Tang Lh

Costs and financial feasibility of malaria elimination

Summary The marginal costs and benefits of converting malaria programmes from a control to an elimination goal are central to strategic decisions, but empirical evidence is scarce. We present a conceptual framework to assess the economics of elimination and analyse a central component of that framework—potential short-term to medium-term financial savings. After a review that showed a dearth of existing evidence, the net present value of elimination in five sites was calculated and compared with effective control. The probability that elimination would be cost-saving over 50 years ranged from 0% to 42%, with only one site achieving cost-savings in the base case. These findings show that financial savings should not be a primary rationale for elimination, but that elimination might still be a worthy investment if total benefits are sufficient to outweigh marginal costs. Robust research into these elimination benefits is urgently needed.

Communicating and Monitoring Surveillance and Response Activities for Malaria Elimination: China's “1-3-7” Strategy

Qi Gao and colleagues describe Chinas 1-3-7 strategy for eliminating malaria: reporting of malaria cases within one day, their confirmation and investigation within three days, and the appropriate public health response to prevent further transmission within seven days.

A single mutation in K13 predominates in Southern China and is associated with delayed clearance of Plasmodium falciparum following artemisinin treatment

BACKGROUND Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and poses a threat to malaria control and elimination. Mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 have been associated with delayed parasite clearance following artemisinin treatment elsewhere in the region, but not yet in China. METHODS Therapeutic efficacy studies of artesunate and dihydroartemisinin-piperaquine were conducted from 2009 to 2012 in the Yunnan Province of China near the border with Myanmar. K13 mutations were genotyped by capillary sequencing of DNA extracted from dried blood spots collected in these clinical trials and in routine surveillance. Associations between K13 mutations and delayed parasite clearance were tested using regression models. RESULTS Parasite clearance half-lives were prolonged after artemisinin treatment, with 44% of infections having half-lives >5 hours (n = 109). Fourteen mutations in K13 were observed, with an overall prevalence of 47.7% (n = 329). A single mutation, F446I, predominated, with a prevalence of 36.5%. Infections with F446I were significantly associated with parasitemia on day 3 following artemisinin treatment and with longer clearance half-lives. CONCLUSIONS Plasmodium falciparum infections in southern China displayed markedly delayed clearance following artemisinin treatment. F446I was the predominant K13 mutation and was associated with delayed parasite clearance.

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

BackgroundMalaria 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.MethodsThe 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.ResultsIt 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(P < 0.01). Strong positive correlations were found for malaria incidence time series lagging one to three months behind rainfall (r > 0.4) and lagging zero to two months behind temperature and relative humidity (r > 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 (P < 0.01), 0.451(P < 0.05) and 0.432(P < 0.05), respectively.ConclusionMeteorological 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.

Therapeutic efficacy of artesunate in the treatment of uncomplicated Plasmodium falciparum malaria and anti-malarial, drug-resistance marker polymorphisms in populations near the China-Myanmar border

BackgroundThe aim of this study was to evaluate the clinical outcome after seven-day artesunate monotherapy for uncomplicated Plasmodium falciparum malaria in Yingjiang County along the China-Myanmar border and investigate genetic polymorphisms in the P. falciparum chloroquine-resistance transporter (pfcrt), multidrug resistance 1 (pfmdr1), dihydrofolate reductase (pfdhfr), dihydropteroate synthase (pfdhps) and ATPase (pfatp6) genes.MethodsPatients ≥ one year of age with fever (axillary temperature ≥37.5°C) or history of fever and P. falciparum mono-infection were included. Patients received anti-malarial treatment with artesunate (total dose of 16 mg/kg over seven days) by directly observed therapy. After a 28-day follow-up, treatment efficacy and effectiveness were assessed based on clinical and parasitological outcomes. Treatment failure was defined as recrudescence of the original parasite and distinguished with new infection confirmed by PCR. Analysis of gene mutation and amplification were performed by nested polymerase chain reaction.ResultsSixty-five patients were enrolled; 10 withdrew from the study, and six were lost to follow-up. All but two patients demonstrated adequate clinical and parasitological response; 12 had detectable parasitaemia on day 3. These two patients were confirmed to be new infection by PCR. The efficacy of artesunate was 95.9%. The pfcrt mutation in codon 76 was found in all isolates (100%), and mutations in codons 71 and 72 were found in 4.8% of parasite isolates. No mutation of pfmdr1 (codons 86 or 1246) was found. Among all samples, 5.1% were wild type for pfdhfr, whereas the other samples had mutations in four codons (51, 59, 108 and 164), and mutations in pfdhps (codons 436, 437, 540 and 581) were found in all isolates. No samples had mutations in pfatp6 codons 623 or 769, but two new mutations (N683K and R756K) were found in 4.6% and 9.2% of parasite isolates, respectively.ConclusionPlasmodium falciparum infection was associated with slow parasite clearance and suspected artemisinin resistance at the China-Myanmar border area. The prevalence of pfcrt 76 T and markers for SP resistance are still high. It should be strengthened further on parasite clearance time or clearance half life to confirm the resistance status, and molecular epidemiology should provide complementary information to assess the appropriateness of current policies based on artemisinin derivatives.

Molecular epidemiology of drug resistance markers of Plasmodium falciparum in Yunnan Province, China

BackgroundThe mutations in Plasmodium falciparum chloroquine resistance transporter (pfcrt), multidrug resistance 1 (pfmdr1), dihydrofolate reductase (pfdhfr), dihydropteroate synthase (pfdhps) and ATPase (pfatp6) genes were associated with anti-malaria drug resistance. The aim of this study was to investigate the prevalence of polymorphisms in pfcrt, pfmdr1, pfdhfr, pfdhps and pfatp6 in Yunnan Province. Finger-prick blood samples were collected from malaria-positive patients from Yunnan Province in 2009-2010. Single-nucleotide polymorphisms (SNPs) in the resistance-related genes were analysed by various PCR-based methods.ResultsA total of 108 blood samples were collected. Although chloroquine has not been used to treat falciparum malaria for nearly 30 years, 95.3% of the parasites still carried the pfcrt K76T mutation, whereas the majority of isolates displayed the wild-type pfmdr1 N86 and D1246 sequences. The molecular level of sulphadoxine–pyrimethamine resistance in P. falciparum was high. The most prevalent mutation was pfdhfr C59R (95.9%), whereas the frequencies of the quadruple, triple and double mutants were 22.7% (N51I/C59R/S108N/I164L), 51.5% (N51I/C59R/S108N, N51I/C59R/I164L and C59R/S108N/ I164L) and 21.6% (N51I/ C59R, C59R/S108N and C59R/I164L), respectively. A437G (n = 77) and K540E (n = 71) were the most prevalent mutations in pfdhps, and 52.7% of the samples were double mutants, among which A437G/K540E was the most common double mutation (37/49). Quadruple mutants were found in 28.0% (26/93) of samples. A total of 8.6% of isolates (8/93) carried the S436A/A437G/A581G triple mutation. No mutations were found in pfatp6 codons 623 or 769, but another two mutations (N683K and R756K) were found in 4.6% (3/97) and 9.2% (6/97) of parasite isolates, respectively.ConclusionsThis study identified a high frequency of mutations in pfcrt, pfdhfr and pfdhps associated with CQ and SP resistance in P. falciparum and no mutations linked to artemisinin resistance (pfatp6). Molecular epidemiology should be included in routine surveillance protocols and used to provide complementary information to assess the appropriateness of the current national anti-malarial drug policy.

Lessons from malaria control to elimination: case study in Hainan and Yunnan provinces.

Reduction patterns of Plasmodium falciparum and P. vivax malaria transmission and the role of an integrated strategy of case management and vector control are compared between different ecological zones. The epidemiology of malaria in Hainan and Yunnan provinces was disparate, even though distinct malaria control strategies have been adapted to different situations based on risk group, vector behaviours, local health infrastructure, and environmental conditions. The island Hainan appears to be victorious in eliminating malaria. However, there is still a long way to go to prevent the reintroduction of malaria in Hainan province and eliminating malaria in the border areas of Yunnan province. This review of the experiences and challenges from malaria control to elimination in Hainan and Yunnan provinces of southern China will provide a basis for the future elimination of malaria in the whole country.