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1.
Am J Trop Med Hyg ; 98(3): 791-796, 2018 03.
Article in English | MEDLINE | ID: mdl-29313476

ABSTRACT

Childhood vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in Cambodia in January 2015. Baseline data regarding circulating serotypes are scarce. All microbiology laboratories in Cambodia were contacted for identification of stored isolates of Streptococcus pneumoniae from clinical specimens taken before the introduction of PCV13. Available isolates were serotyped using a multiplex polymerase chain reaction method. Among 166 identified isolates available for serotyping from patients with pneumococcal disease, 4% were isolated from upper respiratory samples and 80% were from lower respiratory samples, and 16% were invasive isolates. PCV13 serotypes accounted for 60% (95% confidence interval [CI] 52-67) of all isolates; 56% (95% CI 48-64) of noninvasive and 77% (95% CI 57-89) of invasive isolates. Antibiotic resistance was more common among PCV13 serotypes. This study of clinical S. pneumoniae isolates supports the potential for high reduction in pneumococcal disease burden and may serve as baseline data for future monitoring of S. pneumoniae serotypes circulation after implementation of PCV13 childhood vaccination in Cambodia.


Subject(s)
Pneumonia, Pneumococcal/epidemiology , Pneumonia, Pneumococcal/microbiology , Serogroup , Streptococcus pneumoniae/classification , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Bacterial Typing Techniques , Bronchoalveolar Lavage Fluid/microbiology , Cambodia/epidemiology , Child , Child, Preschool , Drug Resistance, Multiple, Bacterial , Female , Humans , Infant , Laboratories, Hospital , Male , Mass Vaccination , Middle Aged , Pneumococcal Vaccines , Pneumonia, Pneumococcal/immunology , Pneumonia, Pneumococcal/prevention & control , Sputum/microbiology , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/immunology , Streptococcus pneumoniae/isolation & purification , Vaccines, Conjugate
2.
Emerg Microbes Infect ; 5(9): e104, 2016 Sep 21.
Article in English | MEDLINE | ID: mdl-27651091

ABSTRACT

Human enterovirus 71 (EV-A71) causes hand, foot and mouth disease (HFMD). EV-A71 circulates in many countries and has caused large epidemics, especially in the Asia-Pacific region, since 1997. In April 2012, an undiagnosed fatal disease with neurological involvement and respiratory distress occurred in young children admitted to the Kantha Bopha Children's Hospital in Phnom Penh, Cambodia. Most died within a day of hospital admission, causing public panic and international concern. In this study, we describe the enterovirus (EV) genotypes that were isolated during the outbreak in 2012 and the following year. From June 2012 to November 2013, 312 specimens were collected from hospitalized and ambulatory patients and tested by generic EV and specific EV-A71 reverse transcription PCR. EV-A71 was detected in 208 clinical specimens while other EVs were found in 32 patients. The VP1 gene and/or the complete genome were generated. Our phylogenetic sequencing analysis demonstrated that 80 EV-A71 strains belonged to the C4a subgenotype and 3 EV-A71 strains belonged to the B5 genotype. Furthermore, some lineages of EV-A71 were found to have appeared in Cambodia following separate introductions from neighboring countries. Nineteen EV A (CV-A6 and CV-A16), 9 EV B (EV-B83, CV-B3, CV-B2, CV-A9, E-31, E-2 and EV-B80) and 4 EV C (EV-C116, EV-C96, CV-A20 and Vaccine-related PV-3) strains were also detected. We found no molecular markers of disease severity. We report here that EV-A71 genotype C4 was the main etiological agent of a large outbreak of HFMD and particularly of severe forms associated with central nervous system infections. The role played by other EVs in the epidemic could not be clearly established.


Subject(s)
Disease Outbreaks , Enterovirus A, Human/genetics , Epidemics , Hand, Foot and Mouth Disease/epidemiology , Hand, Foot and Mouth Disease/mortality , Adolescent , Adult , Cambodia/epidemiology , Child , Child, Preschool , Enterovirus A, Human/classification , Enterovirus A, Human/isolation & purification , Enterovirus A, Human/pathogenicity , Female , Genome, Viral , Genotype , Hand, Foot and Mouth Disease/virology , Hospitalization , Humans , Infant , Male , Phylogeny , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Young Adult
3.
PLoS One ; 11(3): e0152529, 2016.
Article in English | MEDLINE | ID: mdl-27028323

ABSTRACT

Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1-77) presenting with influenza-like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV) and EV71. Influenza was found in 168 cases (29%) and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (<20%). Western Cambodian H1N1(2009) isolate genomes were more closely related to 10 earlier Cambodia isolates (94.4% genome conservation) than to 13 Thai isolates (75.9% genome conservation), despite sharing the majority of the amino acid changes with the Thai references. Most genes showed signatures of purifying selection. Viral culture detected only adenovirus (5.7%) and parainfluenza virus (3.8%), while non-polio enteroviruses (10.3%) were detected among 164 culture-negative samples including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9 using nested RT-PCR methods. A single specimen of EV71 was found. Despite proximity to Thailand, influenza epidemiology of these western Cambodian isolates followed patterns observed elsewhere in Cambodia, continuing to support current vaccine and treatment recommendations from the Cambodian National Influenza Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin genes, require further investigation in light of an increasingly important role of permissive mutations in influenza virus evolution. Further research about the burden of adenovirus and non-polio enteroviruses as etiologic agents in acute respiratory infections in Cambodia is also needed.


Subject(s)
Enterovirus Infections , Enterovirus/genetics , Influenza A Virus, H1N1 Subtype/genetics , Influenza, Human , Picornaviridae Infections , Rhinovirus/genetics , Adolescent , Adult , Aged , Cambodia , Child , Child, Preschool , Enterovirus Infections/epidemiology , Enterovirus Infections/genetics , Humans , Infant , Influenza, Human/epidemiology , Influenza, Human/genetics , Middle Aged , Picornaviridae Infections/epidemiology , Picornaviridae Infections/genetics , Sentinel Surveillance
4.
Int J Infect Dis ; 44: 11-5, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26854199

ABSTRACT

Mass gatherings at major international sporting events put millions of international travelers and local host-country residents at risk of acquiring infectious diseases, including locally endemic infectious diseases. The mosquito-borne Zika virus (ZIKV) has recently aroused global attention due to its rapid spread since its first detection in May 2015 in Brazil to 22 other countries and other territories in the Americas. The ZIKV outbreak in Brazil, has also been associated with a significant rise in the number of babies born with microcephaly and neurological disorders, and has been declared a 'Global Emergency by the World Health Organization. This explosive spread of ZIKV in Brazil poses challenges for public health preparedness and surveillance for the Olympics and Paralympics which are due to be held in Rio De Janeiro in August, 2016. We review the epidemiology and clinical features of the current ZIKV outbreak in Brazil, highlight knowledge gaps, and review the public health implications of the current ZIKV outbreak in the Americas. We highlight the urgent need for a coordinated collaborative response for prevention and spread of infectious diseases with epidemic potential at mass gatherings events.


Subject(s)
Public Health , Zika Virus Infection/epidemiology , Zika Virus , Brazil/epidemiology , Disease Outbreaks/prevention & control , Humans , Infant , Microcephaly/epidemiology , Microcephaly/virology , Sports , World Health Organization , Zika Virus Infection/complications
5.
PLoS One ; 9(10): e110713, 2014.
Article in English | MEDLINE | ID: mdl-25340711

ABSTRACT

BACKGROUND: The Cambodian National Influenza Center (NIC) monitored and characterized circulating influenza strains from 2009 to 2011. METHODOLOGY/PRINCIPAL FINDINGS: Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from patients who fulfilled case definitions for influenza-like illness, acute lower respiratory infections and event-based surveillance. Each year in Cambodia, influenza viruses were detected mainly from June to November, during the rainy season. Antigenic analysis show that A/H1N1pdm09 isolates belonged to the A/California/7/2009-like group. Circulating A/H3N2 strains were A/Brisbane/10/2007-like in 2009 before drifting to A/Perth/16/2009-like in 2010 and 2011. The Cambodian influenza B isolates from 2009 to 2011 all belonged to the B/Victoria lineage represented by the vaccine strains B/Brisbane/60/2008 and B/Malaysia/2506/2004. Sequences of the M2 gene obtained from representative 2009-2011 A/H3N2 and A/H1N1pdm09 strains all contained the S31N mutation associated with adamantanes resistance except for one A/H1N1pdm09 strain isolated in 2011 that lacked this mutation. No reduction in the susceptibility to neuraminidase inhibitors was observed among the influenza viruses circulating from 2009 to 2011. Phylogenetic analysis revealed that A/H3N2 strains clustered each year to a distinct group while most A/H1N1pdm09 isolates belonged to the S203T clade. CONCLUSIONS/SIGNIFICANCE: In Cambodia, from 2009 to 2011, influenza activity occurred throughout the year with peak seasonality during the rainy season from June to November. Seasonal influenza epidemics were due to multiple genetically distinct viruses, even though all of the isolates were antigenically similar to the reference vaccine strains. The drug susceptibility profile of Cambodian influenza strains revealed that neuraminidase inhibitors would be the drug of choice for influenza treatment and chemoprophylaxis in Cambodia, as adamantanes are no longer expected to be effective.


Subject(s)
Influenza, Human/epidemiology , Influenza, Human/virology , Orthomyxoviridae/physiology , Animals , Antigens, Viral/immunology , Cambodia/epidemiology , Dogs , Drug Resistance, Viral , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/isolation & purification , Influenza B virus/genetics , Influenza B virus/isolation & purification , Influenza Vaccines/immunology , Influenza, Human/immunology , Madin Darby Canine Kidney Cells , Orthomyxoviridae/immunology , Orthomyxoviridae/isolation & purification , Phylogeny , Seasons
6.
Bull World Health Organ ; 92(5): 318-30, 2014 May 01.
Article in English | MEDLINE | ID: mdl-24839321

ABSTRACT

OBJECTIVE: To characterize influenza seasonality and identify the best time of the year for vaccination against influenza in tropical and subtropical countries of southern and south-eastern Asia that lie north of the equator. METHODS: Weekly influenza surveillance data for 2006 to 2011 were obtained from Bangladesh, Cambodia, India, Indonesia, the Lao People's Democratic Republic, Malaysia, the Philippines, Singapore, Thailand and Viet Nam. Weekly rates of influenza activity were based on the percentage of all nasopharyngeal samples collected during the year that tested positive for influenza virus or viral nucleic acid on any given week. Monthly positivity rates were then calculated to define annual peaks of influenza activity in each country and across countries. FINDINGS: Influenza activity peaked between June/July and October in seven countries, three of which showed a second peak in December to February. Countries closer to the equator had year-round circulation without discrete peaks. Viral types and subtypes varied from year to year but not across countries in a given year. The cumulative proportion of specimens that tested positive from June to November was > 60% in Bangladesh, Cambodia, India, the Lao People's Democratic Republic, the Philippines, Thailand and Viet Nam. Thus, these tropical and subtropical countries exhibited earlier influenza activity peaks than temperate climate countries north of the equator. CONCLUSION: Most southern and south-eastern Asian countries lying north of the equator should consider vaccinating against influenza from April to June; countries near the equator without a distinct peak in influenza activity can base vaccination timing on local factors.


Subject(s)
Influenza, Human/epidemiology , Influenza, Human/virology , Orthomyxoviridae/isolation & purification , Asia, Southeastern/epidemiology , Humans , Influenza Vaccines , Influenza, Human/prevention & control , Nasal Mucosa/virology , Orthomyxoviridae/immunology , Seasons , Tropical Climate
7.
J Infect Dev Ctries ; 8(2): 202-7, 2014 Feb 13.
Article in English | MEDLINE | ID: mdl-24518630

ABSTRACT

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.


Subject(s)
Disease Outbreaks , Influenza A Virus, H5N1 Subtype/isolation & purification , Influenza in Birds/epidemiology , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Antiviral Agents/therapeutic use , Azerbaijan/epidemiology , Child , Child, Preschool , Female , Humans , Indonesia/epidemiology , Infant , Influenza in Birds/transmission , Influenza, Human/drug therapy , Male , Middle Aged , Oseltamivir/therapeutic use , Pakistan/epidemiology , Poultry , Risk Factors , Turkey/epidemiology , Young Adult
9.
Int J Equity Health ; 12: 82, 2013 Oct 04.
Article in English | MEDLINE | ID: mdl-24090286

ABSTRACT

INTRODUCTION: Human influenza infection poses a serious public health threat in Cambodia, a country at risk for the emergence and spread of novel influenza viruses with pandemic potential. Prior pandemics demonstrated the adverse impact of influenza on poor communities in developing countries. Investigation of healthcare resource distribution can inform decisions regarding resource mobilization and investment for pandemic mitigation. METHODS: A health facility survey performed across Cambodia obtained data on availability of healthcare resources important for pandemic influenza response. Focusing on five key resources considered most necessary for treating severe influenza (inpatient beds, doctors, nurses, oseltamivir, and ventilators), resource distributions were analyzed at the Operational District (OD) and Province levels, refining data analysis from earlier studies. Resources were stratified by respondent type (hospital vs. District Health Office [DHO]). A summary index of distribution inequality was calculated using the Gini coefficient. Indices for local spatial autocorrelation were measured at the OD level using geographical information system (GIS) analysis. Finally, a potential link between socioeconomic status and resource distribution was explored by mapping resource densities against poverty rates. RESULTS: Gini coefficient calculation revealed variable inequality in distribution of the five key resources at the Province and OD levels. A greater percentage of the population resides in areas of relative under-supply (28.5%) than over-supply (21.3%). Areas with more resources per capita showed significant clustering in central Cambodia while areas with fewer resources clustered in the northern and western provinces. Hospital-based inpatient beds, doctors, and nurses were most heavily concentrated in areas of the country with the lowest poverty rates; however, beds and nurses in Non-Hospital Medical Facilities (NHMF) showed increasing concentrations at higher levels of poverty. CONCLUSIONS: There is considerable heterogeneity in healthcare resource distribution across Cambodia. Distribution mapping at the local level can inform policy decisions on where to stockpile resources in advance of and for reallocation in the event of a pandemic. These findings will be useful in determining future health resource investment, both for pandemic preparedness and for general health system strengthening, and provide a foundation for future analyses of equity in health services provision for pandemic mitigation planning in Cambodia.


Subject(s)
Delivery of Health Care/organization & administration , Influenza, Human/epidemiology , Pandemics , Resource Allocation/organization & administration , Cambodia/epidemiology , Geographic Mapping , Humans , Poverty/statistics & numerical data , Socioeconomic Factors
10.
BMC Public Health ; 13: 549, 2013 Jun 06.
Article in English | MEDLINE | ID: mdl-23738818

ABSTRACT

BACKGROUND: Southeast Asia has been identified as a potential epicentre of emerging diseases with pandemic capacity, including highly pathogenic influenza. Cambodia in particular has the potential for high rates of avoidable deaths from pandemic influenza due to large gaps in health system resources. This study seeks to better understand the course and cost-of-illness for cases of highly pathogenic avian influenza in Cambodia. METHODS: We studied the 18 laboratory-confirmed cases of avian influenza subtype H5N1 identified in Cambodia between January 2005 and August 2011. Medical records for all patients were reviewed to extract information on patient characteristics, travel to hospital, time to admission, diagnostic testing, treatment and disease outcomes. Further data related to costs was collected through interviews with key informants at district and provincial hospitals, the Ministry of Health and non-governmental organisations. An ingredient-based approach was used to estimate the total economic cost for each study patient. Costing was conducted from a societal perspective and included both financial and opportunity costs to the patient or carer. Sensitivity analysis was undertaken to evaluate potential change or variation in the cost-of-illness. RESULTS: Of the 18 patients studied, 11 (61%) were under the age of 18 years. The majority of patients (16, 89%) died, eight (44%) within 24 hours of hospital admission. There was an average delay of seven days between symptom onset and hospitalisation with patients travelling an average of 148 kilometres (8-476 km) to the admitting hospital. Five patients were treated with oseltamivir of whom two received the recommended dose. For the 16 patients who received all their treatment in Cambodia the average per patient cost of H5N1 influenza illness was US$300 of which 85.0% comprised direct medical provider costs, including diagnostic testing (41.2%), pharmaceuticals (28.4%), hospitalisation (10.4%), oxygen (4.4%) and outpatient consultations (0.6%). Patient or family costs were US$45 per patient (15.0%) of total economic cost. CONCLUSION: Cases of avian influenza in Cambodia were characterised by delays in hospitalisation, deficiencies in some aspects of treatment and a high fatality rate. The costs associated with medical care, particularly diagnostic testing and pharmaceutical therapy, were major contributors to the relatively high cost-of-illness.


Subject(s)
Influenza A Virus, H5N1 Subtype , Influenza, Human/epidemiology , Adolescent , Adult , Aged , Cambodia/epidemiology , Child , Child, Preschool , Cost of Illness , Female , Hospitalization/economics , Humans , Infant , Influenza, Human/economics , Male , Middle Aged
11.
Int J Health Geogr ; 11: 53, 2012 Dec 14.
Article in English | MEDLINE | ID: mdl-23241450

ABSTRACT

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.


Subject(s)
Delivery of Health Care , Health Resources/supply & distribution , Influenza, Human/epidemiology , Pandemics , Surge Capacity , Asia, Southeastern/epidemiology , Geographic Mapping , Humans , Medical Staff, Hospital/supply & distribution , Surveys and Questionnaires
12.
BMC Public Health ; 12: 870, 2012 Oct 12.
Article in English | MEDLINE | ID: mdl-23061807

ABSTRACT

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.


Subject(s)
Disaster Planning/organization & administration , Health Care Rationing/methods , Influenza, Human/epidemiology , Pandemics/prevention & control , Software , Asia/epidemiology , Computer Simulation , Decision Making , Humans , Models, Theoretical , Public Health Administration
13.
J Infect Dis ; 206(9): 1359-66, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22927451

ABSTRACT

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.


Subject(s)
Antiviral Agents/administration & dosage , Influenza A Virus, H5N1 Subtype/drug effects , Influenza, Human/drug therapy , Influenza, Human/virology , Oseltamivir/administration & dosage , Adolescent , Adult , Aged , Antiviral Agents/pharmacology , Child , Child, Preschool , Female , Humans , Infant , Influenza, Human/complications , Influenza, Human/mortality , Male , Middle Aged , Oseltamivir/pharmacology , Respiratory Insufficiency/mortality , Respiratory Insufficiency/virology , Secondary Prevention , Survival Analysis , Treatment Outcome , Young Adult
14.
PLoS One ; 7(2): e31800, 2012.
Article in English | MEDLINE | ID: mdl-22363739

ABSTRACT

BACKGROUND: Southeast Asia has been the focus of considerable investment in pandemic influenza preparedness. Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia. METHODS AND FINDINGS: We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a mathematical transmission model to simulate a "mild-to-moderate" pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as "avoidable" mortalities), particularly in poorer areas. Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan. Other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. However, geographic patterns observed within and across territories remained similar for the range of parameter values explored. CONCLUSIONS: The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths.


Subject(s)
Health Resources/supply & distribution , Health Resources/statistics & numerical data , Healthcare Disparities/statistics & numerical data , Influenza, Human/economics , Influenza, Human/mortality , Pandemics/statistics & numerical data , Asia/epidemiology , Geography , Gross Domestic Product/statistics & numerical data , Health Resources/economics , Healthcare Disparities/economics , Humans , Models, Biological , Pandemics/economics
15.
Am J Trop Med Hyg ; 86(2): 246-253, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22302857

ABSTRACT

The agents of human febrile illness can vary by region and country suggesting that diagnosis, treatment, and control programs need to be based on a methodical evaluation of area-specific etiologies. From December 2006 to December 2009, 9,997 individuals presenting with acute febrile illness at nine health care clinics in south-central Cambodia were enrolled in a study to elucidate the etiologies. Upon enrollment, respiratory specimens, whole blood, and serum were collected. Testing was performed for viral, bacterial, and parasitic pathogens. Etiologies were identified in 38.0% of patients. Influenza was the most frequent pathogen, followed by dengue, malaria, and bacterial pathogens isolated from blood culture. In addition, 3.5% of enrolled patients were infected with more than one pathogen. Our data provide the first systematic assessment of the etiologies of acute febrile illness in south-central Cambodia. Data from syndromic-based surveillance studies can help guide public health responses in developing nations.


Subject(s)
Dengue/epidemiology , Fever/epidemiology , Fever/etiology , Influenza, Human/epidemiology , Malaria/epidemiology , Acute Disease , Adolescent , Adult , Bacteria/isolation & purification , Bacteria/pathogenicity , Cambodia/epidemiology , Child , Dengue/complications , Developing Countries , Female , Orthohantavirus/isolation & purification , Orthohantavirus/pathogenicity , Hepatitis E virus/isolation & purification , Hepatitis E virus/pathogenicity , Humans , Influenza, Human/complications , Malaria/complications , Male , Orientia tsutsugamushi/isolation & purification , Orientia tsutsugamushi/pathogenicity , Prevalence , Public Health , Rickettsia/isolation & purification , Rickettsia/pathogenicity , Specimen Handling , Young Adult
17.
J Clin Microbiol ; 49(10): 3504-13, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21865418

ABSTRACT

Human respiratory syncytial virus (HRSV) is the leading cause of hospitalization of children aged <5 years due to respiratory illness in industrialized countries, and pneumonia is the leading cause of mortality among children aged <5 years worldwide. Although HRSV was first identified in 1956, a preventative vaccine has yet to be developed. Here we report the results of the first study to investigate the circulation and genetic diversity of HRSV in Cambodia among an all-ages population over 5 consecutive years. The incidences of HRSV infection among all-ages outpatient and hospitalized populations were equivalent, at 9.5% and 8.2%, respectively. Infection was most prevalent among children aged <5 years, with bronchiolitis being the most frequently observed clinical syndrome in the same age group. Circulation of HRSV was seasonal, typically coinciding with the rainy season between July and November annually. Strains belonging to HRSV groups A and B were detected with equivalent frequencies; however, we observed a potentially biennial shift in the predominant circulating HRSV genotype. The majority of HRSV group B strains belonged to the recently described BA genotype, with the exception of 10 strains classified as belonging to a novel HRSV group B genotype, SAB4, first reported here.


Subject(s)
Genetic Variation , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Virus, Human/classification , Respiratory Syncytial Virus, Human/genetics , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Cambodia/epidemiology , Child , Child, Preschool , Cluster Analysis , Female , Genotype , Humans , Infant , Infant, Newborn , Male , Middle Aged , Molecular Epidemiology , Molecular Sequence Data , Phylogeny , RNA, Viral/genetics , Respiratory Syncytial Virus, Human/isolation & purification , Seasons , Sequence Analysis, DNA , Young Adult
18.
J Trop Pediatr ; 57(4): 241-4, 2011 Aug.
Article in English | MEDLINE | ID: mdl-20068031

ABSTRACT

A cohort of Japanese encephalitis (JE) survivors in Cambodia and Viet Nam were assessed at least 4 months after hospital discharge in order to understand the extent of disability after JE. We used a simple assessment tool which focuses on the impact on daily life. In total, 64 disability assessments were conducted: 38 in Cambodia and 26 in Viet Nam. In Cambodia, 4 (11%) children had severe sequelae, suggesting the children would likely be dependent, 15 (39%) had moderate sequelae and 17 (45%) had mild sequelae. In Viet Nam, two (8%) persons had severe sequelae, five (19%) had moderate sequelae and eight (31%) had mild sequelae. In many JE-endemic areas there are no multi-disciplinary teams with sophisticated equipment to assess patients after JE disease. This assessment tool can assist with patient management and generate data to support the need for programmes to prevent disease and improve outcomes for survivors.


Subject(s)
Cognition Disorders/diagnosis , Cognition Disorders/etiology , Disabled Children , Encephalitis, Japanese/complications , Encephalitis, Japanese/diagnosis , Quality of Life , Adolescent , Cambodia/epidemiology , Child , Child Behavior Disorders/diagnosis , Child Behavior Disorders/etiology , Child, Preschool , Cognition Disorders/mortality , Cohort Studies , Disability Evaluation , Disabled Children/statistics & numerical data , Encephalitis, Japanese/mortality , Female , Follow-Up Studies , Humans , Infant , Male , Prognosis , Risk Assessment , Sentinel Surveillance , Severity of Illness Index , Vietnam/epidemiology
19.
Southeast Asian J Trop Med Public Health ; 41(5): 1104-15, 2010 Sep.
Article in English | MEDLINE | ID: mdl-21073031

ABSTRACT

Low income countries in Southeast Asia are in a region at risk of emerging infectious diseases, notably SARS, H5N1 influenza and H1N1 influenza. Efforts have focused largely upon early outbreak response, though with the emergence of pandemic influenza, countries in the region are having to prepare to implement mitigation measures. We review the challenges for strategy and operation faced by two low income countries, Cambodia and Lao People's Democratic Republic (PDR), and highlight successes in planing and implementation to date as well as identifying needs and challenge that may hinder the future effectiveness of control measures.


Subject(s)
Disaster Planning , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Pandemics/prevention & control , Cambodia/epidemiology , Humans , Influenza, Human/virology , Laos/epidemiology
20.
BMC Public Health ; 10: 322, 2010 Jun 08.
Article in English | MEDLINE | ID: mdl-20529345

ABSTRACT

BACKGROUND: Since 2003, Asia-Pacific, particularly Southeast Asia, has received substantial attention because of the anticipation that it could be the epicentre of the next pandemic. There has been active investment but earlier review of pandemic preparedness plans in the region reveals that the translation of these strategic plans into operational plans is still lacking in some countries particularly those with low resources. The objective of this study is to understand the pandemic preparedness programmes, the health systems context, and challenges and constraints specific to the six Asian countries namely Cambodia, Indonesia, Lao PDR, Taiwan, Thailand, and Viet Nam in the prepandemic phase before the start of H1N1/2009. METHODS: The study relied on the Systemic Rapid Assessment (SYSRA) toolkit, which evaluates priority disease programmes by taking into account the programmes, the general health system, and the wider socio-cultural and political context. The components under review were: external context; stewardship and organisational arrangements; financing, resource generation and allocation; healthcare provision; and information systems. Qualitative and quantitative data were collected in the second half of 2008 based on a review of published data and interviews with key informants, exploring past and current patterns of health programme and pandemic response. RESULTS: The study shows that health systems in the six countries varied in regard to the epidemiological context, health care financing, and health service provision patterns. For pandemic preparation, all six countries have developed national governance on pandemic preparedness as well as national pandemic influenza preparedness plans and Avian and Human Influenza (AHI) response plans. However, the governance arrangements and the nature of the plans differed. In the five developing countries, the focus was on surveillance and rapid containment of poultry related transmission while preparation for later pandemic stages was limited. The interfaces and linkages between health system contexts and pandemic preparedness programmes in these countries were explored. CONCLUSION: Health system context influences how the six countries have been preparing themselves for a pandemic. At the same time, investment in pandemic preparation in the six Asian countries has contributed to improvement in health system surveillance, laboratory capacity, monitoring and evaluation and public communications. A number of suggestions for improvement were presented to strengthen the pandemic preparation and mitigation as well as to overcome some of the underlying health system constraints.


Subject(s)
Disaster Planning/organization & administration , Disease Outbreaks/prevention & control , Influenza, Human/prevention & control , Asia , Health Resources/supply & distribution , Health Services , Humans , Influenza A Virus, H5N1 Subtype , Risk Factors
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