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Tanya M Laidlaw1,2 *, Andrew Menzies-Gow3 *, Scott Caveney,4 Joseph K Han,5 Nicole Martin,6,7 Elliot Israel,8 Jason K Lee,9,10 Jean-Pierre Llanos,11 Neil Martin,12,13 Ayman Megally,14 Bhavini Parikh,14 Sylvia Vong,15 Tobias Welte,16 Jonathan Corren17 1Jeff and Penny Vinik Center for Allergic Diseases Research, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Boston, MA, USA; 2Department of Medicine, Harvard Medical School, Boston, MA, USA; 3Royal Brompton and Harefield Hospitals, School of Immunology and Microbial Sciences, King’s College London, London, UK; 4Global Development, Inflammation, R&D, Amgen, Thousand Oaks, CA, USA; 5Department of Otolaryngology, Head and Neck Surgery, Eastern Virginia Medical School, Norfolk, VA, USA; 6Biometrics, Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Waltham, MA, USA; 7Cytel Inc, Waltham, MA, USA; 8Divisions of Pulmonary and Critical Care Medicine and Allergy and Clinical Immunology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 9Evidence Based Medical Educator Inc., Toronto, ON, Canada; 10Toronto Allergy and Asthma Clinic, Toronto, ON, Canada; 11Global Medical Affairs, Amgen, Thousand Oaks, CA, USA; 12Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 13University of Leicester, Leicester, UK; 14Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 15Translational Science and Experimental Medicine, Early Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA; 16Department of Respiratory Medicine and German Center for Lung Research, Hannover Medical School, Hannover, Germany; 17David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA*These authors contributed equally to this workCorrespondence: Tanya M Laidlaw, Jeff and Penny Vinik Center for Allergic Diseases Research, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, 60 Fenwood Road, Boston, MA, 02115, USA, Email tlaidlaw@bwh.harvard.eduPurpose: Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced annualized asthma exacerbation rates (AAERs) versus placebo, irrespective of baseline disease characteristics, and improved lung function and symptom control versus placebo in adults and adolescents with severe, uncontrolled asthma. We assessed the efficacy of tezepelumab in patients with severe asthma with or without nasal polyps (NPs) in the 2 years before randomization in NAVIGATOR.Methods: Patients with severe asthma (N=1059) were randomized (1:1) and received tezepelumab 210 mg or placebo every 4 weeks subcutaneously for 52 weeks. Prespecified exploratory analyses included: AAER over 52 weeks and changes from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 second, Sino-Nasal Outcome Test (SNOT)-22 scores, and asthma control and health-related quality life (HRQoL) outcomes in NP subgroups. Changes from baseline in fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total immunoglobulin E (IgE), eosinophil-derived neurotoxin (EDN), matrix metalloproteinase-10 (MMP-10), and serum interleukin (IL)-5, IL-6, IL-8 and IL-13 were assessed (post hoc).Results: Tezepelumab reduced the AAER over 52 weeks versus placebo by 85% (95% confidence interval [CI]: 72, 92; n=118) and 51% (95% CI: 40, 60; n=941) in patients with and without NPs, respectively. At week 52, tezepelumab improved lung function, asthma control and HRQoL versus placebo in patients with and without NPs. Tezepelumab reduced SNOT-22 total scores (least-squares mean difference versus placebo [95% CI]) in patients with NPs at 28 weeks (– 12.57 points [– 19.40, – 5.73]) and 52 weeks (– 10.58 points [– 17.75, – 3.41]). At week 52, tezepelumab reduced blood eosinophil counts and FeNO, IgE, IL-5, IL-13, EDN and MMP-10 levels versus placebo, irrespective of NP status.Conclusion: Tezepelumab resulted in clinically meaningful improvements in sino-nasal symptoms and asthma outcomes in patients with severe asthma with comorbid NPs.Graphical Abstract: Plain Language Summary: Asthma is a long-term condition caused by ongoing inflammation of the lower airways. The main symptoms are difficulty breathing, coughing, wheezing and shortness of breath. Approximately 41% of patients with severe asthma also have chronic rhinosinusitis with nasal polyps, a condition that affects the upper airways and sinuses. Nasal polyps are painless soft growths inside your nose that can keep growing if not treated. Symptoms include nasal congestion with mucus, facial pain and a reduced sense of smell or taste. People with both severe asthma and nasal polyps often have severe symptoms.Thymic stromal lymphopoietin (TSLP) is a signaling molecule released by cells lining the airways in response to airborne triggers, such as smoke, pollen and viruses. TSLP activates several pathways that cause inflammation in the airways, leading to asthma symptoms. Tezepelumab is a biologic treatment that targets the very start of these inflammatory pathways by blocking TSLP.The 1-year-long clinical trial called “NAVIGATOR” reported that tezepelumab reduced asthma attacks and improved lung function and asthma symptom control compared with placebo in patients with severe asthma that was not controlled with their current medicines. This analysis of data from NAVIGATOR looked at patients with both severe asthma and nasal polyps, showing that tezepelumab treatment improved sino-nasal symptoms compared with placebo. Tezepelumab also reduced asthma attacks and improved asthma symptoms, regardless of a patient’s medical history of nasal polyps. The effects of tezepelumab in patients with severe nasal polyps are being investigated in another clinical trial called “WAYPOINT”.Keywords: chronic rhinosinusitis, nasal polyps, SNOT-22, thymic stromal lymphopoietin

Reports on the effect of mismatch strain on energy band in III-IV alloy semiconductors. Benefits of III-IV compound semiconductors; Epilayers used in the study.

Piperaquine (PQ) is an antimalarial drug that is highly protein-bound. Variation in plasma protein contents may affect the pharmacokinetic (PK) exposure of unbound drug, leading to alteration of clinical outcomes. All published methods for determination of PQ in human plasma measure the total PQ including both bound and unbound PQ to plasma proteins. There is no published method for unbound PQ determination. Here we report an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for determination of PQ in human plasma filtrate prepared by filtering human plasma through Millipore Microcon® centrifugal filters (10k NMWL). The filter cup had to be treated with 5% benzalkonium chloride to reduce non-specific binding to the filter devices before filtration of plasma samples. Multiple reactions monitoring (MRM) of the ion pairs m/z 535/288 for PQ and m/z 541/294 for the internal standard (IS) was selected for quantification. When electrospray ionization (ESI+) was used, paradoxical matrix effect was observed despite the structure similarity of the deuterated IS: Ion suppression for PQ versus ion enhancement for the PQ-d6, even though they were closely eluted: 0.62 min versus 0.61 min. Separation was achieved on Evo C18 column (50 × 2.1 mm, 1.7 μm, Phenomenex Inc.) eluted with 10 mM NH4OH and MeCN. When atmospheric pressure chemical ionization in positive mode (APCI+) was used for ion source, matrix effect diminished. Separation was achieved on a PFP column (30 × 2.1 mm, 1.7 μm, Waters, Corp.) eluted with aqueous 20 mM ammonium formate 0.14% trifluoroacetic acid (A) and methanol-acetonitrile (4:1, v/v) containing 0.1% trifluoroacetic acid (B) at 0.8 mL/min flow rate in a gradient mode: 30–30–80–80–30–30%B (0–0.1–1.0–1.40–1.41–1.50 min). The retention time was 0.67 min for both PQ and the IS. The method was validated with a linear calibration range from 20 to 5,000 pg/mL and applied to clinical samples.

BackgroundHydroxychloroquine (HCQ) and azithromycin (AZM) are antimalarial drugs recently reported to be active against severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2), which is causing the global COVID-19 pandemic. In an emergency response to the pandemic, we aimed to develop a quantitation method for HCQ, its metabolites desethylhydroxychloroquine (DHCQ) and bisdesethylchloroquine (BDCQ), and AZM in human plasma.MethodsLiquid chromatography tandem mass spectrometry was used to develop the method. Samples (20 μL) are extracted by solid-phase extraction and injected onto the LC-MS/MS system equipped with a PFP column (2.0 × 50 mm, 3 μm). ESI+ and MRM are used for detection. Ion pairs m/z 336.1→247.1 for HCQ, 308.1→179.1 for DHCQ, 264.1→179.1 for BDCQ, and 749.6→591.6 for AZM are selected for quantification. The ion pairs m/z 342.1→253.1, 314.1→181.1, 270.1→181.1, and 754.6→596.6 are selected for the corresponding deuterated internal standards (IS) HCQ-d4, DHCQ-d4, BDCQ-d4, and AZM-d5. The less abundant IS ions from 37Cl were used to overcome the interference from the analytes.ResultsUnder optimized conditions, retention times are 0.78 min for BDCQ, 0.79 min for DHCQ, 0.92 min for HCQ and 1.87 min for AZM. Total run time is 3.5 min per sample. The calibration ranges are 2-1000 ng/mL for HCQ and AZM, 1-500 ng/mL for DHCQ and 0.5-250 ng/mL for BDCQ; samples above the range are validated for up to 10-fold dilution. Recoveries of the method ranged from 88.9-94.4% for HCQ, 88.6-92.9% for DHCQ, 88.7-90.9% for BDCQ, and 98.6%-102% for AZM. The IS normalized matrix effect were within (100±10) % for all 4 analytes. Blood samples are stable for at least 6 hr at room temperature. Plasma samples are stable for at least 66 hr at room temperature, 38 days at -70°C, and 4 freeze-thaw cycles.ConclusionsAn LC-MS/MS method for simultaneous quantitation of HCQ, DHCQ, BDCQ, and AZM in human plasma was developed and validated for clinical studies requiring fast turnaround time and small samples volume.

To determine the origin of influenza A virus (H5N1) epizootics in Cambodia, we used maximum-likelihood and Bayesian methods to analyze the genetic sequences of subtype H5N1 strains from Cambodia and neighboring areas. Poultry movements, rather than repeated reintroduction of subtype H5N1 viruses by wild birds, appear to explain virus circulation and perpetuation. [ABSTRACT FROM AUTHOR]

BACKGROUND: We conducted investigations in 2 villages in Cambodia where outbreaks of influenza H5N1 occurred among humans and poultry to determine the frequency of and risk factors for H5N1 virus transmission. METHODS: During May 2006, approximately 7 weeks after outbreaks of influenza H5N1 among poultry occurred, villagers living near households of 2 patients with influenza H5N1 were interviewed about potential H5N1 exposures and had blood samples obtained for H5N1 serological testing by microneutralization assay. A seropositive result was defined as an influenza H5N1 neutralizing antibody titer of 1:80, with confirmation by Western blot assay. A case-control study was conducted to identify risk factors for influenza H5N1 virus infection. Control subjects, who had seronegative results of tests, were matched with H5N1-seropositive persons by village residence, households with an influenza H5N1-infected poultry flock, sex, and age. RESULTS: Seven (1.0%) of 674 villagers tested seropositive for influenza H5N1 antibodies and did not report severe illness; 6 (85.7%) were male. The 7 H5N1-seropositive persons, all of whom were aged

To determine potential risk for bird-to-human transmission during influenza A virus (H5N1) outbreaks among backyard poultry in rural Cambodia, we collected environmental specimens. Viral RNA was detected in 27 (35%) of 77 specimens of mud, pond water, water plants, and soil swabs. Our results underscore the need for regular disinfection of poultry areas. [ABSTRACT FROM AUTHOR]

Abstract Background Poultry represents an important sector in animal production, with backyard flocks representing a huge majority, especially in the developing countries. In these countries, villagers raise poultry to meet household food demands and as additional sources of incomes. Backyard production methods imply low biosecurity measures and high risk of infectious diseases, such as Newcastle disease or zoonosis such as Highly Pathogenic Avian Influenza (HPAI). We reviewed literature on biosecurity practices for prevention of infectious diseases, and published recommendations for backyard poultry and assessed evidence of their impact and feasibility, particularly in developing countries. Documents were sourced from the Food and Agriculture Organization (FAO) website, and from Pubmed and Google databases. Results A total of 62 peer-reviewed and non-referred documents were found, most of which were published recently (after 2004) and focused on HPAI/H5N1-related biosecurity measures (64%). Recommendations addressed measures for flock management, feed and water management, poultry trade and stock change, poultry health management and the risk to humans. Only one general guideline was found for backyard poultry-related biosecurity; the other documents were drawn up for specific developing settings and only engaged their authors (e.g. consultants). These national guidelines written by consultants generated recommendations regarding measures derived from the highest standards of commercial poultry production. Although biosecurity principles of isolation and containment are described in most documents, only a few documents were found on the impact of measures in family poultry settings and none gave any evidence of their feasibility and effectiveness for backyard poultry. Conclusions Given the persistent threat posed by HPAI/H5N1 to humans in developing countries, our findings highlight the importance of encouraging applied research toward identifying sustained and adapted biosecurity measures for smallholder poultry flocks in low-income countries.

Abstract Background In many Asian countries, Klebsiella pneumoniae (KP) is the second pathogen responsible for community-acquired pneumonia. Yet, very little is known about KP etiology in ALRI in Cambodia, a country that has one of the weakest medical infrastructures in the region. We present here the first clinico-radiological description of KP community-acquired ALRI in hospitalized Cambodian patients. Methods Through ALRI surveillance in two provincial hospitals, KP was isolated from sputum and blood cultures, and identified by API20E gallery from patients ≥ 5 years-old with fever and respiratory symptoms onset ≤14 days. Antibiotics susceptibility testing was provided systematically to clinicians when bacteria were isolated. We collected patients' clinical, radiological and microbiological data and their outcome 3 months after discharge. We also compared KP-related with other bacteria-related ALRI to determine risk factors for KP infection. Results From April 2007 to December 2009, 2315 ALRI patients ≥ 5 years-old were enrolled including 587 whose bacterial etiology could be assigned. Of these, 47 (8.0%) had KP infection; their median age was 55 years and 68.1% were females. Reported prior medication was high (42.5%). Patients' chest radiographs showed pneumonia (61.3% including 39% that were necrotizing), preexisting parenchyma lesions (29.5%) and pleural effusions alone (4.5%) and normal parenchyma (4.5%). Five patients had severe conditions on admission and one patient died during hospitalization. Of the 39 patients that were hospital discharged, 14 died including 12 within 1 month after discharge. Only 13 patients (28%) received an appropriate antibiotherapy. Extended-spectrum beta-lactamases (ESBL) - producing strains were found in 8 (17.0%) patients. Female gender (Odds ratio (OR) 2.1; p = 0.04) and diabetes mellitus (OR 3.1; p = 0.03) were independent risk factors for KP-related ALRI. Conclusions KP ALRI in Cambodia has high fatality rate, are more frequently found in women, and should be considered in diabetic patients. The extremely high frequency of ESBL-producing strains in the study is alarming in the context of uncontrolled antibiotic consumption and in absence of microbiology capacity in most public-sector hospitals.

Abstract Background Melioidosis is a disease caused by Burkholderia pseudomallei and considered endemic in South-East Asia but remains poorly documented in Cambodia. We report the first series of hospitalized pulmonary melioidosis cases identified in Cambodia describing clinical characteristics and outcomes. Methods We characterized cases of acute lower respiratory infections (ALRI) that were identified through surveillance in two provincial hospitals. Severity was defined by systolic blood pressure, cardiac frequency, respiratory rate, oxygen saturation and body temperature. B. pseudomallei was detected in sputum or blood cultures and confirmed by API20NE gallery. We followed up these cases between 6 months and 2 years after hospital discharge to assess the cost-of-illness and long-term outcome. Results During April 2007 - January 2010, 39 ALRI cases had melioidosis, of which three aged ≤2 years; the median age was 46 years and 56.4% were males. A close contact with soil and water was identified in 30 patients (76.9%). Pneumonia was the main radiological feature (82.3%). Eleven patients were severe cases. Twenty-four (61.5%) patients died including 13 who died within 61 days after discharge. Of the deceased, 23 did not receive any antibiotics effective against B. pseudomallei. Effective drugs that were available did not include ceftazidime. Mean total illness-related costs was of US$65 (range $25-$5000). Almost two-thirds (61.5%) incurred debt and 28.2% sold land or other belongings to pay illness-related costs. Conclusions The observed high fatality rate is likely explained by the lack or limited access to efficient antibiotics and under-recognition of the disease among clinicians, which led to inappropriate therapy.

Abstract Background The frequency of bloodborne pathogen healthcare-associated infections is thought to be high in developing Southeast Asian Countries. The underlying social-cultural logics contributing to the risks of transmission are rarely studied. This report provides some insights on the social and cultural factors that shape hygiene practices in Cambodian health care settings. Methods We conducted qualitative surveys in various public and private health facilities in Phnom Penh, the capital city and in provinces. We observed and interviewed 319 participants, health care workers and patients, regarding hygiene practices and social relationships amongst the health care staff and with patients. We also examined the local perceptions of hygiene, their impact on the relationships between the health care staff and patients, and perceptions of transmission risks. Data collection stem from face to face semi-structured and open-ended interviews and focus group discussions with various health care staffs (i.e. cleaners, nurses, midwives and medical doctors) and with patients who attended the study health facilities. Results Overall responses and observations indicated that hygiene practices were burdened by the lack of adequate materials and equipements. In addition, many other factors were identified to influence and distort hygiene practices which include (1) informal and formal social rapports in hospitals, (2) major infection control roles played by the cleaners in absence of professional acknowledgment. Moreover, hygiene practices are commonly seen as an unessential matter to be devoted to low-ranking staff. Conclusion Our anthropological findings illustrate the importance of comprehensive understanding of hygiene practices; they need to be considered when designing interventions to improve infection control practices in a Cambodian medical setting.

Abstract Background Dengue is endemic in Cambodia (pop. estimates 14.4 million), a country with poor health and economic indicators. Disease burden estimates help decision makers in setting priorities. Using recent estimates of dengue incidence in Cambodia, we estimated the cost of dengue and its burden using disability adjusted life years (DALYs). Methods Recent population-based cohort data were used to calculate direct and productive costs, and DALYs. Health seeking behaviors were taken into account in cost estimates. Specific age group incidence estimates were used in DALYs calculation. Results The mean cost per dengue case varied from US$36 - $75 over 2006-2008 respectively, resulting in an overall annual cost from US$3,327,284 in 2008 to US$14,429,513 during a large epidemic in 2007. Patients sustain the highest share of costs by paying an average of 78% of total costs and 63% of direct medical costs. DALY rates per 100,000 individuals ranged from 24.3 to 100.6 in 2007-2008 with 80% on average due to premature mortality. Conclusion Our analysis confirmed the high societal and individual family burden of dengue. Total costs represented between 0.03 and 0.17% of Gross Domestic Product. Health seeking behavior has a major impact on costs. The more accurate estimate used in this study will better allow decision makers to account for dengue costs particularly among the poor when balancing the benefits of introducing a potentially effective dengue vaccine.

Abstract Background There is little information about influenza disease among the Cambodian population. To better understand the dynamics of influenza in Cambodia, the Cambodian National Influenza Center (NIC) was established in August 2006. To continuously monitor influenza activity, a hospital based sentinel surveillance system for ILI (influenza like illness) with a weekly reporting and sampling scheme was established in five sites in 2006. In addition, hospital based surveillance of acute lower respiratory infection (ALRI) cases was established in 2 sites. Methods The sentinel sites collect weekly epidemiological data on ILI patients fulfilling the case definition, and take naso-pharyngeal specimens from a defined number of cases per week. The samples are tested in the Virology Unit at the Institut Pasteur in Phnom Penh. From each sample viral RNA was extracted and amplified by a multiplex RT-PCR detecting simultaneously influenza A and influenza B virus. Influenza A viruses were then subtyped and analyzed by hemagglutination inhibition assay. Samples collected by the ALRI system were tested with the same approach. Results From 2006 to 2008, influenza circulation was observed mainly from June to December, with a clear seasonal peak in October shown in the data from 2008. Conclusion Influenza activity in Cambodia occurred during the rainy season, from June to December, and ended before the cool season (extending usually from December to February). Although Cambodia is a tropical country geographically located in the northern hemisphere, influenza activity has a southern hemisphere transmission pattern. Together with the antigenic analysis of the circulating strains, it is now possible to give better influenza vaccination recommendation for Cambodia.

Abstract Background The average annual reported dengue incidence in Cambodia is 3.3/1,000 among children < 15 years of age (2002–2007). To estimate the economic burden of dengue, accurate cost-of-illness data are essential. We conducted a prospective, community-based, matched case-control study to assess the cost and impact of an episode of dengue fever and other febrile illness on households in rural Cambodia. Methods In 2006, active fever surveillance was conducted among a cohort of 6,694 children aged ≤ 15 years in 16 villages in Kampong Cham province, Cambodia. Subsequently, a case-control study was performed by individually assigning one non-dengue febrile control from the cohort to each laboratory-confirmed dengue case. Parents of cases and controls were interviewed using a standardized questionnaire to determine household-level, illness-related expenditures for medical and non-medical costs, and estimated income loss (see Additional file 1). The household socio-economic status was determined and its possible association with health seeking behaviour and the ability to pay for the costs of a febrile illness. Additional File 1 2006 cost study survey questionnaire, Cambodia. the questionnaire represents the data collection instrument that was developed and used during the present study. Click here for file Results Between September and November 2006, a total of 60 household heads were interviewed: 30 with dengue-positive and 30 with dengue-negative febrile children. Mean total dengue-related costs did not differ from those of other febrile illnesses (31.5 vs. 27.2 US$, p = 0.44). Hospitalization almost tripled the costs of dengue (from 14.3 to 40.1 US$) and doubled the costs of other febrile illnesses (from 17.0 to 36.2 US$). To finance the cost of a febrile illness, 67% of households incurred an average debt of 23.5 US$ and higher debt was associated with hospitalization compared to outpatient treatment (US$ 23.1 vs. US$ 4.5, p < 0.001). These costs compared to an average one-week expenditure on food of US$ 9.5 per household (range 2.5–21.3). In multivariate analysis, higher socio-economic status (odds ratio [OR] 4.4; 95% confidence interval [CI] 1.4–13.2), duration of fever (OR 2.1; 95%CI 1.3–3.5), and age (OR 0.8; 95%CI 0.7–0.9) were independently associated with hospitalization. Conclusion In Cambodia, dengue and other febrile illnesses pose a financial burden to households. A possible reason for a lower rate of hospitalization among children from poor households could be the burden of higher illness-related costs and debts.

Abstract Background In Cambodia, estimates of the malaria burden rely on a public health information system that does not record cases occurring among remote populations, neither malaria cases treated in the private sector nor asymptomatic carriers. A global estimate of the current malaria situation and associated risk factors is, therefore, still lacking. Methods A large cross-sectional survey was carried out in three areas of multidrug resistant malaria in Cambodia, enrolling 11,652 individuals. Fever and splenomegaly were recorded. Malaria prevalence, parasite densities and spatial distribution of infection were determined to identify parasitological profiles and the associated risk factors useful for improving malaria control programmes in the country. Results Malaria prevalence was 3.0%, 7.0% and 12.3% in Sampovloun, Koh Kong and Preah Vihear areas. Prevalences and Plasmodium species were heterogeneously distributed, with higher Plasmodium vivax rates in areas of low transmission. Malaria-attributable fevers accounted only for 10–33% of malaria cases, and 23–33% of parasite carriers were febrile. Multivariate multilevel regression analysis identified adults and males, mostly involved in forest activities, as high risk groups in Sampovloun, with additional risks for children in forest-fringe villages in the other areas along with an increased risk with distance from health facilities. Conclusion These observations point to a more complex malaria situation than suspected from official reports. A large asymptomatic reservoir was observed. The rates of P. vivax infections were higher than recorded in several areas. In remote areas, malaria prevalence was high. This indicates that additional health facilities should be implemented in areas at higher risk, such as remote rural and forested parts of the country, which are not adequately served by health services. Precise malaria risk mapping all over the country is needed to assess the extensive geographical heterogeneity of malaria endemicity and risk populations, so that current malaria control measures can be reinforced accordingly.

Abstract Background Injection overuse and unsafe injection practices facilitate transmission of bloodborne pathogens such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Anecdotal reports of unsafe and unnecessary therapeutic injections and the high prevalence of HBV (8.0%), HCV (6.5%), and HIV (2.6%) infection in Cambodia have raised concern over injection safety. To estimate the magnitude and patterns of such practices, a rapid assessment of injection practices was conducted. Methods We surveyed a random sample of the general population in Takeo Province and convenience samples of prescribers and injection providers in Takeo Province and Phnom Penh city regarding injection-related knowledge, attitudes, and practices. Injection providers were observed administering injections. Data were collected using standardized methods adapted from the World Health Organization safe injection assessment guidelines. Results Among the general population sample (n = 500), the overall injection rate was 5.9 injections per person-year, with 40% of participants reporting receipt of ≥ 1 injection during the previous 6 months. Therapeutic injections, intravenous infusions, and immunizations accounted for 74%, 16% and 10% of injections, respectively. The majority (>85%) of injections were received in the private sector. All participants who recalled their last injection reported the injection was administered with a newly opened disposable syringe and needle. Prescribers (n = 60) reported that 47% of the total prescriptions they wrote included a therapeutic injection or infusion. Among injection providers (n = 60), 58% recapped the syringe after use and 13% did not dispose of the used needle and syringe appropriately. Over half (53%) of the providers reported a needlestick injury during the previous 12 months. Ninety percent of prescribers and injection providers were aware HBV, HCV, and HIV were transmitted through unsafe injection practices. Knowledge of HIV transmission through "dirty" syringes among the general population was also high (95%). Conclusion Our data suggest that Cambodia has one of the world's highest rates of overall injection usage, despite general awareness of associated infection risks. Although there was little evidence of reuse of needles and syringes, support is needed for interventions to address injection overuse, healthcare worker safety and appropriate waste disposal.

Objective: Dengue has been reportable in Cambodia since 1980. Virological surveillance began in 2000 and sentinel surveillance was established at six hospitals in 2001. Currently, national surveillance comprises passive and active data collection and reporting on hospitalized children aged 0-15 years. This report summarizes surveillance data collected since 1980. Methods: Crude data for 1980-2001 are presented, while data from 2002-2008 are used to describe disease trends and the effect of vector control interventions. Trends in dengue incidence were analysed using the Prais-Winsten generalized linear regression model for time series. Findings: During 1980-2001, epidemics occurred in cycles of 3-4 years, with the cycles subsequently becoming less prominent. For 2002-2008 data, linear regression analysis detected no significant trend in the annual reported age-adjusted incidence of dengue (incidence range: 0.7-3.0 per 1000 population). The incidence declined in 2.7% of the 185 districts studied, was unchanged in 86.2% and increased in 9.6%. The age-specific incidence was highest in infants aged < 1 year and children aged 4-6 years. The incidence was higher during rainy seasons. All four dengue virus (DENV) serotypes were permanently in circulation, though the predominant serotype has alternated between DENV-3 and DENV-2 since 2000. Although larvicide has been distributed in 94 districts since 2002, logistic regression analysis showed no association between the intervention and dengue incidence. Conclusion: The dengue burden remained high among young children in Cambodia, which reflects intense transmission. The national vector control programme appeared to have little impact on disease incidence. Copyright © 20010 World Health Organization [ABSTRACT FROM AUTHOR]