scholarly journals MODELING POST-KALA-AZAR DERMAL LEISHMANIASIS AS AN INFECTION RESERVOIR FOR VISCERAL LEISHMANIASIS

2019 ◽  
Vol 27 (1) ◽  
pp. 221-239
Author(s):  
ANDREA CALDERÓN ◽  
RYAN LANDRITH ◽  
NHAN LE ◽  
ILEANA MUÑOZ ◽  
CHRISTOPHER M. KRIBS

Visceral Leishmaniasis (VL) is a potentially fatal disease caused by the protozoan parasite Leishmania donovani. This disease is a health problem for the very poor because it results in thousands of deaths and illnesses every year. Some countries, such as India and Bangladesh, have started programs to reduce the occurrences of VL by focusing on early diagnosis and complete treatment of VL. Post-Kala-azar Dermal Leishmaniasis (PKDL) is a cutaneous manifestation of Leishmaniasis that can occur following the incomplete treatment of VL. Diagnosis and treatment of PKDL are limited in affected regions, and PKDL has been identified as a possible reservoir for infection. This study develops a mathematical model of the relationship between the level of PKDL treatment and the incidences of VL during a given period. The results indicate a nearly linear relationship between PKDL treatment rates and the percent reduction of VL incidences. With the current treatments available and considering achievable levels of treatment, the model predicts that up to 20% of VL cases could be prevented by treating new PKDL cases. Hypothetical combined treatment initiatives including bed nets and insecticide spraying are also considered. Results suggest that the population of individuals with PKDL is certainly a significant factor in the transmission of L. donovani infection, with treatment of new cases particularly important.

2016 ◽  
Vol 101 (6) ◽  
pp. 561-567 ◽  
Author(s):  
Eduard E Zijlstra

Visceral leishmaniasis (VL or kala-azar) is most endemic in Asia and Africa and commonly affects young children. It is usually caused byLeishmania donovaniorLeishmania infantumthat are transmitted by Phlebotomine sand flies. Transmission may be anthroponotic or zoonotic or both, depending on the endemic area. Clinical features include fever, hepatosplenomegaly, weight loss and pancytopenia. Younger age, malnutrition and immunosuppression (HIV infection, use of immunosuppressive drugs) are risk factors. Many infections remain asymptomatic. Diagnosis is made by demonstration of theLeishmaniaparasite in aspirates of lymph node, bone marrow or spleen. Serological tests such as rK39 strip test are widely used but the sensitivity varies. qPCR is useful to detect low numbers of parasites and to monitor treatment. Treatment is with AmBisome monotherapy in most areas but with drug combinations elsewhere. HIV co-infected patients are most difficult to treat and often relapse. Control efforts focus on case finding, availability of diagnostic tools, reservoir control and protection from sand flies (insecticides, bed nets). There is no human vaccine.


Planta Medica ◽  
2007 ◽  
Vol 73 (09) ◽  
Author(s):  
E Xingi ◽  
D Smirlis ◽  
S Bisti ◽  
V Myrianthopoulos ◽  
P Magiatis ◽  
...  

mSphere ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Sanya Chadha ◽  
N. Arjunreddy Mallampudi ◽  
Debendra K. Mohapatra ◽  
Rentala Madhubala

ABSTRACT Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis. Increasing resistance and severe side effects of existing drugs have led to the need to identify new chemotherapeutic targets. Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous and are required for protein synthesis. aaRSs are known drug targets for bacterial and fungal pathogens. Here, we have characterized and evaluated the essentiality of L. donovani lysyl-tRNA synthetase (LdLysRS). Two different coding sequences for lysyl-tRNA synthetases are annotated in the Leishmania genome database. LdLysRS-1 (LdBPK_150270.1), located on chromosome 15, is closer to apicomplexans and eukaryotes, whereas LdLysRS-2 (LdBPK_300130.1), present on chromosome 30, is closer to bacteria. In the present study, we have characterized LdLysRS-1. Recombinant LdLysRS-1 displayed aminoacylation activity, and the protein localized to the cytosol. The LdLysRS-1 heterozygous mutants had a restrictive growth phenotype and attenuated infectivity. LdLysRS-1 appears to be an essential gene, as a chromosomal knockout of LdLysRS-1 could be generated when the gene was provided on a rescuing plasmid. Cladosporin, a fungal secondary metabolite and a known inhibitor of LysRS, was more potent against promastigotes (50% inhibitory concentration [IC50], 4.19 µM) and intracellular amastigotes (IC50, 1.09 µM) than were isomers of cladosporin (3-epi-isocladosporin and isocladosporin). These compounds exhibited low toxicity to mammalian cells. The specificity of inhibition of parasite growth caused by these inhibitors was further assessed using LdLysRS-1 heterozygous mutant strains and rescue mutant promastigotes. These inhibitors inhibited the aminoacylation activity of recombinant LdLysRS. Our data provide a framework for the development of a new class of drugs against this parasite. IMPORTANCE Aminoacyl-tRNA synthetases are housekeeping enzymes essential for protein translation, providing charged tRNAs for the proper construction of peptide chains. These enzymes provide raw materials for protein translation and also ensure fidelity of translation. L. donovani is a protozoan parasite that causes visceral leishmaniasis. It is a continuously proliferating parasite that depends heavily on efficient protein translation. Lysyl-tRNA synthetase is one of the aaRSs which charges lysine to its cognate tRNA. Two different coding sequences for lysyl-tRNA synthetases (LdLysRS) are present in this parasite. LdLysRS-1 is closer to apicomplexans and eukaryotes, whereas LdLysRS-2 is closer to bacteria. Here, we have characterized LdLysRS-1 of L. donovani. LdLysRS-1 appears to be an essential gene, as the chromosomal null mutants did not survive. The heterozygous mutants showed slower growth kinetics and exhibited attenuated virulence. This study also provides a platform to explore LdLysRS-1 as a potential drug target.


2019 ◽  
Vol 49 (2) ◽  
pp. 141-143
Author(s):  
Nazar Abdalla

Cutaneous leishmaniasis (CL) is a parasitic disease which has a biphasic life cycle; infection by promastigotes from the sandfly reaches a wound where it is phagocytosed by macrophages, producing the amastigote (the Leishmania donovani body) in the host. A protozoan parasite transmitted by the phlebotomous sandfly causes human leishmaniasis. Cutaneous forms include classical cutaneous, mucocutaneous and post-kala-azar dermal leishmaniasis. It affects c. 300 million individuals in more than 90 nations around the globe. The cutaneous form in the Old World is caused at low altitudes mainly by L. major (which has an animal reservoir, rodents such as mouse) and in swampy regions and high altitudes by L. tropica (which has no animal reservoir). L. aethiopica and L. major lead to disseminated ulcers in Saudi Arabia, Yemen, Iraq, Iran, Pakistan, India, Tunisia, Sudan and Ethiopia, whose main electrophoretic isozyme pattern Zymodeme in Saudi Arabia is LON-4.


2019 ◽  
Vol 6 (1) ◽  
pp. 12-15
Author(s):  
Ishrat Sharmin ◽  
AKM Quamruzzaman ◽  
Rezina Parveen ◽  
M Abdulah Yusuf ◽  
Rashida Akter Khanam

Background: Newly developed KAtex test can be used as a non invasive tool for diagnosis of Kala-azar. Objectives: The aim of the present study was to compare KAtex, Bone marrow aspiration and DAT to diagnose VL. Methodology: This cross-sectional study was carried out in the Department of Microbiology at Dhaka Medical College, Dhaka, Bangladesh in collaboration with the Department of Parasitology, Institute of Epidemiology, Disease Control and Research (IEDCR), Dhaka, Bangladesh for a period of one year. Clinically suspected Kala-azar (VL) cases of different age and sex attending IEDCR, Dhaka from different Kala-azar endemic areas of Bangladesh were selected for this study. Patients having fever for more than 2 weeks, with or without splenomegaly, having history of loss of body weight following onset of fever were clinically suspected as Kala-azar cases. Microscopy and culture was performed in bone marrow (BM). KAtex was performed with urine sample. Agglutination of sensitized latex indicated presence of Leishmania donovani antigen in urine and thereby visceral leishmaniasis. No agglutination indicates absence of antigen in urine. DAT was done with serums of all cases. Result: Among 130 clinically suspected VL cases, 70 (53.85%) cases were BM positive and 60(46.15%) cases were BM negative. All the 70 BM positive cases were positive by KAtex and DAT. Among 60 BM negative cases, 15 were positive by KAtex and 23 were positive by DAT. The sensitivity of KAtex was 100.0% and specificity was 75.0%. The sensitivity of DAT was 100.0% and specificity is 61.6%. Conclusion: In conclusion, KAtex test is a good diagnostic tool for the detection of VL in comparison with DAT. Bangladesh Journal of Infectious Diseases, June 2019;6(1):12-15


2009 ◽  
Vol 29 (2) ◽  
pp. 67-73 ◽  
Author(s):  
Durga Datt Joshi

Introduction: Visceral leishmaniasis (VL) or Kala-azar is a potentially fatal vector-borne (sand fly phlebotomies spp) zoonotic disease caused by a protozoan parasite, Leishmania donovani. In Nepal, the disease is restricted to the Eastern Terai region which lies adjacent to the Bihar state of India. Although leishmaniasis is regarded as a significant health problem in Nepal by the Ministry of Health, there is no active case detection programme in the country. Objective: Objectives of this study were to determine the up-to-date morbidity and mortality trend for VL in children of Nepal. Method: The epidemiological surveillance team from the NZFHRC visited to eight zonal hospitals in Terai region during the month from September to December of each year 2003 to 2007. The morbidity and mortality data up to the year 2007 were collected every year. The team has also collected 66 blood serum samples of which 18 samples from children were collected for the diagnosis. Results: A total 25890 cases with 599 deaths were reported during the year 1980-2006. The case fatality rate (CFR) varied from 0.23% to 13.2%. Districtwise analysis showed that, during 2003, highest incidence was in Mahottari district (184/100,000), followed by Sarlahi (100/100,000) and Sunsari (96/100,000). The highest CFR was in Dhanusha (2.9%) followed by Bara (2.4%) and Saptari (2.0%). Majority (70.9%) of persons affected by VL were aged 15 years and above, followed by 10-14 years (13.9%), 5-9 years (11.9%) and 1-4 years (3.3%). VL cases recorded from different district of Nepal for the year 2004, 2005, 2006 and 2007 are recorded. CFR for the year 2004, 2005, 2006 and 2007 were 3.2%, 3.7%, 16.67% and 11.42% respectively. Conclusions: There should be regular surveillance research work to be carried out in endemic area. Mass public health education, to make the people aware about preventive aspects of the disease is important. The possibility of the existence of animal reservoirs as zoonotic disease should also be considered. This disease is very much serious in children below 15 years of age both in male and female, therefore it is essential to have paediatrician post at least in all VL six endemic districts. Key words: Epidemiology, Leishmaniasis, Kala-azar, Sandfly   doi: 10.3126/jnps.v29i2.2041 J. Nepal Paediatr. Soc. Vol 29, No. 2, pp.67-73


2016 ◽  
Vol 43 (2) ◽  
pp. 189-199 ◽  
Author(s):  
Hamida Khanum ◽  
Sultan Uz Zaman ◽  
Sabina Yesmin ◽  
Sharmin Musa ◽  
Hasina Banu ◽  
...  

Investigation on knowledge, attitude and practice (KAP) of inhabitants and professionals for treatment, prevention and control of visceral leishmaniasis carried out on 519 inhabitants and 92 professionals of 6 districts (Panchagarh, Thakurgaon, Dinajpur, Bogra, Pabna and Shirajgonj) of Bangladesh. About 79.2% inhabitants agreed that they have heard about kala-azar disease. Regarding the transmission of kala-azar, 22.7% respondents answered by mosquito, about 38.3% said long period and irregular fever, 7.5% inhabitants knew enlargement of spleen and liver as sign and symptom of kala-azar. Among the professionals, about 80.4% of them have the correct knowledge regarding the specific agent (Leishmania donovani) of kala-azar. Investigation on knowledge, attitude and practice (KAP) of inhabitants and professional, 89.1% and 69.6% believe that spleen and liver are affected in kala-azar, 39.1% to 51.1% professionals understand that lymph nodes, blood and skin are involved as tissues due to kala-azar. Among the professionals, about 80.4% of them have the correct knowledge regarding the specific agent (L. donovani) of kala-azar.Bangladesh J. Zool. 43(2): 189-199, 2015


2017 ◽  
Vol 5 (1) ◽  
pp. 430-441
Author(s):  
Belal Abdallah A. Adam ◽  
Moawia Mukhtar Hassan ◽  
Osman Mohammed Abd Elnour ◽  
Ahmed Hamid Awadallah

Visceral leishmaniasis (VL; kala-azar) is one of the most important parasitic tropical diseases in Sudan   and the Sudan is considered to be one of the most important foci in the world. The visceral leishmaniasis has been described in Sudan since the beginning of the twentieth century. In Sudan, VL is caused by Leishmania donovani complex: MON 18, MON 30 and MON 82 zymodemes and  The proven vector is Phlebotomus (Larroussius) orientalis, in this study a survey was carried out to identify the principal vector of VL based on Leishmania infection, morphological characters and to determine some ecological aspects of the sand flies prevalent in the area . Ten species of sand flies were recorded, three Phlebotomus species and seven Sergentomyia species of these sandflies, P. rodhaini was collected only from Acacia seyal/Balanities aegyptiaca at the Island whereas S. hunti was collected from the Acacia nilotica forest only of the total collections, P. orientalis representing 3.80% (248 specimens) of the total collection and P. papatasi were 3.11% of the collection. Sand flies identification was done under a binocular microscope at 40x (magnification). The main features used for sand flies identification were the sperm theca of the female, the termination of the male and the pharyngeal and the ciboria toothed structures of both sexes. According to results of this study we recommended the following:  more studies are needed in the future to determine the transmission season, and infection rates of Leishmania parasites in human and the animal host in this area. Annually Entomological surveys must be done to determine density of Sand fly Vectors and Encourage the use of personal protection tools (ITNs), repellents, and improving of houses to avoid bite of sand fly.


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