bluuebunny/crossref_metadata_2025 huggingface dataset:
Arabidopsis phosphatidylglycerophosphate synthase 1 is essential for chloroplast differentiation, but is dispensable for mitochondrial function
Authors: Babiychuk Elena , Müller Frank , Eubel Holger , Braun Hans‐Peter , Frentzen Margrit , Kushnir Sergei
Published: March 2003

Genetic dissection of the lipid bilayer composition provides essential in vivo evidence for the role of individual lipid species in membrane function. To understand the in vivo role of the anionic phospholipid, phosphatidylglycerol, the loss‐of‐function mutation was identified and characterized in the Arabidopsis thaliana gene coding for phosphatidylglycerophosphate synthase 1, PGP1. This mutation resulted in pigment‐deficient plants of the xantha type in which the biogenesis of thylakoid membranes was severely compromised. The PGP1 gene coded for a precursor polypeptide that was targeted in vivo to both plastids and mitochondria. The activity of the plastidial PGP1 isoform was essential for the biosynthesis of phosphatidylglycerol in chloroplasts, whereas the mitochondrial PGP1 isoform was redundant for the accumulation of phosphatidylglycerol and its derivative cardiolipin in plant mitochondrial membranes. Together with findings in cyanobacteria, these data demonstrated that anionic phospholipids play an important, evolutionarily conserved role in the biogenesis and function of the photosynthetic machinery. In addition, mutant analysis suggested that in higher plants, mitochondria, unlike plastids, could import phosphatidylglycerol from the endoplasmic reticulum.
Preoperative autologous blood deposition in support of gynaecological repair procedures
Authors: Wang  , Lau  , Herst  , Drutz  , Fernandes
Published: March 2003

Autologous blood transfusion was evaluated in gynaecological repair procedures including abdominal/vaginal hysterectomy with vaginal repair, post‐hysterectomy vaginal suspension and fixation, uni/bilateral salpingo‐oophorectomy with vaginal colpopexy and sling procedures. A total of 247 autologous units were collected from 95 patients at the regional blood centre with 1–3 units (mean 2.6 units) deposition from each patient. One hundred and ninety of all collected units were transfused (collection/transfusion ratio = 1.3). Of these patients, 86 (90.5%) received autologous blood; 12 (13%) being transfused with 1 unit, 44 (46%) with 2 units and 30 (32%) with 3 units. Two of these patients received additional homologous blood. The average preoperative haemoglobin level was 119 g L−1and average post‐operative haemoglobin level was 105 g L−1. The post‐operative Hb level was used as a retrospective indicator for the requirement for blood transfusion. The results show that overall 75% of patients had post‐operative haemoglobin levels ≤ 110 and 33% of patients with Hb levels < 100, respectively. These results suggest that preoperative autologous blood deposition may be appropriate in the patients undergoing reconstructive gynaecological repair procedures since there was a high rate of usage of autologous blood and low post‐operative haemoglobin in a significant proportion of patients.
Gene frequencies of eight human platelet‐specific antigens in Koreans
Authors: Seo  , Park  , Kim  , Furihata  , Ueno  , Han
Published: March 2003

Human platelet‐specific antigens (HPAs) are found on platelet membrane glycoproteins and are the target of platelet alloantibodies that mediate platelet destruction in neonatal alloimmune thrombocytopenia (NAIT), post‐transfusion purpura (PTP) and refractoriness to platelet transfusion therapy. The biallelic polymorphism of all HPA systems is known to be due to a substitution of a single base pair. This study was performed to investigate the frequency of the HPA genes in Koreans, based on these substitutions. The genotypes of eight HPA systems were determined by polymerase chain reaction using sequence‐specific primers (PCR–SSP) for HPA‐1, ‐2, ‐4, ‐5, and ‐8 and restriction fragment length polymorphism (RFLP) for HPA‐3, ‐6, and ‐7. The gene frequencies obtained from 200 unrelated Koreans were 0.99 and 0.01 for HPA‐1a and ‐1b, 0.92 and 0.08 for HPA‐2a and ‐2b, 0.55 and 0.45 for HPA‐3a and ‐3b, 0.99 and 0.01 for HPA‐4a and ‐4b, 0.98 and 0.02 for HPA‐5a and ‐5b, and 0.98 and 0.02 for HPA‐6a and ‐6b. All the individuals tested were homozygotes for HPA‐7a and HPA‐8a. It has been reported that the HPA‐1b antigen is extremely rare (less than 0.3%) in Oriental populations, but this study suggests that the frequency of this antigen in Koreans (2.0%) is higher than in Japanese and Chinese populations.
Risk of hepatitis C infection in neonates transfused with blood from donors infected with hepatitis C
Authors: O'Riordan  , Conroy  , Nourse  , Yap  , McDonald  , Kaminski  , Leong  , Lawlor  , Davoren  , Strong  , Davidson  , Lloyd  , Power
Published: March 2003

This look‐back study was undertaken to identify newborn infants who had been infected with the hepatitis C virus (HCV) as a result of transfusions received before the introduction of routine screening in 1991 and to determine the transmission rates and persistence of transfusion‐transmitted HCV infection acquired in the neonatal period.

A total of 24 infants, transfused between 1980 and 1991, were identified as having received potentially infected blood from 11 blood donors. Ten of the donors had been administered batches of anti‐D in 1977 known to have transmitted HCV genotype 1b infection. HCV RNA was detected in five of these donors when tested in 1994–95; the past donations of five of the donors, who had received anti‐D immunoglobulin and had serological evidence of previous HCV infection but who were PCR negative when tested in 1994–95, were considered of lower risk. The source and time of acquisition of HCV infection for the one remaining donor in the study was not determined.

Twenty‐one (88%) of the 24 children were living at time of lookback. The median age at transfusion was 12 days. The median age at time of testing was 6.3 years. One child, who tested negative, was excluded from further analysis of HCV transmission, due to incomplete transfusion records. Overall, 12 of 20 (60%) children tested were positive for anti‐HCV and seven (35%) were HCV RNA positive. Twelve (71%) of the 17 recipients of viraemic blood were ELISA positive and seven (41%) were PCR positive. Resolved HCV infection, as determined by ELISA pos, RIBA pos or indeterminate and PCR negativity, occurred in five of 12 (42%). In many instances there was more than one recipient per HCV infected donation. All of the reported children are clinically asymptomatic. However, the duration of HCV infection is relatively short and there is evidence of a degree of hepatitis in five of the seven children who are HCV RNA positive as judged by mildly elevated transaminase levels. The three who have undergone liver biopsy show mild hepatitis.

The lower rates of persistence of HCV infection in this study may be due to the young age at exposure or to the source of infection which for all but one of the children was linked to one HCV genotype from female donors. Sharing of units of blood among multiple infants should be discouraged.
An audit of error rates in a UK district hospital transfusion laboratory
Authors: Galloway  , Woods  , Whitehead  , Baird  , Stainsby
Published: March 2003

We have audited the error rates of our transfusion laboratory and compared these with error rates reported in the transfusion literature. Error rates were calculated using workload data from the department. The majority of errors that were detected were preanalytical and related to inadequate or incomplete data provided on the sample or request form. These errors were all corrected prior to any further action being taken on that request. The main analytical errors were transcription errors in entering patient identification information into the laboratory computer by transfusion staff together with the incorrect performance of blood group testing. For postanalytical errors the main errors were failure of nursing staff to follow procedures for the collection of blood components prior to transfusion. There were no serious consequences identified of the errors detected in this study. It was difficult to compare these results with those published in the literature in view of the different methodologies that have been reported when error rates have been determined. A standard method should be developed in the UK for calculating error rates so that laboratories can benchmark their performance against comparable organizations.
Economic analysis of erythropoietin use in orthopaedic surgery
Authors: Coyle  , Lee  , Fergusson  , Laupacis
Published: March 2003

The aim was to assess the cost‐effectiveness of erythropoietin (EPO) to reduce patients' exposure to perioperative allogenic blood products in orthopaedic surgery. The use of EPO was assessed for EPO used alone and for EPO to augment preoperative autologous donation (PAD).  A decision analytical model was designed incorporating (i) the risk of receiving allogeneic blood, (ii) the costs of blood products, (iii) the likelihood of developing transfusion‐related diseases, (iv) the costs of transfusion‐related diseases, (v) the impact of transfusion‐related diseases on patient morbidity and mortality and (vi) the effect of EPO upon the probability of transfusion. The efficacy of EPO was derived from data from a meta‐analysis of published randomized trials. Estimates for the other parameters were obtained by a systematic review of the literature.  EPO alone led to only modest incremental benefit compared to no intervention for orthopaedic surgery (0.000024 life‐years gained per patient). As an augmentation to PAD, EPO also led to modest benefits (0.000006 life‐years gained per patient). For EPO compared to no intervention, the incremental cost per life‐year gained was $66 million (Canadian). For EPO to augment PAD, the incremental cost per life‐year gained was $329 million (Canadian). Detailed sensitivity analysis did not reveal any circumstances in which the cost‐effectiveness ratios reached a level generally considered attractive.  On the basis of cost‐effectiveness, the use of EPO to reduce perioperative allogeneic transfusions in orthopaedic surgery did not meet criteria conventionally considered acceptable.
The murine monoclonal antibody NaM26‐4C6 identifies a common structure on band 3 and glycophorin C
Authors: Loirat  , Czerwinski  , Duk  , Blanchard
Published: March 2003

The murine monoclonal antibody NaM26‐4C6 (IgM class), obtained from the splenocytes of a BALB/c mouse immunized with human umbilical cord red blood cells, was characterized by agglutination test and immunoblotting analysis. The structure of the NaM26‐4C6 epitope was further elucidated by using a series of peptides synthesized on pins. The antibody agglutinated untreated and chymotrypsin‐treated but not trypsin‐ or neuraminidase‐treated human erythrocytes. Agglutination‐inhibition test demonstrated that the antibody recognizes an epitope located on the N‐terminal trypsin‐sensitive portion of glycophorin C. The antibody bound on immunoblots to glycophorin C, and also to the band 3 protein and its 69‐kDa N‐terminal fragment but did not bind to desialylated and de‐O‐glycosylated glycophorin C. Peptide mapping allowed localization of the binding site on the 23‐kDa N‐terminal intracellular peptide of band 3. The antibody binds to the amino‐acid sequences 22EDPDIP27 of band 3 protein and 15SLEPDPGM22 of glycophorin C, and residues D and P were found to be essential. The new epitope identified by NaM26‐4C6 corresponds to a linear amino acid sequence located on the N‐terminal intracellular portion of band 3 and to a more complex structure involving oligosaccharide chains on the N‐terminal extracellular domain of GPC.
Bruising following blood donation, its management and the response and subsequent return rates of affected donors
Authors: Ranasinghe  , Harrison
Published: March 2003

A study was undertaken to determine the incidence of bruising among blood donors and to analyse their response to the management of this complication. A total of 52 510 donors were bled at 476 consecutive donor sessions held by the Brentwood Centre during a 4‐month period. Of these, 344 donors (0.66%) were found to have developed bruises following venepuncture. The incidence of bruising among males was 0.35% and that among females was 0.98%.  All bruised donors were managed by the Centre nursing and medical staff. One hundred and sixty‐one donors informed the Centre that they were fully satisfied with the way their bruising was managed. Of 329 bruised donors who remained in the panel, 249 (75.7%) attended subsequent blood donor sessions in response to routine invitations, showing that the majority of bruised donors continued to donate blood. This response was compared with that of a control group of donors who did not develop any complications and there was no significant difference in the return rates between the two groups.
The BCSH guideline on addressograph labels: experience at a cardiothoracic unit and findings of a telephone survey
Authors: Cummins  , Sharp  , Vartanian  , Dawson  , Amin  , Halil
Published: March 2003

In 1998 we implemented a BCSH recommendation that addressograph labels should not be used on blood transfusion specimen tubes. Over a 12‐month period before the ban was introduced our laboratory received 5964 red cell transfusion requests, 182 (3.1%) of which contained an error in the identification details (ID) supplied on the request form and/or specimen. Three of these errors were of the ‘wrong patient’ type, i.e. the sample belonged to a different patient from the one whose ID appeared on the specimen tube and request form. Over the 12 months after the ban was introduced 511 (8.1%) of 6326 requests contained a labelling error, an increase in error rate of 165%; no wrong‐patient errors were identified, however. In a survey, seven (29.2%) of 24 transfusion laboratories in the UK accepted specimens labelled with addressograph stickers; in four of these cases a local blood transfusion committee had agreed that the BCSH guideline should not be followed. We believe the BCSH guideline is valid; its implementation, however, has major financial and workload implications, which probably explains why many hospitals apparently do not comply with it.
Murine monoclonal antibodies reactive with a human monoclonal anti‐RhD antibody (BRAD‐5)
Authors: Walker  , Andrew  , Kumpel  , Austin
Published: March 2003

BRAD‐3 and BRAD‐5 are human monoclonal antibodies that recognize the RhD antigen on red blood cells. Both antibodies are currently in clinical trials for use as a replacement for polyclonal anti‐RhD in the prophylactic treatment of haemolytic disease of the newborn. We have produced three murine IgG1 antibodies that cause agglutination of cells sensitized with BRAD‐5 and also block binding of BRAD‐5 to its target antigen. Using a haemagglutination assay, these antibodies, 1D7, 2E6 and 3B1, have shown specificity for BRAD‐5 as they did not bind to other monoclonal anti‐RhD antibodies of differing specificity or derived from other donors. This assay has also been used to show a lack of reactivity with anti‐RhD antibodies present in 198 human serum samples from 44 anti‐RhD immune individuals. The three anti‐BRAD‐5 antibodies have been shown to recognize different epitopes on the BRAD‐5 molecule using a blocking ELISA. These antibodies appear to recognize private idiotopes on BRAD‐5 that were not detectable in RhD immune sera, and therefore they will be of use for monitoring BRAD‐5 in clinical trials.
Neonatal alloimmune thrombocytopenia (NATP) caused by anti‐BAKa (HPA‐3a) maternal antibody detectable only in reactions with intact platelets
Authors: Curtis B. R. , McFarland J. G. , Harrison C. R. , Ebert D. D. , Aster R. H.
Published: March 2003

The first child of pt 1 (NZ) was born with generalized petechiae and a platelet count of 9000/µL. Three random‐platelet transfusions were given during the first week, and the platelet count rose to normal about Day 10. Pt 2 (AG) had given birth to an infant with severe thrombocytopenia 11 years previously. At 22 weeks of her second pregnancy, an umbilical vein platelet count was 56,000/µL. IV IgG was given and she was delivered at 38 weeks of an infant with extensive ecchymoses and a platelet count of 6000/µL. The infant was given IV IgG and three transfusions of washed maternal platelets, but achieved a stable platelet count in the normal range only after 44 days.

By DNA‐based typing, both mothers were HPA‐3b/b and both fathers were HPA 3a/a. No other maternal/paternal incompatibilities were found. In flow cytometry, sera from both mothers reacted with platelets positive for HPA‐3a (Baka) and failed to react with platelets homozygous for HPA‐3b. On repeated occasions, however, the sera failed to give positive reactions against HPA‐3a positive platelets in MAIPA, modified antigen capture ELISA (MACE) and antigen capture ELISA (ACE), in contrast to other anti‐HPA‐3a abs. Negative reactions were also obtained when the mild detergent octyl glucoside was used for platelet lysis, rather than Triton X‐100.

The findings indicate that these two alloantibodies recognize an epitope that is present on GPIIb/IIIa in its native state but is lost when platelets are lysed, even with mild detergent. In these cases, the antibodies were detected on the basis of their reactions with intact platelets in flow cytometry but this would not have been possible if HLA antibodies, often found in pregnant women, had been present.
The immunogenicity of Gov alloantigens is comparable to that of the HPA‐5 system
Authors: Smith G. , Berry J. , Murphy C. , Ranasinghe E. , Metcalfe P. , Ouwehand W. H.
Published: March 2003

The 175 kDa glycosylphosphatidylinositol (GPI)‐linked glycoprotein CD109 carries the bi‐allelic platelet system, Gov. To date, detection of Gov antibodies has relied on the immunoprecipitation of radio‐labelled CD109. We have modified the monoclonal antibody‐specific immobilization of platelet antigen assay for the detection of Gov antibodies. Screening of 605 archived patient samples referred for neonatal alloimmune thrombocytopenia (NAITP, n = 305); post‐transfusion purpura (PTP, n = 60); and platelet refractoriness (PR, n = 240) revealed 14 Gov antibodies (10 anti‐Gova, 4 anti‐Govb) which equals the number of HPA‐5 antibodies detected in the 605 samples. There is no obvious linkage between the HLA class II type and the ability to mount an immune response. Phenotyping of 113 donors by MAIPA showed frequencies of 19·5%, 40·7% and 39·8% for ‘aa, ab and bb’, respectively, with ‘a’ and ‘b’ allele frequencies of 0·40 and 0·60. Cloning of the CD109 gene and determination of the molecular basis of the Gov antigens has become relevant now that it has been established that Gov alloantibodies are more frequent than previously thought.
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.
Isoimmune neonatal neutropenia due to anti‐Fcgamma RIIIb antibody in a mother with an Fcgamma RIIIb deficiency
Authors: Maślanka K. , Guz K. , Uhrynowska M. , Żupańska B.
Published: March 2003

A rare case of neutropenia in a newborn due to anti‐Fcgamma RIIIb antibody is described. The newborn, born from the 5th pregnancy, had severe infection and no neutrophils. Full clinical and neutrophil count recovery was observed when the child was 5 weeks old. In maternal serum, panreactive granulocyte alloantibodies were detected. The mother's and her two sisters' granulocytes appeared to be Fcgamma RIIIb deficient as found using pheno‐ and genotyping methods. All of them were healthy. The anti‐Fcgamma RIIIb specificity of antibodies was identified by the monoclonal antibody immunobilization of neutrophil antigen assay. Such antibodies were not found in both sisters with the Fcgamma RIIIb deficiency, although they were pregnant, one of them on the seventh occasion.
Transfusion practice in Helsinki University Central Hospital: an analysis of diagnosis‐related groups (DRG)
Authors: Syrjälä M. T. , Kytöniemi I. , Mikkolainen K. , Ranimo J. , Lauharanta J.
Published: March 2003

. Transfusion data combined with data automatically recorded in hospital databases provides an outstanding tool for blood utilization reporting. When the reporting is performed with an online analytical processing (OLAP) tool, real time reporting can be provided to blood subscribers. When this data is combined with a common patient classification system, Diagnosis‐Related Groups (DRG), it is possible to produce statistical results, that are similar in different institutions and may provide a means for international transfusion bench‐marking and cost comparison. We use a DRG classification to describe the transfusion practice in Helsinki University Central Hospital. The key indicators include the percentage of transfused patients, the number of transfused units and costs in different DRG groups, as well as transfusion rates per DRG weighted treatment episodes. Ninety‐three per cent of all transfusions could be classified into different DRGs. The largest blood‐using DRG group was acute adult leukaemia (DRG 473), which accounted for 10·4% of all transfusion costs. The 13 largest blood consuming DRGs accounted for half the total costs in 1998. Currently, there is a lack of an internationally accepted standardized way to report institutional or national transfusion practices. DRG‐based transfusion reporting might serve as a means for transfusion benchmarking and thus aid studies of variations in transfusion practice.
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.
Malaria anticircumsporozoite antibodies in dutch soldiers returning from sub‐saharan africa
Authors: Bwire R. , Slootman E. J. H. , Slootman E. J. H. , Verhave J. P. , Bruins J. , Docters van Leeuwen W. M.
Published: March 2003

One hundred and twenty‐five Dutch servicemen returning from central Africa after a short deployment were enrolled in a study aimed at assessing the effectiveness of malaria prevention measures. None of the persons developed an episode of clinically overt malaria during or after deployment, and no antibodies against blood stages of Plasmodium falciparum could be found. However, antibodies against the circumsporozoite protein (CS) of P. falciparum were demonstrable in 14 persons (11.2% of the study population) by an ELISA test using the recombinant CS‐antigen R32tet32, while one person only was positive in an IFA test based on schizonts of P. fieldi as antigen. We concluded that the anti‐CS‐positive servicemen were probably bitten by mosquitoes carrying P. falciparum parasites while the IFA‐positive person was possibly infected by P. vivax, P. ovale or P. malariae parasites. There was no significant association between the different antimalaria preventive measures and the development of anti‐CS antibodies. Therefore mefloquine prophylaxis as the single most widely used preventive measure in this group of servicemen was possibly a major contributing factor in averting development of overt malaria.
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.
Immunogenicity of Haemophilus influenzae‐diphtheria CRM197 protein conjugate vaccine (HbOC) in Libyan infants
Authors: Hadida M. , Cuevas L. E. , Moghadami A. , Baccoosh M. , Gurgel R. Q. , Hart C. A.
Published: March 2003

Summary The immunogenicity of the HbOC, a Haemophilus influenzae type b conjugate vaccine, was evaluated in a randomized clinical trial of Arab children resident in Tripoli. The HbOC vaccine was given as part of a three‐dose series at 2, 3 and 4 months of age together with hepatitis B, OPV and DPT to 90 children. Anti‐H. influenzae antibody levels were compared with 81 infants receiving hepatitis B, OPV and DPT but not the HbOC vaccine. The immunogenicity and safety of HbOC was as high as that observed in industrialised countries. There were no major complications, and fever and temporary local discomfort were observed in fewer than approximately 2% of the infants. Infants receiving the HbOC vaccine had an increase in Hib antibodies with only one dose. Geometric mean anti‐Hib antibody levels were 0.41, 1.36 and 2.91 mg/ml after one, two and three doses. After two doses, all children had antibody levels above 0.20 mg/ml and the lowest antibody concentration was 0.80 mg/ml. Antibody levels in our children are similar to those observed in Europe and the USA and it is thus likely that HbOC will provide good clinical protection in this population. As most of the children develop antibody titres above or near 1 mg/ml, it is likely that they are protected even with two doses of the vaccine. The anti‐Hib antibody levels observed are similar to those in studies from Europe where hepatitis B vaccine is not routinely given.
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.
Changing clinical and biological manifestations of dengue during the dengue‐2 epidemic in French Polynesia in 1996/97 – description and analysis in a prospective study
Authors: Deparis  , Murgue  , Roche  , Cassar  , Chungue
Published: March 2003

In August 1996 dengue‐2 virus was detected in French Polynesia for the first time since 1976. A prospective study was conducted from November 1996 to April 1997. Each time one of 7 physicians suspected dengue, the patient was enrolled and epidemiological, clinical and biological data were recorded. Dengue diagnosis was confirmed by virus isolation and IgM detection. The aims of this study were to find clinical and biological predictive factors constituting a specific profile of dengue (DF) and dengue haemorrhagic fever (DHF/DSS) and to assess the possibility of diagnosing dengue at primary health care level using clinical criteria and basic laboratory parameters. Of 298 clinically suspect cases, 196 (66%) were confirmed as dengue. The association of macular rash, pruritis, low platelet count and leukopenia was statistically predictive of dengue but not clinically, since these four signs occur in many other viral infections. As the prevalence of clinical and biological manifestations varied over time in our study, a specific profile useful for dengue diagnosis cannot be defined. With six cases of DHF, the morbidity of this dengue‐2 outbreak was very low despite the sequential infection scheme DEN‐3/DEN‐2. The clinical expression of dengue could depend on a specific virus strain circulating in a specific population in a particular place, with varying virulence over time.
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.
Rapid economic growth and ‘the four Ds’ of disruption, deprivation, disease and death: public health lessons from nineteenth‐century Britain for twenty‐first‐century China?
Authors: Szreter Simon
Published: March 2003

Summary Rapid economic growth has always entailed serious disruption: environmental, ideological, and political. As a result the relationship between economic growth and public health is complex since such disruption always threatens to spill over into deprivation, disease and death. The populations of most current high‐income, high‐life expectancy countries of ‘the West’ endured several decades of severely compromised health when they first experienced industrialization in the last century. Although health technologies have moved on, the social, administrative and political disruption accompanying economic growth can still impede the delivery of health improvements. The case history of 19th‐century laissez‐faire Britain is explored in some detail to demonstrate the importance of these social and political forces, particularly the relative vigour and participatory nature of local government, linking to recent work on the importance of social capital in development. For a country like China today, paradoxically, there is nothing that needs such careful planning as a ‘free market’ economy.
Bancroftian filariasis on Pemba Island, Zanzibar, Tanzania: An update on the status in urban and semi‐urban communities
Authors: Pedersen E. M. , Kilama W. L. , Swai A. B. M. , Kihamia C. M. , Rwiza H. , Kisumku U. M.
Published: March 2003

Summary Cross‐sectional clinical, parasitological and entomological surveys for bancroftian filariasis were conducted in Konde, Chake Chake and Kengeja, three urban and semiurban communities on Pemba Island, and the results were compared with similar surveys done 15 years earlier. The overall prevalences of clinical manifestations among males aged 15 years or more (n= 614) was remarkably similar to those recorded 15 years earlier: elephantiasis 1.4% in 1975 and 1.1% in 1990; hydrocele, 22.4% and 21.8%, respectively. However, when the communities were compared individually, there was a reduction in the hydrocele prevalence in Konde from 22.4% to 11.5% and an increase in Kengeja from 27.0% to 35.5%. The overall microfilarial prevalence found during night blood surveys of all individuals aged 1 year or more (n= 2687) was 9.7%, compared to 14.2% recorded in 1975. The reduction was most pronounced in Konde. Of 1052 female mosquitoes caught with CDC light traps, 95% were Culex quinquefasciatus and 5%Anopheles gambiae s.l. Infective larvae of Wuchereria bancrofti were found only in the former. The filariasis situation in urban and semiurban communities on Pemba Island appears not to have changed considerably over the last 15 years.
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.
Genetic epidemiology of host predisposition microfilaraemia in human loiasis
Authors: Garcia A. , Abel L. , Cot M. , Richard P. , Ranque S. , Feingold J. , Demenais F. , Boussinesq M. , Chippaux J‐P.
Published: March 2003

Summary Evidence is accumulating from experimental and human studies that genetic factors are involved both in the control of infectious diseases and in the regulation of infection levels and clinical presentation. So far few studies have investigated the role of these genetic factors in human infection by the filarial parasite Loa loa. We present a segregation analysis on 74 nuclear families who live in the tropical rainforest of southern Cameroun and are exposed to homogeneous loiasis transmission. The results indicate that there is a genetic predisposition to be microfilaraemic and that predisposed subjects might be genetically unable to mount an efficient immune response against loiasis antigens. This individual susceptibility could explain at least in part why the prevalence of infection (microfilaraemic individuals) does not usually exceed 30% of the exposed population in hyperendemic regions. Further genetic studies, based on linkage analysis using both familial information and genetic markers, will help to identify the nature of the genetic factors predisposing to microfilaraemia.