Assessment of the knowledge of graphical symbols labelled on malaria rapid diagnostic tests in four international settings

<p>Abstract</p> <p>Background</p> <p>Graphical symbols on <it>in vitro </it>diagnostics (IVD symbols) replace the need for text in different languages and are used on malaria rapid diagnostic tests (RDTs) marketed worldwide. The present study assessed the comprehension of IVD symbols labelled on malaria RDT kits among laboratory staff in four different countries.</p> <p>Methods</p> <p>Participants (n = 293) in Belgium (n = 96), the Democratic Republic of the Congo (DRC, n = 87), Cambodia (n = 59) and Cuba (n = 51) were presented with an anonymous questionnaire with IVD symbols extracted from ISO 15223 and EN 980 presented as stand-alone symbols (n = 18) and in context (affixed on RDT packages, n = 16). Responses were open-ended and scored for correctness by local professionals.</p> <p>Results</p> <p>Presented as stand-alone, three and five IVD symbols were correctly scored for comprehension by 67% and 50% of participants; when contextually presented, five and seven symbols reached the 67% and 50% correct score respectively. 'Batch code' scored best (correctly scored by 71.3% of participants when presented as stand-alone), 'Authorized representative in the European Community' scored worst (1.4% correct). Another six IVD symbols were scored correctly by less than 10% of participants: 'Do not reuse', '<it>In vitro </it>diagnostic medical device', 'Sufficient for', 'Date of manufacture', 'Authorised representative in EC', and 'Do not use if package is damaged'. Participants in Belgium and Cuba both scored six symbols above the 67% criterion, participants from DRC and Cambodia scored only two and one symbols above this criterion. Low correct scores were observed for safety-related IVD symbols, such as for 'Biological Risk' (42.7%) and 'Do not reuse' (10.9%).</p> <p>Conclusion</p> <p>Comprehension of IVD symbols on RDTs among laboratory staff in four international settings was unsatisfactory. Administrative and outreach procedures should be undertaken to assure their acquaintance by end-users.</p

External quality assessment of malaria microscopy in the Democratic Republic of the Congo

<p>Abstract</p> <p>Background</p> <p>External quality assessments (EQA) are an alternative to cross-checking of blood slides in the quality control of malaria microscopy. This study reports the findings of an EQA of malaria microscopy in the Democratic Republic of the Congo (DRC).</p> <p>Methods</p> <p>After validation, an EQA slide panel and a questionnaire were delivered to diagnostic laboratories in four provinces of DRC. The panel included three samples for diagnosis (sample 1: <it>Plasmodium falciparum</it>, 177,000/μl, sample 2: <it>P. falciparum</it>, 2,500/μl, sample 3: no parasites seen), one didactic sample (Howell-Jolly bodies) and one sample for assessing the quality of staining. Participating laboratories were addressed and selected through the network of the National Tuberculosis Control Programme. Participants were asked to return the responses together with a stained thin and thick blood film for evaluation of Giemsa stain quality.</p> <p>Results</p> <p>Among 174 participants (response rate 95.1%), 26.2% scored samples 1, 2 and 3 correctly and 34.3%, 21.5% and 5.8% of participants reported major errors in one, two or three samples respectively. Major errors included reporting "no malaria" or "non-<it>falciparum </it>malaria" for <it>Plasmodium falciparum</it>-positive samples 1 and 2 (16.1% and 34.9% of participants respectively) and "<it>P. falciparum</it>" for <it>Plasmodium </it>negative sample 3 (24.0%). Howell-Jolly bodies (didactic sample) were not recognized by any of the participants but reported as "<it>P. falciparum</it>" by 16.7% of participants. With parasite density expressed according to the "plus system", 16.1% and 21.5% of participants scored one "+" different from the reference score for samples 1 and 2 respectively and 9.7% and 2.9% participants scored more than two "+" different. When expressed as counts of asexual parasites/μl, more than two-thirds of results were outside the mean ± 2SD reference values. The quality of the Giemsa stain was poor, with less than 20% slides complying with all criteria assessed. Only one quarter of participants purchase Giemsa stain from suppliers of documented reliability and half of participants use a buffered staining solution. One third of participants had participated in a formal training about malaria diagnosis, half of them earlier than 2007.</p> <p>Conclusion</p> <p>The present EQA revealed a poor quality of malaria microscopy in DRC.</p

Modeling of information recording and selective etching processes in inorganic resists

Theoretical consideration and computer modeling of information pit recording and etching processes in chalcogenide vitreous semiconductors are proposed, namely we demonstrate how to record and develop information pits with the necessary shape and sizes in the inorganic resist using focused Gaussian laser beam and selective etching. It has been shown that phototransformed region cross-section could be almost trapezoidal or parabolic depending on the resist material optical absorption, recording beam power, exposure, etchant selectivity and etching time. Namely, during the laser illumination and thermal heating caused by it, photosensitive material is the quasi-equilibrium microscopic mixture of the transformed and nontransformed phases with different optical absorption coefficients: temperature dependent near the absorption edge «transformed» coefficient бe and almost independent coefficient α0 . If αe ≤ α0 e after thermal heating, the photo-transformed region «bleaches» and the pit depth increases more rapidly under the following laser power increasing. If αe > α0 , the phototransformed region «darkens» and the pit depth increases sub-linearly or even saturates under the following laser power increasing. Thus, almost parabolic or flattened pits appear when αe ≥ α0, whereas the pits with elongated tops appear when αe << α0. After illumination, the spatial distribution of photo-transformed material fraction was calculated using the Kolmogorov-Awrami equation. Analyzing obtained results, we derived a rather simple approximate analytical expression for the dependence of the phototransformed region width and depth on the recording Gaussian beam power, radius and exposure time. Then the selective etching process was simulated numerically. The obtained results quantitatively describe the characteristics of pits recorded by the Gaussian laser beam in thin layers of As₄₀S₆₀ chalcogenide semiconductor. Our model open possibilities how to select the necessary recording procedure and etching conditions in order to obtain pits with the optimum shape and sizes.Запропоновано теоретичний розгляд та комп’ютерне моделювання процесів запису інформації та селективного травлення в халькогенідних напівпровідниках. Змодульовано процес одержання інформаційних питів необхідної форми та розміру у неорганічному резисті, використовуючи сфокусований гаусівський лазерний пучок та селективне травлення. Показано, що переріз фототрансформованої області змінюється від майже трапецієвидного до параболічного в залежності від коефіцієнта оптичного поглинання, потужності лазерного пучка, експозиції, селективності травника та часу травлення. Просторовий розподіл долі фототрансформованого матеріалу розраховано з рівняння Колмогорова-Аврами. Проаналізовано одержані результати й виведено досить простий наближений аналітичний вираз для залежності ширини та висоти фототрансформованої області від потужності лазерного пучка, його радіусу, часу експонування та селективності травника. Одержані результати добре описують характеристики пітів, записаних у тонких шарах халькогеніду As₄₀S₆₀. Модель відкриває реальну можливість добору умов запису та травлення резисту, необхідних для одержання пітів з оптимальними розмірами.Предложено теоретическое рассмотрение и компьютерное моделирование процессов записи информации и селективного травления в халькогенидных полупроводниках. Смоделирован процесс получения информационных питов необходимой формы и размеров в неорганическом резисте, используя сфокусированный гауссовский лазерный пучок и селективное травление. Показано, что сечение фототрансформированной области может изменяться от практически трапециевидного до параболического в зависимости от коэффициента оптического поглощения, мощности лазерного пучка, экспозиции, селективности травителя и времени травления. Пространственное распределение доли фототрансформированного материала рассчитано из уравнения Колмогорова-Аврами. Проанализированы полученные результаты и выведено достаточно простое приближенное аналитическое выражение для зависимости ширины и высоты фототрансформированной области от мощности лазерного пучка, его радиуса, времени экспонирования и селективности травителя. Полученные результаты хорошо описывают характеристики питов, записанных в тонких слоях халькогенида As₄₀S₆₀. Модель открывает реальную возможность выбора условий записи и травления резиста, необходимых для получения питов с оптимальными размерами

Immunogenicity of an Extended Dose Interval for the Ad26.ZEBOV, MVA-BN-Filo Ebola Vaccine Regimen in Adults and Children in the Democratic Republic of the Congo

During the 2018–2020 Ebola virus disease outbreak in Democratic Republic of the Congo, a phase 3 trial of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine (DRC-EB-001) commenced in Goma, with participants being offered the two-dose regimen given 56 days apart. Suspension of trial activities in 2020 due to the COVID-19 pandemic led to some participants receiving a late dose 2 outside the planned interval. Blood samples were collected from adults, adolescents, and children prior to their delayed dose 2 vaccination and 21 days after, and tested for IgG binding antibodies against Ebola virus glycoprotein using the Filovirus Animal Nonclinical Group (FANG) ELISA. Results from 133 participants showed a median two-dose interval of 9.3 months. The pre-dose 2 antibody geometric mean concentration (GMC) was 217 ELISA Units (EU)/mL (95% CI 157; 301) in adults, 378 EU/mL (281; 510) in adolescents, and 558 EU/mL (471; 661) in children. At 21 days post-dose 2, the GMC increased to 22,194 EU/mL (16,726; 29,449) in adults, 37,896 EU/mL (29,985; 47,893) in adolescents, and 34,652 EU/mL (27,906; 43,028) in children. Participants receiving a delayed dose 2 had a higher GMC at 21 days post-dose 2 than those who received a standard 56-day regimen in other African trials, but similar to those who received the regimen with an extended interval

Syphilis screening and treatment in pregnant women in Kinshasa, Democratic Republic of the Congo and in Lusaka, Zambia: a cross-sectional study [version 1; referees: 2 approved]

Background: Congenital syphilis is associated with perinatal deaths, preterm births and congenital malformations. Low rates of syphilis screening during pregnancy and treatment of those found seropositive have been reported in the Democratic Republic of the Congo (DRC) and Zambia. We report the rates on antenatal syphilis screening, the seroprevalence of syphilis infection, and the frequency of antibiotic treatment in pregnant women screened positive for syphilis during their attendance at antenatal care (ANC) clinics in Kinshasa, DRC and Lusaka, Zambia. Methods: Women attending their first ANC were enrolled consecutively during a 9-month period in 16 and 13 ANC clinics in Kinshasa and Lusaka respectively, in the context of the baseline period of a cluster trial. Study personnel collected data on women’s characteristics, the syphilis screening practices, the test results, and the frequency of treatment, that were done under routine ANC conditions and registered in the clinic records. Results: 4,153 women in Kinshasa and 18,097 women in Lusaka were enrolled. The frequency of screening at the first visit was 59.7% (n= 2,479) in Kinshasa, and 27.8% (n=5,025) in Lusaka. Screening test availability varied. In the periods in which tests were available the screening rates were 92.8% in Kinshasa and 52.0% in Lusaka. The frequency of women screened seropositive was 0.4% (n=10) in Kinshasa and 2.2% (n=109) in Lusaka. Respectively, 10% (n=1) and 11.9% (n= 13) among seropositive women received treatment at the first visit. Conclusions: The results of the study show that screening for syphilis in pregnancy is not universal even when supplies are available. Our ongoing trial will evaluate the impact of a behavioral intervention on changing health providers’ practices to increase screening and treatment rates when supplies are available

Development and Evaluation of Quantitative Immunoglobulin G Enzyme-Linked Immunosorbent Assay for the Diagnosis of Coronavirus Disease 2019 Using Truncated Recombinant Nucleocapsid Protein as Assay Antigen

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Real-time RT-PCR is the most commonly used method for COVID-19 diagnosis. However, serological assays are urgently needed as complementary tools to RT-PCR. Hachim et al. 2020 and Burbelo et al. 2020 demonstrated that anti-nucleocapsid(N) SARS-CoV-2 antibodies are higher and appear earlier than the spike antibodies. Additionally, cross-reactive antibodies against N protein are more prevalent than those against spike protein. We developed a less cross-reactive immunoglobulin G (IgG) indirect ELISA by using a truncated recombinant SARS-CoV-2 N protein as assay antigen. A highly conserved region of coronaviruses N protein was deleted and the protein was prepared using an E. coli protein expression system. A total of 177 samples collected from COVID-19 suspected cases and 155 negative control sera collected during the pre-COVID-19 period were applied to evaluate the assay’s performance, with the plaque reduction neutralization test and the commercial SARS-CoV-2 spike protein IgG ELISA as gold standards. The SARS-CoV-2 N truncated protein-based ELISA showed similar sensitivity (91.1% vs. 91.9%) and specificity (93.8% vs. 93.8%) between the PRNT and spike IgG ELISA, as well as also higher specificity compared to the full-length N protein (93.8% vs. 89.9%). Our ELISA can be used for the diagnosis and surveillance of COVID-19

External quality assessment on the use of malaria rapid diagnostic tests in a non-endemic setting

<p>Abstract</p> <p>Background</p> <p>Malaria rapid diagnostic tests (RDTs) are increasingly used as a tool for the diagnosis of malaria, both in endemic and in non-endemic settings. The present study reports the results of an external quality assessment (EQA) session on RDTs in a non-endemic setting.</p> <p>Methods</p> <p>After validation of antigen stability during shipment at room temperature, three clinical samples and a questionnaire were sent to clinical laboratories in Belgium and the Grand Duchy of Luxembourg using malaria RDTs. Participants were asked to report the results of the RDTs as observations (visibility of the RDT control and test lines) and interpretations (report as formulated to the clinician). In addition, participants were invited to fill in a questionnaire on the place of RDTs in the diagnostic strategy of malaria.</p> <p>Results</p> <p>A total of 128/133 (96.2%) of clinical laboratories using RDTs participated. Six three-band and one four-band RDT brands were used. Analytical errors were rare and included (i) not recognizing invalid RDT results (1.6%) and (ii) missing the diagnosis of <it>Plasmodium falciparum </it>(0.8%). Minor errors were related to RDT test result interpretation and included (i) reporting "RDT positive" without species identification in the case of <it>P. falciparum </it>and non-<it>falciparum </it>species (16.9% and 6.5% respectively) and (ii) adding incorrect comments to the report (3.2%). Some of these errors were related to incorrect RDT package insert instructions such as (i) not reporting the possibility of mixed species infection in the case of <it>P. falciparum </it>and <it>Plasmodium vivax </it>(35.5% and 18.5% respectively) and (ii) the interpretation of <it>P. vivax </it>instead of non-falciparum species at the presence of a pan-species antigen line (4.0%). According to the questionnaire, 48.8% of participants processed ≤20 requests for malaria diagnosis in 2009. During opening hours, 93.6% of 125 participants used RDTs as an adjunct to microscopy but outside opening hours, nearly one third of 113 participants relied on RDTs as the primary (4.4%) or the single tool (25.7%) for malaria diagnosis.</p> <p>Conclusion</p> <p>In this non-endemic setting, errors in RDT performance were mainly related to RDT test line interpretations, partly due to incorrect package insert instructions. The reliance on RDTs as the primary or the single tool for the diagnosis of malaria outside opening hours is of concern and should be avoided.</p

Management of latent Mycobacterium tuberculosis infection:WHO guidelines for low tuberculosis burden countries

ABSTRACT Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of &lt;100 per 100000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing an

Delivery and Safety of a Two-Dose Preventive Ebola Virus Disease Vaccine in Pregnant and Non-Pregnant Participants during an Outbreak in the Democratic Republic of the Congo

During the 2018–2020 Ebola virus disease (EVD) outbreak, residents in Goma, Democratic Republic of the Congo, were offered a two-dose prophylactic EVD vaccine. This was the first study to evaluate the safety of this vaccine in pregnant women. Adults, including pregnant women, and children aged ≥1 year old were offered the Ad26.ZEBOV (day 0; dose 1), MVA-BN-Filo (day 56; dose 2) EVD vaccine through an open-label clinical trial. In total, 20,408 participants, including 6635 (32.5%) children, received dose 1. Fewer than 1% of non-pregnant participants experienced a serious adverse event (SAE) following dose 1; one SAE was possibly related to the Ad26.ZEBOV vaccine. Of the 1221 pregnant women, 371 (30.4%) experienced an SAE, with caesarean section being the most common event. No SAEs in pregnant women were considered related to vaccination. Of 1169 pregnancies with a known outcome, 55 (4.7%) ended in a miscarriage, and 30 (2.6%) in a stillbirth. Eleven (1.0%) live births ended in early neonatal death, and five (0.4%) had a congenital abnormality. Overall, 188/891 (21.1%) were preterm births and 79/1032 (7.6%) had low birth weight. The uptake of the two-dose regimen was high: 15,328/20,408 (75.1%). The vaccine regimen was well-tolerated among the study participants, including pregnant women, although further data, ideally from controlled trials, are needed in this crucial group