Field evaluation of validity and feasibility of Pan-Lassa rapid diagnostic test for Lassa fever in Abakaliki, Nigeria: a prospective diagnostic accuracy study.

BACKGROUND: Lassa fever is a viral haemorrhagic fever with few options for diagnosis and treatment; it is also under-researched with knowledge gaps on its epidemiology. A point-of-care bedside test diagnosing Lassa fever, adhering to REASSURED criteria, is not currently available but is urgently needed in west African regions with high Lassa fever burden. We aimed to assess the validity and feasibility of a rapid diagnostic test (RDT) to confirm Lassa fever in people in Nigeria. METHODS: We estimated the diagnostic performance of the ReLASV Pan-Lassa RDT (Zalgen Labs, Frederick, MD, USA) as a research-use-only test, compared to RT-PCR as a reference standard, in 217 participants at a federal tertiary hospital in Abakaliki, Nigeria. We recruited participants between Feb 17, 2022, and April 17, 2023. The RDT was performed using capillary blood at the patient bedside and using plasma at the laboratory. The performance of the test, based on REASSURED criteria, was assessed for user friendliness, rapidity and robustness, sensitivity, and specificity. FINDINGS: Participants were aged between 0 and 85 years, with a median age of 33·0 years (IQR 22·0-44·3), and 24 participants were younger than 18 years. 107 (50%) participants were women and 109 (50%) were men; one participant had missing sex data. Although the specificity of the Pan-Lassa RDT was high (>90%), sensitivity at bedside using capillary blood was estimated as 4% (95% CI 1-14) at 15 min and 10% (3-22) at 25 min, far below the target of 90%. The laboratory-based RDT using plasma showed better sensitivity (46% [32-61] at 15 min and 50% [36-64] at 25 min) but did not reach the target sensitivity. Among the 52 PCR-positive participants with Lassa fever, positive RDT results were associated with lower cycle threshold values (glycoprotein precursor [GPC] gene mean 30·3 [SD 4·3], Large [L] gene mean 32·3 [3·7] vs GPC gene mean 24·5 [3·9], L gene mean 28·0 [3·6]). Personnel conducting the bedside test procedure reported being hindered by the inconvenient use of full personal protective equipment and long waiting procedures before a result could be read. INTERPRETATION: The Pan-Lassa RDT is not currently recommended as a diagnostic or screening tool for suspected Lassa fever cases. Marked improvement in sensitivity and user friendliness is needed for the RDT to be adopted clinically. There remains an urgent need for better Lassa fever diagnostics to promote safety of in-hospital care and better disease outcomes in low-resource settings. FUNDING: Médecins Sans Frontières.

Association between BNT162b2 vaccination and health-related quality of life up to 18 months post-SARS-CoV-2 infection in Israel.

We determined whether COVID-19 vaccination was associated with Quality of Life (QoL) changes among individuals previously infected with SARS-CoV-2 in Israel. Using a validated questionnaire, we collected information about socio-demographics, SARS-CoV-2 infection, COVID-19 vaccination and QoL (using the EQ-5D-5L tool) 3-18 months post-infection among adults tested for SARS-CoV-2 by polymerase chain reaction in Northern Israel between March 2020-June 2022. We compared post-COVID QoL between those vaccinated against COVID-19 at the time of infection and those not, using an adjusted linear regression model, stratified by time elapsed since infection. Of 951 participants, mean EQ-5D Utility Index (EQ-5D UI) was 0.82 (SD = 0.26) and 0.83 (SD = 0.25) among the 227 double and 250 triple vaccinated respectively, compared to 0.76 (SD = 0.33) among those who received 0 dose (n = 243). The size of the effect of vaccination was small (Cohen's d = 0.2). In the adjusted model, previously infected individuals vaccinated with two or more doses reported a QoL score post- infection 0.05 points higher (CI = 0.01-0.10, p = 0.02) compared with those unvaccinated when infected. No association between vaccination and QoL was detected beyond 12 months post-infection. Vaccination with two or more doses of COVID19 vaccine, or at least the BNT162b2 vaccine, may modestly mitigate QoL losses associated with post-acute COVID-19 symptoms, at least in the first 12 months post-infection.

Changes in Quality of Life Following SARS-CoV-2 Infection Among Jewish and Arab Populations in Israel: A Cross-Sectional Study.

Objectives: The long-term impact of COVID-19 on health inequalities is under-researched. We investigated changes in health-related inequalities following SARS-CoV-2 infection between the Jewish majority and the Arab/Druze minority in Israel. Methods: Patients with a positive SARS-CoV-2 RT-PCR test processed from one of the Northern-Israeli government hospitals between 03/2021 and 05/2022 were invited to participate. We collected socio-demographic, COVID-19-related, and health-related quality of life (HRQoL) information using a validated questionnaire. We compared pre- and post COVID-19 HRQoL changes between Jews and Arabs/Druze, up to 12+ months post-infection using an adjusted linear regression model. Results: Among the 881 included participants the average post-COVID HRQoL score was lower among Arabs/Druze than Jews (0.83 vs. 0.88; p = 0.005). Until 12 months post-infection, HRQoL changes were similar for Arabs/Druze and Jews. After 12 months, HRQoL dropped significantly more among Arabs/Druze than among Jews (0.11 points difference between the groups; p = 0.014), despite adjusting for socioeconomic variables. Conclusion: 12 months post-infection, COVID-19 affected the HRQoL of Arabs/Druze more than Jews, with the gap not fully explained by socio-economic differences. The COVID-19 pandemic may widen pre-existing long-term health inequalities.

Surveillance of diphtheria in the Netherlands between 2000-2021: cutaneous diphtheria supersedes the respiratory form.

BACKGROUND: Diphtheria is a severe respiratory or cutaneous infectious disease, caused by exotoxin producing Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis. Diphtheria is once again prevalent due to breakdown of immunisation programmes, social disruption and unrest. AIM: This study describes the notified diphtheria cases in the Netherlands between 2000-2021 and isolates that were sent to the National Institute for Public Health and the Environment (RIVM). METHODS: File investigation was performed including all notified cases and isolates of C. diphtheriae, C. ulcerans and C. pseudotuberculosis that were tested for toxin production using a toxin-PCR and Elek test. An exploratory review was performed to understand transmission in populations with a high vaccination uptake. RESULTS: Eighteen diphtheria notifications were made with confirmed toxigenic C. diphtheriae (n = 9) or ulcerans (n = 9) between 2000 and 2021. Seventeen (94.4%) presented with a cutaneous infection. All cases with a suspected source abroad (n = 8) concerned infection with C. diphtheriae. In contrast, 9/10 cases infected in the Netherlands were caused by C. ulcerans, a zoonosis. Secondary transmission was not reported. Isolates of C. ulcerans sent to the RIVM produced more often the diphtheria exotoxin (11/31; 35%) than C. diphtheriae (7/89; 7.9%). CONCLUSION: Both human-to-human transmission of C. diphtheriae and animal-to-human transmission of C. ulcerans rarely occurs in the Netherlands. Cases mainly present with a cutaneous infection. Travel-related cases remain a risk for transmission to populations with low vaccination coverage, highlighting the importance of immunization and diphtheria control measures.

Associations between reported post-COVID-19 symptoms and subjective well-being, Israel, July 2021 - April 2022.

The impact of individual symptoms reported post-COVID-19 on subjective well-being (SWB) is unknown. We described associations between SWB and selected reported symptoms following SARS-CoV-2 infection. We analysed reported symptoms and subjective well being from 2295 participants (of which 576 reporting previous infection) in an ongoing longitudinal cohort study taking place in Israel. We estimated changes in SWB associated with reported selected symptoms at three follow-up time points (3-6, 6-12 and 12-18 months post infection) among participants reporting previous SARS-CoV-2 infection, adjusted for key demographic variables, using linear regression. Our results suggest that the biggest and most sustained changes in SWB stems from non-specific symptoms (fatigue -7.7 percentage points (pp), confusion/ lack of concentration -10.7 pp, and sleep disorders -11.5pp, P < 0.005), whereas the effect of system-specific symptoms, such as musculoskeletal symptoms (weakness in muscles and muscle pain) on SWB, are less profound and more transient. Taking a similar approach for other symptoms and following individuals over time to describe trends in SWB changes attributable to specific symptoms will help understand the post-acute phase of COVID-19 and how it should be defined and better managed. Post-acute COVID19 symptoms were associated with a significant decrease in subjective well being up to 18 months after initial infection.

Long-term Chikungunya sequelae and quality of life 2.5 years post-acute disease in a prospective cohort in Curaçao.

BACKGROUND: Little is known about the persistence and impact of non-rheumatic symptoms after acute chikungunya disease. We have studied the clinical presentation and long-term impact of rheumatic and non-rheumatic symptoms on health related quality of life (QoL) 2.5 years after disease onset. Additionally, the validity of the Curaçao Long-Term Chikungunya Sequelae (CLTCS) score in classifying disease severity over time was evaluated. METHODOLOGY/PRINCIPAL FINDINGS: This prospective cohort study followed 248 chikungunya patients. Symptoms and SF-36 QoL were evaluated during baseline and follow-up at 2.5 years using questionnaires. Chikungunya disease status was classified using the CLTCS-score. At 2.5 years after disease onset patients were classified as being recovered (43%), mildly (35%) or highly (22%) affected. In comparison to mildly affected, highly affected patients reported the highest prevalence of ongoing rheumatic and non-rheumatic/psychological symptoms, with increased prevalence of arthralgia in the lower extremities (p = .01) and fatigue (p = .049) over time, and higher pain intensity (p < .001). Compared to mildly affected, being highly affected was associated with weakness in the lower extremities (OR: 1.90; CI: 1.29-2.80, p = .001) and worsened physical and mental QoL impairment. CONCLUSIONS: Patients are both physically and psychologically affected by rheumatic and non-rheumatic symptoms of long-term chikungunya disease. The CLTCS-score is an easy to use instrument for classifying long-term chikungunya disease severity and impact and can facilitate health care providers in identifying highly affected patients who are prone to develop severe QoL impairment. Highly affected patients are recommended to be treated in a multidisciplinary setting to improve physical and psychological functioning, and QoL.

Understanding risk communication for prevention and control of vector-borne diseases: A mixed-method study in Curaçao.

BACKGROUND: Risk communication (RC) is an essential tool for the prevention and control of diseases as it impacts risk perception, increases awareness and might change behaviour. It is the interactive exchange of information about risks among experts and people. Effective RC can minimize the impact that diseases such as dengue, chikungunya and Zika have on populations. This study aimed to understand RC regarding vector-borne diseases in its social context and from the viewpoint of the audience to strengthen RC strategies in Curaçao. METHODS: In 2015, a cross-sectional mixed-method study applying focus group discussions (n = 7), in-depth interviews (n = 20) and a structured survey questionnaire (n = 339) was done in Curaçao. The study was designed based on the Health Belief Model and the Theory of Planned Behaviour. In addition, the Social Amplification of Risk Framework and the theory of cultural schemas were applied to understand RC in the social context. RESULTS: Television, radio and newspapers were the most important channels of information regarding dengue and chikungunya. Moreover, individuals also reported receiving information via social media, the internet and family/friends. Interestingly, the use of internet to obtain information diminished with age, while females were more likely to use internet compared to men. These key findings were statistically significant. An important outcome was that the risk perception towards chikungunya at the beginning of the outbreak was attenuated. This might be due to the (perceived) lack of RC before the epidemic. This same risk perception was amplified later during the outbreak by the increased exposure to information. Lastly, we show how cultural schemas influence people's perception regarding preventive measures and treatment of chikungunya and dengue. CONCLUSIONS: Data obtained emphasise the importance of understanding the user of media platforms and sharing information in a timely fashion through a transparent process with the content that convinces people of the seriousness of the matter.

Knowledge, Attitudes, and Preventive Practices Regarding Dengue in Maracay, Venezuela.

Dengue, a viral mosquito-borne disease currently affects more than 2.5 billion people living in endemic areas worldwide. In vector control, social mobilization and community behavioral changes are of crucial importance. Here, we identified the factors influencing community dengue preventive practices in a high-transmission urban area in Venezuela. Between September 2013 and February 2014, a cross-sectional study at the household level was carried out in Maracay city, Venezuela. A precoded questionnaire was used to obtain information on people's knowledge, attitudes, and use of preventive practices in relation to dengue. Concomitantly, entomological data was collected from households. In 80% of the 105 included households, 1-5 preventive practices (e.g., repellents, insecticides) against mosquito bites were used. However, 57% of the examined houses had potential Aedes breeding sites indoors and/or outdoors, most of which positive for Aedes spp. larvae/pupae. Preventive practices were associated with a previous dengue infection (P = 0.030) and a better knowledge on dengue symptoms and transmission route (P = 0.020). In turn, knowledge was associated with feeling at risk (P < 0.001), a previous dengue infection (P = 0.010), and reported exposure to information sources of dengue (P = 0.011). Even though the knowledge level of the community over transmission ways was high, and most of the individuals took measures to avoid mosquito bites, potential mosquito breeding sites were present in almost two-thirds of the examined properties. Health promotion activities in Venezuela should aim at raising awareness at the community level on the importance of combining mosquito bite prevention with removal of breeding sites in and around the households.

Consequences of a recent past dengue infection for acute and long-term chikungunya outcome: A retrospective cohort study in Curaçao.

BACKGROUND: Dengue and chikungunya co-infections are an emerging threat to public health in tropical and sub-tropical areas. This study investigates acute and long-term clinical presentation patterns of chikungunya against a backdrop of preceding dengue infection and determines predicting factors for long-term chikungunya sequelae. METHODS: A retrospective cohort study was performed in 2015, including 299 previously confirmed chikungunya cases, of which 162 subjects were assessed for dengue serology at disease onset. RESULTS: Those with previous dengue infection (35.2% of the examined population) had a similar acute disease presentation, and suffered (not statistically significantly) more frequently from long-term musculoskeletal and neuropsychological symptoms compared to chikungunya-only patients. Patients with a preceding dengue infection (vs. those without) (OR = 4.17; p = 0.004), female sex (OR = 3.17; p = 0.034) and pre-existing joint disease (OR = 2.95; p = 0.031) had a higher risk of developing aggravated long-term chikungunya. Chronic disease (sequelae lasting >90 days) was predicted by an age between 41 and 60 (OR = 3.07; p = 0.009) and concomitant cardiovascular disease (OR = 4.08; p = 0.010), but not by a preceding dengue infection. CONCLUSIONS: This study suggests several predicting factors of, and a possible link between preceding dengue and chikungunya infection and aggravated long-term sequelae, which should be interpreted in the light of the limitations of this study.

Health-related impact on quality of life and coping strategies for chikungunya: A qualitative study in Curaçao.

INTRODUCTION: Chikungunya is an emerging public health problem in tropical and subtropical regions, due to ongoing transmission and its incapacitating acute disease phase, and chronic sequelae. The disease is responsible for a major impact on Health Related Quality of Life (HRQoL), which may last several years. To our knowledge, this study is the first qualitative examination of HRQoL and coping strategies of chikungunya-infected individuals. METHODS: Qualitative research methods consisted of 20 in-depth interviews and seven Focus Group Discussions (FGDs), n = 50. Analysis was based on the principles of the grounded theory. RESULTS: Different impacts on HRQoL were reported. The physical and emotional domains of the HRQoL were mainly affected by chikungunya, while social and individual financial consequences were limited. Individual financial impact was limited through the universal health care program of Curaçao. Long-term lingering musculoskeletal and other manifestations caused significant pain and limited mobility. Hence, participants experienced dependency, impairment of normal daily life activities, moodiness, hopelessness, a change of identity, and insecurity about their future. The unpredictable nature and consequences of chikungunya gave rise to various coping strategies. Problem-focused coping styles led to higher uptake of medical care and were linked to more negative impact of HRQoL, whereas emotional coping strategies focusing on acceptance of the situation were linked to less uptake of medical care and more positive impact on HRQoL. CONCLUSIONS: This study provides an in-depth understanding of acute and long-term HRQoL impact of chikungunya. The results can better inform health promotion policies and interventions. Messages to the public should focus on promoting healthy and efficient coping strategies, in order to prevent additional stress in affected individuals.

Long-term Chikungunya Sequelae in Curaçao: Burden, Determinants, and a Novel Classification Tool.

Background: Beyond the acute illness phase, chikungunya constitutes a public health problem given its chronic disease phase, which may include long-term arthralgia, arthritis, fatigue, and depression. Currently, there is no consensus on how to define chikungunya chronicity. Methods: A comprehensive cross-sectional survey was performed in Curaçao in June and July 2015 to evaluate 304 adult laboratory-confirmed chikungunya patients 3-16 months after diagnosis. We developed a novel tool, the Curaçao Long-Term Chikungunya Sequelae (CLTCS) score, to classify chronic chikungunya disease and estimate its burden regarding disease duration, clinical presentation, and impact on quality of life. Results: Disease persistence was estimated to be 79% one month after symptom onset and 64% after 400 days. Chikungunya persistence was characterized by higher proportions of arthralgia, weakness, myalgia, and age 41-60 years. Individuals were classified as "highly affected," "mildly affected," and "recovered." "Highly affected" disease status was associated with clinical complaints (arthralgia, weakness, loss of vitality, and being diabetic) and major decreases in quality-of-life scores. Conclusions: In the Caribbean, a high proportion of chikungunya patients remains chronically affected. We propose the CLTCS as a suitable score to easily and rapidly classify the severity of chikungunya chronic disease and to assess the need for symptom-alleviating treatment.

Community participation in mosquito breeding site control: an interdisciplinary mixed methods study in Curaçao.

BACKGROUND: As the arboviral diseases dengue, chikungunya and Zika emerge in the Americas, so does the need for sustainable vector control policies. To successfully achieve mosquito control, joint efforts of both communities and governments are essential. This study investigates this important, but by-and-large neglected topic. METHODS: In June and July 2015, a cross-sectional mixed methods study applying a survey questionnaire (response rate of 82.5%; n = 339), in-depth interviews (n = 20) and focus group discussions (n = 7; 50 participants) was performed in Curaçao. The study was designed based on an integrated theoretical framework of the Health Belief Model and the Theory of Planned Behaviour. RESULTS: Participants showed a good knowledge of, and a high-level performance of mosquito breeding site control (MBSC) practices. Personal protection against mosquitoes (e.g. topical repellents) was perceived as relatively less effective thus practiced to lower extent compared to MBSC practices (i.e. larval source management). A lower intention to perform MBSC was independently associated with: (i) satisfaction on governmental MBSC (P = 0.012); (ii) barriers to perform MBSC practices, i.e. 'Government doesn't control other breeding sites' (P = 0.005), 'Don't know how to control breeding sites' (P = 0.041), and 'a mosquito does not transmit dengue' (P = 0.016), (iii) attitudes towards MBSC (P = 0.001) and self-efficacy (person's perceived ability to act) to perform MBSC (P = 0.002). Mixed-methods evidence highlights three possible ways of improving community participation in MBSC. First, it highlights the need for ongoing media coverage, targeting (i) communities' perceptions on transmission routes of dengue and chikungunya, and (ii) presence of car tires in yards. Secondly, it shows that promotion of governmental activities in MBSC can enhance MBSC of communities, if people develop a sense of responsibility to perform MBSC at their own properties. Thirdly, this study describes the presence of key persons in communities, who could be engaged in mosquito control policies to improve MBSC in neighbourhoods. CONCLUSION: This study reveals gaps between policy and communities' lived realities. These gaps might be overcome with the proposed interventions, resulting in a higher performance of MBSC in the community in Curaçao. Furthermore, this study shows how interdisciplinary mixed methods research can provide important, comprehensive, and in-depth insights to inform mosquito control policies.

Health Seeking Behaviour and Treatment Intentions of Dengue and Fever: A Household Survey of Children and Adults in Venezuela.

BACKGROUND: Dengue in Venezuela is a major public health problem with an increasing incidence of severe cases. Early diagnosis and timely treatment influences the outcome of dengue illness, as delay in care-seeking is significantly associated with complications leading to severe dengue. We aimed to understand patterns of health seeking behaviour (HSB) in individuals exposed to high dengue incidence in order to improve early attendance to health centres. METHODS: Between September 2013 and February 2014 a cross-sectional household survey was performed in Maracay, Venezuela. Intended HSB of adults and children's parents/guardians was assessed with respect to fever or suspected dengue. Data was collected through structured questionnaires from 105 individuals. RESULTS: Most individuals felt at risk of dengue and believed it could be a deadly disease. In the case of suspected dengue, the majority (60%) would choose to first seek medical help versus first treating at home, in contrast to 11% in the case of fever. Amongst those who decided to visit a doctor, a suspected dengue infection would prompt them to search medical help earlier than if having only fever (p<0.001). Multivariate analysis modelling showed that the independent factors associated with the intention to firstly visit a doctor versus treating at home in the case of dengue were feeling at risk (OR = 3.29; p = 0.042) and being an adult (as opposed to caring for a child as a parent/guardian; OR = 3.33, p = 0.021), while having had a previous dengue infection (OR = 0.29; p = 0.031) and living in the neighbourhood Caña de Azúcar (OR = 0.28, p = 0.038) were negatively associated with seeking medical care as their first action. CONCLUSION: Knowledge of HSB related to dengue is scarce in the Americas, our study attempts to contribute to a better understanding of HSB in this region. Improving early dengue disease recognition and awareness may enhance prompt attendance to medical care in affected populations and thereby reduce mortality and severity of dengue. Especially for those with a previous dengue infection, efforts have to be made to promote prompt health centre attendance.