Last data update: Apr 28, 2025. (Total: 49156 publications since 2009)
Records 1-16 (of 16 Records) |
Query Trace: Subramaniam G[original query] |
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Attitudes toward COVID-19 illness and COVID-19 vaccination among pregnant women: a cross-sectional multicenter study during August-December 2020 (preprint)
Battarbee AN , Stockwell MS , Varner M , Newes-Adeyi G , Daugherty M , Gyamfi-Bannerman C , Tita AT , Vorwaller K , Vargas C , Subramaniam A , Reichle L , Galang RR , Powers E , Lucca-Susana M , Parks M , Chen TJ , Razzaghi H , Dawood FS . medRxiv 2021 2021.03.26.21254402 Objective Evaluate pregnant women’s attitudes toward COVID-19 illness and vaccination and identify factors associated with vaccine acceptability.Study Design Cross-sectional survey among pregnant women enrolled in a prospective COVID-19 cohort study in Salt Lake City, UT, Birmingham, AL, and New York, NY, August 9– December 10, 2020. Women were eligible if they were 18-50 years old and <28 weeks of gestation. Upon enrollment, women completed surveys regarding concerns about COVID-19 illness and likelihood of getting COVID-19 vaccine if one were available during pregnancy. Vaccine acceptability was defined as a response of “very likely” or “somewhat likely” on a 4-point Likert scale. Factors associated with vaccine acceptability were assessed with multivariable logistic regression.Results Of 939 pregnant women eligible for the main cohort study, 915 (97%) consented to participate. Among these 915 women, 39% self-identified as White, 23% Black, 33% Hispanic, and 4% Other. Sixty-two percent received an influenza vaccine last season. Seventy-two percent worried about getting sick with COVID-19. If they were to get sick, 92% worried about harm to their pregnancy and 80% about harm to themselves. Only 41% reported they would get a vaccine. Of women who were unlikely to get vaccinated, the most frequently cited concern was vaccine safety for their pregnancy (82%). Non-Hispanic Black and Hispanic women had lower odds of accepting a vaccine compared with non-Hispanic White women (adjusted odds ratios (aOR) 0.4, 95%CI 0.2–0.6 for both). Receipt of influenza vaccine during the previous season was associated with higher odds of vaccine acceptability (aOR 2.1, 95%CI 1.5-3.0).Conclusion Although most pregnant women worried about COVID-19 illness, <50% were willing to get vaccinated during pregnancy. Racial and ethnic disparities in plans to accept COVID-19 vaccine highlight the need to prioritize strategies to address perceived barriers among groups at high risk for COVID-19.Competing Interest StatementAll authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; author CGB has an unrestricted grant from SMFM/AMAG to study prematurity.Funding StatementFunding: This study was funded by the US Centers for Disease Control and Prevention through Contract # 75D30120C08150 with Abt Associates.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Centralized Institutional Review Board approval was obtained (IRB-AAAT1906), and informed consent was obtained from all participants. The Columbia University Medical Center IRB served as the centralized IRB for this study.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData will automatically be sequestered by site. |
Community-based surveys for Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions in selected regions of mainland Tanzania (preprint)
Bakari C , Jones S , Subramaniam G , Mandara CI , Chiduo MG , Rumisha S , Chacky F , Molteni F , Mandike R , Mkude S , Njau R , Herman C , Nace DP , Mohamed A , Udhayakumar V , Kibet CK , Nyanjom SG , Rogier E , Ishengoma DS . medRxiv 2020 2020.05.12.20097766 Background Despite recent reports of false negative results among histidine-rich protein 2 (HRP2) based-malaria rapid diagnostic tests (mRDTs) caused by pfhrp2/3 gene deletions in different countries, there is paucity of data in Tanzania.Methods This study assessed the status of pfhrp2/3 deletions in 7,543 blood samples using laboratory multiplex antigen detection (Plasmodium lactate dehydrogenase - pLDH, aldolase, and HRP2). Samples showing mRDT false negativity or aberrant relationship of HRP2 to pan-Plasmodium antigens were genotyped for pfhrp2/3genes.Results Of all samples, 2,417 (32.0%) were positive for any Plasmodium antigens while 5,126 (68.0%) were negative. About 99.8% (n=2,411) of antigen positive samples had HRP2, but 6 (0.2%) had only pLDH and/or pAldolase. Thirteen samples had atypical relationships between pan-Plasmodium antigens and HRP2, but were positive by PCR. An additional 16 samples with negative HRP2 mRDTs but positive by microscopy were also chosen; all giving 35 samples genotyped for pfhrp2/3. Of 35 samples, 4 (11.4%) failed to consistently amplify positive control genes (pfmsp1 and pfmsp2), and pfhrp2 and pfhrp3 genes were successfully amplified in 31 (88.6%) samples.Conclusions Lack of pfhrp2 and/or pfhrp3 genes deletions in Plasmodium falciparum parasites supports continued use of HRP2-based mRDTs for routine malaria diagnosis in Tanzania.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe field component of this study was supported by The Global Fund through National Malaria Control Programme of the Tanzanian Ministry of Health. The CDC laboratory work was supported by Malaria Branch and Catherine Bakari’s MSc studies was funded by the Developing Excellence in Leadership and Genomics for Malaria Elimination (DELGEME) project with funding from the Developing Excellence in Leadership and Training (DELTAS) Africa Initiative, of the African Academy of Sciences (AAS).Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request |
Portable and cost-effective genetic detection and characterization of Plasmodium falciparum hrp2 using the MinION sequencer.
Sabin S , Jones S , Patel D , Subramaniam G , Kelley J , Aidoo M , Talundzic E . Sci Rep 2023 13 (1) 2893 ![]() ![]() The prevalence of Plasmodium falciparum hrp2 (pfhrp2)-deleted parasites threatens the efficacy of the most used and sensitive malaria rapid diagnostic tests and highlights the need for continued surveillance for this gene deletion. While PCR methods are adequate for determining pfhrp2 presence or absence, they offer a limited view of its genetic diversity. Here, we present a portable sequencing method using the MinION. Pfhrp2 amplicons were generated from individual samples, barcoded, and pooled for sequencing. To overcome potential crosstalk between barcodes, we implemented a coverage-based threshold for pfhrp2 deletion confirmation. Amino acid repeat types were then counted and visualized with custom Python scripts following de novo assembly. We evaluated this assay using well-characterized reference strains and 152 field isolates with and without pfhrp2 deletions, of which 38 were also sequenced on the PacBio platform to provide a standard for comparison. Of 152 field samples, 93 surpassed the positivity threshold, and of those samples, 62/93 had a dominant pfhrp2 repeat type. PacBio-sequenced samples with a dominant repeat-type profile from the MinION sequencing data matched the PacBio profile. This field-deployable assay can be used alone for surveilling pfhrp2 diversity or as a sequencing-based addition to the World Health Organization's existing deletion surveillance protocol. |
Development and characterization of secondary standards for nucleic acid amplification technology (NAAT) assays for detection of hepatitis E virus.
Fares-Gusmao Rafaelle, Jiang Zhen, Subramaniam Sakthivel, Visser Bryan J, Scott Alysia, Ishida Yuji, Saito Takeshi, Baylis Sally A, McGivern David R, . Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 2022 157105325 . Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 2022 157105325 ![]() Fares-Gusmao Rafaelle, Jiang Zhen, Subramaniam Sakthivel, Visser Bryan J, Scott Alysia, Ishida Yuji, Saito Takeshi, Baylis Sally A, McGivern David R, . Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 2022 157105325 |
Attitudes Toward COVID-19 Illness and COVID-19 Vaccination among Pregnant Women: A Cross-Sectional Multicenter Study during August-December 2020.
Battarbee AN , Stockwell MS , Varner M , Newes-Adeyi G , Daugherty M , Gyamfi-Bannerman C , Tita AT , Vorwaller K , Vargas C , Subramaniam A , Reichle L , Galang RR , Powers E , Lucca-Susana M , Parks M , Chen TJ , Razzaghi H , Dawood FS . Am J Perinatol 2021 39 (1) 75-83 OBJECTIVE: The aim of the study was to evaluate pregnant women's attitudes toward COVID-19 illness and vaccination and identify factors associated with vaccine acceptability. STUDY DESIGN: This was a cross-sectional survey among pregnant women enrolled in a prospective COVID-19 cohort study in Salt Lake City, UT, Birmingham, AL, and New York, NY, from August 9 to December 10, 2020. Women were eligible if they were 18 to 50 years old and <28 weeks of gestation. Upon enrollment, women completed surveys regarding concerns about COVID-19 illness and likelihood of getting COVID-19 vaccine if one were available during pregnancy. Vaccine acceptability was defined as a response of "very likely" or "somewhat likely" on a 4-point Likert scale. Factors associated with vaccine acceptability were assessed with multivariable logistic regression. RESULTS: Of 939 pregnant women eligible for the main cohort study, 915 (97%) consented to participate. Among these 915 women, 39% self-identified as White, 23% Black, 33% Hispanic, and 4% Other. Sixty-two percent received an influenza vaccine last season. Seventy-two percent worried about getting sick with COVID-19. If they were to get sick, 92% worried about harm to their pregnancy and 80% about harm to themselves. Only 41% reported they would get a vaccine. Of women who were unlikely to get vaccinated, the most frequently cited concern was vaccine safety for their pregnancy (82%). Non-Hispanic Black and Hispanic women had lower odds of accepting a vaccine compared with non-Hispanic White women (adjusted odds ratios [aOR] 0.4, 95% CI 0.2-0.6 for both). Receipt of influenza vaccine during the previous season was associated with higher odds of vaccine acceptability (aOR 2.1, 95% CI 1.5-3.0). CONCLUSION: Although most pregnant women worried about COVID-19 illness, <50% were willing to get vaccinated during pregnancy. Racial and ethnic disparities in plans to accept COVID-19 vaccine highlight the need to prioritize strategies to address perceived barriers among groups at high risk for COVID-19. KEY POINTS: · Less than half of pregnant patients stated they would get a COVID-19 vaccine.. · Protecting their baby was the most common reason for acceptance and refusal of the COVID-19 vaccine.. · Patients of minority race/ethnicity and those without prior influenza vaccination were less likely to accept the COVID-19 vaccine.. |
Therapeutic Efficacy of Artemisinin-Based Combination Therapies in Democratic Republic of the Congo and Investigation of Molecular Markers of Antimalarial Resistance.
Moriarty LF , Nkoli PM , Likwela JL , Mulopo PM , Sompwe EM , Rika JM , Mavoko HM , Svigel SS , Jones S , Ntamabyaliro NY , Kaputu AK , Lucchi N , Subramaniam G , Niang M , Sadou A , Ngoyi DM , Muyembe Tamfum JJ , Schmedes SE , Plucinski MM , Chowell-Puente G , Halsey ES , Kahunu GM . Am J Trop Med Hyg 2021 105 (4) 1067-1075 ![]() Routine assessment of the efficacy of artemisinin-based combination therapies (ACTs) is critical for the early detection of antimalarial resistance. We evaluated the efficacy of ACTs recommended for treatment of uncomplicated malaria in five sites in Democratic Republic of the Congo (DRC): artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Children aged 6-59 months with confirmed Plasmodium falciparum malaria were treated with one of the three ACTs and monitored. The primary endpoints were uncorrected and polymerase chain reaction (PCR)-corrected 28-day (AL and ASAQ) or 42-day (DP) cumulative efficacy. Molecular markers of resistance were investigated. Across the sites, uncorrected efficacy estimates ranged from 63% to 88% for AL, 73% to 100% for ASAQ, and 56% to 91% for DP. PCR-corrected efficacy estimates ranged from 86% to 98% for AL, 91% to 100% for ASAQ, and 84% to 100% for DP. No pfk13 mutations previously found to be associated with ACT resistance were observed. Statistically significant associations were found between certain pfmdr1 and pfcrt genotypes and treatment outcome. There is evidence of efficacy below the 90% cutoff recommended by WHO to consider a change in first-line treatment recommendations of two ACTs in one site not far from a monitoring site in Angola that has shown similar reduced efficacy for AL. Confirmation of these findings in future therapeutic efficacy monitoring in DRC is warranted. |
Incidence, Clinical Characteristics, and Risk Factors of SARS-CoV-2 Infection among Pregnant Individuals in the United States.
Dawood FS , Varner M , Tita A , Newes-Adeyi G , Gyamfi-Bannerman C , Battarbee A , Bruno A , Daugherty M , Reichle L , Vorwaller K , Vargas C , Parks M , Powers E , Lucca-Susana M , Gibson M , Subramaniam A , Cheng YJ , Feng PJ , Ellington S , Galang RR , Meece J , Flygare C , Stockwell MS . Clin Infect Dis 2021 74 (12) 2218-2226 BACKGROUND: Data about the risk of SARS-CoV-2 infection among pregnant individuals are needed to inform infection prevention guidance and counseling for this population. METHODS: We prospectively followed a cohort of pregnant individuals during August 2020-March 2021 at three U.S. sites. The three primary outcomes were incidence rates of any SARS-CoV-2 infection, symptomatic infection, and asymptomatic infection, during pregnancy during periods of SARS-CoV-2 circulation. Participants self-collected weekly mid-turbinate nasal swabs for SARS-CoV-2 RT-PCR testing, completed weekly illness symptom questionnaires, and submitted additional swabs with COVID-19-like symptoms. An overall SARS-CoV-2 infection incidence rate weighted by population counts of women of reproductive age in each state was calculated. RESULTS: Among 1098 pregnant individuals followed for a mean of 10 weeks, nine percent (99/1098) had SARS-CoV-2 infections during the study. Population weighted incidence rates of SARS-CoV-2 infection were 10.0 per 1,000 (95% confidence interval [CI] 5.7-14.3) person-weeks for any infection, 5.7 per 1,000 (95% CI 1.7-9.7) for symptomatic infections, and 3.5 per 1,000 (95% CI 0-7.1) for asymptomatic infections. Among 96 participants with SARS-CoV-2 infection and symptom data, the most common symptoms were nasal congestion (72%), cough (64%), headache (59%), and change in taste or smell (54%); 28% had measured or subjective fever. The median symptom duration was 10 days (IQR6-16 days). CONCLUSION: Pregnant individuals had a 1% risk of SARS-CoV-2 infection per week. Study findings provide information about SARS-CoV-2 infection risk during pregnancy to inform counseling for pregnant individuals about infection prevention practices, including COVID-19 vaccination. |
Respiratory Viral Infections and Infection Prevention Practices among Women with Acute Respiratory Illness during Delivery Hospitalizations during the 2019-2020 Influenza Season
Dawood FS , Varner M , Munoz F , Stockwell MS , Suyama J , Li DK , Tita A , Mathias L , Shakib JH , Piedra PA , Gyamfi-Bannerman C , Weissman A , Ferber J , Battarbee AN , Wesley MG , Vorwaller K , Powers E , Gibson M , Bond N , Santarcangelo P , Avadhanula V , Newes-Adeyi G , Hunt DR , Subramaniam A , Sanusi A , Boone A , Ogokeh C , Macio I , Odouli R , Thind P , Vargas CY , Almonte C , Galang R , Shapiro-Mendoza C , Campbell AP . J Infect Dis 2021 225 (1) 50-54 We conducted a cross-sectional study of pregnant women with acute respiratory illness during delivery hospitalizations in influenza season to describe clinical testing for respiratory viruses and infection prevention practices. Women had nasal swabs tested for influenza and other respiratory viruses. Among 91 enrolled women, 22 (24%) had clinical testing for influenza. Based on clinical and study testing combined, 41/91 (45%) women had samples positive for respiratory viruses. The most common virus was influenza (17/91, 19%); 53% (9/17) of influenza virus infections were identified through study testing alone. Only 16% of women were on droplet precautions. Peripartum respiratory infections may be underrecognized. |
Community-based surveys for Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions in selected regions of mainland Tanzania.
Bakari C , Jones S , Subramaniam G , Mandara CI , Chiduo MG , Rumisha S , Chacky F , Molteni F , Mandike R , Mkude S , Njau R , Herman C , Nace DP , Mohamed A , Udhayakumar V , Kibet CK , Nyanjom SG , Rogier E , Ishengoma DS . Malar J 2020 19 (1) 391 ![]() BACKGROUND: Histidine-rich protein 2 (HRP2)-based malaria rapid diagnostic tests (RDTs) are effective and widely used for the detection of wild-type Plasmodium falciparum infections. Although recent studies have reported false negative HRP2 RDT results due to pfhrp2 and pfhrp3 gene deletions in different countries, there is a paucity of data on the deletions of these genes in Tanzania. METHODS: A community-based cross-sectional survey was conducted between July and November 2017 in four regions: Geita, Kigoma, Mtwara and Ruvuma. All participants had microscopy and RDT performed in the field and provided a blood sample for laboratory multiplex antigen detection (for Plasmodium lactate dehydrogenase, aldolase, and P. falciparum HRP2). Samples showing RDT false negativity or aberrant relationship of HRP2 to pan-Plasmodium antigens were genotyped to detect the presence/absence of pfhrp2/3 genes. RESULTS: Of all samples screened by the multiplex antigen assay (n = 7543), 2417 (32.0%) were positive for any Plasmodium antigens while 5126 (68.0%) were negative for all antigens. The vast majority of the antigen positive samples contained HRP2 (2411, 99.8%), but 6 (0.2%) had only pLDH and/or aldolase without HRP2. Overall, 13 samples had an atypical relationship between a pan-Plasmodium antigen and HRP2, but were positive by PCR. An additional 16 samples with negative HRP2 RDT results but P. falciparum positive by microscopy were also chosen for pfhrp2/3 genotyping. The summation of false negative RDT results and laboratory antigen results provided 35 total samples with confirmed P. falciparum DNA for pfhrp2/3 genotyping. Of the 35 samples, 4 (11.4%) failed to consistently amplify positive control genes; pfmsp1 and pfmsp2 and were excluded from the analysis. The pfhrp2 and pfhrp3 genes were successfully amplified in the remaining 31 (88.6%) samples, confirming an absence of deletions in these genes. CONCLUSIONS: This study provides evidence that P. falciparum parasites in the study area have no deletions of both pfhrp2 and pfhrp3 genes. Although single gene deletions could have been missed by the multiplex antigen assay, the findings support the continued use of HRP2-based RDTs in Tanzania for routine malaria diagnosis. There is a need for the surveillance to monitor the status of pfhrp2 and/or pfhrp3 deletions in the future. |
One-step PCR: A novel protocol for determination of pfhrp2 deletion status in Plasmodium falciparum.
Jones S , Subramaniam G , Plucinski MM , Patel D , Padilla J , Aidoo M , Talundzic E . PLoS One 2020 15 (7) e0236369 ![]() ![]() Histidine-rich protein 2 (HRP2) detecting rapid diagnostic tests (RDTs) have played an important role in enabling prompt malaria diagnosis in remote locations. However, emergence of pfhrp2 deleted parasites is threatening the efficacy of RDTs, and the World Health Organization (WHO) has highlighted surveillance of these deletions as a priority. Nested PCR is used to confirm pfhrp2 deletion but is costly and laborious. Due to spurious amplification of paralogue pfhrp3, the identity of nested exon 1 PCR product must be confirmed by sequencing. Here we describe a new one-step PCR method for detection of pfhrp2. To determine sensitivity and specificity, all PCRs were performed in triplicate. Using photo-induced electron transfer (PET) PCR detecting 18srRNA as true positive, one-step had comparable sensitivity of 95.0% (88.7-98.4%) to nested exon 1, 99.0% (94.6-99.9%) and nested exon 2, 98.0% (93.0-99.8%), and comparable specificity 93.8% (69.8-99.8%) to nested exon 1 100.0% (79.4-100.0%) and nested exon 2, 100.0% (74.4-100.0%). Sequencing revealed that one step PCR does not amplify pfhrp3. Logistic regression models applied to measure the 95% level of detection of the one-step PCR in clinical isolates provided estimates of 133p/μL (95% confidence interval (CI): 3-793p/μL) for whole blood (WB) samples and 385p/μL (95% CI: 31-2133 p/μL) for dried blood spots (DBSs). When considering protocol attributes, the one-step PCR is less expensive, faster and more suitable for high throughput. In summary, we have developed a more accurate PCR method that may be ideal for the application of the WHO protocol for investigating pfhrp2 deletions in symptomatic individuals presenting to health care facilities. |
Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: a WHO-coordinated, prospective, international, observational cohort study
Kleinschmidt I , Bradley J , Knox TB , Mnzava AP , Kafy HT , Mbogo C , Ismail BA , Bigoga JD , Adechoubou A , Raghavendra K , Cook J , Malik EM , Nkuni ZJ , Macdonald M , Bayoh N , Ochomo E , Fondjo E , Awono-Ambene HP , Etang J , Akogbeto M , Bhatt RM , Chourasia MK , Swain DK , Kinyari T , Subramaniam K , Massougbodji A , Oke-Sopoh M , Ogouyemi-Hounto A , Kouambeng C , Abdin MS , West P , Elmardi K , Cornelie S , Corbel V , Valecha N , Mathenge E , Kamau L , Lines J , Donnelly MJ . Lancet Infect Dis 2018 18 (6) 640-649 BACKGROUND: Scale-up of insecticide-based interventions has averted more than 500 million malaria cases since 2000. Increasing insecticide resistance could herald a rebound in disease and mortality. We aimed to investigate whether insecticide resistance was associated with loss of effectiveness of long-lasting insecticidal nets and increased malaria disease burden. METHODS: This WHO-coordinated, prospective, observational cohort study was done at 279 clusters (villages or groups of villages in which phenotypic resistance was measurable) in Benin, Cameroon, India, Kenya, and Sudan. Pyrethroid long-lasting insecticidal nets were the principal form of malaria vector control in all study areas; in Sudan this approach was supplemented by indoor residual spraying. Cohorts of children from randomly selected households in each cluster were recruited and followed up by community health workers to measure incidence of clinical malaria and prevalence of infection. Mosquitoes were assessed for susceptibility to pyrethroids using the standard WHO bioassay test. Country-specific results were combined using meta-analysis. FINDINGS: Between June 2, 2012, and Nov 4, 2016, 40 000 children were enrolled and assessed for clinical incidence during 1.4 million follow-up visits. 80 000 mosquitoes were assessed for insecticide resistance. Long-lasting insecticidal net users had lower infection prevalence (adjusted odds ratio [OR] 0.63, 95% CI 0.51-0.78) and disease incidence (adjusted rate ratio [RR] 0.62, 0.41-0.94) than did non-users across a range of resistance levels. We found no evidence of an association between insecticide resistance and infection prevalence (adjusted OR 0.86, 0.70-1.06) or incidence (adjusted RR 0.89, 0.72-1.10). Users of nets, although significantly better protected than non-users, were nevertheless subject to high malaria infection risk (ranging from an average incidence in net users of 0.023, [95% CI 0.016-0.033] per person-year in India, to 0.80 [0.65-0.97] per person year in Kenya; and an average infection prevalence in net users of 0.8% [0.5-1.3] in India to an average infection prevalence of 50.8% [43.4-58.2] in Benin). INTERPRETATION: Irrespective of resistance, populations in malaria endemic areas should continue to use long-lasting insecticidal nets to reduce their risk of infection. As nets provide only partial protection, the development of additional vector control tools should be prioritised to reduce the unacceptably high malaria burden. FUNDING: Bill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development. |
Insecticide-treated nets and protection against insecticide-resistant malaria vectors in Western Kenya
Ochomo E , Chahilu M , Cook J , Kinyari T , Bayoh NM , West P , Kamau L , Osangale A , Ombok M , Njagi K , Mathenge E , Muthami L , Subramaniam K , Knox T , Mnavaza A , Donnelly MJ , Kleinschmidt I , Mbogo C . Emerg Infect Dis 2017 23 (5) 758-764 Insecticide resistance might reduce the efficacy of malaria vector control. In 2013 and 2014, malaria vectors from 50 villages, of varying pyrethroid resistance, in western Kenya were assayed for resistance to deltamethrin. Long-lasting insecticide-treated nets (LLIN) were distributed to households at universal coverage. Children were recruited into 2 cohorts, cleared of malaria-causing parasites, and tested every 2 weeks for reinfection. Infection incidence rates for the 2 cohorts were 2.2 (95% CI 1.9-2.5) infections/person-year and 2.8 (95% CI 2.5-3.0) infections/person-year. LLIN users had lower infection rates than non-LLIN users in both low-resistance (rate ratio 0.61, 95% CI 0.42-0.88) and high-resistance (rate ratio 0.55, 95% CI 0.35-0.87) villages (p = 0.63). The association between insecticide resistance and infection incidence was not significant (p = 0.99). Although the incidence of infection was high among net users, LLINs provided significant protection (p = 0.01) against infection with malaria parasite regardless of vector insecticide resistance. |
Presence of the knockdown resistance mutation, Vgsc-1014F in Anopheles gambiae and An. arabiensis in western Kenya.
Ochomo E , Subramaniam K , Kemei B , Rippon E , Bayoh NM , Kamau L , Atieli F , Vulule JM , Ouma C , Gimnig J , Donnelly MJ , Mbogo C . Parasit Vectors 2015 8 (1) 616 ![]() INTRODUCTION: The voltage gated sodium channel mutation Vgsc-1014S (kdr-east) was first reported in Kenya in 2000 and has since been observed to occur at high frequencies in the local Anopheles gambiae s.s. POPULATION: The mutation Vgsc-1014F has never been reported from An. gambiae Complex complex mosquitoes in Kenya. FINDINGS: Molecularly confirmed An. gambiae s.s. (hereafter An. gambiae) and An. arabiensis collected from 4 different parts of western Kenya were genotyped for kdr from 2011 to 2013. Vgsc-1014F was observed to have emerged, apparently, simultaneously in both An. gambiae and An. arabiensis in 2012. A portion of the samples were submitted for sequencing in order to confirm the Vgsc-1014F genotyping results. The resulting sequence data were deposited in GenBank (Accession numbers: KR867642-KR867651, KT758295-KT758303). A single Vgsc-1014F haplotype was observed suggesting, a common origin in both species. CONCLUSION: This is the first report of Vgsc-1014F in Kenya. Based on our samples, the mutation is present in low frequencies in both An. gambiae and An. arabiensis. It is important that we start monitoring relative frequencies of the two kdr genes so that we can determine their relative importance in an area of high insecticide treated net ownership. |
Design of a study to determine the impact of insecticide resistance on malaria vector control: a multi-country investigation
Kleinschmidt I , Mnzava AP , Kafy HT , Mbogo C , Bashir AI , Bigoga J , Adechoubou A , Raghavendra K , Knox TB , Malik EM , Nkuni ZJ , Bayoh N , Ochomo E , Fondjo E , Kouambeng C , Awono-Ambene HP , Etang J , Akogbeto M , Bhatt R , Swain DK , Kinyari T , Njagi K , Muthami L , Subramaniam K , Bradley J , West P , Massougbodji A , Okê-Sopoh M , Hounto A , Elmardi K , Valecha N , Kamau L , Mathenge E , Donnelly MJ . Malar J 2015 14 282 BACKGROUND: Progress in reducing the malaria disease burden through the substantial scale up of insecticide-based vector control in recent years could be reversed by the widespread emergence of insecticide resistance. The impact of insecticide resistance on the protective effectiveness of insecticide-treated nets (ITN) and indoor residual spraying (IRS) is not known. A multi-country study was undertaken in Sudan, Kenya, India, Cameroon and Benin to quantify the potential loss of epidemiological effectiveness of ITNs and IRS due to decreased susceptibility of malaria vectors to insecticides. The design of the study is described in this paper. METHODS: Malaria disease incidence rates by active case detection in cohorts of children, and indicators of insecticide resistance in local vectors were monitored in each of approximately 300 separate locations (clusters) with high coverage of malaria vector control over multiple malaria seasons. Phenotypic and genotypic resistance was assessed annually. In two countries, Sudan and India, clusters were randomly assigned to receive universal coverage of ITNs only, or universal coverage of ITNs combined with high coverage of IRS. Association between malaria incidence and insecticide resistance, and protective effectiveness of vector control methods and insecticide resistance were estimated, respectively. RESULTS: Cohorts have been set up in all five countries, and phenotypic resistance data have been collected in all clusters. In Sudan, Kenya, Cameroon and Benin data collection is due to be completed in 2015. In India data collection will be completed in 2016. DISCUSSION: The paper discusses challenges faced in the design and execution of the study, the analysis plan, the strengths and weaknesses, and the possible alternatives to the chosen study design. |
Pyrethroid susceptibility of malaria vectors in four districts of western Kenya
Ochomo E , Bayoh NM , Kamau L , Atieli F , Vulule J , Ouma C , Ombok M , Njagi K , Soti D , Mathenge E , Muthami L , Kinyari T , Subramaniam K , Kleinschmidt I , Donnelly MJ , Mbogo C . Parasit Vectors 2014 7 (1) 310 BACKGROUND: Increasing pyrethroid resistance in malaria vectors has been reported in western Kenya where long lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the mainstays of vector control. To ensure the sustainability of insecticide-based malaria vector control, monitoring programs need to be implemented. This study was designed to investigate the extent and distribution of pyrethroid resistance in 4 Districts of western Kenya (Nyando, Rachuonyo, Bondo and Teso). All four Districts have received LLINs while Nyando and Rachuonyo Districts have had IRS campaigns for 3-5 years using pyrethroids. This study is part of a programme aimed at determining the impact of insecticide resistance on malaria epidemiology. METHODS: Three day old adult mosquitoes from larval samples collected in the field, were used for bioassays using the WHO tube bioassay, and mortality recorded 24 hours post exposure. Resistance level was assigned based on the 2013 WHO guidelines where populations with <90% mortality were considered resistant. Once exposed, samples were identified to species using PCR. RESULTS: An. arabiensis comprised at least 94% of all An. gambiae s.l. in Bondo, Rachuonyo and Nyando. Teso was a marked contrast case with 77% of all samples being An. gambiae s.s. Mortality to insecticides varied widely between clusters even in one District with mortality to deltamethrin ranging from 45-100%, while to permethrin the range was 30-100%. Mortality to deltamethrin in Teso District was < 90% in 4 of 6 clusters tested in An arabiensis and <90% in An. gambiae s.s in 5 of 6 clusters tested. To permethrin, mortality ranged between 5.9-95%, with <90% mortality in 9 of 13 and 8 of 13 in An. arabiensis and An. gambiae s.s. respectively. Cluster specific mortality of An. arabiensis between permethin and deltamethrin were not correlated (Z = 2.9505, P = 0.2483). CONCLUSION: High levels of pyrethroid resistance were observed in western Kenya. This resistance does not seem to be associated with either species or location. Insecticide resistance can vary within small geographical areas and such heterogeneity may make it possible to evaluate the impact of resistance on malaria and mosquito parameters within similar eco-epidemiological zones. |
Genomic analysis of the causative agents of coccidiosis in domestic chickens.
Reid AJ , Blake DP , Ansari HR , Billington K , Browne HP , Bryant JM , Dunn M , Hung SS , Kawahara F , Miranda-Saavedra D , Malas T , Mourier T , Naghra H , Nair M , Otto TD , Rawlings ND , Rivailler P , Sanchez-Flores A , Sanders M , Subramaniam C , Tay YL , Woo Y , Wu X , Barrell B , Dear PH , Doerig C , Gruber A , Ivens AC , Parkinson J , Rajandream MA , Shirley MW , Wan KL , Berriman M , Tomley FM , Pain A . Genome Res 2014 24 (10) 1676-85 ![]() Global production of chickens has trebled in the past two decades and they are now the most important source of dietary animal protein worldwide. Chickens are subject to many infectious diseases that reduce their performance and productivity. Coccidiosis, caused by apicomplexan protozoa of the genus Eimeria, is one of the most important poultry diseases. Understanding the biology of Eimeria parasites underpins development of new drugs and vaccines needed to improve global food security. We have produced annotated genome sequences of all seven species of Eimeria that infect domestic chickens, which reveal the full extent of previously described repeat-rich and repeat-poor regions and show that these parasites possess the most repeat-rich proteomes ever described. Furthermore, while no other apicomplexan has been found to possess retrotransposons, Eimeria is home to a family of chromoviruses. Analysis of Eimeria genes involved in basic biology and host-parasite interaction highlights adaptations to a relatively simple developmental life cycle and a complex array of co-expressed surface proteins involved in host cell binding. |
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