Burden, cost of disease and optimization of clinical practice of human cystic echinococcosis in Mongolia

Our goal was to facilitate prevention and control of cystic echinococcosis (CE) in Mongolia by measuring the disease burden and societal cost, investigating the zoonotic linkages, and identifying the key challenges in clinical management of CE with proposed improvement. The disease is caused by the larval stage of Echinococcus granulosus sensu lato, and transmitted between dogs and various species of ungulates and also transmitted to humans. In humans, large cystic lesions can occur, mainly in the liver and lungs. Mongolia is one of the areas most affected by CE. The numbers of dogs and livestock are high, and a nomadic herding lifestyle is commonly practiced in most parts of the country. However, existing health services in Mongolia for CE barely reach the targeted populations, and CE cases are only detected at a late stage. For adequate diagnosis and treatment, herders must often travel hundreds of kilometers. Surgical procedures and hospitalization, travel costs, and lifelong disability following complicated surgeries are common for most patients. There is very limited information on infection in livestock populations due to the lack of public slaughterhouses and animal surveillance tools in the country. We collected data on human CE cases from hospital records, statistical departments, and ultrasound examination records. Estimates of the reported incidence were used to calculate disability-adjusted life years (DALYs). To estimate the economic cost, we interviewed 65 patients who had CE surgery. The societal cost, including direct medical, direct non-medical and indirect costs, was estimated. We investigated the zoonotic linkages using the data of surgical CE cases and the livestock population of four species, including sheep, goats, cattle, and camels. To support the statistical analysis, samples were collected from CE infected animals in an endemic province. The subspecies identification, genetic diversity and haplotype network analysis were conducted. To understand the current clinical management of CE, we organized Focus Group Discussions (FGD), surveyed health professionals using a questionnaire. The ultrasound cyst images were reviewed by international experts to critically contrast current national practice with WHO-Informal Working Group on Echinococcosis (WHO-IWGE) guideline. Key challenges and further potential improvements were discussed during a workshop with Mongolian and international experts to reach consensus for standardization of clinical practice. The incidence of surgical cases, diagnosed cases, and total cases including undiagnosed cases was estimated to be 2.2 per 100 000, 15 per 100 000 and 60 per 100 000 person-years, respectively. The DALY was estimated to be 11461 for total cases including undiagnosed cases and 3017 for diagnosed cases. The total societal cost due to human CE is USD 2.7million which equals 0.024% of total gross domestic product (GDP). The cost decreases to USD 0.3million when the productivity loss of undiagnosed and diagnosed cases is excluded. The impact on the household economies is high for surgical cases where 76% of the direct cost is paid by the patients. In total out-of-pocket expense, the cost of albendazole contributed most. US images of 84 patients were staged and assessed for interrater-agreement. The average raw agreement was 77.2%. Unweighted Kappa coefficient and weighted Kappa was 0.57 and 0.59, respectively. Mean proportion of images judged as stages CE1, CE2, CE3a, CE3b, CE4 and CL were 0.59, 0.01, 0.19, 0.08, 0.03 and 0.11 respectively. 40 cysts met the inclusion criteria of treatment modality analysis. The mean proportion of cases with a single cyst assigned to medical, percutaneous treatment, surgery and watch & wait were 52.5% (95% CI 42-65), 25.8% (95% CI 15-30), 5.1% (95% CI 0-10) and 3.3% (95% CI 0.0-10), respectively. 13.3% (95% CI 5–25) of cysts were staged as CL and therefore assigned to further diagnostic requirement. The incidence of surgical CE cases increased by a factor of 1.71 for one interquartile range increment in the density of the camel population. No significant association was observed with other livestock species. The samples collected from 96 camels and 15 goats in an endemic region showed a CE prevalence of 19.7% and 6.7%, respectively. All livestock CE were caused by E.granulosus s.l. G6/7 (formerly identified as E.granulosus canadensis G6/7) of the of the E. granulosus s.l. complex. Four haplotypes were identified within the livestock samples, two of which had not been previously reported. A common haplotype was identified between humans, camels, goats, and a wolf, all of which were within the same geographical area. A mixed infection of E. granulosus s.l. G6/G7 with different haplotypes in the intermediate host was identified first time. This is the first estimate of the burden and societal cost of human CE in Mongolia. Mongolia has a substantial proportion of the population suffering from cystic echinococcosis. The disease causes a significant amount of loss to society and household economy. Access to fully equipped treatment centers is limited by geographic distance and economic resources. Availability of albendazole is sparse,and the price is high. WHO-IWGE guidelines are not implemented for allocating patients within the four treatment options based on CE cyst staging, with the result that all CE patients are referred for surgical treatment. This creates an unnecessary high-risk approach for patients who could either be treated with albendazole or percutaneously or observed. Our study revealed evidence that camels play an important role contributing to human CE in Mongolia, which is a critical information for further control and prevention of CE

Patients with cystic echinococcosis in the three national referral centers of Mongolia: A model for CE management assessment.

BACKGROUND:Mongolia is one of the endemic countries for cystic echinococcosis (CE), a zoonotic disease caused by the larval stage of Echinococcus granulosus. The goal of this study is to describe the current clinical management of CE in Mongolia, to capture the distribution of cyst stages of patients treated, and to contrast current practice with WHO-IWGE expert consensus. METHODS:Hospital records of CE patients treated between 2008 and 2015 at the three state hospitals and fulfilling the inclusion criterion 'discharge diagnosis CE' (ICD 10 code B.67.0-67.9) were reviewed. Demographical, geographical, clinical and ultrasonography (US) data were extracted and analyzed. The annual surgical incidence was estimated. The digital copies of US cyst images were independently staged by three international experts following the WHO CE cyst classification to determine the proportions of patients which ideally would have been assigned to the WHO recommended treatment modalities surgery, percutaneous, medical (benzimidazole) treatment and watch & wait. RESULTS:A total of 290 patient records fulfilled the inclusion criteria of the study. 45.7% of patients were below 15 years of age. 73.7% of CE cysts were located in abdominal organs, predominantly liver. US images of 84 patients were staged and assessed for interrater-agreement. The average raw agreement was 77.2%. Unweighted Kappa coefficient and weighted Kappa was 0.57 and 0.59, respectively. Mean proportions of images judged as stages CE1, CE2, CE3a, CE3b, CE4 and CL were 0.59, 0.01, 0.19, 0.08, 0.03 and 0.11, respectively. 40 cysts met the inclusion criteria of treatment modality analysis. The mean proportions of cases with a single cyst assigned to medical, percutaneous treatment, surgery and watch & wait were 52.5% (95% CI 42-65), 25.8% (95% CI 15-30), 5.1% (95% CI 0-10) and 3.3% (95% CI 0-10), respectively. 13.3% (95% CI 5-25) of cysts were staged as CL and therefore assigned to further diagnostic requirement. CONCLUSION:WHO CE cyst classification and WHO-IWGE expert consensus on clinical CE management is not implemented in Mongolia. This results in exclusively surgical treatment, an unnecessary high risk approach for the majority of patients who could receive medical, percutaneous treatment or observation (watch & wait). Introduction of WHO-IWGE expert consensus and training in ultrasound CE cyst staging would be highly beneficial for patients and the health care services

Evidence for camels (Camelus bactrianus) as the main intermediate host of Echinococcus granulosus sensu lato G6/G7 in Mongolia

Cystic echinococcosis (CE), the parasitic disease caused by the larval stage of Echinococcus granulosus sensu lato (s.l.), is a global public health problem. In Mongolia, despite wide distribution of human CE, not enough information is available on the prevalence and molecular characterization of CE in livestock and its zoonotic linkage with human cases. We investigated the distribution of human CE cases and livestock population using statistical models to get insight into the zoonotic linkage. The incidence of human CE cases increased by a factor of 1.71 for one interquartile range increment in the density of the camel population. No significant association was observed with other livestock species. The samples collected from 96 camels and 15 goats in an endemic region showed a CE prevalence of 19.7% and 6.7%, respectively. All livestock CE were E. granulosus s.l. G6/G7 species of the E. granulosus s.l. complex. The genetic diversity was investigated using the haplotype network based on full cox1 gene analysis of the samples collected from livestock CE and nucleotide sequences previously reported from human CE and wild canids infection in Mongolia. Four haplotypes were identified within the livestock samples, two of which had not been previously reported. A common haplotype was identified among humans, camels, goats, and a wolf, all of which were within the same geographical area. A mixed infection of E. granulosus s.l. G6/G7 with different haplotypes in the intermediate host was identified. To the best of our knowledge, this is the most comprehensive description of the current epidemiological situation of CE in Mongolia with substantial evidence that camels might be the main intermediate host of E. granulosus s.l. G6/G7 in Mongolia. Moreover, our result presents the first report in the country to provide insight into the prevalence of E. granulosus s.l. G6/G7 in livestock

Assignment of CE cysts of the study population to WHO-IWGE recommended treatment modalities on the basis of retrospective cyst staging by three international experts.

<p>In uncomplicated CE cysts WHO-IWGE recommended assignment of patients to the four treatment modalities surgery, percutaneous methods, drug treatment (albendazole, mebendazole) and watch & wait is based on cysts stage and size (three groups). <b>A</b> Three size groups and the average percentages of WHO cysts stages in the study population as retrospectively staged by three international reviewers. Although there was a small percentage (1%) of CE2 identified by the three reviewers (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006686#pntd.0006686.g003" target="_blank">Fig 3</a>) this stage could not be included into the analysis because the information on cyst size was lacking. CE5 was excluded since none of the reviewers attributed one of the cysts presented for retrospective staging to CE5. <b>B</b> Based on the matrix in A, the probability of assignment of patients to the WHO-IWGE recommended treatment modalities is presented. The grey shading of the cells in A and B matrices correspond to each other. Cysts staged as CL would have needed further diagnostic work up.</p

Average CE surgical incidence in each province for the period 2008–2015.

<p>Abbreviations: BO-Bayan-Olgii, UV-Uvs, HD-Khovd, ZA-Zavkhan, GA-Gobi-Altai, BH-Bayankhongor, OH-Ovorkhangai, AH- Arkhangai, HG-Khubsgul, BU-Bulgan, DA-Darkhan, SE-Selenge, ER- Orkhon, UB-Ulaanbaatar, DU-Dundgobi, OG-Omnogobi, TO- Tov, DG-Dornogobi, HN-Khentii, DD-Dornod, GS-Gobisumber., SB-Sukhbaatar.</p

Selection of CE surgical case records.

<p>(a) 290 records (patients) in the 3 state hospitals in Mongolia fulfilled the inclusion criterion ‘discharge diagnosis CE’ (ICD 10 code B.67.0–67.9); (b) 12 records (patients) were excluded because the patients have not been operated on (4 surgeries postponed, 3 post-surgical conditions, 4 calcified cysts not needing surgery, 1 no information), 11 because of missing surgical information, 20 records belonged to 15 patients who were re-admitted once or twice; (c) 247 cases were analyzed.</p

Demography, socio-economic status (SES) and geographical data of the patients.

<p>Demography, socio-economic status (SES) and geographical data of the patients.</p

A path to cooperation between China and Mongolia towards the control of echinococcosis under the Belt and Road Initiative

Health is the core of development. Health cooperation between countries plays a pivotal role under the Belt and Road Initiative (B&amp;R). In 2013, China launched its B&amp;R to improve the international cooperation of which health was an important component. As one of the neglected zoonotic diseases, echinococcosis has become a public health concern and is on top of the government agenda among neglected zoonosis in Mongolia. The transmission of the disease involves animal husbandry, and its characteristics determine the prevention and control of such diseases which requires cross-sector collaboration and comprehensive prevention and control strategies. Taking echinococcosis as an entry point and adopting a 'Mongolia-led, China-supported, and results-sharing' approach to public health cooperation will not only contribute to the advancement of Mongolia's national health coverage, but also promoting China's capacity to engage in global health. In this way, it contributes to meeting the sustainable development goals, especially goal 3, target 3.3: by 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases. This paper provides an overview on how the cooperation between China and Mongolia under the context of B&amp;R was initiated, planned and moved forward to implementation. The experience may provide a good model and inform policy and practice for other bilateral cooperations