Leishmaniasis In China Research Articles

Optimization of the control strategy and research priorities to combat the resurgence of visceral leishmaniasis in China

Leishmaniasis is a zoonotic parasitic disease caused by Leishmania infection and transmitted by sandflies. There are three main forms of leishmaniasis, including cutaneous leishmaniasis, visceral leishmaniasis and mucocutaneous leishmaniasis. China is mainly endemic for visceral leishmaniasis, which is a class C notifiable infectious disease in the country. Following concerted efforts, the transmission of visceral leishmaniasis had been controlled in most endemic foci of China by the end of 1958, with a few cases reported in western China. Due to global climate changes and population mobility, resurgence of visceral leishmaniasis has recently occurred in historical endemic areas of central and western China, which is characterized by gradual expansion of endemic areas and remarkable rebounding epidemics. Hereby, we summarize the national and global epidemiology and control strategy of visceral leishmaniasis, propose 8 key research areas and 12 key research topics for visceral leishmaniasis control, and recommend the establishment of the joint prevention and control mechanism of "human-animals-vectors" and the working mechanism of animal prevention for human diseases based on the One Health approach, so as to combat the resurgence of visceral leishmaniasis in China.

Transmission Risk Prediction and Evaluation of Mountain-Type Zoonotic Visceral Leishmaniasis in China Based on Climatic and Environmental Variables

With global warming and socioeconomic developments, there is a tendency toward the emergence and spread of mountain-type zoonotic visceral leishmaniasis (MT-ZVL) in China. Timely identification of the transmission risk and spread of MT-ZVL is, therefore, of great significance for effectively interrupting the spread of MT-ZVL and eliminating the disease. In this study, 26 environmental variables—namely, climatic, geographical, and 2 socioeconomic indicators were collected from regions where MT-ZVL patients were detected during the period from 2019 to 2021, to create 10 ecological niche models. The performance of these ecological niche models was evaluated using the area under the receiver-operating characteristic curve (AUC) and true skill statistic (TSS), and ensemble models were created to predict the transmission risk of MT-ZVL in China. All ten ecological niche models were effective at predicting the transmission risk of MT-ZVL in China, and there were significant differences in the mean AUC (H = 33.311, p < 0.05) and TSS values among these ten models (H = 26.344, p < 0.05). The random forest, maximum entropy, generalized boosted, and multivariate adaptive regression splines showed high performance at predicting the transmission risk of MT-ZVL (AUC > 0.95, TSS > 0.85). Ensemble models predicted a transmission risk of MT-ZVL in the provinces of Shanxi, Shaanxi, Henan, Gansu, Sichuan, and Hebei, which was centered in Shanxi Province and presented high spatial clustering characteristics. Multiple ensemble ecological niche models created based on climatic and environmental variables are effective at predicting the transmission risk of MT-ZVL in China. This risk is centered in Shanxi Province and tends towards gradual radiation dispersion to surrounding regions. Our results provide insights into MT-ZVL surveillance in regions at high risk of MT-ZVL.

Label-Free Quantitative Proteomic Analysis of Three Strains of Viscerotropic Leishmania Isolated from Patients with Different Epidemiological Types of Visceral Leishmaniasis in China.

There are three epidemiological types of visceral leishmaniasis in China, which are caused by Leishmania strains belonging to the L. donovani complex. The mechanisms underlying their differences in the population affected, disease latency, and animal host, etc., remain unclear. We investigated the protein abundance differences among Leishmania strains isolated from three types of visceral leishmaniasis endemic areas in China. Promastigotes of the three Leishmania strains were cultured to the log phase and harvested. The protein tryptic digests were analyzed with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS), followed by label-free quantitative analysis. The MS experiment was performed on a Q Exactive mass spectrometer. Raw spectra were quantitatively analyzed with the MaxQuant software (ver 1.3.0.5) and matched with the reference database. Differentially expressed proteins were analyzed using the bioinformatics method. The MS analysis wasrepeatedthreetimes for each sample. A total of 5012 proteins were identified across the KS-2, JIASHI-5 and SC6 strains in at least 2 of the three samples replicate. Of them, 1758 were identified to be differentially expressed at least between 2 strains, including 349 with known names. These differentially expressed proteins with known names are involved in biological functions such as energy and lipid metabolic process, nucleotide acid metabolic process, amino acid metabolic process, response to stress, cell membrane/cytoskeleton, cell cycle and proliferation, biological adhesion and proteolysis, localization and transport, regulation of the biological process, and signal transduction. The differentially expressed proteins and their related biological functions may shed light on the pathogenicity of Leishmania and targets for the development of vaccines and medicines.

Spatio-temporal clustering of Mountain-type Zoonotic Visceral Leishmaniasis in China between 2015 and 2019.

With several decades of concerted control efforts, visceral leishmaniasis(VL) eradication had almost been achieved in China. However, VL cases continue to be detected in parts of western China recent years. Using data of reported cases, this study aimed to investigate the epidemiology and spatio⁃temporal distribution, of mountain-type zoonotic visceral leishmaniasis (MT-ZVL) in China between the years 2015 and 2019. Epidemiological data pertaining to patients with visceral leishmaniasis (VL) were collected in Gansu, Shaanxi, Sichuan, Shanxi, Henan and Hebei provinces between the years 2015 and 2019. Joinpoint regression analysis was performed to determine changes in the epidemic trend of MT-ZVL within the time period during which data was collected. Spatial autocorrelation of infection was examined using the Global Moran's I statistic wand hotspot analysis was carried out using the Getis-Ord Gi* statistic. Spatio-temporal clustering analysis was conducted using the retrospective space-time permutation flexible spatial scanning statistics. A total of 529 cases of MT-ZVL were detected in the six provinces from which data were collected during the study time period, predominantly in Gansu (55.0%), Shanxi (21.7%), Shaanxi (12.5%) and Sichuan (8.9%) provinces. A decline in VL incidence in China was observed during the study period, whereas an increase in MT-ZVL incidence was observed in the six provinces from which data was obtained (t = 4.87, P < 0.05), with highest incidence in Shanxi province (t = 16.91, P < 0.05). Significant differences in the Moran's I statistic were observed during study time period (P < 0.05), indicating spatial autocorrelation in the spatial distribution of MT-ZVL. Hotspot and spatial autocorrelation analysis revealed clustering of infection cases in the Shaanxi-Shanxi border areas and in east of Shanxi province, where transmission increased rapidly over the study duration, as well as in well know high transmission areas in the south of Gansu province and the north of the Sichuan province. It indicates resurgence of MT-ZVL transmission over the latter three years of the study. Spatial clustering of infection was observed in localized areas, as well as sporadic outbreaks of infection.

Leishmaniasis Diagnosis via Metagenomic Next-Generation Sequencing.

Leishmaniasis is a vector-borne disease caused by Leishmania. Although the incidence of leishmaniasis in China is currently low, it has not been completely eradicated. In 2019, visceral leishmaniasis was diagnosed in three patients using bone marrow microscopic examination and metagenomic next-generation sequencing (mNGS). The bone marrow mNGS results from the three patients indicated that 99.9, 99.6, and 30.3% of non-human reads matched the Leishmania genome, and plasma mNGS results from one of the patients revealed that 46.2% of non-human reads matched the Leishmania genome. In the second patient's plasma, no Leishmania sequences were detected by plasma mNGS, and the third patient's plasma was unavailable. The pathogen in all three patients was identified as Leishmania infantum. Leishmania amastigotes were observed by microscopic examination of bone marrow smears in all three patients, but were not found in peripheral blood smears. This indicates that the sensitivity of mNGS is higher than that of smear microscopy and that mNGS can be used to identify Leishmania at the species level. All three patients were elderly male farmers, two from Shanxi and one from Beijing. All three patients had splenomegaly and pancytopenia. Originally, these patients were misdiagnosed and treated for extended periods in other hospitals. Diagnoses of visceral leishmaniasis took place 6, 2, and 2 months after the onset of symptoms in the three patients. In conclusion, this study confirms that bone marrow mNGS can be used to quickly and accurately confirm a diagnosis in patients with suspected leishmaniasis.

Prevalence of visceral leishmaniasis in China in 2018

Prevalence of visceral leishmaniasis in China in 2018

Contributions of the National Institute of Parasitic Diseases to the control of visceral leishmaniasis in China.

Visceral leishmaniasis (VL) caused by Leishmania spp. is an important vector-borne disease prevalent in China. VL was rampant in the vast area of China north of the Yangtze River before the founding of the People's Republic of China in 1949. As a result of strenuous interventions, the disease was basically eliminated in most of the former epidemic areas in 1958-60. At present, only sporadic cases occur in the western regions of China. In the process, National Institute of Parasitic Diseases at China CDC and the Chinese Center for Tropical Diseases Research (NIPD-CTDR) have achieved great impact in controlling the diseases as well as in research on Leishmania spp. This review summarized the contribution of experts from NIPD-CTDR to the control and elimination of VL in various aspects, such as understanding the epidemiological features of VL, confirmation of VL vectors and their distribution, development of control tools including diagnostics and insecticides, monitoring and evaluation supported by information management, technical supports to the control programmes, as well as analysis of the challenges faced. At the same time, it puts forward constructive suggestions for the ultimate interruption of VL transmission in China.

Observation on growth and reproduction of various Leishmania isolates in different culture media

To compare the growth and reproduction of the promastigotes of Leishmania isolates from various endemic areas of visceral leishmaniasis in China in various culture media, so as to provide experimental evidence for selecting an appropriate medium for the culture of Leishmania. A total of 3 × 105 promastigotes of KS-2, Cy and JIASHI-5 Leishmania isolates were inoculated into 1 mL NNN medium, 1 mL M199 medium supplemented with 20% fetal bovine serum medium, 1 mL M199 medium supplemented with 20% horse serum medium, and 1 mL brain heart infusion medium containing heme, respectively. All media were placed at 22 ℃ under a sterile condition, and the number of promastigotes was counted continuously for 8 days under a microscope. The growth curve was plotted for the three Leishmania isolates. The promastigotes of KS-2, Cy and JIASHI-5 Leishmania isolates all grew and reproduced in the NNN medium, the M199 medium supplemented with 20% fetal bovine serum medium, and the M199 medium supplemented with 20% horse serum medium. The number of promastigotes of KS-2, Cy and JIASHI-5 Leishmania isolates was all significantly higher in the NNN medium than in the M199 medium supplemented with 20% fetal bovine serum medium, and the M199 medium supplemented with 20% horse serum medium at various time points of culture (all P values < 0.05), and the number of promastigotes of the KS-2 isolate was all significantly greater than that of the Cy and JIASHI-5 isolates in the NNN medium, the M199 medium supplemented with 20% fetal bovine serum medium, and the M199 medium supplemented with 20% horse serum medium at various time points of culture (all P values < 0.05). In ad dition, the promastigotes of KS-2, Cy and JIASHI-5 Leishmania isolates failed to grow and reproduce in the brain heart infusion medium. The growth and reproduction of the promastigotes of various Leishmania isolates from various endemic areas of visceral leishmaniasis in China vary in the same culture medium, and the growth and reproduction of a Leishmania isolate vary in different culture media. The NNN medium best fits for the culture of Leishmania isolates in the endemic areas of visceral leishmaniasis in China.

Transmission risk matrix assessment of imported leishmaniasis in China

To assess the risk of imported leishmaniasis in China, offering scientific evidences for leishmaniasis prevention and control. The expert consultation method was used to establish a risk index system, and the risk matrix was used to evaluate the risk scales of leishmaniasis. This risk assessment indicator system included 3 first-grade indexes and 13 second-grade indexes to the aspect of risk probability. Five indexes were also included on the aspect of the risk hazard severity in this system. The transmission risk matrix assessment showed that the risk of imported leishmaniasis transmission in China was in low risk level. This risk matrix assessment is applied for the transmission of imported leishmaniasis in China in the first time, indicating the potential risk of imported leishmaniasis in China.

Diversity of bacteriome associated with Phlebotomus chinensis (Diptera: Psychodidae) sand flies in two wild populations from China.

Sand fly Phlebotomus chinensis is a primary vector of transmission of visceral leishmaniasis in China. The sand flies have adapted to various ecological niches in distinct ecosystems. Characterization of the microbial structure and function will greatly facilitate the understanding of the sand fly ecology, which would provide critical information for developing intervention strategy for sand fly control. In this study we compared the bacterial composition between two populations of Ph. chinensis from Henan and Sichuan, China. The phylotypes were taxonomically assigned to 29 genera of 19 families in 9 classes of 5 phyla. The core bacteria include Pseudomonas and enterobacteria, both are shared in the sand flies in the two regions. Interestingly, the endosymbionts Wolbachia and Rickettsia were detected only in Henan, while the Rickettsiella and Diplorickettsia only in Sichuan. The intracellular bacteria Rickettsia, Rickettsiella and Diplorickettsia were reported for the first time in sand flies. The influence of sex and feeding status on the microbial structure was also detected in the two populations. The findings suggest that the ecological diversity of sand fly in Sichuan and Henan may contribute to shaping the structure of associated microbiota. The structural classification paves the way to function characterization of the sand fly associated microbiome.

Spatial analysis of visceral leishmaniasis in the oases of the plains of Kashi Prefecture, Xinjiang Uygur Autonomous Region, China.

BackgroundKashi Prefecture of Xinjiang is one of the most seriously affected areas with anthroponotic visceral leishmaniasis in China. A better understanding of space distribution features in this area was needed to guide strategies to eliminate visceral leishmaniasis from highly endemic areas. We performed a spatial analysis using the data collected in Bosh Klum Township in Xinjiang China.MethodsBased on the report of endemic diseases between 1990 and 2005, three villages with a high number of visceral leishmaniasis cases in Bosh Klum Township were selected. We conducted a household survey to collect the baseline data of kala-azar patients using standard case definitions. The geographical information was recorded with GIS equipment. A binomial distribution fitting test, runs test, and Scan statistical analysis were used to assess the space distribution of the study area.ResultsThe result of the binomial distribution fitting test showed that the distribution of visceral leishmaniasis cases in local families was inconsistent (χ2 = 53.23, P < 0.01). The results of runs test showed that the distribution of leishmaniasis infected families along the channel was not random in the group of more than five infected families. The proportion of this kind of group in all infected families was 63.84 % (113 of 177). In the Scan statistical analysis, spatial aggregation was analyzed by poisson model, which found 3 spatial distribution areas 1) Zone A was located in a center point of 76.153447°E, 39.528477°N within its 1.11 mile radius, where the cumulative life-incidence of leishmaniasis was 1.95 times as high as that in surrounding areas (P < 0.05); 2) Zone B was located in a center point of 76.111968°E, 39.531895°N within its 0.54 mile radius, where the cumulative life-incidence of leishmaniasis was 1.82 times as high as that in surrounding areas (P < 0.01); and 3) Zone C was located in a center point of 76.195427°E, 39.563835°N within its 0.68 mile radius, where the cumulative life-incidence of leishmaniasis was 1.31 times as high as that in surrounding areas (P < 0.05).ConclusionsThe spatial distribution of visceral leishmaniasis-infected families was clustered. Thus, the proper use of this finding would be an improvement in highly endemic areas, which could help identify the types of endemic areas and population at high risk and carry out appropriate measures to prevent and control VL in this area as well.

Visceral Leishmaniasis in China: an Endemic Disease under Control.

Visceral leishmaniasis (VL) caused by Leishmania spp. is an important vector-borne and largely zoonotic disease. In China, three epidemiological types of VL have been described: anthroponotic VL (AVL), mountain-type zoonotic VL (MT-ZVL), and desert-type ZVL (DT-ZVL). These are transmitted by four different sand fly species: Phlebotomus chinensis, P. longiductus, P. wui, and P. alexandri. In 1951, a detailed survey of VL showed that it was rampant in the vast rural areas west, northwest, and north of the Yangtze River. Control programs were designed and implemented stringently by the government at all administrative levels, resulting in elimination of the disease from most areas of endemicity, except the western and northwestern regions. The control programs consisted of (i) diagnosis and chemotherapy of patients, (ii) identification, isolation, and disposal of infected dogs, and (iii) residual insecticide indoor spraying for vector control. The success of the control programs is attributable to massive and effective mobilization of the general public and health workers to the cause. Nationally, the annual incidence is now very low, i.e., only 0.03/100,000 according to the available 2011 official record. The overwhelming majority of cases are reported from sites of endemicity in the western and northwestern regions. Here, we describe in some depth and breadth the current status of epidemiology, diagnosis, treatment, and prevention of the disease, with particular reference to the control programs. Pertinent information has been assembled from scattered literature of the past decades in different languages that are not readily accessible to the scientific community. The information provided constitutes an integral part of our knowledge on leishmaniasis in the global context and will be of special value to those interested in control programs.

A study of phlebotomine sandflies (Diptera: Psychodidae) in Yunnan Province, China. Sergentomyia (Sergentomyia) wangi n. sp.

Among the phlebotomine sandflies collected in a lime-stone cave of 21 degrees 42' N, 10 degrees 23' E and 700 m above sea level on 14th August, Mengyuan, Mengla County, Xishuangbanna District, Yunnan Province, two males of the group fallax of subgenus Sergentomyia are quite different in morphology with those hitherto recorded in the literature. In the present paper its morphology is described with seven figures and the name Sergentomyia wangi is proposed in honor of professor Chao-Tsun Wang for his contribution in study and control of leishmaniasis in China.

Present situation of visceral leishmaniasis in China.

Visceral leishmaniasis or kala azar is a disease that is distributed world-wide from countries around the Mediterranean Sea to Africa, the Middle East, Asia and South America (Fig. 1). Visceral leishmaniasis was highly prevalent in China but since 1958, after a nationwide campaign, it has been brought under control. Only sporadic cases occur in the hilly and newly reclaimed desert areas in NW China.

中国におけるサシチョウバエとレーシュマニュア症の媒介

中国におけるサシチョウバエとレーシュマニュア症の媒介