Latitudinal patterns in stabilizing density dependence of forest communities.

Numerous studies have shown reduced performance in plants that are surrounded by neighbours of the same species1,2, a phenomenon known as conspecific negative density dependence (CNDD)3. A long-held ecological hypothesis posits that CNDD is more pronounced in tropical than in temperate forests4,5, which increases community stabilization, species coexistence and the diversity of local tree species6,7. Previous analyses supporting such a latitudinal gradient in CNDD8,9 have suffered from methodological limitations related to the use of static data10-12. Here we present a comprehensive assessment of latitudinal CNDD patterns using dynamic mortality data to estimate species-site-specific CNDD across 23 sites. Averaged across species, we found that stabilizing CNDD was present at all except one site, but that average stabilizing CNDD was not stronger toward the tropics. However, in tropical tree communities, rare and intermediate abundant species experienced stronger stabilizing CNDD than did common species. This pattern was absent in temperate forests, which suggests that CNDD influences species abundances more strongly in tropical forests than it does in temperate ones13. We also found that interspecific variation in CNDD, which might attenuate its stabilizing effect on species diversity14,15, was high but not significantly different across latitudes. Although the consequences of these patterns for latitudinal diversity gradients are difficult to evaluate, we speculate that a more effective regulation of population abundances could translate into greater stabilization of tropical tree communities and thus contribute to the high local diversity of tropical forests.

Linking fine root lifespan to root chemical and morphological traits-A global analysis.

Fine root lifespan is a critical trait associated with contrasting root strategies of resource acquisition and protection. Yet, its position within the multidimensional "root economics space" synthesizing global root economics strategies is largely uncertain, and it is rarely represented in frameworks integrating plant trait variations. Here, we compiled the most comprehensive dataset of absorptive median root lifespan (MRL) data including 98 observations from 79 woody species using (mini-)rhizotrons across 40 sites and linked MRL to other plant traits to address questions of the regulators of MRL at large spatial scales. We demonstrate that MRL not only decreases with plant investment in root nitrogen (associated with more metabolically active tissues) but also increases with construction of larger diameter roots which is often associated with greater plant reliance on mycorrhizal symbionts. Although theories linking organ structure and function suggest that root traits should play a role in modulating MRL, we found no correlation between root traits associated with structural defense (root tissue density and specific root length) and MRL. Moreover, fine root and leaf lifespan were globally unrelated, except among evergreen species, suggesting contrasting evolutionary selection between leaves and roots facing contrasting environmental influences above vs. belowground. At large geographic scales, MRL was typically longer at sites with lower mean annual temperature and higher mean annual precipitation. Overall, this synthesis uncovered several key ecophysiological covariates and environmental drivers of MRL, highlighting broad avenues for accurate parametrization of global biogeochemical models and the understanding of ecosystem response to global climate change.

Extreme drought impacts have been underestimated in grasslands and shrublands globally.

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function-aboveground net primary production (ANPP)-was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought.

The forest, the cicadas and the holey fluxes: Periodical cicada impacts on soil respiration depends on tree mycorrhizal type.

The emergence of billions of periodical cicadas affects plant and animal communities profoundly, yet little is known about cicada impacts on soil carbon fluxes. We investigated the effects of Brood X cicadas (Magicicada septendecim, M. cassinii and M. septendeculain) on soil CO2 fluxes (RS ) in three Indiana forests. We hypothesized RS would be sensitive to emergence hole density, with the greatest effects occurring in soils with the lowest ambient fluxes. In support of our hypothesis, RS increased with increasing hole density and greater effects were observed near AM-associating trees (which expressed lower ambient fluxes) than near EcM-associating trees. Additionally, RS from emergence holes increased the temperature sensitivity (Q10 ) of RS by 13%, elevating the Q10 of ecosystem respiration. Brood X cicadas increased annual RS by ca. 2.5%, translating to an additional 717 Gg of CO2 across forested areas. As such, periodical cicadas can have substantial effects on soil processes and biogeochemistry.

Immunopathology in human pulmonary tuberculosis: Inflammatory changes in the plasma milieu and impaired host immune cell functions.

Host immune response is key for protection in tuberculosis, but the causative agent, Mycobacterium (M.) tuberculosis, manages to survive despite immune surveillance. Key mechanisms of immune protection have been identified, but the role of immunopathology in the peripheral blood of tuberculosis patients remains unclear. Tuberculosis immunopathology in the blood is characterised by patterns of immunosuppression and hyperinflammation. These seemingly contradictory findings and the pronounced heterogeneity made it difficult to interpret the results from previous studies and to derive implications of immunopathology. However, novel approaches based on comprehensive data analyses and revitalisation of an ancient plasma milieu in vitro assay connected inflammation with immunosuppressive factors in tuberculosis. Moreover, interrelations between the aberrant plasma milieu and immune cell pathology were observed. This review provides an overview of studies on changes in plasma milieu and discusses recent findings linking plasma factors to T-cell and monocyte/macrophage pathology in pulmonary tuberculosis patients.

Traditional healers' perception on scabies causation and management in Ghana.

INTRODUCTION: Scabies is an underdiagnosed skin infestation caused by the Sarcoptes scabiei mite. The infection causes severe itching and a skin rash but can be effectively treated using topical or systemic drugs. Scabies outbreaks are commonly reported in resource-poor countries, including Ghana. Traditional healers play an important role in primary care in rural areas. The role of these traditional healers in the management of scabies has so far not been explored. The aim of this study was therefore to investigate the perceptions of traditional healers regarding the causation and management of scabies. METHODS: A phenomenological qualitative approach was employed. Traditional healers in the Asante Akim North and Central districts in Ghana were approached with an interview request. Using a semi-structured interview protocol, 15 traditional healers were interviewed. The results were coded and analysed, after which seven themes were extrapolated. RESULTS: Scabies infections were frequently reported by traditional healers. Itching and skin rash were unanimously regarded as the major symptoms of scabies. The majority acknowledged the infectious nature of scabies, but no participant reported the causative organism. A dichotomous disease classification was noted, consisting of 'natural' and 'spiritual' variants each with a unique disease profile and management requirements, as reported by the traditional healers. All but two traditional healers reported to treat scabies using almost exclusively herbs and spiritual rituals. CONCLUSION: The majority of traditional healers were open to collaboration with allopathic healthcare providers. Collaboration could broaden the primary care network in rural areas, but mistrust and lack of transparency form potential barriers to collaboration. We, therefore, emphasise the need for additional efforts to investigate strategies for future collaboration.

Differences in PPD- and mitogen-induced T-cell activation marker expression characterize immunopathology in acute tuberculosis patients.

Impaired T-cell responses to mitogens and high T-cell activation marker (TAM) expression on Mycobacterium tuberculosis-specific T-cells characterize immunopathology in patients with tuberculosis (TB). In a study of patients with TB (n = 60) and asymptomatic contacts (controls, n = 37), we found that TB patients had higher CD38+ T-cell proportions specific for M. tuberculosis protein (PPDMtb), yet total proportions of PPDMtb-specific T-cells were comparable. Notably, both activated (CD38+) and total IFN-γ+ T-cells from TB patients had lower mitogen (phytohemagglutinin, PHA)-induced responses. This impaired mitogen response improved the classification efficacy of the TAM-TB assay, especially employing the PPD/PHA-induced T-cell ratio.

Prevalence and determinants of impetigo in Ghana: a cross-sectional study.

INTRODUCTION: Skin diseases such as impetigo pose a significant public health challenge in low resource settings. Despite this, there is a dearth of epidemiological data on the prevalence of this condition in Ghana. METHODS: We conducted a cross sectional study in three settings in Ghana: community members in East Mamprusi district in the North East region, a secondary school in Sekyere East district, and inmates of the Kumasi central prisons both in the Ashanti region. Following a period of training, we performed a standardised skin examination on each participant to assess for scabies and impetigo. We calculated the prevalence of each skin condition and investigated determinants of impetigo. RESULTS/ FINDINGS: Of the 1327 participants [males 64.1% and median age 22 (16-29) years], 746 (56.2%) had scabies and 186 (14%) had impetigo which was usually very mild or mild in severity. Most participants with impetigo also had scabies (161/186, 86.6%). Having an itch [RR 6.05 (95% CI 2.53-14.47)], presence of scabies burrows [RR 1.99 (95% CI 1.54-2.59)], clinical scabies [RR 3.15 (2.11-4.72)] or being in preschool [RR 4.56 (1.78-11.67)] increased the risk for impetigo. A combination of the presence of clinical scabies, age, sex and itch most accurately predicted the odds of having impetigo. CONCLUSIONS: There is substantial burden of impetigo and scabies in Ghana. There is a need to institute measures to improve detection and control of these common dermatoses as part of Universal Health Coverage package to reduce the scourge of the diseases in this setting.

Evaluating the World Health Organization's SkinNTDs App as a Training Tool for Skin Neglected Tropical Diseases in Ghana and Kenya: Cross-Sectional Study.

BACKGROUND: Neglected tropical diseases (NTDs) affect over 1.5 billion people worldwide, primarily impoverished populations in low- and middle-income countries. Skin NTDs, a significant subgroup, manifest primarily as skin lesions and require extensive diagnosis and treatment resources, including trained personnel and financial backing. The World Health Organization has introduced the SkinNTDs app, a mobile health tool designed to train and be used as a decision support tool for frontline health care workers. As most digital health guidelines prioritize the thorough evaluation of mobile health interventions, it is essential to conduct a rigorous and validated assessment of this app. OBJECTIVE: This study aims to assess the usability and user experience of World Health Organization SkinNTDs app (version 3) as a capacity-building tool and decision-support tool for frontline health care workers. METHODS: A cross-sectional study was conducted in Ghana and Kenya. Frontline health care workers dealing with skin NTDs were recruited through snowball sampling. They used the SkinNTDs app for at least 5 days before completing a web-based survey containing demographic variables and the user version of the Mobile Application Rating Scale (uMARS), a validated scale for assessing health apps. A smaller group of participants took part in semistructured interviews and one focus group. Quantitative data were analyzed using SPSS with a 95% CI and P≤.05 for statistical significance and qualitative data using ATLAS.ti to identify attributes, cluster themes, and code various dimensions that were explored. RESULTS: Overall, 60 participants participated in the quantitative phase and 17 in the qualitative phase. The SkinNTDs app scored highly on the uMARS questionnaire, with an app quality mean score of 4.02 (SD 0.47) of 5, a subjective quality score of 3.82 (SD 0.61) of 5, and a perceived impact of 4.47 (SD 0.56) of 5. There was no significant association between the app quality mean score and any of the categorical variables examined, according to Pearson correlation analysis; app quality mean score vs age (P=.37), sex (P=.70), type of health worker (P=.35), country (P=.94), work context (P=.17), frequency of dealing with skin NTDs (P=.09), and dermatology experience (P=.63). Qualitative results echoed the quantitative outcomes, highlighting the ease of use, the offline functionality, and the potential utility for frontline health care workers in remote and resource-constrained settings. Areas for improvement were identified, such as enhancing the signs and symptoms section. CONCLUSIONS: The SkinNTDs app demonstrates notable usability and user-friendliness. The results indicate that the app could play a crucial role in improving capacity building of frontline health care workers dealing with skin NTDs. It could be improved in the future by including new features such as epidemiological context and direct contact with experts. The possibility of using the app as a diagnostic tool should be considered. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/39393.

Mercury Concentrations in Feathers of Albatrosses and Large Petrels at South Georgia: Contemporary Patterns and Comparisons with Past Decades.

Mercury (Hg) is an environmental contaminant that can negatively impact the health of humans and wildlife. Albatrosses and large petrels show some of the highest levels of Hg contamination among birds, with potential repercussions for reproduction and survival. Here, body feather total Hg (THg) concentrations were determined in breeding adults of five species of albatrosses and large petrels in the foraging guild at South Georgia during the mid-2010s. We tested the effects of species, sex and trophic ecology (inferred from stable isotopes) on THg concentrations and compared our results with published values from past decades. Feather THg concentrations differed significantly among species (range: 1.9-49.6 µg g-1 dw), and were highest in wandering albatrosses Diomedea exulans, intermediate in black-browed albatrosses Thalassarche melanophris and northern giant petrels Macronectes halli, and lowest in southern giant petrels M. giganteus and white-chinned petrels Procellaria aequinoctialis. Females were more contaminated than males in all species, potentially due to differences in distributions and diet composition. Across species, THg concentrations were not correlated with feather δ13C or δ15N values, implying that species effects (e.g., breeding and moulting frequencies) may be more important than trophic effects in explaining feather THg concentrations in this foraging guild. Within species, the only significant correlation was between THg and δ13C in wandering albatrosses, which could reflect higher Hg exposure in subtropical waters. Comparisons with THg concentrations from past studies, which reflect contamination from 10 to > 60 years ago, revealed considerable annual variation and some evidence for increases over time for wandering and black-browed albatrosses since before 1950 and from the late 1980s, respectively.

Cost-effectiveness of surgery for degenerative cervical myelopathy in the United Kingdom.

PURPOSE: Degenerative cervical myelopathy (DCM) is the commonest cause of adult spinal cord dysfunction worldwide, for which surgery is the mainstay of treatment. At present, there is limited literature on the costs associated with the surgical management of DCM, and none from the United Kingdom (UK). This study aimed to evaluate the cost-effectiveness of DCM surgery within the National Health Service, UK. MATERIALS AND METHODS: Incidence of DCM was identified from the Hospital Episode Statistics (HES) database for a single year using five ICD-10 diagnostic codes to represent DCM. Health Resource Group (HRG) data was used to estimate the mean incremental surgery (treatment) costs compared to non-surgical care, and the incremental effect (quality adjusted life year (QALY) gain) was based on data from a previous study. A cost per QALY value of <£30,000/QALY (GBP) was considered acceptable and cost-effective, as per the National Institute for Health and Clinical Excellence (NICE) guidance. A sensitivity analysis was undertaken (±5%, ±10% and ±20%) to account for variance in both the cost of admission and QALY gain. RESULTS: The total number of admissions for DCM in 2018 was 4,218. Mean age was 62 years, with 54% of admissions being of working age (18-65 years). The overall estimated cost of admissions for DCM was £38,871,534 for the year. The mean incremental (per patient) cost of surgical management of DCM was estimated to be £9,216 (ranged £2,358 to £9,304), with a QALY gain of 0.64, giving an estimated cost per QALY value of £14,399/QALY. Varying the QALY gain by ±20%, resulted in cost/QALY figures between £12,000 (+20%) and £17,999 (-20%). CONCLUSIONS: Surgery is estimated to be a cost-effective treatment of DCM amongst the UK population.

Multisensory medical illustrations of Buruli ulcer for improved disease detection, help seeking behaviour and adherence to treatment.

Buruli ulcer (BU) is a skin infection caused by Mycobacterium ulcerans and a neglected tropical disease of the skin (skin NTD). Antibiotic treatments are available but, to be effective in the absence of surgery, BU must be detected at its earliest stages (an innocuous-looking lump under the skin) and adherence to prescribed drugs must be high. This study aimed to develop multisensory medical illustrations of BU to support communication with at-risk communities. We used a Think Aloud method to explore community health workers' (n = 6) experiences of BU with a focus on the role of their five senses, since these non-medical disease experts are familiar with the day-to-day challenges presented by BU. Thematic analysis of the transcripts identified three key themes relating to 'Detection,' 'Help Seeking,' and 'Adherence' with a transcending theme 'Senses as key facilitators of health care'. New medical illustrations, for which we coin the phrase "5D illustrations" (signifying the contribution of the five senses) were then developed to reflect these themes. The senses therefore facilitated an enriched narrative enabling the production of relevant and useful visuals for health communication. The medical artist community could utilise sensory experiences to create dynamic medical illustrations for use in practice.

Doxycycline Treatment of Mansonella perstans-Infected Individuals Affects Immune Cell Activation and Causes Long-term T-cell Polarization.

BACKGROUND: Doxycycline is used for treatment of Mansonella perstans infection. Immune modulatory effects of both M. perstans and doxycycline have been described but long-term implications on host immune response are not defined. Here we determined multiple immune parameters of M. perstans-infected individuals before and after doxycycline treatment to characterize doxycycline effects on host T-cell immunity. METHODS: Immune characterization of doxycycline-treated M. perstans-infected individuals was performed as part of an open-label randomized clinical trial. Immune cell population phenotyping by flow cytometry and functional in vitro T-cell assays were performed at baseline, 6 months, and "long term" (18-24 months) after treatment start. Treatment efficacy, based on peripheral blood microfilaria (mf) burden, was correlated with immune parameters and effects on immune response against concomitant Mycobacterium tuberculosis infection were determined. RESULTS: Immune population phenotyping indicated changes in functional T-cell responses after doxycycline treatment. Constitutive and superantigen-induced T-cell activation and polarization towards T-helper type (TH) 1 phenotype at baseline declined after doxycycline treatment, whereas low proportions of TH17 and TH1* cells at baseline increased significantly at follow-up. In accordance, long-term decline in antigen-specific TH1 responses against concomitant M. tuberculosis infection was seen. Notably, only TH17 and TH1* changes after 6 months and TH17 at baseline were negatively correlated with M. perstans microfilaria burden or reduction, whereas long-term changes were not associated with treatment efficacy. CONCLUSIONS: We found long-term immune modulatory effects of doxycycline treatment leading to decreased constitutive T-cell activation, polarization towards TH17/TH1*, and impaired immune response against concomitant M. tuberculosis infection.

Leaf angle as a leaf and canopy trait: Rejuvenating its role in ecology with new technology.

Life on Earth depends on the conversion of solar energy to chemical energy by plants through photosynthesis. A fundamental challenge in optimizing photosynthesis is to adjust leaf angles to efficiently use the intercepted sunlight under the constraints of heat stress, water loss and competition. Despite the importance of leaf angle, until recently, we have lacked data and frameworks to describe and predict leaf angle dynamics and their impacts on leaves to the globe. We review the role of leaf angle in studies of ecophysiology, ecosystem ecology and earth system science, and highlight the essential yet understudied role of leaf angle as an ecological strategy to regulate plant carbon-water-energy nexus and to bridge leaf, canopy and earth system processes. Using two models, we show that leaf angle variations have significant impacts on not only canopy-scale photosynthesis, energy balance and water use efficiency but also light competition within the forest canopy. New techniques to measure leaf angles are emerging, opening opportunities to understand the rarely-measured intraspecific, interspecific, seasonal and interannual variations of leaf angles and their implications to plant biology and earth system science. We conclude by proposing three directions for future research.

Monocyte pathology in human tuberculosis is due to plasma milieu changes and aberrant STAT signalling.

Monocyte-derived macrophages contribute centrally to immune protection in Mycobacterium tuberculosis infection and changes in monocyte phenotype characterize immunopathology in tuberculosis patients. Recent studies highlighted an important role of the plasma milieu in tuberculosis immunopathology. Here, we investigated monocyte pathology in patients with acute tuberculosis and determined tuberculosis plasma milieu effects on phenotype as well as cytokine signalling of reference monocytes. Patients with tuberculosis (n = 37) and asymptomatic contacts (controls n = 35) were recruited as part of a hospital-based study in the Ashanti region of Ghana. Multiplex flow cytometry phenotyping of monocyte immunopathology was performed and effects of individual blood plasma samples on reference monocytes prior to and during treatment were characterized. Concomitantly, cell signalling pathways were analysed to elucidate underlying mechanisms of plasma effects on monocytes. Multiplex flow cytometry visualization characterized changes in monocyte subpopulations and detected higher expression of CD40, CD64 and PD-L1 in monocytes from tuberculosis patients as compared to controls. Aberrant expression normalized during anti-mycobacterial treatment and also CD33 expression decreased markedly. Notably, higher CD33, CD40 and CD64 expression was induced in reference monocytes when cultured in the presence of plasma samples from tuberculosis patients as compared to controls. STAT signalling pathways were affected by the aberrant plasma milieu and higher levels of STAT3 and STAT5 phosphorylation was found in tuberculosis plasma-treated reference monocytes. Importantly, high pSTAT3 levels were associated with high CD33 expression and pSTAT5 correlated with CD40 as well as CD64 expression. These results suggested plasma milieu effects with potential implications on monocyte phenotype and function in acute tuberculosis.

Cytokine-induced transient monocyte IL-7Ra expression and the serum milieu in tuberculosis.

Bacterial components and cytokines induce IL-7 receptor (IL-7Rα) expression in monocytes. Aberrant low IL-7Rα expression of monocytes has been identified as a feature of tuberculosis immunopathology. Here, we investigated the mechanisms underlying IL-7Rα regulation of monocytes and tuberculosis serum effects on IL-7Rα expression. Serum samples from tuberculosis patients and healthy controls, cytokine candidates, and mycobacterial components were analyzed for in vitro effects on IL-7Rα expression of primary monocytes, monocyte-derived macrophages (MDM), and monocyte cell lines. IL-7Rα regulation during culture and the role of FoxO1 were characterized. In vitro activation-induced IL-7Rα expression in human monocytes and serum samples from tuberculosis patients boosted IL-7Rα expression. Although pathognomonic tuberculosis cytokines were not associated with serum effects, we identified cytokines (i.e., GM-CSF, IL-1ß, TNF-α, IFN-γ) that induced IL-7Rα expression in monocytes and/or MDM comparable to mycobacterial components. Blocking of cytokine subsets (i.e., IL-1ß/TNF-α in monocytes, GM-CSF in MDM) largely diminished IL-7Rα expression induced by mycobacterial components. Finally, we showed that in vitro-induced IL-7Rα expression was transient and dependent on constitutive FoxO1 expression in primary monocytes and monocyte cell lines. This study demonstrated the crucial roles of cytokines and constitutive FoxO1 expression for transient IL-7Rα expression in monocytes.

Salmonella enterica in farm environments in the Ashanti Region of Ghana.

BACKGROUND: Salmonella enterica are important foodborne pathogens and the third leading cause of death among diarrheal infections worldwide. This cross-sectional study investigated the frequency of antibiotic-resistant Salmonella enterica in commercial and smallholder farm environments in the Ashanti Region of Ghana. A total of 1490 environmental samples, comprising 800 (53.7%) soil (from poultry, pigs, sheep, goats and cattle farms), 409 (27.4%) pooled poultry fecal and 281 (18.9%) dust (from poultry farms) samples, were collected from 30 commercial and 64 smallholder farms. All samples were processed using standard culture methods. Isolates were identified by biochemical methods and confirmed using the VITEK 2 System. Antibiotic susceptibility testing was carried out by disk diffusion following the EUCAST guidelines. Serotyping was performed using the Kauffman White Le Minor Scheme. RESULTS: The overall Salmonella frequency was 6.0% (n/N = 90/1490); the frequency varied according to the type of sample collected and included: 8.9% for dust (n/N = 25/281), 6.5% for soil (n/N = 52/800) and 3.2% for pooled poultry fecal samples (n/N = 13/409). Salmonella was also recovered from commercial farm environments (8.6%, n/N = 68/793) than from smallholder farms (3.2%, n/N = 22/697) (PR = 2.7, CI: 1.7 - 4.4). Thirty-four different Salmonella serovars were identified, the two most common being Rubislaw (27.8%, n/N = 25/90) and Tamale (12.2%, n/N = 11/90). Serovar diversity was highest in strains from soil samples (70.6%, n/N = 24/34) compared to those found in the dust (35.2%, n/N = 12/34) and in fecal samples (29.4%, n/N = 10/34). Salmonella frequency was much higher in the rainy season (8.4%, n/N = 85/1007) than in the dry season (1.0%, n/N = 5/483) (PR = 8.4, 95% CI: 3.3 - 20.0). Approximately 14.4% (n/N = 13/90) of the isolates were resistant to at least one of the tested antimicrobials, with 84.6% (n/N = 11/13) being resistant to multiple antibiotics. All Salmonella Kentucky (n = 5) were resistant to ciprofloxacin. CONCLUSION: This study showed that farm environments represent an important reservoir for antibiotic-resistant Salmonella, which warrants monitoring and good husbandry practices, especially in commercial farms during the rainy season, to control the spread of this pathogen.

Plasma cytokine levels characterize disease pathogenesis and treatment response in tuberculosis patients.

BACKGROUND: Mycobacterium (M.) tuberculosis-caused immunopathology is characterized by aberrant expression of plasma cytokines in human tuberculosis. Disease severity and long-term anti-mycobacterial treatment are potentially influenced by immunopathology and normalization of plasma cytokine levels during therapy may indicate treatment efficacy and recovery. STUDY DESIGN AND METHODS: In this study, we analyzed the concentrations of selected plasma cytokines (i.e., IL-6, IP-10, IL-10, IL-22, IFNγ, GM-CSF, IL-8) and M. tuberculosis sputum burden in patients with tuberculosis (n = 76). Cytokine levels were compared to healthy contacts (n = 40) and changes under treatment were monitored (i.e., 6 and 16 weeks after treatment start). According to differences in M. tuberculosis sputum burden and conversion, tuberculosis patients were classified as paucibacillary as well as 'rapid' or 'slow' treatment responders. A subgroup of tuberculosis patients had fatal disease courses. RESULTS: Six of seven cytokines were significantly higher in tuberculosis patients as compared to contacts and four of these (i.e., IL-6, IP-10, IL-10, and IL-22) were detectable in the majority of tuberculosis patients. IL-6 showed the strongest discriminating capacity for tuberculosis disease and in combination with IL-10 concentrations efficiently classified paucibacillary tuberculosis cases as well as those with fatal disease outcome. In addition, IL-6 and IP-10 levels decreased significantly after 6 weeks of treatment and analyses of subgroups with differential treatment response showed delayed decline of IL-6 levels in slow treatment responders. CONCLUSIONS: Combinations of different plasma cytokine (namely, IL-6, IL-10, and IP-10) efficiently classified tuberculosis patients with differential mycobacterial burden and especially IL-6 qualified as a biomarker candidate for early treatment response.

Impaired T-cell response to phytohemagglutinin (PHA) in tuberculosis patients is associated with high IL-6 plasma levels and normalizes early during anti-mycobacterial treatment.

PURPOSE: Human tuberculosis is characterized by immunopathology that affects T-cell phenotype and functions. Previous studies found impaired T-cell response to phytohemagglutinin (PHA) in patients with acute tuberculosis. However, the influence of disease severity, affected T-cell subsets, and underlying mechanisms remain elusive. METHODS: Here we investigated PHA-induced and antigen-specific T-cell effector cytokines in tuberculosis patients (n = 55) as well as in healthy asymptomatic contacts (n = 32) from Ghana. Effects of Mycobacterium (M.) tuberculosis sputum burden and treatment response were analyzed and compared during follow-up. Finally, cytokine characteristics of the aberrant plasma milieu in tuberculosis were analyzed as a potential cause for impaired PHA response. RESULTS: PHA-induced IFN-γ expression was significantly lower in sputum-positive tuberculosis patients as compared to both, contacts and paucibacillary cases, and efficiently discriminated the study groups. T-cell responses to PHA increased significantly early during treatment and this was more pronounced in tuberculosis patients with rapid treatment response. Analysis of alternative cytokines revealed distinct patterns and IL-22, as well as IL-10, showed comparable expression to IFN-γ in response to PHA. Finally, we found that high IL-6 plasma levels were strongly associated with impaired IFN-γ and IL-22 response to PHA. CONCLUSION: We conclude that impaired T-cell response to PHA stimulation in acute tuberculosis patients (i) was potentially caused by the aberrant plasma milieu, (ii) affected differentially polarized T-cell subsets, (iii) normalized early during treatment. This study shed light on the mechanisms of impaired T-cell functions in tuberculosis and yielded promising biomarker candidates for diagnosis and monitoring of treatment response.

Memory B-cells are enriched in the blood of patients with acute Buruli ulcer disease: a prospective observational study.

BACKGROUND: Buruli ulcer disease (BUD) caused by Mycobacterium (M.) ulcerans is characterized by necrotic skin lesions. As for other mycobacterial infections, e.g., tuberculosis, the immune response is important for host protection. B-cells may play a role in antimycobacterial immunity but studies characterizing the B-cell repertoire and memory generation in BUD and during the course of treatment are scarce. METHODS: We investigated the adaptive immune cell repertoire in children with BUD and healthy matched controls by flow cytometry. Analyses prior to treatment, also in a study group of patients with tuberculosis, as well as three time points during BUD treatment (i.e., week 8, 16, and 32) were performed. In addition, BUD disease severity as well as treatment response were analysed for association with B-cell repertoire differences. RESULTS: Children with BUD had comparable total B- and T-cell proportions but differed largely in B-cell subsets. Memory B-cell (B mem) proportions were higher in children with BUD whereas regulatory B-cell (B reg) proportions were lower as compared to healthy controls and tuberculosis patients. Lower naïve (B naïve) and higher transitional B-cell (B trans) proportions characterized children with BUD in comparison with tuberculosis patients. Under treatment, B mem proportions decreased significantly whereas proportions of B reg and B naive increased concomitantly in children with BUD. Also, we found significant correlation between lesion size and B mem as well as B reg. However, we did not detect associations between treatment efficacy and B-cell proportions. CONCLUSIONS: These results suggest a role of B-cell subsets in the immune response against M. ulcerans. Furthermore, changes in B-cell subset proportions may be used as markers for treatment monitoring in BUD.