Arnaud Tarantola

Infection risks following accidental exposure to blood or body fluids in health care workers: A review of pathogens transmitted in published cases

Hospital staff and all other human or veterinary health care workers, including laboratory, research, emergency service, or cleaning personnel are exposed to the risk of occupational infection following accidental exposure to blood or body fluids (BBF) contaminated with a virus, a bacteria, a parasite, or a yeast. The human immunodeficiency virus (HIV) or those of hepatitis B (HBV) or C (HCV) account for most of this risk in France and worldwide. Many other pathogens, however, have been responsible for occupational infections in health care workers following exposure to BBF, some with unfavorable prognosis. In developed countries, a growing number of workers are referred to clinicians responsible for the evaluation of occupational infection risks following accidental exposure. Although their principal task remains the evaluation of the risks of HIV, HBV, or HCV transmission and the possible usefulness of postexposure prophylaxis, these experts are also responsible for evaluating risks of occupational infection with other emergent or more rare pathogens and their possible timely prevention. The determinants of the risks of infection and the characteristics of described cases are discussed in this article.

Asymptomatic humans transmit dengue virus to mosquitoes

Significance Our work provides evidence that people who are infected with dengue virus without developing detectable clinical symptoms or prior to the onset of symptoms are infectious to mosquitoes. At a given level of viremia, symptom-free people were markedly more infectious to mosquitoes than clinically symptomatic patients. Our results fundamentally change the current paradigm for dengue epidemiology and control, based on detection of dengue virus-infected cases with apparent illness. Three-quarters of the estimated 390 million dengue virus (DENV) infections each year are clinically inapparent. People with inapparent dengue virus infections are generally considered dead-end hosts for transmission because they do not reach sufficiently high viremia levels to infect mosquitoes. Here, we show that, despite their lower average level of viremia, asymptomatic people can be infectious to mosquitoes. Moreover, at a given level of viremia, DENV-infected people with no detectable symptoms or before the onset of symptoms are significantly more infectious to mosquitoes than people with symptomatic infections. Because DENV viremic people without clinical symptoms may be exposed to more mosquitoes through their undisrupted daily routines than sick people and represent the bulk of DENV infections, our data indicate that they have the potential to contribute significantly more to virus transmission to mosquitoes than previously recognized.

Estimating the burden of Japanese encephalitis virus and other encephalitides in countries of the mekong region.

Diverse aetiologies of viral and bacterial encephalitis are widely recognized as significant yet neglected public health issues in the Mekong region. A robust analysis of the corresponding health burden is lacking. We retrieved 75 articles on encephalitis in the region published in English or in French from 1965 through 2011. Review of available data demonstrated that they are sparse and often derived from hospital-based studies with significant recruitment bias. Almost half (35 of 75) of articles were on Japanese encephalitis virus (JEV) alone or associated with dengue. In the Western Pacific region the WHO reported 30,000–50,000 annual JEV cases (15,000 deaths) between 1966 and 1996 and 4,633 cases (200 deaths) in 2008, a decline likely related to the introduction of JEV vaccination in China, Vietnam, or Thailand since the 1980s. Data on dengue, scrub typhus and rabies encephalitis, among other aetiologies, are also reviewed and discussed. Countries of the Mekong region are undergoing profound demographic, economic and ecological change. As the epidemiological aspects of Japanese encephalitis (JE) are transformed by vaccination in some countries, highly integrated expert collaborative research and objective data are needed to identify and prioritize the human health, animal health and economic burden due to JE and other pathogens associated with encephalitides.

Use of a Text Message-Based Pharmacovigilance Tool in Cambodia: Pilot Study

Background There is no functional pharmacovigilance system in Cambodia to our knowledge. Mobile phone–based tools, such as short message service (SMS) text messages, are increasingly used for surveillance purposes. Objective To pilot-test the FrontlineSMS mobile phone–based tool for notification of adverse events, using Cambodia’s only International Vaccination Center at the Institut Pasteur du Cambodge as a field site. Methods People receiving vaccinations, aged over 18 years, and who owned a cell phone were recruited in the study following informed consent. The names and mobile phone numbers of the participants interviewed were entered each day into the FrontlineSMS software. Two days after being vaccinated, participants received an automatically generated SMS text message asking whether any adverse events had occurred. Their SMS reply was number-coded and exported from the software daily to an Excel spreadsheet and examined before being saved. If the participant replied with a code for a severe adverse event (8 or 9), they were automatically advised to consult the nearest doctor. Results The active surveillance study was conducted over 72 days in the spring of 2012. Patients agreed to be asked by SMS text message whether unwanted events had occurred after vaccination. Of 1331 persons aged over 18 years referred to the vaccination unit, 184 (13.8%) were asked and agreed to participate. When texted for clinical status 48 hours after vaccination, 52 (28.3%) participants did not reply, 101 (54.9%) sent an immediate SMS reply, and 31 (16.8%) sent an SMS reply after additional prompting. Of the initial 184 participants, 132 (71.7%) replied. These 132 participants received 135 vaccine doses and 109 (82.6%) reported no adverse events, whereas 23 (17.4%) reported adverse events, all benign. Conclusions Notification using an SMS-based text message system is already used in Cambodia for syndromic surveillance in health centers and reporting by health care workers. Our results show that such tools can also be useful for notification by patients or health users in Cambodia, especially in an urban setting.

Value of Routine Dengue Diagnostic Tests in Urine and Saliva Specimens.

Background Dengue laboratory diagnosis is essentially based on detection of the virus, its components or antibodies directed against the virus in blood samples. Blood, however, may be difficult to draw in some patients, especially in children, and sampling during outbreak investigations or epidemiological studies may face logistical challenges or limited compliance to invasive procedures from subjects. The aim of this study was to assess the possibility of using saliva and urine samples instead of blood for dengue diagnosis. Methodology/Principal Findings Serial plasma, urine and saliva samples were collected at several time-points between the day of admission to hospital until three months after the onset of fever in children with confirmed dengue disease. Quantitative RT-PCR, NS1 antigen capture and ELISA serology for anti-DENV antibody (IgG, IgM and IgA) detection were performed in parallel on the three body fluids. RT-PCR and NS1 tests demonstrated an overall sensitivity of 85.4%/63.4%, 41.6%/14.5% and 39%/28.3%, in plasma, urine and saliva specimens, respectively. When urine and saliva samples were collected at the same time-points and tested concurrently, the diagnostic sensitivity of RNA and NS1 detection assays was 69.1% and 34.4%, respectively. IgG/IgA detection assays had an overall sensitivity of 54.4%/37.4%, 38.5%/26.8% and 52.9%/28.6% in plasma, urine and saliva specimens, respectively. IgM were detected in 38.1% and 36% of the plasma and saliva samples but never in urine. Conclusions Although the performances of the different diagnostic methods were not as good in saliva and urine as in plasma specimens, the results obtained by qRT-PCR and by anti-DENV antibody ELISA could well justify the use of these two body fluids to detect dengue infection in situations when the collection of blood specimens is not possible.

A Model for a Chikungunya Outbreak in a Rural Cambodian Setting: Implications for Disease Control in Uninfected Areas

Following almost 30 years of relative silence, chikungunya fever reemerged in Kenya in 2004. It subsequently spread to the islands of the Indian Ocean, reaching Southeast Asia in 2006. The virus was first detected in Cambodia in 2011 and a large outbreak occurred in the village of Trapeang Roka Kampong Speu Province in March 2012, in which 44% of the villagers had a recent infection biologically confirmed. The epidemic curve was constructed from the number of biologically-confirmed CHIKV cases per day determined from the date of fever onset, which was self-reported during a data collection campaign conducted in the village after the outbreak. All individuals participating in the campaign had infections confirmed by laboratory analysis, allowing for the identification of asymptomatic cases and those with an unreported date of fever onset. We develop a stochastic model explicitly including such cases, all of whom do not appear on the epidemic curve. We estimate the basic reproduction number of the outbreak to be 6.46 (95% C.I. [6.24, 6.78]). We show that this estimate is particularly sensitive to changes in the biting rate and mosquito longevity. Our model also indicates that the infection was more widespread within the population on the reported epidemic start date. We show that the exclusion of asymptomatic cases and cases with undocumented onset dates can lead to an underestimation of the reproduction number which, in turn, could negatively impact control strategies implemented by public health authorities. We highlight the need for properly documenting newly emerging pathogens in immunologically naive populations and the importance of identifying the route of disease introduction.

Identification of Molecular Markers Associated with Alteration of Receptor-Binding Specificity in a Novel Genotype of Highly Pathogenic Avian Influenza A(H5N1) Viruses Detected in Cambodia in 2013

ABSTRACT Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L). Discovery of quasispecies at position 222 (Q/L), in addition to the absence of the mutations in poultry/environmental samples, suggested that the mutations occurred during human infection and did not transmit further.

Performance of Xpert MTB/RIF and Alternative Specimen Collection Methods for the Diagnosis of Tuberculosis in HIV-Infected Children

BACKGROUND The diagnosis of tuberculosis in human immunodeficiency virus (HIV)-infected children is challenging. We assessed the performance of alternative specimen collection methods for tuberculosis diagnosis in HIV-infected children using Xpert MTB/RIF (Xpert). METHODS HIV-infected children aged ≤13 years with suspected intrathoracic tuberculosis were enrolled in 8 hospitals in Burkina Faso, Cambodia, Cameroon, and Vietnam. Gastric aspirates were taken for children aged <10 years and expectorated sputum samples were taken for children aged ≥10 years (standard samples); nasopharyngeal aspirate and stool were taken for all children, and a string test was performed if the child was aged ≥4 years (alternative samples). All samples were tested with Xpert. The diagnostic accuracy of Xpert for culture-confirmed tuberculosis was analyzed in intention-to-diagnose and per-protocol approaches. RESULTS Of 281 children enrolled, 272 (96.8%) had ≥1 specimen tested with Xpert (intention-to-diagnose population), and 179 (63.5%) had all samples tested with Xpert (per-protocol population). Tuberculosis was culture-confirmed in 29/272 (10.7%) children. Intention-to-diagnose sensitivities of Xpert performed on all, standard, and alternative samples were 79.3% (95% confidence interval [CI], 60.3-92.0), 72.4% (95% CI, 52.8-87.3), and 75.9% (95% CI, 56.5-89.7), respectively. Specificities were ≥97.5%. Xpert combined on nasopharyngeal aspirate and stool had intention-to-diagnose and per-protocol sensitivities of 75.9% (95% CI, 56.5-89.7) and 75.0% (95% CI, 47.6-92.7), respectively. CONCLUSIONS The combination of nasopharyngeal aspirate and stool sample is a promising alternative to methods usually recommended by national programs. Xpert performed on respiratory and stools samples enables rapid confirmation of tuberculosis diagnosis in HIV-infected children. CLINICAL TRIALS REGISTRATION The ANRS (Agence Nationale de Recherche sur le Sida) 12229 PAANTHER (Pediatric Asian African Network for Tuberculosis and HIV Research) 01 study is registered at ClinicalTrials.gov (NCT01331811).

Gaps between research and public health priorities in low income countries: evidence from a systematic literature review focused on Cambodia

BackgroundEvidence-based public health requires that research provides policymakers with reliable and accessible information reflecting the disease threats. We described the scientific production of research in Cambodia and assessed to what extent it provides appropriate insights and implications for practice to guide health policymakers and managers and knowledge relevant for translation.MethodsWe conducted a systematic review of scientific articles published on biomedical research in Cambodia. Regression analysis assessed the trends over time and factors associated with actionable messages in the articles’ abstracts.ResultsFrom 2000 to 2012, 628 articles were published in 237 journals with a significant increase over time (from 0.6/million population to 5.9/million population, slope coefficient 7.6, 95% CI 6.5–8.7, p < 0.001). Most publications on diseases addressed communicable diseases (n = 410, 65.3%). Non-communicable diseases (NCD) were under-addressed (7.7% of all publications) considering their burden (34.5% of the disease burden). Of all articles, 67.8% reported descriptive studies and 4.3% reported studies with a high level of evidence; 27.4% of studies were led by an institution based in Cambodia. Factors associated with an actionable message (n = 73, 26.6%) were maternal health (OR 3.08, 95% CI 1.55–6.13, p = 0.001), the first author’s institution being Cambodian (OR 1.78, 95% CI 1.06–2.98, p = 0.02) and a free access to full article (OR 3.07, 95% CI 1.08–8.70, p = 0.03). Of all articles, 87% (n = 546) were accessible in full text from Cambodia.ConclusionsScientific publications do not fully match with health priorities. Gaps remain regarding NCD, implementation studies, and health system research. A health research agenda would help align research with health priorities. We recommend 1) that the health authorities create an online repository of research findings with abstracts in the local language; 2) that academics emphasize the importance of research in their university teaching; and 3) that the researcher teams involve local researchers and that they systematically provide a translation of their abstracts upon submission to a journal. We conclude that building the bridge between research and public health requires a willful, comprehensive strategy rather than relying solely only publications.

Epidemiological and Virological Characteristics of Influenza Viruses Circulating in Cambodia from 2009 to 2011

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.