Jane Bruce

Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial

Summary Background Vitamin D has a role in regulating immune function, and its deficiency is a suggested risk factor for childhood pneumonia. Our aim was to assess whether oral supplementation of vitamin D3 (cholecalciferol) will reduce the incidence and severity of pneumonia in a high-risk infant population. Methods We did a randomised placebo-controlled trial to compare oral 100 000 IU (2·5 mg) vitamin D3 with placebo given to children aged 1–11 months in Kabul, Afghanistan. Randomisation was by use of a computer-generated list. Vitamin D or placebo was given by fieldworkers once every 3 months for 18 months. Children presenting at the study hospital with signs of pneumonia had their diagnosis confirmed radiographically. Our primary outcome was the first or only episode of radiologically confirmed pneumonia. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00548379. Findings 1524 children were assigned to receive vitamin D3 and 1522 placebo. There was no significant difference between the incidence of first or only pneumonia between the vitamin D (0·145 per child per year, 95% CI 0·129–0·164) and the placebo group (0.137, 0·121–0·155); the incidence rate ratio was 1·06 (95% CI 0·89–1·27). From 652 children during five separate periods of testing serum calcifediol, only one child in each of two testing periods had results greater than 375 nmol/L in the intervention group—a toxic level. Interpretations Quarterly bolus doses of oral vitamin D3 supplementation to infants are not an effective intervention to reduce the incidence of pneumonia in infants in this setting. Funding Wellcome Trust and British Council.

Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial.

Objectives  To determine whether (i) supplementation of oral 100 000 iu of vitamin D3 (cholecalciferol) along with antibiotics will reduce the duration of illness in children with pneumonia; (ii) supplementation will reduce the risk of repeat episodes.

Species Shifts in the Anopheles gambiae Complex: Do LLINs Successfully Control Anopheles arabiensis?

Introduction High coverage of conventional and long-lasting insecticide treated nets (ITNs and LLINs) in parts of E Africa are associated with reductions in local malaria burdens. Shifts in malaria vector species ratio have coincided with the scale-up suggesting that some species are being controlled by ITNs/LLINs better than others. Methods Between 2005–2006 six experimental hut trials of ITNs and LLINs were conducted in parallel at two field stations in northeastern Tanzania; the first station was in Lower Moshi Rice Irrigation Zone, an area where An. arabiensis predominates, and the second was in coastal Muheza, where An. gambiae and An. funestus predominate. Five pyrethroids and one carbamate insecticide were evaluated on nets in terms of insecticide-induced mortality, blood-feeding inhibition and exiting rates. Results In the experimental hut trials mortality of An. arabiensis was consistently lower than that of An. gambiae and An. funestus. The mortality rates in trials with pyrethroid-treated nets ranged from 25–52% for An. arabiensis, 63–88% for An. gambiae s.s. and 53–78% for An. funestus. All pyrethroid-treated nets provided considerable protection for the occupants, despite being deliberately holed, with blood-feeding inhibition (percentage reduction in biting rates) being consistent between species. Veranda exiting rates did not differ between species. Percentage mortality of mosquitoes tested in cone bioassays on netting was similar for An. gambiae and An. arabiensis. Conclusions LLINs and ITNs treated with pyrethroids were more effective at killing An. gambiae and An. funestus than An. arabiensis. This could be a major contributing factor to the species shifts observed in East Africa following scale up of LLINs. With continued expansion of LLIN coverage in Africa An. arabiensis is likely to remain responsible for residual malaria transmission, and species shifts might be reported over larger areas. Supplementary control measures to LLINs may be necessary to control this vector species.

Intermittent Screening and Treatment versus Intermittent Preventive Treatment of Malaria in Pregnancy: A Randomised Controlled Non-Inferiority Trial

Background The effectiveness of intermittent preventive treatment of malaria in pregnancy (IPTp) may be compromised by the spread of resistance to sulphadoxine/pyrimethamine (SP) across Africa. But little informtion exists on alternative drugs for IPTp or alternative strategies for the prevention of malaria in pregnancy. Therefore, we have investigated whether screening with a rapid diagnostic test and treatment of those who are positive (IST) at routine antenatal clinic attendances is as effective and as safe as SP-IPTp in pregnant women. Methods and Findings During antenatal clinic sessions in six health facilities in Ghana held between March 2007 and September 2007, 3333 pregnant women who satisfied inclusion criteria were randomised into three intervention arms (1) standard SP-IPTp, (2) IST and treatment with SP or (3) IST and treatment with amodiaquine+artesunate (AQ+AS). All women received a long-lasting insecticide treated net. Study women had a maximum of three scheduled follow-up visits following enrolment. Haemoglobin concentration and peripheral parasitaemia were assessed between 36 and 40 weeks of gestation. Birth weight was measured at delivery or within 72 hours for babies delivered at home. Parasite prevalence at enrolment in primigravidae and in multigravidae was 29.6% and 10.2% respectively. At 36–40 weeks of gestation the prevalence of asymptomatic parasitaemia was 12.1% in study women overall and was very similar in all treatment groups. The risk of third trimester severe anaemia or low birth weight did not differ significantly between the three treatment groups regardless of gravidity. IST with AQ+AS or SP was not inferior to SP-IPTp in reducing the risk of low birth weight (RD = -1.17[95%CI; -4.39-1.02] for IST-SP vs. SP-IPTp and RD = 0.78[95%CI; -2.11-3.68] for IST-AQAS vs. SP-IPTp); third trimester severe anaemia (RD = 0.29[95%CI; -0.69-1.30] for IST-SP vs. SP-IPTp and RD = -0.36[95%CI;-1.12-0.44] for IST-AQAS vs. SP-IPTp). Conclusion The results of this study suggest that in an area of moderately high malaria transmission, IST with SP or AS+AQ may be a safe and effective strategy for the control of malaria in pregnancy. However, it is important that these encouraging findings are confirmed in other geographical areas and that the impact of IST on placental malaria is investigated. Trial Registration ClinicalTrials.gov NCT00432367 [NCT00432367]

Household ownership and use of insecticide treated nets among target groups after implementation of a national voucher programme in the United Republic of Tanzania: plausibility study using three annual cross sectional household surveys.

Objectives To evaluate the impact of the Tanzania National Voucher Scheme on the coverage and equitable distribution of insecticide treated nets, used to prevent malaria, to pregnant women and their infants. Design Plausibility study using three nationally representative cross sectional household and health facility surveys, timed to take place early, mid-way, and at the end of the roll out of the national programme. Setting The Tanzania National Voucher Scheme was implemented in antenatal services, and phased in on a district by district basis from October 2004 covering all of mainland Tanzania in May 2006. Participants 6115, 6260, and 6198 households (in 2005, 2006, and 2007, respectively) in a representative sample of 21 districts (out of a total of 113). Interventions A voucher worth

Which delivery systems reach the poor? A review of equity of coverage of ever-treated nets, never-treated nets, and immunisation to reduce child mortality in Africa.

2.45 (£1.47, €1.74) to be used as part payment for the purchase of a net from a local shop was given to every pregnant woman attending antenatal services. Main outcome measures Insecticide treated net coverage was measured as household ownership of at least one net and use of a net the night before the survey. Socioeconomic distribution of nets was examined using an asset based index. Results Steady increases in net coverage indicators were observed over the three year study period. Between 2005 and 2007, household ownership of at least one net (untreated or insecticide treated) increased from 44% (2686/6115) to 65% (4006/6198; P<0.001), and ownership of at least one insecticide treated net doubled from 18% (1062/5961) to 36% (2229/6198) in the same period (P<0.001). Among infants under 1 year of age, use of any net increased from 33% (388/1180) to 56% (707/1272; P<0.001) and use of an insecticide treated net increased from 16% (188/1180) to 34% (436/1272; P<0.001). After adjusting for potential confounders, household ownership was positively associated with time since programme launch, although this association did not reach statistical significance (P=0.09). Each extra year of programme operation was associated with a 9 percentage point increase in household insecticide treated net ownership (95% confidence interval −1.6 to 20). In 2005, only 7% (78/1115) of nets in households with a child under 1 year of age had been purchased with a voucher; this value increased to 50% (608/1211) in 2007 (P<0.001). In 2007, infants under 1 year in the least poor quintile were more than three times more likely to have used an insecticide treated net than infants in the poorest quintile (54% v 16%; P<0.001). Conclusions The Tanzania National Voucher Scheme was associated with impressive increases in the coverage of insecticide treated nets over a two year period. Gaps in coverage remain, however, especially in the poorest groups. A voucher system that facilitates routine delivery of insecticide treated nets is a feasible option to “keep up” coverage.

Efficacy, safety, and tolerability of amodiaquine plus sulphadoxine-pyrimethamine used alone or in combination for malaria treatment in pregnancy: a randomised trial

Insecticide-treated nets (ITNs) and childhood vaccination are two of the most powerful interventions available to prevent childhood mortality in Africa, but ITN coverage is still very low. Current debates about how to increase ITN coverage are concerned with the roles of different supply and delivery systems, in particular whether or not commercial net markets have any useful role. Here, we review data available on coverage and equity of coverage of three interventions to prevent childhood mortality. We compiled and analysed data from nationally representative surveys in 26 African countries to compare equity of coverage of (1) the Expanded Programme on Immunisation (EPI), (2) any net, (3) ever-treated nets (ie, ITNs), and (4) never-treated nets (ie, untreated nets; UTNs). We assumed that ever-treated net coverage mostly reflects the activities of public-health programmes and projects, and that never-treated net coverage mostly reflects the activity of local unsubsidised commercial markets. We discuss the validity, limitations, and possible biases of these assumptions. We estimate that 87% of the 8.4 million children protected by nets used UTNs. We used the concentration index (CI) to assess equity of coverage of the interventions. The data shows that never-treated net coverage is surprisingly equitable: overall, and despite substantial regional variations, it is comparable in equity to EPI (median CI(UTN)=0.166, CI(EPI)=0.075; p=0.3). In almost all countries, coverage of ITNs is strongly concentrated in the least poor households, and significantly more inequitable than both UTNs (median CI(ITN)=0.435, mean CI(UTN)=0.158; p<0.001) and EPI (median CI(ITN)=0.435, CI(EPI)=0.075; p<0.001). These results suggest that the public-health value of commercial net markets has been greatly underestimated, and that these markets have so far contributed more to equitable and sustainable coverage of mosquito nets, and hence to the prevention of malaria in Africa, than have the ITNs delivered by public-health systems and projects.

ReviewWhich delivery systems reach the poor? A review of equity of coverage of ever-treated nets, never-treated nets, and immunisation to reduce child mortality in Africa

BACKGROUND The widespread increase in resistance of Plasmodium falciparum to chloroquine and sulphadoxine-pyrimethamine threatens the use of these drugs for malaria treatment in pregnancy. We aimed to assess the safety and efficacy of amodiaquine alone or in combination with sulphadoxine-pyrimethamine as alternative regimens. METHODS Pregnant women with a gestational age of 16 weeks or more who attended antenatal clinics at a district hospital in Ghana were screened for malaria with OptiMAL dipsticks. 900 pregnant women who had a positive test result and P falciparum asexual stage parasitaemia were enrolled and randomly assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, or amodiaquine plus sulphadoxine-pyrimethamine. The primary outcome was parasitological failure by day 28 of treatment. Women were seen on days 3, 7, 14, and 28 after the start of treatment to assess the effect of treatment on peripheral parasitaemia, haemoglobin concentration, white-blood-cell count, and liver function. Additionally, reports of adverse effects were solicited and monitored during follow-up visits. Analysis was by intention to treat. This trial is registered with the US National Institute of Health clinical trials database number NCT00131703. FINDINGS PCR-corrected parasitological failure by day 28 was 14%, 11%, 3%, and 0% in the women assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, and amodiaquine plus sulphadoxine-pyrimethamine, respectively (p<0.0001). No serious liver toxic effects or white-blood-cell dyscrasias were noted. Minor side-effects were reported more often on day 3 by women receiving amodiaquine (86%) or amodiaquine plus sulphadoxine-pyrimethamine (90%) than those receiving sulphadoxine-pyrimethamine (48%) or no antimalarial drugs (34%; p<0.0001 for every comparison). INTERPRETATION Amodiaquine alone or in combination with sulphadoxine-pyrimethamine, although associated with minor side-effects, is effective when used to treat malaria in pregnancy.

A Randomized, Controlled Trial of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine, Amodiaquine, or the Combination in Pregnant Women in Ghana

Insecticide-treated nets (ITNs) and childhood vaccination are two of the most powerful interventions available to prevent childhood mortality in Africa, but ITN coverage is still very low. Current debates about how to increase ITN coverage are concerned with the roles of different supply and delivery systems, in particular whether or not commercial net markets have any useful role. Here, we review data available on coverage and equity of coverage of three interventions to prevent childhood mortality. We compiled and analysed data from nationally representative surveys in 26 African countries to compare equity of coverage of (1) the Expanded Programme on Immunisation (EPI), (2) any net, (3) ever-treated nets (ie, ITNs), and (4) never-treated nets (ie, untreated nets; UTNs). We assumed that ever-treated net coverage mostly reflects the activities of public-health programmes and projects, and that never-treated net coverage mostly reflects the activity of local unsubsidised commercial markets. We discuss the validity, limitations, and possible biases of these assumptions. We estimate that 87% of the 8.4 million children protected by nets used UTNs. We used the concentration index (CI) to assess equity of coverage of the interventions. The data shows that never-treated net coverage is surprisingly equitable: overall, and despite substantial regional variations, it is comparable in equity to EPI (median CI(UTN)=0.166, CI(EPI)=0.075; p=0.3). In almost all countries, coverage of ITNs is strongly concentrated in the least poor households, and significantly more inequitable than both UTNs (median CI(ITN)=0.435, mean CI(UTN)=0.158; p<0.001) and EPI (median CI(ITN)=0.435, CI(EPI)=0.075; p<0.001). These results suggest that the public-health value of commercial net markets has been greatly underestimated, and that these markets have so far contributed more to equitable and sustainable coverage of mosquito nets, and hence to the prevention of malaria in Africa, than have the ITNs delivered by public-health systems and projects.

Cost Implications of Improving Malaria Diagnosis: Findings from North-Eastern Tanzania

BACKGROUND The use of sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment in pregnancy (IPTp) is threatened by the spread of resistance to SP. Therefore, we studied the efficacy, safety, and tolerance of amodiaquine (AQ) or the combination of AQ and SP (SPAQ) as possible alternative treatments. METHODS The study was performed in Ghana from June 2004 through February 2007. Women were individually randomized to receive IPTp with SP (n=1328), AQ (n= 986), or SPAQ (n=1328). Incidences of anemia, peripheral anemia, and placental parasitemia at delivery were assessed for paucigravidae, as were the birth weights of their infants. Delivery outcomes and the incidence of adverse events were investigated for all women. RESULTS The prevalences of anemia (as defined by a hemoglobin concentration of <11.0 g/dL) at delivery were comparable between the SP and AQ groups and between the SP and SPAQ groups. Similarly, there was no significant difference between the SP and AQ groups or between the SP and SPAQ groups with regard to the incidences of low birth weight (LBW). Women who received AQ or SPAQ were more likely to report adverse events than were those who received SP. CONCLUSION The effects of IPTp with AQ or SPAQ on maternal anemia and LBW were comparable to the effects of IPTp with SP; however, IPTp regimens that contain AQ are unlikely to be useful as an alternative to IPTp with SP in Ghana, because of a high frequency of associated adverse events. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT00146783 .