Elisa López-Varela

High tuberculosis burden among people living with HIV in southern Mozambique

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]. High TB burden, in terms of incident cases and case fatality, in PLHIV in a rural district in Mozambique http://ow.ly/DdlZn

Non-tuberculous mycobacteria in children: muddying the waters of tuberculosis diagnosis

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.

Incidence of Tuberculosis Among Young Children in Rural Mozambique

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.

The role of Xpert MTB/RIF in diagnosing pulmonary tuberculosis in post-mortem tissues

The extent to which the Xpert MTB/RIF (Gene Xpert) contributes to tuberculosis (TB) diagnosis in samples other than sputum and cerebrospinal fluid remains uncertain. We aimed to assess the role of Xpert MTB/RIF for detecting M. tuberculosis in post-mortem tissues. We conducted a study among 30 complete diagnostic autopsies (CDA) performed at the Maputo Central Hospital (Mozambique). Lung tissues were screened for TB in all cases. In addition other tissues were tested when compatible lesions were identified in the histological exam. We used in-house real time PCR and LAMP assays to confirm the presence of M. tuberculosis DNA. The diagnosis of tuberculosis at death was established based on microbiological and histopathological results. Eight out of 30 cases (26.7%) were diagnosed of tuberculosis. Xpert had a sensitivity to detect TB in lung tissue of 87.5% (95% CI 47.3–99.7) and a specificity of 95.7% (95% CI: 78.1–99.9). In-house DNA amplification methods and Xpert showed 93.6% concordance for lung tissue and 100% concordance for brain and liver tissues. The final cause of death was attributable to tuberculosis in four cases. Xpert MTB/RIF may represent a valuable, easy-to perform technique for post-mortem TB diagnosis.

Radiological findings in young children investigated for tuberculosis in Mozambique.

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.

High Rates of Non-Tuberculous Mycobacteria Isolation in Mozambican Children with Presumptive Tuberculosis.

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.

Monitoring progress towards the first UNAIDS target: understanding the impact of people living with HIV who re-test during HIV-testing campaigns in rural Mozambique

Awareness of HIV‐infection goes beyond diagnosis, and encompasses understanding, acceptance, disclosure and initiation of the HIV‐care. We aimed to characterize the HIV‐positive population that underwent repeat HIV‐testing without disclosing their serostatus and the impact on estimates of the first UNAIDS 90 target.

Anonymity in HIV testing: implications for public health

1 UNAIDS. 90-90-90. An ambitious treatment target to help end the AIDS epidemic. 2014. http://www.unaids.org/sites/default/files/ media_asset/90-90-90_en_0.pdf (accessed March 1, 2017). 2 Sharma M, Ying R, Tarr G, Barnabas R. Systematic review and meta-analysis of community and facility-based HIV testing to address linkage to care gaps in sub-Saharan Africa. Nature 2015; 528: S77–85. 3 UNAIDS. Ending AIDS: progress towards the 90–90–90 targets. 2017. http://www.unaids. org/sites/default/files/media_asset/Global_ AIDS_update_2017_en.pdf (accessed Aug 17, 2017). 4 Fuente-Soro L, Lopez-Varela E, Augusto O, et al. Awareness of HIV status: the disclosure gap in rural Africa. Conference on retroviruses and opportunistic infections; Boston, USA; March 3–6, 2014. Abstract number 974. 5 Rosner D, Lauterstein RH, Fairchild AL, Bayer R. Unlinked anonymous testing for HIV in developing countries: a new ethical consensus. Public Health Rep 2012; 127: 115–18. 6 WHO. Consolidated guidelines on personcentred HIV patient monitoring and case surveillance. Geneva: World Health Organization, June 2017. http://www.who.int/ hiv/pub/guidelines/person-centred-hivmonitoring-guidelines/en/ (accessed Aug 2, 2017). In most countries in southern Africa, HIV diagnosis and care is provided at a rural level, and patient clinical records are mainly paper based. At the beginning of the epidemic, voluntary anonymous HIV testing was recommended to decrease fear, stigma, and discrimination associated with infection, by eliminating the social and psychological risks associated with HIV. This anonymity introduces several impediments to successful patient management, including the inability to: identify people living with HIV who undergo multiple HIV tests, despite being aware of their positive status; monitor the frequency of HIV seronegative individuals who undergo retesting; track individuals who test seropositive but are not enrolled in care, and therefore not on ART; test sexual partners and children of non-enrolled index cases; and, obtain accurate indicators of new HIV diagnoses, retained patients, or patients lost to follow-up. Countries such as South Africa, Malawi, and Mozambique have modified their HTC policies to include non-anonymous testing, thus acknowledging the shortcomings of anonymity; however, the historical weight of anonymity remains, and, many health facilities continue this practice. The widespread application of the HTC recommendations should include approaches to destigmatise and normalise HIV infection. “It will be impossible to end the epidemic without bringing HIV treatment to all who need it.” This statement by UNAIDS highlights the need for governments of HIV-endemic countries to support the abrogation of anonymous testing and facilitate linkage to care, as with other chronic conditions, and leave no one behind in the fight to end the HIV epidemic.

Adherence to Childhood Tuberculosis Treatment in Mozambique

Background There is limited literature regarding adherence rates for the treatment of tuberculosis (TB) in children. We aimed to describe TB treatment outcomes and adherence as well as to evaluate associated factors to poor adherence in Mozambican children. Methods This is a sub-study of a community TB incidence study among children <3 years of age. Incomplete adherence included the sum of lost-to-follow-up cases plus those with a delay of > 3 weeks to treatment completion. Results Fifty TB treatments were assessed. Forty-four (88.0%) patients completed treatment, two (4.0%) died during treatment and four (8.0%) were lost to follow-up. Incomplete adherence was observed in 31.3% (15 of 48) of cases and was associated with malnutrition or history of a migrant mother. Conclusion Although treatment outcome is overall good, there is still a significant proportion of incomplete adherence. Further larger paediatric TB cohorts and qualitative approaches are needed to assess and confirm potential factors for non-adherence.

Reengagement of HIV-infected children lost to follow-up after active mobile phone tracing in a rural area of Mozambique

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.