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 information 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 enrollment. 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 enrollment 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]

Comparison of PfHRP-2/pLDH ELISA, qPCR and microscopy for the detection of Plasmodium events and prediction of sick visits during a malaria vaccine study.

BACKGROUND: Compared to expert malaria microscopy, malaria biomarkers such as Plasmodium falciparum histidine rich protein-2 (PfHRP-2), and PCR provide superior analytical sensitivity and specificity for quantifying malaria parasites infections. This study reports on parasite prevalence, sick visits parasite density and species composition by different diagnostic methods during a phase-I malaria vaccine trial. METHODS: Blood samples for microscopy, PfHRP-2 and Plasmodium lactate dehydrogenase (pLDH) ELISAs and real time quantitative PCR (qPCR) were collected during scheduled (n = 298) or sick visits (n = 38) from 30 adults participating in a 112-day vaccine trial. The four methods were used to assess parasite prevalence, as well as parasite density over a 42-day period for patients with clinical episodes. RESULTS: During scheduled visits, qPCR (39.9%, N = 119) and PfHRP-2 ELISA (36.9%, N = 110) detected higher parasite prevalence than pLDH ELISA (16.8%, N = 50) and all methods were more sensitive than microscopy (13.4%, N = 40). All microscopically detected infections contained P. falciparum, as mono-infections (95%) or with P. malariae (5%). By qPCR, 102/119 infections were speciated. P. falciparum predominated either as monoinfections (71.6%), with P. malariae (8.8%), P. ovale (4.9%) or both (3.9%). P. malariae (6.9%) and P. ovale (1.0%) also occurred as co-infections (2.9%). As expected, higher prevalences were detected during sick visits, with prevalences of 65.8% (qPCR), 60.5% (PfHRP-2 ELISA), 21.1% (pLDH ELISA) and 31.6% (microscopy). PfHRP-2 showed biomass build-up that climaxed (1813±3410 ng/mL SD) at clinical episodes. CONCLUSION: PfHRP-2 ELISA and qPCR may be needed for accurately quantifying the malaria parasite burden. In addition, qPCR improves parasite speciation, whilst PfHRP-2 ELISA is a potential predictor for clinical disease caused by P. falciparum. TRIAL REGISTRATION: ClinicalTrials.gov NCT00666380

Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: user acceptability

<p>Abstract</p> <p>Background</p> <p>Malaria in pregnancy is associated with increased risks of maternal and foetal complications. Currently, intermittent preventive treatment (IPT) of malaria during pregnancy with sulphadoxine-pyrimethamine (SP) is recommended by the WHO as part of a package of interventions also including insecticide-treated nets and effective case management. However, with increasing resistance to SP, the effectiveness of SP-IPT has been questioned. A randomized controlled trial (RCT) to investigate the relative efficacy of an alternative strategy of intermittent screening and treatment (IST), which involves a rapid diagnostic test for malaria at scheduled ANC visits and treatment of women only if positive, versus SP-IPT has been conducted in Ashanti region, Ghana. This paper reports on a complementary study investigating the acceptability of the different strategies to women enrolled in the trial.</p> <p>Methods</p> <p>Data were collected through twelve focus group discussions with women selected at random from the different arms of the RCT, exploring their experiences and perceptions about antenatal care and their involvement in the trial. Content analysis was used to identify relevant themes to structure the results.</p> <p>Results</p> <p>Five main themes emerged from participants' experiences of ANC and the RCT that would influence their acceptability of malaria prevention strategies during pregnancy: health benefits; drugs received; tests received; other services received; and health worker attitude. Their own health and that of their baby were strong motivations for attending ANC, and reported favourably as an outcome of being in the RCT. Women were not always clear on the biomedical function of drugs or blood tests but generally accepted them due to strong trust in the health staff. Home visits by staff and free ITNs as part of the trial were appreciated. Politeness and patience of health staff was a very strong positive factor.</p> <p>Conclusions</p> <p>Overall, both intermittent screening and treatment and intermittent preventive treatment appeared equally acceptable to pregnant women as strategies for the control of malaria in pregnancy. The women were more concerned about quality of services received, in particular the polite and patient attitude of health staff, and positive health implications for themselves and their babies than about the nature of the intervention.</p