| 1. |
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| 2. |
- Ferreira, Mjv, et al.
(författare)
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Poster Session 3 : Tuesday 5 May 2015, 08
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
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| 5. |
- Barry, A, et al.
(författare)
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Comparative Assessment of the Pharmacovigilance Systems within the Neglected Tropical Diseases Programs in East Africa-Ethiopia, Kenya, Rwanda, and Tanzania
- 2021
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- Monitoring the safety of medicines used in public health programs (PHPs), including the neglected tropical diseases (NTD) program, is a WHO recommendation, and requires a well-established and robust pharmacovigilance system. The objective of this study was to assess the pharmacovigilance systems within the NTD programs in Ethiopia, Kenya, Rwanda, and Tanzania. The East African Community Harmonized Pharmacovigilance Indicators tool for PHPs was used to interview the staff of the national NTD programs. Data on four components, (i) systems, structures, and stakeholder coordination; (ii) data management and signal generation; (iii) risk assessment and evaluation; and (iv) risk management and communication, were collected and analyzed. The NTD programs in the four countries had a strategic master plan, with pharmacovigilance components and mechanisms to disseminate pharmacovigilance information. However, zero individual case safety reports were received in the last 12 months (2017/2018). There was either limited or no collaboration between the NTD programs and their respective national pharmacovigilance centers. None of the NTD programs had a specific budget for pharmacovigilance. The NTD program in all four countries had some safety monitoring elements. However, key elements, such as the reporting of adverse events, collaboration with national pharmacovigilance centers, and budget for pharmacovigilance activity, were limited/missing.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Kabatende, J, et al.
(författare)
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Prevalence, Intensity, and Correlates of Soil-Transmitted Helminth Infections among School Children after a Decade of Preventive Chemotherapy in Western Rwanda
- 2020
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Ingår i: Pathogens (Basel, Switzerland). - : MDPI AG. - 2076-0817. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Preventive chemotherapy (PC) is a WHO-recommended core intervention measures to eliminate Soil-Transmitted Helminths (STH) as a public health problem by 2020, defined as a reduction in prevalence to <1% of moderate or high-intensity infection. We conducted a cross-sectional study to investigate the prevalence, intensity, and correlates of STH after a decade of PC in Rwanda. A total of 4998 school children (5–15 years old) from four districts along Lake Kivu in the western province were screened for STH using Kato-Katz. The overall prevalence of Soil-transmitted helminths among school children was 77.7% (range between districts = 54% to 92%). Trichirus trichiura was the most common STH (66.8%, range between districts = 23% to 88.2%), followed by Ascaris lumbricoides (49.9%, range between district = 28.5% to 63.3%) and hookworms (1.9%, range between districts = 0.6% to 2.9%). The prevalence of single, double and of triple parasite coinfection were 48.6%, 50.3%, and 1.1%, respectively. The overall prevalence of moderate or high-intensity infection for Trichirus trichiura and Ascaris lumbricoides was 7.1% and 13.9, respectively. Multivariate logistic regression model revealed that male sex, district, stunting, and schistosomiasis coinfection as significant predictors of STH infection. Despite a decade of PC implementation, STH remain a significant public health problem in Rwanda.
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| 10. |
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| 11. |
- Kabatende, J, et al.
(författare)
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Efficacy of Single-Dose Albendazole for the Treatment of Soil-Transmitted Helminthic Infections among School Children in Rwanda-A Prospective Cohort Study
- 2023
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Ingår i: Pharmaceuticals (Basel, Switzerland). - : MDPI AG. - 1424-8247. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- Mass drug administration (MDA) of single-dose albendazole to all at-risk populations as preventive chemotherapy (deworming) is recommended by WHO to halt transmission of soil-transmitted helminth (STH) in endemic countries. We assessed the effectiveness of single-dose albendazole against STH infection in the western province of Rwanda, where STH prevalence remains high despite the implementation of preventive chemotherapy for over a decade. Two weeks before the scheduled MDA, 4998 school children (5–15 years old) were screened for STH infections (Ascaris lumbricoides, Trichuris trichiura, and hookworm), and 1526 children who tested positive for at least one type of STH parasite were enrolled and received single-dose albendazole (400 mg) through MDA. A follow-up stool exam was performed at three weeks post-treatment using Kato–Katz. Efficacy was assessed by cure rate (CR), defined as the proportion of children who became egg-free, and egg reduction rates (ERRs) at three weeks post-treatment. The CR and ERR for hookworms (CR = 96.7%, ERR = 97.4%) was above, and for Ascaris lumbricoides (CR = 95.1%, ERR = 94.6%) was borderline compared with the WHO efficacy threshold (CR and ERR ≥ 95%). However, the CR and ERR for T. trichiura (CR = 17.6% ERR = 40.3%) were below the WHO threshold for efficacy (CR and ERR ≥ 50%). Having moderate-to-heavy infection intensity and coinfection with another type of STH parasites were independent risk factors for lower CR and ERR against Trichirus trichiura (p < 0.001). Single-dose albendazole used in the MDA program is efficacious for the treatment and control for hookworms and Ascaris lumbricoides infections but not effective for Trichirus trichiura. An alternative treatment regimen is urgently needed to prevent, control, and eliminate STH as a public health problem.
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| 12. |
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| 13. |
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| 14. |
- Bienvenu, E., et al.
(författare)
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Changes in the Proteome in the Development of Chronic Human Papillomavirus Infection-A Prospective Study in HIV Positive and HIV Negative Rwandan Women
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:23
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Cervical cancer is the predominant cause of female cancer deaths in Sub-Saharan Africa. Chronic infection of the uterine cervix by the human papillomavirus (HPV) is the most important factor for the development of cervical cancer. HPV screening may be used to screen out women at risk of cervical cancer; however, the majority of HPV infections will eventually heal, and at present, there are no screening methods to detect which HPV infections that will become chronic. In the present study, we followed HIV-negative and HIV-positive Rwandan women with cervical HPV infections for two years with repeated samplings from the uterine cervix. We identified protein biomarkers that correlate with the potential risk for women to develop cervical cancer. By including the identified biomarkers in cervical screening programs, we are able, potentially, to identify those women with cervical HPV infections, who should be carefully monitored in the future. Background: Effects on the proteome when a high risk (HR)-HPV infection occurs, when it is cleared and when it becomes chronic were investigated. Moreover, biomarker panels that could identify cervical risk lesions were assessed. Methods: Cytology, HPV screening and proteomics were performed on cervical samples from Rwandan HIV+ and HIV- women at baseline, at 9 months, at 18 months and at 24 months. Biological pathways were identified using the String database. Results: The most significantly affected pathway when an incident HR-HPV infection occurred was neutrophil degranulation, and vesicle-mediated transport was the most significantly affected pathway when an HR-HPV infection was cleared; protein insertion into membrane in chronic HR-HPV lesions and in lesions where HR-HPVs were cleared were compared; and cellular catabolic process in high-grade lesions was compared to that in negative lesions. A four-biomarker panel (EIF1; BLOC1S5; LIMCH1; SGTA) was identified, which was able to distinguish chronic HR-HPV lesions from cleared HR-HPV/negative lesions (sensitivity 100% and specificity 91%). Another four-biomarker panel (ERH; IGKV2-30; TMEM97; DNAJA4) was identified, which was able to distinguish high-grade lesions from low-grade/negative lesions (sensitivity 100% and specificity 81%). Conclusions: We have identified the biological pathways triggered in HR-HPV infection, when HR-HPV becomes chronic and when cervical risk lesions develop. Moreover, we have identified potential biomarkers that may help to identify women with cervical risk lesions.
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| 15. |
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| 16. |
- Mukanyangezi, Marie Francoise, et al.
(författare)
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Persistence rate of cervical human papillomavirus infections and abnormal cytology in Rwanda
- 2019
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Ingår i: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 20:7, s. 485-495
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Tidskriftsartikel (refereegranskat)abstract
- Objectives In this study, we determined the incidence and persistence of human papillomavirus (HPV) strains and of squamous intraepithelial lesions (SIL) or worse cytology in 237 HIV-positive and HIV-negative Rwandan women and whether the interleukin (IL)-28B single nucleotide polymorphism (SNP) at rs12979860 correlated with susceptibility to and persistence of HPV infection. Methods Cervical samples were collected at baseline and after 9, 18 and 24 months for a 40-HPV DNA screening test and a ThinPrep Pap test. Genotyping of the IL-28B SNP rs12979860 was performed using real-time polymerase chain reaction (PCR). Results Chronic high-risk (HR) HPV infections occurred in 56% of HIV-positive women, while no HIV-negative women developed HPV chronicity. High-grade SIL (HSIL) or cancer was diagnosed in 38% of HIV-positive women with persistent HR-HPV infections. HIV and HR-HPV positivity at baseline were factors associated with an increased risk of HPV persistence. Additionally, HR-HPV positivity at baseline was associated with an increased risk of developing HSIL or worse cytology. The unfavourable T/x genotype at rs12979860 is common among Africans, and women with this genotype were found to be more commonly infected with HPV. Conclusions HPV screening in Rwanda may help to identify women at risk of developing cervical cancer and polymorphism in IL-28B may be associated with risk of contracting HPV infection.
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| 17. |
- Mukanyangezi, Marie Francoise, et al.
(författare)
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Screening for human papillomavirus, cervical cytological abnormalities and associated risk factors in HIV-positive and HIV-negative women in Rwanda.
- 2018
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Ingår i: HIV medicine. - : Wiley. - 1468-1293 .- 1464-2662. ; 19:2, s. 152-166
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Tidskriftsartikel (refereegranskat)abstract
- Cervical cancer is the major cause of death from cancer in Africa. We wanted to assess the prevalence of human papillomavirus (HPV) infections and associated risk factors and to determine whether HPV testing could serve as a screening method for squamous intraepithelial lesions (SILs) in Rwanda. We also wanted to obtain a broader understanding of the underlying risk factors for the establishment of HPV infection in Rwanda.A total of 206 HIV-positive women, 172 HIV-negative women and 22 women with unknown HIV status were recruited at the University Teaching Hospitals of Kigali (UTHK) and of Butare (UTHB) in Rwanda. Participants underwent an interview, cervical sampling for a Thinprep Pap test and a screening test analysing 37 HPV strains.Only 27% of HIV-positive women and 7% of HIV-negative women had been screened for cervical cancer before. HPV16 and HPV52 were the most common HPV strains. HIV-positive women were more commonly infected with high-risk (HR) HPV and multitype HPV than HIV-negative women. The sensitivity was 78% and the specificity 87% to detect high-grade SIL (HSIL) with HPV screening. Among HIV-negative women, being divorced was positively associated with HR-HPV infection, while hepatitis B, Trichomonas vaginalis infection and HR-HPV infection were factors positively associated with SILs. Ever having had gonorrhoea was positively associated with HR-HPV infection among HIV-positive women. HR-HPV infection and the number of live births were positively associated with SILs.The currently used quadrivalent vaccine may be insufficient to give satisfactory HPV coverage in Rwanda. HPV Screening may be effective to identify women at risk of developing cervical cancer, particularly if provided to high-risk patients.
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| 18. |
- Mukanyangezi, Marie Francoise, et al.
(författare)
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Sexual risk behaviour in a cohort of HIV-negative and HIV-positive Rwandan women
- 2019
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Ingår i: Epidemiology and Infection. - : Cambridge University Press (CUP). - 0950-2688 .- 1469-4409. ; 147
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Tidskriftsartikel (refereegranskat)abstract
- Here we wanted to assess whether sexual risk behaviour differs dependent by human immunodeficiency virus (HIV) status by following 100 HIV- and 137 HIV+ women recruited at two university teaching hospitals in Rwanda. Women were tested for sexually transmitted infections (STIs; trichomoniasis, syphilis, hepatitis B and C) and for reproductive tract infections (RTIs; candidiasis, bacterial vaginosis (BV)) and were interviewed at baseline and 9 months later. BV was the most prevalent infection, while syphilis was the most common STI with a 9-month incidence of 10.9% in HIV+ women. Only 24.5% of women positive for any RTI/STI contacted their health facility and got treatment. More HIV- women than HIV+ women had had more than one sexual partner and never used condoms during the follow-up period. The use of condoms was affected neither by marital status nor by concomitant STIs besides HIV. Our data highlight the importance of public education regarding condom use to protect against STIs in an era when HIV no longer is a death sentence.
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| 19. |
- Sundell, Jesper, et al.
(författare)
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Effect of efavirenz-based ART on the pharmacokinetics of rifampicin and its primary metabolite in patients coinfected with TB and HIV
- 2021
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Ingår i: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 76:11, s. 2950-2957
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the effects of concomitant efavirenz-based ART and genetic polymorphism on the variability in rifampicin and 25-desacetylrifampicin pharmacokinetics. Patients and methods: Plasma concentrations of rifampicin and 25-desacetylrifampicin from 63 patients coinfected with TB and HIV were analysed by LC-MS/MS followed by non-linear mixed-effects modelling. Patients were genotyped for SLCO1B1 (463 C>A, 388 A>G, 11187 G>A, rs4149015, 521 T>C and 1436 G>C) and SLCO1B3 (334 T>G). Results: One-compartment disposition models described the observations adequately. The oral clearances of rifampicin and 25-desacetylrifampicin were 140% and 110% higher, respectively, in patients on concomitant efavirenz-based ART. Rifampicin bioavailability was also lower in patients on concomitant ART. Further, although not included in the final model, a lower relative bioavailability in carriers of WT SLCO1B3 334 T>G compared with carriers of mutations in the genotype was estimated. Conclusions: The results presented indicate both pre-systemic and systemic induction by efavirenz-based ART affecting rifampicin pharmacokinetics. The described drug-drug interaction has a clinical impact on rifampicin exposure prior to steady state and may impact the early bactericidal activity in patients on efavirenz-based ART.
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| 20. |
- Sundell, Jesper, et al.
(författare)
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Effects of Enzyme Induction and Polymorphism on the Pharmacokinetics of Isoniazid and Rifampin in Tuberculosis/HIV Patients
- 2022
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 66:10
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Tidskriftsartikel (refereegranskat)abstract
- Tuberculosis is the most common cause of death in HIV-infected individuals. Rifampin and isoniazid are the backbones of the current first-line antitubercular therapy. The aim of the present study was to describe the time-dependent pharmacokinetics and pharmacogenetics of rifampin and isoniazid and to quantitatively evaluate the drug-drug interaction between rifampin and isoniazid in patients coinfected with HIV. Plasma concentrations of isoniazid, acetyl-isoniazid, isonicotinic acid, rifampin, and 25-desacetylrifampin from 40 HIV therapy-naive patients were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after the first dose and at steady state of antitubercular therapy. Patients were genotyped for determination of acetylator status and CYP2C19 phenotype. Nonlinear mixed-effects models were developed to describe the pharmacokinetic data. The model estimated an autoinduction of both rifampin bioavailability (0.5-fold) and clearance (2.3-fold). 25-Desacetylrifampin clearance was 2.1-fold higher at steady state than after the first dose. Additionally, ultrarapid CYP2C19 metabolizers had a 2-fold-higher rifampin clearance at steady state than intermediate or extensive metabolizers. An induction of isonicotinic acid formation from isoniazid dependent on total rifampin dose was estimated. Simulations indicated a 30% lower isoniazid exposure at steady state during administration of standard rifampin doses than isoniazid exposure in noninduced individuals. Rifampin exposure was correlated with CYP2C19 polymorphism, and rifampin administration may increase exposure to toxic metabolites by isoniazid in patients. Both findings may influence the risk of treatment failure, resistance development, and toxicity and require further investigation, especially with regard to ongoing high-dose rifampin trials.
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| 21. |
- Sundell, Jesper, et al.
(författare)
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Factors Affecting the Pharmacokinetics of Pyrazinamide and Its Metabolites in Patients Coinfected with HIV and Implications for Individualized Dosing
- 2021
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 65:7
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Tidskriftsartikel (refereegranskat)abstract
- Pyrazinamide is a first-line drug used in the treatment of tuberculosis. High exposure to pyrazinamide and its metabolites may result in hepatotoxicity, whereas low exposure to pyrazinamide has been correlated with treatment failure of first-line antitubercular therapy. The aim of this study was to describe the pharmacokinetics and metabolism of pyrazinamide in patients coinfected with tuberculosis and HIV. We further aimed to identify demographic and clinical factors which affect the pharmacokinetics of pyrazinamide and its metabolites in order to suggest individualized dosing regimens. Plasma concentrations of pyrazinamide, pyrazinoic acid, and 5-hydroxypyrazinamide from 63 Rwandan patients coinfected with tuberculosis and HIV were determined by liquid chromatography-tandem mass spectrometry followed by nonlinear mixed-effects modeling. Females had a close to 50% higher relative pyrazinamide bioavailability compared to males. The distribution volumes of pyrazinamide and both metabolites were lower in patients on concomitant efavirenz-based HIV therapy. Furthermore, there was a linear relationship between serum creatinine and oral clearance of pyrazinoic acid. Simulations indicated that increasing doses from 25 mg/kg of body weight to 35 mg/kg and 50 mg/kg in females and males, respectively, would result in adequate exposure with regard to suggested thresholds and increase probability of target attainment to >0.9 for a MIC of 25 mg/liter. Further, lowering the dose by 40% in patients with high serum creatinine would prevent accumulation of toxic metabolites. Individualized dosing is proposed to decrease variability in exposure to pyrazinamide and its metabolites. Reducing the variability in exposure may lower the risk of treatment failure and resistance development.
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| 22. |
- Sundell, Jesper, et al.
(författare)
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Model-Based Assessment of Variability in Isoniazid Pharmacokinetics and Metabolism in Patients Co-Infected With Tuberculosis and HIV: Implications for a Novel Dosing Strategy
- 2020
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Ingår i: Clinical Pharmacology & Therapeutics. - : Wiley. - 0009-9236 .- 1532-6535. ; 108:1, s. 73-80
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Tidskriftsartikel (refereegranskat)abstract
- Tuberculosis is the most common cause of death in HIV-infected patients. Isoniazid is used as a first-line drug to treat tuberculosis infection. However, variability in isoniazid pharmacokinetics can result in hepatotoxicity or treatment failure. Determination of clinical factors affecting isoniazid pharmacokinetics and metabolic pathways in HIV co-infected patients is therefore critical. Plasma levels of isoniazid, acetyl-isoniazid, and isonicotinic acid from 63 patients co-infected with tuberculosis and HIV were analyzed by liquid chromatography with tandem mass spectrometry followed by nonlinear mixed-effects modeling. Patients were genotyped to determine acetylator status. Patients were either on concomitant efavirenz-based antiretroviral therapy or HIV treatment naive. Clearances of isoniazid were 1.3-fold and 2.3-fold higher in intermediate and rapid acetylators, respectively, compared with slow acetylators. Patients on concomitant efavirenz-based antiretroviral therapy had 64% and 80% higher population predicted clearances of acetyl-isoniazid and isonicotinic acid, respectively, compared with patients who were HIV treatment naive. Both sex and CD4 cell count affected the bioavailability of isoniazid. Variability in isoniazid exposure could be reduced by dose adaptions based on acetylator type and sex in addition to the currently used weight bands. A novel dosing strategy that has the potential to reduce isoniazid-related toxicity and treatment failure is presented.
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| 23. |
- Sundell, Jesper, et al.
(författare)
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Population Pharmacokinetics and Pharmacogenetics of Ethambutol in Adult Patients Coinfected with Tuberculosis and HIV
- 2020
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 64:2
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to characterize the population pharmacokinetics and pharmacogenetics of ethambutol in tuberculosis-HIV-coinfected adult patients. Ethambutol plasma concentrations, determined by liquid chromatography-tandem mass spectrometry, in 63 patients receiving ethambutol as part of rifampin-based fixed-dose combination therapy for tuberculosis were analyzed using nonlinear mixed-effects modeling. A one-compartment disposition model with first-order elimination and four transit compartments prior to first-order absorption was found to adequately describe the concentration-time profiles of ethambutol in plasma. Body weight was implemented as an allometric function on the clearance and volume parameters. Estimates of oral clearance and volume of distribution were 77.4 liters/h and 76.2 liters, respectively. A G/A mutation with regard to CYP1A2 2159 G>A was associated with a 50% reduction in relative bioavailability. Simulations revealed that doses of 30 mg/kg of body weight and 50 mg/kg for G/G and G/A carriers, respectively, would result in clinically adequate exposure. The results presented here suggest that CYP1A2 polymorphism affects ethambutol exposure in this population and that current treatment guidelines may result in underexposure in patients coinfected with tuberculosis and HIV. Based on simulations, a dose increase from 15 to 20 mg/kg to 30 mg/kg is suggested. However, the 50-mg/kg dose required to reach therapeutic exposure in G/A carriers may be inappropriate due to the dose-dependent toxicity of ethambutol. Additional studies are required to further investigate CYP450 polymorphism effects on ethambutol pharmacokinetics.
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| 24. |
- Sundell, Jesper, et al.
(författare)
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Simultaneous quantification of four first line antitubercular drugs and metabolites in human plasma by hydrophilic interaction chromatography and tandem mass spectrometry
- 2019
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Ingår i: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. - : Elsevier BV. - 1570-0232. ; 1105, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- Co-infection of tuberculosis in HIV-patients is a major health concern worldwide and especially so in Sub-Saharan Africa. To enhance the study of potential drug-drug interactions when simultaneously treating the two infections, a liquid chromatography tandem mass spectrometry method was developed for the quantitation of the four first line anti-tuberculosis drugs isoniazid, rifampicin, pyrazinamide, ethambutol and four of their major metabolites in human plasma. Analytes were extracted from 200 μL of plasma using a sequential liquid-liquid extraction with ethyl acetate at neutral and acidic pH. The combined extracts were analyzed by liquid chromatography with mass spectrometric detection in a multiple reaction monitoring mode. The chromatographic separation was performed on a hydrophilic interaction column using a stepwise gradient with two mobile phases consisting of water with 0.3% formic acid and methanol with 0.3% formic acid, respectively. The total run time of each analysis was 4 min. The lower limit of quantification applied was 40 ng/mL for ethambutol, acetylisoniazid and 25-desacetylrifampicin, 60 ng/mL for 5-hydroxypyrazinamide, 80 ng/mL for isoniazid and isonicotinic acid, 200 ng/mL for rifampicin and 320 ng/mL for pyrazinamide. The method was validated according to US Food and Drug Administration guidance. The method exhibited adequate accuracy (87.1–114.9%), precision (CV < 12.8%) and specificity. Recovery and matrix effect were consistent (CV < 11.9%). The extracted samples were stable in the autosampler at 8 °C for up to 24 h as well as after three freeze-thaw cycles (recovery > 86.3%). The method has been shown to be robust for the analysis of the stated drugs and metabolites in human plasma obtained from 73 patients receiving these four first line anti-tuberculosis drugs. © 2018 Elsevier B.V.
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| 25. |
- Upstill-Goddard, Robert C., et al.
(författare)
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The riverine source of CH4 and N2O from the Republic of Congo, western Congo Basin
- 2017
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 14:9, s. 2267-2281
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Tidskriftsartikel (refereegranskat)abstract
- We discuss concentrations of dissolved CH4, N2O, O-2, NO(3)(-)and NH4-, and emission fluxes of CH4 and N2O for river sites in the western Congo Basin, Republic of Congo (ROC). Savannah, swamp forest and tropical forest samples were collected from the Congo main stem and seven of its tributaries during November 2010 (41 samples; wet season) and August 2011 (25 samples; dry season; CH4 and N2O only). Dissolved inorganic nitrogen (DIN: NH4- + NO3-; wet season) was dominated by NO3- (63 +/- 19% of DIN). Total DIN concentrations (1.545.3 mu mol L-1) were consistent with the near absence of agricultural, domestic and industrial sources for all three land types. Dissolved O-2 (wet season) was mostly undersaturated in swamp forest (36 +/- 29 %) and tropical forest (77 +/- 36 %) rivers but predominantly supersaturated in savannah rivers (100 +/- 17 %). The dissolved concentrations of CH4 and N2O were within the range of values reported earlier for sub-Saharan African rivers. Dissolved CH4 was found to be supersaturated (11.2-9553 nmol L-1; 440-354 444 %), whereas N2O ranged from strong undersaturation to supersaturation (3.2-20.6 nmol L-1; 47-205 %). Evidently, rivers of the ROC are persistent local sources of CH4 and can be minor sources or sinks for N2O. During the dry season the mean and range of CH4 and N2O concentrations were quite similar for the three land types. Wet and dry season mean concentrations and ranges were not significant for N2O for any land type or for CH4 in savannah rivers. The latter observation is consistent with seasonal buffering of river discharge by an underlying sandstone aquifer. Significantly higher wet season CH4 concentrations in swamp and forest rivers suggest that CH4 can be derived from floating macrophytes during flooding and/or enhanced methanogenesis in adjacent flooded soils. Swamp rivers also exhibited both low (47 %) and high (205 %) N2O saturation but wet season values were overall significantly lower than in either tropical forest or savannah rivers, which were always supersaturated (103-266 %) and for which the overall means and ranges of N2O were not significantly different. In swamp and forest rivers O-2 saturation co-varied inversely with CH4 saturation (log %) and positively with % N2O. A significant positive correlation between N2O and O-2 saturation in swamp rivers was coincident with strong N2O and O-2 undersaturation, indicating N2O consumption during denitrification in the sediments. In savannah rivers persistent N2O supersaturation and a negative correlation between N2O and O-2 suggest N2O production mainly by nitrification. This is consistent with a stronger correlation between N2O and NH4+ than between N2O and NO3-. Our ranges of values for CH4 and N2O emission fluxes (33-48 705 mu mol CH4 m(-2) d(-1); 1-67 mu mol N(2)Om(2)(-) d(-1)) are within the ranges previously estimated for sub-Saharan African rivers but they include uncertainties deriving from our use of basin-wide values for CH4 and N2O gas transfer velocities. Even so, because we did not account for any contribution from ebullition, which is quite likely for CH4 (at least 20 %), we consider our emission fluxes for CH4 to be conservative.
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