Value for Money and Policy Review of the Economic Cost and Charges Associated with Private and Semi-Private Treatment Services in Public Hospitals - Final Report

This Value for Money and Policy Review (VFM&PR) of the Economic Cost and Charges Associated with Private and Semi-Private Treatment Services in Public Hospitals was initiated by the Department of Health and Children in June 2009 and was conducted under the auspices of the Governmentâ?Ts Value for Money & Policy Review Initiative 2009-2011. The Review was overseen by an independently chaired National Steering Group comprised of senior representatives from the Department of Health and Children, the Department of Finance, and the Health Service Executive (HSE). Download document here Download Explanatory Note  

Value for Money and Policy Review of the Economic Cost and Charges Associated with Private and Semi-Private Treatment Services in Public Hospitals - Interim Report

This report sets out a revised costing methodology and an estimate of the gap which currently exists between private and semi-private bed charges and the average economic cost. While the Steering Group considers the costing methodology proposed as an improvement on the approach taken in previous years and a good overall approximation of the difference on average between economic costs and current charges, it recognises that the current charging regime does not take sufficient account of the variation between different categories of patient. Download document here Note to Readers

Characterization of tumor antigen specific CD8+ T cells and semi-invariant Vα24/Vβ11 NKT cells in tumor invaded liver

Summary: Detailed knowledge on tumor antigen expression and specific immune cells is required for a rational design of immunotherapy for patients with tumor invaded liver. In this study, we confirmed that Cancer/Testis (CT) tumor-associated antigens are frequently expressed in hepatocellular carcinoma (HCC) and searched for the presence of CD8+ T cells specific for these antigens. In 2/10 HLA-A2+ patients with HCC, we found that MAGE-A10 and/or SSX-2 specific CD8+ T cells naturally responded to the disease, since they were enriched in tumor lesions but not in non-tumoral liver. Isolated T cells specifically and strongly killed tumor cells in vitro, suggesting that these CTL were selected in vivo for high avidity antigen recognition, providing the rational for specific immunotherapy of HCC, based on immunization with CT antigens such as MAGE-Al 0 and SSX-2. Type 1 NKT cells express an invariant TCR α chain (Vα24.1α18, paired with Vβ11 in human) and share a specific reactivity to αGalactosylceramide (αGC) presented by CD1d. These cells can display paradoxical immuno-regulatory properties including strong anti-tumor effects upon αGC administration in murine models. To understand why NKT cells were not sufficiently protective against tumor development in patients with tumor invaded liver, we characterized the diversity of Vα24/Vβ11 NKT cells in healthy donors (HD) and cancer patients: NKT cells from HD and patients were generally diverse in terms of TCR β chain (Vβ11) variability and NKT cells from HD showed a variable recognition of αGC loaded CD 1 d multimers. Vα24/ Vβ11 NKT cells can be divided in 3 populations, the CD4, DN (CD4-/CD8-) and CD8 NKT cell subsets that show distinct ability of cytokine production. In addition, our functional analysis revealed that DN and CD8 subsets displayed a higher cytolytic potential and a weaker IFNγ release than the CD4 NKT cell subset. NKT cell subsets were variably represented in the blood of HD and cancer patients. However, HD with high NKT cell frequencies displayed an enrichment of the DN and CD8 subsets, and few of them were suggestive of an oligoclonal expansion in vivo. Comparable NKT cell frequencies were found between blood, non-tumoral liver and tumor of patients. In contrast, we identified a gradual enrichment of CD4 NKT cells from blood to the liver and to the tumor, together with a decrease of DN and CD8 NKT cell subsets. Most patient derived NKT cells were unresponsive upon αGalactosylceramide stimulation ex vivo; NKT cells from few patients displayed a weak responsiveness with different cytokine polarization. The NKT cell repertoire was thus different in tumor tissue, suggesting that CD4 NKT cells infiltrating tumors may be detrimental for protection against tumors and instead may favour the tumor growth/recurrence as recently reported in mice. Résumé en français scientifique : Afin de développer le traitement des patients porteurs d'une tumeur dans le foie par immunothérapie, de nouvelles connaissances sont requises concernant l'expression d'antigènes par les tumeurs et les cellules immunitaires spécifiques de ces antigènes. Nous avons vérifié que des antigènes associés aux tumeurs, tels que les antigènes « Cancer-Testis » (CT), sont fréquemment exprimés par le carcinome hepatocéllulaire (CHC). La recherche de lymphocytes T CD8+ spécifiques (CTL) de ces antigènes a révélé que des CTL spécifiques de MAGE-A10 et/ou SSX-2 ont répondu naturellement à la tumeur chez 2/10 patients étudiés. Ces cellules étaient présentes dans les lésions tumorales mais pas dans le foie adjacent. De plus, ces CTL ont démontré une activité cytolytique forte et spécifique contre les cellules tumorales in vitro, ce qui suggère que ces CTL ont été sélectionnés pour une haute avidité de reconnaissance de l'antigène in vivo. Ces données fournissent une base pour l'immunothérapie spécifique du CHC, en proposant de cibler les antigènes CT tels que MAGE-A10 ou SSX-2. Les cellules NKT de type 1 ont une chaîne α de TCR qui est invariante (chez l'homme, Vα24Jα18, apparié avec Vβ11) et reconnaissent spécifiquement l'αGalactosylceramide (αGC) présenté par CD1d. Ces cellules ont des propriétés immuno¬régulatrices qui peuvent être parfois contradictoires et leur activation par l'αGC induit une forte protection anti-tumorale chez la souris: Afin de comprendre pourquoi ces cellules ne sont pas assez protectrices contre le développement des tumeurs dans le foie chez l'homme, nous avons étudié la diversité des cellules NKT Vα24/Vβ11 d'individus sains (IS) et de patients cancéreux. Les cellules NKT peuvent être sous-divisées en 3 populations : Les CD4, DN (CD4- /CD8-) ou CDS, qui ont la capacité de produire des cytokines différentes. Nos analyses fonctionnelles ont aussi révélé que les sous-populations DN et CD8 ont un potentiel cytolytique plus élevé et une production d'IFNγ plus faible que la sous-population CD4. Ces sous-populations sont représentées de manière variable dans le sang des IS ou des patients. Cependant, les IS avec un taux élevé de cellules NKT ont un enrichissement des sous- populations DN ou CDS, et certains suggèrent qu'il s'agit d'une expansion oligo-clonale in vivo. Les patients avaient des fréquences comparables de cellules NKT entre le sang, le foie et la tumeur. Par contre, la sous-population CD4 était progressivement enrichie du sang vers le foie et la tumeur, tandis que les sous-populations DN ou CD8 était perdues. La plupart des cellules NKT des patients ne réagissaient pas lors de stimulation avec l'αGC ex vivo et les cellules NKT de quelques patients répondaient faiblement et avec des polarisations de cytokines différentes. Ces données suggèrent que les cellules NKT CD4, prédominantes dans les tumeurs, sont inefficaces pour la lutte anti-tumorale et pourraient même favoriser la croissance ou la récurrence tumorale. Donc, une mobilisation spécifique des cellules NKT CD4 négatives par immunothérapie pourrait favoriser l'immunité contre des tumeurs chez l'homme. Résumé en français pour un large public Au sein des globules blancs, les lymphocytes T expriment un récepteur (le TCR), qui est propre à chacun d'entre eux et leur permet d'accrocher de manière très spécifique une molécule appelée antigène. Ce TCR est employé par les lymphocytes pour inspecter les antigènes associés avec des molécules présentatrices à la surface des autres cellules. Les lymphocytes T CD8 reconnaissent un fragment de protéine (ou peptide), qui est présenté par une des molécules du Complexe Majeur d'Histocompatibilité de classe I et tuent la cellule qui présente ce peptide. Ils sont ainsi bien adaptés pour éliminer les cellules qui présentent un peptide issu d'un virus quand la cellule est infectée. D'autres cellules T CD8 reconnaissent des peptides comme les antigènes CT, qui sont produits anormalement par les cellules cancéreuses. Nous avons confirmé que les antigènes CT sont fréquemment exprimés par le cancer du foie. Nous avons également identifié des cellules T CD8 spécifiques d'antigènes CT dans la tumeur, mais pas dans le foie normal de 2 patients sur 10. Cela signifie que ces lymphocytes peuvent être naturellement activés contre la tumeur et sont capables de la trouver. De plus les lymphocytes issus d'un patient ont démontré une forte sensibilité pour reconnaître l'antigène et tuent spécifiquement les cellules tumorales. Les antigènes CT représentent donc des cibles intéressantes qui pourront être intégrés dans des vaccins thérapeutiques du cancer du foie. De cette manière, les cellules T CD8 du patient lui-même pourront être induites à détruire de manière spécifique les cellules cancéreuses. Un nouveau type de lymphocytes T a été récemment découvert: les lymphocytes NKT. Quand ils reconnaissent un glycolipide présenté par la molécule CD1d, ils sont capables, de manière encore incomprise, d'initier, d'augmenter, ou à l'inverse d'inhiber la défense immunitaire. Ces cellules NKT ont démontré qu'elles jouent un rôle important dans la défense contre les tumeurs et particulièrement dans le foie des souris. Nous avons étudié les cellules NKT de patients atteints d'une tumeur dans le foie, afin de comprendre pourquoi elles ne sont pas assez protectrice chez l'homme. Les lymphocytes NKT peuvent être sous-divisés en 3 populations: Les CD4, les DN (CD4-/CD8-) et les CD8. Ces 3 classes de NKT peuvent produire différents signaux chimiques appelés cytokines. Contrairement aux cellules NKT DN ou CDS, seules les cellules NKT CD4 sont capables de produire des cytokines qui sont défavorables pour la défense anti-tumorale. Par ailleurs nous avons trouvé que les cellules NKT CD4 tuent moins bien les cellules cancéreuses que les cellules NKT DN ou CD8. L'analyse des cellules NKT, fraîchement extraites du sang, du foie et de la tumeur de patients a révélé que les cellules NKT CD4 sont progressivement enrichies du sang vers le foie et la tumeur. La large prédominance des NKT CD4 à l'intérieur des tumeurs suggère que, chez l'homme, ces cellules sont inappropriées pour la lutte anti-tumorale. Par ailleurs, la plupart des cellules NKT de patients n'étaient pas capables de produire des cytokines après stimulation avec un antigène. Cela explique également pourquoi ces cellules ne protègent pas contre les tumeurs dans le foie.

Some coccidial parasites of the lizard Amphisbaena alba (Reptilia: Amphisbaenia: Amphisbaenidae)

Five parasites are described in the lizard Amphisbaena alba (Amphisbaenidae) from the state of Pará, North Brazil. Mature oocysts of Choleoeimeria amphisbaenae n. sp., are passed already mature in the faeces. They are ellipsoidal-cylindrical, average 33.7 x 22.8 µm and are devoid of micropyle, oocyst residuum or polar body. The colourless wall is smooth and of 2 layers. The 4 dizoic sporocysts have no Stieda body and average 13 x 9.3 µm. Endogenous stages develop in the epithelial cells of the gall-bladder in the manner described for the genus and may cause extensive tissue damage. Sporulation of Isospora capanemaensis n. sp., is completed 3 days after the oocysts are voided in the faeces. They average 14.8 x 14.5 µm and have no micropyle, oocyst residuum or polar body. The 2 tetrazoic sporocysts are pear-shaped, average 8.6 x 6.6 and have an inconspicuous Stieda body. Endogenous development is in the epithelial cells of the ileum, and heavy infections cause considerable tissue destruction. Multisporocystic oocysts passed in the faeces of one A. alba possibly originated from an invertebrate host ingested by the lizard. A globidium-like cyst in the digestive tract of A. alba measured 105 x 85 µm and contained many hundreds of merozoites. A stained kidney smear of the same lizard revealed the presence of an unidentified parasite producing multinucleate cyst-like stages.

Missing value imputation in longitudinal measures of alcohol consumption

Attrition in longitudinal studies can lead to biased results. The study is motivated by the unexpected observation that alcohol consumption decreased despite increased availability, which may be due to sample attrition of heavy drinkers. Several imputation methods have been proposed, but rarely compared in longitudinal studies of alcohol consumption. The imputation of consumption level measurements is computationally particularly challenging due to alcohol consumption being a semi-continuous variable (dichotomous drinking status and continuous volume among drinkers), and the non-normality of data in the continuous part. Data come from a longitudinal study in Denmark with four waves (2003-2006) and 1771 individuals at baseline. Five techniques for missing data are compared: Last value carried forward (LVCF) was used as a single, and Hotdeck, Heckman modelling, multivariate imputation by chained equations (MICE), and a Bayesian approach as multiple imputation methods. Predictive mean matching was used to account for non-normality, where instead of imputing regression estimates, "real" observed values from similar cases are imputed. Methods were also compared by means of a simulated dataset. The simulation showed that the Bayesian approach yielded the most unbiased estimates for imputation. The finding of no increase in consumption levels despite a higher availability remained unaltered. Copyright (C) 2011 John Wiley & Sons, Ltd.

Influence of counselor characteristics and behaviors on the efficacy of a brief motivational intervention for heavy drinking in young men-a randomized controlled trial.

BACKGROUND: Brief motivational intervention (BMI) has shown promising results to reduce alcohol use in young adults. Knowledge on mechanisms that predict BMI efficacy could potentially improve treatment effect sizes through data that optimize clinical training and implementation. Particularly, little attention has been given to counselor influence on treatment mechanisms. METHODS: We investigated the influence of counselors on BMI efficacy in reducing alcohol use among non-treatment-seeking young men (age 20) screened as hazardous drinkers. Participants were randomly allocated to (i) a group receiving a single BMI from 1 of 18 counselors selected to maximize differences in several of their characteristics (gender, professional status, clinical experience, and motivational interviewing [MI] experience) or (ii) a control group receiving assessment only. Drinking at 3-month follow-up was first compared between the BMI and control groups to assess efficacy. Then, the influence of counselors' characteristics (i.e., gender, professional status, clinical experience, MI experience, BMI attitudes, and expectancies) and within-session behaviors (i.e., measured by the Motivational Interviewing Skill Code) on outcome was tested in regression analyses. RESULTS: There was a significant (p = 0.02) decrease in alcohol use among the BMI group compared to the control group. Counselors that were male, more experienced, that had more favorable BMI attitudes and expectancies, higher MI skills, but surprisingly less MI-consistent behaviors, had significantly better outcomes than the control group while their counterparts did not. CONCLUSIONS: The current study demonstrated BMI efficacy on alcohol use reduction within a sample of non-treatment-seeking young adult males. Moreover, BMI effect was related to interindividual differences among counselors, and results therefore provide recommendations for BMI training and implementation with similar populations.

Use of nicotine substitute prescribed at hourly plus ab libitum intake or ad libitum for heavy smokers willing to quit: a randomized controlled trial.

OBJECTIVE: To assess the impact of instructional guidance in the regular use of use nicotine nasal spray (NNS) on the true use of NNS during the first three weeks of smoking cessation for heavy smokers who are willing to quit. METHODS: This randomized, open, controlled trial included 50 patients who were heavy smokers, were willing to quit, and attending an academic outpatient clinic in Western Switzerland. Patients were randomised to instruction on NNS use as "ad libitum" (administration whenever cravings appear; control group) or to use NNS when craving appears and at least every hour when awake (intervention group). Intakes were monitored using an electronic device fixed in the spray unit (MDILog) during the first three weeks of use. Self reported abstinence from smoking at six months was confirmed by expired-air carbon monoxide. Using intention-to-treat analysis, random-effect GLS regression was used to calculate the mean difference of daily doses between groups controlling for lack of independence between measures from the same individual. RESULTS: One patient was lost to follow-up. At baseline randomization, the group receiving instruction to use NNS hourly included more women, patients with previous desires to quit, and patients with more psychiatric comorbidities and less somatic complaints compared to the group instructed to use NNS with cravings (group imbalance). Both groups self-administered more than the daily recommended dosage of 8 uses. Mean daily usage was 13.6 dose/day and 11.1 dose/day for the group instructed to use NNS hourly and with cravings, respectively. Adjusting for baseline imbalance, the increased daily doses in the intervention group (hourly use) remained nonsignificant compared to ad libitum use (-0.5 dose/day; CI 95% -6.2; 5.3, from day 1 to day 7; and 2.3 dose/day; CI 95% -5.4; 10.0, from day 8 to day 21). Instructing patients to use the NNS daily had no effect on smoking cessation at six months (RR = 0.69; CI 95% 0.34; 1.39). CONCLUSION: Heavy smokers willing to quit use NNS frequently, regardless of the instructions given. Recommending the use of NNS only when craving appears for heavy smokers willing to quit seems acceptable compared to prescribing hourly administration. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00861276.

Dual role of Bmi1 loss in the preservation of photoreceptor layers in the Rd1 mouse

Purpose: In the Rd1 and Rd10 mouse models of retinitis pigmentosa, a mutation in the Pde6ß gene leads to the rapid loss of photoreceptors. As in several neurodegenerative diseases, Rd1 and Rd10 photoreceptors re-express cell cycle proteins prior to death. Bmi1 regulates cell cycle progression through inhibition of CDK inhibitors, and its deletion efficiently rescues the Rd1 retinal degeneration. The present study evaluates the effects of Bmi1 loss in photoreceptors and Müller glia, since in lower vertebrates, these cells respond to retinal injury through dedifferentiation and regeneration of retinal cells. Methods: Cell death and Müller cell activation were analyzed by immunostaining of wild-type, Rd1 and Rd1;Bmi1-/- eye sections during retinal degeneration, between P10 and P20. Lineage tracing experiments use the GFAP-Cre mouse (JAX) to target Müller cells. Results: In Rd1 retinal explants, inhibition of CDKs reduces the amount of dying cells. In vivo, Bmi1 deletion reduces CDK4 expression and cell death in the P15 Rd1;Bmi1-/- retina, although cGMP accumulation and TUNEL staining are detected at the onset of retinal degeneration (P12). This suggests that another process acts in parallel to overcome the initial loss of Rd1;Bmi1-/- photoreceptors. We demonstrate here that Bmi1 loss in the Rd1 retina enhances the activation of Müller glia by downregulation of p27Kip1, that these cells migrate toward the ONL, and that some cells express the retinal progenitor marker Pax6 at the inner part of the ONL. These events are also observed, but to a lesser extent, in Rd1 and Rd10 retinas. At P12, EdU incorporation shows proliferating cells with atypical elongated nuclei at the inner border of the Rd1;Bmi1-/- ONL. Lineage tracing targeting Müller cells is in process and will determine the implication of this cell population in the maintenance of the Rd1;Bmi1-/- ONL thickness and whether downregulation of Bmi1 in Rd10 Müller cells equally stimulates their activation. Conclusions: Our results show a dual role of Bmi1 deletion in the rescue of photoreceptors in the Rd1;Bmi1-/- retina. Indeed, the loss of Bmi1 reduces Rd1 retinal degeneration, and as well, enhances the Müller glia activation. In addition, the emergence of cells expressing a retinal progenitor marker in the ONL suggests Bmi1 as a blockade to the regeneration of retinal cells in mammals.

Serological survey of Babesia bovis, Babesia bigemina, and Anaplasma marginale antibodies in cattle from the semi-arid region of the state of Bahia, Brazil, by enzyme-linked immunosorbent assays

The objectives of this work were to determine the prevalence of Babesia bovis, Babesia bigemina, and Anaplasma marginale detecting antibodies in cattle raised in the semi-arid region of the state of Bahia, Brazil, through indirect enzyme linked immunosorbent assays (ELISA) and to compare the performances of indirect enzyme-linked immunosorbent assays with crude (I-ELISA-CrAnaAg) and recombinant major surface protein-5 (I-ELISA-MSP-5Ag), as antigens to detect antibodies against A. marginale. An stable enzootic area was found in Senhor do Bonfim and Euclides da Cunha for B. bovis that showed 86 and 95.5% of prevalence, respectively, and for B. bigemina with 90.8 and 91.3%. On the other hand, Uauá and Juazeiro, were characterized as enzootically unstable areas, since prevalences were: B. bovis - 63.7 and 56.4% and B. bigemina - 53 and 54.8%, respectively. The prevalence of A. marginale in the four municipalities was above 97% with I-ELISA-CrAnaAg and 94.8% with I-ELISA-MSP-5Ag which is an indication of stable enzootic condition for the rickettsia. The I-ELISA-CrAnaAg and I-ELISA-MSP-5Ag showed a highly significant association (r = 0.977), which means that both ELISA tests are suitable for epidemiological studies of A. marginale.

Evaluation of the GlideScope for tracheal intubation in patients with cervical spine immobilisation by a semi-rigid collar

RAPPORT DE SYNTHÈSE : Chez les patients présentant une pathologie de la colonne cervicale, l'instrumentation des voies aériennes peut s'avérer délicate. En effet, l'impossibilité d'effectuer une extension de la nuque afin d'aligner correctement l'axe oro-pharyngo-trachéal, ainsi que l'ouverture de bouche limitée par la présence d'une minerve cervicale, rendent la laryngoscopie standard extrêmement difficile. Le but de cette étude est de démontrer que l'intubation oro-trachéale avec une minerve cervicale semi-rigide est possible à l'aide d'un vidéolaryngoscope récemment développé, le GlideScope®. Celui-ci est formé d'une lame courbe présentant une angulation accentuée à 60° à partir de son milieu, avec une petite caméra haute résolution et une source lumineuse enchâssées dans la partie inférieure au point d'inflexion. Différents travaux ont montré les avantages du GlideScope® par rapport à la lame de Macintosh standard "pour l'instrumentation des voies aériennes de routine ou en situation difficile. Après acceptation par la Commission d'Ethique, 50 patients, adultes consentants et programmés pour une intervention chirurgicale élective nécessitant une anesthésie générale ont été inclus dans cette étude. Malgré la présence d'une minerve cervicale semi-rigide Philadelphia® Patriot correctement positionnée et la tête fixée à la table d'opération, tous les patients ont pu être intubés a l'aide du GlideScope®. Aucune complication n'a été documentée pendant la procédure ou en post-opératoire. De plus, nous avons démontré que dans cette situation la visualisation des structures laryngées est significativement améliorée grâce au GlideScope®, par rapport à la lame de Macintosh utilisée lors de toute intubation standard. En conclusion, l'intubation oro-trachéale chez les patients ayant une minerve cervicale et la tête fixée est possible à l'aide du GlideScope®. La meilleure façon de sécuriser les voies aériennes chez les patients présentant une instabilité de la colonne cervicale est un sujet fortement débattu. L'utilisation du GlideScope® pourrait s'avérer une alternative intéressante, en particulier dans les situations d'urgence.

Ectasie sclérale semi-annulaire pré-équatoriale chez un patient glaucomateux onchocerquien [Semi-annular pre-equatorial scleral ectasia in a patient with glaucoma and onchocerciasis].

We present the case of a glaucomatous young patient with onchocerciasis who developed a bilateral pre-equatorial scleral staphyloma with an important scleral thinness. The pathogenesis of anterior staphyloma is discussed: mechanical stress from very high ocular pressure, ocular onchocerciasis, scleral ischemia. A better understanding of scleral mechanical resistance could explain scleral thinness without any clinical scleritis.

Identification of human T-cell lymphotropic virus infection in a semi-isolated Afro-Brazilian quilombo located in the Marajó Island (Pará, Brazil)

Antibodies to human T-cell lymphotropic virus-1 and 2 (HTLV-1 and 2) were tested in 259 inhabitants (98 males and 161 females) of four villages of the Marajó Island (Pará, Brazil) using enzyme immunoassays (ELISA and Western blot). Types and subtypes of HTLV were determined by nested polymerase chain reaction (PCR) targeting the pX, env and 5´LTR regions. HTLV-1 infection was detected in Santana do Arari (2.06%) and Ponta de Pedras (1%). HTLV-2 was detected only in Santana do Arari (1.06%). Sequencing of the 5´LTR region of HTLV-1 and the phylogenetic analysis identified the virus as a member of the Cosmopolitan Group, subgroup Transcontinental. Santana do Arari is an Afro-Brazilian community and the current results represent the first report of HTLV-1 infection in a mocambo located in the Brazilian Amazon region.

Clinical spectrum of uncomplicated malaria in semi-immune Amazonians: beyond the " symptomatic " vs " asymptomatic " dichotomy

We analyzed prospectively 326 laboratory-confirmed, uncomplicated malarial infections (46.3% due to Plasmodium vivax, 35.3% due to P. falciparum, and 18.4% mixed-species infections) diagnosed in 162 rural Amazonians aged 5-73 years. Thirteen symptoms (fever, chills, sweating, headache, myalgia, arthralgia, abdominal pain, nausea, vomiting, dizziness, cough, dyspnea, and diarrhea) were scored using a structured questionnaire. Headache (59.8%), fever (57.1%), and myalgia (48.4%) were the most frequent symptoms. Ninety-six (29.4%) episodes, all of them diagnosed during cross-sectional surveys of the whole study population (96.9% by molecular technique only), were asymptomatic. Of 93 symptom-less infections left untreated, only 10 became symptomatic over the next two months following diagnosis. Fever was perceived as " intense " in 52.6% of 230 symptomatic malaria episodes, with no fever reported in 19.1% episodes although other symptoms were present. We found significant differences in the prevalence and perceived intensity of fever and other clinical symptoms in relation to parasite load at the time of diagnosis and patient's age, cumulative exposure to malaria, recent malaria morbidity, and species of malaria parasite. These factors are all likely to affect the effectiveness of malaria control strategies based on active or passive detection of febrile subjects in semi-immune populations.