Pharmacokinetics, Tolerability, and Bacteriological Response of Rifampin Administered at 600, 900, and 1,200 Milligrams Daily in Patients with Pulmonary Tuberculosis.

In a multiple-dose-ranging trial, we previously evaluated higher doses of rifampin in patients for 2 weeks. The objectives of the current study were to administer higher doses of rifampin for a longer period to compare the pharmacokinetics, safety/tolerability, and bacteriological activity of such regimens. In a double-blind, randomized, placebo-controlled, phase II clinical trial, 150 Tanzanian patients with tuberculosis (TB) were randomized to receive either 600 mg (approximately 10 mg/kg of body weight), 900 mg, or 1,200 mg rifampin combined with standard doses of isoniazid, pyrazinamide, and ethambutol administered daily for 2 months. Intensive pharmacokinetic sampling occurred in 63 patients after 6 weeks of treatment, and safety/tolerability was assessed. The bacteriological response was assessed by culture conversion in liquid and solid media. Geometric mean total exposures (area under the concentration-versus-time curve up to 24 h after the dose) were 24.6, 50.8, and 76.1 mg · h/liter in the 600-mg, 900-mg, and 1,200-mg groups, respectively, reflecting a nonlinear increase in exposure with the dose (P < 0.001). Grade 3 adverse events occurred in only 2 patients in the 600-mg arm, 4 patients in the 900-mg arm, and 5 patients in the 1,200-mg arm. No significant differences in the bacteriological response were observed. Higher daily doses of rifampin (900 and 1,200 mg) resulted in a more than proportional increase in rifampin exposure in plasma and were safe and well tolerated when combined with other first-line anti-TB drugs for 2 months, but they did not result in improved bacteriological responses in patients with pulmonary TB. These findings have warranted evaluation of even higher doses of rifampin in follow-up trials. (This study has been registered at ClinicalTrials.gov under identifier NCT00760149.).

Key drivers of the TB epidemic in Suriname and priority actions to reduce incidence and mortality.

BACKGROUND: The WHO has recently published updated guidance for national strategic planning for TB. To address the TB epidemic comprehensively, it is necessary to conduct an epidemiological review as part of the situation analysis in the national strategic plan. METHODS: A descriptive epidemiological study was conducted using data from the national TB register for the period of 2010-2020. Simple frequencies were calculated for demographic and clinical variables. Trends in TB notification rates for the period 2010-2020 were also calculated. RESULTS: TB notification rates between 2011 (24.3/100,000) and 2019 (23.9/100,000) remained almost the same. The HIV status was known for 97.1% of TB cases, 22.7% of whom had HIV co-infection; 10.9% of patients with detected Mycobacterium tuberculosis were also resistant to rifampicin. Case fatality rate for all cases was 13.0%. Of the identified contacts, 66% were screened; 28.3-47.5% of those with TB infection started treatment, 63.3-75.9% of whom completed treatment. CONCLUSION: The review identified the following areas of concern: no decline in TB rates, high proportion of TB-HIV co-infection, high rate of resistance to rifampicin, high case-fatality rates and suboptimal contact investigation care cascade . The review was used to inform interventions and key actions to reduce TB morbidity and mortality in Suriname.

CONTEXTE: L'OMS a récemment publié des orientations actualisées pour la planification stratégique nationale de la TB. Pour faire face à l'épidémie de TB de manière globale, il est nécessaire de procéder à un examen épidémiologique dans le cadre de l'analyse de la situation du plan stratégique national. MÉTHODES: Une étude épidémiologique descriptive a été réalisée à partir des données du registre national de la TB pour la période 2010­2020. Des fréquences simples ont été calculées pour les variables démographiques et cliniques. Les tendances des taux de notification de la TB pour la période 2010­2020 ont également été calculées. RÉSULTATS: Les taux de notification de la TB entre 2011 (24,3/100 000) et 2019 (23,9/100 000) sont restés pratiquement les mêmes. Le statut VIH était connu pour 97,1% des cas de TB, dont 22,7% présentaient une co-infection par le VIH ; 10,9% des patients chez qui Mycobacterium tuberculosis avait été détecté étaient également résistants à la rifampicine. Le taux de létalité pour l'ensemble des cas était de 13,0%. Parmi les contacts identifiés, 66% ont fait l'objet d'un dépistage ; 28,3­47,5% des personnes infectées par la TB ont entamé un traitement, et 63,3­75,9% d'entre elles l'ont achevé. CONCLUSION: L'étude a permis d'identifier les domaines de préoccupation suivants : absence de baisse des taux de TB, proportion élevée de co-infection TB-VIH, taux élevé de résistance à la rifampicine, taux élevé de létalité et cascade de soins sous-optimale en matière d'investigation des contacts. L'étude a été utilisée pour informer les interventions et les actions clés visant à réduire la morbidité et la mortalité dues à la TB au Suriname.

The daily updated Dutch national database on COVID-19 epidemiology, vaccination and sewage surveillance.

The Dutch national open database on COVID-19 has been incrementally expanded since its start on 30 April 2020 and now includes datasets on symptoms, tests performed, individual-level positive cases and deaths, cases and deaths among vulnerable populations, settings of transmission, hospital and ICU admissions, SARS-CoV-2 variants, viral loads in sewage, vaccinations and the effective reproduction number. This data is collected by municipal health services, laboratories, hospitals, sewage treatment plants, vaccination providers and citizens and is cleaned, analysed and published, mostly daily, by the National Institute for Public Health and the Environment (RIVM) in the Netherlands, using automated scripts. Because these datasets cover the key aspects of the pandemic and are available at detailed geographical level, they are essential to gain a thorough understanding of the past and current COVID-19 epidemiology in the Netherlands. Future purposes of these datasets include country-level comparative analysis on the effect of non-pharmaceutical interventions against COVID-19 in different contexts, such as different cultural values or levels of socio-economic disparity, and studies on COVID-19 and weather factors.

TB in migrants residing in the Netherlands for at least 5 years at diagnosis, 2003-2018.

BACKGROUND: One of the challenges of TB elimination in low-incidence countries is the relatively high incidence of TB in migrants in these countries, even after multiple years of residence.OBJECTIVE: To describe and compare TB incidence and characteristics of migrant TB patients residing in the Netherlands for at least (≥)5 years at diagnosis with non-foreign-born TB patients in order to identify additional strategies that could reduce TB incidence in the former group.METHODS: A retrospective cohort study was conducted in migrants from Somalia, Morocco, Suriname, Turkey and Indonesia who were diagnosed with TB in the Netherlands in 2003-2018. TB incidences were calculated and multivariate logistic regression was used to identify differences in characteristics of TB patients per country of birth compared to non-foreign-born patients.RESULTS: TB incidence was highest in individuals from Somalia (162.5/100,000 population in 2018), followed by individuals from Morocco (37.1/100,000). In the non-foreign-born population, TB incidence was 1.2/100,000. Differences in characteristics of TB patients compared to non-foreign-born patients varied by country of birth.CONCLUSION: Our findings underline the importance of being aware of the heterogeneity of TB incidence and characteristics of patients in the migrant population residing ≥5 years in the Netherlands.

Is there an association between socioeconomic status and immune response to infant and childhood vaccination in the Netherlands?

INTRODUCTION: Socioeconomic status (SES) is a well-known determinant of health, but its relation with vaccine-induced immunity is less documented. We explored the association between SES and immunoglobulin G (IgG) levels against vaccine-preventable diseases in vaccinated children in the Dutch National Immunization Programme. METHODS: Data from a population-wide cross-sectional serosurvey in the Netherlands (2006-2007) were used. We compared geometric mean IgG concentrations/titers (GMC/T ratios) against measles, mumps, rubella, Haemophilus influenzae type b (Hib), Neisseria meningococcus type C, diphtheria, tetanus, poliovirus types 1,2,3 and pertussis in children of high versus low SES by linear regression analysis. We included 894 children (0-12 years) at one of two timeframes: 1 month to 1 year, or 1-3 years after vaccination. Mother's educational level and net household income served as binary indicators of SES. RESULTS: Of 58 possible associations of vaccine-induced antibody responses with educational level and 58 with income, 10 (9%) were statistically significant: 2 favouring (that is, with higher IgG levels at) high educational level (for Hib 1 m-1y after vaccination (GMC/T ratio: 2.99, 95%CI: 1.42-6.30) and polio 2 1 m-1y after the 9-year booster dose (1.14, 1.01-1.27)) and 8 favouring low income (polio 1, 2 and 3 1 m-1y after the 11-month booster (0.74, 0.58-0.94; 0.79, 0.64-0.97; 0.72, 0.55-0.95), polio 3 and pertussis 1-3y after the 11-month booster (0.70, 0.56-0.88; pertussis-prn: 0.60, 0.37-0.98; pertussis-ptx: 0.66, 0.47-0.95), mumps and rubella 1-3y after first vaccination (0.73, 0.55-0.97; 0.70, 0.55-0.90), and rubella 1 m-1y after second vaccination (0.83, 0.55-0.90)). After adjustment for multiple testing, none of the differences remained significant. There was no association between SES and proportion of children with protective IgG levels. CONCLUSION: In this explorative study, we found no consistent association between SES and immune response to vaccination in the Netherlands and no association with protective IgG levels. Additional studies in other settings should confirm this finding.

[COVID-19: recovering at home is not easy]. / Covid-19: thuis uitzieken valt niet mee.

OBJECTIVE: To gain insight into 1) the symptoms and the disease process of healthcare professionals (HCPs) who tested positive for COVID-19 and were not hospitalized because of mild symptoms, 2) the impact on their psychological well-being and 3) the experiences with (after) care and infection prevention measures. DESIGN: Explorative mixed-methods study. METHOD: The municipal public health services of Groningen and Fryslân invited all HCPs aged above 18 years who tested positive for COVID-19 between March 18th and April 3rd 2020 to fill out an online questionnaire (n = 109), on average one month after diagnosis. 18 HCPs participated in telephone interviews. RESULTS: Almost all HCPs mentioned fatigue as a long-term symptom, less frequently mentioned were, among other things, feeling physically weak and having a cold. Nearly half of them did not have a fever, two-thirds experienced stress. HCPs with comorbidity had more symptoms. The interviews showed that stress in particular occurred in families with children and because of uncertainty about the duration of infectiousness, with lack of good (after)care. Respondents experienced many negative reactions of people in their environment that felt stigmatizing. The isolation at home was considered bearable. CONCLUSION: A COVID-19 infection has a significant impact on physical and mental health, even in HCPs with mild symptoms. Persistent fatigue in particular hinders patients' functioning. The absence of fever in almost half of the respondents is remarkable, as well as the negative impact on psychological well-being. HCPs are also dissatisfied with after-care. Infection prevention measures were relatively well-adhered too.

Light-emitting diode with various sputum smear preparation techniques to diagnose tuberculosis.

SETTING: Mawenzi Regional Hospital, northern Tanzania. OBJECTIVE: To determine the value of light-emitting diode (LED) microscopy in diagnosing tuberculosis (TB) on bleach-treated and direct sputum smears. DESIGN: Sputum samples were collected from patients suspected of pulmonary TB who presented consecutively at the laboratory for smear evaluation between December 2009 and February 2010. Four smears were prepared from each specimen: conventional Ziehl-Neelsen (ZN), direct auramine, bleach centrifugation and bleach short sedimentation auramine smears. A light microscope was used to examine ZN smears and an LED fluorescent microscope to examine auramine-stained smears. RESULTS: Of the 267 sputum samples examined, respectively 78 (29%), 62 (23%), 74 (28%) and 48 (18%) were acid-fast bacilli (AFB) positive by the bleach centrifugation, bleach short sedimentation, direct auramine and ZN methods. Bleach centrifugation identified 30 (11%) more positives than ZN microscopy (P < 0.001), but was not superior to the direct auramine method (P = 0.46), which yielded 26 (10%) more positives than ZN microscopy (P < 0.001). Fluorescent LED required a shorter smear reading time (1.5 min on average), while the light microscope took 4 min (P < 0.001). CONCLUSION: Fluorescent LED microscopy with direct smear preparation is rapid and effective. Further studies are needed to ascertain its performance under routine conditions.

Community vs. facility-based directly observed treatment for tuberculosis in Tanzania's Kilimanjaro Region.

SETTING: Kilimanjaro Region, northern Tanzania. OBJECTIVE: To assess the effect of the introduction of the patient-centred tuberculosis treatment (PCT) approach-which allows tuberculosis (TB) patients to choose between community and facility-based directly observed treatment (DOT)-on treatment outcomes, and to analyse factors that contribute to opting for community DOT. DESIGN: Retrospective analysis of treatment outcomes of TB patients registered in the Kilimanjaro Region in 2007, differentiating between patients under community vs. facility-based DOT and taking into account demographic factors, disease classification, TB diagnosis and human immunodeficiency virus (HIV) status. RESULTS: Data from 2769 TB patients were analysed. Treatment success rates were respectively 81% and 70% in patients under community vs. facility-based DOT (P < 0.001). Cure rates were respectively 73% and 72% in smear-positive pulmonary TB patients under community vs. facility-based DOT (P = 0.62). Women, children, patients residing in districts other than Hai, patients with newly diagnosed TB and patients with smear-negative pulmonary TB were most likely to be under community DOT. CONCLUSION: The PCT approach was shown to be effective in terms of treatment outcomes. Treatment success rates were higher in patients who opted for community DOT than in patients who chose facility-based DOT (all cases), and were similar in smear-positive pulmonary TB patients under community or facility-based DOT.