Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 109 Records) |
Query Trace: Slutsker L[original query] |
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Defining operational research priorities to improve malaria control and elimination in sub-Saharan Africa: Results from a country-driven research prioritization setting process
Tine R , Herrera S , Badji MA , Daniels K , Ndiaye P , Smith Gueye C , Tairou F , Slutsker L , Hwang J , Ansah E , Littrell M . Malar J 2023 22 (1) 219 BACKGROUND: In order to reignite gains and accelerate progress toward improved malaria control and elimination, policy, strategy, and operational decisions should be derived from high-quality evidence. The U.S. President's Malaria Initiative (PMI) Insights project together with the Université Cheikh Anta Diop of Dakar, Senegal, conducted a broad stakeholder consultation process to identify pressing evidence gaps in malaria control and elimination across sub-Saharan Africa (SSA), and developed a priority list of country-driven malaria operational research (OR) and programme evaluation (PE) topics to address these gaps. METHODS: Five key stakeholder groups were engaged in the process: national malaria programmes (NMPs), research institutions in SSA, World Health Organization (WHO) representatives in SSA, international funding agencies, and global technical partners who support malaria programme implementation and research. Stakeholders were engaged through individual or small group interviews and an online survey, and asked about key operational challenges faced by NMPs, pressing evidence gaps in current strategy and implementation guidance, and priority OR and PE questions to address the challenges and gaps. RESULTS: Altogether, 47 interviews were conducted with 82 individuals, and through the online survey, input was provided by 46 global technical partners. A total of 33 emergent OR and PE topics were identified through the consultation process and were subsequently evaluated and prioritized by an external evaluation committee of experts from NMPs, research institutions, and the WHO. The resulting prioritized OR and PE topics predominantly focused on generating evidence needed to close gaps in intervention coverage, address persistent challenges faced by NMPs in the implementation of core strategic interventions, and inform the effective deployment of new tools. CONCLUSION: The prioritized research list is intended to serve as a key resource for informing OR and PE investments, thereby ensuring future investments focus on generating the evidence needed to strengthen national strategies and programme implementation and facilitating a more coordinated and impactful approach to malaria operational research. |
Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis
Unger HW , Hadiprodjo AJ , Gutman JR , Briand V , Fievet N , Valea I , Tinto H , D'Alessandro U , Landis SH , Ter Kuile F , Ouma P , Oneko M , Mwapasa V , Slutsker L , Terlouw DJ , Kariuki S , Ayisi J , Nahlen B , Desai M , Madanitsa M , Kalilani-Phiri L , Ashorn P , Maleta K , Tshefu-Kitoto A , Mueller I , Stanisic D , Cates J , Van Eijk AM , Ome-Kaius M , Aitken EH , Rogerson SJ . Sci Rep 2023 13 (1) 10310 In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy. |
Healthy vaccinee bias and MenB-FHbp vaccine effectiveness against gonorrhea
Abara WE , Bernstein KT , Lewis FMT , Pathela P , Islam A , Eberhart M , Cheng I , Ternier A , Sanderson Slutsker J , Madera R , Kirkcaldy R . Sex Transm Dis 2023 50 (6) e8-e10 Observational studies demonstrated 30-40% effectiveness of OMV meningococcal serogroup-B vaccines against gonorrhea. To explore whether healthy vaccinee bias influenced such findings, we examined effectiveness of MenB-FHbp, a non-OMV vaccine that is not protective against gonorrhea. MenB-FHbp was ineffective against gonorrhea. Healthy vaccinee bias likely did not confound earlier studies of OMV vaccines. |
Burden of malaria in pregnancy among adolescent girls compared to adult women in 5 sub-Saharan African countries: A secondary individual participant data meta-analysis of 2 clinical trials
Pons-Duran C , Mombo-Ngoma G , Macete E , Desai M , Kakolwa MA , Zoleko-Manego R , Oudragou S , Briand V , Val A , Kabanywanyi AM , Ouma P , Massougbodji A , Sevene E , Cot M , Aponte JJ , Mayor A , Slutsker L , Ramharter M , Menndez C , Gonzlez R . PLoS Med 2022 19 (9) e1004084 BACKGROUND: Malaria is among the top causes of death in adolescent girls (10 to 19 years) globally. Adolescent motherhood is associated with increased risk of adverse maternal and neonatal outcomes. The interaction of malaria, adolescence, and pregnancy is especially relevant in malaria endemic areas, where rates of adolescent pregnancy are high. However, data on burden of malaria among adolescent girls are limited. This study aimed at investigating whether adolescent girls were at a greater risk of experiencing malaria-related outcomes in pregnancy-parasitaemia and clinical disease-than adult women. METHODS AND FINDINGS: An individual secondary participant-level meta-analysis was conducted using data from 5,804 pregnant women participating in 2 malaria prevention clinical trials in Benin, Gabon, Kenya, Mozambique, and Tanzania between 2009 and 2014. Of the sample, 1,201 participants were adolescent girls with a mean age of 17.5 years (standard deviation (SD) 1.3) and 886 (73.8%) of them primigravidae. Among the 4,603 adult women with mean age of 27.0 years (SD 5.4), 595 (12.9%) were primigravidae. Mean gestational age at enrolment was 20.2 weeks (SD 5.2) and 1,069 (18.4%) participants were HIV-infected. Women were followed monthly until the postpartum visit (1 month to 6 weeks after delivery). This study considered outcomes including clinical episodes during pregnancy, peripheral parasitaemia at delivery, and placental malaria. A 2-stage meta-analysis approach was followed by pooling single multivariable regression results into standard DerSimonian-Laird random-effects models. Adolescent girls were more likely than adult women to present with clinical malaria during pregnancy (incidence risk ratio (IRR) 1.70, 95% confidence interval (CI) 1.20; 2.39, p-value = 0.003, I2 = 0.0%, N = 4,092), peripheral parasitaemia at delivery (odds ratio (OR) 2.28, 95% CI 1.46; 3.55, p-value < 0.001, I2 = 0.0%, N = 3,977), and placental infection (OR 1.97, 95% CI 1.31; 2.98, p-value = 0.001, I2 = 1.4%, N = 4,797). Similar associations were observed among the subgroup of HIV-uninfected participants: IRR 1.72 (95% CI 1.22; 2.45, p-value = 0.002, I2 = 0.0%, N = 3,531) for clinical malaria episodes, OR 2.39 (95% CI 1.49; 3.86, p-value < 0.001, I2 = 0.0%, N = 3,053) for peripheral parasitaemia, and OR 1.88 (95% CI 1.06 to 3.33, p-value = 0.03, I2 = 34.9%, N = 3,847) for placental malaria. Among HIV-infected subgroups statistically significant associations were not observed. Similar associations were found in the subgroup analysis by gravidity. The small sample size and outcome prevalence in specific countries limited the inclusion of some countries in the meta-analysis. Furthermore, peripheral parasitaemia and placental malaria presented a considerable level of missing data-12.6% and 18.2% of participants had missing data on those outcomes, respectively. Given the original scope of the clinical trials, asymptomatic malaria infection was only assessed at the end of pregnancy through peripheral and placental parasitaemia. CONCLUSIONS: In this study, we observed that adolescent girls in sub-Saharan Africa (SSA) are more prone to experience clinical malaria episodes during pregnancy and have peripheral malaria and placental infection at delivery than adult women. Moreover, to the best of our knowledge, for the first time this study disaggregates figures and stratifies analyses by HIV infection. Similar associations were found for both HIV-infected and uninfected women, although those for HIV-infected participants were not statistically significant. Our finding suggests that adolescent girls may benefit from targeted malaria prevention strategies even before they become pregnant. |
Diagnostic performance of loop-mediated isothermal amplification and ultra-sensitive rapid diagnostic tests for malaria screening among pregnant women in Kenya.
Samuels AM , Towett O , Seda B , Wiegand RE , Otieno K , Chomba M , Lucchi N , Ljolje D , Schneider K , Gt P , Kwambai TK , Slutsker L , TerKuile FO , Kariuki SK . J Infect Dis 2022 226 (4) 696-707 BACKGROUND: Screen-and-treat strategies with sensitive diagnostic tests may reduce malaria-associated adverse pregnancy outcomes. We conducted a diagnostic accuracy study to evaluate new point-of-care tests to screen pregnant women for malaria at their first antenatal visit in western Kenya. METHODS: Consecutively women were tested for Plasmodium infection by expert-microscopy, conventional rapid diagnostic test (cRDT), ultra-sensitive RDT (usRDT), and loop-mediated isothermal amplification (LAMP). Photo-induced electron-transfer polymerase-chain-reaction (PET-PCR) served as the reference standard. Diagnostic performance was calculated and modelled at low parasite densities. RESULTS: Between May-September 2018, 172 out of 482 screened participants (35.7%) were PET-PCR positive. Relative to PET-PCR, expert-microscopy was least sensitive (40.1%, 95% CI 32.7-47.9), followed by cRDT (49.4%, 41.7-57.1), usRDT (54.7%, 46.9-62.2), and LAMP (68.6%, 61.1-75.5). Test sensitivities were comparable in febrile women (N=90). Among afebrile women (N=392), the geometric-mean parasite density was 29 parasites/L and LAMP (sensitivity=61.9%) and usRDT (43.2%) detected 1.74 (1.31-2.30) and 1.21 (0.88-2.21) more infections than cRDT (35.6%). Per our model, tests performed similarly at densities >200 parasites/L. At 50 parasites/L, the sensitivities were 45%, 56%, 62% and 74% with expert-microscopy, cRDT, usRDT, and LAMP, respectively. CONCLUSIONS: This first-generation usRDT provided moderate improvement in detecting low-density infections in afebrile pregnant women compared to cRDTs. |
Shigellosis cases with bacterial sexually transmitted infections: Population-based data from 6 US jurisdictions, 2007-2016
Ridpath AD , Vanden Esschert KL , Bragg S , Campbell S , Convery C , Cope A , Devinney K , Diesel JC , Kikuchi N , Lee N , Lewis FMT , Matthias J , Pathela P , Pugsley R , Slutsker JS , Schillinger JA , Thompson C , Tingey C , Wilson J , Newman DR , Marsh ZA , Garcia-Williams AG , Kirkcaldy RD . Sex Transm Dis 2022 49 (8) 576-581 BACKGROUND: Shigella species, which cause acute diarrheal disease, are transmitted via fecal-oral and sexual contact. To better understand the overlapping populations affected by Shigella infections and sexually transmitted infections (STIs) in the United States, we examined the occurrence of reported STIs within 24 months among shigellosis case-patients. METHODS: Culture-confirmed Shigella cases diagnosed during 2007-2016 among residents of six U.S. jurisdictions were matched to reports of STIs (chlamydia, gonorrhea, and all stages of syphilis) diagnosed 12 months before or after the shigellosis case. We examined epidemiologic characteristics and reported temporal trends of Shigella cases by sex and species. RESULTS: During 2007-2016, 10,430 shigellosis cases were reported. The annual number of reported shigellosis cases across jurisdictions increased 70%, from 821 cases in 2007 to 1,398 cases in 2016; males saw a larger increase compared to females. Twenty percent of male shigellosis case-patients had an STI reported in the reference period, versus 4% of female case-patients. The percentage of male shigellosis case-patients with an STI increased from 11% (2007) to 28% (2016); the overall percentage among females remained low. CONCLUSIONS: We highlight the substantial proportion of males with shigellosis who were diagnosed with STIs within 24 months and the benefit of matching data across programs. STI screening may be warranted for male shigellosis case-patients. |
Effectiveness of a serogroup B outer membrane vesicle meningococcal vaccine against gonorrhoea: a retrospective observational study
Abara WE , Bernstein KT , Lewis FMT , Schillinger JA , Feemster K , Pathela P , Hariri S , Islam A , Eberhart M , Cheng I , Ternier A , Slutsker JS , Mbaeyi S , Madera R , Kirkcaldy RD . Lancet Infect Dis 2022 22 (7) 1021-1029 BACKGROUND: Declining antimicrobial susceptibility to current gonorrhoea antibiotic treatment and inadequate treatment options have raised the possibility of untreatable gonorrhoea. New prevention approaches, such as vaccination, are needed. Outer membrane vesicle meningococcal serogroup B vaccines might be protective against gonorrhoea. We evaluated the effectiveness of a serogroup B meningococcal outer membrane vesicle vaccine (MenB-4C) against gonorrhoea in individuals aged 16-23 years in two US cities. METHODS: We identified laboratory-confirmed gonorrhoea and chlamydia infections among individuals aged 16-23 years from sexually transmitted infection surveillance records in New York City and Philadelphia from 2016 to 2018. We linked gonorrhoea and chlamydia case records to immunisation registry records to determine MenB-4C vaccination status at infection, defined as complete vaccination (two MenB-4C doses administered 30-180 days apart), partial vaccination (single MenB-4C vaccine dose), or no vaccination (serogroup B meningococcal vaccine naive). Using log-binomial regression with generalised estimating equations to account for correlations between multiple infections per patient, we calculated adjusted prevalence ratios (APR) and 95% CIs to determine if vaccination was protective against gonorrhoea. We used individual-level data for descriptive analyses and infection-level data for regression analyses. FINDINGS: Between Jan 1, 2016, and Dec 31, 2018, we identified 167 706 infections (18 099 gonococcal infections, 124 876 chlamydial infections, and 24 731 gonococcal and chlamydial co-infections) among 109 737 individuals linked to the immunisation registries. 7692 individuals were vaccinated, of whom 4032 (52·4%) had received one dose, 3596 (46·7%) two doses, and 64 (<1·0%) at least three doses. Compared with no vaccination, complete vaccination series (APR 0·60, 95% CI 0·47-0·77; p<0·0001) and partial vaccination series (0·74, 0·63-0·88; p=0·0012) were protective against gonorrhoea. Complete MenB-4C vaccination series was 40% (95% CI 23-53) effective against gonorrhoea and partial MenB-4C vaccination series was 26% (12-37) effective. INTERPRETATION: MenB-4C vaccination was associated with a reduced gonorrhoea prevalence. MenB-4C could offer cross-protection against Neisseria gonorrhoeae. Development of an effective gonococcal vaccine might be feasible with implications for gonorrhoea prevention and control. FUNDING: None. |
Epidemiology of reported HIV and other sexually transmitted infections during the COVID-19 pandemic, New York City.
Braunstein SL , Slutsker JS , Lazar R , Shah D , Hennessy RR , Chen S , Pathela P , Daskalakis DC , Schillinger JA . J Infect Dis 2021 224 (5) 798-803 Early in the COVID-19 crisis, a statewide executive order ("PAUSE") severely restricted the movement of New Yorkers from March 23-June 7, 2020. We used NYC surveillance data for HIV, chlamydia, gonorrhea, and syphilis to describe trends in diagnosis and reporting surrounding PAUSE. During PAUSE, the volume of positive HIV/STI tests, and diagnoses of HIV, chlamydia, gonorrhea, and syphilis declined substantially, reaching a nadir in April before rebounding. Some shifts in characteristics of reported cases were identified. |
Baseline Asymptomatic Malaria Infection and Immunogenicity of rVSVG-ZEBOV-GP Vaccine: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE)
Mahon BE , Simon J , Widdowson MA , Samai M , Rogier E , Legardy-Williams J , Liu K , Schiffer J , Lange J , DeByle C , Pinner R , Schuchat A , Slutsker L , Goldstein S . J Infect Dis 2021 224 (11) 1907-1915 BACKGROUND: The effect of malaria infection on rVSVΔG-ZEBOV-GP (ERVEBO®) immunogenicity is unknown. METHODS: The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) vaccinated 7998 asymptomatic adults with rVSVΔG-ZEBOV-GP during the 2014-6 Ebola epidemic. In STRIVE's immunogenicity sub-study, participants provided blood samples at baseline, 1, 6, and 9-12 months. Anti-glycoprotein (GP) binding and neutralizing antibodies were measured using validated assays. Baseline samples were tested for malaria parasites by PCR. RESULTS: Overall, 506 participants enrolled in the immunogenicity sub-study and had ≥1 post-vaccination antibody titer. Of 499 participants with a result, baseline malaria parasitemia was detected in 73(14.6%). All GP-ELISA and plaque reduction neutralization test (PRNT) geometric mean titers (GMTs) at 1, 6, and 9-12 months were above baseline, and 94.1% of participants seroresponded by GP-ELISA (≥2-fold rise AND ≥200 EU/ml), while 81.5% seroresponded by PRNT (≥4-fold rise) at ≥1 post-vaccination assessment. In participants with baseline malaria parasitemia, the PRNT seroresponse proportion was lower, while PRNT GMTs and GP-ELISA seroresponse and GMTs showed a trend toward lower responses at 6 and 9-12 months. CONCLUSION: Asymptomatic adults with and without malaria parasitemia had robust immune responses to rVSVΔG-ZEBOV-GP persisting for 9-12 months. Responses in those with malaria parasitemia were somewhat lower. |
Assessing the Burden of Infant Deaths due to Herpes Simplex Virus, Human Immunodeficiency Virus, and Congenital Syphilis - United States, 1995-2017
Slutsker JS , Schillinger JA . Sex Transm Dis 2021 48 S4-S10 BACKGROUND: Despite advances in diagnosis and treatment, neonatal infection with herpes simplex virus (HSV) has a high case fatality rate. The national burden of neonatal HSV, and associated deaths, is unknown because this condition is not nationally notifiable. We investigated trends in HSV-related infant deaths, compared to infant deaths from congenital syphilis (CS) and human immunodeficiency virus (HIV). METHODS: Linked birth-death files for infant deaths during 1995-2017 were obtained from the National Center for Health Statistics. These files include infants who were born alive and died in the first 365 days of life and exclude stillbirths. We searched death certificates for disease codes indicating HSV, CS, or HIV, and calculated the frequency and rate of deaths for each infection, overall, by infant sex, and birthing parent age and race/ethnicity. RESULTS: Nationally, 1,591 deaths related to the infections of interest were identified: 1,271 related to HSV (79.9%), 234 HIV (14.7%), and 86 CS (5.4%). HSV-related deaths increased significantly from 0.83/100,000 live-births (95% CI:0.57-1.17) in 1995 to 1.77 (95% CI:1.37-2.24) in 2017. In contrast, HIV-related deaths declined: 1.64/100,000 (95% CI:1.27-2.10) in 1995 to 0.00 in 2017. There was a median of 3 CS-related deaths/year, with elevated frequencies in 1995-1996 and 2017 (n=8). HSV-related death rates were elevated among infants born to birthing parents aged <20 years (4.17/100,000; 95% CI:3.75-4.59) and to Black parents (2.86/100,000; 95% CI:2.58-3.15). CONCLUSIONS: Nationally, HSV-related infant deaths exceeded those caused by HIV and CS and appear to be increasing. Our findings underscore the need for an effective HSV vaccine, test technologies enabling rapid identification of infants exposed to HSV at delivery, and a focus on equity in prevention efforts. |
Mass testing and treatment on malaria in an area of western Kenya
Samuels AM , Odero NA , Odongo W , Otieno K , Were V , Shi YP , Sang T , Williamson J , Wiegand R , Hamel MJ , Kachur SP , Slutsker L , Lindblade KA , Kariuki SK , Desai MR . Clin Infect Dis 2021 72 (6) 1103-1104 We appreciate the thoughtful commentary provided by Hamer and Miller [1] and are pleased that they arrived at many of the same conclusions that we did; however, we would like to clarify a few points. | | First, we wish to correct the statement that, in our trial, mass testing and treatment (MTaT) was only implemented within the core areas of clusters. Rather, MTaT was implemented throughout intervention clusters, which included a core area ranging between 1 and 3 Km in diameter, and a 300-m buffer. As described, to limit contamination, inclusion criteria for the analytic sample required residence within the core area [2, 3]. |
Development of a new barcode-based, multiplex-PCR, next-generation-sequencing assay and data processing and analytical pipeline for multiplicity of infection detection of Plasmodium falciparum.
Mitchell RM , Zhou Z , Sheth M , Sergent S , Frace M , Nayak V , Hu B , Gimnig J , Ter Kuile F , Lindblade K , Slutsker L , Hamel MJ , Desai M , Otieno K , Kariuki S , Vigfusson Y , Shi YP . Malar J 2021 20 (1) 92 BACKGROUND: Simultaneous infection with multiple malaria parasite strains is common in high transmission areas. Quantifying the number of strains per host, or the multiplicity of infection (MOI), provides additional parasite indices for assessing transmission levels but it is challenging to measure accurately with current tools. This paper presents new laboratory and analytical methods for estimating the MOI of Plasmodium falciparum. METHODS: Based on 24 single nucleotide polymorphisms (SNPs) previously identified as stable, unlinked targets across 12 of the 14 chromosomes within P. falciparum genome, three multiplex PCRs of short target regions and subsequent next generation sequencing (NGS) of the amplicons were developed. A bioinformatics pipeline including B4Screening pathway removed spurious amplicons to ensure consistent frequency calls at each SNP location, compiled amplicons by SNP site diversity, and performed algorithmic haplotype and strain reconstruction. The pipeline was validated by 108 samples generated from cultured-laboratory strain mixtures in different proportions and concentrations, with and without pre-amplification, and using whole blood and dried blood spots (DBS). The pipeline was applied to 273 smear-positive samples from surveys conducted in western Kenya, then providing results into StrainRecon Thresholding for Infection Multiplicity (STIM), a novel MOI estimator. RESULTS: The 24 barcode SNPs were successfully identified uniformly across the 12 chromosomes of P. falciparum in a sample using the pipeline. Pre-amplification and parasite concentration, while non-linearly associated with SNP read depth, did not influence the SNP frequency calls. Based on consistent SNP frequency calls at targeted locations, the algorithmic strain reconstruction for each laboratory-mixed sample had 98.5% accuracy in dominant strains. STIM detected up to 5 strains in field samples from western Kenya and showed declining MOI over time (q < 0.02), from 4.32 strains per infected person in 1996 to 4.01, 3.56 and 3.35 in 2001, 2007 and 2012, and a reduction in the proportion of samples with 5 strains from 57% in 1996 to 18% in 2012. CONCLUSION: The combined approach of new multiplex PCRs and NGS, the unique bioinformatics pipeline and STIM could identify 24 barcode SNPs of P. falciparum correctly and consistently. The methodology could be applied to field samples to reliably measure temporal changes in MOI. |
Reduced exposure to malaria vectors following indoor residual spraying of pirimiphos-methyl in a high-burden district of rural Mozambique with high ownership of long-lasting insecticidal nets: entomological surveillance results from a cluster-randomized trial
Wagman JM , Varela K , Zulliger R , Saifodine A , Muthoni R , Magesa S , Chaccour C , Gogue C , Tynuv K , Seyoum A , Dengela D , Saúte F , Richardson JH , Fornadel C , Linton YM , Slutsker L , Candrinho B , Robertson M . Malar J 2021 20 (1) 54 BACKGROUND: The need to develop new products and novel approaches for malaria vector control is recognized as a global health priority. One approach to meeting this need has been the development of new products for indoor residual spraying (IRS) with novel active ingredients for public health. While initial results showing the impact of several of these next-generation IRS products have been encouraging, questions remain about how to best deploy them for maximum impact. To help address these questions, a 2-year cluster-randomized controlled trial to measure the impact of IRS with a microencapsulated formulation of pirimiphos-methyl (PM) in an area with high ownership of long-lasting insecticidal nets (LLINs) was conducted in a high-transmission district of central Mozambique with pyrethroid resistant vectors. Presented here are the results of the vector surveillance component of the trial. METHODS: The 2 year, two-armed trial was conducted in Mopeia District, Zambezia Province, Mozambique. In ten sentinel villages, five that received IRS with PM in October-November 2016 and again in October-November 2017 and five that received no IRS, indoor light trap collections and paired indoor-outdoor human landing collections catches (HLCs) were conducted monthly from September 2016 through October 2018. A universal coverage campaign in June 2017, just prior to the second spray round, distributed 131,540 standard alpha-cypermethrin LLINs across all study villages and increased overall net usage rates in children under 5 years old to over 90%. RESULTS: The primary malaria vector during the trial was Anopheles funestus sensu lato (s.l.), and standard World Health Organization (WHO) tube tests with this population indicated variable but increasing resistance to pyrethroids (including alpha-cypermethrin, from > 85% mortality in 2017 to 7% mortality in 2018) and uniform susceptibility to PM (100% mortality in both years). Over the entire duration of the study, IRS reduced An. funestus s.l. densities by 48% (CI(95) 33-59%; p < 0.001) in indoor light traps and by 74% (CI(95) 38-90%; p = 0.010) during indoor and outdoor HLC, though in each study year reductions in vector density were consistently greatest in those months immediately following the IRS campaigns and waned over time. Overall there was no strong preference for An. funestus to feed indoors or outdoors, and these biting behaviours did not differ significantly across study arms: observed indoor-outdoor biting ratios were 1.10 (CI(95) 1.00-1.21) in no-IRS villages and 0.88 (CI(95) 0.67-1.15) in IRS villages. The impact of IRS was consistent in reducing HLC exposures both indoors (75% reduction: CI(95) 47-88%; p = 0. < 0.001) and outdoors (68% reduction: CI(95) 22-87%; p = 0.012). While substantially fewer Anopheles gambiae s.l. were collected during the study, trends show a similar impact of IRS on this key vector group as well, with a 33% (CI(95) 7-53%; p = 0.019) reduction in mosquitoes collected in light traps and a non-statistically significant 39% reduction (p = 0.249) in HLC landing rates. CONCLUSION: IRS with PM used in addition to pyrethroid-only LLINs substantially reduced human exposures to malaria vectors during both years of the cluster-randomized controlled trial in Mopeia-a high-burden district where the primary vector, An. funestus s.l., was equally likely to feed indoors or outdoors and demonstrated increasing resistance to pyrethroids. Findings suggest that IRS with PM can provide effective vector control, including in some settings where pyrethroid-only ITNs are widely used. Trial registration clinicaltrials.gov , NCT02910934. Registered 22 September 2016, https://www.clinicaltrials.gov/ct2/show/NCT02910934. |
Impact of community-based mass testing and treatment on malaria infection prevalence in a high transmission area of western Kenya: A cluster randomized controlled trial
Samuels AM , Odero NA , Odongo W , Otieno K , Were V , Shi YP , Sang T , Williamson J , Wiegand R , Hamel MJ , Kachur SP , Slutsker L , Lindblade KA , Kariuki SK , Desai MR . Clin Infect Dis 2020 72 (11) 1927-1935 BACKGROUND: Global gains towards malaria elimination have been heterogeneous and have recently stalled. Interventions targeting afebrile malaria infections may be needed to address residual transmission. We studied the efficacy of repeated rounds of community-based mass testing and treatment (MTaT) on malaria infection prevalence in western Kenya. METHODS: Twenty clusters were randomly assigned to three rounds of MTaT per year for two years or control (standard-of-care for testing and treatment at public health facilities along with government sponsored mass long-lasting insecticidal net (LLIN) distributions). During rounds community health volunteers visited all households in intervention clusters and tested all consenting individuals with a rapid diagnostic test. Those positive were treated with dihydroartemisinin-piperaquine. Cross-sectional community infection prevalence surveys were performed in both study arms at baseline and each year after three rounds of MTaT. The primary outcome was the effect size of MTaT on parasite prevalence by microscopy between arms by year adjusted for age, reported LLIN use, enhanced vegetative index, and socio-economic status. RESULTS: Demographic and behavioral characteristics, including LLIN usage, were similar between arms at each survey. MTaT coverage ranged between 75.0-77.5% and 81.9-94.3% between the three rounds in year 1 and year 2, respectively. The adjusted effect size of MTaT on the prevalence of parasitemia between arms was 0.93 (CI: 0.79-1.08) and 0.92 (0.76-1.10) after year 1 and 2, respectively. CONCLUSIONS: MTaT performed three times per year over two years did not reduce malaria parasite prevalence in this high-transmission area. |
Do prescriptions for expedited partner therapy for chlamydia get filled Findings from a multi-jurisdictional evaluation, United States, 2017-2019
Slutsker JS , Tsang LB , Schillinger JA . Sex Transm Dis 2020 47 (6) 376-382 BACKGROUND: Expedited partner therapy (EPT) is commonly provided by prescription, however, the efficacy of this modality is unknown. We examined whether EPT prescriptions are filled when the cost barrier is removed. METHODS: To track EPT prescription fill rates, we used single-use pharmacy vouchers that covered the cost of azithromycin, 1-gram (chlamydia treatment). We recruited clinical sites to distribute vouchers to patients with chlamydia who would receive an EPT prescription under clinic policies. When distributing vouchers, sites recorded and retained: voucher unique identifier, sex and age of index patient, distribution date, and whether partner name was written on the EPT prescription. Pharmacists receiving vouchers entered the identifier, sex and age of presenting person, and redemption date into a standard pharmacy claim transmission system. Data for redeemed vouchers were retrieved from an industry portal and linked with data retained at clinical sites. RESULTS: Thirty-two clinical sites distributed 931 vouchers during 9/2017-01/2019; 382 (41%) were redeemed. Vouchers distributed to patients </=18 years (49/163; 30%) were less likely to be redeemed compared to those distributed to patients >18 years (322/736; 44%; p=0.001). Just over half of vouchers were redeemed the same day (195/351; 56%) and </=1 mile from the clinical site (188/349; 54%). After excluding an outlier site, vouchers accompanied by EPT prescriptions including a partner name (15/27; 56%) were more likely to be redeemed than those lacking a name (83/244; 34%; p=0.03). CONCLUSIONS: Less than half of EPT prescriptions were filled, even when medication was free. Whenever possible, EPT should be provided as drug-in-hand. |
Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: development of study site infrastructure and lessons learned
Odero NA , Samuels AM , Odongo W , Abong'o B , Gimnig J , Otieno K , Odero C , Obor D , Ombok M , Were V , Sang T , Hamel MJ , Kachur SP , Slutsker L , Lindblade KA , Kariuki S , Desai M . Malar J 2019 18 (1) 255 BACKGROUND: Malaria transmission is high in western Kenya and the asymptomatic infected population plays a significant role in driving the transmission. Mathematical modelling and simulation programs suggest that interventions targeting asymptomatic infections through mass testing and treatment (MTaT) or mass drug administration (MDA) have the potential to reduce malaria transmission when combined with existing interventions. OBJECTIVE: This paper describes the study site, capacity development efforts required, and lessons learned for implementing a multi-year community-based cluster-randomized controlled trial to evaluate the impact of MTaT for malaria transmission reduction in an area of high transmission in western Kenya. METHODS: The study partnered with Kenya's Ministry of Health (MOH) and other organizations on community sensitization and engagement to mobilize, train and deploy community health volunteers (CHVs) to deliver MTaT in the community. Within the health facilities, the study availed staff, medical and laboratory supplies and strengthened health information management system to monitor progress and evaluate impact of intervention. RESULTS: More than 80 Kenya MOH CHVs, 13 clinical officers, field workers, data and logistical staff were trained to carry out MTaT three times a year for 2 years in a population of approximately 90,000 individuals. A supply chain management was adapted to meet daily demands for large volumes of commodities despite the limitation of few MOH facilities having ideal storage conditions. Modern technology was adapted more to meet the needs of the high daily volume of collected data. CONCLUSIONS: In resource-constrained settings, large interventions require capacity building and logistical planning. This study found that investing in relationships with the communities, local governments, and other partners, and identifying and equipping the appropriate staff with the skills and technology to perform tasks are important factors for success in delivering an intervention like MTaT. |
Modelling the relationship between malaria prevalence as a measure of transmission and mortality across age groups
Khagayi S , Desai M , Amek N , Were V , Onyango ED , Odero C , Otieno K , Bigogo G , Munga S , Odhiambo F , Hamel MJ , Kariuki S , Samuels AM , Slutsker L , Gimnig J , Vounatsou P . Malar J 2019 18 (1) 247 BACKGROUND: Parasite prevalence has been used widely as a measure of malaria transmission, especially in malaria endemic areas. However, its contribution and relationship to malaria mortality across different age groups has not been well investigated. Previous studies in a health and demographic surveillance systems (HDSS) platform in western Kenya quantified the contribution of incidence and entomological inoculation rates (EIR) to mortality. The study assessed the relationship between outcomes of malaria parasitaemia surveys and mortality across age groups. METHODS: Parasitological data from annual cross-sectional surveys from the Kisumu HDSS between 2007 and 2015 were used to determine malaria parasite prevalence (PP) and clinical malaria (parasites plus reported fever within 24 h or temperature above 37.5 degrees C). Household surveys and verbal autopsy (VA) were used to obtain data on all-cause and malaria-specific mortality. Bayesian negative binomial geo-statistical regression models were used to investigate the association of PP/clinical malaria with mortality across different age groups. Estimates based on yearly data were compared with those from aggregated data over 4 to 5-year periods, which is the typical period that mortality data are available from national demographic and health surveys. RESULTS: Using 5-year aggregated data, associations were established between parasite prevalence and malaria-specific mortality in the whole population (RRmalaria = 1.66; 95% Bayesian Credible Intervals: 1.07-2.54) and children 1-4 years (RRmalaria = 2.29; 1.17-4.29). While clinical malaria was associated with both all-cause and malaria-specific mortality in combined ages (RRall-cause = 1.32; 1.01-1.74); (RRmalaria = 2.50; 1.27-4.81), children 1-4 years (RRall-cause = 1.89; 1.00-3.51); (RRmalaria = 3.37; 1.23-8.93) and in older children 5-14 years (RRall-cause = 3.94; 1.34-11.10); (RRmalaria = 7.56; 1.20-39.54), no association was found among neonates, adults (15-59 years) and the elderly (60+ years). Distance to health facilities, socioeconomic status, elevation and survey year were important factors for all-cause and malaria-specific mortality. CONCLUSION: Malaria parasitaemia from cross-sectional surveys was associated with mortality across age groups over 4 to 5 year periods with clinical malaria more strongly associated with mortality than parasite prevalence. This effect was stronger in children 5-14 years compared to other age-groups. Further analyses of data from other HDSS sites or similar platforms would be useful in investigating the relationship between malaria and mortality across different endemicity levels. |
The safety of atovaquone-proguanil for the prevention and treatment of malaria in pregnancy: A systematic review
Andrejko KL , Mayer RC , Kovacs S , Slutsker E , Bartlett E , Tan KR , Gutman JR . Travel Med Infect Dis 2019 27 20-26 BACKGROUND: Malaria infection poses a significant risk in pregnancy, yet chemoprophylaxis for pregnant women is limited. A systematic review was conducted to evaluate the incidence of adverse outcomes after atovaquone-proguanil (AP) exposure during pregnancy. METHODS: Following PRISMA guidelines, the authors searched PubMed, MEDLINE, and the Malaria in Pregnancy Consortium Library to identify relevant literature including infant outcomes after exposure to atovaquone, proguanil, or AP in pregnancy. Two authors independently screened the titles, abstracts, and full texts, and extracted data into an EpiInfo database. Overall proportions and 95% confidence intervals of adverse outcomes were determined by pooling data across studies. RESULTS: Of 455 records identified, 16 studies were included: ten AP studies and six proguanil studies. The overall proportions and 95% confidence intervals (CI) of adverse outcomes reported for the 446 women exposed to AP include miscarriage (8.08% CI: 5.07, 12.08%), stillbirth (1.05% CI: 0.03, 5.73%), early neonatal death (0% CI: 0, 7.4%), and congenital anomalies (2.56% CI: 1.28, 4.53%). CONCLUSIONS: The limited available data suggest that outcomes following AP exposure during pregnancy are similar to expected rates in similar populations. AP may be a promising option for pregnant women, but further data are needed on its safety in pregnancy. |
Factors contributing to congenital syphilis cases - New York City, 2010-2016
Slutsker JS , Hennessy RR , Schillinger JA . MMWR Morb Mortal Wkly Rep 2018 67 (39) 1088-1093 Congenital syphilis occurs when syphilis is transmitted from a pregnant woman to her fetus; congenital syphilis can be prevented through screening and treatment during pregnancy. Transmission to the fetus can occur at any stage of maternal infection, but is more likely during primary and secondary syphilis, with rates of transmission up to 100% at these stages (1). Untreated syphilis during pregnancy can cause spontaneous abortion, stillbirth, and early infant death. During 2013-2017, national rates of congenital syphilis increased from 9.2 to 23.3 cases per 100,000 live births (2), coinciding with increasing rates of primary and secondary syphilis among women of reproductive age (3). In New York City (NYC), cases of primary and secondary syphilis among women aged 15-44 years increased 147% during 2015-2016. To evaluate measures to prevent congenital syphilis, the NYC Department of Health and Mental Hygiene (DOHMH) reviewed data for congenital syphilis cases reported during 2010-2016 and identified patient-, provider-, and systems-level factors that contributed to these cases. During this period, 578 syphilis cases among pregnant women aged 15-44 years were reported to DOHMH; a congenital syphilis case was averted or otherwise failed to occur in 510 (88.2%) of these pregnancies, and in 68, a case of congenital syphilis occurred (eight cases per 100,000 live births).* Among the 68 pregnant women associated with these congenital syphilis cases, 21 (30.9%) did not receive timely (>/=45 days before delivery) prenatal care. Among the 47 pregnant women who did access timely prenatal care, four (8.5%) did not receive an initial syphilis test until <45 days before delivery, and 22 (46.8%) acquired syphilis after an initial nonreactive syphilis test. These findings support recommendations that health care providers screen all pregnant women for syphilis at the first prenatal care visit and then rescreen women at risk in the early third trimester. |
Reduced nevirapine concentrations among HIV-positive women receiving mefloquine for intermittent preventive treatment for malaria control during pregnancy
Haaland R , Otieno K , Martin A , Katana A , Dinh C , Slutsker L , Menendez C , Gonzalez R , Williamson J , Heneine W , Desai M . AIDS Res Hum Retroviruses 2018 34 (11) 912-915 Clinical trials demonstrated intermittent preventive treatment in pregnancy (IPTp) with mefloquine (MQ) reduced malaria rates among pregnant women, yet an unexpected higher risk of mother to child transmission (MTCT) of HIV among HIV-positive women receiving MQ has also been observed. To determine if interactions between antiretroviral drugs (ARVs) and MQ could contribute to the increased MTCT observed in women receiving MQ, we performed a retrospective cross-sectional analysis of ARVs in peripheral blood plasma (maternal plasma) and cord blood plasma (cord plasma) collected at delivery from 186 mothers participating in a randomized clinical trial of MQ compared to placebo in Kenya. Plasma zidovudine (AZT), lamivudine (3TC) and nevirapine (NVP) concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. ARVs were detected in maternal plasma and cord plasma specimens in similar proportions between the two study arms. Median concentrations of AZT and 3TC were not significantly lower in the MQ arm compared to the placebo arm for maternal plasma and cord plasma (p > 0.05). However, median NVP concentrations were significantly lower in the MQ study arm compared to the placebo study arm in both maternal plasma (1597 ng/mL vs. 2353 ng/mL, Mann-Whitney Rank Sum, p = 0.023) and cord plasma (2038 ng/mL vs. 2434 ng/mL, p = 0.048). Reduced NVP concentrations in maternal and cord plasma of women receiving MQ suggest MQ may affect NVP metabolism for both mother and infant. These results highlight the need to evaluate potential drug-drug interactions between candidate antimalarials and ARVs for use in pregnant women. |
Using reports of latent tuberculosis infection among young children to identify tuberculosis transmission in New York City, 2006-2012
Slutsker JS , Trieu L , Crossa A , Ahuja SD . Am J Epidemiol 2018 187 (6) 1303-1310 The presence of latent tuberculosis infection (LTBI) in young children indicates recent tuberculosis (TB) transmission. We reviewed surveillance reports of children with LTBI to assess whether more follow-up is needed to prevent TB in this high-risk population. Data on all children under 5 years of age who were reported by health-care providers or laboratories to the New York City Department of Health during 2006-2012 were abstracted from the TB surveillance and case management system, and those with LTBI were identified. Potential source cases, defined as any infectious TB case diagnosed in the 2 years before a child was reported and whose residence was within 0.5 miles (0.8 km) of the child's residence, were identified. Neighborhood risk factors for TB transmission were examined. Among 3,511 reports of children under age 5 years, 1,722 (49%) had LTBI. The children were aged 2.9 years, on average, and most (64%) had been born in the United States. A potential source case was identified for 92% of the children; 27 children lived in the same building as a TB patient. Children with potential source cases were more likely to reside in neighborhoods with high TB incidence, poverty, and population density. The high proportion of children born in the United States and the young average age of the cases imply that undetected TB transmission occurred. Monitoring reports could be used to identify places where transmission occurred, and additional investigation is needed to prevent TB disease. |
Health conditions in an adult population in Sierra Leone: Data reported from the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE)
Fombah AE , Goldstein ST , Jarrett OD , Jalloh MI , El-Khorazaty J , Lisk DR , Legardy-Williams J , Pratt DA , George PM , Russell JBW , Schrag SJ , Dawson P , Deen GF , Carr W , Lindblad R , James F , Bah MM , Yillia JF , Sandy JD , Turay PE , Conteh MA , Slutsker L , Mahon BE , Samai M , Seward JF . J Infect Dis 2018 217 S75-s80 Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. |
The epidemiology of syphilis in New York City; historic trends and the current outbreak among men who have sex with men, 2016
Schillinger JA , Slutsker JS , Pathela P , Klingler E , Hennessy RR , Toro B , Blank S . Sex Transm Dis 2018 45 S48-S54 BACKGROUND: Male primary and secondary (P&S) and early latent (EL) syphilis cases have increased markedly in New York City (NYC) after a historic nadir in 1998. The majority of cases are among men-who-have-sex-with-men (MSM). We describe the epidemiology of syphilis among NYC males to provide a model of how one jurisdiction collects, analyzes, interprets, uses, and disseminates local data to guide programmatic activities directed at syphilis control. METHODS: We analyzed trends in reported infectious syphilis cases using routinely collected surveillance and case investigation data. HIV co-infection status was ascertained by routine deterministic match between sexually transmitted infection and HIV surveillance registries, and self-report. We mapped diagnosing facilities to display the relative contribution of different public/private facilities. Characteristics of male syphilis cases diagnosed in public sexual health (SH) clinics were compared to those diagnosed elsewhere. RESULTS: During 2012-2016, male P&S syphilis case rates increased 81%, from 24.8 to 44.8/100,000 (1832 cases); the highest rates were among black non-Hispanic men. Overall, 87.6% (902/1030) of interviewed men in 2016 disclosed >1 male partner. HIV co-infection rates are high among MSM with P&S syphilis (43.4%; 394/907 in 2016), but appear to be decreasing (from 54.1% in 2012). Maps highlighted SH clinics' contribution to diagnosing P&S syphilis cases among men of color. HIV co-infection rates were lower among men with P&S syphilis diagnosed in SH clinics than among those diagnosed elsewhere (34%, SH clinics versus 49%, other settings, p<0.0001). CONCLUSIONS: Syphilis infections continue to increase among MSM in NYC. Novel interventions responsive to the drivers of the current outbreak are needed. |
Infant and child mortality in relation to malaria transmission in KEMRI/CDC HDSS, Western Kenya: validation of verbal autopsy
Amek NO , Van Eijk A , Lindblade KA , Hamel M , Bayoh N , Gimnig J , Laserson KF , Slutsker L , Smith T , Vounatsou P . Malar J 2018 17 (1) 37 BACKGROUND: Malaria transmission reduction is a goal of many malaria control programmes. Little is known of how much mortality can be reduced by specific reductions in transmission. Verbal autopsy (VA) is widely used for estimating malaria specific mortality rates, but does not reliably distinguish malaria from other febrile illnesses. Overall malaria attributable mortality includes both direct and indirect deaths. It is unclear what proportion of the deaths averted by reducing malaria transmission are classified as malaria in VA. METHODS: Both all-cause, and cause-specific mortality reported by VA for children under 5 years of age, were assembled from the KEMRI/CDC health and demographic surveillance system in Siaya county, rural Western Kenya for the years 2002-2004. These were linked to household-specific estimates of the Plasmodium falciparum entomological inoculation rate (EIR) based on high resolution spatio-temporal geostatistical modelling of entomological data. All-cause and malaria specific mortality (by VA), were analysed in relation to EIR, insecticide-treated net use (ITN), socioeconomic status (SES) and parameters describing space-time correlation. Time at risk for each child was analysed using Bayesian geostatistical Cox proportional hazard models, with time-dependent covariates. The outputs were used to estimate the diagnostic performance of VA in measuring mortality that can be attributed to malaria exposure. RESULTS: The overall under-five mortality rate was 80 per 1000 person-years during the study period. Eighty-one percent of the total deaths were assigned causes of death by VA, with malaria assigned as the main cause of death except in the neonatal period. Although no trend was observed in malaria-specific mortality assessed by VA, ITN use was associated with reduced all-cause mortality in infants (hazard ratio 0.15, 95% CI 0.02, 0.63) and the EIR was strongly associated with both all-cause and malaria-specific mortality. 48.2% of the deaths could be attributed to malaria by analysing the exposure-response relationship, though only 20.5% of VAs assigned malaria as the cause and the sensitivity of VAs was estimated to be only 26%. Although VAs assigned some deaths to malaria even in areas where there was estimated to be no exposure, the specificity of the VAs was estimated to be 85%. CONCLUSION: Interventions that reduce P. falciparum transmission intensity will not only significantly reduce malaria-diagnosed mortality, but also mortality assigned to other causes in under-5 year old children in endemic areas. In this setting, the VA tool based on clinician review substantially underestimates the number of deaths that could be averted by reducing malaria exposure in childhood, but has a reasonably high specificity. This suggests that malaria transmission-reducing interventions such as ITNs can potentially reduce overall child mortality by as much as twice the total direct malaria burden estimated from VAs. |
Association of maternal KIR gene content polymorphisms with reduction in perinatal transmission of HIV-1.
Omosun YO , Blackstock AJ , Williamson J , van Eijk AM , Ayisi J , Otieno J , Lal RB , Ter Kuile FO , Slutsker L , Shi YP . PLoS One 2018 13 (1) e0191733 The role of killer cell immunoglobulin-like receptors (KIRs) in the transmission of HIV-1 has not been extensively studied. Here, we investigated the association of KIR gene content polymorphisms with perinatal HIV-1 transmission. The KIR gene family comprising 16 genes was genotyped in 313 HIV-1 positive Kenyan mothers paired with their infants. Gene content polymorphisms were presented as presence of individual KIR genes, haplotypes, genotypes and KIR gene concordance. The genetic data were analyzed for associations with perinatal transmission of HIV. There was no association of infant KIR genes with perinatal HIV-1 transmission. After adjustment for gravidity, viral load, and CD4 cell count, there was evidence of an association between reduction in perinatal HIV-1 transmission and the maternal individual KIR genes KIR2DL2 (adjusted OR = 0.50; 95% CI: 0.24-1.02, P = 0.06), KIR2DL5 (adjusted OR = 0.47; 95% CI: 0.23-0.95, P = 0.04) and KIR2DS5 (adjusted OR = 0.39; 95% CI: 0.18-0.80, P = 0.01). Furthermore, these maternal KIR genes were only significantly associated with reduction in perinatal HIV transmission in women with CD4 cell count >/= 350 cells/ mul and viral load <10000 copies/ml. Concordance analysis showed that when both mother and child had KIR2DS2, there was less likelihood of perinatal HIV-1 transmission (adjusted OR = 0.44; 95% CI: 0.20-0.96, P = 0.039). In conclusion, the maternal KIR genes KIR2DL2, KIR2DL5, KIR2DS5, and KIR2DS2 were associated with reduction of HIV-1 transmission from mother to child. Furthermore, maternal immune status is an important factor in the association of KIR with perinatal HIV transmission. |
Malaria, malnutrition, and birthweight: A meta-analysis using individual participant data
Cates JE , Unger HW , Briand V , Fievet N , Valea I , Tinto H , D'Alessandro U , Landis SH , Adu-Afarwuah S , Dewey KG , Ter Kuile FO , Desai M , Dellicour S , Ouma P , Gutman J , Oneko M , Slutsker L , Terlouw DJ , Kariuki S , Ayisi J , Madanitsa M , Mwapasa V , Ashorn P , Maleta K , Mueller I , Stanisic D , Schmiegelow C , Lusingu JPA , van Eijk AM , Bauserman M , Adair L , Cole SR , Westreich D , Meshnick S , Rogerson S . PLoS Med 2017 14 (8) e1002373 BACKGROUND: Four studies previously indicated that the effect of malaria infection during pregnancy on the risk of low birthweight (LBW; <2,500 g) may depend upon maternal nutritional status. We investigated this dependence further using a large, diverse study population. METHODS AND FINDINGS: We evaluated the interaction between maternal malaria infection and maternal anthropometric status on the risk of LBW using pooled data from 14,633 pregnancies from 13 studies (6 cohort studies and 7 randomized controlled trials) conducted in Africa and the Western Pacific from 1996-2015. Studies were identified by the Maternal Malaria and Malnutrition (M3) initiative using a convenience sampling approach and were eligible for pooling given adequate ethical approval and availability of essential variables. Study-specific adjusted effect estimates were calculated using inverse probability of treatment-weighted linear and log-binomial regression models and pooled using a random-effects model. The adjusted risk of delivering a baby with LBW was 8.8% among women with malaria infection at antenatal enrollment compared to 7.7% among uninfected women (adjusted risk ratio [aRR] 1.14 [95% confidence interval (CI): 0.91, 1.42]; N = 13,613), 10.5% among women with malaria infection at delivery compared to 7.9% among uninfected women (aRR 1.32 [95% CI: 1.08, 1.62]; N = 11,826), and 15.3% among women with low mid-upper arm circumference (MUAC <23 cm) at enrollment compared to 9.5% among women with MUAC ≥ 23 cm (aRR 1.60 [95% CI: 1.36, 1.87]; N = 9,008). The risk of delivering a baby with LBW was 17.8% among women with both malaria infection and low MUAC at enrollment compared to 8.4% among uninfected women with MUAC ≥ 23 cm (joint aRR 2.13 [95% CI: 1.21, 3.73]; N = 8,152). There was no evidence of synergism (i.e., excess risk due to interaction) between malaria infection and MUAC on the multiplicative (p = 0.5) or additive scale (p = 0.9). Results were similar using body mass index (BMI) as an anthropometric indicator of nutritional status. Meta-regression results indicated that there may be multiplicative interaction between malaria infection at enrollment and low MUAC within studies conducted in Africa; however, this finding was not consistent on the additive scale, when accounting for multiple comparisons, or when using other definitions of malaria and malnutrition. The major limitations of the study included availability of only 2 cross-sectional measurements of malaria and the limited availability of ultrasound-based pregnancy dating to assess impacts on preterm birth and fetal growth in all studies. CONCLUSIONS: Pregnant women with malnutrition and malaria infection are at increased risk of LBW compared to women with only 1 risk factor or none, but malaria and malnutrition do not act synergistically. |
Burden and impact of Plasmodium vivax in pregnancy: A multi-centre prospective observational study.
Bardaji A , Martinez-Espinosa FE , Arevalo-Herrera M , Padilla N , Kochar S , Ome-Kaius M , Botto-Menezes C , Castellanos ME , Kochar DK , Kochar SK , Betuela I , Mueller I , Rogerson S , Chitnis C , Hans D , Menegon M , Severini C , Del Portillo H , Dobano C , Mayor A , Ordi J , Piqueras M , Sanz S , Wahlgren M , Slutsker L , Desai M , Menendez C . PLoS Negl Trop Dis 2017 11 (6) e0005606 BACKGROUND: Despite that over 90 million pregnancies are at risk of Plasmodium vivax infection annually, little is known about the epidemiology and impact of the infection in pregnancy. METHODOLOGY AND PRINCIPAL FINDINGS: We undertook a health facility-based prospective observational study in pregnant women from Guatemala (GT), Colombia (CO), Brazil (BR), India (IN) and Papua New Guinea PNG). Malaria and anemia were determined during pregnancy and fetal outcomes assessed at delivery. A total of 9388 women were enrolled at antennal care (ANC), of whom 53% (4957) were followed until delivery. Prevalence of P. vivax monoinfection in maternal blood at delivery was 0.4% (20/4461) by microscopy [GT 0.1%, CO 0.5%, BR 0.1%, IN 0.2%, PNG 1.2%] and 7% (104/1488) by PCR. P. falciparum monoinfection was found in 0.5% (22/4463) of women by microscopy [GT 0%, CO 0.5%, BR 0%, IN 0%, PNG 2%]. P. vivax infection was observed in 0.4% (14/3725) of placentas examined by microscopy and in 3.7% (19/508) by PCR. P. vivax in newborn blood was detected in 0.02% (1/4302) of samples examined by microscopy [in cord blood; 0.05% (2/4040) by microscopy, and 2.6% (13/497) by PCR]. Clinical P. vivax infection was associated with increased risk of maternal anemia (Odds Ratio-OR, 5.48, [95% CI 1.83-16.41]; p = 0.009), while submicroscopic vivax infection was not associated with increased risk of moderate-severe anemia (Hb<8g/dL) (OR, 1.16, [95% CI 0.52-2.59]; p = 0.717), or low birth weight (<2500g) (OR, 0.52, [95% CI, 0.23-1.16]; p = 0.110). CONCLUSIONS: In this multicenter study, the prevalence of P. vivax infection in pregnancy by microscopy was overall low across all endemic study sites; however, molecular methods revealed a significant number of submicroscopic infections. Clinical vivax infection in pregnancy was associated with maternal anemia, which may be deleterious for infant's health. These results may help to guide maternal health programs in settings where vivax malaria is endemic; they also highlight the need of addressing a vulnerable population such as pregnant women while embracing malaria elimination in endemic countries. |
Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: study design and methodology for a cluster randomized controlled trial
Samuels AM , Awino N , Odongo W , Abong'o B , Gimnig J , Otieno K , Shi YP , Were V , Allen DR , Were F , Sang T , Obor D , Williamson J , Hamel MJ , Patrick Kachur S , Slutsker L , Lindblade KA , Kariuki S , Desai M . Malar J 2017 16 (1) 240 Most human Plasmodium infections in western Kenya are asymptomatic and are believed to contribute importantly to malaria transmission. Elimination of asymptomatic infections requires active treatment approaches, such as mass testing and treatment (MTaT) or mass drug administration (MDA), as infected persons do not seek care for their infection. Evaluations of community-based approaches that are designed to reduce malaria transmission require careful attention to study design to ensure that important effects can be measured accurately. This manuscript describes the study design and methodology of a cluster-randomized controlled trial to evaluate a MTaT approach for malaria transmission reduction in an area of high malaria transmission. Ten health facilities in western Kenya were purposively selected for inclusion. The communities within 3 km of each health facility were divided into three clusters of approximately equal population size. Two clusters around each health facility were randomly assigned to the control arm, and one to the intervention arm. Three times per year for 2 years, after the long and short rains, and again before the long rains, teams of community health volunteers visited every household within the intervention arm, tested all consenting individuals with malaria rapid diagnostic tests, and treated all positive individuals with an effective anti-malarial. The effect of mass testing and treatment on malaria transmission was measured through population-based longitudinal cohorts, outpatient visits for clinical malaria, periodic population-based cross-sectional surveys, and entomological indices. |
Maternal Malaria and Malnutrition (M3) initiative, a pooled birth cohort of 13 pregnancy studies in Africa and the Western Pacific
Unger HW , Cates JE , Gutman J , Briand V , Fievet N , Valea I , Tinto H , d'Alessandro U , Landis SH , Adu-Afarwuah S , Dewey KG , Ter Kuile F , Dellicour S , Ouma P , Slutsker L , Terlouw DJ , Kariuki S , Ayisi J , Nahlen B , Desai M , Madanitsa M , Kalilani-Phiri L , Ashorn P , Maleta K , Mueller I , Stanisic D , Schmiegelow C , Lusingu J , Westreich D , van Eijk AM , Meshnick S , Rogerson S . BMJ Open 2016 6 (12) e012697 PURPOSE: The Maternal Malaria and Malnutrition (M3) initiative has pooled together 13 studies with the hope of improving understanding of malaria-nutrition interactions during pregnancy and to foster collaboration between nutritionists and malariologists. PARTICIPANTS: Data were pooled on 14 635 singleton, live birth pregnancies from women who had participated in 1 of 13 pregnancy studies. The 13 studies cover 8 countries in Africa and Papua New Guinea in the Western Pacific conducted from 1996 to 2015. FINDINGS TO DATE: Data are available at the time of antenatal enrolment of women into their respective parent study and at delivery. The data set comprises essential data such as malaria infection status, anthropometric assessments of maternal nutritional status, presence of anaemia and birth weight, as well as additional variables such gestational age at delivery for a subset of women. Participating studies are described in detail with regard to setting and primary outcome measures, and summarised data are available from each contributing cohort. FUTURE PLANS: This pooled birth cohort is the largest pregnancy data set to date to permit a more definite evaluation of the impact of plausible interactions between poor nutritional status and malaria infection in pregnant women on fetal growth and gestational length. Given the current comparative lack of large pregnancy cohorts in malaria-endemic settings, compilation of suitable pregnancy cohorts is likely to provide adequate statistical power to assess malaria-nutrition interactions, and could point towards settings where such interactions are most relevant. The M3 cohort may thus help to identify pregnant women at high risk of adverse outcomes who may benefit from tailored intensive antenatal care including nutritional supplements and alternative or intensified malaria prevention regimens, and the settings in which these interventions would be most effective. |
Intermittent preventive treatment with sulfadoxine-pyrimethamine: More than just an antimalarial?
Gutman J , Slutsker L . Am J Trop Med Hyg 2016 96 (1) 9-10 Malaria in pregnancy is associated with increased risk for both maternal and neonatal adverse outcomes, notably low birthweight and neonatal mortality.1 Since 2004, following studies that showed that intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) reduced the risk of these adverse events,2 the World Health Organization (WHO) recommended IPTp-SP for all areas in Africa with moderate-to-high malaria transmission.3 IPTp-SP is associated with significant reductions in low birthweight, with a protective efficacy of approximately 26% in an analysis of national survey data from 32 countries.4 This impact has been presumed to be a result of the antimalarial effects of SP. Because resistance to SP has increased, particularly in eastern and southern Africa, SP is no longer recommended for treatment of acute malaria illness, even in combination with artemisinins. Despite this, even in areas where the efficacy of SP to clear parasitemia has clearly decreased, IPTp-SP has continued to show benefit for preventing low birthweight.5 Moreover, no other antimalarials have yet been shown to be an ideal replacement for SP for IPTp. Studies evaluating potential alternative IPTp regimens have had mixed outcomes on birthweight,6,7 leading to the hypothesis that SP may exert some of its effect through antibacterial or anti-inflammatory actions.6 In Lusaka, Zambia, where malaria parasite prevalence is < 1%, Stoner and others show that among human immunodeficiency virus (HIV)-positive women, receipt of IPTp-SP was associated with a dose-dependent reduction in the risk of low birthweight, as well as an increase in gestational age, further suggesting a mechanism other than antimalarial activity as an explanation for a reduced risk of low birthweight among women receiving IPTp-SP during pregnancy (Stoner and others). |
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