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Effectiveness of joint 3 + 1 malaria strategy along China-Myanmar cross border areas.

ABSTRACT: BACKGROUND:Cross-border malaria in Laiza City of Myanmar seriously affected Yingjiang County of China and compromised reaching the goal of malaria elimination by 2020. Since 2017, a pilot project on 3 + 1 strategy of joint cross-border malaria prevention and control was carried out for building a malaria buffer in these border areas. Here, 3 were the three preventive lines in China where different focalized approaches of malaria elimination were applied and + 1 was a defined border area in Myanmar where the integrated measures of malaria control were adopted. METHODS:A 5-year retrospective analysis (2015 to 2019) was conducted that included case detection, parasite prevalence and vector surveillance. Descriptive statistics was used and the incidence or rates were compared. The annual parasite incidence and the parasite prevalence rate in + 1 area of Myanmar, the annual importation rate in Yingjiang County of China and the density of An. minimus were statistically significant indictors to assess the effectiveness of the 3 + 1 strategy. RESULTS:In + 1 area of Myanmar from 2015 to 2019, the averaged annual parasite incidence was (59.11 ± 40.73)/1000 and Plasmodium vivax accounted for 96.27% of the total confirmed cases. After the pilot project, the annual parasite incidence dropped 89% from 104.77/1000 in 2016 to 12.18/1000 in 2019, the microscopic parasite prevalence rate dropped 100% from 0.34% in 2017 to zero in 2019 and the averaged density of An. Minimus per trap-night dropped 93% from 1.92 in June to 0.13 in September. The submicroscopic parasite prevalence rate increased from 1.15% in 2017 to 1.66% in 2019 without significant difference between the two surveys (P = 0.084). In Yingjiang County of China, neither indigenous nor introduced case was reported and 100% cases were imported from Myanmar since 2017. The averaged annual importation rate from 2015 to 2019 was (0.47 ± 0.15)/1000. After the pilot project, the annual importation rate dropped from 0.59/1000 in 2016 to 0.28/1000 in 2019 with an overall reduction of 53% in the whole county. The reduction was 67% (57.63/1000 to 18.01/1000) in the first preventive line, 52% (0.20/1000 to 0.10/1000) in the second preventive line and 36% (0.32/1000 to 0.22/1000) in the third preventive line. The averaged density of An. Minimus per trap-night in the first preventive line dropped 94% from 2.55 in June to 0.14 in September, without significant difference from that of + 1 area of Myanmar (Z value = - 1.18, P value = 0.24). CONCLUSION:The pilot project on 3 + 1 strategy has been significantly effective in the study areas and a buffer zone of border malaria was successfully established between Laiza City of Myanmar and Yingjiang County of China.

SUBMITTER: Lin ZR

PROVIDER: S-EPMC8670156 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionMalaria importation can be caused by cross-border movement either of both people and anopheline mosquitoes. However, there still lacks robust evidence of imported malaria caused by Plasmodium spp. infected anopheles along international border areas (border-spill malaria). The objectives of this study were to confirm whether an outbreak of Plasmodium vivax malaria is border-spill malaria and assess the effects of China's public health response along China-Myanmar border.MethodsEpidemiological, parasitological and entomological investigations were conducted to investigate the outbreak of border-spill malaria. Meanwhile, comprehensive interventions were carried out to prevent further transmission and reintroduction of malaria.ResultsRapid diagnostic testing, microscopy and polymerase chain reaction were performed and the infections were confirmed as P. vivax. A total of 22 (9.21%) of 239 workers contracted P. vivax during the outbreak. Multivariate logistic regression analysis identified that the distance of worker shelters in China within 300 meters to the internally displaced person (IDP) camps in Myanmar was a risk factors associated with malaria infection (adjusted odds ratio 7.5920; 95% confidence interval, 2.6079-22.1013; P = 0.0002). After comprehensive interventions, malaria transmission was successfully interpreted and prevented at the project site till the completion of project on 14 January 2020, and recurrence of P. vivax malaria was not detected by the end of 2020.ConclusionThis study provided robust evidence of border-spill malaria along China-Myanmar border. Malaria parasite reservoir and distance travelled by female anopheline mosquitoes are two determinants for border-spill malaria. The public health response to the outbreak indicates that the malaria surveillance and response system works well in preventing reintroduction of malaria. However, prevention of border-spill malaria is still a major challenge in the Yunnan border area, China.

Project description:BackgroundThere is a paucity of data about the susceptibility status of malaria vectors to Public Health insecticides along the Thailand-Myanmar border. This lack of data is a limitation to guide malaria vector-control in this region. The aim of this study was to assess the susceptibility status of malaria vectors to deltamethrin, permethrin and DDT and to validate a simple molecular assay for the detection of knock-down resistance (kdr) mutations in the study area.MethodsAnopheles mosquitoes were collected in four sentinel villages during August and November 2014 and July 2015 using human landing catch and cow bait collection methods. WHO susceptibility tests were carried out to measure the mortality and knock-down rates of female mosquitoes to deltamethrin (0.05%), permethrin (0.75%) and DDT (4%). DNA sequencing of a fragment of the voltage-gated sodium channel gene was carried out to identify knock-down resistance (kdr) mutations at position 1014 in mosquitoes surviving exposure to insecticides.ResultsA total of 6295 Anopheles belonging to ten different species were bioassayed. Resistance or suspected resistance to pyrethroids was detected in An. barbirostris (s.l.) (72 and 84% mortality to deltamethrin (n = 504) and permethrin (n = 493) respectively), An. hyrcanus (s.l.) (33 and 48% mortality to deltamethrin (n = 172) and permethrin (n = 154), respectively), An. jamesii (87% mortality to deltamethrin, n = 111), An. maculatus (s.l.) (85 and 97% mortality to deltamethrin (n = 280) and permethrin (n = 264), respectively), An. minimus (s.l.) (92% mortality, n = 370) and An. vagus (75 and 95% mortality to deltamethrin (n =148) and permethrin (n = 178), respectively). Resistance or suspected resistance to DDT was detected in An. barbirostris (s.l.) (74% mortality, n = 435), An. hyrcanus (s.l.) (57% mortality, n = 91) and An. vagus (97% mortality, n = 133). The L1014S kdr mutation at both heterozygous and homozygous state was detected only in An. peditaeniatus (Hyrcanus Group).ConclusionResistance to pyrethroids is present along the Thailand-Myanmar border, and it represents a threat for malaria vector control. Further investigations are needed to better understand the molecular basis of insecticide resistance in malaria vectors in this area.

Project description:BackgroundThe 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.MethodsThe 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.ResultsDHA-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.ConclusionDHA-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.

Project description:BackgroundSensitive methods for detecting asymptomatic malaria infections are essential for identifying potential transmission reservoirs and obtaining an accurate assessment of malaria epidemiology in low-endemicity areas aiming to eliminate malaria. PCR techniques to detect parasite nucleic acids (DNA or RNA) are among the most commonly used molecular methods. However, most of these methods are of low throughput and cannot be used for large-scale molecular epidemiological studies. A recently developed capture and ligation probe-PCR (CLIP-PCR) is claimed to have the sensitivity of molecular techniques and the high throughput capacity needed for screening purposes. This study aimed to compare several molecular methods for detecting asymptomatic and submicroscopic Plasmodium infections in healthy residents of a malaria-hypoendemic region in Southeast Asia, where malaria elimination is in sight.MethodThis study compared three molecular detection methods side-by-side, namely nested PCR targeting the rRNA genes, nested RT-PCR to detect parasite rRNA, and CLIP-PCR to detect parasite rRNA in 1005 healthy individuals in northeastern Myanmar. For nested PCR and RT-PCR, parasite DNA and total RNA were extracted from ~100 µL of blood, whereas RNA used for CLIP-PCR was from a 3 mm disk of dried blood filter paper. The sensitivity and specificity of these methods were compared with those of conventional light microscopy. In addition, RT-PCR and quantitative RT-PCR (qRT-PCR) targeting the Pvs25 gene in Plasmodium vivax were used to assess gametocyte prevalence in the samples.ResultsLight microscopy detected Plasmodium infections in only 1.19% of the residents harbouring the parasites. CLIP-PCR had slightly better performance and detected Plasmodium infections in 1.89% of the population. Further improvement was achieved by nested PCR to detect parasite DNA, which detected P. vivax and Plasmodium falciparum infections in 2.39% of the residents. The nested RT-PCR targeting rRNA, however, detected as many as 187 (18.61%) individuals having Plasmodium infections with P. vivax being the predominant species (176 P. vivax, 5 P. falciparum and 6 P. falciparum/P. vivax mixed infections). Of the 210 Plasmodium-positive samples detected by all molecular methods, 115 were Pvs25-positive by qRT-PCR, indicating that a large proportion of asymptomatic individuals were gametocyte carriers.ConclusionNested RT-PCR based on the detection of asexual-stage parasite rRNA was the most sensitive, with a more than sixfold higher sensitivity than the other two molecular methods of parasite detection. CLIP-PCR has an increased throughput, but its sensitivity in this study was much lower than those of other molecular methods, which may be partially due to the smaller amount of RNA input used.

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Effectiveness of joint 3 + 1 malaria strategy along China-Myanmar cross border areas.

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