Phase II Proof-of-Concept Trial of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Major Depressive Disorder.

BackgroundWe evaluated the orexin receptor antagonist filorexant (MK-6096) for treatment augmentation in patients with major depressive disorder.MethodsWe conducted a 6-week, double-blind, placebo-controlled, parallel-group, Phase II, proof-of-concept study. Patients with major depressive disorder (partial responders to ongoing antidepressant therapy) were randomized 1:1 to once-daily oral filorexant 10 mg or matching placebo.ResultsDue to enrollment challenges, the study was terminated early, resulting in insufficient statistical power to detect a prespecified treatment difference; of 326 patients planned, 129 (40%) were randomized and 128 took treatment. There was no statistically significant difference in the primary endpoint of change from baseline to week 6 in Montgomery Asberg Depression Rating Scale total score; the estimated treatment difference for filorexant-placebo was -0.7 (with negative values favoring filorexant) (P=.679). The most common adverse events were somnolence and suicidal ideation.ConclusionsThe interpretation of the results is limited by the enrollment, which was less than originally planned, but the available data do not suggest efficacy of orexin receptor antagonism with filorexant for the treatment of depression. (Clinical Trial Registry: clinicaltrials.gov: NCT01554176)

Determinants of compliance with the World Health Organisation recommendations for pregnant women in an urban health centre in The Gambia

In 2001 the World Health Organization drew up recommendations for pregnant women in order to reduce maternal mortality: the first visit to the antenatal clinic to be in the first trimester, at least four visits in total and delivery with a trained birth attendant. This study reports the extent to which pregnant women attending a health centre in The Gambia complied with the recommendations. A cohort of 1611 consecutive pregnant women was recruited. Only 384 (23.9%) women first attended in the first trimester and 568 (41.6%) attended at least four times. Only 15.8% of the women complied with all recommendations. Following multivariate analysis the educational level of the partner was the sole factor associated with both recommendations regarding attendance. This level of compliance reflects widespread ignorance of the value of early antenatal care and frequent visits. Public health programmes require a basic level of education to be effective. (Afr J Reprod Health 2020; 24[3]: 24-32). Keywords: Maternal health, antenatal, first trimester, education, male partner, The Gambia   En 2001, l'Organisation mondiale de la santé a formulé des recommandations pour les femmes enceintes afin de réduire la mortalité maternelle: la première visite à la clinique prénatale doit avoir lieu au premier trimestre, au moins quatre visites au total et l'accouchement avec une accoucheuse qualifiée. Cette étude rapporte dans quelle mesure les femmes enceintes fréquentant un centre de santé en Gambie se sont conformées aux recommandations. Une cohorte de 1611 femmes enceintes consécutives a été recrutée. Seules 384 (23,9%) femmes y ont participé pour la première fois au cours du premier trimestre et 568 (41,6%) y ont assisté au moins quatre fois. Seulement 15,8% des femmes se sont conformées à toutes les recommandations. Suite à une analyse multivariée, le niveau d'éducation du partenaire était le seul facteur associé aux deux recommandations concernant la fréquentation. Ce niveau de conformité reflète l'ignorance généralisée de la valeur des soins prénatals précoces et des visites fréquentes. Les programmes de santé publique nécessitent un niveau d'éducation de base pour être efficaces. Mots-clés: Santé maternelle, prénatale, premier trimestre, éducation, partenaire masculin, Gambi

Impact of routine vaccination against Haemophilus influenzae type b in The Gambia: 20 years after its introduction

Background: In 1997, The Gambia introduced three primary doses of Haemophilus influenzae type b (Hib) conjugate vaccine without a booster in its infant immunisation programme along with establishment of a population-based surveillance on Hib meningitis in the West Coast Region (WCR). This surveillance was stopped in 2002 with reported elimination of Hib disease. This was re-established in 2008 but stopped again in 2010. We aimed to re-establish the surveillance in WCR and to continue surveillance in Basse Health and Demographic Surveillance System (BHDSS) in the east of the country to assess any shifts in the epidemiology of Hib disease in The Gambia. Methods: In WCR, population-based surveillance for Hib meningitis was re-established in children aged under-10 years from 24 December 2014 to 31 March 2017, using conventional microbiology and Real Time Polymerase Chain Reaction (RT-PCR). In BHDSS, population-based surveillance for Hib disease was conducted in children aged 2-59 months from 12 May 2008 to 31 December 2017 using conventional microbiology only. Hib carriage survey was carried out in pre-school and school children from July 2015 to November 2016. Results: In WCR, five Hib meningitis cases were detected using conventional microbiology while another 14 were detected by RT-PCR. Of the 19 cases, two (11%) were too young to be protected by vaccination while seven (37%) were unvaccinated. Using conventional microbiology, the incidence of Hib meningitis per 100 000-child-year (CY) in children aged 1-59 months was 0.7 in 2015 (95% confidence interval (CI) = 0.0-3.7) and 2.7 (95% CI = 0.7-7.0) in 2016. In BHDSS, 25 Hib cases were reported. Nine (36%) were too young to be protected by vaccination and five (20%) were under-vaccinated for age. Disease incidence peaked in 2012-2013 at 15 per 100 000 CY and fell to 5-8 per 100 000 CY over the subsequent four years. The prevalence of Hib carriage was 0.12% in WCR and 0.38% in BHDSS. Conclusions: After 20 years of using three primary doses of Hib vaccine without a booster Hib transmission continues in The Gambia, albeit at low rates. Improved coverage and timeliness of vaccination are of high priority for Hib disease in settings like Gambia, and there are currently no clear indications of a need for a booster dose

Impact of routine vaccination against Haemophilus influenzae type b in The Gambia: 20 years after its introduction.

BACKGROUND: In 1997, The Gambia introduced three primary doses of Haemophilus influenzae type b (Hib) conjugate vaccine without a booster in its infant immunisation programme along with establishment of a population-based surveillance on Hib meningitis in the West Coast Region (WCR). This surveillance was stopped in 2002 with reported elimination of Hib disease. This was re-established in 2008 but stopped again in 2010. We aimed to re-establish the surveillance in WCR and to continue surveillance in Basse Health and Demographic Surveillance System (BHDSS) in the east of the country to assess any shifts in the epidemiology of Hib disease in The Gambia. METHODS: In WCR, population-based surveillance for Hib meningitis was re-established in children aged under-10 years from 24 December 2014 to 31 March 2017, using conventional microbiology and Real Time Polymerase Chain Reaction (RT-PCR). In BHDSS, population-based surveillance for Hib disease was conducted in children aged 2-59 months from 12 May 2008 to 31 December 2017 using conventional microbiology only. Hib carriage survey was carried out in pre-school and school children from July 2015 to November 2016. RESULTS: In WCR, five Hib meningitis cases were detected using conventional microbiology while another 14 were detected by RT-PCR. Of the 19 cases, two (11%) were too young to be protected by vaccination while seven (37%) were unvaccinated. Using conventional microbiology, the incidence of Hib meningitis per 100?000-child-year (CY) in children aged 1-59 months was 0.7 in 2015 (95% confidence interval (CI)?=?0.0-3.7) and 2.7 (95% CI?=?0.7-7.0) in 2016. In BHDSS, 25 Hib cases were reported. Nine (36%) were too young to be protected by vaccination and five (20%) were under-vaccinated for age. Disease incidence peaked in 2012-2013 at 15 per 100?000 CY and fell to 5-8 per 100?000 CY over the subsequent four years. The prevalence of Hib carriage was 0.12% in WCR and 0.38% in BHDSS. CONCLUSIONS: After 20 years of using three primary doses of Hib vaccine without a booster Hib transmission continues in The Gambia, albeit at low rates. Improved coverage and timeliness of vaccination are of high priority for Hib disease in settings like Gambia, and there are currently no clear indications of a need for a booster dose

Serology describes a profile of declining malaria transmission in Farafenni, The Gambia

BACKGROUND: Malaria morbidity and mortality has declined in recent years in a number of settings. The ability to describe changes in malaria transmission associated with these declines is important in terms of assessing the potential effects of control interventions, and for monitoring and evaluation purposes. METHODS: Data from five cross-sectional surveys conducted in Farafenni and surrounding villages on the north bank of River Gambia between 1988 and 2011 were compiled. Antibody responses to MSP-119 were measured in samples from all surveys, data were normalized and expressed as seroprevalence and seroconversion rates (SCR) using different mathematical models. RESULTS: Results showed declines in serological metrics with seroprevalence in children aged one to 5 years dropping from 19 % (95 % CI 15-23 %) in 1988 to 1 % (0-2 %) in 2011 (p value for trend in proportions < 0.001) and the SCR dropping from 0.069 year(-1) (0.059-0.080) to 0.022 year(-1) (0.017-0.028; p = 0.004). The serological data were consistent with previously described drops in both parasite prevalence in children aged 1-5 years (62 %, 57-66 %, in 1988 to 2 %, 0-4 %, in 2011; p < 0.001), and all-cause under five mortality rates (37 per 1000 person-years, 34-41, in 1990 to 17, 15-19, in 2006; p = 0.059). CONCLUSIONS: This analysis shows accurate reconstruction of historical malaria transmission patterns in the Farafenni area using anti-malarial antibody responses. Demonstrating congruence between serological measures, and conventional clinical and parasitological measures suggests broader utility for serology in monitoring and evaluation of malaria transmission

Community psychosocial music intervention (CHIME) to reduce antenatal common mental disorder symptoms in The Gambia: a feasibility trial

Objectives: Examine the feasibility of a Community Health Intervention through Musical Engagement (CHIME) in The Gambia to reduce common mental disorder (CMD) symptoms in pregnant women. Design: Feasibility trial testing a randomised stepped-wedge cluster design. Setting: Four local antenatal clinics. Participants: Women who were 14–24 weeks pregnant and spoke Mandinka or Wolof were recruited into the intervention (n=50) or control group (n=74). Intervention: Music-based psychosocial support sessions designed and delivered by all-female fertility societies. Sessions lasted 1 hour and were held weekly for 6 weeks. Delivered to groups of women with no preselection. Sessions were designed to lift mood, build social connection and provide health messaging through participatory music making. The control group received standard antenatal care. Outcomes: Demographic, feasibility, acceptability outcomes and the appropriateness of the study design were assessed. Translated measurement tools (Self-Reporting Questionnaire (SRQ-20); Edinburgh Postnatal Depression Scale (EPDS)) were used to assess CMD symptoms at baseline, post-intervention and 4-week follow-up. Results: All clinics and 82% of women approached consented to take part. A 33% attrition rate across all time points was observed. 72% in the intervention group attended at least three sessions. Audio and video analysis confirmed fidelity of the intervention and a thematic analysis of participant interviews demonstrated acceptability and positive evaluation. Results showed a potential beneficial effect with a reduction of 2.13 points (95% CI (0.89 to 3.38), p<0.01, n=99) on the SRQ-20 and 1.98 points (95% CI (1.06 to 2.90), p<0.01, n=99) on the EPDS at the post-intervention time point for the intervention group compared with standard care. Conclusion: Results demonstrate that CHIME is acceptable and feasible in The Gambia. To our knowledge, CHIME is the first example of a music-based psychosocial intervention to be applied to perinatal mental health in a low- and middle-income country context

A study protocol for testing the feasibility of a randomised stepped wedge cluster design to investigate a Community Health Intervention through Musical Engagement (CHIME) for perinatal mental health in The Gambia

Abstract: Background: Perinatal mental health problems affect up to one in five women worldwide. Mental health problems in the perinatal period are a particular challenge in low- and middle-income countries (LMICs) where they can be at least twice as frequent as in higher-income countries. It is thus of high priority to develop new low-cost, low-resource, non-stigmatising and culturally appropriate approaches to reduce symptoms of anxiety and depression perinatally, for the benefit of both mother and child. Music-centred approaches may be particularly useful in The Gambia since a range of musical practices that specifically engage pregnant women and new mothers already exist. Methods: This protocol is for a study to examine the feasibility of undertaking a stepped wedge trial to test how a Community Health Intervention through Musical Engagement (CHIME) could be beneficial in alleviating perinatal mental distress in The Gambia. In this study, we plan to recruit 120 pregnant women (n = 60 intervention, n = 60 control) at four antenatal clinics over two 6-week stepped sequences. Women in the intervention will participate in weekly group-singing sessions, led by local Kanyeleng singing groups, for 6 weeks. The control group will receive standard care. We will assess symptoms of anxiety and depression using the Edinburgh Postnatal Depression Scale (EPDS) and the Self-Reporting Questionnaire (SRQ-20). The feasibility of the design will be assessed through recruitment, retention and attrition rates of participants, clinics' adherence to the schedule and completeness of data by site. Qualitative interviews and video and audio recordings will be used to evaluate the acceptability of the intervention. Discussion: This feasibility trial will allow us to determine whether a larger trial with the same intervention and target group is feasible and acceptable in The Gambia. Trial registration: Retrospectively registered (24/01/2019) with Pan African Clinical Trials Registry (PACTR): PACTR201901917619299

Declining Burden of Malaria Over two Decades in a Rural Community of Muheza District, North-Eastern Tanzania.

The recently reported declining burden of malaria in some African countries has been attributed to scaling-up of different interventions although in some areas, these changes started before implementation of major interventions. This study assessed the long-term trends of malaria burden for 20 years (1992--2012) in Magoda and for 15 years in Mpapayu village of Muheza district, north-eastern Tanzania, in relation to different interventions as well as changing national malaria control policies.\ud Repeated cross-sectional surveys recruited individuals aged 0 -- 19 years from the two villages whereby blood smears were collected for detection of malaria parasites by microscopy. Prevalence of Plasmodium falciparum infections and other indices of malaria burden (prevalence of anaemia, splenomegaly and gametocytes) were compared across the years and between the study villages. Major interventions deployed including mobile clinic, bed nets and other research activities, and changes in national malaria control policies were also marked. In Magoda, the prevalence of P. falciparum infections initially decreased between 1992 and 1996 (from 83.5 to 62.0%), stabilized between 1996 and 1997, and further declined to 34.4% in 2004. A temporary increase between 2004 and 2008 was followed by a progressive decline to 7.2% in 2012, which is more than 10-fold decrease since 1992. In Mpapayu (from 1998), the highest prevalence was 81.5% in 1999 and it decreased to 25% in 2004. After a slight increase in 2008, a steady decline followed, reaching <5% from 2011 onwards. Bed net usage was high in both villages from 1999 to 2004 (>=88%) but it decreased between 2008 and 2012 (range, 28% - 68%). After adjusting for the effects of bed nets, age, fever and year of study, the risk of P. falciparum infections decreased significantly by >=97% in both villages between 1999 and 2012 (p < 0.001). The prevalence of splenomegaly (>40% to <1%) and gametocytes (23% to <1%) also decreased in both villages.Discussion and conclusionsA remarkable decline in the burden of malaria occurred between 1992 and 2012 and the initial decline (1992 -- 2004) was most likely due to deployment of interventions, such as bed nets, and better services through research activities. Apart from changes of drug policies, the steady decline observed from 2008 occurred when bed net coverage was low suggesting that other factors contributed to the most recent pattern. These results suggest that continued monitoring is required to determine causes of the changing malaria epidemiology and also to monitor the progress towards maintaining low malaria transmission and reaching related millennium development goals