Malaria from hyperendemicity to elimination in Hekou County on China–Vietnam border: an ecological study

The study was carried out in Hekou County (103°23′–104°17′E, 22°30′–23°02′S; altitude from 76.4 to 2354.1 m), which is located at Red River Valley, southeast of Yunnan Province, China, and shares a border of 193 km with Vietnam (Fig. 1). The county has a population of 104,609 people (2010) living in an area of 1332 km², with a tropical monsoon rainforest climate and an annual mean temperature of 23.0 °C [14]. Anopheles minimus is the primary malaria vector [15, 16]. Indigenous malaria transmission was interrupted at Hekou County in 2011, and it passed the provincial elimination assessment in 4 November, 2015.

The study design was an ecological study. Malaria burden before 1951 and the 64-year dynamics (1952–2015) from malaria hyperendemicity to elimination are described. Association between malaria incidence and socio-economic development and environmental change are analysed by single and bilinear regression.

All available paper records related to malaria surveillance and control activities were reviewed at Hekou County Centre for Disease Control and Prevention (CDC) for collecting data of malaria cases and intervention activities from 1952 to 2007. Chinese Information System for Disease Control and Prevention (CISDCP) began to cover all counties of China from 2008 [17], thus, data on malaria cases and intervention from 2008–2015 were obtained from CISDCP. National and provincial gross domestic product (GDP) and urbanization rate came from the website of the National Bureau of Statistics of the People’s Republic of China. Banana planting area (BPA) was from paper records of Hekou County Bureau of Statistics. Qualitative data was collected by semi-structured, in-depth interviews (SDI) with senior malaria control staff who had worked at Hekou County CDC, Honghe Prefecture CDC and Yunnan Institute of Parasitic Diseases (YIPD) [18, 19]. In addition, almost all available literature on political, social and economic development, the malaria situation and control related to Hekou County were also reviewed.

Before 2010, species of malaria parasites were not registered clearly. A combination of clinical symptoms and results of presumptive treatment with anti-malarial drugs were some of the definitions for malaria cases at that time. In the study, annual malaria incidence (AMI) was used to replace annual parasite incidence as the outcome variable, so the AMI included both microscopy confirmed cases and cured cases by presumptive treatment. The amount and impact of intervention activities were described for each stage in the process from hyperendemicity to elimination, although the quantitative relationship between AMI and intervention activities was not done because of unavailability of sequential data. In linear regression analysis, independent variables for social and economic development were national GDP in billions of China Yuan (CNY) and urbanization rate (%). In Hekou County, banana growing is major part of the economy, which has changed the environment in terms of malaria transmission. Transition from paddy field to banana plantation reduces breeding sites for mosquito larvae, and insecticides used in growing bananas kills mosquitoes. In this reason, BPA (hectares) was used as an independent variable for environmental changes (Fig. 2). In order to obtain a more normal distribution of data, all outcome and independent variables were transformed into common logarithms, and then a linear regression analysis was used to analyse relationships of AMI respectively with GDP, urbanization rate, and BPA from 1952 to 2013 [20]. The number of malaria cases during 2014–2015 was zero, so data of the 2 years could not be taken into the analysis model. The rapid development of society and economy has improved health information system and reduced the data bias from 2000 to 2015, so the analysis model was conducted for years 2000–2013 again. In order to learn the impact of socio-economic development and environmental change, a bilinear regression analysis was conducted to on AMI association with national GDP and BPA, and with urbanization rate and BPA for years 2000–2013 [20].

A formal health service system for malaria surveillance and control in China was not available before 1951. Despite significant differences from different data sources, e.g., the number of deaths from malaria as 12,000 in the report from the French Indo-China Railway Construction Company, to 60,000–70,000 in Chinese literature during the period of the Yunnan railway construction, these records indicated a large number of deaths and frequent outbreaks in Hekou County (Table 1). In 1939, Yunnan Commission of Malaria Control and six Provincial Institutes for Malaria Control (PIMC) were established in the Province, and PIMC 6 was allocated in Hekou County. PIMC 6 organized outreach teams visiting communities to treat malaria, promote use of bed nets, and treat mosquito larvae breeding sites with emerald green (copper acetoarsenit). However, these interventions were terminated because of Japanese military invasion to Yunnan in 1942.

1952–1962 Malaria investigation and control activities were initiated in 1952. According to results of SDI from former senior malaria control staff, a malaria control station (MCS) was established to recruit and train health staff in early 1952, and then a malaria control structure comprised of technical officers from military medicine departments and health sector of central and local governments, community health staff (CHWs) and village malaria control workers (VMCWs) was created. The leaders were political officers who managed technical officers, and technical officers trained, guided and managed CHWs who trained, guided and managed VMCWs. One VMCW was in charge of five to ten households to administer drugs and spray insecticides. Malaria investigation and control activities were initiated in the winter of 1952. Two treatment methods were utilized: (1) presumptive treatment was given to people with enlarged spleens and malaria attack episodes in prior 6 months; (2) intermittent preventive treatment (IPT), once a week, was administered to others. Methods for vector control were treatment of larval breeding sites with insecticides in the low-transmission dry season from December to April, and indoor residual spraying (IRS) in the high-transmission rainy season from May to November; in addition, community mobilization was conducted for environmental management. During those years of low supplies, drugs and insecticides were used as long as they were available. Occasionally obtainable drugs were quinacrine hydrochloride, quinine sulfate, paludrine and/or plasmoquine. Obtainable insecticides were dichlorodiphenyltrichloroethane (DDT) or hexachlorocyolohexane (C6H6C6). These interventions reduced AMI from 358.62 per 1000 person-years (89.32% Plasmodium falciparum of cases) in 1953 to 5.69 per 1000 person-years in 1960 (Table 1; Fig. 3).

1963–1977 In Hekou County in October 1963 the MCS became the Anti-epidemic Station (AES). This was a formal system of primary health care services comprising of three levels of county hospital and AES, township hospitals and village health stations for communicable diseases. The system conducted vector control and parasite treatment regularly, and radical cure treatment in low-transmission seasons. Chloroquine and pamaquine were introduced for malaria treatment in this period. However, anti-malarial efforts were halted by the Great Cultural Revolution from 1966 to 1976. The AES was combined into Hekou County Hospital in 1968, and then detached from the hospital in 1971. This led to under-reporting of malaria; no malaria was reported in 1969 (Table 1; Fig. 3).

1978–2002 A policy of reform and stimulation of economic activities and population movement challenged the public health system. Internal and transnational population migration increased transmission and the spread of malaria. Less attention was paid by governments, and health staff, including CHWs, left for better economic income, which led to continued under-reporting of malaria. When a malaria epidemic broke out in 1987: AMI increased to 34.41 per 1000 person-years and five malaria-related deaths in the year; Honghe Prefecture had the highest number of malaria cases among 17 prefectures in Yunnan Province. Ultimately, deterioration of the malaria situation brought a political will to malaria control. Hehong Prefecture Government invested enough funding for anti-malarial drugs and insecticides. Additionally, artemisinin was registered in China in 1986. Introduction of artemisinin saved the life in control of the epidemic, and then oral and injective artemisinin monotherapy was recommended as the first line drugs for treatment of P. falciprum malaria and artemisinin-based combination therapy (ACTs) as the second line treatment in China. By 2002, AMI was lowered to fewer than one per 1000 person-years (Table 1; Fig. 3).

2003–2009 The Chinese government gave a stronger political commitment to public health after the epidemic of severe acute respiratory syndrome (SARS) in 2003. The Hekou County AES turned into Hekou County CDC. Malaria vector control, surveillance and treatment interventions were strengthened across the county. In addition, the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) grants strengthened core interventions. Intensive effort was made to seek and treat malaria to reduce under-reporting. In 2008, a cross-sectional survey screened 3900 residents by microscopy from 15 originally hyperendemic villages, in which no parasite carrier was detected. By 2008, only 16 malaria cases were reported, and the AMI was lowered to 0.18 per 1000 person-years (Table 1; Fig. 2).

China re-oriented its malaria programme from control to elimination in July 2010. In order to look for infections and to interrupt transmission, the focus was shifted from high levels of coverage of interventions to an emphasis on completeness and timeliness of activities. Methodology of reactive case detection (RACD) was used in eliminating malaria. The ‘1-3-7’ approach was introduced for guiding and monitoring case reports, investigation and response, respectively: reporting of malaria cases within 1 day (24 h), their confirmation and investigation within 3 days, and the appropriate public health response to prevent further transmission within 7 days. Since 2012 no indigenous malaria infections have been detected in Hekou. Only one imported malaria case was found in 2012 and 2013 respectively, and no any malaria case in 2014 and 2015. Yunnan Provincial Health and Family Planning Commission (HFPC) received an application for evaluating malaria elimination from Honghe Prefecture HFPC in September, 2015. A team comprising experts of health system and information management, surveillance, monitoring and evaluation, laboratory diagnosis quality assurance, epidemiology and entomology, conducted an evaluation of malaria elimination based on “China National Guidelines for Malaria Elimination Evaluation and Certification”. Yunnan Province certified the county malaria-free in 4 November, 2015 (Table 1; Fig. 3).

Results of linear regression analysis indicated that AMI was negatively associated with national GDP (NGDP), national urbanization rate (NUR) and BPA. Correlation coefficients (R) were −0.6845 (95% CI −0.7978, −0.6845) for NGDP, −0.7014 (−0.8093, −0.7014) for NUR and −0.5563 (−0.7147, −0.3437) for BPA (Table 2). Analogous results were obtained for Yunnan Provincial GDP (YNGDP) and Yunnan Provincial urbanization rate (YNUR) (Table 2). Years 2000–2015 was a period of rapid socio-economic development and environmental change in China, and the data malaria cases was less biased than prior to 2000–2015. The relationship between AMI and these independent variables was more closely associated in this period (Fig. 4). When a bilinear regression analysis was conducted, R was −0.9103 (−0.9716, −0.7345) for NGDP and BPA, and −0.9055 (−0.9700, −0.7216) for NUR and BPA (Table 2). All these results show that the AMI had a negatively strong correlation with socio-economic development and environmental change.