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: Introduction: Antiretroviral therapy (ART) monitoring using viral load (VL) testing is challenging in high‐burden, limited‐resources settings. Chemokine IP‐10 (interferon gamma‐induced protein 10) strongly correlates with human immunodeficiency virus (HIV) VL. Its determination could serve to predict virological failure (VF) and to triage patients requiring VL testing. We assessed the field performance of a semi‐quantitative IP‐10 lateral flow assay (LFA) for VF screening in South Africa, and the cost‐effectiveness of its implementation in Mozambique. Methods: A cross‐sectional study was conducted between June and December 2021 in three primary health clinics in the Western Cape. Finger prick capillary blood was collected from adults on ART for ≥1 year for direct application onto the IP‐10 LFA (index test) and compared with a plasma VL result ≤1 month prior (reference test). We estimated the area under the receiver operating characteristic curves (AUC), sensitivity and specificity, to evaluate IP‐10 LFA prediction of VF (VL>1000 copies/ml). A decision tree model was used to investigate the cost‐effectiveness of integrating IP‐10 LFA combined with VL testing into the current Mozambican ART monitoring strategy. Averted disability‐adjusted life years (DALYs) and HIV acquisitions, and incremental cost‐effectiveness ratios were estimated. Results: Among 209 participants (median age 38 years and 84% female), 18% had VF. Median IP‐10 LFA values were higher among individuals with VF compared to those without (24.0 vs. 14.6; p Conclusions: The IP‐10 LFA is an effective VF triage test for routine ART monitoring. Combining a highly sensitive, low‐cost IP‐10 LFA‐based screening with targeted VL confirmatory testing could result in significant healthcare quality improvements and cost savings in settings with limited access to VL testing., INTRODUCTION For people living with human immunodeficiency virus (PLHIV) on antiretroviral therapy (ART), viral load (VL) testing is the gold standard approach to timely monitor treatment effectiveness, identify virological failure [...]

In Mozambique, targeted provider-initiated HIV testing and counselling (PITC) is recommended where universal PITC is not feasible, but its effectiveness depends on healthcare providers' training. This study aimed to evaluate the effect of a Ministry of Health training module in targeted PITC on the HIV positivity yield, and identify factors associated with a positive HIV test. We conducted a single-group pre-post study between November 2018 and November 2019 in the triage and emergency departments of four healthcare facilities in Manhiça District, a resource-constrained semi-rural area. It consisted of two two-month phases split by a one-week targeted PITC training module ("observation phases"). The HIV positivity yield of targeted PITC was estimated as the proportion of HIV-positive individuals among those recommended for HIV testing by the provider. Additionally, we extracted aggregated health information system data over the four months preceding and following the observation phases to compare yield in real-world conditions ("routine phases"). Logistic regression analysis from observation phase data was conducted to identify factors associated with a positive HIV test. Among the 7,102 participants in the pre- and post-training observation phases (58.5% and 41.5% respectively), 68% were women, and 96% were recruited at triage. In the routine phases with 33,261 individuals (45.8% pre, 54.2% post), 64% were women, and 84% were seen at triage. While HIV positivity yield between pre- and post-training observation phases was similar (10.9% (269/2470) and 11.1% (207/1865), respectively), we observed an increase in yield in the post-training routine phase for women in triage, rising from 4.8% (74/1553) to 7.3% (61/831) (Yield ratio = 1.54; 95%CI: 1.11–2.14). Age (25–49 years) (OR = 2.43; 95%CI: 1.37–4.33), working in industry/mining (OR = 4.94; 95%CI: 2.17–11.23), unawareness of partner's HIV status (OR = 2.50; 95%CI: 1.91–3.27), and visiting a healer (OR = 1.74; 95%CI: 1.03–2.93) were factors associated with a positive HIV test. Including these factors in the targeted PITC algorithm could have increased new HIV diagnoses by 2.6%. In conclusion, providing refresher training and adapting the current targeted PITC algorithm through further research can help reach undiagnosed PLHIV, treat all, and ultimately eliminate HIV, especially in resource-limited rural areas. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis remains one of the top ten causes of mortality globally. Children accounted for 12% of all TB cases and 18% of all TB deaths in 2022. Paediatric TB is difficult to diagnose with conventional laboratory tests, and chest radiographs remain crucial. However, in low-and middle-income countries with high TB burden, the capacity for radiological diagnosis of paediatric TB is rarely documented and data on the associated radiation exposure limited. Methods: A multicentre, mixed-methods study is proposed in three countries, Mozambique, South Africa and Spain. At the national level, official registry databases will be utilised to retrospectively compile an inventory of licensed imaging resources (mainly X-ray and Computed Tomography (CT) scan equipment) for the year 2021. At the selected health facility level, three descriptive cross-sectional standardised surveys will be conducted to assess radiology capacity, radiological imaging diagnostic use for paediatric TB diagnosis, and radiation protection optimization: a site survey, a clinician-targeted survey, and a radiology staff-targeted survey, respectively. At the patient level, potential dose optimisation will be assessed for children under 16 years of age who were diagnosed and treated for TB in selected sites in each country. For this component, a retrospective analysis of dosimetry will be performed on TB and radiology data routinely collected at the respective sites. National inventory data will be presented as the number of units per million people by modality, region and country. Descriptive analyses will be conducted on survey data, including the demographic, clinical and programmatic characteristics of children treated for TB who had imaging examinations (chest X-ray (CXR) and/or CT scan). Dose exposure analysis will be performed by children's age, gender and disease spectrum. Discussion: As far as we know, this is the first multicentre and multi-national study to compare radiological capacity, radiation protection optimization and practices between high and low TB burden settings in the context of childhood TB management. The planned comparative analyses will inform policy-makers of existing radiological capacity and deficiencies, allowing better resource prioritisation. It will inform clinicians and radiologists on best practices and means to optimise the use of radiological technology in paediatric TB management. [ABSTRACT FROM AUTHOR]

The WHO recommends preventive treatment for all pediatric contacts of a confirmed TB case, but coverage remains low in many high TB burden countries. We aimed to assess the coverage and adherence of the isoniazid preventive therapy (IPT) program among children under 5 years of age with household exposure to an adult pulmonary TB case in a rural district of Southern Mozambique. The estimated IPT coverage was 11.7%. A longer distance to the health center and lower age of the children hindered IPT initiation. Among patients who started IPT, 12/18 (69.9%) were adherent to the 6-month treatment. [ABSTRACT FROM AUTHOR]

Background: The implementation of quality HIV control programs is crucial for the achievement of the UNAIDS 90-90-90 targets and to motivate people living with HIV (PLWHIV) to link and remain in HIV-care. The aim of this mixed method cross-sectional study was to estimate the linkage and long-term retention in care of PLWHIV and to identify factors potentially interfering along the HIV-care continuum in southern Mozambique. Methods: A home-based semi-structured interview was conducted in 2015 to explore barriers and facilitators to the HIV-care cascade among individuals that had been newly HIV-diagnosed in community testing campaigns in 2010 or 2012. Linkage and long-term retention were estimated retrospectively through client self-reports and clinical records. Cohen's Kappa coefficient was calculated to measure the agreement between participant self-reported and documented cascade outcomes. Results: Among the 112 interviewed participants, 24 (21.4%) did not disclose their HIV-positive serostatus to the interviewer. While 84 (75.0%) self-reported having enrolled in care, only 69 (61.6%) reported still being in-care 3–5 years after diagnosis of which 17.4% reported having disengaged and re-engaged. An important factor affecting optimal continuum in HIV-care was the impact of the fear-based authoritarian relationship between the health system and the patient that could act as both driver and barrier. Conclusion: Special attention should be given to quantify and understand repeated cycles of patient disengagement and re-engagement in HIV-care. Strategies to improve the relationship between the health system and patients are still needed in order to optimally engage PLWHIV for long-term periods. [ABSTRACT FROM AUTHOR]

Introduction: Retention in care and reengagement of lost to follow-up (LTFU) patients are priority challenges in pediatric HIV care. We aimed to assess whether a telephone-call active tracing program facilitated reengagement in care (RIC) in the Manhiça District Hospital, Mozambique.Methods: Telephone tracing of LTFU children was performed from July 2016 to March 2017. Both ART (antiretroviral treatment) and preART patients were included in this study. LTFU was defined as not attending the clinic for ≥120 days after last attended visit. Reengagement was determined 3 months after an attempt to contact.Results: A total of 144 children initially identified as LTFU entered the active tracing program and 37 were reached by means of telephone tracing. RIC was 57% (95% CI, 39-72%) among children who could be reached versus 18% (95% CI, 11-26%) of those who could not be reached (p = 0.001).Conclusion: Telephone tracing could be an effective tool for facilitating reengagement in pediatric HIV care. However, the difficulty of reaching patients is an obstacle that can undermine the program. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) remains an important public health concern, especially in poorly resourced settings. TB diagnosis is challenging, particularly for children, who are the most vulnerable to its′ impacts. Lack of knowledge and awareness of the disease compromises prompt diagnosis and treatment compliance. Objective: To gain insights regarding caretakers′ knowledge of the aetiology and prevention of paediatric TB in southern Mozambique, to describe their care-seeking behaviours and to assess the acceptability of diagnostic procedures. Methods: A total of 35 caretakers were interviewed, all of which had children with TB compatible symptoms. Eleven were caretakers of children diagnosed with TB at the health facility, 11 of children for whom TB was excluded as a diagnosis at the health facility and 13 of children with TB compatible symptoms identified in the community. The first two groups took part in a TB incidence study, while the third group did not. All underwent the same semi-structured interviews, the results of which were analysed and compared using content analysis. Results: Even when confronted with signs suggestive of TB, most caretakers never suspected it or misinterpreted the signs, even among caretakers with TB and TB contacts. There was limited knowledge of TB, except among those undergoing treatment. The transgression of social norms was often presented as an explanation for TB in parallel to medically sound causes. The use of traditional care for prevention is widespread, but it varied for treatment purposes. TB diagnostic procedures were considered painful but were unanimously tolerated. Conclusions and significance: Misconceptions of paediatric TB, associated complex care-seeking itineraries and negative feelings of the diagnostic procedures may result in delays, low adherence and lost to follow-up, which needs to be addressed by adequately framed health promotion approaches. [ABSTRACT FROM AUTHOR]

Introduction: Non-tuberculous mycobacteria (NTM) can cause disease which can be clinically and radiologically undistinguishable from tuberculosis (TB), posing a diagnostic and therapeutic challenge in high TB settings. We aim to describe the prevalence of NTM isolation and its clinical characteristics in children from rural Mozambique. Methods: This study was part of a community TB incidence study in children <3 years of age. Gastric aspirate and induced sputum sampling were performed in all presumptive TB cases and processed for smear testing using fluorochrome staining and LED Microscopy, liquid and solid culture, and molecular identification by GenoType® Mycobacterium CM/AS assays. Results: NTM were isolated in 26.3% (204/775) of children. The most prevalent NTM species was M. intracellulare (N = 128), followed by M. scrofulaceum (N = 35) and M. fortuitum (N = 9). Children with NTM were significantly less symptomatic and less likely to present with an abnormal chest radiograph than those with M. tuberculosis. NTM were present in 21.6% of follow-up samples and 25 children had the same species isolated from ≥2 separate samples. All were considered clinically insignificant and none received specific treatment. Children with NTM isolates had equal all cause mortality and likelihood of TB treatment as those with negative culture although they were less likely to have TB ruled out. Conclusions: NTM isolation is frequent in presumptive TB cases but was not clinically significant in this patient cohort. However, it can contribute to TB misdiagnosis. Further studies are needed to understand the epidemiology and the clinical significance of NTM in children. [ABSTRACT FROM AUTHOR]

Background: In Mozambique, there is limited data regarding the monitoring of Tuberculosis (TB) treatment results and determinants of adverse outcomes under routine surveillance conditions. The objectives of this study were to evaluate treatment outcomes among TB patients, analyze factors associated with a fatal outcome and determine the proportion of deaths attributable to TB in the district of Manhiça, Southern Mozambique.Methods: This is a retrospective observational study based on TB patients diagnosed in the period 2011-2012. We used three different data sources: a) TB related variables collected by the National TB Control Program in the district of Manhiça for all TB cases starting treatment in the period 2011-2012. b) Population estimates for the district were obtained through the Mozambican National Statistics Institute. c) Deaths and other relevant demographic variables were collected from the Health and Demographic Surveillance System at Manhiça Health Research Center. WHO guidelines were used to define TB cases and treatment outcomes.Results: Of the 1957 cases starting TB treatment in the period 2011-2012, 294 patients (15.1 %) died during anti-tuberculous treatment. Ten per cent of patients defaulted treatment. The proportion of patients considered to have treatment failure was 1.1 %. HIV infection (OR 2.73; 95 % CI: 1.70-4.38), being male (OR: 1.39; 95 % CI 1.01-1.91) and lack of laboratory confirmation (OR: 1.54; 95 % CI 1.12-2.13) were associated with dying during the course of TB treatment (p value <0.05). The contribution of TB to the overall death burden of the district for natural reasons was 6.5 % (95 % CI: 5.5-7.6), higher for males than for females (7.8 %; 95 % CI: 6.1-9.5 versus 5.4 %; 95 % CI: 4.1-6.8 respectively). The age group within which TB was responsible for the highest proportion of deaths was 30-34 among males and 20-24 among females (20 % of all deaths in both cases).Conclusion: This study shows a very high proportion of fatal outcomes among TB cases starting treatment. There is a high contribution of TB to the overall causes of mortality. These results call for action in order to improve TB (and TB/HIV) management and thus treatment outcomes of TB patients. [ABSTRACT FROM AUTHOR]

Introduction: Chest radiography remains a critical tool for diagnosing intrathoracic tuberculosis (TB) in young children who are unable to expectorate. We describe the radiological findings in children under 3 years of age investigated for TB in the district of Manhiça, southern Mozambique, an area with a high prevalence of TB and HIV. Methods: Digital antero-posterior and lateral projections were performed and reviewed by two independent readers, using a standardized template. Readers included a local pediatrician and a pediatric radiologist blinded to all clinical information. International consensus case definitions for intra-thoracic TB in children were applied. Results: A total of 766 children were evaluated of whom 43 (5.6%) had TB. The most frequent lesion found in TB cases was air space consolidation (65.1%), followed by suggestive hilar lymphadenopathy (17.1%) and pleural effusion (7.0%). Air space consolidation was significantly more common in TB cases than in non-TB cases (odds ratio 8.9; 95% CI: 1.6-50.5), as were hilar lymphadenopathy (OR 17.2; 95% CI: 5.7-52.1). The only case with miliary infiltrates and 3 with pleural effusions occurred in HIV-infected children. Conclusion: Frequent air space consolidation complicates radiological distinction between TB and bacterial pneumonia in young children, underscoring the need for epidemiological contextualization and consideration of all relevant signs and symptoms. [ABSTRACT FROM AUTHOR]

Summary Non-tuberculous mycobacteria (NTM) are a large family of acid-fast bacteria, widespread in the environment. In children, NTM cause lymphadenitis, skin and soft tissue infections, and occasionally also lung disease and disseminated infections. These manifestations can be indistinguishable from tuberculosis on the basis of clinical and radiological findings and tuberculin skin testing. A diagnostic and therapeutic problem for respiratory physicians and other clinicians is therefore evident, particularly in settings where childhood tuberculosis is common, and bacteriological confirmation of any mycobacterial disease is difficult because of low availability of laboratory services in low-resource settings and the inherent paucibacillary nature of mycobacterial disease in childhood. The epidemiology of NTM varies by world region, and attempts to understand the burden of NTM disease and to identify risk factors in the paediatric population are hampered by inadequate mandatory NTM reporting and the overlap of clinical presentation with tuberculosis. The immune response to both NTM and Mycobacterium tuberculosis is based on cellular immunity and relies on the type-1 cytokine pathway. The disruption of this immune response by genetic or acquired mechanisms, such as mendelian susceptibility to mycobacterial disease or HIV, might result in predisposition to mycobacterial infections. Published diagnostic and management guidelines do not provide specific advice for diagnosis of NTM in children, from whom the quantity and quality of diagnostic samples are often suboptimum. Treatment of NTM infections is very different from the treatment of tuberculosis, depends on the strain and anatomical site of infection, and often involves antibiotic combinations, surgery, or both. In this Review, we summarise the epidemiological and clinical features of NTM infection in children, with a specific focus on the implications for public health in settings with a high endemic burden of childhood tuberculosis. [ABSTRACT FROM AUTHOR]

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Background: Tuberculosis (TB) remains a major cause of morbidity and death worldwide, with a significant impact on children, especially those under the age of 5 years. The complex diagnosis of pediatric TB, compounded by limited access to more accurate diagnostic tests, underscores the need for improved tools to enhance diagnosis and care in resource-limited settings., Objective: This study aims to present a telemedicine web platform, BITScreen PTB (Biomedical Image Technologies Screen for Pediatric Tuberculosis), aimed at improving the evaluation of pulmonary TB in children based on digital chest x-ray (CXR) imaging and clinical information in resource-limited settings., Methods: The platform was evaluated by 3 independent expert readers through a retrospective assessment of a data set with 218 imaging examinations of children under 3 years of age, selected from a previous study performed in Mozambique. The key aspects assessed were the usability through a standardized questionnaire, the time needed to complete the assessment through the platform, the performance of the readers to identify TB cases based on the CXR, the association between the TB features identified in the CXRs and the initial diagnostic classification, and the interreader agreement of the global assessment and the radiological findings., Results: The platform's usability and user satisfaction were evaluated using a questionnaire, which received an average rating of 4.4 (SD 0.59) out of 5. The average examination completion time ranged from 35 to 110 seconds. In addition, the study on CXR showed low sensitivity (16.3%-28.2%) but high specificity (91.1%-98.2%) in the assessment of the consensus case definition of pediatric TB using the platform. The CXR finding having a stronger association with the initial diagnostic classification was air space opacification (χ21>20.38, P<.001). The study found varying levels of interreader agreement, with moderate/substantial agreement for air space opacification (κ=0.54-0.67) and pleural effusion (κ=0.43-0.72)., Conclusions: Our findings support the promising role of telemedicine platforms such as BITScreen PTB in enhancing pediatric TB diagnosis access, particularly in resource-limited settings. Additionally, these platforms could facilitate the multireader and systematic assessment of CXR in pediatric TB clinical studies., (©Juan J Gómez-Valverde, Ramón Sánchez-Jacob, José Luis Ribó, H Simon Schaaf, Lara García Delgado, Alicia Hernanz-Lobo, Daniel Capellán-Martín, Ángel Lancharro, Orvalho Augusto, Alberto L García-Basteiro, Begoña Santiago-García, Elisa López-Varela, María J Ledesma-Carbayo. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 01.07.2024.)

Pneumonia is a leading cause of child mortality. However, currently we lack simple, objective, and accurate risk-stratification tools for pediatric pneumonia. Here we test the hypothesis that measuring biomarkers of immune and endothelial activation in children with pneumonia may facilitate the identification of those at risk of death. We recruited children <10 years old fulfilling WHO criteria for pneumonia and admitted to the Manhiça District Hospital (Mozambique) from 2010 to 2014. We measured plasma levels of IL-6, IL-8, Angpt-2, sTREM-1, sFlt-1, sTNFR1, PCT, and CRP at admission, and assessed their prognostic accuracy for in-hospital, 28-day, and 90-day mortality. Healthy community controls, within same age strata and location, were also assessed. All biomarkers were significantly elevated in 472 pneumonia cases versus 80 controls (p<0.001). IL-8, sFlt-1, and sTREM-1 were associated with in-hospital mortality (p<0.001) and showed the best discrimination with AUROCs of 0.877 (95% CI: 0.782 to 0.972), 0.832 (95% CI: 0.729 to 0.935) and 0.822 (95% CI: 0.735 to 0.908), respectively. Their performance was superior to CRP, PCT, oxygen saturation, and clinical severity scores. IL-8, sFlt-1, and sTREM-1 remained good predictors of 28-day and 90-day mortality. These findings suggest that measuring IL-8, sFlt-1, or sTREM-1 at hospital presentation can guide risk-stratification of children with pneumonia, which could enable prioritized care to improve survival and resource allocation., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KCK is a named inventor on a patent “Biomarkers for early determination of a critical or life-threatening response to illness and/or treatment response” held by the University Health Network. EL-V is an editorial board member of PLOS Global Public Health. The remaining authors declare no competing interests., (Copyright: © 2023 Balanza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Malaria remains, in 2022, a major cause of pediatric preventable mortality, with its major burden disproportionately circumscribed to sub-Saharan African countries. Although only ~1 to 2% of malaria cases can be considered severe and potentially life threatening, it is often challenging to identify them so as to prioritize adequate health care and resources. In a recent investigation, M. L. Sarangam, R. Namazzi, D. Datta, C. Bond, et al. (mBio 13:e01325-22, 2022, https://journals.asm.org/doi/10.1128/mbio.01325-22) studied intestinal barrier dysfunction and injury in Ugandan children hospitalized with severe malaria and in healthy community controls. By measuring circulating levels of four different and complementary biomarkers of gut barrier dysfunction and microbial translocation, they demonstrated that intestinal injury is common in pediatric severe malaria (18% of all cases) and is associated with increased mortality, acute kidney injury, acidosis, and endothelial activation. This commentary discusses the prognostic implications of these results, knowledge gaps that remain to be filled, and how findings could be potentially translated into effective interventions to improve outcomes in children with malaria.

The WHO recommends preventive treatment for all pediatric contacts of a confirmed TB case, but coverage remains low in many high TB burden countries. We aimed to assess the coverage and adherence of the isoniazid preventive therapy (IPT) program among children under 5 years of age with household exposure to an adult pulmonary TB case in a rural district of Southern Mozambique. The estimated IPT coverage was 11.7%. A longer distance to the health center and lower age of the children hindered IPT initiation. Among patients who started IPT, 12/18 (69.9%) were adherent to the 6-month treatment., (© The Author(s) [2023]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Genomic studies of the Mycobacterium tuberculosis complex (MTBC) might shed light on the dynamics of its transmission, especially in high-burden settings, where recent outbreaks are embedded in the complex natural history of the disease. To this end, we conducted a 1 year prospective surveillance-based study in Mozambique. We applied whole-genome sequencing (WGS) to 295 positive cultures. We fully characterized MTBC isolates by phylogenetics and dating evaluation, and carried out a molecular epidemiology analysis to investigate further associations with pre-defined transmission risk factors. The majority of strains (49.5%, 136/275) belonged to lineage (L) 4; 57.8 % of them (159/275) were in genomic transmission clusters (cut-off 5 SNPs), and a strikingly high proportion (45.5%) shared an identical genotype (0 SNP pairwise distance). We found two 'likely endemic' clades, comprising 67 strains, belonging to L1.2, which dated back to the late 19th century and were associated with recent spread among people living with human immunodeficiency virus (PLHIV). We describe for the first time the population structure of MTBC in our region, a high tuberculosis (TB)/HIV burden area. Clustering analysis revealed an unforeseen pattern of spread and high rates of progression to active TB, suggesting weaknesses in TB control activities. The long-term presence of local strains in Mozambique, which were responsible for large transmission among HIV/TB-coinfected patients, calls into question the role of HIV in TB transmission.

Millions of children are exposed to tuberculosis (TB) each year, many of which become infected with Mycobacterium tuberculosis . Most children can immunologically contain or eradicate the organism without pathology developing. However, in a minority, the organism overcomes the immunological constraints, proliferates and causes TB disease. Each year a million children develop TB disease, with a quarter dying. While it is known that young children and those with immunodeficiencies are at increased risk of progression from TB infection to TB disease, our understanding of risk factors for this transition is limited. The most immunologically disruptive process that can happen during childhood is infection with another pathogen and yet the impact of co-infections on TB risk is poorly investigated. Many diseases have overlapping geographical distributions to TB and affect similar patient populations. It is therefore likely that infection with viruses, bacteria, fungi and protozoa may impact on the risk of developing TB disease following exposure and infection, although disentangling correlation and causation is challenging. As vaccinations also disrupt immunological pathways, these may also impact on TB risk. In this article we describe the pediatric immune response to M. tuberculosis and then review the existing evidence of the impact of co-infection with other pathogens, as well as vaccination, on the host response to M. tuberculosis . We focus on the impact of other organisms on the risk of TB disease in children, in particularly evaluating if co-infections drive host immune responses in an age-dependent way. We finally propose priorities for future research in this field. An improved understanding of the impact of co-infections on TB could assist in TB control strategies, vaccine development (for TB vaccines or vaccines for other organisms), TB treatment approaches and TB diagnostics.