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Marcel Tanner

Publications and source records attributed to Marcel Tanner.

At least 73 records · Page 4Linked to original sources
PubMed2004

Urbanization in sub-saharan Africa and implication for malaria control.

Malaria not only remains a leading cause of morbidity and mortality, but it also impedes socioeconomic development, particularly in sub-Saharan Africa. Rapid and unprecedented urbanization, going hand-in-hand with often declining economies, might have profound implications for the epidemiology and control of malaria, as the relative disease burden increases among urban dwellers. Reviewing the literature and using a modeling approach, we find that entomologic inoculation rates in cities range from 0 to 54 per year, depending on the degree of urbanization, the spatial location within a city, and overall living conditions. Using the latest United Nations figures on urbanization prospects, nighttime light remotely sensed images, and the "Mapping Malaria Risk in Africa" results on climate suitability for stable malaria transmission, we estimate that 200 million people (24.6% of the total African population) currently live in urban settings where they are at risk of contracting the disease. Importantly, the estimated total surface area covered by these urban settings is only approximately 1.1-1.6% of the total African surface. Considering different plausible scenarios, we estimate an annual incidence of 24.8-103.2 million cases of clinical malaria attacks among urban dwellers in Africa. These figures translate to 6-28% of the estimated global annual disease incidence. Against this background, basic health care delivery systems providing early diagnosis and early treatment and preventive actions through mother and child health programs and the promotion of insecticide-treated bed nets for the rapidly growing numbers of the urban poor must be improved alongside well-tailored and integrated malaria control strategies. We propose environmental management and larviciding within well-specified productive sites as a main feature for such an integrated control approach. Mitigation of the current burden of malaria in urban African settings, in turn, is a necessity for stimulating environmentally and socially sustainable development.

Africa South of the Sahara↗
PubMed2004

Effect of artemether on Schistosoma mansoni: dose-efficacy relationship, and changes in worm morphology and histopathology.

OBJECTIVE: To investigate the effects of artemether on Schistosoma mansoni harboured in mice, with particular consideration on single dose-efficacy relationship, hepatic shift and artemether-induced alterations in worm morphology and histopathology. METHODS: Groups of mice, infected with 21 d old S. mansoni, were treated with artemether at single oral doses of 12.5 mg/kg to 600 mg/kg. Worm burden reduction was assessed 28 d post-treatment. The hepatic shift was investigated in mice infected with 46 d old S. mansoni and treated with artemether at a single oral dose of 400 mg/kg within a period of 14 d post-treatment. Morphological and histopathological observations were made in adult worms in mice, subject to single oral dose of artemether at 400 mg/kg. RESULTS: The minimum effective dose of oral artemether against juvenile worms in mice was 200 mg/kg, resulting in a worm burden reduction of 81%. The hepatic shift commenced 8 h post-treatment, and all worms shifted to the liver 3-7 d post-treatment. Fourteen days post-treatment, 31% of the worms returned to the mesenteric veins. Treatment with artemether resulted in decreased worm body size, expansion of the pharynx and dilation of the gut with marked reduction in pigment. Focal tegumental damage was observed among female worms with adherence of host leukocytes and degeneration of ovary and vitelline glands, as well as atrophy of testis in male worms. Artemether-damaged worms were surrounded and infiltrated by eosinophils. CONCLUSION: The minimum effective dosage of artemether against 21 d old S. mansoni in mice is 200 mg/kg. Artemether also exhibits effect against adult schistosomes, including shrinkage and degeneration, and can lead to worm death. The predominant inflammatory cell surrounded and infiltrated into the artemether-damaged worm is eosinophil.

Animals↗
PubMed2004

Triggering of high-level resistance against Schistosoma mansoni reinfection by artemether in the mouse model.

Artemether, a methyl ether derivative of dihydroartemisinin, not only exhibits antimalarial properties, but also possesses strong activity against schistosomula, the immature stages of a parasitic worm that can cause schistosomiasis. To test if the effect would be similar to that of irradiation with respect to the induction of immunologic protective responses, groups of mice were infected with Schistosoma mansoni cercariae and treated with artemether at 1-3 weeks post-infection. Control mice were either infected with normal cercariae or with cercariae exposed to radiation that permitted early development but not maturation of the parasites. The mice were challenged six weeks after the initial infection, and the mean numbers of schistosomes recovered in the various groups were calculated upon dissection eight weeks post-challenge. The administration of artemether two weeks after the initial infection resulted in 58% protection, while giving the drug three weeks post-infection increased the level of protection to 81%. This level of protection is as high as that normally obtained by immunization with irradiated cercariae (84% in the present study) and is superior to the level of resistance obtained with any individual schistosome vaccine candidate antigen thus far reported.

Animals↗
PubMed2003

Selection and reversal of Plasmodium berghei resistance in the mouse model following repeated high doses of artemether.

Artemether, a derivative of artemisinin, is effectively used for the treatment of malaria without any clinically relevant resistance to date. Artemether has also been developed as an antischistosomal agent, exhibiting highest activity against immature parasites. Here, we employ a rodent model and investigate whether the proposed artemether treatment schedule to prevent schistosome-attributable morbidity might select for Plasmodium berghei resistance. Mice infected with an ANKA strain of P. berghei were treated with artemether at either 47 mg/kg or 300 mg/kg. Once every 7-10 days, parasitized erythrocytes were passed to the next group of mice, receiving the same doses of artemether, for 50 passages. Resistance development was slow but increased considerably over the final ten passages. At the higher dose of artemether, the indices of resistance were 4.8 and 8.8 after 40 and 50 passages, respectively. Importantly, resistance was unstable, since sensitivity reverted to near-normal after five passages without drug pressure. A moderate index of P. berghei resistance and no apparent reversibility was found in comparative experiments employing pyronaridine. In conclusion, the pace of resistance development in P. berghei to repeated high doses of artemether is slow and reversible.

Animals↗
PubMed2003

Cost-effectiveness of social marketing of insecticide-treated nets for malaria control in the United Republic of Tanzania.

OBJECTIVE: To assess the costs and consequences of a social marketing approach to malaria control in children by means of insecticide-treated nets in two rural districts of the United Republic of Tanzania, compared with no net use. METHODS: Project cost data were collected prospectively from accounting records. Community effectiveness was estimated on the basis of a nested case-control study and a cross-sectional cluster sample survey. FINDINGS: The social marketing approach to the distribution of insecticide-treated nets was estimated to cost 1560 US dollars per death averted and 57 US dollars per disability-adjusted life year averted. These figures fell to 1018 US dollars and 37 US dollars, respectively, when the costs and consequences of untreated nets were taken into account. CONCLUSION: The social marketing of insecticide-treated nets is an attractive intervention for preventing childhood deaths from malaria.

Bedding and Linens↗
PubMed2003

Quality and comparison of antenatal care in public and private providers in the United Republic of Tanzania.

OBJECTIVE: To compare the quality of public and private first-tier antenatal care services in Dar es Salaam, United Republic of Tanzania, using defined criteria. METHODS: Structural attributes of quality were assessed through a checklist, and process attributes, including interpersonal and technical aspects, through observation and exit interviews. A total of 16 health care providers, and 166 women in the public and 188 in the private sector, were selected by systematic random sampling for inclusion in the study. Quality was measured against national standards, and an overall score calculated for the different aspects to permit comparison. FINDINGS: The results showed that both public and private providers were reasonably good with regard to the structural and interpersonal aspects of quality of care. However, both were poor when it came to technical aspects of quality. For example, guidelines for dispensing prophylactic drugs against anaemia or malaria were not respected, and diagnostic examinations for the assessment of gestation, anaemia, malaria or urine infection were frequently not performed. In all aspects, private providers were significantly better than public ones. CONCLUSION: Approaches to improving quality of care should emerge progressively as a result of regular quality assessments. Changes should be introduced using an incremental approach addressing few improvements at a time, while ensuring participation in, and ownership of, every aspect of the strategy by health personnel, health planners and managers and also the community.

Adolescent↗
PubMed2003

Schistosoma japonicum: In vitro effects of artemether combined with haemin depend on cultivation media and appraisal of artemether products appearing in the media.

We recently found that the exposure of schistosomes in vitro to artemether plus haemin can lead to parasite death, while exposure to each compound singly had no effect. Since these observations might be relevant to understanding the mechanism of action of artemether against schistosomes, we conducted additional experiments. First, we performed a comparative appraisal of Schistosoma japonicum survival after incubation in two media, namely Hanks' balanced salt solution (HBSS) and RPMI 1640, supplemented with inactivated calf serum, antibiotics and different concentrations of artemether and/or haemin. Worm mortalities were consistently higher and occurred faster in HBSS when compared to RPMI 1640. Second, we investigated the behaviour of artemether in different chemical systems, including reduced glutathione or cysteine, in the presence of haemin or ferrous sulfate. Cleavage of the endoperoxide bridge of artemether occurred in all experiments, consistently forming five different products, of which one has not been described previously. Third, RPMI 1640 and HBSS media were supplemented with artemether and haemin in the presence of S. japonicum. The consumption of artemether in RPMI 1640 was much faster than in HBSS. Trace amounts of artemether and five free radical reaction products of artemether could be detected in RPMI 1640 after 24-48 h. In contrast, large amounts of artemether remained without the formation of free radical products in HBSS under the same conditions. These findings coincide with significantly higher schistosome mortalities employing HBSS instead of RPMI 1640. Our results suggest that it is artemether or an active metabolite thereof (most likely a carbon-centred free radical), rather than any free radical reaction product that is harmful for the worms. We speculate that schistosomes ingest artemether and cleave it in their gut. This cleavage is induced by haemin or another iron-containing molecule. These findings might be a further step forward in elucidating the mechanism of action of artemether against schistosomes.

Animals↗
PubMed2003

Molecular monitoring in malaria vaccine trials.

Molecular techniques offer new approaches for malaria field trials, particularly PCR techniques, which facilitate accurate diagnosis of Plasmodium infections and increase the power of estimates of vaccine effects on malaria prevalence or incidence. Molecular methods also help to assess selective effects of vaccines. Longitudinal genotyping data can be used to initiate novel analyses of parasite dynamics, including estimates of incidence of infection with individual parasite clones and duration of infections. In addition, high-throughput methods can be used to apply these techniques routinely in randomized controlled trials, as well as programme-based evaluations of malaria control.

Animals↗
PubMed2003

Evaluation of efficacy of community-based vs. institutional-based direct observed short-course treatment for the control of tuberculosis in Kilombero district, Tanzania.

Tuberculosis (TB) has reappeared as a serious public health problem. Non-compliance to antituber-culous drug treatment is cited as one of the major obstacles to the containment of the epidemic. Compliance may be optimized by Directly Observed Treatment (DOT) and short-course treatment regimens. Since 1986, Tanzanian TB patients have received daily DOT at health facilities for the first 2 months of the treatment course. However, adherence and cure rates have been falling as the number of TB cases continues to increase and the burden on already stretched health facilities threatens to become unmanageable. We used an open cluster randomized controlled trial to compare community-based DOT (CBDOT) using a short-course drug regimen with institutional-based DOT (IBDOT). A total of 522 (301 IBDOT and 221 CBDOT) patients with sputum-positive TB were recruited. Overall, there was no significant difference in conversion and cure rates between the two strategies [M-H pooled odds ratio (OR) 0.62; 95% confidence interval (CI) 0.23, 1.71 and OR = 1.58; 95% CI 0.32, 7.88, respectively] suggesting that CBDOT may be a viable alternative to IBDOT. CBDOT may be particularly useful in parts of the country where people live far from health facilities.

Adult↗
PubMed2003

Random spatial distribution of Schistosoma mansoni and hookworm infections among school children within a single village.

Schistosomes and soil-transmitted helminths currently infect a third of the world's human population. An important feature of these parasitic infections is their focal distribution, which has significant implications for control. Only a few studies have been carried out at the microepidemiological scale, comparing infection levels among individuals or households within a single village. In this study, data are presented from a cross-sectional survey, examining all children attending a primary school in rural Côte d'Ivoire over several consecutive days for Schistosoma mansoni, soil-transmitted helminths, and intestinal protozoa. All houses in the main village were mapped, and school children were linked to these households for small-area spatial analyses. Comparison between the 260 school children who live within the main village and the 89 children who reside in nearby settlements revealed significant differences in the overall prevalence and intensity of infections with S. mansoni and hookworm, confirming the focal nature of these 2 parasites. On the other hand, S. mansoni and hookworm infections exhibited random spatial patterns within the main village. The validity of these results is discussed in the context of this epidemiological setting, drawing attention to the issue of scale. Our findings have direct implications for intervention because they call for a uniform, community-wide approach to control schistosomiasis and soil-transmitted helminthiasis. Implementation can be relatively straightforward, and the proposed control approach might be cost-effective and prove sustainable.

Adolescent↗
PubMed2003

Randomized, double-blind, placebo-controlled trial of oral artemether for the prevention of patent Schistosoma haematobium infections.

Artemether is an efficacious antimalarial drug that also displays antischistosomal properties. Laboratory studies have found that artemether curtails the development of adult worms of Schistosoma japonicum, S. mansoni and S. haematobium, and thus prevents morbidity. These findings have been confirmed in clinical trials for the former two parasites; administered orally once every 2-3 weeks, artemether significantly reduced the incidence and intensity of patent infections. Here, we present the first randomized, double-blind, placebo-controlled trial of artemether against S. haematobium, done in a highly endemic area of Côte d'Ivoire. Urine specimens from 440 schoolchildren were examined over 4 consecutive days, followed by two systematic praziquantel treatments 4 weeks apart. S. haematobium-negative children were randomized to receive 6 mg/kg artemether (N = 161) or placebo (N = 161). Medication was administered orally for a total of six doses once every 4 weeks. Adverse events were assessed 72 hours after medication, and perceived illness episodes were monitored throughout the study period. Incidence and intensity of S. haematobium infections, and microhematuria and macrohematuria were assessed 3 weeks after the final dosing. We also monitored malaria parasitemia and treated positive cases with sulfadoxine-pyrimethamine (SP). Oral artemether was well tolerated. The incidence of patent S. haematobium infections in artemether recipients was significantly lower than in placebo recipients (49% versus 65%, protective efficacy: 0.25, 95% CI: 0.08-0.38, P = 0.007). The geometric mean infection intensity in the artemether group was less than half that of the placebo recipients (3.4 versus 7.4 eggs/10 mL urine, P < 0.001). Heavy S. haematobium infections, microhematuria and macrohematuria, and the incidence of malaria parasitemia were all significantly lower in artemether recipients. In conclusion, previous findings of efficacy of artemether against S. japonicum and S. mansoni were confirmed for S. haematobium, although the protective efficacy was considerably lower. These findings enlarge the scope and potential of artemether and further contribute to discussions of its role as an additional tool for integrated schistosomiasis control.

Administration, Oral↗
PubMed2003

Interactions between Schistosoma haematobium and human immunodeficiency virus type 1: the effects of coinfection on treatment outcomes in rural Zambia.

A prospective cohort study was conducted in two villages in Zambia to compare the efficacy of praziquantel in the treatment of schistosomiasis haematobium in people with and without concomitant infection with human immunodeficiency virus (HIV). Five hundred seven individuals with infected with Schistosoma haematobium were enrolled and followed-up for as long as 12 months after treatment with a single dose of praziquantel. Seventy-three were coinfected with HIV. The study demonstrated that praziquantel is still very effective in the treatment and control of S. haematobium even when there is coinfection with HIV (without symptoms and signs of acquired immunodeficiency syndrome [AIDS]/HIV disease). Resistance to reinfection with S. haematobium is not altered in subjects coinfected with HIV (without symptoms and signs of AIDS/HIV disease). Individuals with coinfection excreted fewer eggs and complained less of hematuria than those without HIV infection, and the sensitivity and positive predictive value of reported hematuria as an indication of heavy infection were lower in the group coinfected with HIV. This observation may have implications for the use of hematuria as an indicator for rapid diagnosis of schistosomiasis in areas where HIV is prevalent.

Adolescent↗
PubMed2002

Ultrastructural alterations in adult Schistosoma mansoni caused by artemether.

Progress has been made over the last decade with the development and clinical use of artemether as an agent against major human schistosome parasites. The tegument has been identified as a key target of artemether, implying detailed studies on ultrastructural damage induced by this compound. We performed a temporal examination, employing a transmission electron microscope to assess the pattern and extent of ultrastructural alterations in adult Schistosoma mansoni harboured in mice treated with a single dose of 400 mg/kg artemether. Eight hours post-treatment, damage to the tegument and subtegumental structures was seen. Tegumental alterations reached a peak 3 days after treatment and were characterized by swelling, fusion of distal cytoplasma, focal lysis of the tegumental matrix and vacuolisation. Tubercles and sensory organelles frequently degenerated or collapsed. Typical features of subtegumental alterations, including muscle fibres, syncytium and parenchyma tissues, were focal or extensive lysis, vacuolisation and degeneration of mitochondria. Severe alterations were also observed in gut epithelial cells and vitelline cells of female worms. Our findings of artemether-induced ultrastructural alterations in adult S. mansoni confirm previous results obtained with juvenile S. mansoni and S. japonicum of different ages.

Animals↗
PubMed2002

Paediatric referrals in rural Tanzania: the Kilombero District Study - a case series.

BACKGROUND: Referral is a critical part of appropriate primary care and of the Integrated Management of Childhood Illness (IMCI) strategy. We set out to study referrals from the aspect both of primary level facilities and the referral hospital in Kilombero District, southern Tanzania. Through record review and a separate prospective study we estimate referral rates, report on delays in reaching referral care and summarise the appropriateness of pediatric referral cases in terms of admission to the pediatric ward at a district hospital METHODS: A sample of patient records from primary level government health facilities throughout 1993 were summarised by age, diagnosis, whether a new case or a reattendance, and whether or not they were referred. From August 1994 to July 1995, mothers or carers of all sick children less than five years old attending the Maternal and Child Health (MCH) clinic or outpatient department (OPD) of SFDDH were interviewed using a standard questionnaire recording age, sex, diagnosis, place of residence, whether the child was admitted to the paediatric ward, and whether the child was referred. RESULTS: From record review, only 0.6% of children from primary level government facilities were referred to a higher level of care. At the referral hospital, 7.8 cases per thousand under five catchment population had been referred annually. The hospital MCH clinic and OPD were generally used by children who lived nearby: 91% (n = 7,166) of sick children and 75% (n = 607) of admissions came from within 10 km. Of 235 referred children, the majority (62%) had come from dispensaries. Almost half of the referrals (48%) took 2 or more days to arrive at the hospital. Severe malaria and anaemia were the leading diagnoses in referred children, together accounting for a total of 70% of all the referrals. Most referred children (167/235, 71%) were admitted to the hospital paediatric ward. CONCLUSIONS: The high admission rate among referrals suggests that the decision to refer is generally appropriate, but the low referral rate suggests that too few children are referred. Our findings suggest that the IMCI strategy may need to be adapted in sparsely-populated areas with limited transport, so that more children may be managed at peripheral level and fewer children need referral.

Journal Article↗
PubMed2002

Transmission electron microscopic observations on ultrastructural damage in juvenile Schistosoma mansoni caused by artemether.

Artemether, a derivative of the antimalarial artemisinin, has been shown to induce rapid and extensive alteration to the tegument of juvenile Schistosoma japonicum, S. mansoni and S. haematobium. Less is known with regard to ultrastructural damage caused by artemether; therefore, the present work was designed to assess the damage in juvenile S. mansoni. Mice infected with S. mansoni were treated intragastrically with a single dose of 400 mg/kg artemether 21 days post-infection. Between 8 h and 14 days after treatment groups of two mice were sacrificed, and schistosomula recovered for transmission electron microscopic observations. Ultrastructural damage was seen in the tegument, subtegumental musculature, parenchymal tissues and gastrodermis. It was already apparent 8 h after drug administration and increased gradually to reach a peak, 7 days post-treatment. Tegumental alterations were characterised by swelling, vesiculation and degeneration of sensory structures. Damage in subtegumental musculature, parenchymal tissues and gastrodermis included swelling, focal or extensive lysis, and decrease in granular endoplasmatic reticulum. Fourteen days after treatment ultrastructural damage was still seen in most schistosomula, however, there was partial repair in some specimens. The ability of artemether to cause extensive ultrastructural damage to juvenile S. mansoni correlates with its schistosomicidal effects and confirms earlier findings with S. japonicum.

Animals↗