A Non-Inferiority,Individually Randomized Trial of Intermittent Screening and Treatment versus Intermittent Preventive Treatment in the Control of Malaria in Pregnancy

Background

The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP) in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT) and treatment of positive women (ISTp) is an alternative approach.

Methods and Findings

An open, individually randomized, non-inferiority trial of IPTp-SP versus ISTp was conducted in 5,354 primi- or secundigravidae in four West African countries with a low prevalence of resistance to SP (The Gambia, Mali, Burkina Faso and Ghana). Women in the IPTp-SP group received SP on two or three occasions whilst women in the ISTp group were screened two or three times with a RDT and treated if positive for malaria with artemether-lumefantrine (AL). ISTp-AL was non-inferior to IPTp-SP in preventing low birth weight (LBW), anemia and placental malaria, the primary trial endpoints. The prevalence of LBW was 15.1% and 15.6% in the IPTp-SP and ISTp-AL groups respectively (OR = 1.03 [95% CI: 0.88, 1.22]). The mean hemoglobin concentration at the last clinic attendance before delivery was 10.97g/dL and 10.94g/dL in the IPTp-SP and ISTp-AL groups respectively (mean difference: -0.03 g/dL [95% CI: -0.13, +0.06]). Active malaria infection of the placenta was found in 24.5% and in 24.2% of women in the IPTp-SP and ISTp-AL groups respectively (OR = 0.95 [95% CI 0.81, 1.12]). More women in the ISTp-AL than in the IPTp-SP group presented with malaria parasitemia between routine antenatal clinics (310 vs 182 episodes, rate difference: 49.4 per 1,000 pregnancies [95% CI 30.5, 68.3], but the number of hospital admissions for malaria was similar in the two groups.

Conclusions

Despite low levels of resistance to SP in the study areas, ISTp-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria transmission is low and for the prevention of malaria in HIV positive women receiving cotrimoxazole prophylaxis in whom SP is contraindicated.

Trial Registration

ClinicalTrials.gov NCT01084213 Pan African Clinical trials Registry PACT201202000272122     

Fate and efficiency of N fertilizers applied to pearl millet in Niger

Field studies were conducted in Niger using ¹⁵N-labeled fertilizers to assess the fate and efficiency of fertilizer N in pearl millet (Pennisetum glaucum [L.] R.Br.) production. Total plant uptake of fertilizer N was low in all cases (20%–37%), and losses were severe (25%–53%). The majority of N remaining in the soil was found in the 0- to 15-cm layer though some enrichment at lower depths was found when the N fertilizer was calcium ammonium nitrate (CAN). In a comparison of urea placement methods (band, broadcast, or point placement), no significant differences in ¹⁵N uptake or yield were noted though point placement did exacerbate ¹⁵N loss. The mechanism of N loss is believed to have been ammonia volatilization. Yields were similar whether urea or CAN was used, but ¹⁵N uptake from CAN was higher. A statistical model was developed relating millet yield and N response to midseason rainfall. In drought years, no N response was found, whereas in years of good rainfall a response was found of 15 kg grain for each kilogram of N applied (at 30 kg N ha^-1 rate).     

Effects of fertility management strategies on phosphorus bioavailability in four West African soils

Low phosphorus (P) in acid sandy soils of the West African Sudano-Sahelian zone is a major limitation to crop growth. To compare treatment effects on total dry matter (TDM) of crops and plant available P (P-Bray and isotopically exchangeable P), field experiments were carried out for 2 years at four sites where annual rainfall ranged from 560 to 850 mm and topsoil pH varied between 4.2 and 5.6. Main treatments were: (i) crop residue (CR) mulch at 500 and 2000 kg ha^–1, (ii) eight different rates and sources of P and (iii) cereal/legume rotations including millet (Pennisetum glaucum L.), sorghum [Sorghum bicolor (L.) Moench], cowpea (Vigna unguiculata Walp.) and groundnut (Arachis hypogaea L.). For the two Sahelian sites with large CR-induced differences in TDM, mulching did not modify significantly the soils' buffering capacity for phosphate ions but led to large increases in the intensity factor (C_P) and quantity of directly available soil P (E _1min). In the wetter Sudanian zone lacking effects of CR mulching on TDM mirrored a decline of E _1min with CR. Broadcast application of soluble single superphosphate (SSP) at 13 kg P ha^–1 led to large increases in C _P and quantity of E _1min at all sites which translated in respective TDM increases. The high agronomic efficiency of SSP placement (4 kg P ha^–1) across sites could be explained by consistent increases in the quantity factor which confirms the power of the isotopic exchange method in explaining management effects on crop growth across the region.     

Isolation and characterization of microsatellite markers for the threatened African endemic tree species Pterocarpus erinaceus Poir.

To study the genetic diversity and structure of the forest species Pterocarpus erinaceus Poir., seventeen polymorphic nuclear microsatellite markers were isolated and characterized, using next‐generation sequencing. Three hundred and sixty‐five (365) individuals were analyzed within fifteen (15) West African populations. The number of alleles for these loci varied from 4 to 30, and the heterozygosity varied from 0.23 to 0.82. The seventeen (17) primers designed here will allow characterizing the genetic diversity of this threaten species on its natural stands and to better understand the population differentiation mechanisms shaping it.     

Long- and short-term effects of crop residues on aluminum toxicity,phosphorus availability and growth of pearl millet in an acid sandy soil

Pasture swards containing perennial ryegrass (Lolium perenne L.) alone or with one of five different white clover (Trifolium repens L.) cultivars were examined for production and transfer of fixed nitrogen (N) to grass under dairy cow grazing. Grass-only swards produced 21% less than mixed clover-grass swards during the second year after sowing. Production from grass-only plots under a mowing and clipping removal regime was 44% less than from grass-only plots under grazing. Much of this difference could be attributed to N transfer. In swards without clover, the ryegrass component also decreased in favour of other grasses.The average amount of fixed N in herbage from all clover cultivars was 269 kg N ha^–1 yr^–1. Above-ground transfer of fixed N to grasses (via cow excreta) was estimated at 60 kg N ha^–1 yr^–1. Below-ground transfer of fixed N to grasses was estimated at 70 kg N ha^–1 yr^–1 by ¹⁵N dilution and was similar for all clover cultivars. Thus, about 50% of grass N was met by transfer of fixed N from white clover during the measurement year. Short-term measurements using a ¹⁵N foliar-labelling method indicated that below-ground N transfer was largest during dry summer conditions.     

Effect of crop residues on root growth and phosphorus acquisition of pearl millet in an acid sandy soil in Niger

The effect of long-term (1983–1988) applications of crop residues (millet straw, 2–4 t ha^-1 yr^–1) and/or mineral fertilizer (30 kg N, 13 kg P and 25 kg K ha^-1 yr^-1) on uptake of phosphorus (P) and other nutrients, root growth and mycorrhizal colonization of pearl millet (Pennisetum glaucum L.) was examined for two seasons (1987 and 1988) on an acid sandy soil in Niger. Treatments of the long-term field experiment were: control (–CR–F), mineral fertilizer only (–CR+F), crop residues only (+CR–F), and crop residues plus mineral fertilizer (+CR+F).In both years, total P uptake was similar for +CR–F and –CR+F treatments (1.6–3.5 kg P ha^-1), although available soil P concentration (Bray I P) was considerably lower in +CR–F (3.2 mg P kg^-1 soil) than in –CR+F (7.4) soil. In the treatments with mineral fertilizers (–CR+F; +CR+F), crop residues increased available soil P concentrations (Bray I P) from 7.4 to 8.9 mg kg^-1 soil, while total P uptake increased from 3.6 to 10.6 kg P ha^-1. In 1987 (with 450 mm of rainfall), leaf P concentrations of 30-day-old millet plants were in the deficiency range, but highest in the +CR+F treatment. In 1988 (699 mm), leaf P concentrations were distinctly higher, and again highest in the +CR+F treatment. In the treatments without crop residues (–CR–F; –CR+F), potassium (K) concentrations in the leaves indicated K deficiency, while application of crop residues (+CR–F; +CR+F) substantially raised leaf K concentrations and total K uptake. Leaf concentrations of calcium (Ca) and magnesium (Mg) were hardly affected by the different treatments.In the topsoil (0–30 cm), root length density of millet plants was greater for +CR+F (6.5 cm cm^-3) than for +CR–F (4.5 cm cm^-3) and –CR+F (4.2 cm cm^-3) treatments. Below 30 cm soil depth, root length density of all treatments declined rapidly from about 0.6 cm cm^-3 (30–60 cm soil depth) to 0.2 cm cm^-3 (120–180 cm soil depth). During the period of high uptake rates of P (42–80 DAP), root colonization with vesicular-arbuscular mycorrhizal (VAM) fungi was low in 1987 (15–20%), but distinctly higher in 1988 (55–60%). Higher P uptake of +CR+F plants was related to a greater total root length in 0–30 cm and also to a higher P uptake rate per unit root length (P influx). Beneficial effects of crop residues on P uptake were primarily attributed to higher P mobility in the soil due to decreased concentrations of exchangeable Al, and enhancement of root growth. In contrast, the beneficial effect of crop residues on K uptake was caused by direct K supply with the millet straw.     

The effect of soil tillage and fertilizer use on pearl millet yields in Niger

Farmers in Niger generally do not plow their fields and are therefore unable to incorporate phosphate. Experiments were conducted in Niger to assess the effect of soil tillage, P source, and fertilizer placement on yields of pearl millet (Pennisetum glaucum [L.] R. Br.). Treatments included single superphosphate (SSP) or ground Tahoua phosphate rock (PRT) incorporated into the soil during tillage or SSP surface applied after tillage. In plots which were not tilled, P sources (SSP, PRT, and PAPR-partially acidulated rock) were broadcast on the soil surface with no incorporation. In order to improve P efficiency under zero tillage, P was point placed in the soil near the plant with either broadcast or point-placed urea. Treatments in which tillage was used showed a slight though nonsignificant yield increase over untilled plots. The yield increase did not appear to be due to phosphate incorporation but rather to direct tillage effects on early plant growth. In a comparison of SSP with PRT or PAPR broadcast on soils not receiving tillage, PRT performed poorly relative to the other P sources. SSP outyielded PAPR and PRT in 1986, but in subsequent years, no significant difference was found between PAPR and SSP. Point placement of P or N near the plant did not significantly increase yields over broadcast treatments even though the millet was planted with wide 1×1 m spacing.