Pooled Multicenter Analysis of Cardiovascular Safety and Population Pharmacokinetic Properties of Piperaquine in African Patients with Uncomplicated Falciparum Malaria.

Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicenter trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90-ms mean QTc prolongation per 100-ng/ml increase in piperaquine concentration. The effect of piperaquine on absolute QTc interval estimated a mean maximum QTc interval of 456 ms (50% effective concentration of 209 ng/ml). Simulations from the pharmacokinetic-pharmacodynamic models predicted 1.98 to 2.46% risk of having QTc prolongation of >60 ms in all treatment settings. Although piperaquine administration resulted in QTc prolongation, no cardiovascular adverse events were found in these patients. Thus, the use of dihydroartemisinin-piperaquine should not be limited by this concern. (This study has been registered at ClinicalTrials.gov under identifier NCT02199951.).

A Multicenter Cost-of-Illness and Long-term Socioeconomic Follow-up Study in the Severe Typhoid Fever in Africa Program: Study Protocol.

BACKGROUND: There are limited data on typhoid fever cost of illness (COI) and economic impact from Africa. Health economic data are essential for measuring the cost-effectiveness of vaccination or other disease control interventions. Here, we describe the protocol and methods for conducting the health economic studies under the Severe Typhoid Fever in Africa (SETA) program. METHODS: The SETA health economic studies will rely on the platform for SETA typhoid surveillance in 4 African countries-Burkina Faso, Ethiopia, Ghana, and Madagascar. A COI and long-term socioeconomic study (LT-SES) will be its components. The COI will be assessed among blood culture-positive typhoid fever cases, blood culture-negative clinically suspected cases (clinical cases), and typhoid fever cases with pathognomonic gastrointestinal perforations (special cases). Repeated surveys using pretested questionnaires will be used to measure out-of-pocket expenses, quality of life, and the long-term socioeconomic impact. The cost of resources consumed for diagnosis and treatment will be collected at health facilities. RESULTS: Results from these studies will be published in peer-reviewed journals and presented at scientific conferences to make the data available to the wider health economics and public health research communities. CONCLUSIONS: The health economic data will be analyzed to estimate the average cost per case, the quality of life at different stages of illness, financial stress due to illness, and the burden on the family due to caregiving during illness. The data generated are expected to be used in economic analysis and policy making on typhoid control interventions in sub-Saharan Africa.

The Severe Typhoid Fever in Africa Program: Study Design and Methodology to Assess Disease Severity, Host Immunity, and Carriage Associated With Invasive Salmonellosis.

BACKGROUND: Invasive salmonellosis is a common community-acquired bacteremia in persons residing in sub-Saharan Africa. However, there is a paucity of data on severe typhoid fever and its associated acute and chronic host immune response and carriage. The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to address these research gaps and contribute to the control and prevention of invasive salmonellosis. METHODS: A prospective healthcare facility-based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Defined inclusion criteria were used for screening of eligible patients for enrollment into the study. Enrolled patients with confirmed invasive salmonellosis by blood culture or patients with clinically suspected severe typhoid fever with perforation were eligible for clinical follow-up. Asymptomatic neighborhood controls and immediate household contacts of each case were enrolled as a comparison group to assess the level of Salmonella-specific antibodies and shedding patterns. Healthcare utilization surveys were performed to permit adjustment of incidence estimations. Postmortem questionnaires were conducted in medically underserved areas to assess death attributed to invasive Salmonella infections in selected sites. RESULTS: Research data generated through SETA aimed to address scientific knowledge gaps concerning the severe typhoid fever and mortality, long-term host immune responses, and bacterial shedding and carriage associated with natural infection by invasive salmonellae. CONCLUSIONS: SETA supports public health policy on typhoid immunization strategy in Africa.

Chromosomal and plasmid-mediated fluoroquinolone resistance in human Salmonella enterica infection in Ghana.

BACKGROUND: Salmonella infection poses significant public health threat globally, especially in resource-limited countries. Emergence and spread of antibiotic resistant strains to fluoroquinolones have led to treatment failures and increased mortality in Salmonella infection. However, there is dearth of information regarding mechanisms of resistance to fluoroquinolones in Ghana. This study therefore sought to identify chromosomal mutations and plasmid-mediated resistance as possible mechanisms of fluoroquinolone resistance from clinical isolates in Ghana. METHODS: This was a retrospective study of archived isolates biobanked at Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana. Isolates were obtained from blood, stool and oropharynx samples at two hospitals, between May, 2016 and January, 2018. Salmonella identification was done using standard microbiological protocols and antibiotic susceptibility testing performed by Kirby-Bauer disc diffusion method. Isolates with intermediate susceptibility and/or resistance to nalidixic acid and/or ciprofloxacin were selected and examined for chromosomal mutations by Sanger sequencing and plasmid-mediated resistance by PCR. RESULTS: Of 133 biobanked isolates cultured, 68 (51.1%) and 16 (12%) were identified as Salmonella Typhi and non-typhoidal Salmonella (NTS), respectively. Sequence analysis of gyrA gene revealed the presence of 5 different nonsynonymous mutations, with the most frequent mutation (Ile203Ser) occurring in 12 out of 13 isolates tested. Gyrase B (gyrB) gene had 1 nonsynonymous mutation in 3 out of 13 isolates, substituting phenylalanine with leucine at codon 601 (Phe601Leu). No mutation was observed in parC and parE genes. Two NTS isolates were found to harbour qnrS plasmid-mediated resistant gene of molecular size 550 bp with high ciprofloxacin MIC of 0.5 µg/ml. CONCLUSION: This study reports for the first time in Ghana plasmid-mediated fluoroquinolone resistant gene qnrS in Salmonella clinical isolates. Nonsynonymous mutations of gyrA and gyrB genes likely to confer Salmonella reduced susceptibility to ciprofloxacin were also reported.

Integrating use of point-of-care circulating cathodic antigen rapid diagnostic tests by community health workers during mass drug administration campaigns to improve uptake of praziquantel treatment among the adult population at Kome Island, North-Western Tanzania: a cluster randomized community trial.

BACKGROUND: The major drawback of the community-based mass drug administration (MDA) approach against schistosomiasis is that treatment is offered blindly without testing for the targeted infection. This partly contributes to the low treatment coverage. One approach to overcome this limitation is to introduce a diagnostic component in the treatment approach. This will improve drug uptake and compliance to treatment. This study is conducted to assess the feasibility and acceptability of integrating point-of-care Circulating Cathodic Antigen (POC-CCA) test to community-based directed MDA in improving treatment coverage and compliance with treatment among adults. METHODS: This is a randomized control community trial in which 30 clusters were randomly assigned to either an intervention or control arm to evaluate two interventions on treatment coverage and compliance with treatment. In each cluster, 150 adult participants were enrolled. Community Health Workers (CHW) in both arms were trained on all aspects of praziquantel (PZQ) distribution and management of mild side effects. In the intervention arm, CHWs had additional training on how to use POC-CCA to diagnose intestinal schistosomiasis. In the intervention arm, participants were tested using POC-CCA test for presence of intestinal schistosomiasis and treated based on test results, while in the control arm, participants were treated with PZQ without testing. The primary outcome measure was the proportion of participants provided with PZQ between the two arms and geographical clusters. Secondary outcomes were prevalence of S. mansoni infection based on the POC-CCA test conducted by CHWs, ability of CHWs to use the POC-CCA test accurately and safely and community acceptability of the POC-CCA test results from CHWs. Both quantitative and qualitative techniques have been used to collect data at study endpoint. DISCUSSION: The study will generate evidence on the importance of integrating a diagnostic component into the community directed MDA conducted by CHWs. Findings will generate discussion on the current MDA policy and practice in Tanzania. TRIAL REGISTRATION: PACTR201804003343404 (25/4/2018).

Treatment outcomes in a safety observational study of dihydroartemisinin/piperaquine (Eurartesim(®)) in the treatment of uncomplicated malaria at public health facilities in four African countries.

BACKGROUND: Dihydroartemisinin-piperaquine (DHA-PQ) is one of five WHO recommended artemisinin combination therapy (ACT) for the treatment of uncomplicated malaria. However, little was known on its post-registration safety and effectiveness in sub-Saharan Africa. DHA-PQ provides a long post-treatment prophylactic effect against re-infection; however, new infections have been reported within a few weeks of treatment, especially in children. This paper reports the clinical outcomes following administration of DHQ-PQ in real-life conditions in public health facilities in Burkina Faso, Ghana, Mozambique, and Tanzania for the treatment of confirmed uncomplicated malaria. METHODS: An observational, non-comparative, longitudinal study was conducted on 10,591 patients with confirmed uncomplicated malaria visiting public health facilities within seven health and demographic surveillance system sites in four African countries (Ghana, Tanzania, Burkina Faso, Mozambique) between September 2013 and April 2014. Patients were treated with DHA-PQ based on body weight and followed up for 28 days to assess the clinical outcome. A nested cohort of 1002 was intensely followed up. Clinical outcome was assessed using the proportion of patients who reported signs and symptoms of malaria after completing 3 days of treatment. RESULTS: A total of 11,097 patients were screened with 11,017 enrolled, 94 were lost to follow-up, 332 withdrew and 10,591 (96.1%) patients aged 6 months-85 years met protocol requirements for analysis. Females were 52.8 and 48.5% were <5 years of age. Malaria was diagnosed by microscopy and rapid diagnostic test in 69.8% and 29.9%, respectively. At day 28, the unadjusted risk of recurrent symptomatic parasitaemia was 0.5% (51/10,591). Most of the recurrent symptomatic malaria patients (76%) were children <5 years. The mean haemoglobin level decreased from 10.6 g/dl on day 1 to 10.2 g/dl on day 7. There was no significant renal impairment in the nested cohort during the first 7 days of follow-up with minimal non-clinically significant changes noted in the liver enzymes. CONCLUSION: DHA-PQ was effective and well tolerated in the treatment of uncomplicated malaria and provides an excellent alternative first-line ACT in sub-Saharan Africa.

Prospective observational study to evaluate the clinical safety of the fixed-dose artemisinin-based combination Eurartesim® (dihydroartemisinin/piperaquine), in public health facilities in Burkina Faso, Mozambique, Ghana, and Tanzania.

BACKGROUND: The World Health Organization recommends artemisinin-based combination (ACT) for the treatment of uncomplicated malaria. Post-licensure safety data on newly registered ACT is critical for evaluating their risk/benefit profile in malaria endemic countries. The clinical safety of the newly registered combination, Eurartesim®, following its introduction into the public health system in four African countries was assessed. METHODS: This was a prospective, observational, open-label, non-comparative, longitudinal, multi-centre study using cohort event monitoring. Patients with confirmed malaria had their first dose observed and instructed on how to take the second and the third doses at home. Patients were contacted on day 5 ± 2 to assess adherence and adverse events (AEs). Spontaneous reporting of AEs was continued till day 28. A nested cohort who completed full treatment course had repeated electrocardiogram (ECG) measurements to assess effect on QTc interval. RESULTS: A total of 10,925 uncomplicated malaria patients were treated with Eurartesim®. Most patients,95% (10,359/10,925), did not report any adverse event following at least one dose of Eurartesim®. A total of 797 adverse events were reported. The most frequently reported, by system organ classification, were infections and infestations (3. 24%) and gastrointestinal disorders (1. 37%). In the nested cohort, no patient had QTcF > 500 ms prior to day 3 pre-dose 3. Three patients had QTcF > 500 ms (509 ms, 501 ms, 538 ms) three to four hours after intake of the last dose. All the QTcF values in the three patients had returned to <500 ms at the next scheduled ECG on day 7 (470 ms, 442 ms, 411 ms). On day 3 pre- and post-dose 3, 70 and 89 patients, respectively, had a QTcF increase of ≥ 60 ms compared to their baseline, but returned to nearly baseline values on day 7. CONCLUSION: Eurartesim® single course treatment for uncomplicated falciparum malaria is well-tolerated. QT interval prolongation above 500 ms may occur at a rate of three per 1,002 patients after the third dose with no association of any clinical symptoms. QT interval prolongation above 60 ms was detected in less than 10% of the patients without any clinical abnormalities.

Pneumococcal conjugate vaccination schedules in infants-acquisition, immunogenicity, and pneumococcal conjugate and yellow fever vaccine co-administration study: statistical analysis plan.

RATIONALE: The effectiveness of immunisation with pneumococcal conjugate vaccine (PCV) has been demonstrated in many countries. However, the global impact of PCV is limited by its cost, which has prevented its introduction in some countries. Reducing the cost of PCV programmes will facilitate further vaccine introductions and improve the sustainability of PCV in low-income countries when they transition from subsidised vaccine supply. We are conducting a large, population-level, cluster-randomised field trial (PVS) of an alternative reduced-dose schedule of PCV compared to the standard schedule. We are also conducting a nested sub-study at the individual level to investigate the immunogenicity of the two schedules and their effects on pneumococcal carriage acquisition (PVS-AcqImm). METHODS AND DESIGN: PVS-AcqImm is a prospective, cluster-randomised trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months compared to the standard of three primary doses scheduled at 6, 10, and 14 weeks of age. Sub-groups within the alternative schedule group receive yellow fever vaccine separately or co-administered with PCV at 9 months of age. The primary endpoints are (a) concentrations of vaccine-type anti-pneumococcal IgG at 18 months of age, (b) proportions with yellow fever neutralising antibody titre ≥ 1:8 4 weeks after separate or co-administration of PCV and yellow fever vaccines, and (c) rate of nasopharyngeal vaccine-type pneumococcal acquisition from 10-14 months of age. Participants and field staff are not masked to group allocation while measurement of the laboratory endpoints is masked. Approximately equal numbers of participants are resident in each of 28 randomly allocated geographic clusters (14 clusters in each group); 784 enrolled for acquisition measurements and 336 for immunogenicity measurements. PURPOSE: This statistical analysis plan (SAP) describes the PVS-AcqImm cohort and follow-up criteria to be used in different analyses. The SAP defines the endpoints and describes how adherence to the interventions will be presented. We describe the approach to analyses and how we will account for the effect of clustering. Defining the SAP prior to the conduct of analysis will avoid bias in analyses that may arise from prior knowledge of trial findings. TRIAL REGISTRATION: ISRCTN, ISRCTN7282161328. Registered on 28 November 2019. https://www.isrctn.com/ISRCTN72821613 . PROTOCOL: MRCG SCC number 1670, LSHTM Ref 17683. Current protocol version: 6.0, 24 May 2021. Version: 1.0 (5 April 2023); SAP revisions-none.

Ochrobactrum anthropi sepsis in a 15-month-old child: A case report.

Key Clinical Message: Ochrobactrum anthropi (O. anthropi), a rare opportunistic pathogen, caused sepsis in a malnourished 15-month-old African child. Early detection and appropriate antibiotics led to full recovery, highlighting the importance of robust surveillance for emerging pathogens in vulnerable populations. Abstract: While rarely causing infections, O. anthropi, a non-fermenting, obligately aerobic, flagellated gram-negative bacillus, demonstrates oxidase positivity and indole negativity. Traditionally, Ochrobactrum spp is considered a low threat due to its environmental abundance and mild virulence. It is, however, a multidrug-resistant bacteria known for causing opportunistic infections in humans. O. anthropi is typically associated with catheter-related bloodstream infections. The first documented case was in 1998; most cases have been reported in developed countries. We present a case of O. anthropi sepsis in a malnourished child in sub-Saharan Africa. We report a case involving a 15-month-old African female who presented with symptoms and signs of protein-energy malnutrition and sepsis. The blood culture revealed O.anthropi. We treated the child with the empirical first-line antibiotics per the national guidelines, intravenous ampicillin and gentamicin for a week, and the child fully recovered. This report describes a rare case of O. anthropi sepsis with malnutrition in an African female child. O. anthropi is an emerging pathogen causing opportunistic infections in both immunocompetent and immunocompromised patients. We report that early bacterial detection, appropriate antibiotic susceptibility and antimicrobial management based on local antibiogram data may be essential for excellent patient outcomes. Additionally, we recommend more robust surveillance to detect such rare emerging pathogens.

Community-acquired multidrug-resistant Enterobacter cloacae sepsis in a 25-month-old child in rural Gambia: A case report.

Enterobacter cloacae is the leading cause of morbidity and mortality in the genus Enterobacter. It mostly causes nosocomial infections, especially in children, the elderly and those with underlying diseases. However, cases of community-acquired bacteraemia caused by E. cloacae have been reported. The increasing inclination of E. cloacae to cause multidrug-resistant infections has made it particularly challenging to treat. A 25-month-old male child presented to a rural hospital in The Gambia with a one-week history of persistent high-grade fever, dyspnoea, and anorexia. Two days before presentation, he began to have generalized tonic-clonic seizures. On examination, he was found to be febrile, dyspnoeic, pale, and tachycardic. He had a modified Glasgow Coma Scale score of 9/15. Investigations revealed an elevated C-reactive protein, low haemoglobin, and elevated white blood cell count. Cerebrospinal fluid culture did not yield any growth. E. cloacae was isolated from a blood culture taken on the day of admission. The pathogen was resistant to all available antibiotics. He was transfused with whole blood and initially treated empirically with amoxicillin-clavulanic acid and gentamicin. The former was changed to cefuroxime because the child had not improved. The child died nine days after admission. Although E. cloacae is primarily known for causing nosocomial infections, fatal community-acquired infections also occur. This case report demonstrates the difficulty in treating multidrug-resistant E. cloacae in a low-resource setting and its propensity to cause fatal infections.

Directly observed social contact patterns among school children in rural Gambia.

INTRODUCTION: School-aged children play a major role in the transmission of many respiratory pathogens due to high rate of close contacts in schools. The validity and accuracy of proxy-reported contact data may be limited, particularly for children when attending school. We observed social contacts within schools and assessed the accuracy of proxy-reported versus observed physical contact data among students in rural Gambia. METHODS: We enrolled school children who had also been recruited to a survey of Streptococcus pneumoniae carriage and social contacts. We visited participants at school and observed their contact patterns within and outside the classroom for two hours. We recorded the contact type, gender and approximate age of the contactee, and class size. We calculated age-stratified contact matrices to determine in-school contact patterns. We compared proxy-reported estimated physical contacts for the subset of participants (18 %) randomised to be observed on the same day for which the parent or caregiver reported the school contacts. RESULTS: We recorded 3822 contacts for 219 participants from 114 schools. The median number of contacts was 15 (IQR: 11-20). Contact patterns were strongly age-assortative, and mainly involved physical touch (67.5 %). Those aged 5-9 years had the highest mean number of contacts [19.0 (95 %CI: 16.7-21.3)] while the ≥ 15-year age group had fewer contacts [12.8 (95 %CI: 10.9-14.7)]. Forty (18 %) participants had their school-observed contact data collected on the same day as their caregiver reported their estimated physical contacts at school; only 22.5 % had agreement within ±2 contacts between the observed and reported contacts. Fifty-eight percent of proxy-reported contacts were under-estimates. CONCLUSIONS: Social contact rates observed among pupils at schools in rural Gambia were high, strongly age-assortative, and physical. Reporting of school contacts by proxies may underestimate the effect of school-age children in modelling studies of transmission of infections. New approaches are needed to quantify contacts within schools.

Under-5 mortality surveillance in low-income and middle-income countries: insights from two Health and Demographic Surveillance Systems in rural Gambia.

Without complete data on under-5 mortality, tracking progress towards achieving Sustainable Development Goal 3.2 will be challenging. Such data are also needed to ensure proper planning and prioritisation of scarce resources in low-income and middle-income countries. However, most low-income and middle-income countries have weak Civil Registration and Vital Statistics (CRVS) systems, leaving a critical gap in understanding under-5 mortality dynamics. This paper outlines a community-based approach to enhance under-5 mortality surveillance in low-income countries, using The Gambia as a case study. The methodology involves Health and Demographic Surveillance Systems (HDSSs) in Basse and Fuladu West, employing unique identification numbers, periodical household visits and collaboration with communities, village reporters and project field workers to ensure comprehensive data collection. Verbal autopsies (VAs) are conducted by trained field workers, and causes of death are determined using the physician-certified VA method. Between 1 September 2019 and 1 September 2023, 1333 deaths were detected, for which causes of death were determined for 97.1% (1294 of 1333). The most common causes of death detected were acute respiratory infections including pneumonia, sepsis, diarrhoeal diseases and birth asphyxia. Challenges include the cost of maintaining the HDSSs, poor road infrastructure, Electronic Data Capture transition challenges, and the need for national integration of HDSS data into the CRVS system. The success of this model highlights its potential for scalable and adaptable under-5 mortality surveillance in resource-limited settings.

Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study.

BACKGROUND: Typhoid Fever remains a major cause of morbidity and mortality in low-income settings. The Severe Typhoid in Africa programme was designed to address regional gaps in typhoid burden data and identify populations eligible for interventions using novel typhoid conjugate vaccines. METHODS: A hybrid design, hospital-based prospective surveillance with population-based health-care utilisation surveys, was implemented in six countries in sub-Saharan Africa. Patients presenting with fever (≥37·5°C axillary or ≥38·0°C tympanic) or reporting fever for three consecutive days within the previous 7 days were invited to participate. Typhoid fever was ascertained by culture of blood collected upon enrolment. Disease incidence at the population level was estimated using a Bayesian mixture model. FINDINGS: 27 866 (33·8%) of 82 491 participants who met inclusion criteria were recruited. Blood cultures were performed for 27 544 (98·8%) of enrolled participants. Clinically significant organisms were detected in 2136 (7·7%) of these cultures, and 346 (16·2%) Salmonella enterica serovar Typhi were isolated. The overall adjusted incidence per 100 000 person-years of observation was highest in Kavuaya and Nkandu 1, Democratic Republic of the Congo (315, 95% credible interval 254-390). Overall, 46 (16·4%) of 280 tested isolates showed ciprofloxacin non-susceptibility. INTERPRETATION: High disease incidence (ie, >100 per 100 000 person-years of observation) recorded in four countries, the prevalence of typhoid hospitalisations and complicated disease, and the threat of resistant typhoid strains strengthen the need for rapid dispatch and implementation of effective typhoid conjugate vaccines along with measures designed to improve clean water, sanitation, and hygiene practices. FUNDING: The Bill & Melinda Gates Foundation.

Optimal evaluation of crop residues for gasification in Ghana using integrated multi-criterial decision making techniques.

Lack of sustainable feedstock quantity and quality has been reported to be one of the major challenges confronting operations of gasifier plants in Ghana. In this paper, TOPSIS (Technique for order of Preference by Similarity to Ideal Solution) COPRAS (Complex Proportional Assessment) and VIKOR (Multi-criteria Optimisation and Compromise Solution) were used to select optimal crop residues for sustainable gasification in Ghana among thirteen residue types. The Analytical Hierarchy Process (AHP) was used as weighting criteria for the three Multi-Criteria Decision-Making (MCDM) techniques. Thirteen criteria based on particle size, proximate, ultimate analysis, calorific values, and quantity of residues were used. Five scenarios were considered; ranking of individual feedstock, consideration of the combination of the feedstock grouped under four categories. The ultimate and proximate analysis of the various crop residues as determined were generally within recommended levels as reported in the literature. Cashew shells and cassava peels have the highest heating value and annual technical residue potential of 23.4 MJ/kg and 880,750 tonnes respectively. Ranking of the individual crop residues confirmed cassava peels as the best alternatives of all the three MCDM techniques. The average rankings of the alternatives from the three MCDM in the order of best to worst are cassava peels, maize stalk, cocoa pod husk, maize cobs, rice straw, shea nut husk, groundnut husk, Palm kernel shells, EFB, rice husk, coconut husk/shells, cashew shells, and shea nut cake. Rankings of the alternatives under the four categories considered showed that feedstock blends containing four residues or more offer better opportunities for sustainable gasification than individual feedstock. Statistical analysis shows that there is a very strong, positive correlation between VIKOR, COPRAS, and TOPSIS. The strongest correlation is between VIKOR and TOPSIS with spearman's rank correlation index of 0.98. The analysis was sensitive to the weight of the strategy of group utility, recoverability ratio, residue-to-product ratio and annual crop production figures. It is recommended that optimal gasifier design and operational conditions taken into consideration the various feedstocks and their combination as determined from this study must be studied.

Prevalence and risk factors of hypertension among public servants in Ejisu-Juaben municipality, Ghana.

OBJECTIVES: We determined the prevalence and risk factors of hypertension among public servants of Ejisu Juaben municipality. RESULTS: The overall prevalence of hypertension was 29.3% (95%CI:22.5-36.1%) and only 8.6% of the participants were aware of their hypertensive status. Respondents who were > 40 years were twice as likely to develop hypertension compared to those who were ≤ 40 years [adjusted odds ratio (AOR) = 2.37, 95% confidence interval (CI) 1.05-5.32]. Those who were married were 2.54 times more likely to be hypertensive compared with those unmarried [AOR = 2.54, 95%CI: 1.06-6.08]. Compared to health workers, Judicial and Security service workers were almost five times more likely to be hypertensive [AOR = 4.77, 95%CI: 1.20-18.96]. Being overweight [AOR = 2.25, 95%CI: 1.06-6.41] and obese [AOR = 4.80, 95%CI: 1.82-12.91] was associated with increased odds of hypertension. The prevalence of hypertension among the participants in this study is high. Employee wellness programs are needed at workplaces and the Ghana Health Service must adopt targeted intervention programs such as regular screening for non-communicable diseases and promotion of physical activities at the workplace.

Emergency preparedness capacity of a university hospital in Ghana: a cross-sectional study.

Background: The health and safety of people are often endangered during emergencies and disasters. Efficient emergency management systems ensure that mitigation, preparedness, response, and recovery actions exist to preserve the health, safety, and welfare of the public. Failure to carry out appropriate responses can have adverse consequences for both emergency responders and casualties; hence, the need for emergency preparedness. This study sought to assess the state of emergency preparedness capacity of the Kwame Nkrumah University of Science and Technology hospital in Ghana. Methods: A facility-based cross-sectional study was conducted between December 2018 and February 2019 using three guidelines developed respectively by the World Health Organization, the Ministry of Health-Ghana, and the Ghana Health Service. The hospital's emergency preparedness was assessed regarding the emergency policies, plan, protocol, equipment, and medications. Results: Overall, the hospital's emergency preparedness level was weak (57.36%). Findings revealed that the hospital had inadequate emergency equipment, and supplies for emergency care delivery, especially during upsurge. It also did not have an emergency planning committee. There were noticeable deficiencies in some emergency resources such as chest tubes, basic airway supplies, and many emergency drugs. Other vital emergency tools such as pulse oximeter, thermometer, and emergency medications were inadequate. The hospital had a strong emergency plan and policies on assessment (77.8% and 78%) respectively. Conclusion: The Kwame Nkrumah University of Science and Technology hospital is not prepared sufficiently for an emergency surge, and this poses a major health challenge. Emergency items must be made available, and the organization and planning of emergency service provisions must be improved to avoid preventable deaths during an emergency surge.

Verbal autopsy analysis of childhood deaths in rural Gambia.

BACKGROUND: In low-resource settings, it is challenging to ascertain the burden and causes of under-5 mortality as many deaths occur outside health facilities. We aimed to determine the causes of childhood deaths in rural Gambia using verbal autopsies (VA). METHODOLOGY: We used WHO VA questionnaires to conduct VAs for deaths under-5 years of age in the Basse and Fuladu West Health and Demographic Surveillance Systems (HDSS) in rural Gambia between September 01, 2019, and December 31, 2021. Using a standardized cause of death list, two physicians assigned causes of death and discordant diagnoses were resolved by consensus. RESULTS: VAs were conducted for 89% (647/727) of deaths. Of these deaths, 49.5% (n = 319) occurred at home, 50.1% (n = 324) in females, and 32.3% (n = 209) in neonates. Acute respiratory infection including pneumonia (ARIP) (33.7%, n = 137) and diarrhoeal diseases (23.3%, n = 95) were the commonest primary causes of death in the post-neonatal period. In the neonatal period, unspecified perinatal causes of death (34.0%, n = 71) and deaths due to birth asphyxia (27.3%, n = 57) were the commonest causes of death. Severe malnutrition (28.6%, n = 185) was the commonest underlying cause of death. In the neonatal period, deaths due to birth asphyxia (p-value<0.001) and severe anaemia (p-value = 0.03) were more likely to occur at hospitals while unspecified perinatal deaths (p-value = 0.01) were more likely to occur at home. In the post-neonatal period, deaths due to ARIP (p-value = 0.04) and diarrhoeal disease (p-value = 0.001) were more likely to occur among children aged 1-11 months and 12-23 months respectively. CONCLUSION: According to VA analysis of deaths identified within two HDSS in rural Gambia, half of deaths amongst children under-5 in rural Gambia occur at home. ARIP and diarrhoea, and the underlying cause of severe malnutrition remain the predominant causes of child mortality. Improved health care and health-seeking behaviour may reduce childhood deaths in rural Gambia.

Impact of the COVID-19 pandemic on a clinical trial of pneumococcal vaccine scheduling (PVS) in rural Gambia.

The COVID-19 pandemic represents an unprecedented challenge for clinical research. The Pneumococcal Vaccine Schedules (PVS) study is a non-inferiority, interventional trial in which infants resident in 68 geographic clusters are randomised to two different schedules for pneumococcal vaccination. From September 2019 onwards, all infants resident in the study area became eligible for trial enrolment at all Expanded Programme on Immunisation (EPI) clinics in the study area. Surveillance for clinical endpoints is conducted at all 11 health facilities in the study area. PVS is conducted as a collaboration between the Medical Research Council Unit The Gambia (MRCG) at LSHTM and the Gambian Ministry of Health (MoH). The COVID-19 pandemic caused many disruptions to PVS. MRCG instructed interventional studies that participant enrolment be suspended on 26 March 2020, and a public health emergency was declared in The Gambia on 28 March 2020. Enrolment in PVS restarted on 1 July 2020 and was suspended again on 5 August 2020 after The Gambia experienced a sharp increase in COVID-19 cases in late July 2020 and restarted again on 1 September 2020. During periods of suspended enrolment of infants at EPI clinics, PVS continued safety surveillance at health facilities, albeit with disruptions. During the periods of suspended enrolment, infants who had been enrolled before 26 March 2020 continued to receive the PCV schedule to which they had been randomly allocated based on their village of residence, whereas all other infants received the standard PCV schedule. Throughout 2020 and 2021, the trial faced numerous technical and operational challenges: disruption to MoH delivery of EPI services and clinical care at health facilities; episodes of staff illness and isolation; disruption of MRCG transport, procurement, communications and human resource management; and also a range of ethical, regulatory, sponsorship, trial monitoring and financial challenges. In April 2021, a formal review concluded that the pandemic had not compromised the scientific validity of PVS and that the trial should continue as per protocol. The continuing challenges that COVID-19 poses to PVS, and other clinical trials will persist for some time.

Attendance and vaccination at immunization clinics in rural Gambia before and during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has affected the delivery of essential health services, such as routine immunization. We assessed the impact of the pandemic on the uptake of routine immunization in rural Gambia. METHODS: We collected real-time vaccine administration data in the Basse and Fuladu West Health & Demographic Surveillance Systems from September 01, 2019, to December 31, 2020. We assessed the monthly number of Expanded Program on Immunization (EPI) clinic attendances and vaccines administered, comparing data during the baseline period (September 01, 2019-March 31, 2020), COVID-19 interruption period (April 01-June 30, 2020), initial recovery period (Jul 01-September 30, 2020) and the late recovery period (October 01-December 31, 2020). RESULTS: Compared to the baseline period, there was an overall average monthly decline of 13.4% in EPI attendance and 38.3% reduction in average monthly immunizations during the interruption period. This decrease was particularly noticeable for Bacille Calmette-Guérin (BCG) (47.2%), birth dose hepatitis B (Hep B) (46.9%), 1st dose pentavalent (Penta1) (43.1%), 1st dose pneumococcal conjugate vaccine (PCV1) (42.4%), and measles vaccines (15.5%). Comparing the late recovery to baseline period, average monthly EPI attendance was 5.3% higher, with 1.9% increase in average monthly immunizations. Monthly immunizations for BCG were 3.0% greater, 2.5% greater for Hep B, 22.7% greater for oral polio vaccine (OPV1), 2.0% less for Penta1, 19.2% less for Penta2, and 2.6% less for PCV1. CONCLUSION: The reduced EPI attendance during the pandemic interruption period lasted only 3 months. Significant recovery in EPI attendance occurred during the late recovery period, while rates of monthly immunization returned to pre-pandemic levels for most antigens. EPI programmes should implement strategies to deliver missed antigens when infants do present to EPI clinics, aware that missed doses may be age dependent.

Pneumococcal vaccine schedules (PVS) study: a cluster-randomised, non-inferiority trial of an alternative versus standard schedule for pneumococcal conjugate vaccination-statistical analysis plan.

RATIONALE: The effectiveness of universal immunisation with pneumococcal conjugate vaccine (PCV) has been evident in many countries. However, the global impact of PCV is limited by its cost, which has prevented its introduction in several countries. Reducing the cost of PCV programmes may facilitate vaccine introduction in some countries and improve the sustainability of PCV in EPIs in low-income countries when they transition away from subsidised vaccine supply. METHODS AND DESIGN: PVS is a real-world field trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. the alternative '1+1' schedule) compared to the standard schedule of three primary doses scheduled at 6, 10, and 14 weeks of age (i.e. the standard '3+0' schedule). Delivery of the interventions began in late 2019 in 68 geographic clusters and will continue for 4 years. The primary endpoint is the prevalence of nasopharyngeal vaccine-type pneumococcal carriage in children aged 2-260 weeks with clinical pneumonia in year 4. Secondary endpoints are the prevalence of vaccine-type pneumococcal carriage among all ages in year 4 and the incidence of radiological pneumonia in children enrolled to receive the interventions. Additional disease and carriage endpoints are included. PURPOSE: This statistical analysis plan (SAP) describes the cohorts and populations, and follow-up criteria, to be used in different analyses. The SAP defines the endpoints and describes how adherence to the interventions will be presented. We describe how analyses will account for the effect of clustering and stratified randomisation. The SAP defines the approach to non-inferiority and other analyses. Defining the SAP early in the trial will avoid bias in analyses that may arise from prior knowledge of trial findings.