Biomedical subjects
M Tanner
Publications and source records attributed to M Tanner.
The development of malaria vaccines: SPf66--what next?
Malaria, especially that caused by Plasmodium falciparum, is the most important parasitic disease of man. The complexity of the life cycle, the transmission dynamics in different endemic settings, and the spread of resistance to various drugs by the parasite and to insecticides by the vector render control strategies very difficult. An effective vaccine against malaria would represent a major strengthening of control. Research efforts to identify and select antigens for vaccine development have been substantial, particularly in the past 20 years. Various molecules from the pre-erythrocytic, asexual blood and sexual stages have been described and tested in experimental systems, and some may become interesting vaccine candidates. A crucial step was taken with the development of SPf66, a synthetic polypeptide based on pre-erythrocytic and asexual blood-stage proteins of Plasmodium falciparum. The concept of the SPf66 vaccine is not the prevention of clinical malaria but reduction of morbidity, and it is thus suitable for endemic areas, particularly Africa. The clinical phase III trials so far undertaken in Latin America and in Africa have clearly documented the safety, immunogenicity and partial efficacy of SPf66 against clinical malaria. The efficacy estimates of all trials are below those we generally demand from vaccines and when we aim to induce sterile immunity. Therefore, a large number of issues at the field and laboratory levels, such as ways of optimizing efficacy (doses, timing, age of vaccination), and understanding the mechanisms of action and effectiveness, need to be investigated before one can consider the public health use of SPf66 as a component of an integrated malaria control programme. The substantial tasks ahead involve (1) improving the vaccine which we have and (2) devising and testing new vaccines which may prove more efficacious. Malaria vaccines are now a reality, and the achievements of SPf66 to date, the ongoing research efforts with other vaccine candidates, and the potential of DNA vaccines make it possible to predict that widespread use of an efficacious vaccine no longer represents an unrealistic target.
Malaria and Casual Sex: What Travelers Know and How They Behave.
Background: Travelers to the tropics have been reported to comply poorly with recommendations regarding malaria and AIDS. This study addresses the problem of influencing travelers' behavior through different approaches to conveying advice. Method: 3509 people attending a large travel clinic were randomly allocated to different interventions, including brochures about the implications of "sex tourism" and the possibility of participating in a contest assessing knowledge of malaria and AIDS. A comparison group (n = 607) of travelers to Kenya was contacted at an airport. Anonymous, self-administered questionnaires were sent to all travelers after their return. Results: Compliance with chemosuppressive regimen for malaria was 87%. Well-informed travelers did not protect themselves more efficiently against malaria. The efficacy of a given intervention was found to vary according to the age, sex, or travel experience of the participants. Of travelers, 51% reported casual sex abroad (M/F: 69/31). Thirty-eight percent of these contacts were unprotected. Casual sex abroad and condom use were correlated with a history of casual sex in the home country. Condom use was especially low in young women, who were also more likely to have casual sex with fellow travelers than with local partners. Eight percent of the "sex tourism" brochure readers had engaged in casual sex with local partners (all travelers, 4%). Conclusions: Lack of knowledge does not appear to be the problem. Travelers need to be motivated to put their knowledge into practice. Our results suggest that risks relating to malaria and AIDS are perceived in a different manner and that counseling should be individualized. Contest questions can help start a discussion on ethical and health-responsible behavior. The target group of the "sex tourism" brochure was reached, but their behavior appears not to have changed. Objective criteria can help physicians recognize "high-risk" travelers. Travelers need to be made aware that they may encounter environments conducive to risky behavior and that, while abroad, they may react in unexpected ways.
Cytotoxic T lymphocytes to Plasmodium falciparum epitopes in an area of intense and perennial transmission in Tanzania.
Studies in The Gambia have provided indirect evidence that cytotoxic T lymphocytes (CTL) play a protective role against malaria in humans and recently, using allele-specific HLA class I peptide motifs, several peptide epitopes for CTL in four pre-erythrocytic Plasmodium falciparum antigens have been identified in naturally exposed Gambians. However, CTL levels were low, suggesting that boosting these low levels by immunization might provide substantial protection. In the Kilombero valley of Tanzania, malaria transmission is holoendemic and 300 times more intense than in The Gambia. We report here that several of the epitopes identified in The Gambia are also recognized in naturally exposed, partially immune Tanzanian adults and that levels of CTL are similar to or slightly higher than in Gambian subjects, despite the much higher inoculation rate. We report a new HLA-A2.1-restricted epitope from the thrombospondin-related anonymous protein (TRAP) and we demonstrate that peptide epitopes in TRAP are naturally processed for recognition by CTL from naturally exposed humans. The common allele of a variable HLA-B7-restricted epitope in the circumsporozoite protein behaved as an altered peptide ligand (APL) with respect to CTL cognate for a rarer allelic variant of this epitope, suggesting that APL antagonism may occur in natural CTL responses to P. falciparum. The moderate levels of CTL observed, even in this area of intense malaria transmission, points to the need to assess candidate vaccines aimed at increasing CTL levels.
Plasmodium falciparum malaria in the first year of life in an area of intense and perennial transmission.
A longitudinal study of Plasmodium falciparum malaria in infants in Idete village, south-eastern Tanzania, was conducted over a period of 14 months in order to determine the incidence of P. falciparum infection and clinical malaria in the first year of life. Of 1356 blood slides from cross-sectional surveys, 52.1% were positive for asexual stages of P. falciparum. There were marked increases in P. falciparum prevalence, parasite densities, overall fever incidence and the incidence of malaria fevers with age for the first 6 months of life. The average attack rate, estimated from a reversible catalytic model, was 0.029 per day with a slight increase with age but there was no initial period of protection against infection in neonates. Estimated average duration of infections was 64 days, with infections in older infants lasting much longer than those contracted during the first 2 months of life. These results support the hypotheses that the main effect of passively transferred maternal immunity to malaria is in the control of asexual stage parasites, and that the level of clinical immunity depends upon the extent of recent exposure to parasites. Infants as young as 4 months of age are at high risk of clinical attacks. Intervention programmes against malaria in areas of the highest transmission should therefore be designed to include this group.
Helminth infections, morbidity indicators and schistosomiasis treatment history in three villages, Dongting Lake region, PR China.
In order to estimate the public health impact of helminth infections, and to provide baseline data for interventions, parasitological and morbidity surveys were conducted among inhabitants of three villages in Dongting Lake region, Hunan Province, China. Ascaris lumbricoides was found to be the most common helminth infection, followed by Trichuris trichiura and Schistosoma japonicum. Left liver enlargement was the most common indicator of morbidity. Observed numbers of multiple species infections closely correlated with expected figures generated from a simple probabilistic model. Heterogeneity was observed in age and sex-standardized infection and morbidity prevalences among the villages and occupations. Males had higher levels of infection, were more likely to suffer morbidity, and were more likely to have been treated for schistosomiasis than women. The prevalence of each morbidity indicator was positively correlated with the number of times of treatment for schistosomiasis, and negatively correlated with number of years since last treatment. The results imply that treatment history for S. japonicum infection may be a good indicator of current morbidity risk.
Hepatitis A in a Chinese urban population: the spectrum of social and behavioural risk factors.
BACKGROUND: Viral hepatitis is a major public health problem in China. Hepatitis A infections represent a substantial proportion of these, particularly in urban centres. Little is known about the social and behavioural factors in the urban household environment that influence the transmission of hepatitis A. METHODS: We conducted a register-based case-control study to investigate the risk factor patterns for hepatitis A in the general population of the City of Wuhan, in the PR China. Cases were selected from district-based health registers. One control, matched for sex and age, was identified from the case's neighbourhood. Home-based interviews combined with household observation were performed to obtain information on social, behavioural and economic risk factors and the household's indoor and outdoor environment. Analysis included conditional logistic regression. RESULTS: Hepatitis A infection was associated with a variety of social and household-related factors, like handwashing habits (after working in the garden: adjusted odds ratio [OR] = 8.24, 95% confidence interval [CI]: 1.5-44.2, before food preparation: OR = 4.68, 95% CI: 1.8-12.0; before eating: OR = 4.92, 95% CI: 1.5-15.7), and the source of fresh vegetables (OR = 3.90, 95% CI: 1.6-9.8). Hygiene in the kitchen and the household surroundings and the disposal of children's stools in vegetable gardens or refuse pits were significantly associated with univariate analysis only. The lack of possession of luxury consumer items as a surrogate indicator for income was significantly associated with the disease (OR = 2.47, 95% CI: 1.0-6.1). The study clearly established that exposure to health and hygiene education was less in the group of hepatitis A cases when compared to healthy controls (OR = 2.80, 95% CI: 0.9-8.3). CONCLUSION: The results of this study underline how social and behavioural factors are important determinants for hepatitis A in urban Chinese populations. These issues could be addressed by appropriate health and hygiene education targeted at high risk groups, and by strengthening existing procedures for monitoring and control of food hygiene.
Duration of protection and age-dependence of the effects of the SPf66 malaria vaccine in African children exposed to intense transmission of Plasmodium falciparum.
The SPf66 synthetic vaccine is safe and partly efficacious against Plasmodium falciparum malaria among children 1-5 years old. The estimated vaccine efficacy [VE] for all clinical episodes over a period of 18 months after the third dose is 25% (95% confidence interval [CI], 1%-44%; P = .044). The observed temporal variations in efficacy could have been due to chance (likelihood ratio chi 2 = 13.8, 8 df; P = .086). Efficacy against clinical malaria did not vary significantly with age (chi 2 = 1.07, 4 df; P = .90). Overall parasite density was 21% lower in vaccine recipients than in the placebo group (95% CI, 0%-38%; P = .044). Further development of SPf66 may require trials to evaluate safety, immunogenicity, and efficacy when administered in the first year of life, together with other vaccines contained in the Expanded Programme of Immunization schedule.
The morbidity attributable to Schistosoma japonicum infection in 3 villages in Dongting Lake region, Hunan province, PR China.
In common with other helminth infections, symptoms associated with Schistosoma japonicum infection have a low specificity, and many infections are asymptomatic. The presence of the parasite in a sick individual from an endemic area does not mean that S. japonicum is the aetiological agent. However, estimates of the proportion of all symptomatic episodes in a community attributable to S. japonicum infection can be used to determine its public health impact. Using parasitological and morbidity survey data from 3 villages in China, the fractions of diarrhoea, bloody stool, and abdominal pain episodes that were attributable to S. japonicum infection were estimated. The association between hepatomegaly and S. japonicum infection was also assessed. For all morbidity indicators, it was found that individuals with higher infection intensities were at greater risk of morbidity. The highest risk indicator of morbidity associated with S. japonicum infection was bloody stools. Logistic regression revealed that factors related to village and sex were important confounders of the relation between infection and the risk of morbidity. The fraction of the population in each village estimated to be suffering morbidity attributable to S. japonicum infection was low, due to the low prevalence of infection. However, the results suggest that some sick individuals may have been diagnosed as false negatives for S. japonicum infection.
Prevalence of iodine deficiency disorders and goitre in Chad.
A nationwide sample survey was conducted in Chad to establish the prevalence of iodine deficiency disorders (IDD). The country was stratified into the Sahel zone and the Sudan zone, the latter including the city of N'Djamena. The analysis followed a stratification whereby the city of N'Djamena was also separately analysed. A total of 1171 people between 10 and 20 years of age were included in the survey. The overall weighted prevalence of goitre, evaluated by a clinical examination, was 63%. In the Sudan zone the prevalence was 70%, in the Sahel zone 64% and for the capital, N'Djamena, 25%. There were significant differences in the frequency of goitre between the three zones. Females-as established in surveys from other areas and countries-had goitre significantly more often. The prevalence of cretinism varied between 0 and 1.2%, and was highest in the Sahel zone. Amongst the sampled population of the Sudan zone, 33% had less than 20 micrograms/l of urinary iodine, indicating severe iodine deficiency. In the Sahel zone and in N'Djamena the figures reached 8 and 1%. There were high levels of thiocyanate anions in urine reaching medians between 21 and 27 mg/l in the geographical stratas. This probably decreases the bio-availability of iodine. These data show that there is a high endemicity of goitre in Chad and provide a basis for interventions as part of a national action plan against IDD, which will be adapted to the social, cultural and economic situation of the country and to available health services.
Lead-contaminated house dust and urban children's blood lead levels.
OBJECTIVES: This study assessed the relationship between lead-contaminated house dust and urban children's blood lead levels. METHODS: A random-sample survey was used to identify and enroll 205 children, 12 to 31 months of age, who had resided in the same house since at least 6 months of age. Children's blood and household dust, water, soil, and paint were analyzed for lead, and interviews were conducted to ascertain risk factors for elevated blood lead (> or = 10 micrograms/dL). RESULTS: Children's mean blood lead level was 7.7 micrograms/dL. In addition to dust lead loading (micrograms of lead per square foot), independent predictors of children's blood lead were Black race, soil lead levels, ingestion of soil or dirt, lead content and condition of painted surfaces, and water lead levels. For dust lead standards of 5 micrograms/sq ft, 20 micrograms/sq ft, and 40 micrograms/sq ft on noncarpeted floors, the estimated percentages of children having blood lead levels at or above 10 micrograms/dL were 4%, 15%, and 20%, respectively, after adjusting for other significant covariates. CONCLUSIONS: Lead-contaminated house dust is a significant contributor to lead intake among urban children who have low-level elevations in blood lead. A substantial proportion of children may have blood lead levels of at least 10 micrograms/dL at dust lead levels considerably lower than current standards.
Different approaches to modeling the cost-effectiveness of schistosomiasis control.
The limited economic resources available for health care in developing countries necessitates the involvement of cost analysis in the planning of any control intervention. A number of studies have undertaken cost-effectiveness analysis of schistosomiasis control, and the methodologies utilized in both cost and effectiveness evaluation are discussed. In attempting to relate cost to effectiveness, most studies have utilized static models expressing effectiveness in terms of coverage (drug delivery) or cure rate (infection prevalence reduction). These immediate output measures do not consider the long-term impact of control nor the effect on disease. An alternative approach is to use a model of the transmission dynamics of the parasite to permit evaluation of the long-term impact of control. An example of a population dynamic approach to cost-effectiveness analysis that can assess the impact of treatment on infection and disease due to the intestinal nematodes is presented to illustrate the potential of this approach in modeling the cost-effectiveness of schistosomiasis control.
Validation of reagent sticks in diagnosing urinary schistosomiasis in an urban setting.
In view of the established potential of reagent sticks for detecting haematuria, a pilot survey to validate their use in the diagnosis of urinary schistosomiasis in an urban setting was done at Kinyerezi primary school of Ilala district in Dar es salaam. From 404 pupils screened for the disease, 273 were positive for the eggs by microscopy (filtration method), giving a prevalence of 67.6% and 253 (92.6%) of those who were positive by microscopy were also positive for haematuria by reagent sticks. Out of 131 who had no disease, 113 (86.2%) were negative for haematuria by the reagent sticks. These findings indicate a high sensitivity and specificity of microhaematuria by the reagent sticks (92.6% and 86.2%) respectively. Taking microscopy as a standard test, macrohaematuria had a sensitivity and specificity of 40.6% and 90% respectively, for urinary schistosomiasis. The accuracy of microhaematuria by reagent sticks was 90% compared to macrohaematuria which was only 56.6%. The use of reagent sticks test in detecting microhaematuria is thus recommended as a valid and rapid diagnostic test for urinary schistosomiasis in the present setting.
Utilisation of government and private health services in Dar es Salaam.
Following the liberalisation of medical practice in Tanzania since the early 1990's, and the introduction of user fees in public hospitals in 1993, a household survey evaluated utilisation of health care in Dar es Salaam. A sample of 6,589 inhabitants was interviewed in April 1995 by means of a two-stage cluster sampling technique. Of the respondents, 32% reported some use of health care within the previous two weeks. Among these respondents, 35% had used government health services, 41% had used private services and self-treatment was chosen by 27%. The user patterns identified reveal that adults aged 15-49 years used government health service least often. Use of government services clearly decreased as the level of education, socioeconomic class and wealth status of the zone of residence of the ill person increased. Conversely in the study sample, there was an apparent tendency for people with a high level of education or belonging to a rich socio-economic class to use private facilities more often. The data also indicate that already after two years the private sector plays an important role in providing medical care and that a two-tier system of health care delivery is developing. In order to render the private sector complementary to public services, there is need for a coherent policy on legislation, development, regulation and control of private sector health services as well as a monitoring system to reinforce the policies.
Activity and thermostability of the small self-splicing group I intron in the pre-tRNA(lle) of the purple bacterium Azoarcus.
The 205-nt group I intron located in the pre-tRNA(lle) from the bacterium Azoarcus sp.BH72 is the smallest self-splicing group I intron identified to date. Comparative sequence analysis has placed this intron and the Anabaena pre-tRNA(Leu) intron into the same subgroup, IC3; we now compare their activity and stability. Unlike the Anabaena intron, the Azoarcus intron has two transitions in the kinetics of the first step of splicing. The faster transition occurs with a larger k(cat)/K(m) than that of the Anabaena or other group I introns, due to a rapid K(cat) (5 min(-1) at 32 degrees C) and a low K(m) for guanosine (17 microM). The excised intron circularizes by releasing a trinucleotide from the 5' end of the intron, another property unlike the Anabaena intron. Although it is smaller in size, the Azoarcus intron retains activity at higher temperatures, higher concentrations of urea, and higher pH than the Anabaena intron. Melting curves show that tertiary structure is disrupted at a lower temperature in the Anabaena intron. Some structural features that may explain the unusual stability of the Azoarcus intron include a G-C rich secondary structure and the presence of two 11-nt motifs, which are known to interact strongly with GAAA loops in group I and group II introns. The disruption of one of these interactions by substituting the Anabaena structural element in fact lowered the thermal stability of the Azoarcus intron. Thus, even superficially similar group I introns from the same structural subgroup can differ significantly in activity and stability.
Magnetic resonance imaging in assessment of rejection of a kidney allograft in the rat: effect of the somatostatin analogue SMS 201-995.
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Prevalence of third molars in dental practice attenders aged over 35 years.
There is a lack of information in the United Kingdom on the prevalence of third molars in older patients. The aim of this study was therefore to define the pattern of lower third molar retention in UK dental practice attenders aged 35 years and over. A random sample of 599 eligible patients from a rural dental practice were included in the study. Information was obtained from clinical notes and panoramic radiographs. Data collected included age, gender, presence or absence of lower third molars, number of teeth present in the lower arch and eruption status. Two hundred and sixty-four (44.1 per cent) had at least one lower third molar present (mean age = 57.1 years) while 335 (55.9 per cent) had no lower third molars (mean age = 50.2 years). The data suggest that a greater proportion of men than women retain at least one lower third molar although this finding was not statistically significant. Seventy per cent of retained lower third molars reported in the study were fully erupted. Sixty per cent were vertically placed. There was an association between age and number of teeth present (chi 2 = 38.85, 4DF, P < 0.05), older patients having fewer lower teeth. These data suggest that a large number of patients can expect to keep their lower third molars beyond the age of 35 years and that in many cases a conservative "wait and see' policy for lower third molars in the early twenties is appropriate.
Traditional healers in Tanzania: the treatment of malaria with plant remedies.
In order to collect ethnobotanical information about antimalarial plants which is essential for the further evaluation of the efficacy of plants an antimalarial remedies, we investigated the management of malaria with traditional herbal remedies, including the use, preparation and administration, by traditional healers in Tanzania. Interviews with traditional healers were conducted in different rural and urban places in Tanzania: in the Kilombero valley (Kilombero/Ulanga District), on the main island of Ukerewe (Ukerewe District), in the region near Bukoba town (Bukoba district), and in the settlement of Dar es Salaam (largest city in Tanzania). The results of the study show that all traditional healers treat malaria with herbal remedies consisting of one to five different plants. The list of plants which they use for antimalarial treatment contains a large number of species from different families. Multiple citations of plants by different healers were rare. Most of the respondents attributed to the plants mentioned, or to the remedies made from them, specific effects and sometimes side effects, explaining and illustrating their use or non-use for different patients or manifestations of the disease/illness.