Infectious Diseases - Research Publications
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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.
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ItemPlasmodium falciparum-Mediated Induction of Human CD25hiFoxp3hi CD4 T Cells Is Independent of Direct TCR Stimulation and Requires IL-2, IL-10 and TGFβ(PUBLIC LIBRARY SCIENCE, 2009-08)CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) regulate disease-associated immunity and excessive inflammatory responses, and numbers of CD4(+)CD25(+)Foxp3(+) Tregs are increased during malaria infection. The mechanisms governing their generation, however, remain to be elucidated. In this study we investigated the role of commonly accepted factors for Foxp3 induction, TCR stimulation and cytokines such as IL-2, TGFbeta and IL-10, in the generation of human CD4(+)CD25(+)Foxp3(+) T cells by the malaria parasite Plasmodium falciparum. Using a co-culture system of malaria-infected red blood cells (iRBCs) and peripheral blood mononuclear cells from healthy individuals, we found that two populations of Foxp3(hi) and Foxp3(int) CD4(+)CD25(hi) T cells with a typical Treg phenotype (CTLA-4(+), CD127(low), CD39(+), ICOS(+), TNFRII(+)) were induced. Pro-inflammatory cytokine production was confined to the Foxp3(int) subset (IFNgamma, IL-4 and IL-17) and inversely correlated with high relative levels of Foxp3(hi) cells, consistent with Foxp3(hi) CD4 T cell-mediated inhibition of parasite-induced effector cytokine T cell responses. Both Foxp3(hi) and Foxp3(int) cells were derived primarily from proliferating CD4(+)CD25(-) T cells with a further significant contribution from CD25(+)Foxp3(+) natural Treg cells to the generation of the Foxp3(hi) subset. Generation of Foxp3(hi), but not Foxp3(int), cells specifically required TGFbeta1 and IL-10. Add-back experiments showed that monocytes expressing increased levels of co-stimulatory molecules were sufficient for iRBC-mediated induction of Foxp3 in CD4 T cells. Foxp3 induction was driven by IL-2 from CD4 T cells stimulated in an MHC class II-dependent manner. However, transwell separation experiments showed that direct contact of monocytes with the cells that acquire Foxp3 expression was not required. This novel TCR-independent and therefore antigen-non specific mechanism for by-stander CD4(+)CD25(hi)Foxp3(+) cell induction is likely to reflect a process also occurring in vivo as a consequence of immune activation during malaria infection, and potentially a range of other infectious diseases.
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ItemThe relationship of Plasmodium falciparum humeral immunity with HIV-1 immunosuppression and treatment efficacy in Zambia(BMC, 2009-11-18)BACKGROUND: HIV-1 infection affects malaria humeral immunity during pregnancy, but data for non-pregnant adults are lacking. This study reports the impact of HIV-1 infection and other variables on the level of malaria humeral immunity in adults with clinical malaria and whether humeral immune suppression was a risk factor for treatment failure. METHODS: Sera of 224 HIV-1 infected and 115 uninfected adults were compared for IgG to merozoite antigens AMA-1 and MSP2 (3D7 and FC27 types) determined by ELISA, and for IgG to the Variant Surface Antigens (VSA) of three different parasite line E8B, A4 and HCD6 determined by flow cytometry. RESULTS: Compared to HIV-1 uninfected adults, AMA-1 IgG was lower in HIV-1 infected (P = 0.02) and associated with low CD4 count AMA-1 IgG (P = 0.003). Low IgG to all three merozoite antigens was associated with less anemia (P = 0.03). High parasite load was associated with low MSP2 IgG 3D7 and FC27 types (P = 0.02 and P = 0.08). Antibody levels to VSA did not differ between HIV-1 infected and uninfected adults. However, low VSA IgGs were associated with high parasite load (P
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ItemMalaria during pregnancy and foetal haematological status in Blantyre, Malawi(BMC, 2005-08-25)BACKGROUND: Although maternal anaemia often stems from malaria infection during pregnancy, its effects on foetal haemoglobin levels are not straightforward. Lower-than-expected cord haemoglobin values in malarious versus non-malarious regions were noted by one review, which hypothesized they resulted from foetal immune activation to maternal malaria. This study addressed this idea by examining cord haemoglobin levels in relation to maternal malaria, anaemia, and markers of foetal immune activation. METHODS: Cord haemoglobin levels were examined in 32 malaria-infected and 58 uninfected women in Blantyre, Malawi, in relation to maternal haemoglobin levels, malaria status, and markers of foetal haematological status, hypoxia, and inflammation, including TNF-alpha, TGF-beta, and ferritin. All women were HIV-negative. RESULTS: Although malaria was associated with a reduction in maternal haemoglobin (10.8 g/dL vs. 12.1 g/dL, p < 0.001), no reduction in cord haemoglobin and no significant relationship between maternal and cord haemoglobin levels were found. Cord blood markers of haematological and hypoxic statuses did not differ between malaria-infected and uninfected women. Maternal malaria was associated with decreased TGF-beta and increased cord ferritin, the latter of which was positively correlated with parasitaemia (r = 0.474, p = 0.009). Increased cord ferritin was associated with significantly decreased birth weight and gestational length, although maternal and cord haemoglobin levels and malaria status had no effect on birth outcome. CONCLUSION: In this population, cord haemoglobin levels were protected from the effect of maternal malaria. However, decreased TGF-beta and elevated ferritin levels in cord blood suggest foetal immune activation to maternal malaria, which may help explain poor birth outcomes.