Infection status with zoonotic trematode metacercariae in fish from Lao PDR.

Studies on the infection status with fishborne zoonotic trematode (FZT) metacercariae were reviewed with our data, which obtained from the fish survey in 8 administrative localities, i.e., Vientiane Municipality, Luang Prabang, Xieng Khouang, Vientiane, Khammuane, Savannakhet, Saravane and Champasak Provinces of Lao PDR (Laos) in 10 times. Total 1046 freshwater fishes (69 species) were examined with the artificial digestion method from 2002 to 2011. Total 6 species of zoonotic trematode, i.e., Opisthorchis viverrini, Haplorchis taichui, Haplorchis yokogawai, Haplorchis pumilio, Centrocestus formosanus and Procerovum varium, metacercariae were detected in fishes from Laos. The metacercariae of O. viverrini were detected in 284 (37.9%) out of 749 fishes (26 spp.), and their average density was 297 per fish infected. The prevalences of 4 heterophyid species, i.e., H. taichui, H. yokogawai, H. pumilio and C. formosanus, metacercariae were 45.4% (out of 941 fishes in 46 spp. examined), 45.1% (811 fishes in 35 spp.), 8.8% (457 fishes in 11 spp.) and 18.1% (475 fishes in 13 spp.), their average densities were 291, 218, 4 and 15 per fish infected respectively. The endemicities of O. viverrini metacercariae were much higher in fishes from Savannakhet Province and Vientiane Municipality (2002). Those of H. taichui metacercariae were much higher in fishes from Khammuane and Luang Prabang (2011) Provinces. By the present study, it was confirmed that some species of FZT metacercariae are highly prevalent in fishes from Laos.

Data quality and timeliness of outbreak reporting system among countries in Greater Mekong subregion: Challenges for international data sharing.

Cross-border disease transmission is a key challenge for prevention and control of outbreaks. Variation in surveillance structure and national guidelines used in different countries can affect their data quality and the timeliness of outbreak reports. This study aimed to evaluate timeliness and data quality of national outbreak reporting for four countries in the Mekong Basin Disease Surveillance network (MBDS). Data on disease outbreaks occurring from 2010 to 2015 were obtained from the national disease surveillance reports of Cambodia, Lao PDR, Myanmar, and Vietnam. Data included total cases, geographical information, and dates at different timeline milestones in the outbreak detection process. Nine diseases or syndromes with public health importance were selected for the analysis including: dengue, food poisoning & diarrhea, severe diarrhea, diphtheria, measles, H5N1 influenza, H1N1 influenza, rabies, and pertussis. Overall, 2,087 outbreaks were reported from the four countries. The number of outbreaks and number of cases per outbreak varied across countries and diseases, depending in part on the outbreak definition used in each country. Dates on index onset, report, and response were >95% complete in all countries, while laboratory confirmation dates were 10%-100% incomplete in most countries. Inconsistent and out of range date data were observed in 1%-5% of records. The overall timeliness of outbreak report, response, and public communication was within 1-15 days, depending on countries and diseases. Diarrhea and severe diarrhea outbreaks showed the most rapid time to report and response, whereas diseases such as rabies, pertussis and diphtheria required a longer time to report and respond. The hierarchical structure of the reporting system, data collection method, and country's resources could affect the data quality and timeliness of the national outbreak reporting system. Differences in data quality and timeliness of outbreak reporting system among member countries should be considered when planning data sharing strategies within a regional network.

Echinostoma ilocanum Infection in Two Residents of Savannakhet Province, Lao PDR.

Adult specimens of Echinostoma ilocanum (Garrison, 1908) Odhner, 1911 (Trematoda: Echinostomatidae) were recovered from 2 riparian people who resided along the Mekong River in Savannakhet Province, Lao PDR. In fecal examinations done by the Kato-Katz technique, they revealed echinostome eggs together with eggs of Opisthorchis viverrini (and minute intestinal fluke eggs) and hookworms. To recover the adult flukes, they were treated with praziquantel 30-40 mg/kg in a single dose and purged with magnesium salts. A total of 658 adult fluke specimens were recovered from the 2 people; 456 from case 1 and 202 from case 2. Specimens from case 1 consisted of 335 echinostomes (301 E. ilocanum and 34 species undetermined), 120 O. viverrini, and 1 Haplorchis taichui, and those from case 2 consisted of 36 E. ilocanum, 134 O. viverrini, and 32 H. taichui. Thus, the number of E. ilocanum specimens was 337 in total (average per person, 168.5). From this study, it is suggested that foodborne intestinal flukes and liver flukes are highly prevalent along the Mekong River in Savannakhet Province. The present report describes for the first time human infections with E. ilocanum in Lao PDR.

Ultrasonographic investigation of cholangiocarcinoma in Lao PDR.

Opisthorchis viverrini is a group 1 carcinogen that causes cholangiocarcinoma (CCA). Although opisthorchiasis is known to be severely endemic to several areas along the Mekong River in Lao PDR, the CCA status of residents of this region is still under investigation. In this study, we analyzed the results of abdominal ultrasonography (US) performed on 6113 residents in 9 provinces (Vientiane Municipality, Savannakhet, Phongsaly, Khammouane, Saravane, Champasak, Vientiane, Xieng Khuouang, and Luang Prabang provinces) of Lao PDR from 2007 to 2011. Overall, 51 cases (0.83%) were detected with suspected CCA. The CCA rates in Vientiane Municipality and in Savannakhet and Khammouane provinces were 1.45%, 1.58%, and 1.09%, respectively. However, in the other 6 provinces, the rate of CCA averaged only 0.26%. In the 3 provinces with higher rates of CCA, bile duct dilatation (grade ≥ 2) was also significantly more prevalent (P < 0.0001). These results are concordant with previous reports showing a higher endemicity of opisthorchiasis in Vientiane Municipality and in Savannakhet and Khammouane provinces.

Intestinal Helminths Recovered from Humans in Xieng Khouang Province, Lao PDR with a Particular Note on Haplorchis pumilio Infection.

A survey of intestinal helminths was undertaken in riparian people in Xieng Khouang Province, Lao PDR. Fecal specimens were collected from 643 people (289 males and 354 females) residing in 4 districts (Nonghet, Kham, Phoukout, and Pek) and were examined by the Kato-Katz technique. The overall helminth egg positive rate was 41.2%, and hookworms revealed the highest prevalence (32.7%) followed by Trichuris trichiura (7.3%) and Ascaris lumbricoides (5.6%). The positive rate for small trematode eggs (STE), which may include Opisthorchis viverrini, heterophyids, and lecithodendriids, was 4.4%. For recovery of adult helminths, 12 STE or nematode/cestode egg-positive people were treated with 40 mg/kg praziquantel and 15 mg/kg pyrantel pamoate, and then purged. Mixed infections with 2 Haplorchis species (H. pumilio and H. taichui), Centrocestus formosanus, Opisthorchis viverrini, a species of cestode (Taenia saginata), and several species of nematodes including hookworms and Enterobius vermicularis were detected. The worm load for trematodes was the highest for H. pumilio with an average of 283.5 specimens per infected person followed by C. formosanus, H. taichui, and O. viverrini. The worm load for nematodes was the highest for hookworms (21.5/infected case) followed by E. vermicularis (3.2/infected case). The results revealed that the surveyed areas of Xieng Khouang Province, Lao PDR are endemic areas of various species of intestinal helminths. The STE found in the surveyed population were verified to be those of heterophyids, particularly H. pumilio.

Infection Status of Zoonotic Trematode Metacercariae in Fishes from Vientiane Municipality and Champasak Province in Lao PDR.

The infection status of fishborne zoonotic trematode (FZT) metacercariae was investigated in fishes from 2 localities of Lao PDR. Total 157 freshwater fishes (17 species) were collected in local markets of Vientiane Municipality and Champasak Province in December 2010 and July 2011, and each fish was examined by the artificial digestion method. Total 6 species of FZT metacercariae, i.e., Opisthorchis viverrini, Haplorchis taichui, Haplorchis yokogawai, Haplorchis pumilio, Centrocestus formosanus, and Procerovum varium, were detected in fishes from Vientiane Municipality. The metacercariae of O. viverrini were detected in 50 (49.5%) out of 101 fishes (6 species), and their average number was 154 per fish infected. The remaining 5 species of heterophyid metacercariae were detected in 36.8%, 65.8%, 9.4%, 23.9%, and 5.1% fishes examined, and their average densities were 12, 1,038, 4, 15, and 13 per infected fish, respectively. In fishes from Champasak Province, 3 species of FZT metacercariae, i.e., O. viverrini, H. taichui, and H. yokogawai, were detected. Only 2 O. viverrini metacercariae were found in only 1 Barbonymus schwanefeldi. The metacercariae of H. taichui and H. yokogawai were detected in 60.0% and 50.0% of fishes examined, and their average densities were 47 and 28 per fish infected. By the present study, it has been confirmed that several species of FZT metacercariae are prevalent in fishes from Vientiane Municipality, with P. varium being a new member of FZT in Lao PDR. In comparison, FZT metacercariae are less prevalent in fishes from Champasak Province.

Epidemiological study of Japanese encephalitis virus in Vientiane, Lao PDR, in 1990s.

Phylogenetic analysis of Japanese encephalitis virus (JEV) was conducted using core-premembrane and envelope gene sequence data of two strains from Vientiane, Lao People's Democratic Republic, in 1993 and five from Okinawa, Japan, in 2002 and 2003, and previously published strains. The two Vientiane strains designated as LaVS56 and LaVS145 belonged to genotype 1 (G1) and the same subcluster of G1 as Australian strain in 2000, Thai strains in 1982-1985 and 2004-2005, and Vietnamese strain in 2005, but were distinct from the subcluster of recently distributing G1 strains widely in Asia including Okinawan strains and recent Lao strain in 2009. These clusters with own distinct distributions indicated involvements of different mechanisms and routes of spreading viruses and clarified that Australian G1 strain is from Southeast Asia, not from East Asia. Both Vientiane strains were antigenically close to P19-Br (G1, isolate, Thailand), but distinct from Nakayama (G3, prototype strain, Japan), Beijing-1 (G3, laboratory strain, China), and JaGAr#01 (G3, laboratory strain, Japan), demonstrated by cross-neutralization tests using polyclonal antisera. These results together with seroepidemiologic study conducted in Vientiane strongly suggest that diversified JEV cocirculated there in early 1990s.

Risk factors for Opisthorchis viverrini and minute intestinal fluke infections in Lao PDR, 2009-2011.

The purpose of this report is to compare the prevalence of Opisthorchis viverrini/minute intestinal fluke (Ov/MIF) in Lao People's Democratic Republic according to different regions and evaluate the effect of ingestion of raw freshwater fish on the infection. Demographic data, behavioral data, and symptoms were obtained, and the Kato-Katz method was used for the diagnosis of Ov/MIF. In total, 3,046 individuals were enrolled. The risk factors associated with acquisition of Ov/MIF were raw fish consumption and province. Khong Island showed the highest prevalence (odds ratio = 80.1, 95% confidence interval = 47.9-133.9, P < 0.001) compared with other districts, and raw fish consumption was related to Ov/MIF infection. Administration of praziquantel to entire populations, education (avoiding consumption of raw food dishes and improved hygiene), and access to clean water and sanitation should be considered.

Prevalence of Haplorchis taichui among humans and fish in Luang Prabang Province, Lao PDR.

This study confirmed the prevalence of the intestinal fluke Haplorchis taichui (Trematoda: Heterophyidae) among people and fish in Luang Prabang Province, Lao PDR. Fecal specimens were collected from 559 riparian people (229 males and 330 females), residing in 4 Districts (Luang Prabang, Xieng Ngeun, Pak Ou, and Nam Bak) and were examined by the Kato-Katz fecal smear technique. The overall helminth egg positive rate was 64.9%. The positive rate for small trematode eggs (STE), which may include H. taichui and other heterophyids, Opisthorchis viverrini, and lecithodendriids, was 15.2%. For recovery of adult helminths, 10 STE-positive people were treated with 40mg/kg praziquantel and 15mg/kg pyrantel pamoate, and then purged. Mixed infections with 3 Haplorchis species (H. taichui, H. pumilio, and H. yokogawai), a species of cestode (Taenia saginata), and several species of nematodes including Enterobius vermicularis and hookworms were found. The worm load for trematodes was exclusively high for H. taichui with an average of 7691 specimens per infected person, followed by H. yokogawai (8.3 specimens) and H. pumilio (4.1 specimens). Out of 207 freshwater fish (17 species) purchased in a market in Luang Prabang District, 138 (67%) harboured H. taichui metacercariae (metacercarial burden per fish; 520). Lower prevalence of fish and lower metacercarial density were observed for H. yokogawai (52% and 50 per fish, respectively) and H. pumilio (18% and 3 per fish, respectively). STE found in the surveyed population of Luang Prabang Province were verified to be those of intestinal fukes, particularly H. taichui.

Prevalence of helminthic infections among inhabitants of Lao PDR.

The prevalence of helminthic infections was surveyed on a total of 6,178 residents (males 2,549 and females 3,629) in 102 villages of 9 provinces in Lao PDR between 2007 and 2011 under the project of Korea-Laos Collaborative Project for Control of Foodborne Trematode Infections in Lao PDR. Fecal specimens were collected and examined by the Kato-Katz thick smear and Stoll's egg counting techniques. The overall liver/intestinal helminth egg positive rate was 71.9% with a single or mixed infections with Opisthorchis viverrini and minute intestinal flukes (Ov/MIF), Ascaris lumbricoides, hookworms, Trichuris trichiura, Trichostrongylus sp., echinostomes, Taenia spp., and others. Ov/MIF revealed the highest prevalence (55.6%) followed by hookworms (27.8%) and T. trichiura (6.5%). The endemic regions with the highest prevalence of Ov/MIF were Savannakhet, Khammouane, Vientiane (Nam Ngum), Champasak (Khong Island), and Saravane Province. High prevalences of A. lumbricoides (33.8%), hookworms (47.8%), and T. trichiura (32.6%) were observed in Phongsaly, Luang Prabang, and Vientiane (Nam Ngum) areas, respectively. The results of this study highlight helminth parasites of current public health significance in different areas of Lao PDR.

Recognizing true H5N1 infections in humans during confirmed outbreaks.

INTRODUCTION: The goal of this study was to evaluate whether any characteristics that are evident at presentation for urgent medical attention could be used to differentiate cases of H5N1 in the absence of viral testing. METHODOLOGY: Information about exposure to poultry, clinical signs and symptoms, treatments, and outcomes was abstracted from existing data in the global avian influenza registry (www.avianfluregistry.org) using standardized data collection tools for documented and possible cases of H5N1 infection who presented for medical attention between 2005-2011 during known H5N1 outbreaks in Azerbaijan, Indonesia, Pakistan and Turkey. RESULTS: Demography, exposure to poultry, and presenting symptoms were compared, with only the common symptoms of fever and headache presenting significantly more frequently in confirmed H5N1 cases than in possible cases. Reported exposure to  infected humans was also more common in confirmed cases. In contrast, unexplained respiratory illness, sore throat, excess sputum production, and rhinorrhea were more frequent in possible cases. Overall, oseltamivir treatment showed a survival benefit, with the greatest benefit shown in H5N1 cases who were treated within two days of symptom onset (51% reduction in case fatality). CONCLUSION: Since prompt treatment with antivirals conferred a strong survival benefit for H5N1 cases, presumptive antiviral treatment should be considered for all possible cases presenting during an outbreak of H5N1 as a potentially life-saving measure.

Hyperendemicity of Haplorchis taichui infection among riparian people in Saravane and Champasak province, Lao PDR.

In this study, we found that Haplorchis taichui, a heterophyid intestinal fluke, is highly prevalent, with heavy worm loads, among riparian people in Saravane and Champasak province, Lao PDR. Fecal specimens were collected from 1,460 people (717 men and 743 women) in 12 riparian (Mekong river) districts and were examined by the Kato-Katz fecal smear technique. The overall helminth egg positive rate was 78.8% and 66.4% in Saravane and Champasak province, respectively. The positive rate for small trematode eggs (STE), which included H. taichui and other heterophyids, Opisthorchis viverrini, and lecithodendriids, was 69.9% and 46.3% in Saravane and Champasak province, respectively. To obtain adult flukes, 30 STE-positive people were treated with 40 mg/kg praziquantel and then purged. Whole diarrheic stools were collected 4-5 times for each person and searched for fluke specimens using a stereomicroscope. Mixed infections with various species of trematodes (H. taichui, Haplorchis pumilio, O. viverrini, Prosthodendrium molenkampi, Centrocestus formosanus, and Echinochasmus japonicus) and a species of cestode (Taenia saginata) were found. However, the worm load was exceptionally high for H. taichui compared with other trematode species, with an average of 21,565 and 12,079 specimens per infected person in Saravane and Champasak province, respectively, followed by H. pumilio (41.9 and 22.5, respectively) and O. viverrini (9.4 and 1.5, respectively). These results show that diverse species of intestinal and liver flukes are prevalent among riparian people in Saravane and Champasak province, Lao PDR, with H. taichui being the exceptionally dominant species.

Current status of human taeniasis in Lao People's Democratic Republic.

Human taeniasis was investigated in Lao People's Democratic Republic (Lao PDR) between 2000 and 2011 as part of the nation's helminthiasis survey. A total of 55,038 inhabitants, including 29,846 school children, were examined using the Kato-Katz and scotch-tape anal swab method, and morphological observation of adult worms. Molecular identification of Taenia tapeworms was performed by multiplex PCR or DNA sequence analysis of the mitochondrial cox1 gene. Taenia eggs were present at a rate of 1.5% (845/55,038) in the subject population. Adult tapeworms were identified as T. solium or T. saginata by analyzing the collectable stool specimens (n=126). Three specimens identified as T. solium were found in Luang Prabang, while the remaining 123 specimens, which were T. saginata, were found in Bokeo, Bolikhamxay, Champasak, Houaphan, Khammouane, Luang Namta, Luang Prabang, Oudomxay, Phongsaly, Saysomboune, Saravane, Savannakhet, Xayaboury, Xekong, Xieng Khouang Province, and Vientiane Municipality.

Fishborne trematode metacercariae in Luang Prabang, Khammouane, and Saravane Province, Lao PDR.

Fishborne trematode (FBT) metacercariae were investigated in fish from 3 Provinces of Lao PDR. Total 242 freshwater fish of 40 species were collected in local markets of Luang Prabang (59 fish of 16 species), Khammouane (81 fish of 19 species), and Saravane (97 fish of 14 species), and each of them was examined by artificial digestion method. Four species of metacercariae (Opisthorchis viverrini, Haplorchis taichui, Haplorchis yokogawai, and Centrocestus formosanus) were detected. O. viverrini was detected in 35 fish (14.5%), and their density was 252 per infected fish (Luang Prabang, 88 metacercariae in 5 fish; Khammouane, 187 in 6 fish; Saravane, 303 in 24 fish). H. taichui was found in 102 fish (42.1%), and their density was 485 per infected fish (Luang Prabang, 260 metacercariae in 38 fish; Khammouane, 1,084 in 23 fish; Saravane, 359 in 41 fish). H. yokogawai was detected in 92 fish (38.0%), and their density was 222 per infected fish (Luang Prabang, 362 metacercariae in 17 fish; Khammouane, 126 in 20 fish; Saravane, 214 in 55 fish). Metacercariae of C. formosanus were found in 8 fish (3.3%), and their density was 3 per infected fish. In the present study, it has been confirmed that FBT metacercariae, in particular, H. taichui, H. yokogawai, and O. viverrini, are highly prevalent in fish from Luang Prabang, Khammouane, and Saravane Province, Lao PDR.

Mekong Basin Disease Surveillance (MBDS): a trust-based network.

The Mekong Basin Disease Surveillance (MBDS) network was formally established in 2001 through a Memorandum of Understanding signed by six Ministers of Health of the countries in the Greater Mekong sub-region: Cambodia, China (Yunnan and Guangxi), Lao PDR, Myanmar, Thailand and Vietnam. The main areas of focus of the network are to: i) improve cross-border infectious disease outbreak investigation and response by sharing surveillance data and best practices in disease recognition and reporting, and by jointly responding to outbreaks; ii) develop expertise in epidemiological surveillance across the countries; and iii) enhance communication between the countries. Comprised of senior health officials, epidemiologists, health practitioners, and other professionals, the MBDS has grown and matured over the years into an entity based on mutual trust that can be sustained into the future. Other regions have started emulating the network's pioneering work. In this paper, we describe the development of MBDS, the way in which it operates today, and some of its achievements. We present key challenges the network has faced and lessons its members have learned about how to develop sufficient trust for health and other professionals to alert each other to disease threats across national borders and thereby more effectively combat these threats.

Centrocestus formosanus (Heterophyidae): human infections and the infection source in Lao PDR.

In Lao People's Democratic Republic (PDR), we detected 7 patients infected with Centrocestus formosanus (1-122 adult specimens) after praziquantel treatment and purgation, together with several other trematode species including Opisthorchis viverrini and Haplorchis taichui. The patients were all men, 23-42 yr-of-age. Three subjects were from Vientiane Municipality and 1 each were from Khammouane, Saravane, Champassak, and Xiengkhouang Province. The patients had frequently eaten raw freshwater fish and were experiencing variable degrees of epigastric pain and indigestion accompanied by occasional diarrhea, although the relationship of these symptoms with C. formosanus infection was unclear. Centrocestus formosanus specimens were ovoid, 0.46 mm (0.41-0.52 mm) long, and 0.18 mm (0.16-0.20 mm) wide (n = 10) and were equipped with 32 circumoral spines on the oral sucker. The uterine eggs were 33.2 µm long (31.8-34.9 µm) and 18.5 µm wide (17.4-19.8 µm) (n = 20). Analysis of the nucleotide sequence of the 18S ribosomal RNA gene of our specimens (Laotian isolate) revealed 100% homology with that of an isolate from the United States reported in GenBank. Several species of freshwater fish collected from Xiengkhouang Province revealed a 17.0% prevalence (9 of 53 fish examined) for C. formosanus metacercariae. The results suggest that human C. formosanus infections have been masked by other trematode infections.

An analysis of health system resources in relation to pandemic response capacity in the Greater Mekong Subregion.

BACKGROUND: There is increasing perception that countries cannot work in isolation to militate against the threat of pandemic influenza. In the Greater Mekong Subregion (GMS) of Asia, high socio-economic diversity and fertile conditions for the emergence and spread of infectious diseases underscore the importance of transnational cooperation. Investigation of healthcare resource distribution and inequalities can help determine the need for, and inform decisions regarding, resource sharing and mobilisation. METHODS: We collected data on healthcare resources deemed important for responding to pandemic influenza through surveys of hospitals and district health offices across four countries of the GMS (Cambodia, Lao PDR, Thailand, Vietnam). Focusing on four key resource types (oseltamivir, hospital beds, ventilators, and health workers), we mapped and analysed resource distributions at province level to identify relative shortages, mismatches, and clustering of resources. We analysed inequalities in resource distribution using the Gini coefficient and Theil index. RESULTS: Three quarters of the Cambodian population and two thirds of the Laotian population live in relatively underserved provinces (those with resource densities in the lowest quintile across the region) in relation to health workers, ventilators, and hospital beds. More than a quarter of the Thai population is relatively underserved for health workers and oseltamivir. Approximately one fifth of the Vietnamese population is underserved for beds and ventilators. All Cambodian provinces are underserved for at least one resource. In Lao PDR, 11 percent of the population is underserved by all four resource items. Of the four resources, ventilators and oseltamivir were most unequally distributed. Cambodia generally showed higher levels of inequalities in resource distribution compared to other countries. Decomposition of the Theil index suggests that inequalities result principally from differences within, rather than between, countries. CONCLUSIONS: There is considerable heterogeneity in healthcare resource distribution within and across countries of the GMS. Most inequalities result from within countries. Given the inequalities, mismatches, and clustering of resources observed here, resource sharing and mobilization in a pandemic scenario could be crucial for more effective and equitable use of the resources that are available in the GMS.

Capacity building in response to pandemic influenza threats: Lao PDR case study.

The Lao People's Democratic Republic (PDR) committed to pandemic detection and response preparations when faced with the threat of avian influenza. Since 2006, the National Center for Laboratory and Epidemiology of Lao PDR has developed credible laboratory, surveillance, and epidemiological (human) capacity and as a result was designated a World Health Organization National Influenza Center in 2010. The Lao PDR experience in building influenza capacities provides a case study of the considerable crossover effect of such investments to augment the capacity to combat emerging and re-emerging diseases other than influenza.

Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator.

BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.

Determinants of antiviral effectiveness in influenza virus A subtype H5N1.

BACKGROUND: Oseltamivir is widely used as treatment for influenza virus A subtype H5N1 (hereafter, "H5N1") infection but, like any intervention, is not always effective. METHODS: We used Avian Influenza Registry data from 10 countries to examine the risk of death in 215 patients with confirmed H5N1 infection who were treated with oseltamivir, according to viral clade, age, respiratory failure, and adjunctive treatment with corticosteroids or antibiotics. RESULTS: The median age of infected individuals was 18 years, and 50% were male. The highest fatality rate occurred in a country with clade 2.1 virus circulation, and the lowest occurred in countries with clade 2.2 virus circulation (P < .001). In univariate analyses, age of ≤5 years and treatment ≤2 days after symptom onset were protective against fatality. When accounting for all risk factors, early initiation of oseltamivir was found to be particularly effective in individuals without respiratory failure (odds ratio, 0.17; P = .04). Patients who had advanced respiratory failure requiring ventilatory support at the time of oseltamivir initiation were more likely to die from the episode of H5N1 infection than patients who did not (P < .001). Adjunctive therapy did not improve the likelihood of surviving the episode. CONCLUSIONS: Oseltamivir is especially effective for treating H5N1 infection when given early and before onset of respiratory failure. The effect of viral clade on fatality and treatment response deserves further investigation.