The degree of volume depletion in severe malaria is currently unknown, although knowledge of fluid compartment volumes can guide therapy. To assist management of severely ill children, and to test the hypothesis that volume changes in fluid compartments reflect disease severity, we measured body compartment volumes in Gabonese children with malaria.Total body water volume (TBW) and extracellular water volume (ECW) were estimated in children with severe or moderate malaria and in convalescence by tracer dilution with heavy water and bromide, respectively. Intracellular water volume (ICW) was derived from these parameters. Bioelectrical impedance analysis estimates of TBW and ECW were calibrated against dilution methods, and bioelectrical impedance analysis measurements were taken daily until discharge. Sixteen children had severe and 19 moderate malaria. Severe childhood malaria was associated with depletion of TBW (mean [SD] of 37  ml/kg, oSignificant hypovolaemia does not exacerbate complications of severe or moderate malaria. As rapid rehydration of children with malaria may have risks, we suggest that fluid replacement regimens should aim to correct fluid losses over 12–24 h. Some investigators have suggested that children with malaria need a lot of fluids. But this paper casts doubt on this assumption, and assesses a novel way to assess fluid balance ICW is calculated by subtraction of the ECW from the TBW.Malaria claims one million lives annually, with more than 90% of these being those of children in sub-Saharan Africa . Most deTracer dilution methods are expensive and invasive and cannot be repeated at short intervals. Therefore, we simultaneously calibrated a noninvasive technique of bioelectrical impedance analysis (BIA)  to estimWe hypothesised that volume changes in fluid compartments would reflect disease severity in malaria and that these changes would be related to established markers of disease severity . We alsoThe study was conducted at the Albert Schweitzer Hospital, Lambaréné, Gabon, and Centre Hospitalier de Libreville, Gabon. It was approved by the ethics committees of the International Foundation of the Albert Schweitzer Hospital, the Gabonese Ministry of Health, and the University of Tübingen.Plasmodium falciparum in thick or thin blood films. Severe malaria was malaria with one or more of the following features: blood lactate ≥ 5 mmol/l, blood glucose ≤ 2.2 mmol/l, Blantyre coma score ≤ 2, or repeated, observed seizures  is plasma sodium concentration (millimoles/litre), [glucose] is plasma glucose concentration (millimoles/litre), [urea] is plasma urea concentration (millimoles/litre), 1.86 is a correction factor as sodium chloride is only 93% dissociated, and 0.93 is the assumed proportion of water in plasma.where OG is osmol gap, MO is measured osmolality, ) time from admission to administration of tracers was 54 (37–84) min, during which complications such as convulsions or hypoglycaemia were treated. The baseline characteristics of children are given in p > 0.5). There was rapid correction of vital signs in all children (2O with no significant rise in the first 24 h.The volume of fluid (including blood) given in the first 4 h of the study was similar in children with severe  and moderate  malaria  but not for moderate cases (p = 0.109). The mean (SD) TBW was lower in severe than moderate malaria at admission: 524 (44) ml/kg versus 555 (50) ml/kg (p = 0.052). The mean (SD) change in TBW between admission and follow up was 48 (42) ml/kg and 12 (37) ml/kg for severe and moderate cases, respectively. Individual data from the children with severe malaria are shown in Volume determinations using isotope dilution were available at baseline in all but one of the children with severe malaria. The values for the TBW, ECW, and ICW are given in p = 0.045). Admission ICW measurements were significantly lower in children with severe malaria than in those with moderate malaria (p < 0.001).Bromide space (ECW) measurements were available in all but two children with severe malaria and in all but one of the children with moderate malaria. At baseline, the mean (SD) ECW was significantly lower in children with moderate than in those with severe malaria (2 divided by impedance at 50 kHz (H2/Z50) and measured TBW. The ‘best fit' regression equation to predict TBW from BIA was derived using the variables age, weight, and H2/Z50 :As predicted by theory , there wA is age (months), H is height (centimetres), W is weight (kilograms), and Z50 is impedance at 50 KHz frequency. Disease severity and gender did not contribute significantly to this model, allowing data from admission to be pooled in this prediction equation. Repeating the analysis using impedances measured at other frequencies (4–1012 kHz) did not show a clear advantage, so all data for TBW prediction are given for measurement at 50 kHz.where H2/R0 emerged as the strongest predictive term :By contrast, ECW was not significantly associated with age or weight, and in agreement with previous studies in babies  H2/R0 H is height (centimetres), and 0R is resistance at zero frequency. Again, disease severity and gender did not contribute significantly to this model. Prediction equations based on segmental BIA data for ECW and TBW were inferior to whole body BIA models and are therefore not shown here.where Errors in BIA estimates of TBW and ECW compared to values measured by isotope dilution are displayed with 95% limits of agreement in Fluid volume estimates were available from BIA in 14 children with moderate and 11 with severe malaria on admission and 16 with moderate and 12 with severe malaria at discharge. Values for the TBW, ECW, and ICW are shown in p = 0.034). TBW increased from admission to discharge in children with severe malaria by 37 (33) ml/kg or 6.7% (6.0%) , but there were no significant changes in TBW for children with moderate malaria between admission and discharge.BIA-determined TBW was significantly lower in those with severe compared with moderate malaria (mean [SD] of 539  versus 5p = 0.002). ICW remained unchanged between admission and discharge in children with moderate malaria. In the severe malaria group mean (SD) of ICW at admission was 40 (22) ml/kg, or 11.7% (11.0%) lower at admission than at discharge (p = 0.002). There were no differences in the fluid volume measurements of the four children with adverse and those with good outcomes.ECW did not differ between the severe and moderate groups on admission and did not change significantly between admission and discharge. Serial measurements of ECW did not show any rise during the first 4 d after admission, at discharge, or at day 28 in children with severe or moderate malaria (data not shown). ICW at admission was significantly lower in the severe malaria group than in the moderate malaria group, with a mean (SD) of 293 (17) ml/kg versus 325 (28) ml/kg . For those with moderate malaria the deficit was not significant: −0.3% (4.6%) /−0.9%  (p = 0.41). As predicted, the deficits in weight and TBW were correlated .Admission weight relative to the weight at discharge showed a mean (SD)/median  percentage deficit of −4.3% (4.4%)/−4.0%  for the children with severe malaria on admission (p = 0.036). Plasma potassium concentration and osmolality were higher in children with severe than in those with moderate malaria . Plasma urea and creatinine were significantly higher in those with severe malaria. Osmol gap was significantly higher in children with severe than in those with moderate malaria (p < 0.001), with 15/16 children in the severe group having an osmol gap greater than 8.2 mOsm (considered high in United States children [The concentrations of plasma electrolytes are shown in children ).We have shown that severe childhood malaria is associated with mild dehydration in most cases, with a mean (SD) depletion of TBW of 37 (33) ml/kg, or 6.7% (6.0%). Only 3/16 children 19%) in our study had moderate volume depletion (> 60–90 ml/kg), and none were severely dehydrated (> 100 ml/kg) . Moderat% in our Our findings suggest that the degree of dehydration in children with severe malaria is unlikely to be a primary pathological process in the evolution of the disease. These findings are also consistent with our previous suggestion that hyperlactataemia arises from tissue hypoxia resulting from microvascular obstruction by infected erythrocytes ,22 ratheOur estimates of fluid compartment volumes in children after recovery from malaria are entirely consistent with previous work in children  , althougIn sepsis, ECW increases by up to 50% of TBW because capillary permeability increases by up to 300% of normal. There are no significant increases in ECW in children with severe malaria, confirming earlier studies that indicate that sepsis and malaria syndromes result from different pathophysiological processes ,28. StudHyponatraemia  has beenWhat are the implications of our findings for optimal fluid replacement therapy in malaria? We cannot answer precisely on the basis of measuring fluid compartment volumes because regimens are sometimes designed not only to correct existing fluid deficits and to provide maintenance requirements, but also to rehydrate more vigorously to maintain circulating volume. Such approaches are advocated by others for different populations of children with severe malaria, for example, in a series of studies published from Kilifi, Kenya ,5,34. HoThere are risks to over-vigorous fluid administration just as there are with inadequate fluid replacement, particularly in hospitals where measuring plasma electrolyte concentrations and providing assisted ventilation are difficult. These risks include pulmonary  and cereA correlation between capillary refill time and blood lactate concentrations but none with fluid volume status suggests that prolongation of capillary refill time may be due to the common underlying process of microvascular obstruction.Our findings do not support the widespread use of aggressive fluid volume replacement in children with severe malaria. Clearly, volume depletion indicated by hypotension or by CVP measurements requires more aggressive therapy, but wherever possible plasma electrolyte concentrations should be closely monitored. Because of elevated requirements for glucose in childhood severe malaria (3–6 mg/kg/min) , there iThe tracer dilution techniques that we have used are expensive and time-consuming and consequently not amenable to large-scale deployment. We took this opportunity to calibrate a much simpler methodology (BIA) to derive TBW and ECW and validated BIA estimations in this population. We are now using BIA measurements to assess much larger numbers of patients . BIA is an excellent noninvasive screening tool that should detect subgroups of children with severe malaria who may be severely volume depleted.Although we have known for many years what causes malaria, how it is passed from person to person by mosquito, and how to treat the infection, more than a million people still die of malaria every year, mostly children under five years living in Africa. Children are affected most because they have not had the chance to develop the resistance to malaria that normally builds up over a lifetime when living in places with malaria. As well as being given specific drug treatments against the malaria, children are also often given fluids into their veins, as they appear dehydrated.The researchers studied children who were sick with malaria and measured how dehydrated the children were. To do the measurements, they used an accepted technique that required injections into the vein, and also a newer, simpler method that used electrodes. Neither technique suggested that any of the children were severely dehydrated.The study suggests that severe dehydration isn't a big problem in children with severe malaria. So it may not be necessary to give lots of fluids into the vein. The new technique for measuring dehydration will need to be assessed in larger studies: this study is small, so the results may not be entirely accurate.http://www.who.int/topics/malaria/en/).The World Health Organization is coordinating many of the initiatives to combat malaria (http://www.mmv.org/pages/page_main.htm).Medicines for Malaria Venture is trying to develop new affordable antimalarial drugs (


We are pleased that Dr. Maitland and colleagues consider our data on volume status (intra- and extracellular) of Gabonese children to be important. We did not consider our children with severe malaria to have intravascular volume depletion for the following reasons. When we measured central venous pressures in a proportion of children on admission, there was no evidence of intravascular volume depletion (median [interquartile range] = 6.5 [3–7.5] cm water), and these values did not change significantly over 24 h, suggesting that our severely ill children had adequate filling pressures. Consistent with this observation, our severely ill children improved rapidly when markers of tissue hypoxia  were serially monitored and children were managed with a relatively conservative fluid replacement regimen. Interestingly, extracellular volume was not increased at admission or afterwards either. Capillary leakage, which commonly accompanies hypovolaemia associated with septic shock, was therefore unlikely to be a significant pathophysiological process in these children with malaria. There may be differences in the severe syndromes of malaria seen in different geographical locations, perhaps accounting for the clinical features attributable to compensated hypovolemic shock reported by Maitland and colleagues. Such differences can be assessed using simple and recently calibrated bioelectrical impedance analysis methodology as well as other techniques that monitor intravascular volumes. The design of optimal fluid management regimens for children with severe malaria can thus be informed not only by theoretical considerations, but also by appropriate physiological assessments.


In most parts of the world, microscopy is still the gold standard for diagnosing malaria. An online tool could help to improve your diagnostic skills An online tool allows microscopists to test their knowledge Malaria kills over one million people in Africa each year and contributes 10% of the continent's burden of disease . In thisMalaria affects at least 200–300 million people every year and causes from 1–2 million deaths—mostly children under five and pregnant women in sub-Saharan Africa [Malaria is not limited to Africa—40% of the world's population is at risk of acquiring the disease —and it iDespite the efforts of a global campaign to roll back the disease, the number of deaths from malaria is increasing in Africa . This stThere is another important reason why correct diagnosis matters. Because of rising drug resistance in Africa, the conventional drugs for treating malaria—chloroquine and sulfadoxine-pyrimethamine—are now failing in up to 80% of cases . There iPlasmodium falciparum [We still regard microscopy as the gold standard for the diagnosis and characterisation of malaria infection . Modern lciparum —althoughlciparum ,17—but tSome authors have suggested that these new tests should not be considered a complete substitute for direct microscopic examination of blood smears . We agreP. falciparum or three P. vivax parasites per microlitre of blood [Analysis of DNA by the polymerase chain reaction (PCR) may be a useful tool for diagnosis of malaria when the results of conventional techniques are negative, especially since PCR allows accurate species identification . And wheof blood . Howeverof blood . Even inhttp://www.rph.wa.gov.au/labs/haem/malaria/index.html). The materials are now available in English, French, and Spanish. One of the most important features is a “Test and Teach” section to allow microscopists to develop and sharpen their skills in malaria diagnosis  has been sent on request to institutions and centres in 149 countries, a number that does not include unauthorised (pirated) copies of the CD-ROM. The number of hits to the site (the number of pages or images of the site that are accessed) has risen dramatically, from 1,500 to over 100,000 per week.Graham.Icke@health.wa.gov.au.Through a circulated questionnaire with a 63% response rate, we have received feedback from users in 15 countries. Respondents said they valued the content, presentation, and usefulness of the online information. Who is using the material? A wide range of people—from students through to experienced personnel, and from clinicians to scientific, research, and technical staff. Many tropical medicine institutions have requested copies of the CD-ROM to supplement their own training programs. We have discussed the project at scientific conferences around the world and in scientific journals, advertising the fact that this educational material is freely available. Institutions wishing to obtain a free copy of the CD-ROM should contact E-mail: We also became aware that unauthorised copies of the CD-ROM were being produced. Although there is a real need to guarantee the integrity of the information on the CD-ROMs and ensure proper credit for the authors and patrons, our main aim is to spread the “good word”, and such unauthorised copies are a powerful aid to distribution. Given that there is no need to recoup profit from this project, our only concern is its usefulness. Consequently, we have welcomed the production of these pirated copies, on condition that they were of good quality and were made freely available at no cost.The Internet and associated technologies make it possible for educators with a desire to teach to contact those with a need to learn, regardless of the geographical distances involved. By enlisting assistance from international colleagues, language barriers can be overcome. In addition to the English, French, and Spanish versions, we are aware that our project has been translated into German, Thai, and Vietnamese and has been distributed through small regional health group networks.There can be little doubt that these new technologies have the potential to revolutionise information dissemination, with particularly significant implications for healthcare professionals in developing countries. The malaria educational program could be a model on which future health education programs are based. With rapidly increasing access to these new information technologies, health care professionals from anywhere in the world can now join the global health community.


Acidosis is a major cause of death in patients with malaria, although what causes acidosis is still unclear. One possibility is that hypovolemia contributes to the problem, and that rehydration therapy could be of benefit. Now, Sanjeev Krishna and colleagues have shown that in children with severe malaria dehydration is not severe and is not correlated with other measures of disease severity. “The optimum resuscitation approach in severe childhood malaria remains to be defined,” says Nick White , the academic editor of the paper. “The relative advantages of blood, colloids, and crystalloids need to be characterized.”Every year around 200 million people worldwide contract malaria, of whom over a million die. The vast majority of those who die are children under five years, mostly in Africa, since young children have had little chance to acquire any immunity. Fluid resuscitation is generally considered to be a cornerstone of treatment—but how much fluid should be given? Some researchers believe that surrogate signs of fluid depletion—such as tachycardia, reduced capillary refill time, and reduced urine excretion—suggest that there is substantial volume depletion. The reason that the amount of fluid given matters so much is that giving too much, especially of hypotonic solutions, can lead to electrolyte imbalance, especially hyponatremia and hypokalemia.Research efforts have been hampered by not having an easy way to assess in patients the fluid depletion in different compartments of the body, i.e., total body water and extracellular and intracellular water volume. Krishna and colleagues used heavy-water distribution to calculate the total body water and bromide distribution to determine the extracellular volume in 19 children with moderately severe malaria and 16 with severe malaria in Gabon. By subtracting extracellular volume from total body water, they were able to calculate intracellular volume for each child. They also used a less invasive and more rapid method of determining water volumes based on using bioelectrical impedance to calculate the volume.None of the children were severely dehydrated (defined as more than 100 ml/kg depletion), and only three of the children with severe anemia had fluid depletion, which was moderate (60–90 ml/kg depletion). “This challenges the view that dehydration is a major contributor to the pathology of this frequently lethal disease,” says White.So based on these data, obtained from a carefully studied, albeit small group of children, what should people who treat children with malaria do? The authors' first recommendation is that clinicians should think again about how vigorously they rehydrate children, and if they have access to ways of assessing fluid volume more precisely, they should do so . And certainly the methods used by Krishna and colleagues should undergo wider testing in larger groups of children to confirm their usefulness. Until the worldwide efforts to prevent malaria come to fruition, refining the management of infected children will remain a cornerstone of the efforts against this devastating disease.


The relationship between the burden of uncomplicated malaria and transmission intensity is unclear and a better understanding of this relationship is important for the implementation of intervention programmes.A 6-month longitudinal study monitoring risk factors for anaemia and febrile malaria episodes was conducted among individuals aged below 20 years, residing in three villages of different altitude in areas of high, moderate and low malaria transmission intensity in North-Eastern Tanzania.Plasmodium falciparum was the only significant parasitic determinant of anaemia. Interestingly, children who carried low-density parasitaemia at the start of the study had a lower risk of contracting a febrile malaria episode but a higher risk of anaemia during the study period, than children who were slide negative at this point in time.The burden of anaemia and malarial fever fell mainly on the youngest children and was highest in the village with high transmission intensity. Although a considerable percentage of individuals in all villages carried intestinal worms, logistic regression models indicated that Young children living in the high transmission village carried a very high anaemia burden, which could be attributed to malaria. The overall incidence of febrile malaria was also highest in the high transmission village particularly among those under five years of age. These data suggest that in rolling back malaria, available resources in prevention programmes should primarily be focussed on young children, particularly those residing in areas of high malaria transmission. Plasmodium falciparum malaria remains an important public health problem in sub-Saharan Africa. To develop and assess the efficacy of control measures, it is important to obtain a better understanding of how the malaria disease burden is distributed among population groups and how this burden is affected by changes in malaria transmission intensity ) had normal haemoglobin levels during the July and September cross sectional surveys, while 44 developed anaemia during the study (mean age (years) and 95% Cl: 7.9 ). Logistic regression models correcting for age showed that the risk of developing anaemia during the study was 4.4 times (p = 0.038) higher in individuals carrying low-density parasitaemia in April than in those who were slide negative (Table This prospective longitudinal study was designed to compare the burden of uncomplicated malaria in three similar villages situated in areas of markedly different transmission intensity. Not surprisingly, the study showed that individuals living in the village with very high malaria transmission carried a markedly higher burden of both anaemia and febrile malaria episodes compared to villagers at the sites with lower transmission. This result is in agreement with results from previous studies in the area . The vilP. falciparum carriage at the beginning of the study influenced the risk of developing febrile malaria episodes or anaemia during the following study period. Interestingly, multivariate logistic regression models indicated that children carrying low-density parasitaemia during the first cross sectional survey were at a lower risk of developing a febrile malaria episode than children without detectable parasitaemia or children with higher levels of parasitaemia. This apparent protective effect of low-grade parasitaemia was recently also reported in a study from Ghana [The longitudinal design of our study allowed an exploration of whether om Ghana , but in The overall burden of malaria morbidity was found to be highest in the high-transmission area, where infants and children carried a very high malaria burden in the form of febrile episodes and anaemia. Populations in the areas of moderate and low transmission suffered a significantly lower morbidity. Therefore, in order to roll back malaria, available resources in malaria control programmes should focus on underfives residing in the high-transmission areas.JPAL and LSV participated in the planning of the study, carried out field surveys, analysed the data and drafted the manuscript. BPM participated in designing the study, carried out field surveys and managed the data. CJD participated in study planning, in the fieldwork and in editing of the manuscript. CJ participated in the planning of the study and conducted the socio-economic analysis of study villages. JA and ZXS participated in the field surveys and performed microscopy of all blood smears. AYK, MML and TGT participated in study planning, coordination, and analysis of data. All authors participated in the paper writing and approved the final manuscript.


Malaria continues to claim one to two million lives a year, mainly those of children in sub-Saharan Africa. Reduction in mortality depends, in part, on improving the quality of hospital care, the training of healthcare workers and improvements in public health. This study examined the prognostic indicators of severe falciparum malaria in Gabonese children.Plasmodium falciparum infection and one or more features of severe malaria were enrolled.An observational study examining the clinical presentations and laboratory features of severe malaria was conducted at the Centre Hospitalier de Libreville, Gabon over two years. Febrile children aged from 0 to 10 years with Most children presenting with severe falciparum malaria were less than 5 years (92.3% of 583 cases). Anaemia was the most frequent feature of severe malaria (67.8% of cases), followed by respiratory distress (31%), cerebral malaria (24%) hyperlactataemia (16%) and then hypoglycaemia (10%). Anaemia was more common in children under 18 months old, while cerebral malaria usually occurred in those over 18 months. The overall case fatality rate was 9%. The prognostic indicators with the highest case fatality rates were coma/seizures, hyperlactataemia and hypoglycaemia, and the highest case fatality rate was in children with all three of these features.Prompt and appropriate, classification and treatment of malaria helps identify the most severely ill children and aids early and appropriate management of the severely ill child. Plasmodium falciparum infection is very rare after the age of 5 years in highly endemic areas. Presentations of severe malaria are different at different ages and in areas with different levels of transmission. In Gabon, a country of about 1.2 million people, malaria is the main cause of neurological, haematological and infectious emergencies at the Centre Hospitalier de Libreville (CHL), the country's tertiary referral centre [Each year 500 million infections and up to 2.7 millions deaths are attributable to malaria , about 9l centre . Previoul centre ,5,9. Thel centre . In Afril centre . Better This study was carried out in the CHL between 1st August 2000 and 31st July 2002. The CHL is the largest public hospital in the country, situated in Libreville, the capital city . Services at the CHL include an Emergency Department (20 beds), a Paediatrics Unit (80 beds) and an Intensive Care Unit (12 beds). Ethical permission for the study was granted by the Gabonese Ministry of Health.pro-forma sheet. A blood sample (2 ml) was drawn (anti-coagulated with EDTA) for quantitative examination of a blood film for malarial parasites using the Lambaréné method [P. falciparum in 100 high power fields of a thick film. The schematic process of the inclusion is shown in Figure Febrile children were referred the study team and seen on admission by a Malaria Clinical Research Unit (MCRU) clinician, summary data were recorded on a é method , measureé method . Blood fP. falciparum seen on blood film) and had one or more of the following features of severity: [Febrile children (or those with history of fever in the last 48 hours) were considered for inclusion in the study if they were: aged 0 to 10 years of age (inclusive), had malaria  without a loading dose, followed by oral quinine when tolerated. Pyrexial children received paracetamol suppositories . Seizures were controlled with diazepam . Severe anaemia was corrected by transfusion of packed red cells (15 ml/kg over 4 hours) screened for blood borne infections. Hypoglycaemia was treated with a slow intravenous injection of hypertonic glucose 40 % at a dose of 1 ml/kg. Nasal oxygen at 6 1/minute was given to children with respiratory distress.An MCRU clinician performed a full physical examination daily until discharge for each child. Laboratory assessments including parasitaemia, blood glucose and lactate were performed during hospitalization as necessary. The outcome  was recorded.2 tests with Yates' correction or Fisher's exact test. ANOVA test were used for multiple comparisons of variances, with Tukey's post hoc test. Assessments of prognostic factors were conducted with logistic regression model. A p value < 0.05 was considered as significant. Specific prevalence for each subgroup has been defined as the ratio of the number of cases observed in this sub-group over the population of this same sub-group. Hyperlactataemia is usually defined as a blood lactate concentration of ≥ 5 mmol/L. As the Accusport has been found to have poor agreement with the gold standard YSI 2300 [Statistical analysis was carried out with Epi info 6.04  and Stata Statistical Software . Normality of data distribution was checked using either Shapiro-Wilks or Kolmogrov -Smirnov test. Normally distributed data were analysed by two-tailed Student's T test and non-normally distributed data with the Mann-Whitney U statistic. Proportions were compared with χYSI 2300  or YSI 1YSI 2300 , a definP. falciparum. A lower prevalence of malaria was seen in children aged< 6 months . Specific prevalence of malaria rises after the 6 first months of life until it reaches a maximum at 47 months (47.5%), after which it declines again. Severe anaemia was most frequent in children less than 24 months old with 68 % of the cases of severe malarial anaemia occurring before this age. In contrast, the highest specific prevalence of cerebral malaria was found in children aged > 12 months. Sixty five percent of cases of cerebral malaria occurred in children aged between 12–48 months.During the study period (1st August 2000-31st July 2002), 8,036 febrile children were screened for malaria at the hospital. The data for 7,980 of these children were analysed: 4,368 male (54.5%) and 3,612 female (45.5%). Seventy-five percent these were less than 5 years of age. 3,156 (39.3%) of the 8,036 febrile children screened in the MCRU had a positive blood film for The admission clinical, laboratory and parasitological characteristics of the 583 children with severe malaria are shown in the Figure Severe anaemia was the commonest feature of severe malaria present in 395  of the children. Neurological presentations (either coma or repeated convulsions) were present in 228 (39.2%) of the children. Respiratory distress occurred in 181 (31%) of the children ; hyperlactataemia in 73 (15.7%) and hypoglycaemia in 33 (6.2%) of the children with severe malaria. Hyperparasitaemia (> = 20% of circulating infected red blood cells) was relatively rare, occurring in only 24 (4.1%) of the children with severe malaria.Renal failure, acute pulmonary oedema and spontaneous bleeding are uncommon complications of childhood malaria ,9,10 andFigure Of 583 patients, 52 died , giving an overall case fatality rate of 8.9%. Seven children were lost to follow-up. Forty seven deaths (90%) occurred within the first 24 hours after admission.Neurological sequelae were present in 27 (5 %) of the 531 survivors. The case fatality rate was significantly higher in females than males . Children who died were older than those who survived (mean (SD) = 35.4 (41.9) vs. 25.0 (18.2) months, p = 0.0009).Of the 52 deaths in the course of the study, 32 (61.5%) presented with cerebral malaria, 32 (61.5%) presented with respiratory distress, and 20 (50% of the 40 with measurements) had hyperlactataemia.Thirty (60%) of the children who died presented with convulsions, and 13 (25%) with hypoglycaemia. Twenty four (46.2%) of those who died had severe anaemia. Mortalities in each sub-group demonstrated that hyperparasitaemia  and severe anaemia  had a better prognosis than cerebral malaria  and hypoglycaemia . Thirty-two (17.7%) of the 181 patients with RD died, as did 30 (11%) of the 264 patients with convulsions and 20 (27.4 %) of the 73 patients with hyperlactataemia.A multiple logistic regression model identified coma , hyperlactataemia , respiratory distress  and hypoglycaemia  as independent predictors of a fatal outcome. Severe anaemia, hyperparasitaemia and thrombocytopaenia were not shown to be predictors of death  with severe malaria were afebrile on admission as observed elsewhere [Fever is a characteristic feature of lsewhere . Self-meSevere anaemia was the most frequent feature of severity in this study, but was associated with decreased mortality. A similar observation in a recent Ghanaian study showed a better outcome in children with severe anaemia . These fDespite the increasing toll of HIV infection, and the continuing burden of diarrhoeal disease, malnutrition and respiratory tract infections, malaria remains a major cause of childhood death in endemic regions . The oveThe independent prognostic indicators in this study were cerebral malaria, respiratory distress, hypoglycaemia and hyperlactataemia. These observations are entirely consistent with a large number of studies where the independent predictors of a fatal outcome in malaria are impaired consciousness and metabolic dysfunction  ,14,16-18Estimates of the prevalence of hypoglycaemia have been reported in Africa, ranging from 8% to 34% ,29. In sThe definition of hyperlactataemia used in this study was a blood lactate concentration higher than the conventional cut-off (≥ 5 mmol/L). This was necessary because of the limitations of the analyser used, but probably means that the frequency of true hyperlactataemia was underestimated. The Accusport™ analyser used has been shown to have poor agreement with "gold standard" machines ,15,30.Hyperlactataemia is a frequent and serious complication of severe malaria in childhood ,9,10, whThese differences may partly be explained by low inter-observer agreement for this variable, geographical variations in disease pattern as well as differing definitions of severe malaria. Results from many studies consistently show that respiratory distress is a life-threatening syndrome in childhood malaria ,33. RespThe clinical and laboratory presentations of severe malaria are described in a hospitalized population of children in Gabon. The severe cases are likely to be only the "tip of the iceberg", many children living far from health care units may die whilst travelling to the nearest hospital. Most deaths from malaria occurred in the first 24 hours of admission, which highlights the need for early recognition of the most severely ill children. Early diagnosis and classification of severe malaria would allow appropriate management, including basic adjunctive therapy such as to prevent hypoglycaemia, and better use of scarce healthcare resources. Together these improvements could contribute to a reduction in the intractably high mortality due to the disease.AD is a MCRU clinician. He participated to the study and wrote the article. PN conducted the study for his MD thesis. RT and MB are paediatricians who participated in the study. TP is a UK collaborator who participated in the study and helped write the article. MM was involved with the intensive care of the children. UMR participated in the study as a MCRU clinician. JJ helped to write the article. EK did all the statistical analysis. ENM, PK, SK and MK coordinated the realization of the study and edited the final version approved by all authors.


Malaria takes a heavy toll in Niger, one of the world's poorest countries. Previous evaluations conducted in the context of the strategy for the Integrated Management of Childhood Illness, showed that 84% of severe malaria cases and 64 % of ordinary cases are not correctly managed. The aim of this survey was to describe epidemiological, clinical and biological features of malaria among <5 year-old children in the paediatric department of the National Hospital of Niamey, Niger's main referral hospital.th to October 25th. Microscopic diagnosis of malaria, complete blood cell counts and measurement of glycaemia were performed in compliance with the routine procedure of the laboratory. Epidemiological data was collected through interviews with mothers.The study was performed in 2003 during the rainy season from July 25256 children aged 3–60 months were included in the study. Anthropometrics and epidemiological data were typical of a very underprivileged population: 58% of the children were suffering from malnutrition and all were from poor families. Diagnosis of malaria was confirmed by microscopy in 52% of the cases. Clinical symptoms upon admission were non-specific, but there was a significant combination between a positive thick blood smear and neurological symptoms, and between a positive thick blood smear and splenomegaly. Thrombopaenia was also statistically more frequent among confirmed cases of malaria. The prevalence of severe malaria was 86%, including cases of severe anaemia among < 2 year-old children and neurological forms after 2 years of age. Overall mortality was 20% among confirmed cases and 21% among severe cases.The study confirmed that malaria was a major burden for the National Hospital of Niamey. Children hospitalized for malaria had an underprivileged background. Two distinctive features were the prevalence of severe malaria and a high mortality rate. Medical and non-medical underlying factors which may explain such a situation are discussed. Malaria accounts for 1 in 5 of all children deaths in Africa. Late presentation, misdiagnosis, inadequate management, unavailability or stock-outs of effective drugs are factors that influence high case-fatality rates even among hospital in-patients  is to esNiger is situated in the eastern part of West Africa in the Sahelo-Saharan zone. It is a landlocked country surrounded by Algeria, Libya, Chad, Nigeria, Benin, Burkina-Faso and Mali. The country's climate is a rainy season from June to October and a dry season during the rest of the year. The hottest months are April and May.th of 175 countries with an annual GDP of about $160 per capita (2001). The demographic situation is characterized by a population of 11,544,000 inhabitants (2002) which is expected to double by 2025 with an annual growth rate of 3.5% (1999–2002). The infant and child mortality rate is 255‰ and 63% of the population live below the poverty line ($1 per day per person) [According to the Human Development Index (UNDP 2003), Niger ranks 174The Bamako Initiative of 1987 was adopted by Niger but in a context of extreme poverty, the generalization of the cost recovery may have an impact on the access to health facilities, which should be assessed.Plasmodium falciparum is the predominant species partially associated with Plasmodium malariae and less frequently with Plasmodium ovale, according to geographical variations [Malaria is endemic in Niger with 97% of the population exposed to the risk of malaria , but somriations .Anopheles gambiae and Anopheles arabiensis may play a substantial role in malaria transmission but Anopheles funestus which was no longer found after 1970 seems to have reappeared in several sudano-sahelian zones of Niger [Among the anopheles of epidemiological importance, only of Niger ,11.Resistance to chloroquine was first described in 1991  but few Malaria remains a main cause of morbidity in Niger with an average of 850,000 cases per annum, corresponding to an annual incidence of 80‰ inhabitants, and 33.97% of reported deaths are due to malaria . These eIn Niger, as in many sub-Saharan countries, malaria takes a heavy toll, especially among young children in poor households. An evaluation – conducted in 2003 by the University Research Corporation  in the cA high proportion of deaths in the National Hospital of Niamey (NHN) is related to malaria. The poor quality of medical care makes it difficult to assess the real burden of malaria in terms of mortality and morbidity. Misdiagnosis is likely to be quite common, either in excess or default. The objective of the present prospective study was to describe the epidemiological, biological and clinical features of cases of malaria in children in the paediatric department of the NHN in order to recommend more relevant decision-making and interventions.th to October 25th, which is the peak transmission period. The NHN is the country's main referral hospital and has 852 beds. The paediatric department has two sections: section A (60 beds) for children from 0 to 24 months, and section B (60 beds) for children from 25 months to 15 years of age. A majority of patients come from the urban community of Niamey but some may be referred from all parts of the country.The study was carried out in the NHN during the rainy season of 2003 from July 25Children from 3 months to 5 years of age (60 months) admitted to Paediatric department A or B for presumed malaria were included in the study and treated following procedures normally used in the department: children went through the emergency department where a clinical examination was performed by doctors or by medical students in their final year, venous blood was drawn for biological tests , confirmed cases of malaria were treated intravenously with quinine twice a day for 2–3 days, followed by oral treatment .Upon admission, or within 24 hours, a physician conducted interviews with mothers in order to collect epidemiological data. Information such as age of the parents, number of siblings, the child's rank in relation to siblings, care-seeking previously to hospitalization, delay between the onset of disease and admission to the NHN, and treatment before hospitalization, was collected. The socio-economic background of households was evaluated through the Niamey neighbourhood where children originated from, the educational level of the mother (whether illiterate or not), the occupation of the mother and father, and the existence or non existence of a regular salary.Biological tests were performed along the routine procedures of the NHN's laboratory. Thick and thin blood smears were prepared and stained following standard procedures: Giemsa 10% for 20 minutes  for thick smear, and rapid staining  for thin smear. A thick smear was declared negative only after examination of 200 fields (obj × 100). All smears were checked the following day by a different technician. Parasitaemia was measured on thin smear and expressed as a percentage of parasitised red blood cells. Haematological tests – haemoglobin concentration, hematocrit and complete blood cell count – were performed automatically using a KX21 (Sysmex). The blood glucose rate was performed with a COBAS Mira (Roche) using the glucose oxidase technique .P. falciparum on thick smear and at least one of the following clinical or biological criteria : coma , impaired consciousness (Blantyre >2 and < 5), repeated convulsions (≥ 2/24 hours), prostration, respiratory distress, jaundice, metabolic acidosis (bicarbonates < 15 mmol/L), severe anaemia (Hb < 5 g/dL or Ht < 15%), hyperparasitaemia (parasitaemia > 4% in non-immune patients), macroscopic haemoglobinuria, renal failure, collapse (TAS < 60 mmHg before 5 years of age), abnormal bleeding or pulmonary oedema (X-ray criterion). The conditions in the NHN in 2003 made it impossible to asses acidosis, renal failure (based on creatinine) and pulmonary oedema. Only the following criteria could be considered: coma, impaired consciousness, convulsions, respiratory distress, jaundice, abnormal bleeding, severe anaemia, hyperparasitaemia, hypoglycaemia.According to the 2000 WHO criteria , severe Children were weighed. The index weight-for-age (weight/age ratio) was calculated and analysed with the Epi-Info software, based on the reference population defined by the US National Center for Health Statistics.(NCHS). Malnutrition was defined as a weight/age ratio more than 2 SD below the NCHS's reference population . MalnutrVersion 6 of the program Epi-Info was used for statistical analysis. ANOVA and Kruskal Wallis tests were used for mean comparisons whenever appropriate. Proportions were compared using chi-square tests. Bivariate odds ratio and their 95% confidence intervals were calculated to measure the combination between fatal outcome and different variables. For all tests, a p-value below 0.05 was considered significant.The routine management of the children was not changed. Verbal consent was obtained from the parents after informing them in their native language. The parents were allowed to remove their child from the study at any time during follow-up. All data was entered anonymously into a database and identification numbers were coded. No ethnic data was registered. The protocol was submitted to and approved by the Ministry of Public Health and Endemic Diseases Control's National Malaria Control Program.256 children were recorded over the 3 month survey: 138 males, 118 females (sex ratio = 1.17). The average age was 20.2 months: 3–12 months, n = 103 (40%), 13–24 months, n = 103 (40%) and 25–60 months, n = 50 (20%). The average age of parents was 27 years for the mothers, 39 years for the fathers. The number of living siblings averaged 2.8, and 35% of the children were first born. All children came from the urban community of Niamey, and 241/256 (94 %) from poor neighbourhoods: unsanitary neighbourhoods, near the river or near permanent ponds, some of them without electricity or tap water. The educational level of the mothers was low: 246/256 (96%) were illiterate, and 248/256 (97%) were home workers. Only 58/256 fathers (23%) had a monthly fixed income . The others had unsteady jobs with no stable income.77 children out of 217 documented files for this item (35%) were considered malnourished and 42% dehydrated as a result of clinical examination. The percentage of malnutrition, however, was 58% based on the weight/age ratio, of which 30% were moderate and 28% severe cases of malnutrition. The youngest children (under 2 years old), particularly the 13–24 months age group, which corresponds to the weaning period, were most affected , digestive disorder (51%) and convulsions (19%). These symptoms were often combined  had a positive thick blood smear. The percentage of treated children was the same among children with a negative thick blood smear as among those with a positive one (87% versus 86%). Both groups had quite a similar corrected axillary temperature (38.6° with positive thick smear versus 38.4°).The clinical presentation of children admitted to hospital with a respective prevalence of the various observed symptoms is summarised in Table 3, we found that thrombopaenia was statistically combined with a positive blood smear  . 94 % of children had anaemia (haemoglobin < 11 g/dL). This massive proportion of anaemia was observed in both groups: 95% versus 92% (NS) for "simple anaemia" (haemoglobin < 11 g/dL), and 42% versus 31% (NS) for severe anaemia (haemoglobin < 5 g/dL) (Table 114/132 children with a positive blood smear (86%) met the criteria of severe malaria according to the clinical and biological criteria explored in this study. The most frequent criteria were convulsions (71/114 = 62%) and severe anaemia (55/114 = 48%)  on the biological diagnosis. Non-specific clinical diagnosis followed by a presumptive treatment carried out without any biological confirmation, with an almost total absence of written follow-up in the management of children, are elements showing how difficult it is to diagnose malaria attacks in endemic areas. Both theoretical and practical parameters interfering in the diagnosis of malaria have been reviewed by Rogier .A particularly high percentage of severe malaria cases (86 %) was noted in the study population. Five children aged 6 months or under (one of them aged 3 months) were suffering from severe malaria, confirming the existence of severe malaria among very young children as already pointed out in other studies ,29. The The overall case fatality rate of malaria was 20% among confirmed cases and 21% among severe cases. These values are higher than those observed in other African countries also based on 2000 WHO criteria: 11.9% in Ethiopia , 12% in pfcrt (T76) mutation which confers chloroquine resistance [pfcrt mutation was present in 10/30 samples . These preliminary results need to be completed but such a level of genotypic drug resistance clearly seems insufficient to explain the high mortality rate observed at the NHN. Other implied factors have to be identified.However, such a level of hospital mortality among children who have already received treatment before admission could indicate an increase in the level of chloroquine resistance. Data on resistance is still insufficient in Niger but studies are presently being carried out. Detection of the sistance  was perfOne of them is anaemia. As the prevalence of severe anaemia is very high, the capacity of the blood bank to provide blood in a short time is an important factor in reducing mortality. Transfusion facilities are woefully inadequate in the NHN.This survey conducted at the National Hospital of Niamey during the 2003 rainy season was an opportunity to examine the features of childhood malaria in a referral hospital of one of the world's lowest income countries. One of the dominant features in the NHN is that malaria affects an underprivileged population already affected by malnutrition. Only 52% of presumed cases are parasitologically confirmed. The rate of severe cases is high (86%) with two main clinical presentations: severe anaemia in less than 2-year old children and neurological form between 2 and 5-year old children. The mortality rate (21% among severe cases) is higher than established by most previously published data.The study highlights several underlying factors that contribute to such an alarming situation:(1) Patient factors: poor socio-economic background leading to multiple difficulties in getting access to healthcare , and also the persistence of traditional beliefs interfering with care seeking behaviour.(2) Provider factors: the recovery of medical care costs, although essential for the financial survival of the hospital, leads to multiple difficulties for the patient as seen above. Healthcare quality standards are also too low at all levels of the health organization, not just because of technical deficiencies (e.g. deficiency in intensive care units or in transfusion supplies) but also because of the inadequate training and attitudes of health-care workers.All these factors need to be taken into account in order to find ways of improving the management of malaria in children. A recent awareness initiative is under way at the NHN, and several initiatives are being taken towards a gradual involvement of the hospital in a quality-oriented policy. But such local interventions will not reach their goal if extra efforts are not made at all levels to fight against disadvantages in the access to health facilities.FGA was an initiator of the study and took part in its development, supervised laboratory staff, took part in the analysis of the data, and wrote this article. EA was an initiator of the study, took part in its development, coordinated the clinical study, took part in the analysis of the data and in the writing of the paper. VL and MG took part in the development of the study, collected clinical and epidemiological data, and analysed the data. MLI conducted molecular tests in the Institut Pasteur de Madagascar. HK and HB supervised medical and nursing staff in the paediatric department. All authors have read and approved the final manuscript.


The purpose of this study was to investigate the scale recalibration construct of response shift and its relationship to glycemic control in children with diabetes.At year 1, thirty-eight children with type 1 diabetes attending a diabetes summer camp participated. At baseline and post-camp they completed the Problem Areas in Diabetes (PAID) questionnaire. Post-camp, the PAID was also completed using the 'thentest' method, which requires a retrospective judgment about their baseline functioning. At year 2, fifteen of the original participants reported their HbA1c.PAID scores significantly decreased from baseline to post-camp. An even larger difference was found between thentest and post-camp scores, suggesting scale recalibration. There was a significant positive correlation between year 1 HbA1c and thentest scores. Partial correlation analysis between PAID thentest scores and year 2 HbA1c, controlling for year 1 HbA1c, showed that higher PAID thentest scores were associated with higher year 2 HbA1c.Results from this small sample suggest that children with diabetes do show scale recalibration, and that it may be related to glycemic control. Diabetes is one of the most common chronic diseases of childhood. Adjustment to the disease and the demands of its complex regimen are formidable tasks even for adults. Children face these demands in the context of already challenging normative developmental tasks. Understanding children's diabetes-related problems can inform intervention designed to improve medical outcomes and quality of life for this population.antecedents , interact with a catalyst  to elicit psychological mechanisms  in order to accommodate the catalyst. Response shift then influences one's quality of life evaluation  would children show evidence of scale recalibration? And 2) if scale recalibration does occur, is it related to diabetes control?Participants were children attending an overnight summer camp for children with diabetes, and their families. The camp draws mostly northern New England families. Each year campers age 8–15 attend a 2-week session. The majority of the staff also has diabetes.One week prior to the two-week camp session, a letter was sent to the parents of campers, describing the study. Parents were sent a consent form for themselves, an assent form for their child, a survey of disease and demographic data, and a questionnaire for them to review and administer to their child. Parents were asked to let the child complete the questionnaire as independently as possible. Upon their arrival at camp, the materials were collected from parents.really doing before?" It was emphasized that they were not to recall their original responses, but rather to provide a renewed judgment. All children heard instructions in which there were examples of no scale recalibration, as well as positive and negative scale recalibration. All children claimed to understand the task. If the investigator suspected poor comprehension, the child was asked to retell the directions to the investigators.At the end of the two-week camp session, child participants were asked to complete the assessments again as a traditional posttest. They were also asked to complete the questionnaire using the thentest approach. They were given the instructions "I would like you to answer this questionnaire based on how you now think you were doing before camp. In other words, now that you have been to camp, how do you think you were Just prior to the camp session the following year, the disease and demographic surveys were sent to parents whose children had participated in year 1. Upon their arrival at camp, the materials were collected from parents. See figure t-rt = 0.83) [The PAID is a 20-item questionnaire that taps into patient's subjective feelings about difficulties with their diabetes . Problem = 0.83) . In examany decrease in HbA1c leads to decreased risk for complications [Parents completed a survey of demographic and disease variables including age, duration of disease, number of unscheduled doctor and emergency medical appointments in the past year, and years spent at diabetes camp. Parents also reported their child's most recent HbA1c, the average blood glucose concentration over the preceding 6–10 weeks. Children were required to have an HbA1c test prior to coming to camp, and parents were required by the camp to bring the lab results with them to the first day of camp. Normal values are <6.0, and the goal for people with diabetes is generally <7.0. HbA1c is the gold standard indicator of blood sugar, or glycemic control . FurtherInternal consistency reliability of the PAID with this sample was investigated by calculating Cronbach's coefficient alpha. Differences between PAID pretest, posttest, and thentest scores were analyzed with paired samples t-tests. Group differences were analyzed with independent t-tests. The relationship between HbA1c and scale recalibration was investigated by calculating zero order and partial correlations.Thirty-two percent of campers (n = 38) and parents (n = 38) handed in completed questionnaires on the first day of camp. There were no apparent differences between responders and non-responders in age, sex, HbA1c, duration of diabetes, and type of treatment regimen, the data for which were available to the investigator in aggregated form. At year 1, on average participants were 12 years old, had diabetes for approximately 6 years and had been attending diabetes camp for 3 years. Glycemic control was suboptimal, HbA1c M = 8.2.At year 2, 40% of year 1 campers participated, yielding a subset of n = 15. Approximately half of the attrition was due to lack of interest in completing the study, and the other half was due to families not returning to camp the second year. The subset of 15 participants was very similar to the larger group at year 1, except of course for being slightly older because they had aged 1 year. Mean HbA1c did not change from year 1  to year 2 . See Table PAID scores showed good internal consistency, baseline PAID Cronbach's alpha =.92, posttest PAID Cronbach's alpha = .94, and thentest PAID Cronbach's alpha = .96. These coefficients are similar to those found with adults  [fewer problems at baseline than they were originally aware of .PAID data were analyzed with a paired samples t-test. Perceived problems decreased significantly from baseline  to posttest , t(38) = 3.12, *p <.01. See table There was no association between age or number of years at diabetes camp on the one hand and baseline PAID, posttest PAID, thentest PAID, absolute value of scale recalibration, or direction of scale recalibration on the other hand.The association between HbA1c and scale recalibration was investigated. Baseline HbA1c levels were significantly positively correlated with thentest scores, r = .35, *p < .05. Higher HbA1c was associated with higher thentest scores. Neither PAID baseline scores , nor PAID posttest scores  were related to HbA1c. Groups who reported a positive vs. negative scale recalibration effect were compared. Those with a positive scale recalibration had nonsignificantly higher HbA1c compared to those with a negative scale recalibration .One-year follow up data were available for a subset of 15 children. PAID thentest scores were associated with year 2 HbA1c. Partial correlation analysis between PAID thentest scores and year 2 HbA1c, controlling for year 1 HbA1c, showed that higher PAID thentest scores were correlated with higher year 2 HbA1c, r = .58, *p < .05. Neither PAID pretest scores  nor PAID posttest scores  were correlated with year 2 HbA1c. Statistical comparison of groups who reported a positive vs. negative scale recalibration was not possible due to small n in each group and very low statistical power. Nonetheless, it is worth noting that means were in the same direction and of similar magnitude to those seen at baseline. Those with a positive scale recalibration had nonsignificantly higher year 2 HbA1c compared to those with a negative scale recalibration (M = 8.2 vs. 7.7).This study explored response shift in children attending diabetes summer camp. Specifically, it asked whether children with diabetes evidence scale recalibration, and if so, whether scale recalibration is related to glycemic control. Children with diabetes did in fact show scale recalibration, suggesting that response shift occurs in children with diabetes. Children provided renewed judgment of their pretest functioning, reporting that, on average, they had been experiencing more diabetes-related problems than they were originally aware of. Furthermore, scale recalibration was related to glycemic control. In year 1 cross sectional analysis, children with higher thentest scores had higher HbA1c. Higher thentest scores were also related to higher HbA1c at one-year follow up, even after taking into account baseline HbA1c. Furthermore, there was a trend for an association between the direction of scale recalibration and glycemic control. Children whose retrospective assessment of diabetes related problems increased showed nonsignificantly higher HbA1c at both baseline and at one-year follow up, compared to children whose retrospective assessment of diabetes related problems decreased. The high level of diabetes-related problems observed in these children relative to adults, and their relatively poor glycemic control relative to clinical guidelines, speaks to the need for investigation of this population.These results raise as many questions as they answer. First, what are the mechanisms that could cause such a scale recalibration? Sprangers and Schwartz  suggest Another question that arises is how the scale recalibration influences subsequent glycemic control. One might hope that children who had this experience – a realization that their diabetes was more problematic than they had originally perceived – would make healthy behavior changes such as testing blood sugar more frequently and come back to camp the next year in tighter glycemic control. However, this was not the case. It is well documented that having the awareness of a health related problem is not in itself enough to induce behavior change. Knowledge of an unsatisfactory state of affairs is a necessary, but insufficient, condition for behavior change. Other factors are also needed such as skills, problem solving ability, readiness, self-efficacy, and the belief that such behavior changes will make a difference in health outcomes. In children, parental involvement is also key – a child's awareness and behaviors occur in the context of parental control. Furthermore, in diabetes, it is documented that increased adherence to the regimen does not always lead to a direct benefit in glycemic control. There are numerous reasons, not measured in this study, that may have prevented renewed judgment about diabetes-related problems from translating into glycemic improvement.It is important to note that age and the number of years that children have attended diabetes summer camp was not associated with scale recalibration. Returning campers presumably had had reasonably similar prior camp experiences. Yet, the scale recalibration still occurred. It is possible that response shift in general, and scale recalibration specifically, occur repeatedly over time, with each significant disease related experience. This would certainly concur with anecdotal accounts that repeated years at camp serve as 'booster sessions' that reinforce previous experiences and benefits.If replicated, these findings may point to an opening for intervention. These data suggest that children in poor diabetes control who participate in an intervention can reflect upon their previous functioning and provide a renewed, and perhaps more accurate, judgment regarding diabetes problems. This may be a good time to intervene on skills, problem solving, motivation, self-efficacy, and health beliefs. Perhaps children who see their diabetes in a new light will be primed to receive an intervention that will produce health behavior change and subsequent glycemic control. Anecdotally, campers report that when they leave camp they are very motivated to improve diabetes self-management at home in order to maintain gains made at camp. However, they also report that after several months, the motivation declines to baseline levels, and self-management relapses. Campers who return annually describe the need for 'booster' camp sessions.at all in children. This finding is important to two lines of investigation [studying response shift explicitly, as the subject of investigation. Such studies could describe whether and how quality of life or diabetes-related problems change over the lifespan, and how response shift affects these changes. Response shift may also be important for pediatric treatment outcome research. Outcome studies may benefit from taking response shift into account when detecting treatment effects. However, neither approach is feasible until it can first be adequately demonstrated that response shift occurs in children.Irrespective of any treatment implications, this study highlights the importance of response shift in research using self-report measures with children. Attention to response shift in research with adults has been advocated for several years, but to date the phenomenon of response shift has not been investigated in children. The importance of these findings is not only the relationship of scale recalibration to glycemic control, but the evidence of scale recalibration tigation . ObservaThese data need to be interpreted with caution, given several limitations of this study. First, there was a low response rate (32%) which may reflect selection bias. However, comparison of responders with non-responders showed no differences in age, sex, HbA1c, duration of diabetes, or diabetes treatment regimen. Second, these children were from White, predominantly middle class families in New England, which certainly limits the generalization of its findings. Third, disease variables were reported by parents. However, each child was required to have the written results of a physical exam performed prior to camp that included the most recent HbA1c information. Thus, parents had accurate HbA1c information available to them when completing the parent questionnaire, decreasing potential unreliability of HBA1c data. Fourth, the PAID has not typically been used with children and it is not known how much parental help was necessary to complete the baseline PAID. However, high internal consistency coefficients similar to those found with adult type 1 diabetes patients suggest that the PAID performed well. A control group was not simultaneously studied, so alternative explanations for PAID changes cannot be ruled out.Finally, despite its increasingly popular use, the thentest has limitations that warrant attention. These limitations are primarily related to the difficulty in interpreting observed differences between pretest and thentest scores. That is, what appears to be a thentest effect could also be attributed to memory difficulties, social desirability, recall bias, effort justification, or unreliability of the measure. There are several ways to increase the confidence with which one can interpret thentest results. First, keeping the timeframe of recall to the minimum necessary to answer the research question reduces the possibility of memory difficulties . Second,Children with diabetes exhibit scale recalibration in their reporting of diabetes-related problems after a 2-week summer camp experience. The small sample and uncontrolled design pose limitations, but results suggest that scale recalibration is related to glycemic control, both cross-sectionally and prospectively at 1 year follow-up. The children in this study endorsed more diabetes-related problems than published adult samples, and have suboptimal glycemic control, underscoring the need for further investigation of disease-related quality of life in this population.Further research should specify conditions under which response shifts would be expected to occur and those in which they would not be expected to occur, and matched samples from each circumstance should be compared for response shift. Other core constructs of response shift such as reconceptualization and change in values should also be investigated. Individual differences such as family variables, or personality traits such as optimism may influence the magnitude and direction of response shift. The mechanisms of response shift should be investigated. These areas are ripe for investigation.


Plasmodium falciparum is most frequent and severe in first-time mothers, and increases the risk of infant mortality in their offspring. Placental malaria may increase the susceptibility of infants to malaria parasitemia, but evidence for this effect is inconclusive.In endemic areas, placental malaria due to p for interaction = 0.008, Type 3 likelihood ratio test). Offspring of PM-negative primigravidae had lower odds of parasitemia during infancy  than offspring of PM-negative multigravidae, and offspring of PM-positive primigravidae had the lowest odds . In contrast, offspring of PM-positive multigravidae had significantly higher odds of parasitemia .During 2002–2004, we monitored parasitemia in 453 infants, including 69 who were born to mothers with placental malaria, in a region of northeastern Tanzania where malaria transmission is intense. We used a Cox proportional hazards model to evaluate the time from birth to first parasitemia, and a generalized estimating equations logistic regression model to evaluate risk of any parasitemia throughout the first year of life. Compared with infants whose mothers did not have placental malaria at delivery (“PM-negative”), offspring of mothers with placental malaria at delivery (“PM-positive”) were 41% more likely to experience their first parasitemia at a younger age . The odds of parasitemia throughout infancy were strongly modified by the interaction between placental malaria and gravidity (Although parasitemia is more frequent in primigravid than multigravid women, the converse is true in their offspring, especially in offspring of PM-positive women. While placental malaria is known to increase mortality risk for first-born infants, it surprisingly reduced their risk of parasitemia in this study. Placental malaria of multigravidae, on the other hand, is a strong risk factor for parasitemia during infancy, and therefore preventive antimalarial chemotherapy administered to multigravid women close to term may reduce the frequency of parasitemia in their offspring. Children of mothers with placental malaria were more likely to exhibit parasitemia within their first year. First-born children were at a lower risk, regardless of whether their mothers had placental malaria. Plasmodium falciparum is the accumulation of infected erythrocytes (IEs) in the placenta , infant presented with suggestive signs or symptoms [n = 8], or suffered HIV/AIDS-related death [n = 4] during follow-up) were also excluded . During the period of this study, HIV-seropositivity rates were 7.5% among women who agreed to undergo antenatal testing. After exclusions, a total of 453 infants remained for analyses presented in this report.Infants whose data are reported in this study were enrolled between September 2002 and September 2003, and were followed throughout the first year of life. During the recruitment period, 495 mothers gave consent to participate and delivered at the Muheza Designated District Hospital. Excluded from the analyses were ten twin infants, four stillbirths, three early neonatal deaths, and six neonates who were not examined beyond 4 wk of age because their families moved out of the study area. Infants with any evidence of HIV infection , or 54 wk of age, whichever occurred first.We examined the frequency distribution of maternal and infant characteristics according to PM status (parasitemia or no parasitemia) or gravidity  using a chi-squared test for categorical variables and Student's Cox regression analysis was used to determine whether the risk of first parasitemia was associated with PM at delivery. The dependent variable was time between birth and first positive diagnosis measured in weeks. The following variables were considered to be potential confounders a priori and were included in the model: gravidity , transmission season at time of birth (high or low), and bed net use in a household. According to the incidence of parasitemia among 3- to 12-mo-old infants in Muheza (unpublished data), the high transmission seasons in both 2003 and 2004 occurred from May through October, and the low transmission seasons occurred from November through April. Residence location was grouped into six categories by geographical area and distance to nearest health center. In order to allow for a different baseline hazard for each location, we used a stratified Cox regression model . All var2) was also included in the model because there appeared to be a curvilinear relationship between age and parasitemia. Offspring of secundigravidae versus multigravidae had similar probability of parasitemia during infancy , and therefore were combined for the final analysis. We assessed for effect modification between PM and gravidity by including an interaction term in the regression model and tested for significance using a Type 3 likelihood ratio test. Because the interaction term was significant (p = 0.008), results are presented stratified by primigravidae (no previous pregnancies) and secundi/multigravidae (one or more previous pregnancies). Treatment intensity  was also assessed as a potential effect modifier in the different gravidity groups. Offspring of the four groups  did not significantly differ in the frequency of antimalarial treatments using the Kruskal-Wallis test (p = 0.20). Therefore, treatment intensity would not have a significant bias effect on the assessment of the relationship between gravidity, PM status, and other factors, and was not included in the final models.To assess the effect of PM at delivery on the probability of infant parasitemia throughout infancy, generalized estimating equations logistic regression models were constructed with a first-order autoregressive working correlation structure  and model-based standard errors . This mep-values are two-sided, and confidence intervals (CIs) were calculated at the 95% level. Statistical significance was set at p ≤ 0.05. Data analyses were conducted using STATA version 8.0 , Statview version 5.0, and SAS version 9.0 software .All p = 0.03). Although the mean placental parasite density of PM-positive women did not differ significantly between birth months, the four highest density placental parasitemias occurred in three primigravidae  and one secundigravida (23.3% parasitemia) during the high transmission seasons. Reported usage of sulfadoxine-pyrimethamine for IPT against malaria during pregnancy was high (69.7%), but did not significantly differ between PM-positive and PM-negative mothers. Reported IPT usage was also similar among different gravidity groups , as was bed net usage . Residence area was not associated with gravidity group .PM was identified in 69 (15.2%) of the mothers. PM-positive women were more likely to be younger and to be experiencing first-time pregnancies than PM-negative women . Among pp = 0.67). Sixty-three (13.9%) infants were lost to follow-up between 4 and 54 wk of age (moved or parent[s] withdrew consent), including six of the 69 infants born to PM-positive mothers. Thirteen infants died before reaching 54 wk of age; three (4.4%) of those from PM-positive mothers and ten (2.6%) of those from PM-negative mothers.Offspring of PM-positive mothers were similar to those of PM-negative mothers by several measures, including gender, birth month, and residence . Of the Two hundred and sixty (57.4%) infants in the study cohort experienced at least one episode of parasitemia by the age of 54 wk. Of the 193 infants who did not experience parasitemia, 138 (71.5%) were followed for at least 1 y. The median time to first parasitemia was 38 wk (95% CI 34–42) with a 75% probability of remaining free of parasitemia up to 18 wk of age. Of the 63 infants lost to follow-up, 17 (27.0%) presented with parasitemia before dropping out of the study.p = 0.48). Among offspring of secundigravidae, the median time to first parasitemia for infants born to PM-positive mothers was 27 wk (95% CI 14–54) compared with 52 wk (95% CI 38–54) for infants born to PM-negative mothers (p = 0.06). Among offspring of multigravidae, the median time to first parasitemia for infants born to PM-positive mothers was 22 wk (95% CI 10–38) compared with 37 wk (95% CI 32–46) for infants born to PM-negative mothers (p = 0.01).The median time to first parasitemia for infants born to PM-positive mothers was 32 wk (95% CI 21–38) compared with 39 wk (95% CI 35–46) for offspring of PM-negative mothers . The effp = 0.27), the effect of PM on infant risk appeared to vary across gravidity groups after adjustment for potential confounders  times that of infants born to PM-negative mothers, after adjustment for gravidity, transmission season at time of birth, area of residence, and bed net usage . AlthougThe age-specific prevalence of parasitemia during infancy differed by gravidity and PM status of the mother regardless of transmission season . Blood-sResults from generalized estimating equations logistic regression analysis of the interaction between gravidity and PM on the odds of parasitemia are presented in P. falciparum parasitemia during infancy. Overall, offspring of PM-positive mothers experienced their first parasitemia at a significantly younger age than offspring of PM-negative mothers, and the risk of early first parasitemia was highest among offspring of PM-positive multigravidae. The risk of any parasitemia during infancy was strongly modified by an interaction between PM and gravidity. Offspring of PM-negative primigravidae had a decreased risk of parasitemia, while offspring of PM-positive primigravidae had the lowest risk. In contrast, offspring of PM-positive multigravidae had an increased risk of parasitemia.In this prospective cohort study of 453 mother–offspring pairs, both PM and maternal gravidity influenced the risk of P. falciparum in infants born to PM-positive mothers [Our results are the first to identify an effect of maternal gravidity to modify malaria risk in offspring during infancy. An earlier study in southern Cameroon observed an increased age-specific prevalence of  mothers , but did mothers .Because PM had been suggested to increase susceptibility during infancy ,21, we ePM during the antenatal period may be influencing infant outcomes, separate from any effect of neonatal exposure occurring at delivery, and could explain the reduced risk of parasitemia among offspring of PM-negative primigravidae. In areas of stable transmission, primigravid women are parasitemic more frequently , and expFactors such as area of residence, season of observation, and HIV may increase the risk of parasitemia in both mother and offspring, and therefore may confound an analysis of maternal parasitemia and infant susceptibility. However, our adjusted analyses suggest that these confounding factors would not fully explain the results. Although the incidence of parasitemia during infancy differed significantly between villages in this study (unpublished data), the frequency of PM did not . Nor didBehavioral and environmental factors may vary with gravidity and could account for some gravidity-dependent relationships. An increased number of children in multigravid households would possibly attract more mosquitoes or increase the proportion of mosquitoes that are infective, thereby increasing malaria exposure among offspring of multigravidae. However, this would not explain why PM at delivery decreases malaria risk in offspring of primigravidae. Conversely, the increased frequency of fever in primigravid women may cause them to consume more antimalarials, which could be transferred to the fetus or infant and reduce infant parasitemia. However, reported usage of antimalarials during pregnancy was similar among the different gravidity groups. Furthermore, PM was associated with a risk of parasitemia throughout infancy, and is unlikely to be accounted for by ingestion of antimalarials at term.P. falciparum MSP-1 antigen were lower among offspring of PM-positive mothers [P. falciparum, as well as the effect of placental inflammation to modulate the infant's antibody and cellular responses against the parasite.Our findings suggest that PM decreases susceptibility in the offspring of primigravidae, and increases susceptibility in the offspring of multigravidae. Among primigravidae, the pronounced inflammatory response to PM could confer protection, for example by reducing parasitemia  and ther mothers , and it P. falciparum parasitemia and disease in young children.The findings of the present study establish a conundrum. PM at delivery greatly reduced the odds of parasitemia in offspring born to primigravid women, yet earlier studies reported that PM was the strongest risk factor for severe morbidity –34 and mP. falciparum parasitemia in their offspring, but more research is needed to predict its effect on malaria-related disease and death. The benefits of malaria prevention during pregnancy may extend beyond its effect on birth outcomes, and should be studied in randomized clinical trials with careful attention to PM status at delivery and outcomes during early childhood.In summary, PM decreases the risk of parasitemia among offspring of primigravidae but increases the risk among offspring of multigravidae. Traditionally, pregnancy malaria has been thought to affect the offspring primarily through low birth weight or maternal anemia, which are risk factors for neonatal and infant mortality. The present findings indicate that pregnancy malaria may also have prolonged effects on immunity and susceptibility to malaria in the offspring, and that these effects are strongly influenced by maternal gravidity. Further investigation of these relationships with assessment of other potential confounders, as well as their impact on infant morbidity and mortality, is needed with larger cohort studies. A preventive dose of antimalarial chemotherapy delivered to secundigravid or multigravid women in the last 1–2 wk before term may reduce In areas where malaria is common, most adult women have acquired some level of immunity against the malaria parasite. However, during pregnancy, many experience a new type of malaria infection in their placenta. This placental malaria is particularly severe during first-time pregnancy. Pregnant women with placental malaria often give birth to babies with a low birth weight, and these babies have an increased risk of dying as infants.The connection between placental malaria and low birth weight is well established. However, it is not clear whether placental malaria makes it more likely for infants to get infected with malaria parasites themselves, and this is the question the researchers addressed in this study.They studied a total of 453 infants, of which 69 were born to mothers with placental malaria. Of those 69 infants, 31 were born to first-time mothers, and 38 to mothers who had given birth before. The researchers then followed those infants for a year and checked how often during that time they had parasites in their blood. Surprisingly, the researchers found that children followed one of two opposing patterns, depending on their birth order. Children from first-time mothers were less likely to have parasites in their blood, especially children whose mothers had placental malaria. Children from other mothers were more likely to have parasites in their blood, especially children whose mothers had placental malaria.These results suggest that both the number of previous pregnancies and placental malaria affect an infant's chances of developing malaria. It might be that in first-time mothers placental malaria stimulates the infant's immune system and this somehow protects the baby against malaria, but at present this is just speculation. Also, the study is relatively small, and the connections between the number of previous pregnancies, placental malaria, and the chances of an infant getting malaria need to be tested in other studies.The following Web sites provide information about malaria.Wikipedia pages on malaria:http://en.wikipedia.org/wiki/MalariaWHO pages on malaria, which contain a section on malaria and pregnancy:http://www.who.int/topics/malaria/en/MedlinePlus pages on malaria:http://www.nlm.nih.gov/medlineplus/malaria.htmlUNICEF page on malaria with links:http://www.childinfo.org/eddb/Malaria/