Mother-to-child transmission of HIV-1: association with malaria prevention, anaemia and placental malaria

Objectives

Malaria infection may impact on mother‐to‐child transmission (MTCT) of HIV‐1. Prevention of malaria in pregnancy could thus potentially affect MTCT of HIV. We studied the impact of intermittent preventive treatment during pregnancy (IPTp) on HIV‐1 MTCT in southern Mozambique.

Methods

A total of 207 HIV‐positive Mozambican pregnant women were enrolled in the study as part of a randomized placebo‐controlled trial of two‐dose sulfadoxine‐pyrimethamine (SP) IPTp in women receiving single‐dose nevirapine to prevent MTCT of HIV. HIV RNA viral load, maternal anaemia and peripheral and placental malaria were assessed at delivery. Infant HIV status was determined by DNA polymerase chain reaction (PCR) at 1 month of age.

Results

There were 19 transmissions of HIV in 153 mother–infant pairs. IPTp with SP did not have a significant impact on MTCT (11.8% in the SP group vs. 13.2% in the placebo group; P=0.784) or on maternal HIV RNA viral load [16 312 (interquartile range {IQR} 4076–69 296) HIV‐1 RNA copies/mL in the SP group vs. 18 274 (IQR 5471–74 104) copies/mL in the placebo group; P=0.715]. In multivariate analysis, maternal HIV RNA viral load [adjusted odds ratio (AOR) 19.9; 95% confidence interval (CI) 2.3–172; P=0.006] and anaemia (haematocrit <33%; AOR 7.5; 95% CI 1.7–32.4; P=0.007) were independent risk factors for MTCT. Placental malaria was associated with a decrease in MTCT (AOR 0.23; 95% CI 0.06–0.89; P=0.034).

Conclusions

IPTp with SP was not associated with a significant impact on MTCT of HIV. Maternal anaemia was an independent risk factor for MTCT.     

The changing epidemiology of malaria in Ifakara Town, southern Tanzania

Between 1995 and 2000 there were marked changes in the epidemiology of malaria in Ifakara, southern Tanzania. We documented these changes using parasitological and clinical data from a series of community- and hospital-based studies involving children up to the age of 5 years. There was a right shift and lowering in the age-specific parasite prevalence in the community-based cohort studies. The incidence of clinical malaria in placebo-receiving infants in additional study cohorts dropped from 0.8 in 1995 to 0.43 episodes per infant per year in 2000, an incidence rate ratio of 0.53 (95% confidence interval: 0.404, 0.70, P<0.0001). At the same time, there was an increase in the total number of malaria admissions and a marked right shift in the age pattern of these admissions (median age in 1995 1.55 years vs. 2.33 in 2000, P<0.0001). However, the burden of malaria deaths remained in infants. We discuss how these dramatic changes in the epidemiology of malaria may have arisen from the use of currently available malaria control tools. Caution is required in the interpretation of hospital-based data as it is likely to underestimate the impact of anaemia on mortality in the community, where most paediatric deaths occur. Even in low/moderate malaria transmission settings, where older children suffer most malaria episodes, targeting effective malaria control at infants may produce important reductions in infant mortality caused by malaria.     

Correlación entre la expresión del receptor dopaminérgico D2 y presencia de movimientos involuntarios anormales (MIA) en un modelo de disquinesia en ratas Wistar hemiparkinsonizadas

Parkinson's disease (PD) is characterised by motor alterations, which are commonly treated with L-DOPA. However, long-term L-DOPA use may cause dyskinesia. Although the pathogenic mechanism of L-DOPA-induced dyskinesia is unclear, the condition has been associated with alterations in dopamine receptors, among which D2 receptors (D2R) have received little attention. This study aims to: (i) develop and standardise an experimental model of L-DOPA-induced dyskinesia in rats with hemiparkinsonism; and (ii) evaluate the correlation between D2R expression and presence of abnormal involuntary movements (AIM). We allocated 21 male Wistar rats into 3 groups: intact controls, lesioned rats (with neurotoxin 6-OHDA), and dyskinetic rats (injected with L-DOPA for 19 days). Sensorimotor impairment was assessed with behavioural tests. Dyskinetic rats gradually developed AIMs during the treatment period; front leg AIMs were more severe and locomotor AIMs less severe (P < .05). All AIMs were significantly evident from day 5 and persisted until the last day of injection. D2R density was greater in the striatum and the medial anterior brain of the lesioned and dyskinetic rats than in those of controls. Our results suggest an association between D2R expression and locomotor AIMs. We conclude that RD2 is involved in L-DOPA-induced dyskinesia.     

Changes in psychiatric admission MMPI profiles over a period of 15 to 20 years

An attempt was made to compare admission MMPI profiles of a matched sample of psychiatric inpatients over a 15- to 20-year period. For both males and females, significant decreases in MMPI indices of psychopathology occurred. Possible reasons for this decrease are presented.     

Knowledge, Perceptions, and Experiences of Dominicans with Diabetes

Dominicans, one of the fastest growing Hispanic subgroups in New York City (NYC), have a high rate of diabetes. A qualitative study exploring Dominicans’ knowledge, perceptions, and experiences in managing their diabetes was conducted. There were a total of 40 participants who were Spanish speaking Dominicans, 40–74?years of age, diagnosed with diabetes and NYC residents. Four focus groups were conducted in Spanish, which were recorded and then transcribed into English. Content analysis was used to analyze the text of the focus groups. Different themes emerged from the data, with apparent gaps in diabetes knowledge and of awareness of risk for diabetes complications.     

Systematic review of case reports concerning adults suffering from neutropenic enterocolitis

Introduction Neutropenic enterocolitis (NEC) is a well recognised clinical-pathological and life-threatening complication in patients suffering from several conditions, including solid and haematological malignancies or aplastic anaemia. Objective This review was aimed at evaluating overall NEC mortality rate, describing clinical diagnostic findings and therapeutical interventions reported in the literature and generating a hypothesis regarding factors influencing mortality and surgical intervention. Materials and Methods An advanced search was made in Medline, Embase, Lilacs and Google. Additional strategies included manual search of specific journals. Reports were considered if they described case definition, inclusion and exclusion criteria.Results. 275 cases were selected; 109 were from individual data and 40 from grouped data. Comparing data between case reports and case series revealed no significant differences related to mortatity, surgical intervention, sex or age. Higher mortality (χ²=7.51 p=0.006) was found in women (50%) compared to men (28%). No significant difference was found between antibiotic combinations and mortality (χ²=12.85 df 13 p=0.45). Mortality (χ²=3.89 df 1, p=0.049), surgical intervention (χ²=7.64 df 1, p=0.006) and duration of diarrhoea (χ²=4.71 df 1, p=0.045) were significantly different in 26.4% of individuals using antifungal agents; death occurred in 81% of patients! who did not receive such medication compared to 19% individuals reported as being treated with antifungal agents. Conclusion The current evidence suggests that antifungal agents should be used early in patients suffering from NEC. However, this hypothesis must be evaluated in multi-centric, randomised controlled trials.     

The safety and efficacy of sulfadoxine-pyrimethamine,amodiaquine, and their combination in the treatment of uncomplicated Plasmodium falciparum malaria

The safety and efficacy of amodiaquine (AQ), sulfadoxine-pyrimethamine (SP), and coadministered AQ+SP was assessed in 351 Tanzanian children (age range, 6-59 months) with uncomplicated Plasmodium falciparum malaria. This open, randomized study followed the 28-day World Health Organization (WHO) protocol and evaluated safety using clinical and laboratory parameters. Children receiving SP were more likely to vomit during follow-up (32% vs. 17%: P = 0.03), and SP alone resulted in prolonged fever clearance times. Although Day 7 and Day 14 clinical and parasitological cure rates were similar, by Day 28 45% of children treated with AQ demonstrated R1 resistance and 27.5% were clinical failures compared with 25% and 6.3%, respectively, for SP alone. Coadministered AQ+SP was safe, combined the greater clinical (96.2%) and parasitological (64.2%) efficacy of SP with the more rapid symptom resolution of AQ, and reduced the incidence of gametocytemia during follow-up (AQ+SP 12.6% vs. SP 29.9%; P = 0.001). The level of R1 resistance to SP may herald a rapid decline in its efficacy as SP drug pressure increases. Coadministration of AQ+SP may delay this.     

Derivation and validation of guidelines for stool cultures for enteropathogenic bacteria other than Clostridium difficile in hospitalized adults

CONTEXT: The yield of in-hospital stool cultures performed more than 72 hours after admission is low, and a commonly used policy dictates that laboratories reject these cultures to save costs. However, enteropathogenic bacteria other than Clostridium difficile (EPB) may cause nosocomial illness that would be missed by use of such a "3-day rule." OBJECTIVE: To develop guidelines for hospital use of stool cultures that are sensitive to clinically relevant cases of sporadic and epidemic nosocomial diarrhea. DESIGN: Five-part study that incorporated a derivation sample based on retrospective chart review and a prospective cohort study (including cost savings analysis), and a validation sample based on retrospective chart review. SETTING: Four European academic health care centers. PATIENTS: Derivation sample: 1735 adult inpatients from whom 3416 stool cultures were obtained during a 19-month period (1995-1997) and 68 adult inpatients for whom EPB were grown from stool cultures during a 10-year period (1988-1998); validation sample: 65 patients with sporadic isolation of EPB (1993-1998), 56 patients involved in 2 nosocomial Salmonella outbreaks (1992 and 1997), and 330 patients who had stool cultures performed (1998). MAIN OUTCOME MEASURE: Performance of derived criteria in detecting pathogenic bacteria and outbreaks and reducing total number of stool cultures performed. RESULTS: Stool cultures grew EPB in 3.3% of samples obtained 72 hours after admission was not associated with clinical symptoms or signs but was associated with community-acquired diarrhea (24%), age 65 years or older with preexisting comorbid disease (25%), neutropenia (13%), HIV infection (10%), and nondiarrheal manifestations of enteric infections (16%). Twelve percent were asymptomatic carriers. These characteristics were used to create criteria for selecting patients for whom stool cultures would be indicated. These criteria were applied post hoc to a series of 1025 stool cultures; the number of stool cultures would have been reduced by 52% and no clinically significant cases would have been missed. Annual savings to a 355-bed institution would be approximately $7800 for reagent costs and 75 hours of technician time. In the validation samples, only 2 patients of 65 who had EPB would not have been identified, and neither required treatment. If the 3-day rule had been applied, 52 cases would not have been identified, 28 of which required antibiotic treatment. CONCLUSION: Our modified 3-day rule for use in selecting cases for stool culture is sensitive to sporadic and epidemic cases of nosocomial diarrhea in hospitalized adults.     

Cholesterol biosynthesis regulation and protein changes in rat liver following treatment with fluvastatin

The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is a key regulator in cholesterol biosynthesis and HMG CoA reductase inhibitors (statins) have become a widely prescribed family of lipid lowering agents. Cholesterol synthesis occurs predominantly in liver which is the target organ of statins. We studied the effects of fluvastatin (Lescol®), a member of the statin family, on hepatic protein regulation. Male F344 rats treated with 0.8 mg/kg per day fluvastatin or 24 mg/kg per day fluvastatin for 7 days showed treatment-related changes in 58 liver proteins (P<0.005). Major effects were evident in the cholesterol biosynthesis pathway including the induction of enzymes upstream and downstream of the target enzyme HMG CoA reductase. Treatment also triggered alterations in key enzymes of carbohydrate metabolism and was associated with changes in a heterogeneous set of cellular stress proteins involved in cytoskeletal structure, calcium homeostasis and protease activity. The latter set of protein alterations indicates that hepatotoxicity is associated with high-dose treatment. Based on the results it is suggested that HMG-CoA synthase and isopentenyl-diphosphate delta-isomerase may be explored as alternative drug targets and that the induction levels of these enzymes may serve as a measure of potency of individual statin drugs. It is proposed that efficacy and cellular stress markers discovered in this study may be used in a high throughput screen (HTS) assay format to compare efficiently and accurately the therapeutic windows of different members of the statin family.