Imported and indigenous Plasmodium Vivax and Plasmodium Falciparum malaria in the Hubei Province of China, 2005-2019.

BACKGROUND: The Hubei Province in China reported its last indigenous malaria case in September 2012, but imported malaria cases, particularly those related to Plasmodium vivax and Plasmodium falciparum, threaten Hubei's malaria-free status. This study investigated the epidemiological changes in P. vivax and P. falciparum malaria in this province to provide scientific evidence for preventing malaria resurgence. METHODS: The prevalence, demographic characteristics, seasonal features, and geographical distribution of malaria were assessed using surveillance data and were compared across three stages: control stage (2005-2009) and elimination stages I (2010-2014) and II (2015-2019). RESULTS: In 2005-2019, 8483 malaria cases were reported, including 5599 indigenous P. vivax cases, 275 imported P. vivax cases, 866 imported P. falciparum cases, and 1743 other cases. Imported P. falciparum cases accounted for 0.07% of all cases reported in 2005, but increased to 78.81% in 2019. Most imported P. vivax and P. falciparum malaria occurred among males, aged 21-60 years, during elimination stages I and II. The number of regions affected by imported P. falciparum and P. vivax increased markedly in Hubei from the control stage to elimination stage II. Overall, 1125 imported P. vivax and P. falciparum cases were detected from 47 other nations. Eight imported cases were detected from other provinces in China. From the control stage to elimination stage II, the number of cases of malaria imported from African countries increased, and that of cases imported from Southeast Asian countries decreased. CONCLUSIONS: Although Hubei has achieved malaria elimination, it faces challenges in maintaining this status. Hence, imported malaria surveillance need to be strengthened to reduce the risk of malaria re-introduction.

Characteristics of imported Plasmodium ovale spp. and Plasmodium malariae in Hubei Province, China, 2014-2018.

BACKGROUND: There have been an increasing number of imported cases of malaria in Hubei Province in recent years. In particular, the number of cases of Plasmodium ovale spp. and Plasmodium malariae significantly increased, which resulted in increased risks during the malaria elimination phase. The purpose of this study was to acquire a better understanding of the epidemiological characteristics of P. ovale spp. and P. malariae imported to Hubei Province, China, so as to improve case management. METHODS: Data on all malaria cases from January 2014 to December 2018 in Hubei Province were extracted from the China national diseases surveillance information system (CNDSIS). This descriptive study was conducted to analyse the prevalence trends, latency periods, interval from onset of illness to diagnosis, and misdiagnosis of cases of P. ovale spp. and P. malariae malaria. RESULTS: During this period, 634 imported malaria cases were reported, of which 87 P. ovale spp. (61 P. ovale curtisi and 26 P. ovale wallikeri) and 18 P. malariae cases were confirmed. The latency periods of P. ovale spp., P. malariae, Plasmodium vivax, and Plasmodium falciparum differed significantly, whereas those of P. ovale curtisi and P. ovale wallikeri were no significant difference. The proportion of correct diagnosis of P. ovale spp. and P. malariae malaria cases were 48.3% and 44.4%, respectively, in the hospital or lower-level Centers for Disease Control and Prevention (CDC). In the Provincial Reference Laboratory, the sensitivity of microscopy and rapid diagnostic tests was 94.3% and 70.1%, respectively, for detecting P. ovale spp., and 88.9% and 38.9%, respectively, for detecting P. malariae. Overall, 97.7% (85/87) of P. ovale spp. cases and 94.4% (17/18) of P. malariae cases originated from Africa. CONCLUSION: The increase in the number of imported P. ovale spp. and P. malariae cases, long latency periods, and misdiagnosis pose a challenge to this region. Therefore, more attention should be paid to surveillance of imported cases of P. ovale spp. and P. malariae infection to reduce the burden of public health and potential risk of malaria.

Epidemiological characteristics of malaria from control to elimination in Hubei Province, China, 2005-2016.

BACKGROUND: Hubei Province, China, has been operating a malaria elimination programme. This study aimed at investigating the epidemiologic characteristics of malaria in Hubei Province (2005-2016) to plan resource allocation for malaria elimination. METHODS: Data on all malaria cases from 2005 to 2016 in all counties of Hubei Province were extracted from a web-based reporting system. The numbers of indigenous and imported cases during the disease control (2005-2010) and elimination (2011-2016) stages, as well as their spatiotemporal distribution, were compared. RESULTS: A total of 8109 malaria cases were reported from 2005 to 2016 (7270 and 839 cases during the control and elimination stages, respectively). Between 2005 and 2010, indigenous malaria cases comprised the majority of total cases (7114/7270; 97.9%), and Plasmodium vivax malaria cases accounted for most malaria cases (5572/7270; 76.6%). No indigenous malaria cases have been reported in Hubei Province since 2013. Imported malaria cases showed a gradually increasing trend from 2011 to 2016, Plasmodium falciparum was the predominant species in these cases, and the number of counties with imported cases increased from 4 in 2005 to 47 in 2016. During the control and elimination stages, the most likely spatial clusters for indigenous cases included 13 and 11 counties, respectively. However, the cluster of indigenous malaria cases has not been identified since September 2011. For imported cases, the most likely cluster and three secondary clusters during both stages were identified. CONCLUSIONS: Hubei Province has made significant achievements in controlling and eliminating malaria; however, the region now faces some challenges associated with the increasing number and distribution of imported malaria cases. Priorities for malaria elimination should include better management of imported malaria cases, prevention of secondary malaria transmission, and ensuring the sustainability of malaria surveillance.

Evaluation of performance for malaria diagnosis in health facilities by five provincial reference laboratories of China.

Introduction: The provincial malaria diagnosis reference laboratories review and assess malaria cases diagnosed in health facilities for supporting the malaria elimination efforts and preventing re-transmission of imported malaria. The study aimed to evaluate the detection capability of malaria diagnosis in China from 2014 to 2021. Methods: Data on malaria cases reported in the provincial-level administrative divisions (PLADs) of Anhui, Henan, Hubei, Guangxi, and Zhejiang from 2014 to 2021 were collected and analyzed. Results: In total, 5,770 malaria cases were reported from 2014 to 2021, and 99.05% (5,715/5,770) were submitted to the provincial malaria diagnosis reference laboratories. The median time between malaria cases being reported and the samples being received by reference laboratories was 6 days (Interquartile range, IQR:3-12 days) from 2017 to 2021. Diagnosis of 5,680 samples in the laboratory were confirmed by provincial reference laboratories, including 3,970 cases of Plasmodium falciparum, 414 of P. vivax, 1,055 of P. ovale, 158 of P. malariae, 1 of P. knowlesi, and 82 of mixed infections. Plasmodium species of 5,141 confirmed cases were consistent with the initial diagnosis, with a species accuracy rate of 90.53% (5,141/5,679). The accuracy of P. falciparum diagnosis in health facilities was higher than that of non-falciparum species. The inconsistency between microscopy and nested polymerase chain reaction (nPCR) results of confirmatory diagnosis was mainly in malaria-positive versus malaria-negative cases, as well as in mixed versus single infection cases. Conclusion: The provincial malaria diagnosis reference laboratories have played an important role in ensuring the accuracy and reliability of Plasmodium diagnosis in health facilities. However, the results of this study imply that capacity training for the identification of Plasmodium species in health facilities is warranted.

SCF and TLR4 ligand cooperate to augment the tumor-promoting potential of mast cells.

Mast cells may have either antitumor or tumor-promoting potential. Nevertheless, mast cells in tumor microenvironment have been found to promote tumor growth. So far the mechanisms underlying the modulation of mast cell function in tumor microenvironment remains to be fully elucidated. Here, we report that tumor-promoting potential of mast cells could be augmented by molecules released from damaged tumor cells through cooperative stimulation of stem cell factor (SCF) and ligand for Toll-like receptor 4 (TLR4). Co-simulation with SCF and TLR4 ligand inhibited mast cell degranulation, but efficiently induced the production and secretion of VEGF, PDGF, and IL-10. Although TLR4 ligand alone may induce IL-12 expression in mast cells, co-stimulation with SCF and TLR4 ligand induced the expression of IL-10, but not IL-12, in mast cells. The phosphorylation of GSK3ß was crucial for the effect of SCF and TLR4 ligand. In addition to inducing phosphorylation of GSK3ß at Ser9 through PI3K pathway, SCF and TLR4 ligand cooperated to induce phosphorylation of GSK3ß at Tyr216 by simultaneous activation of ERK and p38MAPK pathways. Both phospho-Ser9 and phospho-Tyr216 of GSK3ß were required for IL-10 expression induced by SCF/TLR4 ligand, whereas suppressive effect of SCF/TLR4 ligand on mast cell degranulation was related to phospho-Tyr216. Importantly, the effect of SCF and TLR4 ligand on mast cells could be abrogated by inhibiting phosphorylation of GSK3ß at Tyr216. These findings disclose the mechanisms underlying the modulation of mast cell function in tumor microenvironment, and suggest that inhibiting GSK3ß in mast cells will be beneficial to the treatment of cancer.

Tumor cell-released TLR4 ligands stimulate Gr-1+CD11b+F4/80+ cells to induce apoptosis of activated T cells.

Gr-1(+)CD11b(+)F4/80(+) cells play important roles in tumor development and have a negative effect on tumor immunotherapy. So far, the mechanisms underlying the regulation of their immunosuppressive phenotype by classical and alternative macrophage activation stimuli are not well elucidated. In this study, we found that molecules from necrotic tumor cells (NTC-Ms) stimulated Gr-1(+)CD11b(+)F4/80(+) cells to induce apoptosis of activated T cells but not nonstimulated T cells. The apoptosis-inducing capacity was determined by higher expression levels of arginase I and IL-10 relative to those of NO synthase 2 and IL-12 in Gr-1(+)CD11b(+)F4/80(+) cells, which were induced by NTC-Ms through TLR4 signaling. The apoptosis-inducing capacity of NTC-Ms-stimulated Gr-1(+)CD11b(+)F4/80(+) cells could be enhanced by IL-10. IFN-gamma may reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells only if their response to IFN-gamma was not attenuated. However, the potential of Gr-1(+)CD11b(+)F4/80(+) cells to express IL-12 in response to IFN-gamma could be attenuated by tumor, partially due to the existence of active STAT3 in Gr-1(+)CD11b(+)F4/80(+) cells and NTC-Ms from tumor. In this situation, IFN-gamma could not effectively reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells. Tumor immunotherapy with 4-1BBL/soluble programmed death-1 may significantly reduce, but not abolish the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells in local microenvironment. Blockade of TLR4 signaling could further reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and enhance the suppressive effect of 4-1BBL/soluble form of programmed death-1 on tumor growth. These findings indicate the relationship of distinct signaling pathways with apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and emphasize the importance of blocking TLR4 signaling to prevent the induction of T cell apoptosis by Gr-1(+)CD11b(+)F4/80(+) cells.

Efforts to eliminate schistosomiasis in Hubei province, China: 2005-2018.

BACKGROUND: The Hubei province is one of the most schistosomiasis-epidemic-prone provinces in China. A series of strategies were adopted by the government to curb the rebound schistosomiasis endemic status that has prevailed since the early 2000s. This study aimed to elucidate the trends of schistosomiasis transmission and to appraise the effectiveness of the integrated control strategy in lake and marshland areas. METHODS: Surveillance data of schistosomiasis in the Hubei province between 2005 and 2018 were analyzed, including conventional health control measures, integrated strategies, and measures that focused on the infection source. According to the local annual plan for schistosomiasis control in endemic counties, previous measures were human and snail control and surveillance. Residents aged 6-65 years were screened by an immunological detection method called indirect hemagglutination assay (IHA) after the transmission season each year. All residents who tested positive were then asked to provide a fecal sample for examination by the miracidium hatching technique (MHT) to detect the presence of schistosomes. Moreover, systematic snail surveys were conducted as a part of the combined environmental sampling method. The latter included integrated strategies and measures that focused on the infection source. Bovine stool samples were also collected and concurrently assessed using the MHT by the agriculture department, river-hardening slope protection was constructed by the water conservancy department, and forestation promotion was conducted by the forest department. The effectiveness of the integrated control strategy was assessed using two indicators of resident and livestock infection rates and three indicators of snail epidemics across all endemic areas. RESULTS: From 2005 to 2018, a total of 28. 46 million and 2. 05 million residents were assessed by immunological (IHA) and etiological (MHT) detection techniques, respectively. Snail surveys and molluscicide application were performed in 2. 26 hectares and 0. 37 hectares, respectively. Moreover, 2. 60 million bovines were assessed by etiological detection techniques (MHT). The river-hardening slope protection project was implemented in 503 places, and 46 thousand hectares in endemic areas underwent environmental modification. Forestation was implemented at an area of 0. 15 million hectares. Between 2005 and 2018, the epidemic indicators, including resident and livestock infection rates and the infested areas and infection rate of snails, all presented downward trends. The resident infection rate decreased from 3. 78% in 2005 to 0% in 2016, which persisted through 2018. The livestock infection rate decreased from 5. 63% in 2005 to 0% in 2013, which also persisted through 2018. From 2005 to 2018, the snail-inhabited area was slightly reduced, but the area of infected snails decreased to 0 in 2012; this persisted through 2018. All counties met the goal for schistosomiasis infection control, transmission control, and disruption of schistosomiasis activity in 2008, 2013, and 2018 separately. That means the goal has been achieved in each stage. CONCLUSIONS: The decline of the schistosomiasis epidemic rate demonstrates that the Chinese government was successful in meeting its public health goal in Hubei province. In the next decade, precision interventions must be implemented in endemic counties with a relatively low epidemic status to achieve the goals of the Outline of the Healthy China 2030 Plan. A similar strategy can be applied in other countries to eliminate schistosomiasis globally.

Epidemiology of Plasmodium falciparum Malaria and Risk Factors for Severe Disease in Hubei Province, China.

This study aimed to describe the epidemiology of Plasmodium falciparum malaria and identify risk factors for severe disease in Hubei Province, China, using a case-based survey of retrospective data from 2013 to 2018. From 2013 to 2018, a total of 763 imported malaria cases were reported in Hubei Province; 69.2% (528/763) cases were caused by P. falciparum species. The proportion of malaria caused by P. falciparum increased from 66.7% in 2013 to 74.0% in 2018 (χ2 = 21.378, P < 0.05). Plasmodium falciparum malaria was reported in 77 counties of Hubei Province. The majority of imported P. falciparum cases originated from Africa (98.9%, 522/528); 9.7% (51/528) of patients infected with P. falciparum developed severe malaria. Three deaths (case fatality rate: 0.6%) were related to imported P. falciparum malaria. Risk factors for severe malaria were being female (odds ratio [OR] = 3.593, 95% CI: 1.003-12.874), age ≥ 50 years (OR = 2.674, 95% CI: 1.269-5.634), > 3 days between symptom onset and diagnosis (OR = 2.383, 95% CI: 1.210-4.693), and the first-visit medical institution at the township level or lower (OR = 2.568, 95% CI: 1.344-4.908). Malaria prevention should be undertaken among high-risk groups, infection with P. falciparum should be detected early to prevent severe disease and death, and healthcare providers in health facilities at the township level should be trained on early recognition of malaria.

[Protective effect of mouse 2.5s nerve growth factor on PC12 cells from injury induced by 2, 5-hexanedione].

OBJECTIVE: To explore whether the nerve growth factor has protective effects on PC12 cells from injury induced by 2, 5-hexanedione. METHODS: With PC12 cells as the model of neurons, different concentrations of NGF were added into the culture of PC12 cells. Then cell viability was tested with MTT. The DNA fragment was observed with agarose gel electrophoresis. The apoptosis ratio was tested with flow cytometry (FACS). The p53 protein was detected with western blot. The differences among the groups were compared. RESULTS: Cell viabilities were increased with the increase of the concentrations of NGF (P < 0.05). The DNA fragment, the apoptosis ratio and the expression of p53 were all decreased with the increase of the concentrations of NGF (P < 0.05). CONCLUSION: The NGF might have direct nutritional effects on PC12 cells, and protect them from injury induced by 2, 5 HD. Moreover, it might also have anti-apoptosis effect to some extent.

[Epidemiological analysis of malaria prevalence in Hubei Province in 2013].

OBJECTIVE: To explore the endemic situation of malaria in Hubei Province in 2013, so as to put forward effective elimination strategies and measures. METHODS: The data of malaria cases were searched from the Disease Reporting Information System of Chinese Center for Disease Control and Prevention and analyzed with the descriptive epidemiological method for the epidemiological characteristics of malaria in Hubei Province in 2013. RESULTS: A total of 129 malaria cases were reported in Hubei Province in 2013 with the incidence of 0.02/10,000, and all of them were imported cases, in which 86 cases with Plasmodium falciparum infection, 32 cases with P. vivax infection, 7 cases with P. ovale infection and 4 cases with P. malariae infection. The distribution of malaria cases was concentrated in Wuhan City (76 cases), Yichang City (10 cases), Xiangyang City (7 cases) and Huangshi City (6 cases), accounting for 76.74% of the total cases. There was no significant seasonal variation in the reporting time of the cases. Totally 99.22% of the cases were male, the age distribution concentrated mainly on 20-49 years. The occupation distribution concentrated mainly on the worker, farmer, cadre staff and migrant worker. The main original areas of the imported cases were Africa (111 cases, 86.05%) and Asia (17 cases, 13.18%). CONCLUSIONS: There is no local malaria cases reported in Hubei Province in 2013, however, the imported malaria cases are increased. Therefore, it is necessary to further strengthen the multi-sector collaboration of vector control, while the health education should be intensified especially in the key population.