High burden of viral respiratory co-infections in a cohort of children with suspected pulmonary tuberculosis.

BACKGROUND: The presentation of pulmonary tuberculosis (PTB) in young children is often clinically indistinguishable from other common respiratory illnesses, which are frequently infections of viral aetiology. As little is known about the role of viruses in children with PTB, we investigated the prevalence of respiratory viruses in children with suspected PTB at presentation and follow-up. METHODS: In an observational cohort study, children < 13 years were routinely investigated for suspected PTB in Cape Town, South Africa between December 2015 and September 2017 and followed up for 24 weeks. Nasopharyngeal aspirates (NPAs) were tested for respiratory viruses using multiplex PCR at enrolment, week 4 and 8. RESULTS: Seventy-three children were enrolled [median age 22.0 months; (interquartile range 10.0-48.0); 56.2% male and 17.8% HIV-infected. Anti-tuberculosis treatment was initiated in 54.8%; of these 50.0% had bacteriologically confirmed TB. At enrolment, ≥1 virus were detected in 95.9% (70/73) children; most commonly human rhinovirus (HRV) (74.0%). HRV was more frequently detected in TB cases (85%) compared to ill controls (60.6%) (p = 0.02). Multiple viruses were detected in 71.2% of all children; 80% of TB cases and 60.6% of ill controls (p = 0.07). At follow-up, ≥1 respiratory virus was detected in 92.2% (47/51) at week 4, and 94.2% (49/52) at week 8. CONCLUSIONS: We found a high prevalence of viral respiratory co-infections in children investigated for PTB, irrespective of final PTB diagnosis, which remained high during follow up. Future work should include investigating the whole respiratory ecosystem in combination with pathogen- specific immune responses.

National hospital readiness for COVID-19 in Lesotho: evidence for oxygen ecosystem strengthening.

SETTING: Sub-Saharan African country, Lesotho, during the SARS-CoV-2 COVID-19 pandemic. OBJECTIVE: To evaluate COVID-19 hospital capacity in Lesotho. DESIGN: We conducted a pragmatic assessment of all public hospitals in Lesotho using a WHO COVID-19 hospital assessment tool during July 2020 (baseline), with targeted follow-up in December 2020. We adapted the WHO tool into a questionnaire with a focus on hospital services and included oxygen ecosystem elements (pulse oximeters, oxygen, and advanced respiratory care). We converted qualitative questionnaire answers into quantitative ordinal variables and used standard statistics for analysis. RESULTS: At baseline, we found all 12 questionnaire domains demonstrate both hospital preparedness and weakness in infection prevention and control. Key baseline gaps were lack of a dedicated team, and insufficient personal protective equipment and space for donning and doffing. Substantial limitations were noted in hypoxemia diagnosis and treatment; information management and care coordination pathways were also suboptimal. Targeted follow-up after 5 months revealed improvement in the availability of pulse oximetry, oxygen capacity, and heated high-flow nasal cannula devices. CONCLUSION: Our baseline findings may reflect uneven early pandemic care quality; targeted follow-up suggests strengthening of the oxygen ecosystem.

LIEU: Pays d'Afrique subsaharienne, Lesotho, pendant la pandémie de COVID-19 due au SARS-CoV-2. OBJECTIF: Évaluer les capacités hospitalières relatives à la COVID-19 au Lesotho. MÉTHODE: Nous avons réalisé une évaluation pragmatique de tous les hôpitaux publics du Lesotho en utilisant un outil d'évaluation hospitalière de l'OMS pour la COVID-19 pendant le mois de juillet 2020 (point de référence), avec un suivi ciblé en décembre 2020. Nous avons adapté l'outil de l'OMS en un questionnaire se concentrant sur les services hospitaliers. Nous y avons inclus les éléments relatifs à l'écosystème de l'oxygène (oxymètres de pouls, oxygène et soins respiratoires avancés). Nous avons converti les réponses au questionnaire qualitatif en variables ordinales quantitatives et avons utilisé des méthodes statistiques standards pour l'analyse. RÉSULTATS: Au point de référence, nous avons observé que l'ensemble des 12 thèmes abordés par le questionnaire a indiqué une certaine capacité de réaction et des faiblesses en matière de prévention et de contrôle des infections des hôpitaux. Les lacunes clés initiales étaient l'absence d'une équipe dédiée, un équipement de protection individuelle insuffisant et un manque d'espace dédié pour enfiler et enlever cet équipement. Des limites conséquentes ont été observées pour le diagnostic et le traitement de l'hypoxémie. La gestion de l'information et la coordination des soins étaient également sous-optimales. Le suivi ciblé après 5 mois a révélé une amélioration en matière de disponibilité des oxymètres de pouls, des capacités en oxygène et des canules nasales chauffées à haut débit. CONCLUSION: Nos résultats au point de référence peuvent refléter une qualité des soins inégale au début de la pandémie. Le suivi ciblé suggère qu'il conviendrait de renforcer l'écosystème de l'oxygène.

A novel mechanism for chaperone-mediated telomerase regulation during prostate cancer progression.

Telomerase activity has been detected in >85% of all malignant human cancers, including 90% of prostate carcinomas. Using a well-characterized experimental prostate cancer system, we have found that telomerase activity is notably increased (>10-fold) during tumorigenic conversion. Expression profiles of the telomerase components (hTR and hTERT) revealed no substantive changes, which suggests a nontranscriptional mechanism for increased activity. Because the hsp90 chaperone complex functionally associates with telomerase, we investigated that relationship and found that along with telomerase activity, a number of hsp90-related chaperones are markedly elevated during transformation, as well as in advanced prostate carcinomas. Using the nontumorigenic cell protein extract as the source of telomerase, addition of purified chaperone components enhanced reconstitution of telomerase activity, which suggests a novel mechanism of increased telomerase assembly via a hsp90 chaperoning process during prostate cancer progression.

Non-invasive ventilation with bubble CPAP is feasible and improves respiratory physiology in hospitalised Malawian children with acute respiratory failure.

BACKGROUND: In low-income countries and those with a high prevalence of HIV, respiratory failure is a common cause of death in children. However, the role of non-invasive ventilation with bubble continuous positive airway pressure (bCPAP) in these patients is not well established. METHODS: A prospective observational study of bCPAP was undertaken between July and September 2012 in 77 Malawian children aged 1 week to 14 years with progressive acute respiratory failure despite oxygen and antimicrobial therapy. RESULTS: Forty-one (53%) patients survived following bCPAP treatment, and an HIV-uninfected single-organ disease subgroup demonstrated bCPAP success in 14 of 17 (82%). Compared with children aged ≧60 months, infants of 0-2 months had a 93% lower odds of bCPAP failure (odds ratio 0·07, 95% confidence interval 0·004-1·02, P  =  0·05). Following commencement of bCPAP, respiratory physiology improved, the average respiratory rate decreased from 61 to 49 breaths/minute (P  =  0·0006), and mean oxygen saturation increased from 92·1% to 96·1% (P  =  0·02). CONCLUSIONS: bCPAP was well accepted by caregivers and patients and can be feasibly implemented into a tertiary African hospital with high-risk patients and limited resources.

Bubble continuous positive airway pressure in a human immunodeficiency virus-infected infant.

World Health Organization-classified very severe pneumonia due to Pneumocystis jirovecii infection is recognized as a life-threatening condition in human immunodeficiency virus (HIV) infected infants. We recount the use of nasal bubble continuous positive airway pressure (BCPAP) in an HIV-infected African infant with very severe pneumonia and treatment failure due to suspected infection with P. jirovecii. We also examine the potential implications of BCPAP use in resource-poor settings with a high case index of acute respiratory failure due to HIV-related pneumonia, but limited access to mechanical ventilation.