Clonorchiasis and opisthorchiasis: epidemiology, transmission, clinical features, morbidity, diagnosis, treatment, and control.

Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are important liver flukes that cause a considerable public health burden in eastern Asia, southeastern Asia, and eastern Europe, respectively. The life cycles are complex, involving humans, animal reservoirs, and two kinds of intermediate hosts. An interplay of biological, cultural, ecological, economic, and social factors drives transmission. Chronic infections are associated with liver and biliary complications, most importantly cholangiocarcinoma. With regard to diagnosis, stool microscopy is widely used in epidemiologic surveys and for individual diagnosis. Immunologic techniques are employed for screening purposes, and molecular techniques facilitate species differentiation in reference laboratories. The mainstay of control is preventive chemotherapy with praziquantel, usually combined with behavioral change through information, education and communication, and environmental control. Tribendimidine, a drug registered in the People's Republic of China for soil-transmitted helminth infections, shows potential against both C. sinensis and O. viverrini and, hence, warrants further clinical development. Novel control approaches include fish vaccine and biological control. Considerable advances have been made using multi-omics which may trigger the development of new interventions. Pressing research needs include mapping the current distribution, disentangling the transmission, accurately estimating the disease burden, and developing new diagnostic and treatment tools, which would aid to optimize control and elimination measures.

Amplification-free CRISPR/Cas detection technology: challenges, strategies, and perspectives.

Rapid and accurate molecular diagnosis is a prerequisite for precision medicine, food safety, and environmental monitoring. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)-based detection, as a cutting-edged technique, has become an immensely effective tool for molecular diagnosis because of its outstanding advantages including attomolar level sensitivity, sequence-targeted single-base specificity, and rapid turnover time. However, the CRISPR/Cas-based detection methods typically require a pre-amplification step to elevate the concentration of the analyte, which may produce non-specific amplicons, prolong the detection time, and raise the risk of carryover contamination. Hence, various strategies for target amplification-free CRISPR/Cas-based detection have been developed, aiming to minimize the sensitivity loss due to lack of pre-amplification, enable detection for non-nucleic acid targets, and facilitate integration in portable devices. In this review, the current status and challenges of target amplification-free CRISPR/Cas-based detection are first summarized, followed by highlighting the four main strategies to promote the performance of target amplification-free CRISPR/Cas-based technology. Furthermore, we discuss future perspectives that will contribute to developing more efficient amplification-free CRISPR/Cas detection systems.

The empirical support for the radical cure strategy for eliminating Plasmodium vivax in China.

BACKGROUND: With the recent certification by World Health Organization that the People's Republic of China is malaria-free, it is timely to consider how elimination of malaria was completed in People's Republic of China over the last 7 decades. Of the four widespread species of human malaria, Plasmodium vivax was the last to be eliminated by the national program of China. Understanding the incubation periods and relapses patterns of P. vivax through historical data from China is relevant for planning disease elimination in other malaria-endemic countries, with residual P. vivax malaria. METHODS: We collated data from both published and unpublished malaria parasite inoculation experiments conducted between 1979 and 1988 with parasites from different regions of the People's Republic of China. The studies had at least two years of follow-up. We categorized P. vivax incubation patterns via cluster analysis and investigated relapse studies by adapting a published within-host relapse model for P. vivax temperate phenotypes. Each model was fitted using the expectation-maximization (EM) algorithm initialized by hierarchical model-based agglomerative clustering. RESULTS: P. vivax parasites from the seven studies of five southern and central provinces in the People's Republic of China covering geographies ranging from the south temperate to north tropical zones. The parasites belonged to two distinct phenotypes: short- (10-19 days) or long-incubation (228-371 days). The larger the sporozoite inoculation, the more likely short incubation periods were observed, and with more subsequent relapses (Spearman's rank correlation between the number of inoculated sporozoites and the number of relapses of 0.51, p-value = 0.0043). The median of the posterior distribution for the duration of the first relapse interval after primary infection was 168.5 days (2.5% quantile: 89.7; 97.5% quantile: 227.69 days). The predicted survival proportions from the within-host model fit well to the original relapse data. The within-host model also captures the hypnozoite activation rates and relapse frequencies, which consequently influences the transmission possibility of P. vivax. CONCLUSIONS: Through a within-host model, we demonstrate the importance of clearance of hypnozoites. A strategy of two rounds of radical hypnozoite clearance via mass drug administration (MDA) deployed during transmission (summer and autumn) and non-transmission (late spring) seasons had a pronounced effect on outbreaks during the malaria epidemics in China. This understanding can inform malaria control strategies in other endemic countries with similar settings.

China's long march to malaria elimination: a case of adaptive management.

Since the 1950s, China has transitioned from a malaria pandemic country with tens of millions of annual cases, through phases of local control and elimination, to sustained national malaria elimination efforts. This marks the first time a country in the World Health Organization (WHO) Western Pacific region has been certified malaria-free in more than 3 decades. This article provides an innovative approach to understanding China's malaria elimination journey. A number of articles and commentaries have analysed the effectiveness of specific technical approaches implemented in China. Our argument is that we need to look beyond these, and consider the ways in which policy development and implementation capacities have been fostered to support the dynamic change management. The article makes a number of arguments. First is the pragmatic adaptiveness of policies and strategies-and implementation capacities. Second, China has invested in building systems as well as capacities to support the elimination of parasitic diseases, including malaria. Third, the country has both benefited from, and contributed to, global health collaboration on malaria elimination. The ongoing work by the authors is identifying a number of key factors.

Schistosomiasis in the People's Republic of China - down but not out.

Schistosomiasis has been subjected to extensive control efforts in the People's Republic of China (China) which aims to eliminate the disease by 2030. We describe baseline results of a longitudinal cohort study undertaken in the Dongting and Poyang lakes areas of central China designed to determine the prevalence of Schistosoma japonicum in humans, animals (goats and bovines) and Oncomelania snails utilizing molecular diagnostics procedures. Data from the Chinese National Schistosomiasis Control Programme (CNSCP) were compared with the molecular results obtained.Sixteen villages from Hunan and Jiangxi provinces were surveyed; animals were only found in Hunan. The prevalence of schistosomiasis in humans was 1.8% in Jiangxi and 8.0% in Hunan determined by real-time polymerase chain reaction (PCR), while 18.3% of animals were positive by digital droplet PCR. The CNSCP data indicated that all villages harboured S. japonicum-infected individuals, detected serologically by indirect haemagglutination assay (IHA), but very few, if any, of these were subsequently positive by Kato-Katz (KK).Based on the outcome of the IHA and KK results, the CNSCP incorporates targeted human praziquantel chemotherapy but this approach can miss some infections as evidenced by the results reported here. Sensitive molecular diagnostics can play a key role in the elimination of schistosomiasis in China and inform control measures allowing for a more systematic approach to treatment.

Molecular surveillance of pfcrt, pfmdr1 and pfk13-propeller mutations in Plasmodium falciparum isolates imported from Africa to China.

BACKGROUND: The emergence and spread of multidrug resistance poses a significant risk to malaria control and eradication goals in the world. There has been no indigenous malaria cases reported in China since 2017, and China is approaching national malaria elimination. Therefore, anti-malarial drug resistance surveillance and tracking the emergence and spread of imported drug-resistant malaria cases will be necessary in a post-elimination phase in China. METHODS: Dried blood spots were obtained from Plasmodium falciparum-infected cases returned from Africa to China between 2012 and 2015, prior to anti-malarial drug treatment. Whole DNA were extracted and known polymorphisms relating to drug resistance of pfcrt, pfmdr1 gene, and the propeller domain of pfk13 were evaluated by nested PCR and sequencing. The haplotypes and prevalence of these three genes were evaluated separately. Chi-squared test and Fisher's exact test were used to evaluate differences among the different sub-regions of Africa. A P value < 0.05 was used to evaluate differences with statistical significance. The maps were created using ArcGIS. RESULTS: A total of 731 P. falciparum isolates were sequenced at the pfcrt locus. The wild type CVMNK was the most prevalent haplotype with prevalence of 62.8% and 29.8% of the isolates showed the triple mutant haplotype CVIET. A total of 434 P. falciparum isolates were successfully sequenced and pfmdr1 allelic variants were observed in only codons 86, 184 and 1246. Twelve haplotypes were identified and the prevalence of the wild type pfmdr1 NYD was 44.1%. The single mutant pfmdr1 in codons 86 and 184 was predominant but the haplotype NYY with single mutation in codon 1246 was not observed. The double mutant haplotype YFD was common in Africa. About 1,357 isolates were successfully sequenced of pfk13-propeller domain, the wild type was found in 1,308 samples (96.4%) whereby 49 samples (3.6%) had mutation in pfk13. Of 49 samples with pfk13 mutations, 22 non-synonymous and 4 synonymous polymorphic sites were confirmed. The A578S was the most common mutation in pfk13-propeller domain and three mutations associated with artemisinin resistance (M476I, R539T, P553L) were identified in three isolates. CONCLUSION: This study provides evidence that could give insight into potential issues with anti-malarial drug resistance to inform national drug policy in China in order to treat imported cases.

From Plasmodium vivax outbreak to elimination: lessons learnt from a retrospective analysis of data from Guantang.

BACKGROUND: Malaria was once a serious public health problem in China, with Plasmodium vivax the major species responsible for more than 90% of local transmission. Following significant integrated malaria control and elimination programmes, malaria burden declined, and since 2017 China has not recorded any indigenous case. To understand the historical malaria transmission patterns and epidemic characteristics in China and insights useful to guide P. vivax malaria control and elimination elsewhere, a retrospective study was carried out. METHODS: Historical data from a pilot study conducted in Guantang, Luyi in central China from 1971-1995, were digitized. The data included monthly numbers of reported cases, febrile cases, parasite carriage rates, the neonatal infection rate, and entomological data regarding Anopheles sinensis. RESULTS: Following 25 years of continuous integrated malaria control activities, malaria incidence in Guantang decreased from 4,333 cases per 10,000 in 1970 before integrated implementation to 0.23 cases per 10,000 in 1991, and no cases in 1992-1995. Some fluctuations in incidence were observed between 1977 and 1981. During the period parasite rates, antibody levels and the neonatal infection rate also decreased. The pattern of seasonality confirmed that P. vivax in Henan Province was primarily of the long incubation type (temperate) during non-transmission period. The findings retrospectively provide a scientific basis for the implementation of mass campaigns of liver stage hypnozoite clearance. Entomological studies indicated that An. sinensis was the only vector, and it preferred bovine to human hosts, predominantly biting and resting outdoors. Mosquito densities declined between 1971 and 1984. CONCLUSION: The integrated malaria control approach in Guantang effectively controlled malaria and achieved elimination. Analysis of the effectiveness of the programme can provide guidance to other regions or countries with similar ecological settings aiming to move from malaria control to elimination. There is a potential challenge in the maintenance of non-transmission status owing to imported cases and the long dormancy of liver stage hypnozoites.

Genetic diversity of Plasmodium falciparum and genetic profile in children affected by uncomplicated malaria in Cameroon.

BACKGROUND: Malaria is a major public health problem in Cameroon. The study of the genetic diversity within parasite population is essential for understanding the mechanism underlying malaria pathology and to determine parasite clones profile in an infection, for proper malaria control strategies. The objective of this study was to perform a molecular characterization of highly polymorphic genetic markers of Plasmodium falciparum, and to determine allelic distribution with their influencing factors valuable to investigate malaria transmission dynamics in Cameroon. METHODS: A total of 350 P. falciparum clinical isolates were characterized by genotyping block 2 of msp-1, block 3 of msp-2, and region II of glurp gene using nested PCR and DNA sequencing between 2012 and 2013. RESULTS: A total of 5 different genotypes with fragment sizes ranging from 597 to 817 bp were recorded for GLURP. Overall, 16 MSP-1 genotypes, including K1, MAD20 and RO33 were identified, ranging from 153 to 335 bp. A peculiarity about this study is the RO33 monomorphic pattern revealed among the Pfmsp-1 allelic type. Again, this study identified 27 different Pfmsp-2 genotypes, ranging from 140 to 568 bp in size, including 15 belonging to the 3D7-type and 12 to the FC27 allelic families. The analysis of the MSP-1 and MSP-2 peptides indicates that the region of the alignment corresponding K1 polymorphism had the highest similarity in the MSP1and MSP2 clade followed by MAD20 with 93% to 100% homology. Therefore, population structure of P. falciparum isolates is identical to that of other areas in Africa, suggesting that vaccine developed with K1 and MAD20 of Pfmsp1 allelic variant could be protective for Africa children but these findings requires further genetic and immunological investigations. The multiplicity of infection (MOI) was significantly higher (P < 0.05) for Pfmsp-2 loci (3.82), as compare with Pfmsp-1 (2.51) and heterozygotes ranged from 0.55 for Pfmsp-1 to 0.96 for Pfmsp-2. CONCLUSION: High genetic diversity and allelic frequencies in P. falciparum isolates indicate a persisting high level of transmission. This study advocate for an intensification of the malaria control strategies in Cameroon. Trial registration This study was approved by Cameroon National Ethics Committee. It is a randomized controlled trial retrospectively registered in NIH U.S. National Library of Medicine, ClinicalTrials.gov on the 28/11/2016 at https://clinicaltrials.gov/ct2/show/NCT02974348 with the registration number NCT02974348.

No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China-Myanmar border.

BACKGROUND: The emergence and spread of artemisinin resistance in Plasmodium falciparum poses a threat to malaria eradication, including China's plan to eliminate malaria by 2020. Piperaquine (PPQ) resistance has emerged in Cambodia, compromising an important partner drug that is widely used in China in the form of dihydroartemisinin (DHA)-PPQ. Several mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 (k13) are associated with artemisinin resistance and have arisen spread in the Great Mekong subregion, including the China-Myanmar border. Multiple copies of the plasmepsin II/III (pm2/3) genes, located on chromosome 14, have been shown to be associated with PPQ resistance. METHODS: The therapeutic efficacy of DHA-PPQ for the treatment of uncomplicated P. falciparum was evaluated along the China-Myanmar border from 2010 to 2014. The dry blood spots samples collected in the efficacy study prior DHA-PPQ treatment and from the local hospital by passive detection were used to amplify k13 and pm2. Polymorphisms within k13 were genotyped by capillary sequencing and pm2 copy number was quantified by relative-quantitative real-time polymerase chain reaction. Treatment outcome was evaluated with the World Health Organization protocol. A linear regression model was used to estimate the association between the day 3 positive rate and k13 mutation and the relationship of the pm2 copy number variants and k13 mutations. RESULTS: DHA-PPQ was effective for uncomplicated P. falciparum infection in Yunnan Province with cure rates > 95%. Twelve non synonymous mutations in the k13 domain were observed among the 268 samples with the prevalence of 44.0% and the predominant mutation was F446I with a prevalence of 32.8%. Only one sample was observed with multi-copies of pm2, including parasites with and without k13 mutations. The therapeutic efficacy of DHA-PPQ was > 95% along the China-Myanmar border, consistent with the lack of amplification of pm2. CONCLUSION: DHA-PPQ for uncomplicated P. falciparum infection still showed efficacy in an area with artemisinin-resistant malaria along the China-Myanmar border. There was no evidence to show PPQ resistance by clinical study and molecular markers survey. Continued monitoring of the parasite population using molecular markers will be important to track emergence and spread of resistance in this region.

Effectiveness of the innovative 1,7-malaria reactive community-based testing and response (1, 7-mRCTR) approach on malaria burden reduction in Southeastern Tanzania.

BACKGROUND: In 2015, a China-UK-Tanzania tripartite pilot project was implemented in southeastern Tanzania to explore a new model for reducing malaria burden and possibly scaling-out the approach into other malaria-endemic countries. The 1,7-malaria Reactive Community-based Testing and Response (1,7-mRCTR) which is a locally-tailored approach for reporting febrile malaria cases in endemic villages was developed to stop transmission and Plasmodium life-cycle. The (1,7-mRCTR) utilizes existing health facility data and locally trained community health workers to conduct community-level testing and treatment. METHODS: The pilot project was implemented from September 2015 to June 2018 in Rufiji District, southern Tanzania. The study took place in four wards, two with low incidence and two with a higher incidence. One ward of each type was selected for each of the control and intervention arms. The control wards implemented the existing Ministry of Health programmes. The 1,7-mRCTR activities implemented in the intervention arm included community testing and treatment of malaria infection. Malaria case-to-suspect ratios at health facilities (HF) were aggregated by villages, weekly to identify the village with the highest ratio. Community-based mobile test stations (cMTS) were used for conducting mass testing and treatment. Baseline (pre) and endline (post) household surveys were done in the control and intervention wards to assess the change in malaria prevalence measured by the interaction term of 'time' (post vs pre) and arm in a logistic model. A secondary analysis also studied the malaria incidence reported at the HFs during the intervention. RESULTS: Overall the 85 rounds of 1,7-mRCTR conducted in the intervention wards significantly reduced the odds of malaria infection by 66% (adjusted OR 0.34, 95% CI 0.26,0.44, p < 0001) beyond the effect of the standard programmes. Malaria prevalence in the intervention wards declined by 81% (from 26% (95% CI 23.7, 7.8), at baseline to 4.9% (95% CI 4.0, 5.9) at endline). In villages receiving the 1,7-mRCTR, the short-term case ratio decreased by over 15.7% (95% CI - 33, 6) compared to baseline. CONCLUSION: The 1,7-mRCTR approach significantly reduced the malaria burden in the areas of high transmission in rural southern Tanzania. This locally tailored approach could accelerate malaria control and elimination efforts. The results provide the impetus for further evaluation of the effectiveness and scaling up of this approach in other high malaria burden countries in Africa, including Tanzania.

Genetic diversity of Biomphalaria pfeifferi, the intermediate host of Schistosoma mansoni in Shamva district, Zimbabwe: role on intestinal schistosomiasis transmission.

The fresh water snail Biomphalaria pfeifferi is the intermediate host for Schistosoma mansoni, which causes human intestinal schistosomiasis in Zimbabwe. Despite the medical importance of this intermediate host, there are no current data on its molecular characterization in Zimbabwe. In 2016, human water contact sites were identified in four communities in Madziwa area, Shamva district, Zimbabwe. The survey sites were recorded and mapped using a global positioning system. A 655 bp region of the mitochondrial cytochrome oxidase subunit I gene was amplified in 70 B. pfeifferi snails. The sequence data were analysed to determine the relationships between the individual snails, their inter, intra population diversity and structure. Overall, four unique cox1 haplotypes, with a haplotype diversity of 0.608, were identified in the snails. One haplotype spanned across most of the sites. There was no clear geographical clustering of haplotypes. The mean diversity among the haplotypes was very low (0.009), while the net divergence among the collection sites ranged from 0.000 to 0.026. The diversity within and between the sites was 0.017 and 0.012 respectively. This data advances our knowledge of the understanding of the population structure of B. pfeifferi in Madziwa area, Zimbabwe, with the high occurrence of one haplotype indicating the possibility of a recent bottleneck followed by population expansion. The population genetic structure of B. pfeifferi snails described here has provided an opportunity to investigate the contribution of snail genetics to variation in disease burden; and development of control strategies that exploit genetic differences in susceptibility to parasites.

Detection of novel piroplasmid species and Babesia microti and Theileria orientalis genotypes in hard ticks from Tengchong County, Southwest China.

To reveal the genetic diversity of Babesia microti and Theileria orientalis in Southwest China, we conducted a molecular survey of piroplasms in hard ticks in a China-Myanmar border county. Host infesting and questing ticks were collected from Tengchong County in 2013 and 2014. Piroplasm infection in ticks was detected by PCR, and then, phylogenetic analysis was conducted to study the genetic diversity of the pathogens identified in ticks. All in all, six piroplasm species comprising of B. microti; B. orientalis; a novel Babesia species designated Babesia sp. Tengchong, China; T. orientalis; T. luwenshuni; and an as yet undescribed piroplasmid species referred to as Piroplasmid sp. Tengchong, China, have been identified after screening goat- and cattle-attached ticks. In addition, B. bigemina has been identified by screening questing ticks. Phylogenetic analysis based on the 18S rRNA and partial ß-tubulin gene revealed two novel potentially zoonotic genotypes designated B. microti Tengchong-Type A and B. The T. orientalis genotypes identified in the present study represent the seven known genotypes 1-5, 7, and N3 as revealed by phylogenetic analysis of 18S rRNA and MPSP genes. Importantly, an additional genotype designated N4 has also been identified in this study, which brings the number of recognized T. orientalis genotypes to a total of twelve. Thus, besides the two novel species, Babesia sp. Tengchong, China, closely related to Babesia species isolated from yak and Piroplasmid sp. Tengchong, China, our study demonstrates that additional novel B. microti and T. orientalis genotypes exist in Southwest China.

Contribution of Plasmodium immunomics: potential impact for serological testing and surveillance of malaria.

Introduction: Plasmodium vivax (Pv) and P. knowlesi account together for a considerable share of the global burden of malaria, along with P. falciparum (Pf). However, inaccurate diagnosis and undetectable asymptomatic/submicroscopic malaria infections remain very challenging. Blood-stage antigens involved in either invasion of red blood cells or sequestration/cytoadherence of parasitized erythrocytes have been immunomics-characterized, and are vital for the detection of malaria incidence. Areas covered: We review the recent advances in Plasmodium immunomics to discuss serological markers with potential for specific and sensitive diagnosis of malaria. Insights on alternative use of immunomics to assess malaria prevalence are also highlighted. Finally, we provide practical applications of serological markers as diagnostics, with an emphasis on dot immunogold filtration assay which holds promise for malaria diagnosis and epidemiological surveys. Expert commentary: The approach largely contributes to Pf and Pv research in identifying promising non-orthologous antigens able to detect malaria incidence and to differentiate between past and recent infections. However, further studies to profiling naturally acquired immune responses are expected in order to help discover/validate serological markers of no cross-seroreactivity and guide control interventions. More so, the application of immunomics to knowlesi infections would help validate the recently identified antigens and contribute to the discovery of additional biomarkers of exposure, immunity, or both.

Kelch 13 propeller gene polymorphism among Plasmodium falciparum isolates in Lagos, Nigeria: Molecular Epidemiologic Study.

OBJECTIVE: To assess polymorphism in Kelch 13 gene of Plasmodium falciparum isolates in Lagos, Nigeria. METHODS: 195 Plasmodium falciparum-positive dried blood spots collected from individuals that accessed diagnostic care at some health facilities and during community surveys across several Local Government Areas of Lagos State, Nigeria, were investigated for the presence of mutations in the K13 gene by nested polymerase chain reaction (PCR) using haplotype-specific probes and sequencing. RESULTS: Three mutant genotypes of K13 gene were observed: A578S in 0.5%, D464N in 0.5% and Q613H in 1.5%. The frequency of K13 polymorphism was 3.1%, while the remaining parasite population had the wild K13 propeller genes. CONCLUSION: No validated Kelch 13 polymorphism associated with artemisinin resistance was seen among P. falciparum isolates from Lagos, Nigeria. As no clinical study was done, this could not be correlated with artemisinin sensitivity.

OBJECTIF: Evaluer le polymorphisme du gène Kelch 13 dans les isolats de Plasmodium falciparum à Lagos, au Nigéria. MÉTHODES: 195 gouttes de sang séchées positives pour Plasmodium falciparum recueillies auprès d'individus ayant accédé à des soins de diagnostic dans certains centres de santé et lors d'enquêtes communautaires menées dans plusieurs zones du gouvernement local de l'Etat de Lagos, au Nigéria, ont été examinées pour rechercher la présence de mutations du gène K13 par la réaction en chaîne imbriquée de la polymérase (PCR) en utilisant des sondes spécifiques à l'haplotype et par le séquençage. RÉSULTATS: Trois génotypes mutants du gène K13 ont été observés: A578S dans 0,5%, D464N dans 0,5% et Q613H dans 1,5%. La fréquence du polymorphisme K13 était de 3,1%, alors que la population parasitaire restante avait les gènes sauvages de l'hélice K13. CONCLUSION: Aucun polymorphisme validé de Kelch 13 associé à une résistance à l'artémisinine n'a été observé parmi les isolats de P. falciparum de Lagos, au Nigéria. Aucune étude clinique n'ayant été réalisée, il n'a pas été possible d'établir une corrélation entre cette observation et la sensibilité à l'artémisinine.

Epidemiological characterization of malaria in rural southern Tanzania following China-Tanzania pilot joint malaria control baseline survey.

BACKGROUND: Malaria is an important public health problem in Tanzania. The latest national malaria data suggests rebound of the disease in the country. Anopheles arabiensis, a mosquito species renowned for its resilience against existing malaria vector control measures has now outnumbered the endophagic and anthrophilic Anopheles gambiae sensu stricto as the dominant vector. Vector control measures, prophylaxis and case management with artemisinin-based combination therapy (ACT) are the main control interventions. This paper presents and discusses the main findings from a baseline household survey that was conducted to determine malaria parasite prevalence and associated risk exposures prior to piloting the T3-initiative of World Health Organization integrated with Chinese malaria control experience aimed at additional reduction of malaria in the area. METHODS: The study was conducted from 4 sub-district divisions in Rufiji District, southern Tanzania: Ikwiriri, Kibiti, Bungu, and Chumbi. Malaria transmission is endemic in the area. It involved 2000 households that were randomly selected from a list of all households that had been registered from the area. Residents in sampled households were interviewed on a range of questions that included use of long-lasting insecticidal nets (LLINs) the night prior to the interview and indicators of socio-economic status. Blood drops were also collected on blood slides that were examined for malaria parasites using microscopes. RESULTS: The study observed an average malaria parasite prevalence of 13% across the selected site. Its distribution was 5.6, 12.8, 16.7, and 18% from Ikwiriri, Kibiti, Bungu, and Chumbi wards, respectively. The corresponding LLIN use discovered were 57.5% over the district. The highest usage was observed from Ikwiriri at 69.6% and the lowest from Bungu at 46.3%. A statistically significant variation in parasitaemia between socio-economic quintiles was observed from the study. Males were more parasitaemic than females (p value = 0.000). DISCUSSION AND CONCLUSION: The findings have been discussed in the light of results from Tanzania Demographic and Health Survey-Malaria Indicator Survey, 2015-2016 and other related studies, together with goals and targets set for malaria control. The paper also discusses the observed parasitaemia in relation to reported LLIN use and its distribution by some important factors as they were explored from the study. It has been concluded that malaria burden is now concentrated on the fringes of the settlements where the poorest section of the population is concentrated and LLIN usage is lower than the national average and targets set by national and global malaria control initiatives.

Ready for malaria elimination: zero indigenous case reported in the People's Republic of China.

BACKGROUND: Malaria was once one of the most serious public health problems in China. However, the disease burden has sharply declined and epidemic areas have shrunk after the implementation of an integrated malaria control and elimination strategy, especially since 2000. In this review, the lessons were distilled from the Chinese national malaria elimination programme and further efforts to mitigate the challenges of malaria resurgence are being discussed. METHODS: A retrospective evaluation was performed to assess the changes in malaria epidemic patterns from 1950 to 2017 at national level. The malaria data before 2004 were collected from paper-based annual reports. After 2004, each of the different cases from the Infectious Diseases Information Reporting Management System (IDIRMS) was closely examined and scrutinized. An additional documenting system, the National Information Management System for Malaria, established in 2012 to document the interventions of three parasitic diseases, was also examined to complete the missing data from IDIRMS. RESULTS: From 1950 to 2017, the occurrence of indigenous malaria has been steeply reduced, and malaria-epidemic regions have substantially shrunk, especially after the launch of the national malaria elimination programme. There were approximately 30 million malaria cases annually before 1949 with a mortality rate of 1%. A total of 5999 indigenous cases were documented from 2010 to 2016, with a drastic reduction of 99% over the 6 years (2010, n = 4262; 2016, n = 3). There were indigenous cases reported in 303 counties from 18 provinces in 2010, but only 3 indigenous cases were reported in 2 provinces nationwide in 2016. While in 2017, for the first time, zero indigenous case was reported in China, and only 7 of imported cases were in individuals who died of Plasmodium falciparum infection. CONCLUSION: Malaria elimination in China is a country-led and country-owned endeavour. The country-own efforts were a clear national elimination strategy, supported by two systems, namely a case-based surveillance and response system and reference laboratory system. The country-led efforts were regional and inter-sectoral collaboration as well as sustained monitoring and evaluation. However, there are still some challenges, such as the maintenance of non-transmission status, the implementation of a qualified verification and assessment system, and the management of imported cases in border areas, through regional cooperation. The findings from this review can probably help improving malaria surveillance systems in China, but also in other elimination countries.

Clonorchiasis.

On Aug 21, 1875, James McConnell published in The Lancet his findings from a post-mortem examination of a 20-year-old Chinese man--undertaken at the Medical College Hospital in Calcutta, India--in whom he found Clonorchis sinensis in the bile ducts. Now, exactly 140 years later, we have a sound understanding of the lifecycle of this liver fluke, including key clinical, diagnostic, and epidemiological features. Developments in the so-called -omics sciences have not only advanced our knowledge of the biology and pathology of the parasite, but also led to the discovery of new diagnostic, drug, and vaccine targets. C sinensis infection is primarily related to liver and biliary disorders, especially cholangiocarcinoma. Clonorchiasis mainly occurs in east Asia, as a result of the region's social-ecological systems and deeply rooted cultural habit of consuming raw freshwater fish. The Kato-Katz technique, applied on fresh stool samples, is the most widely used diagnostic approach. Praziquantel is the treatment of choice and has been considered for preventive chemotherapy. Tribendimidine showed good safety and therapeutic profiles in phase 2 trials and warrants further investigation. Still today, the precise distribution, the exact number of infected people, subtle morbidities and pathogenesis, and the global burden of clonorchiasis are unknown. Integrated control strategies, consisting of preventive chemotherapy; information, education, and communication; environmental management; and capacity building through intersectoral collaboration should be advocated.