Bartonella spp., Borrelia spp., and piroplasmid are increasingly recognized as vector-borne pathogens worldwide, with documented circulation in arthropod vectors and animal reservoirs in Brazil. The purpose of this study was to assess whether Bartonella exposure and/or infection were associated with specific clinical and epidemiological characteristics in HIV-infected symptomatic patients living in Brazil. The second aim was to determine if infection with a piroplasmid or Borrelia species might be detected in these patients. Epidemiological and medical history were collected for each of 75 HIV-positive participants. In a blinded manner, we assessed the presence of anti-Bartonella antibodies by indirect immunofluorescence assays (IFA) using B. henselae, B. koehlerae, B. quintana, and B. vinsonii berkhoffii (genotypes I and II) as antigens. A cut-off dilution of 1:64 was selected as a seroreactivity titer. We evaluated infection by amplifying Bartonella spp., Borrelia spp., and piroplasmid DNA from blood using quantitative polymerase chain reaction (qPCR) and digital PCR (dPCR). qPCR was performed before and after BAPGM (Bartonella alpha-Proteobacteria Growth Medium)-enriched blood culture for up to 28 days, and statistical analyses were conducted in an exploratory framework. Seroreactivity to at least one Bartonella antigen was found in 47/75 (62.7
African animal trypanosomoses (AAT), caused by protozoans of the genus Trypanosoma and transmitted by tsetse flies (Glossina spp.), significantly impede socio-economic growth in Africa. Mozambique harbours four main tsetse species, and there is widespread presence of pathogenic trypanosomes in both wildlife and domestic animals. Moreover, human–livestock–wildlife interfaces increase the risk of disease spillover. The objective of this study was to identify the diversity of tsetse flies, trypanosomes, vertebrate blood meal hosts and microbiome composition at the human–wildlife–livestock interface in Mozambique, and to explore the associations among these components relevant to AAT transmission cycle. We collected tsetse flies in two Mozambican National Parks (Maputo National Park—MNP, Gorongosa National Park—GNP) and their respective surrounding buffer zones (MBZ, GBZ) where agricultural activities occur. Each collected specimen was identified using taxonomic keys. A subsample (200) was then selected for DNA extraction from the whole flies, and several barcodes were amplified and sequenced to identify the diversity of trypanosomes, blood meal sources, and microbiome diversity. We identified 2291 tsetse flies representing four species (G. austeni, G. brevipalpis, G. morsitans, G. pallidipes) with varying trypanosome prevalences (65–90
In 2015, the LeishVet group published a comprehensive review on feline leishmaniosis (FeL) caused by Leishmania infantum, highlighting the growing interest in the disease despite the limited availability of evidence-based studies at the time. Over the past decade, considerable advances have been made in various aspects of animal leishmaniosis, including FeL. Veterinary awareness has increased, and diagnostic support is more widely available. However, current knowledge on FeL still largely comes from case reports and small case series studies, with fewer analytical studies and a lower evidence level compared to canine leishmaniosis. In response, the LeishVet group reviewed recent progress and provided updated recommendations based on key international publications, clinical expertise and expert consensus. A series of questions was formulated to address the main aspects of FeL most relevant for veterinary practitioners, including etiology, transmission, epidemiology (including geographical distribution and risk factors), immunology, clinical presentations and clinicopathological findings, the role of coinfections and/or comorbidities, diagnosis, prognosis formulation based on clinical staging, treatment, monitoring and prevention of FeL. The answers are largely supported by visual aids (tables, figures, and algorithms). This updated review paper focuses mainly on L. infantum infection and disease in domestic cats as it is the species of Leishmania most frequently diagnosed in cats. Two specific questions have also been dedicated to infection in wild felids and Leishmania spp. other than L. infantum, for supporting veterinary specialists in wildlife and zoo medicine and taking in consideration that globalization opens new challenges to practitioners.
Despite its importance for Culicoides-borne disease risk assessment, the winter activity of species of this biting midge genus remains poorly characterized. Moreover, information on virus circulation in winter-active Culicoides vectors, both under endemic conditions and during outbreaks, is almost non-existent. UV-light traps to collect Culicoides biting midges were operated once a week for 24 h in cattle, sheep, goat and horse stables at 12 to 55 locations during four consecutive winter periods (November 1 to March 31, 2021 to 2025) throughout Germany. Collected females of the genus Culicoides were morphologically assigned to Obsoletus Group or Pulicaris Complex. Temperature data were recorded to relate biting midge activity to temperatures. Screening for bluetongue virus (BTV), Schmallenberg virus and epizootic hemorrhagic disease virus was done by real-time RT-PCR on 1,581 pools (46,358 females) of both groups collected before (winter 2022/2023) and during the BTV serotype 3 (BTV-3) outbreak (winters 2023/2024 and 2024/2025). Culicoides collections displayed notable variation between sites and months. November and March accounted for 95
Culicoides biting midges are hematophagous vectors of arboviruses in livestock, and characterizing their occurrence patterns is fundamental to disease surveillance. Field collections show substantial year-to-year variation, complicating characterization of dominant-species occurrence from a single season or site. This study integrated five years of Culicoides collection data from livestock-associated sites in the Republic of Korea to describe species composition, year-to-year variation, site-level dominance, and seasonal occurrence patterns of dominant species, while screening collected Culicoides for selected arboviruses of veterinary importance. Culicoides spp. were collected biweekly from May to October during 2021–2025 at nine livestock-associated sites (seven cattle sheds and two racetracks) using ultraviolet blacklight traps. Specimens were identified morphologically, with molecular confirmation by COI sequencing when required. All pooled samples were screened by RT-PCR for bluetongue virus (BTV), African horse sickness virus (AHSV), and Simbu serogroup viruses. Descriptive summaries of species composition, year-to-year variation, site-level dominance, and seasonal occurrence were complemented by PERMANOVA and NMDS based on Bray–Curtis dissimilarities as supplementary analyses. A total of 41,259 individuals were collected from 476 collection events, of which 277 were positive, and 199 yielded no Culicoides. The community was strongly dominated by three species (C. arakawae, C. punctatus, and C. oxystoma), which together accounted for 95.1
Understanding population dynamics is fundamental for predicting species persistence and extinction, yet remains challenging because of the complex interplay among ecological, environmental, and anthropogenic factors. Population dynamics are regulated by intrinsic processes, such as negative density-dependence, driven by factors, including resource competition during larval development, and Allee effects, which can arise through mechanisms such as mate limitation at low population densities. While negative density-dependence is well-understood, Allee effects have received comparatively less attention despite important implications for conservation and population management. For disease vectors, both negative density-dependence and Allee effects can influence whether populations persist, rebound following control, or are driven to elimination. In malaria mosquitoes, negative density-dependence at the larval stages is well-known to regulate population growth, whereas Allee effects have not been empirically demonstrated, and their potential implications and interactions with negative density-dependence remain poorly understood. This study addresses this gap using a population simulation model to evaluate the trade-offs between negative density-dependence and potential mate-finding Allee effects and their implications for vector control. It is possible that, depending on the vector control strategy, Allee effects could become important at low densities and push populations closer to extinction. A stochastic stage-structured population simulation model representing a simplified mosquito life cycle was developed. Negative density-dependence and mate-finding Allee effects were incorporated as processes affecting larval survival and total fecundity, respectively. Their effects were examined by varying the strength of both processes independently and jointly, under different vector control scenarios: control, sustained and shorter-term interventions (here, immolating larvicides) that reduced larval population. When considered separately, neither negative density-dependence nor mate-finding Allee effects had a substantial long-term effect on population persistence, although negative density-dependence substantially altered equilibrium abundance. However, their combined effects accelerated population decline and increased the likelihood of extinction as the strength of both processes increased. Because Allee effects operate on low population abundances, sustained interventions were able to reduce mosquito populations to levels, where Allee effects became important, thereby increasing the probability of extinction. In contrast, short-term interventions led to population rebound, driven by negative density-dependence as formulated in the simulation. Understanding less-studied regulatory processes such as Allee effects can support vector control by identifying stages of the vector life cycle that are either resilient or vulnerable to interventions. The results suggest that, if present, the mate-finding Allee effects and density-dependent resource competition considered in this study could potentially be leveraged to accelerate vector control and support the elimination of vector-borne diseases, such as malaria.
Dengue virus (DENV) and chikungunya virus (CHIKV), transmitted primarily by Aedes mosquitoes, represent growing public health threats in Kenya and across sub-Saharan Africa. In the absence of licensed vaccines for either disease in Africa, targeted vector control remains the primary prevention strategy, making accurate knowledge of Aedes species distributions essential. Global inventories of Aedes species are severely under-representative for Kenya, with existing repositories documenting fewer than 200 unique locations. No comprehensive, geocoded national inventory integrating published, unpublished, and digital sources has previously been assembled. Three complementary approaches were used to assemble a national geocoded inventory of Aedes species in Kenya including (i) a systematic review of peer-reviewed literature, theses, and conference abstracts; (ii) digitisation of unpublished archival reports from the Ministry of Health, Division of Insect-Borne/Vector-Borne Diseases (DIBD/DVBD), regional and municipal councils; and (iii) cross-referencing with Global Biodiversity Information Facility (GBIF) and Walter Reed Biosystematics Unit’s (WRBU) VectorMap repositories. Data were extracted using a standardised template, de-duplicated, and geocoded using Global Positioning System (GPS) coordinates, Google Earth, or census enumeration area shapefiles. Aedes species were classified as principal or possible secondary vectors based on confirmed field detection and, for the principal vector, an established role in transmission during dengue and chikungunya outbreaks reported in Kenya. A total of 1,802 time-site records were identified across 855 unique locations between 1901 and 2024, documenting 104 Aedes species. Unpublished archival records contributed 51
Hemorrhagic fever with renal syndrome (HFRS) poses a substantial public health burden in China. With its complex topography and rich biodiversity, Southwest China has historically been an endemic area for this natural focal disease. Currently, traditional environmental factors associated with transmission here are increasingly outweighed by anthropogenic forces, notably population agglomeration. Driven by these shifting dynamics, HFRS incidence and endemic ranges are expanding, yet systematic, regional-scale assessments remain scarce. Consequently, this study employs ecological niche modeling to map potential high-risk zones. Ultimately, we aim to explore the primary factors associated with HFRS prevalence amid the complex interplay of natural environments and human activities. Surveillance data of HFRS cases in Southwest China from 2014 to 2023 were obtained from the China Information System for Disease Control and Prevention (CISDCP). A Maximum Entropy (MaxEnt) model was constructed by integrating occurrence records with multisource environmental variables, including meteorological, socioeconomic, and land cover factors. Model performance was evaluated using the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC), and the Jackknife test was employed to quantify the contribution of each variable. The MaxEnt model demonstrated robust predictive performance with a mean AUC of 0.902. Population density was identified as the predominant predictor (73.5
Wolbachia are obligatory bacterial endosymbionts of Dirofilaria immitis heartworms, necessary for worm development, reproductive capability, and viability. We quantitatively examined microfilariae and Wolbachia in doxycycline-treated, heartworm-positive dogs. Microfilaremic heartworm-positive dogs were identified in municipalities within the target areas of Rio de Janeiro and enrolled in this study. Dog owners agreed to allow blood draws from their dogs on day 0 and days 60 and 90 (± 5 days), and to administer doxycycline 10 mg/kg BID for 28 days, with weekly phone follow-up to help ensure compliance. Modified Knott’s tests were performed on each experimental day; a portion of each sample was retained and frozen at − 20 °C, and the remaining quantities were submitted for digital PCR (dPCR) of microfilarial and Wolbachia burdens. None of the dogs enrolled in the study received any macrocyclic lactone during the study. Thirty-one microfilaremic dogs completed the study, with 27 remaining microfilaremic throughout. Wolbachia were cleared from 25 of the dogs by day 90, demonstrating that the doxycycline dose was fully effective in those cases. Interestingly, 6 dogs remained dPCR positive on the quantitative assessment, and the proportions of Wolbachia/D. immitis on days 60 and 90 were significantly (p < .0001) lower than on day 0. Results of the comparisons of proportions for day 60 vs. day 90 were not statistically significant (p = 0.3127). This study demonstrates that Wolbachia DNA may persist in some dogs for 90 days after doxycycline-only therapy. These data may reflect the lack of macrocyclic lactone use or higher adult burdens in some dogs; however, it is not possible to confidently conclude these factors entirely underpin our observations. We suggest that further studies should investigate whether this is related to lack of efficacy of doxycycline in certain Wolbachia subpopulations or to other factors.
Trichinella spiralis (T. spiralis) is a globally prevalent food-borne parasite whose infection triggers robust inflammation and modulates host immunity to facilitate immune escape. Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, is widely expressed in immune cells and regulates inflammation, while dendritic cells (DCs) possess a complete GABAergic system and play a pivotal role in T. spiralis-induced inflammation. However, systematic research on whether T. spiralis infection mediates immunomodulation by acting on the GABAergic system in DCs remains insufficient. This study employed in vivo and in vitro experiments to explore the underlying mechanism. In vitro, cell viability assay, quantitative real-time PCR (qPCR), and Western blotting were employed to detect the toxic side effects, inflammatory response, and impacts of T. spiralis excretory-secretory (ES) products, GABA, and the GABA-A receptor agonist muscimol (Mus) on DC2.4 cells. In vivo, a T. spiralis-infected BALB/c mouse model was established to verify the mechanism. Results showed that ES products regulated DC2.4 cells’ inflammatory factors and GABAergic system in a concentration-dependent and time-dependent manner; GABA and Mus inhibited the TLR4/MyD88/NF-κB pathway, balanced inflammatory and anti-inflammatory cytokines, and exerted anti-inflammatory effects. Pre-gavage of GABA can activate splenic DCs, improve pathological damage, and regulate immune response in infected mice. In conclusion, T. spiralis infection participates in immune regulation by modulating DCs’ GABAergic system, and exogenous GABA or Mus exerts anti-inflammatory effects, providing an experimental basis and new directions for trichinellosis intervention.
Apical membrane antigen 1 (AMA1) family proteins contribute to host-cell invasion in apicomplexan parasites, but the function of sporozoite AMA1 (sporoAMA1) in Toxoplasma gondii remains unclear. We identified distinct forms of the sporoAMA1 protein in bradyzoites, sexual stages and oocysts. Although endogenous tagging failed to detect fluorescence, transcripts were readily detected by RT-PCR. Functional analyses showed that sporoAMA1 is dispensable for tachyzoite growth but required for efficient cyst formation, chronic infection, oocyst production and sporulation. These findings reveal that sporoAMA1 contributes to multiple developmental processes associated with chronic infection and transmission in T. gondii.
Filarial nematodes transmitted by mosquitos cause significant burdens and important stigma in the affected communities. Focal transmission of Wuchereria bancrofti and Brugia malayi was detected incidentally during blood surveys conducted for a program of malaria elimination in Karen state, Myanmar. The objective of this study was to assess filariae infections in selected mosquito species collected in these villages striving to identify the potential vectors, characterise their biting behaviours and estimate the entomological indices of transmission. Cross-sectional entomological surveys were conducted in September 2019 in six villages. Mosquitos were captured over 24-h diel cycles using the human-landing catch and cow-baited trap collection methods, and identified with dichotomic morphological identification keys. A subset of the specimens of potential vector species was randomly selected and tested with a filariasis PCR assay targeting the parasites 5S rRNA gene. For positive Aedes specimens, correct identification of the filariae and vector species was confirmed with DNA sequencing of the filariasis and mosquito cytochrome c oxidase subunit 1 PCR products. Overall 5.2
Echinococcus multilocularis (Em), causing human alveolar echinococcosis (AE), is ranked as the third most impacting food-borne zoonotic parasitic disease globally. Since the 1980s, the Em range expansion from central Europe and the increment of human AE cases have raised public health concerns. However, the status of Em occurrence in many marginal regions remains uncertain, as well as which intermediate hosts maintain Em life cycle across its European range. We followed the same approach used in the last Europe-wide systematic review and meta-analysis covering the 1968–2014 period. We aimed at summarising the data on Em true prevalence in wild and domestic hosts in 2015–2025. Our study revealed significant increments in pooled true prevalence in red foxes from eastern Austria, Denmark, southeast-central and southeast France, southwestern Germany, southwestern Hungary, northeastern Italy, northwestern and southeastern Poland, Slovenia, East Middle Sweden, and Switzerland. Conversely, Em pooled true prevalence significantly decreased in both red foxes and raccoon dogs from Latvia, in Arctic foxes from Svalbard Islands, Norway, in raccoon dogs from northeastern Germany, in red foxes from east-central and northeastern France, and northeastern Poland, and in water voles from northern Switzerland. Moreover, Em emerged for the first time in red foxes from Bosnia and Herzegovina, central Italy, and Serbia. Regarding other carnivores, Em true pooled prevalence was assessed for the first time in raccoon dogs from Denmark and Estonia, in golden jackals from Bosnia and Herzegovina, Croatia, southern Hungary, Serbia, and Slovenia, in grey wolves from southeast-central and southeastern France, central Italy, and Slovakia, in domestic dogs from northeastern France, northwestern Italy, southeastern Poland, and eastern Turkey, and in domestic cats from southeastern Poland, central-east and northeastern France. Moreover, we highlighted the Em identification in novel definitive (European wildcat, Eurasian lynx, and Eurasian badger) and intermediate hosts (Harting’s and Persian voles, Macedonian mouse, and European brown hare). The updated evidence supports a heterogeneous picture rather than a uniform continental trend, with persistent transmission in historical endemic cores alongside new reports at several edges and records from additional species. The scale-dependent results underscore the need to prioritise spatially standardised surveillance of competent hosts.
Guangxi is one of the regions where clonorchiasis is endemic, with Hengzhou City notably standing out as a high-burden area for Clonorchis sinensis (C. sinensis) infection. This study aims to evaluate the prevalence of C. sinensis infection and compare the performance of available diagnostic methods to guide more precise clinical practices. This cross-sectional study included 1,220 hospitalized patients who provided fecal and serum samples in April–May 2025. Evaluated diagnostic methods included the reference standard hydrochloric acid-ether centrifugal sedimentation (HCl-EC), KU-F40 automated feces analyzer, direct smear (DS), and enzyme-linked immunosorbent assay (ELISA). Qualitative results were compared via Cochran’s Q test, followed by pairwise Bonferroni-corrected McNemar tests. Diagnostic performance metrics were calculated from 2 × 2 contingency tables. Sex and age subgroup analyses used McNemar or exact McNemar tests. Concordance of positive results and infection intensity was analyzed with Pearson’s chi-square test. The relationship between ELISA OD values and EPG counts was assessed using Spearman’s rank correlation analysis, and OD values were compared among infection intensity groups using the Kruskal–Wallis test with Dunn’s post hoc test. Using HCl-EC (reference standard), 362 patients (29.7
The American Heartworm Society (AHS) recommends diagnosing canine heartworm (HW) infection using both antigen and microfilaria detection tests. Antigen–antibody immune complexes may block antigen detection. Therefore, the AHS recommends immune complex dissociation (ICD) via heat treatment for discordant cases. The trūRapid™ FOUR antigen test kit (Antech Diagnostics) is a novel commercially available point-of-care (POC) device. This study evaluated the performance of trūRapid™ FOUR compared to other commercially available POC tests, namely SNAP® 4Dx® Plus (IDEXX), VETSCAN® Flex4 (Zoetis), and a plate-based assay, DiroCHEK® (Zoetis), for early detection of HW infection in experimentally infected dogs. Archival frozen serum samples from six purpose-bred beagles experimentally infected with Dirofilaria immitis were collected weekly for 5.5 months, from week 1 to week 22 post-infection. Sera were tested for the detection of HW antigen, pre- and post-ICD, via heat treatment (103 °C for 10 min in a heat block) using each of the commercial antigen tests. DiroCHEK® results were interpreted using optical density readings. HW antigen was not detected in samples collected from week 1 through week 19. In week 20, the trūRapid™ FOUR, SNAP® 4Dx® Plus, and VETSCAN® Flex4 detected HW antigen in one out of six samples (16.7
The p43 (Tm-DLP-1) protein secreted by the murine whipworm Trichuris muris binds matrix proteoglycans and interacts with IL-13, the combined effects of which likely mediates the chronic infection by these parasites. In fluorescence-based competition experiments we recently showed that p43 and its orthologue in the whipworm of humans, Trichuris trichiura, both bind fatty acids including the precursors of signalling lipids important in immune and inflammatory reactions. In this context there is a difference between those ligands a protein may bind in such experiments and those present in the protein directly secreted by the parasites. We here report, using solvent extraction and liquid chromatography–mass spectrometry, that native p43 secreted into serum-free media by adult T. muris worms contains precursors of signalling lipids eicosapentaenoic acid, docosahexaenoic acid, and the bioactive 5,6-epoxyeicosatrienoic acid (5.6-EET), and 15-hydroxyeicosatetraenoic acids (15-HETE) that could contribute to p43’s potent immunomodulatory activity. Several types of lipid-binding protein released by parasitic nematodes have been shown to have immunomodulatory activities, but this is the first time that such a protein has been found to be released by the parasites already loaded with bioactive lipids.
Timing of spay-neuter surgery in heartworm-positive dogs has been a concern, primarily due to perceived risk of anesthetic complications secondary to cardiovascular compromise. In shelter settings, timing of spay-neuter surgery impacts length of stay and ultimate chance of adoption for heartworm-positive dogs, yet up to 13
Although Dirofilaria repens induces perivascular proliferation in subcutaneous nodules, the molecular factors driving this angiogenic response remain unknown. The objective of this study is to investigate the activation of the angiogenic mechanism in an in vitro model of human vascular endothelial cells (HUVECs) stimulated with D. repens somatic antigen (DrSA) and Dr20/22 protein, identifying the key pathways underlying the vascular pathology caused by the parasite. After 24 h of stimulation with vascular endothelial growth factor A (VEGF-A), DrSA, Dr20/22, DrSA+VEGF-A, and Dr20/22+VEGF-A, cell viability was assessed, and proteins from the cell lysate and supernatant of HUVEC cultures were processed. Proteomic profiles were analysed by data-independent acquisition/label-free quantitation/liquid chromatography–tandem mass spectrometry (DIA-LFQ LC–MS/MS), and bioinformatics analyses (Gene Ontology, enrichment pathway analysis) were performed to identify proteins differentially expressed in relation to the angiogenic process in subcutaneous dirofilariasis. Supernatant analysis showed that DrSA+VEGF-A and Dr20/22+VEGF-A induced the most robust pro-angiogenic response compared to single treatments. Co-stimulation significantly upregulated key secreted proteins, including angiopoietin-2 (ANGPT2), cadherin-5 (CDH5), and multimerin-1 (MMRN1). This synergistic secretome, characterized by enriched angiogenesis pathways, identifies secreted endothelial cell-specific molecule 1 (ESM1) and matrix metalloproteinase-2 (MMP2) as primary drivers of vascular activation and remodelling in the host–parasite interface. DrSA and Dr20/22 act as key molecular drivers that manipulate host angiogenesis. While their synergy with VEGF-A clarifies the origin of vascular changes in subcutaneous dirofilariasis, further research is essential to fully characterize the specific pathways governing vascular pathology and subcutaneous nodule formation. These investigations will deepen the scientific understanding of host–parasite interactions and the disease's clinical etiopathogenesis.
Canine heartworm disease, caused by Dirofilaria immitis, is characterized by a marked inflammatory response largely driven by its endosymbiotic bacterium Wolbachia pipientis. Doxycycline is routinely incorporated into treatment protocols to reduce Wolbachia burden and the associated pathology. Although the standard recommended dosage is 10 mg/kg every 12 h for 28–30 days, evidence comparing lower dosages under clinical conditions remains limited. This study aimed to compare the effects of two doxycycline dosages on inflammatory and immune markers in dogs naturally infected with D. immitis during the pre-adulticidal phase of treatment. Seventy-seven dogs naturally infected with D. immitis were randomly allocated to receive doxycycline at either 10 mg/kg (n = 39) or 5 mg/kg (n = 38) every 12 h for 30 days, in combination with a single oral dose of ivermectin (6 µg/kg) administered at treatment initiation. Serum concentrations of C-reactive protein (CRP) and cortisol were measured at baseline (day 0) and after treatment completion (day 30). Anti-recombinant Wolbachia surface protein (rWSP) antibody levels were determined by ELISA. Intra- and intergroup comparisons were performed using non-parametric statistical tests. Both doxycycline regimens resulted in a significant reduction in CRP concentrations from day 0 to day 30 (p < 0.05), indicating a decrease in systemic inflammation. No significant differences were observed between dosages in the magnitude of CRP reduction. Cortisol concentrations showed a non-significant downward trend in both groups, while anti-rWSP antibody levels remained stable throughout the study period. No significant intergroup differences were detected for any evaluated parameter. Doxycycline administered at 5 mg/kg every 12 h for 30 days showed a comparable short-term biomarker response to the standard 10 mg/kg regimen during the pre-adulticidal phase. Lower doxycycline dosages may represent a potential alternative with possible benefits in terms of tolerance, compliance, and antimicrobial stewardship, although these aspects were not directly evaluated in the present study.
