Using real-time modelling to inform the 2017 Ebola outbreak response in DR Congo.

Important policy questions during infections disease outbreaks include: i) How effective are particular interventions?; ii) When can resource-intensive interventions be removed? We used mathematical modelling to address these questions during the 2017 Ebola outbreak in Likati Health Zone, Democratic Republic of the Congo (DRC). Eight cases occurred before 15 May 2017, when the Ebola Response Team (ERT; co-ordinated by the World Health Organisation and DRC Ministry of Health) was deployed to reduce transmission. We used a branching process model to estimate that, pre-ERT arrival, the reproduction number was R = 1.49 (95% credible interval ( 0.67, 2.81 ) ). The risk of further cases occurring without the ERT was estimated to be 0.97 (97%). However, no cases materialised, suggesting that the ERT's measures were effective. We also estimated the risk of withdrawing the ERT in real-time. By the actual ERT withdrawal date (2 July 2017), the risk of future cases without the ERT was only 0.01, indicating that the ERT withdrawal decision was safe. We evaluated the sensitivity of our results to the estimated R value and considered different criteria for determining the ERT withdrawal date. This research provides an extensible modelling framework that can be used to guide decisions about when to relax interventions during future outbreaks.

A simulation-based approach for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data.

Tracking pathogen transmissibility during infectious disease outbreaks is essential for assessing the effectiveness of public health measures and planning future control strategies. A key measure of transmissibility is the time-dependent reproduction number, which has been estimated in real-time during outbreaks of a range of pathogens from disease incidence time series data. While commonly used approaches for estimating the time-dependent reproduction number can be reliable when disease incidence is recorded frequently, such incidence data are often aggregated temporally (for example, numbers of cases may be reported weekly rather than daily). As we show, commonly used methods for estimating transmissibility can be unreliable when the timescale of transmission is shorter than the timescale of data recording. To address this, here we develop a simulation-based approach involving Approximate Bayesian Computation for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data. We first use a simulated dataset representative of a situation in which daily disease incidence data are unavailable and only weekly summary values are reported, demonstrating that our method provides accurate estimates of the time-dependent reproduction number under such circumstances. We then apply our method to two outbreak datasets consisting of weekly influenza case numbers in 2019-20 and 2022-23 in Wales (in the United Kingdom). Our simple-to-use approach will allow accurate estimates of time-dependent reproduction numbers to be obtained from temporally aggregated data during future infectious disease outbreaks.

Exact calculation of end-of-outbreak probabilities using contact tracing data.

A key challenge for public health policymakers is determining when an infectious disease outbreak has finished. Following a period without cases, an estimate of the probability that no further cases will occur in future (the end-of-outbreak probability) can be used to inform whether or not to declare an outbreak over. An existing quantitative approach (the Nishiura method), based on a branching process transmission model, allows the end-of-outbreak probability to be approximated from disease incidence time series, the offspring distribution and the serial interval distribution. Here, we show how the end-of-outbreak probability under the same transmission model can be calculated exactly if data describing who-infected-whom (the transmission tree) are also available (e.g. from contact tracing studies). In that scenario, our novel approach (the traced transmission method) is straightforward to use. We demonstrate this by applying the method to data from previous outbreaks of Ebola virus disease and Nipah virus infection. For both outbreaks, the traced transmission method would have determined that the outbreak was over earlier than the Nishiura method. This highlights that collection of contact tracing data and application of the traced transmission method may allow stringent control interventions to be relaxed quickly at the end of an outbreak, with only a limited risk of outbreak resurgence.

Improved inference of time-varying reproduction numbers during infectious disease outbreaks.

Accurate estimation of the parameters characterising infectious disease transmission is vital for optimising control interventions during epidemics. A valuable metric for assessing the current threat posed by an outbreak is the time-dependent reproduction number, i.e. the expected number of secondary cases caused by each infected individual. This quantity can be estimated using data on the numbers of observed new cases at successive times during an epidemic and the distribution of the serial interval (the time between symptomatic cases in a transmission chain). Some methods for estimating the reproduction number rely on pre-existing estimates of the serial interval distribution and assume that the entire outbreak is driven by local transmission. Here we show that accurate inference of current transmissibility, and the uncertainty associated with this estimate, requires: (i) up-to-date observations of the serial interval to be included, and; (ii) cases arising from local transmission to be distinguished from those imported from elsewhere. We demonstrate how pathogen transmissibility can be inferred appropriately using datasets from outbreaks of H1N1 influenza, Ebola virus disease and Middle-East Respiratory Syndrome. We present a tool for estimating the reproduction number in real-time during infectious disease outbreaks accurately, which is available as an R software package (EpiEstim 2.2). It is also accessible as an interactive, user-friendly online interface (EpiEstim App), permitting its use by non-specialists. Our tool is easy to apply for assessing the transmission potential, and hence informing control, during future outbreaks of a wide range of invading pathogens.

Determination of fendiline and gallopamil by capillary isotachophoresis.

Capillary isotachophoresis was applied for the determination of fendiline and gallopamil--calcium antagonists--in serum. The cationic electrolyte system containing Na+ with acetic acid as a counter constituent was used as a leading electrolyte with the pH 4.7 and the terminating electrolyte was beta-alanine. Most of the proteins were precipitated with methanol, ethanol and dimethylketone. The lowest limits of quantitation were obtained for the pretreatment of serum with methanol. The recoveries of both compounds varied from 91.3 to 97.5%. The relative standard deviations varied from 0.6 to 7.7%.

Determination of ibuprofen and naproxen in tablets.

Ibuprofen and naproxen have been quantified in tablets by capillary isotachophoresis. Hydrochloric acid (10 mmol/l) adjusted with creatinine to pH 5.0 plus 0.1% polyvinylpyrrolidone was used as the leading electrolyte and 10 mmol/l 4-morpholineethanesulfonic acid as the terminating electrolyte. Linearity was observed from 40.0 to 200.0 mg/l of ibuprofen (naproxen), with a coefficient of determination (r2) of 0.999. Good quantitation was obtained in short analysis time. The isotachophoretic results were compared with those obtained by the fluorescence spectrometry. Experimental parameters for ibuprofen were: lambdaEX=224 nm and lambdaEM=290 nm. Experimental parameters for naproxen were: lambdaEX=230 nm and lambdaEM=355 nm. The calibration plot was found to be linear in the range 0.4-2.4 mg/l for ibuprofen and 5.0-20.0 microg/l for naproxen. The minimal sample pretreatment and relatively low running cost make isotachophoresis a good alternative to existing methods.

Isotachophoretic determination of naproxen in the presence of its metabolite in human serum.

An isotachophoretic method with conductivity detection was developed to determine naproxen in the presence of its metabolite 6-O-desmethylnaproxen in human serum. The leading electrolyte contained 10 mM hydrochloric acid, beta-alanine, pH 4.0 and 0.1% methylhydroxypropylcellulose. The terminating electrolyte was 10 mM 2-(N-morpholino)ethanesulfonic acid-tris(hydroxymethyl)aminomethane, pH 6.9, containing 20% (v/v) of ethanol. Naproxen was determined in serum supernatant after simple deproteination of the sample with ethanol. The isotachophoretic results were compared with those obtained by synchronous fluorescence spectrometry.

Spectrofluorimetric and isotachophoretic determination of maprotiline in human blood serum.

Maprotiline determination in blood serum samples was investigated by the use of both capillary isotachophoresis and spectrofluorimetric techniques. The analyte had to be enriched before determination and extraction with n-heptane was used for this purpose. The preliminary separation enabled the determination of maprotiline in blood serum at therapeutic concentration levels.

Determination of four selective serotonin reuptake inhibitors by capillary isotachophoresis.

We determined an optimal electrolyte system for isotachophoresis (ITP) with conductivity detection of citalopram, fluoxetine, fluvoxamine and sertraline. The analysis conditions were applied to the determination of these selective serotonin re-uptake inhibitors in antidepressant drugs. It is shown that capillary ITP with conductivity detection is a simple and quick method for the determination of citalopram, fluoxetine, fluvoxamine and sertraline in drugs.

Determination of some antirheumatics by capillary isotachophoresis.

Isotachophoresis (ITP) was applied for the determination of some antirheumatic drugs (fenoprofen, naproxen, ibuprofen, and ketoprofen) in human serum. The leading electrolyte contained hydrochloric acid (10 mmol x L(-1)), creatinine (pH 4.5) and methylhydroxyethyl cellulose (0.1%). The terminating electrolyte was 2-(N-morpholino)ethanesulfonic acid (10 mmol x L(-1)) adjusted with tris(hydroxymethyl)aminomethane to pH 6.9. The ITP separations were carried out in column-coupling configuration of the separation unit provided with a preseparation column of 160 x 0.8 mm inner diameter (ID) and analytical column of 160 x 0.3 mm ID. The limit of detection for ibuprofen, fenoprofen, and naproxen in serum by direct sampling was 0.008, 0.005 and 0.004 mmol x L(-1). The limit of detection for ketoprofen in serum after ethanol precipitation was 0.001 mmol x L(-1).

Electrophoretic methods in the analysis of beverages.

A review of the applications of electrophoresis to the determination of various compounds in beverage samples, namely beer, hard drinks, juice, milk, soft drinks, tea and wine, is presented.

Determination of non-steroidal anti-inflammatory drugs in biological fluids.

The present paper summarizes the methods of determination of non-steroidal anti-inflammatory drugs in biological fluids. CZE, HPLC, HPTLC, GC-MS are analytical techniques, which are capable of a separation of arylpropionic acids.

Determination of fenoprofen in serum by capillary isotachophoresis.

A isotachophoretic method with conductivity detection was developed and validated to directly determine fenoprofen in human serum. The leading electrolyte contained hydrochloric acid (10 mmol/l), 6-aminocaproic acid (pH 4.8) and polyvinylpyrrolidone (0.1%). The terminating electrolyte was 4-morpholineethanesulfonic acid (5 mmol/l). The calibration curve was linear over the concentration range 0.02-0.40 mmol/l. Within-day standard deviation ranged from 0.001 to 0.004 and between-day standard deviation ranged from 0.001 to 0.004. The limit of determination was 0.02 mmol/l. The assay was employed to determine serum concentration of fenoprofen in patients.

Determination of inorganic ions in food and beverages by capillary electrophoresis.

A review of the applications of electrophoresis to the determination of inorganic anions (sulphate, sulphite, phosphate, nitrate, nitrite and halides) and inorganic cations (ammonium, alkali and alkaline metals and trace elements) in food and beverages is presented.

Isotachophoretic determination of bisoprolol, clonidine, disopyramide and tolazoline in human fluids.

Separation and determination of bisoprolol, clonidine, disopyramide and tolazoline in control serum and in human urine was investigated by capillary isotachophoresis. The drugs were separated by using the cationic electrolyte system. viz., sodium acetate buffer (pH 4.64) (c1 = 10 mM)-beta-alanine. The compounds were almost totally isolated from serum by solid-phase extraction using a Sep-Pak C18 cartridge. The recovery of compounds varied from 87 to 99%. The linear calibration range was studied to apply the method to real human fluids. The limit of determination of the drugs was 40.0 micrograms/ml serum. The limit of determination by direct sampling for bisoprolol is 3 micrograms/ml urine.

Determination of some cardiovascular drugs in serum and urine by capillary isotachophoresis.

The separation and determination of amiloride, metoprolol, deacetylmetipranolol, labetalol and furosemide in human serum and urine by capillary isotachophoresis were investigated. Amiloride and beta-blockers were separated by cationic isotachophoresis in the electrolyte system sodium morpholinoethanesulfonate buffer (pH 5.5) (cL = 10 mM)-glutamic acid. Furosemide was separated using the anionic electrolyte system histidine hydrochloride buffer (pH 6.2) (cL = 10 mM)-morpholinopropanesulfonic acid. Endogenous and the possible exogenous compounds were almost totally removed from serum and urine by solid-phase extraction using a Separon SGX C18 cartridge. The recovery of compounds varied from 98.2 to 103.2%. The linearity range for the compounds was 50-1000 ng/ml. The relative standard deviations varied from 0.1 to 5.6%. The overall limits of determination ranged from 32 to 46 ng/ml of urine and from 39 to 46 ng/ml of serum, depending of the type of drugs.

[Determination of serum vancomycin using capillary isotachophoresis]. / Stúdium moznosti stanovenia vankomycínu v sére kapilárnou izotachoforézou.

The paper aims to study the possibilities of determining vancomycin in the serum by the method of capillary isotachophoresis. The leading electrolyte contained Na+ as the leading ion, morpholinoethanesulphonic acid as the counter-ion (pH 6,2), and methylhydroxyethyl cellulose as the additive. The terminating electrolyte was morpholinoethanesulphonic acid. The conductivity detector was employed for detection. Ethanol was selected for precipitation of proteins. The yield of vancomycin from the serum was 89-91%. The calibration curve is linear in an interval of 0.02-0.5 microgram (the absolutely dosed amount). The limit of vancomycin determination in the serum is 4 micrograms/ml. The method was employed to determine vancomycin in the serum of patients. The obtained results correlated well with those obtained by fluorescent polarizing immunoanalysis (TDx) in a concentration interval of 4-30 micrograms/ml.