R0: Host Longevity Matters.

The basic reproduction ratio, R0, is a fundamental concept in epidemiology. It is defined as the total number of secondary infections brought on by a single primary infection, in a totally susceptible population. The value of R0 indicates whether a starting epidemic reaches a considerable part of the population and causes a lot of damage, or whether it remains restricted to a relatively small number of individuals. To calculate R0 one has to evaluate an integral that ranges over the duration of the infection of the host. This duration is, of course, limited by remaining host longevity. So, R0 depends on remaining host longevity and in this paper we show that for long-lived hosts this aspect may not be ignored for long-lasting infections. We investigate in particular how this epidemiological measure of pathogen fitness depends on host longevity. For our analyses we adopt and combine a generic within- and between-host model from the literature. To find the optimal strategy for a pathogen from an evolutionary point of view, we focus on the indicator [Formula: see text], i.e., the optimum of R0 as a function of its replication and mutation rates. These are the within-host parameters that the pathogen has at its disposal to optimize its strategy. We show that [Formula: see text] is highly influenced by remaining host longevity in combination with the contact rate between hosts in a susceptible population. In addition, these two parameters determine whether a killer-like or a milker-like strategy is optimal for a given pathogen. In the killer-like strategy the pathogen has a high rate of reproduction within the host in a short time span causing a relatively short disease, whereas in the milker-like strategy the pathogen multiplies relatively slowly, producing a continuous small amount of offspring over time with a small effect on host health. The present research allows for the determination of a bifurcation line in the plane of host longevity versus contact rate that forms the boundary between the milker-like and killer-like regions. This plot shows that for short remaining host longevities the killer-like strategy is optimal, whereas for very long remaining host longevities the milker-like strategy is advantageous. For in-between values of host longevity, the contact rate determines which of both strategies is optimal.

Children´s priorities to improve the acceptability of MDR-TB treatment: qualitative data from South Africa.

BACKGROUND: Multidrug-resistant TB (MDR-TB) treatment for children frequently includes unpalatable drugs with low overall acceptability. This can negatively impact children and their caregivers´ treatment experiences and is an important contributor to poor adherence, and potentially, poor treatment outcomes. Children and their caregivers´ preferences for MDR-TB treatment are not well documented. We describe children and caregivers´ priorities to inform future MDR-TB treatment regimens.METHODS: We conducted a cross-sectional qualitative study at a TB hospital in South Africa using semi-structured interviews and participatory research activities with caregivers and children routinely diagnosed and treated for MDR-TB between June and August 2018.RESULTS: We conducted 15 interviews with children and their caregivers. Children ranged from 2 to 17 years of age (median age: 8.3 years). Children and caregivers had an overall negative experience of MDR-TB treatment. Children and caregivers described how future MDR-TB drugs and regimens should prioritise sweeter flavours, fewer pills, brighter colours, and formulations that are easy to prepare and administer and dispensed in colourful, small and discrete packaging.CONCLUSIONS: MDR-TB treatment acceptability remains low, and negatively impacts children and their caregivers´ treatment experiences. Improving the overall acceptability of MDR-TB treatment requires engaging with children and their caregivers to better understand their priorities for new treatment regimens and child-friendly formulations.

Early interactions with newly diagnosed TB patients in hospital can support linkage to care.

BACKGROUND: In South Africa, failure to link individuals diagnosed with TB to care remains an important gap in the TB care cascade. Compared to people diagnosed at primary healthcare (PHC) facilities, people diagnosed in hospitals are more likely to require additional support to be linked with PHC TB treatment services. We describe a patient interaction process to support linkage to TB care. METHODS: We implemented a step-by-step early patient interaction process with 84 adults newly diagnosed with TB in one district hospital in Khayelitsha, Cape Town, South Africa (August 2020-March 2021). We confirmed patient contact details, provided TB and health information, shared information on accessing care at PHC facilities and answered patients' questions in their home language. RESULTS: Most patients (54/84, 64%) provided updated telephone numbers, and 19/84 (23%) reported changes in their physical address. Patients welcomed practical and health information in their home language. The majority (74/84, 88%) were linked to care after hospital discharge. CONCLUSIONS: A simple early patient interaction process implemented as part of routine care is a feasible strategy to facilitate early TB treatment initiation and registration.

CONTEXTE: En Afrique du Sud, l'incapacité à relier les personnes dont la TB a été diagnostiquée aux soins reste une lacune importante dans la cascade des soins antituberculeux. Comparativement aux personnes diagnostiquées dans les établissements de soins de santé primaires (PHC), les personnes diagnostiquées dans les hôpitaux sont plus susceptibles d'avoir besoin d'un soutien supplémentaire pour être reliées aux services de traitement de la TB des PHC. Nous décrivons un processus d'interaction avec le patient pour favoriser le lien avec les soins antituberculeux. MÉTHODES: Nous avons mis en œuvre un processus d'interaction précoce, étape par étape, avec 84 adultes chez qui la TB a été récemment diagnostiquée dans un hôpital de district de Khayelitsha, au Cap, en Afrique du Sud (août 2020­mars 2021). Nous avons confirmé les coordonnées des patients, fourni des informations sur la TB et la santé, partagé des informations sur l'accès aux soins dans les établissements de PHC et répondu aux questions des patients dans leur langue maternelle. RÉSULTATS: La plupart des patients (54/84 ; 64%) ont fourni des numéros de téléphone actualisés, et 19/84 (23%) ont signalé des changements dans leur adresse physique. Les patients ont apprécié les informations pratiques et ceux ayant trait à la santé dans leur langue maternelle. La majorité d'entre eux (74/84 ; 88%) ont été reliés aux soins après leur sortie de l'hôpital. CONCLUSIONS: Un processus simple d'interaction précoce avec le patient, mis en œuvre dans le cadre des soins de routine, est une stratégie réalisable pour faciliter l'initiation et l'enregistrement précoce du traitement de la TB.

Reasons for poor uptake of TB preventive therapy in South Africa.

BACKGROUND: South Africa has one the highest TB and HIV burdens globally. TB preventive therapy (TPT) reduces the risk of TB disease and TB-related mortality in adults and children living with HIV and is indicated for use in TB-exposed HIV-negative individuals and children. TPT implementation in South Africa remains suboptimal. METHODS: We conducted a pragmatic review of TPT implementation using multiple data sources, including informant interviews (n = 134), semi-structured observations (n = 93) and TB patient folder reviews in 31 health facilities purposively selected across three high TB burden provinces. We used case descriptive analysis and thematic coding to identify barriers and facilitators to TPT implementation. RESULTS: TPT programme implementation was suboptimal, with inadequate monitoring even in health districts with well-functioning TB services. Health workers reported scepticism about TPT effectiveness, deprioritised TPT in practice and expressed divergent opinions about the cadres of staff responsible for implementation. Service- and facility-level barriers included ineffective contact tracing, resource shortages, lack of standardised reporting mechanisms and insufficient patient education on TPT. Patient-level barriers included socio-economic factors. CONCLUSIONS: Improving TPT implementation will require radically simplified and more feasible systems and training for all cadres of health workers. Partnership with communities to stimulate demand driven service uptake can potentially facilitate implementation.

CONTEXTE: L'Afrique du Sud a l'une des charges de TB et de VIH les plus élevées au monde. La thérapie préventive contre la TB (TPT) réduit le risque de TB maladie et de mortalité liée à la TB chez les adultes et les enfants vivant avec le VIH et est indiquée chez les personnes et les enfants séronégatifs exposés à la TB. La mise en œuvre du TPT en Afrique du Sud reste sous-optimale. MÉTHODES: Nous avons procédé à un examen pragmatique de la mise en œuvre du TPT à l'aide de plusieurs sources de données, notamment des entretiens avec des informateurs (n = 134), des observations semi-structurées (n = 93) et des examens de dossiers de patients atteints de TB dans 31 établissements de santé sélectionnés à dessein dans trois provinces fortement touchées par la TB. Nous avons utilisé une analyse descriptive des cas et un codage thématique pour identifier les obstacles et les facilitateurs de la mise en œuvre du programme TPT. RÉSULTATS: La mise en œuvre du programme TPT était sousoptimale, avec un suivi inadéquat, y compris dans les districts sanitaires où les services de lutte contre la TB fonctionnaient correctement. Les agents de santé ont fait part de leur scepticisme quant à l'efficacité de la TPT, n'ont pas accordé la priorité à la TPT dans la pratique et ont exprimé des opinions divergentes sur les cadres du personnel responsables de la mise en œuvre. Les obstacles au niveau des services et des établissements comprennent l'inefficacité de la recherche des contacts, la pénurie de ressources, l'absence de mécanismes de déclaration standardisés et l'insuffisance de l'éducation des patients sur la TPT. Les obstacles au niveau des patients comprenaient des facteurs socio-économiques. CONCLUSIONS: L'amélioration de la mise en œuvre des TPT nécessitera des systèmes radicalement simplifiés et plus réalisables ainsi qu'une formation pour tous les cadres du personnel de santé. Un partenariat avec les communautés pour stimuler l'adoption de services axés sur la demande peut potentiellement faciliter la mise en œuvre.

A novel approach for eliciting adolescent MDR-TB treatment tolerability: qualitative data from South Africa.

SETTING: Treatment tolerability among adolescents diagnosed with multidrug-resistant tuberculosis (MDR-TB) is underexplored. We present qualitative study data from adolescents participating in an observational cohort in the Western Cape, South Africa.OBJECTIVE: To elicit adolescent experiences of MDR-TB diagnosis and treatment with qualitative body-mapping activities and discussions.DESIGN: Adolescents in an observational MDR-TB cohort received routine toxicity and audiology screenings from clinicians. We enrolled eight participants (age 10-16 years) to participate in additional body-mapping activities and in-depth interviews. A thematic deductive analysis was conducted. We present a comparison of the clinical assessments and qualitative discussions.RESULTS: Adolescent participants reported few adverse effects on standard toxicity and audiology reports. Only nausea and vomiting were reported in >10% of cases, all of which were grade 1 (causing no/minimal interference) adverse effects (AEs). However, when comparing toxicity reports with qualitative body-mapping activities and interviews, we found previously unreported AEs (neurosensory alteration, neuromuscular weakness, pain); underestimated severity of AEs (nausea, itching); and missed psychosocial symptoms (signs of depression).CONCLUSION: Adolescents receiving treatment for MDR-TB experienced treatment-related AEs that were not reported during routine clinical assessments. Psychosocial experiences of adolescents are not taken into account. More research is needed to understand the experiences of this vulnerable group. We recommend that drug safety monitoring be adapted to include more creative and patient-driven reporting mechanisms for vulnerable groups, including children.