Malaria rapid diagnostic tests in elimination settings--can they find the last parasite?

Rapid diagnostic tests (RDTs) for malaria have improved the availability of parasite-based diagnosis throughout the malaria-endemic world. Accurate malaria diagnosis is essential for malaria case management, surveillance, and elimination. RDTs are inexpensive, simple to perform, and provide results in 15-20 min. Despite high sensitivity and specificity for Plasmodium falciparum infections, RDTs have several limitations that may reduce their utility in low-transmission settings: they do not reliably detect low-density parasitaemia (≤200 parasites/µL), many are less sensitive for Plasmodium vivax infections, and their ability to detect Plasmodium ovale and Plasmodium malariae is unknown. Therefore, in elimination settings, alternative tools with higher sensitivity for low-density infections (e.g. nucleic acid-based tests) are required to complement field diagnostics, and new highly sensitive and specific field-appropriate tests must be developed to ensure accurate diagnosis of symptomatic and asymptomatic carriers. As malaria transmission declines, the proportion of low-density infections among symptomatic and asymptomatic persons is likely to increase, which may limit the utility of RDTs. Monitoring malaria in elimination settings will probably depend on the use of more than one diagnostic tool in clinical-care and surveillance activities, and the combination of tools utilized will need to be informed by regular monitoring of test performance through effective quality assurance.

In-vivo efficacy of amodiaquine-artesunate in children with uncomplicated Plasmodium falciparum malaria in western Kenya.

OBJECTIVES: To assess the efficacy of amodiaquine-artesunate in an area with high chloroquine resistance in western Kenya. METHODS: Twenty-eight day in-vivo efficacy trial of amodiaquine-artesunate in 103 children aged 6-59 months in western Kenya with smear-confirmed uncomplicated Plasmodium falciparum malaria. RESULTS: The 28-day uncorrected adequate clinical and parasitological response (ACPR) was 69.0%, with 15.5% Late Clinical Failure and 15.5% Late Parasitologic Failure rates. The PCR-corrected 28-day ACPR was 90.2%. Clinical risk factors for recurrent infection (recrudescences and reinfections) were lower axillary temperature at enrollment and low weight-for-age Z-score. The presence of single nucleotide polymorphisms pfcrt 76T and pfmdr1 86Y at baseline was associated with increased risk of recurrent infections, both reinfections and recrudescences. CONCLUSION: Although artemether-lumefantrine (Coartem) is the first line ACT in Kenya, amodiaquine-artesunate is registered as an option for treatment of uncomplicated P. falciparum and remains an effective alternative to Coartem in western Kenya. Continued amodiaquine monotherapy in the private sector may jeopardize the future use of amodiaquine-artesunate as an alternative artemisinin-based combination therapy.

Astereopsis caused by traumatic brain injury.

Impaired depth perception (astereopsis) has been observed in a variety of cerebral pathologies affecting the posterior parietal lobe. In the current study of 93 consecutive head trauma admissions, 24% had complete astereopsis and 41% performed more than 2 SDs below the orthopedic control group mean. Degree of impairment was related to Glascow Coma Scale score, length of posttraumatic amnesia, reduced visuospatial and memory abilities, and the presence of intracranial pathology of the parietal lobes. Impairment was also related to trauma severity in patients without any visualized intracranial pathology, presumably due to diffuse axonal shearing. Clinically meaningful impairment was observed in 25% of this group; 10% had complete astereopsis. Stereoacuity screening requires 1 to 2 minutes. Undetected astereopsis may increase risk for subsequent motor vehicle accidents or falls.

Increasing functional communication through relaxation training and neuromuscular feedback.

The following research examined the effects of behavioural relaxation training and biofeedback on ataxic tremor of an adult with acquired brain injury. The participant was taught relaxation techniques before biofeedback was introduced. Once he was proficient in relaxation, these skills were then used as a foundation for biofeedback training. Specific skills, facilitating the use of a letter board, were taught when the participant was able to relax the appropriate musculature to criterion. The results demonstrated that the participant learned how to significantly decrease the severity of tremor. As a result, he became more proficient at communicating via his letter board. Collateral effects were increased attempts at communication and fewer episodes of anger.

Infection with GB virus C and reduced mortality among HIV-infected patients.

BACKGROUND: The flavivirus GB virus C (GBV-C, also designated hepatitis G virus) was identified in a search for hepatitis viruses, but no disease is currently known to be associated with it. We investigated the relation between coinfection with GBV-C and the long-term outcome in patients infected with the human immunodeficiency virus (HIV). METHODS: A total of 197 HIV-positive patients were followed prospectively beginning in 1993 or 1994. Of these patients, 33 (16.8 percent) tested positive for GBV-C RNA, 112 (56.9 percent) had detectable antibodies against the GBV-C envelope protein E2, and 52 (26.4 percent) had no marker of GBV-C infection and were considered unexposed. We assessed the relation between GBV-C infection and the progression of HIV disease. We also tested 169 GBV-C-positive plasma samples with a quantitative branched-chain DNA (bDNA) assay in order to investigate possible correlations between GBV-C viral load and both the CD4+ cell count and the HIV load. RESULTS: Among the patients who tested positive for GBV-C RNA, survival was significantly longer, and there was a slower progression to the acquired immunodeficiency syndrome (AIDS) (P<0.001 for both comparisons). Survival after the development of AIDS was also better among the GBV-C-positive patients. The association of GBV-C viremia with reduced mortality remained significant in analyses stratified according to age and CD4+ cell count. In an analysis restricted to the years after highly active antiretroviral therapy became available, the presence of GBV-C RNA remained predictive of longer survival (P=0.02). The HIV load was lower in the GBV-C-positive patients than in the GBV-C-negative patients. The GBV-C load correlated inversely with the HIV load (r=-0.33, P<0.001) but did not correlate with the CD4+ cell count. CONCLUSIONS: Coinfection with GBV-C is associated with a reduced mortality rate in HIV-infected patients. GBV-C is not known to cause any disease, but it is possible that its presence leads to an inhibition of HIV replication. However, GBV-C infection could also be a marker for the presence of other factors that lead to a favorable HIV response.

A treatment selection model for weight reduction in adults with acquired brain injury: applications and preliminary findings.

This article presents a unique method for providing weight management assistance to persons who have experienced an acquired brain injury (ABI). Most of the available literature on this topic deals with weight loss methods for individuals who are not faced with the cognitive and behavioural challenges inherent in this population. A treatment selection protocol will be described that allows for appropriate selection of behavioural weight loss interventions. Interventions are based upon specific cognitive and behavioural difficulties that individuals with acquired brain injury may present. A detailed case study will also be presented depicting successful use of the treatment selection model with an adult male with an acquired brain injury.

Hepatocellular carcinoma in Egyptians with and without a history of hepatitis B virus infection: association with hepatitis C virus (HCV) infection but not with (HCV) RNA level.

The aim of this study was to analyze the association of hepatocellular carcinoma (HCC) with hepatitis C virus (HCV) in Egypt, using hepatitis B virus (HBV) and hepatitis E virus (HEV) as virus controls. In addition, the association of HCC with HCV RNA levels among persons seropositive for HCV was analyzed. We compared 131 patients with proven HCC, 247 with bladder cancer, and 466 healthy hospital employees. Age, sex, and place of residence were recorded to study confounding factors. Among the healthy controls, 16% were seropositive for HCV, 21% for HBV, and 31% for HEV. When healthy controls were age-matched with HCC patients, the latter were significantly (P < 0.001) more often HCV seropositive (67%) than were the controls (30%). The seropositivity for HBV and HEV did not differ significantly in frequency between the two groups. The seropositivity for HCV was also significantly (P < 0.001) more often found in HCC patients (76%) than in BC patients (47%), with seroprevalences for HBV and HEV not differing significantly in these age-matched groups. In HBV-negative HCC and bladder cancer patients, seroprevalence for HCV was significantly (P = 0.002) higher in HCC patients (68%) than in bladder cancer patients (36%). This difference was even more pronounced (P < 0.001) in HBV-positive HCC and bladder cancer patients (78% versus 52%, respectively). Of HCV-seropositive individuals, 49% were HCV RNA positive by branched DNA assay, and of these, 96% were infected by HCV genotype 4. No correlation between HCV RNA load and seropositivity of HBV or age or disease state was found. Infection with HCV and HCV-HBV double infection, but not HBV or HEV infection alone, is strongly correlated with HCC in Egypt.

Quantitative antibody responses to structural (Core) and nonstructural (NS3, NS4, and NS5) hepatitis C virus proteins among seroconverting injecting drug users: impact of epitope variation and relationship to detection of HCV RNA in blood.

To gain insight into the natural history of hepatitis C virus (HCV), 13 human immunodeficiency virus (HIV)-seronegative injecting drug users were studied who seroconverted for HCV as determined by third-generation enzyme-linked immunosorbent assay, showed an ensuing antibody response to HCV, and were not treated with any antiviral drugs during follow-up. Subjects included 13 untreated HIV-negative individuals, of whom 5 (38.5%) apparently cleared HCV and were polymerase chain reaction (PCR)-negative in at least 3 consecutive samples, 3 (23.1%) showed transient viremia and were PCR-negative in 1 sample during the study period, and the other 5 (38.5%) showed persistent viremia. Viremia was determined longitudinally by reverse-transcription PCR (RT-PCR) and quantified by branched DNA (bDNA). HCV genotypes were determined on serial samples during follow-up. Quantitative antibody levels to core, NS3, NS4, and NS5 were determined using the Chiron RIBA HCV-titering Strip Immunoblot Assay, which is based on HCV genotype 1. The antibody responses to core, NS3, NS4, and NS5 were erratic. In individuals infected with HCV genotype 1, significantly higher median antibody responses to core (P =.02) and to NS4 (P =.04) were found as compared with those infected with other genotypes, showing a significant impact of HCV genotype specificity of the assay. In groups infected with HCV genotype 1, significantly higher median NS3 antibody titers (2.61 relative intensity [RI] vs. 0.38 RI; P =.003) were found in the individuals with persistent viremia than in those with apparent resolution of HCV RNA in blood. In groups infected with genotypes other than genotype 1, significantly higher median NS3 antibody titers (0.89 RI vs. 0.03 RI; P =.0004) and NS5 antibody titers (1.86 RI vs. 0.01 RI; P =.006) were found in the individuals with persistent viremia than in those with apparent resolution of HCV RNA in blood. Individuals with viral persistence had higher HCV-RNA loads with higher antibody responses as compared with individuals with apparent viral clearance from blood. Apparent viral clearance from blood was observed in an unexpectedly high percentage (38.5%), associated with a significant decrease of antibodies to NS3, independent of HCV genotype, as compared with individuals with persistent viremia (P <.005). Apparent viral clearance from blood with gradual loss of antibodies to various HCV proteins, independent of HCV genotype, was observed in 4 of the 5 individuals within approximately 1 year after HCV seroconversion, whereas 1 of these individuals apparently cleared the virus from blood, with complete seroreversion.

Hepatitis C virus serotype-specific core and NS4 antibodies in injecting drug users participating in the Amsterdam cohort studies.

In the present study, the RIBA HCV serotyping SIA was evaluated with a cohort of injecting drug users. Serotyping may be a rapid and cost-effective method of determining genotypes in cohort studies. In this study, hepatitis C virus (HCV) antibody-positive sera from a cohort of 331 chronically infected injecting drug users, of which 167 were coinfected with human immunodeficiency virus (HIV), were serotyped by the RIBA HCV Serotyping SIA. Among the 331 specimens, serotype-specific antibodies were detected in 250 (sensitivity, 75. 5%), in which serotype 1 was predominant (57.2%), followed by serotype 3 (26.8%). Among the 331 specimens, 164 were HIV negative, and serotype-specific antibodies were detected in 151 (sensitivity, 92.1%), in which serotype 1 was predominant (59.6%), followed by serotype 3 (33.8%). For a subset of 58 samples taken from 19 chronically infected HCV seroconverters with a mean follow-up of 5 years, serotypes were compared with genotypes, which were determined by a line probe assay (HCV LiPa) and by direct sequencing of the products obtained by nested PCR of the 5' untranslated region. Among the 58 samples with known genotypes, serotype-specific antibodies were detected in 38 (total sensitivity, 65.5%), with a specificity of 78.9%. Thirty of these serotypeable samples revealed a serotype that corresponded to the genotype in the 58 samples (total positive predictive value, 51.7%). Of the 58 samples, 23 were coinfected with HIV, and when these were excluded, the total sensitivity increased to 76.5%, with a total specificity of 80.8% and a total positive predictive value of 61.8%. The serotyping assay showed a high total sensitivity (96.3%) for samples positive by HCV RIBA, version 3.0, with four bands. We conclude that the sensitivity of the RIBA HCV serotyping SIA is limited by the immunocompetence of the HCV-infected host. In general, samples from HIV-negative individuals containing genotype 1a had higher sensitivity, specificity, and concordance in the serotyping assay compared with genotyping, whereas samples containing genotype 3a were found to be more cross-reactive and untypeable. Therefore, the prevalence of genotypes other than genotype 1 could be underestimated if they are determined by serotyping, and improvements in specificity are recommended.

Searching for the meaning of the Category Test and the Wisconsin Card Sort Test: a comparative analysis.

The Category Test (CT) and the Wisconsin Card Sort Test (WCST) have long been the major instruments used for the assessment of "frontal lobe" brain damage. These tests have often been used interchangeably by clinicians. However, research to date has disagreed on the extent to which these tests can be interpreted in a similar manner. The current paper examined the interrelationships between the tests in 112 mixed brain injured clients. The results showed relatively small correlations between the tests in the range of .4 to .6 which were eliminated when age, education, premorbid IQ (Vocabulary) and spatial skills (Block Design) were used as covariates. Regression analyses showed clear differences in which WAIS-R tests predicted each test, while factor analysis revealed little overlap between the tests except for a small relationship between the number of WCST categories completed and CT errors. The CT appeared to reflect spatial and spatial analysis skills while the WCST reflected verbal analysis and sequential skills. The results clearly indicate that the tests are not interchangeable and do not reflect the same underlying cognitive skills nor can they be interpreted in the same manner for neuropsychological purposes.

Evidence that both HIV and HIV-induced immunodeficiency enhance HCV replication among HCV seroconverters.

The objective of this retrospective cohort study is to assess the mechanism by which human immunodeficiency virus type 1 (HIV) influences hepatitis C virus (HCV) replication in injecting drug users. Virological (HCV and HIV RNA levels) and immunological (CD4+, CD8+ cell counts, and anti-CD3 reactivity) parameters were determined in 19 HCV seroconverters in sequential samples over a period of 1 to 9 years. Among these subjects, 10 were HIV-seronegative (HIVneg), 4 were HIV-seropositive (HIVpos), and 5 seroconverted for HIV (HIVsc) during the observation period. HCV RNA levels were higher in HIVpos subjects than in HIVneg subjects. In subjects seroconverting for HIV, HCV, RNA levels increased significantly immediately after HIV seroconversion (P < 0.0001), while they remained stable over time in HIVpos and HIVneg subjects. HCV RNA correlated inversely with CD4+ cell counts in both the HIVpos population (R = -0.22, P < 0.05) and the HIVneg population (R = -0.45, P < 0.0001). In addition, when subjects were stratified according to CD4+ cell counts a significant difference was found in HCV RNA levels between HIVpos and HIVneg subjects with CD4+ cell counts > 500 cells/microliter (P = 0.001), but not in the population with CD4+ cell counts < 500 cells/microliter. In no population was a correlation found between HCV RNA levels and CD8+ cell counts or anti-CD3 reactivity. Both HIV infection and CD4+ cell counts are apparently associated with HCV RNA levels. The direct association, independent of CD4+ cell counts, between HIV infection and HCV replication appears to be stronger than the association between HIV-induced CD4+ cell decline and HCV replication. We conclude that (i) HCV replication is in some way directly influenced by the presence of HIV; (ii) HCV-specific host immunity controls, in part, HCV replication; and (iii) HCV replication increases when the immune system is impaired by HIV.

Different hepatitis C virus (HCV) RNA load profiles following seroconversion among injecting drug users without correlation with HCV genotype and serum alanine aminotransferase levels.

Hepatitis C virus (HCV) infection often persists in association with chronic hepatitis. Different factors have been proposed to determine the clinical outcome of HCV infection. The aim of this study was to examine three different factors of HCV infection among injecting drug users. Nineteen untreated HCV seroconverters were tested longitudinally for the presence of HCV RNA by reverse transcriptase (RT) PCR, and results were quantified by the branched-DNA (bDNA) assay. HCV genotypes were determined with the first sample taken after HCV seroconversion. To assess the natural course of infection, serum alanine aminotransferase (ALT) levels were measured at three stages in every individual. The concordance between bDNA and RT-PCR was 98.9%. Three distinct patterns were found, according to the HCV RNA load after seroconversion during a mean follow-up period of 5 years (range, 1 to 8 years). HCV genotype 1a was predominant (52.6%). There was a significant increase in serum ALT levels (mean 55.5 U/liter) in the early phase of HCV infection, compared with basal serum ALT levels before HCV seroconversion and at the end of the follow-up period. Three distinct HCV RNA load profiles were found, without apparent relationship to genotype and serum ALT levels in the first 5 years of HCV infection.

Self-management in the treatment of ataxia: a case study in reducing ataxic tremor through relaxation and biofeedback.

This study examined the effects of relaxation training and biofeedback on the ataxic tremor of an adult with an acquired brain injury. The participant was taught relaxation techniques before biofeedback was introduced. Once he was proficient in relaxation, these skills we used as a foundation for biofeedback training. Specific skills crucial to the performance of activities of daily living were trained once the participant was able to control the appropriate musculature according to an individualized criterion level. These skills included eating and the transfer of liquids in a glass. The results demonstrated that the participant learned to decrease the amount of tremor that he experienced. As a result he was better able to feed himself and to drink from a glass with less staff assistance than he had previously required.

Road to awareness: an individualized training package for increasing knowledge and comprehension of personal deficits in persons with acquired brain injury.

Research suggests that awareness of one's deficits may be a significant factor in the recovery process after acquired brain injuries (ABI). Various methods have been employed to teach awareness of the potential sequelae of ABI. The present study extended the use of a board game format to teach awareness to adults with ABI who exhibited serious unwanted behaviours. It used an individualized training package in conjunction with a game format in order to more specifically target individual client awareness of personal deficits in two areas: cognition and behaviour. Training focused on the first three levels within Bloom's Cognitive Taxonomy: knowledge, comprehension, and application. Components of both the multiple-baseline and multiple-probe design were used to demonstrate experimental control. All three participants responded favourably to training, as evidenced by increases in percentage of questions answered correctly during the game sessions and in pre/post-generalization probes in both cognitive and behavioural categories.

The effect of ankle stabilizers on athletic performance. A randomized prospective study.

The ankle is the site of more than one third of all injuries that occur to male basketball players. Although ankle bracing may prevent injury, many players believe that braces restrict athletic performance. This belief discourages use of braces and obviates the injury protection that bracing provides. The objectives of this study were to 1) determine whether athletic performance (in four basketball-related activities) was affected by three ankle brace designs (Universal, Kallassy, and Air-Stirrup ankle training brace), 2) determine whether specific braces are better for specific athletic activities, and 3) determine whether athletic performance changes with brace use. Twelve high school basketball players wore each brace type while vertical jumping, standing long jumping, cone running, and 18.3-meter shuttle running at two test times (initially and after 1 week of acclimation). Our data showed that these braces had no significant effects on athletic performance. No brace affected athletic performance in one specific activity more than another, and athletic performance did not change with brace use. We concluded that prophylactic ankle bracing does not inhibit athletic performance.

Anti-M4 antibodies measured by a sulphite oxidase ELISA in patients with both anti-centromere and anti-M2 antibodies.

In this study the clinical features of patients with a serological overlap between scleroderma and primary biliary cirrhosis (PBC) were analysed. The entity was defined by the presence of both anti-centromere antibody (ACA) and anti-mitochondrial antibodies to the M2 antigen, pyruvate dehydrogenase. In addition the sera were assayed for anti-mitochondrial antibodies to the M4 antigen measured by an ELISA to sulphite oxidase (SO). First, anti-M2 was detected, not only in 58 out of 60 patients with PBC but also in eight out of 61 patients with ACA. These sera, together with sera from 53 normals and 99 from patients with various connective tissue diseases were then evaluated for anti-SO, which has been proposed by Klein and Berg to be a marker of progressive liver disease. Again, a high proportion (62%) of sera from patients with PBC were positive for anti-SO, and three of the eight patients who had ACA and anti-M2 also reacted with SO. We subsequently identified and included for study a further 10 patients positive for ACA and anti-M2, making a total of 18 patients with this profile. Features of limited cutaneous scleroderma were present in 94% and evidence of liver disease in 56%. Eight out of the 18 patients had anti-SO, and of these four had PBC, two had abnormal biochemical liver function tests but two had no evidence of liver disease. These data confirm that detection of anti-SO is limited to an anti-M2 subpopulation, and may be a marker for liver involvement with prognostic significance in scleroderma patients with ACA.

Adherence and accuracy. Self-medication during inpatient psychiatric treatment.

1. The goals of the Medication Education and Self-Administration Program were to develop a way to assess inpatient self-medication accuracy; create a comprehensive intervention that would address individual characteristics that may produce nonadherence; and evaluate the effectiveness of the intervention. 2. The majority of program participants demonstrated significant errors within days when given the opportunity to administer their own medications, suggesting that participants' in-hospital self-administration may be an accurate predictor of postdischarge performance. 3. Even in cases where training failed to influence self-administered performance, program participation provided valuable information that guided subsequent treatment decisions and programmatic refinements.