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Biomedical subjects

M Tanner

Publications and source records attributed to M Tanner.

At least 91 records · Page 5Linked to original sources
PubMed2000

Apparent tolerance of Plasmodium falciparum in infants in a highly endemic area.

The incidence of fever among infants in the village of Idete in the Morogoro region of Tanzania was analyzed in relation to densities of Plasmodium falciparum parasites in the peripheral blood. Parasite densities in both fever cases and in asymptomatic infants, were compared and a Bayesian non-parametric mixture decomposition algorithm was used to estimate the proportion of fevers attributable to malaria and hence the incidence of clinical malaria. Age group-specific densities of peripheral parasitaemia showed little seasonality, but the clinical malaria incidence showed a clear peak in the wet season in children aged less than 9 months. Estimates of the parasitaemia-specific incidence of clinical malaria were used to quantify apparent tolerance of parasites, and indicated that clinical episodes occurred on average at lower parasite densities during the wet season than in the dry season. These patterns could reflect differences in levels of anti-toxic immunity, but the nature of the seasonal differences supports the alternative explanation that the variation in apparent tolerance may be an effect of changes in the ratio of peripheral parasite densities to the sequestered mass.

Age Factors↗
PubMed2000

Humoral immune responses during a malaria vaccine trial in Tanzanian infants.

The development of a malaria vaccine is a priority for improved and sustained malaria control. Optimal use of a vaccine in Africa will only be achieved if it can be delivered through the Expanded Programme of Immunization (EPI). We have completed a trial of the peptide vaccine SPf66 in Tanzanian infants, given alongside the EPI vaccines. This paper describes the humoral responses to SPf66 and the EPI vaccines. A total of 1207 infants were recruited into a two-arm, double-blind, individually randomized placebo-controlled trial of SPf66. The objectives of the trial were to determine the safety, immunogenicity and efficacy of SPf66 and to assess interactions with EPI vaccines when three doses of SPf66 were delivered alongside the EPI vaccines. Cross-sectional surveys were carried out to asses seroconversion rates to the EPI vaccines and the antibody response to SPf66 (NANP)50 and Plasmodium falciparum lysates. Seroconversion rates to EPI vaccines were high and no statistically significant differences in prevalence or titres were found between SPf66 and placebo recipients. IgG antibodies against SPf66 (NANP)50 and whole P. falciparum lysate were present in high titres in mothers of recruited children at the time of birth. Vaccination with SPf66 stimulated a good anti-SPf66 IgG response which declined to preimmunization levels by 2 years of age and which was not associated with protection against clinical malaria. The vaccine induced no IgG antibodies against (NANP)50 or P. falciparum lysates. SPf66 stimulated a humoral immune response when given to very young infants and did not interfere with seroconversion to EPI vaccines. The response to SPf66 was qualitatively different from that seen in older children, in whom SPf66 has been shown to be moderately efficacious. This difference raises concerns about the difficulties of immunizing very young infants who need to be targeted by antimalarial vaccination programs.

Animals↗
PubMed2000

Health seeking and perceived causes of tuberculosis among patients in Manila, Philippines.

Inefficient case finding is an important stumbling block to successful control of tuberculosis (TB). Multiple health seeking may account for delayed case finding. Health-seeking behaviour, health seeking delay, perceived causes, and perceived quality of care related to TB were studied in interviews with 319 sputum smear-positive TB patients. The patients were treated in 22 governmental health centres of Malabon, a municipality of Metro Manila, Philippines. Only 29% of the respondents had gone first to a health centre after onset of TB-related symptoms, and more than half (53%) had initially consulted a private doctor. A chest X-ray was obtained for nearly everyone (97%). Two thirds of the patients (66%) had received a prescription for drugs, and 29% had purchased and taken anti-TB drugs for at least three weeks before they came to a governmental health centre. Concerning community interactions, 36% said they knew at least one person who had been treated for TB without success. The health seeking delay after symptom onset was relatively short - 64% of the respondents said they went to a health facility within 1 month. Case studies illustrate the rationale for health seeking and explain delayed initiation of appropriate treatment for many patients. Findings underscore the need for and indicate approaches to health communication for improved control of TB. Our findings from interview narratives also suggest that improved interpersonal skills of health centre staff and co-ordination between the private doctors and the health centres may substantially improve services for TB patients.

Adult↗
PubMed2000

Efficacy of praziquantel against Schistosoma mansoni with particular consideration for intensity of infection.

Chemotherapy with praziquantel is the cornerstone of schistosomiasis control. In view of recent concern about tolerance or resistance to praziquantel, monitoring its efficacy in different epidemiological settings is required. We report a study among 253 schoolchildren in an area highly endemic for Schistosoma mansoni in western Côte d'Ivoire. After examining four consecutive stool specimens from each child, the first praziquantel treatment at 60 mg/kg divided into two doses was administered. Four weeks later, stool specimens were again screened over 4 consecutive days and revealed a cure rate of 71.6% and an egg reduction rate of 79.9%. There was a significant association between cure rate and intensity of infection prior to treatment with highest cure rates observed in light infections (P < 0.01). Praziquantel, at a single dose of 40 mg/kg, was again administered 35 days after the first treatment. The overall cure and egg reduction rates increased considerably. The association between cure rate and intensity of infection prior to the second treatment was significant but less pronounced. Twenty-two children remained S. mansoni positive after the two chemotherapy campaigns, and interestingly, many of these were only identified after repeated stool examinations. We argue that pre-patent infections may account for some of these 'treatment failures'. However, further studies in other endemic settings are needed, with parasitological diagnoses having a high sensitivity.

Adolescent↗
PubMed2000

Practical issues in obtaining child assent for research.

This article describes ways to engage children in clinical research through a carefully planned assent process. When assent is handled well, children may gain a sense of control over their choice to participate in research, which may in turn enhance their cooperation in the process. Ways to engage children in the assent process, the historical development of consent and assent, and discussion of the issues surrounding parental consent and child assent are presented. Practical suggestions are provided to make research participation a positive and appealing process for children.

Child↗
PubMed2000

Maternal mortality in a rural district of southeastern Tanzania: an application of the sisterhood method.

BACKGROUND: Deaths from maternal causes represent the leading cause of death among women of reproductive age in most developing countries. It is estimated that the highest risk occurs in Africa, with 20% of world births but 40% of the world maternal deaths. The level of maternal mortality is difficult to assess especially in countries without an adequate vital registration system. Indirect techniques are an attractive cost-effective tool to provide estimates of orders of magnitude for maternal mortality. METHOD: The level of maternal mortality estimated by the sisterhood method is presented for a rural district in the Morogoro Region of Southeastern Tanzania and the main causes of maternal death are studied. Information from region-specific data using the sisterhood method is compared to data from other sources. RESULTS: The maternal mortality ratio (MMR) was 448 maternal deaths per 100,000 live births (95%CI : 363-534 deaths per 100,000 live births). Maternal causes accounted for 19% of total mortality in this age group. One in 39 women who survive until reproductive age will die before age 50 due to maternal causes. The main cause of death provided by hospital data was puerperal sepsis (35%) and postpartum haemorrhage (17%); this is compatible with the main causes reported for maternal death in settings with high levels of maternal mortality, and similar to data for other regions in Tanzania. The sisterhood method provides data comparable with others, together with a cost-effective and reliable estimate for the determination of the magnitude of maternal mortality in the rural Kilombero District.

Adolescent↗
PubMed2000

Induction of angiotensin II subtype 2 receptor-mediated blood pressure regulation in synthetic diet-fed rats.

OBJECTIVE: Chronic feeding of a purified synthetic diet induces renin-angiotensin system-dependent moderate high blood pressure in normal Sprague-Dawley rats. The present study was designed to characterize the angiotensin II (Ang II) receptor type 2 (AT2)-specific mechanism of blood pressure regulation in these rats. METHODS: The effect of the AT2 receptor antagonist PD123319 (PD) on blood pressure was examined in vivo in synthetic diet-fed rats. Ang II-dependent contraction of aortic rings prepared from the synthetic diet-fed rats was also investigated. RESULTS: After 8 weeks of feeding the synthetic diet, the mean arterial pressure (MAP) was significantly elevated above levels measured in control rats (117 +/- 2 versus 102 +/- 3 mmHg, P < 0.05). Intravenous administration of PD to conscious hypertensive rats elicited an immediate dose-dependent increase in MAP that was sustained for approximately 7.4 min with 3 mg/kg PD. The angiotensin converting enzyme inhibitor captopril, but not the Ang II type 1 receptor blocker losartan, significantly attenuated the effect of PD on blood pressure. PD did not increase the plasma level of catecholamines. The PD-dependent blood pressure increase was not observed in normotensive control rats. Aortic ring assays revealed that functional activation of the AT2 receptor occurs only in the hypertensive rats, and this AT2 response is abolished by indomethacin (5 micromol/l) but not by Nomega-nitro-L-arginine methyl ester (100 Fmol/l). CONCLUSION: These results clearly demonstrate that AT2 receptor-mediated blood pressure regulation is functional in this experimental model of hypertension. Furthermore, cyclooxygenase metabolites might be the key mediators for the AT2 receptor-mediated blood pressure-lowering action.

Angiotensin II↗
PubMed2000

Tegumental changes in adult Schistosoma mansoni harbored in mice treated with artemether.

A detailed temporal examination was made of alterations induced by artemether in the tegument of adult Schistosoma mansoni worms using scanning electron microscopy (SEM). Mice infected with S. mansoni cercariae 42 days previously were treated intragastrically with artemether at a single dose of 400 mg/kg. Groups of 3 mice were killed at 24 hr, 72 hr, and 7 days after treatment; the worms were collected by perfusion and examined by SEM. Twenty-four hours after artemether treatment, focal damage to the tubercles on the tegumental surface of male worms was seen. In both male and female worms, there was focal swelling and fusion of tegumental ridges, and sometimes peeling. After 72 hr, the damage to the tegument had increased, especially in female worms, with extensive swelling, fusion, and peeling of the tegumental ridges. In the most severely damaged worms, host leukocytes were seen to be adhered to the damaged tegument. Damage to the oral sucker was also occasionally seen in both male and female worms. Seven days after treatment, the appearance of the tegument had returned to normal in some male and female worms, whereas others still showed apparent damage. The results demonstrate that artemether damages the tegument of adult S. mansoni, and the intensity of damage is more severe in female worms than in males.

Animals↗
PubMed2000

Simple anamnestic questions and recalled water-contact patterns for self-diagnosis of Schistosoma mansoni infection among schoolchildren in western Côte d'Ivoire.

A study to determine the diagnostic performance of simple anamnestic questions and recalled water-contact patterns for self-diagnosis of Schistosoma mansoni infection was carried out in western C te d'Ivoire. A total of 322 schoolchildren were screened over four consecutive days with the Kato-Katz technique to assess S. mansoni and concurrent geohelminth infections. Children were individually interviewed by teachers using a standardized questionnaire asking about symptoms, reported diseases, and water-contact patterns. The cumulative infection prevalence of S. mansoni was 76.4%. Univariate statistics revealed a significant association between the level of S. mansoni infection and three recalled water contact patterns: (1) fishing with nets, (2) swimming/bathing and (3) crossing rivers, but no significant association with reported symptoms and/or reported diseases. Multivariate analysis revealed significant adjusted odds ratios (OR) for crossing the river Tchéorbour (OR = 3.90, P = 0.007), crossing the river Sonbour (OR = 3.90, P = 0.008) and swimming/bathing in the latter (OR = 3.28, P = 0.017). The diagnostic performance of these water-contact patterns was characterized by high specificities but low sensitivities, hence negative predictive values. In the village studied here, recalled water-contact patterns were more useful variables than anamnestic questions for schoolchildren's self-diagnosis of S. mansoni infection, but no generalization of these findings beyond this population is possible at this time.

Adolescent↗
PubMed2000

Cost-effectiveness of iron supplementation and malaria chemoprophylaxis in the prevention of anaemia and malaria among Tanzanian infants.

Prerequisites for effective interventions against severe anaemia and malaria among infants are economic evaluations to aid the setting of priorities and the making of health policy. In the present study we analysed the cost and effectiveness of three control strategies hypothetically delivered through the Expanded Programme on Immunization (EPI). For the prevention of severe anaemia and from the perspective of the health provider, the cost-effectiveness ratios were, respectively, US$ 8, US$ 9, and US$ 21 per disability-adjusted life year (DALY) for malaria chemoprophylaxis with Deltaprim (a combination of 3.125 mg pyrimethamine and 25 mg dapsone) + iron, Deltaprim alone, or iron supplementation alone. For malaria prevention, Deltaprim + iron cost US$ 9.7 per DALY and Deltaprim alone cost US$ 10.2 per DALY. From a sociocultural perspective the cost-effectiveness ratios ranged from US$ 9 to US$ 26 for severe anaemia prevention and from US$ 11 to US$ 12 for the prevention of clinical malaria. These ratios were highly cost-effective, as defined by the World Bank's proposed threshold of less than US$ 25 per DALY for comparative assessments. Furthermore, all the preventive interventions were less costly than the current malaria and anaemia control strategies that rely on clinical case management. This economic analysis supports the inclusion of both malaria chemoprophylaxis and iron supplementation delivered through EPI as part of the control strategies for these major killers of infants in parts of sub-Saharan Africa.

Anemia, Iron-Deficiency↗
PubMed2000

Microheterogeneity of serogroup A (subgroup III) Neisseria meningitidis during an outbreak in northern Ghana.

During a meningitis outbreak in the eastern subdistrict of the Kassena-Nankana District of the Upper East Region of Ghana, we analysed cerebrospinal fluid from suspected meningitis cases for the most common causative organisms. In 50 of 92 samples analysed, serogroup A Neisseria meningitidis were detected. The ages of serogroup A N. meningitidis patients ranged from 4 months to 64 years. The case fatality ratio was 20%. Coma or stupor on presentation worsened the prognosis. All serogroup A N. meningitidis isolates recovered revealed the A: 4: P1.9, 20 phenotype characteristic for the subgroup III clonal grouping. No evidence for resistance to penicillin G, chloramphenicol, cefotaxime, ciprofloxacin, rifampicin or tetracycline was found. All strains were resistant to sulphadiazine. Restriction analysis patterns of opa, iga and ingA genes were characteristic for the majority of N. meningitidis serogroup A subgroup III bacteria isolated in Africa after the 1987 epidemic in Mecca. Differences in pulsed-field gel electrophoresis patterns of NheI and SpeI digested DNA revealed microheterogeneity among the Ghanaian isolates.

Adolescent↗
PubMed2000

Rapid screening for Schistosoma mansoni in western Côte d'Ivoire using a simple school questionnaire.

The distribution of schistosomiasis is focal, so if the resources available for control are to be used most effectively, they need to be directed towards the individuals and/or communities at highest risk of morbidity from schistosomiasis. Rapid and inexpensive ways of doing this are needed, such as simple school questionnaires. The present study used such questionnaires in an area of western Côte d'Ivoire where Schistosoma mansoni is endemic; correctly completed questionnaires were returned from 121 out of 134 schools (90.3%), with 12,227 children interviewed individually. The presence of S. mansoni was verified by microscopic examination in 60 randomly selected schools, where 5047 schoolchildren provided two consecutive stool samples for Kato-Katz thick smears. For all samples it was found that 54.4% of individuals were infected with S. mansoni. Moreover, individuals infected with S. mansoni reported "bloody diarrhoea", "blood in stools" and "schistosomiasis" significantly more often than uninfected children. At the school level, Spearman rank correlation analysis showed that the prevalence of S. mansoni significantly correlated with the prevalence of reported bloody diarrhoea (P = 0.002), reported blood in stools (P = 0.014) and reported schistosomiasis (P = 0.011). Reported bloody diarrhoea and reported blood in stools had the best diagnostic performance (sensitivity: 88.2%, specificity: 57.7%, positive predictive value: 73.2%, negative predictive value: 78.9%). The study, which is probably the largest of its kind ever undertaken in Africa, revealed a moderate diagnostic performance of questionnaires for identifying individuals and/or communities at high risk from S. mansoni.

Adolescent↗
PubMed2000

Artemether, an effective new agent for chemoprophylaxis against shistosomiasis in China: its in vivo effect on the biochemical metabolism of the Asian schistosome.

Conventional drug chemotherapy against human schistosomiasis currently relies on treatment with praziquantel to eliminate adult schistosome worm pairs. The use of praziquantel for control purposes is limited, however, by high rates of post-treatment re-infection with subsequent parasite egg deposition and host end-organ damage. Artemether, a methyl ether derivative of the anti-malarial drug quinghaosu, was discovered recently to also have anti-schistosomal properties. Because artemether selectively targets the larval migratory stages of the parasite, known as schistosomulae, it blocks the development of ovipositing adult schistosome worm pairs in the vasculature. On this basis, we have since shown in clinical trials conducted in China that artemether has proven benefit as an agent for chemoprophylaxis. In vivo studies using laboratory animals suggest that artemether causes damage to the tegument and musculature of schistosomulae. Artemether may exert its helminthotoxic effect through synergy with hemin or related heme-containing compounds. Schistosomes recovered from artemether treated laboratory animals have increased glycogen phosphorylase activity, but decreased glucose uptake. These findings may account for their decreased glycogen content, relative to schistosomes recovered from untreated laboratory animals. The artemether-damaged schistosomes also have decreased activities of a number of enzymes and enzyme systems, including glycolysis. This might suggest common pathways by which artemether may target human parasites that live in the bloodstream.

Animals↗
PubMed1999

Lipopolysaccharides and cytokines downregulate the angiotensin II type 2 receptor in rat cardiac fibroblasts.

The present study examines the effect of lipopolysaccharides and proinflammatory cytokines on the expression of the second isoform of the angiotensin II receptor (AT(2)), which may have a role in lowering collagen deposition in cardiac tissue. Cardiac fibroblasts express high levels of both angiotensin II type 1 (AT(1)) and type 2 receptors. Incubation with lipopolysaccharides for 24 h dose- and time-dependently decreased angiotensin II AT(2) receptor expression with no apparent difference in the affinity. Actinomycin D, cycloheximide, N(omega)-nitro-L-arginine methyl ester and the protein tyrosine kinase inhibitor herbimycin A, but not the protein kinase C inhibitors bisindolylmaleimide and calphostin C, abolished the inhibitory action of lipopolysaccharides. The cytokines interleukin-1beta and tissue necrosis factor-alpha mimicked the effect of lipopolysaccharides. All three compounds induced inducible nitric oxide synthase (iNOS). The nitric oxide donor sodium nitroprusside and the cGMP analog 8-bromoguanosine cyclic monophosphate downregulated angiotensin II AT (2) receptor expression. The findings are consistent with the pathway in which lipopolysaccharides or cytokines induce iNOS. The data suggest that lipopolysaccharide- or cytokine-dependent induction of iNOS and resultant production of nitric oxide leads to the production of cGMP, which in turn downregulates expression of the angiotensin II AT (2) receptor in cardiac fibroblasts.

Animals↗
PubMed1999

Antibody isotype responses, infection and re-infection for Schistosoma japonicum in a marshland area of China.

Antibody isotype responses to adult worm antigen (AWA) of Schistosoma japonicum and two recombinant proteins (paramyosin (PMY) and a 22 kDa tegumental membrane-associated antigen (TEG)) were analyzed in 137 individuals from an area moderately endemic for schistosomiasis in the Dongting Lake region, Hunan Province, China. The prevalence and geometric mean (GM) intensity of infection before the implementation of curative chemotherapy were 28.5% and 234.4 epg, respectively, but 9 months after treatment the prevalence (6.6%) and intensity (38.3 epg) had decreased. There was no significant difference in either the prevalence or intensity of infection between males and females. Specific IgG (total), IgG4, IgG2, IgA and IgE responses to AWA, PMY and TEG were measured by ELISA. Males produced significantly (P < 0.05) more anti-AWA total IgG, IgE, IgA, IgG4 and IgG2 antibodies, and anti-TEG IgG2 antibody than their female counterparts. The OD450 levels of anti-AWA, PMY and TEG antibody isotypes did not present clear age-dependent trends except for peak levels of anti-AWA IgG4 antibodies evident among subjects 20-29 years of age. The total IgG and IgG4 antibody profiles against AWA correlated well with current S. japonicum infections while anti-AWA IgG2, IgA and IgE antibodies did not show such an association. Anti-AWA-specific IgE antibody levels were positively correlated (r = 0.55) with anti-AWA specific IgG4 antibody levels. In addition, the overall percentage of responders (using a cut-off value obtained from normal controls) to all isotypes to AWA were higher than those observed for both the recombinant antigens. Only 18.2%, 16.8% and 7.3% of the study population were IgE responders to AWA, PMY and TEG. A longer follow-up period is required before we can more fully understand the role of IgE, if any, in protective immunity against schistosomiasis japonica.

Adolescent↗
PubMed1999

Mixtures of proportional hazards regression models.

This paper presents a mixture model which combines features of the usual Cox proportional hazards model with those of a class of models, known as mixtures-of-experts. The resulting model is more flexible than the usual Cox model in the sense that the log hazard ratio is allowed to vary non-linearly as a function of the covariates. Thus it provides a flexible approach to both modelling survival data and model checking. The method is illustrated with simulated data, as well as with multiple myeloma data.

Aged↗