Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-17 (of 17 Records) |
Query Trace: Abdallah R[original query] |
---|
Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru.
Akinyi S , Hayden T , Gamboa D , Torres K , Bendezu J , Abdallah JF , Griffing SM , Quezada WM , Arrospide N , De Oliveira AM , Lucas C , Magill AJ , Bacon DJ , Barnwell JW , Udhayakumar V . Sci Rep 2013 3 2797 The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times. |
A Public Health Research Agenda for Managing Infodemics: Methods and Results of the First WHO Infodemiology Conference.
Calleja N , AbdAllah A , Abad N , Ahmed N , Albarracin D , Altieri E , Anoko JN , Arcos R , Azlan AA , Bayer J , Bechmann A , Bezbaruah S , Briand SC , Brooks I , Bucci LM , Burzo S , Czerniak C , De Domenico M , Dunn AG , Ecker UKH , Espinosa L , Francois C , Gradon K , Gruzd A , Gülgün BS , Haydarov R , Hurley C , Astuti SI , Ishizumi A , Johnson N , Johnson Restrepo D , Kajimoto M , Koyuncu A , Kulkarni S , Lamichhane J , Lewis R , Mahajan A , Mandil A , McAweeney E , Messer M , Moy W , Ndumbi Ngamala P , Nguyen T , Nunn M , Omer SB , Pagliari C , Patel P , Phuong L , Prybylski D , Rashidian A , Rempel E , Rubinelli S , Sacco P , Schneider A , Shu K , Smith M , Sufehmi H , Tangcharoensathien V , Terry R , Thacker N , Trewinnard T , Turner S , Tworek H , Uakkas S , Vraga E , Wardle C , Wasserman H , Wilhelm E , Würz A , Yau B , Zhou L , Purnat TD . JMIR Infodemiology 2021 1 (1) e30979 BACKGROUND: An infodemic is an overflow of information of varying quality that surges across digital and physical environments during an acute public health event. It leads to confusion, risk-taking, and behaviors that can harm health and lead to erosion of trust in health authorities and public health responses. Owing to the global scale and high stakes of the health emergency, responding to the infodemic related to the pandemic is particularly urgent. Building on diverse research disciplines and expanding the discipline of infodemiology, more evidence-based interventions are needed to design infodemic management interventions and tools and implement them by health emergency responders. OBJECTIVE: The World Health Organization organized the first global infodemiology conference, entirely online, during June and July 2020, with a follow-up process from August to October 2020, to review current multidisciplinary evidence, interventions, and practices that can be applied to the COVID-19 infodemic response. This resulted in the creation of a public health research agenda for managing infodemics. METHODS: As part of the conference, a structured expert judgment synthesis method was used to formulate a public health research agenda. A total of 110 participants represented diverse scientific disciplines from over 35 countries and global public health implementing partners. The conference used a laddered discussion sprint methodology by rotating participant teams, and a managed follow-up process was used to assemble a research agenda based on the discussion and structured expert feedback. This resulted in a five-workstream frame of the research agenda for infodemic management and 166 suggested research questions. The participants then ranked the questions for feasibility and expected public health impact. The expert consensus was summarized in a public health research agenda that included a list of priority research questions. RESULTS: The public health research agenda for infodemic management has five workstreams: (1) measuring and continuously monitoring the impact of infodemics during health emergencies; (2) detecting signals and understanding the spread and risk of infodemics; (3) responding and deploying interventions that mitigate and protect against infodemics and their harmful effects; (4) evaluating infodemic interventions and strengthening the resilience of individuals and communities to infodemics; and (5) promoting the development, adaptation, and application of interventions and toolkits for infodemic management. Each workstream identifies research questions and highlights 49 high priority research questions. CONCLUSIONS: Public health authorities need to develop, validate, implement, and adapt tools and interventions for managing infodemics in acute public health events in ways that are appropriate for their countries and contexts. Infodemiology provides a scientific foundation to make this possible. This research agenda proposes a structured framework for targeted investment for the scientific community, policy makers, implementing organizations, and other stakeholders to consider. |
Cost analysis of the positive health check intervention to suppress HIV viral load and retain patients in HIV clinical care
Shrestha RK , Galindo CA , Courtenay-Quirk C , Harshbarger C , Abdallah I , Marconi VC , DallaPiazza M , Swaminathan S , Somboonwit C , Lewis MA , Khavjou OA . J Public Health Manag Pract 2023 29 (3) 326-335 CONTEXT: Digital video-based behavioral interventions are effective tools for improving HIV care and treatment outcomes. OBJECTIVE: To assess the costs of the Positive Health Check (PHC) intervention delivered in HIV primary care settings. DESIGN, SETTING, AND INTERVENTION: The PHC study was a randomized trial evaluating the effectiveness of a highly tailored, interactive video-counseling intervention delivered in 4 HIV care clinics in the United States in improving viral suppression and retention in care. Eligible patients were randomized to either the PHC intervention or the control arm. Control arm participants received standard of care (SOC), and intervention arm participants received SOC plus PHC. The intervention was delivered on computer tablets in the clinic waiting rooms. The PHC intervention improved viral suppression among male participants. A microcosting approach was used to assess the program costs, including labor hours, materials and supplies, equipment, and office overhead. PARTICIPANTS: Persons with HIV infection, receiving care in participating clinics. MAIN OUTCOME MEASURES: The primary outcome was the number of patients virally suppressed, defined as having fewer than 200 copies/mL by the end of their 12-month follow-up. RESULTS: A total of 397 (range across sites [range], 95-102) participants were enrolled in the PHC intervention arm, of whom 368 participants (range, 82-98) had viral load data at baseline and were included in the viral load analyses. Of those, 210 (range, 41-63) patients were virally suppressed at the end of their 12-month follow-up visit. The overall annual program cost was $402 274 (range, $65 581-$124 629). We estimated the average program cost per patient at $1013 (range, $649-$1259) and the cost per patient virally suppressed at $1916 (range, $1041-$3040). Recruitment and outreach costs accounted for 30% of PHC program costs. CONCLUSIONS: The costs of this interactive video-counseling intervention are comparable with other retention in care or reengagement interventions. |
Effectiveness of an interactive, highly tailored "video doctor" intervention to suppress viral load and retain patients with HIV in clinical care: A randomized clinical trial
Lewis MA , Harshbarger C , Bann C , Marconi VC , Somboonwit C , Piazza MD , Swaminathan S , Burrus O , Galindo C , Borkowf CB , Marks G , Karns S , Zulkiewicz B , Ortiz A , Abdallah I , Garner BR , Courtenay-Quirk C . J Acquir Immune Defic Syndr 2022 91 (1) 58-67 BACKGROUND: To determine whether Positive Health Check, a highly tailored video doctor intervention, can improve viral suppression and retention in care. SETTING: Four clinics that deliver HIV primary care. METHODS: A hybrid type 1 effectiveness-implementation randomized trial design was used to test study hypotheses. Participants (N = 799) who were not virally suppressed, were new to care, or had fallen out of care were randomly assigned to receive Positive Health Check or the standard of care alone. The primary endpoint was viral load suppression, and the secondary endpoint was retention in care, both assessed at 12 months, using an intention-to-treat approach. A priori subgroup analyses based on sex assigned at birth and race were examined as well. RESULTS: There were no statistically significant differences between Positive Health Check (N = 397) and standard of care (N = 402) for either endpoint. However, statistically significant group differences were identified from a priori subgroup analyses. Male participants receiving Positive Health Check were more likely to achieve suppression at 12 months than male participants receiving standard of care adjusted risk ratio [aRR] [95% confidence interval (CI)] = 1.14 (1.00 to 1.29), P = 0.046}. For retention in care, there was a statistically significant lower risk for a 6-month visit gap in the Positive Health Check arm for the youngest participants, 18-29 years old [aRR (95% CI) = 0.55 (0.33 to 0.92), P = 0.024] and the oldest participants, 60-81 years old [aRR (95% CI) = 0.49 (0.30 to 0.81), P = 0.006]. CONCLUSIONS: Positive Health Check may help male participants with HIV achieve viral suppression, and younger and older patients consistently attend HIV care. REGISTRY NAME: Positive Health Check Evaluation Trial. Trial ID: 1U18PS004967-01. URL: https://clinicaltrials.gov/ct2/show/NCT03292913. |
Positive Health Check intervention tool usage during a feasibility pilot in HIV primary care clinics
Galindo CA , Freeman A , Abdallah I , Courtenay-Quirk C . AIDS Care 2022 35 (1) 1-6 Positive Health Check (PHC), an interactive, web-based intervention, provides tailored behavioral health messages to support people with HIV in their HIV care. Users interact with a virtual doctor and based on responses to tailoring questions, PHC delivers relevant content modules addressing treatment initiation, medication adherence, retention in care, sexual risk reduction, mother-to-child transmission, and injection drug use. During a one-month feasibility pilot of PHC, patients in four HIV primary care clinics were invited to use PHC and tool usage metrics were collected and assessed. Descriptive analyses were conducted to characterize how the tool was used based on behavioral risk scenarios presented.Ninety-seven patients accessed PHC as part of the pilot, with 68 (70.1%) completing the intervention on average in 15 min. Out of 85 patients who viewed behavioral tips and commitments, 66 (77.7%) selected at least one tip to practice and 41 (48.2%) made at least one commitment to ask their provider a question. Patients spent the most time with adherence and sexual risk reduction content. The high level of tool engagement suggests that PHC was acceptable to patients regardless of length of time since diagnosis. PHC can be completed within a single visit and is a promising tool for PWH. |
Cross-border malaria in the triple border region between Brazil, Venezuela and Guyana
Abdallah R , Louzada J , Carlson C , Ljolje D , Udhayakumar V , Oliveira-Ferreira J , Lucchi NW . Sci Rep 2022 12 (1) 1200 The state of Roraima, in Brazil, has recently seen an increase in the number of reported Plasmodium falciparum infections believed to be imported from neighboring countries. The objective of this study was to determine the prevalence of Plasmodium species among patients attending malaria health posts in Roraima and quantify the infections attributable to imported malaria. This cross-sectional case study was carried out between March 2016 and September 2018. Study participants were recruited as they exited the malaria health post. Information about residence, occupation and travel history was collected using a questionnaire. A dried blood spot was collected and used for malaria diagnosis by PCR. A total of 1222 patients were enrolled. Of the 80% Plasmodium positive samples, 50% were P. falciparum, 34% P. vivax, 8% mixed P. falciparum/P. vivax and 0.2% mixed P. falciparum/P. ovale infections and 8% tested positive for Plasmodium, but the species could not be identified. 80% of the malaria patients likely acquired infections in Venezuela and the remaining 20% acquired in Guyana, Brazil, Suriname and French Guyana. 50% of the study participants reported to be working in a mine. Results from this study support the hypothesis that imported malaria contribute to the bulk of malaria diagnosed in Roraima. These findings are in keeping with previous findings and should be considered when developing malaria control interventions. |
Detection of malaria parasites in samples from returning US travelers using the Alethia® Malaria Plus LAMP assay.
Ljolje D , Abdallah R , Lucchi NW . BMC Res Notes 2021 14 (1) 128 OBJECTIVE: In this study, the performance of a commercially available malaria LAMP assay (Alethia® Malaria Plus LAMP) was evaluated using retrospective clinical samples obtained from travelers returning to the United States of America (USA). Recently, several laboratories in non-malaria endemic countries evaluated the use of the loop mediated isothermal amplification (LAMP) assays for the diagnosis of imported malaria cases. These tests are simpler than polymerase-chain reaction (PCR)-based assays and were shown to have high sensitivity. Much of malaria diagnoses in the USA, is undertaken at the state level using mainly microscopy and rapid diagnostic tests (RDTs). However, molecular tools offer greater sensitivity over microscopy and RDTs. A reliable, easy to perform molecular assay can provide a test of choice for the accurate detection of malaria parasites in places where expert microscopy is lacking and/or for the detection of low-parasite density infections. RESULTS: The Alethia® Malaria Plus LAMP assay was easy to use, had similar test performances as the real-time PCR reference test and results were obtained faster (within 1 h) than the reference test. The sensitivity of the assay was 100% with a kappa score of 1 when compared to the reference PET-PCR assay. |
Molecular and epidemiological characterization of imported malaria cases in Chile.
Escobar DF , Lucchi NW , Abdallah R , Valenzuela MT , Udhayakumar V , Jercic MI , Chenet SM . Malar J 2020 19 (1) 289 BACKGROUND: Chile is one of the South American countries certified as malaria-free since 1945. However, the recent increase of imported malaria cases and the presence of the vector Anopheles pseudopunctipennis in previously endemic areas in Chile require an active malaria surveillance programme. METHODS: Specimens from 268 suspected malaria cases-all imported-collected between 2015 and 2018 at the Public Health Institute of Chile (ISP), were diagnosed by microscopy and positive cases were included for epidemiological analysis. A photo-induced electron transfer fluorogenic primer real-time PCR (PET-PCR) was used to confirm the presence of malaria parasites in available blood samples. Sanger sequencing of drug resistance molecular markers (pfk13, pfcrt and pfmdr1) and microsatellite (MS) analysis were performed in confirmed Plasmodium falciparum samples and results were related to origin of infection. RESULTS: Out of the 268 suspected cases, 65 were Plasmodium spp. positive by microscopy. A total of 63% of the malaria patients were male and 37% were female; 43/65 of the patients acquired infections in South American endemic countries. Species confirmation of available blood samples by PET-PCR revealed that 15 samples were positive for P. falciparum, 27 for Plasmodium vivax and 4 were mixed infections. The P. falciparum samples sequenced contained four mutant pfcrt genotypes (CVMNT, CVMET, CVIET and SVMNT) and three mutant pfmdr1 genotypes (Y184F/S1034C/N1042D/D1246Y, Y184F/N1042D/D1246Y and Y184F). MS analysis confirmed that all P. falciparum samples presented different haplotypes according to the suspected country of origin. Four patients with P. vivax infection returned to the health facilities due to relapses. CONCLUSION: The timely detection of polymorphisms associated with drug resistance will contribute to understanding if current drug policies in the country are appropriate for treatment of imported malaria cases and provide information about the most frequent resistant genotypes entering Chile. |
A landscape of genomic alterations at the root of a near-untreatable tuberculosis epidemic.
Klopper M , Heupink TH , Hill-Cawthorne G , Streicher EM , Dippenaar A , de Vos M , Abdallah AM , Limberis J , Merker M , Burns S , Niemann S , Dheda K , Posey J , Pain A , Warren RM . BMC Med 2020 18 (1) 24 BACKGROUND: Atypical Beijing genotype Mycobacterium tuberculosis strains are widespread in South Africa and have acquired resistance to up to 13 drugs on multiple occasions. It is puzzling that these strains have retained fitness and transmissibility despite the potential fitness cost associated with drug resistance mutations. METHODS: We conducted Illumina sequencing of 211 Beijing genotype M. tuberculosis isolates to facilitate the detection of genomic features that may promote acquisition of drug resistance and restore fitness in highly resistant atypical Beijing forms. Phylogenetic and comparative genomic analysis was done to determine changes that are unique to the resistant strains that also transmit well. Minimum inhibitory concentration (MIC) determination for streptomycin and bedaquiline was done for a limited number of isolates to demonstrate a difference in MIC between isolates with and without certain variants. RESULTS: Phylogenetic analysis confirmed that two clades of atypical Beijing strains have independently developed resistance to virtually all the potent drugs included in standard (pre-bedaquiline) drug-resistant TB treatment regimens. We show that undetected drug resistance in a progenitor strain was likely instrumental in this resistance acquisition. In this cohort, ethionamide (ethA A381P) resistance would be missed in first-line drug-susceptible isolates, and streptomycin (gidB L79S) resistance may be missed due to an MIC close to the critical concentration. Subsequent inadequate treatment historically led to amplification of resistance and facilitated spread of the strains. Bedaquiline resistance was found in a small number of isolates, despite lack of exposure to the drug. The highly resistant clades also carry inhA promoter mutations, which arose after ethA and katG mutations. In these isolates, inhA promoter mutations do not alter drug resistance, suggesting a possible alternative role. CONCLUSION: The presence of the ethA mutation in otherwise susceptible isolates from ethionamide-naive patients demonstrates that known exposure is not an adequate indicator of drug susceptibility. Similarly, it is demonstrated that bedaquiline resistance can occur without exposure to the drug. Inappropriate treatment regimens, due to missed resistance, leads to amplification of resistance, and transmission. We put these results into the context of current WHO treatment regimens, underscoring the risks of treatment without knowledge of the full drug resistance profile. |
Molecular Surveillance for Polymorphisms Associated with artemisinin-based combination therapie Resistance in Plasmodium falciparum Isolates Collected in the State of Roraima, Brazil.
Lucchi NW , Abdallah R , Louzada J , Udhayakumar V , Oliveira-Ferreira J . Am J Trop Med Hyg 2019 102 (2) 310-312 Given that the C580Y polymorphism in the Plasmodium falciparum propeller domain of the kelch 13 gene (pfk13) was documented in Guyana, monitoring for mutations associated with antimalarial resistance was undertaken in neighboring Roraima state in Brazil. Polymorphisms in the pfmdr1 and pfk13 genes were investigated in 275 P. falciparum samples. No pfk13 mutations were observed. Triple mutants 184F, 1042D, and 1246Y were observed in 100% of the samples successfully sequenced for the pfmdr1 gene, with 20.1% of these having an additional mutation at codon 1034C. Among them, 2.5% of samples harbored two copies of the pfmdr1 gene. We found no evidence of the spread of C580Y parasites to Roraima state, Brazil. As previously observed, the 184F, 1042D, and 1246Y mutations in the pfmdr1 gene appear to be fixed in this region. Continued molecular surveillance is essential to detect any potential migration or local emergence of artemisinin-resistant mutation. |
Percutaneous emergence of Gnathostoma spinigerum following praziquantel treatment
Sapp SGH , Kaminski M , Abdallah M , Bishop HS , Fox M , Ndubuisi M , Bradbury RS . Trop Med Infect Dis 2019 4 (4) A Bangladeshi patient with prior travel to Saudi Arabia was hospitalized in the United States for a presumptive liver abscess. Praziquantel was administered following a positive Schistosoma antibody test. Ten days later, a subadult worm migrated to the skin surface and was identified morphologically as Gnathostoma spinigerum. This case highlights the challenges of gnathostomiasis diagnosis, raising questions on potential serologic cross-reactivity and the possible role of praziquantel in stimulating outward migration of Gnathostoma larvae/subadults. |
Deletion of Plasmodium falciparum Histidine-Rich Protein 2 (pfhrp2) and Histidine-Rich Protein 3 (pfhrp3) Genes in Colombian Parasites.
Murillo Solano C , Akinyi Okoth S , Abdallah JF , Pava Z , Dorado E , Incardona S , Huber CS , Macedo de Oliveira A , Bell D , Udhayakumar V , Barnwell JW . PLoS One 2015 10 (7) e0131576 A number of studies have analyzed the performance of malaria rapid diagnostic tests (RDTs) in Colombia with discrepancies in performance being attributed to a combination of factors such as parasite levels, interpretation of RDT results and/or the handling and storage of RDT kits. However, some of the inconsistencies observed with results from Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-based RDTs could also be explained by the deletion of the gene that encodes the protein, pfhrp2, and its structural homolog, pfhrp3, in some parasite isolates. Given that pfhrp2- and pfhrp3-negative P. falciparum isolates have been detected in the neighboring Peruvian and Brazilian Amazon regions, we hypothesized that parasites with deletions of pfhrp2 and pfhrp3 may also be present in Colombia. In this study we tested 100 historical samples collected between 1999 and 2009 from six Departments in Colombia for the presence of pfhrp2, pfhrp3 and their flanking genes. Seven neutral microsatellites were also used to determine the genetic background of these parasites. In total 18 of 100 parasite isolates were found to have deleted pfhrp2, a majority of which (14 of 18) were collected from Amazonas Department, which borders Peru and Brazil. pfhrp3 deletions were found in 52 of the100 samples collected from all regions of the country. pfhrp2 flanking genes PF3D7_0831900 and PF3D7_0831700 were deleted in 22 of 100 and in 1 of 100 samples, respectively. pfhrp3 flanking genes PF3D7_1372100 and PF3D7_1372400 were missing in 55 of 100 and in 57 of 100 samples. Structure analysis of microsatellite data indicated that Colombian samples tested in this study belonged to four clusters and they segregated mostly based on their geographic region. Most of the pfhrp2-deleted parasites were assigned to a single cluster and originated from Amazonas Department although a few pfhrp2-negative parasites originated from the other three clusters. The presence of a high proportion of pfhrp2-negative isolates in the Colombian Amazon may have implications for the use of PfHRP2-based RDTs in the region and may explain inconsistencies observed when PfHRP2-based tests and assays are performed. |
Variation in Plasmodium falciparum Histidine-Rich Protein 2 (Pfhrp2) and Plasmodium falciparum Histidine-Rich Protein 3 (Pfhrp3) Gene Deletions in Guyana and Suriname.
Akinyi Okoth S , Abdallah JF , Ceron N , Adhin MR , Chandrabose J , Krishnalall K , Huber CS , Goldman IF , Macedo de Oliveira A , Barnwell JW , Udhayakumar V . PLoS One 2015 10 (5) e0126805 Guyana and Suriname have made important progress in reducing the burden of malaria. While both countries use microscopy as the primary tool for clinical diagnosis, malaria rapid diagnostic tests (RDTs) are useful in remote areas of the interior where laboratory support may be limited or unavailable. Recent reports indicate that histidine-rich protein 2 (PfHRP2)-based diagnostic tests specific for detection of P. falciparum may provide false negative results in some parts of South America due to the emergence of P. falciparum parasites that lack the pfhrp2 gene, and thus produce no PfHRP2 antigen. Pfhrp2 and pfhrp3 genes were amplified in parasite isolates collected from Guyana and Suriname to determine if there were circulating isolates with deletions in these genes. Pfhrp3 deletions were monitored because some monoclonal antibodies utilized in PfHRP2-based RDTs cross-react with the PfHRP3 protein. We found that all 97 isolates from Guyana that met the inclusion criteria were both pfhrp2- and pfhrp3-positive. In Suriname (N = 78), 14% of the samples tested were pfhrp2-negative while 4% were pfhrp3-negative. Furthermore, analysis of the genomic region proximal to pfhrp2 and pfhrp3 revealed that genomic deletions extended to the flanking genes. We also investigated the population substructure of the isolates collected to determine if the parasites that had deletions of pfhrp2 and pfhrp3 belonged to any genetic subtypes. Cluster analysis revealed that there was no predominant P. falciparum population substructure among the isolates from either country, an indication of genetic admixture among the parasite populations. Furthermore, the pfhrp2-deleted parasites from Suriname did not appear to share a single, unique genetic background. |
In vivo efficacy of sulphadoxine-pyrimethamine for the treatment of asymptomatic parasitaemia in pregnant women in Machinga District, Malawi
Gutman J , Mwandama D , Wiegand RE , Abdallah J , Iriemenam NC , Shi YP , Mathanga DP , Skarbinski J . Malar J 2015 14 (1) 197 BACKGROUND: The effectiveness of sulphadoxine-pyrimethamine (SP) intermittent preventive treatment of malaria in pregnancy (IPTp) might be compromised by high prevalence of resistance-associated Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations. As a proxy for IPTp-SP effectiveness, the in vivo efficacy of SP to clear parasitaemia and prevent reinfection in asymptomatic parasitaemic pregnant women in an area with high SP resistance prevalence was assessed. METHODS: Pregnant women 16-26 weeks' gestation with asymptomatic parasitaemia presenting for antenatal care were given IPTp-SP and followed for 42 days. The primary outcome was polymerase chain reaction (PCR) uncorrected 42-day survival rate; the per cent of patients without recrudescence or reinfection by day 42. PCR was used to distinguish recrudescence from reinfection. DNA was sequenced to detect resistance-associated dhfr and dhps mutations. RESULTS: Of 245 pregnant women included in the intention-to-treat analysis, 93.9% cleared their parasitaemia by day 7. The day 42 PCR-uncorrected survival rate was 58.1% (95% confidence interval (CI) 51.5-65.7) and day 42 PCR-corrected survival was 68.7% (CI 61.4-76.0). Recrudescence was more common among primi- than among multigravid women; recrudescence rate 33.3% (CI 25.1-42.4%) versus 21.4% (CI 15.0-29.0%) (log rank test p-value 0.006). The quintuple mutant was present in nearly all samples (95%), while 2% were sextuple mutants with an additional mutation at dhps A581G. CONCLUSIONS: SP efficacy for acute malaria treatment has been compromised by resistance, but SP retains partial activity among pregnant women with asymptomatic parasitaemia, and thus might be useful for IPTp. Nonetheless, research on non-SP IPTp regimens should continue. TRIAL REGISTRATION: ClinicalTrials.gov NCT01120145 . |
Prevalence of pfhrp2 and pfhrp3 gene deletions in Puerto Lempira, Honduras.
Abdallah JF , Okoth SA , Fontecha GA , Torres RE , Banegas EI , Matute ML , Bucheli ST , Goldman IF , de Oliveira AM , Barnwell JW , Udhayakumar V . Malar J 2015 14 (1) 19 BACKGROUND: Recent studies have demonstrated the deletion of the histidine-rich protein 2 (PfHRP2) gene (pfhrp2) in field isolates of Plasmodium falciparum, which could result in false negative test results when PfHRP2-based rapid diagnostic tests (RDTs) are used for malaria diagnosis. Although primary diagnosis of malaria in Honduras is determined based on microscopy, RDTs may be useful in remote areas. In this study, it was investigated whether there are deletions of the pfhrp2, pfhrp3 and their respective flanking genes in 68 P. falciparum parasite isolates collected from the city of Puerto Lempira, Honduras. In addition, further investigation considered the possible correlation between parasite population structure and the distribution of these gene deletions by genotyping seven neutral microsatellites. METHODS: Sixty-eight samples used in this study, which were obtained from a previous chloroquine efficacy study, were utilized in the analysis. All samples were genotyped for pfhrp2, pfhrp3 and flanking genes by PCR. The samples were then genotyped for seven neutral microsatellites in order to determine the parasite population structure in Puerto Lempira at the time of sample collection. RESULTS: It was found that all samples were positive for pfhrp2 and its flanking genes on chromosome 8. However, only 50% of the samples were positive for pfhrp3 and its neighboring genes while the rest were either pfhrp3-negative only or had deleted a combination of pfhrp3 and its neighbouring genes on chromosome 13. Population structure analysis predicted that there are at least two distinct parasite population clusters in this sample population. It was also determined that a greater proportion of parasites with pfhrp3-(and flanking gene) deletions belonged to one cluster compared to the other. CONCLUSION: The findings indicate that the P. falciparum parasite population in the municipality of Puerto Lempira maintains the pfhrp2 gene and that PfHRP2-based RDTs could be considered for use in this region; however continued monitoring of parasite population will be useful to detect any parasites with deletions of pfhrp2. |
Genetic backgrounds of the Plasmodium falciparum chloroquine resistant transporter (pfcrt) alleles in Pakistan.
Rawasia WF , Sridaran S , Patel JC , Abdallah J , Ghanchi NK , Barnwell JW , Escalante AA , Udhayakumar V , Beg MA . Infect Genet Evol 2012 12 (2) 278-81 Chloroquine (CQ) resistance in Plasmodium falciparum has been associated with point mutations in the P. falciparum CQ resistance transporter gene (pfcrt). Previous studies have shown 4-5 independent origins for CQ resistant pfcrt alleles globally, two in South America, one each in Southeast Asia, Papua New Guinea (PNG) and Philippines. In Asia, at least two different alleles corresponding to amino acids 72-76 (CVIET and SVMNT) have been found. The CVIET allele originated in Southeast Asia and then spread to Asia and Africa as well. The SVMNT allele, originating from PNG, has been found in India. This study was undertaken to investigate the genetic background of the CQ resistant pfcrt haplotypes in Pakistan. We genotyped microsatellite markers surrounding the pfcrt gene (six different markers at -12.3, -4.8, -1, 1.5, 3.9, 18.8kb) in 114 clinical isolates of P. falciparum collected from different regions in Pakistan. Microsatellite analysis showed a significant reduction in genetic variation among the mutant SVMNT pfcrt alleles when compared to wild type alleles. The predominant SVMNT haplotype found in this study shared the same microsatellite haplotype found in both PNG and India. Two isolates with CVIET haplotypes showed similar microsatellite background to those found in Africa and Asia. In conclusion, this study suggests that CQ resistant SVMNT haplotypes in India and Pakistan have a common ancestral origin similar to that of Papua New Guinean isolates. |
Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders
Atladottir HO , Thorsen P , Ostergaard L , Schendel DE , Lemcke S , Abdallah M , Parner ET . J Autism Dev Disord 2010 40 (12) 1423-30 Exposure to prenatal infection has been suggested to cause deficiencies in fetal neurodevelopment. In this study we included all children born in Denmark from 1980, through 2005. Diagnoses of autism spectrum disorders (ASDs) and maternal infection were obtained through nationwide registers. Data was analyzed using Cox proportional hazards regression. No association was found between any maternal infection and diagnosis of ASDs in the child when looking at the total period of pregnancy: adjusted hazard ratio = 1.14 (CI: 0.96-1.34). However, admission to hospital due to maternal viral infection in the first trimester and maternal bacterial infection in the second trimester were found to be associated with diagnosis of ASDs in the offspring, adjusted hazard ratio = 2.98 (CI: 1.29-7.15) and adjusted hazard ratio = 1.42 (CI: 1.08-1.87), respectively. Our results support prior hypotheses concerning early prenatal viral infection increasing the risk of ASDs. |
- Page last reviewed:Feb 1, 2024
- Page last updated:Apr 29, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure