Dogmas and misunderstandings in East Coast fever

East Coast fever (ECF) is the most important tick-borne disease in eastern, central and southern Africa and caused an estimated loss of US $186 million in 1989 in the 11 countries where it occurs. It was brought to southern Africa with cattle from Tanzania in 1901 and, over the next 3 years, devastated the cattle that had survived the rinderpest pandemic of the 1890s. Chemical control of ticks using arsenical compounds was introduced in the early 1900s and became the main control measure for both ticks and the diseases they transmit. This method of control has become less reliable over the last 30 years for many reasons, including reduced government spending on livestock and extension, the cost of acaricides, acaricide resistance, poor management of dips and spray races, and poor application of cattle movement control and quarantine. Significant advances in immunization and treatment have been made in the last 30 years, and more robust integrated strategies combining immunization, reduced frequency of chemical control and treatment are being adopted or considered. Throughout its history, ECF has been a source of great anxiety and cost to farmers, and of intense interest to research workers. Many dogmas and misconceptions have become established, some of which still flourish while others took years to demolish. This paper briefly reviews these as well as the history of the disease and explores recent epidemiological findings and their relevance to applying effective control.     

A recombinant fusion protein derived from dog hookworm inhibits autoantibody‐induced dermal–epidermal separation ex vivo

The proteins secreted by parasitic nematodes are evolutionarily optimized molecules with unique capabilities of suppressing the immune response of the host organism. Neutrophil inhibitory factor (NIF), which is secreted by the dog hookworm Ancylostoma caninum, binds to the β2 integrin CD11b/CD18, which is expressed on human neutrophils, eosinophils, monocytes and macrophages and inhibits neutrophil‐dependent lung injury and neutrophil invasion of ischaemic brain tissue. Neutrophils are key players in the pathogenesis of subepidermal autoimmune blistering diseases (sAIBDs), and their pathogenic activities are crucially dependent on β2 integrin functionality. Based on the template of single‐stranded, dimerizing antibody derivatives, which are already used in cancer treatment, we designed a novel biologic, NIF‐IGHE‐CH4, comprising NIF and the dimerizing but otherwise inert constant heavy subdomain 4 (CH4) of human IgE (IGHE). This molecule was evaluated in a variety of in vitro assays, demonstrating its ability to inhibit pathogenically relevant neutrophil functions such as migration, adhesion and spreading, and release of reactive oxygen species. Finally, we confirmed that NIF‐IGHE‐CH4 inhibits blister formation in an ex vivo assay of sAIBD. These results suggest that NIF‐IGHE‐CH4 is a novel potential anti‐inflammatory drug for the treatment of neutrophil‐mediated diseases such as sAIBDs. This study promotes the drugs from bugs concept and encourages further research and development focused on turning parasite proteins into useful anti‐inflammatory biologics.     

Protection and pathology during parasite infection: IL‐10 strikes the balance

The host response to infection requires an immune response to be strong enough to control the pathogen but also restrained, to minimize immune‐mediated pathology. The conflicting pressures of immune activation and immune suppression are particularly apparent in parasite infections, where co‐evolution of host and pathogen has selected many different compromises between protection and pathology. Cytokine signals are critical determinants of both protective immunity and immunopathology, and, in this review, we focus on the regulatory cytokine IL‐10 and its role in protozoan and helminth infections. We discuss the sources and targets of IL‐10 during parasite infection, the signals that initiate and reinforce its action, and its impact on the invading parasite, on the host tissue, and on coincident immune responses.     

Divergent investment strategies of Acacia myrmecophytes and the coexistence of mutualists and exploiters

Ant-plant interactions represent a diversity of strategies, from exploitative to mutualistic, and how these strategies evolve is poorly understood. Here, we link physiological, ecological, and phylogenetic approaches to study the evolution and coexistence of strategies in the Acacia–Pseudomyrmex system. Host plant species represented 2 different strategies. High-reward hosts produced significantly more extrafloral nectar (EFN), food bodies, and nesting space than low-reward hosts, even when being inhabited by the same species of ant mutualist. High-reward hosts were more effectively defended against herbivores and exploited to a lower extent by nondefending ants than low-reward hosts. At the phenotypic level, secretion of EFN and ant activity were positively correlated and a mutualistic ant species induced nectar secretion, whereas a nondefending exploiter did not. All of these mechanisms contribute to the stable association of high-reward hosts with defending ant species. However, exploiter ants are less dependent on the host-derived rewards and can colonize considerable proportions of the low-reward hosts. Mapping these strategies onto phylogenetic trees demonstrated that the low-reward hosts represent the derived clade within a monophyletic group of obligate ant plants and that the observed exploiter ant species evolved their strategy without having a mutualistic ancestor. We conclude that both types of host strategies coexist because of variable net outcomes of different investment–payoff regimes and that the effects of exploiters on the outcome of mutualisms can, thus, increase the diversity within the taxa involved.     

Antiparasitic protozoan vaccines

Parasitic infections caused by pathogenic protozoa affect over 1 billion people worldwide and impose a substantial health and economic burden, particularly on inter-tropical less-developed countries where they are more prevalent. Despite encouraging progress in vaccine development, chemotherapy remains the single most effective, efficient and inexpensive means to control most parasitic infections [1]. However, day to day parasites are becoming increasingly resistant to drugs currently in use, such as Plasmodium towards chloroquine, lending to the start of a promising future for vaccines. Patent applications regarding vaccines for the prevention, control and diagnosis of parasitic protozoan infections are reviewed for the period December 1996 - October 2000. However, vaccines for some of the protozoan infections do not appear in the literature in the period reviewed; only, vaccines against malaria, leishmaniasis, trypanosomiasis, cryptosporidiosis, pneumocystosis, eimeriosis, toxoplasmosis and neosporosis, as well as Babesia microti infections have been found.     

Feeding Period Required by Amblyomma aureolatum Ticks for Transmission of Rickettsia rickettsii to Vertebrate Hosts

Rocky Mountain spotted fever is endemic to the São Paulo metropolitan area, Brazil, where the etiologic agent, Rickettsia rickettsii, is transmitted to humans by adult Amblyomma aureolatum ticks. We determined the minimal feeding period required by A. aureolatum nymphs and adults to transmit R. rickettsii to guinea pigs. Unfed nymphs and unfed adult ticks had to be attached to the host for >10 hours to transmit R. rickettsii. In contrast, fed ticks needed a minimum of 10 minutes of attachment to transmit R. rickettsii to hosts. Most confirmed infections of Rocky Mountain spotted fever in humans in the São Paulo metropolitan area have been associated with contact with domestic dogs, the main host of A. aureolatum adult ticks. The typical expectation that transmission of tickborne bacteria to humans as well as to dogs requires ≥2 hours of tick attachment may discourage persons from immediately removing them and result in transmission of this lethal bacterium.     

Cutaneous leishmaniasis treated with itraconazole

Leishmaniasis is a human disease produced by a parasite of the Leishmania genus transmitted by prick of an infected female sandfly. The disease occurs clinically with either cutaneous, mucocutaneous or visceral form, depending on the infective species and the immune status of the patient. Antimonial drugs are the current treatment of choice for all clinical forms. We report a case of cutaneous Leishmaniasis in a young girl successfully treated with itraconazole.     

西藏儿童青少年肠道蠕虫感染情况的抽样调查

１９８８—１９９０年及１９９２年８—１２月，采用改良加藤法先后在西藏４地、市对５—２０岁儿童、青少年４９１０人进行了肠道蠕虫感染情况的调查。其中，粪检在校中、小学生２４３９人和社会上儿童与青少年（５－２０岁）人群２４７１人，分别查见蠕虫感染者１０１３例和４１６例，其感染率分别为４１．５％和１６．８％。经χ２检验，两者间差别具有极显著意义（χ２＝３６２．８７５６，Ｐ＜０．００１）。本次共查见肠道蠕虫１１种，上述两组人群主要５种寄生虫感染率分别为：蛔虫３１．８％和１０．４％、鞭虫１３．５％和３．９％、带绦虫３．４％和６．６％、钩虫１．０％和０．４％、蛲虫０．２％和０．３％。结果表明；在校学生和社会上５—２０岁人群中蠕虫感染率间差别具有极显著意义，地理环境、生活习惯、年龄及民族是影响儿童、青少年感染肠道蠕虫的重要因素。     

Evaluation of a rapid diagnostic test specific for Plasmodium vivax

Plasmodium vivax is the only human malaria indigenous to the Republic of Korea (ROK). A rapid and sensitive diagnostic test (RDT) that detects P. vivax is appropriate for evaluating suspected malaria patients with no travel history abroad. The RDTs, SD Malaria Antigen P.v (SD diagnostic, Kyonggi, ROK) specific for P. vivax and the well documented OptiMAL (DiaMed, Cressier, Switzerland) were compared among 282 volunteers for specificity and sensitivity of P. vivax and Plasmodium falciparum malaria infections against Giemsa-stained blood smears read by an experienced microscopist. A total of 137 volunteers were diagnosed with P. vivax, 45 cases (returned travellers from overseas) were diagnosed with P. falciparum and 100 healthy volunteers were diagnosed as negative for malaria. Correspondingly, the SD Malaria Antigen P.v test identified P. vivax infections in 128/137 malaria patients (93.4%) and 0/100 (0%) healthy volunteers. Three patients identified with P. falciparum also were interpreted as P. vivax by the SD Malaria Antigen P.v test; however, these patients were later confirmed as mixed infections of P. vivax and P. falciparum by polymerase chain reaction. OptiMAL interpreted the three mixed infections only as P. falciparum and detected 130/137 (94.9%) patients with P. vivax. The sensitivity of the SD Malaria Antigen P.v test decreased from 100% (>5000 parasite/microl) to 81.3% (1-100 parasites/microl) as parasitaemia levels declined. For the regions where P. vivax is the primary malaria parasite, the SD P. vivax-specific rapid diagnostic test may be useful for screening suspected malaria patients when sufficient material and human resources (e.g. trained microscopists) are unavailable for malaria diagnosis.     

Plasmodium falciparum-inhibitory monoclonal antibodies produced by human hybridomas

Stable human hybridomas were generated that produced inhibitory anti-Plasmodium falciparum monoclonal antibodies. Peripheral blood lymphocytes, obtained from adults in Liberia, a malaria endemic area, were immortalized with Epstein-Barr virus and then fused with KR4, a human, lymphoblastoid cell line. Stable hybridomas that produced anti-P. falciparum monoclonal antibody were identified by an ELISA assay that used the trophozoite and schizont antigens of both the Honduras I and FCR3 parasite strains. Monoclonal antibodies produced by selected hybridomas derived from lymphocytes of two individuals were subsequently studied. The anti-parasite antibodies were produced at 1-3 micrograms/ml in culture supernatants. All of the monoclonal antibodies bound specifically to trophozoites and schizonts of both strains of parasite in an indirect immunofluorescence assay and inhibited production of ring stage parasites by more than 90% when added to trophozoite or schizont containing erythrocytes in culture. Western immunoblot analysis of antigens obtained from trophozoites and schizonts (parasite age span of 36 to 48 h) was performed using either affinity purified or ammonium sulfate-concentrated monoclonal antibody. Antibody from three hybridomas which bound primarily to antigens of the Honduras 1 strain had Mr of approximately 140,000, 130,000 and 123,000.