72 research outputs found
DoctorVox: A new device for voice therapy and vocal training
No full textdoctorVOX is a new patented device designed by the author to provide voice therapy, vocal training and vocal humidification. This device is easy to carry and is safe to be used anywhere. It is intended to assist voice therapy and to serve as a supportingIzmir University Faculty of Medicine, Otolaryngology Department, Izmir, Turkey; Dokuz Eylül University State Conservatory Vocal Arts Department, Main Art Division of Opera, Izmir, Turkey; Ege University State Turkish Music Conservatory Liberal Arts Divis
Clinical and parasitological response to oral chloroquine and primaquine in uncomplicated human Plasmodium knowlesi infections.
No full textBACKGROUND: Plasmodium knowlesi is a cause of symptomatic and potentially fatal infections in humans. There are no studies assessing the detailed parasitological response to treatment of knowlesi malaria infections in man and whether antimalarial resistance occurs.
METHODS: A prospective observational study of oral chloroquine and primaquine therapy was conducted in consecutive patients admitted to Kapit Hospital, Sarawak, Malaysian Borneo with PCR-confirmed single P. knowlesi infections. These patients were given oral chloroquine for three days, and at 24 hours oral primaquine was administered for two consecutive days, primarily as a gametocidal agent. Clinical and parasitological responses were recorded at 6-hourly intervals during the first 24 hours, daily until discharge and then weekly to day 28. Vivax malaria patients were studied as a comparator group.
RESULTS: Of 96 knowlesi malaria patients who met the study criteria, 73 were recruited to an assessment of the acute response to treatment and 60 completed follow-up over 28 days. On admission, the mean parasite stage distributions were 49.5%, 41.5%, 4.0% and 5.6% for early trophozoites, late trophozoites, schizonts and gametocytes respectively. The median fever clearance time was 26.5 [inter-quartile range 16-34] hours. The mean times to 50% (PCT50) and 90% (PCT90) parasite clearance were 3.1 (95% confidence intervals [CI] 2.8-3.4) hours and 10.3 (9.4-11.4) hours. These were more rapid than in a group of 23 patients with vivax malaria 6.3 (5.3-7.8) hours and 20.9 (17.6-25.9) hours; P = 0.02). It was difficult to assess the effect of primaquine on P. knowlesi parasites, due to the rapid anti-malarial properties of chloroquine and since primaquine was administered 24 hours after chloroquine. No P. knowlesi recrudescences or re-infections were detected by PCR.
CONCLUSIONS: Chloroquine plus primaqine is an inexpensive and highly effective treatment for uncomplicated knowlesi malaria infections in humans and there is no evidence of drug resistance. Further studies using alternative anti-malarial drugs, including artemisinin derivatives, would be desirable to define optimal management strategies for P. knowlesi
Orangutans not Infected with Plasmodium vivax or P. cynomolgi, Indonesia
No full textAfter orangutans in Indonesia were reported as infected
with Plasmodium cynomolgi and P. vivax, we conducted
phylogenetic analyses of small subunit ribosomal RNA gene
sequences of Plasmodium spp. We found that these orangutans
are not hosts of P. cynomolgi and P. vivax. Analysis
of >1 genes is needed to identify Plasmodium spp. infecting
orangutans
Severe malaria - a case of fatal Plasmodium knowlesi infection with post-mortem findings: a case report.
No full textBACKGROUND: Zoonotic malaria caused by Plasmodium knowlesi is an important, but newly recognized, human pathogen. For the first time, post-mortem findings from a fatal case of knowlesi malaria are reported here.
CASE PRESENTATION: A formerly healthy 40 year-old male became symptomatic 10 days after spending time in the jungle of North Borneo. Four days later, he presented to hospital in a state of collapse and died within two hours. He was hyponatraemic and had elevated blood urea, potassium, lactate dehydrogenase and amino transferase values; he was also thrombocytopenic and eosinophilic. Dengue haemorrhagic shock was suspected and a post-mortem examination performed. Investigations for dengue virus were negative. Blood for malaria parasites indicated hyperparasitaemia and single species P. knowlesi infection was confirmed by nested-PCR. Macroscopic pathology of the brain and endocardium showed multiple petechial haemorrhages, the liver and spleen were enlarged and lungs had features consistent with ARDS. Microscopic pathology showed sequestration of pigmented parasitized red blood cells in the vessels of the cerebrum, cerebellum, heart and kidney without evidence of chronic inflammatory reaction in the brain or any other organ examined. Brain sections were negative for intracellular adhesion molecule-1. The spleen and liver had abundant pigment containing macrophages and parasitized red blood cells. The kidney had evidence of acute tubular necrosis and endothelial cells in heart sections were prominent.
CONCLUSIONS: The overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria. Post-mortem findings in this case were unexpectedly similar to those that define fatal falciparum malaria, including cerebral pathology. There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain. These results suggest that further study of knowlesi malaria will aid the interpretation of, often conflicting, information on malaria pathophysiology in humans
Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.
No full textEmerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p = <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region
Emerg Infect Dis
No full textMultilocus microsatellite genotyping of Plasmodium knowlesi isolates previously indicated 2 divergent parasite subpopulations in humans on the island of Borneo, each associated with a different macaque reservoir host species. Geographic divergence was also apparent, and independent sequence data have indicated particularly deep divergence between parasites from mainland Southeast Asia and Borneo. To resolve the overall population structure, multilocus microsatellite genotyping was conducted on a new sample of 182 P. knowlesi infections (obtained from 134 humans and 48 wild macaques) from diverse areas of Malaysia, first analyzed separately and then in combination with previous data. All analyses confirmed 2 divergent clusters of human cases in Malaysian Borneo, associated with long-tailed macaques and pig-tailed macaques, and a third cluster in humans and most macaques in peninsular Malaysia. High levels of pairwise divergence between each of these sympatric and allopatric subpopulations have implications for the epidemiology and control of this zoonotic species
Emerg Infect Dis
No full textPopulation genetic analysis revealed that Plasmodium knowlesi infections in Malaysian Borneo are caused by 2 divergent parasites associated with long-tailed (cluster 1) and pig-tailed (cluster 2) macaques. Because the transmission ecology is likely to differ for each macaque species, we developed a simple genotyping PCR to efficiently distinguish between and survey the 2 parasite subpopulations. This assay confirmed differences in the relative proportions in areas of Kapit division of Sarawak state, consistent with multilocus microsatellite analyses. Analyses of 1,204 human infections at Kapit Hospital showed that cluster 1 caused approximately two thirds of cases with no significant temporal changes from 2000 to 2018. We observed an apparent increase in overall numbers in the most recent 2 years studied, driven mainly by increased cluster 1 parasite infections. Continued monitoring of the frequency of different parasite subpopulations and correlation with environmental alterations are necessary to determine whether the epidemiology will change substantially
Emerg Infect Dis
No full textTo monitor the incidence of Plasmodium knowlesi infections and determine whether other simian malaria parasites are being transmitted to humans, we examined 1,047 blood samples from patients with malaria at Kapit Hospital in Kapit, Malaysia, during June 24, 2013-December 31, 2017. Using nested PCR assays, we found 845 (80.6%) patients had either P. knowlesi monoinfection (n = 815) or co-infection with other Plasmodium species (n = 30). We noted the annual number of these zoonotic infections increased greatly in 2017 (n = 284). We identified 6 patients, 17-65 years of age, with P. cynomolgi and P. knowlesi co-infections, confirmed by phylogenetic analyses of the Plasmodium cytochrome c oxidase subunit 1 gene sequences. P. knowlesi continues to be a public health concern in the Kapit Division of Sarawak, Malaysian Borneo. In addition, another simian malaria parasite, P. cynomolgi, also is an emerging cause of malaria in humans
Contribution of Plasmodium knowlesi to multi-species human malaria infections in North Sumatera, Indonesia
No full textBackground
As Indonesia works towards the goal of malaria elimination, information is lacking on malaria
epidemiology from some western provinces. As a basis for studies of antimalarial efficacy, we set out
to survey parasite carriage in three communities in North Sumatera Province.
Methods
A combination of active and passive detection of infection was carried out among communities in
Batubara, Langkat and South Nias regencies. Finger-prick blood samples from consenting individuals
of all ages provided blood films for microscopic examination and blood spots on filter paper.
Plasmodium species were identified by nested PCR of rRNA genes, and a novel assay which amplifies
a conserved sequence specific for the sicavar gene family of P. knowlesi.
Results
614 of 3,731 participants (16.5%) were positive for malaria parasites by microscopy. PCR detected
parasite DNA in samples from 1,169 individuals (31.3%). In total, 377 participants (11.8%) harboured
P. knowlesi. Also present were P. vivax (14.3%), P. falciparum (10.5%) and P. malariae (3.4%).
Conclusions
Amplification of sicavar is a specific and sensitive test for the presence of P. knowlesi DNA in
humans. Subpatent and asymptomatic multi-species parasitaemia is relatively common in North
Sumatera, and so PCR-based surveillance is required to support control and elimination activities
Long term outlook for the world economy : issues and projections for the 1990s
No full textThe authors argue that, at the broad level of global analysis, there are good reasons to be optimistic about the 1990s. First, there are favorable supply side developments in many of the high income countries. Second, considerable scope exists for a recovery of private consumption and investment in the debt stricken developing countries, as well as in Eastern Europe and the USSR. The 1990s will see a continuation of the process of economic integration currently under way, emcompassing mainly the industrialized and the newly industrializing economies, propelled by rapid technological progress and increased competition in international markets, and taking place against a backdrop of policy reforms, economic restructuring, and political liberalization that has been gathering momentum since the early 1980s. According to the authors, the expected pattern of international trade and investment flows in the 1990s is likely to perpetuate two tracks of growth in the developing world. While it may be expected to be high in many Asian industrializing economies, relatively high population growth and low private investment will probably continue to depress living standards in many countries in Latin America and Sub-Saharan Africa. The differences in investment rates of the 1980s between the higher-income and other developing countries will, if not reversed, tend to widen the productivity and technology gap between them.Environmental Economics&Policies,Achieving Shared Growth,Economic Conditions and Volatility,Inequality,Economic Theory&Research
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