Slipknot or Crystallographic Error: A Computational Analysis of the Plasmodium falciparum DHFR Structural Folds.

The presence of protein structures with atypical folds in the Protein Data Bank (PDB) is rare and may result from naturally occurring knots or crystallographic errors. Proper characterisation of such folds is imperative to understanding the basis of naturally existing knots and correcting crystallographic errors. If left uncorrected, such errors can frustrate downstream experiments that depend on the structures containing them. An atypical fold has been identified in P. falciparum dihydrofolate reductase (PfDHFR) between residues 20-51 (loop 1) and residues 191-205 (loop 2). This enzyme is key to drug discovery efforts in the parasite, necessitating a thorough characterisation of these folds. Using multiple sequence alignments (MSA), a unique insert was identified in loop 1 that exacerbates the appearance of the atypical fold-giving it a slipknot-like topology. However, PfDHFR has not been deposited in the knotted proteins database, and processing its structure failed to identify any knots within its folds. The application of protein homology modelling and molecular dynamics simulations on the DHFR domain of P. falciparum and those of two other organisms (E. coli and M. tuberculosis) that were used as molecular replacement templates in solving the PfDHFR structure revealed plausible unentangled or open conformations of these loops. These results will serve as guides for crystallographic experiments to provide further insights into the atypical folds identified.

[Hepatitis C in a psychiatric setting: A forgotten reservoir?] / Hépatite C en milieu psychiatrique : un réservoir oublié ?

Hepatitis C is a transmissible hepatic and extra-hepatic disease caused by the hepatitis C virus (HCV). HCV develops into a chronic infection among approximately 70% of the contaminated subjects. Chronic HCV infection is estimated to affect between 0.5% and 1 % of the general population in France, which causes an important burden of disease, in particular due to the occurrence of cirrhosis and liver cancer. New antiviral drugs now allow to cure more than 95% of patients in just a few weeks of treatment with very limited safety issues. This therapeutic revolution has led the World Health Organization and many national governments to aim for an elimination of HCV, which has been defined as a 90%-reduction of the incidence rate, and a 65%-reduction in the number of HCV-related deaths on the basis of the 2015 figures. In this respect, the French Ministry of Health has recently decided to extend the ability to prescribe the new antiviral drugs to any physician. However, the elimination campaign of HCV will also need to correctly identify, screen, and treat the main target populations. If people who inject drugs (PWIDs) certainly constitute the most important population concerned by the challenge of HCV elimination, more hidden reservoirs in which HCV transmission can insidiously evolve should be identified and specifically targeted as well. Inpatient psychiatric populations might constitute one of these hidden reservoirs. International data suggest that chronic HCV infection affects approximately 5% of psychiatric inpatients in Europe. This very high prevalence estimate can in part be due to the very frequent psychiatric disorders found among the current or former PWIDs. However, a part of the seropositive patients does not report a history of drug use, and other factors could contribute to the increased risk of contamination in this population including atypical routes of transmission related to institutional promiscuity. Exploring the general profile and risk-behaviors of the psychiatric inpatients found infected by the HCV is thus warranted for future studies. Screening and treating HCV in the specific population of psychiatric patients is part of the general public health objective of eliminating HCV at a national level. Moreover, it also directly fits into the individualized psychiatric care. Many recent data suggest that HCV also has a neural tropism, in particular within glial cells, such as astrocytes or oligodendrocytes. As such, HCV foments inflammatory processes in the brain and contributes to cognitive impairments and psychiatric symptoms such as anxiety or depression. At the individual level, treating HCV infection can improve the psychiatric state and increase patients' outcomes in terms of well-being and quality of life. For all these reasons, the field of psychiatry needs local and national actions for informing and training professionals about HCV screening and treating modalities. Patient and family associations also need to be involved in this general effort of micro-elimination. A key role should be assigned to the general practitioners embedded within inpatient psychiatric units. They are the best fitted professionals to screen, treat, and empower patients, to inform and train other caregivers of the psychiatric field, and to act as a relay with hepatology teams if required. Hospital pharmacists are other important stakeholders. In a national context in which the funding of psychiatric care, including medications, is based on predefined funding envelops, innovative initiatives will have to be set up by local or national health authorities, in partnership with pharmacists, to allow for the treatment of psychiatric inpatients. In conclusion, the world of psychiatry is a possible hidden reservoir of HCV and, as such, a part of the challenge for eliminating the virus. Patients, families, and caregivers will have to be correctly sensitized and trained to play their role in the process. Specific investigations will be required to better understand why such an increased prevalence of HCV is observed in this population. Specific adaptations of the cascade of care within psychiatric settings, including access to treatment, will need to be designed, implemented, and evaluated for reaching micro-elimination of HCV in psychiatry.

Need for systematic screening for IGD in adolescent psychiatric inpatients.

Psychiatric comorbidities are frequent in adolescents with internet gaming disorder (IGD). In contrast, the proportion of IGD among adolescents hospitalized for a psychiatric disorder has not been documented yet. In addition, parental ratings of IGD could be useful for diagnosis, but very few data exist on this issue. The objectives of this study were to: (1) assess the prevalence of IGD among adolescent psychiatric inpatients, using the Ten-Item Internet Gaming Disorder Test (IGDT-10), and (2) assess the parental version developed for this study (IGDT-10-P). A total of 102 patients, aged from 12 to 17 years old, were included from four psychiatric units of the French region Auvergne-Rhône-Alpes, during a 6-month inclusion period. Adolescents completed the IGDT-10 while one of their parents completed the IGDT-10-P. The inclusion rate among the eligible population was 57.95%. The prevalence of IGD in the sample, based on the IGDT-10 and IGDT-10-P, was 6.00% and 12.79%, respectively. Psychometric features of the IGDT-10-P indicated excellent internal consistency, a good model fit to the one factor model in confirmatory factor analysis, a strong correlation with gaming time, and a moderate correlation with the IGDT-10. Our results support the need for a systematic screening of IGD among adolescents hospitalized for a psychiatric disorder. Future studies should aim to confirm and explain the prevalence gap between self- and parent-reported criteria.

[Screening tools for cannabis use disorders and their adaptation to DSM-5: A literature review]. / Les outils de repérage pour les troubles de l'usage du cannabis et leur adaptation au DSM-5 : une revue de littérature.

OBJECTIVES: Cannabis use is widespread in France, particularly among adolescents and young adults, and can induce severe somatic, psychiatric and social consequences. Early identification and appropriate care of cannabis use disorders thus constitute a major public health issue. Standardized questionnaires based on patient self-reporting are recognized as the best option for identifying cannabis use disorders because of their reliability and simplicity. METHODS: We conducted a narrative literature review on cannabis use assessment tools on PubMed and selected cannabis-specific questionnaires, validated for adolescent and/or adult populations, from scientific articles in English or French between 1995 and 2010. RESULTS: Sixteen questionnaires were found according to the inclusion criteria. The CAGE-cannabis, the CAST, the CUDIT and its revised version the CUDIT-R, the PUM and the SDS are the only ones that have good characteristics for a short screening tool adapted to daily clinical practice, namely to be brief (fewer than 10 questions) and quick handover (less than 10minutes). Only the CAST has been validated in French, and the CUDIT-R is currently being validated. In the DSM-5, diagnoses of abuse or addiction have been grouped into a single diagnosis of cannabis use disorders with different levels of severity. It is relevant that tools used for screening take into account these new diagnostic concepts. The CUDIT-R is currently the only one to be validated based on DSM-5 diagnostic criteria. CONCLUSION: Among the many questionnaires available, few are suited for daily clinical practice in France because of their complexity, their long duration or the absence of a validated French translation. The CUDIT-R has good psychometric characteristics, is simple to use, and has been validated according to the criteria of DSM-5. These questionnaires are obviously not a substitute for a clinical diagnosis and must be followed by a specialist's evaluation. However, they remain an interesting mediation, encouraging a patient's awareness and commitment to care.

Economical optimization of a breeding scheme by selective phenotyping of the calibration set in a multi-trait context: application to bread making quality.

KEY MESSAGE: Trait-assisted genomic prediction approach is a way to improve genetic gain by cost unit, by reducing budget allocated to phenotyping or by increasing the program's size for the same budget. This study compares different strategies of genomic prediction to optimize resource allocation in breeding schemes by using information from cheaper correlated traits to predict a more expensive trait of interest. We used bread wheat baking score (BMS) calculated for French registration as a case study. To conduct this project, 398 lines from a public breeding program were genotyped and phenotyped for BMS and correlated traits in 11 locations in France between 2000 and 2016. Single-trait (ST), multi-trait (MT) and trait-assisted (TA) strategies were compared in terms of predictive ability and cost. In MT and TA strategies, information from dough strength (W), a cheaper trait correlated with BMS (r = 0.45), was evaluated in the training population or in both the training and the validation sets, respectively. TA models allowed to reduce the budget allocated to phenotyping by up to 65% while maintaining the predictive ability of BMS. TA models also improved the predictive ability of BMS compared to ST models for a fixed budget (maximum gain: + 0.14 in cross-validation and + 0.21 in forward prediction). We also demonstrated that the budget can be further reduced by approximately one fourth while maintaining the same predictive ability by reducing the number of phenotypic records to estimate BMS adjusted means. In addition, we showed that the choice of the lines to be phenotyped can be optimized to minimize cost or maximize predictive ability. To do so, we extended the mean of the generalized coefficient of determination (CDmean) criterion to the multi-trait context (CDmulti).

[The serotonin syndrome: An updated literature review]. / Le syndrome sérotoninergique : une revue actualisée de la littérature.

The serotonin syndrome is a potentially deadly complication resulting from drug adverse effect, drug-drug interaction or overdose involving one or more serotonergic molecules, e.g., antidepressants, psychostimulants and sometimes an "ignored" serotonergic compound. The serotonin syndrome typically consists of a clinical triad including cognitive/behavioral, neurovegetative and neuromuscular features. However, this syndrome is characterized by major clinical heterogeneity, making the diagnosis difficult in practice. Moreover, many practitioners are quite unaware of this syndrome. Available scores and classifications can help physicians in their diagnosis approach. Knowing the responsible molecules, their potential interactions and mechanisms of action can help preventing this complication allowing therapeutic education among patients. This updated article reviews the clinical presentation, prevention, management, and pathophysiology of the serotonin syndrome, and addresses the most recent advances in pharmacogenetics regarding this syndrome.

[Consultation/liaison addiction medicine: Tools and specificities]. / L'addictologie de liaison : outils et spécificités.

Since the 1970s, the concept of "consultation/liaison (CL) psychiatry" has pertained to specialized mobile teams which meet inpatients hospitalized in non-psychiatric settings to offer them on-the-spot psychiatric assessment, treatment, and, if needed, adequate referral. Since the birth of CL psychiatry, a long set of theoretical books and articles has aimed at integrating CL psychiatry into the wider scope of psychosomatic medicine. In the year 2000, a circular issued by the Health Ministry defined the organization of "CL addiction services" in France. Official CL addiction teams are named "Équipes de Liaison et de Soins en Addictologie" (ELSAs) which are separated from CL psychiatry units. Though this separation can be questioned, it actually emphasizes that the work provided by CL addiction teams has some very specific features. The daily practice of ELSAs somewhat differs from that of psychiatric CL teams. Addictive behaviors often result from progressive substance misuse. In this respect, the ELSAs' practice frequently involves screening, brief intervention, and referral to treatment (SBIRT) interventions, which are rather specific of addiction medicine and consist more of prevention interventions than actual addiction treatment. Moreover, for patients with characterized substance use disorders substantial skills in motivational interviewing are required in ELSA consultations. Though motivational interviewing is not specific to addiction medicine, its regular use is uncommon for other liaison teams in France. Furthermore, substance misuse can induce many types of acute or delayed substance-specific medical consequences. These consequences are often poorly known and thus poorly explored by physicians of other specialties. ELSAs have therefore the role of advising their colleagues for a personalized somatic screening among patients with substance misuse. In this respect, the service undertaken by ELSAs is not only based on relational skills but also comprises a somatic expertise. This specificity differs from CL psychiatry. Moreover, several recent studies have shown that in some cases it was useful to extend liaison interventions for addiction into outpatient consultations that are directly integrated in the consultation units of certain specialties (e.g., hepatology, emergency, or oncology). Such a partnership can substantially enhance patients' motivation and addiction outcome. This specificity is also hardly transposable in CL psychiatry. In France, addiction medicine is an inter-specialty that is not fully-integrated into psychiatry. This separation is also applied for CL services which emphasizes real differences in the daily practices and in intervention frameworks. Regardless, CL psychiatry units and ELSAs share many other features and exhibit important overlaps in terms of targeted populations and overall missions. These overlaps are important to conjointly address, with the aim to offer integrated and collaborative services, within the hospital settings of other medical specialties.

Evaluation by undergraduate medical students of a role-playing training program on the management of acute states of agitation.

OBJECTIVES: Acute states of agitation (ASAs) are frequent in daily medical practice. However, training on real ASAs raises technical and ethical issues, whereas lecture-based teaching hardly addresses some educational objectives, e.g., improving relational skills and team-based coordination. Simulation-based medical education (SBME) is a promising medium to train students on managing ASAs. We have recently implemented a role-playing training module on ASAs. In this scenario, four to five students play the role of the staff, while a trained professional actor plays the agitated patient. A subsequent standardized debriefing is conducted by a senior psychiatrist. A first wave of 219 students participated in a one-session training of this ASA module in June 2015. They completed pre-session and post-session questionnaires aiming to collect "proof-of-concept" data. METHODS: The pre-session questionnaire investigated: previous experience of ASA among students during their clinical training; previous participation in a role-playing SBME; and perceived knowledge of the good practice rules for managing ASAs. The post-session questionnaire investigated among the students if: they thought having been able to appropriately manage the simulated ASA; they found the SBME medium more fitted for training than real situations; they found that the SBME session faithfully reproduced a real ASA; and the session was found useful for transmitting the skills on correct management of ASA. The average level of stress induced by the training was assessed using a numerical rating scale (0-10). RESULTS: Two hundred and six of the 219 students completed the pre-session questionnaire (63% females; response rate 96.7%). A hundred and thirty four students played the scenario and completed the post-session questionnaire (65.7% females; response rate 100%). 38.3% of the responders reported having previously experienced a situation of ASA in their practice, and 31.1% deemed to know the good practices rules for managing an ASA. In post-session, 29.9% of the participants considered that they appropriately managed the ASA, 79.9% deemed that the role-playing session faithfully reproduced a real ASA, and 97% deemed that this SBME was more fitted and useful than a real clinical situation to improve their medical skills. Bivariate analyses revealed that the post-session responses and level of stress were not influenced by previous experience on ASA, previous participation in a SBME role-playing session, or thinking to know the rules for managing ASAs. CONCLUSION: SBME role-playing training appears a promising, realistic, and well-accepted method for teaching the management of ASA.

Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study.

BACKGROUND: Drug resistance is one of the greatest challenges of malaria control programmes, with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy (ACT) partner drugs critical to elimination efforts. Markers of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern Cameroon. METHODS: Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through cross-sectional surveys from May 2013 to March 2014 along the slope of mount Cameroon. Plasmodium falciparum malaria parasitaemic blood, screened by light microscopy, was depleted of leucocytes using CF11 cellulose columns and the parasite genotype ascertained by sequencing on the Illumina HiSeq platform. RESULTS: A total of 259 participants were enrolled in this study from three different altitudes. While some alleles associated with drug resistance in pfdhfr, pfmdr1 and pfcrt were highly prevalent, less than 3% of all samples carried mutations in the pfkelch13 gene, none of which were amongst those associated with slow artemisinin parasite clearance rates in Southeast Asia. The most prevalent haplotypes were triple mutants Pfdhfr I 51 R 59 N 108 I 164(99%), pfcrt- C72V73 I 74 E 75 T 76 (47.3%), and single mutants PfdhpsS436 G 437K540A581A613(69%) and Pfmdr1 N86 F 184D1246 (53.2%). CONCLUSIONS: The predominance of the Pf pfcrt CVIET and Pf dhfr IRN triple mutant parasites and absence of pfkelch13 resistance alleles suggest that the amodiaquine and pyrimethamine components of AS-AQ and SP may no longer be effective in their role while chloroquine resistance still persists in southwestern Cameroon.

[Misuse and dependence on prescription opioids: Prevention, identification and treatment]. / Mésusage et dépendance aux opioïdes de prescription : prévention, repérage et prise en charge.

Since the 1990s, the use of prescription opioids has largely spread, which has brought a real progress in the treatment of pain. The long-term use of prescription opioid is sometimes required, and may lead to pharmacological tolerance and withdrawal symptoms, i.e. pharmacological dependence on prescription opioids. Occasionally, this may also lead to misuse of prescription opioids (MPO). MPO preferentially occurs in vulnerable individuals, i.e., those with a young age, history of other addictive or psychiatric disorders, especially anxious and depressive disorders. MPO is associated with numerous complications, including an increased risk of fatal overdose. Prevention of MPO begins before the opioid prescription, with the identification of potential vulnerability factors. A planned and personalized monitoring should be systematically implemented. In vulnerable patients, contractualizing the prescription is warranted. During follow-up, the relevance of the prescription should be regularly reconsidered, according to the benefit observed on pain and the potential underlying signs of MPO. Patients with suspected MPO should be referred early to pain or addiction centers. The treatment of MPO should be based on multidisciplinary strategies, involving both the addiction and pain aspects: progressive opioid withdrawal, non-pharmacological measures against pain, or switching to medication-assisted treatment of addiction (i.e., buprenorphine or methadone).

Bread wheat milling behavior: effects of genetic and environmental factors, and modeling using grain mechanical resistance traits.

KEY MESSAGE: Genetic (Pinb-D1 alleles) and environment (through vitreousness) have important effects on bread wheat milling behavior. SKCS optimal values corresponding to soft vitreous or hard mealy grains were defined to obtain the highest total flour yield. Near-isogenic lines of bread wheat that differ in hardness, due to distinct puroindoline-b alleles (the wild type, Pinb-D1a, or the mutated forms, Pinb-D1b or Pinb-D1d), were grown in different environments and under two nitrogen fertilization levels, to study genetic and environmental effects on milling behavior. Milling tests used a prototype mill, equipped with two break steps, one sizing step, and two reduction steps, and this enabled 21 individual or aggregated milling fractions to be collected. Four current grain characters, thousand grain weight, test weight, grain diameter, and protein content, were measured, and three characters known to influence grain mechanical resistance, NIRS hardness, SKCS hardness index, and grain vitreousness (a character affecting the grain mechanical behavior but generally not studied). As expected, the wild type or mutated forms of Pinb-D1 alleles led to contrasted milling behavior: soft genotypes produced high quantities of break flour and low quantities of reduction flour, whereas reverse quantities were observed for hard genotypes. This different milling behavior had only a moderate influence on total flour production. NIRS hardness and vitreousness were, respectively, the most important and the second most important grain characters to explain milling behavior. However, contrary to NIRS hardness, vitreousness was only involved in endosperm reduction and not in the separation between the starchy endosperm and the outer layers. The highest flour yields were obtained for SKCS values comprised between 30 and 50, which corresponded either to soft vitreous or hard mealy grains. Prediction equations were defined and showed a good accuracy estimating break and reduction flours portions, but should be used more cautiously for total flour.

Stratifying delays for assessment by type of substance to improve the probability of attendance in outpatient services.

AIMS: 1) To confirm the association between delay for assessment (DFA) and probability of first-time attendance in outpatient substance use disorder (SUD) treatment. 2) To evaluate whether this association varies by the type of primary substance for which the assessment was requested. 3) To assess the possibility of estimating differential DFAs to conform to equal probabilities of attendance across various types of primary substance. METHODS: A prospective observational cohort of consecutive patients (N=1015) who requested a first-time assessment appointment at a publicly funded outpatient SUD treatment center in France between January 2014 and December 2015 was conducted. Logistic regression analyses were performed to evaluate associations between DFA (after log-transformation) and attendance and to provide estimates of attendance probability over time by the type of primary substance. FINDINGS: After adjusting for gender, age and referral status, the attendance rate was observed to decrease significantly with longer DFA (OR=0.54; 95%CI: 0.44-0.66). The strength of this association differed across types of primary substance (p for heterogeneity <0.0001), with the strongest association being found for opioids (adjusted OR=0.21; 95%CI: 0.10-0.45). DFA was also associated with attendance for alcohol (OR=0.51; 95%CI: 0.37-0.71) and cannabis (OR=0.60; 95%CI: 0.37-0.96), but not for tobacco (OR=0.95; 95%CI: 0.60-1.50). Differential DFAs reflecting equal probabilities of attendance across types of substance could be estimated. CONCLUSION: Our study suggests that the approach of stratifying DFAs by the type of primary substance could be helpful to improve the probability of first-time attendance in outpatient SUD treatment services.

Malaria, helminths, co-infection and anaemia in a cohort of children from Mutengene, south western Cameroon.

BACKGROUND: Malaria and helminthiases frequently co-infect the same individuals in endemic zones. Plasmodium falciparum and helminth infections have long been recognized as major contributors to anaemia in endemic countries. Several studies have explored the influence of helminth infections on the course of malaria in humans but how these parasites interact within co-infected individuals remains controversial. METHODS: In a community-based longitudinal study from March 2011 to February 2012, the clinical and malaria parasitaemia status of a cohort of 357 children aged 6 months to 10 years living in Mutengene, south-western region of Cameroon, was monitored. Following the determination of baseline malaria/helminths status and haemoglobin levels, the incidence of malaria and anaemia status was determined in a 12 months longitudinal study by both active and passive case detection. RESULTS: Among all the children who completed the study, 32.5 % (116/357) of them had at least one malaria episode. The mean (±SEM) number of malaria attacks per year was 1.44 ± 0.062 (range: 1-4 episodes) with the highest incidence of episodes occuring during the rainy season months of March-October. Children <5 years old were exposed to more malaria attacks [OR = 2.34, 95 % CI (1.15-4.75), p = 0.019] and were also more susceptible to anaemia [OR = 2.24, 95 % CI (1.85-4.23), p = 0.013] compared to older children (5-10 years old). Likewise children with malaria episodes [OR = 4.45, 95 % CI (1.66-11.94), p = 0.003] as well as those with asymptomatic parasitaemia [OR = 2.41, 95 % CI (1.58-3.69) p < 0.001] were susceptible to anaemia compared to their malaria parasitaemia negative counterparts. Considering children infected with Plasmodium alone as the reference, children infected with helminths alone were associated with protection from anaemia [OR = 0.357, 95 % CI (0.141-0.901), p = 0.029]. The mean haemoglobin level (g/dl) of participants co-infected with Plasmodium and helminths was higher (p = 0.006) compared to participants infected with Plasmodium or helminths alone. CONCLUSION: Children below 5 years of age were more susceptible to malaria and anaemia. The high prevalence of anaemia in this community was largely due to malaria parasitaemia. Malaria and helminths co-infection was protective against anaemia.

Plasmodium falciparum merozoite surface protein 1 block 2 gene polymorphism in field isolates along the slope of mount Cameroon: a cross - sectional study.

BACKGROUND: Malaria remains a major global health burden despite the intensification of control efforts, due partly to the lack of an effective vaccine. Information on genetic diversity in natural parasite populations constitutes a major impediment to vaccine development efforts and is limited in some endemic settings. The present study characterized diversity by investigating msp1 block 2 polymorphisms and the relationship between the allele families with ethnodemographic indices and clinical phenotype. METHOD: Individuals with asymptomatic parasitaemia (AP) or uncomplicated malaria (UM) were enrolled from rural, semi-rural and semi-urban localities at varying altitudes along the slope of mount Cameroon. P. falciparum malaria parasitaemic blood screened by light microscopy was depleted of leucocytes using CF11 cellulose columns and the parasite DNA genotyped by nested PCR. RESULTS: Length polymorphism was assessed in 151 field isolates revealing 64 (5) and 274 (22) distinct recombinant and major msp1 allelic fragments (genotypes) respectively. All family specific allelic types (K1, MAD20 and RO33) as well as MR were observed in the different locations, with K1 being most abundant. Eighty seven (60 %) of individuals harbored more than one parasite clone, with a significant proportion (p = 0.009) in rural compared to other settings. AP individuals had higher (p = 0.007) K1 allele frequencies but lower (p = 0.003) mean multiplicity of genotypes per infection (2.00 ± 0.98 vs. 2.56 ± 1.17) compared to UM patients. CONCLUSIONS: These results indicate enormous diversity of P. falciparum in the area and suggests that allele specificity and complexity may be relevant for the progression to symptomatic disease.

Determinants of infant susceptibility to malaria during the first year of life in South Western cameroon.

Background. Falciparum malaria is an important pediatric infectious disease that frequently affects pregnant women and alters infant morbidity. However, the impact of some prenatal and perinatal risk factors such as season and intermittent preventive treatment during pregnancy (IPTp) on neonatal susceptibility has not been fully elucidated. Methods. A cohort of 415 infants born to women who were positive and negative for malaria was monitored in a longitudinal study in Southwestern Cameroon. The clinical and malaria statuses were assessed throughout, whereas paired maternal-cord and 1-year-old antimalarial antibodies were assayed by enzyme-linked immunosorbent assay. Infant susceptibility to malaria was ascertained after accounting for IPTp and season in the statistical analysis. Results. Malaria prevalence was higher in women (P = .039) who delivered during the rainy season and their infants (P = .030) compared with their dry season counterparts. Infants born to women who were positive for malaria (6.40 ± 2.83 months) were older (P = .028) than their counterparts who were negative for malaria (5.52 ± 2.85 months) when they experienced their first malaria episode. Infants born in September-November (adjusted odds ratio [OR] = 0.31, 95% confidence interval [CI] = 0.13-0.72) and to mothers on 1 or no IPTp-sulfadoxine/pyrimethamine (SP) dose (adjusted OR = 0.51, 95% CI = 0.28-0.91) were protected, whereas those born in the rainy season (adjusted OR = 2.82, 95% CI = 1.21-6.55) were susceptible to malaria. Conclusions. Intermittent preventive treatment during pregnancy and month of birth have important implications for infant susceptibility to malaria, with 2 or more IPTp-SP dosage possibly reducing immunoglobulin M production.

Interventions for Increasing Subsequent Alcohol Treatment Utilisation Among Patients with Alcohol Use Disorders from Somatic Inpatient Settings: A Systematic Review.

AIMS: Alcohol Use Disorders (AUDs) are common in medical and surgical hospital wards. Brief Interventions (BIs) for reducing alcohol use and consequences are generally inefficacious in this population. Because there is evidence that receipt of formal treatment could be useful, we performed a systematic review to determine efficacious interventions for increasing subsequent alcohol treatment from these settings. METHODS: A systematic literature search of articles published prior to December 2013 to identify articles describing randomised controlled trials (RCTs) in three electronic databases: PubMed, PsycINFO and The Cochrane Library. Data were extracted independently by one reviewer and were checked by a second reviewer. Because of heterogeneity between study groups in treatment utilisation during the follow-up, a meta-analysis was considered inappropriate and a qualitative synthesis was conducted. RESULTS: From the 5030 identified records, only 5 RCTs, including 1113 patients with AUDs, met inclusion criteria. No evidence of efficacy in increasing subsequent treatment utilisation was reported for inpatient BIs alone, but interventions with post-discharge sessions might be beneficial. Increased treatment utilisation was generally associated with favourable drinking outcomes. CONCLUSIONS: Given the small number of included studies and the presence of several alternative methodological explanations for the present findings, no firm conclusions could be drawn on efficacious interventions for increasing subsequent treatment utilisation among somatic inpatients with AUDs. However the findings support efforts to explore this under-researched area.

The effect of Insecticide Treated Nets (ITNs) on Plasmodium falciparum infection in rural and semi-urban communities in the south west region of Cameroon.

Insecticide Treated Nets (ITNs) have been shown to reduce morbidity and mortality, but coverage and proper utilization continues to be moderate in many parts of sub-Saharan Africa. The gains made through a nationwide free distribution were explored as well as the effect on malaria prevalence in semi-urban and rural communities in south western Cameroon. A cross sectional survey was conducted between August and December 2013. Information on net possession, status and use were collected using a structured questionnaire while malaria parasitaemia was determined on Giemsa-stained blood smears by light microscopy. ITN ownership increased from 41.9% to 68.1% following the free distribution campaign, with 58.3% (466/799) reportedly sleeping under the net. ITN ownership was lower in rural settings (adjusted OR = 1.93, 95%CI = 1.36-2.74, p<0.001) and at lower altitude (adjusted OR = 1.79, 95%CI = 1.22-2.62, p = 0.003) compared to semi-urban settings and intermediate altitude respectively. Conversely, ITN usage was higher in semi-urban settings (p = 0.002) and at intermediate altitude (p = 0.002) compared with rural localities and low altitude. Malaria parasitaemia prevalence was higher in rural (adjusted OR = 1.63, 95%CI = 1.07-2.49) compared to semi-urban settings and in those below 15 years compared to those 15 years and above. Overall, participants who did not sleep under ITN were more susceptible to malaria parasitaemia (adjusted OR = 1.70, 95%CI = 1.14-2.54, p = 0.009). Despite the free distribution campaign, ITN ownership and usage, though improved, is still low. As children who reside in rural settings have greater disease burden (parasitemia) than children in semi-urban settings, the potential gains on both reducing inequities in ITN possession as well as disease burden might be substantial if equitable distribution strategies are adopted.