Clinical evidence of the role of Methanobrevibacter smithii in severe acute malnutrition

International audienceAbstract Gut microbial dysbiosis has been shown to be an instrumental factor in severe acute malnutrition (SAM) and particularly, the absence of Methanobrevibacter smithii, a key player in energy harvest. Nevertheless, it remains unknown whether this absence reflects an immaturity or a loss of the microbiota. In order to assess that, we performed a case–control study in Mali using a propensity score weighting approach. The presence of M. smithii was tested using quantitative PCR on faeces collected from SAM children at inclusion and at discharge when possible or at day 15 for controls. M. smithii was highly significantly associated with the absence of SAM, detected in 40.9% controls but only in 4.2% cases (p < 0.0001). The predictive positive value for detection of M. smithii gradually increased with age in controls while decreasing in cases. Among children providing two samples with a negative first sample, no SAM children became positive, while this proportion was 2/4 in controls (p = 0.0015). This data suggests that gut dysbiosis in SAM is not an immaturity but rather features a loss of M. smithii . The addition of M. smithii as a probiotic may thus represent an important addition to therapeutic approaches to restore gut symbiosis

Table_2_Shifts in the clinical epidemiology of severe malaria after scaling up control strategies in Mali.pdf

A decrease in malaria incidence following implementation of control strategies such as use of artemisinin-based combination therapies, insecticide-impregnated nets, intermittent preventive treatment during pregnancy and seasonal malaria chemoprevention (SMC) has been observed in many parts of Africa. We hypothesized that changes in malaria incidence is accompanied by a change in the predominant clinical phenotypes of severe malaria. To test our hypothesis, we used data from a severe malaria case-control study that lasted from 2014–2019 to describe clinical phenotypes of severe forms experienced by participants enrolled in Bandiagara, Bamako, and Sikasso, in Mali. We also analyzed data from hospital records of inpatient children at a national referral hospital in Bamako. Among 97 cases of severe malaria in the case-control study, there was a predominance of severe malarial anemia (49.1%). The frequency of cerebral malaria was 35.4, and 16.5% of cases had a mixed clinical phenotype (concurrent cerebral malaria and severe anemia). National referral hospital record data in 2013–15 showed 24.3% of cases had severe malarial anemia compared to 51.7% with cerebral malaria. In the years after SMC scale-up, severe malarial anemia cases increased to 30.1%, (P = 0.019), whereas cerebral malaria cases decreased to 45.5% (P = 0.025). In addition, the predominant age group for each severe malaria phenotype was the 0–1-year-olds. The decrease in malaria incidence noted with the implementation of control strategies may be associated with a change in the clinical expression patterns of severe malaria, including a potential shift in severe malaria burden to age groups not receiving seasonal malaria chemoprevention.</p

Table_3_Shifts in the clinical epidemiology of severe malaria after scaling up control strategies in Mali.pdf

A decrease in malaria incidence following implementation of control strategies such as use of artemisinin-based combination therapies, insecticide-impregnated nets, intermittent preventive treatment during pregnancy and seasonal malaria chemoprevention (SMC) has been observed in many parts of Africa. We hypothesized that changes in malaria incidence is accompanied by a change in the predominant clinical phenotypes of severe malaria. To test our hypothesis, we used data from a severe malaria case-control study that lasted from 2014–2019 to describe clinical phenotypes of severe forms experienced by participants enrolled in Bandiagara, Bamako, and Sikasso, in Mali. We also analyzed data from hospital records of inpatient children at a national referral hospital in Bamako. Among 97 cases of severe malaria in the case-control study, there was a predominance of severe malarial anemia (49.1%). The frequency of cerebral malaria was 35.4, and 16.5% of cases had a mixed clinical phenotype (concurrent cerebral malaria and severe anemia). National referral hospital record data in 2013–15 showed 24.3% of cases had severe malarial anemia compared to 51.7% with cerebral malaria. In the years after SMC scale-up, severe malarial anemia cases increased to 30.1%, (P = 0.019), whereas cerebral malaria cases decreased to 45.5% (P = 0.025). In addition, the predominant age group for each severe malaria phenotype was the 0–1-year-olds. The decrease in malaria incidence noted with the implementation of control strategies may be associated with a change in the clinical expression patterns of severe malaria, including a potential shift in severe malaria burden to age groups not receiving seasonal malaria chemoprevention.</p

Image_1_Shifts in the clinical epidemiology of severe malaria after scaling up control strategies in Mali.pdf

A decrease in malaria incidence following implementation of control strategies such as use of artemisinin-based combination therapies, insecticide-impregnated nets, intermittent preventive treatment during pregnancy and seasonal malaria chemoprevention (SMC) has been observed in many parts of Africa. We hypothesized that changes in malaria incidence is accompanied by a change in the predominant clinical phenotypes of severe malaria. To test our hypothesis, we used data from a severe malaria case-control study that lasted from 2014–2019 to describe clinical phenotypes of severe forms experienced by participants enrolled in Bandiagara, Bamako, and Sikasso, in Mali. We also analyzed data from hospital records of inpatient children at a national referral hospital in Bamako. Among 97 cases of severe malaria in the case-control study, there was a predominance of severe malarial anemia (49.1%). The frequency of cerebral malaria was 35.4, and 16.5% of cases had a mixed clinical phenotype (concurrent cerebral malaria and severe anemia). National referral hospital record data in 2013–15 showed 24.3% of cases had severe malarial anemia compared to 51.7% with cerebral malaria. In the years after SMC scale-up, severe malarial anemia cases increased to 30.1%, (P = 0.019), whereas cerebral malaria cases decreased to 45.5% (P = 0.025). In addition, the predominant age group for each severe malaria phenotype was the 0–1-year-olds. The decrease in malaria incidence noted with the implementation of control strategies may be associated with a change in the clinical expression patterns of severe malaria, including a potential shift in severe malaria burden to age groups not receiving seasonal malaria chemoprevention.</p

Table_1_Shifts in the clinical epidemiology of severe malaria after scaling up control strategies in Mali.pdf

A decrease in malaria incidence following implementation of control strategies such as use of artemisinin-based combination therapies, insecticide-impregnated nets, intermittent preventive treatment during pregnancy and seasonal malaria chemoprevention (SMC) has been observed in many parts of Africa. We hypothesized that changes in malaria incidence is accompanied by a change in the predominant clinical phenotypes of severe malaria. To test our hypothesis, we used data from a severe malaria case-control study that lasted from 2014–2019 to describe clinical phenotypes of severe forms experienced by participants enrolled in Bandiagara, Bamako, and Sikasso, in Mali. We also analyzed data from hospital records of inpatient children at a national referral hospital in Bamako. Among 97 cases of severe malaria in the case-control study, there was a predominance of severe malarial anemia (49.1%). The frequency of cerebral malaria was 35.4, and 16.5% of cases had a mixed clinical phenotype (concurrent cerebral malaria and severe anemia). National referral hospital record data in 2013–15 showed 24.3% of cases had severe malarial anemia compared to 51.7% with cerebral malaria. In the years after SMC scale-up, severe malarial anemia cases increased to 30.1%, (P = 0.019), whereas cerebral malaria cases decreased to 45.5% (P = 0.025). In addition, the predominant age group for each severe malaria phenotype was the 0–1-year-olds. The decrease in malaria incidence noted with the implementation of control strategies may be associated with a change in the clinical expression patterns of severe malaria, including a potential shift in severe malaria burden to age groups not receiving seasonal malaria chemoprevention.</p

Image_2_Shifts in the clinical epidemiology of severe malaria after scaling up control strategies in Mali.pdf

A decrease in malaria incidence following implementation of control strategies such as use of artemisinin-based combination therapies, insecticide-impregnated nets, intermittent preventive treatment during pregnancy and seasonal malaria chemoprevention (SMC) has been observed in many parts of Africa. We hypothesized that changes in malaria incidence is accompanied by a change in the predominant clinical phenotypes of severe malaria. To test our hypothesis, we used data from a severe malaria case-control study that lasted from 2014–2019 to describe clinical phenotypes of severe forms experienced by participants enrolled in Bandiagara, Bamako, and Sikasso, in Mali. We also analyzed data from hospital records of inpatient children at a national referral hospital in Bamako. Among 97 cases of severe malaria in the case-control study, there was a predominance of severe malarial anemia (49.1%). The frequency of cerebral malaria was 35.4, and 16.5% of cases had a mixed clinical phenotype (concurrent cerebral malaria and severe anemia). National referral hospital record data in 2013–15 showed 24.3% of cases had severe malarial anemia compared to 51.7% with cerebral malaria. In the years after SMC scale-up, severe malarial anemia cases increased to 30.1%, (P = 0.019), whereas cerebral malaria cases decreased to 45.5% (P = 0.025). In addition, the predominant age group for each severe malaria phenotype was the 0–1-year-olds. The decrease in malaria incidence noted with the implementation of control strategies may be associated with a change in the clinical expression patterns of severe malaria, including a potential shift in severe malaria burden to age groups not receiving seasonal malaria chemoprevention.</p

Model-based assessment of Chikungunya and O’nyong-nyong virus circulation in Mali in a serological cross-reactivity context

International audienceSerological surveys are essential to quantify immunity in a population but serological cross-reactivity often impairs estimates of the seroprevalence. Here, we show that modeling helps addressing this key challenge by considering the important cross-reactivity between Chikungunya (CHIKV) and O’nyong-nyong virus (ONNV) as a case study. We develop a statistical model to assess the epidemiology of these viruses in Mali. We additionally calibrate the model with paired virus neutralization titers in the French West Indies, a region with known CHIKV circulation but no ONNV. In Mali, the model estimate of ONNV and CHIKV prevalence is 30% and 13%, respectively, versus 27% and 2% in non-adjusted estimates. While a CHIKV infection induces an ONNV response in 80% of cases, an ONNV infection leads to a cross-reactive CHIKV response in only 22% of cases. Our study shows the importance of conducting serological assays on multiple cross-reactive pathogens to estimate levels of virus circulation

Author Correction: Model-based assessment of Chikungunya and O’nyong-nyong virus circulation in Mali in a serological cross-reactivity context

International audienc