Point-of-care testing performed by healthcare professionals outside the hospital setting: consensus based recommendations from the IFCC Committee on Point-of-Care Testing (IFCC C-POCT).

The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Point-of-Care Testing (C-POCT) supports the use of point-of-care testing (POCT) outside of the hospital setting performed by healthcare professionals without formal laboratory education because of its numerous benefits. However, these benefits are associated with risks that must be managed, to ensure the provision of reliable test results and minimize harm to the patient. Healthcare professionals, local regulatory bodies, accredited laboratories as well as manufacturers should actively be engaged in education, oversight and advice to ensure that the healthcare professional selects the appropriate equipment and is able to analyze, troubleshoot and correctly interpret the point-of-care (POC) test results.

Continuous glucose monitoring in a healthy population: understanding the post-prandial glycemic response in individuals without diabetes mellitus.

Continuous glucose monitoring has become a common adjunct in the management of Diabetes Mellitus. However, there has been a recent trend among individuals without diabetes using these devices as a means of monitoring their health. The increased visibility of glucose data has allowed users to study the effect lifestyle has upon post-prandial glucose levels. Although post-prandial hyperglycemia is well understood in the setting of diabetes, its impact in individuals without diabetes is less well defined. This article reviews the factors which contribute to post-prandial hyperglycemia in individuals without diabetes and how the data obtained from continuous glucose monitoring can be used to improve an individual's metabolic health.

Density-dependent impact of the human malaria parasite Plasmodium falciparum gametocyte sex ratio on mosquito infection rates.

Malaria parasites produce male and female life cycle stages (gametocytes) that must fertilize to achieve successful colonization of the mosquito. Gametocyte sex ratios have been shown to be under strong selection pressure both as an adaptive response to a worsening blood environment for transmission and according to the number of co-infecting clones in the vertebrate. Evidence for an impact of sex ratio on the transmission success of Plasmodium falciparum has, however, been more controversial. Theoretical models of fertilization predict that increasingly male sex ratios will be favoured at low gametocyte densities to ensure fertilization. Here, we analyse in vitro transmission studies of P. falciparum to Anopheles gambiae mosquitoes and test this prediction. We find that there is a discernible effect of sex ratio on transmission but which is dependent upon the gametocyte density. While increasingly male sex ratios do give higher transmission success at low gametocyte densities, they reduce success at higher densities. This therefore provides empirical confirmation that sex ratio has an immediate impact on transmission success and that it is density-dependent. Identifying the signals used by the parasite to alter its sex ratio is essential to determine the success of transmission-blocking vaccines that aim to impede the fertilization process.

Sex determination in malaria parasites.

A century ago, W. G. MacCallum identified distinct male and female forms in malaria parasites of both birds and humans. Since then, scientists have been puzzled by the high female-to-male ratios of parasites in Plasmodium infections and by the mechanism of sex determination. The sex ratio of malaria parasites was shown to become progressively more male as conditions that allow motility and subsequent fertilization by the male parasites become adverse. This resulted from an increased immune response against male gametes, which coincides with intense host erythropoietic activity. Natural and artificial induction of erythropoiesis in vertebrate hosts provoked a shift toward male parasite production. This change in parasite sex ratio led to reduced reproductive success in the parasite, which suggests that sex determination is adaptive and is regulated by the hematologic state of the host.

Mating patterns in malaria parasite populations of Papua New Guinea.

Description of the genetic structure of malaria parasite populations is central to an understanding of the spread of multiple-locus drug and vaccine resistance. The Plasmodium falciparum mating patterns from madang, Papua New Guinea, where intense transmission of malaria occurs, are described here. A high degree of inbreeding occurs in the absence of detectable linkage disequilibrium. This contrasts with other studies, indicating that the genetic structure of malaria parasite populations is neither clonal nor panmictic but will vary according to the transmission characteristics of the region.

Aggregation in malaria parasites places limits on mosquito infection rates.

Gametocytes are responsible for the transmission of malaria parasites, Plasmodium spp., from man to mosquito. Although transmission success, as measured by the proportion of mosquitoes infected, generally increases with gametocyte density, the proportion of parasites that are gametocytes is always paradoxically only a few percent of the asexual blood parasites. To address this paradox, we analyse transmission data sets from an urban and an adjacent rural setting in Cameroon to elucidate whether there are discernable lower and upper limits to Plasmodium falciparum gametocyte density that are linked to transmission success. We find that there exists a lower gametocyte density at which mosquito infection rates considerably increase. In addition, we identify upper gametocyte densities at which mosquito infection rates level off. Greatest increases in infection rates occur at low gametocyte densities and coincide with maximum oocyst aggregation within the infected mosquito population. This aggregated oocyst distribution remains despite increases in gametocyte density and ever-decreasing gains in mosquito infection rates. There is increasing suggestion that malaria parasites have evolved sex allocation strategies to ensure transmission in response to a changing, transmission-blocking environment. Here transmission-blocking immunity is proposed not only to ensure low density gametocyte transmission success but also to impose upper limits on transmission success.

Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections.

BACKGROUND: Evolutionary theory suggests that the selection pressure on parasites to maximize their transmission determines their optimal host exploitation strategies and thus their virulence. Establishing the adaptive basis to parasite life history traits has important consequences for predicting parasite responses to public health interventions. In this study we examine the extent to which malaria parasites conform to the predicted adaptive trade-off between transmission and virulence, as defined by mortality. The majority of natural infections, however, result in sub-lethal virulent effects (e.g. anaemia) and are often composed of many strains. Both sub-lethal effects and pathogen population structure have been theoretically shown to have important consequences for virulence evolution. Thus, we additionally examine the relationship between anaemia and transmission in single and mixed clone infections. RESULTS: Whereas there was a trade-off between transmission success and virulence as defined by host mortality, contradictory clone-specific patterns occurred when defining virulence by anaemia. A negative relationship between anaemia and transmission success was found for one of the parasite clones, whereas there was no relationship for the other. Notably the two parasite clones also differed in a transmission phenotype (gametocyte sex ratio) that has previously been shown to respond adaptively to a changing blood environment. In addition, as predicted by evolutionary theory, mixed infections resulted in increased anaemia. The increased anaemia was, however, not correlated with any discernable parasite trait (e.g. parasite density) or with increased transmission. CONCLUSIONS: We found some evidence supporting the hypothesis that there is an adaptive basis correlating virulence (as defined by host mortality) and transmission success in malaria parasites. This confirms the validity of applying evolutionary virulence theory to biomedical research and adds support to the prediction that partially effective vaccines may select for increasingly virulent malaria parasite strains. By contrast, there was no consistent correlation between transmission and sub-lethal anaemia, a more common outcome of malaria infection. However, overall, the data are not inconsistent with the recent proposal that sub-lethal effects may impose an upper limit on virulence. Moreover, clone specific differences in transmission phenotypes linked to anaemia do suggest that there is considerable adaptive potential relating anaemia and transmission that may lead to uncertain consequences following intervention strategies.

Transmission intensity and Plasmodium falciparum diversity on the northwestern border of Thailand.

Genetic analysis of the number of Plasmodium falciparum genotypes per infected person in regions of holoendemic and hyperendemic malaria suggest that in areas of lower transmission intensity, significantly fewer parasite genotypes per infected person should be found. A predominance of single clone infections in the human population could generate the controversial clonal population structure proposed for P. falciparum by Tibayrenc and others. Characterization of P. falciparum from individuals on the Thai-Burmese border, an area of hypoendemic transmission, revealed a higher number of genotypes per infected person than that predicted. Possible reasons for this observation are discussed, with particular attention paid to human migration and multidrug resistance.

Application of genetic markers to the identification of recrudescent Plasmodium falciparum infections on the northwestern border of Thailand.

Parasite genotyping by the polymerase chain reaction was used to distinguish recrudescent from newly acquired Plasmodium falciparum infections in a Karen population resident on the northwestern border of Thailand where malaria transmission is low (one infection/person/year). Plasmodium falciparum infections were genotyped for allelic variation in three polymorphic antigen loci, merozoite surface proteins-1 and -2 (MSP-1 and -2) and glutamaterich protein (GLURP), before and after antimalarial drug treatment. Population genotype frequencies were measured to provide the baseline information to calculate the probability of a new infection with a different or the same genotype to the initial pretreatment isolate. Overall, 38% of the infections detected following treatment had an identical genotype before and up to 121 days after treatment. These post-treatment genotypes were considered recrudescent because of the low (< 5%) probability of repeated occurrence by chance in the same patient. This approach allows studies of antimalarial drug treatment to be conducted in areas of low transmission since recrudescences can be distinguished confidently from newly acquired infections.

Estimation of malaria transmission from humans to mosquitoes in two neighbouring villages in south Cameroon: evaluation and comparison of several indices.

Malaria transmission from humans to mosquitoes was assessed in two neighbouring villages in a rural area near Yaoundé, Cameroon during high and low transmission seasons during 1998-2000, using several indices previously evaluated in different areas endemic for malaria but never directly compared. These indices were estimated from human parasitological data and mosquito infection rates and, for each individual, thick blood films were prepared at the same time as experimental infection of laboratory-bred mosquitoes. Among the 685 volunteers examined, the prevalence of Plasmodium falciparum gametocyte carriers was 16%, and 8% of individuals were able to infect mosquitoes. The percentage of mosquitoes that became infected by feeding on the infectious individuals was 21%. Children aged < 10 years contributed to about 75% of the infectious reservoir, although they constituted only 35% of the total population. Differences were found between the transmission seasons and the villages, and varied according to the index examined. Although there were more infectious individuals in one of the two villages, they were less infectious than those in the other village during the high transmission season. Comparative analysis of the transmission indices suggests the existence of functioning transmission-blocking immunity in one of the villages, which until now has been only hypothetically considered to play a role in malaria transmission in a natural setting. The epidemiological value of all the indices used and their accuracy in estimating the human infectious reservoir and its natural or induced variations are discussed.

Genetic analysis of Plasmodium falciparum infections on the north-western border of Thailand.

Genetic characterization of Plasmodium falciparum infections in north-western Thailand, a region of low transmission intensity (1 infection/person each year), has found a comparable number of parasite genotypes per infected person to regions with hyperendemic malaria. Clone multiplicity and parasite diversity were found to be homogeneous across 129 infected individuals comprising a range of age-groups (1.32 parasite genotypes; n = 98), patients (aged 2-16 years) with recrudescent infections (1.54; n = 13), and pregnant women (1.61; n = 18). Individuals belonging to groups with a high risk of infection, as deduced by clinical epidemiology, did not harbour a higher number of clones per infection, nor greater parasite diversity than low-risk groups. In fact, multiple genotype infections were as common in low-risk groups, suggesting that there is frequent transmission of polyclonal infections from a single inoculum, rather than superinfection. Such a polyclonal transmission system would enable generation of extensive parasite diversity by recombination, despite the low level of transmission. However, co-infection with P. vivax was associated with fewer P. falciparum genotypes per infection.

Hypersensitivity to electrical stimulation of auditory nuclei follows hearing loss in cats.

The purpose of the study was to determine if permanent, sound-induced hearing loss altered behaviorally measured thresholds for the detection of electrical stimulation applied to auditory nuclei. Electrodes were placed in cochlear nucleus and inferior colliculus in four cats. Behaviorally measured thresholds for the detection of brief trains of electrical pulses were determined before and after a 48 h exposure to a 1 kHz tone of approximately 110 dB SPL. The mean decrease in electrical stimulation threshold as a result of the sound exposure was 10.4 dB. The ongoing electrical activity (in microV, rms) recorded from the electrodes showed a mean 2.2 dB decrease after the sound exposure. In some electrodes, there was partial recovery towards pre-exposure levels for stimulation threshold and for ongoing activity, but typically, the changes persisted until the animals were terminated 30 days later. The magnitudes of the decreases in stimulation threshold and background activity proved not to be highly correlated. The permanent auditory threshold shift across all cats and all frequencies was 19 dB. This mild hearing loss produced a marked alteration in certain characteristics of the central auditory mechanisms.

Expansion of epidemic dengue viral infections to Pakistan.

OBJECTIVES: Antibodies to dengue viruses have occasionally been reported in individuals in Pakistan, but the frequency of occurrence of dengue infection in Pakistan is unclear. The first confirmed dengue hemorrhagic fever outbreak in Pakistan occurred in 1994. In October 1995, the authors investigated an outbreak of a febrile illness among employees of a construction contractor at a power generation plant in Baluchistan, Pakistan, to determine the cause of illness and recommend appropriate preventive measures. METHODS: The work site and living arrangements were inspected, a questionnaire was administered, and serum samples were collected from all consenting contractor employees and their families if they lived at the camp. Sera were analyzed for IgM against dengue virus, using an enzyme-linked immunosorbent assay. RESULTS: Interviews were conducted with 76 persons (mean age, 42y); 95% were men. Forty-two persons (55%) reported having experienced fever, headache, or myalgia in the preceding 6 weeks. Fifty-seven subjects (75%) had IgM antibodies against at least one dengue serotype; 45 subjects (59%) had IgM antibodies against dengue serotype 2. CONCLUSION: This was an outbreak of dengue fever due to multiple serotypes of dengue virus. This confirms that epidemic dengue infection was present in southern Pakistan for 2 consecutive years.

An immunologic investigation of atypical gingivostomatitis.

A fluorescent antibody investigation was conducted to determine first the difference, if any, in the presence of tissue-bound antibodies in normal gingiva and atypical gingivostomatitis gingiva, and second to determine if the serum of atypical gingivostomatitis patients had auto-antibodies directed against any specific structures of normal gingiva. The immunofluorescent tests produced two signficant results: 1. Most of the mononuclear inflammatory cells present in AGS gingiva had an antibody halo on the cell membrane surface. This could indicate that AGS is the result of hypersensitivity reaction. 2. The serum of AGS patients did not contain detectable auto-antibodies for normal gingiva which would be one indication that AGS is not an autoimmune disease.

Sex ratio adjustment in Plasmodium gallinaceum.

The sex ratio of the avian malaria parasite, Plasmodium gallinaceum, was examined during the course of infection in its natural host, the chicken. Infections can have two possible outcomes: death of the host resulting from anaemia or self-cure and survival. In lethal infections the sex ratio remained female biased throughout, whereas in self-curing infections, the sex ratio became progressively less female biased. We examined the consequences of altering sex ratio for parasite transmission success using a theoretical fertilisation model and hypothesise that an immune response specifically effective against the male gametes would provide a selective explanation for the observed sex ratio adjustment. Previous studies have demonstrated that there is an efficient anti-gamete antibody response as an infection is cleared by the host. We performed in vitro mosquito infection studies comparing mosquito infection rates with naive serum replacement and showed that decomplemented serum from curing infections is transmission blocking, whereas serum from lethal infections is not. We discuss aspects of the malaria parasite-host interaction which might provide the selective pressure for such observed sex ratio adjustment.

Interpleural block - part 2.

Interpleural blockade is effective in treating unilateral surgical and non-surgical pain from the chest and upper abdomen in both the acute and chronic settings. It has been shown to provide safe, high-quality analgesia after cholecystectomy, thoracotomy, renal and breast surgery, and for certain invasive radiological procedures of the renal and hepatobiliary systems. It has also been used successfully in the treatment of pain from multiple rib fractures, herpes zoster, complex regional pain syndromes, thoracic and abdominal cancer, and pancreatitis. The technique is simple to learn and has both few contra-indications and a low incidence of complications. In the second of two reviews, the authors cover the applications, complications, contra-indications and areas for future research.