Health economic evaluation of 2-dose and 3-dose rotavirus vaccines in children below 5 years of age in Morocco.

Following the introduction of rotavirus vaccination into the Moroccan National Immunization Program, the prevalence of the disease has decreased by nearly 50%. However, evidence on the economic value of rotavirus vaccinations in Morocco is limited. This health economic analysis evaluated, from both country payer and societal perspectives, the costs and the cost-effectiveness of three rotavirus vaccines using a static, deterministic, population model in children aged < 5 years in Morocco. Included vaccines were HRV (2-dose schedule), HBRV (3-dose schedule) and BRV-PV 1-dose vial (3-dose schedule). One-way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty in model inputs. The model predicted that vaccination with HRV was estimated to result in fewer rotavirus gastroenteritis events (-194 homecare events, -57 medical visits, -8 hospitalizations) versus the 3-dose vaccines, translating into 7 discounted quality-adjusted life years gained over the model time horizon. HRV was associated with lower costs versus HBRV from both the country payer (-$1.8 M) and societal (-$4.1 M) perspectives, and versus BRV-PV 1-dose vial from the societal perspective (-$187,000), dominating those options in the cost-effectiveness analysis. However, costs of BRV-PV 1-dose vial were lower than HRV from the payer perspective, resulting in an ICER of approximately $328,376 per QALY, above the assumed cost effectiveness threshold of $3,500. Vaccination with a 2-dose schedule of HRV may be a cost-saving option and could lead to better health outcomes for children in Morocco versus 3-dose schedule rotavirus vaccines.

Changes in pneumococcal serotypes distribution and penicillin resistance in healthy children five years after generalization of PCV10.

Objective: Streptococcus pneumoniae (S. pneumoniae) nasopharyngeal carriage has significantly decreased after the generalization of pneumococcal vaccination worldwide. This study sought to investigate changes in S. pneumoniae carriage rates, serotype distribution and penicillin non-susceptibility following the generalization of 10-valent pneumococcal conjugate vaccine. Methods: A prospective study was conducted in Marrakesh, Morocco, between 2017 and 2018, among healthy children attending vaccination centers. We collected nasopharyngeal swabs and questionnaire data for each child. Using univariate logistic regression, we analyzed the association between S. pneumoniae carriage and various risk factors. Comparisons of serotype diversity and penicillin resistance between 2017 and 2018 and the period before introduction of vaccination (2008-2009, n = 660) were performed using Simpson index and the chi-squared test, respectively. Results: During 2017-2018, 515 children aged between 6 and 36 months participated. The S. pneumoniae carriage rate was 43.3%. Looking at the distribution serotypes, the rate of PCV10 serotypes rate was only 9.6%. Among non-vaccine serotypes, an increase in serotypes 6C/6D (22; 14%), 19B/19C (17; 10.8%), and 15B/15C (11; 7%) was observed. A particular increase in serotype diversity was also observed after the generalization of PCV10 (p < 0.001). S. pneumoniae non-susceptible to penicillin decreased, reaching a rate of 26.6% in 2017-2018. Conclusion: The significant change in S. pneumoniae carriage, serotype distribution, and penicillin resistance highlights the effectiveness of the pneumococcal conjugate vaccine among children in Marrakesh, Morocco.

Multidrug-resistant Enterobacterales responsible for septicaemia in a neonatal intensive care unit in Morocco.

OBJECTIVES: Neonatal sepsis caused by multidrug-resistant (MDR) bacteria has a high morbidity and mortality, especially in low- and middle-income countries. Here, the molecular mechanisms of multidrug resistance in bacteria responsible for neonatal sepsis were determined. METHODS: From July to December 2019, documented bacteraemia from 524 neonates hospitalised in a neonatal intensive care unit in Morocco were collected. Whole-genome sequencing was used to characterise the resistome; multi-locus sequence typing was used to investigate phylogeny. RESULTS: Among the 199 cases of documented bacteraemia, 40 (20%) and 20 (10%) were caused by MDR Klebsiella pneumoniae and Enterobacter hormaechei, respectively. Of these, 23 (38.5%) were early neonatal infections (≤3 days of life). Twelve different sequence types (STs) were observed among K. pneumoniae isolates, the most prevalent being ST1805 (n = 10) and ST307 (n = 8). Twenty-one K. pneumoniae isolates (53%) possessed the blaCTX-M-15 gene, six of which co-produced OXA-48; two, NDM-7; and two, OXA-48 and NDM-7. The blaOXA-48 gene was present in 11 K. pneumoniae isolates (27.5%); blaNDM-1, in 13 (32.5%); and blaNDM-7, in 4 (10.0%). Eighteen E. hormaechei isolates (90.0%) produced an extended-spectrum ß-lactamase (ESBL). Three were SHV-12 producers that co-produced CMY-4 and NDM-1, and 15 were CTXM-15 producers, of which 6 co-produced OXA-48. Twelve different STs belonging to three different E. hormaechei subspecies were observed, with one to four isolates. K. pneumoniae and E. hormaechei isolates belonging to the same ST had less than 20 single nucleotide polymorphism differences and were found throughout the study period, highlighting their endemic presence in the neonatal intensive care unit. CONCLUSION: Thirty percent of neonatal sepsis cases (23 early and 37 late) were caused by highly drug-resistant carbapenemase- and/or ESBL-producing Enterobacterales.

Tuberculous otomastoiditis complicated by thrombosis of the sigmoid sinus in an infant.

Otomastoiditis is a rare and exceptional complication of tuberculosis; its pathogenesis has been debated since its recognition as a distinct condition. The evolution and prognosis in general are modified after the end of antituberculosis treatment. In our observation, we report the case of an infant with tuberculous otomastoiditis complicated by sigmoid sinus thrombosis.

Digestive manifestations of Covid-19 in children: a retrospective study.

Background: The world is currently facing a pandemic due to a new species of the Coronaviridae family called SARS-CoV-2, discovered in the city of Wuhan in China in December 2019. The WHO has named the resulting disease COVID-19 (Coronavirus Disease 2019). It has been a global health problem due to its major socio-economic damage. The aim of this study was to show the prevalence of gastrointestinal and hepatic manifestations in symptomatic children with COVID-19. Methods: We performed a retrospective study, including 36 symptomatic children infected by SARS-CoV-2 hospitalized at the mother and child hospital of university hospital of Mohammed VI, Marrakech in Morocco, over a period of 7 months. Clinical and biological manifestations of the digestive system were evaluated for all patients. Results: The digestive symptomatology came in second place after the respiratory manifestations. 14 patients (38.89 % of symptomatic patients) in our study had digestive symptoms on admission: 12 (33.33%) presented with diarrhea, 4 (11.11%) had abdominal pain and only one child (2.78%) had vomiting. Aspartate aminotransferase (AST) was elevated in one patient, while alanine transaminase (ALT) was elevated in 6 patients. The prothrombin level was normal in all patients. All patients were discharged with good general condition without morbidity and mortality. Conclusion: This study concludes with the high prevalence of digestive manifestations of COVID-19 in symptomatic children. There were no severe clinical or biological abnormalities in our study. Digestive manifestations during COVID-19 in children are frequent, which requires the awareness of health professionals.

Flaxseed extract reduces tissue accumulation and enhances urinary excretion of chondroitin sulphate in the rat: a possible new path in substrate reduction therapy for mucopolysaccharidosis.

CONTEXT: Chondroitin 6 sulphate (C6S) is a glycosaminoglycan (GAG) whose accumulation is notable in mucopolysaccharidosis type IVA and VII. Flaxseed, Linum usitatissimum L. (Linaceae) (FS), is reported to have comparable properties to those of soybean, a source of genistein, a potential new treatment for MPSs. OBJECTIVE: We assess the effect of total ethanol flaxseed extract (EFSE) in an animal model of C6S accumulation. MATERIALS AND METHODS: The study was performed in adult male Wistar rats (n = 24) for 15 successive days. The animals were divided into four groups: (1) control injected with physiological saline buffer, (2) intoxicated rats injected intraperitoneally with C6S, (3) intoxicated with C6S and treated with EFSE, and (4) treated with EFSE. All groups were subjected to histopathological and biochemical studies. The antioxidant and phytochemical properties of EFSE were examined. RESULTS: Dry EFSE contains total phenols (6.28 mg EAG/g), condensed tannins (2.98 mg ECAT/g) and flavonoids (0.44 mg ECAT/g) with high antioxidant potential [RPE (IC50 = 8.37 ± 0.176), DPPH (IC50 = 12.79 ± 0.273)]. The LD50 is higher than 5000 mg/kg. The histopathological examination showed an accumulation of C6S in the C6S intoxicated group, which disappeared in the C6S-EFSE treated group. GAGs assays showed an increased excretion in the C6S intoxicated group and increased excretion of 14% in the C6S-EFSE group compared to the C6S group. DISCUSSION AND CONCLUSIONS: EFSE showed significant potential for chelation. Its use for the treatment of GAG accumulation could be suggested and generalized to a larger study population.

Implementation of a prospective study for enhancing surveillance of invasive bacterial infections in North Africa.

OBJECTIVES: We implemented a project named MENINGSTOP in three countries of North Africa (Algeria, Morocco and Tunisia). The main objective was to use real-time PCR to detect, identify and type the three main agents (Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae) responsible for invasive bacterial infections (IBI). METHODS: The protocol of WHO and US CDC for real-time PCR was used to detect and type the three bacterial agents in clinical samples. We also designated two quality exercises using an external interlaboratory study and cross-testing of 10% of randomly selected samples. RESULTS: Among the 752 samples tested, 18% were positive for one of the three agents. N. meningitidis was the most frequent globally reaching 9% of all samples (7% to 17% range) followed by S. pneumoniae 8% of all samples (6% to 15%). Group B meningococci was the most frequent (74% of all positive samples for meningococci and ranging from 50% to 90%). Quality assurance showed >85% correlation scores. CONCLUSIONS: Real-time PCR can help improving epidemiological surveillance. Data confirm the prevalence of meningococci B. Our project adds a reliable tool to enhance surveillance and to help decision making in vaccination strategies against IBI.

Varicella Zoster Virus Meningitis with Absence of Rash in an Immunocompetent Child.

Only a few cases in the literature have ever reported the reactivation of the varicella zoster virus (VZV) in children especially in the case of immunocompetent patients. It is an uncommon situation that may lead to several neurological complications. We report varicella zoster virus (VZV) meningitis in a 14-year-old healthy boy with no antecedent of rash. On his cerebrospinal fluid (CSF) examination, VZV DNA was detected. The rapid HIV test was negative. The treatment using acyclovir (20 mg/kg/8h) was effective, and the child's clinical condition rapidly improved.

Update of a colorimetric method for quantitative determination of galactose in blood samples: A simple and rapid method for the early detection of inherited metabolic diseases.

BACKGROUND: A colorimetric microassay for the quantitative determination of galactose in the blood was taken and updated. This method helps in diagnosis and follow-up of several inherited metabolic diseases connected to galactose metabolism deficiency such as galactosemia, glycogenosis, glycosylation, tyrosinemia and citrin deficiency. Galactose assay in the blood presents difficulties due to interference with glucose. In this study, we update a method to get around these difficulties. METHOD: This procedure was based on the incubation of whole blood with orcinol in a strongly acidic solution to form a galactose and glucose complexes able to absorb at two different wavelengths. RESULTS: The standard curve analysis for the individual solutions of these two sugars showed a wide range of linearity from 0 to 200 mg / l. Under optimal experimental conditions, the stirring time of the orcinol is 3 minutes, the heating time of the reaction is 20 minutes at 56 ° C, and the duration of the incubation in the dark is 40 minutes. The analysis is carried out on fresh blood. The maximum absorbance of galactose and glucose is respectively 569 nm and 421 nm. An adapted diagnosis algorithm was developed based on our results. CONCLUSION: this method could help in screening and identifying patients with hypergalactosemia that need further investigations. It could represent a promising method for neonatal screening in countries with limited resources.

Hydropneumothorax Revealing a Pneumoblastoma in Children.

Pneumoblastoma is a rare primary childhood tumor. We report the observation of an infant aged 2 years and 8 months who presented with dry cough and dyspnea. The physical examination found mixed pleural effusion syndrome on the right. The chest X-ray revealed a right pneumothorax. Biology has shown leukocytosis at 16,000/mm3. The CT scan revealed parenchymal air cystic lesions affecting the outer segment of the middle lobe mimicking a pulmonary malformation. Thoracic drainage brought back 100 ml of the fluid. Two months later, when a pyopneumothorax appeared, a medium lobectomy was performed. Pathological study specimen showed a high-grade type II pneumoblastoma The extension assessment identified a secondary hepatic location. Chemotherapy has been indicated. This observation illustrates the diagnosis challenge of pneumoblastoma in children.

Laboratory abnormalities in children with novel Coronavirus Disease 2019.

The novel Coronavirus disease 2019 continues to be a worldwide pandemic. Yet, little is still known about the biological features of this emergent infection in children. In this prospective study, we collected 68 children infected with SARS-COV-2 from March 2020 to May 2020, in Marrakesh, Morocco. No severe cases were observed in this cohort, and 66% of the patients were asymptomatic. The main laboratory abnormalities were hematological, as we found Leucopoenia in 4.4% of the cases, hyperleukocytosis in 1.6%. Neutropenia was found in 5 patients (7%) and only 2 cases (3%) had Lymphopenia. The inflammation and coagulation biomarkers were normal in the majority of the cases, as for liver and kidney function. Lactate dehydrogenase (LDH) serum levels were elevated in 8 cases (11.67%). The COVID-19 in children seems to have mild course and better outcome than in adults, which impacts the laboratory findings in this category. More studies must be conducted to learn more about the laboratory abnormalities in pediatric COVID-19.

[An unusual case of cardiomyopathy showing carnitine palmitoyltransferase deficiency]. / Une cardiomyopathie révélant un déficit en carnitine palmitoyltransférase I: à propos d'un cas inhabituel.

Carnitine palmitoyltransferase deficiencies (CPD) are rare and caused by a defect in fatty acid oxidation. We here report the case of a 10-year-old patient with no particular previous history presenting with acute dyspnea associated with productive cough, fever and impaired general condition. The patient was polypneic with tachycardia, mitral systolic murmur and no sign of heart failure. Chest x-ray showed cardiomegaly and echocardiography revealed hypokinetic dilated cardiomyopathy. Carnitine palmitoyltransferase deficiency was diagnosed. Management was based on treatment for heart disease and strict hypopidic and hyperglucidic diet. Three months later, the patient presented with decompensated heart failure due to infection caused by antibiotic-resistant Aeromonas caviae identified in blood culture. CPD should be suspected in patients with dilated cardiomyopathy. This would enable early management which influences prognosis.

Toxic shock syndrome and pyomyositis: about an unusual case.

Pyomyositis is a pyogenic infection of skeletal muscle with abscess formation. It is a rare disease with nonspecific symptoms which requires a rapid diagnosis and treatment. Magnetic resonance imaging is considered the gold standard for early diagnosis and to rule out other etiologies. This article reports an atypical presentation of pyomyositis revealed by a toxic staphylococcal shock syndrome in an 8-year-old boy.

Case Report of Central Precocious Puberty in a Female: Role of Environmental Pollutants?

A 5-year-old girl was brought to Department of Pediatric Endocrinology and Diabetes for premature breast development since 4 months. Her medical antecedents and family history were uneventful. From investigations she was diagnosed as a case of central precocious puberty. Identification of pesticides in farms surrounding their house indicates that this early stimulation of the hypothalamic-pituitary-gonadal axis was linked to the estrogen-like activity of endocrine-disrupting compounds.

Usefulness of urinary glycosaminoglycans assay for a mucopolysaccharidosis-specific screening.

BACKGROUND: Mucopolysaccharidoses (MPS), a group of inherited metabolic disorders characterized by the accumulation of glycosaminoglycans, can be diagnosed early through newborn screening programs. Establishing newborn screening in Morocco is a challenging task for multiple economic and social reasons. Screening in a Moroccan population using 1,9-dimethylmethylene blue urinary glycosaminoglycan (GAG) assays may allow for an earlier diagnosis of MPS. We studied the feasibility of implementing screening in Moroccan children as an alternative to national newborn screening. We determined the reference ranges for GAGs in the Moroccan population, their stability during transport, the effectiveness of this test as a screening procedure for MPS in patients, and its use as a screening test for MPS in the Imssouane region, where the rate of consanguineous marriage is 38%. METHODS: Using dimethylmethylene blue assays, urine samples of 47 MPS patients were analyzed, together with urine samples from healthy controls (n = 368, age ranging from 1 month to 25 years), and from Imssouane region children (n = 350, age ranging from 6 months to 24 month). Precision, linearity, recovery, limits, and stability were tested. RESULTS: Urinary GAGs reference values are age and ethnicity dependent. The validation parameters established displayed great precision and accuracy leading to recoveries according to internationally accepted values for bioanalytical methods. Urinary GAGs were stable for a maximum of 7 weeks at 40 °C. Screening of Imssouane children resulted in the detection of a 6-month-old child, diagnosed with MPS I. CONCLUSIONS: Our results demonstrate the usefulness of quantifying glycosaminoglycans for early screening of MPS.

Implementation of an Affordable Method for MPS Diagnosis from Urine Screening to Enzymatic Confirmation: Results of a Pilot Study in Morocco.

BACKGROUND: Rapid and accurate diagnosis of mucopolysaccharidoses (MPS) is still a challenge due to poor access to screening and diagnostic methods and to their extensive clinical heterogeneity. The aim of this work is to perform laboratory biochemical testing for confirming the diagnosis of mucopolysaccharidosis (MPS) for the first time in Morocco. METHODS: Over a period of twelve months, 88 patients suspected of having Mucopolysaccharidosis (MPS) were referred to our laboratory. Quantitative and qualitative urine glycosaminoglycan (GAG) analyses were performed, and enzyme activity was assayed on dried blood spots (DBS) using fluorogenic substrates. Enzyme activity was measured as normal, low, or undetectable. RESULTS: Of the 88 patients studied, 26 were confirmed to have MPS; 19 MPS I (Hurler syndrome; OMIM #607014/Hurler-Scheie syndrome; OMIM #607015), 2 MPS II (Hunter syndrome; OMIM #309900), 2 MPS IIIA (Sanfilippo syndrome; OMIM #252900), 1 MPS IIIB (Sanfilippo syndrome; OMIM #252920) and 2 MPS VI (Maroteaux-Lamy syndrome; OMIM #253200). Parental consanguinity was present in 80.76% of cases. Qualitative urinary glycosaminoglycan (uGAGs) assays showed abnormal profiles in 31 cases, and further quantitative urinary GAG evaluation and Thin Layer Chromatography (TLC) provided important additional information about the likely MPS diagnosis. The final diagnosis was confirmed by specific enzyme activity analysis in the DBS samples. CONCLUSIONS: The present study shows that the adoption of combined urinary substrate analysis and enzyme assays using dried blood spots can facilitate such diagnosis, offer an important tool for an appropriate supporting care, and a specific therapy, when available.

[Bird fancier's disease in a child: about a rare and unusual case]. / La maladie du poumon des éleveurs d´oiseaux chez un enfant: à propos d´un cas rare et inhabituel.

Bird fancier's disease falls within the spectrum of hypersensitivity pneumonitis secondary to immuno-allergic reaction to avian antigens. This occurs only rarely in children. It is found in two-thirds of patients with hypersensitivity pneumonitis. Diagnosis is not so easy. It is based on a body of clinical evidence. We here report the peculiar case of a 7-year-old girl with a family history of atopic disease initially treated as asthma based on the presence of wheezing and dyspnea and cough without improvement. The patient had worsening of symptoms such as dyspnea at rest complicated by cyanosis in respiratory distress. All of this took place in a context of alteration of general state. Clinical examination showed growth retardation, perioral cyanosis with digital hippocratism. Lung auscultation revealed bilateral crackling sounds. Chest X-ray objectified bilateral interstitial syndrome. Chest computed tomography (CT) scan showed diffuse ground-glass opacities. Laboratory tests revealed hypereosinophilia with hyper-IgE and excluded tuberculosis, cystic fibrosis, immune deficiency. In a second stage interview contact with birds was reported. Serological tests for bird fancier's disease were positive. The patient received inhaled corticosteroids associated with avoidance of exposure to birds. After a follow-up of 2 months, outcome was favorable. Given that the signs of bird fancier's disease are non-specific, this should be suspected in patients with respiratory symptoms associated with exposure to avian antigens.

Strengthening national teams of experts to support HPV vaccine introduction in Eastern Mediterranean countries: Lessons learnt and recommendations from an international workshop.

Several countries have started to introduce the HPV vaccine into their national immunisation programme, with the majority of these countries being high or upper-middle income countries. Currently, 91 countries have introduced the HPV vaccine globally. One of the regions lagging behind in the introduction of the HPV vaccine is the Eastern Mediterranean Region, with currently only Libya and the United Arab Emirates having introduced the HPV vaccine. In order to support countries in the Eastern Mediterranean Region with their decision-making process for HPV vaccine introduction, a regional workshop was organised to explore the current status of HPV vaccine introduction plans in the Eastern Mediterranean countries, gaps in information about HPV disease burden in the region and the need for quality HPV data to make an informed decision to introduce the HPV vaccine, socio-cultural and religious challenges with HPV vaccine introduction, and the role of NITAGs in formulating recommendations for HPV vaccine introduction. Participating countries reflected on their respective status of decision making process about HPV vaccine introduction; they discussed any needs for operational research to support the decision-making process; and highlighed technical and financial support that might be required from partners to assist with HPV vaccine introduction. Recommendations were made on how to advance the decision-making process for HPV vaccine introduction. The workshop increased the awareness of the need of data on burden of disease and the associated benefits of HPV vaccination in Eastern Mediterranean countries. The importance of collaboration between different programmes including: immunisation, adolescent health, school health, sexual and reproductive health and cancer control programmes was clearly emphasized.

[Cerebral venous thrombosis in children: about a series of 12 cases]. / Thrombose veineuse cérébrale de l'enfant: à propos d'une série de 12 cas.

Cerebral venous thrombosis (CVT) is rare in children. Its clinical features and its cause vary. Prognosis is dreadful due to the risk of death and neurosensory sequelae. This study aims to examine the clinical, radiological and etiological profile of CVTs in children and to evaluate the role of antithrombotic treatment. We conducted a retrospective study in the Department of Paediatrics and Paediatric Resuscitation at the Center Hospital University Mohammad VI (CHU) in Marrakech, Morocco, over a period of nine years and ten months (January 2008-October 2018). We collected data from the medical records of all patients aged between 1 months and 15 years with CVT confirmed by imaging. We listed 12 cases of CVT. The average age of patients was 6.4 years. Sex ratio was 1.4. Acute onset occurred in 7 cases. The main clinical features of CVT included seizures (7 cases), focal neurologic signs (7 cases) and signs of intracranial hypertension (IH) (6 cases). CT scan and/or magnetic resonance imaging (MRI) revealed an involvement of the superficial venous network in 8 cases and extended venous involvement in 3 cases. In six cases CVT was caused by an infection, with a case of dehydration, two cases of systemic disease and a case of homocystinuria. However, the cause of the disease was unknown in two patients. Seven children were treated with antithrombotic therapy with good clinico-radiological outcome in 5 cases. Two children died and 3 others had neurological sequelae. In children, CVTs are characterized by a vast variety of clinical features and causes. The effect of anticoagulant therapy was demonstrated despite the absence of a standardized therapeutic protocol.

[Acceptability of human papilloma virus vaccine: parent survey]. / Acceptabilité du vaccin antivirus du papillome humain: enquête auprès des parents.

This study aims to evaluate the extent of human papilloma virus vaccine awareness among parents of girls in vaccine age group, their acceptability of the vaccine and factors associated with refusal. We conducted a survey among parents of girls aged 8-15 years, followed-up for several diseases in the Department of Pediatrics at the University Hospital Mohamed VI in Marrakech, Morocco, on parents' profile, their awareness of cancer of the cervix, HPV and HPV vaccine, the acceptance of HPV vaccine for their daughters and the arguments related to refusal. Ninety six questionnaires were included in the analysis. Cancer of the cervix was considered frequent for 58% of parents. Only 5% of parents knew about HPV vaccine. Media were the source of information in all cases. Nobody had no idea about the cost of the vaccine and its tolerance. No girl was vaccinated against HPV. Sixty-three per cent of parents want their daughters to be vaccinated, this rate increased by 82% after awareness. Thirteen per cent of the parents were hesitant while 24% refused to vaccinate their daughters mainly due to side effects (51%). Parents refusing vaccine were predominantly males with medium socioeconomic status and cultural level and were unaware of the virus and the vaccine in 91% of cases. This study highlights the reasons for parents' reluctance towards HPV vaccine in order to optimize strategies for effective communication with parents.