Epidemiological, clinical, and public health response characteristics of a large outbreak of diphtheria among the Rohingya population in Cox's Bazar, Bangladesh, 2017 to 2019: A retrospective study.

BACKGROUND: Unrest in Myanmar in August 2017 resulted in the movement of over 700,000 Rohingya refugees to overcrowded camps in Cox's Bazar, Bangladesh. A large outbreak of diphtheria subsequently began in this population. METHODS AND FINDINGS: Data were collected during mass vaccination campaigns (MVCs), contact tracing activities, and from 9 Diphtheria Treatment Centers (DTCs) operated by national and international organizations. These data were used to describe the epidemiological and clinical features and the control measures to prevent transmission, during the first 2 years of the outbreak. Between November 10, 2017 and November 9, 2019, 7,064 cases were reported: 285 (4.0%) laboratory-confirmed, 3,610 (51.1%) probable, and 3,169 (44.9%) suspected cases. The crude attack rate was 51.5 cases per 10,000 person-years, and epidemic doubling time was 4.4 days (95% confidence interval [CI] 4.2-4.7) during the exponential growth phase. The median age was 10 years (range 0-85), and 3,126 (44.3%) were male. The typical symptoms were sore throat (93.5%), fever (86.0%), pseudomembrane (34.7%), and gross cervical lymphadenopathy (GCL; 30.6%). Diphtheria antitoxin (DAT) was administered to 1,062 (89.0%) out of 1,193 eligible patients, with adverse reactions following among 229 (21.6%). There were 45 deaths (case fatality ratio [CFR] 0.6%). Household contacts for 5,702 (80.7%) of 7,064 cases were successfully traced. A total of 41,452 contacts were identified, of whom 40,364 (97.4%) consented to begin chemoprophylaxis; adherence was 55.0% (N = 22,218) at 3-day follow-up. Unvaccinated household contacts were vaccinated with 3 doses (with 4-week interval), while a booster dose was administered if the primary vaccination schedule had been completed. The proportion of contacts vaccinated was 64.7% overall. Three MVC rounds were conducted, with administrative coverage varying between 88.5% and 110.4%. Pentavalent vaccine was administered to those aged 6 weeks to 6 years, while tetanus and diphtheria (Td) vaccine was administered to those aged 7 years and older. Lack of adequate diagnostic capacity to confirm cases was the main limitation, with a majority of cases unconfirmed and the proportion of true diphtheria cases unknown. CONCLUSIONS: To our knowledge, this is the largest reported diphtheria outbreak in refugee settings. We observed that high population density, poor living conditions, and fast growth rate were associated with explosive expansion of the outbreak during the initial exponential growth phase. Three rounds of mass vaccinations targeting those aged 6 weeks to 14 years were associated with only modestly reduced transmission, and additional public health measures were necessary to end the outbreak. This outbreak has a long-lasting tail, with Rt oscillating at around 1 for an extended period. An adequate global DAT stockpile needs to be maintained. All populations must have access to health services and routine vaccination, and this access must be maintained during humanitarian crises.

A One-Health Quantitative Model to Assess the Risk of Antibiotic Resistance Acquisition in Asian Populations: Impact of Exposure Through Food, Water, Livestock and Humans.

Antimicrobial resistance (AMR) has become a major threat worldwide, especially in countries with inadequate sanitation and low antibiotic regulation. However, adequately prioritizing AMR interventions in such settings requires a quantification of the relative impacts of environmental, animal, and human sources in a One-Health perspective. Here, we propose a stochastic quantitative risk assessment model for the different components at interplay in AMR selection and spread. The model computes the incidence of AMR colonization in humans from five different sources: water or food consumption, contacts with livestock, and interhuman contacts in hospitals or the community, and combines these incidences into a per-year acquisition risk. Using data from the literature and Monte-Carlo simulations, we apply the model to hypothetical Asian-like settings, focusing on resistant bacteria that may cause infections in humans. In both scenarios A, illustrative of low-income countries, and B, illustrative of high-income countries, the overall individual risk of becoming colonized with resistant bacteria at least once per year is high. However, the average predicted incidence of colonization was lower in scenario B at 0.82 (CrI [0.13, 5.1]) acquisitions/person/year, versus 1.69 (CrI [0.66, 11.13]) acquisitions/person/year for scenario A. A high percentage of population with no access to improved water on premises and a high percentage of population involved in husbandry are shown to strongly increase the AMR acquisition risk. The One-Health AMR risk assessment framework we developed may prove useful to policymakers throughout Asia, as it can easily be parameterized to realistically reproduce conditions in a given country, provided data are available.

Seroprevalence and Transmission of Human Influenza A(H5N1) Virus before and after Virus Reassortment, Cambodia, 2006-2014.

Thirty-five human influenza A(H5N1) cases were reported in Cambodia during 2013-2014 after emergence of a clade 1.1.2 reassortant virus. We tested 881 villagers and found 2 cases of pauci- or asymptomatic infection. Seroprevalence after emergence of the reassortant strain (0.2%) was lower than the aggregate seroprevalence of 1.3% reported in earlier studies.

Assessment of Ebola virus disease preparedness in the WHO South-East Asia Region.

OBJECTIVE: To conduct assessments of Ebola virus disease preparedness in countries of the World Health Organization (WHO) South-East Asia Region. METHODS: Nine of 11 countries in the region agreed to be assessed. During February to November 2015 a joint team from WHO and ministries of health conducted 4-5 day missions to Bangladesh, Bhutan, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand and Timor-Leste. We collected information through guided discussions with senior technical leaders and visits to hospitals, laboratories and airports. We assessed each country's Ebola virus disease preparedness on 41 tasks under nine key components adapted from the WHO Ebola preparedness checklist of January 2015. FINDINGS: Political commitment to Ebola preparedness was high in all countries. Planning was most advanced for components that had been previously planned or tested for influenza pandemics: multilevel and multisectoral coordination; multidisciplinary rapid response teams; public communication and social mobilization; drills in international airports; and training on personal protective equipment. Major vulnerabilities included inadequate risk assessment and risk communication; gaps in data management and analysis for event surveillance; and limited capacity in molecular diagnostic techniques. Many countries had limited planning for a surge of Ebola cases. Other tasks needing improvement included: advice to inbound travellers; adequate isolation rooms; appropriate infection control practices; triage systems in hospitals; laboratory diagnostic capacity; contact tracing; and danger pay to staff to ensure continuity of care. CONCLUSION: Joint assessment and feedback about the functionality of Ebola virus preparedness systems help countries strengthen their core capacities to meet the International Health Regulations.

Environmental contamination and risk factors for transmission of highly pathogenic avian influenza A(H5N1) to humans, Cambodia, 2006-2010.

BACKGROUND: Highly pathogenic avian influenza A (H5N1) virus has been of public health concern since 2003. Probable risk factors for A(H5N1) transmission to human have been demonstrated in several studies or epidemiological reports. However, transmission patterns may differ according to demographic characteristics of the population and local practices. This article aggregates these data from three studies with data collected in the previous surveys in 2006 and 2007 to further examine the risks factors associated with presence of anti-A(H5) antibodies among villagers residing within outbreak areas. METHODS: We aggregated 5-year data (2006-2010) from serology survey and matched case-control studies in Cambodia to further examine the risks factors associated with A(H5N1) infection among villagers in the outbreak areas. RESULTS: Serotesting among villagers detected 35 (1.5 % [0-2.6]) positive cases suggesting recent exposure to A(H5N1) virus. Practices associated with A(H5N1) infection among all ages were: having poultry cage or nesting area under or adjacent to the house (OR: 6.7 [1.6-28.3]; p = 0.010) and transporting poultry to market (OR: 17.6 [1.6-193.7]; p = 0.019). Practices found as risk factors for the infection among age under 20 years were swimming/bathing in ponds also accessed by domestic poultry (OR: 4.6 [1.1-19.1]; p = 0.038). Association with consuming wild birds reached borderline significance (p = 0.066). CONCLUSION: Our results suggest that swimming/bathing in contaminated pond water and close contact with poultry may present a risk of A(H5N1) transmission to human.

Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis.

BACKGROUND: Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy. METHODS: We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival. RESULTS: A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log(10) copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P=0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients. CONCLUSIONS: Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health; CAMELIA ClinicalTrials.gov number, NCT01300481.).

Early response to the emergence of influenza A(H7N9) virus in humans in China: the central role of prompt information sharing and public communication.

PROBLEM: In 2003, China's handling of the early stages of the epidemic of severe acute respiratory syndrome (SARS) was heavily criticized and generally considered to be suboptimal. APPROACH: Following the SARS outbreak, China made huge investments to improve surveillance, emergency preparedness and response capacity and strengthen public health institutions. In 2013, the return on these investments was evaluated by investigating China's early response to the emergence of avian influenza A(H7N9) virus in humans. LOCAL SETTING: Clusters of human infection with a novel influenza virus were detected in China - by national surveillance of pneumonia of unknown etiology - on 26 February 2013. RELEVANT CHANGES: On 31 March 2013, China notified the World Health Organization (WHO) of the first recorded human infections with A(H7N9) virus. Poultry markets - which were rapidly identified as a major source of transmission of A(H7N9) to humans - were closed down in the affected areas. Surveillance in humans and poultry was heightened and technical guidelines were quickly updated and disseminated. The health authorities collaborated with WHO in risk assessments and risk communication. New cases were reported promptly and publicly. LESSONS LEARNT: The relevant infrastructures, surveillance systems and response capacity need to be strengthened in preparation for future emergencies caused by emerging or existing disease threats. Results of risk assessments and other data should be released promptly and publicly and such release should not jeopardize future publication of the data in scientific journals. Coordination between public health and veterinary services would be stronger during an emergency if these services had already undertaken joint preparedness planning.

Acute lower respiratory infections in ≥ 5 year -old hospitalized patients in Cambodia, a low-income tropical country: clinical characteristics and pathogenic etiology.

BACKGROUND: Few data exist on viral and bacterial etiology of acute lower respiratory infections (ALRI) in ≥ 5 year -old persons in the tropics. METHODS: We conducted active surveillance of community-acquired ALRI in two hospitals in Cambodia, a low-income tropical country. Patients were tested for acid-fast bacilli (AFB) by direct sputum examination, other bacteria by blood and/or sputum cultures, and respiratory viruses using molecular techniques on nasopharyngeal/throat swabs. Pulmonologists reviewed clinical/laboratory data and interpreted chest X-rays (CXR) to confirm ALRI. RESULTS: Between April 2007 - December 2009, 1,904 patients aged ≥5 years were admitted with acute pneumonia (50.4%), lung sequelae-associated ALRI (24.3%), isolated pleural effusions (8.9%) or normal CXR-related ALRI (17.1%); 61 (3.2%) died during hospitalization. The two former diagnoses were predominantly due to bacterial etiologies while viral detection was more frequent in the two latter diagnoses. AFB-positive accounted for 25.6% of acute pneumonia. Of the positive cultures (16.8%), abscess-prone Gram-negative bacteria (39.6%) and Haemophilus influenzae (38.0%) were most frequent, followed by Streptococcus pneumoniae (17.7%). Of the identified viruses, the three most common viruses included rhinoviruses (49.5%), respiratory syncytial virus (17.7%) and influenza viruses (12.1%) regardless of the diagnostic groups. Wheezing was associated with viral identification (31.9% vs. 13.8%, p < 0.001) independent of age and time-to-admission. CONCLUSIONS: High frequency of H. influenzae and S. pneumoniae infections support the need for introduction of the respective vaccines in the national immunization program. Tuberculosis was frequent in patients with acute pneumonia, requiring further investigation. The relationship between respiratory viruses and wheezing merits further studies.

Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis.

BACKGROUND: The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years. METHODS: We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality. FINDINGS: We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49-162 million) new cases of influenza (data from nine studies), 20 million (13-32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1-2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28,000-111,500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting. INTERPRETATION: Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available. FUNDING: WHO; Bill & Melinda Gates Foundation.

Klebsiella pneumoniae related community-acquired acute lower respiratory infections in Cambodia: clinical characteristics and treatment.

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.

Biosecurity measures for backyard poultry in developing countries: a systematic review.

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.

Contact tracing indicators for COVID-19: Rapid scoping review and conceptual framework.

BACKGROUND: Contact tracing is one of the key interventions in response to the COVID-19 pandemic but its implementation varies widely across countries. There is little guidance on how to monitor contact tracing performance, and no systematic overview of indicators to assess contact tracing systems or conceptual framework for such indicators exists to date. METHODS: We conducted a rapid scoping review using a systematic literature search strategy in the peer-reviewed and grey literature as well as open source online documents. We developed a conceptual framework to map indicators by type (input, process, output, outcome, impact) and thematic area (human resources, financial resources, case investigation, contact identification, contact testing, contact follow up, case isolation, contact quarantine, transmission chain interruption, incidence reduction). RESULTS: We identified a total of 153 contact tracing indicators from 1,555 peer-reviewed studies, 894 studies from grey literature sources, and 15 sources from internet searches. Two-thirds of indicators were process indicators (102; 67%), while 48 (31%) indicators were output indicators. Only three (2%) indicators were input indicators. Indicators covered seven out of ten conceptualized thematic areas, with more than half being related to either case investigation (37; 24%) or contact identification (44; 29%). There were no indicators for the input area "financial resources", the outcome area "transmission chain interruption", and the impact area "incidence reduction". CONCLUSIONS: Almost all identified indicators were either process or output indicators focusing on case investigation, contact identification, case isolation or contact quarantine. We identified important gaps in input, outcome and impact indicators, which constrains evidence-based assessment of contact tracing systems. A universally agreed set of indicators is needed to allow for cross-system comparisons and to improve the performance of contact tracing systems.

A study of the genetic variability of human respiratory syncytial virus (HRSV) in Cambodia reveals the existence of a new HRSV group B genotype.

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.

Pulmonary melioidosis in Cambodia: a prospective study.

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.

Social and cultural dimensions of hygiene in Cambodian health care facilities.

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 equipment. 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.

Use of a multiplex PCR/RT-PCR approach to assess the viral causes of influenza-like illnesses in Cambodia during three consecutive dry seasons.

Acute respiratory infections are a major cause of mortality and morbidity worldwide. Using multiplex PCR/RT-PCR methods for the detection of 18 respiratory viruses, the circulation of those viruses during 3 consecutive dry seasons in Cambodia was described. Among 234 patients who presented with influenza-like illness, 35.5% were positive for at least one virus. Rhinoviruses (43.4%), parainfluenza (31.3%) viruses and coronaviruses (21.7%) were the most frequently detected viruses. Influenza A virus, parainfluenza virus 4 and SARS-coronavirus were not detected during the study period. Ninety apparently healthy individuals were included as controls and 10% of these samples tested positive for one or more respiratory viruses. No significant differences were observed in frequency and in virus copy numbers for rhinovirus detection between symptomatic and asymptomatic groups. This study raises questions about the significance of the detection of some respiratory viruses, especially using highly sensitive methods, given their presence in apparently healthy individuals. The link between the presence of the virus and the origin of the illness is therefore unclear.

National dengue surveillance in Cambodia 1980-2008: epidemiological and virological trends and the impact of vector control.

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.

Cost and disease burden of dengue in Cambodia.

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.

Monitoring COVID-19 where capacity for testing is limited: use of a three-step analysis based on test positivity ratio.

In an effort to monitor coronavirus disease 2019 (COVID-19), many countries have been calculating the ratio of cases confirmed to tests performed (test positivity ratio - TPR). While inferior to sentinel surveillance, TPR has the benefit of being easily calculated using readily available data; however, interpreting TPR and its trends can be complex because both the numerator and the denominator are constantly changing. We describe a three-step process where the ratio of relative increase in cases to relative increase in tests is accounted for in an adjusted TPR. This adjusted value more appropriately reflects the case number and factors out the effect of changes in the number of tests done. Unadjusted and adjusted TPRs are then assessed step-wise with reference to the epidemic curve and the cumulative numbers of cases and tests. Use of this three-step analysis and its potential use in guiding public health interventions are demonstrated for selected countries and subnational areas of the World Health Organization South-East Asia Region, together with the Republic of Korea as a reference. To date, application of the three-step analysis to data from countries of the region has signalled potential inadequacies of testing strategies. Further work is needed on approaches to support countries where testing capacity is likely to remain constrained. One example would be enumeration of the average number of tests needed to detect one COVID-19 case, which could be stratified by factors such as location and population. Such data would allow evidence-informed strategies that best balance the highest detection rate with the prevailing testing capacity.

Impact of vaccines on antimicrobial resistance.

DRIVERS OF ANTIMICROBIAL RESISTANCE: Antibiotic use drives the development and spread of resistant bacterial infections. Antimicrobial resistance (AMR) has become a prolific global issue, due to significant increases in antibiotic use in humans, livestock and agriculture, inappropriate use (under-dosing and over-prescribing), and misuse of antibiotics (for viral infections where they are ineffective). Fewer new antibiotics are being developed. THE PROBLEM OF AMR: AMR is now considered a key threat to global health, leading to more mortality and increased healthcare costs threatening future conduct of routine medical procedures. Traditional approaches to address AMR include antibiotic stewardship, better hygiene/infection control, promoting antibiotic research and development, and restricting use for agricultural purposes. VACCINES AS A TOOL TO REDUCE AMR: While antibiotic development is declining, vaccine technology is growing. This review shows how vaccines can decrease AMR by preventing bacterial and viral infections, thereby reducing the use/misuse of antibiotics, and by preventing antibiotic-resistant infections. Vaccines are less likely to induce resistance. Some future uses and developments of vaccines are also discussed. CONCLUSIONS: Vaccines, along with other approaches, can help reduce AMR by preventing (resistant) infections and reducing antibiotic use. Industry and governments must focus on the development of novel vaccines and drugs against resistant infections to successfully reduce AMR. A graphical abstract is available online.