Geographical origin of Plasmodium vivax in the Hainan Island, China: insights from mitochondrial genome.

BACKGROUND: Hainan Province, China, has been an endemic region with high transmission of Plasmodium falciparum and Plasmodium vivax. Indigenous malaria caused by P. vivax was eliminated in Hainan in 2011, while imported vivax malaria remains. However, the geographical origin of P. vivax cases in Hainan remains unclear. METHODS: Indigenous and imported P. vivax isolates (n = 45) were collected from Hainan Province, and the 6 kb mitochondrial genome was obtained. Nucleotide (π) and haplotype (h) diversity were estimated using DnaSP. The numbers of synonymous nucleotide substitutions per synonymous site (dS) and nonsynonymous nucleotide substitutions per nonsynonymous site (dN) were calculated using the SNAP program. Arlequin software was used to estimate the genetic diversity index and assess population differentiation. Bayesian phylogenetic analysis of P. vivax was performed using MrBayes. A haplotype network was generated using the NETWORK program. RESULTS: In total, 983 complete mitochondrial genome sequences were collected, including 45 from this study and 938 publicly available from the NCBI. Thirty-three SNPs were identified, and 18 haplotypes were defined. The haplotype (0.834) and nucleotide (0.00061) diversity in the Hainan populations were higher than China's Anhui and Guizhou population, and the majority of pairwise FST values in Hainan exceeded 0.25, suggesting strong differentiation among most populations except in Southeast Asia. Most Hainan haplotypes were connected to South/East Asian and China's others haplotypes, but less connected with populations from China's Anhui and Guizhou provinces. Mitochondrial lineages of Hainan P. vivax belonged to clade 1 of four well-supported clades in a phylogenetic tree, most haplotypes of indigenous cases formed a subclade of clade 1, and the origin of seven imported cases (50%) could be inferred from the phylogenetic tree, but five imported cases (42.8%) could not be traced using the phylogenetic tree alone, necessitating epidemiological investigation. CONCLUSIONS: Indigenous cases in Hainan display high genetic (haplotype and nucleotide) diversity. Haplotype network analysis also revealed most haplotypes in Hainan were connected to the Southeast Asian populations and divergence to a cluster of China's other populations. According to the mtDNA phylogenetic tree, some haplotypes were shared between geographic populations, and some haplotypes have formed lineages. Multiple tests are needed to further explore the origin and expansion of P. vivax populations.

Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model.

BACKGROUND: Pancreatic cancer is one of the most aggressive malignancies without effective targeted therapies. MUC1 has emerged as a potential common target for cancer therapy because it is overexpressed in a variety of different cancers including the majority of pancreatic cancer. However, there are still no approved monoclonal antibody drugs targeting MUC1 have been reported. Recently, we generated a humanized MUC1 antibody (HzMUC1) specific to the interaction region between MUC1-N and MUC1-C. In this study, we generated the antibody drug conjugate (ADC) by conjugating HzMUC1 with monomethyl auristatin (MMAE), and examined the efficacy of HzMUC1-MMAE against the MUC1-positive pancreatic cancer in vitro and in vivo. METHODS: Western blot and immunoprecipitation were used to detect MUC1 in pancreatic cancer cells. MUC1 localization in pancreatic cancer cells was determined by confocal microscopy. HzMUC1 was conjugated with the monomethyl auristatin (MMAE), generating the HzMUC1-MMAE ADC. Colony formation assay and flow cytometry were used to assess the effects of the HzMUC1-MMAE cell viability, cell cycle progression and apoptosis. Capan-2 and CFPAC-1 xenograft model were used to test the efficacy of HzMUC1-MMAE against pancreatic cancer. RESULTS: HzMUC1 antibody binds to MUC1 on the cell surface of pancreatic cancer cells. HzMUC1-MMAE significantly inhibited cell growth by inducing G2/M cell cycle arrest and apoptosis in pancreatic cancer cells. Importantly, HzMUC1-MMAE significantly reduced the growth of pancreatic xenograft tumors by inhibiting cell proliferation and enhancing cell death. CONCLUSION: Our results indicate that HzMUC1-ADC is a promising novel targeted therapy for pancreatic cancer. HzMUC1-ADC should also be an effective drug for the treatment of different MUC1-positive cancers.

Genetic diversity of Plasmodium vivax population before elimination of malaria in Hainan Province, China.

BACKGROUND: Hainan Province is one of the most severe endemic regions with high transmission of Plasmodium falciparum and Plasmodium vivax in China. However, the incidence of P. falciparum and P. vivax has dropped dramatically since 2007 and a national elimination malaria programme (NEMP) was launched after 2010. To better understand the genetic information on P. vivax population before elimination of malaria in Hainan Province, the extent of genetic diversity of P. vivax isolates in Hainan Province was investigated using four polymorphic genetic markers, including P. vivax merozoite surface proteins 1, 3α, and 3ß (pvmsp-1, pvmsp-3α, and pvmsp-3ß) and circumsporozoite protein (pvcsp). METHODS: Isolates of P. vivax (n = 27) from Hainan Province were collected from 2009 to 2010 and pvmsp-1 and pvcsp were analysed by DNA sequencing, respectively. Using polymerase chain reaction-restriction fragment length polymorphism were analysed in pvmsp-3α, and pvmsp-3ß. RESULTS: The DNA sequencing analysis on pvmsp1 revealed that there were three allele types: Salvador-1 (Sal-1), Belem and recombinant (R) types. Among them, Sal-1 type was a dominant strain with eight variant subtypes (88.9%), whereas R- (3.7%) and Belem-type strains (7.4%) had one variant subtypes, respectively. All the isolates carried pvcsp with VK210 type accounting for 85.2% (23/27 isolates) and VK247 type accounting for 14.8% (4/27). Only type A and type B alleles were successfully amplified in pvmsp-3α gene, and a high level of polymorphism was observed in pvmsp-3α. Considering pvmsp-3ß gene, type A was the predominant type in 17 isolates (63%), whereas type B was dominant in only ten isolates (37%). CONCLUSION: The present data indicate that there was high degree of genetic diversity among P. vivax population in Hainan Province of China during the pre-elimination stage of malaria, with 26 unique haplotypes observed among 27 samples.

Sensitivity of Plasmodium falciparum to antimalarial drugs in Hainan Island, China.

Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time (22.5 ± 10.6 hr) and the mean parasite clearance time (27.3 ± 12.2 hr) showed no statistical significance with different genders, ages, temperatures, or parasite density (P > 0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (P < 0.0001). The resistance intensities decreased as follows: chloroquine > piperaquine > pyronarididine > artesunate. The inhibitory dose 50 (IC50) was 3.77 × 10(-6) mol/L, 2.09 × 10(-6) mol/L, 0.09 × 10(-6) mol/L, and 0.05 × 10(-6) mol/L, and the mean concentrations for complete inhibition (CIMC) of schizont formation were 5.60 × 10(-6) mol/L, 9.26 × 10(-6) mol/L, 0.55 × 10(-6) mol/L, and 0.07 × 10(-6) mol/L, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.

Prevention measures and socio-economic development result in a decrease in malaria in Hainan, China.

BACKGROUND: Historically, the incidence of malaria in the Hainan Province, China has been high. However, since 2001 the malaria incidence in Hainan has decreased due to large-scale, public educational, promotional campaigns and the adoption of preventative measures against malaria following the fast growth of socio-economic development. The present study analysed the correlation between prevention measures and social economic development on the incidence of malaria in Hainan from 2001 to 2013. METHODS: The data of malaria preventative measures and socio-economic development were collected from various cities and counties in Hainan Province from 2001 to 2013 and analysed by the grey correlation analysis system. RESULTS: Seasonal preventive medication and local fiscal revenue increases are significantly related to the reduction of malaria incidence from 2001 to 2013 (R1 = 0.751677; R5 = 0.764795). CONCLUSION: Malaria prevention and control measures and local economic development in Hainan decreased malaria incidence from 2001 to 2013.

Eliminating Plasmodium falciparum in Hainan, China: a study on the use of behavioural change communication intervention to promote malaria prevention in mountain worker populations.

BACKGROUND: In the island of Hainan, the great majority of malaria cases occur in mountain worker populations. Using the behavioral change communication (BCC) strategy, an interventional study was conducted to promote mountain worker malaria prevention at a test site. This study found the methods and measures that are suitable for malaria prevention among mountain worker populations. METHODS: During the Plasmodium falciparum elimination stage in Hainan, a representative sampling method was used to establish testing and control sites in areas of Hainan that were both affected by malaria and had a relatively high density of mountain workers. Two different methods were used: a BCC strategy and a conventional strategy as a control. Before and after the intervention, house visits, core group discussions, and structural surveys were utilized to collect qualitative and quantitative data regarding mountain worker populations (including knowledge, attitudes, and practices [KAPs]; infection status; and serological data), and these data from the testing and control areas were compared to evaluate the effectiveness of BCC strategies in the prevention of malaria. RESULTS: In the BCC malaria prevention strategy testing areas, the accuracy rates of malaria-related KAP were significantly improved among mountain worker populations. The accuracy rates in the 3 aspects of malaria-related KAP increased from 37.73%, 37.00%, and 43.04% to 89.01%, 91.53%, and 92.25%, respectively. The changes in all 3 aspects of KAP were statistically significant (p < 0.01). In the control sites, the changes in the indices were not as marked as in the testing areas, and the change was not statistically significant (p > 0.05). Furthermore, in the testing areas, both the percentage testing positive in the serum malaria indirect fluorescent antibody test (IFAT) and the number of people inflicted decreased more significantly than in the control sites (p < 0.01). CONCLUSION: The use of the BCC strategy significantly improved the ability of mountain workers in Hainan to avoid malarial infection. Educational and promotional materials and measures were developed and selected in the process, and hands-on experience was gained that will help achieve the goal of total malaria elimination in Hainan.

A case of Plasmodium ovale wallikeri infection in a Chinese worker returning from West Africa.

In contrast to the gradual reduction in the number of locally transmitted malaria cases in China, the number of imported malaria cases has been increasing since 2008. Here, we report a case of a 39-year-old Chinese man who acquired Plasmodium ovale wallikeri infection while staying in Ghana, West Africa for 6 months in 2012. Microscopic examinations of Giemsa-stained thin and thick blood smears indicated Plasmodium vivax infection. However, the results of rapid diagnostic tests, which were conducted 3 times, were not in agreement with P. vivax. To further check the diagnosis, standard PCR analysis of the small-subunit rRNA gene was conducted, based on which a phylogeny tree was constructed. The results of gene sequencing indicated that this malaria is a variant of P. ovale (P. ovale wallikeri). The infection in this patient was not a new infection, but a relapse of the infection from the one that he had contracted in West Africa.

Factors Contributing to the Pre-Elimination of Malaria from Hainan Island, China, 1986-2009.

Malaria was endemic in Hainan Island, China, for a lengthy period before its elimination. Here, we aim to gain a better understanding of malaria elimination by assessing and quantifying the relative effects of longitudinal changes in specific antimalarial interventions, socioeconomic development approaches, and malaria vectors on malaria prevalence in Hainan during the 1986-2009 pre-elimination period. Annual data were collected on the incidence of malaria, the number of residents protected by drugs (RPD), the number of residents protected by vector control, the presence of Anopheles minimus and Anopheles dirus, the annual per capita income of rural residents, major cash crop (rubber plantation) areas, the literacy rate of adult rural residents, and the rate of reinforced concrete house construction in rural areas. Backward stepwise multiple linear regression models were developed to identify the factors associated with the annual malaria incidence (AMI). The AMI declined from 20.3 to 0.8 per 10,000 population from 1986 to 2009; this decrease was significantly associated with an increase in the number of RPD and improved literacy rate among rural adults. The results of this study implied that the sustained distribution of antimalarial drugs and increase in education levels in risk areas significantly impacted the reduction and elimination of malaria infection in Hainan. We suggest that these findings could be applicable to malaria-endemic areas in Southeast Asia with similar natural and socioeconomic environments to Hainan and where malaria incidence has decreased to a low level.

Surveillance and Control of Malaria Vectors in Hainan Province, China from 1950 to 2021: A Retrospective Review.

Malaria is a serious mosquito-borne tropical disease impacting populations in tropical regions across the world. Malaria was previously hyperendemic in Hainan Province. Due to large-scale anti-malarial intervention, malaria elimination in the province was achieved in 2019. This paper reviews the literature on the ecology, bionomics, and control of malaria vectors in Hainan from 1951 to 2021. We searched PubMed, and the China national knowledge infrastructure (CNKI) database for relevant articles published and included three other important books published in Chinese or English in order to summarize research on species, distribution, vectorial capacity, ecology, the resistance of malaria vectors to insecticides, and malaria vector control in Hainan Province. A total of 239 references were identified, 79 of which met the criteria for inclusion in our review. A total of six references dealt with the salivary gland infection of Anophelines, six with vectorial capacity, 41 with mosquito species and distribution, seven with seasonality, three with blood preference, four with nocturnal activity, two with flight distance, 13 with resistance to insecticides, and 14 with vector control. Only 16 published papers met the criteria of addressing malaria vectors in Hainan over the last 10 years (2012-2021). Anopheles dirus and Anopheles minimus are primary malaria vectors, mainly distributed in the southern and central areas of Hainan. Indoor residual spraying with DDT and the use of ITNs with pyrethroid insecticides were the main interventions taken for malaria control. Previous studies on ecology, bionomics, and resistance of vectors provided scientific evidence for optimizing malaria vector control and contributed to malaria elimination in Hainan Province. We hope our study will contribute to preventing malaria reestablishment caused by imported malaria in Hainan. Research on malaria vectors should be updated to provide scientific evidence for malaria vector control strategies post-elimination as the ecology, bionomics, and resistance of vectors to insecticides may change with changes in the environment.

Prevalence of antifolate drug resistance markers in Plasmodium vivax in China.

The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax, as antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009-2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.

Prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd) and clinical implication for safe use of primaquine in malaria-endemic areas of Hainan Province, China.

Primaquine, the only licensed antimalarial drug for eradication of Plasmodium vivax and Plasmodium ovale malaria, may cause acute hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd) during treatment. The different prevalence and distribution patterns of G6PDd in Hainan, the ancient malaria-endemic area, are unclear. This study included 5,622 suspected malaria patients between 2009 and 2011 in 11 counties of Hainan. Glucose-6-phosphate dehydrogenase deficiency prevalence was determined using the fluorescent spot test (FST) and malaria patients was confirmed by a positive light microscopy. The G6PDd prevalence for different ethnic groups, genders, and counties were calculated and compared using χ2-test. Spatial cluster and Spearman rank correlation of G6PDd prevalence and malaria incidence were analyzed. The overall G6PDd prevalence of study population was 7.45%. The G6PDd prevalence of males, Li ethnic minority, and malaria patients was significantly higher than that of females, Han ethnic majority, and non-malarial patients (p < 0.01), respectively. The spatial cluster of G6PDd and malaria located in south-western and central-southern Hainan, respectively, with no significant correlation. The study provides essential information on G6PDd prevalence in ancient malaria-endemic areas of Hainan Province. We also highlight the need for a better understanding of the mechanisms underlying the relationship between G6PDd prevalence and malaria incidence. These findings provide a reference for the safety of the primaquine-based intervention, even after malaria elimination.

Zoledronic acid induces ferroptosis by reducing ubiquinone and promoting HMOX1 expression in osteosarcoma cells.

Aims: Ferroptosis plays important roles in tumorigenesis and cancer therapy. Zoledronic acid is known to inhibit the activity of farnesyl pyrophosphate synthase, a key enzyme in the mevalonate pathway. We examined whether zoledronic acid can inhibit the growth of osteosarcoma cells by inducing ferroptosis. Methods: Cell viability was analyzed by using CCK8 reagent and counting cells with trypan blue exclusion. Ferroptosis markers including lipid peroxide and PTGS2 expression were examined by flow cytometry, western blot, and quantitative PCR analyses. Cellular ubiquinone content was determined using high performance liquid chromatography. Ferrostatin-1 and RSL3 were used as the ferroptosis inhibitor and inducer respectively. Results: Zoledronic acid treatment decreased cell viability and promoted the increase in lipid peroxide content and PTGS2 expression. Addition of ferrostatin-1 reverted these effects of zoledronic acid on osteosarcoma cells, supporting a role of zoledronic acid in inducing ferroptosis. Mechanistically, zoledronic acid significantly decreased ubiquinone, a metabolite of the mevalonate pathway. Treating cells with exogenous ubiquinone prevented zoledronic acid-induced ferroptosis and decrease in the growth of osteosarcoma cells. In addition, zoledronic acid enhanced the expression of HMOX1, whereas knockdown of HMOX1 inhibited the zoledronic acid-induced increase in lipid peroxide level and decrease in cell growth. Finally, zoledronic acid together with RSL3 significantly enhanced the inhibitory effect on the growth of osteosarcoma cells. Conclusion: Our results indicate that zoledronic acid induces ferroptosis by decreasing ubiquinone content and promoting HMOX1 expression in osteosarcoma cells. Zoledronic acid together with ferroptosis inducer may be a promising new strategy for the treatment of osteosarcoma.

Malaria elimination on Hainan Island despite climate change.

Background: Rigorous assessment of the effect of malaria control strategies on local malaria dynamics is a complex but vital step in informing future strategies to eliminate malaria. However, the interactions between climate forcing, mass drug administration, mosquito control and their effects on the incidence of malaria remain unclear. Methods: Here, we analyze the effects of interventions on the transmission dynamics of malaria (Plasmodium vivax and Plasmodium falciparum) on Hainan Island, China, controlling for environmental factors. Mathematical models were fitted to epidemiological data, including confirmed cases and population-wide blood examinations, collected between 1995 and 2010, a period when malaria control interventions were rolled out with positive outcomes. Results: Prior to the massive scale-up of interventions, malaria incidence shows both interannual variability and seasonality, as well as a strong correlation with climatic patterns linked to the El Nino Southern Oscillation. Based on our mechanistic model, we find that the reduction in malaria is likely due to the large scale rollout of insecticide-treated bed nets, which reduce the infections of P. vivax and P. falciparum malaria by 93.4% and 35.5%, respectively. Mass drug administration has a greater contribution in the control of P. falciparum (54.9%) than P. vivax (5.3%). In a comparison of interventions, indoor residual spraying makes a relatively minor contribution to malaria control (1.3%-9.6%). Conclusions: Although malaria transmission on Hainan Island has been exacerbated by El Nino Southern Oscillation, control methods have eliminated both P. falciparum and P. vivax malaria from this part of China.

Erratum: Author Correction: Malaria elimination on Hainan Island despite climate change.

[This corrects the article DOI: 10.1038/s43856-022-00073-z.].

Surveillance and response systems driving malaria elimination in the mountain areas of Hainan Province.

Hainan Province is in a tropical area of China and previously experienced serious P. falciparum and P. vivax malaria epidemics. After nearly 70 consecutive years of malaria prevention and control, malaria in Hainan has gradually been eliminated. To achieve the elimination of malaria, Hainan enacted six stages: investigative research and pilot prevention and control, large-scale antimalaria measures, adjustment of strategies for prevention and control, joint prevention and control measures, global funding of routine malaria control, and malaria elimination. Different strategies for malaria control were adopted at different stages. Malaria was most prevalent in the mountainous areas of central and southern Hainan, which contain a high-risk population (the forest goers) and two highly effective malaria vectors (An. dirus and An. minimus). Forest goers have been a high-risk population for malaria in Hainan since their identification in the 1990s. This paper summarizes malaria monitoring in forest goers and the response of forest goers to malaria control and elimination, distilling specific malaria control and elimination measures via case studies in Hainan Province. Two case studies in the malaria control stage demonstrated different measures for outbreaks and sporadic cases in forest goers. In view of the malaria outbreak in Sanya during the elimination stage, three-layered strategies (TLSs) were implemented to control outbreaks and improve control measures. Moreover, this paper also illustrates specific management measures to prevent malaria retransmission from sporadic imported malaria cases during the elimination phase. Hainan finally eliminated malaria in 2020. However, the risk of malaria retransmission is still high due to the prevalence of effective malaria vectors in Hainan, and forest goers are still a high-risk population for malaria retransmission.

The relationship between rising temperatures and malaria incidence in Hainan, China, from 1984 to 2010: a longitudinal cohort study.

BACKGROUND: The influence of rising global temperatures on malaria dynamics and distribution remains controversial, especially in central highland regions. We aimed to address this subject by studying the spatiotemporal heterogeneity of malaria and the effect of climate change on malaria transmission over 27 years in Hainan, an island province in China. METHODS: For this longitudinal cohort study, we used a decades-long dataset of malaria incidence reports from Hainan, China, to investigate the pattern of malaria transmission in Hainan relative to temperature and the incidence at increasing altitudes. Climatic data were obtained from the local meteorological stations in Hainan during 1984-2010 and the WorldClim dataset. A temperature-dependent R0 model and negative binomial generalised linear model were used to decipher the relationship between climate factors and malaria incidence in the tropical region. FINDINGS: Over the past few decades, the annual peak incidence has appeared earlier in the central highland regions but later in low-altitude regions in Hainan, China. Results from the temperature-dependent model showed that these long-term changes of incidence peak timing are linked to rising temperatures (of about 1·5°C). Further, a 1°C increase corresponds to a change in cases of malaria from -5·6% (95% CI -4·5 to -6·6) to -9·2% (95% CI -7·6 to -10·9) from the northern plain regions to the central highland regions during the rainy season. In the dry season, the change in cases would be 4·6% (95% CI 3·7 to 5·5) to 11·9% (95% CI 9·8 to 14·2) from low-altitude areas to high-altitude areas. INTERPRETATION: Our study empirically supports the idea that increasing temperatures can generate opposing effects on malaria dynamics for lowland and highland regions. This should be further investigated and incorporated into future modelling, disease burden calculations, and malaria control, with attention for central highland regions under climate change. FUNDING: Scientific and Technological Innovation 2030: Major Project of New Generation Artificial Intelligence, National Natural Science Foundation of China, Beijing Natural Science Foundation, National Key Research and Development Program of China, Young Elite Scientist Sponsorship Program by CAST, Research on Key Technologies of Plague Prevention and Control in Inner Mongolia Autonomous Region, and Beijing Advanced Innovation Program for Land Surface Science.

An innovative three-layer strategy in response to a quartan malaria outbreak among forest goers in Hainan Island, China: a retrospective study.

BACKGROUND: An outbreak of Plasmodium malariae infection among forest goers in Sanya City of Hainan Island, China was reported in 2015. In response to this outbreak, an innovative three-layer strategy (TLS) targeted forest goers was adapted based on the 1-3-7 approach. MAIN TEXT: Key elements of TLS are: (i) The village with five malaria cases and adjacent villages were set as the first layer. All residents including forest goers were taken as the high-risk population (HRP). Active case detection (ACD) by blood smear microscopy and PCR was selected as the primary measure, and passive case detection (PCD) as complementary measure. One case was identified under TLS implementation. (ii) The township with cases (Gaofeng Town) and the nearby towns were chosen as the second layer. Only forest goers were screened by ACD, while PCD as a routine screening method. 7831 blood smears collected by ACD and PCD and tested with negative results. (iii) The city with cases (Sanya City) and others 12 counties/county-level cities were selected as the third layer. Malaria cases were monitored passively. A total of 77,555 blood slides were screened by PCD with zero positive sample. For each layer, the malaria vector mosquitoes were monitored using light traps, cattle-baited/human-bait traps. Anopheles minimus (dominant species), An. sinensis and An. dirus were captured. Vector control measures mainly include insecticide residual spraying and long-lasting insecticide nets. The capacity of clinicians, public health practitioners and laboratory technicians has been improved through training. During 2016‒2018, TLS and chemoprophylaxis were implemented in the same areas. In the first layer, all residents were monitored by ACD, and malaria chemoprophylaxis were distributed, 89.5% of forest goers were using chemoprophylaxis against malaria. The blood smears (3126 by ACD plus 1516 by PCD) were with zero positive results. Chemoprophylaxis and ACD were offered to forest goers once a year, and PCD in residents as a complementary measure in the second and third layer, 77.8% and 95.1% of forest goers received chemoprophylaxis. In each layer, vector surveillance and control of malaria and trainings for medical staff were still in place. CONCLUSIONS: TLS was effective in blocking the outbreak by P. malariae among forest goers in Hainan in malaria elimination stage. However, whether it could prevent the malaria resurgence in the post-elimination phase needs to be further assessed.

[Adsorption Characteristics of Phosphate on Cerium Modified Water Hyacinth Biochar].

A cerium-modified water hyacinth biochar adsorbent(Ce-BC) was developed through co-precipitation-pyrolysis to remove phosphate from wastewater. The study investigated the effects of Ce-BC dosing, wastewater pH, reaction time, and coexisting competing ions on the adsorption process. The results showed that the best adsorption performance was achieved with a maximum adsorption capacity of 35.00 mg·g-1 at a Ce-BC dosage of 0.4 g·L-1 and an initial pH range of 3-10 in the phosphate solution. The adsorption process of phosphate by the Ce-BC followed the quasi-second-order kinetic model, and a phosphate removal efficiency of 98% within 1 h was achieved. In addition, Ce-BC had a strong anti-competitive anion interference and a good regeneration ability; after four cycles of regeneration, the adsorption efficiency remained above 90%. Characterization using field emission scanning electron microscopy-energy dispersive spectrometry(FESEM-EDS), Fourier-transform infrared spectroscopy(FTIR), X-ray diffraction(XRD), and X-ray photoelectron spectroscopy(XPS) showed that the adsorption mechanism of Ce-BC with respect to phosphate mainly involved ligand exchange and inner sphere complexation. The Ce-BC adsorbent prepared in this study effectively removed and recovered phosphates found in domestic sewage, thereby avoiding the eutrophication of water bodies as well as enabling the recovery and utilization of phosphorus resources.

[Treatment of unstable femoral neck fracture with posteromedial comminutations by cannulated screws and medial bracing plate combined with bone allograft].

OBJECTIVE: To evaluate the effectiveness of unstable femoral neck fracture with posteromedial comminutations treated by cannulated screws and medial bracing plate combined with bone allograft. METHODS: The clinical data of 18 patients with unstable femoral neck fracture with posteromedial comminutations treated by cannulated screws and medial bracing plate combined with bone allograft between July 2016 and March 2020 were retrospectively analyzed. The age ranged from 22 to 64 years, with a median age of 43 years. The causes of injury included 11 cases of falling injury, 3 cases of traffic accident injury, and 4 cases of fall from height injury. According to Garden classification, the femoral neck fracture was classified as type Ⅲ in 3 cases, type Ⅳ in 15 cases, and all patients were type Ⅲ according to Pauwels classification. The time from injury to operation was 1-5 days, with an average of 2.3 days. The fracture healing time and complications were recorded. The quality of fracture reduction was evaluated by Garden index immediately after operation; at last follow-up, the degree of femoral neck shortening was determined by Zlowodzki method, Harris score was used to evaluate hip function. RESULTS: The operation time was 62-98 minutes (mean, 75 minutes); intraoperative blood loss was 101-220 mL (mean, 153 mL). Cannulated screws guide wire was inserted 3-5 times (mean, 4 times). Intraoperative fluoroscopy was performed 9-21 times (mean, 15 times). The hospital stay was 5-11 days (mean, 7.2 days). All the patients were followed up 12-40 months with an average of 17.3 months. There was no postoperative complication such as accumulated pneumonia, lower extremity deep venous thrombosis, nail cutting, nail withdrawal, internal fixation fracture, and so on. There was no fracture nonunion and osteonecrosis of the femoral head during the follow-up; the fracture healing time was 7-15 weeks, with an average of 12.1 weeks. The quality of fracture reduction was evaluated immediately after operation, the results were grade Ⅰ in 15 cases and grade Ⅱ in 3 cases. At last follow-up, there were 2 cases with femoral neck shortening less than 5 mm and 1 case with 5-10 mm. The incidence of femoral neck shortening was 16.7%. The Harris score of hip joint was 73-97, with an average of 93.5; among them, 12 cases were rated as excellent, 3 cases as good, and 3 cases as fair, with an excellent and good rate of 83.3%. CONCLUSION: For the treatment of unstable femoral neck fracture with posteromedial comminutations, cannulated screws and medial bracing plate combined with bone allograft are dramatically effective due to earlier weight bearing, faster fracture healing, and better hip function recovery.

Spatiotemporal distribution of malaria and the association between its epidemic and climate factors in Hainan, China.

BACKGROUND: Hainan is one of the provinces most severely affected by malaria epidemics in China. The distribution pattern and major determinant climate factors of malaria in this region have remained obscure, making it difficult to target countermeasures for malaria surveillance and control. This study detected the spatiotemporal distribution of malaria and explored the association between malaria epidemics and climate factors in Hainan. METHODS: The cumulative and annual malaria incidences of each county were calculated and mapped from 1995 to 2008 to show the spatial distribution of malaria in Hainan. The annual and monthly cumulative malaria incidences of the province between 1995 and 2008 were calculated and plotted to observe the annual and seasonal fluctuation. The Cochran-Armitage trend test was employed to explore the temporal trends in the annual malaria incidences. Cross correlation and autocorrelation analyses were performed to detect the lagged effect of climate factors on malaria transmission and the auto correlation of malaria incidence. A multivariate time series analysis was conducted to construct a model of climate factors to explore the association between malaria epidemics and climate factors. RESULTS: The highest malaria incidences were mainly distributed in the central-south counties of the province. A fluctuating but distinctly declining temporal trend of annual malaria incidences was identified (Cochran-Armitage trend test Z = -25.14, P < 0.05). The peak incidence period was May to October when nearly 70% of annual malaria cases were reported. The mean temperature of the previous month, of the previous two months and the number of cases during the previous month were included in the model. The model effectively explained the association between malaria epidemics and climate factors (F = 85.06, P < 0.05, adjusted R(2) = 0.81). The autocorrelations of the fitting residuals were not significant (P > 0.05), indicating that the model extracted information sufficiently. There was no significant difference between the monthly predicted value and the actual value (t = -1.91, P = 0.08). The R(2) for predicting was 0.70, and the autocorrelations of the predictive residuals were not significant (P > 0.05), indicating that the model had a good predictive ability. DISCUSSION: Public health resource allocations should focus on the areas and months with the highest malaria risk in Hainan. Malaria epidemics can be accurately predicted by monitoring the fluctuations of the mean temperature of the previous month and of the previous two months in the area. Therefore, targeted countermeasures can be taken ahead of time, which will make malaria surveillance and control in Hainan more effective and simpler. This model was constructed using relatively long-term data and had a good fit and predictive validity, making the results more reliable than the previous report. CONCLUSIONS: The spatiotemporal distribution of malaria in Hainan varied in different areas and during different years. The monthly trends in the malaria epidemics in Hainan could be predicted effectively by using the multivariate time series model. This model will make malaria surveillance simpler and the control of malaria more targeted in Hainan.