Infectious Diseases - Research Publications
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ItemNo Preview AvailablePoint-of-care testing and treatment of sexually transmitted and genital infections to improve birth outcomes in high-burden, low-resource settings (WANTAIM): a pragmatic cluster randomised crossover trial in Papua New Guinea(ELSEVIER SCI LTD, 2024-04)BACKGROUND: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis have been associated with adverse maternal and perinatal outcomes, but there is conflicting evidence on the benefits of antenatal screening and treatment for these conditions. We aimed to determine the effect of antenatal point-of-care testing and immediate treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis on preterm birth, low birthweight, and other adverse maternal and perinatal outcomes compared with current standard of care, which included symptom-based treatment without laboratory confirmation. METHODS: In this pragmatic cluster randomised crossover trial, we enrolled women (aged ≥16 years) attending an antenatal clinic at 26 weeks' gestation or earlier (confirmed by obstetric ultrasound), living within approximately 1 h drive of a study clinic, and able to provide reliable contact details at ten primary health facilities and their catchment communities (clusters) in Papua New Guinea. Clusters were randomly allocated 1:1 to receive either the intervention or control (standard care) in the first phase of the trial. Following an interval (washout period) of 2-3 months at the end of the first phase, each cluster crossed over to the other group. Randomisation was stratified by province. Individual participants were informed about trial group allocation only after completing informed consent procedures. The primary outcome was a composite of preterm birth (livebirth before 37 weeks' gestation), low birthweight (<2500 g), or both, analysed according to the intention-to-treat population. This study is registered with ISRCTN Registry, ISRCTN37134032, and is completed. FINDINGS: Between July 26, 2017, and Aug 30, 2021, 4526 women were enrolled (2210 [63·3%] of 3492 women in the intervention group and 2316 [62·8%] of 3687 in the control group). Primary outcome data were available for 4297 (94·9%) newborn babies of 4526 women. The proportion of preterm birth, low birthweight, or both, in the intervention group, expressed as the mean of crude proportions across clusters, was 18·8% (SD 4·7%) compared with 17·8% in the control group (risk ratio [RR] 1·06, 95% CI 0·78-1·42; p=0·67). There were 1052 serious adverse events reported (566 in the intervention group and 486 in the control group) among 929 trial participants, and no differences by trial group. INTERPRETATION: Point-of-care testing and treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis did not reduce preterm birth or low birthweight compared with standard care. Within the subgroup of women with N gonorrhoeae, there was a substantial reduction in the primary outcome. FUNDING: UK Department of Health and Social Care; UK Foreign, Commonwealth and Development Office; UK Medical Research Council; the Wellcome Trust; the Australian National Health and Medical Research Council; and Swiss National Science Foundation.
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ItemNo Preview AvailableAntibody to Plasmodium falciparum Variant Surface Antigens, var Gene Transcription, and ABO Blood Group in Children With Severe or Uncomplicated Malaria(OXFORD UNIV PRESS INC, 2023-10-18)BACKGROUND: Antibodies to variant surface antigens (VSAs) such as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) may vary with malaria severity. The influence of ABO blood group on antibody development is not understood. METHODS: Immunoglobulin G antibodies to VSAs in Papua New Guinean children with severe (n = 41) or uncomplicated (n = 30) malaria were measured by flow cytometry using homologous P falciparum isolates. Isolates were incubated with ABO-matched homologous and heterologous acute and convalescent plasma. RNA was used to assess var gene transcription. RESULTS: Antibodies to homologous, but not heterologous, isolates were boosted in convalescence. The relationship between antibody and severity varied by blood group. Antibodies to VSAs were similar in severe and uncomplicated malaria at presentation, higher in severe than uncomplicated malaria in convalescence, and higher in children with blood group O than other children. Six var gene transcripts best distinguished severe from uncomplicated malaria, including UpsA and 2 CIDRα1 domains. CONCLUSIONS: ABO blood group may influence antibody acquisition to VSAs and susceptibility to severe malaria. Children in Papua New Guinea showed little evidence of acquisition of cross-reactive antibodies following malaria. Var gene transcripts in Papua New Guinean children with severe malaria were similar to those reported from Africa.
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ItemNo Preview AvailableCorrection: Does Malaria Affect Placental Development? Evidence from In Vitro Models(Public Library of Science (PLoS), 2013)
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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 AvailableChemoprophylaxis and treatment of malaria.( 1994-09)Prevention of malaria morbidity relies on the use of personal protection from mosquito bites, appropriate chemoprophylactic drugs, and early investigation of symptoms in returning travellers. Malaria chemoprophylaxis must be tailored to the individual patient's travel and personal needs, and no chemoprophylaxis is completely effective. Chloroquine alone is adequate for those areas with P vivax, or sensitive P falciparum but in most circumstances the choice will be between mefloquine and doxycycline. The specific area visited, the time spent there and the individual's medical history will help determine the final choice.
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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.