We used a prospective, open-label randomized trial to evaluate two treatment regimens in Tanzania... more We used a prospective, open-label randomized trial to evaluate two treatment regimens in Tanzanian children two months to four years of age presenting to a hospital with a packed cell volume (PCV) < 25%. Treatment was either standard (14 days of ferrous sulfate and an antimalarial) or extended (three months of ferrous sulfate and three antimalarial treatments). The prevalence of
Hepatitis G virus (HGV) RNA was detected in 18 of 133 pregnant women from Tanzania without known ... more Hepatitis G virus (HGV) RNA was detected in 18 of 133 pregnant women from Tanzania without known risk factors for HGV infection and in 7 of 18 children born to HGV RNA-positive mothers. Molecular evidence of mother-to-infant transmission was obtained only for three of seven children. HGV RNA was also detected in 4 of 42 children born to non-HGV-infected women. Thus, mechanisms other than materno-filial may play an important role in HGV transmission during early childhood.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2011
Factors involved in the development of resistance to sulphadoxine-pyrimethamine (SP) by Plasmodiu... more Factors involved in the development of resistance to sulphadoxine-pyrimethamine (SP) by Plasmodium falciparum, particularly in the context of intermittent preventive treatment during pregnancy (IPTp), are not well known. We aimed to determine the impact of IPTp and human immunodeficiency virus (HIV) infection on molecular markers of SP resistance and the clinical relevance of resistant infections. SP resistance alleles were determined in peripheral (n = 125) and placental (n = 145) P. falciparum isolates obtained from pregnant women enrolled in a randomized, placebo-controlled trial of IPTp in Manhiça, Mozambique. Prevalence of quintuple mutant infections was 12% (23 of 185 isolates) in pregnant women who received placebo and 24% (20 of 85 isolates) in those who received SP (P = .031). When the last IPTp dose was administered at late pregnancy, mutant infections at delivery were more prevalent in placental samples (7 [23%] of 30, samples) than in peripheral blood samples (2 [7%] of ...
The major public health consequences of malaria in pregnancy have long been acknowledged. However... more The major public health consequences of malaria in pregnancy have long been acknowledged. However, further information is still required for development and implementation of a malaria vaccine specifically directed to prevent malaria in pregnant women and improve maternal, fetal and infant outcomes. The WHO Malaria Vaccine Advisory Committee (MALVAC) provides guidance to the WHO on strategic priorities and research needs for development of vaccines to prevent malaria. Here we summarize the discussions and conclusions of a MALVAC scientific forum meeting on considerations in the development of vaccines to prevent malaria in pregnant women. This report includes brief summaries of what is known, and major knowledge gaps in disease burden estimation, pathogenesis and immunity, and the challenges with current preventive strategies for malaria in pregnancy. We conclude with the formulation of a conceptual framework for research and development for vaccines to prevent malaria in pregnant w...
Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a pote... more Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a potential malaria control strategy. There is concern about the impact that increasing in vivo resistance to SP has on the efficacy of IPTi, as well as about the potential contribution of IPTi to increases in resistance. We compared the frequency of clinical episodes of malaria caused by P. falciparum parasites with mutations in dhfr and dhps among sick children who received SP or placebo in the context of a randomized, double-blind, placebo-controlled IPTi trial in Mozambique. Half of the children who received placebo harbored quintuple-pure mutant parasites. Nevertheless, the protective efficacy of IPTi within the 35 days after the third dose was 70.8% (95% confidence interval [CI], 40.7%-85.6%). Between month 2 after the third IPTi dose and the end of the follow-up period, children receiving SP harbored more dhps codon 437 mixed infections (odds ratio [OR], 10.56 [95% CI, 1.30-86.14]) and fewer dhps double-pure mutant parasites (OR, 0.43 [95% CI, 0.22-0.84]) than did placebo recipients. IPTi appears to be associated with some changes in the prevalence of genotypes involved in SP resistance. In the face of a high prevalence of quintuple-mutant parasites, SP exhibited a high level of efficacy in the prevention of new episodes of malaria in infants.
Journal of immunology (Baltimore, Md. : 1950), Jan 27, 2015
Pregnancy triggers immunological changes aimed to tolerate the fetus. However, it has not been pr... more Pregnancy triggers immunological changes aimed to tolerate the fetus. However, it has not been properly addressed whether similar changes occur in tropical areas with high infection pressure and whether these changes render women more susceptible to infectious diseases. We compared the frequencies of T cell subsets, including regulatory T cells, in pregnant and nonpregnant women from Papua New Guinea, a high malaria transmission area, and from Spain, a malaria-free country. We also assessed the relationship among these cellular subsets, malaria infection, and delivery outcomes. CD4(+)FOXP3(+)CD127(low) T cells (Tregs) were decreased in pregnant women in both countries but were not associated with malaria infection or poor delivery outcomes. An expansion of IFN-γ-producing cells and intracytoplasmic IFN-γ levels was found in pregnant compared with nonpregnant women only in Papua New Guinea. Increased CD4(+)IL-10(+)IFN-γ(+) frequencies and Treg-IFN-γ production were found in women wit...
The Journal of antimicrobial chemotherapy, Jan 25, 2015
Streptococcus agalactiae constitutes an important cause of neonatal infections in sub-Saharan Afr... more Streptococcus agalactiae constitutes an important cause of neonatal infections in sub-Saharan Africa. Sulfadoxine/pyrimethamine-the current intermittent preventive treatment of malaria in pregnancy (IPTp)-has proven in vitro activity against group B Streptococcus (GBS). Because of specific drug resistance to sulfadoxine/pyrimethamine, mefloquine-an antimalarial without in vitro activity against GBS-was evaluated as a potential alternative. This study assessed the potential of sulfadoxine/pyrimethamine-IPTp to reduce the prevalence of GBS colonization in pregnant women in Gabon when compared with the inactive control mefloquine-IPTp. Pregnant women participating in a randomized controlled clinical trial evaluating mefloquine-IPTp versus sulfadoxine/pyrimethamine-IPTp were invited to participate and recto-vaginal swabs were collected at delivery for detection of GBS colonization. Prevalence of recto-vaginal GBS colonization was compared between IPTp regimens and risk factor and birth ...
Transactions of The Royal Society of Tropical Medicine and Hygiene, 2002
We assessed the inter-observer agreement in identification of a range of 24 clinical signs associ... more We assessed the inter-observer agreement in identification of a range of 24 clinical signs associated with disease presentation in 327 children aged 0·41) although there was only fair agreement (Kappa-score 0·21-0·40) in the detection of neck stiffness and chest indrawing and slight agreement in the detection of dehydration (Kappa-score 0·199). All objective neurological signs were less reliably assessed in infants
Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is ... more Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in sub-Saharan Africa. However, studies reporting the effect of IPTp on malaria-specific immunity are scarce and are based on findings in human immunodeficiency virus (HIV)-negative primigravidae. Plasma samples obtained from 302 pregnant women (177 who were HIV negative, 88 who were HIV positive, and 37 who were of unknown HIV status) participating in a placebo-controlled trial of IPTp with SP (IPTp-SP) were analyzed for the presence of antibodies against merozoite antigens, whole asexual parasites, and variant surface antigens from chondroitin sulfate A-binding and nonbinding lines. Antibody levels were compared between intervention groups, and their association with morbidity outcomes was assessed. HIV-positive mothers receiving SP had lower levels of peripheral antibodies against apical membrane antigen-1 and variant surface antigens, as well as lower levels of cord antibodies against erythrocyte-binding antigen-175 and parasite lysate, than did HIV-positive placebo recipients. No difference between intervention groups was observed among HIV-negative mothers. High antibody levels were associated with maternal infection and an increased risk of a first malaria episode in infants. Antibody responses were not consistently associated with reduced maternal anemia, prematurity, or low birth weight. The IPTp-associated reduction in antibodies in HIV-infected women, but not in HIV-uninfected women, may reflect a higher efficacy of the intervention in preventing malaria among HIV-positive mothers. This reduction did not translate into an enhanced risk of malaria-associated morbidity in mothers and infants. Trial registration. Clinicaltrials.gov identifier NCT00209781.
BACKGROUND: There is a widespread notion, based on limited information, that in areas of stable m... more BACKGROUND: There is a widespread notion, based on limited information, that in areas of stable malaria transmission most pregnant women with Plasmodium falciparum infection are asymptomatic. This study aim to characterize the clinical presentation of malaria in African pregnant women and to evaluate the adequacy of case management based on clinical complaints. METHODS: A hospital-based descriptive study between August 2003
In this study, we analyzed the human immunodeficiency type 1 (HIV-1) viruses circulating between ... more In this study, we analyzed the human immunodeficiency type 1 (HIV-1) viruses circulating between 1999 and 2004 in antiretroviral-naive women from a rural area of southern Mozambique. Nucleotide sequencing of the HIV-1 long terminal repeat (LTR) U3, envelope (env) C2V3C3, and protease (pr) genomic regions was performed from women sera samples collected in 1999 and 2004. Phylogenetic analysis revealed that all amplified sequences belonged to subtype C. Although env sequences were predominantly CCR5-tropic (R5), CXCR4-tropic (X4) variants were also identified (13%). Both 1999 and 2004 sequences were widely dispersed across multiple clusters and were related to different reference sequences from neighboring countries. Sequences from 2004 showed significantly more nucleotide genetic diversity than sequences from 1999. Importantly, genetic diversification was also observed at the pr and env amino acid level, suggesting that positive selection forces were implicated in the viral diversification. These results indicate the rapid spread and diversification of subtype C virus in Mozambique where HIV-1 prevalence in the Manhiça antenatal clinic reached 23% in 2004.
We used a prospective, open-label randomized trial to evaluate two treatment regimens in Tanzania... more We used a prospective, open-label randomized trial to evaluate two treatment regimens in Tanzanian children two months to four years of age presenting to a hospital with a packed cell volume (PCV) < 25%. Treatment was either standard (14 days of ferrous sulfate and an antimalarial) or extended (three months of ferrous sulfate and three antimalarial treatments). The prevalence of
Hepatitis G virus (HGV) RNA was detected in 18 of 133 pregnant women from Tanzania without known ... more Hepatitis G virus (HGV) RNA was detected in 18 of 133 pregnant women from Tanzania without known risk factors for HGV infection and in 7 of 18 children born to HGV RNA-positive mothers. Molecular evidence of mother-to-infant transmission was obtained only for three of seven children. HGV RNA was also detected in 4 of 42 children born to non-HGV-infected women. Thus, mechanisms other than materno-filial may play an important role in HGV transmission during early childhood.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2011
Factors involved in the development of resistance to sulphadoxine-pyrimethamine (SP) by Plasmodiu... more Factors involved in the development of resistance to sulphadoxine-pyrimethamine (SP) by Plasmodium falciparum, particularly in the context of intermittent preventive treatment during pregnancy (IPTp), are not well known. We aimed to determine the impact of IPTp and human immunodeficiency virus (HIV) infection on molecular markers of SP resistance and the clinical relevance of resistant infections. SP resistance alleles were determined in peripheral (n = 125) and placental (n = 145) P. falciparum isolates obtained from pregnant women enrolled in a randomized, placebo-controlled trial of IPTp in Manhiça, Mozambique. Prevalence of quintuple mutant infections was 12% (23 of 185 isolates) in pregnant women who received placebo and 24% (20 of 85 isolates) in those who received SP (P = .031). When the last IPTp dose was administered at late pregnancy, mutant infections at delivery were more prevalent in placental samples (7 [23%] of 30, samples) than in peripheral blood samples (2 [7%] of ...
The major public health consequences of malaria in pregnancy have long been acknowledged. However... more The major public health consequences of malaria in pregnancy have long been acknowledged. However, further information is still required for development and implementation of a malaria vaccine specifically directed to prevent malaria in pregnant women and improve maternal, fetal and infant outcomes. The WHO Malaria Vaccine Advisory Committee (MALVAC) provides guidance to the WHO on strategic priorities and research needs for development of vaccines to prevent malaria. Here we summarize the discussions and conclusions of a MALVAC scientific forum meeting on considerations in the development of vaccines to prevent malaria in pregnant women. This report includes brief summaries of what is known, and major knowledge gaps in disease burden estimation, pathogenesis and immunity, and the challenges with current preventive strategies for malaria in pregnancy. We conclude with the formulation of a conceptual framework for research and development for vaccines to prevent malaria in pregnant w...
Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a pote... more Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a potential malaria control strategy. There is concern about the impact that increasing in vivo resistance to SP has on the efficacy of IPTi, as well as about the potential contribution of IPTi to increases in resistance. We compared the frequency of clinical episodes of malaria caused by P. falciparum parasites with mutations in dhfr and dhps among sick children who received SP or placebo in the context of a randomized, double-blind, placebo-controlled IPTi trial in Mozambique. Half of the children who received placebo harbored quintuple-pure mutant parasites. Nevertheless, the protective efficacy of IPTi within the 35 days after the third dose was 70.8% (95% confidence interval [CI], 40.7%-85.6%). Between month 2 after the third IPTi dose and the end of the follow-up period, children receiving SP harbored more dhps codon 437 mixed infections (odds ratio [OR], 10.56 [95% CI, 1.30-86.14]) and fewer dhps double-pure mutant parasites (OR, 0.43 [95% CI, 0.22-0.84]) than did placebo recipients. IPTi appears to be associated with some changes in the prevalence of genotypes involved in SP resistance. In the face of a high prevalence of quintuple-mutant parasites, SP exhibited a high level of efficacy in the prevention of new episodes of malaria in infants.
Journal of immunology (Baltimore, Md. : 1950), Jan 27, 2015
Pregnancy triggers immunological changes aimed to tolerate the fetus. However, it has not been pr... more Pregnancy triggers immunological changes aimed to tolerate the fetus. However, it has not been properly addressed whether similar changes occur in tropical areas with high infection pressure and whether these changes render women more susceptible to infectious diseases. We compared the frequencies of T cell subsets, including regulatory T cells, in pregnant and nonpregnant women from Papua New Guinea, a high malaria transmission area, and from Spain, a malaria-free country. We also assessed the relationship among these cellular subsets, malaria infection, and delivery outcomes. CD4(+)FOXP3(+)CD127(low) T cells (Tregs) were decreased in pregnant women in both countries but were not associated with malaria infection or poor delivery outcomes. An expansion of IFN-γ-producing cells and intracytoplasmic IFN-γ levels was found in pregnant compared with nonpregnant women only in Papua New Guinea. Increased CD4(+)IL-10(+)IFN-γ(+) frequencies and Treg-IFN-γ production were found in women wit...
The Journal of antimicrobial chemotherapy, Jan 25, 2015
Streptococcus agalactiae constitutes an important cause of neonatal infections in sub-Saharan Afr... more Streptococcus agalactiae constitutes an important cause of neonatal infections in sub-Saharan Africa. Sulfadoxine/pyrimethamine-the current intermittent preventive treatment of malaria in pregnancy (IPTp)-has proven in vitro activity against group B Streptococcus (GBS). Because of specific drug resistance to sulfadoxine/pyrimethamine, mefloquine-an antimalarial without in vitro activity against GBS-was evaluated as a potential alternative. This study assessed the potential of sulfadoxine/pyrimethamine-IPTp to reduce the prevalence of GBS colonization in pregnant women in Gabon when compared with the inactive control mefloquine-IPTp. Pregnant women participating in a randomized controlled clinical trial evaluating mefloquine-IPTp versus sulfadoxine/pyrimethamine-IPTp were invited to participate and recto-vaginal swabs were collected at delivery for detection of GBS colonization. Prevalence of recto-vaginal GBS colonization was compared between IPTp regimens and risk factor and birth ...
Transactions of The Royal Society of Tropical Medicine and Hygiene, 2002
We assessed the inter-observer agreement in identification of a range of 24 clinical signs associ... more We assessed the inter-observer agreement in identification of a range of 24 clinical signs associated with disease presentation in 327 children aged 0·41) although there was only fair agreement (Kappa-score 0·21-0·40) in the detection of neck stiffness and chest indrawing and slight agreement in the detection of dehydration (Kappa-score 0·199). All objective neurological signs were less reliably assessed in infants
Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is ... more Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in sub-Saharan Africa. However, studies reporting the effect of IPTp on malaria-specific immunity are scarce and are based on findings in human immunodeficiency virus (HIV)-negative primigravidae. Plasma samples obtained from 302 pregnant women (177 who were HIV negative, 88 who were HIV positive, and 37 who were of unknown HIV status) participating in a placebo-controlled trial of IPTp with SP (IPTp-SP) were analyzed for the presence of antibodies against merozoite antigens, whole asexual parasites, and variant surface antigens from chondroitin sulfate A-binding and nonbinding lines. Antibody levels were compared between intervention groups, and their association with morbidity outcomes was assessed. HIV-positive mothers receiving SP had lower levels of peripheral antibodies against apical membrane antigen-1 and variant surface antigens, as well as lower levels of cord antibodies against erythrocyte-binding antigen-175 and parasite lysate, than did HIV-positive placebo recipients. No difference between intervention groups was observed among HIV-negative mothers. High antibody levels were associated with maternal infection and an increased risk of a first malaria episode in infants. Antibody responses were not consistently associated with reduced maternal anemia, prematurity, or low birth weight. The IPTp-associated reduction in antibodies in HIV-infected women, but not in HIV-uninfected women, may reflect a higher efficacy of the intervention in preventing malaria among HIV-positive mothers. This reduction did not translate into an enhanced risk of malaria-associated morbidity in mothers and infants. Trial registration. Clinicaltrials.gov identifier NCT00209781.
BACKGROUND: There is a widespread notion, based on limited information, that in areas of stable m... more BACKGROUND: There is a widespread notion, based on limited information, that in areas of stable malaria transmission most pregnant women with Plasmodium falciparum infection are asymptomatic. This study aim to characterize the clinical presentation of malaria in African pregnant women and to evaluate the adequacy of case management based on clinical complaints. METHODS: A hospital-based descriptive study between August 2003
In this study, we analyzed the human immunodeficiency type 1 (HIV-1) viruses circulating between ... more In this study, we analyzed the human immunodeficiency type 1 (HIV-1) viruses circulating between 1999 and 2004 in antiretroviral-naive women from a rural area of southern Mozambique. Nucleotide sequencing of the HIV-1 long terminal repeat (LTR) U3, envelope (env) C2V3C3, and protease (pr) genomic regions was performed from women sera samples collected in 1999 and 2004. Phylogenetic analysis revealed that all amplified sequences belonged to subtype C. Although env sequences were predominantly CCR5-tropic (R5), CXCR4-tropic (X4) variants were also identified (13%). Both 1999 and 2004 sequences were widely dispersed across multiple clusters and were related to different reference sequences from neighboring countries. Sequences from 2004 showed significantly more nucleotide genetic diversity than sequences from 1999. Importantly, genetic diversification was also observed at the pr and env amino acid level, suggesting that positive selection forces were implicated in the viral diversification. These results indicate the rapid spread and diversification of subtype C virus in Mozambique where HIV-1 prevalence in the Manhiça antenatal clinic reached 23% in 2004.
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Papers by Clara Menendez