bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel mis‐sense mutation in the platelet glycoprotein CD36 is associated with protection from malaria
Authors: Pain A. , Kai O. , Urban B. , Casals‐Pascual C. , Marsh K. , Roberts D. 
Published: March 2003

Severe malaria is caused at least in part by the adhesion of malaria‐infected erythrocytes to endothelium and other host cells. Although many host proteins including CD36, are receptors for infected erythrocytes it has proved difficult to establish the pathological significance of particular host–parasite interactions.CD36 deficiency is common in Africans and we hypothesized that mutations in the Cd36 gene may confer protection from malaria. The common mutation leading to CD36 deficiency in Japanese is absent in Africans. We therefore sequenced the Cd36 gene from two Afro‐Americans who did not express CD36 and identified a novel mutation from T to G in the Cd36 gene leading to a stop codon (TAT‐TAG). In a large case‐control of severe malaria we found heterozygotes for the T‐G mutation were present in 121/693 (17·4%) of the controls but only 95/693 (13·7%) of malaria cases and is therefore associated with protection form malaria (P = 0·039, OR 0·74, 95% CI (0·55–0·99). Furthermore, the association of the mutation with protection was greater in those children with more severe disease.We suggest that this and other polymorphisms of Cd36 gene exist as balanced polymorphisms in malaria endemic areas and may predispose people to other diseases in adult life. Understanding the polymorphisms of the Cd36 gene may be useful in platelet immunology and help in understanding the genetic epidemiology of not only malaria but also common diseases in Africans.
A 4‐nucleotide deletion in intron 2 of the HPA 1a allele of GPIIIa interferes with the PCR‐SSP genotyping
Authors: Killie M. K. , Jaegtvik S. , Husebekk A. , Skogen B. 
Published: March 2003

Typing of platelet specific antigens by polymerase chain reaction using allele‐specific primers (PCR‐SSP) is a valuable tool in diagnosing alloimmune thrombocytopenia. To avoid post‐PCR processing of the samples, we have adopted the Taqman™ allelic discrimination technique for typing in the HPA 1 system. By comparing the results of this test system with PCR‐SSP, we found a discrepancy in one sample out of 1000. This sample was HPA 1bb in PCR‐SSP and HPA 1ab in the Taqman™ assay. The HPA 1ab phenotype was confirmed with two assays: first, monoclonal immobilization of platelets antigens assay (MAIPA) using antibody with HPA 1a and HPA 1b specificity and, second, flow cytometric analysis of the platelets with the same antisera. In addition, DNA sequencing of the polymorphic site related to the HPA 1 system revealed a heterozygous pattern. However, when the region in intron 2 of the GPIIIa gene corresponding to the consensus primer in the PCR‐SSP assay was sequenced, we found a 4‐nucleotide deletion in the HPA 1a allele interfering with the 3′ end of the consensus primer. Consequently, the amplification of this allele could not take place. Although this gene defect is located in an intron area, and thus do not have any significance for protein expression, it is located so close to the HPA 1 polymorphic site that it may influence on test systems designed to type for HPA 1 (Skogen et al. Transfusion 1994; 34: 955–960). Therefore, we strongly suggest avoiding this region of the gene when choosing primers/probes in the construction of PCR test systems for HPA 1.
Cellular immune response of Mastomys and gerbils in experimental filariasis
Authors: Misra Shailja , Mukherjee Monisha , Dikshit Manisha , Chatterjee R. K. 
Published: March 2003

Summary objective To determine mitogenic and antigen‐specific cellular immune responses of two species of rodents, viz. Merionesunguiculatus and Mastomyscoucha to assess the usefulness of the A. viteae/Mastomys model for cellular immune studies in experimental filariasis. methods Lymphocyte blast transformation test (LTT) using spleen cells of normal and A. viteae infected animals. results The proliferative response of gerbils was much higher than that of Mastomys to both ConA and filarial antigens. Cells of both species of rodents did not respond to microfilarial (mf) antigen, however, their mitogenic response differed during infection. Some degree of nonspecific suppression was observed in gerbils during prepatent and patent stages of infection, while Mastomys revealed highest proliferation during patent microfilaraemia. Mastomys cells did not respond to adult or mf antigen,while adult‐specific proliferation was detected in the case of gerbils. conclusion The A. viteae/gerbil model shows more similarity to human filarial infection regarding cellular immune response. Markedly low responsiveness of a high percentage of Mastomys and wide variations in the cellular response to nonspecific mitogen limit the usefulness of Mastomyscoucha in immunological studies, especially cellular immunity.
Patterns of antimicrobial use and antimicrobial resistance among healthy children in Bolivia
Authors: Bartoloni Alessandro , Cutts Felicity , Leoni Silvia , Austin Christopher C. , Mantella Antonia , Guglielmetti Paolo , Roselli Mimmo , Salazar Esteban , Paradisi Franco 
Published: March 2003

Summary objective  To determine the incidence of antimicrobial‐resistant, nonpathogenic Escherichia coli among healthy children aged 6–72 months in Camiri town and a rural village, Javillo, in south‐eastern Bolivia. method  A community‐based survey: stool samples were obtained from 296 healthy children selected by modified cluster sampling in Camiri and all 25 eligible children in Javillo. E. coli isolates were tested for antimicrobial susceptibility according to the standard disc diffusion method. By a questionnaire survey of 12 pharmacies and by using simulated patients, we investigated the antimicrobial availability and the usage patterns in Camiri town. results  In Camiri, over 90%, and in Javillo over 70% of children carried E. coli resistant to ampicillin, trimethoprim‐sulphamethoxazole (TMP/SMX) or tetracycline. Overall, 63% of children carried E. coli with multiple resistance to ampicillin, TMP/SMX, tetracycline and chloramphenicol. In the simulated patients study, antimicrobials were dispensed inappropriately for 92% of adults and 40% of children with watery diarrhoea, and were under‐prescribed for males with urethral discharge (67%) or females with fever and dysuria (58%). The dose and/or duration of antimicrobials dispensed was almost always too low. conclusion Our study showed a disturbingly high prevalence of carriage of nonpathogenic E. coli resistant to antimicrobials. The prevalence of resistance to ampicillin and TMP/SMX was higher than that previously reported in developing countries. The existence of a large reservoir of resistance genes in healthy individuals in developing countries represents a threat to the success of antimicrobial therapy throughout the world. Programmes to improve rational and effective drug use in developing countries are urgently needed.
Improved injection practices after the introduction of treatment and sterility guidelines in Tanzania
Authors: Vos Jennechien , Gumodoka Balthazar , Van Asten Henri A. , Van Asten Henri A. , Berege Zacharias A. , Dolmans Wil M. , Borgdorff Martien W. , Borgdorff Martien W. 
Published: March 2003

Summaryobjective To evaluate the effect of introduction of treatment and sterilization guidelines on the number of avoidable injections and on the sterility of needles and syringes. methods In 1991, 66 randomly selected health units in Mwanza Region, Tanzania, were visited and factors were determined that might contribute to HIV transmission by injections. In a workshop with all senior health workers from the region, findings were presented and treatment and sterilization guidelines developed. Thereafter, seminars were held at each health centre of the region. Four months after the intervention, data were collected at the same health facilities in order to assess changes in prescribing practices, sterilization procedures, and sterility of needles and syringes. results The knowledge on indications for injections improved markedly for paramedical staff. The proportion of outpatients receiving an injection dropped from 23% to 10% and the proportion of patients receiving an avoidable injection dropped from 16% to 6%. Procedures for sterilization, keeping sterilized equipment, and administration of injections improved. A smaller proportion of sterilized needles and syringes tended to be contaminated in dispensaries, but this reduction from 44% to 22% was not significant. conclusion Considerable improvement in knowledge, prescription practices and sterility procedures was observed at dispensary level after carrying out a training programme.
Assessment of central nervous system involvement in gambiense trypanosomiasis: value of the cerebro‐spinal white cell count
Authors: Miezan Tanoe W. , Meda Honoré A. , Doua Félix , Yapo Félix B. , Baltz Théo 
Published: March 2003

objective To assess, in a clinical setting, the comparative values of conventional criteria used in the diagnosis of central nervous system (CNS) involvement in Trypanosoma brucei gambiense sleeping sickness: white cell count (WCC) in cerebrospinal fluid (CSF) > 5 × 106 cells/l; total protein concentration in CSF > 40 mg/100 ml); evidence of trypanosomes in CSF following double centrifugation (DC). method In vitro culture of CSF was used as the gold standard. results The study showed that WCC is, by itself, as sensitive for the diagnosis of the CNS involvement as the usually recommended combination of three conventional criteria. The specificity of WCC is improved while the sensitivity is reduced when the cut‐off point is set at a higher value (WCC > 10 × 106/l). conclusion In poorly equiped laboratories, the diagnosis of CNS involvement in patients with confirmed systemic infection should be based only on the WCC. However, a pilot study is needed to assess the feasibility and reliability of the WCC handled by ‘front line’ personnel, for different cut‐off values.
Discrepancy in plasma melarsoprol concentrations between HPLC and bioassay methods in patients with T. gambiense sleeping sickness indicates that melarsoprol is metabolized
Authors: Bronner  , Brun  , Doua  , Ericsson  , Burri  , Keiser  , Miézan  , Boa  , Rombo  , Gustafsson  
Published: March 2003

Summary
objective  With the use of a specific high‐performance liquid chromatography (HPLC) method and a bioassay which determines trypanocidal activity concentrations of melarsoprol were assassed in plasma, urine and cerebrospinal fluid (CSF) from 8 patients with late‐stage Trypanosoma gambiense sleeping sickness. The aim was to unravel to what extent the bioassay codetermines biologically active metabolites of melarsoprol. methods  Subjects were given one dose of melarsoprol i.v. per day for 4 days (1.2, 2.4, 3.0–3.6, 3.0–3.6 mg per kg b.w., respectively). Plasma samples were obtained before the first melarsoprol injection, immediately after and at 1 h, 24 h and 5 days after the 4th injection. Urine was collected before melarsoprol therapy and at 24 h after the 4th injection. CSF samples were taken once before treatment and at 24 h after the 4th injection. results  HPLC analyses showed that plasma concentrations immediately after the 4th injection varied from 2200 to 15 900 nmol/l; dropping to 0–1800 nmol/l at 1 h; and to undetectable levels at 24 h. In urine small amounts of melarsoprol were recovered. Melarsoprol could not be detected in CSF by HPLC. Immediately after injection, bioassay analyses showed plasma concentrations of the same magnitude as HPLC assays but at 1 h they were 4–65‐fold higher than the levels assessed by HPLC. Even 24 h and 5 days after the 4th injection there was significant but decreasing activity. Urine levels were 40–260‐fold higher than the measured HPLC concentrations, whereas there was low but detectable activity in CSF. conclusion  Results indicate that melarsoprol is rapidly eliminated from plasma. The significant trypanocidal activity determined by bioassay and simultaneuos low or undetectable levels of melarsoprol assayed by HPLC indicate that the compound is transformed into metabolites with parasiticidal activity.
Retinal manifestations of HIV‐1 and HIV‐2 infections among hospital patients in The Gambia, West Africa
Authors: Jaffar Shabbar , Ariyoshi Koya , Frith Peggy , Okouchi Yuka , Sabally Sehu , Ajewole Tunde , Bailey Robin , Sang Lee Pak , Corrah Tumani , Johnson Gordon , Faal Hannah , Whittle Hilton 
Published: March 2003

Summary
background In developed countries, 50–75% of AIDS patients develop retinal complications and about 20–40% acquire cytomegalavirus (CMV) retinitis. We conducted a cross‐sectional survey to determine prevalence of these in The Gambia where both HIV‐1 and HIV‐2 infection are present and the prevalence of HIV‐1 is rising. method All patients attending hospital whose percentage CD4 + cells (CD4%) was below 14, the level associated typically with an AIDS diagnosis, and one half of those whose CD4% was 14 or above were asked to join the study. Fifty‐six HIV‐1, 52 HIV‐2 and 12 dually infected patients were recruited. Photographs of the fundi were taken and interpreted independently. The findings were related to the patients' percentage CD4 + cells. results The CD4% was < 14 in 40 patients and < 7 in 17 patients. Thirty‐six patients were male. No cases of CMV retinitis were found. Four patients whose CD4% were 4, 5, 11 and 23 had cotton wool spots ranging in number from 1 to 14 for any one patient. The prevalence of cotton wool spots was 8% (95% CI, 0–16%) among patients with CD4% below 14 and 12% (95% CI, 0–27) among patients with CD4% below 7. One of the 4 patients had associated microaneurysm and blot haemorrhages typical of more advanced HIV microvasculopathy. conclusion CMV retinitis is less common in The Gambia than in developed countries. Non‐infectious retinopathy may also be less common.
Population structure of recrudescent Plasmodium falciparum isolates from Western Uganda
Authors: Jelinek T. , Kilian A. H. D , Westermeier A. , Pröll S. , Kabagambe G. , Nothdurft H. D. , von Sonnenburg F. , Löscher T. 
Published: March 2003

Summary It has been proposed that polymorphisms of the Merozoite Surface Protein 1 and 2 (MSP1 and MSP2) and the Glutamate Rich Protein (GLURP) genes can be considered as genetic markers for the genotyping of field populations of Plasmodium falciparum. During a field study on in vivo drug resistance against chloroquine, sulphadoxine/pyrimethamine (S/P) and cotrimoxazole in West Uganda, sensitive and resistant isolates were collected from patients by fingerprick for genotyping. 59 (72.8%) of the 81 P. falciparum samples isolated at day 0 showed multiclonal infection with 2–7 clones. Among the isolates we investigated, presence of the allelic family MAD20 of MSP1 at day 0 was significantly (P = 0.0041) associated with decreased resistance to antimalarials. Use of this method in a field study on in vivo drug resistance demonstrates another potential application of genotyping as a tool for epidemiological investigations.
Control of zoophilic malaria vectors by applying pyrethroid insecticides to cattle
Authors: Hewitt Sean , Rowland Mark 
Published: March 2003

Summary The principal method of malaria control in South and West Asia – indoor residual spraying – is extravagant with insecticide. A more efficent way of deploying insecticide might be to apply it on livestock since the malaria vectors in the region are highly zoophilic. A series of investigations assessed the potential of cattle treated with pyrethroid to control zoophilic mosquitoes. Permethrin, deltamethrin, and lambdacyhalothrin were applied to cattle using a sponge at concentrations of 0.5 g/m2, 0.025 g/m2, and 0.025 g/m2, respectively. ‘Whole animal’ insecticide bioassays that simulated natural mosquito‐host contact were used to measure insecticidal and behavioural effects on wild host‐seeking mosquitoes. The bioassays were performed on both sheltered and outdoor grazing animals for up to 45 days post‐treatment. The possibility that treatments might cause diversion of host‐seeking vectors from cattle to people nearby was also investigated. At the doses tested deltamethrin had the most pronounced and longest‐lasting effect, reducing the proportion of bloodfed survivors by over 50% for the first two weeks. The majority of mosquitoes affected by the insecticide were killed before feeding. Insecticidal impact was generally lower on grazing than on sheltered animals. There was no diversion of host‐seeking mosquitoes from treated cattle to nearby humans at any stage after treatment. The application of insecticide to livestock using a campaign approach may prove an effective means of controlling malaria in the region. At the doses tested deltamethrin is the most appropriate insecticide for this purpose.
Cellular immune responses of a Senegalese community recently exposed to Schistosoma mansoni: correlations of infection level with age and inflammatory cytokine production by soluble egg antigen‐specific cells
Authors: Marguerite M. , Gallissot M.‐C. , Diagne M. , Moreau C. , Diakkhate M.‐M. , Roberts M. , Remoue F. , Thiam A. , Decam CH. , Rogerie F. , Cottrez F. , Neyrinck J.‐L. , Butterworth A. E. , Sturrock R. F. , Piau J.‐P. , Daff B. , Niang M. , Wolowczuk I. , Riveau G. , Auriault C. , Capron A. 
Published: March 2003

Summary A recently reported epidemic of Schistosoma mansoni infection in Senegal provided an opportunity to study the dynamics of the development of immunity to human schistosomiasis. We report here on the cell‐mediated immune response in a population of 99 females and 95 males, with particular emphasis on the relationship between intensity of infection and age. We found that the intensity of infection correlated negatively with age in females but not in males. In men and women, both Th1‐and Th2‐type cytokines were detected upon in vitro stimulation of PBMCs with soluble egg antigen (SEA) or soluble adult worm antigens (SWAP). In the female group, SEA‐induced PBMC proliferation was associated with the production of IFN‐γ, IL‐2 and IL‐5, all of which correlated negatively with intensity of infection. Most cytokine production correlated positively with age. Spontaneous production of TNF‐α, IL‐6 and IL‐10 was higher in the infected population than in an uninfected control group. Our results suggest that immunity to infection could be more pronounced in the female population and associated with a Th0/1 + 2 pattern of cytokine secretion mediated by soluble egg antigen (SEA).
The impact of population level deworming on the haemoglobin levels of schoolchildren in Tanga, Tanzania
Authors: Beasley N. M. R. , Tomkins A. M. , Hall A. , Kihamia C. M. , Lorri W. , Nduma B. , Issae W. , Nokes C. , Bundy D. A. P. 
Published: March 2003

Summary The impact of albendazole (400 mg) and praziquantel (40 mg/kg body weight) treatment of schoolchildren was compared with placebo according to the presence of anaemia (haemoglobin concentration < 11.0 g/dl) and heavy (> 5000 epg) or light (< 5000 epg) hookworm egg load. The study was conducted in rural Tanga. Medication was administered in September 1994 and children were followed‐up in January 1995. Overall, anthelminthic treatment reduced the fall in haemoglobin concentration compared with that observed in the placebo group (− 0.11 g/dl vs. − 0.35 g/dl; P = 0.02). Anthelminthic treatment was of greatest benefit to the 9% of children with both anaemia and heavy hookworm egg load (+ 0.67 g/dl vs. − 0.67 g/dl) and was also of significant benefit to the 38% of children with anaemia and light hookworm egg load (+ 0.07 g/dl vs. − 0.21 g/dl). It was of no significant benefit to children who were not anaemic. This study suggests that single‐dose anthelminthic treatment distributed in schools in this area achieves haematological benefits in nearly half of children infected with S. haematobium and geohelminths (37% of total population).
HIV heterogeneity and proximity of homestead to roads in rural South Africa: an exploration using a geographical information system
Authors: Tanser Frank , LeSueur David , Solarsh Geoff , Wilkinson David 
Published: March 2003

Summary objective  To describe heterogeneity of HIV prevalence among pregnant women in Hlabisa health district, South Africa and to correlate this with proximity of homestead to roads.methods  HIV prevalence measured through anonymous surveillance among pregnant women and stratified by local village clinic. Polygons were created around each clinic, assuming women attend the clinic nearest their home. A geographical information system (GIS) calculated the mean distance from homesteads in each clinic catchment to nearest primary (1°) and to nearest primary or secondary (2°) road.results  We found marked HIV heterogeneity by clinic catchment (range 19–31% (P < 0.001). A polygon plot demonstrated lower HIV prevalence in catchments remote from 1° roads. Mean distance from homesteads to nearest 1° or 2° road varied by clinic catchment from 1623 to 7569 m. The mean distance from homesteads to a 1° or 2° road for each clinic catchment was strongly correlated with HIV prevalence (r = 0.66; P = 0.002).conclusions  The substantial HIV heterogeneity in this district is closely correlated with proximity to a 1° or 2° road. GIS is a powerful tool to demonstrate and to start to analyse this observation. Further research is needed to better understand this relationship both at ecological and individual levels, and to develop interventions to reduce the spread of HIV infection.
Efficacy of sulphadoxine‐pyrimethamine for acute uncomplicated malaria due to Plasmodium falciparum in Malawian children under five years old
Authors: Nwanyanwu Okey C. , Ziba Charles , Macheso Allan , Kazembe Peter 
Published: March 2003

Summary In 1993, Malawi replaced chloroquine (CQ) with sulphadoxine‐pyrimethamine (SP) as its first‐line treatment for uncomplicated malaria in children < 5 years of age. To assess the efficacy of SP after 5 years of widespread use, we undertook this study at 7 sites in 6 districts of Malawi. Febrile children < 5 years attending the outpatient clinics of selected hospitals whose parents consented were enrolled in the study if they had an axillary temperature of ≥ 37.5 °C and pure Plasmodium falciparum parasitaemia of ≥ 2000 asexual parasites/mm3. They were then followed for 14 days or until clinical failure. Parasitological resistance rates (RII and RIII) ranged from 7% to 19%. Resistance was higher in the north than in the central and southern regions, although this difference was not statistically significant. Resistance rates were a mean 19% during the rainy season vs. 12% in the dry season (P > 0.05). 80% of parasitological resistance was at the RII level. Of all children who failed parasitologically (90/641), 84 (93%) had no fever on day 7 and their mothers did not report them as being ill; only 6 of 641 (0.9%) patients met the WHO criteria for clinical treatment failure. Regardless of study site, 75% of mothers reported their children as having improved by day 3; 90% reported improvement by day 7, and all reported improvement by day 14. None of the children experienced any serious adverse reactions and none died. We found that after more than 5 years of widespread use of SP in Malawi, its efficacy remains acceptable for treatment of uncomplicated malaria, and it should therefore be retained as first‐line treatment.