Associations between malaria in pregnancy and neonatal neurological outcomes.

OBJECTIVE: To compare neurological functioning of neonates born to mothers with and without malaria in pregnancy. METHODS: Pregnant women presenting at Korle Bu Teaching Hospital, Ghana were recruited into this prospective observational study. Malaria exposure was determined by clinically documented antenatal malaria infection; parasitemia in maternal, placental, or umbilical cord blood; or placental histology. Neurological functioning was assessed using the Hammersmith Neonatal Neurological Examination within 48 hours of birth. Performance was classified as "optimal" or "suboptimal" by subdomain and overall. RESULTS: Between November 21, 2018 and February 10, 2019, a total of 211 term-born neonates, of whom 27 (13%) were exposed to malaria in pregnancy, were included. In the reflexes subdomain, exposed neonates tended to score lower (adjusted mean difference -0.34, 95% confidence interval -0.70 to 0.03), with an increased risk (adjusted risk ratio 1.63, 95% confidence interval 1.09 to 2.44) of suboptimal performance compared with unexposed neonates. There were no significant between-group differences in scores or optimality classification for the remaining subdomains and overall. CONCLUSIONS: Malaria-exposed neonates had similar neurological functioning relative to unexposed neonates, with differences confined to the reflexes subdomain, suggesting potential underlying neurological immaturity or injury. Further studies are needed to confirm these findings and determine the significance of malaria in pregnancy on long-term neurological outcomes.

Rubinstein-Taybi syndrome in diverse populations.

Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant disorder, caused by loss-of-function variants in CREBBP or EP300. Affected individuals present with distinctive craniofacial features, broad thumbs and/or halluces, and intellectual disability. RSTS phenotype has been well characterized in individuals of European descent but not in other populations. In this study, individuals from diverse populations with RSTS were assessed by clinical examination and facial analysis technology. Clinical data of 38 individuals from 14 different countries were analyzed. The median age was 7 years (age range: 7 months to 47 years), and 63% were females. The most common phenotypic features in all population groups included broad thumbs and/or halluces in 97%, convex nasal ridge in 94%, and arched eyebrows in 92%. Face images of 87 individuals with RSTS (age range: 2 months to 47 years) were collected for evaluation using facial analysis technology. We compared images from 82 individuals with RSTS against 82 age- and sex-matched controls and obtained an area under the receiver operating characteristic curve (AUC) of 0.99 (p < .001), demonstrating excellent discrimination efficacy. The discrimination was, however, poor in the African group (AUC: 0.79; p = .145). Individuals with EP300 variants were more effectively discriminated (AUC: 0.95) compared with those with CREBBP variants (AUC: 0.93). This study shows that clinical examination combined with facial analysis technology may enable earlier and improved diagnosis of RSTS in diverse populations.

A genomic infection control study for Staphylococcus aureus in two Ghanaian hospitals.

BACKGROUND: Whole genome sequencing analysis (WGSA) provides the best resolution for typing of bacterial isolates and has the potential for identification of transmission pathways. The aim of the study was to apply WGSA to elucidate the possible transmission events involved in two suspected Staphylococcus aureus hospital outbreaks in Ghana and describe genomic features of the S. aureus isolates sampled in the outbreaks. METHODS: The study was carried out at Korle-Bu Teaching Hospital and Lekma Hospital where the suspected outbreaks occurred in 2012 and 2015, respectively. The S. aureus isolates collected from the two hospitals were from three sources including carriage, invasive disease, and the environment. Whole genome sequencing of the S. aureus isolates was performed and the sequence reads were mapped to the S. aureus reference genome of strain USA300_FPR3757. A maximum-likelihood phylogenetic tree was reconstructed. Multilocus sequence typing together with the analysis of antimicrobial resistance and virulence genes were performed by short read mapping using the SRST2. RESULTS: The S. aureus isolates belonged to diverse sequence types (STs) with ST15 and ST152 most common. All isolates carried the blaZ gene, with low prevalence of tetK and dfrG genes also observed. All isolates were mecA negative. The pvl genes were common and observed in distinct lineages that revealed diverse Sa2int phages. At Korle-Bu Teaching Hospital, the genomics data indicated several transmission events of S. aureus ST15 involving contamination of various surfaces in the pediatric emergency ward where the outbreak occurred. CONCLUSION: The pattern of dissemination of the ST15 clone in the emergency ward of Korle-Bu Teaching Hospital highlights a basic problem with disinfection of environmental surfaces at the hospital. Diverse phage population rather than a single highly transmissible phage type likely mediates the high prevalence of pvl genes among the S. aureus isolates.

Pneumonia in Ghana-a need to raise the profile.

Despite the high mortality, pneumonia retains a relatively low profile among researchers, funders and policymakers. Here we reflect on the problems and priorities of pneumonia in Ghana, briefly review the evidence base and reflect upon in-person discussions between Southampton-based authors MGH and JB and academic, clinical and policy colleagues in Ghana. The discussions took place in Accra in August 2017.

Colonisation of antibiotic resistant bacteria in a cohort of HIV infected children in Ghana.

Antibiotic use not only selects for resistance in pathogenic bacteria, but also in commensal flora of exposed individuals. Little is known epidemiologically about antibiotic resistance in relation to people with HIV infection in sub-Saharan Africa. This study investigated the carriage of antibiotic resistant bacteria among HIV infected children at a tertiary hospital in Ghana. One hundred and eighteen HIV positive children were recruited at the Korle-Bu Teaching Hospital in Ghana and nasopharyngeal specimens were collected from them. The specimens were cultured for bacteria, and the isolates were identified by standard microbiological methods. Antibiotic susceptibility tests were carried out on selected bacterial organisms by the Kirby Bauer method. Bacteria isolated from the study subjects included Moraxella catarrhalis (39.8%), coagulase negative staphylococci (33.1%), Streptococcus pneumoniae (30.5%), diptheroids (29.7%), viridian streptococci (27.1%), Staphylococcus aureus (22.0%), Citrobacter spp. (4.2%) and Neisseria meningitidis (0.9%). Prevalence of antibiotic resistance of S. pneumoniae ranged from 5.6% (ceftriaxone) to 58.3% (cotrimoxazole), M. catarrhalis ranged from 2.1% (gentamicin) to 80.6% (ampicillin), and S. aureus ranged from 7.7% (cefoxitin) to 100% (penicillin). The prevalence of multiple drug resistance was 16.7% for S. pneumoniae, 57.4% for M. catarrhalis and 84.6% for S. aureus. HIV infected children in the study area commonly carry multi-drug resistant isolates of several pathogenic bacteria such as S. aureus and S. pneumoniae. Infections arising in these patients that are caused by S. aureus and S. pneumoniae could be treated with ceftriaxone and cefoxitin respectively.

Pneumococcal carriage among HIV infected children in Accra, Ghana.

BACKGROUND: Pneumococcal carriage is the precursor for development of pneumococcal disease, and is also responsible for transmission of the organism from person-to-person. In Africa, little is known about the pneumococcus in relation to people with HIV infection. The aim of the study was to investigate the epidemiology of pneumococcal carriage among HIV infected children visiting a tertiary hospital in Ghana, including the carriage prevalence, risk factors and serotype distribution. METHOD: This was a cross sectional study carried out from February to May, 2015 at the HIV Paediatric Clinic of the Korle-Bu Teaching Hospital in Accra, Ghana. One hundred and eighteen HIV infected children were recruited and nasopharyngeal (NP) swabs were collected from them. Epidemiological data on demographic, household and clinical features of the study participants were also collected. The NP specimens were cultured for Streptococcus pneumoniae and the isolates were serotyped by latex agglutination. The data of the study was analysed using STATA 11 (Strata Corp, College Station, TX, USA). RESULTS: Prevalence of pneumococcal carriage among the HIV infected children was 27.1% (95% CI: 19.1 to 35.1) and the only factor significantly associated with pneumococcal carriage was the presence of respiratory symptoms (OR, 2.63; CI, 1.06-6.53; p = 0.034). The most prevalent pneumococcal serotype among the study participants was serotype 19F (24.4%), followed by 16F (22%). Serotype coverage of the 13-valent Pneumococcal Conjugate Vaccine in this study was 41.5%. Multiple carriage of pneumococcal serotypes among the positive carriage cases was 34.3%. CONCLUSION: Pneumococcal carriage occurred in more than a quarter of the study population and was characterized by predominance of non-vaccine serotypes as well as a high prevalence of multiple carriage. Presence of respiratory symptoms appears to be a major determinant of pneumococcal carriage among the study population.

Human enteroviruses are not the cause of neurological impairments in children at the Korle-Bu Teaching Hospital.

INTRODUCTION: Convulsions associated with fever and acute onset of unknown aetiology with case fatalities have become a long observed medical condition at the Child Health Department of the Korle-Bu Teaching Hospital. Children admitted to the department with seizures of undetermined origin and fever has been a source of diagnostic confusion. Studies from the Asia Pacific region suggest a link with non-polio enteroviruses. The aim of the study was to investigate the association between non-polio enterovirus and acute encephalopathy causing neurological morbidity in children. METHODS: One hundred and fifty cerebrospinal fluid (CSF), throat swab and serum samples were collected from participants at the Child Health Department of the Korle-Bu Teaching Hospital for virus isolation and characterization. Samples were cultured on cells and positive culture assayed by microneutralisation. Direct PCR as well as multiplex PCR were used to detect other viral agents present. RESULTS: Enterovirus isolation rate was approximately 0.67%. Intratypic differentiation by molecular characterization identified a poliovirus from vaccine origin. Further screening by real-time RT-PCR identified the virus as normal Sabin and not vaccine-derive poliovirus. No arbovirus was however detected. CONCLUSION: Non-polio enteroviruses and chikugunya virus were found not to be the etiologic agent responsible for the convulsion with neurologic morbidity observed in the Ghanaian children. Investigation for other viral agents is recommended.

Vaccination against pneumococcus in West Africa: perspectives and prospects.

BACKGROUND: Pneumococcal vaccination has become obligatory due to the enormous burden of pneumococcal diseases. Quite recently, pneumococcal conjugate vaccines have been developed, and have been shown to be superior to the previous polyvalent polysaccharide vaccine of the organism. Pneumococcal conjugate vaccines (PCVs) are being introduced in many West African countries and it is important to understand the expected performance, relevance, and limitations of these vaccines in the subregion. AIM: The objective of the study presented here was to provide epidemiological insights into PCVs in West Africa based on the prevailing pneumococcal serotypes in the subregion. METHODS: A systematic review was carried out on pneumococcal serotypes causing invasive and noninvasive diseases in West Africa. Studies included in the review were those that reported at least 20 serotyped pneumococcal isolates and which were conducted prior to the introduction of PCVs in the region in 2009. The proportion of pneumococcal disease associated with each serotype as well as the serotype coverage of various PCVs (PCV7, PCV10, and PCV13) were calculated. RESULTS: The data covered 718 serotyped pneumococcal isolates from six West African countries: Burkina Faso, Ghana, Nigeria, Mali, Senegal, and The Gambia. The 718 isolates covered more than 20 serotypes. Serotype 1 was the most prevalent serotype (32%), followed by serotype 5 (15%), serotype 6 (7%), serotype 2 (6%), serotype 3 (6%), and serotype 12 (5%). The estimated serotype coverage of PCVs among the West African countries was 2%-36% for PCV7, 39%-80% for PCV10, and 65%-87% for PCV13. CONCLUSION: A pneumococcal capsular vaccine for use in West Africa must contain serotypes 1 and 5, the most important serotypes responsible for pneumococcal disease in the region. Consequently, while PCV10 and PCV13 are generally suitable for use in West Africa, PCV7 is unsuitable.

Reversible audiometric threshold changes in children with uncomplicated malaria.

Background. Plasmodium falciparum malaria, as well as certain antimalarial drugs, is associated with hearing impairment in adults. There is little information, however, on the extent, if any, of this effect in children, and the evidence linking artemisinin combination therapies (ACTs) with hearing is inconclusive. Methods. Audiometry was conducted in children with uncomplicated malaria treated with artesunate-amodiaquine (n = 37), artemether-lumefantrine (n = 35), or amodiaquine (n = 8) in Accra, Ghana. Audiometry was repeated 3, 7, and 28 days later and after 9 months. Audiometric thresholds were compared with those of a control group of children (n = 57) from the same area. Findings. During the acute stage, hearing threshold levels of treated children were significantly elevated compared with controls (P < 0.001). The threshold elevations persisted up to 28 days, but no differences in hearing thresholds were evident between treated children and controls after 9 months. The hearing thresholds of children treated with the two ACT regimens were comparable but lower than those of amodiaquine-treated children during acute illness. Interpretation. Malaria is the likely cause of the elevated hearing threshold levels during the acute illness, a finding that has implications for learning and development in areas of intense transmission, as well as for evaluating potential ototoxicity of new antimalarial drugs.

Invasive disease and paediatric carriage of Streptococcus pneumoniae in Ghana.

This study was carried out primarily to evaluate the public health burden related to Streptococcus pneumoniae in Ghana and to provide related preliminary molecular epidemiological data on the organism. Invasive and nasopharyngeal specimens were screened for S. pneumoniae, and isolates were subjected to serotyping, multilocus sequence typing (MLST) and antibiotic susceptibility testing. Overall, the prevalence of S. pneumoniae in cerebrospinal fluid (CSF) was 1.7%, in blood was 0.2%, and in nasopharyngeal specimens was 15.3%. The prevalence of multiple drug resistance among the isolates was 48.6%, while the percentage resistance to various drugs was in the range of 11.1-84.0%. Serotyping of the S. pneumoniae isolates showed 7 different serotypes (3, 6B, 9, 10, 14, 16 and 23F). The extent of coverage of serotypes by the 7-valent pneumococcal conjugate vaccine was 57.1%, for the 10-valent vaccine was 57.1%, and for the 13-valent vaccine was 71.4%. MLST of 7 housekeeping genes of the organism showed a high level of genetic diversity among the isolates. S. pneumoniae appears to be an important organism in invasive infections in Ghana, being the most prevalent organism in CSF in this study. The high multiple drug resistance of the organism observed heightens the public health burden, which may be controlled by pneumococcal conjugate vaccines to a large extent.

Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with one year follow-up.

BACKGROUND: Artesunate-amodiaquine (AS+AQ) and artemether-lumefantrine (AM-L) are efficacious artemisinin combination therapy (ACT) regimens that have been widely adopted in sub-Saharan Africa. However, there is little information on the efficacy of these regimens on subsequent episodes beyond 28 days, or on the safety of repeated treatments. METHODS: Children aged six months to 14 years with uncomplicated malaria were randomly assigned to treatment with AS+AQ (n = 116), or AM-L (n = 111). Recruited subjects were followed-up, initially for 28 days, and then monthly for up to one year. All subsequent attacks of uncomplicated malaria after 28 days were treated with the same regimen as at randomization. Investigations aimed at determining efficacy and side effects were conducted. RESULTS: Adequate clinical and parasitological response in subjects with evaluable end-points were, 97.1% (100/103) and 98.2% (107/109) on day 14, and 94.2% (97/103) and 95.3% (102/107) on day 28 in the AM-L and AS+AQ groups, respectively. Similar results were obtained after PCR correction. The incidence of malaria attacks in the year following recruitment was similar between the two treatment groups (p = 0.93). There was a high incidence of potentially AQ-resistant parasites in the study area. The incidence of adverse events, such as pruritus, fatigue and neutropaenia were similar in the two treatment groups. No patient showed signs of hearing impairment, and no abnormal neurological signs were observed during one year of follow-up. Other adverse events were mild in intensity and overlapped with known malaria symptomatology. No adverse event exacerbation was observed in any of the subjects who received multiple treatment courses with these ACT regimens during one year follow-up. CONCLUSION: AS+AQ and AM-L were efficacious for treatment of children with uncomplicated malaria in Ghana and drug-related adverse events were rare in treated subjects during one year of follow-up. The high prevalence of potentially AQ resistant parasites raises questions about the utility of AQ as a partner drug for ACT in Ghana. The efficacy of AS+AQ in Ghana requires, therefore, continuous monitoring and evaluation. TRIAL REGISTRATION: NCT 00406146 http://www.clinicaltrials.gov.