Towards the elimination of visceral leishmaniasis as a public health problem in east Africa: reflections on an enhanced control strategy and a call for action

Alvar, Jorge; Boer, Margriet den; Dagne, Daniel Argaw

doi:10.1016/s2214-109x(21)00392-2

Cited by 46 publications

(64 citation statements)

References 20 publications

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“…Therefore, it begs the question what are the host cell reservoirs of the parasite in chronic infections? The complex interactions of host and parasitic factors that determine the pathophysiology, clinical variability, susceptibility/resistance and chronicity are intensely studied towards achieving the goals of control and elimination of VL (Alvar et al, 2021, Poulaki et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Dual scRNA-Seq analysis reveals rare and uncommon parasitized cell populations in chronic L. donovani infection

Karagiannis¹,

Gannavaram²,

Verma

et al. 2022

Preprint

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Although phagocytic cells are documented targets of Leishmania parasites, it is unclear whether these parasites can infect other cell types. In this study, we describe a computational approach that exploits scRNA-seq to simultaneously analyze the transcriptomic signatures of the host cell and to identify rare and uncommon cells that harbor Leishmania donovani in the spleen and bone marrow. Individual cells were annotated as parasitized based on the presence of L. donovani transcripts that were detected with high accuracy. This unbiased approach allowed identification of heterogenous parasitized cell populations that cannot be detected by conventional methods. Consistent with previous studies, analysis of spleen cells isolated from L. donovani infected mice revealed inflammatory monocytes as the dominant parasitized cells. In addition, megakaryocytes, basophils , and NK cells were found to be the rare cells infected in the spleen. Unexpectedly, hematopoietic stem cells (HSCs), not known to be phagocytic, were the dominant cells parasitized cell in the bone marrow. In addition, eosinophils, megakaryocytes, and basal cells were the rare bone marrow cells found to be infected. scRNA-seq analysis revealed known phagocytic receptors FcγR and CD93 are expressed on HSCs . In vitro studies using purified HSCs showed that these cells can phagocytize L. donovani. Parasitized HSCs were also detectable in the bone marrow of mouse infected with L donovani. . This unbiased dual scRNA-seq approach enables identification of rare and uncommon parasitized cells that could be involved in pathogenesis, persistence, and protective immunity. Further, such approach could be used to study pathogenesis of other infectious agents.

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Section: Introductionmentioning

confidence: 99%

Dual scRNA-Seq analysis reveals rare and uncommon parasitized cell populations in chronic L. donovani infection

Karagiannis¹,

Gannavaram²,

Verma

et al. 2022

Preprint

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“…While in South-Eastern Asia the Kala-Azar Elimination Programme represented a joint regional approach for the fight against Leishmaniosis, in Eastern Africa a shared strategy does not yet exist and VL is still a major public health problem [ 65 , 73 ]. The WHO road map for neglected tropical diseases 2021–2030 established among its main objectives the reduction of the case-fatality rate of VL below 1% in Eastern Africa countries, thanks to the enhancement of diagnostic and therapeutic tools and preventive resources for transmission and vector control [ 74 ].…”

Section: Therapymentioning

confidence: 99%

Visceral Leishmaniasis: Epidemiology, Diagnosis, and Treatment Regimens in Different Geographical Areas with a Focus on Pediatrics

et al. 2022

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Visceral Leishmaniasis (VL) is a vector-borne disease caused by an intracellular protozoa of the genus Leishmania that can be lethal if not treated. VL is caused by Leishmania donovani in Asia and in Eastern Africa, where the pathogens’ reservoir is represented by humans, and by Leishmania infantum in Latin America and in the Mediterranean area, where VL is a zoonotic disease and dog is the main reservoir. A part of the infected individuals become symptomatic, with irregular fever, splenomegaly, anemia or pancytopenia, and weakness, whereas others are asymptomatic. VL treatment has made progress in the last decades with the use of new drugs such as liposomal amphotericin B, and with new therapeutic regimens including monotherapy or a combination of drugs, aiming at shorter treatment duration and avoiding the development of resistance. However, the same treatment protocol may not be effective all over the world, due to differences in the infecting Leishmania species, so depending on the geographical area. This narrative review presents a comprehensive description of the clinical picture of VL, especially in children, the diagnostic approach, and some insight into the most used pharmacological therapies available worldwide.

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“…With the neglected disease considered as low priority for investment in most affected countries, there is minimal funding towards addressing VL and a lack of sustainability in the implementation of current activities. Migration and population displacement resulting partly from climate/environmental changes and civil unrest further contribute to high incidences of VL (18,19). Civil unrest and VL epidemics tend to occur among immunologically naïve migrants entering VL-endemic areas or when Leishmania-infected individuals migrate to new areas and establish additional foci of disease (20).…”

Section: Political Instabilitymentioning

confidence: 99%

“…Research gaps due to lack of resources have resulted in limited understanding and oversight of the role of zoonotic transmission and treatment of reservoirs, or infection carrying/ transmitting animals. This limited understanding of vectors and reservoirs of the disease has led to limited one-health strategies for control (18). The research gap between academia and health policy makers result in missed opportunities to translate research outcomes into policies and disease control approaches.…”

Section: Researchmentioning

confidence: 99%

“…Other endemic countries in East Africa must be guided and supported to develop their strategic plans, similar to what was done in Kenya. Given the cross-border movement of populations in East Africa and climate change which is enlarging the habitat amenable to breeding of key vector species, a regional strategy (modeled after the Southeast Asian strategy) that ensures coordination across borders in East Africa is imperative (18,43).…”

Section: Strategic Plansmentioning

confidence: 99%

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Moving from control to elimination of Visceral Leishmaniasis in East Africa

Makau-Barasa¹,

Ochol²,

Yotebieng³

et al. 2022

Front. Trop. Dis

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Visceral leishmaniasis (VL) is arguably one of the deadliest neglected tropical diseases. People in poverty bear the largest burden of the disease. Today, the largest proportion of persons living with VL reside in the Eastern African countries of Ethiopia, Kenya, Somalia, South Sudan, and Sudan. These East African countries are among the top 10 countries reporting the highest number of cases and deaths. If left undiagnosed and untreated, VL almost always results in death. Subsequently, there is a need for integrated efforts across human, animal, and vector-control programs to address the scourge of VL in East Africa. In the East African region, the challenges including socio-cultural beliefs, poor health system, political instability, and limited epidemiological understanding impede the implementation of effective VL control strategies. The availability of funding, as well as diagnostics and treatment options, are also devastatingly limited. Furthermore, given the realities of climate change and population movement in the region, to effectively address the scourge of visceral leishmaniasis in East Africa, a regional approach is imperative. In this paper, we highlight some of the key challenges and opportunities to effectively move towards an effective control, and eventually elimination, of VL in East Africa. To do this, we underline the need for a fully integrated program in East Africa, inclusive of effective diagnostics and treatment, to effectively reduce and eliminate the burden of VL in the region, subsequently paving the way to achieve global elimination goals.

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Towards the elimination of visceral leishmaniasis as a public health problem in east Africa: reflections on an enhanced control strategy and a call for action

Cited by 46 publications

References 20 publications

Dual scRNA-Seq analysis reveals rare and uncommon parasitized cell populations in chronic L. donovani infection

Dual scRNA-Seq analysis reveals rare and uncommon parasitized cell populations in chronic L. donovani infection

Visceral Leishmaniasis: Epidemiology, Diagnosis, and Treatment Regimens in Different Geographical Areas with a Focus on Pediatrics

Moving from control to elimination of Visceral Leishmaniasis in East Africa

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