Neglected etiologies of prolonged febrile illnesses in tropical and subtropical regions: A systematic review.

BACKGROUND: Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious etiologies of "prolonged fevers" (persistent febrile illnesses, PFI) and to quantify relative contributions of selected neglected target diseases with limited diagnostic options, often overlooked, causing inadequate antibiotic prescriptions, or requiring prolonged and potentially toxic treatments. METHODS: We performed a systematic review of articles addressing the infectious etiologies of PFI in adults and children in sub-/tropical low- and middle-income countries (LMICs) using the PRISMA guidelines. A list of target diseases, including neglected parasites and zoonotic bacteria (e.g., Leishmania and Brucella), were identified by infectious diseases and tropical medicine specialists and prioritized in the search. Malaria and tuberculosis (TB) were not included as target diseases due to well-established epidemiology and diagnostic options. Four co-investigators independently extracted data from the identified articles while assessing for risk of bias. RESULTS: 196 articles from 52 countries were included, 117 from Africa (33 countries), 71 from Asia (16 countries), and 8 from Central and -South America (3 countries). Target diseases were reported as the cause of PFI in almost half of the articles, most frequently rickettsioses (including scrub typhus), relapsing fever borreliosis (RF-borreliosis), brucellosis, enteric fever, leptospirosis, Q fever and leishmaniasis. Among those, RF-borreliosis was by far the most frequently reported disease in Africa, particularly in Eastern Africa. Rickettsioses (including scrub typhus) were often described in both Africa and Asia. Leishmaniasis, toxoplasmosis and amoebiasis were the most frequent parasitic etiologies. Non-target diseases and non-tropical organisms (Streptococcus pneumoniae, Escherichia coli, and non-typhoidal Salmonella spp) were documented in a fifth of articles. CONCLUSIONS: Clinicians faced with PFI in sub-/tropical LMICs should consider a wide differential diagnosis including enteric fever and zoonotic bacterial diseases (e.g., rickettsiosis, RF-borreliosis and brucellosis), or parasite infections (e.g., leishmaniasis) depending on geography and syndromes. In the absence of adequate diagnostic capacity, a trial of antibiotics targeting relevant intra-cellular bacteria, such as doxycycline or azithromycin, may be considered.

[Monkeypox: a new emerging infectious threat?] / Variole du singe : une nouvelle menace infectieuse émergente ?

Monkeypox, caused by the mpox virus, is an emerging infectious eruptive disease, endemic in some African countries, that spread rapidly worldwide from May to December 2022. This new epidemic differs from the previous African ones by its mode of transmission, essentially through intimate contact and/or sexual intercourse, and by the fact that in more than 90 % of cases it affects men who have sex with men. Severe forms of the disease, responsible for significant mortality, have been described in immunosuppressed patients. A third-generation vaccine is available for high-risk groups and several international randomized controlled studies are evaluating the efficacy of tecovirimat. While it is impossible to know whether we will see a new epidemic wave in 2023, only a collective commitment to information sharing will ensure adequate surveillance and an appropriate and rapid preventive and therapeutic answer.

La variole du singe, due au virus mpox, est une maladie infectieuse éruptive émergente, endémique dans certains pays d'Afrique, qui s'est étendue mondialement de mai à décembre 2022. Cette nouvelle épidémie se distingue des précédentes, africaines, par son mode de transmission, essentiellement des contacts intimes et/ou des rapports sexuels, et par le fait qu'elle touche dans plus de 90 % des cas des hommes ayant des relations sexuelles avec d'autres hommes. Des formes graves, responsables d'une mortalité significative, ont été décrites chez des patients immunodéprimés. Un vaccin de troisième génération est disponible pour les groupes à haut risque et plusieurs études internationales randomisées et contrôlées évaluent l'efficacité du técovirimat. S'il est impossible d'exclure ou d'affirmer une nouvelle explosion épidémique en 2023, seul un engagement collectif en faveur d'un partage d'informations permettra d'assurer une réponse préventive et thérapeutique appropriée et rapide.

A Case of Mpox Reinfection.

A healthy young man first diagnosed with mpox in May 2022 presented again in November 2022 with anal proctitis and a positive polymerase chain reaction on a rectal swab for Monkeypox virus after a recent trip to Brazil, where he engaged in condomless sexual intercourse with multiple male partners.

The human gut mycobiome and the specific role of Candida albicans: where do we stand, as clinicians?

BACKGROUND: The so-called 'mycobiome' has progressively acquired interest and increased the complexity of our understanding of the human gut microbiota. Several questions are arising concerning the role of fungi (and in particular of Candida albicans), the so-called 'mycobiome', that has been neglected for a long time and only recently gained interest within the scientific community. There is no consensus on mycobiome normobiosis because of its instability and variability. This review aims to raise awareness about this interesting topic and provide a framework to guide physicians faced with such questions. OBJECTIVES: To summarize current knowledge and discuss current and potential implications of the mycobiome in clinical practice. SOURCES: We performed a review of the existing literature in Medline Pubmed. CONTENT: This review identifies several studies showing associations between specific mycobiome profiles and health. Fungi represent a significant biomass within the microbiota and several factors, such as diet, sex, age, co-morbidities, medications, immune status and inter-kingdom interactions, can influence its structure and population. The human gut mycobiota is indeed a key factor for several physiological processes (e.g. training of the immune system against infections) and pathological processes (e.g. immunological/inflammatory disorders, inflammatory bowel diseases, metabolic syndromes). Moreover, the mycobiome (and C. albicans in particular) could influence an even broader spectrum of conditions such as psychiatric diseases (depression, schizophrenia, bipolar disorder) or chronic viral infections (human immunodeficiency virus, hepatitis B virus); moreover, it could be implicated in tumorigenesis. IMPLICATIONS: Candida albicans is a well-known opportunistic pathogen and a major component of the mycobiome but its role in the gastrointestinal tract is still poorly understood. From a potential screening biomarker to a key factor for several pathological processes, its presence could influence or even modify our clinical practice.

Human gnathostomiasis in Sri Lanka: an underreported disease?

A healthy young man from Sri Lanka, currently living in Switzerland, consulted at the University Hospital of Geneva with a history of painful erythema and swelling of the left forearm. Laboratory tests showed a slight eosinophilia. Western blot serology for Gnathostoma spp, inconclusive at presentation, became positive 2 weeks later.

Heated, Humidified High-Flow Nasal Cannula vs Nasal Continuous Positive Airway Pressure for Respiratory Distress Syndrome of Prematurity: A Randomized Clinical Noninferiority Trial.

IMPORTANCE: Heated, humidified high-flow nasal cannula (HHHFNC) has gained increasing popularity as respiratory support for newborn infants thanks to ease of use and improved patient comfort. However, its role as primary therapy for respiratory distress syndrome (RDS) of prematurity needs to be further elucidated by large, randomized clinical trials. OBJECTIVE: To determine whether HHHFNC provides respiratory support noninferior to nasal continuous positive airway pressure (nCPAP) or bilevel nCPAP (BiPAP) as a primary approach to RDS in infants older than 28 weeks' gestational age (GA). DESIGN, SETTING, AND PARTICIPANTS: An unblinded, monocentric, randomized clinical noninferiority trial at a tertiary neonatal intensive care unit. Inborn infants at 29 weeks 0 days to 36 weeks 6 days of GA were eligible if presenting with mild to moderate RDS requiring noninvasive respiratory support. Criteria for starting noninvasive respiratory support were a Silverman score of 5 or higher or a fraction of inspired oxygen higher than 0.3 for a target saturation of peripheral oxygen of 88% to 93%. Infants were ineligible if they had major congenital anomalies or severe RDS requiring early intubation. Infants were enrolled between January 5, 2012, and June 28, 2014. INTERVENTIONS: Randomization to either HHHFNC at 4 to 6 L/min or nCPAP/BiPAP at 4 to 6 cm H2O. MAIN OUTCOMES AND MEASURES: Need for mechanical ventilation within 72 hours from the beginning of respiratory support. The absolute risk difference in the primary outcome and its 95% confidence interval were calculated to determine noninferiority (noninferiority margin, 10%). An intention-to-treat analysis was performed. RESULTS: A total of 316 infants were enrolled in the study: 158 in the HHHFNC group (mean [SD] GA, 33.1 [1.9] weeks; 52.5% female) and 158 in the nCPAP/BiPAP group (mean [SD] GA, 33.0 [2.1] weeks; 47.5% female). The use of HHHFNC was noninferior to nCPAP with regard to the primary outcome: failure occurred in 10.8% vs 9.5% of infants, respectively (95% CI of risk difference, -6.0% to 8.6% [within the noninferiority margin]; P = .71). Significant between-group differences in secondary outcomes were not found between the HHHFNC and nCPAP/BiPAP groups, including duration of respiratory support (median [interquartile range], 4.0 [2.0 to 6.0] vs 4.0 [2.0 to 7.0] days; 95% CI of difference in medians, -1.0 to 0.5; P = .45), need for surfactant (44.3% vs 46.2%; 95% CI of risk difference, -9.8 to 13.5; P = .73), air leaks (1.9% vs 2.5%; 95% CI of risk difference, -3.3 to 4.5; P = .70), and bronchopulmonary dysplasia (4.4% vs 5.1%; 95% CI of risk difference, -3.9 to 7.2; P = .79). CONCLUSIONS AND RELEVANCE: In this study, HHHFNC showed efficacy and safety similar to those of nCPAP/BiPAP when applied as a primary approach to mild to moderate RDS in preterm infants older than 28 weeks' GA. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02570217.