The effects of temephos, permethrin and malathion selection on the fitness and fecundity of Aedes aegypti.

The recent scale-up of insecticide use has led to the rapid spread of insecticide resistance (IR) in mosquito populations across the world. Previous work has suggested that IR mechanisms could influence mosquito life-history traits, leading to alterations in fitness and key physiological functions. This study investigates to what extent mosquito fitness may be affected in a colony of Aedes aegypti after selection with temephos, permethrin or malathion insecticides. We measured immature development, sex ratio, adult longevity, energetic reserves under different rearing conditions and time points, ingested bloodmeal volume, mosquito size, male and female reproductive fitness and flight capability in the unexposed offspring of the three selected strains and unselected strain. We found that insecticide selection does have an impact on mosquito fitness traits in both male and female mosquitoes, with our temephos-exposed strain showing the highest immature development rates, improved adult survival, larger females under crowded rearing and increased sperm number in males. In contrast, this strain showed the poorest reproductive success, demonstrating that insecticide selection leads to trade-offs in life-history traits, which have the potential to either enhance or limit disease transmission potential.

Consensus statement on measures to promote equitable authorship in the publication of research from international partnerships.

Despite the acknowledged injustice and widespread existence of parachute research studies conducted in low- or middle-income countries by researchers from institutions in high-income countries, there is currently no pragmatic guidance for how academic journals should evaluate manuscript submissions and challenge this practice. We assembled a multidisciplinary group of editors and researchers with expertise in international health research to develop this consensus statement. We reviewed relevant existing literature and held three workshops to present research data and holistically discuss the concept of equitable authorship and the role of academic journals in the context of international health research partnerships. We subsequently developed statements to guide prospective authors and journal editors as to how they should address this issue. We recommend that for manuscripts that report research conducted in low- or middle-income countries by collaborations including partners from one or more high-income countries, authors should submit accompanying structured reflexivity statements. We provide specific questions that these statements should address and suggest that journals should transparently publish reflexivity statements with accepted manuscripts. We also provide guidance to journal editors about how they should assess the structured statements when making decisions on whether to accept or reject submitted manuscripts. We urge journals across disciplines to adopt these recommendations to accelerate the changes needed to halt the practice of parachute research.

Modelling the Impact of Vector Control on Lymphatic Filariasis Programs: Current Approaches and Limitations.

Vector control is widely considered an important tool for lymphatic filariasis (LF) elimination but is not usually included in program budgets and has often been secondary to other policy questions in modelling studies. Evidence from the field demonstrates that vector control can have a large impact on program outcomes and even halt transmission entirely, but implementation is expensive. Models of LF have the potential to inform where and when resources should be focused, but often simplify vector dynamics and focus on capturing human prevalence trends, making them comparatively ill-designed for direct analysis of vector control measures. We review the recent modelling literature and present additional results using a well-established model, highlighting areas of agreement between model predictions and field evidence, and discussing the possible determinants of existing disagreements. We conclude that there are likely to be long-term benefits of vector control, both on accelerating programs and preventing resurgence.

Modelling strategies to break transmission of lymphatic filariasis--aggregation, adherence and vector competence greatly alter elimination.

BACKGROUND: With ambitious targets to eliminate lymphatic filariasis over the coming years, there is a need to identify optimal strategies to achieve them in areas with different baseline prevalence and stages of control. Modelling can assist in identifying what data should be collected and what strategies are best for which scenarios. METHODS: We develop a new individual-based, stochastic mathematical model of the transmission of lymphatic filariasis. We validate the model by fitting to a first time point and predicting future timepoints from surveillance data in Kenya and Sri Lanka, which have different vectors and different stages of the control programme. We then simulate different treatment scenarios in low, medium and high transmission settings, comparing once yearly mass drug administration (MDA) with more frequent MDA and higher coverage. We investigate the potential impact that vector control, systematic non-compliance and different levels of aggregation have on the dynamics of transmission and control. RESULTS: In all settings, increasing coverage from 65 to 80 % has a similar impact on control to treating twice a year at 65 % coverage, for fewer drug treatments being distributed. Vector control has a large impact, even at moderate levels. The extent of aggregation of parasite loads amongst a small portion of the population, which has been estimated to be highly variable in different settings, can undermine the success of a programme, particularly if high risk sub-communities are not accessing interventions. CONCLUSION: Even moderate levels of vector control have a large impact both on the reduction in prevalence and the maintenance of gains made during MDA, even when parasite loads are highly aggregated, and use of vector control is at moderate levels. For the same prevalence, differences in aggregation and adherence can result in very different dynamics. The novel analysis of a small amount of surveillance data and resulting simulations highlight the need for more individual level data to be analysed to effectively tailor programmes in the drive for elimination.

Evidence for subdivision within the M molecular form of Anopheles gambiae.

The principal vector of malaria in sub-Saharan Africa, Anopheles gambiae is subdivided into two molecular forms M and S. Additionally, several chromosomal forms, characterized by the presence of various inversion polymorphisms, have been described. The molecular forms M and S each contain several chromosomal forms, including the Savanna, Mopti and Forest forms. The M and S molecular forms are now considered to be the reproductive units within A. gambiae and it has recently been argued that a low recombination rate in the centromeric region of the X chromosome has facilitated isolation between these forms. The status of the chromosomal forms remains unclear however. Therefore, we studied genetic differentiation between Savanna S, Forest S, Forest M and Mopti M populations using microsatellites. Genetic differentiation between Savanna S and Forest S populations is very low (F(ST) = 0.0053 +/- 0.0049), even across large distances. In comparison, the Mopti M and Forest M populations show a relatively high degree of genetic differentiation (F(ST) = 0.0406 +/- 0.0054) indicating that the M molecular form may not be a single entity, but could be subdivided into at least two distinct chromosomal forms. Previously it was proposed that inversions have played a role in the origin of species within the A. gambiae complex. We argue that a possible subdivision within the M molecular form could be understood through this process, with the acquisition of inversions leading to the expansion of the M molecular form into new habitat, dividing it into two distinct chromosomal forms.

An unusual distribution of the kdr gene among populations of Anopheles gambiae on the island of Bioko, Equatorial Guinea.

In West Africa, Anopheles gambiae exists in discrete subpopulations known as the M and S molecular forms. Although these forms occur in sympatry, pyrethroid knock-down resistance (kdr) is strongly associated with the S molecular form. On the island of Bioko, Equatorial Guinea we found high frequencies of the kdr mutation in M form individuals (55.8%) and a complete absence of kdr in the S form. We also report the absence of the kdr allele in M and S specimens from the harbour town of Tiko in Cameroon, representing the nearest continental population to Bioko. The kdr allele had previously been reported as absent in populations of An. gambiae on Bioko. Contrary to earlier reports, sequencing of intron-1 of this sodium channel gene revealed no fixed differences between M form resistant and susceptible individuals. The mutation may have recently arisen independently in the M form on Bioko due to recent and intensive pyrethroid application.

Parasitism at the ecosystem level in the Baltic Sea.

The Baltic Sea is characterized by organisms that can tolerate brackish water. Because of the Sea's history during glacial times, its flora and fauna (and also their parasites) can be traced to marine, freshwater and genuine brackish elements beside glacial relics. Snails, planktonic copepods, benthic amphipods and isopods are important intermediate hosts of diverse helminths; in addition polychaetes, bivalves and fishes may also act as final hosts. The most important final hosts, beside fishes, were seals and birds; these were able to disperse the parasites over the whole of the Baltic. Decreasing salinity from west to east limits the distribution of many parasites. Several marine and genuine brackish water species have almost spread over the whole Baltic. Freshwater species, however, have a lower tolerance than marine species and are only rarely found in the western part. A serious problem in the Baltic is eutrophication which can lead to massive abundances of generalist parasites, in host populations as well as host individuals. The final stage of this influence can cause a general decrease of host abundance and, as a consequence, of all kinds of parasites, due to oxygen deficiency. In comparison with the species spectrum of other brackish waters in Europe, the Baltic presents some endemic parasites as well as sharing parasite species with the Mediterranean and even the Black Sea.

Relevance of the number of positive bottles in determining clinical significance of coagulase-negative staphylococci in blood cultures.

Coagulase-negative staphylococci (CNS) are the most commonly isolated contaminants from blood cultures, yet they frequently cause true infections. Determining the clinical significance of CNS is difficult, and clinicians often consider the number of positive bottles within a set of blood culture bottles in their assessment. Therefore, in three separate studies, we counted the number of positive bottles within blood culture sets comprising two, three, or four bottles in order to predict whether or not CNS were clinically significant isolates (CSI) in adult patients with suspected sepsis. Each culture was evaluated by independent, published clinical criteria to determine its clinical importance. Of 486 positive sets that included two adequately filled bottles, 127 (26%) CNS were CSI, 329 (67%) were contaminants, and 30 (6%) were indeterminate as a cause of sepsis. Among CSI, 39 and 61% were isolated from one and two bottles, respectively. The positive predictive value for sepsis was 18% when one bottle was positive and 37% when both bottles were positive. Of 235 positive sets that included three adequately filled bottles, 81 (34%) were CSI, 109 (46%) were contaminants, and 45 (19%) were indeterminate as a cause of sepsis. Of CSI, 43, 38, and 19% were found in one, two, and three bottles, respectively. The positive predictive value for sepsis was 28, 52, and 30% when one, two and three bottles were positive. Of 303 positive blood culture sets that included four adequately filled bottles, 64 (21%) were considered CSI, 197 (65%) were contaminants, and 42 (14%) were indeterminate as a cause of sepsis. Of CSI, 27, 28, 19, and 27% were found in one, two, three, and four bottles, respectively. The positive predictive value for sepsis was 11, 30, 34, and 37% when one, two, three, and four bottles were positive. We conclude that the number of culture bottles positive in a given culture set cannot reliably predict the clinical significance of the CNS isolated and, therefore, should not be used as a criterion for determining whether or not an isolate represents true infection or contamination.

Human immunodeficiency virus type 1 drug resistance testing: a comparison of three sequence-based methods.

The use of genotypic assays for determining drug resistance in human immunodeficiency virus (HIV) type 1 (HIV-1)-infected patients is increasing. These tests lack standardization and validation. The aim of this study was to evaluate several tests used for the determination of HIV-1 drug resistance. Two genotypic tests, the Visible Genetics TruGene HIV-1 Genotyping Kit and the Applied Biosystems HIV Genotyping System, were compared using 22 clinical samples. Genotyping results were also obtained from an independent reference laboratory. The Visible Genetics and Applied Biosystems genotyping tests identified similar mutations when differences in the drug databases and reference strains were taken into account, and 19 of 21 samples were equivalent. The concordance between the two assays was 99% (249 of 252 mutation sites). Mutations identified by the reference laboratory varied the most among those identified by the three genotypic tests, possibly because of differences in the databases. The concordance of the reference laboratory results with the results of the other two assays was 80% (201 of 252). Samples with 500 to 750 HIV RNA copies/ml could be sequenced by the Visible Genetics and Applied Biosystems assays using 1 ml of input. The Visible Genetics and Applied Biosystems assays both generated an accurate sequence. However, the throughput of the Visible Genetics assay is more limited and may require additional instruments. The two assays differ technically but are similar in overall complexity. Data analysis in the two assays is straightforward, but only the reports provided by Visible Genetics contain information relating mutations to drug resistance. HIV drug resistance genotyping by sequencing is a complex technology which presents a challenge for analysis, interpretation, and reporting.

Controlled comparison of BacT/ALERT FAN aerobic medium and BATEC fungal blood culture medium for detection of fungemia.

Yeasts are an increasingly common cause of nosocomial bloodstream infections. Methods for their detection are many; controlled comparisons are few. The vented FAN aerobic blood culture medium has been shown to be superior to the standard BacT/ALERT aerobic medium for the detection of fungemia as well as bacteremia. The BACTEC selective fungal medium (FM) (BD Biosciences, Sparks, Md.) allowed detection of more episodes of fungemia than did a resin-containing medium with equal volumes of blood cultured. Therefore, we compared vented FAN to FM for the ability to recover fungi from the blood of patients who were at increased risk of having fungemia. From 5,109 cultures processed for which both FAN and FM bottles were adequately filled, fungi were recovered from 87 cultures. Of these, 47 were detected with both bottles, 12 were detected with FAN only, and 28 were detected with FM only (P < 0.05). FAN was the first bottle positive for 36 of the 47 cultures for which both bottles yielded the same fungus, whereas the FM bottle was the first bottle positive for 11 cultures (P < 0.001). A total of 54 episodes of fungemia were identified, with 40 detected by both media, 4 detected only by FAN, and 10 detected only by FM (P value, not significant). We conclude that the vented FAN aerobic bottle is comparable to the FM bottle for detection of episodes of yeast infection but has the added benefit of detecting bacteria.

Unusual presentation of thoracic Pneumocystis carinii infection in a patient with acquired immunodeficiency syndrome.

Pleura-based masses and hilar adenopathy were seen on a chest radiograph of a patient with acquired immunodeficiency syndrome who had a history of Pneumocystis carinii infection. The differential diagnosis of such a presentation is discussed in light of atypical and extrapulmonary manifestations of P. carinii infection in a patient receiving prophylaxis with dapsone.

Effect of indomethacin on peritoneal protein loss in a rabbit model of peritonitis.

BACKGROUND: Although various inflammatory mediators have been previously shown to be released into the peritoneal cavity during peritonitis in peritoneal dialysis patients, those that are involved in governing changes in peritoneal permeability to small solutes and protein remain incompletely defined. METHODS: We determined the importance of prostanoid production in the enhanced protein loss observed during acute peritonitis by inhibition experiments using indomethacin, an inhibitor of cyclooxygenase activity. The association between changes in peritoneal permeability and the generation of inflammatory mediators after adding Escherichia coli to peritoneal dialysate was first examined in series 1 experiments. Series 2 experiments then determined the effect of intraperitoneal administration of indomethacin (75 microg/mL) on changes in peritoneal permeability after adding E. coli to peritoneal dialysate. All experiments were performed in male New Zealand White rabbits (2.6 to 3.4 kg body weight) using an eight-hour dwell of dialysate containing 2.5% glucose. Peritoneal permeability to creatinine and protein was assessed by time-dependent changes in the dialysate to plasma concentration ratios of these solutes. RESULTS: Series 1 experiments showed enhanced leukocyte migration into the peritoneal cavity and increased peritoneal permeability to protein during bacterial challenge that was accompanied by an increase in the dialysate concentrations of prostaglandin E2 (PGE2), 6-keto-PGF1alpha, and interleukin-8, but not nitrate + nitrite (a measure of local nitric oxide production). Inhibition of prostanoid production by intraperitoneal administration of indomethacin in series 2 experiments resulted in lower dialysate concentrations of PGE2 and 6-keto-PGF1alpha and in lower peritoneal permeability to protein, both to control levels. No effect of indomethacin on transperitoneal migration of leukocytes or the generation of interleukin-8 was observed. CONCLUSIONS: Enhanced production of prostanoids likely plays an important role in governing the increase in peritoneal permeability to protein during acute, bacterial peritonitis in the rabbit.

Comparison of iodophor and alcohol pledgets with the Medi-Flex blood culture prep kit II for preventing contamination of blood cultures.

Iodophor and alcohol pledgets were compared with the Medi-Flex Prep Kit II for skin disinfection before venipuncture. Of 12,367 blood cultures collected, 6,362 were done with conventional pledgets and 6, 005 were done with Medi-Flex kits. Contamination occurred in 351 of 6,362 blood cultures (5.5%; range, 3.7 to 8.1%) with conventional pledgets versus 328 of 6,005 (5.5%; range, 3.5 to 7.5%) with Medi-Flex kits.

Community-acquired bacterial pneumonias.

Community-acquired bacterial pneumonias are among the most common of infectious diseases. The diagnosis of the etiological agent is becoming more challenging and more critical as new organisms are recognized as pathogens, and as well established agents become increasingly resistant to antimicrobial agents. The value of clinical microbiology laboratory data in the management of pneumonia is controversial. A well recognized, published guideline suggests that no laboratory studies be performed. Yet common practice and a more recent guideline advocate routine collection of sputum for Gram's stain and culture, along with traditional blood work. Given the increasing need to distinguish among a long list of possible pathogens and the need to recognize antibiotic resistance, it seems most prudent to include microbiological studies. This information can be used to guide initial therapy, and perhaps limit the overutilization of broad-spectrum antimicrobials. However, a prerequisite for the use of all cunently available test methods is their deployment in patients for whom there is clinical and radiographic evidence of pneumonia because recovery of a microorganism, especially from sputum, will occur with or without this clinical condition.

Parasite communities of the Salzhaff (Northwest Mecklenburg, Baltic Sea) II. Guild communities, with special regard to snails, benthic crustaceans, and small-sized fish.

Metazoan parasites of guilds of benthic snails and crustaceans and of four fish families--Gobiidae, Gasterosteidae, Syngnathidae, and Zoarcidae--were investigated off the brackish Salzhaff area (Southwest Baltic) in the semienclosed Salzhaff and the near Rerik Riff in the free Baltic. Comparisons revealed greater similarities in parasite populations and communities within the fish guilds than between them. According to an evaluation of the core-/satellite-species concept using abundance values, the most important parasites of fish were some generalists, such as Cryptocotyle spp., Podocotyle atomon, and Diplostomum spathaceum, as well as some specialists, such as Acanthostomum balthicum, Thersitina gasterostei, and Aphalloides timmi. These specialists revealed high degrees of prevalence in their main hosts and lower degrees in one or two by-hosts. Additional importance is assigned to parasites that cause harm to their hosts due to their large size, e.g., Schistocephalus spp., or via massive infestation, e.g., several digenean metacercariae. Because specialists were more prominent in snails and fish from the Rerik Riff, the correlation of host numbers with prevalence resulted in only a slight increase instead of a more rapid rise in regression among crustaceans and fish from the entire Salzhaff, where the generalists were more prevalent. The selected host guilds demonstrated the entire life cycles of three digeneans (P. atomon, A. balthicum, A. timmi), one acanthocephalan (Echinorhynchus gadi), and one nematode (Hysterothylacium sp.). The prevalence increased in these cycles from host level to host level and attained relatively high values in all guilds. The parasite fauna of the Salzhaff area is influenced by eutrophication stress, which leads to a high level of productivity and, consequently, to great densities in primary consumers such as snails and crustaceans. These are attractive for several secondary consumers such as fish and birds, which is the reason for the existence of at least 24 autogenic and 20 allogenic parasite species at this locality. The slight surplus of the first category indicates a yet-balanced environment in the investigation area.

Increased protein loss during peritonitis associated with peritoneal dialysis is neutrophil dependent.

BACKGROUND: Peritonitis in peritoneal dialysis patients is accompanied by an enhanced migration of neutrophils (PMNs) and increased protein loss into the peritoneal cavity; however, the role of PMNs in governing increased protein loss during peritonitis associated with peritoneal dialysis is unknown. METHODS: We determined the importance of PMNs in governing changes in peritoneal permeability to protein in New Zealand White rabbits in which acute peritonitis was induced by adding 4 x 106 colony-forming units of Escherichia coli to 35 mL/kg of 0.9% saline dialysate. The total leukocyte and PMN migration into the peritoneal cavity was assessed by differential cell counts in the dialysate, and peritoneal permeability to protein was evaluated by calculating the dialysate to plasma concentration ratio for total protein as a function of time during a six- or eight-hour dwell. In series 1 experiments, leukocytes were depleted from the rabbit circulation by an intravenous injection of mustine (1.2 mg/kg) three days before the experiment; in series 2 experiments, integrin-dependent PMN migration into the peritoneal cavity was inhibited by an intravenous injection of monoclonal antibody (mAb) 60.3 (2 mg/kg) directed against the integrin CD18 on leukocytes five minutes before the experiment. RESULTS: In series 1 experiments, mustine decreased circulating leukocytes by 82 +/- 5% (mean +/- SEM) and circulating PMNs by 93 +/- 3%. Total leukocyte and PMN migration into the peritoneal cavity and peritoneal permeability to protein were decreased in mustine-treated rabbits after exposure to E. coli in the dialysate to levels similar to those found in rabbits without bacterial peritonitis. In series 2 experiments, an intravenous injection of anti-CD18 antibody also abrogated both the enhanced PMN migration into the peritoneal cavity and the increased peritoneal permeability to protein after exposure to E. coli in the dialysate. CONCLUSIONS: PMN migration into the peritoneal cavity is integrin dependent. Increased protein loss during acute, gram-negative bacterial peritonitis in a rabbit model of peritoneal dialysis is PMN dependent.

Infectious diarrhea: pathogens and treatment.

Infectious diarrhea is the most common infectious disease syndrome worldwide resulting in more than five million deaths annually. The greatest morbidity and mortality is seen among children younger than two years of age. A variety of bacterial, viral and parasitic pathogens are responsible for the various syndromes. A combination of host susceptibility and organism virulence factors is responsible for disease. Most episodes of gastroenteritis are self-limited. The hallmark of patient management is strict attention to fluid and electrolyte disturbances. Antimotility agents should be used with caution if at all in children, but may be helpful in adults with travelers' diarrhea. Antimicrobial therapy may shorten the duration of diarrhea in some illnesses, but use is restricted due to emergence of resistance or due to lack of availability in some countries. Newer strategies for prevention include vaccine development.

Modeling empiric antibiotic therapy evaluation of QID.

At AMIA 1997, we reported on the design and development of a new computer-based tool, called QID, for empiric antibiotic decision support. QID was designed to help physicians identify the antibiotic regimens with the highest probability of covering the pathogens that are most likely to be present in individual patients. QID creates a list of antibiotics, ordered by potential benefit in treatment, for a patient with a suspected infection before culture results are available. Since our initial publication, a "before and after" study has been done using 20 internal medicine residents and the same number of internal medicine attendings. In order to test the hypothesis that physician's would make more appropriate empiric antibiotic choices with the aid of QID, we chose University of Utah physicians and had each evaluate four infectious disease cases that were abstracted from medical record infectious disease cases. Immediately following their initial review and determination of antibiotic therapy for each case, the study participants were presented with QID's antibiotic recommendations on the same case to see if this information would change their initial drug regimen. The tool was shown to have a greater impact on the most difficult cases but statistically improved scores overall (p < .001). Details of our study design and results are presented.

Acute infection with Sin Nombre hantavirus without pulmonary edema.

Acute infection with Sin Nombre virus has been associated with development of hantavirus cardiopulmonary syndrome (HCPS), a severe cardiopulmonary illness with respiratory failure and shock. We present two cases of Sin Nombre hantavirus infections that did not lead to marked pulmonary complications in two otherwise healthy young adults from Utah and California. Sin Nombre virus causes a wider spectrum of disease severity than has been previously reported.