Mpox outbreak in Rio de Janeiro, Brazil: A translational approach.

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.

Unraveling the diversity and dissemination dynamics of antimicrobial resistance genes in Enterobacteriaceae plasmids across diverse ecosystems.

AIM: The objective of this study was to investigate the antimicrobial resistance genes (ARGs) in plasmids of Enterobacteriaceae from soil, sewage, and feces of food-producing animals and humans. METHODS AND RESULTS: The plasmid sequences were obtained from the NCBI database. For the identification of ARG, comprehensive antibiotic resistance database (CARD), and ResFinder were used. Gene conservation and evolution were investigated using DnaSP v.6. The transfer potential of the plasmids was evaluated using oriTfinder and a MOB-based phylogenetic tree was reconstructed using Fastree. We identified a total of 1064 ARGs in all plasmids analyzed, conferring resistance to 15 groups of antibiotics, mostly aminoglycosides, beta-lactams, and sulfonamides. The greatest number of ARGs per plasmid was found in enterobacteria from chicken feces. Plasmids from Escherichia coli carrying multiple ARGs were found in all ecosystems. Some of the most abundant genes were shared among all ecosystems, including aph(6)-Id, aph(3'')-Ib, tet(A), and sul2. A high level of sequence conservation was found among these genes, and tet(A) and sul2 are under positive selective pressure. Approximately 62% of the plasmids carrying at least one ARG were potentially transferable. Phylogenetic analysis indicated a potential co-evolution of Enterobacteriaceae plasmids in nature. CONCLUSION: The high abundance of Enterobacteriaceae plasmids from diverse ecosystems carrying ARGs reveals their widespread distribution and importance.

A case management strategy to reduce falls in older people with a history of falls: A randomized controlled trial.

The present study aimed to determine whether a remotely delivered intervention, based on an individual case management, can reduce falls and their consequences in community-dwelling older people with a history of multiple falls. In this randomized controlled trial, 32 participants were randomized to the intervention group, which comprised a 16-week case management program involving a multidimensional assessment, targeted interventions according to the identified fall risk factors, and development of individualized care plans. The intervention was performed by trained gerontologists, under weekly supervision of professionals with experience in falls. The control group (n = 30) received usual care. Falls were monitored over 12 months with monthly falls calendars and telephone calls. Remotely delivered case management presented an 82 % uptake of recommendations. There was a trend toward a reduced fall incidence in the intervention vs control group, with lower fall, fall injury and fracture rates in the intervention group compared with the control group at both the 16-week and 12-month time-points, with the difference statistically significant for injurious fall rates at 12 months - IRR=0.18 (95 % CI = 0.04 to 0.74).

Cancer patients admitted in the emergency department: A single-centre observational study.

OBJECTIVE: This study aims to analyse patients' clinical profiles seen at an emergency unit of a public oncology reference hospital in Belo Horizonte, Brazil. METHODS: This is a cross-sectional, observational, retrospective study, with data collection through patients' medical records seen between 2016 and 2018. The identification of patients was carried out through research on hospital admission authorization guides. RESULTS: A total of 2932 medical records were evaluated, of which only 21.5% were cancer patients. A cancer diagnosis was made for 21.5% of patients during hospitalisation. In this group, pain and weight loss are frequent symptoms, and haematological diseases (15.2%) were the most frequent tumour type. Patients with a previous cancer diagnosis presented the most prevalent tumour breast (18.3%) and altered consciousness level as a leading symptom. Analgesics were the most prescribed drugs in both groups. CONCLUSION: This study showed two distinct groups of cancer patients: with or without a previous cancer diagnosis. However, these two groups are comparable in almost all the variables analysed. Therefore, we believe that the factors that could guide the care in an emergency are related to education on cancer symptoms for the population to contribute to an early diagnosis and cancer training for emergency department (ED) professionals' to better monitor advanced-stage patients for symptom management.

Physiological and Transcriptomic Changes in the Hypothalamic-Neurohypophysial System after 24 h of Furosemide-Induced Sodium Depletion.

BACKGROUND/AIMS: Furosemide is a loop diuretic widely used in clinical practice for the treatment of oedema and hypertension. The aim of this study was to determine physiological and molecular changes in the hypothalamic-neurohypophysial system as a consequence of furosemide-induced sodium depletion. METHODS: Male rats were sodium depleted by acute furosemide injection (10 and 30 mg/kg) followed by access to low sodium diet and distilled water for 24 h. The renal and behavioural consequences were evaluated, while blood and brains were collected to evaluate the neuroendocrine and gene expression responses. RESULTS: Furosemide treatment acutely increases urinary sodium and water excretion. After 24 h, water and food intake were reduced, while plasma angiotensin II and corticosterone were increased. After hypertonic saline presentation, sodium-depleted rats showed higher preference for salt. Interrogation using RNA sequencing revealed the expression of 94 genes significantly altered in the hypothalamic paraventricular nucleus (PVN) of sodium-depleted rats (31 upregulated and 63 downregulated). Out of 9 genes chosen, 5 were validated by quantitative PCR in the PVN (upregulated: Ephx2, Ndnf and Vwf; downregulated: Caprin2 and Opn3). The same genes were also assessed in the supraoptic nucleus (SON, upregulated: Tnnt1, Mis18a, Nr1d1 and Dbp; downregulated: Caprin2 and Opn3). As a result of these plastic transcriptome changes, vasopressin expression was decreased in PVN and SON, whilst vasopressin and oxytocin levels were reduced in plasma. CONCLUSIONS: We thus have identified novel genes that might regulate vasopressin gene expression in the hypothalamus controlling the magnocellular neurons secretory response to body sodium depletion and consequently hypotonic stress.

Applications of an electronic nose in the prediction of oxidative stability of stored biodiesel derived from soybean and waste cooking oil.

Waste cooking oil (WCO) is a valuable feedstock for the synthesis of biodiesel but the product exhibits poor oxidative stability. Techniques available for assessing this parameter are generally expensive and time-consuming, hence the purpose of this study was to develop and validate a rapid and reliable predictive system based on signals from the sensors of a commercial hand-held e-nose instrument. Biodiesels were synthesized from soybean oil and six samples of WCO, and their physicochemical characteristics and oxidative stabilities determined before and after storage in different types of containers for 30 or 60 days at room temperature or 43 °C. Linear regression models were constructed based on principal component analysis of the signals generated by all 32 e-nose sensors and stochastic modeling of signal profiles from individual sensors. The regression model with principal components as predictors was unable to explain the oxidative stability of biodiesels, while the regression model with stochastic parameters (combining signals from 11 sensors) as predictors showed an excellent goodness of fit (R2 = 0.91) with a 45-sample training set and a good quality of prediction (R2 = 0.84) with a 18-sample validation set. The proposed e-nose system was shown to be accurate and efficient and could be used to advantage by producers/distributors of biodiesel in the assessment fuel quality.

Teaching Tip Using Play-Doh to Enhance the Perceived Learning of Veterinary Medicine.

Teaching anatomy to veterinary students is challenging, and using two-dimensional (2D) representations may limit the opportunity for learners to make the connections required to fully appreciate the complex structures involved and the relationships between them. This research considered the implementation of three-dimensional (3D) modeling using Play-Doh with learners to consider whether they were able to make effective representations that may then support further learning. The evidence from teacher observations and student feedback suggests that, despite some initial hesitation surrounding the use of what some might perceive as a toy in the higher education classroom, the learners believed that the approach allowed improvement in terms of their understanding, knowledge retention and recall. They reported that the approach enabled greater visualization of the structures they were representing. For teachers, the approach has the advantage that the material is cheap, readily available, easily manipulated, can be reused, and needs no sophisticated technology.

Renovascular hypertension elevates pulmonary ventilation in rats by carotid body-dependent mechanisms.

The two kidney-one clip (2K1C) renovascular hypertension depends on the renin-angiotensin system and sympathetic overactivity. The maintenance of 2K1C hypertension also depends on inputs from the carotid bodies (CB), which when activated stimulate the respiratory activity. In the present study, we investigated the importance of CB afferent activity for the ventilatory responses in 2K1C hypertensive rats and for phrenic and hypoglossal activities in in situ preparations of normotensive rats treated with angiotensin II. Silver clips were implanted around the left renal artery of male Holtzman rats (150 g) to induce renovascular hypertension. Six weeks after clipping, hypertensive 2K1C rats showed, in conscious state, elevated resting tidal volume and minute ventilation compared with the normotensive group. 2K1C rats also presented arterial alkalosis, urinary acidification, and amplified hypoxic ventilatory response. Carotid body removal (CBR), 2 wk before the experiments (4th week after clipping), significantly reduced arterial pressure and pulmonary ventilation in 2K1C rats but not in normotensive rats. Intra-arterial administration of angiotensin II in the in situ preparation of normotensive rats increased phrenic and hypoglossal activities, responses that were also reduced after CBR. Results show that renovascular hypertensive rats exhibit increased resting ventilation that depends on CB inputs. Similarly, angiotensin II increases phrenic and hypoglossal activities in in situ preparations of normotensive rats, responses that also depend on CB inputs. Results suggest that mechanisms that depend on CB inputs in renovascular hypertensive rats or during angiotensin II administration in normotensive animals increase respiratory drive.

Decadal losses of canopy-forming algae along the warm temperate coastline of Brazil.

The loss of canopy-forming seaweeds from urbanized coasts has intensified in response to warming seas and non-climatic pressures such as population growth and declining water quality. Surprisingly, there has been little information on the extent of historical losses in the South-western Atlantic, which limits our ability to place this large marine ecosystem in a global context. Here, we use meta-analysis to examine long-term (1969-2017) changes to the cover and biomass of Sargassum spp. and structurally simple algal turfs along more than 1,000 kilometres of Brazil's warm temperate coastline. Analysis revealed major declines in canopy cover that were independent of season (i.e., displaying similar trends for both summer and winter) but varied with coastal environmental setting, whereby sheltered bays experienced greater losses than coastal locations. On average, covers of Sargassum spp. declined by 2.6% per year, to show overall losses of 52% since records began (ranging from 20% to 89%). This contrasted with increases in the cover of filamentous turfs (24% over the last 27 years) which are known to proliferate along human-impacted coasts. To test the relative influence of climatic versus non-climatic factors as drivers of this apparent canopy-to-turf shift, we examined how well regional warming trends (decadal changes to sea surface temperature) and local proxies of coastal urbanization (population density, thermal pollution, turbidity and nutrient inputs) were able to predict the changes in seaweed communities. Our results revealed that the most pronounced canopy losses over the past 50 years were at sites exhibiting the greatest degree of coastal warming, the highest population growth and those located in semi-enclosed sheltered bays. These findings contribute knowledge on the drivers of canopy loss in the South-western Atlantic and join with global efforts to understand and mitigate declines of marine keystone species.

Transcription factor CREB3L1 regulates vasopressin gene expression in the rat hypothalamus.

Arginine vasopressin (AVP) is a neurohypophysial hormone regulating hydromineral homeostasis. Here we show that the mRNA encoding cAMP responsive element-binding protein-3 like-1 (CREB3L1), a transcription factor of the CREB/activating transcription factor (ATF) family, increases in expression in parallel with AVP expression in supraoptic nuclei (SONs) and paraventicular nuclei (PVNs) of dehydrated (DH) and salt-loaded (SL) rats, compared with euhydrated (EH) controls. In EH animals, CREB3L1 protein is expressed in glial cells, but only at a low level in SON and PVN neurons, whereas robust upregulation in AVP neurons accompanied DH and SL rats. Concomitantly, CREB3L1 is activated by cleavage, with the N-terminal domain translocating from the Golgi, via the cytosol, to the nucleus. We also show that CREB3L1 mRNA levels correlate with AVP transcription level in SONs and PVNs following sodium depletion, and as a consequence of diurnal rhythm in the suprachiasmatic nucleus. We tested the hypothesis that CREB3L1 activates AVP gene transcription. Both full-length and constitutively active forms of CREB3L1 (CREB3L1CA) induce the expression of rat AVP promoter-luciferase reporter constructs, whereas a dominant-negative mutant reduces expression. Rat AVP promoter deletion constructs revealed that CRE-like and G-box sequences in the region between -170 and -120 bp are important for CREB3L1 actions. Direct binding of CREB3L1 to the AVP promoter was shown by chromatin immunoprecipitation both in vitro and in the SON itself. Injection of a lentiviral vector expressing CREB3L1CA into rat SONs and PVNs resulted in increased AVP biosynthesis. We thus identify CREB3L1 as a regulator of AVP transcription in the rat hypothalamus.

Validation of a sleep staging classification model for healthy adults based on two combinations of a single-channel EEG headband and wrist actigraphy.

STUDY OBJECTIVES: The aim of this study was to develop a sleep staging classification model capable of accurately performing on different wearable devices. METHODS: Twenty-three healthy participants underwent a full-night type I polysomnography and used two device combinations: (A) flexible single-channel electroencephalogram (EEG) headband + actigraphy (n = 12) and (B) rigid single-channel EEG headband + actigraphy (n = 11). The signals were segmented into 30-second epochs according to polysomnographic stages (scored by a board-certified sleep technologist; model ground truth) and 18 frequency and time features were extracted. The model consisted of an ensemble of bagged decision trees. Bagging refers to bootstrap aggregation to reduce overfitting and improve generalization. To evaluate the model, a training dataset under 5-fold cross-validation and an 80-20% dataset split was used. The headbands were also evaluated without the actigraphy feature. Participants also completed a usability evaluation (comfort, pain while sleeping, and sleep disturbance). RESULTS: Combination A had an F1-score of 98.4% and the flexible headband alone of 97.7% (error rate for N1: combination A = 9.8%; flexible headband alone = 15.7%). Combination B had an F1-score of 96.9% and the rigid headband alone of 95.3% (error rate for N1: combination B = 17.0%; rigid headband alone = 27.7%); in both, N1 was more confounded with N2. CONCLUSIONS: We developed an accurate sleep classification model based on a single-channel EEG device, and actigraphy was not an important feature of the model. Both headbands were found to be useful, with the rigid one being more disruptive to sleep. Future research can improve our results by applying the developed model in a population with sleep disorders. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Actigraphy, Wearable EEG Band and Smartphone for Sleep Staging; URL: https://clinicaltrials.gov/study/NCT04943562; Identifier: NCT04943562. CITATION: Melo MC, Vallim JRS, Garbuio S, et al. Validation of a sleep staging classification model for healthy adults based on 2 combinations of a single-channel EEG headband and wrist actigraphy. J Clin Sleep Med. 2024;20(6):983-990.

Effects of a Multifactorial Program with Case Management for Falls Prevention on Functional Outcomes in Community-Dwelling Older People: A Randomized Clinical Study.

Falls are among the top 10 causes of years lived with disability in people aged 75 and over. Preventive programs like case management (CM) are crucial. OBJECTIVES: To evaluate the effects of a multifactorial fall prevention program based on CM on physical performance, the presence of pain, and the risk of falls and fractures in older people who have suffered falls. METHODS: This randomized, single-blind clinical trial with parallel groups, Intervention Group (IG) and Control Group (CG), was composed of 55 older people with a history of falling, living in the community. All participants underwent an initial assessment via video call (containing anamnesis, timed up-and-go test, falls risk score, short physical performance battery, and clinical frax). The IG underwent CM, the physical exercise protocol, and the cognitive stimulation protocol. The CG was monitored through telephone calls and received general health and fall guidance. RESULTS: No significant results were found in the physical capacity, the presence of pain, the risk of falls, or the fractures between the Intervention and Control Groups and between assessments. CONCLUSION: This program was not effective in improving functional performance, but it was important for characterizing pain and the probability of fracture in the next 10 years in this population.

Four-week inhibition of the renin-angiotensin system in spontaneously hypertensive rats results in persistently lower blood pressure with reduced kidney renin and changes in expression of relevant gene networks.

AIMS: Prevention of human hypertension is an important challenge and has been achieved in experimental models. Brief treatment with renin-angiotensin system (RAS) inhibitors permanently reduces the genetic hypertension of the spontaneously hypertensive rat (SHR). The kidney is involved in this fascinating phenomenon, but relevant changes in gene expression are unknown. METHODS AND RESULTS: In SHR, we studied the effect of treatment between 10 and 14 weeks of age with the angiotensin receptor blocker, losartan, or the angiotensin-converting enzyme inhibitor, perindopril [with controls for non-specific effects of lowering blood pressure (BP)], on differential RNA expression, DNA methylation, and renin immunolabelling in the kidney at 20 weeks of age. RNA sequencing revealed a six-fold increase in renin gene (Ren) expression during losartan treatment (P < 0.0001). Six weeks after losartan, arterial pressure remained lower (P = 0.006), yet kidney Ren showed reduced expression by 23% after losartan (P = 0.03) and by 43% after perindopril (P = 1.4 × 10-6) associated with increased DNA methylation (P = 0.04). Immunolabelling confirmed reduced cortical renin after earlier RAS blockade (P = 0.002). RNA sequencing identified differential expression of mRNAs, miRNAs, and lncRNAs with evidence of networking and co-regulation. These included 13 candidate genes (Grhl1, Ammecr1l, Hs6st1, Nfil3, Fam221a, Lmo4, Adamts1, Cish, Hif3a, Bcl6, Rad54l2, Adap1, Dok4), the miRNA miR-145-3p, and the lncRNA AC115371. Gene ontogeny analyses revealed that these networks were enriched with genes relevant to BP, RAS, and the kidneys. CONCLUSION: Early RAS inhibition in SHR resets genetic pathways and networks resulting in a legacy of reduced Ren expression and BP persisting for a minimum of 6 weeks.

An Evaluation of the Antibacterial, Antileishmanial, and Cytotoxic Potential of the Secondary Metabolites of Streptomyces sp. ARH (A3).

This study aimed to evaluate the antibacterial, leishmanicidal, and cytotoxic potential of metabolites produced by bacteria isolated from rhizosphere soil samples. The bacterium was identified by genome sequencing as Streptomyces kronopolitis. A preliminary screening was carried out for the antimicrobial activity of S. kronopolitis, demonstrating activity against Staphylococcus aureus ATCC 6538, Corynebacterium diphtheriae ATCC 27010, C. diphtheriae ATCC 27012, and Mycobacterium abscessus, with inhibition halos of sizes 25, 36, 29, and 33 mm, respectively. To obtain secondary metabolites, the bacteria were subjected to submerged fermentation, and the metabolites were extracted using the liquid-liquid method with ethyl acetate. There was a similar MIC for M. abscessus and the two strains of C. diphtherium, reaching a concentration of 12.5 µg/mL, while that of S. aureus was 0.048 µg/mL. Assays for leishmanicidal activity and cytotoxicity against HEp-2 cells and red blood cells were performed. The metabolite showed an IC50 of 9.0 ± 0.9 µg/mL and CC50 of 221.2 ± 7.0 µg/mL. This metabolite does not have hemolytic activity and is more selective for parasites than for mammalian cells, with a selectivity index of 24.6. Thus, the studied metabolite may be a strong candidate for the development of less toxic drugs to treat diseases caused by pathogens.

3-D technology used to accurately understand equine ileocolonic aganglionosis.

Ileocolonic aganglionosis (ICA) is the congenital and hereditary absence of neurons that constitute the enteric nervous system and has been described in various species including humans - Hirschsprung's disease - and horses - overo lethal white syndrome (OLWS). Hirschsprung's disease affects circa 1 in 5,000 live births. At best, this disease means an inability to absorb nutrients from food (humans). At worse, in horses, it always means death. Despite our general understanding of the functional mechanisms underlying ICA, there is a paucity of reliable quantitative information about the structure of myenteric and submucosal neurons in healthy horses and there are no studies on horses with ICA. In light of these uncertainties, we have used design-based stereology to describe the 3-D structure - total number and true size - of myenteric and submucosal neurons in the ileum of ICA horses. Our study has shown that ICA affects all submucosal neurons and 99% of myenteric neurons. The remaining myenteric neurons (0.56%) atrophy immensely, i.e. 63.8%. We believe this study forms the basis for further research, assessing which subpopulation of myenteric neurons are affected by ileocolonic aganglionosis, and we would like to propose a new nomenclature to distinguish between a complete absence of neurons - aganglionosis - and a weaker form of the disease which we suggest naming 'hypoganglionosis'. Our results are a step forward in understanding this disease structurally.

Manual blood exchange transfusion does not significantly contribute to parasite clearance in artesunate-treated individuals with imported severe Plasmodium falciparum malaria.

BACKGROUND: Exchange transfusion (ET) has remained a controversial adjunct therapy for the treatment of severe malaria. In order to assess the relative contribution of ET to parasite clearance in severe malaria, all patients receiving ET as an adjunct treatment to parenteral quinine or to artesunate were compared with patients treated with parenteral treatment with quinine or artesunate but who did not receive ET. ET was executed using a standardized manual isovolumetric exchange protocol. METHODS: All patients in the Rotterdam Malaria Cohort treated for severe P. falciparum malaria at the Institute for Tropical Diseases of the Harbour Hospital between 1999 and 2011 were included in this retrospective follow-up study. Both a two-stage approach and a log-linear mixed model approach were used to estimate parasite clearance times (PCTs) in patients with imported malaria. Severe malaria was defined according to WHO criteria. RESULTS: A total of 87 patients with severe malaria was included; 61 received intravenous quinine, whereas 26 patients received intravenous artesunate. Thirty-nine patients received ET as an adjunct treatment to either quinine (n = 23) or artesunate (n = 16). Data from 84 of 87 patients were suitable for estimation of parasite clearance rates. PCTs were significantly shorter after administration of artesunate as compared with quinine. In both models, ET did not contribute significantly to overall parasite clearance. CONCLUSION: Manual exchange transfusion does not significantly contribute to parasite clearance in artesunate-treated individuals. There may be a small effect of ET on parasite clearance under quinine treatment. Institution of ET to promote parasite clearance in settings where artesunate is available is not recommended, at least not with manually executed exchange procedures.

Severity of imported malaria: protective effect of taking malaria chemoprophylaxis.

BACKGROUND: Although chemoprophylaxis remains an important strategy for preventing malaria in travellers, its effectiveness may be compromised by lack of adherence. Inappropriate use of chemoprophylaxis is likely to increase the risk of acquiring malaria, but may probably also worsen the severity of imported cases. The aim of this study was to assess the impact of use of malaria chemoprophylaxis on clinical features and outcome of imported malaria. METHODS: Demographic, clinical and laboratory data of patients included in the Rotterdam Malaria Cohort between 1998 and 2011 were systematically collected and analysed. Patients were classified as self-reported compliant or non-compliant users or as non-users of chemoprophylaxis. Severe malaria was defined using the 2010 WHO criteria. RESULTS: Details on chemoprophylaxis were available for 559 of the 604 patients, of which 64.6% were non-users, 17.9% were inadequate users and 17.5% reported to be adequate users. The group of non-users was predominated by patients with African ethnicity, partial immunity and people visiting friends and relatives. The majority contracted Plasmodium falciparum malaria. In contrast, compliant users acquired non-falciparum malaria more frequently, had significant lower P. falciparum loads on admission, shorter duration of hospitalization and significant lower odds for severe malaria as compared with non-users. Patients with P. falciparum malaria were more likely to have taken their chemoprophylaxis less compliantly than those infected with non-P. falciparum species. Multivariate analysis showed that self-reported adequate prophylaxis and being a partially immune traveller visiting friends and relatives was associated with significantly lower odds ratio of severe malaria. In contrast, age, acquisition of malaria in West-Africa and being a non-immune tourist increased their risk significantly. CONCLUSIONS: Compliant use of malaria chemoprophylaxis was associated with significantly lower odds ratios for severe malaria as compared with non-compliant users and non-users of chemoprophylaxis. After correction for age, gender and immunity, this protective effect of malaria chemoprophylaxis was present only in individuals who adhered compliantly to use of chemoprophylaxis. Patients with P. falciparum malaria were more likely to have used their chemoprophylaxis less compliantly than patients with non-P. falciparum malaria who were more likely to have contracted malaria in spite of compliant use of chemoprophylaxis.

Predictive value of lymphocytopenia and the neutrophil-lymphocyte count ratio for severe imported malaria.

BACKGROUND: Lymphocytopenia has frequently been described in patients with malaria, but studies on its association with disease severity have yielded conflicting results. The neutrophil/lymphocyte count ratio (NLCR) has been introduced as a parameter for systemic inflammation in critically ill patients and was found, together with lymphocytopenia, to be a better predictor of bacteraemia than routine parameters like C-reactive protein and total leukocyte count. In the present study, the predictive value of the NLCR and lymphocytopenia for severe disease was evaluated in patients with imported malaria. METHODS: All patients diagnosed with malaria at the Harbour Hospital between January 1st 1999 and January 1st 2012 with differential white cell counts determined within the first 24 hours after admission were included in this retrospective study. Severe malaria was defined according to the WHO criteria. The performance of the NLCR and lymphocytopenia as a marker of severe malarial disease was compared back-to-back with that of C-reactive protein as a reference biomarker. RESULTS: A total of 440 patients (severe falciparum malaria n = 61, non-severe falciparum malaria n = 259, non-falciparum malaria n=120) were included in the study. Lymphocytopenia was present in 52% of all patients and the median NLCR of all patients was 3.2. Total lymphocyte counts and NLCR did not differ significantly between groups. A significant correlation of total leukocyte count and NLCR, but not lymphocyte count, with parasitaemia was found. ROC analysis revealed a good negative predictive value but a poor positive predictive value of both lymphocytopenia and NLCR and performance was inferior to that of C-reactive protein. After complete parasite clearance a significant rise in total leukocyte count and lymphocyte count and a significant decrease in NLCR was observed. CONCLUSION: The NLCR was found to correlate with parasitaemia, but both lymphocytopenia and the NLCR were inferior to C-reactive protein as markers for severe disease in patients with imported malaria. The NLCR and lymphocytopenia are not useful as predictive markers for severe disease in imported malaria in the acute care setting.