Infectious Diseases - Research Publications
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ItemMalaria prevention in the expatriate and long-term traveller(Therapeutic Guidelines Limited, 2002-01-01)The prevention of malaria in expatriates and long-term travellers is complex. The traveller's doctor needs to consider the destination, the nature of the travel, the effectiveness and potential adverse effects of antimalarial medication, and the general health of the traveller. A preventative regimen can be devised combining several strategies including mosquito avoidance measures, chemoprophylaxis, emergency standby treatment and rapid self-diagnosis of malaria.
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ItemNo Preview AvailableAssessment of susceptibility of Plasmodium falciparum to chloroquine, quinine, mefloquine, sulfadoxine-pyrimethamine and artemisinin in southern Viet Nam(ROYAL SOC TROPICAL MEDICINE, 2001)Resistance to antimalarial chemotherapy is a major concern for malaria control in Viet Nam. In this study undertaken in 1998, 65 patients with uncomplicated Plasmodium falciparum malaria were monitored for 28 days after completion of a 5-day treatment course with artemisinin. Overall 36.9% (24/65) of patients had recurrent parasitaemia during the surveillance period. P. falciparum isolates were tested for sensitivity in vitro to chloroquine, mefloquine, quinine, sulfadoxine-pyrimethamine and results were compared to those from a similar study in 1995. Increased parasite sensitivity to sulfadoxine-pyrimethamine, chloroquine and quinine was demonstrated, with significantly lower mean EC50 and EC99 values in 1998 compared to 1995. Parasite sensitivity to mefloquine did not differ significantly in the 2 surveys. Isolates were also tested for sensitivity in vitro to artemisinin in the 1998 survey. The mean EC50 was 0.03 mumol/L and the EC99 was 0.94 mumol/L. Parasite sensitivity to artemisinin will need to be monitored in view of its increasing use in Viet Nam.
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ItemNo Preview AvailableImported malaria treated in Melbourne, Australia: Epidemiology and clinical features in 246 patients(OXFORD UNIV PRESS INC, 2001)BACKGROUND: Imported malaria is increasing in nonendemic countries, including Australia. The objective of this study was to describe the epidemiology and clinical features of travelers with imported malaria presenting to a specialist infectious diseases hospital. METHODS: A retrospective case series of 246 consecutively admitted inpatients with laboratory confirmed malaria. The main outcome measures were the proportion of patients infected with each malaria species, and relationship between species and country of birth, area of acquisition, adequacy of chemoprophylaxis, clinical features, laboratory investigations, and treatment. RESULTS: Plasmodium vivax caused 182 (68.9%) episodes, Plasmodium falciparum caused 71 (26.9%), Plasmodium ovale caused 5 (1.9%), and Plasmodium malariae 1 (0.4%). Fifty-six percent of patients reported chemoprophylaxis use. People born in a country with endemic malaria (36.6%) were less likely to have used chemoprophylaxis. Malaria was most commonly acquired in Papua New Guinea and Southeast Asia. The median times to diagnosis after return to Australia for P. falciparum and P. vivax infections were 1 and 9 weeks respectively. The longest interval between last arrival in Australia and presentation with P. falciparum malaria was 32 weeks. Fever (96%), headache (74%), and a tender or palpable spleen (40%), were the most common clinical features. Diarrhea was more common in P. falciparum, and rigors in P. vivax infections. Thrombocytopenia (71%), abnormal liver function tests and an elevated C-reactive protein (85%) were common. Six patients had severe falciparum malaria but no deaths occurred during the study period. CONCLUSION: Malaria remains a health threat for those traveling in endemic areas and is associated with failure to use chemoprophylaxis appropriately. Nonspecific clinical features may lead to delayed diagnosis and misdiagnosis. Malaria should be suspected in the febrile traveler, regardless of birthplace, prophylaxis, symptomatology, or the time that has elapsed since leaving the malarious area.
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ItemNo Preview AvailableRegional differences in the response of Plasmodium vivax malaria to primaquine as anti-relapse therapy(AMER SOC TROP MED & HYGIENE, 2007-02)We used logistic regression to assess effectiveness of primaquine as Plasmodium vivax anti-relapse therapy using data extracted from studies of P. vivax relapses in Brazil, India, and Thailand. The risk of relapse in Thailand was 10 times that in India and twice that in Brazil. In comparison with no primaquine treatment, the risk of relapse decreased by approximately 80% for a total adult primaquine regimen of 210 mg and by > or =95% for regimens of 315 mg and 420 mg. In addition, we used logistic regression to estimate the risk of P. vivax relapse according to weight-based primaquine dose using data from case studies. There was a three-fold increase in the likelihood of successful treatment of each additional milligram of primaquine per kilogram of body weight. Tailoring primaquine therapy to a region requires consideration of factors including body weight, natural relapse rates, and local response to primaquine.
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ItemNo Preview AvailableIncomplete Immunity and Missed Vaccination Opportunities in East African Immigrants Settling in Australia(Springer, 2008-06-01)BACKGROUND: Immigrants and refugees are at particular risk of incomplete immunisation and may be unaware of their vaccination status. There is a paucity of data on the immunisation status of adult immigrants from African countries. AIMS: To review the immunisation status of adult immigrants from East Africa, and to identify missed opportunities for vaccination. METHODS: A community survey was conducted using self-reported vaccination status, Mantoux skin tests, and serological testing for immunity to hepatitis B, tetanus, diphtheria and measles. RESULTS: Proven inadequate immunity against at least one of tetanus (67%), hepatitis B (41%), diphtheria (34%) or measles (3%) was found among 100/126 (81%) participants despite a median of seven visits to vaccine providers since immigration. A positive Mantoux test occurred in 17% of participants. CONCLUSIONS: Pre- and post-arrival health assessments are currently failing to address vaccination needs in recently arrived East African adult immigrants. Immigrants should have their immunisation status assessed, with opportunistic vaccination provided wherever possible.
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ItemThe Profile of Health Problems in African Immigrants Attending an Infectious Disease Unit in Melbourne, Australia(AMER SOC TROP MED & HYGIENE, 2009-05)The number of African immigrants living in Western countries is increasing. A retrospective audit of sub-Saharan African patients attending the infectious diseases clinics of a Melbourne teaching hospital was performed. A total of 375 patients were included. Helicobacter pylori gastritis was diagnosed in 60% of those tested (35/58), schistosomiasis in 41% (84/206), chronic hepatitis B in 19% (32/167), and strongyloidiasis in 18% (32/179). Active tuberculosis (TB) affected 18% (51/276) and latent TB 55% (152/276). Pathologic parasites were detected in stool in 21% (31/145). Vitamin D deficiency (< 50 nmol/L) affected 73% (139/191), anemia 17% (52/312), iron deficiency 15% (22/151), and low neutrophil count 25% (78/312). Infectious diseases, vitamin D deficiency, anemia, and latent TB were common in sub-Saharan African immigrants. Clinicians need to be aware of these conditions to meet the health needs of this group. Comprehensive health checks should be encouraged for new arrivals, particularly from high-risk areas.
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ItemThe effectiveness of 4 monthly albendazole treatment in the reduction of soil-transmitted helminth infections in women of reproductive age in Viet Nam(ELSEVIER SCI LTD, 2009-07-15)Soil-transmitted helminth (STH) infections are endemic in northern Viet Nam where the climate and agricultural practices, such as the use of human excreta as fertiliser and the use of wastewater for irrigation, favour transmission. An intervention was conducted in Yen Bai Province, north-west Viet Nam, to measure the effectiveness of single dose albendazole (400mg) administered every 4 months for reducing the prevalence of STH infections in women of reproductive age. Stool samples were collected from women before the intervention and 3 and 12 months post-intervention. Information on a range of demographic and socio-economic variables was also collected to measure the major risk factors for high STH burden in this area. The prevalence of hookworm, Ascaris lumbricoides and Trichuris trichiura infection in the baseline sample of 366 women were 76.2%, 19.2% and 29.1%, respectively. In the women who were surveyed at baseline and again at 3 and 12 months after the intervention (n=118) cure rates were 71.3% for hookworm, 87.0% for A. lumbricoides and 81.4% for T. trichiura by the end of the 12 month study period (i.e. after three doses of albendazole). The main risk factor for hookworm infection was if women worked outside (odds ratio (OR)=3.2 (95% Confidence Interval (CI) 1.6-6.2), P=0.001) and the major risk factor for A. lumbricoides and T. trichiura infection was a lack of education. Low educational attainment was also the strongest risk factor for co-infection with all three species of STH (OR=7.5 (95% CI 3.4-16.4), P<0.001). The high rates of hookworm infection in this area of Viet Nam and the high cure rates for all three species of STH with 4 monthly albendazole treatment suggest that this programme should be expanded to all endemic areas in Viet Nam. The study also highlights the important contribution of education to women's health.
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ItemDifferential var gene expression in the organs of patients dying of falciparurn malaria(WILEY, 2007-08)Sequestration of parasitized erythrocytes in the microcirculation of tissues is thought to be important in the pathogenesis of severe falciparum malaria. A major variant surface antigen, var/Plasmodium falciparum erythrocyte membrane protein 1, expressed on the surface of the infected erythrocyte, mediates cytoadherence to vascular endothelium. To address the question of tissue-specific accumulation of variant types, we used the unique resource generated by the clinicopathological study of fatal paediatric malaria in Blantyre, Malawi, to analyse var gene transcription in patients dying with falciparum malaria. Despite up to 102 different var genes being expressed by P. falciparum populations in a single host, only one to two of these genes were expressed at high levels in the brains and hearts of these patients. These major var types differed between organs. However, identical var types were expressed in the brains of multiple patients from a single malaria season. These results provide the first evidence of organ-specific accumulation of P. falciparum variant types and suggest that parasitized erythrocytes can exhibit preferential binding in the body, supporting the hypothesis of cytoadherence-linked pathogenesis.
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ItemCharacterization of VAR2CSA-deficient Plasmodium falciparum-infected erythrocytes selected for adhesion to the BeWo placental cell line(BMC, 2008-03-26)BACKGROUND: Malaria in pregnancy is characterized by accumulation of infected erythrocytes (IE) in the placenta. The key ligand identified as mediating this process is a Plasmodium falciparum erythrocyte membrane protein 1 family member, termed VAR2CSA. VAR2CSA appears to be the main ligand responsible for adhesion to chondroitin sulphate A (CSA). Whether other PfEMP1 molecules can also mediate placental adhesion, independent of CSA binding, is unclear. METHODS: The parasite line CS2 carrying a disrupted var2csa gene (CS2KO) was selected for adhesion to the BeWo choriocarcinoma cell line, which has been proposed as a model for placental malaria. The selected and control IE were tested for adhesion to placental sections and flow cytometry was used to measure recognition of IE by three serum sets from malaria-exposed men and women. RESULTS: Wild-type CS2 adhere to BeWo and placental tissue via CSA. CS2KO IE were successfully selected for adhesion to BeWo, and adhered by a CSA-independent mechanism. They bound to immobilized ICAM-1 and CD36. BeWo-selected CS2KO bound at moderate levels to placental sections, but most binding was to placental villi rather than to the syncytiotrophoblast to which IE adherence occurs in vivo. This binding was inhibited by a blocking antibody to CD36 but not to ICAM-1. As expected, sera from malaria-exposed adults recognized CS2 IE in a gender and parity dependent manner. In one serum set, there was a similar but less pronounced pattern of antibody binding to selected CS2KO IE, but this was not seen in two others. One var gene, It4var19, was particularly abundant in the selected line and was detected as full length transcripts in BeWo-selected IE, but not unselected CS2KO. CONCLUSION: This study suggests that IE with characteristics similar to the CS2KO have a limited role in the pathogenesis of placental malaria. VAR2CSA appear to be the major ligand for placental adhesion, and could be the basis for a vaccine against pregnancy malaria.
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ItemSevere vivax malaria: Newly recognised or rediscovered?(PUBLIC LIBRARY SCIENCE, 2008-06)Stephen Rogerson and Richard Carter discuss two new studies that challenge current dogma by suggesting that vivax malaria can cause severe disease.