Carlos Ascaso

Diagnostic accuracy and case management of clinical malaria in the primary health services of a rural area in south-eastern Tanzania.

Malaria control continues to rely on the diagnosis and prompt treatment of both suspected and confirmed cases through the health care structures. In south‐eastern Tanzania malaria is one of the leading causes of morbidity and mortality. The absence of microscopic examination in most of the health facilities implies that health workers must rely on clinical suspicion to identify the need of treatment for malaria. Of 1558 randomly selected paediatric consultations at peripheral health facilities throughout Kilombero District, 41.1% were diagnosed by the attending health worker as clinical malaria cases and 42.5% prescribed an antimalarial. According to our malaria case definition of fever or history of fever with asexual falciparum parasitaemia of any density, 25.5% of all children attending the health services had malaria. This yielded a sensitivity of 70.4% (IC95%=65.9–74.8%) and a specificity of 68.9% (IC95%=66.2–71.5%). Accordingly, 30.4% of confirmed cases left with no antimalarial treatment. Among malaria‐diagnosed patients, 10% were underdosed and 10.5% were overdosed. In this area, as in many African rural areas, the low diagnostic accuracy may imply that the burden of malaria cases may be overestimated. Greater emphasis on the functioning and quality of basic health services in rural endemic areas is required if improved case management of malaria is to help roll back this scourge.

Deterioration of esophageal motility with age : A manometric study of 79 healthy subjects

OBJECTIVES:Data are limited on the effect of age on esophageal function. We evaluated whether aging influences the motor activity of the esophagus.METHODS:Standard esophageal manometry was performed in 79 healthy, nonpaid volunteers of both sexes, 18–73 yr of age. Lower (LES) and upper esophageal sphincter (UES) characteristics and the properties of esophageal peristaltic waves were assessed by age groups: ≤25 yr, 26–35 yr, 36–45 yr, 46–55 yr, 56–65 yr, and >65 yr.RESULTS:Age correlated inversely with LES pressure and length, UES pressure and length, and peristaltic wave amplitude and velocity, and correlated directly with the proportion of simultaneous contractions. Age was inversely correlated with the upper limits of normality (95th percentiles) of LES pressure (r =−0.943, p= 0.005), UES pressure (r =−0.943, p= 0.005), middle and lower peristaltic wave amplitude (r =−0.947, p= 0.004, and r =−0.844, p= 0.035, respectively), upper/middle peristaltic progression speed (r =−0.943, p= 0.005), and the proportion of simultaneous contractions (r = 0.926, p= 0.008), but not with the lower normal limits (5th percentiles) of these variables. Gender did not affect esophageal motility variables. The 95th percentiles of LES pressure differed by 20 mm Hg, those of lower peristaltic amplitude by 82 mm Hg, and those of percent simultaneous contractions by a factor of 2, between the younger and the older age groups.CONCLUSIONS:The results suggest that normal esophageal motility deteriorates with advancing age. Thus, age-related normality limits of esophageal pressures should be considered before establishing the manometric diagnosis of hypercontractile esophageal motility disorders.

Inhibin, follicle-stimulating hormone, and age as predictors of ovarian response in in vitro fertilization cycles stimulated with gonadotropin-releasing hormone agonist-gonadotropin treatment.

OBJECTIVE Our purpose was to determine the relative power of basal inhibin and follicle-stimulating hormone (defined before treatment) and the womans age both as single and combined predictors of ovarian response in an in vitro fertilization program where pituitary desensitization was routinely used. STUDY DESIGN The study was a retrospective analytic investigation of 120 women undergoing the first cycle of in vitro fertilization. Forty consecutive cycles canceled because of poor follicular response were initially selected. As a control group, the nearest completed in vitro fertilization cycles before and after each canceled cycle (i.e., the closest cycles in temporal relationship to the index cycle) were used. RESULTS The mean age and basal follicle-stimulating hormone level were significantly higher in the canceled than in the control group, whereas the basal inhibin level was significantly higher in the latter. Follicle-stimulating hormone and inhibin alone, with an accuracy (predictive value of ovarian response) of 70%, were better predictors of cancellation than age was. Any two or all three of these variables studied did not improve the predictive value of follicle-stimulating hormone or inhibin alone. CONCLUSION Age is a poorer predictor than pretreatment basal follicle-stimulating hormone and inhibin levels for ovarian response in in vitro fertilization cycles stimulated with gonadotropin-releasing hormone agonist-gonadotropin treatment. Basal follicle-stimulating hormone and inhibin have similar predictive properties and could therefore be used interchangeably.

Effects of Thyroid Hormone on mRNAs of Phosphoglycerate Mutase Subunits in Rat Muscle during Development

Background: We previously showed that triiodothyronine (T3) stimulates muscle phosphoglycerate mutase (PGAM) activity and isozyme transition in rat skeletal and cardiac muscles. Methods: The effects of T3 on PGAM types B and M subunit expression in rat muscle during development are reported. Results: T3 administration during the first 21 days of rat life more than doubles type M PGAM mRNA levels, but produces minor effects on type B PGAM mRNA levels. The antihormone propylthiouracil (PTU) slightly decreases both type B and M mRNA levels, but this decrease is not statistically significant. Conclusion: Thyroid hormone influences PGAM mRNA isozyme levels differently and increases type M mRNA.

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

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

Cerebellar Cortex Delayed Maturation in Sudden Infant Death Syndrome

The cerebellum shows afferent and efferent connections with intrinsic bulbar nuclei and plays an important role in respiration and cardiovascular control. Pathological and neurochemical abnormalities of bulbar nuclei including the arcuate nucleus have been postulated in sudden infant death syndrome (SIDS). Most of these abnormalities have been related to impairment in brain development. The cerebellar cortex has a well-documented evolution from fetal life until infancy; thus, it may be a very good model to assess brain maturation in SIDS. The present study was conducted to investigate changes in the cerebellar cortex in 19 SIDS cases compared with 12 age-related controls using morphological, quantitative, and statistical approaches. Five-μm paraffin sections from the midsagittal cerebellar vermis were stained with hematoxylin and eosin (H&E). Immunohistochemical staining was carried out using a polyclonal antiserum to glial fibrillary acidic protein (GFAP). Each case consisted of a 25-μm parallel paraffin section stained with H&E, where the cerebellar external granular layer (EGL) cell density was obtained in one field magnification (X 1,000) using an optical dissector procedure on the basis of a stereological method. A statistically significant high EGL cell density, mostly related to the presence of immature bipolar, elongated neuronal cells of the premigratory zone with hyperchromatic, oval or poor differentiated nuclei, was observed in SIDS. In these cases, EGL expressed immunoreactivity for GFAP mainly in the subpial and the postmitotic zone. These findings demonstrate a delayed or slower decline in the number of EGL neurons in SIDS, suggesting either a prolongation of the growth phase related to postnatal cerebellar foliation or a delay in inward migration. These results suggest that in SIDS there is delayed maturation of the cerebellar cortex/EGL, which may support the hypothesized cardiopulmonary control dysfunction, leading to death in a vulnerable period of postnatal development.

Malaria in southern Mozambique: Malariometric indicators and malaria case definition in Manhiça district

A total of 2057 children aged <10 years were selected at random from a demographic surveillance system and enrolled in 4 malariometric cross-sectional surveys in different seasons in Manhiça district in southern Mozambique. Plasmodium falciparum accounted for 90% of all malaria infections and the prevalence of asexual P. falciparum ranged from 13.7-21.7% at the end of the dry season to 30.5-34.0% at the end of rainy season. In order to determine the malaria attributable fraction (MAF) of fever, 1021 children from a nearby hospital acted as fever cases and from this separate case-control study the crude MAF was 36%, showing a marked age dependency. Plasmodium falciparum is the most common malaria species in Manhiça. This malaria-mesoendemic area has year-round transmission. The importance of other non-malarial fever-causing conditions among infants was highlighted. Malaria appeared to be a major contributory factor to anaemia in the area.

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

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

Population screening for hemochromatosis: a study in 5370 Spanish blood donors

BACKGROUND/AIMS Hereditary hemochromatosis is associated with homozygosity for C282Y mutation in the HFE gene, elevated serum transferrin saturation and excess iron deposits throughout the body. We conducted a population-based study in Spain to asses the prevalence of the HFE mutations and their effect on iron parameters. METHODS We screened 5370 blood donors for the C282Y and H63D HFE mutations by allele-specific polymerase chain reaction. Serum iron, serum ferritin and transferrin saturation were also measured. RESULTS We have found eight (five men and three women) blood donors who are C282Y homozygotes (0.15%) and 74 C282Y/H63D compound heterozygotes (1.38%). Four out of the eight C282Y homozygotes, all men, had high serum ferritin and transferrin saturation values. No woman was detected with both iron parameters increased. Only one of the 74 C282Y/H63D compound heterozygotes showed elevated serum ferritin and transferrin saturation values (penetrance 1.35%). Serum ferritin and transferrin saturation were significantly higher in C282Y homozygous men as compared with the rest of the genotypes. CONCLUSIONS The C282Y/C282Y genotype frequency in Spain is 1 in 1004. The C282Y/C282Y genotype is clearly associated with an increase in iron parameters. Biochemical expression of the disease was found in 80% of the C282Y/C282Y men.

Apolipoprotein E4 allele frequency in Spanish Alzheimer and control cases

We have found an APOE epsilon 4 allelic frequency of 0.289 (95% CI 0.195-0.383) in Spanish AD patients (n = 88; average age = 71.2 +/- 9.37) and of 0.061 (95% CI 0.023-0.099) in age-matched controls (n = 147; average age = 71.5 +/- 10.29). Remarkably no ApoE 4/4 subjects were observed in any of the age-matched control groups compared to a total of 22 AD patients with the ApoE 4/4 phenotype. The combined odds ratio for subjects with one or two epsilon 4 alleles in the present study is 6.25 (95% CI 3.13-12.60), which is one of the highest so far reported. Altogether our results suggest a trans-European difference in the ApoE epsilon 4 frequency but no differences in the strength of the association between APOE4 and AD.