Isoprenoid biosynthesis in Plasmodium falciparum.

Malaria kills nearly 1 million people each year, and the protozoan parasite Plasmodium falciparum has become increasingly resistant to current therapies. Isoprenoid synthesis via the methylerythritol phosphate (MEP) pathway represents an attractive target for the development of new antimalarials. The phosphonic acid antibiotic fosmidomycin is a specific inhibitor of isoprenoid synthesis and has been a helpful tool to outline the essential functions of isoprenoid biosynthesis in P. falciparum. Isoprenoids are a large, diverse class of hydrocarbons that function in a variety of essential cellular processes in eukaryotes. In P. falciparum, isoprenoids are used for tRNA isopentenylation and protein prenylation, as well as the synthesis of vitamin E, carotenoids, ubiquinone, and dolichols. Recently, isoprenoid synthesis in P. falciparum has been shown to be regulated by a sugar phosphatase. We outline what is known about isoprenoid function and the regulation of isoprenoid synthesis in P. falciparum, in order to identify valuable directions for future research.

Evaluation of the routine use of amoxicillin as part of the home-based treatment of severe acute malnutrition.

OBJECTIVE: To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food. METHODS: This retrospective cohort study compared data from the treatment of two groups of children in Malawi aged 6-59 months with uncomplicated severe acute malnutrition. The standard protocol group received a 7-day course of amoxicillin at the onset of treatment. The alternate protocol group received no antibiotics. All children were treated with the same ready-to-use therapeutic food. The primary outcome was nutritional recovery, defined as achieving a weight-for-height Z-score > -2 without oedema. RESULTS: Four hundred and ninety-eight children were treated according to the standard protocol with amoxicillin, and 1955 were treated under the alternate protocol without antibiotics. The group of children treated with amoxicillin was slightly older and more stunted at baseline. The recovery rate for children who received amoxicillin was worse at 4 weeks (40%vs. 71%) but similar after up to 12 weeks of therapy (84%vs. 86%), compared to the children treated without antibiotics. Regression modelling indicated that this difference at 4 weeks was most strongly associated with the receipt of amoxicillin. CONCLUSIONS: This review of two therapeutic feeding programmes suggests that children with severe acute malnutrition who were treated without amoxicillin did not have an inferior rate of recovery. Given the limitations of this retrospective analysis, a prospective trial is warranted to determine the effect of antibiotics on recovery from uncomplicated malnutrition with home-based therapy.

Consuming cassava as a staple food places children 2-5 years old at risk for inadequate protein intake, an observational study in Kenya and Nigeria.

BACKGROUND: Inadequate protein intake is known to be deleterious in animals. Using WHO consensus documents for human nutrient requirements, the protein:energy ratio (P:E) of an adequate diet is > 5%. Cassava has a very low protein content. This study tested the hypothesis that Nigerian and Kenyan children consuming cassava as their staple food are at greater risk for inadequate dietary protein intake than those children who consume less cassava. METHODS: A 24 hour dietary recall was used to determine the food and nutrient intake of 656 Nigerian and 449 Kenyan children aged 2-5 years residing in areas where cassava is a staple food. Anthropometric measurements were conducted. Diets were scored for diversity using a 12 point score. Pearson's Correlation Coefficients were calculated to relate the fraction of dietary energy obtained from cassava with protein intake, P:E, and dietary diversity. RESULTS: The fraction of dietary energy obtained from cassava was > 25% in 35% of Nigerian children and 89% of Kenyan children. The mean dietary diversity score was 4.0 in Nigerian children and 4.5 in Kenyan children, although the mean number of different foods consumed on the survey day in Nigeria was greater than Kenya, 7.0 compared to 4.6. 13% of Nigerian and 53% of Kenyan children surveyed had inadequate protein intake. The fraction of dietary energy derived from cassava was negatively correlated with protein intake, P:E, and dietary diversity. Height-for age z score was directly associated with protein intake and negatively associated with cassava consumption using regression modeling that controlled for energy and zinc intake. CONCLUSIONS: Inadequate protein intake was found in the diets of Nigerian and Kenyan children consuming cassava as a staple food. Inadequate dietary protein intake is associated with stunting in this population. Interventions to increase protein intake in this vulnerable population should be the focus of future work.

Children consuming cassava as a staple food are at risk for inadequate zinc, iron, and vitamin A intake.

Cassava contains little zinc, iron, and beta-carotene, yet it is the primary staple crop of over 250 million Africans. This study used a 24-hour dietary recall to test the hypothesis that among healthy children aged 2-5 years in Nigeria and Kenya, cassava's contribution to the childrens' daily diets is inversely related to intakes of zinc, iron, and vitamin A. Dietary and demographic data and anthropometric measurements were collected from 449 Kenyan and 793 Nigerian children. Among Kenyan children 89% derived at least 25% of their dietary energy from cassava, while among the Nigerian children 31% derived at least 25% of energy from cassava. Spearman's correlation coefficient between the fraction of dietary energy obtained from cassava and vitamin A intake was r = -0.15, P < 0.0001, zinc intake was r = -0.11, P < 0.0001 and iron intake was r = -0.36, P < 0.0001. In Kenya, 59% of children consumed adequate vitamin A, 22% iron, and 31% zinc. In Nigeria, 17% of children had adequate intake of vitamin A, 57% iron, and 41% zinc. Consumption of cassava is a risk factor for inadequate vitamin A, zinc and/or iron intake.

The use of home-based therapy with ready-to-use therapeutic food to treat malnutrition in a rural area during a food crisis.

When the international community declared a famine in Malawi in January of 2006, emergency food aid reached only populations with pre-existing health care services. To treat the widespread childhood malnutrition in Machinga district, a rural area lacking health care facilities, in February 2006 five outpatient therapeutic programs were implemented that utilized home-based therapy and ready-to-use therapeutic food. Children with severe malnutrition, defined as the presence of edema and/or a weight-for-height less than 70% of the reference standard, were enrolled in the program. Two senior clinical nurses trained village health aides in each of the five communities. Children visited the health aides biweekly. During the visits, health aides collected demographic and anthropometric information and distributed a 2-week supply of ready-to-use therapeutic food, providing 175 kcal/kg/d. Treatment continued for 8 weeks; children were discharged before 8 weeks if they reached a weight-for-height more than 100% of the reference standard, or required admission to the hospital due to systemic infection or recurrence of edema. Of the 826 children enrolled, 775 (93.7%) recovered, 13 (1.8%) remained malnourished, 30 (3.6%) defaulted, and 8 (0.9%) died. Mean weight gained was 2.7+/-3.7 g/kg/d, height gained 0.3+/-0.9 mm/d, and mid-upper arm circumference gained 0.2+/-0.3 mm/d. Home-based therapy with ready-to-use therapeutic food administered by village health aides is an effective approach to treating malnutrition during food crises in areas lacking health services.