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The role of lysosomes in the healing process of cutaneous leishmaniasis.

Biopsy material in early and late stages of cutaneous leishmaniasis was obtained. The ultrastructural study using acid phosphatase reaction as a marker for lysosomes showed that in early stages parasites proliferate undisturbed within macrophage cytoplasm. At later stages numerous degenerating parasites were seen and macrophage lysosomes were observed adhering to and pouring their contents into the parasite. It is assumed that activated macrophages control intracellular parasitism by lysosomal activity.

Adult↗

Strategic use of anthelmintics for parasitic nematodes in cattle and sheep.

Treatment regimes for the control of parasitic nematodes in cattle and sheep are reviewed. The advantages and disadvantages of each strategy are outlined and the veterinarian's judgement of the management and economic constraints involved when recommending a particular system to a client is emphasised.

Animals↗

Schistosomiasis vaccines: Farewell to the God of Plague?

Control and even eradication of schistosomiasis have been achieved in some countries using integrated measures but this disease remains endemic in 74 countries with 600 million at risk of whom 200 million are currently infected. The application of control measures, particularly population-based chemotherapy, has in many countries greatly reduced the incidence of serious disease manifestations, but vaccines are urgently needed to supplement existing control measures. Great advances are being made in vaccine development and the first clinical trials are expected to begin shortly.

Animals↗

Immunodiagnosis of trichinellosis: efficacy of somatic antigen in early detection of human trichinellosis.

Crude antigens prepared from the infective stage larvae of Trichinella spiralis were used for antibody detection by indirect ELISA and Western blotting in serum samples taken from trichinellosis patients and from normal, parasite-free controls. The serum specimens were collected from acute ill, symptomatic patients on the first day of treatment (Day 0), and then two months (M2) and 4 months (M4) later. The sensitivities of the indirect ELISA and Western blotting on Day 0 were 81% and 92%, respectively. Both tests were 100% sensitive for M2 and M4 serum samples. Every serum sample from the parasite-free controls tested negative by both immunological assays, indicating 100% specificity. Crude somatic antigens can therefore be used for the early detection of human trichinellosis (acute trichinellosis).

Adolescent↗

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 4. Perceptions of the causes of malaria and of its treatment and prevention in the study area.

Perceptions of the causes of malaria, its treatment and prevention were studied among 996 adults, selected randomly from 73 villages and hamlets in a rural area of The Gambia. Structured questionnaires and other interview techniques were used for data collection. Malaria has no specific name in the study area; it is referred to commonly as Fula kajewo (Fula fever). Only 28% of the respondents knew that mosquitoes transmitted malaria. However, most people believed correctly that August to October was the main malaria season. Eighty-six per cent of the subjects were bed net users. The majority of nets were produced locally, usually white in colour and made of sheeting fabrics. Usage of nets was correlated with ethnic group, age and polygamy but not with education, income, occupation or ownership of certain items which indicate high social status. Analysis of expenditure on mosquito coils indicated that non-users of nets spent 43% more on coils than did users. Bed nets have been used for a long time in the study area; 98% of users saw their parents using them during their childhood.

Adult↗

Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells.

Post HIV-1 entry, productive HIV-1 infection of primary T cells requires overcoming several cellular blocks to provirus establishment and replication. Activation of unknown host intracellular events overcomes such inhibitory steps and is concomitant with HIV-1 replication. We show that the transcription factor NFATc was sufficient as a cellular factor to induce a highly permissive state for HIV-1 replication in primary CD4+ T cells. NFATc overcame a blockade at reverse transcription and permitted active HIV-1 replication. Pharmacologic blockade of endogenous NFAT activity by FK506 or CsA inhibited synthesis of reverse transcription and also potently blocked HIV-1 replication. T cells therefore can become competent for HIV-1 replication by control of regulated host factors such as the NFATc transcription factor. The host mechanisms regulated by such permissivity factors are potential targets for anti-HIV-1 therapy.

CD4-Positive T-Lymphocytes↗

Ivermectin dose assessment without weighing scales.

Described are two alternatives to the weighing of patients for assessing the dose of ivermectin for use in mass chemotherapy campaigns against onchocerciasis. The first method uses height to separate patients into four dosing categories (1/2, 1, 11/2 and 2 tablets), while the second involves estimating one of these dosing categories according to an individual's physical appearance, without making any measurements. Data for the height-based method were obtained from 6373 people who were taking part in a placebo-controlled trial of ivermectin in northern Nigeria. Use of an arbitrary trade-off of approximately 100 people "overdosed" for every person "underdosed" would lead to 0.5% of the population being underdosed by 1/2 tablet, 46.5% being dosed correctly, 51.7% being overdosed by 1/2 tablet, and 1.2% being overdosed by 1 tablet. The physical appearance approach involved three observers and 779 subjects. A total of 82% of the observers' estimates were "correct", with all the incorrect dosing deviating by only 1/2 tablet from the dose that the subjects should have received.

Adult↗

A new serum hydatid antigen detection test for diagnosis of cystic echinococcosis.

Cystic echinococcosis (CE) is a major public health problem with a worldwide distribution in both humans and animals. Diagnosis of this disease by simple and rapid immunoassays is a priority. The objective of the present study was to standardize and evaluate the latex agglutination test (LAT) as a simple test for the detection of circulating hydatid antigen in serum. The subjects in this study included 141 patients in the following groups: surgically confirmed CE cases (18), ultrasound-proven cases (26), presumptive CE cases (47), controls with other parasitic disease (25), and healthy controls (25). A polystyrene latex (0.81 microm) suspension was used as a carrier particle for hydatid antibodies in the test. The latex particles were sensitized with hyperimmune hydatid antiserum raised in rabbits. The hydatid antibody-sensitized latex particles were used for the detection of hydatid antigens in serum. The results of the study showed that the LAT could detect the circulating hydatid antigen in 13 (72%) of 18 patients with surgically confirmed CE, 17 (65%) of 26 patients with ultrasound-proven CE, and 19 (40%) of 47 presumptive cases of CE. The test detected antigen in 1 (4%) of 25 controls with other parasitic disease, and no antigen was detected in the serum of 25 healthy controls. The LAT showed a sensitivity of 72%, a specificity of 98%, a positive predictive value of 93%, and a negative predictive value of 91%. The present study is the first report of the LAT for the detection of hydatid antigen in serum in the diagnosis of CE.

Adult↗

Socioeconomic development, health interventions and mortality decline in Costa Rica.

Costa Rica, whose life expectancy was 74 years by 1985, has reached a health level comparable to a developed country. The health achievements of this country are product of political and socioeconomic circumstances as well as of right public health policies. Until about 1970 the features of Costa Rica mortality, although somewhat better than the Latin American average, evolved in a similar way to the rest of the region. In particular, the decades of 1940s and 1950s saw dramatic improvements in life expectancy, thanks mainly to the import of low-cost, high-effectiveness health technologies. In the 1970s, however, Costa Rica departed from a regional pattern of stagnation and managed to close the gap with developed countries in terms of mortality levels. A dramatic decline in the infant mortality rate from 60 to 19 per 1,000 took place in this decade. The main determinants of this breakthrough were health interventions, notably a primary health care program, even though favorable socioeconomic conditions and a reduced fertility also played a role. Ecological data and other evidence suggest that up to three fourths of the mortality decline was accounted for contemporary improvements in public health services, with about 40 percent attributable to primary health care interventions. Furthermore, by targeting interventions on the less privileged population, these interventions had the merit of reducing geographic and socioeconomic differentials in child mortality.

Cause of Death↗

ShAR2beta, a divergent nicotinic acetylcholine receptor subunit from the blood fluke Schistosoma.

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that mediate the fast actions of the neurotransmitter, acetylcholine. Invertebrate nAChRs are of interest as they are targets of widely-selling insecticides and drugs that control nematode parasites. Here, we report the cloning of ShAR2beta, a candidate nAChR subunit from the blood fluke, Schistosoma haematobium, which is the third trematode nAChR subunit to be characterized. While ShAR2beta possesses key structural features common to all nAChRs, its amino acid sequence shares considerably low identity with those of insect, nematode and vertebrate nAChR subunits. In particular, the second transmembrane domain of ShAR2beta, which lines the ion channel, bears unusual amino acid residues which will likely give rise to a receptor with distinct functional properties. Phylogenetic analysis shows that ShAR2beta is a divergent nAChR subunit that may define a clade of trematode-specific subunits. We discuss our findings in the context of potentially exploiting this receptor as a target for controlling schistosome parasites.

Amino Acid Sequence↗

Incidence of malaria among children living near dams in northern Ethiopia: community based incidence survey.

OBJECTIVE: To assess the impact of construction of microdams on the incidence of malaria in nearby communities in terms of possibly increasing peak incidence and prolonging transmission. DESIGN: Four quarterly cycles of malaria incidence surveys, each taking 30 days, undertaken in eight at risk communities close to dams paired with eight control villages at similar altitudes but beyond flight range of mosquitoes. SETTING: Tigray region in northern Ethiopia at altitudes of 1800 to 2225 m. SUBJECTS: About 7000 children under 10 years living in villages within 3 km of microdams and in control villages 8-10 km distant. MAIN OUTCOME MEASURES: Incidence of malaria in both communities. RESULTS: Overall incidence of malaria for the villages close to dams was 14.0 episodes/1000 child months at risk compared with 1.9 in the control villages-a sevenfold ratio. Incidence was significantly higher in both communities at altitudes below 1900 m. CONCLUSIONS: There is a need for attention to be given to health issues in the implementation of ecological and environmental development programmes, specifically for appropriate malaria control measures to counteract the increased risks near these dams.

Adolescent↗

[An epidemiological survey to discover the probable places of infection with sleeping sickness in the Central African Republic].

The sleeping sickness focus at Nola-Bilolo in the forest region was the subject of a survey of 142 patients in order to discover their probable places of infection. Seventy of these patients had been detected by active case-finding during a survey conducted in January-February 1991; the other 12 had been discovered by passive case-finding during 1990. The sample of actively detected patients is significantly younger (average 22 +/- 3 years) than the sample detected passively (30 +/- 3 years). This survey highlights the geographical heterogeneity of transmission in the focus. The places where infection is highest are M'Poyo, which with 18% of cases forms the epicentre of the focus and the main reservoir of infecting flies, followed by Bilolo (9%), Mékara (8%), Modigui-Kouna, Ziendi and Domissili (7%). The patients, 95% of whom belong to the M'Bimou tribe, all engage in agriculture; the main activities are coffee-growing for men and the steeping of casava in the river for women. These two activities determine the main places and times of human-tsetse contact. The information obtained by listing the cases detected passively from medical registers is inadequate for locating the places of transmission. The information gathered during active case-finding campaigns by the mobile teams offers a better approach. The method used here, which is recommended, consists of matching the replies given by the patients about their points of contact with the tsetse flies, not just with their places of residence but also with their successive movements and their places of work. The rigour demanded by this kind of approach can only be ensured by a specific survey. This survey also made it possible to demonstrate substantial movements from village to village, which appear to be characteristic of this focus. The results indicate that poorly targeted vector control is likely to be doomed to failure. The study makes it possible to specify priority areas for vector control by trapping and to avoid a "blind" control strategy whereby the whole focus is swamped with traps. The latter strategy is not financially feasible for many countries of tropical Africa.

Adolescent↗

The National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention: a new administrative structure for schistosomiasis control.

Since more than 5 decades, the overall responsibility for the national programme on schistosomiasis control in China resides at the government level, i.e. Ministry of Health. Day-to-day activities are carried out by independent provincial parasitic institutes situated in the endemic areas. Along with the general economic development and the steady progress in the medical sciences, successful developments in control and research of the parasitic diseases in the country were achieved. This necessitated a corresponding reorganization of the administrative structures which has taken place at several levels. In January 2002, the Chinese Centre for Disease Control and Prevention was reorganized and the Institute of Parasitic Diseases in Shanghai became part of this new organization under the name of the National Institute of Parasitic Diseases to better reflect its new role. By assigning all administrative tasks regarding research and control of parasitic diseases under the umbrella of one administrative central laboratory, the new task force for epidemiological surveys and direction of parasitic control programmes is well suited to respond to the daunting challenges of the future. The new institution has only existed for a few years but has already become a well-functioning force with a broad contact net of national and international experts on research and control of parasitic diseases.

Academies and Institutes↗

Receptor-specific adhesion and clinical disease in Plasmodium falciparum.

One important factor in the virulence of infections with Plasmodium falciparum is the adherence of infected erythrocytes to small vessel endothelium. In infections that lead to serious, life-threatening disease accumulation of large numbers of infected cells in particular organs is thought to lead to organ dysfunction or failure. This is of particular relevance when the affected organ is the brain, leading to the development of cerebral malaria. Many different endothelial receptors for infected red blood cells have been identified. Some receptors such as CD36 and thrombospondin are used by all parasite isolates, whereas others such as intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule (VCAM) are used by a subset of field and laboratory isolates. While it has been speculated that the ability to bind or affinity of binding to a particular endothelial receptor may be related to the pattern of disease, only studies with limited numbers of patients have been carried out to date and these have been in general inconclusive. Here we have taken parasite isolates from 150 patients with defined clinical syndromes as well as isolates from 50 healthy but parasitized community controls and quantitatively assessed their binding to purified endothelial receptors in vitro. Our results show that disregarding the level of adhesion, all parasites bind to CD36, most bind to ICAM-1, few bind to VCAM, and almost none bind to E-selectin. In assessing the degree of binding we show that 1) binding to all receptors was reduced in parasites taken from severely anemic patients; 2) binding to CD36 is identical in parasites from cerebral malaria patients and community controls but slightly elevated in parasites from nonsevere cases; and 3) binding to ICAM-1 is highest in cerebral malaria patients. Because rosette formation by uninfected cells has also been a phenotype associated with disease severity and one that may interfere in vitro with receptor binding, we also assessed rosette formation in all isolates. In this study the highest level of rosette-forming parasites was found in the anemic group and not the cerebral malaria group. Stratifying the data for the frequency of rosette formation showed that the above results were not significantly altered by this phenomenon. Our data are not consistent with a role for binding to CD36 in the development of severe disease but show an association between the degree of binding to ICAM-1 and clinical illness in nonanemic patients.

Anemia↗

Parasitic diseases: opportunities and challenges in the 21st century.

The opportunities and challenges for the study and control of parasitic diseases in the 21st century are both exciting and daunting. Based on the contributions from this field over the last part of the 20th century, we should expect new biologic concepts will continue to come from this discipline to enrich the general area of biomedical research. The general nature of such a broad category of infections is difficult to distill, but they often depend on well-orchestrated, complex life cycles and they often involve chronic, relatively well-balanced host/parasite relationships. Such characteristics force biological systems to their limits, and this may be why studies of these diseases have made fundamental contributions to molecular biology, cell biology and immunology. However, if these findings are to continue apace, parasitologists must capitalize on the new findings being generated though genomics, bioinformatics, proteomics, and genetic manipulations of both host and parasite. Furthermore, they must do so based on sound biological insights and the use of hypothesis-driven studies of these complex systems. A major challenge over the next century will be to capitalize on these new findings and translate them into successful, sustainable strategies for control, elimination and eradication of the parasitic diseases that pose major public health threats to the physical and cognitive development and health of so many people worldwide.

Allergy and Immunology↗

Genetic control of immunity to parasites: adoptive transfer of immunity between inbred strains of mice characterized by rapid and slow immune expulsion of Trichinella spiralis.

Adoptive transfer of immunity with immune mesenteric lymph node cells (IMLNC) was used to analyse the roles of immune and inflammatory events in determining the strain-characteristic time of expulsion of Trichinella spiralis from mice. Transfer of IMLNC within and between three rapidly responding strains (NIH, SWR, DBA1-all H-2q) resulted in accelerated worm expulsion, worm loss commencing before day 8 in each case. When NIH cells were transferred to slow-responder B10 congenic mice (B10G-H-2q) mice, immunity was evident at 8 days as a reduction in worm fecundity and only by 12 days as a reduction in worm numbers. A similar result was obtained when B10G cells were given to B10G recipients. In the reciprocal transfer, IMLNC from B10G transferred immunity to NIH as effectively and as rapidly as did NIH cells. Cells capable of transferring immunity were present in B10G mice as early as 4 days after infection, even though worm expulsion in this strain does not occur until after day 12. Thus following heterologous transfers of IMLNC, the time of worm expulsion was determined by the response of the recipient, and presumably by the ability to generate intestinal inflammatory changes. Earlier work has shown that the strain-characteristic time of worm expulsion is genetically determined, but not by H-2 linked genes. A corollary of the present work is that non-H-2 linked genes control the generation of intestinal inflammatory changes in T. spiralis infections. H-2 genes may control lymphocyte responsiveness to infection and the haplotype H-2q may determine a rapid response. Comparisons are made with the genetic control of resistance to Listeria monocytogenes and possible mechanisms are discussed.

Animals↗