The recent expansion of mpox in Africa is characterized by a dramatic increase in zoonotic transmission (clade Ia) and the emergence of a new clade Ib that is transmitted from human to human by close contact. Clade Ia does not pose a threat in areas without zoonotic reservoirs. But clade Ib may spread widely, as did clade IIb which has spread globally since 2022 among men who have sex with men. It is not clear whether controlling clade Ib will be more difficult than clade IIb. The population at risk potentially counts 100 million but only a million vaccine doses are expected in the next year. Surveillance is needed with exhaustive case detection, polymerase chain reaction confirmation, clade determination, and about severe illness. Such data is needed to identify routes of transmission and core transmitters, such as sex workers. Health care workers are vaccinated to ensure their protection, but this will not curb mpox transmission. With the recent inequitable distribution of COVID-19 vaccines in mind, it is a global responsibility to ensure that low-income nations in the mpox epicenter have meaningful access to vaccines. Vaccination serves not only to reduce mortality in children but limit the risk of future mpox variants emerging that may spread in human populations globally.
BACKGROUND
Circulating markers of immune and endothelial activation risk stratify infection syndromes agnostic to disease aetiology. However, their utility in children presenting from the community remains unclear.
METHODS
This study recruited children aged 1-59 months presenting with community-acquired acute febrile illnesses to seven hospitals in Bangladesh, Cambodia, Indonesia, Laos, and Viet Nam. Clinical parameters and biomarker concentrations were measured at presentation. The outcome measure was death or receipt of vital organ support within two days of enrolment. Prognostic performance of endothelial (Ang-1, Ang-2, sFlt-1) and immune (CHI3L1, CRP, IP-10, IL-1ra, IL-6, IL-8, IL-10, PCT, sTNFR-1, sTREM-1, suPAR) activation markers, WHO Danger Signs, and two validated severity scores (LqSOFA, SIRS) was compared.
RESULTS
3,423 participants were recruited. 133 met the outcome (weighted prevalence: 0.34%; 95% CI 0.28-0.41). sTREM-1 exhibited highest prognostic accuracy (AUC 0.86; 95% CI 0.82-0.90), outperforming WHO Danger Signs (AUC 0.75; 95% CI 0.70-0.80; p < 0.001), LqSOFA (AUC 0.74; 95% CI 0.70-0.78; p < 0.001), and SIRS (AUC 0.63; 95% CI 0.58-0.68; p < 0.001). Discrimination of immune and endothelial activation markers was particularly strong for children who deteriorated later in the course of their illness. Compared to WHO Danger Signs, an sTREM-1-based triage strategy improved recognition of children at risk of progression to life-threatening infection (sensitivity: 0.80 vs. 0.72), while maintaining comparable specificity (0.81 vs. 0.79).
CONCLUSIONS
Measuring circulating markers of immune and endothelial activation may help earlier recognition of febrile children at risk of poor outcomes in resource-constrained community settings.
In its earliest phases, Ebola virus disease's rapid-onset, high fever, and gastrointestinal symptoms are largely indistinguishable from other infectious illnesses. We aimed to characterise the clinical indicators associated with Ebola virus disease to improve outbreak response.
METHODS
In this retrospective analysis, we assessed routinely collected data from individuals with possible Ebola virus disease attending 30 Ebola health facilities in two provinces of the Democratic Republic of the Congo between Aug 1, 2018, and Aug 28, 2019. We used logistic regression analysis to model the probability of Ebola infection across 34 clinical variables and four types of possible Ebola virus disease exposures: contact with an individual known to have Ebola virus disease, attendance at any funeral, health facility consultation, or consultation with an informal health practitioner.
FINDINGS
Data for 24 666 individuals were included. If a patient presented to care in the early symptomatic phase (ie, days 0–2), Ebola virus disease positivity was most associated with previous exposure to an individual with Ebola virus disease (odds ratio [OR] 11·9, 95% CI 9·1–15·8), funeral attendance (2·1, 1·6–2·7), or health facility consultations (2·1, 1·6–2·8), rather than clinical parameters. If presentation occurred on day 3 or later (after symptom onset), bleeding at an injection site (OR 33·9, 95% CI 12·7–101·3), bleeding gums (7·5, 3·7–15·4), conjunctivitis (2·4, 1·7–3·4), asthenia (1·9, 1·5–2·3), sore throat (1·8, 1·3–2·4), dysphagia (1·8, 1·4–2·3), and diarrhoea (1·6, 1·3–1·9) were additional strong predictors of Ebola virus disease. Some Ebola virus disease-specific signs were less prevalent among vaccinated individuals who were positive for Ebola virus disease when compared with the unvaccinated, such as dysphagia (–47%, p=0·0024), haematemesis (–90%, p=0·0131), and bleeding gums (–100%, p=0·0035).
INTERPRETATION
Establishing the exact time an individual first had symptoms is essential to assessing their infection risk. An individual's exposure history remains of paramount importance, especially in the early phase. Ebola virus disease vaccination reduces symptom severity and should also be considered when assessing the likelihood of infection. These findings about symptomatology should be translated into practice during triage and should inform testing and quarantine procedures.