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Obesity and chronic disease are increasing problems in refugee populations. Afghani refugees undergoing hepatitis B vaccination between January 2015 and December 2017 at a general practice clinic received dietary counselling sessions in Dari by native speaking clinicians. Anthropometry, blood pressure, fasting lipids and liver function tests were measured at both visits with results compared over time. 110/119 refugees requiring hepatitis B vaccination were recruited into the study. Mean BMI was lower at follow up visits (25.4 vs 26.1 by wilcoxon signed rank test p 0.04) with 72 of 110 participants losing a median of 2 kg between visits (range 0.5–14 kg) a mean of 206 days after the initial consultation. Median triglyceride levels were lower at the second visit than the first (1.4 vs 1.3 mmol/L Wilcoxon signed rank test Z = 3.5, p 0.0004). This cohort of refugees lost weight and showed a small improvement in triglyceride levels between visits.

© 2019 The Author(s). Background: Direct supplementation or food fortification with iron are two public health initiatives intended to reduce the prevalence of iron deficiency (ID) and iron deficiency anaemia (IDA) in 4-24-month-old infants. In most high-income countries where IDA prevalence is < 15%, the recommended daily intake levels of iron from supplements and/or consumption of fortified food products are at odds with World Health Organisation (WHO) guidelines that recommend shorter-term (3 months/year) supplementation only in populations with IDA prevalence > 40%. Emerging concerns about delayed neurological effects of early-life iron overexposure have raised questions as to whether recommended guidelines in high-income countries are unnecessarily excessive. This systematic review will gather evidence from supplementation/fortification trials, comparing health outcomes in studies where iron-replete children did or did not receive additional dietary iron; and determine if replete children at study outset were not receiving additional iron show changes in haematological indices of ID/IDA over the trial duration. Methods: We will perform a systematic review of the literature, including all studies of iron supplementation and/or fortification, including study arms with confirmed iron-replete infants at the commencement of the trial. This includes both dietary iron intervention or placebo/average dietary intakes. One reviewer will conduct searches in electronic databases of published and ongoing trials (Medline, Web of Science, Scopus, CENTRAL, EBSCO [e.g. CINAHL Complete, Food Science and Technology Abstracts], Embase, ClinicalTrials.gov, ClinicalTrialsRegister.eu and who.it/trialsearch), digital theses and dissertations (WorldCat, Networked Digital Library of Theses and Dissertations, DART-Europe E-theses Portal, Australasian Digital Theses Program, Theses Canada Portal and ProQuest). For eligible studies, one reviewer will use a data extraction form, and a secon

Newly arrived migrants to the EU/EEA (arrival within the past five years), as well as other migrant groups in the region, might be under-immunised and lack documentation of previous vaccinations, putting them at increased risk of vaccine-preventable diseases circulating in Europe. We therefore performed a systematic review conforming to PRISMA guidelines (PROSPERO CRD42016045798) to explore: (i) interventions that improve vaccine uptake among migrants; and (ii) cost-effectiveness of vaccination strategies among this population. We searched MEDLINE, Embase, CINAHL, and Cochrane Database of Systematic Reviews (CDSR) between 1 January 2006 to 18 June 2018. We included three primary intervention studies performed in the EU/EEA or high-income countries and one cost effectiveness study relevant to vaccinations in migrants. Intervention studies showed small but promising impact only on vaccine uptake with social mobilization/community outreach, planned vaccination programs and education campaigns. Targeting migrants for catch-up vaccination is cost effective for presumptive vaccination for diphtheria, tetanus, and polio, and there was no evidence of benefit of carrying out pre-vaccination serological testing. The cost-effectiveness is sensitive to the seroprevalence and adherence to vaccinations of the migrant. We conclude that scarce but direct EU/EEA data suggest social mobilization, vaccine programs, and education campaigns are promising strategies for migrants, but more research is needed. Research should also study cost effectiveness of strategies. Vaccination of migrants should continue to be a public heath priority in EU/EEA.

© 2018 Elsevier Ltd Iron mediates many biochemical processes in neural networks that proliferate during brain development. Insufficient iron causes irreversible neurodevelopmental deficits, and most high-income countries recommend that infants older than 4–6 months receive additional iron via food fortification or supplementation to prevent iron-deficiency anaemia. Now that the prevalence of iron-deficiency anaemia in children has decreased to less than 10% in most developed countries, concerns that the recommended intakes far exceed those required to prevent iron-deficiency anaemia have been raised, and emerging evidence suggests that iron overexposure could be linked to adverse outcomes later in life. In this Viewpoint, we discuss the importance of iron for neurodevelopment, investigate the biochemical markers used to assess iron stores, summarise the disparity in public health policies among high-income countries, and discuss the potential association between iron overexposure and adverse neurological outcomes later in life. We present a case for new studies to establish the optimal amount of iron that both prevents deficiency and reduces the potential risk of long-term negative health outcomes.

BACKGROUND: Anemia affects over 500 million women, and in pregnancy is associated with impaired maternal and infant outcomes. Intermittent antenatal iron supplementation is an attractive alternative to daily dosing; however, the impact of this strategy on infant outcomes remains unclear. We compared the effect of intermittent antenatal iron supplementation with daily iron supplementation on maternal and infant outcomes in rural Viet Nam. METHODS AND FINDINGS: This cluster randomised trial was conducted in Ha Nam province, Viet Nam. 1,258 pregnant women (< 16 wk gestation) in 104 communes were assigned to daily iron-folic acid (IFA), twice weekly IFA, or twice weekly multiple micronutrient (MMN) supplementation. Primary outcome was birth weight. Mean birth weight was 3,148 g (standard deviation 416). There was no difference in the birth weights of infants of women receiving twice weekly IFA compared to daily IFA (mean difference [MD] 28 g; 95% CI -22 to 78), or twice weekly MMN compared to daily IFA (MD -36.8 g; 95% CI -82 to 8.2). At 32 wk gestation, maternal ferritin was lower in women receiving twice weekly IFA compared to daily IFA (geometric mean ratio 0.73; 95% CI 0.67 to 0.80), and in women receiving twice weekly MMN compared to daily IFA (geometric mean ratio 0.62; 95% CI 0.57 to 0.68), but there was no difference in hemoglobin levels. Infants of mothers who received twice weekly IFA had higher cognitive scores at 6 mo of age compared to those who received daily IFA (MD 1.89; 95% CI 0.23 to 3.56). CONCLUSIONS: Twice weekly antenatal IFA or MMN did not produce a clinically important difference in birth weight, when compared to daily IFA supplementation. The significant improvement in infant cognitive outcomes at 6 mo of age following twice weekly antenatal IFA requires further exploration, and provides additional support for the use of intermittent, rather than daily, antenatal IFA in populations with low rates of iron deficiency. TRIAL REGISTRATION: Australia

BACKGROUND: Hookworm infections are significant public health issues in South-East Asia. In women of reproductive age, chronic hookworm infections cause iron deficiency anaemia, which, upon pregnancy, can lead to intrauterine growth restriction and low birth weight. Low birth weight is an important risk factor for neonatal and infant mortality and morbidity. METHODOLOGY: We investigated the association between neonatal birth weight and a 4-monthly deworming and weekly iron-folic acid supplementation program given to women of reproductive age in north-west Vietnam. The program was made available to all women of reproductive age (estimated 51,623) in two districts in Yen Bai Province for 20 months prior to commencement of birth weight data collection. Data were obtained for births at the district hospitals of the two intervention districts as well as from two control districts where women did not have access to the intervention, but had similar maternal and child health indicators and socio-economic backgrounds. The primary outcome was low birth weight. PRINCIPAL FINDINGS: The birth weights of 463 infants born in district hospitals in the intervention (168) and control districts (295) were recorded. Twenty-six months after the program was started, the prevalence of low birth weight was 3% in intervention districts compared to 7.4% in control districts (adjusted odds ratio 0.29, 95% confidence interval 0.10 to 0.81, p = 0.017). The mean birth weight was 124 g (CI 68 - 255 g, p<0.001) greater in the intervention districts compared to control districts. CONCLUSIONS/SIGNIFICANCE: The findings of this study suggest that providing women with regular deworming and weekly iron-folic acid supplements before pregnancy is associated with a reduced prevalence of low birth weight in rural Vietnam. The impact of this health system-integrated intervention on birth outcomes should be further evaluated through a more extensive randomised-controlled trial.

BACKGROUND: We undertook an observational follow-up study of schistosomiasis serology in both travelers and immigrants in a nonendemic country to determine the natural history of schistosomiasis antibody titer post-adequate treatment in those who have not been reexposed. METHODS: Longitudinal study of all adult travelers and immigrants presenting to the Royal Melbourne Hospital, Australia with positive schistosomiasis serology (titer >1: 64) between July 1995 and December 2005. All patients were treated with praziquantel and followed up clinically and serologically for a period up to 30 months. RESULTS: A total of 58 patients were included in the study including 26 travelers and 32 immigrants. Antibody titers often increased in the first 6 to 12 months post-treatment, especially in immigrants. After 30 months of post-treatment, 68% of travelers and 35% of immigrants (p < 0.01) achieved a fourfold antibody decline. CONCLUSIONS: Schistosomiasis antibody titers varied after adequate treatment. Therefore an increase in titer in the first 6 to 12 months or a failure to reduce after 3 years should not automatically justify re-treatment.

BACKGROUND: There is increasing interest in underlying socio-cultural, economic, environmental and health-system influences on the persistence of malaria. Vietnam is a Mekong regional 'success story' after dramatic declines in malaria incidence following introduction of a national control program providing free bed-nets, diagnosis and treatment. Malaria has largely retreated to pockets near international borders in central Vietnam, where it remains a burden particularly among impoverished ethnic minorities. In these areas commune and village health workers are lynchpins of the program. This study in the central province of Quang Tri aimed to contribute to more effective malaria control in Vietnam by documenting the non-biological pathways to malaria persistence in two districts. METHODS: Multiple and mixed (qualitative and quantitative) methods were used. The formative stage comprised community meetings, observation of bed-net use, and focus group discussions and semi-structured interviews with health managers, providers and community. Formative results were used to guide development of tools for the assessment stage, which included a provider quiz, structured surveys with 160 community members and 16 village health workers, and quality check of microscopy facilities and health records at district and commune levels. Descriptive statistics and chi-square analysis were used for quantitative data. RESULTS: The study's key findings were the inadequacy of bed-nets (only 45% of households were fully covered) and sub-optimal diagnosis and treatment at local levels. Bed-net insufficiencies were exacerbated by customary sleeping patterns and population mobility. While care at district level seemed good, about a third of patients reportedly self-discharged early and many were lost to follow-up. Commune and village data suggested that approximately half of febrile patients were treated presumptively, and 10 village health workers did not carry artesunate to treat the potentia

Chronic hepatitis B virus (HBV) infection is a major health problem in sub-Saharan Africa, where prevalence is > or =8%, and is increasingly seen in African immigrants to developed countries. A retrospective audit of the medical records of 383 immigrants from sub-Saharan Africa attending the infectious diseases clinics at the Royal Melbourne Hospital was performed from 2003 to 2006. The HBV, human immunodeficiency virus (HIV) and hepatitis C virus (HCV) serological results are reported, with a focus on the isolated core antibody HBV pattern (detection of anti-HBc without detection of HBsAg or anti-HBs). Two-thirds (118/174, 68%) of those tested had evidence of HBV infection with detectable anti-HBc. Chronic HBV infection (serum HBsAg detected) was identified in 38/174 (22%) and resolved HBV infection (both serum anti-HBs and anti-HBc detected) in 45/174 (26%). The isolated core antibody pattern was identified in 35/174 (20%), of whom only 1/35 (3%) had detectable serum HBV DNA on PCR testing, indicating occult chronic HBV (OCHB). Only 8/56 (14%) patients with negative anti-HBc had serological evidence of vaccination (serum anti-HBs detected). HIV infection was detected in 26/223 (12%). HCV antibodies were detected in 10/241 (4%), of whom 8 (80%) had detectable HCV RNA. Viral co-infection was detected in only 2/131 (1.5%) patients tested for all three viruses. The isolated core antibody HBV pattern was common among sub-Saharan African patients in our study. These patients require assessment for OCHB infection and monitoring for complications of HBV.

Administration of a birth dose of hepatitis B vaccine (HepB vaccine) to neonates is recommended to prevent mother-to-infant transmission and chronic infection with the hepatitis B virus (HBV). Although manufacturers recommend HepB vaccine distribution and storage at 2-8 degrees C, recognition of the heat stability of hepatitis B surface antigen stimulated research into its use after storage at, or exposure to, ambient or high temperatures. Storage of HepB vaccine at ambient temperatures would enable birth dosing for neonates delivered at home in remote areas or at health posts lacking refrigeration. This article reviews the current evidence on the thermostability of HepB vaccine when stored outside the cold chain (OCC). The reports reviewed show that the vaccines studied were safe and effective whether stored cold or OCC. Field and laboratory data also verifies the retained potency of the vaccine after exposure to heat. The attachment of a highly stable variety of a vaccine vial monitor (measuring cumulative exposure to heat) on many HepB vaccines strongly supports policies allowing their storage OCC, when this will benefit birth dose coverage. We recommend that this strategy be introduced to improve birth dose coverage, especially in rural and remote areas. Concurrent monitoring and evaluation should be undertaken to affirm the safe implementation of this strategy, and assess its cost, feasibility and effect on reducing HBV infection rates. Meanwhile, release of manufacturer data verifying the potency of currently available HepB vaccines after exposure to heat will increase confidence in the use of vaccine vial monitors as a managerial tool during storage of HepB vaccine OCC.

The heat stability of hepatitis B vaccine (HepB vaccine) should enable its storage outside the cold chain (OCC), increasing access to the birth dose in areas lacking refrigeration. We compared the immunogenicity of a locally produced vaccine among infants who received three doses stored within the cold chain (n = 358) or for whom the first dose was stored OCC for up to one month (n = 748). Serum was collected from these infants at age 9-18 months. The vaccine was protective in 80.3% of all infants. There were no differences in the prevalence of a protective level of antibody or antibody titer among groups of infants according to storage strategy. Differences in antibody titer between certain groups of infants could be explained by different vaccination schedules. Where birth dose coverage will be improved, HepB vaccine can be taken OCC for up to one month without affecting its immunogenicity.

BACKGROUND: In developed countries, asymptomatic chronic Strongyloides stercoralis infection occurs in immigrants from endemic regions of the world. Accurate and reliable means of diagnosis and follow-up are required for effective management. The role of S stercoralis enzyme-linked immunosorbent assay (ELISA) in this context was examined. METHODS: In this study, 95 asymptomatic Laotian immigrants living in Melbourne, Australia, for an average of 12 years, were screened for S stercoralis infection using stool microscopy, eosinophil count, and serology by ELISA. Twenty-two patients with a positive ELISA were treated with albendazole, 400 mg twice daily for 3 days, and monitored with serology, fecal microscopy, and eosinophil counts at 2, 6, 12, and 36 months after treatment. RESULTS: Patients with moderately reactive baseline ELISA and no eosinophilia had no significant change in either measure over the 36 months of follow-up. All patients with a strongly reactive baseline ELISA showed a reduction in reactivity over the first 6 months of treatment. However, in 50% of these patients, reactivity increased between 12 and 36 months, suggesting treatment failure and relapse of infection. One patient had confirmed treatment failure based on the development of hyperinfection syndrome. CONCLUSION: The results support evidence that serology is a valuable tool in monitoring treatment responses in patients with suspected strongyloidiasis and highlights the need to ensure that S stercoralis is completely eradicated after treatment.

OBJECTIVE: Infection with hepatitis B (HBV) and hepatitis C (HCV) viruses is relatively common throughout South-East Asia and chronic infection can lead to severe consequences. This study assesses knowledge about HBV and HCV and estimates the seroprevalence of markers for these viruses in immigrants from Laos and Cambodia. METHODS: Ninety-five Laotian (aged 18-82 years) and 234 Cambodian (15-92 years) immigrants participated in separate community-based surveys conducted during 1998 and 2002, respectively. Participants completed a questionnaire on health status and level of knowledge about viral hepatitis. Blood samples were collected and tested for the presence of HBV and HCV markers. RESULTS: Nine per cent of Laotian and 8% of Cambodian participants were infected with HBV. While 49% of Laotian and 64% of Cambodian participants showed evidence of previous exposure to HBV, 30% and 9%, respectively, were vulnerable to infection. The seroprevalence of antibodies to HCV was 3% in the Laotian and 8% in the Cambodian participants. Between one-fifth and one-third of the Laotians and Cambodians who had heard of HBV and HCV knew of possible transmission routes for the viruses. Most of those with HBV or HCV infection were unaware they were infected. CONCLUSIONS: These findings indicate a significant prevalence of undetected HBV and HCV infections and an urgent need for the provision of culturally relevant information about viral hepatitis in immigrants of South-East Asian origin.

The following study was conducted as part of a review of management systems at a Provincial Health Department (Kampong Cham Province) and a National Health Programme (National Immunization Program) in 2002-2003 in Cambodia. The aim of this paper is to identify, analyse and recommend those management system factors that are critical to the success of health management performance, with a particular focus on provincial management. The review has identified critical success factors associated with health management performance at the sub-national level that include a stronger role for effective human resource management in health sector reform, elevation of the status of planning in senior level management, and the development of a more comprehensive and transparent finance system. These success factors will position the provincial level of health management to respond more effectively to the reform challenges of administrative de-concentration and political decentralization that are currently underway across a range of government sectors in Cambodia.

We report a recent case of toxic shock syndrome associated with menstruation which illustrates that this syndrome still occurs, even when tampons are used appropriately. A potential diagnostic test for the syndrome is also discussed.

There are limited prospective data for Haemophilus influenzae type b (Hib) disease in Asia, where some countries are considering vaccine introduction. A prospective population-based study was conducted to measure the incidence of Hib meningitis in children in two northern provinces of Thailand. Children <5 years with symptoms consistent with bacterial meningitis were enrolled in the study if inclusion criteria were met. The study enrolled 598 children with clinical meningitis, 76% of whom received lumbar puncture. The rate of probable bacterial meningitis was 26.6/100,000 children <5 years per year. There were four cases of laboratory confirmed Hib meningitis (rate 3.8/100,000 children <5 years per year). These findings suggest a relatively low incidence of Hib meningitis. However, additional data from studies of pneumonia are needed to define the Hib disease burden in Thailand.

To ascertain hepatitis B virus (HBV) infection rates for Vietnam, we surveyed HBV markers in two districts of Thanh Hoa province. We randomly selected 536 infants (9- < or = 18 months old), 228 children (4 to < or = 6 years old), 219 adolescents (14 to < or = 16 years old), and 596 adults (25 to < or = 40 years old). On questioning, none of those surveyed had received vaccine against HBV. Hepatitis B virus surface antigen (HBsAg) and total HBV core antibody (anti-HBc) were measured in all specimens, and HBV e antigen (HBeAg) in those positive for HBsAg, and HBV surface antibody (anti-HBs) were measured in all others. Current infection (HBsAg+) rates were infants = 12.5%, children = 18.4%, adolescents = 20.5%, and adults = 18.8%. Current or previous infection (HBsAg+, anti-HBc+, or anti-HBs+) increased with age (infants = 19.6%, children = 36.4%, adolescents = 55.3%, adults = 79.2%). Rates of HBeAg among those HBsAg+ were infants = 85.1%, children = 88.1%, adolescents = 71.1%, and adults = 30.4%. The epidemiology of HBV in Vietnam resembles that of many southeast Asian nations before introduction of vaccine. Immunization of newborns will have enormous impact on HBV-related morbidity and mortality there.

The prevalence of and risk factors for vitamin D deficiency were examined for recent adult immigrants from East Africa living in Melbourne. Demographic data were collected via a face-to-face questionnaire and risk factors predicting deficiency were examined. Suboptimal levels <25 nmol/L were found in 61 patients (53%; 74% of women; 20% of men). Lower levels were more likely in: (i) patients with a longer duration of residence in Australia, (ii) patients who were mostly covered when outdoors and (iii) women. Routine assessment for vitamin D deficiency should be considered for male and female immigrants from East Africa.

Combined vaccines have been advocated as an efficient method of paediatric vaccine delivery. This study examined the performance and cost implications for the use of combined DTP-HB vaccine in the Thai immunisation program. Separate DTP and HB and then combined DTP-HB vaccines were used in the infant immunisation program in Chiangrai Province during a 4-year period. DTP vaccination coverage was maintained with the combined vaccine and HB coverage was improved (95.7% for DTP-HB1, 95.2% for DTP-HB2 and 93.8% for DTP-HB3). Seroconversion rates for anti-HBs rose from a baseline of 88.4 to 94.8% with use of the combined vaccine. Seroconversion rates for anti-D (97.5%) and anti-P (89.6%) were higher in the separate vaccine regimen. Although this study was not able to demonstrate that DTP-HB vaccine was more cost saving than the vaccines given separately as baseline vaccine coverage was already high, in settings where coverage rates are much lower the increased cost of combined vaccines may be more justifiable.

The diagnosis and management of parasitic diseases of the central nervous system (CNS) is difficult, even for infectious diseases physicians and neurologists. Furthermore, few overviews of the spectrum of causative helminths and clinical syndromes have been published. In the present study, we review the seven most common parasitic diseases of the CNS: (i) cysticercosis, (ii) neuroschistosomiasis, (iii) paragonimiasis, (iv) angiostrongyliasis, (v) hydatid disease, (vi) sparganosis and (vii) gnathostomiasis. Major syndromes of parasitic disease of the CNS and their differential causes are discussed, including: (i) cystic lesions, (ii) enhancing granulomas (with and without creeping subcutaneous eruptions), (iii) eosinophilic meningoencephalitis and (iv) spinal cord disease. Specific risk factors that predispose to these infections are also discussed and particular attention is drawn to the situation in Australia.

During the period 1974-91 large numbers of Southeast Asian immigrants and refugees were resettled in Western countries, including Australia. Health screening during this period demonstrated that intestinal parasite infections were common. A cross-sectional survey of 95 Laotian settlers who arrived in Australia on average 12 years prior to the study was conducted to determine if chronic intestinal parasite infections were prevalent in this group. Twenty-three participants had positive Strongyloides stercoralis test results (22 with positive serology, including I with S. stercoralis larvae detected in faeces and another with larvae and equivocal serology). Of these 23 participants, 18 (78%) had an elevated eosinophil count. Two patients had eggs of Opisthorchis spp. identified by faecal microscopy. The detection of chronic strongyloidiasis in Laotian settlers is a concern because of the potential serious morbidity associated with this pathogen.

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.

Hepatitis B (HB) immunization was introduced as part of the expanded programme on immunization (EPI) in two provinces in Thailand and evaluated over a four year period. Three doses of HB vaccine were offered to 60,980 newborns at birth, 2 and 6 months of age. The overall coverage for complete HB immunization was 90.4%. Serosurveys of randomly selected children under the age of 5 years were undertaken before and at the end of the project. Levels of HBsAg positivity were reduced by 85%, and there was a corresponding 70% increase in protective immunity. These findings demonstrate that HB immunization can be successfully integrated into EPI without adverse effect on coverage rates of other antigens, and results in a marked reduction in the rate of chronic carriage of HB virus in preschool age children.

OBJECTIVE: To determine the proportion of Australian travellers to Africa at risk of Schistosoma infection, and the proportion of those infected. DESIGN AND PARTICIPANTS: Retrospective postal survey of 360 patients who had attended Fairfield Hospital travel clinic in 1994 and stated an intention to travel to Malawi, Zimbabwe or Botswana. MAIN OUTCOME MEASURES: Self-reported risk status for Schistosoma infection. For those at risk, results of an indirect haemagglutination assay (IHA). For those with IHA titres > or = 1:32, results of enzyme-linked immunosorbent assay, urine microscopy and eosinophil count. RESULTS: 360 letters were sent; 35 were returned to sender. Of the 325 remaining, 250 (77%) either responded or had an IHA test; 19 of these were still overseas or did not travel. 117/231 (51%) returned travellers considered themselves at risk of infection. Significantly fewer older patients reported exposure (chi 2 = 66.6; P < 0.001). 109/117 (93%) of those at risk had IHA tests and 18 had titres > or = 1:32. Subsequent testing indicated infection in 10/117 travellers (8.5%; 95% CI, 4.2%-15.2%). CONCLUSION: Our findings indicate that a considerable number of Australian travellers to Africa are at risk of schistosomiasis, and some are infected. As complications can be serious, screening is recommended for individuals with any risk of infection, and treatment should be offered to those infected.

The susceptibility of patients with AIDS to certain opportunistic infections is due to defective cell-mediated immunity. The contribution of direct infection of macrophages with HIV-1 to this defect is unknown. To address this issue, we infected normal human monocyte-derived macrophages with a monocytotropic strain of HIV-1 and examined their ability to phagocytose and kill the opportunistic pathogen, Toxoplasma gondii. Phagocytosis of heat-killed T. gondii was reduced in HIV-infected macrophages compared with mock-infected controls. Opsonization of heat-killed T. gondii increased phagocytosis by both mock- and HIV-infected macrophages, but phagocytosis in HIV-infected cultures remained lower than in controls. Internalization of live T. gondii by macrophages was unaffected by HIV infection. Intracellular replication of live T. gondii was enhanced by HIV infection, as shown in four experiments, each using monocyte-derived macrophages from a different donor. Treatment of HIV-infected macrophages with IFN-gamma decreased parasite replication but not to control levels. These findings suggest that infection of macrophages by HIV may be a contributing factor to the reactivation of T. gondii infection in patients with AIDS.

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.

Why does Plasmodium falciparum cause severe illness in some but not all infections? How is clinical immunity acquired? These questions have intrigued investigators since the clinical epidemiology of malaria was first described. The search for answers to both questions has highlighted the changes that take place at the surface of infected red blood cells during the last half of the erythrocytic cycle. These changes specify the antigenic and adhesive or cytoadherence phenotypes for the infected cell. Now the antigenic and adhesive phenotypes appear to be linked and together undergo clonal variation. In this article David Roberts, Beverley-Ann Biggs, Graham Brown and Christopher Newbold explain how clonal phenotypic variation and the linkage between adhesive and antigenic types contribute to our understanding of naturally acquired immunity and of pathogenesis of severe malaria.

Erythrocytes (E) infected with asexual forms of malaria parasites exhibit surface antigenic variation. In Plasmodium falciparum infections, the variant Ag is the P. falciparum E membrane protein 1 (PfEMP1). This molecule may also mediate the adherence of infected E to host venular endothelium. We show here that parasite lines selected for increased adherence to endothelial cells have undergone antigenic variation. Three adherent lines selected from the same P. falciparum clone reacted with the same agglutinating antiserum that failed to agglutinate the parental clone. Immunoprecipitation experiments with the agglutinating anti-serum demonstrated that the selected lines expressed cross-reactive forms of PfEMP1 that were of higher m.w. and antigenically distinct from PfEMP1 of the parental clone. When one of the adherent lines was cloned in the absence of selection, a range of variant antigenic types emerged with differing cytoadherence phenotypes. These findings show that selection for cytoadherence in vitro favors the emergence of antigenic variants of P. falciparum and suggest that the requirement for cytoadherence in vivo may restrict the range of antigenic variants of P. falciparum in natural infections.

Antigenic variation of infectious organisms is a major factor in evasion of the host immune response. However, there has been no definitive demonstration of this phenomenon in the malaria parasite Plasmodium falciparum. In this study, cloned parasites were examined serologically and biochemically for the expression of erythrocyte surface antigens. A cloned line of P. falciparum gave rise to progeny that expressed antigenically distinct forms of an erythrocyte surface antigen but were otherwise identical. This demonstrates that antigenic differences on the surface of P. falciparum-infected erythrocytes can arise by antigenic variation of clonal parasite populations. The antigenic differences were shown to result from antigenic variation of the parasite-encoded protein, the P. falciparum erythrocyte membrane protein 1.

The survival of Plasmodium falciparum-infected erythrocytes is enhanced by the sequestration of mature trophozoites and schizonts from the peripheral circulation. Cytoadherence of infected erythrocytes in vivo is associated with the presence of knobs on the erythrocyte surface, but we and others have shown recently that cytoadherence to C32 melanoma cells may occur in vitro in the absence of knobs. We show here that a knobless clone of P. falciparum adheres to the leukocyte differentiation antigen, CD36, suggesting that binding to CD36 is independent of the presence of knobs on the surface of the infected erythrocyte. This clone showed little cytoadherence to immobilized thrombospondin or to endothelial cells expressing the intercellular adhesion molecule 1. Furthermore, an Mr approximately 300-kD trypsin-sensitive protein doublet was immunoprecipitated from knobless trophozoite-infected erythrocytes. Finding a P. falciparum erythrocyte membrane protein 1 (PfEMP1)-like molecule on these infected erythrocytes is consistent with a role for PfEMP1 in cytoadherence to CD36 and C32 melanoma cells.

We have previously described a colorimetric test, designated an amplified DNA assay (ADA), for specific segments of DNA amplified by polymerase chain reactions (PCRs), suited to diagnostic applications. This relied on binding the amplified DNA via a sequence in one oligodeoxyribonucleotide (oligo) to the DNA-binding protein GCN4 coated on the wells of a microtiter dish. Avidin-peroxidase was then bound to biotin at the 5' end of the other oligo and detected colorimetrically. Two successive PCRs with nested oligos were utilized. We describe here several modifications that greatly simplify the ADA. First, we bind the DNA to a glutathione S-transferase-GCN4 fused polypeptide (GST-GCN4) and avidin-peroxidase simultaneously, rather than successively. Second, we carry out the two successive PCRs in the one reaction mixture, using the thermal stabilities of oligos of differing lengths to separate the two reactions. Third, PCRs can be performed in the wells of a microtiter dish and the amplified DNA captured and detected via GST-GCN4 immobilized on beads attached to the lid of the microtiter dish. Hence it is only necessary to pipette the DNA sample once, and up to 96 samples can then be handled simultaneously.

We show that chromosome 9 in all isolates and clones of Plasmodium falciparum examined so far exists as one of two distinctly different forms, a large form about 1.9 megabases long or a smaller form about 25% shorter. Physical maps of chromosome 9 from independent clones with large and small forms of chromosome 9, and from an isolate with the large form and 3 derived clones with the small form reveal the underlying structural basis of this size polymorphism. The small form differs from the large only in that there are subtelomeric deletions at each end, one of these deletions involving about 0.45 megabases. Remarkably, the breakpoints map within about +/- 1% of the total chromosome length for each of these populations. We discuss some possible mechanisms for this.

Malaria continues to be a major international public health problem but many Australians who travel overseas are ill-informed of the risk of infection and have inadequate protection against this potentially fatal disease. Management is complicated by the resurgence of malaria in areas that have previously had satisfactory control programmes, and the emergence of resistance to chloroquine and other drugs. This article focuses on prevention of malaria in travellers. The more important issue of malaria control for populations residing in endemic areas is beyond the scope of this review.

P. falciparum is the cause of the lethal form of malaria which results in thousands of deaths each year. The primary cause of death, cerebral malaria, is associated with the sequestration of erythrocytes infected with the mature stages of P. falciparum (trophozoites and schizonts) in the post capillary venules of the brain. The identification of the parasite protein(s) involved in this process will provide important vaccine candidate molecules and knowledge about the pathological processes involved in cell-cell adhesion in general. The mechanism of cytoadherence is studied in vitro using cultured lines of P. falciparum which bind to umbilical vein endothelial cells and C32 amelanotic melanoma cells. Mature stages of the parasite may induce knob-like protrusions in the erythrocyte membrane, and it was previously thought that ‘knobs’ were necessary although not sufficient for cytoadherence to occur both in vitro and during natural infection. We have derived a clone of the Brazilian isolate of P. falciparum, ITG2F6, and selected for cytoadherence by repeated passage over amelanotic melanoma cells. Chromosome analysis using pulsed-field gradient electrophoresis and DNA amplification using the polymerase chain reaction reveal that this clone has deleted the gene coding for knobs. Furthermore, cytoadherence which is independent of knobs occurs via the receptor for the platelet protein, thrombospondin.