Visceral leishmaniasis (VL) is an infectious disease caused by protozoa of the genus Leishmania. Sporadic cases are observed in nonendemic areas and often associated with limited foci; therefore, the ...disease is easily overlooked. In addition, other diseases have similar clinical symptoms, which make it difficult for clinicians to make an accurate diagnosis and to provide effective treatment. We identified visceral leishmaniasis in a 4-year-old child in Pikine, Senegal. The patient was admitted to the Pikine National Teaching Hospital for haemorrhagic, tumoral, and infectious syndromes. At admission, the patient presented with epistaxis and gingivorrhagia, a severe anaemic syndrome poorly tolerated, a systemic inflammatory response syndrome with fever at 39.5°C, a tumoral syndrome with 11 cm of hepatomegaly and 12 cm of type IV splenomegaly, and noninflammatory macropoly adenopathies. A spinal cord puncture was performed, and direct microscopy examination of the sample after GIEMSA staining revealed amastigote forms of Leishmania. The PCR amplification of extracted DNA from the bone marrow aspiration using specific primers for VL (forward and reverse) confirmed that VL was responsible for the infection. A treatment with meglumine antimoniate (Glucantime) was given and it gave a successful outcome with remission of clinical symptoms and favourable evolution with 3 months hindsight. Conclusion. This visceral leishmaniasis case diagnosis in Senegal has shown that, apart from haematological malignancies, this disease must be considered in combination with a tumor syndrome, haemorrhagic syndrome, and infectious syndrome.
IntroductionIn 2020, an estimated 150 million children under the age of 5 years were stunted. Stunting results from early-life adversity and it is associated with significant physical and cognitive ...deficit, lifelong socioeconomic disadvantage and reduced life expectancy. There is a need to understand the causes of stunting and its effects in order to develop strategies to avoid it and to mitigate the consequences once stunting has occurred. Epigenetics is an important mechanism through which early-life factors are thought to influence biological function, with long-term consequences. We describe a series of epigenetic studies designed to understand how early-life adversity results in stunting and to inform the development of practical tools such as predictive markers and therapeutic targets. This work is part of the UKRI GCRF Action Against Stunting Hub.Methods and analysisThe project—in India, Indonesia and Senegal—comprises an observational study of mothers, fathers, and offspring (n=500) spanning the first 1000 days of life, and an intervention study in each country. Epigenetic status (DNA methylation) is determined in saliva from babies collected within 1 month of birth and again at 18 months of age, and from mothers and fathers around the time of birth. Epigenome-wide analysis is carried out using the Illumina EPIC array, augmented by high-definition sequencing approaches. Statistical analysis is carried out at the level of candidate genes/regions, higher dimensional epigenetic states and epigenome-wide association. Data analysis focuses on the determinants of stunting, the effectiveness of interventions, population comparisons and the link between epigenetics and other thematic areas, which include anthropometry, microbiome, gut health, parasitology, cognition, nutrition, food hygiene and water sanitation, food systems and the home environment.Ethics and disseminationThis study has been approved by the relevant Ethics Committees in Indonesia, India and Senegal, and the UK. Research data will be published and posted in public repositories.
Artemisinin Combination Therapies (ACT) stand as the most potent antimalarial treatments. In response to the emergence of ACT-resistant malaria parasites in Southeast Asia, the World Health ...Organization (WHO) has recommended continuous monitoring of the effectiveness of ACT and other antimalarials. To address this need, we collected dried blood spots from malaria patients during a 42-days drug efficacy trial evaluating the efficacy of Artesunate plus Amodiaquine (ASAQ), Artemether Plus Lumefantrine (AL) and Dihydroarthemisinine plus Piperaquine (DHAPQ) on simple P. falciparum malaria in 2017. Blood samples were collected on Day 0, prior to the patients' initial ACT dose, and on any days of recurrent parasitemia. Genetic markers such as Merozoite Surface Protein 1 (MSP1) and Merozoite Surface Protein 2 (MSP2) were genotyped to differentiate between recrudescence and re-infestation cases. Furthermore, PCR Single Specific Oligonucleotide Probes combined with-ELISA platform (PCR-SSOP-ELISA) and PCR-RFLP techniques were used to identify Pfcrt 72-76 mutant haplotype and Pfmdr1_86Y allele associated with chloroquine and amodiaquine resistance, respectively. Out of the 320 patients enrolled in the study, only 43 (13.43%) experienced relapses. Upon PCR correction, our analysis revealed that recrudescent infections affected 13 patients, with 8 in the ASAQ group, 5 in the AL group, and none in the DHAPQ group. Notably, no early treatment failures (within the first 3 days of treatment) were observed, and all recurrences occurred between Day 21 and Day 42. The prevalence of the Pfcrt wild-type haplotype CVMNK and Pfmdr N86 allele was 67.03% and 97.70%, respectively. In contrast, the mutant types CVIET and 86Y were found at 32.97% and 2.3%, respectively. The high prevalence of the CVMNK wild haplotype suggests that the parasites remain sensitive to chloroquine, while the low prevalence of the 86Y mutants indicates continued effectiveness of amodiaquine. Furthermore, the low prevalence of strains exhibiting the combination of CVIET and 86Y suggests that the use of multiple antimalarials is valuable for resistance control. Notably, none of the relapse cases carried the 86Y mutation or the combination of 86Y and CVIET.Artemisinin Combination Therapies (ACT) stand as the most potent antimalarial treatments. In response to the emergence of ACT-resistant malaria parasites in Southeast Asia, the World Health Organization (WHO) has recommended continuous monitoring of the effectiveness of ACT and other antimalarials. To address this need, we collected dried blood spots from malaria patients during a 42-days drug efficacy trial evaluating the efficacy of Artesunate plus Amodiaquine (ASAQ), Artemether Plus Lumefantrine (AL) and Dihydroarthemisinine plus Piperaquine (DHAPQ) on simple P. falciparum malaria in 2017. Blood samples were collected on Day 0, prior to the patients' initial ACT dose, and on any days of recurrent parasitemia. Genetic markers such as Merozoite Surface Protein 1 (MSP1) and Merozoite Surface Protein 2 (MSP2) were genotyped to differentiate between recrudescence and re-infestation cases. Furthermore, PCR Single Specific Oligonucleotide Probes combined with-ELISA platform (PCR-SSOP-ELISA) and PCR-RFLP techniques were used to identify Pfcrt 72-76 mutant haplotype and Pfmdr1_86Y allele associated with chloroquine and amodiaquine resistance, respectively. Out of the 320 patients enrolled in the study, only 43 (13.43%) experienced relapses. Upon PCR correction, our analysis revealed that recrudescent infections affected 13 patients, with 8 in the ASAQ group, 5 in the AL group, and none in the DHAPQ group. Notably, no early treatment failures (within the first 3 days of treatment) were observed, and all recurrences occurred between Day 21 and Day 42. The prevalence of the Pfcrt wild-type haplotype CVMNK and Pfmdr N86 allele was 67.03% and 97.70%, respectively. In contrast, the mutant types CVIET and 86Y were found at 32.97% and 2.3%, respectively. The high prevalence of the CVMNK wild haplotype suggests that the parasites remain sensitive to chloroquine, while the low prevalence of the 86Y mutants indicates continued effectiveness of amodiaquine. Furthermore, the low prevalence of strains exhibiting the combination of CVIET and 86Y suggests that the use of multiple antimalarials is valuable for resistance control. Notably, none of the relapse cases carried the 86Y mutation or the combination of 86Y and CVIET.
IntroductionChild stunting has a complex aetiology, especially in the first 1000 days of life. Nutrition interventions alone have not produced expected impacts in reducing/preventing child stunting, ...indicating the importance of understanding the complex interplay between environmental, physiological and psychological factors influencing child nutritional status. This study will investigate maternal and child nutrition, health and well-being status and associated factors through the assessment of: (1) anthropometry, (2) biomarkers of nutrition and health status, (3) dietary intakes, (4) fetal growth and development, (5) infant morbidity, (6) infant and young child feeding (IYCF) and (7) perinatal maternal stress, depression and social support.MethodsThis study will be conducted in a prospective pregnancy cohort in India, Indonesia and Senegal. Pregnant women will be recruited in the second (Indonesia, Senegal) and third (India) trimester of pregnancy, and the mother and infant dyads followed until the infant is 24 months of age. During pregnancy, anthropometric measures will be taken, venous blood samples will be collected for biochemical assessment of nutrition and health status, dietary intakes will be assessed using a 4-pass-24-hour dietary recall method (MP24HR), fetal ultrasound for assessment of fetal growth. After birth, anthropometry measurements will be taken, venous blood samples will be collected, MP24HR will be conducted, infant morbidity and IYCF practices will be assessed and a sample of breastmilk will be collected for nutrient composition analyses. Perinatal maternal stress, depression, social support and hair cortisol levels (stress) will be measured. The results from this study will be integrated in an interdisciplinary analysis to examine factors influencing infant growth and inform global efforts in reducing child stunting.Ethics and disseminationEthical approval was granted by the Ethics Committee of the London School of Hygiene and Tropical Medicine (17915/RR/17513); National Institute of Nutrition (ICMR)-Ministry of Health and Family Welfare, Government of India (CR/04/I/2021); Health Research Ethics Committee, University of Indonesia and Cipto Mangunkusumo Hospital (KET-887/UN2.F1/ETIK/PPM.00.02/2019); and the Comité National d'Ethique pour la Recherche en Santé, Senegal (Protocole SEN19/78); the Royal Veterinary College (URN SR2020-0197) and the International Livestock Research Institute Institutional Research Ethics Committee (ILRI-IREC2020-33). Results will be published in peer-reviewed journals and disseminated to policy-makers and participating communities.
