Browsing by Author "Kironde, Fred"

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    Malaria Burden in Pregnancy at Mulago National Referral Hospital in Kampala, Uganda
    (Malaria Research and Treatment, 2020) Namusoke, Fatuma; Rasti, Niloofar; Kironde, Fred; Wahlgren, Mats; Mirembe, Florence
    Pregnancy-associated malaria is a major global health concern. To assess the Plasmodium falciparum burden in pregnancy we conducted a cross-sectional study atMulago Hospital in Kampala, Uganda.Malaria prevalence by each of three measures—peripheral smear, placental smear, and placental histology was 9%(35/391), 11.3% (44/389), and 13.9% (53/382) respectively. Together, smear and histology data yielded an infection rate of 15.5% (59/380) of active infections and 4.5% (17/380) of past infections; hence 20% had been or were infected when giving birth. A crude parity dependency was observed with main burden being concentrated in gravidae 1 through gravidae 3. Twenty-two percent were afflicted by anaemia and 12.2% delivered low birthweight babies. Active placental infection and anaemia showed strong association (OR = 2.8) whereas parity and placental infection had an interactive effect on mean birthweight (P = .036). Primigravidae with active infection and multigravidae with past infection delivered on average lighter babies. Use of bednet protected significantly against infection (OR = 0.56) whilst increased haemoglobin level protected against lowbirthweight (OR = 0.83) irrespective of infection status. Albeit a high attendance at antenatal clinics (96.8%), there was a poor coverage of insecticide-treated nets (32%) and intermittent preventive antimalarial treatment (41.5%).
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    Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin
    (National Academy of Sciences, 2006) Rasti, Niloofar; Namusoke, Fatuma; Cheˆne, Arnaud; Chen, Qijun; Staalsoe, Trine; Klinkert, Mo-Quen; Mirembe, Florence; Kironde, Fred; Wahlgren, Mats
    The harmful effects of pregnancy-associated malaria (PAM) are engendered by the heavy sequestration of Plasmodium falciparum parasitized RBCs in the placenta. It is well documented that this process is mediated by interactions of parasite-encoded variant surface antigens and placental receptors. A P. falciparum erythrocyte membrane protein 1 variant, VAR2CSA, and the placental receptor chondroitin sulfate A (CSA) are currently the focus of PAM research. A role for immunoglobulins (IgG and IgM) from normal human serum and hyaluronic acid as additional receptors in placental sequestration have also been suggested. We show here (i) that CSA and nonimmune IgG IgM binding are linked phenotypes of in vitro-adapted parasites, (ii) that a VAR2CSA variant shown to bind CSA also harbors IgG- and IgM-binding domains (DBL2-X, DBL5- , and DBL6- ), and (iii) that IgG and IgM binding and adhesion to multiple receptors (IgG IgM HA CSA) rather than the exclusive binding to CSA is a characteristic of fresh Ugandan placental isolates. These findings are of importance for the understanding of the pathogenesis of placental malaria and have implications for the ongoing efforts to develop a global PAM vaccine.
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    Rapid increase in resistance of Plasmodium falciparum to chloroquine-Fansidar in Uganda and the potential of amodiaquine-Fansidar as a better alternative
    (Acta Tropica, 2005) Sendagire, Hakim; Kaddumukasa, Mark; Ndagire, Dorothy; Aguttu, Clare; Nassejje, Maureen; Pettersson, Madeleine; Swedberg, Gote; Kironde, Fred
    Combinations of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) [CQSP] as the first line agents in Uganda have replaced CQ monotherapy. The idea of the combination is to delay the development of malaria resistance to either drug when used alone. We compared the clinical, parasitological and molecular findings of two studies with treatment arms of CQSP, amodiaquine (AQ) plus SP (AQSP) both done in 2003 with a study done 1 year earlier (2002) using SP alone. There was a notable decrease in adequate clinical response (ACR) by day 14 from 92.7% with SP to 80% with the combination CQSP, a year later. AQSP combination was found to have the best effect (94.3% ACR). There were no early treatment failures in the AQSP group. However, treatment failures were recorded at 20% on day 14 and 43% on day 28 for CQSP treatment and 5.7% by day 14 and 28.8% by day 28 in the AQSP group. The number of mutations that are associated with SP resistance increased from 2002 to 2003 at all loci monitored, from 83.8 to 100% at codon 108, 58.7 to 76% at codon 59 in the DHFR gene, and from 58.8 to 86% at codon 437 and 33 to 43% at codon 540 in the DHPS gene. We conclude that there has been a rapid development of resistance since the introduction of the new policy guidelines. AQSP was found to be a superior drug combination compared to CQSP and could be used as a low cost alternative at the moment.
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    Uropathogenic Escherichia coli Isolates from Pregnant Women in Different Countries
    (Journal of clinical microbiology, 2012) Ramos, Nubia L.; Sekikubo, Musa; Thi Ngoc Dzung, Dang; Kosnopfel, Corinna; Kironde, Fred; Mirembe, Florence; Braunera, Annelie
    Urinary tract infection (UTI) is common during pregnancy and can be associated with negative outcomes for both the mother and fetus. Increased risk of infection among these patients has been attributed to physiological changes, and less focus has been placed on Escherichia coli, the most frequent causative agent. We investigated the virulence properties of isolates causing UTI in pregnant women in Sweden, Uganda, and Vietnam, as well as nonpregnant women in Sweden. Although phylogenetic group B2 was the most prevalent group, more Ugandan isolates belonged to group B1, associated with commensal strains, than isolates from other countries. Adherence to and invasion of urothelial cells, key events in the infection process, were low among group B1 isolates from pregnant Swedish women compared to those from nonpregnant patients. Similar levels of adherence and invasion were seen in isolates from pregnant women in Uganda and Vietnam. More biofilm was formed by group B2 isolates than by those belonging to group B1 and by Ugandan group B2 isolates than by those from pregnant Swedish and Vietnamese women. The antigen 43a-encoding gene, fluACFT073, was most prevalent among Ugandan isolates. Expression of the biofilm components, curli and cellulose, was low among all isolates. Multidrug resistance was more common among isolates from Uganda and Vietnam than among those from Swedish patients. We suggest that while bacterial virulence properties play an important role in UTI during pregnancy, physiological changes in the host may contribute more to the incidence of infection caused by less virulent E. coli.
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    Validity of self-reported use of sulphadoxine-pyrimethamine intermittent presumptive treatment during pregnancy (IPTp): a cross-sectional study
    (Malaria Journal, 2012) Namusoke, Fatuma; Ntale, Muhammad; Wahlgren, Mats; Kironde, Fred; Mirembe, Florence
    Malaria in pregnancy is a major health problem that can cause maternal anaemia, stillbirth, spontaneous abortion, low birth weight and intra-uterine stunting. The WHO recommends use of sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria during pregnancy (IPTp) in endemic areas. Towards monitoring and assessing IPTp coverage in the population, the Roll Back Malaria Partnership recommends the use of self-reported data. The aim of this study was to assess the validity of self-reported IPTp by testing for sulphadoxine in maternal blood at delivery. Two hundred and four pregnant women were consented and enrolled in a cross-sectional study in Mulago National Referral Hospital in Kampala Uganda. - Participants who reported a history of taking sulpha-containing drugs like co-trimoxazole , those who were not sure of dates relating to last menstrual period or who took IPTp within the first 20 weeks of gestation were excluded from the study. Data on demographic characteristics, obstetric history, and delivery outcome were collected. At birth, maternal venous blood was taken off aseptically and used to make thick blood smears for malaria parasites and plasma for determining sulphadoxine using high performance liquid chromatography (HPLC).