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.

Tuberculosis (TB) remains an important public health concern, and a leading cause of disease and death worldwide. Mozambique is one of the few high TB burden countries where TB figures have not improved in recent years, with an estimated TB incidence in 2013 of 552 cases per 100 000 population [1]. With 58% of all notified TB cases being HIV-positive, Mozambique also has one of the highest TB/HIV co-infection rates. Published data on the burden of TB or HIV disease in the country are scarce, and improving epidemiological surveillance has been identified as an urgent step to improve TB control [2]

Background: Tuberculosis (TB) contributes significantly to child morbidity and mortality. This study aimed to estimate the minimum community-based incidence rate of TB among children <3 years of age in Southern Mozambique. Methods: Between October 2011 and October 2012, in the Manhiça District Health and Demographic Surveillance System, we enrolled prospectively all presumptive TB cases younger than 3 years of age through passive and active case finding. Participants included all children who were either symptomatic or were close contacts of a notified adult smear-positive pulmonary TB. Children were clinically evaluated at baseline and follow-up visits. Investigation for TB disease included chest radiography, HIV and tuberculin skin testing as well as gastric aspirate and induced sputum sampling, which were processed for smear, culture and mycobacterial molecular identification. Results: During the study period, 13,764 children <3 years contributed to a total of 9575 person-year. Out of the 789 presumptive TB cases enrolled, 13 had TB culture confirmation and 32 were probable TB cases. The minimum community-based incidence rate of TB (confirmed plus probable cases) was 470 of 100,000 person-year (95% confidence interval: 343–629 of 100,000). HIV co-infection was present in 44% of the TB cases. Conclusion: These data highlight the huge burden of pediatric TB. This study provides one of the first prospective population-based incidence data of childhood tuberculosis and adds valuable information to the global effort of producing better estimates, a critical step to inform public health policy.

Introduction An estimated 30,000 children develop multidrug-resistant (MDR) tuberculosis (TB) each year, with only a small proportion diagnosed and treated. This field has historically been neglected due to a perception that children with MDR-TB are challenging to diagnose and treat. Diagnostic and therapeutic developments in adults have improved paediatric management, yet further paediatric-specific research and wider implementation of evidence-based practices are required. Areas covered This review combines the most recent data with expert opinion to highlight best practice in the evaluation, diagnosis, treatment and support of children and adolescents with MDR-TB disease. A literature search of PubMed was carried out on topics related to MDR-TB in children. This review provides practical advice on MDR-TB prevention and gives updates on new regimens and novel treatments. The review also addresses host-directed therapy, comorbid conditions, special populations, psychosocial support, and post-TB morbidity, as well as identifying outstanding research questions. Expert opinion Increased availability of molecular diagnostics has the potential to aid with the diagnosis of MDR-TB in children. Shorter MDR-TB disease treatment regimens have made therapy safer and shorter and further developments with novel agents and repurposed drugs should lead to additional improvements. The evidence base for MDR-TB preventive therapy is increasing.

Background: HIV-infected men have higher rates of delayed diagnosis, reduced antiretroviral treatment (ART) retention and mortality than women. We aimed to assess, by gender, the first two UNAIDS 90 targets in rural southern Mozambique. Methods: This analysis was embedded in a larger prospective cohort enrolling individuals with new HIV diagnosis between May 2014-June 2015 from clinic and home-based testing (HBT). We assessed gender differences between steps of the HIV-cascade. Adjusted HIV-community prevalence was estimated using multiple imputation (MI). Results: Among 11,773 adults randomized in HBT (7084 female and 4689 male), the response rate before HIV testing was 48.7% among eligible men and 62.0% among women (p<0.001). MI did not significantly modify all-age HIV-prevalence for men but did decrease prevalence estimates in women from 36.4%to 33.0%. Estimated proportion of HIV-infected individuals aware of their status was 75.9% for men and 88.9% for women. In individuals <25 years, we observed up to 22.2% disparity in awareness of serostatus between genders. Among individuals eligible for ART, similar proportions of men and women initiated treatment (81.2% and 85.9%, respectively). Fourfold more men than womenwere in WHO stage III/IV AIDS at first clinical visit. Once on ART, men had a twofold higher 18-month loss to follow-up rate than women. Conclusion: The contribution of missing HIV-serostatus data differentially impacted indicators of HIV prevalence and of achievement of UNAIDS targets by age and gender and men were missing long before the second 90. Increased efforts to characterize missing men and their needs will and their needs will allow us to urgently address the barriers to men accessing care and ensure men are not left behind in the UNAIDS 90-90-90 targets achievement.