Local anaesthetic cream for the alleviation of pain during venepuncture in Tanzanian schoolchidren

The analgesic effect and the usefulness of EMLA cream 5% in connection with venous blood-sampling was investigated in 42 Tanzanian schoolchildren. Approximately 2.5 g EMLA was applied to the right cubital fossa for a minimum of 120 min. The analgesic effect was pronounced - 93% of the venepunctures were pain-free and no child experienced severe pain. No adverse reactions were observed and the children could continue normal school work during the application time

Acute haemolysis in childhood falciparum malaria

Acute haemolysis associated with clinical episodes of high-level Plasmodium falciparum parasitaemia was studied in 20 children from an holoendemic area (coastal Tanzania). The change in blood haemoglobin (Hb) concentration ranged from -46 to +5 g/L during the 72-h observation period and was linearly related to maximum parasitaemia. Balance studies between loss of blood Hb, increase in plasma Hb and appearance of Hb in the urine indicated that extravascular clearance of red cells was the predominant mode of erythrocyte clearance. Most subjects, however, showed minor signs of intravascular haemolysis. The plasma Hb was ≪1% of blood Hb and haemoglobinuria was detected in 14/20 children but the excretion of Hb in urine was \u3c0.5% of total Hb loss. Haemoglobinuria was, however, a marker of severe haemolysis, since the maximum blood Hb loss in children without haemoglobinuria was 10 g/L. Erythrocyte-bound opsonins known to induce erythrophagocytosis, i.e., complement C3c fragments and autologous IgG, were increased in all patients. In the patients with major haemolysis, the changes correlated to the haemolysis over time. Hence, a similar mechanism for predominantly extravascular erythrocyte clearance may be operative in acute malarial anaemia, normal erythrocyte senescence and other forms of acute haemolysis

Efficacy and safety of the six-dose regimen of artemether-lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: A pooled analysis of individual patient data

Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5-25 kg. A total of 544 patients with uncomplicated P. falciparum malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis. Analysis of day 28 cure rate based on the intention-to-treat and evaluable populations yielded corrected cure rates for the six-dose regimen of 93% and 96% compared with 61% and 76%, respectively, for the four-dose regimen (P \u3c 0.0001 for both comparisons). Similarly high cure rates were achieved with the six-dose regimen in non-immune infants weighing as little as 5 kg. The six- and four-dose regimens were equally well tolerated. The main finding of this analysis is that the six-dose regimen of coartemether is safe and more efficacious than the four-dose regimen in children. Copyright © 2006 by The American Society of Tropical Medicine and Hygiene

Plasma zinc concentrations are depressed during the acute phase response in children with falciparum malaria

Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (\u3c9.2 μmol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = -0.24, P \u3c 0.0001) and the degree of parasitemia (r = -0.19, P \u3c 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response. © 2005 American Society for Nutritional Sciences

Prenatal allostatic load and preterm birth: A systematic review

Objective: Allostatic load refers to cumulative neuroendocrine burden and has been postulated to mediate and moderate physiological and psychological stress-related responses. This may have important implications for the risk of preterm birth. This systematic review examines the evidence on the association between prenatal allostatic load and preterm birth. Data sources: A comprehensive search of seven electronic databases was conducted from inception to August 23, 2022 to identify all English-language observational and mixed methods studies examining allostatic load and preterm birth with no year or geographic restrictions. Study eligibility criteria: Studies were included if they measured allostatic load, evaluated as the cumulative effect of any combination of more than one allostatic load biomarker, during pregnancy. Studies must have observed preterm birth, defined as \u3c 37 weeks\u27 gestational age, as a primary or secondary outcome of interest. Study appraisal and synthesis methods: The Quality In Prognosis Studies tool was used to evaluate risk of bias within included studies. A narrative synthesis was conducted to explore potential associations between allostatic load and preterm birth, and sources of heterogeneity. Results: Three prospective cohort studies were identified and revealed mixed evidence for an association between allostatic load and preterm birth. One study reported a statistically significant association while the other two studies reported little to no evidence for an association. Heterogeneity in when and how allostatic load was measured, limitations in study design and cohort socio-demographics may have contributed to the mixed evidence. Conclusions: This review provides insight into key individual-, community-, and study-level characteristics that may influence the association between allostatic load and preterm birth. Knowledge gaps are identified as foci for future research, including heterogeneity in allostatic load biomarkers and allostatic load index algorithms as well as pregnancy-specific considerations for allostatic load measurement. Further investigation of the allostatic load framework in the context of perinatal mental health is needed to advance understandings of maternal, infant, and child health

Age, temperature, and parasitaemia predict chloroquine treatment failure and anaemia in children with uncomplicated Plasmodium falciparum malaria

The prevalence of chloroquine-resistant Plasmodium falciparum malaria has been increasing in sub-Saharan Africa and parts of South America over the last 2 decades, and has been associated with increased anaemia-associated morbidity and higher mortality rates. Prospectively collected clinical and parasitological data from a multicentre study of 788 children aged 6-59 months with uncomplicated P. falciparum malaria were analysed in order to identify risk factors for chloroquine treatment failure and to assess its impact on anaemia after therapy. The proportion of chloroquine treatment failures (combined early and late treatment failures) was higher in the central-eastern African countries (Tanzania, 53%; Uganda, 80%; Zambia, 57%) and Ecuador (54%) than in Ghana (36%). Using logistic regression, predictors of early treatment failure included younger age, higher baseline temperature, and greater levels of parasitaemia. We conclude that younger age, higher initial temperature, and higher baseline parasitaemia predict early treatment failure and a higher probability of worsening anaemia between admission and days 7 or 14 post-treatment

High resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic Plasmodium populations

Background: Emergence and spread of drug resistance to every anti-malarial used to date, creates an urgent need for development of sensitive, specifc and feld-deployable molecular tools for detection and surveillance of validated drug resistance markers. Such tools would allow early detection of mutations in resistance loci. The aim of this study was to compare common population signatures and drug resistance marker frequencies between two populations with diferent levels of malaria endemicity and history of anti-malarial drug use: Tanzania and Sénégal. This was accomplished by implementing a high resolution melting assay to study molecular markers of drug resistance as compared to polymerase chain reaction–restriction fragment length polymorphism (PCR/RFLP) methodology. Methods: Fifty blood samples were collected each from a lowly malaria endemic site (Sénégal), and a highly malaria endemic site (Tanzania) from patients presenting with uncomplicated Plasmodium falciparum malaria at clinic. Data representing the DHFR were derived using both PCR–RFLP and HRM assay; while genotyping data representing the DHPS were evaluated in Senegal and Tanzania using HRM. Msp genotyping analysis was used to characterize the multiplicity of infection in both countries. Results: A high prevalence of samples harbouring mutant DHFR alleles was observed in both population using both genotyping techniques. HRM was better able to detect mixed alleles compared to PCR/RFLP for DHFR codon 51 in Tanzania; and only HRM was able to detect mixed infections from Senegal. A high prevalence of mutant alleles in DHFR (codons 51, 59, 108) and DHPS (codon 437) were found among samples from Sénégal while no mutations were observed at DHPS codons 540 and 581, from both countries. Overall, the frequency of samples harbouring either a single DHFR mutation (S108N) or double mutation in DHFR (C59R/S108N) was greater in Sénégal compared to Tanzania Conclusion: Here the results demonstrate that HRM is a rapid, sensitive, and feld-deployable alternative technique to PCR–RFLP genotyping that is useful in populations harbouring more than one parasite genome (polygenomic infections). In this study, a high levels of resistance polymorphisms was observed in both dhfr and dhps, among samples from Tanzania and Sénégal. A routine monitoring by molecular markers can be a way to detect emergence of resistance involving a change in the treatment policy

Effect of zinc on the treatment of Plasmodium falciparum malaria in children: A randomized controlled trial

Background: Zinc supplementation in young children has been associated with reductions in the incidence and severity of diarrheal diseases, acute respiratory infections, and malaria. Objective: The objective was to evaluate the potential role of zinc as an adjunct in the treatment of acute, uncomplicated falciparum malaria; a multicenter, double-blind, randomized placebo-controlled clinical trial was undertaken. Design: Children (n = 1087) aged 6 mo to 5 y were enrolled at sites in Ecuador, Ghana, Tanzania, Uganda, and Zambia. Children with fever and ≥ 2000 asexual forms of Plasmodium falciparum/μL in a thick blood smear received chloroquine and were randomly assigned to receive zinc (20 mg/d for infants, 40 mg/d for older children) or placebo for 4 d. Results: There was no effect of zinc on the median time to reduction of fever (zinc group: 24.2 h; placebo group: 24.0 h; P = 0.37), a ≥75% reduction in parasitemia from baseline in the first 72 h in 73.4% of the zinc group and in 77.6% of the placebo group (P = 0.11), and no significant change in hemoglobin concentration during the 3-d period of hospitalization and the 4 wk of follow-up. Mean plasma zinc concentrations were low in all children at baseline (zinc group: 8.54 ± 3.93 μmol/L; placebo group: 8.34 ± 3.25 μmol/L), but children who received zinc supplementation had higher plasma zinc concentrations at 72 h than did those who received placebo (10.95 ± 3.63 compared with 10.16 ± 3.25 μmol/L, P \u3c 0.001). Conclusion: Zinc does not appear to provide a beneficial effect in the treatment of acute, uncomplicated falciparum malaria in preschool children

Malaria-related mortality based on verbal autopsy in an area of low endemicity in a predominantly rural population in Ethiopia

<p>Abstract</p> <p>Background</p> <p>Although malaria is one of the most important causes of death in Ethiopia, measuring the magnitude of malaria-attributed deaths at community level poses a considerable difficulty. Nevertheless, despite its low sensitivity and specificity, verbal autopsy (VA) has been the most important technique to determine malaria-specific cause of death for community-based studies. The present study was undertaken to assess the magnitude of malaria mortality in a predominantly rural population of Ethiopia using VA technique at Butajira Rural Health Programme (BRHP) Demographic Surveillance Site (DSS).</p> <p>Methods</p> <p>A verbal autopsy was carried out for a year from August 2003 to July 2004 for all deaths identified at BRPH-DSS. Two trained physicians independently reviewed each VA questionnaire and indicated the most likely causes of death. Finally, all malaria related deaths were identified and used for analysis.</p> <p>Results</p> <p>A verbal autopsy study was successfully conducted in 325 deaths, of which 42 (13%) were attributed to malaria. The majority of malaria deaths (47.6%) were from the rural lowlands compared to those that occurred in the rural highlands (31%) and urban (21.4%) areas. The proportional mortality attributable to malaria was not statistically significant among the specific age groups and ecological zones. Mortality from malaria was reckoned to be seasonal; 57% occurred during a three-month period at the end of the rainy season between September and November. About 71% of the deceased received some form of treatment before death, while 12 (28.6%) of those who died neither sought care from a traditional healer nor were taken to a conventional health facility before death. Of those who sought treatment, 53.3% were first taken to a private clinic, 40% sought care from public health facilities, and the remaining two (6.7%) received traditional medicine. Only 11.9% of the total malaria-related deaths received some sort of treatment within 24h after the onset of illness.</p> <p>Conclusion</p> <p>The results of this study suggest that malaria plays a considerable role as a cause of death in the study area. Further data on malaria mortality with a relatively large sample size for at least two years will be needed to substantially describe the burden of malaria mortality in the study area.</p