Achievements of the national malaria control and elimination program in the People’s Republic of China:the Atlas of Malaria Transmission in China

In 2017,China achieved the target of zero indigenous malaria case for the first time,and has been certified as malaria free by World Health Organization in 2021.To further summarize the historical achievements and technical experiences of the elimination program,a project on the Roadmap Analysis and Verification for Malaria Elimination in China was carried out.Results of the project were compiled and published as the Atlas of Malaria Transmission in China(The Atlas).The Atlas using modern digital information technologies,has been supported by various data from 24 malaria endemic provinces of China since 1950,to assess the changes in malaria epidemic patterns from 1950 to 2019 at national and provincial levels.The Atlas is designed as two volumes,including a total of 1850 thematic maps and more than 130 charts,consisting of introductory maps,thematic maps of malaria epidemic and control at national and provincial levels.It objectively and directly shows the epidemic history,evolution process,and great achievements of the national malaria control and elimination program in China.The Atlas has important reference value for summing up historical experience in the national malaria elimination program of China,and malaria control and elimination in other endemic countries in the world.

Laboratory diagnosis for malaria in the elimination phase in China:efforts and challenges

Malaria remains a global health challenge,although an increasing number of countries will enter pre-elimination and elimination stages.The prompt and precise diagnosis of symptomatic and asymptomatic carriers of Plasmodium parasites is the key aspect of malaria elimination.Since the launch of the China Malaria Elimination Action Plan in 2010,China has formulated clear goals for malaria diagnosis and has established a network of malaria diagnostic laboratories within medical and health institutions at all levels.Various external quality assessments were implemented,and a national malaria diagnosis reference laboratory network was established to strengthen the quality assurance in malaria diagnosis.Notably,no indigenous malaria cases have been reported since 2017,but the risk of re-establishment of malaria transmission cannot be ignored.This review summarizes the lessons about malaria diagnosis in the elimination phase,primarily including the establishments of laboratory networks and quality control in China,to better improve malaria diagnosis and maintain a malaria-free status.A reference is also provided for countries experiencing malaria elimination.

Malaria Deaths—China,2011–2020

Introduction:The malaria deaths(MDs)caused by imported Plasmodium falciparum has become a great challenge.This article analyzed MDs in China in 2011−2020 to provide evidence-based data for further strategies and interventions adjustment.Methods:Individual data via the National Notifiable Disease Reporting System(NNDRS)in 2011−2020 were collected.The Plasmodium species,case classification,temporal and spatial distribution,and source of MDs were analyzed to explore MD characteristics.The Parasitic Diseases Information Reporting Management System(PDIRMS)of MDs in 2013−2020 which explored clinical symptom and treatment was also collected and analyzed.Results:A total of 165 MDs with a mortality rate of 0.5%were recorded in the NNDRS from 2011 to 2020.Among them,164(99.4%)died due to imported malaria cases,1(0.6%)died of indigenous case reported in Yunnan in 2013.The number of MDs showed a decreasing trend from 2011(n=30)to 2020(n=6).The MDs consisted of 160(97.0%)P.falciparum cases,1(0.6%)mixed infection case,and 4(2.4%)clinical diagnosed cases.The MDs were mainly reported in Guangdong(n=18,10.9%),Sichuan(n=17,10.3%),Beijing(n=15,9.1%)and Henan(n=15,9.1%).The PDIRMS had reported 121 MDs from 2013−2020,and 46.3%(n=56)of MDs exhibited severe brain damage,and most of the patients(n=95,78.5%)were administrated by artemisinin combination therapy injection form.Conclusions:The total MDs decreased in China,and a delay in diagnosis and treatment is the main causes of MDs.Therefore,two actions are needed to prevent MDs,including improving health education for key populations such as migrant workers who come to and return from endemic regions and maintaining malaria diagnosis and treatment capabilities of clinicians in medical facilities.

Imported Malaria Cases--China,2012–2018

Introduction:In 2017,no indigenous malaria cases were reported in China,but imported malaria was a challenge for the elimination program.This study analyzed the status and trends of imported malaria in China from 2012 to 2018 to provide evidence for further strategies and adjustments to current interventions.Methods:Data on individuals were collected from the Parasitic Diseases Information Reporting Management System(PDIRMS)from 2012 to 2018.Plasmodium species,case classification,temporal distribution,spatial distribution,and source of imported cases were analyzed to investigate imported malaria characteristics.Results:In total,21,376 malaria cases were recorded in the PDIRMS from 2012 to 2018.Among them,20,938(98.0%)cases were imported malaria cases(IMCs).The number and proportion of IMCs increased from 2012(n=2,474,91.0%)to 2018(n=2,511,99.7%).IMCs consisted of 13,510(64.5%)P.falciparum,4,803(22.9%)P.vivax,1,725(8.2%)P.ovale,376(1.8%)P.malariae,2(0.01%)P.knowlesi,348(1.7%)mixed infections,and 174(0.8%)clinically-diagnosed cases.The proportion of imported P.falciparum cases increased from 2012(n=1403,57.4%)to 2018(n=1655,66.0%),while imported P.vivax cases showed a decreasing trend from 2012(n=901,43.7%)to 2018(n=352,14.0%).IMCs were mainly reported in Yunnan(n=2,922,14.0%),Guangxi(n=2,827,13.5%),and Jiangsu(2,067,9.9%).IMCs were reported throughout the entire year,and the highest number of IMCs was reported in June 2013.IMCs originated from 67 countries from 4 continents,and the largest proportion were from Myanmar(n=3,081,14.7%)and Ghana(n=2,704,12.9%).Conclusion and Implications for Public Health Practice:The total number of IMCs increased in China.Therefore,two actions are needed to continue the elimination of malaria in China:prevent reestablishment caused by imported P.vivax because Anopheles sinensis is still widely distributed;and ensure timely diagnosis and appropriate treatment to avoid fatal cases caused by imported P.falciparum.

Malaria profiles and challenges in artemisinin resistance containment in Myanmar

Background:This study examined evolving malaria profiles from January,2010 to December,2014 to evaluate achievements and challenges of implementing measures to prevent and control spread of artemisinin resistance in Myanmar.Methods:Using National Malaria Control Programme(NMCP)data,a cross-sectional descriptive study of 52 townships in artemisinin-resistant containment areas in Myanmar was conducted.Annual program data were analysed,and trends over time are graphically presented.Results:In the 52 study townships populated by 8.7 million inhabitants,malaria incidence showed a decreasing trend from 10.54 per 1000 population in 2010 to 2.53 in 2014,and malaria mortalities also decreased from 1.83 per 100000 population in 2010 to 0.17 in 2014.The proportion of confirmed to total tested malaria cases also decreased from 6 to 1%,while identification of cases improved.All cases from all parasites species,including Plasmodium falciparum,decreased.Coverage of LLIN(long-lasting insecticidal net)/ITN(insecticide-treated mosquito nets)and indoor residual spraying(IRS)was high in targeted areas with at-risk persons,even though the total population was not covered.In addition to passive case detection(PCD),active case detection(ACD)was conducted in hard-to-reach areas and worksites where mobile migrant populations were present.ACD improved in most areas from 2012 to 2014,but continues to need to be strengthened.Conclusions:The findings provide useful data on the malaria situation in artemisinin-resistant initiative areas,which may be useful for the NMCP to meet its elimination goal.These profiles could contribute to better planning,implementation,and evaluation of intervention activities.

Malaria Diagnosis and Verification--China,2017–2018

What is already known about this topic?Prompt,accurate diagnosis is an essential part of malaria elimination strategies.Insufficient malaria diagnosis capacity will be a potential risk for malaria reintroduction.What is added by this report?Health facilities at the county and prefectural levels were the most concentrated facilities for initial diagnosis of malaria(68.2%)and confirmation(76.4%).More than 65%of cases could not be diagnosed within 1 day of onset,and only 89.4%of laboratory-confirmed cases were accurate.What are the implications for public health practice?Malaria health education should be strengthened to improve public awareness and health professionals’vigilance of malaria,thereby shortening the diagnostic intervals.In addition,the capacity of malaria diagnosis,especially Plasmodium speciation,should be improved to ensure accurate diagnosis and appropriate treatment.

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.

International non-governmental organizations’provision of communitybased tuberculosis care for hard-to-reach populations in Myanmar,2013-2014

Background:National tuberculosis(TB)programs increasingly engage with international non-governmental organizations(INGOs),especially to provide TB care in complex settings where community involvement might be required.In Myanmar,however,there is limited data on how such INGO community-based programs are organized and how effective they are.In this study,we describe four INGO strategies for providing community-based TB care to hard-to-reach populations in Myanmar,and assess their contribution to TB case detection.Methods:We conducted a descriptive study using program data from four INGOs and the National TB Program(NTP)in 2013-2014.For each INGO,we extracted information on its approach and key activities,the number of presumptive TB cases referred and undergoing TB testing,and the number of patients diagnosed with TB and their treatment outcomes.The contribution of INGOs to TB diagnosis in their selected townships was calculated as the proportion of INGO-diagnosed new TB cases out of the total NTP-diagnosed new TB cases in the same townships.Results:All four INGOs implemented community-based TB care in challenging contexts,targeting migrants,post-conflict areas,the urban poor,and other vulnerable populations.Two recruited community volunteers via existing community health volunteers or health structures,one via existing community leaderships,and one directly involved TB infected/affected individuals.Two INGOs compensated volunteers via performance-based financing,and two provided financial and in-kind initiatives.All relied on NTP laboratories for diagnosis and TB drugs,but provided direct observation treatment support and treatment follow-up.A total of 21995 presumptive TB cases were referred for TB diagnosis,with 7383(34%)new TB cases diagnosed and almost all(98%)successfully treated.The four INGOs contributed to the detection of,on average,36%(7383/20663)of the total new TB cases in their respective townships(range:15-52%).Conclusion:Community-based TB care supported by INGOs successfully achieved TB case detection in hard-toreach and vulnerable populations.This is vital to achieving the World Health Organization End TB Strategy targets.Strategies to ensure sustainability of the programs should be explored,including the need for longer-term commitment of INGOs.

Engagement of public and private medical facilities in tuberculosis care in Myanmar:contributions and trends over an eight-year period

Background:As part of the WHO End TB strategy,national tuberculosis(TB)programs increasingly aim to engage all private and public TB care providers.Engagement of communities,civil society organizations and public and private care provider is the second pillar of the End TB strategy.In Myanmar,this entails the public-public and public-private mix(PPM)approach.The public-public mix refers to public hospital TB services,with reporting to the national TB program(NTP).The public-private mix refers to private general practitioners providing TB services including TB diagnosis,treatment and reporting to NTP.The aim of this study was to assess whether PPM activities can be scaled-up nationally and can be sustained over time.Methods:Using 2007-2014 aggregated program data,we collected information from NTP and non-NTP actors on 1)the number of TB cases detected and their relative contribution to the national case load;2)the type of TB cases detected;3)their treatment outcomes.Results:The total number of TB cases detected per year nationally increased from 133,547 in 2007 to 142,587 in 2014.The contribution of private practitioners increased from 11%in 2007 to 18%in 2014,and from 1.8%to 4.6%for public hospitals.The NTP contribution decreased from 87%in 2007 to 77%in 2014.A similar pattern was seen in the number of new smear(+)TB cases(31%of all TB cases)and retreatment cases,which represented 7.8%of all TB cases.For new smear(+)TB cases,adverse outcomes were more common in public hospitals,with more patients dying,lost to follow up or not having their treatment outcome evaluated.Patients treated by private practitioners were more frequently lost to follow up(8%).Adverse treatment outcomes in retreatment cases were particularly common(59%)in public hospitals for various reasons,predominantly due to patients dying(26%)or not being evaluated(10%).In private clinics,treatment failure tended to be more common(8%).Conclusions:The contribution of non-NTP actors to TB detection at the national level increased over time,with the largest contribution by private practitioners involved in PPM.Treatment outcomes were fair.Our findings confirm the role of PPM in national TB programs.To achieve the End TB targets,further expansion of PPM to engage all public and private medical facilities should be targeted.

Antimalarial Drug Resistance Surveillance in China,2016–2020

Introduction:Antimalarial drug resistance,especially artemisinin resistance,has been a global threat to reduce morbidity and mortality and to eliminate malaria.Antimalarial drug resistance surveillance could provide evidence for the efficacy of a national drug policy for treatment of all reported malaria cases.Methods:The therapeutic efficacy of dihydroartemisinin-piperaquine(DHA-PPQ)and chloroquine(CQ)for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax infection,respectively,was evaluated by enrolling patients between 2016 and 2020.Surveillance of molecular markers involved collecting blood samples by passive or active detection and amplifying the drug resistance genes Pfcrt,Pfmdr1,Pfdhfr,Pfdhps,and PfK13.Results:DHA-PPQ and CQ were effective for the treatment of P.falciparum and P.vivax infections,with cure rates>90%and 100%,respectively.Among the 2,492 samples,the Pfcrt wild-type CVMNK was the most frequent haplotype(70.1%,1,747/2,492),while 19.4%(484/2,492)displayed the triple mutant haplotype CVIET.In total of 228 isolates with sequencing in Pfdhfr and Pfdhps,high mutant prevalence of 98.7%and 95.2%were detected,respectively.A total of 54 non-synonymous mutations in the PfK13 propeller domain were confirmed with a prevalence of 3.5%(87/2,483),and the most common mutation was A578S,with a proportion of 16.1%(14/87),followed by Q613E(6.9%,6/87).Conclusion and Implications for Public Health Practice:DHA-PPQ and CQ,the first line drugs for P.falciparum and P.vivax treatment,showed efficacy in China.Molecular markers showed high levels of polymorphism and resistance,which revealed an early warning of drug resistance in imported cases.