MOESM1 of Donor support for quality assurance and pharmacovigilance of anti-malarials in malaria-endemic countries

Additional file 1. Pharmacovigilance quantitative methods and codes

Summary of study outcomes – Iron Treatment vs. Malaria Risk.

<p>CI: confidence interval. CQ: chloroquine. OR: odds ratio. PF: <i>Plasmodium falciparum</i>. RR: risk ratio.</p

Technologies for confirmation testing.

<p>*Technologies that cost <$10,000 USD = low cost,$10,000–100,000 USD = medium cost and >$100,000 USD = high cost.</p><p>** Suitability for use in LMIC scores were assigned as: 1 point for not requiring sample preparation, 1 point for not requiring laboratory supplies, 1 point for fast speed, 1 for not requiring electricity, 2 points for requiring minimal training and 1 point for requiring a laboratory technician, 2 points for being portable and 1 point for requiring a basic laboratory.</p>∧<p>GC-MS represents the combination of a sample preparation technology, ionization technology and mass detector which is portable. This is the only mass detector combination that is portable.</p

Summary of included studies for iron deficiency and malaria risk in pregnancy.

<p>ANC: antenatal clinic. CQ: Chloroquine. CTX: Cotrimoxazole. EIR: Entomologic inoculation rate (# infectious bites/person/year). IPTp-SP: Intermittent presumptive treatment in pregnancy with sulfadoxine-pyrimethmine. ITN: Insecticide treated bed net. MiP: malaria in pregnancy. MQ: Mefloquine. PF: <i>Plasmodium falciparum</i>. PV: <i>Plasmodium vivax.</i></p>a<p>Author contacted and additional information was obtained.</p>b<p>Ferritin <30 ng/mL with CRP< = 8.2 ng/mL or ferritin<70 ng/mL with CRP>8.2 ng/mL.</p>c<p>Serum ferritin <10 (μg/L) or Erthyrocyte protoporphyrin >70 (μmol/mol heme).</p>d<p>Author contacted and author responded, but no additional information was available.</p>e<p>Serum ferritin ≤16 ng/mL.</p>f<p>Selected based on hemoglobin status (<70 g/L, 70–90 g/L, 90–110 g/L, 110–150, and >150).</p>g<p>Serum ferritin ≤15 ng/mL.</p>h<p>sTfR:log ferritin ratio >1.6.</p>i<p>red cell zinc protoporhyrin/heme >2.7 μg/g hemoglobin.</p

Summary of study outcomes – Iron biomarkers vs. malaria risk, and outcomes not presented in forest plot.

<p>CI: confidence interval. IQR: Interquartal range.</p

Geometric mean difference in ferritin among pregnant women infected with malaria compared to pregnant women without malaria.

<p>Footnote: CI: confidence interval. SD: standard deviation. *Van Santen 2011 and Massawe 2002: study population primigravidae. Abrams 2005 and Ouedraogo 2012: study population HIV(-) women. The weight for each study is indicated as a grey block around the risk estimate. For Dreyfuss 2000, the malaria parasitemia was limited to <i>P. Vivax</i> in Asia. All other studies were conducted in Africa where <i>P. falciparum</i> is the predominant species.</p

Summary of included studies for iron supplementation and malaria risk in pregnancy.

<p>AA: Hemoglobin genotype AA. AS: Hemoglobin genotype AS. ANC: antenatal clinic. CQ: Chloroquine. CTX: Cotrimoxazole. D: days. EIR: Entomologic inoculation rate (# infectious bites/person/year). FA: Folic Acid. Hct: hematocrit. IPTp-SP: Intermittent presumptive treatment in pregnancy with sulfadoxine-pyrimethmine. ITN: Insecticide treated bed net. MQ: Mefloquine. PCR: polymerase chain reaction used to detect malaria. PF: <i>Plasmodium falciparum</i>. PV: <i>Plasmodium vivax.</i> RCT: randomized controlled trial.</p

Malaria parasitemia among iron deficient and non-deficient participants, by definition of iron deficiency at the time of delivery.

<p>Footnote: BS: bloodsmear. CI: confidence interval. CRP: C-reactive protein. EP: Erthyrocyte protoporphyrin. Hb: hemoglobin. sTfR: Soluble transferrin receptor. *Adjusted odds ratios used: Kabyemela 2008: odds ratio adjusted for gravidity. Senga 2011: odds ratio adjusted for gravidity, age, and blood group. Placental histology in Senga 2011: active infection defined by acute or chronic infection (parasites alone, or parasites in the presence of haemozoin). No placental infection defined by the absence of parasites and haemozoin. ** Ferritin 30/CRP 8.3: Ferritin <30 ng/mL & CRP< = 8.2 ng/mL or ferritin <70 ng/mL & CRP>8.2 ng/mL. The weight for each study is indicated as a grey block around the risk estimate.</p

Malaria parasitemia by blood smear among iron deficient and non-deficient participants, by definition of iron deficiency during pregnancy.

<p>Footnote: CI: confidence interval. CRP: C-Reactive Protein. EP: Erthyrocyte protoporphyrin. Hb: hemoglobin. *Use of adjusted odds ratios: Kapito-Tembo 2010: odds ratio adjusted for CD4 count, gravidity, and intestinal infections, Dreyfuss: odds ratio adjusted for hookworm infection, serum retinol and trimester of pregnancy. **Iron deficiency definition: Ferritin <30 ng/mL & CRP< = 8.2 ng/mL or ferritin <70 ng/mL & CRP>8.2 ng/mL. The weight for each study is indicated as a grey block around the risk estimate. For Dreyfuss 2000, malaria parasitemia was limited to <i>P. vivax</i> in Asia. All other studies were conducted in Africa where <i>P. falciparum</i> is the predominant species.</p

Mean difference in transferrin saturation, serum iron and total iron binding capacity among pregnant women infected with malaria compared to pregnant women without malaria.

<p>Footnote: CI: confidence interval. SD: standard deviation. *Van Santen 2011: study population primigravidae. The weight for each study is indicated as a grey block around the risk estimate. Removal of the study of Eteng 2010, an outlier for Serum Iron and Total Iron Binding Capacity, gives the following results: Pooled mean difference serum iron (μmol/L): −1.13, −2.57 to 0.31, I² 27.3%; Pooled mean difference Total Iron Binding Capacity (μmol/L): 0.13, −0.67 to 0.92, I-squared 0%.</p