Coinfections of malaria and sexually transmitted and reproductive tract infections in pregnancy in sub-Saharan Africa: a systematic review and individual participant data meta-analysis protocol.

INTRODUCTION: Malaria infection and curable sexually transmitted infections and reproductive tract infections (STIs/RTIs) adversely impact pregnancy outcomes. In sub-Saharan Africa, the prevalence of malaria and curable STIs/RTIs is high and, where coinfection is common, combination interventions may be needed to improve pregnancy outcomes. The aim of this systematic review is to estimate the prevalence of malaria and curable STI/RTI coinfection during pregnancy, risk factors for coinfection and prevalence of associated adverse pregnancy outcomes. METHODS AND ANALYSIS: We will use three electronic databases, PubMed, EMBASE and Malaria in Pregnancy Library to identify studies involving pregnant women attending routine antenatal care facilities in sub-Saharan Africa and reporting malaria and curable STI/RTI test results, published in any language since 2000. We will search databases in the second quarter of 2023 and repeat the search before completion of our analyses. The first two authors will screen titles and abstracts, selecting studies that meet inclusion criteria and qualify for full-text screening. If agreement on inclusion/exclusion cannot be reached, the last author will serve as arbiter. We will extract data from eligible publications for a study-level meta-analysis. We will contact research groups of included studies and request individual participant data for meta-analysis. The first two authors will conduct a quality appraisal of included studies using the GRADE system. The last author will adjudicate if the first two authors do not agree on any appraisals. We will conduct sensitivity analyses to test the robustness of effect estimates over time (by decade and half-decade periods), geography (East/Southern Africa vs West/Central Africa), gravidity (primigravidae, secundigravidae, multigravidae), treatment type and dosing frequency, and malaria transmission intensity. ETHICS AND DISSEMINATION: We obtained ethics approval from the London School of Hygiene & Tropical Medicine (LSHTM Ethics Ref: 26167). Results of this study will be disseminated via peer-reviewed publication and presentation at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42021224294

Global estimates of pregnancies at risk of Plasmodium falciparum and Plasmodium vivax infection in 2020 and changes in risk patterns since 2000.

BACKGROUND: Women are at risk of severe adverse pregnancy outcomes attributable to Plasmodium spp. infection in malaria-endemic areas. Malaria control efforts since 2000 have aimed to reduce this burden of disease. METHODS: We used data from the Malaria Atlas Project and WorldPop to calculate global pregnancies at-risk of Plasmodium spp. infection. We categorised pregnancies as occurring in areas of stable and unstable P. falciparum and P. vivax transmission. We further stratified stable endemicity as hypo-endemic, meso-endemic, hyper-endemic, or holo-endemic, and estimated pregnancies at risk in 2000, 2005, 2010, 2015, 2017, and 2020. FINDINGS: In 2020, globally 120.4M pregnancies were at risk of P. falciparum, two-thirds (81.0M, 67.3%) were in areas of stable transmission; 85 2M pregnancies were at risk of P. vivax, 93.9% (80.0M) were in areas of stable transmission. An estimated 64.6M pregnancies were in areas with both P. falciparum and P. vivax transmission. The number of pregnancies at risk of each of P. falciparum and P. vivax worldwide decreased between 2000 and 2020, with the exception of sub-Saharan Africa, where the total number of pregnancies at risk of P. falciparum increased from 37 3M in 2000 to 52 4M in 2020. INTERPRETATION: Historic investments in malaria control have reduced the number of women at risk of malaria in pregnancy in all endemic regions except sub-Saharan Africa. Population growth in Africa has outpaced reductions in malaria prevalence. Interventions that reduce the risk of malaria in pregnancy are needed as much today as ever

Cardiac safety of dihydroartemisinin-piperaquine and sulfadoxine pyrimethamine among pregnant women with and without asymptomatic parasitaemia in Tanzania: results from an open-label, parallel-group, randomised phase II trial

Background: Dihydroartemisinin-Piperaquine (DP) can induce transient prolongation of the corrected QT interval (QTc) and is a candidate for use with sulfadoxine-pyrimethamine (SP) in intermittent preventive treatment of malaria in pregnancy (IPTp). Pregnancy can alter pharmacokinetics of antimalarial drugs. Acute malaria infection can increase QTc prolongation. Whether DP alters cardiac function in pregnant women with or without asymptomatic parasitaemia is not well characerised. Methods: This was an open-label, parallel-group, randomised phase 2 study among pregnant women in Handeni, Tanzania (NCT02909712). Women were screened for P. falciparum by microscopy and, if positive, received a rapid diagnostic test (RDT). If RDT-positive, they received DP or SP, and the next microscopy-negative woman was randomly allocated to receive DP or SP. Enrolment and allocation continued in this alternating manner to reach 200 (50/group): Grp 1 (neg; SP), Grp 2 (pos; SP), Grp 3 (neg: DP), Grp 4 (pos: DP). Standard 12-lead ECGs were used to record cardiac function in triplicate. DP groups were measured on day 0 (predose), day 2 (predose and hours 3,4,5,6,7,8), and day 7; SP groups had day 0 (predose), and day 7 ECGs. Results: DP resulted in QTcF prolongation that peaked ~30 msec at 5-h post dose 3 on day 2 (schedule: days 0,1,2). The mean maximum increase was slightly more in group 4 compared to group 3 (33.1 vs 29.1 msec). On day 7, QTcF returned to baseline in group 3; a small and non-clinically significant increase of 3.4 (90%CI: 0.3, 6.5) msec was still present among RDT-positive women. QTcB measurements were similar. There was a marked decrease in heart rate (HR) among all DP recipients on day 2, which appeared greater in group 4 compared to group 3 (13.3 vs 8.9 bpm), baseline HR was higher in group 4 than group 3 (92.7 vs 88.5 bpm). This potentially represents a regression towards the mean. On day 7, HR had returned to baseline in both groups. Conclusion: Parasite presence did not alter the effect of DP on the different ECG parameters with the possible exception of HR. No marked differences were observed between pregnant women with and without asymptomatic parasitaemia

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Fetal growth and birth weight are independently reduced by malaria infection and curable sexually transmitted and reproductive tract infections in Kenya, Tanzania, and Malawi: A pregnancy cohort study

Objective Malaria and sexually transmitted and reproductive tract infections (STIs/RTIs) are highly prevalent in sub-Saharan Africa and associated with poor pregnancy outcomes. We investigated the individual and combined effects of malaria and curable STIs/RTIs on fetal growth in Kenya, Tanzania, and Malawi. Methods This study was nested within a randomized trial comparing monthly intermittent preventive treatment for malaria in pregnancy with sulfadoxine-pyrimethamine versus dihydroartemisinin-piperaquine, alone or combined with azithromycin. Fetal weight gain was assessed by serial prenatal ultrasound. Malaria was assessed monthly, and Treponema pallidum, Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis and bacterial vaginosis at enrolment and in the third trimester. The effect of malaria and STIs/RTIs on fetal weight/birthweight Z-scores was evaluated using mixed-effects linear regression. Results 1,435 pregnant women had fetal/birth weight assessed 3,950 times. Compared to women without malaria or STIs/RTIs (n=399), malaria-only (n=267), STIs/RTIs-only (n=410) or both (n=353) were associated with reduced fetal growth (adjusted mean difference in fetal/birth weight Z-score [95% CI]: malaria=-0.18 [-0.31,-0.04], p=0.01]; STIs/RTIs=-0.14 [-0.26,-0.03], p=0.01]; both=-0.20 [-0.33,-0.07], p=0.003). Paucigravidae experienced the greatest impact. Conclusion Malaria and STIs/RTIs are associated with poor fetal growth especially among paucigravidae women with dual infections. Integrated antenatal interventions are needed to reduce the burden of both malaria and STIs/RTIs

Registered replication report on Fischer, Castel, Dodd, and Pratt (2003)

The attentional spatial-numerical association of response codes (Att-SNARC) effect (Fischer, Castel, Dodd, & Pratt, 2003)—the finding that participants are quicker to detect left-side targets when the targets are preceded by small numbers and quicker to detect right-side targets when they are preceded by large numbers—has been used as evidence for embodied number representations and to support strong claims about the link between number and space (e.g., a mental number line). We attempted to replicate Experiment 2 of Fischer et al. by collecting data from 1,105 participants at 17 labs. Across all 1,105 participants and four interstimulus-interval conditions, the proportion of times the effect we observed was positive (i.e., directionally consistent with the original effect) was .50. Further, the effects we observed both within and across labs were minuscule and incompatible with those observed by Fischer et al. Given this, we conclude that we failed to replicate the effect reported by Fischer et al. In addition, our analysis of several participant-level moderators (finger-counting habits, reading and writing direction, handedness, and mathematics fluency and mathematics anxiety) revealed no substantial moderating effects. Our results indicate that the Att-SNARC effect cannot be used as evidence to support strong claims about the link between number and space

Registered Replication Report on Fischer, Castel, Dodd, and Pratt (2003)

The attentional spatial-numerical association of response codes (Att-SNARC) effect (Fischer, Castel, Dodd, & Pratt, 2003)—the finding that participants are quicker to detect left-side targets when the targets are preceded by small numbers and quicker to detect right-side targets when they are preceded by large numbers—has been used as evidence for embodied number representations and to support strong claims about the link between number and space (e.g., a mental number line). We attempted to replicate Experiment 2 of Fischer et al. by collecting data from 1,105 participants at 17 labs. Across all 1,105 participants and four interstimulus-interval conditions, the proportion of times the effect we observed was positive (i.e., directionally consistent with the original effect) was .50. Further, the effects we observed both within and across labs were minuscule and incompatible with those observed by Fischer et al. Given this, we conclude that we failed to replicate the effect reported by Fischer et al. In addition, our analysis of several participant-level moderators (finger-counting habits, reading and writing direction, handedness, and mathematics fluency and mathematics anxiety) revealed no substantial moderating effects. Our results indicate that the Att-SNARC effect cannot be used as evidence to support strong claims about the link between number and space