Evaluation of the national policy of single screening and treatment for the prevention of malaria in pregnancy in two districts in Eastern Indonesia: health provider perceptions

Background Malaria in pregnancy has devastating consequences for both the expectant mother and baby. Annually, 88.2 (70%) of the 125.2 million pregnancies in malaria endemic regions occur in the Asia–Pacific region. The control of malaria in pregnancy in most of Asia relies on passive case detection and prevention with long-lasting insecticide-treated nets. Indonesia was the first country in the region to introduce, in 2012, malaria screening at pregnant women’s first antenatal care visit to reduce the burden of malaria in pregnancy. The study assessed health providers’ acceptability and perceptions on the feasibility of implementing the single screening and treatment (SST) strategy in the context of the national programme in two endemic provinces of Indonesia. Methods Qualitative data were collected through in-depth interviews with 86 health providers working in provision of antenatal care (midwives, doctors, laboratory staff, pharmacists, and heads of drug stores), heads of health facilities and District Health Office staff in West Sumba and Mimika districts in East Nusa Tenggara and Papua provinces, respectively. Results Health providers of all cadres were accepting of SST as a preventive strategy, showing a strong preference for microscopy over rapid diagnostic tests (RDTs) as the method of screening. Implementation of the policy was inconsistent in both sites, with least extensive implementation reported in West Sumba compared to Mimika. SST was predominantly implemented at health centre level using microscopy, whereas implementation at community health posts was said to occur in less than half the selected health facilities. Lack of availability of RDTs was cited as the major factor that prevented provision of SST at health posts, however as village midwives cannot prescribe medicines women who test positive are referred to health centres for anti-malarials. Few midwives had received formal training on SST or related topics. Conclusions The study findings indicate that SST was an acceptable strategy among health providers, however implementation was inconsistent with variation across different localities within the same district, across levels of facility, and across different cadres within the same health facility. Implementation should be re-invigorated through reorientation and training of health providers, stable supplies of more sensitive RDTs, and improved data capture and reporting

Prevalence of malaria infection in pregnant women compared with children for tracking malaria transmission in sub-Saharan Africa: a systematic review and meta-analysis

Background In malarious areas, pregnant women are more likely to have detectable malaria than are their nonpregnant peers, and the excess risk of infection varies with gravidity. Pregnant women attending antenatal clinic for their fi rst visit are a potential pragmatic sentinel group to track the intensity of malaria transmission; however, the relation between malaria prevalence in children, a standard measure to estimate malaria endemicity, and pregnant women has never been compared. Methods We obtained data on malaria prevalence in pregnancy from the Malaria in Pregnancy Library (January, 2015) and data for children (0–59 months) were obtained from recently published work on parasite prevalence in Africa and the Malaria in Pregnancy Library. We used random eff ects meta-analysis to obtain a pooled prevalence ratio (PPR) of malaria in children versus pregnant women (during pregnancy, not at delivery) and by gravidity, and we used metaregression to assess factors aff ecting the prevalence ratio. Findings We used data from 18 sources that included 57 data points. There was a strong linear relation between the prevalence of malaria infection in pregnant women and children (r=0·87, p<0·0001). Prevalence was higher in children when compared with all gravidae (PPR=1·44, 95% CI 1·29–1·62; I²=80%, 57 studies), and against multigravidae (1·94, 1·68–2·24; I²=80%, 7 studies), and marginally higher against primigravidae (1·16, 1·05–1·29; I²=48%, 8 studies). PPR was higher in areas of higher transmission. Interpretation Malaria prevalence in pregnant women is strongly correlated with prevalence data in children obtained from household surveys, and could provide a pragmatic adjunct to survey strategies to track trends in malaria transmission in Africa

Mefloquine for preventing malaria in pregnant women

Background: The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for malaria for all women who live in moderate to high malaria transmission areas in Africa. However, parasite resistance to sulfadoxine-pyrimethamine has been increasing steadily in some areas of the region. Moreover, HIV-infected women on cotrimoxazole prophylaxis cannot receive sulfadoxine-pyrimethamine because of potential drug interactions. Thus, there is an urgent need to identify alternative drugs for prevention of malaria in pregnancy. One such candidate is mefloquine. Objectives: To assess the effects of mefloquine for preventing malaria in pregnant women, specifically, to evaluate: • the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women; and • the impact of HIV status, gravidity, and use of insecticide-treated nets on the effects of mefloquine.Search methods: We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), the Malaria in Pregnancy Library, and two trial registers up to 31 January 2018. In addition, we checked references and contacted study authors to identify additional studies, unpublished data, confidential reports, and raw data from published trials. Selection criteria: Randomized and quasi-randomized controlled trials comparing mefloquine IPT or mefloquine prophylaxis against placebo, no treatment, or an alternative drug regimen. Data collection and analysis: Two review authors independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when required. Dichotomous outcomes were compared using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes using mean differences (MDs). We have presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach for the following main outcomes of analysis: maternal peripheral parasitaemia at delivery, clinical malaria episodes during pregnancy, placental malaria, maternal anaemia at delivery, low birth weight, spontaneous abortions and stillbirths, dizziness, and vomiting. Main results: Six trials conducted between 1987 and 2013 from Thailand (1), Benin (3), Gabon (1), Tanzania (1), Mozambique (2), and Kenya (1) that included 8192 pregnant women met our inclusion criteria. Two trials (with 6350 HIV-uninfected pregnant women) compared two IPTp doses of mefloquine with two IPTp doses of sulfadoxine-pyrimethamine. Two other trials involving 1363 HIV-infected women compared three IPTp doses of mefloquine plus cotrimoxazole with cotrimoxazole. One trial in 140 HIV-infected women compared three doses of IPTp-mefloquine with cotrimoxazole. Finally, one trial enrolling 339 of unknown HIV status compared mefloquine prophylaxis with placebo. Study participants included women of all gravidities and of all ages (four trials) or > 18 years (two trials). Gestational age at recruitment was > 20 weeks (one trial), between 16 and 28 weeks (three trials), or ≤ 28 weeks (two trials). Two of the six trials blinded participants and personnel, and only one had low risk of detection bias for safety outcomes. When compared with sulfadoxine-pyrimethamine, IPTp-mefloquine results in a 35% reduction in maternal peripheral parasitaemia at delivery (RR 0.65, 95% CI 0.48 to 0.86; 5455 participants, 2 studies; high-certainty evidence) but may have little or no effect on placental malaria infections (RR 1.04, 95% CI 0.58 to 1.86; 4668 participants, 2 studies; low-certainty evidence). Mefloquine results in little or no difference in the incidence of clinical malaria episodes during pregnancy (incidence rate ratio (IRR) 0.83, 95% CI 0.65 to 1.05, 2 studies; high-certainty evidence). Mefloquine decreased maternal anaemia at delivery (RR 0.84, 95% CI 0.76 to 0.94; 5469 participants, 2 studies; moderate-certainty evidence). Data show little or no difference in the proportions of low birth weight infants (RR 0.95, 95% CI 0.78 to 1.17; 5641 participants, 2 studies; high-certainty evidence) and in stillbirth and spontaneous abortion rates (RR 1.20, 95% CI 0.91 to 1.58; 6219 participants, 2 studies; I2 statistic = 0%; high-certainty evidence). IPTp-mefloquine increased drug-related vomiting (RR 4.76, 95% CI 4.13 to 5.49; 6272 participants, 2 studies; high-certainty evidence) and dizziness (RR 4.21, 95% CI 3.36 to 5.27; participants = 6272, 2 studies; high-certainty evidence). When compared with cotrimoxazole, IPTp-mefloquine plus cotrimoxazole probably results in a 48% reduction in maternal peripheral parasitaemia at delivery (RR 0.52, 95% CI 0.30 to 0.93; 989 participants, 2 studies; moderate-certainty evidence) and a 72% reduction in placental malaria (RR 0.28, 95% CI 0.14 to 0.57; 977 participants, 2 studies; high-certainty evidence) but has little or no effect on the incidence of clinical malaria episodes during pregnancy (IRR 0.76, 95% CI 0.33 to 1.76, 1 study; high-certainty evidence) and probably no effect on maternal anaemia at delivery (RR 0.94, 95% CI 0.73 to 1.20; 1197 participants, 2 studies; moderate-certainty evidence), low birth weight rates (RR 1.20, 95% CI 0.89 to 1.60; 1220 participants, 2 studies; moderate-certainty evidence), and rates of spontaneous abortion and stillbirth (RR 1.12, 95% CI 0.42 to 2.98; 1347 participants, 2 studies; very low-certainty evidence). Mefloquine was associated with higher risks of drug-related vomiting (RR 7.95, 95% CI 4.79 to 13.18; 1055 participants, one study; high-certainty evidence) and dizziness (RR 3.94, 95% CI 2.85 to 5.46; 1055 participants, 1 study; high-certainty evidence). Authors' conclusions: Mefloquine was more efficacious than sulfadoxine-pyrimethamine in HIV-uninfected women or daily cotrimoxazole prophylaxis in HIV-infected pregnant women for prevention of malaria infection and was associated with lower risk of maternal anaemia, no adverse effects on pregnancy outcomes (such as stillbirths and abortions), and no effects on low birth weight and prematurity. However, the high proportion of mefloquine-related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women

Insecticide-Treated Nets for the Prevention of Malaria in Pregnancy: A Systematic Review of Randomised Controlled Trials

BACKGROUND: Protection from malaria with insecticide-treated bednets (ITNs) during pregnancy is widely advocated, but evidence of benefit has been inconsistent. We undertook a systematic review of randomised trials. METHODS AND FINDINGS: Three cluster-randomised and two individually randomised trials met the inclusion criteria; four from Africa (n = 6,418) and one from Thailand (n = 223). In Africa, ITNs compared to no nets increased mean birth weight by 55 g (95% confidence interval [CI] 21–88), reduced low birth weight by 23% (relative risk [RR] 0.77, 95% CI 0.61–0.98), and reduced miscarriages/stillbirths by 33% (RR 0.67, 0.47–0.97) in the first few pregnancies. Placental parasitaemia was reduced by 23% in all gravidae (RR 0.77, 0.66–0.90). The effects were apparent in the cluster-randomised trials and the one individually randomised trial in Africa. The trial in Thailand, which randomised individuals to ITNs or untreated nets, showed reductions in anaemia and fetal loss in all gravidae, but not reductions in clinical malaria or low birth weight. CONCLUSIONS: ITNs used throughout pregnancy or from mid-pregnancy onwards have a beneficial impact on pregnancy outcome in malaria-endemic Africa in the first few pregnancies. The potential impact of ITNs in pregnant women and their newborns in malaria regions outside Africa requires further research

Evaluation of the national policy of single screening and treatment for the prevention of malaria in pregnancy in two districts in Eastern Indonesia: health provider perceptions.

BACKGROUND: Malaria in pregnancy has devastating consequences for both the expectant mother and baby. Annually, 88.2 (70%) of the 125.2 million pregnancies in malaria endemic regions occur in the Asia-Pacific region. The control of malaria in pregnancy in most of Asia relies on passive case detection and prevention with long-lasting insecticide-treated nets. Indonesia was the first country in the region to introduce, in 2012, malaria screening at pregnant women's first antenatal care visit to reduce the burden of malaria in pregnancy. The study assessed health providers' acceptability and perceptions on the feasibility of implementing the single screening and treatment (SST) strategy in the context of the national programme in two endemic provinces of Indonesia. METHODS: Qualitative data were collected through in-depth interviews with 86 health providers working in provision of antenatal care (midwives, doctors, laboratory staff, pharmacists, and heads of drug stores), heads of health facilities and District Health Office staff in West Sumba and Mimika districts in East Nusa Tenggara and Papua provinces, respectively. RESULTS: Health providers of all cadres were accepting of SST as a preventive strategy, showing a strong preference for microscopy over rapid diagnostic tests (RDTs) as the method of screening. Implementation of the policy was inconsistent in both sites, with least extensive implementation reported in West Sumba compared to Mimika. SST was predominantly implemented at health centre level using microscopy, whereas implementation at community health posts was said to occur in less than half the selected health facilities. Lack of availability of RDTs was cited as the major factor that prevented provision of SST at health posts, however as village midwives cannot prescribe medicines women who test positive are referred to health centres for anti-malarials. Few midwives had received formal training on SST or related topics. CONCLUSIONS: The study findings indicate that SST was an acceptable strategy among health providers, however implementation was inconsistent with variation across different localities within the same district, across levels of facility, and across different cadres within the same health facility. Implementation should be re-invigorated through reorientation and training of health providers, stable supplies of more sensitive RDTs, and improved data capture and reporting

Collateral-flow measurements in humans by myocardial contrast echocardiography: validation of coronary pressure-derived collateral-flow assessment

AIMS: Myocardial blood flow (MBF) is the gold standard to assess myocardial blood supply and, as recently shown, can be obtained by myocardial contrast echocardiography (MCE). The aims of this human study are (i) to test whether measurements of collateral-derived MBF by MCE are feasible during elective angioplasty and (ii) to validate the concept of pressure-derived collateral-flow assessment. METHODS AND RESULTS: Thirty patients with stable coronary artery disease underwent MCE of the collateral-receiving territory during and after angioplasty of 37 stenoses. MCE perfusion analysis was successful in 32 cases. MBF during and after angioplasty varied between 0.060-0.876 mL min(-1) g(-1) (0.304+/-0.196 mL min(-1) g(-1)) and 0.676-1.773 mL min(-1) g(-1) (1.207+/-0.327 mL min(-1) g(-1)), respectively. Collateral-perfusion index (CPI) is defined as the rate of MBF during and after angioplasty varied between 0.05 and 0.67 (0.26+/-0.15). During angioplasty, simultaneous measurements of mean aortic pressure, coronary wedge pressure, and central venous pressure determined the pressure-derived collateral-flow index (CFI(p)), which varied between 0.04 and 0.61 (0.23+/-0.14). Linear-regression analysis demonstrated an excellent agreement between CFI(p) and CPI (y=0.88 x +0.01; r(2)=0.92; P<0.0001). CONCLUSION: Collateral-derived MBF measurements by MCE during angioplasty are feasible and proved that the pressure-derived CFI exactly reflects collateral relative to normal myocardial perfusion in humans

Intermittent screening and treatment or intermittent preventive treatment compared to current policy of single screening and treatment for the prevention of malaria in pregnancy in Eastern Indonesia: acceptability among health providers and pregnant women.

BACKGROUND: The control of malaria in pregnancy in much of Asia relies on screening asymptomatic women for malaria infection, followed by passive case detection and prevention with insecticide-treated nets. In 2012, Indonesia introduced screening for malaria by microscopy or rapid diagnostic tests (RDTs) at pregnant women's first antenatal care (ANC) visit to detect and treat malaria infections regardless of the presence of symptoms. Acceptability among health providers and pregnant women of the current 'single screen and treat' (SSTp) strategy compared to two alternative strategies that were intermittent preventive treatment (IPTp) and intermittent screening and treatment (ISTp) was assessed in the context of a clinical trial in two malaria endemic provinces of Eastern Indonesia. METHODS: Qualitative data were collected through in-depth interviews with 121 health providers working in provision of antenatal care, heads of health facilities and District Health Office staff. Trial staff were also interviewed. Focus group discussions were conducted with 16 groups of pregnant women (N = 106) to discuss their experiences of each intervention in the trial. RESULTS: Health providers and pregnant women were receptive to screening for malaria at every ANC visit due to the increased opportunity to detect and treat asymptomatic infections. A primary concern for providers was the accuracy and availability of RDTs used for screening in the SSTp and ISTp arms, which they considered less accurate than microscopy. Providers had reservations about giving anti-malarials presumptively as IPTp, due to concerns of causing potential harm to mother and baby and as a possible driver of drug resistance. Pregnant women were accepting of all three interventions. Women in the IPTp arm were happy to take anti-malarials presumptively to protect themselves and their babies against malaria. CONCLUSIONS: The findings indicate that, within a trial context, malaria screening of pregnant women at every ANC visit ISTp was an acceptable strategy among both health providers and pregnant women owing to an existing culture of screening and treatment. The adoption of IPTp however would require a considerable shift in health provider attitudes and a clear communication strategy. By contrast, pregnant women welcomed the opportunity to prevent malaria infections during pregnancy

Differential Association of Gene Content Polymorphisms of Killer Cell Immunoglobulin-Like Receptors with Placental Malaria in HIV− and HIV+ Mothers

Pregnant women have abundant natural killer (NK) cells in their placenta, and NK cell function is regulated by polymorphisms of killer cell immunoglobulin-like receptors (KIRs). Previous studies report different roles of NK cells in the immune responses to placental malaria (PM) and human immunodeficiency virus (HIV-1) infections. Given these references, the aim of this study was to determine the association between KIR gene content polymorphism and PM infection in pregnant women of known HIV-1 status. Sixteen genes in the KIR family were analyzed in 688 pregnant Kenyan women. Gene content polymorphisms were assessed in relation to PM in HIV-1 negative and HIV-1 positive women, respectively. Results showed that in HIV-1 negative women, the presence of the individual genes KIR2DL1 and KIR2DL3 increased the odds of having PM, and the KIR2DL2/KIR2DL2 homozygotes were associated with protection from PM. However, the reverse relationship was observed in HIV-1 positive women, where the presence of individual KIR2DL3 was associated with protection from PM, and KIR2DL2/KIR2DL2 homozygotes increased the odds for susceptibility to PM. Further analysis of the HIV-1 positive women stratified by CD4 counts showed that this reverse association between KIR genes and PM remained only in the individuals with high CD4 cell counts but not in those with low CD4 cell counts. Collectively, these results suggest that inhibitory KIR2DL2 and KIR2DL3, which are alleles of the same locus, play a role in the inverse effects on PM and PM/HIV co-infection and the effect of KIR genes on PM in HIV positive women is dependent on high CD4 cell counts. In addition, analysis of linkage disequilibrium (LD) of the PM relevant KIR genes showed strong LD in women without PM regardless of their HIV status while LD was broken in those with PM, indicating possible selection pressure by malaria infection on the KIR genes

Establishment of the Ivermectin Research for Malaria Elimination Network: updating the research agenda

The potential use of ivermectin as an additional vector control tool is receiving increased attention from the malaria elimination community, driven by the increased importance of outdoor/residual malaria transmission and the threat of insecticide resistance where vector tools have been scaled-up. This report summarizes the emerging evidence presented at a side meeting on "Ivermectin for malaria elimination: current status and future directions" at the annual meeting of the American Society of Tropical Medicine and Hygiene in New Orleans on November 4, 2014. One outcome was the creation of the "Ivermectin Research for Malaria Elimination Network" whose main goal is to establish a common research agenda to generate the evidence base on whether ivermectin-based strategies should be added to the emerging arsenal to interrupt malaria transmission