features of Bihar kala-azar (including post kala-azar dermal leishmaniasis). Trans R Soc Trop Med Hyg 78: 391–398.CP Thakur1984Epidemiological, clinical and therapeutic features of Bihar kala-azar (including post kala-azar dermal leishmaniasis).Trans R Soc Trop Med Hyg78391398
  75. 75. Ahluwalia IB, Bern C, Wagatsuma Y, Costa C, Chowdhury R, et al. (2004) Visceral leishmaniasis: consequences to women in a Bangladeshi community. J Womens Health (Larchmt) 13: 360–364.IB AhluwaliaC. BernY. WagatsumaC. CostaR. Chowdhury2004Visceral leishmaniasis: consequences to women in a Bangladeshi community.J Womens Health (Larchmt)13360364
  76. 76. Thakur CP (2000) Socio-economics of visceral leishmaniasis in Bihar (India). Transactions of the Royal Society of Tropical Medicine and Hygiene 94: 156–157.CP Thakur2000Socio-economics of visceral leishmaniasis in Bihar (India).Transactions of the Royal Society of Tropical Medicine and Hygiene94156157
  77. 77. Adhikari SR, Maskay NM (2003) The economic burden of Kala-azar in households of the Danusha and Mahottari districts of Nepal. Acta Tropica 88: 1–2.SR AdhikariNM Maskay2003The economic burden of Kala-azar in households of the Danusha and Mahottari districts of Nepal.Acta Tropica8812
  78. 78. Rijal S, Koirala S, Van der Stuyft P, Boelaert M (2006) The economic burden of visceral leishmaniasis for households in Nepal. Trans R Soc Trop Med Hyg. S. RijalS. KoiralaP. Van der StuyftM. Boelaert2006The economic burden of visceral leishmaniasis for households in Nepal.Trans R Soc Trop Med Hyg
  79. 79. Meheus F, Boelaert M, Baltussen R, Sundar S (2006) Costs of patient management of visceral leishmaniasis in Muzaffarpur, Bihar, India. Trop Med Int Health 11: 1715–1724.F. MeheusM. BoelaertR. BaltussenS. Sundar2006Costs of patient management of visceral leishmaniasis in Muzaffarpur, Bihar, India.Trop Med Int Health1117151724
  80. 80. Sundar S (2001) Drug resistance in Indian visceral leishmaniasis. Trop Med Int Health 6: 849–854.S. Sundar2001Drug resistance in Indian visceral leishmaniasis.Trop Med Int Health6849854
  81. 81. Sundar S, More DK, Singh MK, Singh VP, Sharma S, et al. (2000) Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis 31: 1104–1107.S. SundarDK MoreMK SinghVP SinghS. Sharma2000Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic.Clin Infect Dis3111041107
  82. 82. Brasil Ministério da Saúde (2006) Manual de Vigilância e Controle da Leishmaniose Visceral. Brasilia, Brasil: Brasil Ministério da Saúde, Secretaria de Vigilância em Saúde. Brasil Ministério da Saúde2006Manual de Vigilância e Controle da Leishmaniose VisceralBrasilia, BrasilBrasil Ministério da Saúde, Secretaria de Vigilância em Saúde182
  83. 83. Costa CH, Pereira HF, Araujo MV (1990) [Visceral leishmaniasis epidemic in the State of Piaui, Brazil, 1980–1986]. Rev Saude Publica 24: 361–372.CH CostaHF PereiraMV Araujo1990[Visceral leishmaniasis epidemic in the State of Piaui, Brazil, 1980–1986].Rev Saude Publica24361372
  84. 84. World Health Organization (2002) Urbanization: an increasing risk factor for visceral leishmaniasis. Weekly Epidemiological Record 77: 365–370.World Health Organization2002Urbanization: an increasing risk factor for visceral leishmaniasis.Weekly Epidemiological Record77365370
  85. 85. Arias JR, Monteiro PS, Zicker F (1996) The reemergence of visceral leishmaniasis in Brazil. Emerg Infect Dis 2: 145–146.JR AriasPS MonteiroF. Zicker1996The reemergence of visceral leishmaniasis in Brazil.Emerg Infect Dis2145146
  86. 86. Costa CH, Werneck GL, Rodrigues L Jr, Santos MV, Araujo IB, et al. (2005) Household structure and urban services: neglected targets in the control of visceral leishmaniasis. Ann Trop Med Parasitol 99: 229–236.CH CostaGL WerneckL. Rodrigues JrMV SantosIB Araujo2005Household structure and urban services: neglected targets in the control of visceral leishmaniasis.Ann Trop Med Parasitol99229236
  87. 87. Werneck GL, Costa CH, Walker AM, David JR, Wand M, et al. (2007) Multilevel modelling of the incidence of visceral leishmaniasis in Teresina, Brazil. Epidemiol Infect 135: 195–201.GL WerneckCH CostaAM WalkerJR DavidM. Wand2007Multilevel modelling of the incidence of visceral leishmaniasis in Teresina, Brazil.Epidemiol Infect135195201
  88. 88. Jeronimo SM, Oliveira RM, Mackay S, Costa RM, Sweet J, et al. (1994) An urban outbreak of visceral leishmaniasis in Natal, Brazil. Trans R Soc Trop Med Hyg 88: 386–388.SM JeronimoRM OliveiraS. MackayRM CostaJ. Sweet1994An urban outbreak of visceral leishmaniasis in Natal, Brazil.Trans R Soc Trop Med Hyg88386388
  89. 89. Rabello A, Orsini M, Disch J (2003) Leishmania/HIV co-infection in Brazil: an appraisal. Ann Trop Med Parasitol 97: Suppl 117–28.A. RabelloM. OrsiniJ. Disch2003Leishmania/HIV co-infection in Brazil: an appraisal.Ann Trop Med Parasitol97Suppl 11728
  90. 90. World Health Organization (2007) Leishmaniasis and HIV co-infection. Geneva, Switzerland.World Health Organization2007Leishmaniasis and HIV co-infectionGeneva, Switzerland
  91. 91. Dantas-Torres F, Brandao-Filho SP (2006) [Geographical expansion of visceral leishmaniasis in the State of Pernambuco]. Rev Soc Bras Med Trop 39: 352–356.F. Dantas-TorresSP Brandao-Filho2006[Geographical expansion of visceral leishmaniasis in the State of Pernambuco].Rev Soc Bras Med Trop39352356
  92. 92. Courtenay O, Quinnell RJ, Garcez LM, Shaw JJ, Dye C (2002) Infectiousness in a cohort of brazilian dogs: why culling fails to control visceral leishmaniasis in areas of high transmission. J Infect Dis 186: 1314–1320.O. CourtenayRJ QuinnellLM GarcezJJ ShawC. Dye2002Infectiousness in a cohort of brazilian dogs: why culling fails to control visceral leishmaniasis in areas of high transmission.J Infect Dis18613141320
  93. 93. Barão SC, de Fonseca Camargo-Neves VL, Resende MR, da Silva LJ (2007) Human asymptomatic infection in visceral leishmaniasis: a seroprevalence study in an urban area of low endemicity. Preliminary results. Am J Trop Med Hyg 77: 1051–1053.SC BarãoVL de Fonseca Camargo-NevesMR ResendeLJ da Silva2007Human asymptomatic infection in visceral leishmaniasis: a seroprevalence study in an urban area of low endemicity. Preliminary results.Am J Trop Med Hyg7710511053
  94. 94. Instituto Nacional de Salud de Colombia (2006) Informe 2006 Leishmaniasis. Bogota, Colombia.Instituto Nacional de Salud de Colombia2006Informe 2006 LeishmaniasisBogota, Colombia
  95. 95. Llanos-Cuentas A, Tulliano G, Araujo-Castillo R, Miranda-Verastegui C, Santamaria-Castrellon G, et al. (2008) Clinical and parasite species risk factors for pentavalent antimonial treatment failure in cutaneous leishmaniasis in Peru. Clin Infect Dis 46: 223–231.A. Llanos-CuentasG. TullianoR. Araujo-CastilloC. Miranda-VerasteguiG. Santamaria-Castrellon2008Clinical and parasite species risk factors for pentavalent antimonial treatment failure in cutaneous leishmaniasis in Peru.Clin Infect Dis46223231
  96. 96. Davies CR, Llanos-Cuentas EA, Sharp SJ, Canales J, Leon E, et al. (1997) Cutaneous leishmaniasis in the Peruvian Andes: factors associated with variability in clinical symptoms, response to treatment, and parasite isolation rate. Clin Infect Dis 25: 302–310.CR DaviesEA Llanos-CuentasSJ SharpJ. CanalesE. Leon1997Cutaneous leishmaniasis in the Peruvian Andes: factors associated with variability in clinical symptoms, response to treatment, and parasite isolation rate.Clin Infect Dis25302310
  97. 97. Calvopina M, Armijos RX, Marco JD, Uezato H, Kato H, et al. (2006) Leishmania isoenzyme polymorphisms in Ecuador: relationships with geographic distribution and clinical presentation. BMC Infect Dis 6: 139.M. CalvopinaRX ArmijosJD MarcoH. UezatoH. Kato2006Leishmania isoenzyme polymorphisms in Ecuador: relationships with geographic distribution and clinical presentation.BMC Infect Dis6139
  98. 98. Rotureau B (2006) Ecology of the leishmania species in the Guianan ecoregion complex. Am J Trop Med Hyg 74: 81–96.B. Rotureau2006Ecology of the leishmania species in the Guianan ecoregion complex.Am J Trop Med Hyg748196
  99. 99. Tojal da Silva AC, Cupolillo E, Volpini AC, Almeida R, Romero GA (2006) Species diversity causing human cutaneous leishmaniasis in Rio Branco, state of Acre, Brazil. Trop Med Int Health 11: 1388–1398.AC Tojal da SilvaE. CupolilloAC VolpiniR. AlmeidaGA Romero2006Species diversity causing human cutaneous leishmaniasis in Rio Branco, state of Acre, Brazil.Trop Med Int Health1113881398
  100. 100. Campbell-Lendrum D, Dujardin JP, Martinez E, Feliciangeli MD, Perez JE, et al. (2001) Domestic and peridomestic transmission of American cutaneous leishmaniasis: changing epidemiological patterns present new control opportunities. Mem Inst Oswaldo Cruz 96: 159–162.D. Campbell-LendrumJP DujardinE. MartinezMD FeliciangeliJE Perez2001Domestic and peridomestic transmission of American cutaneous leishmaniasis: changing epidemiological patterns present new control opportunities.Mem Inst Oswaldo Cruz96159162
  101. 101. Brasil Ministério da Saúde (2000) Manual de Controle da Leishmaniose Tegumentar Americana. Brasilia, Brasil: Brasil Ministério da Saúde, Fundação Nacional de Saúde. Brasil Ministério da Saúde2000Manual de Controle da Leishmaniose Tegumentar AmericanaBrasilia, BrasilBrasil Ministério da Saúde, Fundação Nacional de Saúde62
  102. 102. Barrett TV, Senra MS (1989) Leishmaniasis in Manaus, Brazil. Parasitol Today 5: 255–257.TV BarrettMS Senra1989Leishmaniasis in Manaus, Brazil.Parasitol Today5255257
  103. 103. Alcais A, Abel L, David C, Torrez ME, Flandre P, et al. (1997) Risk factors for onset of cutaneous and mucocutaneous leishmaniasis in Bolivia. Am J Trop Med Hyg 57: 79–84.A. AlcaisL. AbelC. DavidME TorrezP. Flandre1997Risk factors for onset of cutaneous and mucocutaneous leishmaniasis in Bolivia.Am J Trop Med Hyg577984
  104. 104. Martinez E, Le Pont F, Torrez M, Telleria J, Vargas F, et al. (1998) A new focus of cutaneous leishmaniasis due to Leishmania amazonensis in a Sub Andean region of Bolivia. Acta Trop 71: 97–106.E. MartinezF. Le PontM. TorrezJ. TelleriaF. Vargas1998A new focus of cutaneous leishmaniasis due to Leishmania amazonensis in a Sub Andean region of Bolivia.Acta Trop7197106
  105. 105. Velez ID, Hendrickx E, Robledo SM, del Pilar Agudelo S (2001) [Gender and cutaneous leishmaniasis in Colombia]. Cad Saude Publica 17: 171–180.ID VelezE. HendrickxSM RobledoS. del Pilar Agudelo2001[Gender and cutaneous leishmaniasis in Colombia].Cad Saude Publica17171180
  106. 106. Weigel MM, Armijos RX, Racines RJ, Zurita C, Izurieta R, et al. (1994) Cutaneous leishmaniasis in subtropical Ecuador: popular perceptions, knowledge, and treatment. Bull Pan Am Health Organ 28: 142–155.MM WeigelRX ArmijosRJ RacinesC. ZuritaR. Izurieta1994Cutaneous leishmaniasis in subtropical Ecuador: popular perceptions, knowledge, and treatment.Bull Pan Am Health Organ28142155
  107. 107. Davies CR, Reithinger R, Campbell-Lendrum D, Feliciangeli D, Borges R, et al. (2000) The epidemiology and control of leishmaniasis in Andean countries. Cad Saude Publica 16: 925–950.CR DaviesR. ReithingerD. Campbell-LendrumD. FeliciangeliR. Borges2000The epidemiology and control of leishmaniasis in Andean countries.Cad Saude Publica16925950
  108. 108. Vega JC, Sanchez BF, Montero LM, Montana R, Del Pilar Mahecha M, et al. (2007) Short communication: The cost-effectiveness of cutaneous leishmaniasis patient management during an epidemic in Chaparral, Colombia in 2004. Trop Med Int Health 12: 1540–1544.JC VegaBF SanchezLM MonteroR. MontanaM. Del Pilar Mahecha2007Short communication: The cost-effectiveness of cutaneous leishmaniasis patient management during an epidemic in Chaparral, Colombia in 2004.Trop Med Int Health1215401544
  109. 109. Tayeh A, Jalouk L, Cairncross S (1997) Twenty years of cutaneous leishmaniasis in Aleppo, Syria. Trans R Soc Trop Med Hyg 91: 657–659.A. TayehL. JaloukS. Cairncross1997Twenty years of cutaneous leishmaniasis in Aleppo, Syria.Trans R Soc Trop Med Hyg91657659
  110. 110. World Health Organization (2002) Cutaneous leishmaniasis, Afghanistan. Wkly Epidemiol Rec 77: 246.World Health Organization2002Cutaneous leishmaniasis, Afghanistan.Wkly Epidemiol Rec77246
  111. 111. Hewitt S, Reyburn H, Ashford R, Rowland M (1998) Anthroponotic cutaneous leishmaniasis in Kabul, Afghanistan: vertical distribution of cases in apartment blocks. Trans R Soc Trop Med Hyg 92: 273–274.S. HewittH. ReyburnR. AshfordM. Rowland1998Anthroponotic cutaneous leishmaniasis in Kabul, Afghanistan: vertical distribution of cases in apartment blocks.Trans R Soc Trop Med Hyg92273274
  112. 112. Reithinger R, Aadil K, Kolaczinski J, Mohsen M, Hami S (2005) Social impact of leishmaniasis, Afghanistan. Emerg Infect Dis 11: 634–636.R. ReithingerK. AadilJ. KolaczinskiM. MohsenS. Hami2005Social impact of leishmaniasis, Afghanistan.Emerg Infect Dis11634636
  113. 113. Thompson SK (1991) Stratified adaptive cluster sampling. Biometrika 78: 389–397.SK Thompson1991Stratified adaptive cluster sampling.Biometrika78389397
  114. 114. Cattand P, Jannin J, Lucas P (2001) Sleeping sickness surveillance: an essential step towards elimination. Trop Med Int Health 6: 348–361.P. CattandJ. JanninP. Lucas2001Sleeping sickness surveillance: an essential step towards elimination.Trop Med Int Health6348361
  115. 115. King CH, Dangerfield-Cha M (2008) The unacknowledged impact of chronic schistosomiasis. Chronic Illn 4: 65–79.CH KingM. Dangerfield-Cha2008The unacknowledged impact of chronic schistosomiasis.Chronic Illn46579