Type of infectious disease affects glucose metabolism and liver glycogen content in Surinamese children: malaria vs. pneumonia.

BACKGROUND AND AIM: Fasting is an important risk factor for hypoglycemia in children with malaria or pneumonia. Young children are more at risk because of impaired endogenous glucose production presumably due to smaller liver glycogen stores. The aim of this study was to measure the effect of a bolus of glucagon on glucose kinetics, as an indicator of glycogen content, in fasted children with malaria and pneumonia. METHODS: After a 16-h controlled fast, plasma glucose concentration and endogenous glucose production were measured using [6,6-2H2]glucose in six children with severe malaria and 12 children with severe pneumonia who were 1-5 years of age before and after a bolus glucagon. RESULTS: Basal glucose concentration and endogenous glucose production were higher in children with malaria, p=0.034 and p=0.010, respectively. After glucagon, the increase in the plasma glucose concentration was higher in children with malaria (52±26% vs. 31±23%, p=0.029). Also, the increase in glucose production was higher in children with malaria (106±42% vs. 70±52%, p=0.023). There were no differences in the fasting duration or duration of illness. CONCLUSIONS: This is the first study to show infectious disease-related differences in the adaptation of glucose metabolism to fasting in young children. It was found that basal glucose concentration and endogenous glucose production were higher in children with malaria. The increase in plasma glucose concentration and endogenous glucose production in response to glucagon was higher in children with malaria, indicating smaller glycogen stores in children with pneumonia.

Evidence of an increased incidence of day 3 parasitaemia in Suriname: an indicator of the emerging resistance of Plasmodium falciparum to artemether.

The emerging resistance to artemisinin derivatives that has been reported in South-East Asia led us to assess the efficacy of artemether-lumefantrine as the first line therapy for uncomplicated Plasmodium falciparum infections in Suriname. This drug assessment was performed according to the recommendations of the World Health Organization in 2011. The decreasing number of malaria cases in Suriname, which are currently limited to migrating populations and gold miners, precludes any conclusions on artemether efficacy because adequate numbers of patients with 28-day follow-up data are difficult to obtain. Therefore, a comparison of day 3 parasitaemia in a 2011 study and in a 2005/2006 study was used to detect the emergence of resistance to artemether. The prevalence of day 3 parasitaemia was assessed in a study in 2011 and was compared to that in a study in 2005/2006. The same protocol was used in both studies and artemether-lumefantrine was the study drug. Of 48 evaluable patients in 2011, 15 (31%) still had parasitaemia on day 3 compared to one (2%) out of 45 evaluable patients in 2005/2006. Overall, 11 evaluable patients in the 2011 study who were followed up until day 28 had negative slides and similar findings were obtained in all 38 evaluable patients in the 2005/2006 study. The significantly increased incidence of parasite persistence on day 3 may be an indication of emerging resistance to artemether.

Fasting predisposes to hypoglycemia in Surinamese children with severe pneumonia, and young children are more at risk.

The objective of this study was to investigate glucose kinetics during controlled fasting in children with severe pneumonia. Plasma glucose concentration, endogenous glucose production and gluconeogenesis were measured in 12 Surinamese children (six young: 1-3 years, six older: 3-5 years) with severe pneumonia during a controlled 16 h fast using stable isotopes [6,6-(2)H2]glucose and (2)H2O at a hospital-based research facility. On admission, the glucose concentrations were comparable in both groups: young children: 5.1 ± 1.3 mmol/l, older children: 4.8 ± 0.6 mmol/l, p = 0.685, with a decrease during the first 8 h of fasting in the young children only to 3.6 ± 0.5, p = 0.04. Glucose production was comparable in both groups: young: 24.5 ± 8.3, older: 24.9 ± 5.9 µmol/kg(•)min, p = 0.926. Between 8 and 16 h of fasting, the glucose concentration decreased comparably in both groups (young: - 0.9 ± 0.7, p = 0.004; older: -1.0 ± 0.4 mmol/l, p = 0.001), as did glucose production (young: -6.8 ± 6.3, p = 0.003; older: -5.3 ± 3.4 µmol/kg(•)min, p = 0.001). Gluconeogenesis decreased in young children only: -5.0 ± 7.4, p = 0.029. We conclude that fasting predisposes to hypoglycemia in children with severe pneumonia. Young children are more at risk than older children. Glucose production is an important determinant of the plasma glucose concentration in young children with pneumonia, indicating an inability to reduce glucose usage. Our results are largely in agreement with the literature on the adaptation of glucose metabolism in children with malaria, although there seem to be disease-specific differences in the regulation of gluconeogenesis.

Primaquine double dose for 7 days is inferior to single-dose treatment for 14 days in preventing Plasmodium vivax recurrent episodes in Suriname.

BACKGROUND: Recurrent episodes of Plasmodium vivax are caused by dormant liver stages of the parasite, which are not eradicated by choloroquine. Therefore, effective treatment also includes the use of primaquine (PQ). However, this secondary preventive therapy is often not effective, mostly due to poor adherence to the relatively long treatment course, justifying a comparative study of the efficacy of different durations of PQ treatment. MATERIALS AND METHODS: We included patients presenting with an acute and documented P. vivax infection from January 2006 to February 2008. All patients received chloroquine 25 mg/kg over a 3-day period. Subsequently, patients in group 7D received PQ 30 mg/day for 7 days, and patients in group 14D received standard PQ 15 mg/day for 14 days. All doses were given under supervision and patients were followed up for at least 6 months. The Kaplan-Meier method was used to estimate cumulative probability of recurrence up to 12 months after treatment initiation stratified by treatment group. Cox regression was used to assess possible determinants for recurrent parasitemia. RESULTS: Forty-seven of the 79 included patients (59.5%) were allocated to group 7D and 32 patients (40.5%) were allocated to group 14D. Recurrent parasitemia was detected in 31.9% of the cases in group 7D compared to 12.5% of the cases in group 14D (hazard ratio [HR] =3.36, 95% CI 1.11-10.16). Cumulative probability for recurrent parasitemia at 3, 6, and 12 months was 0.201 (95% CI 0.106-0.362), 0.312 (95% CI 0.190-0.485), and 0.424 (95% CI 0.274-0.615) for group 7D and 0.100 (95% CI 0.033-0.279), 0.100 (95% CI 0.033-0.279), and 0.138 (95% CI 0.054-0.327) for group 14D, respectively. When adjusted for possible confounders, differences in recurrent parasitemia remained significant between the two regimens in Cox regression analysis. CONCLUSION: More than 30% of the patients receiving shorter treatment course had recurrent parasitemia, suggesting that the standard dose of 15 mg/day PQ for 14 days is more efficacious than 30 mg for 7 days in preventing P. vivax recurrent episodes. Furthermore, we suggest that P. vivax treatment in Suriname should be changed to PQ 30 mg/day for 14 days, as per Center for Disease Control and Prevention recommendation, in light of a recurrence rate of over 10%, even in group 14D.

Assessing parasite clearance during uncomplicated Plasmodium falciparum infection treated with artesunate monotherapy in Suriname.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum is suspected when the day 3 parasitemia is >10% when treated with artemisinin-based combination therapy or if >10% of patients treated with artemisinin-based combination therapy or artesunate monotherapy harbored parasites with half-lives ≥5 hours. Hence, a single-arm prospective efficacy trial was conducted in Suriname for uncomplicated P. falciparum infection treated with artesunate-based monotherapy for 3 days assessing day 3 parasitemia, treatment outcome after 28 days, and parasite half-life. METHODS: The study was conducted in Paramaribo, the capital of Suriname, from July 2013 until July 2014. Patients with uncomplicated Plasmodium falciparum infection were included and received artesunate mono-therapy for three days. Day 3 parasitaemia, treatment outcome after 28 days and parasite half-life were determined. The latter was assessed with the parasite clearance estimator from the WorldWide Antimalarial Resistance Network (WWARN). RESULTS: Thirty-nine patients were included from July 2013 until July 2014. The day 3 parasitemia was 10%. Eight patients (20.5%) could be followed up until day 28 and showed adequate clinical and parasitological response. Parasite half-life could only be determined from ten data series (25.7%). The median parasite half-life was 5.16 hours, and seven of these data series had a half-life ≥5 hours, still comprising 17.9% of the total data series. CONCLUSION: The low follow-up rate and the limited analyzable data series preclude clear conclusions about the efficacy of artesunate monotherapy in Suriname and the parasite half-life, respectively. The emergence of at least 17.9% of data series with a parasite half-life ≥5 hours supports the possible presence of artemisinin resistance.

Disease concepts and treatment by tribal healers of an Amazonian forest culture.

BACKGROUND: The extensive medicinal plant knowledge of Amazonian tribal peoples is widely recognized in the scientific literature and celebrated in popular lore. Despite this broad interest, the ethnomedical systems and knowledge of disease which guide indigenous utilization of botanical diversity for healing remain poorly characterized and understood. No study, to our knowledge, has attempted to directly examine patterns of actual disease recognition and treatment by healers of an Amazonian indigenous culture. METHODS: The establishment of traditional medicine clinics, operated and directed by elder tribal shamans in two remote Trio villages of the Suriname rainforest, presented a unique investigational opportunity. Quantitative analysis of clinic records from both villages permitted examination of diseases treated over a continuous period of four years. Cross-cultural comparative translations were articulated of recorded disease conditions through ethnographic interviews of elder Trio shamans and a comprehensive atlas of indigenous anatomical nomenclature was developed. RESULTS: 20,337 patient visits within the period 2000 to 2004 were analyzed. 75 disease conditions and 127 anatomical terms are presented. Trio concepts of disease and medical practices are broadly examined within the present and historical state of their culture. CONCLUSION: The findings of this investigation support the presence of a comprehensive and highly formalized ethnomedical institution within Trio culture with attendant health policy and conservation implications.

Evidence of an increased incidence of day 3 parasitaemia in Suriname: an indicator of the emerging resistance of Plasmodium falciparum to artemether

The emerging resistance to artemisinin derivatives that has been reported in South-East Asia led us to assess the efficacy of artemether-lumefantrine as the first line therapy for uncomplicated Plasmodium falciparum infections in Suriname. This drug assessment was performed according to the recommendations of the World Health Organization in 2011. The decreasing number of malaria cases in Suriname, which are currently limited to migrating populations and gold miners, precludes any conclusions on artemether efficacy because adequate numbers of patients with 28-day follow-up data are difficult to obtain. Therefore, a comparison of day 3 parasitaemia in a 2011 study and in a 2005/2006 study was used to detect the emergence of resistance to artemether. The prevalence of day 3 parasitaemia was assessed in a study in 2011 and was compared to that in a study in 2005/2006. The same protocol was used in both studies and artemether-lumefantrine was the study drug. Of 48 evaluable patients in 2011, 15 (31%) still had parasitaemia on day 3 compared to one (2%) out of 45 evaluable patients in 2005/2006. Overall, 11 evaluable patients in the 2011 study who were followed up until day 28 had negative slides and similar findings were obtained in all 38 evaluable patients in the 2005/2006 study. The significantly increased incidence of parasite persistence on day 3 may be an indication of emerging resistance to artemether.