Hasil untuk "Infectious and parasitic diseases"

Marília Bordignon Antonio, Thiago S. Torres, Paula M. Luz et al.

Abstract Introduction HIV stigma negatively impacts multiple outcomes for persons living with HIV (PLHIV). Among older PLHIV, stigma may influence mental health and aging expectation. We aimed to evaluate factors related to HIV stigma and whether depression mediates its association with expectations regarding aging (ERA-12). Design Cross-sectional study of PLHIV ≥ 50 years, on antiretroviral therapy with suppressed viral load, enrolled in the Longitudinal Study of HIV & Aging in Brazil (ELEA-Brasil). Methods We assessed factors related to HIV stigma (12-item Berger, range:12–48, higher = higher stigma) and associated with ERA-12 (range: 0–100, lower = more negative aging expectation). Mediation analysis was performed to evaluate depression (Patient Health Questionnaire-9 [PHQ-9]; range:0–27, higher = higher symptoms) as a mediator of the association between stigma and ERA-12. Univariable and multivariable Poisson and linear regression models were applied, adjusted for demographics, time since HIV diagnosis, and substance use. Results We enrolled 702 PLHIV (median age 62 years; 64.9% men). Median and interquartile range (IQR) of HIV stigma, ERA-12 and PHQ-9 were 30 (25–35); 36 (22–47) and 3 (1–7) respectively. In adjusted analyses, older age (≥ 70 vs. 50–55 years) and shorter time since HIV diagnosis (10–19 years vs. ≥ 20 years) were significantly associated with lower HIV stigma. In adjusted models, higher HIV stigma (Coefficient = − 12.05 [95%CI − 17.84, − 6.26]) and lower education (Coefficient = − 7.60 [95%CI: − 13.40, − 1.81]) were associated with worse ERA-12. Depressive symptoms may reflect 25% of the overall effect of stigma on ERA-12. Conclusion We observed a high prevalence of HIV stigma, with depressive symptoms consistent with a potential mediating role in aging expectations.

Aline Cecy Rocha de Lima, Wandrey Roberto dos Santos Brito, Luciana Cristina Coelho Pantoja Santos et al.

Introduction: Fas and FasL are known modulators of cellular apoptosis in immunoregulation of the innate immune response, as well as in the elimination of defective cells, and may be associated with antiviral activity of HTLV-1 – infected cells. Understanding the immunological mechanisms involved in the progression of HTLV-1 – associated diseases may contribute to predicting the clinical prognosis of infected individuals. Objective: To evaluate mRNA expression of the apoptotic modulators FAS and FASL in patients infected with HTLV-1. Methods: A total of 54 HTLV-1 – infected individuals were evaluated, including 31 symptomatic patients with virus-associated diseases (HAM, neurological diseases, and rheumatological diseases) and 23 asymptomatic individuals. For FAS and FASL gene expression, RNA was extracted and converted to complementary DNA from all samples, followed by quantification of gene expression by real-time PCR. Plasma IFN-γ (interferon-gamma) levels were measured by ELISA. Statistical analyses used Kruskal–Wallis and Spearman tests. Results: FASL expression levels were higher among asymptomatic patients compared with patients with different HTLV-1 – associated diseases, although without statistical significance (p=0.7030). There was no significant association between FAS expression levels in asymptomatic individuals and patients with HAM (p≥0.9999), neurological diseases (p=0.8409), or rheumatological diseases (p=0.5971). However, FAS expression levels were significantly higher in patients with rheumatological diseases compared with those with neurological diseases (p=0.0432). Comparison of plasma IFN-γ levels between symptomatic and asymptomatic patients showed no statistically significant differences (p=0.2678). In addition, no statistically significant correlation was observed between FAS and FASL gene expression and IFN-γ levels (p≥0.005). Conclusion: Although no significant correlation was observed between FAS, FASL expression and IFN-γ production, the statistically significant difference in FAS expression between patients with rheumatological and neurological diseases suggests a possible role of this gene in immunological modulation associated with different clinical manifestation profiles in HTLV-1–infected patients.

Lili Li, Wei Sun, Congxin Li et al.

We present a typical case of Thelazia callipaeda infection in a patient from China, detailing both diagnosis and treatment. Thelaziasis is a zoonotic parasitic disease caused by a nematode and is transmitted by flies. This case also highlights the importance of monitoring public health for individuals, pets, and the environment.

Blake Piepenbrink, Jessica Abrantes-Figueiredo, Brenton Nash et al.

Background: Healthcare associated infections (HAIs) are important areas of concern as they increase length of hospital stay, increase hospital costs, and have high morbidity and mortality. For instance, central line associated bloodstream infections (CLABSIs) approximately increase length of stay by 13.4 days and increase hospital costs by $43,975. Studies also suggest a 1.5-2.5x increase in mortality in patients who develop CLABSIs. In 2013, the REDUCE MRSA trial compared universal MRSA decolonization to targeted MRSA decolonization in the ICU and found superiority ini reducing positive MRSA cultures and all cause bloodstream infections. We aim to decrease central line associated bloodstream infections at our institution by adopting the REDUCE MRSA trial protocol. Methods and Outcomes: All patients admitted to the medical/surgical ICU and cardiac ICU at St Francis Hospital starting in December of 2023 received daily intranasal mupirocin and chlorhexidine bathing regardless of their MRSA status. The primary outcome assessed was the CLABSI rate per month. The secondary outcomes were the standard infection ratio and CLABSI per central line day. We compared data from 2020-2023 to data after initiation of the protocol in 2024. We used unpaired t testing to assess the CLABSI rate per month and used a negative binomial regression model to calculate the standard infection ratio according to the NHSN 2015 national baseline. Results and Discussion: We had a total of 6 CLABSIs in the ICU this year after initiating universal MRSA decolonization. The number of CLABSIs per month decreased from 0.65 per month from 2020-2023 down to 0.50 per month in 2024. These results, while not statistically significant, are limited by the small sample size since the protocol was just initiated this year. One interesting finding was 5 of the 6 CLABSIs occurred during January through March, which brings up the question if introducing these new changes required time for nursing education and compliance to improve. Conclusions: Our results suggest that universal MRSA decolonization in the ICU may decrease the number of CLABSIs. We will continue to collect more data in the coming years to assess for statistical significance. We recommend further research to assess for potential benefits of universal MRSA decolonization in other areas of the hospital where MRSA infection rates are high like step down units.

Shelley Kester, Katie Passaretti, Mindy Sampson et al.

Background: During the COVID-19 pandemic, rates of central line bloodstream infections (CLABSI) increased nationally. Studies pre-pandemic showed improved CLABSI rates with implementation of a standardized vascular access team (VAT).[PL1] [PL2] [mi3] Varying VAT resources and coverage existed in our 10 acute care facilities (ACF) prior to and during the pandemic. VAT scope also varied in 1) process for line selection during initial placement, 2) ability to place a peripherally inserted central catheter (PICC), midline or ultrasound-guided peripheral IV in patients with difficult vascular access, 3) ownership of daily assessment of central line (CL) necessity, and 4) routine CL dressing changes. We aimed to define and implement the ideal VAT structure and evaluate the impact on CLABSI standardized infection ratios (SIR) and rates prior to and during the pandemic. Methods: A multidisciplinary workgroup including representatives from nursing, infection prevention, and vascular access was formed to understand the current state of VAT responsibilities across all ACFs. The group identified key responsibilities a VAT should conduct to aid in CLABSI prevention. Complete VAT coverage[mi4] was defined as the ability to conduct the identified responsibilities daily. We compared the SIR and CLABSI rates between hospitals who had complete VAT (CVAT) coverage to hospitals with incomplete VAT (IVAT) coverage. Given this work occurred during the pandemic, we further stratified our analysis based on a time frame prior to the pandemic (1/2015 – 12/2019) and intra-pandemic (1/2020 - 12/2022). Results: The multidisciplinary team identified 6 key components of complete VAT coverage: Assessment for appropriate line selection prior to insertion, ability to insert PICC and midlines, daily CL and midline care and maintenance assessments, daily assessment of necessity for CL, and weekly dressing changes for CL and midlines[NA5] . A cross walk of VAT scope (Figure 1) was performed in October 2022 which revealed two facilities (A and E) which met CVAT criteria. Pre-pandemic, while IVAT CLABSI rates and SIR were higher than in CVAT units, the difference was not statistically significant. During the pandemic, however, CLABSI rates and SIR were 40-50% higher in IVAT compared to CVAT facilities (Incident Rate Ratio 1.5, 95% CI 1.1-2.0 and SIR Relative Ratio 1.4, 95% CI1.1-1.9 respectively) (Table 1). Conclusions: CLABSI rates were lower in facilities with complete VAT coverage prior to and during the COVID-19 pandemic suggesting a highly functioning VAT can aid in preventing CLABSIs, especially when a healthcare system is stressed and resources are limited.

Johanna Åhsberg, Stephanie Bjerrum, Vincent Jessey Ganu et al.

Objectives: The COVID-19 pandemic had a disruptive impact on tuberculosis (TB) and HIV services. We assessed the in-hospital TB diagnostic care among people with HIV (PWH) overall and before and during the pandemic. Methods: In this prospective study, adult PWH admitted at three hospitals in Ghana were recruited if they had a positive World Health Organization four-symptom screen or one or more World Health Organization danger signs or advanced HIV. We collected data on patient characteristics, TB assessment, and clinical outcomes after 8 weeks and used descriptive statistics and survival analysis. Results: We enrolled 248 PWH with a median clusters of differentiation 4 count of 80.5 cells/mm3 (interquartile range 24-193). Of those, 246 (99.2%) patients had a positive World Health Organization four-symptom screen. Overall, 112 (45.2%) patients obtained a sputum Xpert result, 66 (46.5%) in the prepandemic and 46 (43.4%) in the pandemic period; P-value = 0.629. The TB prevalence of 46/246 (18.7%) was similar in the prepandemic 28/140 (20.0%) and pandemic 18/106 (17.0%) population; P-value = 0.548. The 8-week all-cause mortality was 62/246 (25.2%), with no difference in cumulative survival when stratifying for the pandemic period; log-rank P-value = 0.412. Conclusion: The study highlighted a large gap in the access to TB investigation and high early mortality among hospitalized PWH, irrespective of the COVID-19 pandemic.

Oghenebrume Wariri, Chris Grundy, Beate Kampmann et al.

Introduction The COVID-19 pandemic caused widespread morbidity and mortality and resulted in the biggest setback in routine vaccinations in three decades. Data on the impact of the pandemic on immunisation in Africa are limited, in part, due to low-quality routine or administrative data. This study examined coverage and timeliness of routine childhood immunisation during the pandemic in The Gambia, a country with an immunisation system considered robust.Methods We obtained prospective birth cohort data of 57 286 children in over 300 communities in two health and demographic surveillance system sites, including data from the pre-pandemic period (January 2015–February 2020) and the three waves of the pandemic period (March 2020–December 2021). We determined monthly coverage and timeliness (early and delayed) of the birth dose of hepatitis B vaccine (HepB0) and the first dose of pentavalent vaccine (Penta1) during the different waves of the pandemic relative to the pre-pandemic period. We implemented a binomial interrupted time-series regression model.Result We observed no significant change in the coverage of HepB0 and Penta1 vaccinations from the pre-pandemic period up until the periods before the peaks of the first and second waves of the pandemic in 2020. However, there was an increase in HepB0 coverage before as well as after the peak of the third wave in 2021 compared with the pre-pandemic period (pre-third wave peak OR = 1.83, 95% CI 1.06 to 3.14; post-third wave period OR=2.20, 95% CI 1.23 to 3.92). There was some evidence that vaccination timeliness changed during specific periods of the pandemic. Early Penta1 vaccination decreased by 70% (OR=0.30, 95% CI 0.12 to 0.78) in the period before the second wave, and delayed HepB0 vaccination decreased by 47% (OR=0.53, 95% CI 0.29 to 0.97) after the peak of the third wave in 2021.Conclusion Despite the challenges of the COVID-19 pandemic, The Gambia’s routine vaccination programme has defied the setbacks witnessed in other settings and remained resilient, with coverage increasing and timeliness improving during the second and third waves. These findings highlight the importance of having adequate surveillance systems to monitor the impact of large shocks to vaccination coverage and timeliness.

Yao Y, Shao C, Li X et al.

Yao Yao,1,&ast; Chunlai Shao,2,&ast; Xiaoye Li,1 Zi Wang,1 Chengchun Zuo,1 Yan Yan,3 Qianzhou Lv1 1Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Yan; Qianzhou Lv, Zhongshan Hospital, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel +86 13916088938, Fax +86 021-64041990, Email yan.yan@zs-hospital.sh.cn; 13916088938@163.comPurpose: The Global Registry of Acute Coronary Events (GRACE) score has proven value in predicting short-term prognosis in non-ST-elevation myocardial infarction (NSTEMI), but it has only moderate discrimination for long-term outcomes. The purpose of this study is to develop and test a multi-biomarker score for better risk stratification and indication of 2-year risk in patients with NSTEMI.Patients and Methods: A total of 6076 consecutive patients with NSTEMI (66 [59– 73] years, 73.1% males) admitted at Zhongshan Hospital, Fudan University were collected in this observational, prospective study between 2012 and 2018 with a 24-month follow-up. The primary endpoint was all-cause death and non-fatal major adverse cardiac events (MACE). A biomarker score ranged from 0 to 12 was constructed. The predictive power of the biomarker score was evaluated alone or combined with the GRACE score by C-statistic, net reclassification index (NRI) and integrated discrimination index (IDI).Results: During a 2-year follow-up, all-cause death occurred in 159 patients (2.6%), and non-fatal MACEs were presented in 709 patients (11.7%). When added to the GRACE score, the biomarker score demonstrated better prognostic accuracy, patient reclassification and risk discrimination for both mortality and non-fatal MACEs at 2 years by improving the C-statistic from 0.714 (0.671– 0.756) and 0.623 (0.600– 0.646) to 0.851 (0.820– 0.882) and 0.721 (0.702– 0.741) with NRI > 25% (P< 0.001) and IDI > 0.30 (P< 0.001).Conclusion: The single use of biomarker score could markedly enhance the prognostic value of concurrent risk stratification tools for 2-year mortality and non-fatal MACEs in NSTEMI. The GRACE score with incorporation of the biomarker score led to more accurate risk reclassification and warrants more consideration in further NSTEMI management.Keywords: risk stratification, prognosis, net reclassification improvement, integrated discrimination improvement

Isaac Okezie Godwin, Ifeoma Mercy Ekejindu, George Uchenna Eleje et al.

Background: Following the World Health Organization (WHO) recommendations for 4-weekly antenatal intermittent preventive treatment of malaria in pregnancy using sulphadoxine-pyrimethamine (IPTp-SP), there is a need to evaluate the drug performance in order to determine their effectiveness as tools in malaria control policy. Objectives: To determine prevalence of cord blood malaria, compliance gap and adverse pregnancy outcomes (anaemia, preterm delivery, spontaneous abortion, intra-uterine foetal death and low birth weight) among antenatal IPTp-SP users compared with non-users. Methods: A cross-sectional analytical study was conducted among consenting 390 participants who were administered a questionnaire, and paired blood samples were collected from the venous blood of participants and neonatal cord immediately after delivery. The participants were categorised as IPTp-SP users and non-users. Adverse pregnancy outcomes were assessed. Neonatal birth weights were also measured within 1 h after delivery. Malaria parasitaemia and anaemia were analysed using standard parasitological and haematological methods of examination. Data were analysed using SPSS version 25 for Windows and p -value of < 0.05 considered significant. Results: Of 390 women, 336 (86.2%) were IPTp-SP users, while 54 (13.8%) were non-users. The compliance gap was 13.8%. Malaria parasitemia in pregnant women (21.7% versus 53.7%; p  < 0.001) and their babies (12.2% versus 25.4%; p  = 0.002) were observed for IPTp-SP users and non-users, respectively. The prevalence of maternal anaemia was 27(8.0%) in IPTp-SP users and 5 (9.3%) in non-users ( p  = 0.789). Mean parasite density was reduced in IPTp-SP users than in non-users ( p  < 0.001). Correlation of birth weight according to their sex showed a weak correlation [correlation coefficient ( r ) = 0.027; p  = 0.736]. Pregnant women with preterm delivery, spontaneous abortion, intra-uterine foetal death, and low birth weight were significantly lower ( p  < 0.001, for all) in IPTp-SP users compared with non-users. Conclusion: Although the compliance gap was low, IPTp-SP users had significantly better pregnancy and foetal outcomes compared with non-users. Efforts should be intensified towards achieving total compliance in IPTp-SP usage by pregnant women.

Bruno José Santos Lima, Gabriel Dantas Lopes, Izailza Matos Dantas Lopes et al.

Introdução: A sífilis congênita (SC) é um problema de saúde pública significativo, complicando cerca de um milhão de gestações por ano em todo o mundo. No Brasil, em 2018, foram notificados no Sinan 26.219 casos de SC, incidência de 9,7/1.000 nascidos vivos, e 241 óbitos pela doença, sendo que Sergipe foi o nono estado com maior incidência, com uma taxa de 9,7 casos/1.000 nascidos vivos. Metodologia: Trata-se de um estudo transversal, retrospectivo, de caráter quantitativo e analítico que foi realizado em uma Maternidade Filantrópica de Aracaju/SE, no período de 2010 a 2019. Os dados foram coletados através dos prontuários de parturientes e recém-nascidos. No estudo foram incluídos os prontuários que apresentaram dados que sugerem o diagnóstico de SC, sendo excluídos aqueles que apresentaram dados insuficientes para o diagnóstico e/ou que não pertenciam ao período do estudo. Resultados: Foram analisados 1303 casos de SC no período de 2010 a 2019, em relação as progenitoras: média de 24,7 ± 6,2 anos, 49% habitavam na capital, sendo que 88,6% habitavam regiões urbanas, e 1,4% residiam em outro estado. A maioria eram multíparas, com uma média de 2,3 ± 1,5 filhos, e 24,2% já tiveram algum aborto. Além disso, 50,7% tinham menos de 8 anos de estudo e a média de consultas do pré-natal foi de 5,9 ± 2,8 consultas. Em relação ao tratamento, 78,8% realizaram o tratamento adequado e apenas 5,4% não trataram. Já os parceiros, 29,6% foram tratados de forma inadequada e 30,4% não receberam tratamento. Sobre os lactentes, 50,7% eram de meninos e 49,3% de meninas, média de peso de 3.162,7 ± 598,6 gramas, sendo que 81,7% nasceram com peso adequado e 11,3% com baixo peso ao nascer. Nos exames, 34% tiveram alteração em uma radiografia de ossos longos, 0,8% em uma fundoscopia e 3,9% no teste da orelhinha, porém 64,5% não realizaram ou levaram o resultado da fundoscopia e 53,9% do teste da orelhinha. No tratamento, 65,4% foram tratados com Penicilina Cristalina, 18,3% com Penicilina Procaína,13,9% com Benzetacil e 1,4% com Ceftriaxona, apenas 1 caso não tratou. Conclusão: A SC acomete principalmente mulheres multíparas, jovens e com baixa escolaridade, ocasionando uma maior incidência de baixo peso ao nascer e uma alta prevalência de alterações ósseas nos nascituros. Além disso, é perceptível a necessidade de conscientização da população, tendo em vista a baixa realização da triagem neonatal e a discrepância na adesão dos parceiros ao tratamento adequado.

R. Amin, M. Goweida, A. Bedda et al.

Fengmin Huo, Fuzhen Zhang, Yi Xue et al.

Objectives: To compare the prevalence of levofloxacin (LFX) resistance and the population structure of Mycobacterium tuberculosis (MTB) with different mutations conferring LFX resistance between 2005 and 2015. Methods: A total 542 MTB isolates were randomly selected from pulmonary tuberculosis (TB) patients in 2005 and 2015 and analyzed regarding minimum inhibitory concentrations (MICs) and quinolone resistance-determining regions (QRDR). Results: One hundred and eleven of the 542 MTB isolates analyzed (20.5%) were resistant to LFX. There were 42 and 69 LFX-resistant isolates from 2005 and 2015, respectively, and MIC high-level LFX resistance was significantly higher in 2015 (40.6%, 28/69) than in 2005 (16.7%, 7/42) (p = 0.02). There were 87 (78.4%) mutations of these 111 LFX-resistant isolates. In addition, a significant difference in proportion was observed in the isolates with mutations in codon 90 of the gyrA gene between 2005 and 2015 (11.9% in 2005 versus 29.0% in 2015, p = 0.04). Conclusions: There was an alarming increase in prevalence of LFX-resistant TB in China between 2005 and 2015. This dynamic change is mostly attributed to the increase in high-level LFX resistance. Moreover, a significant difference was noted in the proportion of LFX-resistant isolates harboring specific mutations within the gyrA gene between 2005 and 2015. Keywords: Tuberculosis, Levofloxacin, Drug resistance, gyrA, China

A. Shariati, F. Fallah, A. Pormohammad et al.

Irritable bowel syndrome (IBS) is a prolonged and disabling functional gastrointestinal disorder with the incidence rate of 18% in the world. IBS could seriously affect lifetime of patients and cause high economic burden on the community. The pathophysiology of the IBS is hardly understood, whereas several possible mechanisms, such as visceral hypersensitivity, irregular gut motility, abnormal brain–gut relations, and the role of infectious agents, are implicated in initiation and development of this syndrome. Different studies demonstrated an alteration in B‐lymphocytes, mast cells (MC), T‐lymphocytes, and cytokine concentrations in intestinal mucosa or systemic circulation that are likely to contribute to the formation of the IBS. Therefore, IBS could be developed in those with genetic predisposition. Infections’ role in initiation and exacerbation of IBS has been investigated by quite several clinical studies; moreover, the possible role of some pathogens in development and exacerbation of this disease has been described. It appears that the main obligatory pathogens correspond with the IBS disease, Clostridium difficile, Escherichia coli, Mycobacterium avium subspecies paratuberculosis, Campylobacter concisus, Campylobacter jejuni, Chlamydia trachomatis, Helicobacter pylori, Pseudomonas aeruginosa, Salmonella spp, Shigella spp, and viruses, particularly noroviruses. A number of pathogenic parasites (Blastocystis, Dientamoeba fragilis, and Giardia lamblia) may also be involved in the progression and exacerbation of the disease. Based on the current knowledge, the current study concludes that the most common bacterial, viral, and parasitic pathogens may be involved in the development and progression of IBS.

Andrés Sánchez Alberti, A. Bivona, N. Cerny et al.

The parasite Trypanosoma cruzi is the causative agent of Chagas disease, a potentially life-threatening infection that represents a major health problem in Latin America. Several characteristics of this protozoan contribute to the lack of an effective vaccine, among them: its silent invasion mechanism, T. cruzi antigen redundancy and immunodominance without protection. Taking into account these issues, we engineered Traspain, a chimeric antigen tailored to present a multivalent display of domains from key parasitic molecules, combined with stimulation of the STING pathway by c-di-AMP as a novel prophylactic strategy. This formulation proved to be effective for the priming of functional humoral responses and pathogen-specific CD8+ and CD4+ T cells, compatible with a Th1/Th17 bias. Interestingly, vaccine effectiveness assessed across the course of infection, showed a reduction in parasite load and chronic inflammation in different proof of concept assays. In conclusion, this approach represents a promising tool against parasitic chronic infections.Chagas disease: protecting from chronic parasitic diseaseAn amalgamation of parasitic proteins may be the first effective vaccine against the as yet untreatable chronic phase of Chagas disease. The infliction, caused by the parasite Trypanosoma cruzi (T. cruzi), is the world’s leading cause of infectious cardiac inflammation and puts one-sixth of the population of Latin America at risk of infection. International collaborators led by Emilio Malchiodi, of the University of Buenos Aires, Argentina, constructed a vaccine (dubbed ‘Traspain’) comprised of key T. cruzi proteins alongside a novel ‘adjuvant’—designed to promote the efficacy of a vaccine by activating inflammatory responses. The chimera and adjuvant combination elicited a promising immune response and also showed the capacity to prevent tissue damage caused by chronic infection. Multi-part vaccines such as Traspain offer an attractive direction for research into vaccines against chronic parasitic infections.

H. Smits, P. Hiemstra, C. U. Prazeres da Costa et al.

Kanokpich Puaprasert, Cindy Chu, Naowarat Saralamba et al.

Abstract Background Plasmodium vivax malaria is characterized by relapses arising from the hypnozoite stages in the liver. The only currently registered drug for radical treatment to prevent relapse is primaquine. Primaquine, a prodrug, requires metabolism through the liver cytochrome CYP2D6 isoenzyme to its active metabolite. Mutations in the CYP2D6 gene may thus affect primaquine efficacy. A SNPs genotyping technique was developed to characterize the CYP2D6 genetic variants and tested this in the patients with Plasmodium vivax infection collected in a Karen population on the Thailand–Myanmar border, where P. vivax malaria is endemic. Methods Direct sequencing of PCR-reamplified products (DSP) was used to uncover exonic CYP2D6 sequence variations. Subsequently, an allele-specific oligonucleotide probe real-time SNPs genotyping (ASO) assay was developed for rapid detection of the four clinically relevant CYP2D6 variants occurring in this population. These two in-house developed assays were used to genotype CYP2D6 mutations in blood samples obtained from 70 Karen adults. Results Results showed a high degree of concordance between the DSP and ASO methods. Six CYP2D6 point mutations were identified within the Karen population: C100T, C1039T, G1661C, G1846A, C2850T and G4180C, at frequencies of 0.43, 0.43, 0.76, 0.02, 0.32 and 0.76, respectively. The CYP2D6*2, *4, *5, *10 and *36 allelic frequencies were 0.33, 0.02, 0.03, 0.40 and 0.01, respectively. Alleles conferring an intermediate CYP2D6 metabolizer phenotype comprised 46% of the total number of alleles. Conclusion The newly developed ASO assay is a reliable and rapid tool for large-scale CYP2D6 genotyping. The high frequency of the CYP2D6*10 allele in the Karen population warrants further assessment of its association with the radical curative efficacy of primaquine.

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L. O. Kettner, T. Henriksen, B. Bay et al.

S. Kache, J. Kang, C. Renault

Fengchen Liu, Travis C. Porco, Abdou Amza et al.

Abstract Background The World Health Organization aims to control blinding trachoma by 2020. Decisions on whether to start and stop mass treatments and when to declare that control has been achieved are currently based on clinical examination data generated in population-based surveys. Thresholds are based on the district-level prevalence of trachomatous inflammation–follicular (TF) in children aged 1–9 years. Forecasts of which districts may and may not meet TF control goals by the 2020 target date could affect resource allocation in the next few years. Methods We constructed a hidden Markov model fit to the prevalence of two clinical signs of trachoma and PCR data in 24 communities from the recent PRET-Niger trial. The prevalence of TF in children in each community at 36 months was forecast given data from earlier time points. Forecasts were scored by the likelihood of the observed results. We assessed whether use of TF with additional TI and PCR data rather than just the use of TF alone improves forecasts, and separately whether incorporating a delay in TF recovery is beneficial. Results Including TI and PCR data did not significantly improve forecasts of TF. Forecasts of TF prevalence at 36 months by the model with the delay in TF recovery were significantly better than forecasts by the model without the delay in TF recovery (p = 0.003). A zero-inflated truncated normal observation model was better than a truncated normal observation model, and better than a sensitivity-specificity observation model. Conclusion The results in this study suggest that future studies could consider using just TF data for forecasting, and should include a delay in TF recovery. Trial registration Clinicaltrials.gov NCT00792922