Conference Material > Abstract
Chandna A, PRIORITISE Study Group, Mahajan R, Gautam P, Mwandigha L, et al.
MSF Scientific Days International 2022. 2022 May 9; DOI:10.57740/hxy9-yk07
INTRODUCTION
In locations where few people have received Covid-19 vaccines, health systems remain vulnerable to spikes in SARS-CoV-2 infections. Triage tools, which could include biomarkers, to identify patients with moderate Covid-19 infection suitable for community-based management would be useful in the event of surges. In consultation with FIND (Geneva, Switzerland) we shortlisted seven biomarkers for evaluation, all measurable using point-of-care tests, and either currently available or in late-stage development.
METHODS
We prospectively recruited unvaccinated adults with laboratory-confirmed Covid-19 presenting to two hospitals in India with moderate symptoms, in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. Moderate disease was defined as oxygen saturation (SpO2) ≥ 94% and respiratory rate < 30 breaths per minute (bpm), in the context of systemic symptoms (breathlessness or fever and chest pain, abdominal pain, diarrhoea, or severe myalgia). All patients had clinical observations and blood collected at presentation, and were followed up for 14 days for the primary outcome, defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/fraction of inspired oxygen (FiO2) < 400; or death. We specified a priori that each model would contain three easily ascertained clinical parameters (age, sex, and SpO2) and one of the seven biomarkers (C-reactive protein (CRP), D-dimer, interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), or soluble urokinase plasminogen activator receptor (suPAR)), to ensure the models would be implementable in high patient-throughput, low-resource settings. We evaluated the models’ discrimination, calibration, and clinical utility in a held-out external temporal validation cohort.
ETHICS
Ethical approval was given by the ethics committees of AIIMS and CMC, India, the Oxford Tropical Research Ethics Committee, UK; and by the MSF Ethics Review Board.
ClinicalTrials.gov number, NCT04441372.
RESULTS
426 participants were recruited, of which 89 (21.0%) met the primary outcome. 257 participants comprised the development, and 166 the validation, cohorts. The three models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72 to 0.74) and calibration (calibration slopes: 1.01 to 1.05) in the held-out validation cohort. Furthermore, they provided greater utility than a model containing the clinical parameters alone (c-statistic = 0.66; calibration slope = 0.68). The inclusion of either NLR or suPAR improved predictive performance such that the ratio of correctly to incorrectly discharged patients increased from 10:1 to 23:1 or 25:1 respectively. Including IL-6 resulted in a similar proportion (~21%) of correctly discharged patients as the clinical model, but without missing any patients requiring supplemental oxygen.
CONCLUSION
We present three clinical prediction models that could help clinicians identify patients with moderate Covid-19 suitable for community-based management. These models are readily implementable and, if validated, could be of particular relevance for resource-limited settings.
CONFLICTS OF INTEREST
None declared.
In locations where few people have received Covid-19 vaccines, health systems remain vulnerable to spikes in SARS-CoV-2 infections. Triage tools, which could include biomarkers, to identify patients with moderate Covid-19 infection suitable for community-based management would be useful in the event of surges. In consultation with FIND (Geneva, Switzerland) we shortlisted seven biomarkers for evaluation, all measurable using point-of-care tests, and either currently available or in late-stage development.
METHODS
We prospectively recruited unvaccinated adults with laboratory-confirmed Covid-19 presenting to two hospitals in India with moderate symptoms, in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. Moderate disease was defined as oxygen saturation (SpO2) ≥ 94% and respiratory rate < 30 breaths per minute (bpm), in the context of systemic symptoms (breathlessness or fever and chest pain, abdominal pain, diarrhoea, or severe myalgia). All patients had clinical observations and blood collected at presentation, and were followed up for 14 days for the primary outcome, defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/fraction of inspired oxygen (FiO2) < 400; or death. We specified a priori that each model would contain three easily ascertained clinical parameters (age, sex, and SpO2) and one of the seven biomarkers (C-reactive protein (CRP), D-dimer, interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), or soluble urokinase plasminogen activator receptor (suPAR)), to ensure the models would be implementable in high patient-throughput, low-resource settings. We evaluated the models’ discrimination, calibration, and clinical utility in a held-out external temporal validation cohort.
ETHICS
Ethical approval was given by the ethics committees of AIIMS and CMC, India, the Oxford Tropical Research Ethics Committee, UK; and by the MSF Ethics Review Board.
ClinicalTrials.gov number, NCT04441372.
RESULTS
426 participants were recruited, of which 89 (21.0%) met the primary outcome. 257 participants comprised the development, and 166 the validation, cohorts. The three models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72 to 0.74) and calibration (calibration slopes: 1.01 to 1.05) in the held-out validation cohort. Furthermore, they provided greater utility than a model containing the clinical parameters alone (c-statistic = 0.66; calibration slope = 0.68). The inclusion of either NLR or suPAR improved predictive performance such that the ratio of correctly to incorrectly discharged patients increased from 10:1 to 23:1 or 25:1 respectively. Including IL-6 resulted in a similar proportion (~21%) of correctly discharged patients as the clinical model, but without missing any patients requiring supplemental oxygen.
CONCLUSION
We present three clinical prediction models that could help clinicians identify patients with moderate Covid-19 suitable for community-based management. These models are readily implementable and, if validated, could be of particular relevance for resource-limited settings.
CONFLICTS OF INTEREST
None declared.
Journal Article > Meta-AnalysisFull Text
Lancet. 2010 November 8; Volume 376 (Issue 9753); DOI:10.1016/S0140-6736(10)61924-1
Dondorp AM, Fanello CI, Hendriksen IC, Gomes E, Seni A, et al.
Lancet. 2010 November 8; Volume 376 (Issue 9753); DOI:10.1016/S0140-6736(10)61924-1
Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria.
Journal Article > Short ReportFull Text
Malar J. 2018 January 27; Volume 17 (Issue 1); 53.; DOI:10.1186/s12936-018-2202-z
Peto TJ, Debackere M, Etienne W, Vernaeve L, Tripura R, et al.
Malar J. 2018 January 27; Volume 17 (Issue 1); 53.; DOI:10.1186/s12936-018-2202-z
Two mass drug administrations (MDA) against falciparum malaria were conducted in 2015-16, one as operational research in northern Cambodia, and the other as a clinical trial in western Cambodia. During an April 2017 workshop in Phnom Penh the field teams from Médecins Sans Frontières and the Mahidol-Oxford Tropical Medicine Research Unit discussed lessons for future MDAs.
Journal Article > ResearchFull Text
BMC Med. 2016 October 27; Volume 14 (Issue 1); 171.; DOI:10.1186/s12916-016-0701-8
Leang R, Khu NH, Mukaka M, Debackere M, Tripura R, et al.
BMC Med. 2016 October 27; Volume 14 (Issue 1); 171.; DOI:10.1186/s12916-016-0701-8
BACKGROUND
In 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf.
METHODS
By reviewing primaquine's pharmacology, we defined a therapeutic dose range of 0.15-0.38 mg base/kg (9-22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1-20 mg) were tested using a modelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247 with other infections); age distributions were: 0.5-4 years (20.0 %, n = 5640), 5-12 years (9.1 %, n = 2559), 13-17 years (9.1 %, n = 2550), and ≥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to calculated mg base/kg doses and proportions of individuals receiving a therapeutic dose.
RESULTS
Four age-dosing bands were defined: (1) 0.5-4 years, (2) 5-9 years, (3) 10-14 years, and (4) ≥15 years to receive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 % (1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median (1st-99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15-0.38), (2) 0.29 (0.18-0.45), (3) 0.27 (0.15-0.39), and (4) 0.29 (0.20-0.42).
CONCLUSIONS
This age-based SLDPQ regimen could contribute substantially to malaria elimination and requires urgent evaluation in Cambodia and other countries with similar anthropometric characteristics. It guides primaquine manufacturers on suitable tablet strengths and doses for paediatric-friendly formulations. Development of similar age-based dosing recommendations for Africa is needed.
In 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf.
METHODS
By reviewing primaquine's pharmacology, we defined a therapeutic dose range of 0.15-0.38 mg base/kg (9-22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1-20 mg) were tested using a modelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247 with other infections); age distributions were: 0.5-4 years (20.0 %, n = 5640), 5-12 years (9.1 %, n = 2559), 13-17 years (9.1 %, n = 2550), and ≥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to calculated mg base/kg doses and proportions of individuals receiving a therapeutic dose.
RESULTS
Four age-dosing bands were defined: (1) 0.5-4 years, (2) 5-9 years, (3) 10-14 years, and (4) ≥15 years to receive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 % (1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median (1st-99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15-0.38), (2) 0.29 (0.18-0.45), (3) 0.27 (0.15-0.39), and (4) 0.29 (0.20-0.42).
CONCLUSIONS
This age-based SLDPQ regimen could contribute substantially to malaria elimination and requires urgent evaluation in Cambodia and other countries with similar anthropometric characteristics. It guides primaquine manufacturers on suitable tablet strengths and doses for paediatric-friendly formulations. Development of similar age-based dosing recommendations for Africa is needed.
Journal Article > ReviewFull Text
von Seidlein L, Peto TJ, Tripura R, Pell C, Yeung S, et al.
2019 May 7; Volume 35 (Issue 6); DOI:10.1016/j.pt.2019.03.011
The emergence and spread of drug resistance in the Greater Mekong Subregion (GMS) have added urgency to accelerate malaria elimination while reducing the treatment options. The remaining foci of malaria transmission are often in forests, where vectors tend to bite during daytime and outdoors, thus reducing the effectiveness of insecticide-treated bed nets. Limited periods of exposure suggest that chemoprophylaxis could be a promising strategy to protect forest workers against malaria. Here we discuss three major questions in optimizing malaria chemoprophylaxis for forest workers: which antimalarial drug regimens are most appropriate, how frequently the chemoprophylaxis should be delivered, and how to motivate forest workers to use, and adhere to, malaria prophylaxis.
Journal Article > ResearchFull Text
Malar J. 2021 September 9; Volume 20 (Issue 1); 366.; DOI:10.1186/s12936-021-03886-w
Taylor WRJ, Hoglund RM, Peerawaranun P, Nguyen TN, Hien TT, et al.
Malar J. 2021 September 9; Volume 20 (Issue 1); 366.; DOI:10.1186/s12936-021-03886-w
BACKGROUND
In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax.
METHODS
The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen.
RESULTS
The proposed weight-based regimen has 5 dosing bands: (i) 5-7 kg, 5 mg, resulting in 0.71-1.0 mg/kg/day; (ii) 8-16 kg, 7.5 mg, 0.47-0.94 mg/kg/day; (iii) 17-40 kg, 15 mg, 0.38-0.88 mg/kg/day; (iv) 41-80 kg, 30 mg, 0.37-0.73 mg/kg/day; and (v) 81-100 kg, 45 mg, 0.45-0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6-11 months, 5 mg, 0.43-1.0 mg/kg/day; (ii) 1-5 years, 7.5 mg, 0.35-1.25 mg/kg/day; (iii) 6-14 years, 15 mg, 0.30-1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35-1.07 mg/kg/day.
CONCLUSION
The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.
In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax.
METHODS
The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen.
RESULTS
The proposed weight-based regimen has 5 dosing bands: (i) 5-7 kg, 5 mg, resulting in 0.71-1.0 mg/kg/day; (ii) 8-16 kg, 7.5 mg, 0.47-0.94 mg/kg/day; (iii) 17-40 kg, 15 mg, 0.38-0.88 mg/kg/day; (iv) 41-80 kg, 30 mg, 0.37-0.73 mg/kg/day; and (v) 81-100 kg, 45 mg, 0.45-0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6-11 months, 5 mg, 0.43-1.0 mg/kg/day; (ii) 1-5 years, 7.5 mg, 0.35-1.25 mg/kg/day; (iii) 6-14 years, 15 mg, 0.30-1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35-1.07 mg/kg/day.
CONCLUSION
The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.
Journal Article > ResearchFull Text
Clin Infect Dis. 2022 March 21; Volume ciac224; DOI:10.1093/cid/ciac224
Chandna A, Mahajan R, Gautam P, Mwandigha L, Gunasekaran K, et al.
Clin Infect Dis. 2022 March 21; Volume ciac224; DOI:10.1093/cid/ciac224
BACKGROUND
In locations where few people have received COVID-19 vaccines, health systems remain vulnerable to surges in SARS-CoV-2 infections. Tools to identify patients suitable for community-based management are urgently needed.
METHODS
We prospectively recruited adults presenting to two hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex and SpO2) and one of seven shortlisted biochemical biomarkers measurable using commercially-available rapid tests (CRP, D-dimer, IL-6, NLR, PCT, sTREM-1 or suPAR), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration and clinical utility of the models in a held-out temporal external validation cohort.
RESULTS
426 participants were recruited, of whom 89 (21.0%) met the primary outcome. 257 participants comprised the development cohort and 166 comprised the validation cohort. The three models containing NLR, suPAR or IL-6 demonstrated promising discrimination (c-statistics: 0.72 to 0.74) and calibration (calibration slopes: 1.01 to 1.05) in the validation cohort, and provided greater utility than a model containing the clinical parameters alone.
CONCLUSIONS
We present three clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.
In locations where few people have received COVID-19 vaccines, health systems remain vulnerable to surges in SARS-CoV-2 infections. Tools to identify patients suitable for community-based management are urgently needed.
METHODS
We prospectively recruited adults presenting to two hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex and SpO2) and one of seven shortlisted biochemical biomarkers measurable using commercially-available rapid tests (CRP, D-dimer, IL-6, NLR, PCT, sTREM-1 or suPAR), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration and clinical utility of the models in a held-out temporal external validation cohort.
RESULTS
426 participants were recruited, of whom 89 (21.0%) met the primary outcome. 257 participants comprised the development cohort and 166 comprised the validation cohort. The three models containing NLR, suPAR or IL-6 demonstrated promising discrimination (c-statistics: 0.72 to 0.74) and calibration (calibration slopes: 1.01 to 1.05) in the validation cohort, and provided greater utility than a model containing the clinical parameters alone.
CONCLUSIONS
We present three clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.
Protocol > Research Study
BMJ Open. 2021 January 25; Volume 11 (Issue 1); e045826.; DOI:10.1136/bmjopen-2020-045826
Chandna A, Aderie EM, Ahmad R, Arguni E, Ashley EA, et al.
BMJ Open. 2021 January 25; Volume 11 (Issue 1); e045826.; DOI:10.1136/bmjopen-2020-045826
INTRODUCTION
In rural and difficult-to-access settings, early and accurate recognition of febrile children at risk of progressing to serious illness could contribute to improved patient outcomes and better resource allocation. This study aims to develop a prognostic clinical prediction tool to assist community healthcare providers identify febrile children who might benefit from referral or admission for facility-based medical care.
METHODS AND ANALYSIS
This prospective observational study will recruit at least 4900 paediatric inpatients and outpatients under the age of 5 years presenting with an acute febrile illness to seven hospitals in six countries across Asia. A venous blood sample and nasopharyngeal swab is collected from each participant and detailed clinical data recorded at presentation, and each day for the first 48 hours of admission for inpatients. Multianalyte assays are performed at reference laboratories to measure a panel of host biomarkers, as well as targeted aetiological investigations for common bacterial and viral pathogens. Clinical outcome is ascertained on day 2 and day 28.Presenting syndromes, clinical outcomes and aetiology of acute febrile illness will be described and compared across sites. Following the latest guidance in prediction model building, a prognostic clinical prediction model, combining simple clinical features and measurements of host biomarkers, will be derived and geographically externally validated. The performance of the model will be evaluated in specific presenting clinical syndromes and fever aetiologies.
ETHICS AND DISSEMINATION
The study has received approval from all relevant international, national and institutional ethics committees. Written informed consent is provided by the caretaker of all participants. Results will be shared with local and national stakeholders, and disseminated via peer-reviewed open-access journals and scientific meetings.
TRIAL REGISTRATION NUMBER NCT04285021.
In rural and difficult-to-access settings, early and accurate recognition of febrile children at risk of progressing to serious illness could contribute to improved patient outcomes and better resource allocation. This study aims to develop a prognostic clinical prediction tool to assist community healthcare providers identify febrile children who might benefit from referral or admission for facility-based medical care.
METHODS AND ANALYSIS
This prospective observational study will recruit at least 4900 paediatric inpatients and outpatients under the age of 5 years presenting with an acute febrile illness to seven hospitals in six countries across Asia. A venous blood sample and nasopharyngeal swab is collected from each participant and detailed clinical data recorded at presentation, and each day for the first 48 hours of admission for inpatients. Multianalyte assays are performed at reference laboratories to measure a panel of host biomarkers, as well as targeted aetiological investigations for common bacterial and viral pathogens. Clinical outcome is ascertained on day 2 and day 28.Presenting syndromes, clinical outcomes and aetiology of acute febrile illness will be described and compared across sites. Following the latest guidance in prediction model building, a prognostic clinical prediction model, combining simple clinical features and measurements of host biomarkers, will be derived and geographically externally validated. The performance of the model will be evaluated in specific presenting clinical syndromes and fever aetiologies.
ETHICS AND DISSEMINATION
The study has received approval from all relevant international, national and institutional ethics committees. Written informed consent is provided by the caretaker of all participants. Results will be shared with local and national stakeholders, and disseminated via peer-reviewed open-access journals and scientific meetings.
TRIAL REGISTRATION NUMBER NCT04285021.
Journal Article > ResearchFull Text
Malar J. 2016 September 1; Volume 15 (Issue 1); 446.; DOI:10.1186/s12936-016-1487-z
Falq G, Van der Bergh R, de Smet M, Etienne W, Nguon C, et al.
Malar J. 2016 September 1; Volume 15 (Issue 1); 446.; DOI:10.1186/s12936-016-1487-z
BACKGROUND
In Cambodia, elimination of artemisinin resistance through direct elimination of the Plasmodium falciparum parasite may be the only strategy. Prevalence and incidence at district and village levels were assessed in Chey Saen district, Preah Vihear province, North of Cambodia. Molecular and clinical indicators for artemisinin resistance were documented.
METHODS
A cross sectional prevalence survey was conducted at village level in the district of Chey Saen from September to October 2014. Plasmodium spp. was assessed with high volume quantitative real-time polymerase chain reaction (qPCR). Plasmodium falciparum-positive samples were screened for mutations in the k13-propeller domain gene. Treatment effectiveness was established after 28 days (D28) using the same qPCR technique. Data from the provincial surveillance system targeting symptomatic cases, supported by Médecins Sans Frontières (MSF), were used to assess incidence.
RESULTS
District P. falciparum prevalence was of 0.74 % [0.41; 1.21]; village prevalence ranged from 0 to 4.6 % [1.4; 10.5]. The annual incidence of P. falciparum was 16.8 cases per 1000 inhabitants in the district; village incidence ranged from 1.3 to 54.9 for 1000 inhabitants. Two geographical clusters with high number of cases were identified by both approaches. The marker for artemisinin resistance was found in six samples out of the 11 tested (55 %). 34.9 % of qPCR blood analysis of symptomatic patients were still positive at D28.
CONCLUSIONS
The overall low prevalence of P. falciparum was confirmed in Chey Saen district in Cambodia, while there were important variations between villages. Symptomatic cases had a different pattern and were likely acquired outside the villages. It illustrates the importance of prevalence surveys in targeting interventions for elimination. Mutations in the k13-propeller domain gene (C580Y), conferring artemisinin resistance, were highly prevalent in both symptomatic and asymptomatic cases (realizing the absolute figures remain low). Asymptomatic individuals could be an additional reservoir for artemisinin resistance. The low effectiveness of dihydroartemisinin-piperaquine (DHA-PPQ) for symptomatic cases indicates that PPQ is no longer able to complement the reduced potency of DHA to treat falciparum malaria and highlights the need for an alternative first-line treatment.
In Cambodia, elimination of artemisinin resistance through direct elimination of the Plasmodium falciparum parasite may be the only strategy. Prevalence and incidence at district and village levels were assessed in Chey Saen district, Preah Vihear province, North of Cambodia. Molecular and clinical indicators for artemisinin resistance were documented.
METHODS
A cross sectional prevalence survey was conducted at village level in the district of Chey Saen from September to October 2014. Plasmodium spp. was assessed with high volume quantitative real-time polymerase chain reaction (qPCR). Plasmodium falciparum-positive samples were screened for mutations in the k13-propeller domain gene. Treatment effectiveness was established after 28 days (D28) using the same qPCR technique. Data from the provincial surveillance system targeting symptomatic cases, supported by Médecins Sans Frontières (MSF), were used to assess incidence.
RESULTS
District P. falciparum prevalence was of 0.74 % [0.41; 1.21]; village prevalence ranged from 0 to 4.6 % [1.4; 10.5]. The annual incidence of P. falciparum was 16.8 cases per 1000 inhabitants in the district; village incidence ranged from 1.3 to 54.9 for 1000 inhabitants. Two geographical clusters with high number of cases were identified by both approaches. The marker for artemisinin resistance was found in six samples out of the 11 tested (55 %). 34.9 % of qPCR blood analysis of symptomatic patients were still positive at D28.
CONCLUSIONS
The overall low prevalence of P. falciparum was confirmed in Chey Saen district in Cambodia, while there were important variations between villages. Symptomatic cases had a different pattern and were likely acquired outside the villages. It illustrates the importance of prevalence surveys in targeting interventions for elimination. Mutations in the k13-propeller domain gene (C580Y), conferring artemisinin resistance, were highly prevalent in both symptomatic and asymptomatic cases (realizing the absolute figures remain low). Asymptomatic individuals could be an additional reservoir for artemisinin resistance. The low effectiveness of dihydroartemisinin-piperaquine (DHA-PPQ) for symptomatic cases indicates that PPQ is no longer able to complement the reduced potency of DHA to treat falciparum malaria and highlights the need for an alternative first-line treatment.
Journal Article > ResearchFull Text
Int J Health Geogr. 2016 October 24; Volume 15 (Issue 1); 37.; DOI:10.1186/s12942-016-0064-6
Grist EP, Fleqq JA, Humphreys G, Mas IS, Anderson TJC, et al.
Int J Health Geogr. 2016 October 24; Volume 15 (Issue 1); 37.; DOI:10.1186/s12942-016-0064-6
BACKGROUND
Artemisinin-resistant Plasmodium falciparum malaria parasites are now present across much of mainland Southeast Asia, where ongoing surveys are measuring and mapping their spatial distribution. These efforts require substantial resources. Here we propose a generic 'smart surveillance' methodology to identify optimal candidate sites for future sampling and thus map the distribution of artemisinin resistance most efficiently.
METHODS
The approach uses the 'uncertainty' map generated iteratively by a geostatistical model to determine optimal locations for subsequent sampling.
RESULTS
The methodology is illustrated using recent data on the prevalence of the K13-propeller polymorphism (a genetic marker of artemisinin resistance) in the Greater Mekong Subregion.
CONCLUSION
This methodology, which has broader application to geostatistical mapping in general, could improve the quality and efficiency of drug resistance mapping and thereby guide practical operations to eliminate malaria in affected areas.
Artemisinin-resistant Plasmodium falciparum malaria parasites are now present across much of mainland Southeast Asia, where ongoing surveys are measuring and mapping their spatial distribution. These efforts require substantial resources. Here we propose a generic 'smart surveillance' methodology to identify optimal candidate sites for future sampling and thus map the distribution of artemisinin resistance most efficiently.
METHODS
The approach uses the 'uncertainty' map generated iteratively by a geostatistical model to determine optimal locations for subsequent sampling.
RESULTS
The methodology is illustrated using recent data on the prevalence of the K13-propeller polymorphism (a genetic marker of artemisinin resistance) in the Greater Mekong Subregion.
CONCLUSION
This methodology, which has broader application to geostatistical mapping in general, could improve the quality and efficiency of drug resistance mapping and thereby guide practical operations to eliminate malaria in affected areas.