Clinical indicators for bacterial co-infection in Ghanaian children with P. falciparum infection.

Differentiation of infectious causes in severely ill children is essential but challenging in sub- Saharan Africa. The aim of the study was to determine clinical indicators that are able to identify bacterial co-infections in P. falciparum infected children in rural Ghana. In total, 1,915 severely ill children below the age of 15 years were recruited at Agogo Presbyterian Hospital in Ghana between May 2007 and February 2011. In 771 (40%) of the children malaria parasites were detected. This group was analyzed for indicators of bacterial co-infections using bivariate and multivariate regression analyses with 24 socio-economic variables, 16 terms describing medical history and anthropometrical information and 68 variables describing clinical symptoms. The variables were tested for sensitivity, specificity, positive predictive value and negative predictive value. In 46 (6.0%) of the children with malaria infection, bacterial co-infection was detected. The most frequent pathogens were non-typhoid salmonellae (45.7%), followed by Streptococcus spp. (13.0%). Coughing, dehydration, splenomegaly, severe anemia and leukocytosis were positively associated with bacteremia. Domestic hygiene and exclusive breastfeeding is negatively associated with bacteremia. In cases of high parasitemia (>10,000/μl), a significant association with bacteremia was found for splenomegaly (OR 8.8; CI 1.6-48.9), dehydration (OR 18.2; CI 2.0-166.0) and coughing (OR 9.0; CI 0.7-118.6). In children with low parasitemia, associations with bacteremia were found for vomiting (OR 4.7; CI 1.4-15.8), severe anemia (OR 3.3; CI 1.0-11.1) and leukocytosis (OR 6.8 CI 1.9-24.2). Clinical signs of impaired microcirculation were negatively associated with bacteremia. Ceftriaxone achieved best coverage of isolated pathogens. The results demonstrate the limitation of clinical symptoms to determine bacterial co-infections in P. falciparum infected children. Best clinical indicators are dependent on the parasitemia level. Even with a moderate sensitivity of >60%, only low positive predictive values can be obtained due to low prevalence of bacteremia. Rapid testing for distinguishing parasitemia and bacteremia is essential

A randomized trial on effectiveness of artemether-lumefantrine versus artesunate plus amodiaquine for unsupervised treatment of uncomplicated Plasmodium falciparum malaria in Ghanaian children

<p>Abstract</p> <p>Background</p> <p>Numerous trials have demonstrated high efficacy and safety of artemisinin-based combination therapy (ACT) under supervised treatment. In contrast, effectiveness studies comparing different types of ACT applied unsupervised are scarce. The aim of this study was to compare effectiveness, tolerability and acceptance of artesunate plus amodiaquine (ASAQ) against that of artemether-lumefantrine (AL) in Ghanaian children with uncomplicated <it>Plasmodium falciparum </it>malaria.</p> <p>Methods</p> <p>A randomized open-label trial was conducted at two district hospitals in the Ashanti region, Ghana, an area of intense malaria transmission. A total of 246 children under five years of age were randomly assigned to either ASAQ (Arsucam^®) or AL (Coartem^®). Study participants received their first weight-adjusted dose under supervision. After the parent/guardian was advised of times and mode of administration the respective three-day treatment course was completed unobserved at home. Follow-up visits were performed on days 3, 7, 14 and 28 to evaluate clinical and parasitological outcomes, adverse events, and haematological recovery. Length polymorphisms of variable regions of <it>msp1 </it>and <it>msp2 </it>were determined to differentiate recrudescences from reinfections. Acceptance levels of both treatment regimens were assessed by means of standardized interviews.</p> <p>Results</p> <p>Adequate clinical and parasitological responses after AL and ASAQ treatment were similar (88.3% and 91.7%, respectively). Interestingly, more late clinical failures until day 28 occurred in AL-treated children than in those who received ASAQ (17.5% and 7.3%, respectively; Hazard Ratio 2.41, 95% CI 1.00–5.79, p < 0.05).</p> <p>Haematological recovery and drug tolerability were not found to be significantly different in both study arms. The acceptance of treatment with ASAQ was higher than that with AL (rank-scores 10.6 and 10.3, respectively; p < 0.05).</p> <p>Conclusion</p> <p>Unobserved AL and ASAQ treatment showed high adequate clinical and parasitological responses, though AL was inferior in preventing late clinical failures.</p

Mental health related determinants of parenting stress among urban mothers of young children – results from a birth-cohort study in Ghana and Côte d’Ivoire

Background There are limited data on the parenting stress (PS) levels in sub-Saharan African mothers and on the association between ante- and postnatal depression and anxiety on PS. Methods A longitudinal birth cohort of 577 women from Ghana and Côte d’Ivoire was followed from the 3rd trimester in pregnancy to 2 years postpartum between 2010 and 2013. Depression and anxiety were assessed by the Patient Health Questionnaire depression module (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) at baseline, 3 month, 12 month and 24 month postpartum. PS was measured using the Parenting Stress Index-Short Form (PSI-SF) at 3, 12 and 24 month. The mean total PS score and the subscale scores were compared among depressed vs. non-depressed and among anxious vs. non-anxious mothers at 3, 12 and 24 month postpartum. The proportions of clinical PS (PSI-SF raw score > 90) in depressed vs. non-depressed and anxious vs. non-anxious mothers were also compared. A generalized estimating equation (GEE) approach was used to estimate population-averaged associations between women’s depression/anxiety and PS adjusting for age, child sex, women’s anemia, education, occupation, spouse’s education, and number of sick child visits. Results A total of 577, 531 and 264 women completed the PS assessment at 3 month, 12 month and 24 month postpartum across the two sites and the prevalences of clinical PS at each time point was 33.1%, 24.4% and 14.9% in Ghana and 30.2%, 33.5% and 22.6% in Côte d’Ivoire, respectively. At all three time points, the PS scores were significantly higher among depressed mothers vs. non-depressed mothers. In the multivariate regression analyses, antepartum and postpartum depression were consistently associated with PS after adjusting for other variables. Conclusions Parenting stress is frequent and levels are high compared with previous studies from high-income countries. Antepartum and postpartum depression were both associated with PS, while antepartum and postpartum anxiety were not after adjusting for confounders. More quantitative and qualitative data are needed in sub-Saharan African populations to assess the burden of PS and understand associated mechanisms. Should our findings be replicated, it appears prudent to design and subsequently evaluate intervention strategies

Incidence and characteristics of bacteremia among children in rural Ghana.

The objective of the study was to describe systemic bacterial infections occurring in acutely ill and hospitalized children in a rural region in Ghana, regarding frequency, incidence, antimicrobial susceptibility patterns and associations with anthropometrical data.Blood cultures were performed in all children below the age of five years, who were admitted to Agogo Presbyterian Hospital (APH), Asante Region, Ghana, between September 2007 and July 2009. Medical history and anthropometrical data were assessed using a standardized questionnaire at admission. Incidences were calculated after considering the coverage population adjusted for village-dependent health-seeking behavior.Among 1,196 hospitalized children, 19.9% (n = 238) were blood culture positive. The four most frequent isolated pathogens were nontyphoidal salmonellae (NTS) (53.3%; n = 129), Staphylococcus aureus (13.2%; n = 32), Streptococcus pneumoniae (9.1%; n = 22) and Salmonella ser. Typhi (7.0%; n = 17). Yearly cumulative incidence of bacteremia was 46.6 cases/1,000 (CI 40.9-52.2). Yearly cumulative incidences per 1,000 of the four most frequent isolates were 25.2 (CI 21.1-29.4) for NTS, 6.3 (CI 4.1-8.4) for S. aureus, 4.3 (CI 2.5-6.1) for S. pneumoniae and 3.3 (CI 1.8-4.9) for Salmonella ser. Typhi. Wasting was positively associated with bacteremia and systemic NTS bloodstream infection. Children older than three months had more often NTS bacteremia than younger children. Ninety-eight percent of NTS and 100% of Salmonella ser. Typhi isolates were susceptible to ciprofloxacin, whereas both tested 100% susceptible to ceftriaxone. Seventy-seven percent of NTS and 65% of Salmonella ser. Typhi isolates were multi-drug resistant (MDR). Systemic bacterial infections in nearly 20% of hospitalized children underline the need for microbiological diagnostics, to guide targeted antimicrobial treatment and prevention of bacteremia. If microbiological diagnostics are lacking, calculated antimicrobial treatment of severely ill children in malaria-endemic areas should be considered

Systemic bacteraemia in children presenting with clinical pneumonia and the impact of non-typhoid salmonella (NTS).

BACKGROUND: The diagnosis and antimicrobial treatment of pneumonia in African children in the absence of diagnostic means such as x-ray facilities or microbiological laboratories relies primarily on clinical symptoms presented by the patients. In order to assess the spectrum of bacterial pathogens, blood cultures were performed in children fulfilling the clinical criteria of pneumonia. METHODS: In total, 1032 blood cultures were taken from children between 2 months and 5 years of age who were admitted to a rural hospital in Ghana between September 2007 and July 2009. Pneumonia was diagnosed clinically and according to WHO criteria classified as "non-severe pneumonia" and "severe pneumonia" ("severe pneumonia" includes the WHO categories "severe pneumonia" and "very severe pneumonia"). RESULTS: The proportion of bacteriaemia with non-typhoid salmonella (NTS) was similar in children with pneumonia (16/173, 9.2%) compared to children hospitalized for other reasons (112/859, 13%). NTS were the predominant organisms isolated from children with clinical pneumonia and significantly more frequent than Streptococcus pneumoniae (8/173, 4.6%). Nine percent (9/101) of children presenting with severe pneumonia and 10% (7/72) of children with non-severe pneumonia were infected with NTS. Nineteen out of 123 NTS isolates (15%) were susceptible to aminopenicillins (amoxycillin/ampicillin), 23/127 (18%) to chlorampenicol, and 23/98 (23%) to co-trimoxazole. All NTS isolates were sensitive to ceftriaxone and ciprofloxacin. CONCLUSION: In Sub-saharan Africa, sepsis with NTS should be considered in children with symptoms of pneumonia and aminopenicillins might often not be the adequate drugs for treatment

High seroprevalence of SARS-CoV-2 in Burkina-Faso, Ghana and Madagascar in 2021: a population-based study

Background The current COVID-19 pandemic affects the entire world population and has serious health, economic and social consequences. Assessing the prevalence of COVID-19 through population-based serological surveys is essential to monitor the progression of the epidemic, especially in African countries where the extent of SARS-CoV-2 spread remains unclear. Methods A two-stage cluster population-based SARS-CoV-2 seroprevalence survey was conducted in Bobo-Dioulasso and in Ouagadougou, Burkina Faso, Fianarantsoa, Madagascar and Kumasi, Ghana between February and June 2021. IgG seropositivity was determined in 2,163 households with a specificity improved SARS-CoV-2 Enzyme-linked Immunosorbent Assay. Population seroprevalence was evaluated using a Bayesian logistic regression model that accounted for test performance and age, sex and neighbourhood of the participants. Results Seroprevalence adjusted for test performance and population characteristics were 55.7% [95% Credible Interval (CrI) 49·0; 62·8] in Bobo-Dioulasso, 37·4% [95% CrI 31·3; 43·5] in Ouagadougou, 41·5% [95% CrI 36·5; 47·2] in Fianarantsoa, and 41·2% [95% CrI 34·5; 49·0] in Kumasi. Within the study population, less than 6% of participants performed a test for acute SARS-CoV-2 infection since the onset of the pandemic. Conclusions High exposure to SARS-CoV-2 was found in the surveyed regions albeit below the herd immunity threshold and with a low rate of previous testing for acute infections. Despite the high seroprevalence in our study population, the duration of protection from naturally acquired immunity remains unclear and new virus variants continue to emerge. This highlights the importance of vaccine deployment and continued preventive measures to protect the population at risk

Principal component analysis of socioeconomic factors and their association with malaria in children from the Ashanti Region, Ghana

<p>Abstract</p> <p>Background</p> <p>The socioeconomic and sociodemographic situation are important components for the design and assessment of malaria control measures. In malaria endemic areas, however, valid classification of socioeconomic factors is difficult due to the lack of standardized tax and income data. The objective of this study was to quantify household socioeconomic levels using principal component analyses (PCA) to a set of indicator variables and to use a classification scheme for the multivariate analysis of children < 15 years of age presented with and without malaria to an outpatient department of a rural hospital.</p> <p>Methods</p> <p>In total, 1,496 children presenting to the hospital were examined for malaria parasites and interviewed with a standardized questionnaire. The information of eleven indicators of the family's housing situation was reduced by PCA to a socioeconomic score, which was then classified into three socioeconomic status (poor, average and rich). Their influence on the malaria occurrence was analysed together with malaria risk co-factors, such as sex, parent's educational and ethnic background, number of children living in a household, applied malaria protection measures, place of residence and age of the child and the mother.</p> <p>Results</p> <p>The multivariate regression analysis demonstrated that the proportion of children with malaria decreased with increasing socioeconomic status as classified by PCA (p < 0.05). Other independent factors for malaria risk were the use of malaria protection measures (p < 0.05), the place of residence (p < 0.05), and the age of the child (p < 0.05).</p> <p>Conclusions</p> <p>The socioeconomic situation is significantly associated with malaria even in holoendemic rural areas where economic differences are not much pronounced. Valid classification of the socioeconomic level is crucial to be considered as confounder in intervention trials and in the planning of malaria control measures.</p

Predictive Value of Fever and Palmar Pallor for P. falciparum Parasitaemia in Children from an Endemic Area

INTRODUCTION: Although the incidence of Plasmodium falciparum malaria in some parts of sub-Saharan Africa is reported to decline and other conditions, causing similar symptoms as clinical malaria are gaining in relevance, presumptive anti-malarial treatment is still common. This study traced for age-dependent signs and symptoms predictive for P. falciparum parasitaemia. METHODS: In total, 5447 visits of 3641 patients between 2-60 months of age who attended an outpatient department (OPD) of a rural hospital in the Ashanti Region, Ghana, were analysed. All Children were examined by a paediatrician and a full blood count and thick smear were done. A Classification and Regression Tree (CART) model was used to generate a clinical decision tree to predict malarial parasitaemia a7nd predictive values of all symptoms were calculated. RESULTS: Malarial parasitaemia was detected in children between 2-12 months and between 12-60 months of age with a prevalence of 13.8% and 30.6%, respectively. The CART-model revealed age-dependent differences in the ability of the variables to predict parasitaemia. While palmar pallor was the most important symptom in children between 2-12 months, a report of fever and an elevated body temperature of ≥37.5°C gained in relevance in children between 12-60 months. The variable palmar pallor was significantly (p<0.001) associated with lower haemoglobin levels in children of all ages. Compared to the Integrated Management of Childhood Illness (IMCI) algorithm the CART-model had much lower sensitivities, but higher specificities and positive predictive values for a malarial parasitaemia. CONCLUSIONS: Use of age-derived algorithms increases the specificity of the prediction for P. falciparum parasitaemia. The predictive value of palmar pallor should be underlined in health worker training. Due to a lack of sensitivity neither the best algorithm nor palmar pallor as a single sign are eligible for decision-making and cannot replace presumptive treatment or laboratory diagnosis

A −436C>A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria

Human genetics and immune responses are considered to critically influence the outcome of malaria infections including life-threatening syndromes caused by Plasmodium falciparum. An important role in immune regulation is assigned to the apoptosis-signaling cell surface receptor CD95 (Fas, APO-1), encoded by the gene FAS. Here, a candidate-gene association study including variant discovery at the FAS gene locus was carried out in a case-control group comprising 1,195 pediatric cases of severe falciparum malaria and 769 unaffected controls from a region highly endemic for malaria in Ghana, West Africa. We found the A allele of c.−436C>A (rs9658676) located in the promoter region of FAS to be significantly associated with protection from severe childhood malaria (odds ratio 0.71, 95% confidence interval 0.58–0.88, pempirical = 0.02) and confirmed this finding in a replication group of 1,412 additional severe malaria cases and 2,659 community controls from the same geographic area. The combined analysis resulted in an odds ratio of 0.71 (95% confidence interval 0.62–0.80, p = 1.8×10−7, n = 6035). The association applied to c.−436AA homozygotes (odds ratio 0.47, 95% confidence interval 0.36–0.60) and to a lesser extent to c.−436AC heterozygotes (odds ratio 0.73, 95% confidence interval 0.63–0.84), and also to all phenotypic subgroups studied, including severe malaria anemia, cerebral malaria, and other malaria complications. Quantitative FACS analyses assessing CD95 surface expression of peripheral blood mononuclear cells of naïve donors showed a significantly higher proportion of CD69+CD95+ cells among persons homozygous for the protective A allele compared to AC heterozygotes and CC homozygotes, indicating a functional role of the associated CD95 variant, possibly in supporting lymphocyte apoptosis