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 > Meta-AnalysisFull Text
BMC Med. 2020 February 25; Volume 18 (Issue 1); 47.; DOI:10.1186/s12916-020-1494-3.
Bretscher MT, Dahal P, Griffin J, Stepniewska K, Bassat Q, et al.
BMC Med. 2020 February 25; Volume 18 (Issue 1); 47.; DOI:10.1186/s12916-020-1494-3.
BACKGROUND
The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas.
METHODS
We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment.
RESULTS
We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission.
CONCLUSION
Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.
The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas.
METHODS
We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment.
RESULTS
We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission.
CONCLUSION
Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.
Journal Article > ReviewFull Text
Trans R Soc Trop Med Hyg. 2024 May 1; Online ahead of print; DOI:10.1093/trstmh/trae018
Dahal P, Singh-Phulgenda S, Wilson JM, Cota G, Ritmeijer K, et al.
Trans R Soc Trop Med Hyg. 2024 May 1; Online ahead of print; DOI:10.1093/trstmh/trae018
Blood transfusion remains an important aspect of patient management in visceral leishmaniasis (VL). However, transfusion triggers considered are poorly understood. This review summarises the transfusion practices adopted in VL efficacy studies using the Infectious Diseases Data Observatory VL clinical trials library. Of the 160 studies (1980–2021) indexed in the IDDO VL library, description of blood transfusion was presented in 16 (10.0%) (n=3459 patients) studies. Transfusion was initiated solely based on haemoglobin (Hb) measurement in nine studies, combining Hb measurement with an additional condition (epistaxis/poor health/clinical instability) in three studies and the criteria was not mentioned in four studies. The Hb threshold range for triggering transfusion was 3–8 g/dL. The number of patients receiving transfusion was explicitly reported in 10 studies (2421 patients enrolled, 217 underwent transfusion). The median proportion of patients who received transfusion in a study was 8.0% (Interquartile range: 4.7% to 47.2%; range: 0–100%; n=10 studies). Of the 217 patients requiring transfusion, 58 occurred before VL treatment initiation, 46 during the treatment/follow-up phase and the time was not mentioned in 113. This review describes the variation in clinical practice and is an important initial step in policy/guideline development, where both the patient's Hb concentration and clinical status must be considered.
Journal Article > ResearchFull Text
Malar J. 2013 October 11; Volume 12 (Issue 1); 363.; DOI:10.1186/1475-2875-12-363
Smithuis FM, Kyaw MK, van der Broek I, Katterman N, Rogers C, et al.
Malar J. 2013 October 11; Volume 12 (Issue 1); 363.; DOI:10.1186/1475-2875-12-363
BACKGROUND
Insecticide-treated bed nets (ITN) reduce malaria morbidity and mortality consistently in Africa, but their benefits have been less consistent in Asia. This study's objective was to evaluate the malaria protective efficacy of village-wide usage of ITN in Western Myanmar and estimate the cost-effectiveness of ITN compared with extending early diagnosis and treatment services.
METHODS
A cluster-randomized controlled trial was conducted in Rakhine State to assess the efficacy of ITNs in preventing malaria and anaemia in children and their secondary effects on nutrition and development. The data were aggregated for each village to obtain cluster-level infection rates. In total 8,175 children under 10 years of age were followed up for 10 months, which included the main malaria transmission period. The incidence and prevalence of Plasmodium falciparum and Plasmodium vivax infections, and the biting behaviour of Anopheles mosquitoes in the area were studied concurrently. The trial data along with costs for current recommended treatment practices were modelled to estimate the cost-effectiveness of ITNs compared with, or in addition to extending the coverage of early diagnosis and treatment services.
RESULTS
In aggregate, malaria infections, spleen rates, haemoglobin concentrations, and weight for height, did not differ significantly during the study period between villages with and without ITNs, with a weighted mean difference of -2.6 P. falciparum episodes per 1,000 weeks at risk (95% Confidence Interval -7 to 1.8). In areas with a higher incidence of malaria there was some evidence ITN protective efficacy. The economic analysis indicated that, despite the uncertainty and variability in their protective efficacy in the different study sites, ITN could still be cost-effective, but not if they displaced funding for early diagnosis and effective treatment which is substantially more cost-effective.
CONCLUSION
In Western Myanmar deployment of ITNs did not provide consistent protection against malaria in children living in malaria endemic villages. Early diagnosis and effective treatment is a more cost effective malaria control strategy than deployment of ITNs in this area where the main vector bites early in the evening, often before people are protected by an ITN.
Insecticide-treated bed nets (ITN) reduce malaria morbidity and mortality consistently in Africa, but their benefits have been less consistent in Asia. This study's objective was to evaluate the malaria protective efficacy of village-wide usage of ITN in Western Myanmar and estimate the cost-effectiveness of ITN compared with extending early diagnosis and treatment services.
METHODS
A cluster-randomized controlled trial was conducted in Rakhine State to assess the efficacy of ITNs in preventing malaria and anaemia in children and their secondary effects on nutrition and development. The data were aggregated for each village to obtain cluster-level infection rates. In total 8,175 children under 10 years of age were followed up for 10 months, which included the main malaria transmission period. The incidence and prevalence of Plasmodium falciparum and Plasmodium vivax infections, and the biting behaviour of Anopheles mosquitoes in the area were studied concurrently. The trial data along with costs for current recommended treatment practices were modelled to estimate the cost-effectiveness of ITNs compared with, or in addition to extending the coverage of early diagnosis and treatment services.
RESULTS
In aggregate, malaria infections, spleen rates, haemoglobin concentrations, and weight for height, did not differ significantly during the study period between villages with and without ITNs, with a weighted mean difference of -2.6 P. falciparum episodes per 1,000 weeks at risk (95% Confidence Interval -7 to 1.8). In areas with a higher incidence of malaria there was some evidence ITN protective efficacy. The economic analysis indicated that, despite the uncertainty and variability in their protective efficacy in the different study sites, ITN could still be cost-effective, but not if they displaced funding for early diagnosis and effective treatment which is substantially more cost-effective.
CONCLUSION
In Western Myanmar deployment of ITNs did not provide consistent protection against malaria in children living in malaria endemic villages. Early diagnosis and effective treatment is a more cost effective malaria control strategy than deployment of ITNs in this area where the main vector bites early in the evening, often before people are protected by an ITN.
Journal Article > Meta-AnalysisFull Text
Am J Trop Med Hyg. 2014 July 21; Volume 91 (Issue 4); 833-43.; DOI:10.4269/ajtmh.14-0031
Venkatesan M, Gadalla NB, Stepniewska K, Dahal P, Nsanzabana C, et al.
Am J Trop Med Hyg. 2014 July 21; Volume 91 (Issue 4); 833-43.; DOI:10.4269/ajtmh.14-0031
Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001: were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.
Journal Article > ProtocolFull Text
BMJ Open. 2023 December 14; Volume 13 (Issue 12); e074841.; DOI:10.1136/bmjopen-2023-074841
Munir A, Dahal P, Kumar R, Singh-Phulgenda S, Siddiqui NA, et al.
BMJ Open. 2023 December 14; Volume 13 (Issue 12); e074841.; DOI:10.1136/bmjopen-2023-074841
INTRODUCTION
Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30,000 new cases occurring annually. Despite anaemia being a common haematological manifestation of VL, the evolution of different haematological characteristics following treatment remains poorly understood. An individual participant data meta-analysis (IPD-MA) is planned to characterise the haematological dynamics in patients with VL.
METHODS AND ANALYSIS
The Infectious Diseases Data Observatory (IDDO) VL data platform is a global repository of IPD from therapeutic studies identified through a systematic search of published literature (PROSPERO registration: CRD42021284622). The platform currently holds datasets from clinical trials standardised to a common data format. Corresponding authors and principal investigators of the studies indexed in the IDDO VL data platform meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Mixed-effects multivariable regression models will be constructed to identify determinants of haematological parameters by taking clustering within study sites into account.
ETHICS AND DISSEMINATION
This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data (exempt granted on 29 March 2023, OxTREC REF: IDDO). Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (letter no.: RMRI/EC/30/2022) on 4 July 2022. The results of this analysis will be disseminated at conferences, the IDDO website and peer-reviewed publications in open-access journals. The findings of this research will be critically important for control programmes at regional and global levels, policymakers and groups developing new VL treatments.
Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30,000 new cases occurring annually. Despite anaemia being a common haematological manifestation of VL, the evolution of different haematological characteristics following treatment remains poorly understood. An individual participant data meta-analysis (IPD-MA) is planned to characterise the haematological dynamics in patients with VL.
METHODS AND ANALYSIS
The Infectious Diseases Data Observatory (IDDO) VL data platform is a global repository of IPD from therapeutic studies identified through a systematic search of published literature (PROSPERO registration: CRD42021284622). The platform currently holds datasets from clinical trials standardised to a common data format. Corresponding authors and principal investigators of the studies indexed in the IDDO VL data platform meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Mixed-effects multivariable regression models will be constructed to identify determinants of haematological parameters by taking clustering within study sites into account.
ETHICS AND DISSEMINATION
This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data (exempt granted on 29 March 2023, OxTREC REF: IDDO). Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (letter no.: RMRI/EC/30/2022) on 4 July 2022. The results of this analysis will be disseminated at conferences, the IDDO website and peer-reviewed publications in open-access journals. The findings of this research will be critically important for control programmes at regional and global levels, policymakers and groups developing new VL treatments.
Conference Material > Slide Presentation
Wilson JM, Chowdhury F, Hassan S, Harriss E, Alves F, et al.
MSF Scientific Day International 2024. 2024 May 16; DOI:10.57740/R7W2C8dil
Journal Article > ProtocolFull Text
BMJ Open. 2023 October 28; Volume 13 (Issue 10); e074679.; DOI:10.1136/bmjopen-2023-074679
Kumar R, Dahal P, Singh-Phulgenda S, Siddiqui NA, Munir A, et al.
BMJ Open. 2023 October 28; Volume 13 (Issue 10); e074679.; DOI:10.1136/bmjopen-2023-074679
INTRODUCTION
Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. There is an observed variation in the efficacy of the current first-line therapies across different regions. Such heterogeneity could be a function of host, parasite and drug factors. An individual participant data meta-analysis (IPD-MA) is planned to explore the determinants of treatment outcomes.
METHODS AND ANALYSIS
The Infectious Diseases Data Observatory (IDDO) VL living systematic review (IDDO VL LSR) library is an open-access resource of all published therapeutic studies in VL since 1980. For this current review, the search includes all clinical trials published between 1 January 1980 and 2 May 2021. Studies indexed in the IDDO VL LSR library were screened for eligibility for inclusion in this IPD-MA. Corresponding authors and principal investigators of the studies meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Authors agreeing to participate in this collaborative research were requested to share the IPD using the IDDO VL data platform. The IDDO VL data platform currently holds data sets from clinical trials standardised to a common data format and provides a unique opportunity to identify host, parasite and drug determinants of treatment outcomes. Multivariable regression models will be constructed to identify determinants of therapeutic outcomes using generalised linear mixed-effects models accounting for within-study site clustering.
ETHICS AND DISSEMINATION
This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data (Exempt granted on 29 March 2023, OxTREC REF: IDDO) Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (Letter no: RMRI/EC/30/2022) on 04-07-2022. The results of this IPD-MA will be disseminated at conferences, IDDO website and any peer-reviewed publications. All publications will be open source. Findings of this research will be critically important for the control programmes at regional/global levels, policy makers and groups developing new VL treatments.
Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. There is an observed variation in the efficacy of the current first-line therapies across different regions. Such heterogeneity could be a function of host, parasite and drug factors. An individual participant data meta-analysis (IPD-MA) is planned to explore the determinants of treatment outcomes.
METHODS AND ANALYSIS
The Infectious Diseases Data Observatory (IDDO) VL living systematic review (IDDO VL LSR) library is an open-access resource of all published therapeutic studies in VL since 1980. For this current review, the search includes all clinical trials published between 1 January 1980 and 2 May 2021. Studies indexed in the IDDO VL LSR library were screened for eligibility for inclusion in this IPD-MA. Corresponding authors and principal investigators of the studies meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Authors agreeing to participate in this collaborative research were requested to share the IPD using the IDDO VL data platform. The IDDO VL data platform currently holds data sets from clinical trials standardised to a common data format and provides a unique opportunity to identify host, parasite and drug determinants of treatment outcomes. Multivariable regression models will be constructed to identify determinants of therapeutic outcomes using generalised linear mixed-effects models accounting for within-study site clustering.
ETHICS AND DISSEMINATION
This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data (Exempt granted on 29 March 2023, OxTREC REF: IDDO) Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (Letter no: RMRI/EC/30/2022) on 04-07-2022. The results of this IPD-MA will be disseminated at conferences, IDDO website and any peer-reviewed publications. All publications will be open source. Findings of this research will be critically important for the control programmes at regional/global levels, policy makers and groups developing new VL treatments.
Conference Material > Abstract
Wilson JM, Chowdhury F, Hassan S, Harriss E, Alves F, et al.
MSF Scientific Day International 2024. 2024 May 16; DOI:10.57740/9SthRqK
INTRODUCTION
Visceral leishmaniasis (VL) is a neglected tropical disease prevalent in populations affected by poverty, war, and famine. Without effective treatment, death is the norm. Prognostic models, as used by Médecins Sans Frontières (MSF) in East Africa, are used to identify high-risk patients for intensive management, including hospital admission, treatment with liposomal amphotericin B, broad-spectrum antibiotics, and blood transfusions. We provide a comprehensive and objective resource for policymakers, healthcare providers, and investigators, by identifying, summarising, and appraising the available prognostic models predicting clinical outcomes in patients with VL.
METHODS
We performed a systematic review of published studies that developed, validated, or updated models predicting future clinical outcomes in patients diagnosed with VL. We searched five bibliographic databases (Ovid Embase, Ovid MEDLINE, Web of Science Core Collection, SciELO, and LILACS) on March 1, 2023, for papers published from database inception, with no language restriction. Screening, data extraction, and risk of bias assessment were performed in duplicate. This study is registered with PROSPERO (ID: CRD42023417226).
RESULTS
Eight prognostic model studies, published between 2003 and 2021, were identified describing 12 prognostic model developments and 19 external validations. Nine models were developed in Brazil and three in East Africa by MSF investigators (two developed in South Sudan and one in Ethiopia). In-hospital mortality was the outcome for all but two Brazilian models, which predicted registry-reported mortality. Three models were developed exclusively in adolescents or children. Risk of bias was assessed as high for all model evaluations. Model overfitting due to small sample sizes, leading to optimistic model performance measures and exaggerated risk estimates, was identified for all but one model development. Only half of the presented risk scores were reproducible by following the authors’ methodology.
CONCLUSION
A poorly developed model can result in inaccurate risk estimation, potentially leading to harmful and inequitable decision making. With half of all risk scores incorrectly calculated, and a high risk of bias identified across all model evaluations, caution must be exercised when using these models to guide patient management. In the first systematic review of VL prognostic models, we show that no models predicted treatment failure and relapse, and despite South Asia representing the highest VL burden before 2010, no models were developed in this population. These represent important evidence gaps, which should be prioritised when developing new models. Using the Infectious Diseases Data Observatory repository of VL individual patient data from clinical trials, we are currently building a prognostic model for VL relapse in South Asia, which we hope to serve the ongoing elimination campaign.
Visceral leishmaniasis (VL) is a neglected tropical disease prevalent in populations affected by poverty, war, and famine. Without effective treatment, death is the norm. Prognostic models, as used by Médecins Sans Frontières (MSF) in East Africa, are used to identify high-risk patients for intensive management, including hospital admission, treatment with liposomal amphotericin B, broad-spectrum antibiotics, and blood transfusions. We provide a comprehensive and objective resource for policymakers, healthcare providers, and investigators, by identifying, summarising, and appraising the available prognostic models predicting clinical outcomes in patients with VL.
METHODS
We performed a systematic review of published studies that developed, validated, or updated models predicting future clinical outcomes in patients diagnosed with VL. We searched five bibliographic databases (Ovid Embase, Ovid MEDLINE, Web of Science Core Collection, SciELO, and LILACS) on March 1, 2023, for papers published from database inception, with no language restriction. Screening, data extraction, and risk of bias assessment were performed in duplicate. This study is registered with PROSPERO (ID: CRD42023417226).
RESULTS
Eight prognostic model studies, published between 2003 and 2021, were identified describing 12 prognostic model developments and 19 external validations. Nine models were developed in Brazil and three in East Africa by MSF investigators (two developed in South Sudan and one in Ethiopia). In-hospital mortality was the outcome for all but two Brazilian models, which predicted registry-reported mortality. Three models were developed exclusively in adolescents or children. Risk of bias was assessed as high for all model evaluations. Model overfitting due to small sample sizes, leading to optimistic model performance measures and exaggerated risk estimates, was identified for all but one model development. Only half of the presented risk scores were reproducible by following the authors’ methodology.
CONCLUSION
A poorly developed model can result in inaccurate risk estimation, potentially leading to harmful and inequitable decision making. With half of all risk scores incorrectly calculated, and a high risk of bias identified across all model evaluations, caution must be exercised when using these models to guide patient management. In the first systematic review of VL prognostic models, we show that no models predicted treatment failure and relapse, and despite South Asia representing the highest VL burden before 2010, no models were developed in this population. These represent important evidence gaps, which should be prioritised when developing new models. Using the Infectious Diseases Data Observatory repository of VL individual patient data from clinical trials, we are currently building a prognostic model for VL relapse in South Asia, which we hope to serve the ongoing elimination campaign.
Journal Article > ReviewFull Text
BMC Med. 2018 October 29; Volume 16 (Issue 1); 186.; DOI:10.1186/s12916-018-1177-5
Das D, Grais RF, Okiro EA, Stepniewska K, Mansoor R, et al.
BMC Med. 2018 October 29; Volume 16 (Issue 1); 186.; DOI:10.1186/s12916-018-1177-5
Despite substantial improvement in the control of malaria and decreased prevalence of malnutrition over the past two decades, both conditions remain heavy burdens that cause hundreds of thousands of deaths in children in resource-poor countries every year. Better understanding of the complex interactions between malaria and malnutrition is crucial for optimally targeting interventions where both conditions co-exist. This systematic review aimed to assess the evidence of the interplay between malaria and malnutrition.