Laurence Slutsker

Publications (101)691.49 Total impact

• Article: It is time to rethink tactics in the fight against malaria.

  Laurence Slutsker, S Patrick Kachur
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  ABSTRACT: April 25 marks World Malaria Day, an opportunity for those who work to defeat the illness, to review progress and renew commitments. After a decade of steady success, this year's commemoration of the date is also an opportunity to reconsider current approaches and assess the state of the science needed to keep pace in the global effort to combat malaria.
  Malaria Journal 04/2013; 12(1):140. · 3.19 Impact Factor
• Article: Weighing for results: assessing the effect of IPTp.

  Julie Gutman, Erin Eckert, Viviana Mangiaterra, Azucena Bardají, John J Aponte, Clara Menéndez, Bernard Nahlen, Laurence Slutsker
  The Lancet Infectious Diseases 04/2013; 13(4):292. · 17.39 Impact Factor
• Source

  Available from: Nnaemeka C. Iriemenam

  Article: Association between Immunoglobulin GM and KM Genotypes and Placental Malaria in HIV-1 Negative and Positive Women in Western Kenya.

  Nnaemeka C Iriemenam, Janardan P Pandey, John Williamson, Anna J Blackstock, Ajay Yesupriya, Aryan M Namboodiri, Keith M Rocca, Anna Maria van Eijk, John Ayisi, Juliana Oteino, Renu B Lal, Feiko O Ter Kuile, Richard Steketee, Bernard Nahlen, Laurence Slutsker, Ya Ping Shi
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  ABSTRACT: Immunoglobulin (Ig) GM and KM allotypes, genetic markers of γ and κ chains, are associated with humoral immune responsiveness. Previous studies have shown the relationships between GM6-carrying haplotypes and susceptibility to malaria infection in children and adults; however, the role of the genetic markers in placental malaria (PM) infection and PM with HIV co-infection during pregnancy has not been investigated. We examined the relationship between the gene polymorphisms of Ig GM6 and KM allotypes and the risk of PM infection in pregnant women with known HIV status. DNA samples from 728 pregnant women were genotyped for GM6 and KM alleles using polymerase chain reaction-restriction fragment length polymorphism method. Individual GM6 and KM genotypes and the combined GM6 and KM genotypes were assessed in relation to PM in HIV-1 negative and positive women, respectively. There was no significant effect of individual GM6 and KM genotypes on the risk of PM infection in HIV-1 negative and positive women. However, the combination of homozygosity for GM6(+) and KM3 was associated with decreased risk of PM (adjusted OR, 0.25; 95% CI, 0.08-0.8; P = 0.019) in HIV-1 negative women while in HIV-1 positive women the combination of GM6(+/-) with either KM1-3 or KM1 was associated with increased risk of PM infection (adjusted OR, 2.10; 95% CI, 1.18-3.73; P = 0.011). Hardy-Weinberg Equilibrium (HWE) tests further showed an overall significant positive F(is) (indication of deficit in heterozygotes) for GM6 while there was no deviation for KM genotype frequency from HWE in the same population. These findings suggest that the combination of homozygous GM6(+) and KM3 may protect against PM in HIV-1 negative women while the HIV-1 positive women with heterozygous GM6(+/-) combined with KM1-3 or KM1 may be more susceptible to PM infection. The deficit in heterozygotes for GM6 further suggests that GM6 could be under selection likely by malaria infection.
  PLoS ONE 01/2013; 8(1):e53948. · 4.09 Impact Factor
• Article: Profile: the KEMRI/CDC Health and Demographic Surveillance System--Western Kenya.

  Frank O Odhiambo, Kayla F Laserson, Maquins Sewe, Mary J Hamel, Daniel R Feikin, Kubaje Adazu, Sheila Ogwang, David Obor, Nyaguara Amek, Nabie Bayoh, [......], Anna M van Eijk, Daniel Rosen, Allen Hightower, Peter Ofware, Hellen Muttai, Bernard Nahlen, Kevin DeCock, Laurence Slutsker, Robert F Breiman, John M Vulule
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  ABSTRACT: The KEMRI/Centers for Disease Control and Prevention (CDC) Health and Demographic Surveillance System (HDSS) is located in Rarieda, Siaya and Gem Districts (Siaya County), lying northeast of Lake Victoria in Nyanza Province, western Kenya. The KEMRI/CDC HDSS, with approximately 220 000 inhabitants, has been the foundation for a variety of studies, including evaluations of insecticide-treated bed nets, burden of diarrhoeal disease and tuberculosis, malaria parasitaemia and anaemia, treatment strategies and immunological correlates of malaria infection, and numerous HIV, tuberculosis, malaria and diarrhoeal disease treatment and vaccine efficacy and effectiveness trials for more than a decade. Current studies include operations research to measure the uptake and effectiveness of the programmatic implementation of integrated malaria control strategies, HIV services, newly introduced vaccines and clinical trials. The HDSS provides general demographic and health information (such as population age structure and density, fertility rates, birth and death rates, in- and out-migrations, patterns of health care access and utilization and the local economics of health care) as well as disease- or intervention-specific information. The HDSS also collects verbal autopsy information on all deaths. Studies take advantage of the sampling frame inherent in the HDSS, whether at individual, household/compound or neighbourhood level.
  International Journal of Epidemiology 08/2012; 41(4):977-87. · 6.41 Impact Factor
• Article: Spatial and temporal dynamics of malaria transmission in rural Western Kenya.

  Nyaguara Amek, Nabie Bayoh, Mary Hamel, Kim A Lindblade, John E Gimnig, Frank Odhiambo, Kayla F Laserson, Laurence Slutsker, Thomas Smith, Penelope Vounatsou
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  ABSTRACT: Understanding the relationship between Plasmodium falciparum malaria transmission and health outcomes requires accurate estimates of exposure to infectious mosquitoes. However, measures of exposure such as mosquito density and entomological inoculation rate (EIR) are generally aggregated over large areas and time periods, biasing the outcome-exposure relationship. There are few studies examining the extent and drivers of local variation in malaria exposure in endemic areas. We describe the spatio-temporal dynamics of malaria transmission intensity measured by mosquito density and EIR in the KEMRI/CDC health and demographic surveillance system using entomological data collected during 2002-2004. Geostatistical zero inflated binomial and negative binomial models were applied to obtain location specific (house) estimates of sporozoite rates and mosquito densities respectively. Model-based predictions were multiplied to estimate the spatial pattern of annual entomological inoculation rate, a measure of the number of infective bites a person receive per unit of time. The models included environmental and climatic predictors extracted from satellite data, harmonic seasonal trends and parameters describing space-time correlation. Anopheles gambiae s.l was the main vector species accounting for 86% (n=2309) of the total mosquitoes collected with the remainder being Anopheles funestus. Sixty eight percent (757/1110) of the surveyed houses had no mosquitoes. Distance to water bodies, vegetation and day temperature were strongly associated with mosquito density. Overall annual point estimates of EIR were 6.7, 9.3 and 9.6 infectious bites per annum for 2002, 2003 and 2004 respectively. Monthly mosquito density and EIR varied over the study period peaking in May during the wet season each year. The predicted and observed densities of mosquitoes and EIR showed a strong seasonal and spatial pattern over the study area. Spatio-temporal maps of malaria transmission intensity obtained in this study are not only useful in understanding variability in malaria epidemiology over small areas but also provide a high resolution exposure surface that can be used to analyse the impact of transmission on malaria related and all-cause morbidity and mortality.
  Parasites & Vectors 04/2012; 5:86. · 2.94 Impact Factor
• Source

  Available from: Nnaemeka C. Iriemenam

  Article: Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya.

  Nnaemeka C Iriemenam, Monica Shah, Wangeci Gatei, Anna M van Eijk, John Ayisi, Simon Kariuki, Jodi Vanden Eng, Simon O Owino, Ashima A Lal, Yusuf O Omosun, Kephas Otieno, Meghna Desai, Feiko O ter Kuile, Bernard Nahlen, Julie Moore, Mary J Hamel, Peter Ouma, Laurence Slutsker, Ya Ping Shi
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  ABSTRACT: Resistance to sulphadoxine-pyrimethamine (SP) in Plasmodium falciparum parasites is associated with mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes and has spread worldwide. SP remains the recommended drug for intermittent preventive treatment for malaria in pregnancy (IPTp) and information on population prevalence of the SP resistance molecular markers in pregnant women is limited. Temporal trends of SP resistance molecular markers were investigated in 489 parasite samples collected from pregnant women at delivery from three different observational studies between 1996 and 2009 in Kenya, where SP was adopted for both IPTp and case treatment policies in 1998. Using real-time polymerase chain reaction, pyrosequencing and direct sequencing, 10 single-nucleotide polymorphisms (SNPs) of SP resistance molecular markers were assayed. The prevalence of quintuple mutant (dhfr N51I/C59R/S108N and dhps A437G/K540E combined genotype) increased from 7% in the first study (1996-2000) to 88% in the third study (2008-2009). When further stratified by sample collection year and adoption of IPTp policy, the prevalence of the quintuple mutant increased from 2.4% in 1998 to 44.4% three years after IPTp policy adoption, seemingly in parallel with the increase in percentage of SP use in pregnancy. However, in the 1996-2000 study, more mutations in the combined dhfr/dhps genotype were associated with SP use during pregnancy only in univariable analysis and no associations were detected in the 2002-2008 and 2008-2009 studies. In addition, in the 2008-2009 study, 5.3% of the parasite samples carried the dhps triple mutant (A437G/K540E/A581G). There were no differences in the prevalence of SP mutant genotypes between the parasite samples from HIV + and HIV- women over time and between paired peripheral and placental samples. There was a significant increase in dhfr/dhps quintuple mutant and the emergence of new genotype containing dhps 581 in the parasites from pregnant women in western Kenya over 13 years. IPTp adoption and SP use in pregnancy only played a minor role in the increased drug-resistant parasites in the pregnant women over time. Most likely, other major factors, such as the high prevalence of resistant parasites selected by the use of SP for case management in large non-pregnant population, might have contributed to the temporally increased prevalence of SP resistant parasites in pregnant women. Further investigations are needed to determine the linkage between SP drug resistance markers and efficacy of IPTp-SP.
  Malaria Journal 04/2012; 11:134. · 3.19 Impact Factor
• Source

  Available from: PubMed Central

  Article: The role of public health institutions in global health system strengthening efforts: the US CDC's perspective.

  Peter Bloland, Patricia Simone, Brent Burkholder, Laurence Slutsker, Kevin M De Cock
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  ABSTRACT: Peter Bloland and colleagues from the US CDC lay out the agency's priorities for health systems strengthening efforts.
  PLoS Medicine 04/2012; 9(4):e1001199. · 16.27 Impact Factor
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  Available from: Feiko O ter Kuile

  Article: Differences in selective pressure on dhps and dhfr drug resistant mutations in western Kenya.

  Andrea M McCollum, Kristan A Schneider, Sean M Griffing, Zhiyong Zhou, Simon Kariuki, Feiko Ter-Kuile, Ya Ping Shi, Laurence Slutsker, Altaf A Lal, Venkatachalam Udhayakumar, Ananias A Escalante
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  ABSTRACT: Understanding the origin and spread of mutations associated with drug resistance, especially in the context of combination therapy, will help guide strategies to halt and prevent the emergence of resistance. Unfortunately, studies have assessed these complex processes when resistance is already highly prevalent. Even further, information on the evolutionary dynamics leading to multidrug-resistant parasites is scattered and limited to areas with low or seasonal malaria transmission. This study describes the dynamics of strong selection for mutations conferring resistance against sulphadoxine-pyrimethamine (SP), a combination therapy, in western Kenya between 1992 and 1999, just before SP became first-line therapy (1999). Importantly, the study is based on longitudinal data, which allows for a comprehensive analysis that contrasts with previous cross-sectional studies carried out in other endemic regions. This study used 236 blood samples collected between 1992 and 1999 in the Asembo Bay area of Kenya. Pyrosequencing was used to determine the alleles of dihydrofolate reductase (dhfr) and dihydropterote synthase (dhps) genes. Microsatellite alleles spanning 138 kb around dhfr and dhps, as well as, neutral markers spanning approximately 100 kb on chromosomes 2 and 3 were characterized. By 1992, the South-Asian dhfr triple mutant was already spreading, albeit in low frequency, in this holoendemic Kenyan population, prior to the use of SP as a first-line therapy. Additionally, dhfr triple mutant alleles that originated independently from the predominant Southeast Asian lineage were present in the sample set. Likewise, dhps double mutants were already present as early as 1992. There is evidence for soft selective sweeps of two dhfr mutant alleles and the possible emergence of a selective sweep of double mutant dhps alleles between 1992 and 1997. The longitudinal structure of the dataset allowed estimation of selection pressures on various dhfr and dhps mutants relative to each other based on a theoretical model tailored to P. falciparum. The data indicate that drug selection acted differently on the resistant alleles of dhfr and dhps, as evidenced by fitness differences. Thus a combination drug therapy such as SP, by itself, does not appear to select for "multidrug"-resistant parasites in areas with high recombination rate. The complexity of these observations emphasizes the importance of population-based studies to evaluate the effects of strong drug selection on Plasmodium falciparum populations.
  Malaria Journal 03/2012; 11:77. · 3.19 Impact Factor
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  Available from: Alexis Nzila

  Article: Combination of probenecid-sulphadoxine-pyrimethamine for intermittent preventive treatment in pregnancy.

  Julie Gutman, S Patrick Kachur, Laurence Slutsker, Alexis Nzila, Theonest Mutabingwa
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  ABSTRACT: The antifolate sulphadoxine-pyrimethamine (SP) has been used in the intermittent prevention of malaria in pregnancy (IPTp). SP is an ideal choice for IPTp, however, as resistance of Plasmodium falciparum to SP increases, data are accumulating that SP may no longer provide benefit in areas of high-level resistance. Probenecid was initially used as an adjunctive therapy to increase the blood concentration of penicillin; it has since been used to augment concentrations of other drugs, including antifolates. The addition of probenecid has been shown to increase the treatment efficacy of SP against malaria, suggesting that the combination of probenecid plus SP may prolong the useful lifespan of SP as an effective agent for IPTp. Here, the literature on the pharmacokinetics, adverse reactions, interactions and available data on the use of these drugs in pregnancy is reviewed, and the possible utility of an SP-probenecid combination is discussed. This article concludes by calling for further research into this potentially useful combination.
  Malaria Journal 01/2012; 11:39. · 3.19 Impact Factor
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  Available from: Caryl M Beynon

  Article: Mortality Trends from 2003 to 2009 among Adolescents and Young Adults in Rural Western Kenya Using a Health and Demographic Surveillance System.

  Penelope A Phillips-Howard, Frank O Odhiambo, Mary Hamel, Kubaje Adazu, Marta Ackers, Anne M van Eijk, Vincent Orimba, Anja Van't Hoog, Caryl Beynon, John Vulule, Mark A Bellis, Laurence Slutsker, Kevin Decock, Robert Breiman, Kayla F Laserson
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  ABSTRACT: BACKGROUND: Targeted global efforts to improve survival of young adults need information on mortality trends; contributions from health and demographic surveillance system (HDSS) are required. METHODS AND FINDINGS: This study aimed to explore changing trends in deaths among adolescents (15-19 years) and young adults (20-24 years), using census and verbal autopsy data in rural western Kenya using a HDSS. Mid-year population estimates were used to generate all-cause mortality rates per 100,000 population by age and gender, by communicable (CD) and non-communicable disease (NCD) causes. Linear trends from 2003 to 2009 were examined. In 2003, all-cause mortality rates of adolescents and young adults were 403 and 1,613 per 100,000 population, respectively, among females; and 217 and 716 per 100,000, respectively, among males. CD mortality rates among females and males 15-24 years were 500 and 191 per 100,000 (relative risk [RR] 2.6; 95% confidence intervals [CI] 1.7-4.0; p<0.001). NCD mortality rates in same aged females and males were similar (141 and 128 per 100,000, respectively; p = 0.76). By 2009, young adult female all-cause mortality rates fell 53% (χ(2) for linear trend 30.4; p<0.001) and 61.5% among adolescent females (χ(2) for linear trend 11.9; p<0.001). No significant CD mortality reductions occurred among males or for NCD mortality in either gender. By 2009, all-cause, CD, and NCD mortality rates were not significantly different between males and females, and among males, injuries equalled HIV as the top cause of death. CONCLUSIONS: This study found significant reductions in adolescent and young adult female mortality rates, evidencing the effects of targeted public health programmes, however, all-cause and CD mortality rates among females remain alarmingly high. These data underscore the need to strengthen programmes and target strategies to reach both males and females, and to promote NCD as well as CD initiatives to reduce the mortality burden amongst both gender.
  PLoS ONE 01/2012; 7(11):e47017. · 4.09 Impact Factor
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  Available from: Yusuf Omosun

  Article: Differential association of gene content polymorphisms of killer cell immunoglobulin-like receptors with placental malaria in HIV- and HIV+ mothers.

  Yusuf O Omosun, Anna J Blackstock, Wangeci Gatei, Allen Hightower, Anne Maria van Eijk, John Ayisi, Juliana Otieno, Renu B Lal, Richard Steketee, Bernard Nahlen, Feiko O ter Kuile, Laurence Slutsker, Ya Ping Shi
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  ABSTRACT: Pregnant women have abundant natural killer (NK) cells in their placenta, and NK cell function is regulated by polymorphisms of killer cell immunoglobulin-like receptors (KIRs). Previous studies report different roles of NK cells in the immune responses to placental malaria (PM) and human immunodeficiency virus (HIV-1) infections. Given these references, the aim of this study was to determine the association between KIR gene content polymorphism and PM infection in pregnant women of known HIV-1 status. Sixteen genes in the KIR family were analyzed in 688 pregnant Kenyan women. Gene content polymorphisms were assessed in relation to PM in HIV-1 negative and HIV-1 positive women, respectively. Results showed that in HIV-1 negative women, the presence of the individual genes KIR2DL1 and KIR2DL3 increased the odds of having PM, and the KIR2DL2/KIR2DL2 homozygotes were associated with protection from PM. However, the reverse relationship was observed in HIV-1 positive women, where the presence of individual KIR2DL3 was associated with protection from PM, and KIR2DL2/KIR2DL2 homozygotes increased the odds for susceptibility to PM. Further analysis of the HIV-1 positive women stratified by CD4 counts showed that this reverse association between KIR genes and PM remained only in the individuals with high CD4 cell counts but not in those with low CD4 cell counts. Collectively, these results suggest that inhibitory KIR2DL2 and KIR2DL3, which are alleles of the same locus, play a role in the inverse effects on PM and PM/HIV co-infection and the effect of KIR genes on PM in HIV positive women is dependent on high CD4 cell counts. In addition, analysis of linkage disequilibrium (LD) of the PM relevant KIR genes showed strong LD in women without PM regardless of their HIV status while LD was broken in those with PM, indicating possible selection pressure by malaria infection on the KIR genes.
  PLoS ONE 01/2012; 7(6):e38617. · 4.09 Impact Factor
• Article: Malaria survey in post-earthquake Haiti--2010.

  David Townes, Alexandre Existe, Jacques Boncy, Roc Magloire, Jean-Francois Vely, Ribka Amsalu, Marleen De Tavernier, James Muigai, Sarah Hoibak, Michael Albert, Meredith McMorrow, Laurence Slutsker, S Patrick Kachur, Michelle Chang
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  ABSTRACT: Haiti's Ministry of Public Health and Population collaborated with global partners to enhance malaria surveillance in two disaster-affected areas within 3 months of the January 2010 earthquake. Data were collected between March 4 and April 9, 2010 by mobile medical teams. Malaria rapid diagnostic tests (RDTs) were used for case confirmation. A convenience sample of 1,629 consecutive suspected malaria patients was included. Of these patients, 1,564 (96%) patients had malaria RDTs performed, and 317 (20.3%) patients were positive. Of the 317 case-patients with a positive RDT, 278 (87.7%) received chloroquine, 8 (2.5%) received quinine, and 31 (9.8%) had no antimalarial treatment recorded. Our experience shows that mobile medical teams trained in the use of malaria RDTs had a high rate of testing suspected malaria cases and that the majority of patients with positive RDTs received appropriate antimalarial treatment. Malaria RDTs were useful in the post-disaster setting where logistical and technical constraints limited the use of microscopy.
  The American journal of tropical medicine and hygiene 01/2012; 86(1):29-31. · 2.59 Impact Factor
• Article: Targeting of intermittent preventive treatment for malaria.

  Richard W Steketee, Laurence Slutsker
  The Lancet Infectious Diseases 12/2011; 12(3):168-9. · 17.39 Impact Factor
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  Available from: PubMed Central

  Article: Estimating the burden of malaria: the need for improved surveillance.

  Ivo Mueller, Laurence Slutsker, Marcel Tanner
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  ABSTRACT: Ivo Mueller, Laurence Slutsker, and Marcel Tanner highlight the importance of using complementary methods to estimate the burden of malaria and call for a renewed focus on efficient malaria surveillance.
  PLoS Medicine 12/2011; 8(12):e1001144. · 16.27 Impact Factor
• Article: The combination of indoor residual spraying and insecticide-treated nets provides added protection against malaria compared with insecticide-treated nets alone.

  Mary J Hamel, Peter Otieno, Nabie Bayoh, Simon Kariuki, Vincent Were, Doris Marwanga, Kayla F Laserson, John Williamson, Laurence Slutsker, John Gimnig
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  ABSTRACT: Both insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS) reduce malaria in high malaria transmission areas. The combined effect of these interventions is unknown. We conducted a non-randomized prospective cohort study to determine protective efficacy of IRS with ITNs (ITN + IRS) compared with ITNs alone (ITN only) in preventing Plasmodium falciparum parasitemia. At baseline, participants provided blood samples for malaria smears, were presumptively treated for malaria, and received ITNs. Blood smears were made monthly and at sick visits. In total, 1,804 participants were enrolled. Incidence of P. falciparum parasitemia in the ITN + IRS and ITN only groups was 18 and 44 infections per 100 persons-years at risk, respectively (unadjusted rate ratio = 0.41; 95% confidence interval [CI] = 0.31-0.56). Adjusted protective efficacy of ITN + IRS compared with ITN only was 62% (95% CI = 0.50-0.72). The combination of IRS and ITN might be a feasible strategy to further reduce malaria transmission in areas of persistent perennial malaria transmission.
  The American journal of tropical medicine and hygiene 12/2011; 85(6):1080-6. · 2.59 Impact Factor
• Article: Spatio-temporal modeling of sparse geostatistical malaria sporozoite rate data using a zero inflated binomial model.

  Nyaguara Amek, Nabie Bayoh, Mary Hamel, Kim A Lindblade, John Gimnig, Kayla F Laserson, Laurence Slutsker, Thomas Smith, Penelope Vounatsou
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  ABSTRACT: The proportion of malaria vectors harboring the infectious stage of the parasite (the sporozoite rates) is an important component of measures of malaria transmission. Variation in time and/or space in sporozoite rates contribute substantially to spatio-temporal variation in transmission. However, because most vectors test negative for sporozoites, sporozoite rate data are sparse with large number of observed zeros across locations or over time in the case of longitudinal data. Rarely are appropriate methods and models used in analyzing such data. In this study, Bayesian zero inflated binomial (ZIB) geostatistical models were developed and compared with standard binomial analogues to analyze sporozoite data obtained from the KEMRI/CDC health and demographic surveillance system (HDSS) site in rural Western Kenya during 2002-2004. ZIB models showed a better predictive ability, identified more significant covariates and obtained narrower credible intervals for all parameters compared to standard geostatistical binomial model.
  Spatial and spatio-temporal epidemiology. 12/2011; 2(4):283-90.
• Article: First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children.

  Selidji Todagbe Agnandji, Bertrand Lell, Solange Solmeheim Soulanoudjingar, José Francisco Fernandes, Béatrice Peggy Abossolo, Cornelia Conzelmann, Barbara Gaelle Nfono Ondo Methogo, Yannick Doucka, Arnaud Flamen, Benjamin Mordmüller, [......], Opokua Ofori-Anyinam, Johan Vekemans, Terrell Carter, Didier Leboulleux, Christian Loucq, Afiya Radford, Barbara Savarese, David Schellenberg, Marla Sillman, Preeti Vansadia
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  ABSTRACT: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries. From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories. In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64). The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).
  New England Journal of Medicine 11/2011; 365(20):1863-75. · 53.30 Impact Factor
• Article: A reversal in reductions of child mortality in western Kenya, 2003-2009.

  Mary J Hamel, Kubaje Adazu, David Obor, Maquins Sewe, John Vulule, John M Williamson, Laurence Slutsker, Daniel R Feikin, Kayla F Laserson
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  ABSTRACT: We report and explore changes in child mortality in a rural area of Kenya during 2003-2009, when major public health interventions were scaled-up. Mortality ratios and rates were calculated by using the Kenya Medical Research Institute/Centers for Disease Control and Prevention Demographic Surveillance System. Inpatient and outpatient morbidity and mortality, and verbal autopsy data were analyzed. Mortality ratios for children less than five years of age decreased from 241 to 137 deaths/1,000 live-births in 2003 and 2007 respectively. In 2008, they increased to 212 deaths/1,000 live-births. Mortality remained elevated during the first 8 months of 2009 compared with 2006 and 2007. Malaria and/or anemia accounted for the greatest increases in child mortality. Stock-outs of essential antimalarial drugs during a time of increased malaria transmission and disruption of services during civil unrest may have contributed to increased mortality in 2008-2009. To maintain gains in child survival, implementation of good policies and effective interventions must be complemented by reliable supply and access to clinical services and essential drugs.
  The American journal of tropical medicine and hygiene 10/2011; 85(4):597-605. · 2.59 Impact Factor
• Article: The threat of artemisinin-resistant malaria.

  Arjen M Dondorp, Rick M Fairhurst, Laurence Slutsker, John R Macarthur, Joel G Breman, Philippe J Guerin, Thomas E Wellems, Pascal Ringwald, Robert D Newman, Christopher V Plowe
  New England Journal of Medicine 09/2011; 365(12):1073-5. · 53.30 Impact Factor
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  Available from: PubMed Central

  Article: Triple-antiretroviral prophylaxis to prevent mother-to-child HIV transmission through breastfeeding--the Kisumu Breastfeeding Study, Kenya: a clinical trial.

  Timothy K Thomas, Rose Masaba, Craig B Borkowf, Richard Ndivo, Clement Zeh, Ambrose Misore, Juliana Otieno, Denise Jamieson, Michael C Thigpen, Marc Bulterys, Laurence Slutsker, Kevin M De Cock, Pauli N Amornkul, Alan E Greenberg, Mary Glenn Fowler
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  ABSTRACT: Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT) in resource-limited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretroviral regimen that was designed to maximally suppress viral load in late pregnancy and the first 6 mo of lactation was a safe, well-tolerated, and effective PMTCT intervention. HIV-infected pregnant women took zidovudine, lamivudine, and either nevirapine or nelfinavir from 34-36 weeks' gestation to 6 mo post partum. Infants received single-dose nevirapine at birth. Women were advised to breastfeed exclusively and wean rapidly just before 6 mo. Using Kaplan-Meier methods we estimated HIV-transmission and death rates from delivery to 24 mo. We compared HIV-transmission rates among subgroups defined by maternal risk factors, including baseline CD4 cell count and viral load. Among 487 live-born, singleton, or first-born infants, cumulative HIV-transmission rates at birth, 6 weeks, and 6, 12, and 24 mo were 2.5%, 4.2%, 5.0%, 5.7%, and 7.0%, respectively. The 24-mo HIV-transmission rates stratified by baseline maternal CD4 cell count <500 and ≥500 cells/mm(3) were 8.4% (95% confidence interval [CI] 5.8%-12.0%) and 4.1% (1.8%-8.8%), respectively (p = 0.06); the corresponding rates stratified by baseline maternal viral load <10,000 and ≥10,000 copies/ml were 3.0% (1.1%-7.8%) and 8.7% (6.1%-12.3%), respectively (p = 0.01). None of the 12 maternal and 51 infant deaths (including two second-born infants) were attributed to antiretrovirals. The cumulative HIV-transmission or death rate at 24 mo was 15.7% (95% CI 12.7%-19.4%). This trial shows that a maternal triple-antiretroviral regimen from late pregnancy through 6 months of breastfeeding for PMTCT is safe and feasible in a resource-limited setting. These findings are consistent with those from other trials using maternal triple-antiretroviral regimens during breastfeeding in comparable settings.
  PLoS Medicine 03/2011; 8(3):e1001015. · 16.27 Impact Factor