Echinococcosis: Past and Present Situation in Southeast Asia

In Asia, Southeast Asia is reported as a non-endemic area of the parasite. However, several indigenous echinococcoses in human and animals were reported in several countries, such as Malaysia, Thailand, the Philippines, Indonesia, Vietnam, Cambodia, and Lao People ’ s Democratic Republic (PDR). Most human infections are caused by Echinococcus granulosus and only two cases with E. ortleppi. There was no evidence case with E. multilocularis in Southeast Asia. Echinococcus granulosus infection is prevalent in areas that association with dogs and livestocks that close contact with dogs. The incidence is very low. A total of 49 cases of echinococcosis was identified in Southeast Asia from 1885 to 2015. Of which, at least 31 cases were indigenous, 14 cases were imported, and 4 cases were unknown. Thailand is the most prevalent country with echinococcosis in human, followed by very low incidence in Indonesia, Malaysia, Vietnam, the Philippines, Cambodia and Lao PDR. However, it is very difficult to estimate the real number of human echinococcosis case in Southeast Asia due to the long asymptomatic period that is usually > 5 years. The disease may be more prevalent in Southeast Asia; however, they were underdiagnosed and not reported.


Introduction
Echinococcosis (hydatidosis) is one of the neglected zoonosis caused by adult or larval stage of the cestodes belonging to the genus Echinococcus of the family Taeniidae [1][2][3]. At [4][5][6]. Human alveolar echinococcosis has limited distribution in the northern hemisphere, while cystic echinococcosis is more widely distributed and cosmopolitan, particularly in countries of the temperate zones.
Southeast Asia is reported as non-endemic area of the parasite. However, several indigenous echinococcoses in human and animals were reported in several countries, such as Malaysia, Thailand, the Philippines, Indonesia, Vietnam, Cambodia, and Lao People's Democratic Republic (PDR). Although the surveillance of echinococcosis was not routinely conducted in several countries and the cases were scarcely reported in Southeast Asia. In the recent years, by clinical, radiological, microscopic, and serological aspects, the disease was found in many areas in this region. This situation makes us alert on the possibility of echinococcosis as one of the potential health problems in the Southeast Asia.

Indonesia
Human echinococcosis in Indonesia was first reported in nonindigenous people, in a European with liver hydatidosis in 1885 [7]. Subsequent cases were also confirmed in four European and an Indian in the 1920s [8]. In the late 1930s, a 45-yearold European female was also suspected with Echinococcus infection after stayed for almost 17 years which much contact with dogs in Indonesia [9].
The first indigenous case was diagnosed in a female aged 23 years from the northern part of South Sulawesi in 1988. She was admitted to the hospital with pain in the right under quadrant of the abdomens and in the right part of the hypochondrium, below the right rib. Hepatomegaly or tumor in the right upper quadrant of the abdomen was not found by physical examination. However, a hypoechoic, oval image, with a clear acoustic image on the right, was identified by using ultrasonography. Serological test was not performed, and the diagnosis was confirmed by radiological image examination. The patient has a history of keeping a dog [10].
Another echinococcosis case was reported in a 90-year-old female from Java in 1988. She was hospitalized in Ujung Pandang (Makassar), South Sulawesi with complaint of severe weakness, fainting, and no appetite. A tumor with no malignant cells was identified in the lower right part of the abdomen. Cysts with hypoechoic image on the walls were detected in the pelvis, right upper liver, and upper left abdomen. Fluid aspiration and serological test were not carried out during patient treatment at the hospital. The hydatidosis was confirmed in the right diaphragm arc/liver, omentum, and adnexa by radio-image. She had not kept dog at home [11].
In 1997, subsequent indigenous case, a 26-year-old female from Palu, Central Sulawesi, was administered in the Cipto Mangunkusumo Hospital in Jakarta with chronic and progressive headache, space-occupying lesion, blurred vision since the last 6 months, and vomiting. Bilateral edema of the papilla of the eyes was found without other neurological deficits. Cysts were found in many parts of organs. A hypodense, cystic lesion in the left parietal region of the brain divided by several septa with calcifications was discovered by radio-image with tomography (CT) scan. Historically, he lived in an area that kept many dogs, including her house.
In animals, echinococcosis is reported from goat, sheep, pig, water buffalo, and monkey from Sumatra, Madura, Bali, and Sulawesi. A case with liver, lung, and spleen hydatidosis was first identified in a cattle in Buitenzorg (Bogor, West Java) during meat inspection on 1906. Hydatid cysts were subsequently found from the lungs and liver of cattle in North Sumatra in 1907 [12]. At that time, the hydatid cysts were only detected from imported Australian cattles (nonindigenous echinococcosis was also reported among 46 cattles and 3 pigs in Medan, North Sumatra, in 1916) [13]. In 1929, hydatid cysts in indigenous cattle were found for the first time from Bali. This finding was considered that dogs from Bali were probably reservoirs for the adult worm Echinococcus granulosus. However, the lack of study has caused this to never to be proven [14]. Further cases of echinococcosis in animals were reported back in 1940. A single cyst of Echinococcus was found in the lung of the goat (Capra hircus) and the lung of the buffalo (Buffelus sondaicus) in the Netherlands Indies [15]. In 1947, a total of 45 cysts of Echinococcus unilocularis (E. granulosus) were found in the lungs, kidney, stomach wall, and liver on an old monkey Cynopithecus niger (later on as Macaca tonkeana) from Sulawesi (Celebes) that suddenly died. The first evidence of E. granulosus infection in domestic dogs in Indonesia was reported from the Lindu Valley, Central Sulawesi, in 1972. The dog died suddenly after 18 months with numerous necropsies due to E. granulosus. Subsequent dog with echinococcosis was reported on the shore of Lake Lindu at Tomado village in 1973. The positive eggs of E. granulosus were confirmed by direct smear and formaldehyde-ether from the dog stools. The adult worms of E. granulosus were also identified during the study. The worms were collected from a dead dog on the shore of Lake Lindu at Tomado [16]. Since then, hundreds of dogs have been examined to identify the infection rate of E. granulosus in this area. However, hydatid cysts and adult E. granulosus have not been discovered until now [13].
The disease infection was reported for the first time in this country in 1936 from a 52-year-old male with peritoneum infection in Chiang Mai. The patient finally died due to severe infection without surgical removal and antiparasitic drug [25]. Subsequently, human case of echinococcosis was found in a 16-year-old male with E. granulosus cysts infection in lung in 1952. He is an Indian citizen who previously lived in India. He was diagnosed with echinococcosis while in Bangkok [20]. Another patient, a Thai female, aged 56 years, with lung infection was confirmed to be echinococcosis in 1980 [26]. Infection of E. granulosus cysts in the lung is a common manifestation in Thailand. Five other cases of lung echinococcosis, two females and three males with an age range of 32-71 years old, were also confirmed in between 1980 and 1995 [17, 18, 20-22, 27, 28]. Surgical removals were performed in all patients, and two of them received antiparasitic drug treatment with albendazole. Two cases with renal echinococcosis were subsequently reported in a 39-year-old woman in 1993 and 43-year-old man in 1997. The first patient has recovered after marsupialization; however the second patient died several years after infection and treatment in 2000 [18,29].
The most frequent echinococcosis case in this country is liver infection. At least 12 cases were reported in the period 1960-2007 [18,19,23,27,30,31]. Two cases, 50-year-old male and 50-year-old female, were reported as Thai citizens who had a history of visiting the Middle East in 1994 and 1996, respectively [17,18], while the other two were identified from non-Thai citizens who previously lived in Middle East countries. Middle East countries are known as an endemic area of echinococcosis.
Liver echinococcosis was also reported in a Thai citizen who had a history of traveling to Switzerland in 2004. One subsequent case was recognized as a Nepali citizen who was visiting Thailand in 1995, while three cases were recorded as unknown origin in 1994 and 2004 [30]. In 2007, two cases were reported with echinococcal cystic mass in the liver that was diagnosed through serological testing using an indirect enzyme-linked immunosorbent assay (ELISA) [19]. Physical examination revealed that hepatomegaly or tumor in the right upper quadrant of the abdomen was detected in almost all of liver echinococcosis cases [19,23,27].
The hydatid cysts were also found in the jaw and foot. One case with foot echinococcosis was reported in a Thai 45-year-old female from Nakhon Pathom province in 1989, while jaw echinococcosis was identified in a male, aged 32 years old from Lamphun province [18].
During these periods , animal infection with echinococcosis was never recorded in Thailand. However, hydatid cysts were reported in slaughtered pigs, cattles, and buffalos in Bangkok and Chiang Mai in the past.

Vietnam
Echinococcosis was found in several countries in the Southeast Asian region; however, before 2013, this disease had never been reported to be infected in both animals and humans in Vietnam. The first case of echinococcosis was recorded in a man, aged 42 years, who resides in Thach Thanh district, Thanh Hoa province. This case is also the first indigenous case because he is a farmer who has never traveled abroad. Positive diagnostics are performed by serological tests using ELISA. Patients recovered after treatment with surgery combined with albendazole 800 mg/day for 30 days [5].
The second indigenous case was reported in a woman, aged 48 years, who lived in Phu Yen district, Son La province. She is a medical technician who has never traveled abroad. Positive diagnosis is confirmed by the ELISA test. The observations showed a large number of Echinococcus larvae in both lungs, so that no surgery was performed. She then underwent treatment with albendazole 800 mg/day for 30 days. After 12 months, the patient no longer coughed, and only two small cysts remained in her lungs [5]. Based on morphological and molecular methods, Echinococcus ortleppi was identified as the source of infection in both of cases. This is the first case of E. ortleppi species reported as a cause of echinococcosis in Vietnam and the Southeast Asian region [5,19].
Previous studies revealed that risk factors for transmission of E. ortleppi are more associated with dog and cattle than human. This species was originally described as E. granulosus in dogs from South Africa; however, because it develops mostly in cattle as intermediate hosts, E. ortleppi is more commonly known as cattle strain (Genotype 5) of E. granulosus [32][33][34][35]. Currently, it has also been reported to infect others domestic and wild animals, such as buffaloes, sheep, pigs, goats, camels, monkeys, and porcupine [36][37][38][39][40]. In humans, this species has also been reported to have low pathogenicity and be restricted to infect in certain areas. Infection occurs accidentally through ingestion of parasite eggs [6,41]. Although E. ortleppi infection was reported in two indigenous cases from Vietnam, there is no evidence that E. ortleppi is a autochthonous disease in northern Vietnam. There are no reports of domestic cattles and dogs infected with this tapeworm species in Vietnam. Most likely, the parasite was introduced from another place through cattle that imported into the country [42].

Malaysia
Echinococcosis is very rare in Malaysia. So far, only five cases were reported during more than last five decades. The first human case of pulmonary echinococcosis was reported in a Malay child in 1968. However, there is no detailed information reported during that time. In 1989, a first hepatic hydatidosis was reported in a 59-year-old Indian female. She had complained of fever and right hypochondrial pain for 3 days before inpatient. There was no jaundice. The enlarged liver with span of 17 cm, soft were identified. Ultrasonography examination revealed an encapsulated multiloculated anechoic lesions occurring on the most right of the hepatic lobe. Hydatid cysts and a large cystic lesion were also identified. The patient recovered at 1 year after getting surgical treatment combined with mebendazole 40 mg/kg/day for 30 days postoperatively [32].
The third case was recorded from a 4-year-old girl who was undergoing treatment in a pediatric hospital emergency unit after experiencing repeated cough with high-grade fever, accompanied by severe shortness of breath in 2013. Laboratory investigation was performed with a chest X-ray (CXR) and ultrasound examination. A hypoechoic shadow of a giant cystic lesion and hydatid cyst were detected replacing the whole right lobe of the liver. Surgery was performed, and albendazole was given for 6 months postoperatively. After 1.5 year, the patient demonstrated improved conditions with no recurrence evidence [33].
In 2015, a case of hydatid cyst of the liver was reported in a 55-year-old Chinese-Australian lady. She has migrated from Malaysia to Australia many years ago and works as a nurse assistant. Australia is considered endemic for the disease. There was no history of contact with cattle or dog. This patient presented a long history of abdominal pain, but with no fever or jaundice. She may have experience acute cholangitis, while the hydatid cyst ruptured in the biliary system. The liver cyst showed a calcified wall with only necrotic debris. Laboratory investigation with a chest X-ray, ultrasound examination, and histological analysis strongly suggests patient had chronic hydatid cyst of the liver [34].
The latest record of hydatid hepato-pulmonary fistula caused by E. granulosus case was reported in a 58-year-old Malaysian housewife with no history of recent travel outside the country. In the past 3 years, the patient had complained of pain from the right side of the chest and abdominal pain. For the past month before inpatient, she complained severe repetitive attacks of productive cough with yellowish to dark color of sputum and vomiting that was associated with night sweating and fever. Hydatid cysts were identified on top of the right lobe of the liver by using chest X-ray and computerized tomography (CT) of the chest and abdomen. Hydatid patients recovered after getting surgical treatment [35].

Philippines
Since 1925, only two local cases of human echinococcosis in the lungs have been reported in the Philippines [43,44]. No detailed information was reported regarding Echinococcus infection in human. In animal, Echinococcus cyst was recorded for the first time in a cattle from Los Banos, Laguna, in the 1940s. Echinococcosis in the lungs of a water buffalo and dog were also reported in this country in 1947 [45].

Singapore, Cambodia, Lao People's Democratic Republic, Myanmar, and Timor-Leste
In Singapore, Singh et al. reported two imported cases of the disease in 1991 [46]. Echinococcosis has also been observed in humans, cattle, sheep, and pigs in Laos and Cambodia. However, the disease is considered to be very rare in these countries. No information about hydatid disease in Myanmar and Timor-Leste [19,47].

Discussion
A total of 49 cases of echinococcosis was identified in Southeast Asia from 1885 to 2015. Of which, at least 31 case were indigenous, 14 cases were imported, and 4 cases were unknown. The common clinical manifestations found in patients with echinococcosis are swelling or pressure effects from enlarging cysts and pain due to cyst mass [48][49][50][51]. However, it is very difficult to estimate the real number of human echinococcosis case in Southeast Asia due to the long asymptomatic period that is usually >5 years [3]. Previous studies in China revealed that echinococcosis manifestations usually appear 2-15 years after infection with nonspecific symptoms [52]. With these possible reasons, the disease may be more prevalent in Southeast Asia; however, they were underdiagnosed.
Most human infections are caused by E. granulosus and only two cases with E. ortleppi. There was no evidence case with E. multilocularis in Southeast Asia. Echinococcus granulosus infection is prevalent in areas that association with dogs and livestocks that close contact with dogs [17]. The dog is the definitive host for E. granulosus and the main source of human CE worldwide [53]. Livestock, especially sheep and goats, is the most important domestic intermediate host for E. granulosus. These worm cysts may also infect other herbivore hosts, e.g., donkeys, buffaloes, pigs, camels, cattle, etc., and are involved in E. granulosus transmission [54][55][56].
Hydatid cysts infection is the most common echinococcosis in this region [3, 5, 17-24, 30, 32, 34, 47, 57-60], while only two cases of alveolar echinococcosis were reported in Thailand [25,31]. Of all the recorded cases, liver cyst is a leading cause of echinococcosis in Southeast Asia, followed by cyst infection in the lung, peritoneal, kidney, jaw, and foot. Surgical removal and antiparasitic drug therapy have been shown to be beneficial and effective in the management of echinococcosis.
Besides Thailand, the very low incidence was reported in almost all countries in Southeast Asia. The possible reason for the existence of echinococcosis cases might be different in each country. In Indonesia and Malaysia, where the majority of the population is Muslim, this low case might be caused by Muslims not being encouraged to keep dogs. In addition, under-diagnostic and non-reported cases due to the absence of a routine surveillance system for echinococcosis may also contribute to the low incidence in both countries. In Singapore, the low number of cases is likely due to good urban planning with high-quality health standards, so there is very little potential for food-borne parasitic infections in the country [46]. In several other Southeast Asian countries that are epidemiologically similar to Thailand, namely, Cambodia, Myanmar, and Laos, very few reports of echinococcosis cases may be caused by being underdiagnosed and not reported [17]. The same thing is likely to occur in other Southeast Asian countries, such as the Philippines, Vietnam, and Timor-Leste. Although echinococcosis has not been a serious problem for public health in the region, awareness of the disease is needed. The hydatid cyst diagnosis should be inserted in part of the differential diagnosis of all cystic lesion to find out the magnitude of this disease in Southeast Asia [17,30]. In addition, serological surveys are necessary in each Southeast Asian country to identify the distribution of the disease. Disease surveillance in domestic dogs and livestock is also needed as a prerequisite to understand epidemiological status of echinococcosis in the region.

Conclusions
According to this review, the incidence of echinococcosis in Southeast Asia is very low. Thailand is the most prevalent country with echinococcosis in human, followed by very low incidence in Indonesia, Malaysia, Vietnam, the Philippines, Cambodia, and Lao PDR, and so far there is no report of the disease in Myanmar and Timor-Leste. The disease may be more prevalent; however, there were underdiagnosed and not reported. Disease surveillance in human, domestic dogs, and livestock are necessary in Southeast Asian countries to identify the distribution of the disease. In addition, awareness and strengthening diagnosis for the disease are also needed in part of Echinococcus surveillance to identify the real incidence and magnitude in this region (Figure 1).