Journal Article > LetterFull Text
Clin Infect Dis. 2017 August 1; Volume 65 (Issue 3); DOI:10.1093/cid/cix382
Brooks HM, Jean Paul MK, Claude KM, Houston S, Hawkes MT
Clin Infect Dis. 2017 August 1; Volume 65 (Issue 3); DOI:10.1093/cid/cix382
Journal Article > ResearchFull Text
CPT Pharmacometrics Syst Pharmacol. 2013 November 13; Volume 2 (Issue 11); e83.; DOI:10.1038/psp.2013.59
Kloprogge F, Piola P, Dhorda M, Muwanga S, Turyakira E, et al.
CPT Pharmacometrics Syst Pharmacol. 2013 November 13; Volume 2 (Issue 11); e83.; DOI:10.1038/psp.2013.59
Pregnancy alters the pharmacokinetic properties of many antimalarial compounds. The objective of this study was to evaluate the pharmacokinetic properties of lumefantrine in pregnant and nonpregnant women with uncomplicated Plasmodium falciparum malaria in Uganda after a standard fixed oral artemether-lumefantrine treatment. Dense venous (n = 26) and sparse capillary (n = 90) lumefantrine samples were drawn from pregnant patients. A total of 17 nonpregnant women contributed with dense venous lumefantrine samples. Lumefantrine pharmacokinetics was best described by a flexible absorption model with multiphasic disposition. Pregnancy and body temperature had a significant impact on the pharmacokinetic properties of lumefantrine. Simulations from the final model indicated 27% lower day 7 concentrations in pregnant women compared with nonpregnant women and a decreased median time of 0.92 and 0.42 days above previously defined critical concentration cutoff values (280 and 175 ng/ml, respectively). The standard artemether-lumefantrine dose regimen in P. falciparum malaria may need reevaluation in nonimmune pregnant women.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 2016 October 3; Volume 95 (Issue 6); 1389–1397 .; DOI:10.4269/ajtmh.16-0376
Tiffany A, Moundekeno FP, Traore A, Haile M, Sterk E, et al.
Am J Trop Med Hyg. 2016 October 3; Volume 95 (Issue 6); 1389–1397 .; DOI:10.4269/ajtmh.16-0376
Multiple community-based approaches can aid in quantifying mortality in the absence of reliable health facility data. Community-based sentinel site surveillance that was used to document mortality and the systems utility for outbreak detection was evaluated. We retrospectively analyzed data from 46 sentinel sites in three sous-préfectures with a reinforced malaria control program and one sous-préfecture without (Koundou) in Guinea. Deaths were recorded by key informants and classified as due to malaria or another cause. Malaria deaths were those reported as due to malaria or fever in the 3 days before death with no other known cause. Suspect Ebola virus disease (sEVD) deaths were those due to select symptoms in the EVD case definition. Deaths were aggregated by sous-préfecture and analyzed by a 6-month period. A total of 43,000 individuals were monitored by the surveillance system; 1,242 deaths were reported from July 2011-June 2014, of which 55.2% (N = 686) were reported as due to malaria. Malaria-attributable proportional mortality decreased by 26.5% (95% confidence interval [CI] = 13.9-33.1, P < 0.001) in the program area and by 6.6% (95% CI = -17.3-30.5, P = 0.589) in Koundou. Sixty-eight deaths were classified as sEVD and increased by 6.1% (95% CI = 1.3-10.8, P = 0.021). Seventeen sEVD deaths were reported from November 2013 to March 2014 including the first two laboratory-confirmed EVD deaths. Community surveillance can capture information on mortality in areas where data collection is weak, but determining causes of death remains challenging. It can also be useful for outbreak detection if timeliness of data collection and reporting facilitate real-time data analysis.
Journal Article > ResearchFull Text
Malar J. 2021 December 14; Volume 20 (Issue 1); 464.; DOI:10.1186/s12936-021-04002-8
Bandibabone JB, McLoughlin C, Ndo S, Bantuzeko C, Byabushi V, et al.
Malar J. 2021 December 14; Volume 20 (Issue 1); 464.; DOI:10.1186/s12936-021-04002-8
BACKGROUND
Malaria vector control in the Democratic Republic of the Congo is plagued by several major challenges, including inadequate infrastructure, lack of access to health care systems and preventative measures, and more recently the widespread emergence of insecticide resistance among Anopheles mosquitoes. Across 26 provinces, insecticide resistance has been reported from multiple sentinel sites. However, to date, investigation of molecular resistance mechanisms among Anopheles vector populations in DRC has been more limited.
METHODS
Adult Anopheles gambiae sensu lato (s.l.) and Anopheles funestus s.l. were collected from two sites in Sud-Kivu province and one site in Haut-Uélé province and PCR-screened for the presence of 11 resistance mutations, to provide additional information on frequency of resistance mechanisms in the eastern DRC, and to critically evaluate the utility of these markers for prospective country-wide resistance monitoring.
RESULTS
L1014F-kdr and L1014S-kdr were present in 75.9% and 56.7% of An. gambiae s.l. screened, respectively, with some individuals harbouring both resistant alleles. Across the three study sites, L43F-CYP4J5 allele frequency ranged from 0.42 to 0.52, with evidence for ongoing selection. G119S-ace1 was also identified in all sites but at lower levels. A triple mutant haplotype (comprising the point mutation CYP6P4-I236M, the insertion of a partial Zanzibar-like transposable element and duplication of CYP6AA1) was present at high frequencies. In An. funestus s.l. cis-regulatory polymorphisms in CYP6P9a and CYP6P9b were detected, with allele frequencies ranging from 0.82 to 0.98 and 0.65 to 0.83, respectively.
CONCLUSIONS
This study screened the most up-to-date panel of DNA-based resistance markers in An. gambiae s.l. and An. funestus s.l. from the eastern DRC, where resistance data is lacking. Several new candidate markers (CYP4J5, G119S-ace1, the triple mutant, CYP6P9a and CYP6P9b) were identified, which are diagnostic of resistance to major insecticide classes, and warrant future, larger-scale monitoring in the DRC to inform vector control decisions by the National Malaria Control Programme.
Malaria vector control in the Democratic Republic of the Congo is plagued by several major challenges, including inadequate infrastructure, lack of access to health care systems and preventative measures, and more recently the widespread emergence of insecticide resistance among Anopheles mosquitoes. Across 26 provinces, insecticide resistance has been reported from multiple sentinel sites. However, to date, investigation of molecular resistance mechanisms among Anopheles vector populations in DRC has been more limited.
METHODS
Adult Anopheles gambiae sensu lato (s.l.) and Anopheles funestus s.l. were collected from two sites in Sud-Kivu province and one site in Haut-Uélé province and PCR-screened for the presence of 11 resistance mutations, to provide additional information on frequency of resistance mechanisms in the eastern DRC, and to critically evaluate the utility of these markers for prospective country-wide resistance monitoring.
RESULTS
L1014F-kdr and L1014S-kdr were present in 75.9% and 56.7% of An. gambiae s.l. screened, respectively, with some individuals harbouring both resistant alleles. Across the three study sites, L43F-CYP4J5 allele frequency ranged from 0.42 to 0.52, with evidence for ongoing selection. G119S-ace1 was also identified in all sites but at lower levels. A triple mutant haplotype (comprising the point mutation CYP6P4-I236M, the insertion of a partial Zanzibar-like transposable element and duplication of CYP6AA1) was present at high frequencies. In An. funestus s.l. cis-regulatory polymorphisms in CYP6P9a and CYP6P9b were detected, with allele frequencies ranging from 0.82 to 0.98 and 0.65 to 0.83, respectively.
CONCLUSIONS
This study screened the most up-to-date panel of DNA-based resistance markers in An. gambiae s.l. and An. funestus s.l. from the eastern DRC, where resistance data is lacking. Several new candidate markers (CYP4J5, G119S-ace1, the triple mutant, CYP6P9a and CYP6P9b) were identified, which are diagnostic of resistance to major insecticide classes, and warrant future, larger-scale monitoring in the DRC to inform vector control decisions by the National Malaria Control Programme.
Journal Article > ResearchFull Text
Malar J. 2017 October 28; Volume 16 (Issue 1); 449.; DOI:10.1186/s12936-017-2094-3
Oyet C, Roh ME, Kiwanuka G, Orikiriza P, Wade M, et al.
Malar J. 2017 October 28; Volume 16 (Issue 1); 449.; DOI:10.1186/s12936-017-2094-3
BACKGROUND
Early diagnosis of suspected malaria cases with a rapid diagnostic test (RDT) has been shown to be an effective malaria control tool used in many resource-constrained settings. However, poor quality control and quality assurance hinder the accurate reporting of malaria diagnoses. Recent use of a portable, battery operated RDT reader (Deki Reader™, Fio Corporation) has shown to have high agreement with visual inspection across diverse health centre settings, however evidence of its feasibility and usability during cross sectional surveys are limited. This study aimed to evaluate the performance of the Deki Reader™ in a cross-sectional survey of children from southwestern Uganda.
METHODS
A two-stage, stratified cluster sampling survey was conducted between July and October 2014 in three districts of southwestern Uganda, with varying malaria transmission intensities. A total of 566 children aged 6-59 months were included in the analysis. Blood samples were collected and tested for malaria using: the SD Bioline Malaria Ag Pf/Pan RDT and microscopy. Results were compared between visual inspection of the RDT and by the Deki Reader™. Diagnostic performance of both methods were compared to gold-standard microscopy.
RESULTS
The sensitivity and specificity of the Deki Reader™ was 94.1% (95% CI 69.2-99.6%) and 95.6% (95% CI 93.4-97.1%), respectively. The overall percent agreement between the Deki Reader™ and visual RDT inspection was 98.9% (95% CI 93.2-99.8), with kappa statistic of 0.92 (95% CI 0.85-0.98).
CONCLUSIONS
The findings from this study suggest that the Deki Reader™ is comparable to visual inspection and performs well in detecting microscopy-positive Plasmodium falciparum cases in a household survey setting. However, the reader's performance was highly dependent on ensuring adequate battery life and a work environment free of dirt particles.
Early diagnosis of suspected malaria cases with a rapid diagnostic test (RDT) has been shown to be an effective malaria control tool used in many resource-constrained settings. However, poor quality control and quality assurance hinder the accurate reporting of malaria diagnoses. Recent use of a portable, battery operated RDT reader (Deki Reader™, Fio Corporation) has shown to have high agreement with visual inspection across diverse health centre settings, however evidence of its feasibility and usability during cross sectional surveys are limited. This study aimed to evaluate the performance of the Deki Reader™ in a cross-sectional survey of children from southwestern Uganda.
METHODS
A two-stage, stratified cluster sampling survey was conducted between July and October 2014 in three districts of southwestern Uganda, with varying malaria transmission intensities. A total of 566 children aged 6-59 months were included in the analysis. Blood samples were collected and tested for malaria using: the SD Bioline Malaria Ag Pf/Pan RDT and microscopy. Results were compared between visual inspection of the RDT and by the Deki Reader™. Diagnostic performance of both methods were compared to gold-standard microscopy.
RESULTS
The sensitivity and specificity of the Deki Reader™ was 94.1% (95% CI 69.2-99.6%) and 95.6% (95% CI 93.4-97.1%), respectively. The overall percent agreement between the Deki Reader™ and visual RDT inspection was 98.9% (95% CI 93.2-99.8), with kappa statistic of 0.92 (95% CI 0.85-0.98).
CONCLUSIONS
The findings from this study suggest that the Deki Reader™ is comparable to visual inspection and performs well in detecting microscopy-positive Plasmodium falciparum cases in a household survey setting. However, the reader's performance was highly dependent on ensuring adequate battery life and a work environment free of dirt particles.
Conference Material > Abstract
Robinson E, van Braak F, Rose L, Yadenzi MS
MSF Scientific Days International 2021: Research. 2021 May 19
INTRODUCTION
Protracted conflict in CAR has led to widespread political unrest and fragile health systems. Hyperendemic malaria is the main cause of morbidity. Alongside global calls to prioritise malaria prevention during the COVID-19 pandemic, MSF initiated mass drug administration (MDA) for children aged between three months and 15 years within three communes of the Bossangoa health district between 17 August and 24 November 2020. The MDA comprised three cycles of dihydroartemisin-piperaquine (DHA-PQ), given at four-week intervals. We evaluated coverage and clinical impact of the MDA, and describe community perspectives.
METHODS
We conducted a two-stage cluster household survey between 22 November and 9 December 2020. We undertook structured interviews with the heads of households and with eligible children, focusing on participation in the MDA. Participation was verified against the MDA card, if available. Using routine MSF surveillance data, we compared the following indicators during the MDA intervention to the same periods of time during 2018 and 2019: consultations, confirmed malaria cases, and positivity rates of malaria rapid diagnostic tests (mRDT’s) in MSF facilities in the intervention area, overall and by age group (≥5; <5 years); hospital admissions and in-hospital deaths with a primary diagnosis of severe malaria among children <15 years from the MDA intervention area. Following each cycle we conducted nine focus groups discussions (FGD’s) with caregivers, community leaders, and community health workers (CHW’s) Participants were selected using purposive sampling. The topic guide inluded the key themes of reasons for participation, difficulties encountered, satisfaction, and experiences throughout the MDA.
ETHICS
This study was approved by the MSF Ethics Review Board (ERB) and by the national ERB of CAR.
RESULTS
In total, we distributed 134,117 DHA-PQ courses. Among eligible children, 93.1% (95% confidence interval, CI, 85.6-96.8) received all three cycles. We estimated significant reductions only for confirmed outpatient malaria cases overall (9.2%; 95% CI 5.6-12.8), and among those aged <5 years (20.5%; 95% CI 15.3-25.8). Following the first MDA cycle, FGD participants described positive perceptions and high adherence with regard to MDA, linked with the involvement of community leaders. Participants reported reductions in childhood malaria, as well as reduced household expenditure on healthcare. Rumours about ‘drug trials’ and concerns about side effects were initial reasons for refusal, however these concerns were overcome after seeing the positive impact on participating children. Participants’ recommendations included continuing the programme and expanding eligibility.
CONCLUSION
This is one of the first such MDA’s in CAR; our experience demonstrates MDA is feasible in complex emergencies. Although preliminary analysis of routine surveillance data suggested a limited impact on malaria diagnoses, community acceptance was high. Of note, outpatient surveillance data was limited to three structures in only one commune, and not available for the specific target ages of the MDA. Participants noted positive perceptions of impact, with a desire for repeated MDA’s. Further analysis will help to further elucidate the potential impact, and inform recommendations.
Protracted conflict in CAR has led to widespread political unrest and fragile health systems. Hyperendemic malaria is the main cause of morbidity. Alongside global calls to prioritise malaria prevention during the COVID-19 pandemic, MSF initiated mass drug administration (MDA) for children aged between three months and 15 years within three communes of the Bossangoa health district between 17 August and 24 November 2020. The MDA comprised three cycles of dihydroartemisin-piperaquine (DHA-PQ), given at four-week intervals. We evaluated coverage and clinical impact of the MDA, and describe community perspectives.
METHODS
We conducted a two-stage cluster household survey between 22 November and 9 December 2020. We undertook structured interviews with the heads of households and with eligible children, focusing on participation in the MDA. Participation was verified against the MDA card, if available. Using routine MSF surveillance data, we compared the following indicators during the MDA intervention to the same periods of time during 2018 and 2019: consultations, confirmed malaria cases, and positivity rates of malaria rapid diagnostic tests (mRDT’s) in MSF facilities in the intervention area, overall and by age group (≥5; <5 years); hospital admissions and in-hospital deaths with a primary diagnosis of severe malaria among children <15 years from the MDA intervention area. Following each cycle we conducted nine focus groups discussions (FGD’s) with caregivers, community leaders, and community health workers (CHW’s) Participants were selected using purposive sampling. The topic guide inluded the key themes of reasons for participation, difficulties encountered, satisfaction, and experiences throughout the MDA.
ETHICS
This study was approved by the MSF Ethics Review Board (ERB) and by the national ERB of CAR.
RESULTS
In total, we distributed 134,117 DHA-PQ courses. Among eligible children, 93.1% (95% confidence interval, CI, 85.6-96.8) received all three cycles. We estimated significant reductions only for confirmed outpatient malaria cases overall (9.2%; 95% CI 5.6-12.8), and among those aged <5 years (20.5%; 95% CI 15.3-25.8). Following the first MDA cycle, FGD participants described positive perceptions and high adherence with regard to MDA, linked with the involvement of community leaders. Participants reported reductions in childhood malaria, as well as reduced household expenditure on healthcare. Rumours about ‘drug trials’ and concerns about side effects were initial reasons for refusal, however these concerns were overcome after seeing the positive impact on participating children. Participants’ recommendations included continuing the programme and expanding eligibility.
CONCLUSION
This is one of the first such MDA’s in CAR; our experience demonstrates MDA is feasible in complex emergencies. Although preliminary analysis of routine surveillance data suggested a limited impact on malaria diagnoses, community acceptance was high. Of note, outpatient surveillance data was limited to three structures in only one commune, and not available for the specific target ages of the MDA. Participants noted positive perceptions of impact, with a desire for repeated MDA’s. Further analysis will help to further elucidate the potential impact, and inform recommendations.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 2015 June 1; Volume 92 (Issue 6_Suppl); 39-50.; DOI:10.4269/ajtmh.14-0391
Yeung S, Lawford H, Tabernero P, Nguon C, van Wyk A, et al.
Am J Trop Med Hyg. 2015 June 1; Volume 92 (Issue 6_Suppl); 39-50.; DOI:10.4269/ajtmh.14-0391
Widespread availability of monotherapies and falsified antimalarials is thought to have contributed to the historical development of multidrug-resistant malaria in Cambodia. This study aimed to document the quality of artemisinin-containing antimalarials (ACAs) and to compare two methods of collecting antimalarials from drug outlets: through open surveyors and mystery clients (MCs). Few oral artemisinin-based monotherapies and no suspected falsified medicines were found. All 291 samples contained the stated active pharmaceutical ingredient (API) of which 69% were considered good quality by chemical analysis. Overall, medicine quality did not differ by collection method, although open surveyors were less likely to obtain oral artemisinin-based monotherapies than MCs. The results are an encouraging indication of the positive impact of the country's efforts to tackle falsified antimalarials and artemisinin-based monotherapies. However, poor-quality medicines remain an ongoing challenge that demands sustained political will and investment of human and financial resources.
Journal Article > ResearchFull Text
BMJ Glob Health. 2022 December 1; Volume 7 (Issue 12); e009674.; DOI:10.1136/bmjgh-2022-009674
Van Bortel W, Mariën J, Jacobs BKM, Sinzinkayo D, Sinarinzi P, et al.
BMJ Glob Health. 2022 December 1; Volume 7 (Issue 12); e009674.; DOI:10.1136/bmjgh-2022-009674
BACKGROUND
Long-lasting insecticidal nets (LLINs) are one of the key interventions in the global fight against malaria. Since 2014, mass distribution campaigns of LLINs aim for universal access by all citizens of Burundi. In this context, we assess the impact of LLINs mass distribution campaigns on malaria incidence, focusing on the endemic highland health districts. We also explored the possible correlation between observed trends in malaria incidence with any variations in climate conditions.
METHODS
Malaria cases for 2011—2019 were obtained from the National Health Information System. We developed a generalised additive model based on a time series of routinely collected data with malaria incidence as the response variable and timing of LLIN distribution as an explanatory variable to investigate the duration and magnitude of the LLIN effect on malaria incidence. We added a seasonal and continuous-time component as further explanatory variables, and health district as a random effect to account for random natural variation in malaria cases between districts.
RESULTS
Malaria transmission in Burundian highlands was clearly seasonal and increased non-linearly over the study period. Further, a fast and steep decline of malaria incidence was noted during the first year after mass LLIN distribution (p<0.0001). In years 2 and 3 after distribution, malaria cases started to rise again to levels higher than before the control intervention.
CONCLUSION
This study highlights that LLINs did reduce the incidence in the first year after a mass distribution campaign, but in the context of Burundi, LLINs lost their impact after only 1 year.
Long-lasting insecticidal nets (LLINs) are one of the key interventions in the global fight against malaria. Since 2014, mass distribution campaigns of LLINs aim for universal access by all citizens of Burundi. In this context, we assess the impact of LLINs mass distribution campaigns on malaria incidence, focusing on the endemic highland health districts. We also explored the possible correlation between observed trends in malaria incidence with any variations in climate conditions.
METHODS
Malaria cases for 2011—2019 were obtained from the National Health Information System. We developed a generalised additive model based on a time series of routinely collected data with malaria incidence as the response variable and timing of LLIN distribution as an explanatory variable to investigate the duration and magnitude of the LLIN effect on malaria incidence. We added a seasonal and continuous-time component as further explanatory variables, and health district as a random effect to account for random natural variation in malaria cases between districts.
RESULTS
Malaria transmission in Burundian highlands was clearly seasonal and increased non-linearly over the study period. Further, a fast and steep decline of malaria incidence was noted during the first year after mass LLIN distribution (p<0.0001). In years 2 and 3 after distribution, malaria cases started to rise again to levels higher than before the control intervention.
CONCLUSION
This study highlights that LLINs did reduce the incidence in the first year after a mass distribution campaign, but in the context of Burundi, LLINs lost their impact after only 1 year.
Journal Article > ResearchFull Text
Southeast Asian J Trop Med Public Health. 1995 December 1
Kimerling M, Houth H, Hilderbrand K, Goubert L
Southeast Asian J Trop Med Public Health. 1995 December 1
Chuk district hospital is centrally located in a rural malarious region in southern Cambodia. It was the site of a hospital-based evaluation (KAP assessment and in vivo i.v. quinine/oral tetracycline drug study) done to identify relevant issues for establishing a rational malaria control strategy. The KAP assessment identified the young, male forest worker as the highest risk group. Of 112 study patients, 73% were male and 82% reported various forest activities. The primary reason found for patient delay (8.9 days) in seeking hospital care was self-treatment at home (N = 102, 91%) with drugs purchased through private sellers (104/105). Using the 7-day WHO field test methodology, resistance rates were calculated (N = 22); S1/R1, 73%; R1, 9%; R2, 0%; R3, 18%. A modified version of the 7-day test was used to calculate its utility in this particular rural setting. It showed a negative predictive value of 93% and a positive predictive value of 71%. The case fatality rate for the study period was 2.7%. Information from this study, which correlates a confirmed malaria diagnosis with prior patient behavior and response to anti-malarial therapy, is intended for realizing the goals set forth by the national malaria control program.
Journal Article > LetterFull Text
Clin Infect Dis. 2017 October 30; Volume 65 (Issue 10); 1769-1770.; DOI:10.1093/cid/cix625
Rossi G, de Smet M, Khim N, Kindermans JM, Menard D
Clin Infect Dis. 2017 October 30; Volume 65 (Issue 10); 1769-1770.; DOI:10.1093/cid/cix625