Toni Wandra

Factors associated with case fatality of human H5N1 virus infections in Indonesia: a case series.

BACKGROUND Indonesia has had the most human cases of highly pathogenic avian influenza A (H5N1) and one of the highest case-fatality rates worldwide. We described the factors associated with H5N1 case-fatality in Indonesia. METHODS Between June, 2005, and February, 2008, there were 127 confirmed H5N1 infections. Investigation teams were deployed to investigate and manage each confirmed case; they obtained epidemiological and clinical data from case-investigation reports when possible and through interviews with patients, family members, and key individuals. FINDINGS Of the 127 patients with confirmed H5N1 infections, 103 (81%) died. Median time to hospitalisation was 6 days (range 1-16). Of the 122 hospitalised patients for whom data were available, 121 (99%) had fever, 107 (88%) cough, and 103 (84%) dyspnoea on reaching hospital. However, for the first 2 days after onset, most had non-specific symptoms; only 31 had both fever and cough, and nine had fever and dyspnoea. Median time from onset to oseltamivir treatment was 7 days (range 0-21 days); treatment started within 2 days for one patient who survived, four (36.4%) of 11 receiving treatment within 2-4 days survived, six (37.5%) of 16 receiving treatment within 5-6 days survived, and ten (18.5%) of 44 receiving treatment at 7 days or later survived (p=0.03). Initiation of treatment within 2 days was associated with significantly lower mortality than was initiation at 5-6 days or later than 7 days (p<0.0001). Mortality was lower in clustered than unclustered cases (odds ratio 33.3, 95% CI 3.13-273). Treatment started at a median of 5 days (range 0-13 days) from onset in secondary cases in clusters compared with 8 days (range 4-16) for primary cases (p=0.04). INTERPRETATION Development of better diagnostic methods and improved case management might improve identification of patients with H5N1 influenza, which could decrease mortality by allowing for earlier treatment with oseltamivir.

Human taeniasis and cysticercosis in Asia

CONTEXT Human Taeniasis caused by the pork, Taenia solium, or beef, T saginata, tapeworm arises after eating pork or beef contaminated with metacestodes, the larval stage of these parasites. Taeniasis with T solium can lead to neurocysticercosis and threaten others by accidental ingestion of eggs released from asymptomatic Taeniasis patients. The 2003 World Health Assembly declared that T solium is of worldwide public-health importance, and that it is an eradicable parasitic disease worldwide. Adult taeniid tapeworms expelled from people in almost all Asian countries appeared to be T saginata (the so-called Asian Taenia), even though they ate pork. The organism is now named T asiatica, and has been found in Taiwan, Korea, China, Vietnam, and Indonesia. But it has been difficult to differentiate T saginata from beef and Asian Taenia from pork. STARTING POINT Marshall Lightowlers and colleagues (Int J Parasitol 2003; 33: 1207-17) recently demonstrated that recombinant oncosphere vaccines against several taeniid cestodes, including T ovis, T saginata, T solium, and Echinococcus granulosus, are highly effective. Protection was almost 100%, in the laboratory and in the field. These researchers found several common features, including a predicted secretory signal sequence, and one or two copies of a fibronectin type III domain, each encoded by separate exons within the associated gene. WHERE NEXT? Molecular and immunological techniques, including vaccine research and development of animal models for differentiation of taeniid species in humans, have greatly advanced over the past decade. The clinical importance of infections by these taeniids, including T asiatica, in humans, and the potential for cysticercosis attributable to T asiatica in humans, needs further study.

Resurgence of cases of epileptic seizures and burns associated with cysticercosis in Assologaima, Jayawijaya, Irian Jaya, Indonesia, 1991-95.

Historically, neurocysticercosis (NCC) caused by the larval stage, cysticercus or cysticerci, of the pork tapeworm Taenia solium was recognized in Paniai District, western Irian Jaya Province, Indonesia, in the early 1970s. In the 1990s, we observed a rapid increase in the number of cases of epileptic seizures and burns in Assologaima Sub-District, Jayawijaya District, eastern Irian Jaya. There were totals of 1120 new cases of burns and 293 new cases of epileptic seizures during 1991-95 in Assologaima where the number of inhabitants was 15,939. Histopathological examination of resected cysts from patients and a pig revealed that they were cysticerci of T. solium. DNA analysis of these cysts revealed that the nucleotide sequences of 391 base-pair fragments of the mitochondrial cytochrome c oxidase subunit 1 gene were exactly the same in those from patients and the pig. Although 3 of 391 base-pair fragments might differ from that of T. solium reported previously, there were no differences in the amino-acid sequences. Approximately 67% and 65% of persons with epileptic seizures and with subcutaneous nodules, respectively, showed antibody responses highly specific to cysticercosis. Therefore, most cases of epileptic seizures and burns were considered to be associated with cysticercosis in Irian Jaya.

Evaluation of a loop-mediated isothermal amplification method using fecal specimens for differential detection of Taenia species from humans.

ABSTRACT We compared the performance of loop-mediated isothermal amplification (LAMP) with that of a multiplex PCR method for differential detection of human Taenia parasites in fecal specimens from taeniasis patients. The LAMP method, with no false positives, showed a higher sensitivity (88.4%) than the multiplex PCR (37.2%). Thus, it is expected that the LAMP method has a high value for molecular diagnosis of taeniasis.

Avian influenza A H5N1 infections in Bali Province, Indonesia: a behavioral, virological and seroepidemiological study.

Background  Bali Province was affected by avian influenza H5N1 outbreaks in birds in October 2003. Despite ongoing circulation of the virus, no human infection had been identified by December 2005.

Cysticercosis/taeniasis in Asia and the Pacific

Three taeniid tapeworms infect humans in Asia and the Pacific: Taenia solim, Taenia saginata, and Taenia asiatica. Although there is continuing debate about the definition of a new species, phylogenetic analyses of these parasites have provided multiple lines of evidence that T. asiatica is an independent species and the sister species of T. saginata. Here we review briefly the morphology, pathology, molecular biology, distribution and control options of taeniasis/cysticercosis in Asia and the Pacific and comment on the potential role which dogs may play in the transmission of T. solium. Special attention is focused on Indonesia: taeniasis caused by T. asiatica in North Sumatra, taeniasis/cysticercosis of T. solium and taeniasis of T. saginata in Bali, and taeniasis/cysticercosis of T. solium in Papua (formerly Irian Jaya). Issues relating to the spread of taeniasis/cysticercosis caused by T. solium in Papua New Guinea are highlighted, since serological evidence suggests that cysticercosis occurs among the local residents. The use of modern techniques for detection of taeniasis in humans and cysticercosis in humans, pigs and dogs, with the possible adoption of new control measures will provide a better understanding of the epidemiology of taeniasis/cysticercosis in Asia and the Pacific and lead to improved control of zoonotic and simultaneously meat-borne disease transmission.

Taenia solium Cysticercosis, Irian Jaya, Indonesia

To the Editor: Cysticercosis, a tissue infection caused by accidental ingestion of eggs released from humans harboring the pork tapeworm, Taenia solium (TsCysti), is one of the most serious reemerging parasitic diseases worldwide (1). Taeniasis is an intestinal infection caused by the adult stage of the large tapeworm. Carriers of T. solium acquire infection through eating undercooked pork contaminated with cysticerci (larvae). Although most Indonesian people are Muslim and do not eat pork, infection with T. solium has occurred in some areas or islands where most local people are Christian or Hindi. The area most affected by this infection is Irian Jaya, Indonesia, the western half of New Guinea Island (2–4). In field surveys conducted in 2000 and 2001, we found that 5 (8.6%) of 58 local people and 7 (11%) of 64 local dogs living approximately 1 km from the local capital city, Wamena, in Jayawijaya District, harbored adult tapeworms and cysticerci of T. solium, respectively (5,6). We have further seroepidemiologic data from 1996 and molecular confirmation of subcutaneous nodules (SCN) as cysticerci of the T. solium Asian genotype. We believe this organism is an emergent problem in Irian Jaya. We previously reported that TsCysti was highly endemic in Jayawijaya District, Irian Jaya (2–6). A total of 96 local people >18 years of age from Assologaima, Jayawijaya District, were chosen at random and examined by serologic testing and by administering questionnaires in February 1996 after the local and Indonesian governments gave their ethical approval. The 96 persons were divided into three groups on the basis of a history of epileptic seizures (ES, n=17), physical examination of SCN by palpation (n=32), or good health (including no ES or SCN; n=47). A total of 14 subcutaneous nodules removed from 14 men in both ES and SCN groups were confirmed to be cysticerci of T. solium by morphologic observation and to be T. solium Asian genotype by mitochondrial DNA analysis with cytochrome c oxidase subunit 1 gene (3,7). For serologic analysis, we conducted an enzyme-linked immunosorbent assay (ELISA) that used glycoproteins purified from cyst fluid of T. solium cysticerci by preparative isoelectric focusing (fractions of pH 9.1) (8) in 2001. On the basis of serologic results, 12 (70.6%) of 17, 20 (62.5%) of 32, and 12 (25.5%) of 47 of ES, SCN, and healthy groups, respectively, were infected with the larval stage of T. solium. Serologically positive rates increased to 83.3% (10/12) of people with subcutaneous nodules in the ES group. A follow-up study of seropositive persons in the healthy group in 1997 showed that five of eight persons had ES (two persons), headache (one person), or SCNs in upper arm (two persons). Seropositive persons in all three groups (ES, SCN, and health) were considered to be infected with TsCysti. Persons of the SCN and healthy groups who showed optical density values higher than the cut-off value were considered to have asymptomatic TsCysti cases. The local persons we examined ranged from 18 to 29 years of age (n=30), 30–44 years of age (n=36), and >45 years of age (n=30). Seropositive persons (n=12) from the ES group (n=17) were 18 to 29 years of age (40.0%, 2/5), 30–44 years (71.4%, 5/7), and >45 years (100%, 5/5). The prevalence of TsCysti did not vary statistically by sex (males 53.6% [37/69] versus females 33.3% [9/27], Pearson’s chi-square test, p=0.074). That 14 persons confirmed to have subcutaneous cysticerci of T. solium were seropositive strongly suggests that the serologic test (ELISA) is highly reliable for detecting TsCysti in patients, whether their infection is symptomatic or asymptomatic. In contrast, one of the following scenarios was expected for cases in three of five persons in the ES group who did not have SCN and were seronegative: 1) the case was not due to TsCysti, 2) the case was caused by TsCysti but without antibody response, rather common in cases of a solitary cyst, or 3) the case was caused by TsCysti with calcified cysts and without antibody response. Twelve (approximately 40%) of seronegative persons from the SCN group (n=32) were expected to have cases of TsCysti without antibody response or to have calcified cysts without antibody response. Cases without antibody response would be most expected because of the heavily contaminated environment in Papua (3–6). However, further evaluation with computed tomography or magnetic resonance imaging scans is necessary. Based on serologic results and mitochondrial DNA confirmation of T. solium Asian genotype (3,7), we concluded that 47.9% (46/96) of local people examined at random, 53.6% of men (37/69) and 33.3% of women (9/27) >18 years of age had TsCysti. An additional 30 local people in non–TsCysti-endemic Merauke District underwent serologic testing. One woman had an exceptionally high antibody titer. She was a transmigrant from another island (South Sulawesi Province). Although Paniai, Jayawijaya, and Manokwari Districts are contaminated with T. solium taeniasis and cysticercosis (2–4), no additional critical evidence exists to show that Merauke District has already been contaminated with this parasite. Taeniasis and cysticercosis may have been accidentally introduced into Irian Jaya in 1969 when the country was governed by Indonesia, since the governing body came from Bali, the only area in Indonesia where TsCysti was exclusively endemic (2). The contaminated areas in Irian Jaya have increased from the central area (Paniai), to the east (Jayawijaya) (3), and then to the west (Manokwari), where 54 TsCysti cases have been reported (Papua Province Health Office Services, 1997, unpub. data). We wanted to know if taeniasis/cysticercosis had been introduced into the eastern half of New Guinea Island, called Papua New Guinea (PNG) (9). We had already serologically confirmed that 16 (3.0%) of 541 local residents and Irianese refugees in Alice River villages along the border in PNG had asymptomatic TsCysti (Ito et al., unpub. data). Follow-up surveys will be crucial in several other districts including Merauke District in Irian Jaya, PNG, and other islands such as Timor Island, where most of the population is Christian and many suspected cases have recently been reported by the District Health Office Services (10). Schoolchildren should also be checked so that cases can be detected and treated early. Sustainable education of the local community in Papua, Indonesia, and Papua New Guinea is also necessary.

Taenia solium taeniasis/cysticercosis in Papua, Indonesia in 2001 : detection of human worm carriers

A preliminary study to detect human worm carriers of Taenia solium in Papua (Irian Jaya), Indonesia was carried out using stool examinations for the detection of copro-antigens and adult proglottids after chemotherapy, and confirmation by mitochondrial DNA analysis using expelled proglottids and metacestodes developed in NOD/Shi-scid mice from eggs of expelled proglottids. Approximately 8.6% of the local population in Kama (5/58), 1 km from the local capital city centre, Wamena, were confirmed to harbour adult T. solium using these techniques.

An ocular cysticercosis in Bali, Indonesia caused by Taenia solium Asian genotype

An ocular cysticercosis case of a nine-year-old Balinese girl in Indonesia is reported. She presented with redness and pain in the left eye and showed a cysticercus in the anterior chamber in December 2010. Morphological feature of the cysticercus removed from the anterior chamber indicated that it was an immature cysticercus of Taenia species with no hooklets. However, mitochondrial DNA analysis using a piece of histopathological specimen revealed it a cysticercus of Taenia solium Asian genotype. Serology by immunoblot and ELISA highly specific to cysticercosis was negative.

The first workshop towards the control of cestode zoonoses in Asia and Africa.

The first workshop towards the control of cestode zoonoses in Asia and Africa was held in Asahikawa Medical University, Japan on 15 and 16 Feb 2011. This meeting was fully supported by the Asian Science and Technology Strategic Cooperation Promotion Programs sponsored by the Special Coordination Funds for Promoting Science and Technology, the Ministry of Education Japan (MEXT) for 3 years from 2010 to Akira Ito. A total of 24 researchers from 9 countries joined together and discussed the present situation and problems towards the control of cestode zoonoses. As the meeting was simultaneously for the establishment of joint international, either bilateral or multilateral collaboration projects, the main purposes were directed to 1) how to detect taeniasis/cysticercosis infected patients, 2) how to differentiate Taenia solium from two other human Taenia species, T. saginata and T. asiatica, 3) how to evaluate T. asiatica based on the evidence of hybrid and hybrid-derived adult tapeworms from Thailand and China, 4) how to evaluate T. solium and T. hyaenae and other Taenia species from the wild animals in Ethiopia, and 5) how to detect echinococcosis patients and 6) how to differentiate Echinococcus species worldwide. Such important topics are summarized in this meeting report.