Temporal correlation analysis between malaria and meteorological factors in Motuo County, Tibet

<p>Abstract</p> <p>Background</p> <p>Malaria has been endemic in Linzhi Prefecture in the Tibet Autonomous Region (TAR) over the past 20 years, especially in Motou County with a highest incidence in the country in recent years. Meteorological factors, such as rainfall, temperature and relative humidity in Motou County were unique compared to other areas in Tibet as well as other parts of China, thus the objective of this work was to analyse the temporal correlation between malaria incidence and meteorological factors in Motou County, in order to seek the particular interventions for malaria control.</p> <p>Methods</p> <p>The meteorological and malaria data during 1986-2009 in Motuo County were studied to analyse the statistical relationship between meteorological data time series and malaria incidence data series. Temporal correlation between malaria incidence and meteorological factors were analyzed using several statistical methods. Spearman correlation analysis was conducted to examine the association between monthly malaria incidence and meteorological variables. Cross-correlation analysis of monthly malaria incidence series and monthly meteorological data time series revealed the time lag(s) of meteorological factors preceding malaria at which the series showed strongest correlation. Multiplicative seasonal auto-regressive integrated moving average (SARIMA) models were used in the cross-correlation analysis with pre-whitening which remove seasonality and auto-correlation of meteorological data series. Differenced data analysis which called inter-annual analysis was carried out to find underlying relationship between malaria data series and meteorological data series.</p> <p>Results</p> <p>It has been revealed that meteorological variables, such as temperature, relative humidity and rainfall were the important environmental factors in the transmission of malaria. Spearman correlation analysis demonstrated relative humidity was greatest relative to malaria incidence and the correlation coefficient was 0.543(<it>P </it>< 0.01). Strong positive correlations were found for malaria incidence time series lagging one to three months behind rainfall (<it>r </it>> 0.4) and lagging zero to two months behind temperature and relative humidity (<it>r </it>> 0.5) by the cross-correlation. Correlations were weaker with pre-whitening than without. The cross-correlograms between malaria incidence and various meteorological variables were entirely different. It was fluctuated randomly for temperature but with trend for the other two factors, which showed positive correlated to malaria when lag was from 0 to 5 months and negative from 6 to 12 months. Besides, the inter-annual analysis showed strong correlation between differenced annual malaria incidence and differenced meteorological variables (annual average maximum temperature, annual average relative humidity and annual average rainfall). The correlations coefficients were -0.668 (<it>P </it>< 0.01), 0.451(<it>P </it>< 0.05) and 0.432(<it>P </it>< 0.05), respectively.</p> <p>Conclusion</p> <p>Meteorological variables play important environmental roles in malaria transmission in Motou County. Relative humidity was the greatest influence factors, which affected the mosquito survival directly. The relationship between malaria incidence and rainfall was complex and it was not directly and linearly. The lags of temperature and relative humidity were similar and smaller than that of rainfall. Since the lags of meteorological variables affecting malaria transmission were short, it was difficult to do accurate long-term malaria incidence prediction using meteorological variables.</p

Monitoring resistance of Plasmdium vivax: Point mutations in dihydrofolate reductase gene in isolates from Central China

<p>Abstract</p> <p>Background</p> <p>Malaria still represents a significant public health problem in China, and the cases dramatically increased in Central China after 2001. Antifolate resistance in <it>Plasmodium vivax </it>is caused by point mutations in genes encoding dihydrofolate reductase (<it>pvdhfr</it>) and dihydropteroate synthase (<it>pvdhps</it>). In this study, we used direct sequencing to investigate genetic variation in <it>pvdhfr </it>of malaria patients' samples from Central China.</p> <p>Results</p> <p>Among all the samples, 21.4% were wild-type, whereas mutations were detected at three codons (58, 61 and 117) including single mutant (34.6%) and double mutants (43.8%). The most prevalent mutant allele was the one with double mutation at codons 58 and 117 (24.6%). Three types of single mutation (S58R, T61M and S117N) were found in 2.1%, 11.8% and 20.9% of parasite isolates, respectively. The four <it>P. vivax </it>parasite populations in Central China also differed in <it>pvdhfr </it>allele frequencies.</p> <p>Conclusions</p> <p>This study suggested that <it>P. vivax </it>in Central China may be relatively susceptible to pyrimethamine. And it also highlights genotyping in the <it>pvdhfr </it>genes remains a useful tool to monitor the emergence and spread of <it>P. vivax </it>pyrimethamine resistance.</p

Spatial and temporal distribution of falciparum malaria in China

Background: Falciparum malaria is the most deadly among the four main types of human malaria. Although great success has been achieved since the launch of the National Malaria Control Programme in 1955, malaria remains a serious public health problem in China. This paper aimed to analyse the geographic distribution, demographic patterns and time trends of falciparum malaria in China. Methods: The annual numbers of falciparum malaria cases during 1992–2003 and the individual case reports of each clinical falciparum malaria during 2004–2005 were extracted from communicable disease information systems in China Center for Diseases Control and Prevention. The annual number of cases and the annual incidence were mapped by matching them to corresponding province- and county-level administrative units in a geographic information system. The distribution of falciparum malaria by age, gender and origin of infection was analysed. Time-series analysis was conducted to investigate the relationship between the falciparum malaria in the endemic provinces and the imported falciparum malaria in non-endemic provinces. Results: Falciparum malaria was endemic in two provinces of China during 2004–05. Imported malaria was reported in 26 non-endemic provinces. Annual incidence of falciparum malaria was mapped at county level in the two endemic provinces of China: Yunnan and Hainan. The sex ratio (male vs. female) for the number of cases in Yunnan was 1.6 in the children of 0–15 years and it reached 5.7 in the adults over 15 years of age. The number of malaria cases in Yunnan was positively correlated with the imported malaria of concurrent months in the non-endemic provinces. Conclusion: The endemic area of falciparum malaria in China has remained restricted to two provinces, Yunnan and Hainan. Stable transmission occurs in the bordering region of Yunnan and the hilly-forested south of Hainan. The age and gender distribution in the endemic area is characterized by the predominance of adult men cases. Imported falciparum malaria in the non-endemic area of China, affected mainly by the malaria transmission in Yunnan, has increased both spatially and temporally. Specific intervention measures targeted at the mobile population groups are warranted

Malaria Elimination in the People’s Republic of China: Current Progress, Challenges, and Prospects

In China, the malaria elimination program was launched in 2010 with the objective to eliminate this disease by 2020. Large-scale malaria control and elimination actions have been conducted with significant success since inception of the nationwide program. The incidence of locally acquired malaria has declined sharply along with the concomitant decrease of malaria-endemic areas from 762 counties reporting malaria in 2010 to just two counties adjacent to border areas (Yunnan, China-Myanmar and Tibet, China-India) in 2016. In total, 1723 counties (79%) and 134 prefectures (52%) had completed the malaria elimination internal assessment by the end of 2016. The year 2017 was the first year without report of indigenous malaria cases throughout the country. Hence, this chapter is meant to share the lessons learned from malaria elimination in China benefiting countries on the way to malaria elimination

One-year delayed effect of fog on malaria transmission: a time-series analysis in the rain forest area of Mengla County, south-west China

Background: Malaria is a major public health burden in the tropics with the potential to significantly increase in response to climate change. Analyses of data from the recent past can elucidate how short-term variations in weather factors affect malaria transmission. This study explored the impact of climate variability on the transmission of malaria in the tropical rain forest area of Mengla County, south-west China. Methods: Ecological time-series analysis was performed on data collected between 1971 and 1999. Auto-regressive integrated moving average (ARIMA) models were used to evaluate the relationship between weather factors and malaria incidence. Results: At the time scale of months, the predictors for malaria incidence included: minimum temperature, maximum temperature, and fog day frequency. The effect of minimum temperature on malaria incidence was greater in the cool months than in the hot months. The fog day frequency in October had a positive effect on malaria incidence in May of the following year. At the time scale of years, the annual fog day frequency was the only weather predictor of the annual incidence of malaria. Conclusion: Fog day frequency was for the first time found to be a predictor of malaria incidence in a rain forest area. The one-year delayed effect of fog on malaria transmission may involve providing water input and maintaining aquatic breeding sites for mosquitoes in vulnerable times when there is little rainfall in the 6-month dry seasons. These findings should be considered in the prediction of future patterns of malaria for similar tropical rain forest areas worldwide

Analysis of microRNA profile of Anopheles sinensis by deep sequencing and bioinformatic approaches

Abstract Background microRNAs (miRNAs) are small non-coding RNAs widely identified in many mosquitoes. They are reported to play important roles in development, differentiation and innate immunity. However, miRNAs in Anopheles sinensis, one of the Chinese malaria mosquitoes, remain largely unknown. Methods We investigated the global miRNA expression profile of An. sinensis using Illumina Hiseq 2000 sequencing. Meanwhile, we applied a bioinformatic approach to identify potential miRNAs in An. sinensis. The identified miRNA profiles were compared and analyzed by two approaches. The selected miRNAs from the sequencing result and the bioinformatic approach were confirmed with qRT-PCR. Moreover, target prediction, GO annotation and pathway analysis were carried out to understand the role of miRNAs in An. sinensis. Results We identified 49 conserved miRNAs and 12 novel miRNAs by next-generation high-throughput sequencing technology. In contrast, 43 miRNAs were predicted by the bioinformatic approach, of which two were assigned as novel. Comparative analysis of miRNA profiles by two approaches showed that 21 miRNAs were shared between them. Twelve novel miRNAs did not match any known miRNAs of any organism, indicating that they are possibly species-specific. Forty miRNAs were found in many mosquito species, indicating that these miRNAs are evolutionally conserved and may have critical roles in the process of life. Both the selected known and novel miRNAs (asi-miR-281, asi-miR-184, asi-miR-14, asi-miR-nov5, asi-miR-nov4, asi-miR-9383, and asi-miR-2a) could be detected by quantitative real-time PCR (qRT-PCR) in the sequenced sample, and the expression patterns of these miRNAs measured by qRT-PCR were in concordance with the original miRNA sequencing data. The predicted targets for the known and the novel miRNAs covered many important biological roles and pathways indicating the diversity of miRNA functions. We also found 21 conserved miRNAs and eight counterparts of target immune pathway genes in An. sinensis based on the analysis of An. gambiae. Conclusions Our results provide the first lead to the elucidation of the miRNA profile in An. sinensis. Unveiling the roles of mosquito miRNAs will undoubtedly lead to a better understanding of mosquito biology and mosquito-pathogen interactions. This work lays the foundation for the further functional study of An. sinensis miRNAs and will facilitate their application in vector control

microRNA profiles and functions in mosquitoes.

Mosquitoes are incriminated as vectors for many crippling diseases, including malaria, West Nile fever, Dengue fever, and other neglected tropical diseases (NTDs). microRNAs (miRNAs) can interact with multiple target genes to elicit biological functions in the mosquitoes. However, characterization and function of individual miRNAs and their potential targets have not been fully determined to date. We conducted a systematic review of published literature following PRISMA guidelines. We summarize the information about miRNAs in mosquitoes to better understand their metabolism, development, and responses to microorganisms. Depending on the study, we found that miRNAs were dysregulated in a species-, sex-, stage-, and tissue/organ-specific manner. Aberrant miRNA expressions were observed in development, metabolism, host-pathogen interactions, and insecticide resistance. Of note, many miRNAs were down-regulated upon pathogen infection. The experimental studies have expanded the identification of miRNA target from the 3' untranslated regions (UTRs) of mRNAs of mosquitoes to the 5' UTRs of mRNAs of the virus. In addition, we discuss current trends in mosquito miRNA research and offer suggestions for future studies

Molecular surveillance of artemisinin resistance-related Pfk13 and pfcrt polymorphisms in imported Plasmodium falciparum isolates reported in eastern China from 2015 to 2019

Abstract Background Artemisinin-based combination therapy (ACT) has been recommended as the first-line treatment by the World Health Organization to treat uncomplicated Plasmodium falciparum malaria. However, the emergence and spread of P. falciparum resistant to artemisinins and their partner drugs is a significant risk for the global effort to reduce disease burden facing the world. Currently, dihydroartemisinin-piperaquine (DHA-PPQ) is the most common drug used to treat P. falciparum, but little evidence about the resistance status targeting DHA (ACT drug) and its partner drug (PPQ) has been reported in Shandong Province, China. Methods A retrospective study was conducted to explore the prevalence and spatial distribution of Pfk13 and Pfcrt polymorphisms (sites of 72–76, and 93–356) among imported P. falciparum isolates between years 2015–2019 in Shandong Province in eastern China. Individual epidemiological information was collected from a web-based reporting system were reviewed and analysed. Results A total of 425 P. falciparum blood samples in 2015–2019 were included and 7.3% (31/425) carried Pfk13 mutations. Out of the isolates that carried Pfk13 mutations, 54.8% (17/31) were nonsynonymous polymorphisms. The mutant alleles A578S, Q613H, C469C, and S549S in Pfk13 were the more frequently detected allele, the mutation rate was the same as 9.7% (3/31). Another allele Pfk13 C580Y, closely associated with artemisinin (ART) resistance, was found as 3.2% (2/31), which was found in Cambodia. A total of 14 mutant isolates were identified in Western Africa countries (45.2%, 14/31). For the Pfcrt gene, the mutation rate was 18.1% (77/425). T76T356 and T76 were more frequent in all 13 different haplotypes with 26.0% (20/77) and 23.4% (18/77). The CVIET and CVIKT mutant at loci 72–76 have exhibited a prevalence of 19.5% (15/77) and 3.9% (3/77), respectively. The CVIET was mainly observed in samples from Congo (26.7%, 4/15) and Mozambique (26.7%, 4/15). No mutations were found at loci 97, 101 and 145. For polymorphisms at locus 356, a total of 24 isolates were identified and mainly from Congo (29.2%, 7/24). Conclusion These findings indicate a low prevalence of Pfk13 in the African isolates. However, the emergence and increase in the new alleles Pfcrt I356T, reveals a potential risk of drug pressure in PPQ among migrant workers returned from Africa. Therefore, continuous molecular surveillance of Pfcrt mutations and in vitro susceptibility tests related to PPQ are necessary