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Typhoid remains a disease of major importance world-wide although improvements in public health have made it an exotic disease in developed countries like Australia. Effective antibiotic therapy with the advent of chloramphenicol, which was first used to treat typhoid in the 1940s, has also dramatically altered the natural course of the disease and reduced its mortality rate from around 25% to as low as 1%. The main areas of recent change include the emergence of resistance to previously effective antibiotics, more aggressive intervention in the management of severe typhoid and some of its complications such as perforation, and the development of an oral typhoid vaccine that may replace the equally effective but more unpleasant parenteral vaccination that has been widely used since World War.

During pregnancy, specific variants of Plasmodium falciparum-infected erythrocytes (IEs) can accumulate in the placenta through adhesion to chondroitin sulfate A (CSA) mediated by expression of PfEMP1 encoded by var2csa-type genes. Antibodies against these variants are associated with protection from maternal malaria. We evaluated antibodies among Kenyan, Papua New Guinean, and Malawian men and Kenyan children against two different CSA-binding P. falciparum isolates expressing var2csa variants. Specific IgG was present at significant levels among some men and children from each population, suggesting exposure to these variants is not exclusive to pregnancy. However, the level and prevalence of antibodies was substantially lower overall than exposed multigravidas. IgG-binding was specific and did not represent antibodies to subpopulations of non-CSA-binding IEs, and some sera inhibited IE adhesion to CSA. These findings have significant implications for understanding malaria pathogenesis and immunity and may be significant for understanding the acquisition of immunity to maternal malaria.

Antibodies to variant surface antigens (VSA) including Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) have been associated with protective antimalarial immunity that appears to be variant-specific. This study of adult returned travelers with a single acute P. falciparum infection investigated whether a primary antibody response includes IgG specific for heterologous VSA. We found that 11 of 14 patients had IgG reactive with up to six P. falciparum lines expressing different heterologous PfEMP1 variants, measured by flow cytometry (reactivity greater than two times the mean of the negative control sera was defined as "positive"), with high reactivity (greater than four times the mean of the negative controls) detected in three patients. The dominant variant(s) recognized differed between seropositive individuals. Despite previous evidence that antibody responses to heterologous VSA are short-lived, seven patients had detectable IgG at20 weeks post-infection. Together these data suggest that a single P. falciparum infection can be sufficient to induce antibodies reactive with several PfEMP1 variants, although the repertoire of target epitopes they recognize may still be restricted.

Transcription of the majority of the members of the Plasmodium falciparum var multigene family were analysed in two isolates by a quantitative approach. Both of these isolates had been repeatedly selected for adhesion to chondroitin sulphate A (CSA) and one had also been selected for adhesion to hyaluronic acid (HA). These adhesion phenotypes are expressed by many parasites isolated from placentae and are associated with malaria disease in pregnancy. Increased transcription of the var gene var2csa, or its homologue IT4 var4, was associated with the CSA and HA adhesion phenotypes in all parasites suggesting that it was the dominant, if not the only, var gene that encoded adhesion to CSA in these allogeneic isolates. Some var genes were consistently transcribed at higher levels than others regardless of expressed adhesion phenotypes suggesting a transcriptional hierarchy. Unspliced or partial transcripts were detected for most var genes tested. These atypical var gene transcripts may have implications for the regulation of var gene transcription.

In this study, we detected multiple var gene transcripts within single, mature trophozoite-infected red blood cells (iRBCs) bound to chondroitin sulphate A (CSA). Several of the var detected had previously been demonstrated to encode Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) variants with domains that mediated iRBC adhesion to receptors other than CSA. Parasites expressing the CSA-adherent phenotype transcribed far more of one var than of all others, but this gene was different from the two other var previously purported to encode adhesion to CSA. Previous work suggesting that only single var are transcribed by mature trophozoites needs re-examination in the light of these data from single, infected cells.

In the latter half of this century there has been a dramatic change in the treatment of helminthic infections. Two factors have contributed to this: an understanding of the major differences between helminths and other infectious agents, and the development of effective low-cost, single-dose, broad spectrum drugs. A program of administration of these drugs to school-aged children in developing countries is now being implemented and will result in a significant improvement in their health at a crucial time in their growth and development.

Snakes of the families Viperidae and Elapidae are responsible for the high incidence of morbidity and mortality after snake bites in countries of West Africa, the Indian subcontinent, South-East Asia, New Guinea and Latin America. Envenoming can cause local effects, notably tissue necrosis; and systemic effects, including paralysis, haemostatic disturbances, shock, increased capillary permeability, myocardial damage, rhabdomyolysis and acute renal failure. Specific hyperimmune serum (antivenom) is the mainstay of medical treatment for severe envenoming. Ancillary treatments such as assisted ventilation, repletion of circulating volume, renal dialysis and surgical debridement of necrotic tissues are needed in some cases. Scorpion stings are a common medical problem in middle and southern America, North Africa and the Middle East. Vasodilator drugs are important to counter the effects of massive catecholamine release. Bites by spiders and stings by hymenoptera and marine animals are responsible for deaths and morbidity in some tropical countries.

One decade after the first description of the acquired immunodeficiency syndrome (AIDS), the epidemic has become a world-wide public health problem. Infection with the human immunodeficiency virus (HIV) is now spreading most rapidly among the poorer populations in the industrialised world and in the developing world. It has become the most important cause of death among adults in the major African cities and it absorbs an ever increasing proportion of health care budgets. On a global scale heterosexual intercourse is now the most common mode of transmission of HIV, resulting in a growing problem of transmission of the virus from mother to child. As a result of the AIDS epidemic, the incidence of tuberculosis is rising in virtually all populations. Developing countries face a double, gigantic challenge in an unfavourable economic and political climate: caring for those infected with HIV and preventing new infections.AIDS is a world-wide public health problem spreading most rapidly among poorer populations. 200,000 people in Latin America, the Caribbean, Africa, and Asia had been reported to the World Health Organization (WHO) by early 1992 as having AIDS. Far more people are most likely afflicted, but unidentified as a result of widespread underreporting in the tropics. The WHO Global Program on AIDS estimates that 10 million adults and 1 million children have been infected with HIV since the start of the pandemic; 85% in developing countries. It may be that 1 in 40 adults in sub-Saharan Africa is HIV-seropositive. HIV infection will continue to spread throughout the tropics, especially in Africa South of the Sahara and South and southeast Asia. The cumulative number of infections will probably reach 40 million by the year 2000, of which more than 90% will be in developing countries. Factors supporting the pandemic are: large, young, sexually-active populations; untreated sexually transmitted diseases; lack of circumcision; and frequent sexual intercourse with prostitutes in cities with unbalanced male/female ratios. AIDS has become the most important cause of death among adults in major African cities, absorbing an ever-increasing proportion of heath care budgets. Heterosexual intercourse is the most common mode of HIV transmission. The impact of HIV infection and AIDS as well as the need for prevention in the developing world are discussed.

The 6 enzymes involved in de novo synthesis of pyrimidines were measured in Plasmodium falciparum isolated by saponin lysis from RBC's nonsynchronized and synchronized in vitro cultures. The total activities were found to be dependent on the stage of the P. falciparum cycle. In parasites isolated from synchronized cultures, the highest activities for all enzymes were found at about 27 hr after synchronization in the late trophozoite stage, or just before schizont formation. Merozoites and ring forms contained little de novo activity. The first enzyme of the pathway, carbamyl phosphate synthetase (CPS-II) preferentially utilized glutamine. Ammonia was a poor substrate. CPS-II was unstable in the absence of the cryoprotectants, dimethylsulfoxide and glycerol. The apparent Km for MgATP--was 3.8 +/- 0.7 mM and the enzyme in all morphological forms of P. falciparum (ring, mature trophozoites and schizonts) was inhibited by UTP. The activity of the fourth enzyme of the pathway, dihydroorotate dehydrogenase, appeared to be linked to the cell's respiratory chain; inhibitors of mammalian electron transport such as cyanide, amytal, antimycin A, thenoyltrifluoroacetone and ubiquinone analogs also inhibited the P. falciparum enzyme. The demonstration of the variation of activity of the pyrimidine enzymes correlates with the increased synthesis of nucleic acids in the late trophozoite stage. These observations provide a basis for the testing of the effectiveness of pyrimidine analogs as potential antimetabolites against various forms of the parasite.