Accuracy of Individual Rapid Tests for Serodiagnosis of Gambiense Sleeping Sickness in West Africa

Background

Individual rapid tests for serodiagnosis (RDT) of human African trypanosomiasis (HAT) are particularly suited for passive screening and surveillance. However, so far, no large scale evaluation of RDTs has been performed for diagnosis of Trypanosoma brucei gambiense HAT in West Africa. The objective of this study was to assess the diagnostic accuracy of 2 commercial HAT-RDTs on stored plasma samples from West Africa.

Methodology/Principal findings

SD Bioline HAT and HAT Sero-K-Set were performed on 722 plasma samples originating from Guinea and Côte d’Ivoire, including 231 parasitologically confirmed HAT patients, 257 healthy controls, and 234 unconfirmed individuals whose blood tested antibody positive in the card agglutination test but negative by parasitological tests. Immune trypanolysis was performed as a reference test for trypanosome specific antibody presence. Sensitivities in HAT patients were respectively 99.6% for SD Bioline HAT, and 99.1% for HAT Sero-K-Set, specificities in healthy controls were respectively 87.9% and 88.3%. Considering combined positivity in both RDTs, increased the specificity significantly (p≤0.0003) to 93.4%, while 98.7% sensitivity was maintained. Specificities in controls were 98.7–99.6% for the combination of one or two RDTs with trypanolysis, maintaining a sensitivity of at least 98.1%.

Conclusions/Significance

The observed specificity of the single RDTs was relatively low. Serial application of SD Bioline HAT and HAT Sero-K-Set might offer superior specificity compared to a single RDT, maintaining high sensitivity. The combination of one or two RDTs with trypanolysis seems promising for HAT surveillance.     

Passive surveillance of human African trypanosomiasis in Côte d’Ivoire: Understanding prevalence,clinical symptoms and signs,and diagnostic test characteristics

BackgroundLittle is known about the diagnostic performance of rapid diagnostic tests (RDTs) for passive screening of human African trypanosomiasis (HAT) in Côte d’Ivoire. We determined HAT prevalence among clinical suspects, identified clinical symptoms and signs associated with HAT RDT positivity, and assessed the diagnostic tests’ specificity, positive predictive value and agreement.MethodsClinical suspects were screened with SD Bioline HAT, HAT Sero-K-Set and rHAT Sero-Strip. Seropositives were parasitologically examined, and their dried blood spots tested in trypanolysis, ELISA/Tbg, m18S-qPCR and LAMP. The HAT prevalence in the study population was calculated based on RDT positivity followed by parasitological confirmation. The association between clinical symptoms and signs and RDT positivity was determined using multivariable logistic regression. The tests’ Positive Predictive Value (PPV), specificity and agreement were determined.ResultsOver 29 months, 3433 clinical suspects were tested. The RDT positivity rate was 2.83%, HAT prevalence 0.06%. Individuals with sleep disturbances (p<0.001), motor disorders (p = 0.002), convulsions (p = 0.02), severe weight loss (p = 0.02) or psychiatric problems (p = 0.04) had an increased odds (odds ratios 1.7–4.6) of being HAT RDT seropositive. Specificities ranged between 97.8%-99.6% for individual RDTs, and 93.3–98.9% for subsequent tests on dried blood spots. The PPV of the individual RDTs was below 14.3% (CI 2–43), increased to 33.3% (CI 4–78) for serial RDT combinations, and reached 67% for LAMP and ELISA/Tbg on RDT positives. Agreement between diagnostic tests was poor to moderate (Kappa ≤ 0.60), except for LAMP and ELISA/Tbg (Kappa = 0.66).ConclusionIdentification of five key clinical symptoms and signs may simplify referral for HAT RDT screening. The results confirm the appropriateness of the diagnostic algorithm presently applied, with screening by SD Bioline HAT or HAT Sero-K-Set, supplemented with trypanolysis. ELISA/Tbg could replace trypanolysis and is simpler to perform.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03356665","term_id":"NCT03356665"}}NCT03356665.     

中国埃博拉诊疗中心布局流程的设计与思考

为了应对西非埃博拉病毒病疫情,中国人民解放军援利医疗队在利比里亚建立并独立运营了埃博拉诊疗中心。中心严格按照传染病医院的防护要求和标准,设计科学合理的布局流程,实现有效的感染防控。详细说明了中国埃博拉诊疗中心的布局与流程设计,归纳阐述其特点,并对做好布局流程应把握的几个重点问题进行了探讨。     

Health seeking behavior after the 2013–16 Ebola epidemic: Lassa fever as a metric of persistent changes in Kenema District,Sierra Leone

BackgroundThe West African Ebola epidemic of 2013–2016 killed nearly 4,000 Sierra Leoneans and devastated health infrastructure across West Africa. Changes in health seeking behavior (HSB) during the outbreak resulted in dramatic underreporting and substantial declines in hospital presentations to public health facilities, resulting in an estimated tens of thousands of additional maternal, infant, and adult deaths per year. Sierra Leone’s Kenema District, a major Ebola hotspot, is also endemic for Lassa fever (LF), another often-fatal hemorrhagic disease. Here we assess the impact of the West African Ebola epidemic on health seeking behaviors with respect to presentations to the Kenema Government Hospital (KGH) Lassa Ward, which serves as the primary health care referral center for suspected Lassa fever cases in the Eastern Province of Sierra Leone.Methodology/Principal findingsPresentation frequencies for suspected Lassa fever presenting to KGH or one of its referral centers from 2011–2019 were analyzed to consider the potential impact of the West African Ebola epidemic on presentation patterns. There was a significant decline in suspected LF cases presenting to KGH following the epidemic, and a lower percentage of subjects were admitted to the KGH Lassa Ward following the epidemic. To assess general HSB, a questionnaire was developed and administered to 200 residents from 8 villages in Kenema District. Among 194 completed interviews, 151 (78%) of respondents stated they felt hospitals were safer post-epidemic with no significant differences noted among subjects according to religious background, age, gender, or education. However, 37 (19%) subjects reported decreased attendance at hospitals since the epidemic, which suggests that trust in the healthcare system has not fully rebounded. Cost was identified as a major deterrent to seeking healthcare.Conclusions/SignificanceAnalysis of patient demographic data suggests that fewer individuals sought care for Lassa fever and other febrile illnesses in Kenema District after the West African Ebola epidemic. Re-establishing trust in health care services will require efforts beyond rebuilding infrastructure and require concerted efforts to rebuild the trust of local residents who may be wary of seeking healthcare post epidemic.     

Evaluation of the Diagnostic Accuracy of Prototype Rapid Tests for Human African Trypanosomiasis

BackgroundDiagnosis of human African trypanosomiasis (HAT) remains a challenge both for active screening, which is critical in control of the disease, and in the point-of-care scenario where early and accurate diagnosis is essential. Recently, the first field deployment of a lateral flow rapid diagnostic test (RDT) for HAT, “SD BIOLINE HAT” has taken place. In this study, we evaluated the performance of “SD BIOLINE HAT” and two new prototype RDTs.Conclusions/SignificanceBoth “SD BIOLINE HAT” and the prototype devices performed comparably well to one another and also to the published performance range of the card agglutination test for trypanosomiasis in sensitivity and specificity. The performance of individual antigens enabled us to predict that an all-recombinant antigen RDT can be developed with an accuracy equivalent to “ SD BIOLINE HAT.” Such an RDT would have advantages in simplified manufacture, lower unit cost and assured reproducibility.     

Community-Centered Responses to Ebola in Urban Liberia: The View from Below

BackgroundThe West African Ebola epidemic has demonstrated that the existing range of medical and epidemiological responses to emerging disease outbreaks is insufficient, especially in post-conflict contexts with exceedingly poor healthcare infrastructures. In this context, community-based responses have proven vital for containing Ebola virus disease (EVD) and shifting the epidemic curve. Despite a surge in interest in local innovations that effectively contained the epidemic, the mechanisms for community-based response remain unclear. This study provides baseline information on community-based epidemic control priorities and identifies innovative local strategies for containing EVD in Liberia.Conclusions/SignificanceLocal communities’ strategies and recommendations give insight into how urban Liberian communities contained the EVD outbreak while navigating the systemic failures of the initial state and international response. Communities in urban Liberia adapted to the epidemic using multiple coping strategies. In the absence of health, infrastructural and material supports, local people engaged in self-reliance in order to contain the epidemic at the micro-social level. These innovations were regarded as necessary, but as less desirable than a well-supported health-systems based response; and were seen as involving considerable individual, social, and public health costs, including heightened vulnerability to infection.     

埃博拉病毒/埃博拉病—2014

2014年2月,死亡率极高的埃博拉病(EVD)开始在西部非洲的几内亚暴发流行,接下来,暴发流行出现在塞拉利昂、利比里亚、尼日利亚和塞内加尔另四个西部非洲的国家。现在,几内亚、利比里亚和塞拉利昂的疫情最重。迄今为止,已有4 784人患EVD,且人数仍在倍增,这次暴发流行已成为自40年前EVD被发现以来规模最大的一次,已形成了波及其他地区和国家的巨大危险。在此,综述2014年EVD暴发流行的起因,埃博拉病毒(EBOV)及其传播,EVD的诊断治疗,EBOV疫苗的研制以及EBOV感染的防控。     

Evaluating Subcriticality during the Ebola Epidemic in West Africa

The 2014–2015 Ebola outbreak is the largest and most widespread to date. In order to estimate ongoing transmission in the affected countries, we estimated the weekly average number of secondary cases caused by one individual infected with Ebola throughout the infectious period for each affected West African country using a stochastic hidden Markov model fitted to case data from the World Health Organization. If the average number of infections caused by one Ebola infection is less than 1.0, the epidemic is subcritical and cannot sustain itself. The epidemics in Liberia and Sierra Leone have approached subcriticality at some point during the epidemic; the epidemic in Guinea is ongoing with no evidence that it is subcritical. Response efforts to control the epidemic should continue in order to eliminate Ebola cases in West Africa.     

A participatory epidemiological and One Health approach to explore the community’s capacity to detect emerging zoonoses and surveillance network opportunities in the forest region of Guinea

The Ebola virus disease epidemic that threatened West Africa between 2013 and 2016 was of unprecedented health magnitude. After this health crisis, studies highlighted the need to introduce community-based surveillance systems and to adopt a One Health approach. This study aimed to provide preparatory insights for the definition of a community-based surveillance system for emerging zoonoses such as viral hemorrhagic fevers in Guinea. The objective was to explore the disease detection capacity and the surveillance network opportunities at the community level in two pilot areas in the forest region of Guinea, where the epidemic emerged. Based on a participatory epidemiological and One Health approach, we conducted Focus Group Discussions with human, animal and ecosystem health actors. We used a range of participatory tools, included semi-structured interviews, ranking, scoring and flow diagram, to estimate the local knowledge and perception of diseases and clinical signs and to investigate the existing health information exchange network and its related strengths and weaknesses. The results showed that there is heterogeneity in knowledge of diseases and perception of the clinical signs among actors and that there are preferred and more effective health communication channels opportunities. This preparatory study suggests that it is necessary to adapt the case definitions and the health communication channels to the different actors who can play a role in a future community-based surveillance system and provides recommendations for future surveillance activities to be carried out in West Africa.     

A model of the Ebola epidemics in West Africa incorporating age of infection

A model of an Ebola epidemic is developed with infected individuals structured according to disease age. The transmission of the infection is tracked by disease age through an initial incubation (exposed) phase, followed by an infectious phase with variable transmission infectiousness. The removal of infected individuals is dependent on disease age, with three types of removal rates: (1) removal due to hospitalization (isolation), (2) removal due to mortality separate from hospitalization, and (3) removal due to recovery separate from hospitalization. The model is applied to the Ebola epidemics in Sierra Leone and Guinea. Model simulations indicate that successive stages of increased and earlier hospitalization of cases have resulted in mitigation of the epidemics.     

Acceptability and Willingness-to-Pay for a Hypothetical Ebola Virus Vaccine in Nigeria

BackgroundEbola virus disease is a highly virulent and transmissible disease. The largest recorded fatality from Ebola virus disease epidemic is ongoing in a few countries in West Africa, and this poses a health risk to the entire population of the world because arresting the transmission has been challenging. Vaccination is considered a key intervention that is capable of arresting further spread of the disease and preventing future outbreak. However, no vaccine has yet been approved for public use, although various recombinant vaccines are undergoing trials and approval for public use is imminent. Therefore, this study aimed to determine the acceptability of and willingness-to-pay for Ebola virus vaccine by the public.MethodsThe study was a community-based cross-sectional qualitative and quantitative interventional study conducted in two communities, each in two states in Nigeria. An interviewer-administered questionnaire was used to collect information on respondents’ knowledge of the Ebola virus, the ways to prevent the disease, and their preventive practices, as well as their acceptability of and willingness-to-pay for a hypothetical vaccine against Ebola virus disease. The association between acceptability of the vaccine and other independent variables were evaluated using multivariate regression analysis.ResultsEbola virus disease was considered to be a very serious disease by 38.5% of the 582 respondents (224/582), prior to receiving health education on Ebola virus and its vaccine. Eighty percent (80%) accepted to be vaccinated with Ebola vaccine. However, among those that accepted to be vaccinated, most would only accept after observing the outcome on others who have received the vaccine. More than 87.5% was willing to pay for the vaccine, although 55.2% was of the opinion that the vaccine should be provided free of charge.ConclusionThe level of acceptability of Ebola virus vaccine among respondents was impressive (though conditional), as well as their willingness to pay for it if the vaccine is not publicly funded. In order to achieve a high uptake of the vaccine, information and education on the vaccine should be extensively shared with the public prior to the introduction of the vaccine, and the vaccine should be provided free of charge by government.     

A prospective study to evaluate the accuracy of rapid diagnostic tests for diagnosis of human leptospirosis: Result from THAI-LEPTO AKI study

BackgroundRapid diagnostic tests (RDTs) have become widely used in low-resource settings for leptospirosis diagnostic. This study aims to evaluate the diagnostic performance of the five commercially available RDTs to detect human IgM against Leptospira spp. in Thai population.Methodology/Principal findingsNinety-nine serum samples from Leptospirosis suspicious patients were tested with five RDTs, including Medical Science Public Health, Leptocheck-WB, SD bioline, TRUSTline, and J.Mitra. The case definition was based on MAT, qPCR, and culture results. Diagnostic accuracy was determined based on the first day of enrollment in an overall analysis and stratified according to days post-onset of fever. The five RDTs had overall sensitivity ranging from 1.8% to 75% and specificity ranging from 52.3% to 97.7%. Leptocheck-WB had high sensitivity of 75.0%. The sensitivity of five RDTs increased on days 4–6 post-onset of fever, while the specificity of all tests remained relatively stable at different days post-onset of fever.Conclusions/SignificanceThe tested RDTs showed low sensitivity. Therefore, based on the present study, five commercially available RDTs might not be an appropriate test for acute leptospirosis screening in the Thai population.     

Qualitative evidence syntheses of attitudes and preferences to inform guidelines on infant feeding in the context of Ebola Virus Disease (EVD) transmission risk

BackgroundBreast-feeding holds considerable potential to reduce infant mortality. Feeding choices, already complex, take on additional complexity against a backdrop of the risk of transmissible Ebola Virus. This review describes the factors that influence infant feeding and attitudes of pregnant women, mothers, family members and health practitioners, policy makers and providers (midwives) concerning infant feeding when there is a risk of Mother-to-Child (MTC) transmission of Ebola Virus Disease (EVD).MethodologyA systematic review of qualitative studies identified through rigorous searches of thirteen online databases and additional citation searches of included studies was undertaken. Search terms included breast-feeding, breast-feeding, infant feeding; Ebola; and qualitative, interview(s) and findings. Independent extraction of data by two reviewers using predefined extraction forms. Studies were assessed using the CASP Qualitative checklist.Principal findings5219 references were screened. 38 references related specifically to Ebola, and five papers met the inclusion criteria with data gathered from two settings: Guinea and Sierra Leone. The EVD outbreak had a significant impact on beliefs, attitudes, and resources to support infant feeding practices negatively affecting the nutritional status of children. The evidence from these studies highlight the need for guidance and appropriate psychosocial support need to be available to mothers who display symptoms and become infected and to front-line staff who are giving advice. Communities need to be engaged because stigma and fear may hinder uptake of appropriate interventions. The EVD outbreak caused multi-level system disruption akin to that seen following a natural disaster, meaning that logistics and coordination are critical and need adequate resourcing. Food production and distribution, and malnutrition screening are also disrupted and thereby compounding compromised nutritional status. The limited number of relevant studies highlights the need for further primary research, particularly in translation of messages to local settings.ConclusionsAn EVD outbreak causes multi-level disruption that negatively impacts infant feeding and child care practices. Negative impacts have multiple causes and successful planning for Ebola outbreaks requires that nutrition of infants and young children is a priority. Lessons from the Ebola pandemic have wider applicability to other pandemic contexts including Covid-19.     

Evaluating Clinical Trial Designs for Investigational Treatments of Ebola Virus Disease

BackgroundExperimental treatments for Ebola virus disease (EVD) might reduce EVD mortality. There is uncertainty about the ability of different clinical trial designs to identify effective treatments, and about the feasibility of implementing individually randomised controlled trials during an Ebola epidemic.ConclusionsThe MSA discards ineffective treatments quickly, while reliably providing evidence concerning effective treatments. The MSA is appropriate for the clinical evaluation of EVD treatments.     

海南省2016-2018年A(H1N1)pdm09亚型流感病毒基因特性分析

2009年A(H1N1)pdm09亚型流感病毒在墨西哥暴发,之后在全世界流行。为了解海南省2016-2018年A(H1N1)pdm09亚型流感病毒流行态势,分析血凝素(HA)与神经氨酸酶(NA)基因遗传进化特征与变异情况,本研究从中国流感监测信息系统获取海南省2016-2018年流感病毒病原学监测数据,选取5家流感监测网络实验室分离鉴定的37株A(H1N1)pdm09亚型流感毒株进行HA与NA基因测序,利用MEGA 10.1.8构建HA与NA基因种系进化树,并分析其氨基酸变异情况。结果显示,2016-2018年共出现3次A(H1N1)pdm09亚型流感病毒活动高峰。2017年10月份以后的分离株(4/8)与2018年大部分分离株(21/22)独立于疫苗株A/Michigan/45/2015聚为一个小支,发生20余处HA与NA氨基酸位点变异。与疫苗株A/California/7/2009(2010-2016)相比,2016-2018年流感病毒分离株在HA基因抗原决定簇上发生7处氨基酸变异并有一个潜在糖基化位点,未发现HA基因受体结合位点变异与NA基因耐药性变异。本研究提示,2016-2018年,A(H1N1)pdm09亚型流感病毒逐步发生规律性进化,氨基酸变异频率有增加趋势,今后应持续加强流感病毒病原学监测,密切追踪A(H1N1)pdm09亚型流感病毒基因变异情况,为科学防控提供理论依据。     

Diversity of response to Trypanosoma brucei gambiense infections in the Forecariah mangrove focus (Guinea): perspectives for a better control of sleeping sickness

At a time when human African trypanosomiasis (HAT) elimination again seems a reachable goal in many parts of sub-Saharan Africa, it is becoming increasingly important to characterise the factors involved in disease resurgence or maintenance to develop sustainable control strategies. In this study conducted in the Forecariah mangrove focus in Guinea, HAT patients and serological suspects (SERO) were identified through mass screening of the population with the Card Agglutination Test for Trypanosomiasis (CATT) and were followed up for up to 2 years. Analysis of the samples collected during the follow-up of HAT patients and SERO was performed with PCR (TBR1/TBR2) and the trypanolysis serological test (TL) in order to clarify the role played by these individuals in the epidemiology of HAT. PCR positivity was higher in TL⁺ than in SERO TL⁻ (50% vs. 18%, respectively). Whereas CATT plasma titres decreased both in treated HAT patients and SERO TL⁻, SERO TL⁺ maintained high CATT titres. Four out of 17 SERO TL⁺ developed HAT during the study. These results strongly suggest that SERO TL⁺ individuals are asymptomatic carriers. In the context where disease prevalence is sufficiently low, treating SERO TL⁺ individual may thus be of crucial importance in order to cut transmission.     

The elimination of human African trypanosomiasis: Achievements in relation to WHO road map targets for 2020

BackgroundIn the 20th century, epidemics of human African trypanosomiasis (HAT) ravaged communities in a number of African countries. The latest surge in disease transmission was recorded in the late 1990s, with more than 35,000 cases reported annually in 1997 and 1998. In 2013, after more than a decade of sustained control efforts and steady progress, the World Health Assembly resolved to target the elimination of HAT as a public health problem by 2020. We report here on recent progress towards this goal.Methodology/principal findingsWith 992 and 663 cases reported in 2019 and 2020 respectively, the first global target was amply achieved (i.e. fewer than 2,000 HAT cases/year). Areas at moderate or higher risk of HAT, where more than 1 case/10,000 people/year are reported, shrunk to 120,000 km² for the five-year period 2016–2020. This reduction of 83% from the 2000–2004 baseline (i.e. 709,000 km²) is slightly below the target (i.e. 90% reduction). As a result, the second global target for HAT elimination as a public health problem cannot be considered fully achieved yet. The number of health facilities able to diagnose and treat HAT expanded (+9.6% compared to a 2019 survey), thus reinforcing the capacity for passive detection and improving epidemiological knowledge of the disease. Active surveillance for gambiense HAT was sustained. In particular, 2.8 million people were actively screened in 2019 and 1.6 million in 2020, the decrease in 2020 being mainly caused by COVID-19-related restrictions. Togo and Côte d’Ivoire were the first countries to be validated for achieving elimination of HAT as a public health problem at the national level; applications from three additional countries are under review by the World Health Organization (WHO).Conclusions/significanceThe steady progress towards the elimination of HAT is a testament to the power of multi-stakeholder commitment and coordination. At the end of 2020, the World Health Assembly endorsed a new road map for 2021–2030 that set new bold targets for neglected tropical diseases. While rhodesiense HAT remains among the diseases targeted for elimination as a public health problem, gambiense HAT is targeted for elimination of transmission. The goal for gambiense HAT is expected to be particularly arduous, as it might be hindered by cryptic reservoirs and a number of other challenges (e.g. further integration of HAT surveillance and control into national health systems, availability of skilled health care workers, development of more effective and adapted tools, and funding for and coordination of elimination efforts).     

Community trust of government and non-governmental organizations during the 2014-16 Ebola epidemic in Liberia

The West African Ebola Virus Disease epidemic of 2014-16 cost more than 11,000 lives. Interventions targeting key behaviors to curb transmission, such as safe funeral practices and reporting and isolating the ill, were initially unsuccessful in a climate of fear, mistrust, and denial. Building trust was eventually recognized as essential to epidemic response and prioritized, and trust was seen to improve toward the end of the epidemic as incidence fell. However, little is understood about how and why trust changed during Ebola, what factors were most influential to community trust, and how different institutions might have been perceived under different levels of exposure to the outbreak. In this large-N household survey conducted in Liberia in 2018, we measured self-reported trust over time retrospectively in three different communities with different exposures to Ebola. We found trust was consistently higher for non-governmental organizations than for the government of Liberia across all time periods. Trust reportedly decreased significantly from the start to the peak of the epidemic in the study site of highest Ebola incidence. This finding, in combination with a negative association found between knowing someone infected and trust of both iNGOs and the government, indicates the experience of Ebola may have itself caused a decline of trust in the community. These results suggest that national governments should aim to establish trust when engaging communities to change behavior during epidemics. Further research on the relationship between trust and epidemics may serve to improve epidemic response efficacy and behavior uptake.