The Role of Macrophages in Resistance to Malaria
Mary M. Stevenson in Malaria: Host Responses to Infection, 2017
A large body of information has led to several major findings on the killing of intracellular protozoan parasites. As reviewed by Murray,4 fresh peripheral blood monocytes can kill about 90% of Leishmania donovani promastigotes and 30 to 40% of the amastigotes of this parasite, and about 40% of the trophozoites of T. gondii, in vitro. Cytotoxicity against these parasites is correlated with the oxidative burst capacity of the monocytes. In contrast, monocyte-derived macrophages do not kill these parasites but allow them to multiply. However, the ability of macrophages to inhibit the growth of these parasites or kill them can be restored by treating them with crude T cell-derived lymphokines. The active com- ponent of the lymphokines is γ-interferon. The capacity of monocytes and lymphokine or γ-interferon-activated macrophages to kill Leishmania, for example, is associated with both oxygen-dependent and -independent mechanisms.4 The nature of the oxygen-independent mechanism is as yet unknown.
Enhanced Case Detection through Clinical and Laboratory Methods
Yamuna Deepani Siriwardana in Leishmaniasis in Sri Lanka, 2023
Leishmania donovani are generally accepted as a species transmitted from human to human via the bite of a sandfly. Animal reservoirs that harbour L. donovani are not widely known except for a few reports in the recent past (El-Hassan et al., 1993; Hassan et al., 2009; Jambulingam et al., 2017). Therefore, timely case detection and early treatment with appropriate anti-leishmanials is a main mode of disease control accepted by the WHO (2010). Enhanced clinical suspicion, confirmation through the use of locally appropriate laboratory tools, and timely, accurate, and complete case management with adequate follow-up are key points for success in controlling L. donovani infections in an endemic setting.
Miltefosine
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Leishmania donovani develops resistance to miltefosine through the loss of function of either LdMT (a P-type ATPase) or LdRos3 (a specific b-subunit), two proteins that interact at the plasma membrane to mediate inward translocation of the drug in both promastigote and amastigote stages (Perez-Victoria et al., 2003a; Perez-Victoria et al., 2003b; Perez-Victoria et al., 2006a; Perez-Victoria et al., 2006b; Coelho et al., 2012; Shaw et al., 2016). Resistance is conferred by single, independent loss-of-function point mutations in the LdMT gene (Perez-Victoria et al., 2003b). This mechanism does not confer cross-resistance to other antileishmanial drugs (Seifert et al., 2007).
Emerging therapeutic targets for treatment of leishmaniasis
Published in Expert Opinion on Therapeutic Targets, 2018
Leishmaniasis is a group of manifestations ranging from cutaneous to most severe visceral forms, caused by protozoan parasite Leishmania species. Visceral form of disease, caused by Leishmania donovani, is characterized by prolonged fever (>2 weeks), weight loss, anemia, and splenomegaly. India, Bangladesh, Sudan, South Sudan, Brazil, and Ethiopia together contribute for more than 90% of the global disease burden with 0.3 million new visceral leishmaniasis (VL) cases reported each year. Leishmania parasites cycle between two hosts – human and sandfly – in two distinct life stages, as flagellar promastigote or amastigote form. The promastigotes from sandfly are injected into the human upon blood feeding where they are phagocytosed by circulating monocytes, dendritic cells, and/or neutrophils. Once inside the phagosome these parasites undergo differentiation to non-flagellar amastigote. These amastigotes divide several times until bursting of host cells to infect another cell.
Haemophagocytic lymphohistiocytosis associated with leishmaniasis reactivation: a potential adverse event to anti-tumour necrosis factor-α therapy
Published in Scandinavian Journal of Rheumatology, 2019
KB Bukan, A Nardo-Marino, C Hagdrup, M Boennelycke, MF Breinholdt, C Schöllkopf, HV Nielsen, D El Fassi
Bone marrow examination verified ongoing haemophagocytosis (Figure 1A) and, surprisingly, revealed the presence of leishmania amastigotes (Figure 1B). Leishmaniasis serology by immunofluorescence antibody testing was subsequently performed, and was only borderline positive (titre 1:80). VL infection was confirmed by a leishmania-specific real-time TaqMan-based polymerase chain reaction (PCR) assay targeting the 18S gene. Species identification, sought by PCR followed by sequencing and blast of the internal transcribed spacer (ITS) 1–2 region, revealed the subtype to be the Leishmania donovani complex. In addition, the patient was found to have Epstein–Barr viraemia. The viraemic load was low (6000 copies/mL). The patient was immunoglobulin M (IgM) negative and IgG positive for EBV by serology. The bone marrow was negative for Epstein–Barr encoding regions (EBER) with in situ hybridization. Four days after initiation of HLH treatment, the patient was no longer febrile, ferritin levels had dropped to 83.7 × 103 µg/L, and the ANC and platelet counts had improved to 0.75 × 109/L and 81 × 109/L, respectively. Unfortunately, a massive retroperitoneal bleed from a lumbar artery arose and, despite intensive care and endovascular coiling, the patient succumbed to multiorgan failure, declining further treatment. Because of his rapid clinical deterioration, neither amphotericin B, which may be effective in VL-induced HLH (VL-HLH) (3), nor rituximab, which may alleviate EBV-HLH (1), was initiated.
Andrographolide engineered gold nanoparticle to overcome drug resistant visceral leishmaniasis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Suvadra Das, Asim Halder, Saptarshi Mandal, Mohammad Abu Jafar Mazumder, Tanmoy Bera, Arup Mukherjee, Partha Roy
Drug resistant Leishmania donovani cells were developed as per earlier reports from our group [22]. Briefly, resistance was induced in Leishmania donovani AG83 promastigotes by gradual increasing dose of sodium stibogluconate (SSG) or paromomycin (PMM) in medium 199 with additional supplements [24]. Dose escalation of SSG/PMM was continued until viable population reduced to around 20%. The strain generated with 10% viable cell population of initial count was finally cultured on medium 199 agar plates and a single colony from the culture was selected for further experiments. Drug resistant promastigote phenotypes were differentiated into amastigotes after 120 h of culture in MMA/20 medium in acidic environment (pH 5.5) and 5% CO2/air atmosphere maintained at 37 °C.
Related Knowledge Centers
- Leishmania
- Leishmaniasis
- Mononuclear Phagocyte System
- Phlebotomus
- Spleen
- Visceral Leishmaniasis
- Bone Marrow
- Liver
- Intracellular Parasite
- Lutzomyia