Scientific letter
Tuberculous meningitis due to Mycobacterium africanum in Spain, a case report
Meningitis tuberculosa por Mycobacterium africanum en España, a propósito de un caso
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true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "536" "paginaFinal" => "538" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Nuria Torrellas Bertran, Gemma Garcia Continente, Oscar Villarreal" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Nuria" "apellidos" => "Torrellas Bertran" "email" => array:2 [ 0 => "ntorrellas@hotmail.com" 1 => "ntorrellas@ssibe.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Gemma" "apellidos" => "Garcia Continente" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Oscar" "apellidos" => "Villarreal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Microbiología, Fundació Hospital de Palamós-SSIBE, Gerona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Diagnóstico por Imagen, Fundació Hospital de Palamós-SSIBE, Gerona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Medicina Familiar y comunitaria, ABS Torroella de Montgrí, Fundació Hospital de Palamós- SSIBE, Gerona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Meningitis tuberculosa por <span class="elsevierStyleItalic">Mycobacterium africanum</span> en España, a propósito de un caso" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1660 "Ancho" => 2133 "Tamanyo" => 189306 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Magnetic resonance images. Left: Coronal T1 sequence showing meningeal enhancement, predominantly in the basal cisterns. Right: Axial T2 FLAIR sequence; note the increase in ventricular size with fluid-fluid level in both occipital horns and areas of hyperintensity in the periventricular white matter.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We present the case of a 30-year-old patient, originally from Gambia and resident in Spain for two years, with no relevant medical history or known allergies. The patient came to Accident and Emergency at Palamós Hospital (regional hospital) with a month-long history of headache, photophobia, febricula and general malaise, accompanied in the previous week by hyporexia, generalised asthenia and night sweats. Initial testing, including complete blood count, urinary sediment and acute phase reactants, was normal.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Brain computerised tomography (CT) showed dilation of the supratentorial ventricular system with signs of activity and ependymal effusion. Lumbar puncture revealed cerebrospinal fluid (CSF) glucose levels of 30 mg/dl, proteins 349 mg/dl, leucocytes 350/mm<span class="elsevierStyleSup">3</span>, polymorphonuclear 72% and ADA 14 U/l, suggesting probable bacterial meningitis complicated by hydrocephalus. The patient was admitted to the Intermediate Care Unit (IMCU), and empirical treatment was started with ampicillin, aciclovir, rifampicin and dexamethasone.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Brain magnetic resonance imaging (MRI) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) showed findings consistent with acute meningitis with leptomeningeal uptake, ventriculitis and signs of ischaemic complication in the left internal capsule. CSF polymerase chain reaction (PCR) (GeneXpert MTB/RIF Ultra®) was positive for rifampicin-sensitive <span class="elsevierStyleItalic">Mycobacterium tuberculosis complex</span> (MTBC), and tuberculous meningitis was diagnosed. Tuberculosis treatment was adjusted with rifampicin, isoniazid, streptomycin, linezolid and dexamethasone.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">After 72 hours in the IMCU, the patient’s state of consciousness deteriorated (Glasgow Coma Scale 8) and he became haemodynamically unstable, requiring intubation and transfer to the Intensive Care Unit (ICU) in a more specialised hospital (Hospital J. Trueta, in Girona), where treatment was adjusted to rifampicin, isoniazid, pyrazinamide, ethionamide and dexamethasone.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In the ICU, the patient developed several complications, including left mydriasis and bradycardia secondary to hydrocephalus, receiving treatment with mannitol and external ventricular drainage (EVD), ventriculitis treated with ganciclovir, tracheobronchitis associated with intubation (due to multi-drug-sensitive <span class="elsevierStyleItalic">Escherichia coli</span>) and EVD infection treated with vancomycin and meropenem, eventually becoming haemodynamically stable but neurologically in a coma. Subsequently, the patient developed pneumonia secondary to bronchial aspiration, and treatment was changed to rifampicin, isoniazid, pyrazinamide and levofloxacin, with little response. The patient eventually died four weeks after his initial admission due to respiratory complications and hydrocephalus.</p><p id="par0030" class="elsevierStylePara elsevierViewall">At this same time, at the regional hospital, Lowenstein’s culture was found to be positive and the strain was sent to the reference centre (Vall d’Hebron Hospital) where <span class="elsevierStyleItalic">Mycobacterium africanum</span> (<span class="elsevierStyleItalic">M. africanum</span>) lineage 6 was identified, with the result being received a few days after the patient’s death.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The detection of <span class="elsevierStyleItalic">M. africanum</span> in cases of tuberculous meningitis in Spain introduces a new and worrying aspect to the epidemiology of this disease. Tuberculous meningitis represents a medical challenge due to its serious and potentially lethal nature<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> and is a rare manifestation of extrapulmonary tuberculosis.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Its prevalence in Spain is low, only making up 1% of all tuberculosis cases, but it has an alarming mortality rate of 40–50%, highlighting the urgency of early diagnosis and treatment. Limitations to the management of tuberculous meningitis<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> include its nonspecific clinical presentation, which delays diagnosis, and suboptimal antimicrobial regimens. In addition, although progress has been made with molecular tools, the sensitivity of the available diagnostic techniques is insufficient.</p><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">M. africanum</span> is a member of the MTBC. It was first described in 1968. Its distribution is variable across Africa; it has demonstrated an ability to adapt and evolve in different ecological environments.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> It is exclusively pathogenic for humans. The various lineages and sublineages of <span class="elsevierStyleItalic">M. africanum</span> (L5, L6 and L9) are located in specific areas of Africa. L6 strains are prevalent in countries such as Guinea Bissau, Sierra Leone and Gambia.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Considering that <span class="elsevierStyleItalic">M. africanum</span> is predominant in Africa and that the patient had resided in Spain for the previous two years, it is likely that he had become infected in his country of origin, but that he had remained asymptomatic. Being an immunocompetent patient with no previous history of tuberculosis or signs of pulmonary involvement at the time of his illness, it is of note that meningitis was the first sign of tuberculosis reactivation.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The finding of <span class="elsevierStyleItalic">M. africanum</span> is an indicator of transmissibility and latent tuberculosis infection (LTBI). In our clinical case, the application of recommendations<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> for the screening of LTBI, developed by healthcare professionals and epidemiologists, which include strategies for systematic detection and treatment in risk groups, could have facilitated early detection and appropriate treatment, possibly avoiding the fatal outcome. Preventing active TB through LTBI treatment is a critical component of the WHO’s strategy to eliminate TB.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Creating strategies is crucial to reduce transmission and establish epidemiological links that prevent the spread of the disease.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1660 "Ancho" => 2133 "Tamanyo" => 189306 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Magnetic resonance images. Left: Coronal T1 sequence showing meningeal enhancement, predominantly in the basal cisterns. Right: Axial T2 FLAIR sequence; note the increase in ventricular size with fluid-fluid level in both occipital horns and areas of hyperintensity in the periventricular white matter.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberculous meningitis: more questions, still too few answers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G.E. Thwaites" 1 => "R. van Toorn" 2 => "J. 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