Tuberculosis In HIV-infected Children Research Articles

Proportion of active tuberculosis among HIV-infected children after antiretroviral therapy in Ethiopia: A systematic review and meta-analysis.

Despite effectiveness of antiretroviral therapy in reducing mortality of opportunistic infections among HIV infected children, however tuberculosis (TB) remains a significant cause for morbidity and attributed for one in every three deaths. HIV-infected children face disproportionate death risk during co-infection of TB due to their young age and miniatures immunity makes them more vulnerable. In Ethiopia, there is lack of aggregated data TB and HIV mortality in HIV infected children. We conducted an extensive systematic review of literature using Preferred Reporting of Systematic Review and Meta-Analysis (PRISMA) guideline. Five electronic databases were used mainly Scopus, PubMed, Medline, Web of Science, and Google scholar for articles searching. The pooled proportion of TB was estimated using a weighted inverse variance random-effects meta-regression using STATA version-17. Heterogeneity of the articles was evaluated using Cochran's Q test and I2 statistic. Subgroup analysis, sensitivity test, and Egger's regression were conducted for publication bias. This met-analysis is registered in Prospero-CRD42024502038. In the final met-analysis report, 13 out of 1221 articles were included and presented. During screening of 6668 HIV-infected children for active TB occurrence, 834 cases were reported after ART was initiated. The pooled proportion of active TB among HIV infected children was found 12.07% (95% CI: 10.71-13.41). In subgroup analysis, the Oromia region had 15.6% (95%CI: 10.2-20.6) TB burden, followed by southern Ethiopia 12.8% (95%CI: 10.03-15.67). During meta-regression, missed isoniazid Preventive therapy (IPT) (OR: 2.28), missed contrimoxazole preventive therapy (OR: 4.26), WHO stage III&IV (OR: 2.27), and level of Hgb ≤ 10gm/dl (OR = 3.11.7) were predictors for active TB. The systematic review found a higher proportion of active TB in HIV-infected children in Ethiopia compared to estimated rates in end TB strategy. To prevent premature death during co-infection, implement effective TB screening and cases tracing strategies in each follow up is needed.

The incidence rate of tuberculosis and its associated factors among HIV-positive persons in Sub-Saharan Africa: a systematic review and meta-analysis

BackgroundTuberculosis, along with HIV, is the leading cause of mortality and morbidity globally. Despite the fact that several primary studies have been conducted on the incidence rate of tuberculosis in HIV-infected people in Sub-Saharan Africa, the regional-level tuberculosis incidence rate remains unknown. The objective of this study is to determine the tuberculosis incidence rate and its associated factors in HIV-infected people in Sub-Saharan Africa.MethodsA systematic review and meta-analysis were conducted by searching four databases for studies published in English between January 1, 2000, and November 25, 2022. The study was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. To assess the quality of the studies, the Joanna Briggs Institute critical appraisal checklist was used. A random-effects model meta-analysis was used to determine the pooled incidence of tuberculosis using STATA version 15. The I2 heterogeneity test was used to assess heterogeneity. Subgroup and sensitivity analyses were performed. Funnel plots and Egger’s regression tests were used to investigate publication bias. The pooled estimate predictors of tuberculosis incidence rate with a 95% confidence interval were also determined using the hazard ratio of each factor (HR).ResultsOut of a total of 3339 studies, 43 were included in the analysis. The overall pooled incidence rate of tuberculosis in HIV-infected people was 3.49 per 100 person-years (95% CI: 2.88–4.17). In the subgroup analysis, the pooled incidence rate of tuberculosis in HIV-infected children was 3.42 per 100 person-years (95% CI: 1.78, 5.57), and it was 3.79 per 100 person-years (95% CI: 2.63, 5.15) in adults. A meta-analysis revealed that underweight (AHR = 1.79, 95% CI: 1.61–1.96), low CD4 count (AHR = 1.23, 95% CI: 1.13–1.35), male gender (AHR = 1.43, 95% CI: 1.22–1.64), advanced WHO clinical stages (AHR = 2.29, 95% CI: 1.34–3.23), anemia (AHR = 1.73, 95% CI: 1.34–2.13), bedridden or ambulatory (AHR = 1.87, 95%), lack of isoniazid preventive therapy (AHR = 3.32, 95% CI: 1.08–2.28), and lack of cotrimoxazole (AHR = 1.68, 95% CI: 1.08–2.28) were risk factors for tuberculosis incidence. HIV patients who received antiretroviral therapy had a 0.53 times higher risk of acquiring tuberculosis than HIV patients who did not receive antiretroviral therapy (AHR = 0.53; 95% CI: 0.3–0.77).ConclusionIn this systematic review and meta-analysis study, the incidence rate of tuberculosis among HIV-positive people was higher than the WHO 2022 Africa regional estimated report. To reduce the incidence of tuberculosis among HIV patients, HIV patients should take isoniazid prevention therapy (IPT), cotrimoxazole prophylaxis, and antiretroviral therapy (ART) without interruption, as well as increase the frequency and diversity of their nutritional intake. Active tuberculosis screening should be increased among HIV-infected people.

Research Questions and Priorities for Pediatric Tuberculosis: A Survey of Published Systematic Reviews and Meta-Analyses.

Background Advancing a research agenda designed to meet the specific needs of children is critical to ending pediatric TB epidemic. Systematic reviews are increasingly informing policies in pediatric tuberculosis (TB) care and control. However, there is a paucity of information on pediatric TB research priorities. Methodology. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Library for systematic reviews and meta-analyses on any aspect related to pediatric TB published between 2015 and 2021. We used the UK Health Research Classification System (HRCS) to help us classify the research questions and priorities. Findings. In total, 29 systematic reviews, with 84 research questions, were included in this review. The four most common research topics in the area of detection were 43.33% screening and diagnosis of TB, 23.33% evaluation of treatments and therapeutic interventions, 13.34% TB etiology and risk factors, and 13.34% prevention of disease and conditions and promotion of well-being. The research priorities focused mainly on evaluating TB diagnosis by improving yield through enhanced in specimen collection or preparation and evaluating of bacteriological TB diagnostic tests. Other topics of future research were developing a treatment for TB in children, assessing the use of IPT in reducing TB-associated morbidity, evaluating the prioritization of an IPT-friendly healthcare environment, and providing additional guidance for the use of isoniazid in the prevention of TB in HIV-infected children. Conclusion There is a need for more systematic reviews on pediatric TB. The review identified several key priorities for future pediatric TB research mainly in the domain of (1) “Detection, screening and diagnosis,” “Development of Treatments and Therapeutic Interventions,” and “Prevention of Disease and Conditions, and Promotion of Well-Being.” These domains are very relevant in the research component of the roadmap towards ending TB in children. It also will serve as an additional action in the WHO End TB strategy.

Prevalence of tuberculosis among perinatally exposed to HIV and HIV-infected children and predictors of its development

Purpose of the study. To establish risk factors for tuberculosis (TB) in children perinatally exposed to HIV and HIV-infected for the development of corrective measures.Materials and methods. Outpatient records (form No. 025/y) of 216 children perinatally exposed to HIV and 121 children with HIV infection and their parents (281 individuals) were analyzed. The control group consisted of 100 healthy children. Epidemiological (descriptive, evaluative and analytical) and statistical research methods were used in the study.Results. The likelihood of contact with a patient with an active form of TB was significantly higher in perinatally exposed to HIV and HIV-infected children compared to children in the control group (p 0.001). The risk of TB in HIV-exposed children was 5.3 times higher in foci where both parents were HIV-infected than in foci formed by discordant couples (RR = 5.3; 95% CI 1.7–21.7). Children in study groups who were not vaccinated with BCG had the highest risk of TB compared to children in the control group (RR = 1.9; 95% CI 1.6–2.2).Conclusion. Risk factors for TB in children perinatally exposed to HIV are untimely vaccination against TB or its absence and living in the foci where both parents are HIV-infected. The predictors of the development of TB in HIV-infected children are household contacts with TB patient , late diagnosis of HIV infection, and late prescription of highly active antiretroviral therapy after the formation of severe immunosuppression.

Epidemiological aspects of tuberculosis in HIV infected children

The objective: to assess the methods and time of detection of tuberculosis and HIV infection in children with the co-infection, epidemiological risk factors to develop tuberculosis and effectiveness of preventive measures.Subjects and methods. 75 children in the age from 0 to 14 years old were enrolled in the study. The TB/HIV Group included 25 children with TB/HIV co-infection. The TB Group included 50 HIV negative children with tuberculosis, they made a comparison group.Results: out of 25 children with TB/HIV, only 18 (72%) were aware of perinatal exposure to HIV. HIV infection was confirmed in 11/25 (44%) children during the first months of life, in the remaining 14/25 (56%) it was confirmed later, the latest at 13 years old. In 4 children, HIV infection was detected during examination for tuberculosis. In the TB/HIV Group, in 14/25 (56%) children were exposed to tuberculosis in their families as well as 35/50 (70%) in the TB Group. The positive result of a sputum test of the index case was registered in 7/14 (50%) children of the TB/HIV Group and 19/35 (54.2%) children of the TB Group. Of 25 children of the TB/HIV Group, 17 children (68%) were vaccinated with BCG, and in 9 of them the vaccination was not done properly.

Vaccination among HIV-infected, HIV-exposed uninfected and HIV-uninfected children: a systematic review and meta-analysis of evidence related to vaccine efficacy and effectiveness

ABSTRACTEvidence-based approaches were used in making recommendations for vaccination against vaccine-preventable diseases for HIV-infected and HIV-exposed individuals but with limited substantiation. We conducted a systematic review and meta-analysis with randomized-controlled trials (RCTs), cohort and case–control studies that have efficacy and effectiveness of vaccines in HIV-infected and HIV-exposed children as outcomes. Web of Science, Cochrane Library, PubMed and Scopus databases were searched for articles. Efficacy of 9-valent pneumococcal conjugate vaccine (PCV9) against total vaccine serotype invasive pneumococcal disease was 32% in HIV-infected children and 78% among HIV-uninfected children. Vaccine effectiveness of Bacillus Calmette–Guérin vaccine in preventing tuberculosis in HIV-infected children was zero compared to 59% protection in HIV-unexposed children. Likewise, HIV-uninfected children have better protection against invasive Haemophilus influenzae type b disease than the HIV-infected children. Effectiveness studies of rotavirus vaccines show that HIV-exposed uninfected children have similar protection against rotavirus gastroenteritis compared to the non-exposed children. Children who are severely immunosuppressed are poorly protected against invasive pneumococcal diseases. HIV-infected children tend to have lesser vaccine protection against vaccine-preventable diseases when compared to unexposed children. HIV-infected children who are immunocompetent are more likely to have better vaccine protection against vaccine-preventable diseases than those who are immunosuppressed. The overall quality of the observational studies was very low with very little confidence in the effect estimate. The overall quality of evidence for the RCT outcomes was mainly high. This study reveals a dearth of efficacy and effectiveness studies among HIV-infected and exposed children.

Isoniazid for the Prevention of Tuberculosis in HIV-Infected Children: A Systematic Review and Meta-Analysis.

Isoniazid is recommended for prevention of tuberculosis (TB) in HIV-infected adults, but its efficacy in children living with HIV (CLHIV) is not known. We performed a systematic review to assess the efficacy of isoniazid for the prevention of TB in CLHIV. We searched PubMed, Cochrane Clinical Trial Registry and Google Scholar from inception to December 2016. Any randomized controlled trial assessing the role of isoniazid for the prevention of TB in CLHIV was eligible for inclusion. The primary endpoint was TB incidence; secondary end points were mortality, overall survival and severe adverse events. Dual independent extraction of all data was performed. Data were pooled under a random effects model and summarized either as risk ratio (RR) or hazard ratio along with 95% confidence intervals (CIs). Of 931 references, 3 randomized controlled trials enrolling 977 patients met the inclusion criteria. Pooled results showed a statistically nonsignificant reduction in TB incidence (RR: 0.70; 95% CI: 0.47-1.04; P = 0.07) and mortality (RR: 0.94; 95% CI: 0.39-2.23; P = 0.88) with the use of isoniazid compared with placebo. One study was stopped early because of excess deaths in the placebo arm. However, results from subgroup analysis restricted to only completed trials did not change the overall findings. Isoniazid did not reduce the incidence of TB in CLHIV. All included studies were performed in regions with high prevalence of TB making the overall generalizability limited.

Value of chest X-ray in TB diagnosis in HIV-infected children living in resource-limited countries: the ANRS 12229-PAANTHER 01 study.

To evaluate inter-reader agreement and diagnostic accuracy of chest radiography (CXR) in the diagnosis of tuberculosis (TB) in children with human immunodeficiency virus (HIV) infection. HIV-infected children with clinically suspected TB were enrolled in a prospective study conducted in Burkina Faso, Cambodia, Cameroon and Viet Nam from April 2010 to December 2014. Three readers-a local radiologist, a paediatric pulmonologist and a paediatric radiologist-independently reviewed the CXRs. Inter-reader agreement was then assessed using the κ coefficient. Diagnostic accuracy of CXR was assessed in culture-confirmed cases and controls. A total of 403 children (median age 7.3 years, interquartile range 3.5-9.7; 49.6% males) were enrolled. Inter-reader agreement was as follows: between local radiologist and paediatric pulmonologist, κ = 0.36 (95%CI 0.27-0.45); local radiologist and paediatric radiologist, κ = 0.16 (95%CI 0.08-0.24); and paediatric pulmonologist and paediatric radiologist, κ = 0.30 (95%CI 0.21-0.40). Among 51 cases and 151 controls, after a consensus, CXR had a sensitivity of 71.4% (95%CI 58.8-84.1) and a specificity of 50.0% (95%CI 41.9-58.1). Alveolar opacities and enlarged lymph nodes on CXR had limited specificity for TB (64.7% and 70.2%, respectively). Miliary and/or nodular opacities patterns on CXR were more specific to TB (specificity 94.3%). CXR showed poor-to-fair inter-reader agreement and limited diagnostic accuracy for TB in HIV-infected children, likely due to comorbidities. Radiological criteria for this specific population require further investigation.

Stool Xpert MTB/RIF and urine lipoarabinomannan for the diagnosis of tuberculosis in hospitalized HIV-infected children

Tuberculosis (TB) causes substantial morbidity and mortality in HIV-infected children. Sample collection and the paucibacillary nature of TB in children makes diagnosis challenging. Rapid diagnostic tools using easily obtained specimens are urgently needed. Hospitalized, HIV-infected children aged 12 years or less enrolled in a randomized controlled trial (NCT02063880) comparing urgent to post-stabilization antiretroviral therapy initiation in Kenya underwent TB evaluation. At enrollment, sputum or gastric aspirates were collected for TB culture and Xpert, stool for Xpert, and urine for lipoarabinomannan (LAM). When possible, a second sputum/gastric aspirate for culture was obtained. Stool Xpert and urine LAM performance were compared to reference sputum/gastric aspirate culture. Among 165 HIV-infected children, median age was 24 months [interquartile range (IQR) 13-58], median CD4% was 14.3 (IQR 8.9-22.0%), and 114 (69.5%) had severe immunosuppression. Thirteen (7.9%) children had confirmed TB (positive culture and/or Xpert). Sputum/gastric aspirate Xpert, stool Xpert, and urine LAM sensitivities were 60% [95% confidence interval (CI) 26-88%], 63% (95% CI 25-92%), and 43% (95% CI 10-82%), respectively. Specificity was 98% (95% CI 94-100%) for sputum/gastric aspirate Xpert, 99% (95% CI 95-100%) for stool Xpert, and 91% (95% CI 84-95%) for urine LAM. Stool Xpert and urine LAM sensitivity increased among children with severe immunosuppression [80% (95% CI 28-100) and 60% (95% Cl 15-95%)]. Stool Xpert had similar performance compared with sputum/gastric aspirate Xpert to detect TB. Urine LAM had lower sensitivity and specificity, but increased among children with severe immunosuppression. Stool Xpert and urine LAM can aid rapid detection of TB in HIV-infected children using easily accessible samples.

Isoniazid for preventing tuberculosis in HIV-infected children.

BackgroundTuberculosis (TB) is an important cause of illness and death in HIV‐positive children living in areas of high TB prevalence. We know that isoniazid prophylaxis prevents TB in HIV‐negative children following TB exposure, but there is uncertainty related to its role in TB preventive treatment in HIV‐positive children.ObjectivesTo summarise the effects of TB preventive treatment versus placebo in HIV‐positive children with no known TB contact on active TB, death, and reported adverse events.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, Embase and two trial registers up to February 2017.Selection criteriaWe included trials of HIV‐positive children with and without known TB exposure, randomized to receive TB preventive treatment or placebo.Data collection and analysisTwo review authors independently used the study selection criteria, assessed risk of bias, and extracted data. We assessed effects using risk, incidence rate and hazard ratios and assessed the certainty of evidence using GRADE.Main resultsWe included three trials, involving 991 participants, below the age of 13 years, from South Africa and Botswana. Children were randomized to isoniazid prophylaxis or placebo, given daily or three times weekly. The median length of follow‐up ranged from 5.7 to 34 months; some were on antiretroviral therapy (ART).In HIV‐positive children not on ART, isoniazid prophylaxis may reduce the risk of active TB (hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.11 to 0.87; 1 trial, 240 participants, low certainty evidence), and death (HR 0.46, 95% CI 0.22 to 0.95; 1 trial, 240 participants, low certainty evidence). One trial (182 participants) reported number of children with laboratory adverse events, which was similar between the isoniazid prophylaxis and placebo groups. No clinical adverse events were reported.In HIV‐positive children on ART, we do not know if isoniazid prophylaxis reduces the risk of active TB (risk ratio (RR) 0.76, 95% CI 0.50 to 1.14; 3 trials, 737 participants, very low certainty evidence) or death (RR 1.45, 95% CI 0.78 to 2.72; 3 trials, 737 participants, very low certainty evidence). Two trials (714 participants) reported number of clinical adverse events and three trials (795 participants) reported number of laboratory adverse events; for both categories, the number of adverse events were similar between the isoniazid prophylaxis and placebo groups.Authors' conclusionsIsoniazid prophylaxis given to all children diagnosed with HIV may reduce the risk of active TB and death in HIV‐positive children not on ART in studies from Africa. For children on ART, no clear benefit was detected. .12 April 2019Up to dateAll studies incorporated from most recent searchAll eligible published studies found in the last search (17 Feb, 2017) were included

Tuberculosis in HIV-infected children in Europe, Thailand and Brazil: paediatric TB-HIV EuroCoord study.

Centres participating in the Paediatric European Network for Treatment of AIDS (PENTA), including Thailand and Brazil. To describe the incidence, presentation, treatment and treatment outcomes of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children. Observational study of TB diagnosed in HIV-infected children in 2011-2013. Of 4265 children aged <16 years, 127 (3%) were diagnosed with TB: 6 (5%) in Western Europe, 80 (63%) in Eastern Europe, 27 (21%) in Thailand and 14 (11%) in Brazil, with estimated TB incidence rates of respectively 239, 982, 1633 and 2551 per 100 000 person-years (py). The majority (94%) had acquired HIV perinatally. The median age at TB diagnosis was 6.8 years (interquartile range 3.0-11.5). Over half (52%) had advanced/severe World Health Organization stage immunodeficiency; 67 (53%) were not on antiretroviral therapy (ART) at TB diagnosis. Preventive anti-tuberculosis treatment was given to 23% (n = 23) of 102 children diagnosed with HIV before TB. Eleven children had unfavourable TB outcomes: 4 died, 5 did not complete treatment, 1 had recurrent TB and 1 had an unknown outcome. In univariable analysis, previous diagnosis of acquired immune-deficiency syndrome, not being virologically suppressed on ART at TB diagnosis and region (Brazil) were significantly associated with unfavourable TB outcomes. Most TB cases were from countries with high TB prevalence. The majority (91%) had favourable outcomes. Universal ART and TB prophylaxis may reduce missed opportunities for TB prevention.

Performance of Xpert MTB/RIF and Alternative Specimen Collection Methods for the Diagnosis of Tuberculosis in HIV-Infected Children

The diagnosis of tuberculosis in human immunodeficiency virus (HIV)-infected children is challenging. We assessed the performance of alternative specimen collection methods for tuberculosis diagnosis in HIV-infected children using Xpert MTB/RIF (Xpert). HIV-infected children aged ≤13 years with suspected intrathoracic tuberculosis were enrolled in 8 hospitals in Burkina Faso, Cambodia, Cameroon, and Vietnam. Gastric aspirates were taken for children aged <10 years and expectorated sputum samples were taken for children aged ≥10 years (standard samples); nasopharyngeal aspirate and stool were taken for all children, and a string test was performed if the child was aged ≥4 years (alternative samples). All samples were tested with Xpert. The diagnostic accuracy of Xpert for culture-confirmed tuberculosis was analyzed in intention-to-diagnose and per-protocol approaches. Of 281 children enrolled, 272 (96.8%) had ≥1 specimen tested with Xpert (intention-to-diagnose population), and 179 (63.5%) had all samples tested with Xpert (per-protocol population). Tuberculosis was culture-confirmed in 29/272 (10.7%) children. Intention-to-diagnose sensitivities of Xpert performed on all, standard, and alternative samples were 79.3% (95% confidence interval [CI], 60.3-92.0), 72.4% (95% CI, 52.8-87.3), and 75.9% (95% CI, 56.5-89.7), respectively. Specificities were ≥97.5%. Xpert combined on nasopharyngeal aspirate and stool had intention-to-diagnose and per-protocol sensitivities of 75.9% (95% CI, 56.5-89.7) and 75.0% (95% CI, 47.6-92.7), respectively. The combination of nasopharyngeal aspirate and stool sample is a promising alternative to methods usually recommended by national programs. Xpert performed on respiratory and stools samples enables rapid confirmation of tuberculosis diagnosis in HIV-infected children. The ANRS (Agence Nationale de Recherche sur le Sida) 12229 PAANTHER (Pediatric Asian African Network for Tuberculosis and HIV Research) 01 study is registered at ClinicalTrials.gov (NCT01331811).

Severe manifestations of extrapulmonary tuberculosis in HIV-infected children initiating antiretroviral therapy before 2 years of age

BackgroundEarly initiation of antiretroviral therapy (ART) in HIV-infected infants reduces mortality and opportunistic infections including tuberculosis (TB). However, young HIV-infected children remain at high risk of TB disease following mycobacterial...

Tuberculosis in Pediatric Antiretroviral Therapy Programs in Low- and Middle-Income Countries: Diagnosis and Screening Practices.

The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)-infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge. We describe TB diagnosis and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries participated in the study. Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART included contact history in 41 sites (84%), symptom screening in 38 (88%), and chest Radiograph in 34 sites (79%). The use of diagnostic tools was examined among 146 children diagnosed with TB during the study period. Chest Radiograph was used in 125 (86%) children, sputum microscopy in 76 (52%), induced sputum microscopy in 38 (26%), gastric aspirate microscopy in 35 (24%), culture in 25 (17%), and Xpert MTB/RIF in 11 (8%) children. Induced sputum and Xpert MTB/RIF were infrequently available to diagnose childhood TB, and screening was largely based on symptom identification. There is an urgent need to improve the capacity of ART programs in low- and middle-income countries to exclude and diagnose TB in HIV-infected children.

Incidence and associated factors of pulmonary tuberculosis in HIV-infected children after highly active antiretroviral therapy (HAART) in China: a retrospective study

China is a country with high tuberculosis (TB) incidence but relatively low HIV prevalence. However, due to difficulties in diagnosis and reporting, true burden of HIV-associated TB in children is unknown. The objective of this study was to describe the incidence of pulmonary TB (PTB) after antiretroviral therapy (ART) and to study risk factors. A retrospective study was performed based on routinely collected data from China national pediatric free antiretroviral treatment database. A total of 3365 children under 15 years on ART from July 2005 to October 2012 were included. Multivariable logistic regression was used to detect associated factors. Two thousand nine hundred and ninety (89%) children got infected from HIV-positive mother, with median age of 6.7 (4.1, 10.0) years at highly active antiretroviral therapy (HAART) initiation in this program. Seventy-seven (2.3%) children were diagnosed with PTB after ART during 7.3 years cohort observation. Median time of occurrence was 212 (30–514) days. Overall incidence was 0.83 (0.65–1.01)/100 person-years (py), with the peak of 3.6/100 py in the first 3 months after antiretroviral treatment. WHO stage IV at baseline showed 2 (95% CI 1.0–6.8) times more risk for developing TB. Late clinical stage at ART initiation was shown to relate with TB incidence. PTB coinfection leads to higher mortality. Early diagnosis and treatment of HIV are highly required to reduce HIV-associated morbidity and mortality due to TB.

Tuberculosis and HIV co-infection in children.

HIV is the top and tuberculosis is the second leading cause of death from infectious disease worldwide, with an estimated 8.7 million incident cases of tuberculosis and 2.5 million new HIV infections annually. The World Health Organization estimates that HIV prevalence among children with tuberculosis, in countries with moderate to high prevalence, ranges from 10 to 60%. The mechanisms promoting susceptibility of people with HIV to tuberculosis disease are incompletely understood, being likely caused by multifactorial processes.Paediatric tuberculosis and HIV have overlapping clinical manifestations, which could lead to missed or late diagnosis. Although every effort should be made to obtain a microbiologically-confirmed diagnosis in children with tuberculosis, in reality this may only be achieved in a minority, reflecting their paucibacillary nature and the difficulties in obtain samples. Rapid polymerase chain reaction tests, such as Xpert MTB/RIF assay, are increasingly used in children. The use of less or non invasive methods of sample collection, such as naso-pharyngeal aspirates and stool samples for a polymerase chain reaction-based diagnostic test tests and mycobacterial cultures is promising technique in HIV negative and HIV positive children. Anti-tuberculosis treatment should be started immediately at diagnosis with a four drug regimen, irrespective of the disease severity. Moreover, tuberculosis disease in an HIV infected child is considered to be a clinical indication for initiation of antiretroviral treatment. The World Health Organization recommends starting antiretroviral treatment in children as soon as anti-tuberculosis treatment is tolerated and within 2- 8 weeks after initiating it. The treatment of choice depends on the child’s age and availability of age-appropriate formulations, and potential drug interactions and resistance. Treatment of multi-drug resistant tuberculosis in HIV-infected children follows same principles as for HIV uninfected children. There are conflicting results on effectiveness of isoniazid preventive therapy in reducing incidence of tuberculosis disease in children with HIV.ConclusionData on HIV/TB co-infection in children are still lacking. There are on-going large clinical trials on the prevention and treatment of TB/HIV infection in children that hopefully will help to guide an evidence-based clinical practice in both resource-rich and resource-limited settings.

Prevalence, Characteristics, Management, and Outcome of Pulmonary Tuberculosis in HIV-Infected Children in the TREAT Asia Pediatric HIV Observational Database (TApHOD)

A multicenter, retrospective, observational study was conducted to determine prevalence, characteristics, management, and outcome of pulmonary tuberculosis (PTB) in Asian HIV-infected children in the TREAT Asia Pediatric HIV Observational Database (TApHOD). Data on PTB episodes diagnosed during the period between 12 months before antiretroviral therapy (ART) initiation and December 31, 2009 were extracted. A total of 2678 HIV-infected children were included in TApHOD over a 13-year period; 457 developed PTB, giving a period prevalence of 17.1% (range 5.7-33.0% per country). There were a total of 484 PTB episodes; 27 children had 2 episodes each. There were 21 deaths (4.3%). One third of episodes (n=175/484) occurred after ART initiation at a median of 14.1 months (interquartile range [IQR] 2.5-28.8 months). The median (IQR) CD4+ values were 9.0% (3.0-16.0%) and 183.5 (37.8-525.0) cells/mm(3) when PTB was diagnosed. Most episodes (n=424/436, 97.3%) had abnormal radiographic findings compatible with PTB, whereas half (n=267/484, 55.2%) presented with clinical characteristics of PTB. One third of those tested (n=42/122, 34.4%) had bacteriological evidence of PTB. Of the 156 episodes (32.2%) that were accompanied with extrapulmonary TB, pleuritis was the most common manifestation (81.4%). After treatment completion, most episodes (n=396/484, 81.9%) were recorded as having positive outcomes (cured, treatment completed and child well, and improvement). The prevalence of PTB among Asian HIV-infected children in our cohort was high. Children with persistent immunosuppression remain vulnerable to PTB even after ART initiation.

Isoniazid preventive therapy in HIV-infected and -uninfected children (0 - 14 years)

Isoniazid preventive therapy (IPT) prevents tuberculosis (TB) in immunocompetent children &lt;5 years of age after exposure to an infectious TB source case. Routine IPT has been advocated in all HIV-infected children without TB, but has been controversial. Antiretroviral therapy markedly reduces the risk for TB in HIV-infected children, especially when started early in infancy. In HIV-infected children, as in HIV- uninfected children, we recommend post-exposure IPT after each TB exposure episode; but in HIV-infected children, this should be given irrespective of age or antiretroviral therapy. However, evidence for routine IPT without known exposure to TB in HIV-infected children is not convincing and is therefore not recommended.

Primary Isoniazid Prophylaxis against Tuberculosis in HIV-Exposed Children

The dual epidemic of human immunodeficiency virus (HIV) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa. We conducted a double-blind, randomized, placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period. We randomly assigned 548 HIV-infected and 804 HIV-uninfected infants (91 to 120 days of age) to isoniazid (10 to 20 mg per kilogram of body weight per day) or matching placebo for 96 weeks. All patients received bacille Calmette-Guérin (BCG) vaccination against tuberculosis within 30 days after birth. HIV-infected children had access to antiretroviral therapy. The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection, tuberculosis disease, and death in HIV-uninfected children within 96 to 108 weeks after randomization. Antiretroviral therapy was initiated in 98.9% of HIV-infected children during the study. Among HIV-infected children, protocol-defined tuberculosis or death occurred in 52 children (19.0%) in the isoniazid group and 53 (19.3%) in the placebo group (P=0.93). Among HIV-uninfected children, there was no significant difference in the combined incidence of tuberculosis infection, tuberculosis disease, or death between the isoniazid group (39 children, 10%) and the placebo group (45 children, 11%; P=0.44). The rate of tuberculosis was 121 cases per 1000 child-years (95% confidence interval [CI], 95 to 153) among HIV-infected children as compared with 41 per 1000 child-years (95% CI, 31 to 52) among HIV-uninfected children. There were no significant differences in clinical or severe laboratory toxic effects between treatment groups. Primary isoniazid prophylaxis did not improve tuberculosis-disease-free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine. Despite access to antiretroviral therapy, the burden of tuberculosis remained high among HIV-infected children. (Funded by the National Institutes of Health and Secure the Future; ClinicalTrials.gov number, NCT00080119.).

Tuberculosis in Hiv-Infected Tanzanian children below 14 years

Tuberculosis (TB)-human immunodeficiency virus (HIV) co-infection is an important public health problem. Diagnosis of TB in children usually follows discovery of an adult case, and relies on clinical presentation, sputum examination and chest radiograph. However, clinical features are non-specific, chest radiographs are difficult to interpret, and routine laboratory tests are not helpful. The aim of the current study was to determine the prevalence of TB in HIV-infected children below 14 years attending a tertiary hospital. A cross-sectional study was conducted in HIV-infected children below 14 years of age at Muhimbili National Hospital, in Dar es Salaam, Tanzania, between July 2008 and January 2009. Information on socio-demographic and anthropometric characteristics was collected using a structured questionnaire. Following assessment of clinical presentation, physical examination, tuberculin skin test, and chest radiograph were performed for each child. Two consecutive sputum specimens and blopd sample were collected for microscopy and culture, and CD4 T-lymphocyte percentage test, respectively. Chi-square test was used to compare differences in proportions. Odds ratio (OR) and their 95% confidence interval (CI) are presented as the risk estimator. Of 182 HIV-infected children enrolled in the study, 104 (57.1%) were males. Overall, thirty-seven (20.3%) children had TB. The prevalence of TB was highest in males (78.4%) compared to females (p = 0.003). There was a higher proportion of TB (45.9%) in the age group below 24 months compared to other age groups (p = 0.001). Male gender, history of positive TB contact and severe immunosuppression were found to be significant risk factors for TB while use of antiretroviral therapy was found to be associated with decreased risk for TB. One-fifth of children had TB/HIV co-infection. Presence of four or more clinical manifestations and a low CD4+ T-lymphocyte percentage can be used to predict active TB in HIV-infected children.