Choreoathetosis – an unusual adverse effect of dihydroartemisinin-piperaquine: a case report

Background

Dihydroartemisinin-piperaquine is a combination of dihydroartemisinin and piperaquine which is highly effective in the treatment of uncomplicated falciparum malaria. Its adverse effects are generally tolerable and temporary. Choreoathetosis, an involuntary movement disorder characterized by continuous irregular twisting of the body, is not a documented adverse effect of this medication.

Case presentation

A 41-year-old Cameroonian man of black African ethnicity was brought to our primary care hospital because over the previous 6 hours he had been experiencing involuntary twisting movements of his body and he no longer had control of his limbs. Earlier that day, he had been prescribed an appropriate dose of dihydroartemisinin-piperaquine in our hospital. The abnormal movements started approximately 3 hours after ingesting the first dose of the drug. The review of systems and his past history were unremarkable. On clinical examination, he was conscious and oriented but was unsteady and displayed continuous generalized irregular twisting movements combined with abrupt low amplitude flinging of his limbs. Dihydroartemisinin-piperaquine-induced generalized choreoathetosis was diagnosed. He was sedated with diazepam and dihydroartemisinin-piperaquine was discontinued. The antimalarial drug was substituted with artemether-lumefantrine combination. The clinical progress was good and he was discharged home after 72 hours. No further abnormalities were noted during 7 months of follow-up.

Conclusion

Although dihydroartemisinin-piperaquine is increasingly popular as a well-tolerated/efficacious antimalarial drug, clinicians must note the rare possibility of choreoathetosis as an adverse effect of this medication and educate patients accordingly.

     

Binding of LFA-1 (CD11a) to Intercellular Adhesion Molecule 3 (ICAM-3; CD50) and ICAM-2 (CD102) Triggers Transmigration of Human Immunodeficiency Virus Type 1-Infected Monocytes through Mucosal Epithelial Cells

Transmigration of human immunodeficiency virus (HIV)-infected mononuclear cells through the genital mucosa is one of the possible mechanisms of sexual transmission of HIV. Here, we investigated the transmigration of cell-associated R5-tropic HIV type 1 (HIV-1) through a tight monolayer of human epithelial cells in vitro. We show that this process is dependent on an initial interaction between alphaLbeta2 integrin CD11a/CD18 on infected monocytic cells and intercellular adhesion molecule 2 (ICAM-2; CD102) and ICAM-3 (CD50) on the apical membrane of epithelial cells. The CD50 and CD102 ligands were overexpressed on epithelial cells when the cells were activated by proinflammatory cytokines in the cellular microenvironment. An accumulation of proviral DNA was found in the transmigrated cells, clearly reflecting the preferential transepithelial migration of HIV-1-infected cells under proinflammatory conditions. Our observations provide new insights supporting the hypothesis that HIV-infected mononuclear cells contained in genital secretions from infected individuals may cross the epithelial genital mucosa of an exposed receptive sexual partner, particularly under inflammatory conditions of damaged genital tissue. Understanding the fundamental aspects of the initial HIV entry process during sexual transmission remains a critical step for preventing human infection and developing further vaccinal strategies and virucidal agents.     

Environmental enrichment for nonhuman primates: theory and application

Investigators have an obligation to promote the psychological well-being of nonhuman primates used in research. Considerable emphasis has been placed on providing nonhuman primates with enriched environments as a means to achieve this objective. A framework is provided that consists of a set of hypotheses about well-being, and the extent to which exposure to various enrichment devices and procedures actually promotes well-being is evaluated. Two hypotheses are concerned with fostering species-typical behavior: use (versus nonuse) of the enrichment, and whether use of enrichment helps normalize other aspects of the behavioral repertoire. Two additional hypotheses are concerned with abnormal behavior: whether currently existing enrichment lowers levels of abnormal behavior, and whether it prevents the behavior. This framework is applied to various enrichment strategies ranging from toys and foraging devices to social interaction. Most devices are used by nonhuman primates and thus constitute an important way to enrich the captive environment. However, enrichment devices vary as to their effectiveness in normalizing the behavioral repertoire and eliminating abnormal behavior. Only social contact satisfies the goal of promoting a wide variety of species-typical activities while at the same time reducing or preventing the development of abnormal behavior.     

Analysis of anabolic steroids in the horse: development of a generic ELISA for the screening of 17alpha-alkyl anabolic steroid metabolites

Due to the potential for misuse of a wide range of anabolic steroids in horse racing, a screening test to detect multiple compounds, via a common class of metabolites, would be a valuable forensic tool. An enzyme-linked immunosorbent assay (ELISA) has been developed to detect 17alpha-alkyl anabolic steroid metabolites in equine urine. 16beta-Hydroxymestanolone (16beta,17beta-dihydroxy-17alpha-methyl-5alpha-androstan-3-one) was synthesised in six steps from commercially available epiandrosterone (3beta-hydroxy-5alpha-androstan-17-one). Polyclonal antibodies were raised in sheep, employing mestanolone (17beta-hydroxy-17alpha-methyl-5alpha-androstan-3-one) or 16beta-hydroxymestanolone conjugated to human serum albumin, via a 3-carboxymethyloxime linker, as antigens. Antibody cross-reactivities were determined by assessing the ability of a library of 54 representative steroids to competitively bind the antibodies. Antibodies raised against 16beta-hydroxymestanolone showed excellent cross-reactivities for all of the 16beta,17beta-dihydroxy-17alpha-methyl steroids analysed and an ELISA has been developed to detect these steroid metabolites. Using this 16beta-hydroxymestanolone assay, urine samples from horses administered with stanozolol (17alpha-methyl-pyrazolo[4',3':2,3]-5alpha-androstan-17beta-ol), were analysed raw, following beta-glucuronidase hydrolysis, and following solid-phase extraction (SPE) procedures. The suppressed absorbances observed were consistent with detection of the metabolite 16beta-hydroxystanozolol. Positive screening results were confirmed by comparison with standard LCMS analyses. Antibodies raised against mestanolone were also used to develop an ELISA and this was used to detect metabolites retaining the parent D-ring structure following methandriol (17alpha-methylandrost-5-ene-3beta,17beta-diol) administration. The ELISA methods developed have application as primary screening tools for detection of new and known anabolic steroid metabolites.     

Intrinsic Immunity Shapes Viral Resistance of Stem Cells

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Identifying Malaria Transmission Foci for Elimination Using Human Mobility Data

Humans move frequently and tend to carry parasites among areas with endemic malaria and into areas where local transmission is unsustainable. Human-mediated parasite mobility can thus sustain parasite populations in areas where they would otherwise be absent. Data describing human mobility and malaria epidemiology can help classify landscapes into parasite demographic sources and sinks, ecological concepts that have parallels in malaria control discussions of transmission foci. By linking transmission to parasite flow, it is possible to stratify landscapes for malaria control and elimination, as sources are disproportionately important to the regional persistence of malaria parasites. Here, we identify putative malaria sources and sinks for pre-elimination Namibia using malaria parasite rate (PR) maps and call data records from mobile phones, using a steady-state analysis of a malaria transmission model to infer where infections most likely occurred. We also examined how the landscape of transmission and burden changed from the pre-elimination setting by comparing the location and extent of predicted pre-elimination transmission foci with modeled incidence for 2009. This comparison suggests that while transmission was spatially focal pre-elimination, the spatial distribution of cases changed as burden declined. The changing spatial distribution of burden could be due to importation, with cases focused around importation hotspots, or due to heterogeneous application of elimination effort. While this framework is an important step towards understanding progressive changes in malaria distribution and the role of subnational transmission dynamics in a policy-relevant way, future work should account for international parasite movement, utilize real time surveillance data, and relax the steady state assumption required by the presented model.