Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

Effectiveness of Umonium38 against Burkholderia pseudomallei, Escherichia coli, Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus aureus (MRSA).

AIMS: We investigated the antibacterial efficacy of Umonium38 and Virkon® against Burkholderia pseudomallei, Escherichia coli, Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus aureus (MRSA) up to 14 days following treatment. METHODS AND RESULTS: Umonium38 was diluted to 0.5%, 1.0%, 1.5%, 2.0%, 2.5% and 3%, tested against the bacterial strains at various contact times (15 min to 24 h), and incubated for up to 14 days. A minimum concentration of 0.5% Umonium38 with a contact time of 15 min effectively killed approximately 108 CFU/ml of all four bacterial species. No growth was observed on agar plates from day 0 until day 14 for all six concentrations. The bacteria were also inactivated by a 30-minute treatment time using Virkon® 1% solution. CONCLUSIONS: Umonium38 effectively inactivates B. pseudomallei, E. coli, P. aeruginosa and MRSA at a concentration of ≥ 0.5% with a contact time of at least 15 min. The antimicrobial effect of Umonium38 remained for 14 days.

Gaps and inconsistencies in the current knowledge and implementation of biosafety and biosecurity practices for rickettsial pathogens.

INTRODUCTION: Rickettsia spp. and Orientia spp. are the causes of neglected infections that can lead to severe febrile and systemic illnesses in humans. Implementing proper biosafety practices when handling these pathogens is crucial to ensure a safe and sustainable work environment. It is essential to assess the current knowledge and identify any potential gaps to develop effective measures that minimise the risk of exposure to these pathogens. By doing so, we can establish a comprehensive framework that promotes safety, mitigates hazards, and safeguards the well-being of personnel and the surrounding community. METHODS AND RESULTS: This review aimed to synthesise and determine the evidence base for biosafety precautions for Rickettsia spp. and Orientia spp. pathogens. Enhancing our understanding of the relative infectious risk associated with different strains of Rickettsia and Orientia spp. requires identifying the infectious dose of these pathogens that can cause human disease. The application of risk groups for Rickettsia and Orientia spp. is inconsistent across jurisdictions. There is also incomplete evidence regarding decontamination methods for these pathogens. With regards to Orientia spp. most of the available information is derived from experiments conducted with Rickettsia spp. CONCLUSIONS: Rickettsia and Orientia spp. are neglected diseases, as demonstrated by the lack of evidence-based and specific biosafety information about these pathogens. In the case of Orientia spp., most of the available information is derived from Rickettsia spp., which may not be appropriate and overstate the risks of working with this pathogen. The advent of effective antibiotic therapy and a better understanding of the true hazards and risks associated with pathogen manipulation should inform decisions, allowing a sustainable and safe work environment.

Novel estimation of African swine fever transmission parameters within smallholder villages in Lao P.D.R.

African Swine Fever (ASF) disease transmission parameters are crucial for making response and control decisions when faced with an outbreak, yet they are poorly quantified for smallholder and village contexts within Southeast Asia. Whilst disease-specific factors - such as latent and infectious periods - should remain reasonably consistent, host, environmental and management factors are likely to affect the rate of disease spread. These differences are investigated using Approximate Bayesian Computation with Sequential Monte-Carlo methods to provide disease parameter estimates in four naïve pig populations in villages of Lao People's Democratic Republic. The villages represent smallholder pig farmers of the Northern province of Oudomxay and the Southern province of Savannakhet, and the model utilised field mortality data to validate the transmission parameter estimates over the course of multiple model generations. The basic reproductive number between-pigs was estimated to range from 3.08 to 7.80, whilst the latent and infectious periods were consistent with those published in the literature for similar genotypes in the region (4.72 to 6.19 days and 2.63 to 5.50 days, respectively). These findings demonstrate that smallholder village pigs interact similarly to commercial pigs, however the spread of disease may occur slightly slower than in commercial study groups. Furthermore, the findings demonstrated that despite diversity across the study groups, the disease behaved in a consistent manner. This data can be used in disease control programs or for future modelling of ASF in smallholder contexts.

Global Veterinary Diagnostic Laboratory Equipment Management and Sustainability and Implications for Pandemic Preparedness Priorities1.

Substantial investments into laboratories, notably sophisticated equipment, have been made over time to detect emerging diseases close to their source. Diagnostic capacity has expanded as a result, but challenges have emerged. The Equipment Management and Sustainability Survey was sent to the Veterinary Services of 182 countries in mid-2019. We measured the status of forty types of laboratory equipment used in veterinary diagnostic laboratories. Of the 68,455 items reported from 227 laboratories in 136 countries, 22% (14,894/68,455) were improperly maintained, and 46% (29,957/65,490) were improperly calibrated. Notable differences were observed across World Bank income levels and regions, raising concerns about equipment reliability and the results they produce. Our results will advise partners and donors on how best to support low-resource veterinary laboratories to improve sustainability and fulfill their mandate toward pandemic prevention and preparedness, as well as encourage equipment manufacturers to spur innovation and develop more sustainable products that meet end-users' needs.

Utilising abattoir sero-surveillance for high-impact and zoonotic pig diseases in Lao PDR.

National disease surveillance systems are essential to a healthy pig industry but can be costly and logistically complex. In 2019, Lao People's Democratic Republic (Lao PDR) piloted an abattoir disease surveillance system to assess for the presence of high impact pig diseases (HIPDs) using serological methods. The Lao Department of Livestock and Fisheries (DLF) identified Classical Swine Fever (CSF), Porcine Respiratory and Reproductive Syndrome (PRRS) and Brucella suis as HIPDs of interest for sero-surveillance purposes. Porcine serum samples (n = 597) were collected from six Lao abattoirs in March to December of 2019. Serological enzyme-linked immunosorbent assay (ELISA) methods were chosen for their high-throughput and relatively low-costs. The true seroprevalence for CSF and PRRS seropositivity were 68.7%, 95% CI (64.8-72.3) and 39.5%, 95% CI (35.7-43.5), respectively. The results demonstrated no evidence of Brucella spp. seroconversion. Lao breed pigs were less likely to be CSF seropositive (P < 0.05), whilst pigs slaughtered at <1 year of age were less likely to be PRRS seropositive (P < 0.01). The testing methods could not differentiate between seropositivity gained from vaccine or natural infection, and investigators were unable to obtain the vaccine status of the slaughtered pigs from the abattoirs. These results demonstrate that adequate sample sizes are possible from abattoir sero-surveillance and lifetime health traceability is necessary to understand HIPDs in Lao PDR.

Prevalence of and factors associated with scrub typhus exposure among the hill tribe population living in high incidence areas in Thailand: a cross-sectional study.

BACKGROUND: Scrub typhus is a significant tropical disease, occurring in rural settings and therefore usually afflicting remote agricultural populations who have lower socioeconomic status and limited access to medical care. A large proportion of the hill tribe people in Thailand are financially poor, have limited education, and do not have adequate health care access. This study aimed to estimate the prevalence of and determine factors associated with scrub typhus exposure among the hill tribe population living in high-incidence areas in northern Thailand. METHODS: A cross-sectional study design was used to gather information from hill tribe people aged 18 years and over living in ten hill tribe villages in Mae Fah Luang, Chiang Rai Province, Thailand. Participants who met the inclusion criteria were invited to participate in the study. A validated questionnaire was used as the research instrument, and 5 mL blood samples were taken. Orientia tsutsugamushi IgM and IgG antibodies were detected by enzyme-linked immunosorbent assay (ELISA) and then confirmed by immunofluorescence assay (IFA). Logistic regression was used to detect associations between variables at a significance level of α = 0.05. RESULTS: A total of 485 hill tribe people participated in the study; 57.1% were female, 29.9% were over 60 years of age, 46.4% were from the Akha tribe, and 74.2% had never attended school. The overall prevalence of scrub typhus exposure was 48.0%. In the multivariate model, five variables were found to be associated with scrub typhus exposure. Participants aged over 60 years had a 4.31-fold increased risk (95% CI = 1.73-10.72) of scrub typhus exposure compared to those who were younger than 30 years. Those who were illiterate had a 3.46-fold increased risk (95% CI = 1.93-6.21) of scrub typhus exposure than those who had at least a primary education level. Participants from the Akha tribe had a 2.20-fold increased risk (95% CI = 1.31-3.72) of scrub typhus exposure than those from the Lahu tribe. Subjects who had a history of cutting grass had a 1.85-fold increased risk (95% CI = 1.20-2.84) of scrub typhus exposure. Those who never wore gloves for farming had a 2.12-fold increased risk (95% CI = 1.28-3.49) of scrub typhus exposure than those who wore gloves daily. CONCLUSIONS: There is a high prevalence of scrub typhus exposure among the hill tribe in Thailand. Effective public health interventions to promote scrub typhus awareness and prevention are urgently needed in these populations.

Abattoir-based serological surveillance for transboundary and zoonotic diseases in cattle and swine in Cambodia: a pilot study in Phnom Penh province during 2019 and 2020.

A pilot animal disease surveillance program was implemented at four abattoirs in Phnom Penh, Cambodia, between October 2019 and January 2020. A total of 1141 samples were collected from 477 cattle and 664 swine. Serological testing was performed using commercial antibody ELISA kits for zoonotic and high-impact animal diseases, namely brucellosis, Q fever, classical swine fever (CSF), porcine reproductive and respiratory syndrome (PRRS) and African swine fever (ASF). Only two samples tested positive for Brucella antibodies (0.2%, 95% CI 0.4-0.6, n = 1141). The seroprevalence of Q fever was 0.8% (95% CI 0.3-2.1, n = 477) in the cattle samples, while CSF, PRRS and ASF in pigs were 55.4% (95% CI 51.6-59.2, n = 655), 81.2% (95% CI 78.1-84.0, n = 655) and 2.6% (95% CI 1.6-4.1, n = 664), respectively. All 38 doubtful and 17 positive ASF antibody ELISA samples were negative when tested by real-time PCR. Univariate analyses demonstrated that the factor significantly associated with positive results of ASF was the abattoir location (p-value = 0.002). Based on logistic regression models, significant risk factors for CSF were province of origin (p-value = 1.7 × 10-6), abattoir (p-value = 3.6 × 10-11) and PRRS positivity (p-value = 0.004), and for PRRS were province of origin (p-value = 0.0004) and CSF positivity (p-value = 0.001). In conclusion, the seroprevalences of zoonotic diseases in this study were very low. The high prevalence of CSF and PRRS antibodies were most likely the result of vaccination. All ASF seropositive pigs, including those that gave equivocal results, originated from large-scale Cambodian-based commercial farms, as well as Thailand, which raises questions about possible illegal vaccination or low-pathogenicity ASF variants. The pilot abattoir serological surveillance program described here has the potential to provide a sentinel for incursions of novel and endemic pathogens, although further work is required to demonstrate its capacity to provide information on the longitudinal disease trends.

Improving knowledge, attitudes and practice to prevent COVID-19 transmission in healthcare workers and the public in Thailand.

BACKGROUND: Key infection prevention and control measures to limit transmission of COVID-19 include social distancing, hand hygiene, use of facemasks and personal protective equipment. However, these have limited or no impact if not applied correctly through lack of knowledge, inappropriate attitude or incorrect practice. In order to maximise the impact of infection prevention and control measures on COVID-19 spread, we undertook a study to assess and improve knowledge, attitudes and practice among 119 healthcare workers and 100 general public in Thailand. The study setting was two inpatient hospitals providing COVID-19 testing and treatment. Detailed information on knowledge, attitudes and practice among the general public and healthcare workers regarding COVID-19 transmission and its prevention were obtained from a combination of questionnaires and observations. RESULTS: Knowledge of the main transmission routes, commonest symptoms and recommended prevention methods was mostly very high (> 80%) in both groups. There was lower awareness of aerosols, food and drink and pets as sources of transmission; of the correct duration for handwashing; recommended distance for social/physical distancing; and about recommended types of face coverings. Information sources most used and most trusted were the workplace, work colleagues, health workers and television. The results were used to produce a set of targeted educational videos which addressed many of these gaps with subsequent improvements on retesting in a number of areas. This included improvements in handwashing practice with an increase in the number of areas correctly washed in 65.5% of the public, and 57.9% of healthcare workers. The videos were then further optimized with feedback from participants followed by another round of retesting. CONCLUSIONS: Detailed information on gaps in knowledge, attitudes and practice among the general public and healthcare workers regarding COVID-19 transmission and its prevention were obtained from a combination of questionnaires and observations. This was used to produce targeted educational videos which addressed these gaps with subsequent improvements on retesting. The resulting videos were then disseminated as a resource to aid in efforts to fight COVID-19 in Thailand and worldwide.

Seroepidemiology of Foot and Mouth Disease using passive surveillance techniques in selected provinces of Lao PDR.

Foot and Mouth Disease (FMD) is a high-impact, contagious transboundary animal disease that is endemic in Southeast Asia. Abattoir samples were routinely collected in six selected provinces between March and December 2019. A total of 1280 samples of abattoir animals were tested for FMD Non-Structural Protein (NSP) antibodies to indicate natural infections. Overall, 22.8% were seropositive for FMD NSP antibodies while seroprevalence of cattle (n = 469), buffalo (n = 214), and pigs (n = 597) were 44.6%, 35.0%, and 1.3%, respectively. The highest seroprevalence destination province was Xiengkhouang (35.3% of 272 samples), followed by Savannakhet (27.0% of 244 samples). Risk factors for evidence of natural infection identified by a multivariate logistic regression model included age groups (p-value = 0.02) and origin provinces (p-value = 2.8 × 10-5) of the animals. There were significant differences of FMD NSP seroprevalence between age groups and origin provinces of the animals. The odds ratio of a seropositive result in the less than 1 year old group was 2.5 (95% CI; 1.4, 4.4) when compared to the 3-4 years old group, while the odds ratios for animals that originated from Khammouane and Xiengkhouang provinces were 4.5 (95% CI; 1.1, 18.7) and 2.4 (95% CI; 1.4, 4.1), respectively, when compared to Champasak province. Serotype-specific antibody ELISA for 44 NSP antibody-positive samples revealed evidence of FMD serotypes O and A virus circulation in some provinces. Despite the passive abattoir survey providing useful information on FMD virus previous exposure and geographic locations of the animals, timely information on FMD virus circulation and distribution is also crucial to an effective control program. Alternative approaches to increase the cost-effectiveness of the surveillance network are also discussed.

The Isolation of Orientia tsutsugamushi and Rickettsia typhi from Human Blood through Mammalian Cell Culture: a Descriptive Series of 3,227 Samples and Outcomes in the Lao People's Democratic Republic.

In the Lao People's Democratic Republic (Laos), rickettsial infections, including scrub and murine typhus, account for a significant burden of fevers. The Mahosot Hospital Microbiology Laboratory in Vientiane, Laos, routinely performs rickettsial isolation from hospitalized patients with suspected rickettsioses using mammalian cell culture systems. We review the clinical and laboratory factors associated with successful Orientia tsutsugamushi and Rickettsia typhi isolations from this laboratory over a period of 6 years between 2008 and 2014. The overall isolation success was 7.9% for all samples submitted and 17.3% for samples for which the patient had a positive O. tsutsugamushi or R. typhi rapid diagnostic test (RDT), serology, or PCR. The frequency of successful isolation was highest for samples submitted in November, at the end of the wet season (28.3%). A longer median duration of reported illness, a positive result for a concurrent Orientia or Rickettsia spp. quantitative PCR, and the use of antibiotics by the patient in the week before admission were significantly associated with isolation success (P < 0.05). Buffy coat inoculation and a shorter interval between sample collection and inoculation in the laboratory were associated with a higher frequency of isolation (both P < 0.05). This frequency was highest if cell culture inoculation occurred on the same day as blood sample collection. Factors related to the initial rickettsial bacterial concentration are likely the main contributors to isolation success. However, modifiable factors do contribute to the rickettsial isolation success, especially delays in inoculating patient samples into culture.

Laboratory-acquired Scrub Typhus and Murine Typhus Infections: The Argument for a Risk-based Approach to Biosafety Requirements for Orientia tsutsugamushi and Rickettsia typhi Laboratory Activities.

This study examined the literature on laboratory-acquired infections (LAIs) associated with scrub typhus (Orientia tsutsugamushi) and murine typhus (Rickettsia typhi) research to provide an evidence base for biosafety and biocontainment. Scrub typhus LAIs were documented in 25 individuals, from 1931 to 2000 with 8 (32%) deaths during the preantibiotic era. There were 35 murine typhus LAI reports and no deaths. Results indicated that the highest-risk activities were working with infectious laboratory animals involving significant aerosol exposures, accidental self-inoculation, or bite-related infections. A risk-based biosafety approach for in vitro and in vivo culture of O. tsutsugamushi and R. typhi would require that only high-risk activities (animal work or large culture volumes) be performed in high-containment biosafety level (BSL) 3 laboratories. We argue that relatively low-risk activities including inoculation of cell cultures or the early stages of in vitro growth using low volumes/low concentrations of infectious materials can be performed safely in BSL-2 laboratories within a biological safety cabinet.

A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus.

BACKGROUND: Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy. METHODS: A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse. RESULTS: Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)-confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P < .001). Among R. typhi PCR-positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse. CONCLUSION: In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed. CLINICAL TRIAL REGISTRATION: ISRCTN47812566.

Management of Central Nervous System Infections, Vientiane, Laos, 2003-2011.

During 2003-2011, we recruited 1,065 patients of all ages admitted to Mahosot Hospital (Vientiane, Laos) with suspected central nervous system (CNS) infection. Etiologies were laboratory confirmed for 42.3% of patients, who mostly had infections with emerging pathogens: viruses in 16.2% (mainly Japanese encephalitis virus [8.8%]); bacteria in 16.4% (including Orientia tsutsugamushi [2.9%], Leptospira spp. [2.3%], and Rickettsia spp. [2.3%]); and Cryptococcus spp. fungi in 6.6%. We observed no significant differences in distribution of clinical encephalitis and meningitis by bacterial or viral etiology. However, patients with bacterial CNS infection were more likely to have a history of diabetes than others. Death (26.3%) was associated with low Glasgow Coma Scale score, and the mortality rate was higher for patients with bacterial than viral infections. No clinical or laboratory variables could guide antibiotic selection. We conclude that high-dependency units and first-line treatment with ceftriaxone and doxycycline for suspected CNS infections could improve patient survival in Laos.

Endemic Scrub Typhus in South America.

Scrub typhus is a life-threatening zoonosis caused by Orientia tsutsugamushi organisms that are transmitted by the larvae of trombiculid mites. Endemic scrub typhus was originally thought to be confined to the so called "tsutsugamushi triangle" within the Asia-Pacific region. In 2006, however, two individual cases were detected in the Middle East and South America, which suggested that the pathogen was present farther afield. Here, we report three autochthonous cases of scrub typhus caused by O. tsutsugamushi acquired on Chiloé Island in southern Chile, which suggests the existence of an endemic focus in South America. (Funded by the Chilean Comisión Nacional de Investigación Científica y Tecnológica and the Wellcome Trust.).

Diagnosis of spotted fever group Rickettsia infections: the Asian perspective.

Spotted fever group rickettsiae (SFG) are a neglected group of bacteria, belonging to the genus Rickettsia, that represent a large number of new and emerging infectious diseases with a worldwide distribution. The diseases are zoonotic and are transmitted by arthropod vectors, mainly ticks, fleas and mites, to hosts such as wild animals. Domesticated animals and humans are accidental hosts. In Asia, local people in endemic areas as well as travellers to these regions are at high risk of infection. In this review we compare SFG molecular and serological diagnostic methods and discuss their limitations. While there is a large range of molecular diagnostics and serological assays, both approaches have limitations and a positive result is dependent on the timing of sample collection. There is an increasing need for less expensive and easy-to-use diagnostic tests. However, despite many tests being available, their lack of suitability for use in resource-limited regions is of concern, as many require technical expertise, expensive equipment and reagents. In addition, many existing diagnostic tests still require rigorous validation in the regions and populations where these tests may be used, in particular to establish coherent and worthwhile cut-offs. It is likely that the best strategy is to use a real-time quantitative polymerase chain reaction (qPCR) and immunofluorescence assay in tandem. If the specimen is collected early enough in the infection there will be no antibodies but there will be a greater chance of a PCR positive result. Conversely, when there are detectable antibodies it is less likely that there will be a positive PCR result. It is therefore extremely important that a complete medical history is provided especially the number of days of fever prior to sample collection. More effort is required to develop and validate SFG diagnostics and those of other rickettsial infections.

A history of FMD research and control programmes in Southeast Asia: lessons from the past informing the future.

Foot and mouth disease (FMD) is a major animal health problem within Southeast Asia (SEA). Although Indonesia and more recently the Philippines have achieved freedom from FMD, the disease remains endemic on continental SEA. Control of FMD within SEA would increase access to markets in more developed economies and reduce lost productivity in smallholder and emerging commercial farmer settings. However, despite many years of vaccination by individual countries, numerous factors have prevented the successful control of FMD within the region, including unregulated 'informal' transboundary movement of livestock and their products, difficulties implementing vaccination programmes, emergence of new virus topotypes and lineages, low-level technical capacity and biosecurity at national levels, limited farmer knowledge on FMD disease recognition, failure of timely outbreak reporting and response, and limitations in national and international FMD control programmes. This paper examines the published research of FMD in the SEA region, reviewing the history, virology, epidemiology and control programmes and identifies future opportunities for FMD research aimed at the eventual eradication of FMD from the region.

Biosafety and biosecurity requirements for Orientia spp. diagnosis and research: recommendations for risk-based biocontainment, work practices and the case for reclassification to risk group 2.

Scrub typhus is an important arthropod-borne disease causing significant acute febrile illness by infection with Orientia spp.Using a risk-based approach, this review examines current practice, the evidence base and regulatory requirements regarding matters of biosafety and biosecurity, and presents the case for reclassification from Risk Group 3 to Risk Group 2 along with recommendations for safe working practices of risk-based activities during the manipulation of Orientia spp. in the laboratory.We recommend to reclassify Orientia spp. to Risk Group 2 based on the classification for RG2 pathogens as being moderate individual risk, low community risk. We recommend that low risk activities, can be performed within a biological safety cabinet located in a Biosafety Level (BSL) 2 core laboratory using standard personal protective equipment. But when the risk assessment indicates, such as high concentration and volume, or aerosol generation, then a higher biocontainment level is warranted. For, the majority of animal activities involving Orientia spp., Animal BSL 2 (ABSL2) is recommended however where high risk activities are performed including necropsies, Animal BSL (ABSL3) is recommended.

Rickettsial Illnesses as Important Causes of Febrile Illness in Chittagong, Bangladesh.

We conducted a yearlong prospective study of febrile patients admitted to a tertiary referral hospital in Chittagong, Bangladesh, to assess the proportion of patients with rickettsial illnesses and identify the causative pathogens, strain genotypes, and associated seasonality patterns. We diagnosed scrub typhus in 16.8% (70/416) and murine typhus in 5.8% (24/416) of patients; 2 patients had infections attributable to undifferentiated Rickettsia spp. and 2 had DNA sequence-confirmed R. felis infection. Orientia tsutsugamushi genotypes included Karp, Gilliam, Kato, and TA763-like strains, with a prominence of Karp-like strains. Scrub typhus admissions peaked in a biphasic pattern before and after the rainy season, whereas murine typhus more frequently occurred before the rainy season. Death occurred in 4% (18/416) of cases; case-fatality rates were 4% each for scrub typhus (3/70) and murine typhus (1/28). Overall, 23.1% (96/416) of patients had evidence of treatable rickettsial illnesses, providing important evidence toward optimizing empirical treatment strategies.

Predicting the severity of dengue fever in children on admission based on clinical features and laboratory indicators: application of classification tree analysis.

BACKGROUND: Dengue fever is a re-emerging viral disease commonly occurring in tropical and subtropical areas. The clinical features and abnormal laboratory test results of dengue infection are similar to those of other febrile illnesses; hence, its accurate and timely diagnosis for providing appropriate treatment is difficult. Delayed diagnosis may be associated with inappropriate treatment and higher risk of death. Early and correct diagnosis can help improve case management and optimise the use of resources such as hospital staff, beds, and intensive care equipment. The goal of this study was to develop a predictive model to characterise dengue severity based on early clinical and laboratory indicators using data mining and statistical tools. METHODS: We retrieved data from a study of febrile illness in children at Angkor Hospital for Children, Cambodia. Of 1225 febrile episodes recorded, 198 patients were confirmed to have dengue. A classification and regression tree (CART) was used to construct a predictive decision tree for severe dengue, while logistic regression analysis was used to independently quantify the significance of each parameter in the decision tree. RESULTS: A decision tree algorithm using haematocrit, Glasgow Coma Score, urine protein, creatinine, and platelet count predicted severe dengue with a sensitivity, specificity, and accuracy of 60.5%, 65% and 64.1%, respectively. CONCLUSIONS: The decision tree we describe, using five simple clinical and laboratory indicators, can be used to predict severe cases of dengue among paediatric patients on admission. This algorithm is potentially useful for guiding a patient-monitoring plan and outpatient management of fever in resource-poor settings.