Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen

Human endogenous retroviruses (HERVs) arise from ancient infections of the host germline cells by exogenous retroviruses, constituting 8% of the human genome. Elevated level of envelope transcripts from HERVs-W has been detected in CSF, plasma and brain tissues from patients with Multiple Sclerosis (MS), most of them from Xq22.3, 15q21.3, and 6q21 chromosomes. However, since the locus Xq22.3 (ERVWE2) lack the 5' LTR promoter and the putative protein should be truncated due to a stop codon, we investigated the ERVWE2 genomic loci from 84 individuals, including MS patients with active HERV-W expression detected in PBMC. In addition, an automated search for promoter sequences in 20 kb nearby region of ERVWE2 reference sequence was performed. Several putative binding sites for cellular cofactors and enhancers were found, suggesting that transcription may occur via alternative promoters. However, ERVWE2 DNA sequencing of MS and healthy individuals revealed that all of them harbor a stop codon at site 39, undermining the expression of a full-length protein. Finally, since plaque formation in central nervous system (CNS) of MS patients is attributed to immunological mechanisms triggered by autoimmune attack against myelin, we also investigated the level of similarity between envelope protein and myelin oligodendrocyte glycoprotein (MOG). Comparison of the MOG to the envelope identified five retroviral regions similar to the Ig-like domain of MOG. Interestingly, one of them includes T and B cell epitopes, capable to induce T effector functions and circulating Abs in rats. In sum, although no DNA substitutions that would link ERVWE2 to the MS pathogeny was found, the similarity between the envelope protein to MOG extends the idea that ERVEW2 may be involved on the immunopathogenesis of MS, maybe facilitating the MOG recognizing by the immune system. Although awaiting experimental evidences, the data presented here may expand the scope of the endogenous retroviruses involvement on MS pathogenesis

Analysis of genetic lineages and their correlation with virulence genes in enterococcus faecalis clinical isolates from root canal and systemic infections

Introduction: Enterococcus faecalis is a member of the mammalian gastrointestinal microbiota but has been considered a leading cause of hospital-acquired infections. In the oral cavity, it is commonly detected from root canals of teeth with failed endodontic treatment. However, little is known about the virulence and genetic relatedness among E. faecalis isolates from different clinical sources. This study compared the presence of enterococcal virulence factors among root canal strains and clinical isolates from hospitalized patients to identify virulent clusters of E. faecalis. Methods: Multilocus sequence typing analysis was used to determine genetic lineages of 40 E. faecalis clinical isolates from different sources. Virulence clusters were determined by evaluating capsule (cps) locus polymorphisms, pathogenicity island gene content, and antibiotic resistance genes by polymerase chain reaction. Results: The clinical isolates from hospitalized patients formed a phylogenetically separate group and were mostly grouped in the clonal complex 2, which is a known virulent cluster of E. faecalis that has caused infection outbreaks globally. The clonal complex 2 group comprised capsule-producing strains harboring multiple antibiotic resistance and pathogenicity island genes. On the other hand, the endodontic isolates were more diverse and harbored few virulence and antibiotic resistance genes. In particular, although more closely related to isolates from hospitalized patients, capsuleproducing E. faecalis strains from root canals did not carry more virulence/antibiotic genes than other endodontic isolates. Conclusions: E. faecalis isolates from endodontic infections have a genetic and virulence profile different from pathogenic clusters of hospitalized patients’ isolates, which is most likely due to niche specialization conferred mainly by variable regions in the genome.

Testing for sexually transmitted infections in general practice: cross-sectional study

Background Primary care is an important provider of sexual health care in England. We sought to explore the extent of testing for chlamydia and HIV in general practice and its relation to associated measures of sexual health in two contrasting geographical settings. Methods We analysed chlamydia and HIV testing data from 64 general practices and one genitourinary medicine (GUM) clinic in Brent (from mid-2003 to mid-2006) and 143 general practices and two GUM clinics in Avon (2004). We examined associations between practice testing status, practice characteristics and hypothesised markers of population need (area level teenage conception rates and Index of Multiple Deprivation, IMD scores). Results No HIV or chlamydia testing was done in 19% (12/64) of general practices in Brent, compared to 2.1% (3/143) in Avon. In Brent, the mean age of general practitioners (GPs) in Brent practices that tested for chlamydia or HIV was lower than in those that had not conducted testing. Practices where no HIV testing was done had slightly higher local teenage conception rates (median 23.5 vs. 17.4/1000 women aged 15-44, p = 0.07) and served more deprived areas (median IMD score 27.1 vs. 21.8, p = 0.05). Mean yearly chlamydia and HIV testing rates, in practices that did test were 33.2 and 0.6 (per 1000 patients aged 15-44 years) in Brent, and 34.1 and 10.3 in Avon, respectively. In Brent practices only 20% of chlamydia tests were conducted in patients aged under 25 years, compared with 39% in Avon. Conclusions There are substantial geographical differences in the intensity of chlamydia and HIV testing in general practice. Interventions to facilitate sexually transmitted infection and HIV testing in general practice are needed to improve access to effective sexual health care. The use of routinely-collected laboratory, practice-level and demographic data for monitoring sexual health service provision and informing service planning should be more widely evaluated.

Drug hypersensitivity: flare-up reactions, cross-reactivity and multiple drug hypersensitivity

In drug hypersensitivity, change of drug treatment and continuation with a new drug may result in reappearance of drug hypersensitivity symptoms. This is not uncommon in patients with chronic infections requiring continued and long-lasting antibiotic treatments. For the clinician, the question arises whether these symptoms are due to cross-reactivity, are due to a new sensitization or are a reflection of a multiple drug hypersensitivity syndrome. Based on the p-i concept (pharmacological interaction with immune receptors), we propose that the efficient stimulation of T cells by a drug is the sum of drug-T-cell receptor affinity and readiness of the T cell to react, and therefore not constant. It heavily depends on the state of underlying immune activation. Consequently, drug hypersensitivity diseases, which go along with massive immune stimulations and often high serum cytokine values, are themselves risk factors for further drug hypersensitivity. The immune stimulation during drug hypersensitivity may, similar to generalized virus infections, lower the threshold of T-cell reactivity to drugs and cause rapid appearance of drug hypersensitivity symptoms to the second drug. We call the second hypersensitivity reaction a "flare-up" reaction; this is clinically important, as in most cases the second drug may be tolerated again, if the cofactors are missing. Moreover, the second treatment is often too short to cause a relevant sensitization.

Prevention and control of surgical site infections: review of the Basel Cohort Study

INTRODUCTION: Surgical site infections (SSI) are the most common hospital-acquired infections among surgical patients, with significant impact on patient morbidity and health care costs. The Basel SSI Cohort Study was performed to evaluate risk factors and validate current preventive measures for SSI. The objective of the present article was to review the main results of this study and its implications for clinical practice and future research. SUMMARY OF METHODS OF THE BASEL SSI COHORT STUDY: The prospective observational cohort study included 6,283 consecutive general surgery procedures closely monitored for evidence of SSI up to 1 year after surgery. The dataset was analysed for the influence of various potential SSI risk factors, including timing of surgical antimicrobial prophylaxis (SAP), glove perforation, anaemia, transfusion and tutorial assistance, using multiple logistic regression analyses. In addition, post hoc analyses were performed to assess the economic burden of SSI, the efficiency of the clinical SSI surveillance system, and the spectrum of SSI-causing pathogens. REVIEW OF MAIN RESULTS OF THE BASEL SSI COHORT STUDY: The overall SSI rate was 4.7% (293/6,283). While SAP was administered in most patients between 44 and 0 minutes before surgical incision, the lowest risk of SSI was recorded when the antibiotics were administered between 74 and 30 minutes before surgery. Glove perforation in the absence of SAP increased the risk of SSI (OR 2.0; CI 1.4-2.8; p <0.001). No significant association was found for anaemia, transfusion and tutorial assistance with the risk of SSI. The mean additional hospital cost in the event of SSI was CHF 19,638 (95% CI, 8,492-30,784). The surgical staff documented only 49% of in-hospital SSI; the infection control team registered the remaining 51%. Staphylococcus aureus was the most common SSI-causing pathogen (29% of all SSI with documented microbiology). No case of an antimicrobial-resistant pathogen was identified in this series. CONCLUSIONS: The Basel SSI Cohort Study suggested that SAP should be administered between 74 and 30 minutes before surgery. Due to the observational nature of these data, corroboration is planned in a randomized controlled trial, which is supported by the Swiss National Science Foundation. Routine change of gloves or double gloving is recommended in the absence of SAP. Anaemia, transfusion and tutorial assistance do not increase the risk of SSI. The substantial economic burden of in-hospital SSI has been confirmed. SSI surveillance by the surgical staff detected only half of all in-hospital SSI, which prompted the introduction of an electronic SSI surveillance system at the University Hospital of Basel and the Cantonal Hospital of Aarau. Due to the absence of multiresistant SSI-causing pathogens, the continuous use of single-shot single-drug SAP with cefuroxime (plus metronidazole in colorectal surgery) has been validated.

Early serum procalcitonin, interleukin-6, and 24-hour lactate clearance: useful indicators of septic infections in severely traumatized patients

BACKGROUND: Elevated lactate and interleukin-6 (IL-6) levels were shown to correlate with mortality and multiple organ dysfunction in severely traumatized patients. The purpose of this study was to test whether an association exists between 24-hour lactate clearance, IL-6 and procalcitonin (PCT) levels, and the development of infectious complications in trauma patients. METHODS: A total of 1757 consecutive trauma patients with an Injury Severity Score (ISS) > 16 admitted over a 10-year period were retrospectively analyzed over a 21-day period. Exclusion criteria included death within 72 h of admission (24.5%), late admission > 12 h after injury (16%), and age < 16 years (0.5%). Data are stated as the median (range). RESULTS: Altogether, 1032 trauma patients (76.2% male) with an average age of 38 years, a median ISS of 29 (16-75), and an Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II score of 14 (0-40) were evaluated. The in-hospital mortality (>3 days) was 10%. Patients with insufficient 24-hour lactate clearance had a high rate of overall mortality and infections. Elevated early serum procalcitonin on days 1 to 5 after trauma was strongly associated with the subsequent development of sepsis (p < 0.01) but not with nonseptic infections. The kinetics of IL-6 were similar to those of PCT but did differentiate between infected and noninfected patients after day 5. CONCLUSIONS: This study demonstrates that elevated early procalcitonin and IL-6 levels and inadequate 24-hour lactate clearance help identify trauma patients who develop septic and nonseptic infectious complications. Definition of specific cutoff values and early monitoring of these parameters may help direct early surgical and antibiotic therapy and reduce infectious mortality.

The role of admission blood glucose in outcome prediction of surviving patients with multiple injuries

BACKGROUND: Recent literature demonstrates hyperglycemia to be common in patients with trauma and associated with poor outcome in patients with traumatic brain injury and critically ill patients. The goal of this study was to analyze the impact of admission blood glucose on the outcome of surviving patients with multiple injuries. METHODS: Patients' charts (age >16) admitted to the emergency room of the University Hospital of Berne, Switzerland, between January 1, 2002, and December 31, 2004, with an Injury Severity Score >or=17 and more than one severely injured organ system were reviewed retrospectively. Outcome measurements included morbidity, intensive care unit, and hospital length of stay. RESULTS: The inclusion criteria were met by 555 patients, of which 108 (19.5%) patients died. After multiple regression analysis, admission blood glucose proved to be an independent predictor of posttraumatic morbidity (p < 0.0001), intensive care unit, and hospital length of stay (p < 0.0001), despite intensified insulin therapy on the intensive care unit. CONCLUSIONS: In this population of patients with multiple injuries, hyperglycemia on admission was strongly associated with increased morbidity, especially infections, prolonged intensive care unit, and hospital length of stay independent of injury severity, gender, age, and various biochemical parameters.

Clinical and economic outcomes of serious postoperative infections following resection of common respiratory and gastrointestinal solid tumors

Unlike infections occurring during periods of chemotherapy-induced neutropenia, postoperative infections in patients with solid malignancy remain largely understudied. The purpose of this population-based study was to evaluate the clinical and economic burden, as well as the relationship of hospital surgical volume and outcomes associated with serious postoperative infection (SPI) – i.e., bacteremia/sepsis, pneumonia, and wound infection – following resection of common solid tumors.^ From the Texas Discharge Data Research File, we identified all Texas residents who underwent resection of cancer of the lung, esophagus, stomach, pancreas, colon, or rectum between 2002 and 2006. From their billing records, we identified ICD-9 codes indicating SPI and also subsequent SPI-related readmissions occurring within 30 days of surgery. Random-effects logistic regression was used to calculate the impact of SPI on mortality, as well as the association between surgical volume and SPI, adjusting for case-mix, hospital characteristics, and clustering of multiple surgical admissions within the same patient and patients within the same hospital. Excess bed days and costs were calculated by subtracting values for patients without infections from those with infections computed using multilevel mixed-effects generalized linear model by fitting a gamma distribution to the data using log link.^ Serious postoperative infection occurred following 9.4% of the 37,582 eligible tumor resections and was independently associated with an 11-fold increase in the odds of in-hospital mortality (95% Confidence Interval [95% CI], 6.7-18.5, P < 0.001). Patients with SPI required 6.3 additional hospital days (95% CI, 6.1 - 6.5) at an incremental cost of $16,396 (95% CI, $15,927–$16,875). There was a significant trend toward lower overall rates of SPI with higher surgical volume (P=0.037). ^ Due to the substantial morbidity, mortality, and excess costs associated with SPI following solid tumor resections and given that, under current reimbursement practices, most of this heavy burden is borne by acute care providers, it is imperative for hospitals to identify more effective prophylactic measures, so that these potentially preventable infections and their associated expenditures can be averted. Additional volume-outcomes research is also needed to identify infection prevention processes that can be transferred from higher- to lower-volume providers.^

Risk factors for surgical site infections among patients undergoing major colon surgery in the United States 2007-2009

Background: Surgical site infections (SSIs) after abdominal surgeries account for approximately 26% of all reported SSIs. The Center for Disease Control and Prevention (CDC) defines 3 types of SSIs: superficial incisional, deep incisional, and organ/space. Preventing SSIs has become a national focus. This dissertation assesses several associations with the individual types of SSI in patients that have undergone colon surgery. ^ Methods: Data for this dissertation was obtained from the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP); major colon surgeries were identified in the database that occurred between the time period of 2007 and 2009. NSQIP data includes more than 50 preoperative and 30 intraoperative factors; 40 collected postoperative occurrences are based on a follow-up period of 30 days from surgery. Initially, four individual logistic regressions were modeled to compare the associations between risk factors and each of the SSI groups: superficial, deep, organ/space and a composite of any single SSI. A second analysis used polytomous regression to assess simultaneously the associations between risk factors and the different types of SSIs, as well as, formally test the different effect estimates of 13 common risk factors for SSIs. The final analysis explored the association between venous thromboembolism (VTEs) and the different types of SSIs and risk factors. ^ Results: A total of 59,365 colon surgeries were included in the study. Overall, 13% of colon cases developed a single type of SSI; 8% of these were superficial SSIs, 1.4% was deep SSIs, and 3.8% were organ/space SSIs. The first article identifies the unique set of risk factors associated with each of the 4 SSI models. Distinct risk factors for superficial SSIs included factors, such as alcohol, chronic obstructive pulmonary disease, dyspnea and diabetes. Organ/space SSIs were uniquely associated with disseminated cancer, preoperative dialysis, preoperative radiation treatment, bleeding disorder and prior surgery. Risk factors that were significant in all models had different effect estimates. The second article assesses 13 common SSI risk factors simultaneously across the 3 different types of SSIs using polytomous regression. Then each risk factor was formally tested for the effect heterogeneity exhibited. If the test was significant the final model would allow for the effect estimations for that risk factor to vary across each type of SSI; if the test was not significant, the effect estimate would remain constant across the types of SSIs using the aggregate SSI value. The third article explored the relationship of venous thromboembolism (VTE) and the individual types of SSIs and risk factors. The overall incidence of VTEs after the 59,365 colon cases was 2.4%. All 3 types of SSIs and several risk factors were independently associated with the development of VTEs. ^ Conclusions: Risk factors associated with each type of SSI were different in patients that have undergone colon surgery. Each model had a unique cluster of risk factors. Several risk factors, including increased BMI, duration of surgery, wound class, and laparoscopic approach, were significant across all 4 models but no statistical inferences can be made about their different effect estimates. These results suggest that aggregating SSIs may misattribute and hide true associations with risk factors. Using polytomous regression to assess multiple risk factors with the multiple types of SSI, this study was able to identify several risk factors that had significant effect heterogeneity across the 3 types of SSI challenging the use of aggregate SSI outcomes. The third article recognizes the strong association between VTEs and the 3 types of SSIs. Clinicians understand the difference between superficial, deep and organ/space SSIs. Our results indicate that they should be considered individually in future studies.^

Anti-mosquito midgut antibodies block development of Plasmodium falciparum and Plasmodium vivax in multiple species of Anopheles mosquitoes and reduce vector fecundity and survivorship

The mosquito midgut plays a central role in the sporogonic development of malaria parasites. We have found that polyclonal sera, produced against mosquito midguts, blocked the passage of Plasmodium falciparum ookinetes across the midgut, leading to a significant reduction of infections in mosquitoes. Anti-midgut mAbs were produced that display broad-spectrum activity, blocking parasite development of both P. falciparum and Plasmodium vivax parasites in five different species of mosquitoes. In addition to their parasite transmission-blocking activity, these mAbs also reduced mosquito survivorship and fecundity. These results reveal that mosquito midgut-based antibodies have the potential to reduce malaria transmission in a synergistic manner by lowering both vector competence, through transmission-blocking effects on parasite development, and vector abundance, by decreasing mosquito survivorship and egg laying capacity. Because the intervention can block transmission of different malaria parasite species in various species of mosquitoes, vaccines against such midgut receptors may block malaria transmission worldwide.

Estimates of global and regional potential health gains from reducing multiple major risk factors

Background Estimates of the disease burden due to multiple risk factors can show the potential gain from combined preventive measures. But few such investigations have been attempted, and none on a global scale. Our aim was to estimate the potential health benefits from removal of multiple major risk factors. Methods We assessed the burden of disease and injury attributable to the joint effects of 20 selected leading risk factors in 14 epidemiological subregions of the world. We estimated population attributable fractions, defined as the proportional reduction in disease or mortality that would occur if exposure to a risk factor were reduced to an alternative level, from data for risk factor prevalence and hazard size. For every disease, we estimated joint population attributable fractions, for multiple risk factors, by age and sex, from the direct contributions of individual risk factors. To obtain the direct hazards, we reviewed publications and re-analysed cohort data to account for that part of hazard that is mediated through other risks. Results Globally, an estimated 47% of premature deaths and 39% of total disease burden in 2000 resulted from the joint effects of the risk factors considered. These risks caused a substantial proportion of important diseases, including diarrhoea (92%-94%), lower respiratory infections (55-62%), lung cancer (72%), chronic obstructive pulmonary disease (60%), ischaemic heart disease (83-89%), and stroke (70-76%). Removal of these risks would have increased global healthy life expectancy by 9.3 years (17%) ranging from 4.4 years (6%) in the developed countries of the western Pacific to 16.1 years (43%) in parts of sub-Saharan Africa. Interpretation Removal of major risk factors would not only increase healthy life expectancy in every region, but also reduce some of the differences between regions, The potential for disease prevention and health gain from tackling major known risks simultaneously would be substantial.

Genetic diversity among community methicillin-resistant Staphylococcus aureus strains causing outpatient infections in Australia

Increasing reports of the appearance of novel nonmultiresistant methicillin-resistant Staphylococcus aureus MRSA (MRSA) strains in the community and of the spread of hospital MRSA strains into the community are cause for public health concern. We conducted two national surveys of unique isolates of S. aureus from clinical specimens collected from nonhospitalized patients commencing in 2000 and 2002, respectively. A total of 11.7% of 2,498 isolates from 2000 and 15.4% of 2,486 isolates from 2002 were MRSA. Approximately 54% of the MRSA isolates were nonmultiresistant (resistant to less than three of nine antibiotics) in both surveys. The majority of multiresistant MRSA isolates in both surveys belonged to two strains (strains AUS-2 and AUS-3), as determined by pulsed-field gel electrophoresis (PFGE) and resistogram typing. The 3 AUS-2 isolates and 10 of the 11 AUS-3 isolates selected for multilocus sequence typing (MLST) and staphylococcal chromosomal cassette mec (SCCmec) analysis were ST239-MRSA-III (where ST is the sequence type) and thus belonged to the same clone as the eastern Australian MRSA strain of the 1980s, which spread internationally. Four predominant clones of novel nonmultiresistant MRSA were identified by PFGE, MLST, and SCCmec analysis: ST22-MRSA-IV (strain EMRSA-15), ST1-MRSA-IV (strain WA-1), ST30-MRSA-IV (strain SWP), and ST93-MRSA-IV (strain Queensland). The last three clones are associated with community acquisition. A total of 14 STs were identified in the surveys, including six unique clones of novel nonmultiresistant MRSA, namely, STs 73, 93, 129, 75, and 80sIv and a new ST. SCCmec types IV and V were present in diverse genetic backgrounds. These findings provide support for the acquisition of SCCmec by multiple lineages of S. aureus. They also confirm that both hospital and community strains of MRSA are now common in nonhospitalized patients throughout Australia.

Mathematical modelling of patient risks in a hospital environment, using multiple regression analysis

The aim of this research work was primarily to examine the relevance of patient parameters, ward structures, procedures and practices, in respect of the potential hazards of wound cross-infection and nasal colonisation with multiple resistant strains of Staphylococcus aureus, which it is thought might provide a useful indication of a patient's general susceptibility to wound infection. Information from a large cross-sectional survey involving 12,000 patients from some 41 hospitals and 375 wards was collected over a five-year period from 1967-72, and its validity checked before any subsequent analysis was carried out. Many environmental factors and procedures which had previously been thought (but never conclusively proved) to have an influence on wound infection or nasal colonisation rates, were assessed, and subsequently dismissed as not being significant, provided that the standard of the current range of practices and procedures is maintained and not allowed to deteriorate. Retrospective analysis revealed that the probability of wound infection was influenced by the patient's age, duration of pre-operative hospitalisation, sex, type of wound, presence and type of drain, number of patients in ward, and other special risk factors, whilst nasal colonisation was found to be influenced by the patient's age, total duration of hospitalisation, sex, antibiotics, proportion of occupied beds in the ward, average distance between bed centres and special risk factors. A multi-variate regression analysis technique was used to develop statistical models, consisting of variable patient and environmental factors which were found to have a significant influence on the risks pertaining to wound infection and nasal colonisation. A relationship between wound infection and nasal colonisation was then established and this led to the development of a more advanced model for predicting wound infections, taking advantage of the additional knowledge of the patient's state of nasal colonisation prior to operation.

Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma.

The ability to rearrange the germ-line DNA to generate antibody diversity is an essential prerequisite for the production of a functional repertoire. While this is essential to prevent infections, it also represents the "Achilles heel" of the B-cell lineage, occasionally leading to malignant transformation of these cells by translocation of protooncogenes into the immunoglobulin (Ig) loci. However, in evolutionary terms this is a small price to pay for a functional immune system. The study of the configuration and rearrangements of the Ig gene loci has contributed extensively to our understanding of the natural history of development of myeloma. In addition to this, the analysis of Ig gene rearrangements in B-cell neoplasms provides information about the clonal origin of the disease, prognosis, as well as providing a clinical useful tool for clonality detection and minimal residual disease monitoring. Herein, we review the data currently available on both Ig gene rearrangements and protein patterns seen in myeloma with the aim of illustrating how this knowledge has contributed to our understanding of the pathobiology of myeloma.

Neutrophil Chemotaxis in Multiple Chemoattractant Gradients

Chemotaxis, the phenomenon in which cells move in response to extracellular chemical gradients, plays a prominent role in the mammalian immune response. During this process, a number of chemical signals, called chemoattractants, are produced at or proximal to sites of infection and diffuse into the surrounding tissue. Immune cells sense these chemoattractants and move in the direction where their concentration is greatest, thereby locating the source of attractants and their associated targets. Leading the assault against new infections is a specialized class of leukocytes (white blood cells) known as neutrophils, which normally circulate in the bloodstream. Upon activation, these cells emigrate out of the vasculature and navigate through interstitial tissues toward target sites. There they phagocytose bacteria and release a number of proteases and reactive oxygen intermediates with antimicrobial activity. Neutrophils recruited by infected tissue in vivo are likely confronted by complex chemical environments consisting of a number of different chemoattractant species. These signals may include end target chemicals produced in the vicinity of the infectious agents, and endogenous chemicals released by local host tissues during the inflammatory response. To successfully locate their pathogenic targets within these chemically diverse and heterogeneous settings, activated neutrophils must be capable of distinguishing between the different signals and employing some sort of logic to prioritize among them. This ability to simultaneously process and interpret mulitple signals is thought to be essential for efficient navigation of the cells to target areas. In particular, aberrant cell signaling and defects in this functionality are known to contribute to medical conditions such as chronic inflammation, asthma and rheumatoid arthritis. To elucidate the biomolecular mechanisms underlying the neutrophil response to different chemoattractants, a number of efforts have been made toward understanding how cells respond to different combinations of chemicals. Most notably, recent investigations have shown that in the presence of both end target and endogenous chemoattractant variants, the cells migrate preferentially toward the former type, even in very low relative concentrations of the latter. Interestingly, however, when the cells are exposed to two different endogenous chemical species, they exhibit a combinatorial response in which distant sources are favored over proximal sources. Some additional results also suggest that cells located between two endogenous chemoattractant sources will respond to the vectorial sum of the combined gradients. In the long run, this peculiar behavior could result in oscillatory cell trajectories between the two sources. To further explore the significance of these and other observations, particularly in the context of physiological conditions, we introduce in this work a simplified phenomenological model of neutrophil chemotaxis. In particular, this model incorporates a trait commonly known as directional persistence - the tendency for migrating neutrophils to continue moving in the same direction (much like momentum) - while also accounting for the dose-response characteristics of cells to different chemical species. Simulations based on this model suggest that the efficiency of cell migration in complex chemical environments depends significantly on the degree of directional persistence. In particular, with appropriate values for this parameter, cells can improve their odds of locating end targets by drifting through a network of attractant sources in a loosely-guided fashion. This corroborates the prediction that neutrophils randomly migrate from one chemoattractant source to the next while searching for their end targets. These cells may thus use persistence as a general mechanism to avoid being trapped near sources of endogenous chemoattractants - the mathematical analogue of local maxima in a global optimization problem. Moreover, this general foraging strategy may apply to other biological processes involving multiple signals and long-range navigation.