Factors Associated with Utilization of Insecticide-Treated Nets in Children Seeking Health Care at a Ugandan Hospital: Perspective of Child Caregivers.

J Community Health. 2012 Feb 10;

Authors: Nankinga Z, Muliira JK, Kalyango J, Nankabirwa J, Kiwuwa S, Njama-Meya D, Karamagi C

Abstract
In Uganda malaria causes more morbidity and mortality than any other disease and children below 5 years contribute the biggest percentage of malaria related mortality. Insecticide treated nets (ITNs) are currently one of the most cost effective option for reducing malaria-related morbidity and mortality, however the factors affecting their utilization in Uganda are still not well understood. This study examined the prevalence and factors associated with ITN utilization among children of age 0-12 years seeking health care from a Ugandan hospital using caregiver's reports. A cross sectional design was used to collect data using a semi-structured questionnaire from 418 participants. Binary logistic regression was employed to determine predictors of ITN utilization. Results show that the prevalence of ITN utilization among children seeking health care was 34.2%. ITN utilization was higher among children of age <5 years [37.0, 95% CI 31.81-42.21] as compared to children aged ≥5 years [22.9, 95% CI 13.77-32.01]. Source of mosquito net (OR = 13.53, 95% CI = 6.47-28.27), formal employment by head of household (OR = 6.00, 95% CI = 1.95-18.48), sharing a bed with parent (s) (OR = 2.61, 95% CI = 1.21-5.63) and number of children below 12 years in a household (OR = 0.80, 95% CI = 0.65-0.99), were significant predictors of utilization. ITN utilization among children was below the set national target. The predictors identified by this study reveal opportunities that can be taken advantage of by malaria control programs to achieve the desired rates of utilization and subsequently malaria prevention in children.

PMID: 22323100 [PubMed - as supplied by publisher]

[Efficacy of artemether-lumefantrine in the treatment of uncomplicated malaria in children living in a rural area of Burkina Faso in 2009.]

Bull Soc Pathol Exot. 2012 Feb 9;

Authors: Siribié M, Diarra A, Tiono AB, Soulama I, Sirima SB

Abstract
In order to implement community case management of malaria strategy in a rural area of intense transmission, of children using artemether-lumefantrine combination, we assessed the therapeutic efficacy of the medicine. We conducted an open label and uncontrolled clinical trial in an unique centre from September 2009 to December 2009 in children 6-59 months old who consulted at health facilities for uncomplicated malaria. The primary endpoint was clinical and parasitological cure rate at day 28 corrected by PCR. In total 106 children were enrolled. Parasite clearance at day 2 was 99.04% and the adequate clinical and parasitological response corrected by PCR at day 28 was 90.5%. Our results confirm that artemether-lumefantrine combination is still effective.

PMID: 22322791 [PubMed - as supplied by publisher]

Epilepsy care challenges in developing countries.

Curr Opin Neurol. 2012 Feb 8;

Authors: Kvalsund MP, Birbeck GL

Abstract
PURPOSE OF REVIEW: This review discusses recent literature relevant to the diagnosis and treatment of epilepsy in developing countries with particular attention to underlying causes, natural history, and advances made toward optimizing systems of care and bridging the treatment gap. RECENT FINDINGS: Prospective data suggest that cerebral malaria-induced brain injury may explain the high prevalence of epilepsy in malaria-endemic regions. Population-based mortality studies support the long proposed hypothesis that seizure-related deaths contribute to excessive premature mortality. WHO guidelines have the potential to improve care, but macrolevel barriers related to pharmaceutical regulation and distribution continue to contribute to the treatment gap. Evidence-based guidelines endorsed by the WHO and American Academy of Neurology regarding the optimal management of comorbid epilepsy and HIV may raise awareness regarding critical drug interactions between antiepileptic drugs and antiretrovirals, but are also problematic as the treatment regimen and diagnostic facilities routinely available in developing countries will prevent most healthcare providers from following the recommendations. SUMMARY: New insights into the causes, natural history and best care practices for epilepsy in developing countries are available but without prioritization and action from policy makers, the present treatment gap will likely to persist.

PMID: 22322413 [PubMed - as supplied by publisher]

Novel hybrid molecules based on 15-membered azalide as potential antimalarial agents.

Eur J Med Chem. 2012 Jan 26;

Authors: Starčević K, Pešić D, Toplak A, Landek G, Alihodžić S, Herreros E, Ferrer S, Spaventi R, Perić M

Abstract
Malaria remains the most prevalent tropical disease, and due to the spread of resistant parasites novel therapeutics are urgently needed. Azithromycin has shown potential in malaria treatment so we designed hybrid azalide molecules with the aim to improve activity against and selectivity for the malaria parasite. Novel hybrid molecules comprising 4-aminoquinoline moiety covalently liked to 15-membered azalide scaffold at position C-3' were synthesized and biologically evaluated. Antimalarial testing against Plasmodiumfalciparum sensitive and resistant strains confirmed the improved in vitro activity over azithromycin and chloroquine. Selectivity of the compounds (HepG2 IC(50)/P. falciparum IC(50) ratio) for the parasite was high (100-2700) and their antibacterial activity diminished. Even though oral bioavailability determined for compound 12 was low, novel quinoline C-3'-substituted 15-membered azalides represent an interesting subclass of antimalarial macrolides that need further research and evaluation.

PMID: 22321992 [PubMed - as supplied by publisher]

Effects of co-habitation between Anopheles gambiae s.s. and Culex quinquefasciatus aquatic stages on life history traits.

Parasit Vectors. 2012 Feb 9;5(1):33

Authors: Kweka EJ, Zhou G, Beilhe LB, Dixit A, Afrane Y, Gilbreath TM, Munga S, Nyindo M, Githeko AK, Yan G

Abstract
ABSTRACT: BACKGROUND: The effective measures for the control of malaria and filariasis vectors can be achieved by targeting immature stages of anopheline and culicine mosquitoes in productive habitat. To design this strategy, the mechanisms (like biotic interactions with conspecifc and heterospecific larvae) regulating mosquito aquatic stages survivorship, development time and the size of emerging adults should be understood. This study explored the effect of co-habitation between An. gambiae s.s. and Cx. quinquefasciatus on different life history traits of both species under different densities and constant food supply in the habitats of the same size under semi-natural conditions. METHODS: Experiments were set up with three combinations; Cx. quinquefasciatus alone (single species treatment), An. gambiae s.s. alone (single species treatment); and An. gambiae s.s. with Cx. quiquefasciatus (co-habitation treatment) in different densities in semi field situation. Results: The effect of co-habitation of An. gambiae s.s. and Cx. quinquefasciatus was found to principally affect three parameters. The wing-lengths (a proxy measure of body size) of An. gambiae s.s. in co-habitation treatments were significantly shorter in both females and males than in An. gambiae s.s single species treatments. In Cx. quinquefasciatus, no significant differences in wing-length were observed between the single species and co-habitation treatments. Daily survival rates were not significantly different between co-habitation and single species treatments for both An. gambiae s.s. and Cx. quinquefasciatus. Developmental time was found to be significantly different with single species treatments developing better than co-habitation treatments. Sex ratio was found to be significantly different from the proportion of 0.5 among single and co-habitation treatments species at different densities. Single species treatments had more males than females emerging while in co-habitation treatments more females emerged than males. In this study, there was no significant competitive survival advantage in co-habitation. Conclusion: These results suggest that co-habitation of An. gambiae s.s. and Cx. quinquefasciatus in semi-natural conditions affect mostly An. gambiae s.s. body size. Hence, more has to be understood on the effects of co-habitation of An. gambiae s.s. and Cx. quinquefasciatus in a natural ecology and its possible consequences in malaria and filariasis epidemiology.

PMID: 22321562 [PubMed - as supplied by publisher]

Using CF11 cellulose columns to inexpensively and effectively remove human DNA from Plasmodium falciparum-infected whole blood samples.

Malar J. 2012 Feb 10;11(1):41

Authors: Venkatesan M, Amaratunga C, Campino S, Auburn S, Koch O, Lim P, Uk S, Socheat D, Kwiatkowski DP, Fairhurst RM, Plowe CV

Abstract
ABSTRACT: BACKGROUND: Genome and transcriptome studies of Plasmodium nucleic acids obtained from parasitized whole blood are greatly improved by depletion of human DNA or enrichment of parasite DNA prior to next-generation sequencing and microarray hybridization. The most effective method currently used is a two-step procedure to deplete leukocytes: centrifugation using density gradient media followed by filtration through expensive, commercially available columns. This method is not easily implemented in field studies that collect hundreds of samples and simultaneously process samples for multiple laboratory analyses. Inexpensive syringes, hand-packed with CF11 cellulose powder, were recently shown to improve ex vivo cultivation of Plasmodium vivax obtained from parasitized whole blood. This study was undertaken to determine whether CF11 columns could be adapted to isolate Plasmodium falciparum DNA from parasitized whole blood and achieve current quantity and purity requirements for Illumina sequencing. METHODS: The CF11 procedure was compared with the current two-step standard of leukocyte depletion using parasitized red blood cells cultured in vitro and parasitized blood obtained ex vivo from Cambodian patients with malaria. Procedural variations in centrifugation and column size were tested, along with a range of blood volumes and parasite densities. RESULTS: CF11 filtration reliably produces 500 nanograms of DNA with less than 50% human DNA contamination, which is comparable to that obtained by the two-step method and falls within the current quality control requirements for Illumina sequencing. In addition, a centrifuge-free version of the CF11 filtration method to isolate P. falciparum DNA at remote and minimally equipped field sites in malaria-endemic areas was validated. CONCLUSIONS: CF11 filtration is a cost-effective, scalable, one-step approach to remove human DNA from P. falciparum-infected whole blood samples.

PMID: 22321373 [PubMed - as supplied by publisher]

Malaria transmission in Libreville: results of a one year survey.

Malar J. 2012 Feb 9;11(1):40

Authors: Mourou JR, Coffinet T, Jarjaval F, Cotteaux C, Pradines E, Lydie G, Kombila M, Pages F

Abstract
ABSTRACT: BACKGROUND: In Gabon, vector transmission has been poorly studied. Since the implementation of the Roll Back malaria recommendations, clinical studies have shown a decline in the burden of malaria in Libreville, the capital city of Gabon. To better understand the transmission dynamic in Libreville, an entomological survey was conducted in five districts of the city. METHODS: Mosquitoes were sampled by human landing collection during 1 year in five districts of Libreville: Alibandeng, Beausejour, Camp des Boys and Sotega. Mosquitoes were identified morphologically and by molecular methods. The Plasmodium falciparum circumsporozoite indices were measured by ELISA, and the entomological inoculation rates (EIR) were calculated for all areas. Molecular assessments of pyrethroid knock down resistance (kdr) and of insensitive acetylcholinesterase resistance were conducted. RESULTS: A total of 57,531 mosquitoes were caught during 341 person-nights (161 person-nights indoor and 180 person-nights outdoor) among which, 4,223 were Anopheles gambiae s.l. The average Human Biting Rate fell from 15.5 bites per person during the rainy season to 4.7 during the dry season. The An. gambiae complex population was composed of An. gambiae s.s molecular form S (99.5%), Anopheles melas (0.3%) and An. gambiae s.s. form M (0.2%). Thirty-three out of 4,223 An. gambiae s.l. were found to be infected by P. falciparum (CSP index = 0.78%). The annual EIR was estimated at 33.9 infected bites per person per year ranging from 13 in Alibandeng to 88 in Sotega. No insensitive AChE mutation was identified but both kdr-w and kdr-e mutations were present in An. gambiae molecular form S with a higher frequency of the kdr-w allele (76%) than the kdr-e allele (23.5%). CONCLUSION: Malaria transmission in Libreville occurred mainly during the rainy season but also during the dry season in the five districts. Transmission level is high and seems to be very heterogeneous in the town. Interestingly, the highest EIR was recorded in the most central and urbanized quarter and the lowest in a peripheral area. The decrease of transmission usually seen from peri-urban areas to urban centers is probably more dependent of the socio-economic level of a quarter than of its location in the city. Urban malaria control programmes need to consider the socio economic level of an area rather than the location in the city in order to determine the areas most favourable to malaria transmission.

PMID: 22321336 [PubMed - as supplied by publisher]

Positive diversifying selection on Plasmodium vivax RON2 protein.

Parasitology. 2012 Feb 10;:1-7

Authors: Tang J, Dai Y, Zhang H, Culleton RL, Liu Y, Zhao S, Wang X, Guan X, Kaneko O, Zhu Y

Abstract
SUMMARYPlasmodium rhoptry neck protein 2 (RON2), which is released from the neck portion of the merozoite rhoptries and interacts with the microneme protein Apical Membrane Antigen 1 (AMA1), plays a crucial role in erythrocyte invasion. In this study, we sequenced the Plasmodium vivax RON2 gene from 19 P. vivax isolates collected in central China in order to establish whether this protein is under positive diversifying selection, which may occur as a result of protective host immune pressure†. In comparison with the P. vivax Sal-1 reference line, we found 10 amino acid substitutions dispersed throughout the open reading frame as well as indels caused by polymorphism in a repeat unit (21-23 repeats of (Q/E/K/N/H)(G/D)G(H/L/Y/P)G) in the second tandem repeat region located at amino acid positions 541-650. A McDonald-Kreitman test with RON2 sequences from the primate malaria parasite Plasmodium knowlesi, detected significant departure from neutrality in the PvRON2 3' region (nucleotide positions 2668-6609). These results suggest that the PvRON2 gene has evolved under positive diversifying selection.

PMID: 22321319 [PubMed - as supplied by publisher]

Combination of probenecid-sulphadoxine-pyrimethamine for intermittent preventive treatment in pregnancy.

Malar J. 2012 Feb 9;11(1):39

Authors: Gutman J, Kachur SP, Slutsker L, Nzila A, Mutabingwa T

Abstract
ABSTRACT: The antifolate sulphadoxine-pyrimethamine (SP) has been used in the intermittent prevention of malaria in pregnancy (IPTp). SP is an ideal choice for IPTp, however, as resistance of Plasmodium falciparum to SP increases, data are accumulating that SP may no longer provide benefit in areas of high-level resistance. Probenecid was initially used as an adjunctive therapy to increase the blood concentration of penicillin; it has since been used to augment concentrations of other drugs, including antifolates. The addition of probenecid has been shown to increase the treatment efficacy of SP against malaria, suggesting that the combination of probenecid plus SP may prolong the useful lifespan of SP as an effective agent for IPTp. Here, the literature on the pharmacokinetics, adverse reactions, interactions and available data on the use of these drugs in pregnancy is reviewed, and the possible utility of an SP-probenecid combination is discussed. This article concludes by calling for further research into this potentially useful combination.

PMID: 22321288 [PubMed - as supplied by publisher]

The ecology of Anopheles mosquitoes under climate change: case studies from the effects of deforestation in East African highlands.

Ann N Y Acad Sci. 2012 Feb 9;

Authors: Afrane YA, Githeko AK, Yan G

Abstract
Climate change is expected to lead to latitudinal and altitudinal temperature increases. High-elevation regions such as the highlands of Africa and those that have temperate climate are most likely to be affected. The highlands of Africa generally exhibit low ambient temperatures. This restricts the distribution of Anopheles mosquitoes, the vectors of malaria, filariasis, and O'nyong'nyong fever. The development and survival of larval and adult mosquitoes are temperature dependent, as are mosquito biting frequency and pathogen development rate. Given that various Anopheles species are adapted to different climatic conditions, changes in climate could lead to changes in species composition in an area that may change the dynamics of mosquito-borne disease transmission. It is important to consider the effect of climate change on rainfall, which is critical to the formation and persistence of mosquito breeding sites. In addition, environmental changes such as deforestation could increase local temperatures in the highlands; this could enhance the vectorial capacity of the Anopheles. These experimental data will be invaluable in facilitating the understanding of the impact of climate change on Anopheles.

PMID: 22320421 [PubMed - as supplied by publisher]

The Use and Abuse of Haem in Apicomplexan Parasites.

Antioxid Redox Signal. 2012 Feb 9;

Authors: van Dooren G, Kennedy A, McFadden G

Abstract
Significance. Haem is an essential prosthetic group for most life on Earth. It functions in numerous cellular redox reactions, including in antioxidant defences and at several stages of the electron transport chain in prokaryotes and eukaryotic mitochondria. Haem also functions as a sensor and transport molecule for gases such as oxygen. Haem is a complex organic molecule and can only be synthesised through a multi-enzyme pathway from simpler precursors. Most free-living organisms synthesise their own haem by a broadly conserved metabolic pathway. Parasites are adept at scavenging molecules from their hosts, and haem is no exception. Recent Advances. In this review we examine recent advances in understanding haem usage and acquisition in Apicomplexa, a group of parasites that include the causative agents of malaria, toxoplasmosis and several major parasites of livestock. Critical Issues. Haem is critical to the survival of Apicomplexa, although the functions of haem in these organisms remain poorly understood. Some Apicomplexa likely scavenge haem from their host organisms, while others retain the ability to synthesise haem. Surprisingly, some Apicomplexa may be able to both synthesise and scavenge haem. Several Apicomplexa live in intracellular environments that contain high levels of haem. Since haem is toxic at high concentrations, parasites must carefully regulate intracellular haem levels and develop mechanisms to detoxify excess haem. Indeed, drugs interfering with haem detoxification serve as major antimalarials. Future Directions. Understanding haem requirements and regulation in apicomplexan parasites promises to reveal multiple targets for much-needed therapeutic intervention against these parasites.

PMID: 22320355 [PubMed - as supplied by publisher]

Ecology and conservation biology of avian malaria.

Ann N Y Acad Sci. 2012 Feb 9;

Authors: Lapointe DA, Atkinson CT, Samuel MD

Abstract
Avian malaria is a worldwide mosquito-borne disease caused by Plasmodium parasites. These parasites occur in many avian species but primarily affect passerine birds that have not evolved with the parasite. Host pathogenicity, fitness, and population impacts are poorly understood. In contrast to continental species, introduced avian malaria poses a substantial threat to naive birds on Hawaii, the Galapagos, and other archipelagoes. In Hawaii, transmission is maintained by susceptible native birds, competence and abundance of mosquitoes, and a disease reservoir of chronically infected native birds. Although vector habitat and avian communities determine the geographic distribution of disease, climate drives transmission patterns ranging from continuous high infection in warm lowland forests, seasonal infection in midelevation forests, and disease-free refugia in cool high-elevation forests. Global warming is expected to increase the occurrence, distribution, and intensity of avian malaria across this elevational gradient and threaten high-elevation refugia, which is the key to survival of many susceptible Hawaiian birds. Increased temperatures may have already increased global avian malaria prevalence and contributed to an emergence of disease in New Zealand.

PMID: 22320256 [PubMed - as supplied by publisher]

Polymerase chain reaction-based tests for pan-species and species-specific detection of human Plasmodium parasites.

Transfusion. 2012 Feb 10;

Authors: Mahajan B, Zheng H, Pham PT, Sedegah MY, Majam VF, Akolkar N, Rios M, Ankrah I, Madjitey P, Amoah G, Addison E, Quakyi IA, Kumar S

Abstract
BACKGROUND: There is still a need to improve the sensitivity of polymerase chain reaction (PCR) tests for malaria to detect submicroscopic asexual stage Plasmodium infections during the early phase and chronic, asymptomatic phase of infection when the parasite burden is very low. STUDY DESIGN AND METHODS: The inhibitory effect of hemoglobin (Hb) on PCR limits the volume of blood that can be used in the PCR-based detection of intraerythrocytic Plasmodium parasites. We lysed red blood cells with saponin to reduce the Hb concentration in extracted nucleic acid and, as a result, significantly increased the volume of blood that can be tested by PCR. The analytical sensitivity of the PCR was determined using whole blood spiked with ring-stage Plasmodium falciparum parasites, and its clinical sensitivity by testing blood film-positive and blood film-negative samples from individuals living in an endemic area in Ghana. RESULTS: We have developed a pan-Plasmodium PCR that detects all five human Plasmodium species with the highest analytical sensitivity of two P. falciparum parasites/mL of whole blood and species-specific PCR tests that distinguished between the five human Plasmodium species. Pan-Plasmodium PCR detected 78 of 78 (100%) blood film-positive and 19 of 101 (18.81%) blood film-negative samples from asymptomatic individuals living in Ghana. Pan-Plasmodium PCR was equally sensitive with samples collected as anticoagulated whole blood and clotted blood and in blood collected by finger stick into capillaries. CONCLUSION: We have developed PCR tests with the highest reported sensitivity to date for pan-Plasmodium diagnosis and species-specific diagnosis and detected blood film-negative asymptomatic infections in individuals living in malaria-endemic countries.

PMID: 22320188 [PubMed - as supplied by publisher]

Reduced risk of malaria parasitemia following household screening and treatment: a cross-sectional and longitudinal cohort study.

PLoS One. 2012;7(2):e31396

Authors: Sutcliffe CG, Kobayashi T, Hamapumbu H, Shields T, Mharakurwa S, Thuma PE, Louis TA, Glass G, Moss WJ

Abstract
BACKGROUND: In regions of declining malaria transmission, new strategies for control are needed to reduce transmission and achieve elimination. Artemisinin-combination therapy (ACT) is active against immature gametocytes and can reduce the risk of transmission. We sought to determine whether household screening and treatment of infected individuals provides protection against infection for household members.
METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted in two areas in Southern Province, Zambia in 2007 and 2008/2009. To determine the impact of proactive case detection, households were randomly selected either to join a longitudinal cohort, in which participants were repeatedly screened throughout the year and those infected treated with artemether-lumefantrine, or a cross-sectional survey, in which participants were visited only once. Cross-sectional surveys were conducted throughout the year. The prevalence of RDT positivity was compared between the longitudinal and cross-sectional households at baseline and during follow-up using multilevel logistic regression. In the 2007 study area, 174 and 156 participants enrolled in the cross-sectional and longitudinal groups, respectively. In the 2008/2009 study area, 917 and 234 participants enrolled in the cross-sectional and longitudinal groups, respectively. In both study areas, participants and households in the longitudinal and cross-sectional groups were similar on demographic characteristics and prevalence of RDT positivity at baseline (2007: OR = 0.97; 95% CI:0.46, 2.03 | 2008/2009: OR = 1.28; 95% CI:0.44, 3.79). After baseline, the prevalence of RDT positivity was significantly lower in longitudinal compared to cross-sectional households in both study areas (2007: OR = 0.44; 95% CI:0.20, 0.96 | 2008/2009: OR = 0.16; 95% CI:0.05, 0.55).
CONCLUSIONS/SIGNIFICANCE: Proactive case detection, consisting of screening household members with an RDT and treating those positive with ACT, can reduce transmission and provide indirect protection to household members. A targeted test and treat strategy could contribute to the elimination of malaria in regions of low transmission.

PMID: 22319629 [PubMed - in process]

The CTLA-4 and PD-1/PD-L1 Inhibitory Pathways Independently Regulate Host Resistance to Plasmodium-induced Acute Immune Pathology.

PLoS Pathog. 2012 Feb;8(2):e1002504

Authors: Hafalla JC, Claser C, Couper KN, Grau GE, Renia L, de Souza JB, Riley EM

Abstract
The balance between pro-inflammatory and regulatory immune responses in determining optimal T cell activation is vital for the successful resolution of microbial infections. This balance is maintained in part by the negative regulators of T cell activation, CTLA-4 and PD-1/PD-L, which dampen effector responses during chronic infections. However, their role in acute infections, such as malaria, remains less clear. In this study, we determined the contribution of CTLA-4 and PD-1/PD-L to the regulation of T cell responses during Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM) in susceptible (C57BL/6) and resistant (BALB/c) mice. We found that the expression of CTLA-4 and PD-1 on T cells correlates with the extent of pro-inflammatory responses induced during PbA infection, being higher in C57BL/6 than in BALB/c mice. Thus, ECM develops despite high levels of expression of these inhibitory receptors. However, antibody-mediated blockade of either the CTLA-4 or PD-1/PD-L1, but not the PD-1/PD-L2, pathways during PbA-infection in ECM-resistant BALB/c mice resulted in higher levels of T cell activation, enhanced IFN-γ production, increased intravascular arrest of both parasitised erythrocytes and CD8(+) T cells to the brain, and augmented incidence of ECM. Thus, in ECM-resistant BALB/c mice, CTLA-4 and PD-1/PD-L1 represent essential, independent and non-redundant pathways for maintaining T cell homeostasis during a virulent malaria infection. Moreover, neutralisation of IFN-γ or depletion of CD8(+) T cells during PbA infection was shown to reverse the pathologic effects of regulatory pathway blockade, highlighting that the aetiology of ECM in the BALB/c mice is similar to that in C57BL/6 mice. In summary, our results underscore the differential and complex regulation that governs immune responses to malaria parasites.

PMID: 22319445 [PubMed - in process]

The Role of Animal Models for Research on Severe Malaria.

PLoS Pathog. 2012 Feb;8(2):e1002401

Authors: Craig AG, Grau GE, Janse C, Kazura JW, Milner D, Barnwell JW, Turner G, Langhorne J,

PMID: 22319438 [PubMed - as supplied by publisher]

Acute toxicity studies of aqueous leaf extract of Phyllanthus niruri.

Interdiscip Toxicol. 2011 Dec;4(4):206-10

Authors: Asare GA, Addo P, Bugyei K, Gyan B, Adjei S, Otu-Nyarko LS, Wiredu EK, Nyarko A

Abstract
Phyllanthus niruri is a plant with medicinal properties. It is often used to treat mild malaria and the elimination of renal stones. However, studies on its toxicity are scarce. The study was carried out to determine if the aqueous leaf extract of P. niruri administered to female Sprague-Dawley rats would illicit evidence of toxicity. Fifteen female rats weighing 150-200 g were divided into 3 groups. Rats in Group 1 were given a single low dose (LD) of 2000 mg/kg b.w. of the extract by oral gavage within 24 hrs. Rats in Group 2 were given a single high dose (HD) of 5000 mg/kg b.w. of the extract by oral gavage within 24 hrs. Rats in Group 3 were not given any extract but drinking water and served as the control group (C). All the rats were observed for signs of toxidromes for 14 days. On the 15(th) day, all the rats were sacrificed. Body organs were harvested for macroscopic examination. Urine and blood samples were drawn and analyzed. Hematological tests performed included full blood count and hemoglobin. Biochemical examinations included bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin, alkaline phosphatse (ALP), γ-glutamyltranspeptidase (GGT), urea, and creatinine. The results of the three groups were not significantly different. Examination of the various body organs did not show any abnormality. Thus no toxicity was observed at the levels administered. The LD(50) of the aqueous extract is>5000 mg/kg. b.w.

PMID: 22319255 [PubMed - in process]

Ronald Ross' opposition to Battista Grassi's malaria research.

J Med Biogr. 2011 Nov;19(4):184

Authors: Cook GC

PMID: 22319194 [PubMed - in process]

Nurses' working tasks and MSDs back symptoms: results from a national survey.

Work. 2012 Jan 1;41(0):2449-51

Authors: Serranheira F, Cotrim T, Rodrigues V, Nunes C, Sousa-Uva A

Abstract
Healthcare workers, namely registered nurses (RN), are frequently exposed to work-related musculoskeletal disorders (WRMSDs) risk factors. Identifying the symptoms of these disorders is one of the first epidemiological steps to managing them. This study aims to identify WRMSDs prevalence symptoms in Portuguese RN. During 8 months (2010-2011) the National Public Health School and the Portuguese Registered Nurses Board made a call to all RN to answer an online WRMSDs questionnaire. Respondents (n=2140) are mostly females (77.4%) and work mainly in hospitals (n=1396) and in primary healthcare centers (n=421). Results show high symptoms prevalence (last 12 months) in the lower back (60.6%), the upper back (44.5%), and the neck (48.6%). Nurses' activity, especially patient hygiene in bed, is a strong contributor (p>0.05) to pain in the upper back (OR=1.39 [1.09-1.80]) and lower back (OR=1.4 [1.08-1.84]). Patient holdup without mechanical support has the highest relationship (p>0.05) between work tasks and symptoms in the last 12 months in the upper back (OR=1.50 [1.19-1.90]). Prevalence rates of WRMSDs symptoms in Portuguese nurses are no different from other studies with Swedish, Italian and Greek nurses. Maybe changes in healthcare systems didn't change the way care is delivered and we must rethink how to prevent nurses WRMSDs.

PMID: 22317085 [PubMed - in process]

Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults.

J Antimicrob Chemother. 2012 Feb 8;

Authors: Byakika-Kibwika P, Lamorde M, Okaba-Kayom V, Mayanja-Kizza H, Katabira E, Hanpithakpong W, Pakker N, Dorlo TP, Tarning J, Lindegardh N, de Vries PJ, Back D, Khoo S, Merry C

Abstract
BACKGROUND: Treatment of HIV/malaria-coinfected patients with antiretroviral therapy (ART) and artemisinin-based combination therapy has potential for drug interactions. We investigated the pharmacokinetics of artemether, dihydroartemisinin and lumefantrine after administration of a single dose of 80/480 mg of artemether/lumefantrine to HIV-infected adults, taken with and without lopinavir/ritonavir. METHODS: A two-arm parallel study of 13 HIV-infected ART-naive adults and 16 HIV-infected adults stable on 400/100 mg of lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (ClinicalTrials.gov, NCT 00619944). Each participant received a single dose of 80/480 mg of artemether/lumefantrine under continuous cardiac function monitoring. Plasma concentrations of artemether, dihydroartemisinin and lumefantrine were measured. RESULTS: Co-administration of artemether/lumefantrine with lopinavir/ritonavir significantly reduced artemether maximum concentration (C(max)) and area under the concentration-time curve (AUC) [median (range): 112 (20-362) versus 56 (17-236) ng/mL, P = 0.03; and 264 (92-1129) versus 151 (38-606) ng · h/mL, P < 0.01]. Dihydroartemisinin C(max) and AUC were not affected [66 (10-111) versus 73 (31-224) ng/mL, P = 0.55; and 213 (68-343) versus 175 (118-262) ng · h/mL P = 0.27]. Lumefantrine C(max) and AUC increased during co-administration [2532 (1071-5957) versus 7097 (2396-9462) ng/mL, P < 0.01; and 41 119 (12 850-125 200) versus 199 678 (71 205-251 015) ng · h/mL, P < 0.01]. CONCLUSIONS: Co-administration of artemether/lumefantrine with lopinavir/ritonavir significantly increases lumefantrine exposure, but decreases artemether exposure. Population pharmacokinetic and pharmacodynamic trials will be highly valuable in evaluating the clinical significance of this interaction and determining whether dosage modifications are indicated.

PMID: 22316571 [PubMed - as supplied by publisher]