Epidemiologic changes of a longitudinal surveillance study spanning 51 years of scrub typhus in mainland China.

Scrub typhus may be one of the world's most prevalent, neglected and serious, but easily treatable, febrile diseases. It has become a significant potential threat to public health in China. In this study we used national disease surveillance data to analyze the incidence and spatial-temporal distribution of scrub typhus in mainland China during 1952-1989 and 2006-2018. Descriptive epidemiological methods and spatial-temporal epidemiological methods were used to investigate the epidemiological trends and identify high-risk regions of scrub typhus infection. Over the 51-year period, a total of 182,991 cases and 186 deaths were notified. The average annual incidence was 0.13 cases/100,000 population during 1952-1989. The incidence increased sharply from 0.09/100,000 population in 2006 to 1.93/100,000 population in 2018 and then exponentially increased after 2006. The incidence was significantly higher in females than males (χ2 = 426.32, P < 0.001). Farmers had a higher incidence of scrub typhus than non-farmers (χ2 = 684.58, P < 0.001). The majority of cases each year were reported between July and November with peak incidence occurring during October each year. The trend surface analysis showed that the incidence of scrub typhus increased gradually from north to south, and from east and west to the central area. The spatial autocorrelation analysis showed that a spatial positive correlation existed in the prevalence of scrub typhus on a national scale, which had the characteristic of aggregated distribution (I = 0.533, P < 0.05). LISA analysis showed hotspots (High-High) were primarily located in the southern and southwestern provinces of China with the geographical area expanding annually. These findings provide scientific evidence for the surveillance and control of scrub typhus which may contribute to targeted strategies and measures for the government.

Infestation and distribution of chiggers on the Anderson's white-bellied rats in southwest China.

As a group of ectoparasites, chiggers (larvae of chigger mites) are the exclusive vector of scrub typhus (tsutsugamushi disease). Rodents are the most important hosts of chiggers. The Anderson's niviventer rat, Niviventer andersoni, is an endemic species of rodent in China. However, few studies have involved this endemic rodent species and its ectoparasites including chiggers. According to the field investigation in five provincial regions of southwest China between 2001 and 2019, this paper retrospectively analysed the infestation and distribution of chiggers on the body surface of N. andersoni in southwest China for the first time. From 77 Anderson's niviventer rats captured, a total of 527 chiggers were collected and they were identified as 39 species and nine genera in two subfamilies of family Trombiculidae. Of 39 chigger species identified, Leptotrombidium deliense and L. scutellare are the most important vectors of scrub typhus in China. The overall infestation indexes were PM = 29.87%, MA = 6.84 and MI = 22.91, and the indexes of chigger mite community were Mf = 39, H' = 2.60, E = 0.71 and D = 0.12. The dominant chigger species are L. wenense, L. xiaguanense and L. fujianense with a total Cr = 51.04%, among which L. wenense is one of the six main vectors of scrub typhus in China. The dominant chigger species are of aggregated distribution among different individuals of the rats.

A practical preparation of bicyclic boronates via metal-free heteroatom-directed alkenyl sp2-C‒H borylation.

Bicyclic boronates play critical roles in the discovery of functional materials and antibacterial agents, especially against deadly bacterial pathogens. Their practical and convenient preparation is in high demand but with great challenge. Herein, we report an efficient strategy for the preparation of bicyclic boronates through metal-free heteroatom-directed alkenyl sp2-C‒H borylation. This synthetic approach exhibits good functional group compatibility, and the corresponding boronates bearing halides, aryls, acyclic and cyclic frameworks are obtained with high yields (43 examples, up to 95% yield). Furthermore, a gram-scale experiment is conducted, and downstream transformations of the bicyclic boronates are pursued to afford natural products, drug scaffolds, and chiral hemiboronic acid catalysts.

Infestation of Oriental House Rat (Rattus tanezumi) with Chigger Mites Varies along Environmental Gradients across Five Provincial Regions of Southwest China.

Chigger mites are the exclusive vector of scrub typhus. Based on field investigations of 91 survey sites in 5 provincial regions of Southwest China, this paper reported variations of chigger infestation on the oriental house rat (Rattus tanezumi) along various environmental gradients. A total of 149 chigger species were identified from 2919 R. tanezumi in the 5 provincial regions, and Leptotrombidium deliense (a major vector of scrub typhus in China) was the first dominant chigger species, followed by Ascoschoengastia indica and Walchia ewingi. Rattus tanezumi had a stable overall prevalence (PM = 21.10%), mean abundance (MA = 7.01), and mean intensity (MI = 33.20) of chiggers with the same dominant mites in the whole Southwest China in comparison with a previous report in Yunnan Province, but chigger infestations on R. tanezumi varied along different environmental gradients. Rattus tanezumi in mountainous landscape had a higher infestation load of chiggers with higher species diversity than in flatland landscape. The infestation was higher at lower altitudes and latitudes. A high intensity of vegetation coverage was associated with high infestations. The results reflect the environmental heterogeneity of chiggers on the same host species. Warm climate and high relative humidity are beneficial to chigger infestation on R. tanezumi.

Analysis on infestation and related ecology of chigger mites on large Chinese voles (Eothenomys miletus) in five provincial regions of Southwest China.

Based on a long-term field investigation in the five provincial regions of Southwest China between 2001 and 2019, the present paper studied the infestation and related ecology of chigger mites (chiggers) on the large Chinese vole (Eothenomys miletus), an endemic and dominant rodent species in the regions. A total of 52331 chiggers were collected from 2661 voles, and 52261 mites were identified as 185 species and 13 genera in the family Trombiculidae with very high species diversity. The identified 185 chigger species on E. miletus (a single rodent species) even exceeded those recorded in some countries. The overall infestation prevalence (P m  = 53.96%), mean abundance (MA = 19.64) and mean intensity (MI = 36.39) on E. miletus were much higher than those on some other rodent species in the same regions. Although the species composition showed a moderate similarity (J = 0.63) between male and female hosts (E. miletus), the infestation indices (P m  = 56.25%, MA = 21.67) of chiggers on male hosts were higher than those on the females (P m  = 51.23%, MA = 17.09) (P < 0.05). Two dominant chigger species, Leptotrombidium scutellare (C r  = 19.17%) and L. sinicum (C r  = 11.06%), showed an aggregated distribution pattern among different individuals of their host E. miletus, and a relatively high degree of positive association existed between the two dominant chigger species with PCC = 0.57, DI = 0.60 and OI = 0.62 (x 2  = 857.46, P < 0.001). Leptotrombidium densipunctatum, Walchia koi, Helenicula hsui, L. scutellare and W. ewingi showed a high degree of environmental adaptability to their environments with high niche breadths. The theoretical curve of the species abundance distribution of chigger community on E. miletus was successfully fitted with Preston's lognormal distribution model. Based on the theoretical curve fitting, the expected total number of chigger species on E. miletus was roughly estimated to be 223 species, and 38 chigger species were probably missed in the sampling investigation.

Infestation of chigger mites on Chinese mole shrew, Anourosorex squamipes, in Southwest China and ecological analysis.

The Chinese mole shrew, Anourosorex squamipes Milne-Edwards, 1872, is a common species of insectivorous mammal in Southwest China. Based on field investigations between 2001 and 2019, the present study reports the infestation of chiggers (larvae of chigger mites) on the shrew in Southwest China and certain ecology parameters for the first time. A total of 3169 chiggers were collected from 1694 A. squamipes and they were identified into 72 species and 10 genera in the family Trombiculidae. The overall infestation prevalence (Pm), mean abundance (MA) and mean intensity (MI) of A. squamipes with chiggers reached 11.1%, 1.87 and 16.86, respectively. The species diversity, species composition and infestation of chiggers on A. squamipes fluctuated in different environments (latitudes, altitudes, habitats and landscapes) and on different sexes and ages of the shrew hosts with high heterogeneity and low species similarity. In the established linear regression equation (M* = 0.173 + 1.054 M) for dominant mite Leptotrombidium densipunctatum, both the α and ß values (α = 0.173, ß = 1.054) exceeded the boundary values (F = 4.67, p < 0.05), and therefore the spatial distribution pattern of this mite was determined as an aggregated distribution among different individuals of shrew hosts. The species abundance distribution of the chigger community on A. squamipes conformed to the lognormal distribution, and its curve showed a gradually descending tendency from the rare mite species to the dominant mite species. The curve tendency of species-sample relationship implies that more species of chiggers would be found if the host samples infinitely keep increasing.

Title: Infestation de la musaraigne Anourosorex squamipes par les acariens dans le sud-ouest de la Chine et analyse écologique. Abstract: La musaraigne Anourosorex squamipes Milne-Edwards, 1872 est une espèce commune de mammifère insectivore dans le sud-ouest de la Chine. Sur la base d'enquêtes de terrain entre 2001 et 2019, la présente étude signale pour la première fois l'infestation et certains paramètres écologiques des acariens larvaires sur cette musaraigne dans le sud-ouest de la Chine. Un total de 3169 acariens ont été collectés sur 1694 A. squamipes et ils ont été identifiés en 72 espèces et 10 genres de la famille des Trombiculidae. La prévalence globale de l'infestation (Pm), l'abondance moyenne (MA) et l'intensité moyenne (MI) des acariens sur A. squamipes ont atteint respectivement 11,1 %, 1,87 et 16,86. La diversité des espèces, la composition des espèces et l'infestation des acariens sur A. squamipes ont fluctué selon différents environnements (latitudes, altitudes, habitats et paysages) et selon le sexe et l'âge des hôtes avec une forte hétérogénéité et une faible similitude entre espèces. Dans l'équation de régression linéaire établie (M* = 0,173 + 1054 M) pour l'acarien dominant Leptotrombidium densipunctatum, les valeurs α et ß (α = 0,173, ß = 1,054) dépassaient les valeurs limites (F = 4,67, p < 0,05), et par conséquent, le modèle de distribution spatiale a été déterminé comme une distribution agrégée entre différents individus d'hôtes. La distribution de l'abondance des espèces de la communauté d'acariens sur A. squamipes se conformait à la distribution log-normale et la courbe a montré une tendance progressivement descendante des espèces d'acariens rares à l'espèce d'acarien dominante. La tendance de la courbe de la relation espèce-échantillon implique que davantage d'espèces d'acariens seraient trouvées si l'échantillonnage des hôtes continuaient à augmenter à l'infini.

Epidemiological characteristics and spatiotemporal patterns of scrub typhus in Yunnan Province from 2006 to 2017.

Scrub typhus is an acute infectious disease in humans. A temporal, spatial and epidemiologic study was conducted to understand the characteristics of scrub typhus in Yunnan, to assist public health prevention and control measures. Based on the data on all cases reported in Yunnan during 2006-2017, we characterized the epidemiological features. Spatio-temporal patterns and Q-type cluster method were adopted to analyze the incidence of scrub typhus in Yunnan. In total, 27,838 scrub typhus cases were reported in Yunnan during 2006-2017. Of these, 49.53% (13,787) were male and 50.47% (14,051) were female (P > 0.05). Most patients were farmers (71.70%) (P < 0.05) and children aged 0-5 years (13.16%) (P < 0.01), which accounted for 84.86% of the total cases. An almost 20-fold increase in the number of patients was observed in 2017 (6,337 cases) compared to 2006 (307 cases). Baoshan and Lincang had the most cases accounting for 41.94%, while Diqing had the lowest incidence (only 3 cases). Sixteen municipalities infected were classified into three groups numbered in sequence. The incidence of scrub typhus in Yunnan is high and the annual incidence increased noticeably over time. Our results also indicate that surveillance and public education need to be focused on Baoshan, Lincang and Dehong.

Diastereo- and enantioselective rhodium(III)-catalyzed reductive cyclization of cyclohexadienone-containing 1,6-dienes.

A diastereo- and enantioselective rhodium(III)-catalyzed reductive cyclization of cyclohexadienone-tethered terminal alkenes and (E)-1,2-disubstituted alkenes (1,6-dienes) is reported, providing cis-bicyclic products bearing three contiguous stereocenters with good yields and high diastereo- and enantioselectivities. The kinetic resolution of the racemic precursor is also achieved with good efficiency. Moreover, a subgram-scale experiment, several transformations of the cyclization product, and one-pot preparation of bridged polycyclic frameworks are presented.

Infestation and seasonal fluctuation of chigger mites on the Southeast Asian house rat (Rattus brunneusculus) in southern Yunnan Province, China.

Chigger mites are the common ectoparasites of rodents and the exclusive vector of scrub typhus. The Southeast Asian house rat (Rattus brunneusculus) is an important reservoir host and infectious source of some zoonoses including scrub typhus. From April 2016 to March 2017, a 12-month consecutive investigation was made at Jingha village in southern Yunnan of China, which is an important focus of scrub typhus. The infestation and seasonal fluctuation of chigger mites on R. brunneusculus were studied based on the investigation. From 2,053 captured R. brunneusculus, a total of 99,221 chiggers were collected and identified as comprising 102 species with very high species diversity. The richness (S), diversity index (H'), evenness (E) and dominance index (D) of the chigger community on the rat varied in different months. Of the 102 chigger species, five main species accounted for 84.81% of the total chiggers (84,147/99,221). The five main chiggers were Walchia (W.) micropelta (32.65%), Ascoschoengastia indica (24.68%), Leptotrombidium (L.) deliense (19.02%), W. (W.) turmalis (4.63%) and L. (L.) scutellare (3.83%). Of the five chigger species, L. (L.) deliense and L. (L.) scutellare are the most important vectors of scrub typhus in China. The five chigger species showed different patterns of seasonal fluctuation. The seasonal fluctuation of L. (L.) deliense belonged to summer-autumn type with the highest peak in July, but L.(L.) scutellare mainly appeared in winter and spring with the peak from January to February. The temperature and rainfall were two key factors which influenced the seasonal fluctuation of chigger mites.

Rhodium(III)-Catalyzed Kinetic Resolution of Racemic 1,6-Dienes via Asymmetric Borylative Cyclization.

The rhodium(III)-catalyzed kinetic resolution of racemic nonactivated terminal alkene-tethered cyclohexadienones (1,6-dienes) has been developed with high to excellent selectivities (s up to 458) via asymmetric borylative cyclization, providing recovered cyclohexadienones and cis-hydrobenzofuranones with good to excellent yields and enantioselectivities (up to 99% ee). This reaction shows broad functional group tolerance and allows the further conversions of these two-type products to many optically active derivatives bearing multiple functionalities via Rh, Cu, Pd, and Ag catalysis.

Landscapes with different biodiversity influence distribution of small mammals and their ectoparasitic chigger mites: A comparative study from southwest China.

From a previous field investigation in Yunnan, southwest China between 2001 and 2015, we selected two types of landscapes to make a retrospectively comparative study on the distribution of small mammals and their ectoparasitic chigger mites. One landscape is "mountainous uncultivated land (MUL)" with higher biodiversity, which is located in a famous "World Nature Heritage Site", the Three-Parallel-Rivers Region in the northwest of Yunnan. The other is "cultivated flatland landscape (CFL)" with lower biodiversity, which is located in the south of Yunnan. The landscapes with different biodiversity apparently influenced the distribution of small mammals and their ectoparasitic chigger mites. Much more species of small mammals and mites were found in MUL than in CFL. A total of 3,177 small mammals captured from MUL were identified as 55 species, 30 genera and 10 families in five orders. From these small mammal hosts, 5,882 chigger mites were collected and identified as 127 species, 15 genera and 3 subfamilies in two families. A total of 1,112 small mammals captured from CFL were identified as 19 species, 12 genera and 5 families in three orders. From these hosts, 17,742 chiggers were collected and identified as 86 species, 12 genera and 3 subfamilies in two families. Both the species diversity (S = 55) and community diversity (H = 2.673) of small mammals in MUL were much higher than those in CFL (S = 19; H = 0.926). There were also higher values of ß diversity in MUL than in CFL. Different main reservoir rodent hosts of zoonoses (including tsutsugamushi disease) were found in two types of landscapes. Rattus tanezumi (one main reservoir host) was most abundant in CFL, which accounted for 80.22% of all the small mammals. Another two main reservoir hosts, Eothenomys miletus and Apodemus chevrieri were the dominant species in MUL, but they were not as abundant as R. tanezumi in CFL. Different vector species of chigger mites also existed in MUL and CFL. Leptotrombidium deliense (a main and powerful vector of tsutsugamushi disease in China) and Ascoschoengastia indica (a potential vector of tsutsugamushi disease) were the dominant species of chigger mites in CFL (Cr = 25.81% for A. indica; Cr = 23.47% for L. deliense). Leptotrombidium scutellare (also a main vector of tsutsugamushi disease in China) was the dominant chigger species in MUL (Cr = 26.09%). Higher infestation of vector mites on small mammals was found in the simple landscape with lower biodiversity (CFL) than in the complex landscape with higher biodiversity (MUL). The overall prevalence (P), mean abundance (MA) and mean intensity (MI) of chigger mites on small mammals were much higher in CFL than in MUL. The main vector mite species on their main rodent hosts also showed a higher P, MA and MI in CFL than in MUL.

Species diversity of ectoparasitic chigger mites (Acari: Prostigmata) on small mammals in Yunnan Province, China.

Chigger mites are a large group of arthropods and the larvae of mites are ectoparasites. Some species of ectoparasitic mites (larvae) can be the transmitting vectors of tsutsugamushi disease (scrub typhus). Yunnan Province is located in the southwest of China with complicated topographic landform and high biodiversity, where there are five zoogeographical subregions. Rodents and some other small mammals were trapped and examined for ectoparasitic chigger mites in 29 investigation sites in Yunnan during 2001-2013. From 13,760 individuals and 76 species of small mammal hosts, we collected 274 species of mites, which were identified as comprising 26 genera in two families. The species diversity of chigger mites (274 species) in the present study were not only much higher than that from other provinces of China but also largely exceeded that recorded from other regions and countries in the world. Of the five zoogeographical subregions, both the species diversity and Shannon-Weiner's diversity of mites were the highest in subregion II (southern subregion of Hengduan Mountains) with middle altitudes and middle latitude. Both the species diversity of mites and Shannon-Wiener diversity index showed a parabolic tendency from the low altitude (<500 m) to the high altitude (>3500 m) along the vertical gradients with the peak occurring in the middle-altitude regions (2000-2500 m). Of four dominant hosts, the species richness of mites was highest on Eothenomys miletus (S = 165) and Shannon-Wiener diversity index was highest on Rattus norvegicus (H = 3.13). Along latitude gradients, species richness of chigger mites increased first and then decreased, peaking at 25° to 26° N with 193 mite species. The geographical location, complex topography, and landscape with diverse small mammal hosts in Yunnan Province have contributed to the extremely high species diversity of mites in the province. The large sampling size of small mammal hosts in a wide geographical scope within a long time span also made it possible to have collected so many species of chigger mites.

An updated distribution and hosts: trombiculid mites (Acari: Trombidiformes) associated with small mammals in Yunnan Province, southwest China.

Trombiculid mites (or chigger mites) are a large group of arthropods, and some of these species are vectors of Orientia tsutsugamushi, the causative agent of tsutsugamushi disease (scrub typhus). Yunnan Province is situated in the southwest of China, and its complicated topography, special altitude gradients, and high biodiversity have aroused the interest of many scientists to study the fauna and species diversity of plants and animals. To replenish our former faunal study, this paper listed all the scientific names of trombiculid mites in Yunnan Province, together with their hosts and collection sites (geographical distribution). A total of 120,138 individuals of trombiculid mites were collected from the body surface of 13,760 small mammal hosts (89.06 % of them are rodents) in 29 collection sites (counties) of Yunnan Province from 2001 to 2013. The 120,138 mites were identified as comprising 2 families (Trombiculidae and Leeuwenhoekiidae), 26 genera, and 274 species. The genus Leptotrombidium had the most abundant species (109 species) of 26 genera. Of the six main vectors of scrub typhus in China, five of them were found in Yunnan. Of the 274 chigger mite species, 23 were determined as the newly recorded species (new records), which were found in Yunnan Province for the first time. The identified 274 species of trombiculid mites in the present paper are much more than those from other provinces in China and even largely exceeded the species of trombiculid mites recorded from some other regions and countries in the world. Based on the formula of Chao 1, the total number of chigger mite species in Yunnan was approximately estimated to be 346 species, and about 72 species might have been missed in our sampling process.

Ectoparasitic chigger mites on large oriental vole (Eothenomys miletus) across southwest, China.

An investigation of chigger mites on the large oriental vole, Eothenomys miletus (Rodentia: Cricetidae), was conducted between 2001 and 2013 at 39 localities across southwest China, and 2463 individuals of the vole hosts were captured and examined, which is a big host sample size. From the body surface of E. miletus, 49,850 individuals of chigger mites were collected, and they were identified as comprising 175 species, 13 genera, and 3 subfamilies in 2 families (Trombiculidae and Leeuwenhoekiidae). The 175 species of chigger mites from such a single rodent species (E. miletus) within a certain region (southwest China) extremely exceeded all the species of chigger mites previously recorded from multiple species of hosts in a wide region or a whole country in some other countries, and this suggests that E. miletus has a great potential to harbor abundant species of chigger mites on its body surface. Of 175 mite species, Leptotrombidium scutellare was the most dominant species, which has been proved as one of the main vectors of scrub typhus and the potential vector of haemorrhagic fever with renal syndrome (HFRS) in China. The patchiness index (m*/m) was used to measure the spatial patterns of the dominant chigger mite species, and all the three dominant mite species (L. scutellare, Leptotrombidium sinicum, and Helenicula simena) showed aggregated distributions among the different host individuals. The coefficient of association (V) was adopted to measure the interspecies interaction between the dominant mite species and a slightly positive association existed between L. scutellare and L. sinicum (V = 0.28, P < 0.01), which implies that these two mite species can co-exist on the same species of the host, E. miletus. The tendency curve of species abundance showed that the number of chigger mite species gradually decreased with the increase of mite individuals, and this revealed that most chigger mite species were rare with very few individuals, but few dominant species had abundant individuals. The species-sample relationship indicated that the number of chigger mite species increased with the increase of the host samples. The results suggest that a big host sample size over a wide realm of geographical regions is needed in the field investigation in order to obtain a true picture of species diversity and species composition.

Faunal analysis of chigger mites (Acari: Prostigmata) on small mammals in Yunnan province, southwest China.

This paper studied the species diversity and fauna distribution of chigger mites on small mammals in Yunnan province, southwest Yunnan. In total, 120,138 individuals of chigger mites were collected from 13,760 individual small mammals, and these mites were identified as comprising two families, 26 genera, and 274 species. Of the five zoogeographical subregions, the mite species diversity in subregions I and II was higher than that in subregions III, IV, and V. Four mite species (Leptotrombidium scutellare, Leptotrombidium sinicum, Leptotrombidium deliense, and Helenicula simena) were the most dominant species in the whole province. Several vector species of chigger mites co-existed in Yunnan, and L. deliense (a main vector of scrub typhus in China) was mainly distributed in subregions IV and V with lower latitude and average altitude whereas L. scutellare (also a main vector in China) was mainly distributed in subregions I, II, and III with higher latitude and average altitude. Some geographically widely distributed mite species were also the mites with wide host ranges and low host specificity. The dominant mite species and their clustering tendency in the dendrogram of hierarchical clustering analysis were highly in accordance with the zoogeographical divisions. The species diversity of chigger mites showed a parabolic tendency from the low altitude (<500 m) to the high altitude (>3,500 m) along the vertical gradients and reached the highest value in the middle altitude regions in 2,000-2,500 m. The highest species diversity of the mites and their small mammal hosts happened in the regions around the Hengduan Mountains, which is a hotspot of biodiversity in Asia continent. The host and its sample size, geographical scope, landscape, topography, and some other factors comprehensively influence the species diversity and faunal distribution of chigger mites. A systematic field investigation with a wide geographical scope and large host sample is strongly recommended in the fauna study of chigger mites and other ectoparasites.