scholarly journals Model-based assessment of the safety of community interventions with primaquine in sub-Saharan Africa

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Stijn W. van Beek ◽  
Elin M. Svensson ◽  
Alfred B. Tiono ◽  
Joseph Okebe ◽  
Umberto D’Alessandro ◽  
...  
Keyword(s):  
Artemisinin Resistance ◽  
Sub Saharan Africa ◽  
Severe Anemia ◽  
Nonlinear Mixed Effects Model ◽  
Mild Anemia ◽  
Pediatric Study ◽  
Sub Saharan ◽  
Pre Treatment ◽  
African Setting ◽  
Age And Sex

Abstract Background Single low-dose primaquine (SLD-PQ) is recommended in combination with artemisinin-based combination therapy to reduce Plasmodium falciparum transmission in areas threatened by artemisinin resistance or aiming for malaria elimination. SLD-PQ may be beneficial in mass drug administration (MDA) campaigns to prevent malaria transmission but uptake is limited by concerns of hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The aim of this study was to improve the evidence on the safety of MDA with SLD-PQ in a sub-Saharan African setting. Methods A nonlinear mixed-effects model describing the pharmacokinetics and treatment-induced hemolysis of primaquine was developed using data from an adult (n = 16, G6PD deficient) and pediatric study (n = 38, G6PD normal). The relationship between primaquine pharmacokinetics and hemolysis was modeled using an established erythrocyte lifespan model. The safety of MDA with SLD-PQ was explored through Monte Carlo simulations for SLD-PQ at 0.25 or 0.4 mg/kg using baseline data from a Tanzanian setting with detailed information on hemoglobin concentrations and G6PD status. Results The predicted reduction in hemoglobin levels following SLD-PQ was small and returned to pre-treatment levels after 25 days. G6PD deficiency (African A- variant) was associated with a 2.5-fold (95% CI 1.2–8.2) larger reduction in hemoglobin levels. In the Tanzanian setting where 43% of the population had at least mild anemia (hemoglobin < 11–13 g/dl depending on age and sex) and 2.73% had severe anemia (hemoglobin < 7–8 g/dl depending on age and sex), an additional 3.7% and 6.0% of the population were predicted to develop at least mild anemia and 0.25% and 0.41% to develop severe anemia after 0.25 and 0.4 mg/kg SLD-PQ, respectively. Children < 5 years of age and women ≥ 15 years of age were found to have a higher chance to have low pre-treatment hemoglobin. Conclusions This study supports the feasibility of MDA with SLD-PQ in a sub-Saharan African setting by predicting small and transient reductions in hemoglobin levels. In a setting where a substantial proportion of the population had low hemoglobin concentrations, our simulations suggest treatment with SLD-PQ would result in small increases in the prevalence of anemia which would most likely be transient. Graphical abstract

Effect of a comprehensive clinical care program on disease course in severely ill children with sickle cell anemia in a sub-Saharan African setting

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 834-838 ◽  
Author(s):  
Mohamed Cherif Rahimy ◽  
Annick Gangbo ◽  
Gilbert Ahouignan ◽  
Roselyn Adjou ◽  
Chantal Deguenon ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Parental Education ◽  
Clinical Care ◽  
Care Program ◽  
Clinical Severity ◽  
Sub Saharan Africa ◽  
Physical Growth ◽  
Sub Saharan ◽  
African Setting

Abstract Clinical severity of sickle cell anemia (SS) in Africa may not be solely determined by genetic factors. This study evaluated the effects of intensive parental education and adequate clinical care on the course of SS in children in Benin. SS children referred to the National Teaching Hospital in Cotonou were included in the study. Teaching about SS was repeated frequently, emphasizing the importance of keeping clinic appointments, improving the nutrition of the affected children, and instituting antipneumococcal and antimalarial prophylaxis. Frequency and severity of SS-related events, changes in physical growth, frequency of malarial attacks, causes of transfusion, and causes of death were the principal variables assessed. 236 young children with repeated SS-related acute complications were studied from July 1, 1993, to December 31, 1999 (983 patient-years). A marked reduction in the frequency and severity of SS-related acute events was observed. Improvement in general status and physical growth was noted in 184 patients (78%); in addition, 22 of the remaining 52 patients showed similar improvement after remotivating the parents for compliance. There were 10 deaths, primarily in this cohort of 52 patients. Intensive sociomedical intervention can produce sustained clinical improvement in many severely ill SS children in sub-Saharan Africa.

scholarly journals Malarial Related Myopathies: A Rhabdomyolysis Story

2020 ◽  
pp. 39-51
Author(s):  
Forman Erwin Siagian
Keyword(s):  
Deleterious Effect ◽  
Management Strategy ◽  
Best Practice ◽  
Sub Saharan Africa ◽  
South East Asia ◽  
Severe Anemia ◽  
Vulnerable Group ◽  
Protozoan Infections ◽  
Sub Saharan ◽  
Muscle Capillaries

Malaria is amongst the most prevalent and epidemiologically relevant global parasitic protozoan infections. It is infecting millions of people annually, especially in south east Asia and sub Saharan Africa. Its morbidity and mortality still cannot be controlled entirely and elimination is still far away. Children and pregnant women are among the most vulnerable group in the population. Its pathobiology have related to cause direct or indirect deleterious effect on the patient’s skeletal muscle, named rhabdomyolysis. Eventhough it is very rare, but potentially fatal and lethal. Three mechanism of malaria related rhabdomyolysis are very intense inflammatory response, extensive red cells sequestration in muscle capillaries due to severe anemia and the parasite toxin’s, will  lead to or add risks of complication. Derangement of specific type of muscle, named the skeletal and cardiac, is amongst the earliest sign of severe malaria. Further study need to be conducted in the future, especially on important topics about mechanism and its effect, signaling pathways, best practice on laboratory approach and management strategy best practice.

scholarly journals Three monthly doses of 60 mg/kg praziquantel for Schistosoma haematobium infection is a safe and effective treatment regimen.

2020 ◽  
Author(s):  
Samuel Nkansah Darko ◽  
Henry Hanson ◽  
Sampson Twumasi Ankrah ◽  
Sandra Baffour ◽  
Priscilla Adjei-Kusi ◽  
...  
Keyword(s):  
Renal Function ◽  
Schistosoma Haematobium ◽  
Post Treatment ◽  
Sub Saharan Africa ◽  
Gamma Glutamyl Transferase ◽  
Disease Epidemiology ◽  
Sub Saharan ◽  
Pre Treatment ◽  
And Gender ◽  
Glutamyl Transferase

Abstract Background Praziquantel (PZQ) is the standard treatment for Schistosomiasis in sub-Saharan Africa. However, there is evidence suggesting praziquantel treatment failure in Schistosome infections with associated potential renal impairment. The objective of this study was to determine the effect of three monthly doses of 60 mg/kg/day PZQ on schistosome egg count, liver and renal function during the treatment of urinary schistosomiasis in Ghana. Methods A nested case-control study was designed from a cohort screened for schistosomiasis; 28 schistosomiasis positive cases by microscopy matched with 53 healthy controls by age and gender. The study population was urban dwellers from the Asokwa sub-metropolitan area, Kumasi in Ghana. Participants were within the age range of 6 to 30 years. We assessed Schistosoma haematobium egg counts in urine and its associated impact on liver and renal function at baseline, treatment and post-treatment phases using serum. Results Of the 28 cases and 53 controls, 78.6% and (81.1% were males respectively. Globulin levels before treatment was higher in cases [36.7 (32.8, 40.1) vrs 30.5 (22.4, 33.8) , p=0.005] at pre-treatment but not at post-treatment [35.8 (31.2, 39.1)vrs 37.4 (29.7, 43.0), p= 0.767]. Estimated cure rate was 42.9%, 46.4% and 96.4% after first, second and third dose respectively. Schistosome egg counts dropped significantly (p= 0.001) from before second dose to post-treatment. Similarly, levels of alanine aminotransferase (p=0.001), aspartate aminotransferase (p=0.028) and gamma glutamyl transferase (p=0.001) significantly declined towards post-treatment. Estimated glomerular filtration rate significantly improved from before second dose to post-treatment using both the Chronic Kidney Disease Epidemiology Program (p=0.001) and 4-variable Modification of Diet in Renal Disease (p=0.002) equations. Conclusion Treatment of urinary Schistosoma hematobium infections with a repeated high monthly dose of 60 mg/kg of praziquantel for 3 months is safe and effective.

scholarly journals Ensemble machine learning modeling for the prediction of artemisinin resistance in malaria

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 62
Author(s):  
Colby T. Ford ◽  
Daniel Janies
Keyword(s):  
Machine Learning ◽  
Computational Models ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
Machine Learning Algorithms ◽  
Sub Saharan Africa ◽  
Ensemble Machine Learning ◽  
Sub Saharan ◽  
Underlying Mechanisms

Resistance in malaria is a growing concern affecting many areas of Sub-Saharan Africa and Southeast Asia. Since the emergence of artemisinin resistance in the late 2000s in Cambodia, research into the underlying mechanisms has been underway. The 2019 Malaria Challenge posited the task of developing computational models that address important problems in advancing the fight against malaria. The first goal was to accurately predict artemisinin drug resistance levels of Plasmodium falciparum isolates, as quantified by the IC50. The second goal was to predict the parasite clearance rate of malaria parasite isolates based on in vitro transcriptional profiles. In this work, we develop machine learning models using novel methods for transforming isolate data and handling the tens of thousands of variables that result from these data transformation exercises. This is demonstrated by using massively parallel processing of the data vectorization for use in scalable machine learning. In addition, we show the utility of ensemble machine learning modeling for highly effective predictions of both goals of this challenge. This is demonstrated by the use of multiple machine learning algorithms combined with various scaling and normalization preprocessing steps. Then, using a voting ensemble, multiple models are combined to generate a final model prediction.

scholarly journals Ensemble machine learning modeling for the prediction of artemisinin resistance in malaria

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 62
Author(s):  
Colby T. Ford ◽  
Daniel Janies
Keyword(s):  
Machine Learning ◽  
Computational Models ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
Machine Learning Algorithms ◽  
Sub Saharan Africa ◽  
Ensemble Machine Learning ◽  
Sub Saharan ◽  
Underlying Mechanisms

Resistance in malaria is a growing concern affecting many areas of Sub-Saharan Africa and Southeast Asia. Since the emergence of artemisinin resistance in the late 2000s in Cambodia, research into the underlying mechanisms has been underway. The 2019 Malaria Challenge posited the task of developing computational models that address important problems in advancing the fight against malaria. The first goal was to accurately predict artemisinin drug resistance levels of Plasmodium falciparum isolates, as quantified by the IC50. The second goal was to predict the parasite clearance rate of malaria parasite isolates based on in vitro transcriptional profiles. In this work, we develop machine learning models using novel methods for transforming isolate data and handling the tens of thousands of variables that result from these data transformation exercises. This is demonstrated by using massively parallel processing of the data vectorization for use in scalable machine learning. In addition, we show the utility of ensemble machine learning modeling for highly effective predictions of both goals of this challenge. This is demonstrated by the use of multiple machine learning algorithms combined with various scaling and normalization preprocessing steps. Then, using a voting ensemble, multiple models are combined to generate a final model prediction.

scholarly journals Patterns of uptake of HIV testing in sub‐Saharan Africa in the pre‐treatment era

2012 ◽  
Vol 17 (8) ◽  
Author(s):  
Ide Cremin ◽  
Simon Cauchemez ◽  
Geoffrey P. Garnett ◽  
Simon Gregson
Keyword(s):  
Hiv Testing ◽  
Sub Saharan Africa ◽  
Sub Saharan ◽  
Pre Treatment

Pre-hospital oily chloramphenicol treatment in meningitis outbreaks in low resources environments

2017 ◽  
Vol 47 (4) ◽  
pp. 328-331
Author(s):  
Enrico Rino Bregani ◽  
Matilde Conti ◽  
Caterina Valcarenghi
Keyword(s):  
Bacterial Meningitis ◽  
Hospital Admission ◽  
Early Death ◽  
Sub Saharan Africa ◽  
Line Treatment ◽  
Second Line ◽  
Hospital Referral ◽  
Health Centres ◽  
Sub Saharan ◽  
Pre Treatment

Bacterial meningitis is an important cause of death and disability in sub-Saharan Africa and, with pre-treatment in peripheral health centres, the poorest populations could avoid early death, especially if they live far from hospital. During the 2001 meningitis epidemic in south Chad, Moyen Chari sanitary district peripheral health centres were equipped with oily chloramphenicol (CAP) to administer before hospital referral in suspected cases of meningitis. Eighty-six patients treated with CAP in whom the diagnosis was definitively confirmed subsequently in hospital were compared with patients receiving CAP at hospital admission during the same period. A statistically significant reduction in lethality rate, need of second line treatment or adjunctive antibiotics, and mean hospital stay were confirmed in pre-treated patients.

scholarly journals New Challenges in Malaria Elimination

2021 ◽  
Author(s):  
Susanta Kumar Ghosh ◽  
Chaitali Ghosh
Keyword(s):  
Malaria Elimination ◽  
New Technologies ◽  
Point Of Care ◽  
Artemisinin Resistance ◽  
Sub Saharan Africa ◽  
Chloroquine Resistance ◽  
World Health ◽  
Synthetic Pyrethroids ◽  
Sub Saharan ◽  
Health Organization

In recent years, efforts to eliminate malaria has gained a tremendous momentum, and many countries have achieved this goal — but it has faced many challenges. Recent COVID-19 pandemic has compounded the challenges due to cessation of many on-field operations. Accordingly, the World Health Organization (WHO) has advocated to all malaria-endemic countries to continue the malaria elimination operations following the renewed protocols. The recent reports of artemisinin resistance in Plasmodium falciparum followed by indication of chloroquine resistance in P. vivax, and reduced susceptibility of synthetic pyrethroids used in long lasting insecticide nets are some issues hindering the elimination efforts. Moreover, long distance night migration of vector mosquitoes in sub-Saharan Africa and invasion of Asian vector Anopheles stephensi in many countries including Africa and Southeast Asia have added to the problems. In addition, deletion of histidine rich protein 2 and 3 (Pfhrp2/3) genes in P. falciparum in many countries has opened new vistas to be addressed for point-of-care diagnosis of this parasite. It is needed to revisit the strategies adopted by those countries have made malaria elimination possible even in difficult situations. Strengthening surveillance and larval source management are the main strategies for successful elimination of malaria. New technologies like Aptamar, and artificial intelligence and machine learning would prove very useful in addressing many ongoing issues related to malaria elimination.

scholarly journals Three monthly doses of 60 mg/kg praziquantel for Schistosoma haematobium infection is a safe and effective treatment regimen.

2020 ◽  
Author(s):  
Samuel Nkansah Darko ◽  
Henry Hanson ◽  
Sampson Twumasi Ankrah ◽  
Sandra Baffour ◽  
Priscilla Adjei-Kusi ◽  
...  
Keyword(s):  
Renal Function ◽  
Post Treatment ◽  
Sub Saharan Africa ◽  
Gamma Glutamyl Transferase ◽  
Disease Epidemiology ◽  
Sub Saharan ◽  
Pre Treatment ◽  
Effective Treatment Regimen ◽  
And Gender ◽  
Glutamyl Transferase

Abstract Background: Praziquantel (PZQ) is the standard treatment for Schistosomiasis in sub-Saharan Africa. However, there is evidence suggesting praziquantel treatment failure in Schistosome infections with associated potential renal impairment. The objective of this study was to determine the effect of three monthly doses of 60 mg/kg/day PZQ on schistosome egg count, liver and renal function during the treatment of urinary schistosomiasis in Ghana.Methods: A nested case-control study was designed from a cohort screened for schistosomiasis; 28 schistosomiasis positive cases by microscopy matched with 53 healthy controls by age and gender. The study population was urban dwellers from the Asokwa sub-metropolitan area, Kumasi in Ghana. Participants were within the age range of 6 to 30 years. We assessed Schistosoma haematobium egg counts in urine and its associated impact on liver and renal function at baseline, treatment and post-treatment phases using serum. Results: Of the 28 cases and 53 controls, 78.6% and (81.1% were males respectively. Globulin levels before treatment was higher in cases [36.7 (32.8, 40.1) vrs 30.5 (22.4, 33.8), p=0.005] at pre-treatment but not at post-treatment [35.8 (31.2, 39.1) vrs 37.4 (29.7, 43.0), p= 0.767]. Estimated cure rate was 42.9%, 46.4% and 96.4% after first, second and third dose respectively. Schistosome egg counts dropped significantly (p= 0.001) from before second dose to post-treatment. Similarly, levels of alanine aminotransferase (p=0.001), aspartate aminotransferase (p=0.028) and gamma glutamyl transferase (p=0.001) significantly declined towards post-treatment. Estimated glomerular filtration rate significantly improved from before second dose to post-treatment using both the Chronic Kidney Disease Epidemiology Program (p=0.001) and 4-variable Modification of Diet in Renal Disease (p=0.002) equations. Conclusion: Treatment of urinary Schistosoma hematobium infections with a repeated high monthly dose of 60 mg/kg of praziquantel for 3 months is safe and effective.

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