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Biomedical subjects

M Tanner

Publications and source records attributed to M Tanner.

At least 127 records · Page 7Linked to original sources
PubMed1999

Consequences of multiple infection with Plasmodium falciparum in an area of high endemicity.

Most Plasmodium falciparum infections occur in partially immune hosts in highly endemic areas. In such situations, many hosts are simultaneously infected with multiple parasite genotypes, which must lead to intense competition between different parasite populations. We here summarise a series of studies of multiple infection, mostly using polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) genotyping of the highly polymorphic msp-2 gene. These indicate that chronic infections, characteristic of the partially immune host, appear to protect against super-infecting parasites. This protection is not seen in infants. A consequence is that selection for fast-growing (virulent) parasites, occurs mainly in the youngest, immunologically naïve, hosts. The normal situation for P. falciparum is one in which the host is partially immune, and competition between parasite genotypes in this situation is not expected to result in selection for virulence.

Adolescent↗
PubMed1999

[Diarrhea in urban agricultural workers in Nouakchott in Mauritania].

Nearly 200 million people in the developing world are dependent or urban gardening for food and income. This practice has been accelerated by the droughts of recent decades which have forced more and more migrants into urban areas. Numerous potential health hazards have been attributed to urban gardening but the exact risks in Sahelian areas remain unclear. The purpose of this cross-sectional study was to evaluate the incidence of diarrhea at the Tel Zatar gardening site in urban Nouakchott, Mauritania. In addition, a case-control study was carried out to identify risk factors for diarrhea in function of gardeners' activity and living conditions. Statistical analysis was performed using univariate and logistical regression methods. The annual incidence of diarrhea ranged from 6.9 (IC95 p. 100 = 5.0-8.8) to 8.5 (IC95 p. 100 = 6.2-10.8) episodes per gardener and year. Multivariate analysis identified four significant risk factors. Two of these factors were unrelated to gardening, i.e., not having spent more than USD 3.50 the previous day (odds ratio (OR = 2.8, IC95 p. 100 = 1.01-7.81) and poor food hygiene (cooking outside (OR = 4.69, IC95 p. 100 = 1.06-20.83). The other two factors were regular consumption of raw vegetables (OR = 25.5, IC95 p. 100 = 2.0-32.0) and use of untreated well water (OR = 3.85, IC95 p. 100 = 1.08-14.29). Unprotected well water was the cause of 59.2 p. 100 of diarrheal episodes reported by gardeners at Tel Zatar. The results of this study confirm that vegetable production in urban gardens such as Tel Zatar is associated with health risks. Public health measures should address not only the garden sites but also domestic hygiene.

Adult↗
PubMed1998

Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma.

We report here the molecular cloning of an approximately 1-Mb region of recurrent amplification at 20q13.2 in breast cancer and other tumors and the delineation of a 260-kb common region of amplification. Analysis of the 1-Mb region produced evidence for five genes, ZNF217, ZNF218, and NABC1, PIC1L (PIC1-like), CYP24, and a pseudogene CRP (Cyclophillin Related Pseudogene). ZNF217 and NABC1 emerged as strong candidate oncogenes and were characterized in detail. NABC1 is predicted to encode a 585-aa protein of unknown function and is overexpressed in most but not all breast cancer cell lines in which it was amplified. ZNF217 is centrally located in the 260-kb common region of amplification, transcribed in multiple normal tissues, and overexpressed in all cell lines and tumors in which it is amplified and in two in which it is not. ZNF217 is predicted to encode alternately spliced, Kruppel-like transcription factors of 1,062 and 1,108 aa, each having a DNA-binding domain (eight C2H2 zinc fingers) and a proline-rich transcription activation domain.

Amino Acid Sequence↗
PubMed1998

[Asylum seekers and refugees in general practice: problems and possible developments].

Health and health services provided to asylum seekers and refugees by the Swiss National Health System have so far not been systematically investigated. The aim of this cross-sectional study was to describe the attending asylum seekers and refugees demographically and clinically, to identify main problem areas as perceived by general practitioners and to highlight options and venues for improvements. 272 questionnaires have been filled in by GPs of eight "federal districts" (Kantone) and the consultations of 1477 asylum seekers and refugees have been documented during one month in 193 surgeries. The documented asylum seekers and refugees reflected the distribution of this population in Switzerland. Low consultation rates of asylum seekers and refugees in the majority of surgeries and high diversity of this population in respect to places of origin, education and proficiency in languages appear to be the major determinants of the difficulties in providing adequate health services to them. Readily available information on the past medical history and on the ethnic background of these patients and continuing education on specific topics concerning health care for asylum seekers and refugees were thought to be particularly useful. This needs to be considered in the planning of services for this group. General practitioners specialized in health care for asylum seekers and refugees is an option for providing improved specific services (interpreters, institutional links, culturally adapted medical care).

Adolescent↗
PubMed1998

[Asylum seekers and refugees in the medical polyclinic: a comparison between the Basel, Bern and Geneva polyclinics].

This cross-sectional study describes the state of health of asylum seekers and refugees and the health services provided to them by the medical outpatient departments of three major Swiss university hospitals, Basel, Berne and Geneva. The comparison of outpatient departments differing in organisational structure facilitated the identification of positive and negative determinants of health service provision. Questionnaires have been filled in by all physicians of the three medical outpatient departments (Basel: 10, Berne: 1, Geneva: 36). All consultations of asylum seekers and refugees have been recorded during the study period (Basel: 42, Berne: 93, Geneva: 187). Interviews have been done with the physicians who coordinated the study. During the study period the majority of the patients originated from former Yugoslavia, Turkey, Sri Lanka, Somalia, Angola and Zaire. One of the most prominent features of the population investigated has been its diversity in respect to countries of origin, languages, ability to communicate and education. Diversity and low consultation rates per physician could explain many of the problems which have been observed, e.g. the lack of experience in specific approaches to these patients or difficulties to provide interpreters. To improve the health care for this group of patients in medical outpatient departments small teams of physicians should be selected. By these means adequate levels of experience could be achieved and organizational problems could be dealt with more effectively. In addition, the relationship between specific problems of asylum seekers and refugees and more general issues of the interaction between physicians and patients are discussed in view of tasks in research and training.

Adolescent↗
PubMed1998

[Asylum seekers and refugees in the emergency department].

This cross-sectional study describes the health problems and the health care of asylum seekers and refugees from the point of view of accident & emergency (A & E) physicians at the major hospital in St. Gallen, Switzerland. The physicians filled in a detailed questionnaire and documented all consultations of asylum seekers/refugees and of a control group of patients during eleven weeks (2 x 98 consultations). 76% of these asylum seekers/refugees originated from former Yugoslavia. The distribution of the main ICD-coded diagnoses did not differ between asylum seekers/refugees and the control group after correction for age. In comparison with the asylum seekers and refugees attending GPs, injuries were much more common in the A & E department attenders (37% vs. 8%). Asylum seekers/refugees and the patients in the control group did not differ in respect to being classified as an emergency case (58% vs. 65%). There were also no differences in hospitalisation rates (29% vs. 36%). Asylum seekers/refugees who were registered with a GP attended the A & E department more often during the night than during the day compared to patients who were not registered with a GP. Consultations which have been classified as emergencies occurred more frequently during the day than at night time. The time of residence in Switzerland was negatively associated with the registration with a GP and with being classified as an emergency case. A lack of experience in caring for asylum seekers and refugees and of specific training in this field has been the major complaint by the A & E physicians. Asylum seekers should be introduced to the tasks and functions of the various sectors of the national health care system as early as possible. Registration with a GP in the community should be promoted.

Adolescent↗
PubMed1998

Vitamin D receptor alleles and bone's response to physical activity.

The objective of this prospective controlled study was to determine whether the osteogenic response of bone to mechanical loading is dependent on the vitamin D receptor (VDR) polymorphism. Thirty-five healthy premenopausal women took part in a progressive, high-impact exercise three times a week for a period of 18 months and 45 women served as nonexercising controls. The trainees were divided into three groups: bb (n = 12, 34%); Bb (n = 16, 46%); BB (n = 7, 20%) according to polymorphism at the gene encoding the VDR (BB representing subjects without the restriction enzyme BsmI sites on the two VDR gene alleles). Bone mineral content (BMC) and areal bone mineral density (BMD) were measured at the lumber spine, proximal femur, knee, calcaneus, and dominant distal radius before the beginning of the exercise regimen and at 12 and 18 months of training using dual-energy x-ray absorptiometry (DXA). As an indicator of the total osteogenic effect of the training, SigmaBMC was derived by summing up the BMC values of the loaded sites (i.e., the lower limb sites and the lumbar spine). The mean SigmaBMC increased 2.0% in the bb group, 3.0% in the Bb group, and 2.8% in the BB group (P = 0.184 for the intergroup difference), but only 0. 8% in the controls (exercisers versus controls, P < 0.001). Individuals with the BB genotype of the VDR gene, subjects with whom the BMC can be lower than normal and whose bones can be less responsive to pharmacological therapies than bones of the other individuals, seem to have as good osteogenic response to mechanical loading as subjects with other VDR genotypes. Thus, irrespective of the VDR genotype, physical activity seems to be beneficial for bones of premenopausal women.

Absorptiometry, Photon↗
PubMed1998

Genetic characterization of the malaria parasite Plasmodium falciparum in the transmission from the host to the vector.

The present study followed a Plasmodium falciparum population through its life-cycle at the level of individual hosts and vectors. The aim was to determine to what extent genotypes of the parasite that were found in the host were transmitted to the vector. Mosquitoes were collected that had fed on people sleeping under mosquito nets with holes. Genes determining 2 highly polymorphic merozoite surface proteins, MSP-1 and MSP-2, were used to characterize the parasite by PCR at different stages of the life-cycle. The parasite genotypes found in the host were compared to the genotypes of the oocyst stages after transmission to the mosquitoes. The results show that there was no significant correlation in the rate of oocyst-positive mosquitoes and the presence of parasites in the blood samples. For MSP-1, most of the parasites characterized in the human blood by PCR fragment size were also found afterwards in the oocyst-stage (22 of 29; MSP-2: 17 of 36). This study indicates that there is no selective transmission of distinct genotypes to the vector. In addition, the frequencies of the allelic families of both genes are similar in the blood samples and in the oocysts for the whole population.

Adolescent↗
PubMed1998

Immune responses to Plasmodium falciparum antigens during a malaria vaccine trial in Tanzanian children.

Among Tanzanian children living in an area of intense and perennial malaria transmission, prevalence of naturally acquired IgG antibodies that recognize SPf66, NANP, p190 and a 19 kDa fragment of the merozoite surface protein-1 (MSP-1) is high and increases with age. This possibly reflects the high level of natural exposure of the children to P. falciparum. The prevalences of IgG antibodies that recognize the three putative merozoite derived sequences contained in the malaria vaccine SPf66 (83.1, 55.1 and 35.1) is low but also show some age dependence. Three doses of the SPf66 vaccine induce a strong IgG antibody response against both the SPf66 construct, NANP and the three individual peptides. Vaccination with SPf66 did not result in an increase of anti19 kDa fragment antibodies. This reflects the specificity of the humoral immune response induced by the SPf66 construct. Among vaccinated children, antibody titres against SPf66 decreased over time following the third dose. However, 18 months after the third dose, SPf66 recipients still had significantly higher IgG titres and stimulation indices of peripheral blood mononuclear cells (PBMC) than placebo recipients. Within the vaccine group, there is a trend for increasing anti-SPf66 IgG titre to be associated with decreasing risk of clinical malaria but this was not statistically significant. Results also show the difficulties of establishing whether antibody responses are related to protection in field trials in endemic areas.

Animals↗
PubMed1998

Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with chloroquine to treat acute falciparum malaria in Tanzanian children aged 1-5 years.

A randomized, open trial involving 260 Tanzanian children, aged 1-5 years, with acute Plasmodium falciparum malaria was conducted to evaluate the efficacy of the combination antimalarial CGP 56697 (artemether and benflumetol), and to compare it with chloroquine, the standard drug used for malaria treatment in the Kilombero area. Children who had received rescue medication within the first 48 h or had a negative slide at the same time were excluded. Seven-day parasitological cure rates were 94% (95% CI 88-97.5) for CGP 56697 and 35.4% (95% CI 25.9-45.8) for chloroquine. Using the same definition, the 14-day parasitological cure rates were 86.4% (95% CI 78.5-92.2) for CGP 56697 and 10.3% (95% CI 5.1-18.1) for chloroquine. Gametocytes were more effectively suppressed by CGP 56697 than by chloroquine. There were no major adverse events with either drug. CGP 56697 is highly efficacious against P. falciparum in this area of Tanzania. The study contributes to the discussion on treatment strategies, particularly whether chloroquine may still fulfil its role as first-line drug in an area of high malaria transmission and very high levels of chloroquine resistance.

Acute Disease↗
PubMed1998

Distinction of recrudescences from new infections by PCR-RFLP analysis in a comparative trial of CGP 56 697 and chloroquine in Tanzanian children.

OBJECTIVE: To test the efficacy of a new compound drug (CGP 56697) against acute, uncomplicated falciparum malaria. METHOD: Reappearing parasites were analysed by PCR-RFLP within a randomized controlled trial. 130 patients received chloroquine and 130 patients were treated with CGP 56697. Samples from 96 patients with parasitological failure were tested by PCR-RFLP for MSP2 of Plasmodium falciparum. Seven days after treatment 32 patients of the chloroquine control group with reappearing parasites were tested by PCR and one infection was unequivocally determined as a new infection. After 7 days, in the CGP 56697 group, 6 samples were tested in which one new infection was identified. Similar observations were made one and three weeks later in both groups. RESULTS: Although a high multiplicity of infections on admission was observed, there was no significant correlation between multiplicity and either recrudescence or new infection. Patients in both treatment groups with subsequent recrudescent parasites had higher initial mean parasite densities than patients who cleared. Those of the patients with recrudescent parasites who were treated with CGP 56697 had higher initial parasite densities than those treated with chloroquine. The rate of re-infection increased with time as expected in holoendemic areas and appeared to be higher in chloroquine patients. Generally, CGP 56697 showed a superior clearance rate, successfully cleared higher parasite densities and suppressed new infections over a longer period of time. CONCLUSION: The PCR analysis confirmed that reinfections beyond day 7 are significant in areas highly endemic for malaria and showed the necessity of excluding these when estimating 14 day clearance rates. Provided new infections are excluded, the 28-day clearance rate can also be used to determine the efficacy of antimalarial drugs in highly endemic areas, and adds to our knowledge of drug resistance and dynamics of infections in people living in such areas.

Acute Disease↗
PubMed1998

Schistosoma mansoni, intestinal parasites and perceived morbidity indicators in schoolchildren in a rural endemic area of western Côte d'Ivoire.

There is a great need for rapid and low-cost identification of communities at high risk of intestinal schistosomiasis. We report the development of a questionnaire approach that may do so. In the first phase, 209 schoolchildren from 3 neighbouring villages in a rural area endemic for intestinal schistosomiasis in western Côte d'Ivoire were screened for Schistosoma mansoni and other helminths on 4 consecutive days using Kato-Katz thick smears. Daily infection prevalences of S. mansoni were high (60%-71%) and the cumulative infection prevalence was 92.3%. Infections with hookworms and Ascaris lumbricoides were also frequent, with cumulative prevalences of 60.8% and 38.3%, respectively. On day 3, the presence of Entamoeba histolytica/E. dispar and Giardia lamblia was assessed by a faecal concentration procedure. In the second phase, focus group discussions (FGD) were conducted: in each village one FGD with heavily infected children and one FGD with lightly or S. mansoni-uninfected schoolchildren to assess their perception of morbidity. The aim was to establish local terms indicating S. mansoni infections. 'Diarrhoea', 'blood in the stools', 'stomach disorders' and 4 terms in the local Yacouba/Dioula languages were frequently used by infected children. A simple questionnaire was then developed and the headteachers interviewed all schoolchildren individually. 'Blood in stools', gnon and toto were reported significantly more frequently among moderately and heavily S. mansoni-infected children than by those not or only lightly infected. The term gloujeu indicated borderline significance. The best diagnostic performance was found for 'blood in stool' (sensitivity: 47%; specificity: 76%; positive predictive value: 66%; negative predictive value: 60%). All schistosomiasis infections were treated with a single oral dose of praziquantel (40 mg/kg body weight) and the same questionnaire was re-administered 6 weeks post-treatment. Statistically significantly less children reported having had 'blood in stool' and 'gloujeu' after treatment (McNemar's (chi2-test, P < 0.01). We conclude that 'blood in stool', 'gnon', 'toto' and 'gloujeu' are the most reliable reported symptoms for rapid and low-cost identification of communities that are at high risk of S. mansoni infections in Côte d'Ivoire.

Adolescent↗
PubMed1998

Incidence of Plasmodium falciparum infection in infants in relation to exposure to sporozoite-infected anophelines.

The relationship of the incidence of Plasmodium falciparum infection to entomologic inoculation rates (EIRs) was studied in 163 children less than one year of age in a Tanzanian village to determine likely effects of transmission-reducing interventions on infection incidence. A total of 66,727 Anopheles gambiae s.l. and 17,620 An. funestus mosquitoes were caught in 1,056 light trap collections from 139 houses over a period of more than two years. Time period-specific human biting rates were estimated for 11 village neighborhoods. Sporozoites were detected by ELISA in 4.4% of the An. funestus and 2.5% of the An. gambiae s.l. Eight hundred seventeen pairs of blood slides with approximately two-week intervals between slides were used to estimate incidence of parasitemia by fitting reversible catalytic models to parasite positivity data. Estimated EIRs during the four weeks preceding each intersurvey interval averaged 1.6 (SD = 2.1) per adult per night. Parasites were present at the end of 31% of the 443 intervals that commenced with a parasite-negative slide. Attack rates were comparable with those in western Kenya, and the proportion of bites resulting in human infections was strongly dependent on mosquito density. Incidence of infection increased with the EIR up to approximately one bite from a sporozoite-carrying mosquito per adult per night. However, higher levels of transmission observed locally in the wet season did not result in a correspondingly higher incidence. These data suggest that transmission-reducing measures cannot be expected to reduce incidence of infection at the highest levels of EIR.

Animals↗
PubMed1998

Relationships of malaria morbidity with exposure to Plasmodium falciparum in young children in a highly endemic area.

To study incidence of clinical Plasmodium falciparum malaria in relation to exposure to parasites, attendance of children less than eighteen months old at a village dispensary in a highly endemic area of Tanzania was recorded. Entomologic inoculation rates (EIRs), estimated as a function of time period and place of residence, exceeded one sporozoite positive bite per adult per night in some village neighborhoods during the wet season. Incidence of clinical P. falciparum malaria, defined either as fever with parasitemia or as fever with hyperparasitemia, increased with the EIR over the whole range of exposures. Each 10-fold increase in the EIR corresponded to a 1.6-fold increase in incidence of fever plus parasitemia (95% confidence interval = 1.4-2.0). Therefore reduction of human-vector contacts will probably reduce morbidity incidence even at very high exposures. Incidence showed little relationship to estimated cumulative numbers of inoculations since birth, but decreased steeply with estimated cumulative time infected with trophozoites. This suggests that clinical immunity depends mainly on the extent of exposure to blood-stage antigens, not on the diversity of inocula seen, and thus temporary reductions in human-vector contacts are unlikely to result in subsequent increases in morbidity.

Animals↗
PubMed1998

Evolution of Schistosoma haematobium-related pathology over 24 months after treatment with praziquantel among school children in southeastern Tanzania.

Little is known about the dynamics of pathology due to schistosomiasis following treatment. Public health authorities in endemic areas require such information to decide on the timing of treatment and re-treatment schedules. A study to assess the rate of clearance and reappearance of pathologic lesions due to Schistosoma haematobium using ultrasound has now been carried out in two schools in southeastern Tanzania, an area of moderate-to-high transmission. Baseline data collection found urinary tract pathology in 67% of 533 children. Lesions of the bladder were significantly associated with egg positivity and microhematuria. The attributable fraction estimate of major bladder lesions due to S. haematobium was 75%. In a cohort study, 224 infected children were examined by ultrasound and then treated with a standard dose of 40 mg of praziquantel/kg of body weight. They were re-examined at two, four, six, 12, 18, and 24 months after treatment. Before treatment, 76% had pathologic lesions of the urinary tract. The proportion showing lesions decreased sharply during the first months after treatment to 11% at six months. At 24 months, lesions were detected in 57%, and 11% had developed new severe pathology. In 18 cases, pathology was present throughout, and 34 did not show any pathology throughout the study. This study provides the first detailed report on the evolution of urinary tract pathology due to S. haematobium infections at the community level. The results will help in making decisions on treatment and re-treatment schedules and more generally will provide a basis for designing control strategies in areas of moderate-to-high transmission.

Adolescent↗