Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection. A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and < 37.0 weeks), small for gestational age (SGA, birthweight of < 10th percentile), and placental malaria (defined as deposition of malaria pigment in the placenta with or without parasites) after different treatments of uncomplicated falciparum malaria were assessed by mixed-effects logistic regression, using artemether-lumefantrine, the most used antimalarial, as the reference standard. Registration PROSPERO: CRD42018104013. Of the 22 eligible studies (n = 5015), IPD from16 studies were shared, representing 95.0% (n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine (n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine (n = 1087), artesunate-amodiaquine (n = 775), artesunate-mefloquine (n = 965), and dihydroartemisinin-piperaquine (n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p < 0.001). The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women

AdS_4/CFT_3 duals from M2-branes at hypersurface singularities and their deformations

We construct three-dimensional N=2 Chern-Simons-quiver theories which are holographically dual to the M-theory Freund-Rubin solutions AdS_4 x V_{5,2}/Z_k (with or without torsion G-flux), where V_{5,2} is a homogeneous Sasaki-Einstein seven-manifold. The global symmetry group of these theories is generically SU(2) x U(1) x U(1)_R, and they are hence non-toric. The field theories may be thought of as the n=2 member of a family of models, labelled by a positive integer n, arising on multiple M2-branes at certain hypersurface singularities. We describe how these models can be engineered via generalized Hanany-Witten brane constructions. The AdS_4 x V_{5,2}/Z_k solutions may be deformed to a warped geometry R^{1,2} x T^* S^4/Z_k, with self-dual G-flux through the four-sphere. We show that this solution is dual to a supersymmetric mass deformation, which precisely modifies the classical moduli space of the field theory to the deformed geometry.Comment: 62 pages, 7 figure

Observational cohort study of HIV-infected African children.

Item does not contain fulltextBACKGROUND: Most information about children living with HIV is based on follow up from children identified through mother-to-child transmission studies. Children identified through voluntary counseling and testing (VCT) represent a unique cohort that has not been previously described in the literature. METHODS: Children who were found to have HIV infection through VCT were offered enrollment in this study. They were evaluated monthly and encouraged to return to the clinic any time they were ill. Thorough evaluation was performed for every illness. RESULTS: Forty-five children were enrolled in the study. Many of the participants (33%) had a serious acute disease at the time of enrollment. The most common diagnoses were symptomatic malaria and pneumonia. The children were more ill than adults who were enrolled in a simultaneous study and had a higher death rate (37 versus 15 deaths per 100 person-years of observation). The mortality rate was 22%. Undernutrition and low CD4 cell count were independently associated with increased risk of death. CONCLUSIONS: Malawian children found to be HIV-infected through VCT had a high morbidity and mortality rate, highlighting the potential benefit of trimethoprim-sulfamethizole prophylaxis and available antiretroviral therapy

Impact of HIV-associated immunosuppression on malaria infection and disease in Malawi.

Item does not contain fulltextBACKGROUND: Human immunodeficiency virus (HIV) infection and malaria coexist in much of Africa. Previous studies differ in their findings on the interactions between the 2 infections. METHODS: Adults living with HIV infection in Blantyre, Malawi, were enrolled in a longitudinal observational study from September 2002 to August 2004. Malaria blood smears were obtained monthly and for any illness suggestive of malaria. Complete evaluations of all illness episodes were conducted, regardless of malaria smear results. RESULTS: The incidence of clinical malaria episodes was higher in participants with CD4 cell counts 500 cells/mm3. The trend was preserved when increasingly specific definitions of malaria disease were used. The prevalence of malaria infection was not associated with CD4 cell count. In per-visit analysis, lower CD4 cell counts were associated with higher incidences of pneumonia, sepsis, and tuberculosis but not of malaria. Severe malaria was rare, with only 3 cases in 591 person-years of observation. Parasite density and CD4 cell count were independent risk factors for fever. CONCLUSIONS: Profoundly immunosuppressed adults with HIV infection require more-frequent treatment for uncomplicated malaria, but malaria infection and disease are less strongly associated with HIV-associated immunosuppression than are other opportunistic infections. Where malaria is common, the high incidence of fever found among immunosuppressed adults may lead to misclassification of illness episodes as malaria

A community-based study of the incidence of trimethoprim-sulfamethoxazole-preventable infections in Malawian adults living with HIV.

Item does not contain fulltextThe benefits of trimethoprim-sulfamethoxazole (TS) prophylaxis reported for persons living with HIV in Cote d'Ivoire are difficult to extrapolate to sub-Saharan African countries where bacterial resistance to TS is higher and cross-resistance between TS and sulfadoxine-pyrimethamine (SP) may impair SP efficacy for malaria treatment. We conducted a community-based cohort study to measure the incidence of potentially TS-preventable illnesses in Blantyre, Malawi. We found a high incidence of malaria, invasive bacterial infections, and probable bacterial pneumonias but low rates of Pneumocystis jiroveci pneumonia, isosporiasis, and Toxoplasma encephalitis. Most bacterial isolates were resistant to TS but sensitive to azithromycin, a possible alternative to TS. Clinical trials are needed to determine the role of TS or alternative regimens for prophylaxis against secondary infections among people living with HIV in sub-Saharan Africa. These should also assess benefit in patients receiving antiretroviral therapy

Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis.

Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy and tolerability of different artemisinin-based or quinine-based treatments for malaria in pregnant women. We did a systematic review of interventional or observational cohort studies assessing the efficacy of artemisinin-based or quinine-based treatments in pregnancy. Seven databases (MEDLINE, Embase, Global Health, Cochrane Library, Scopus, Web of Science, and Literatura Latino Americana em Ciencias da Saude) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrials.gov) were searched. The final search was done on April 26, 2019. Studies that assessed PCR-corrected treatment efficacy in pregnancy with follow-up of 28 days or more were included. Investigators of identified studies were invited to share data from individual patients. The outcomes assessed included PCR-corrected efficacy, PCR-uncorrected efficacy, parasite clearance, fever clearance, gametocyte development, and acute adverse events. One-stage IPD meta-analysis using Cox and logistic regression with random-effects was done to estimate the risk factors associated with PCR-corrected treatment failure, using artemether-lumefantrine as the reference. This study is registered with PROSPERO, CRD42018104013. Of the 30 studies assessed, 19 were included, representing 92% of patients in the literature (4968 of 5360 episodes). Risk of PCR-corrected treatment failure was higher for the quinine monotherapy (n=244, adjusted hazard ratio [aHR] 6·11, 95% CI 2·57-14·54, p<0·0001) but lower for artesunate-amodiaquine (n=840, 0·27, 95% 0·14-0·52, p<0·0001), artesunate-mefloquine (n=1028, 0·56, 95% 0·34-0·94, p=0·03), and dihydroartemisinin-piperaquine (n=872, 0·35, 95% CI 0·18-0·68, p=0·002) than artemether-lumefantrine (n=1278) after adjustment for baseline asexual parasitaemia and parity. The risk of gametocyte carriage on day 7 was higher after quinine-based therapy than artemisinin-based treatment (adjusted odds ratio [OR] 7·38, 95% CI 2·29-23·82). Efficacy and tolerability of artemisinin-based combination therapies (ACTs) in pregnant women are better than quinine. The lower efficacy of artemether-lumefantrine compared with other ACTs might require dose optimisation. The Bill & Melinda Gates Foundation, ExxonMobil Foundation, and the University of Oxford Clarendon Fund