TB-human Immunodeficiency Virus Research Articles

Tuberculosis infection prevention and control in rural Papua New Guinea: an evaluation using the infection prevention and control assessment framework

BackgroundPapua New Guinea (PNG) is one of the 14 countries categorised as having a triple burden of tuberculosis (TB), multidrug-resistant TB (MDR TB), and TB-human immunodeficiency virus (HIV) co-infections. TB infection prevention and control (TB-IPC) guidelines were introduced in 2011 by the National Health Department of PNG. This study assesses the implementation of this policy in a sample of district hospitals in two regions of PNG.MethodsThe implementation of TB-IPC policy was assessed using a survey method based on the World Health Organization (WHO) IPC assessment framework (IPCAF) to implement the WHO’s IPC core components. The study included facility assessment at ten district hospitals and validation observations of TB-IPC practices.ResultsOverall, implementation of IPC and TB-IPC guidelines was inadequate in participating facilities. Though 80% of facilities had an IPC program, many needed more clearly defined IPC objectives, budget allocation, and yearly work plans. In addition, they did not include senior facility managers in the IPC committee. 80% (n = 8 of 10) of hospitals had no IPC training and education; 90% had no IPC committee to support the IPC team; 70% had no surveillance protocols to monitor infections, and only 20% used multimodal strategies for IPC activities. Similarly, 70% of facilities had a TB-IPC program without a proper budget and did not include facility managers in the TB-IPC team; 80% indicated that patient flow poses a risk of TB transmission; 70% had poor ventilation systems; 90% had inadequate isolation rooms; and though 80% have personal protective equipment available, frequent shortages were reported.ConclusionsThe WHO-recommended TB-IPC policy is not effectively implemented in most of the participating district hospitals. Improvements in implementing and disseminating TB-IPC guidelines, monitoring TB-IPC practices, and systematic healthcare worker training are essential to improve TB-IPC guidelines’ operationalisation in health settings to reduce TB prevalence in PNG.

Tobacco use as a contributing factor in HIV–TB co- infection – the multidisciplinary approach in the case of an immunosuppressed smoking patient

Abstract Introduction Tuberculosis-HIV co-infection remains a challenge to the clinician largely as a result of the potentiation mutual, which will result in deterioration of the immunological status and increased risk of mortality. Case presentation 37-year-old patient, smoker 5 pack-year (5PA), without pathological history, who is hospitalized in 2021 in an ear, nose and throat otolaryngology (ENT) service in the context of the appearance of laterocervical and axillary polyadenopathy, during the examination histopathologically resulting to be of tuberculous etiology. The transfer was made to the pneumophthisiology clinic where human immunodeficiency virus (HIV) testing was performed it was positive. It was decided to initiate antituberculosis and systemic corticoid treatment with initially favorable evolution, with the association following antiretroviral therapy. The patient develops motor deficits, and the brain magnetic resonance imaging (MRI) examination revealed the presence of two left hemispheric intracranial processes biopsied by neuronavigation, the result of which revealed histopathological changes highly suggestive of granulomatosis. In dynamics, the clinical examination carried out in an infectious disease service highlights the appearance of a pseudotumoral formation, with consistent right sterno-costal fluctuation, which is why it was decided to redirect the case to the thoracic surgery department, where drainage of the formation was practiced with the microbiological detection of Mycobacterium tuberculosis. Discussions The peculiarity of the case resides in the presence of multiple foci of extrapulmonary tuberculosis in a case of tuberculosis-human immunodeficiency virus ( TB-HIV) co-infection, without lung damage, in a patient with apparent compliance to treatment. Conclusions Tuberculosis remains a challenge for the clinician, especially in the case of HIV co-infection, association with mortality and increased morbidity.

604. Effect of rifabutin in dolutegravir dosing: a case series

Abstract Background Tuberculosis (TB) is the leading cause of death in human immunodeficiency virus (HIV) infected people worldwide. Patients with HIV who have latent TB are 20-30 times more likely to develop active TB. Integrated antiretroviral therapy (ART) early in the treatment for tuberculosis is recommended due to improved morbidity and mortality, however, there can be serious drug interactions. Rifamycins are potent inducers of the CYP3A4 isoform, which can cause sub-therapeutic concentrations of anti-retroviral drugs, among these, rifabutin (RBN) is a less potent inducer of CYP3A4. Pharmacokinetic (PK) studies done on healthy adults showed that rifampin decreased dolutegravir (DTG) concentrations by more than 50 % whereas RBN decreased it by 30%. RBN has been preferred given that its favorable pharmacokinetic and toxicity profile. Currently there are no studies examining the use of RBN and DTG in co-infected persons. This is a case series of 4 co-infected patients receiving both agents who underwent PK analysis. Methods Retrospective analysis of patients in the respiratory care unit (RCU) at Jackson Memorial Hospital in Miami. We included adult patients, admitted to the RCU, with a concomitant diagnosis of HIV and active TB disease who received DTG and RBN, and for which DTG and RBN plasma concentrations were measured for therapeutic drug monitoring (TDM). A non-compartmental analysis was performed and the area under the concentration-time curve (AUC) was calculated for DTG and RBN. Results We report 4 patients (Figure 1) that met criteria and underwent PK analysis. All patients with TB who were treated with RBN had low concentrations of DTG, requiring higher doses of DTG (Table 1 & 2). After adjustments based on PK analysis, there was evidence of a favorable response to treatment in 2 patients, with a less than robust in the 2 others. Adequate suppression of viral load could not be determined for 3 of the patients because of the short observation time. Figure 1:Timelines of patients describing admission and HIV and tuberculosis treatment providedDTG, dolutegravir. RFB, rifabutin. VL, viral load. AFB, Acid fast bacilli. LAD, lymphadenopathy. TAF, Tenofovir alafenamide. FTC, Emtricitabine. TDF, Tenofovir Disoproxil Fumarate. INH, Isoniazid. PYZ, Pyrazinamide. BID, twice a day. QD, daily. IRIS, Immune reconstitution inflammatory syndrome. GU, genitourinary. TB, tuberculosis.Table 1:Patients’ pharmacokinetics of DTGAUCX-Y, area under the concentration-time curve from time X to Y hours; AUC0-tau, area under the concentration-time curve from time zero to the end of the dosing interval; DTG, dolutegravir; TDM, therapeutic drug monitoring. a) AUC0-6 was calculated.Table 2:Patients’ pharmacokinetics of RBNAUCX-Y, area under the concentration-time curve from time X to Y hours; AUC0-tau, area under the concentration-time curve from time zero to the end of the dosing interval; RBN, Rifabutin; TDM, therapeutic drug monitoring. a) All RBN doses given every 24 hours, b) RBN value was trace and AUC was not calculated. Conclusion All patients with HIV and TB who were treated with RBN had low concentrations of DTG. This case series demonstrates that for optimal concomitant use of rifabutin and dolutegravir it is highly recommended to use TDM. Prospective clinical studies are needed to further determine the PK interactions between RBN and DTG and virologic response to treatment. Disclosures All Authors: No reported disclosures.

Effect of Gender on Clinical Presentation of Tuberculosis (TB) and Age-Specific Risk of TB, and TB-Human Immunodeficiency Virus Coinfection.

Previous studies have shown gender differences in tuberculosis (TB) incidence; however, gender disparity has not been well documented across granular categorizations of anatomic sites affected by TB and in the presence of human immunodeficiency virus (HIV) coinfection, largely due to small sample size for less common TB clinical presentations and lack of detailed clinical data. The study population included TB cases aged ≥15 years (n = 41, 266) diagnosed in Harare, Zimbabwe. This cross-sectional study estimated male-to-female ratio (M/F ratio) for (1) age-specific TB incidence, (2) age-specific HIV prevalence among incident TB cases, and (3) 9 types of TB defined by affected anatomic site. Males were at a 53% higher risk of TB compared to females (risk ratio [RR] = 1.53; 95% confidence interval [CI], 1.12-2.09). Based on adjusted odds ratios (aORs) from multinomial logistic regression model, the odds of abdominal TB (aOR = 0.51; 95% CI, .39-.68), TB bones/joints/spine (aOR = 0.63; 95% CI, .45-.90), and "other" extrapulmonary TB sites (aOR = 0.69; 95% CI = .59-.81) versus pulmonary TB were lower among males compared to females. The risk of TB-HIV coinfection among males was 17% (RR = .83; 95% CI, .74-.93) and 8% (RR = 0.92; 95% CI, .88-.95) lower in the 15- to 24-year and 25- to 44-year age groups, respectively. This study revealed a nuanced role of gender across finer categorizations of TB, indicating the need for future research to delineate underlying mechanisms driving gender disparities in TB. The finding that women had a greater likelihood of severe forms of TB and TB-HIV coinfection compared to men has important implications for women's health in TB-HIV high-burden settings.

Time to Death and Associated Factors among Tuberculosis Patients in South West Ethiopia: Application of Shared Frailty Model

(1) Background: Tuberculosis is a bacterial disease mainly caused by Mycobacterium tuberculosis. It is one of the major public health problems in the world and now ranks alongside human immunodeficiency virus (HIV) as the leading infectious cause of death. The objective of this study was to investigate the potential risk factors affecting the time to death of TB patients in southwest Ethiopia using parametric shared frailty models. (2) Methods: A retrospective study design was used to collect monthly records of TB patients in three selected hospitals in southwest Ethiopia. The data used in the study were obtained from patients who took part in the directly observed treatment, short-course (DOTS) program from 1 January 2015 to 31 December 2019. The survival probability was analyzed by the Kaplan–Meier method. Log-rank tests and parametric shared frailty models were applied to investigate factors associated with death during TB treatment. (3) Results: Out of the total sample of 604 registered TB patients, 46 (7.6%) died during the study period and 558 (92.4%) were censored. It was found that the median time of death for TB patients was 5 months. Hospitals were used to assess the cluster effect of the frailty model. A Gamma shared frailty model with Weibull distribution for baseline hazard function was selected among all models considered and was used for this study. It was found that the covariates, age, initial weight, extrapulmonary type of TB patient, patient category, and HIV status of TB patient were significant risk factors associated with death status among TB patients. (4) Conclusions: The risk of death was high, especially with cases of HIV co-infected, retreated, and returned-after-treatment categories of TB patients. During the treatment period, the risk of death was high for older TB patients and patients with low baseline body weight measurements. Therefore, health professionals should focus on the identified factors to improve the survival time of TB patients.

COVID-19 Pandemic Disruption on the Management of Tuberculosis Treatment in Indonesia.

The current coronavirus disease 2019 (COVID-19) situation might deteriorate the efforts to eliminate tuberculosis (TB) in Indonesia. This study aimed to review the COVID-19 pandemic disruption on the management of TB treatment in Indonesia. We identified several disruptions due to the pandemic on TB control management. Firstly, there is a potential decrease in the funding for TB treatment. Financial disruptions caused by the COVID-19 pandemic have led to further setbacks. In many countries, including Indonesia, financial and other resources have been reallocated from TB to the COVID-19 response. Secondly, it has been highlighted that all TB services, including case detection and rapid diagnostic, have been disrupted by the pandemic. Thirdly, the pandemic would be associated with the lower quality of care and treatment for TB in Indonesia. It might decrease the enthusiasm of patients with TB, multi-drug resistant (MDR)-TB, and TB-human immunodeficiency virus (HIV) to visit TB hospitals because of social distancing measures by the government. Finally, the COVID-19 pandemic also has impacted critical activities of monitoring, evaluation, and surveillance. There are several lessons from other countries about managing TB treatment during the pandemic, such as combining screening for COVID-19 and TB by applying x-ray technology and artificial intelligence-based software. In addition, the use of telemedicine or telehealth in TB treatment is also beneficial to deliver medication, assess patients’ progress, and inform prevention strategies. To reach the target with the end TB strategy, the government of Indonesia can adopt the World Health Organization's (WHO’s) comprehensive strategies, such as integrated, patient-centered TB care and prevention strategies; bold policies and supportive systems; and intensified research and innovations.

Quantification and correlates of tuberculosis stigma along the tuberculosis testing and treatment cascades in South Africa: a cross-sectional study

BackgroundSouth Africa has one of the world’s worst tuberculosis (TB) (520 per 100 000 population) and TB-human immunodeficiency virus (HIV) epidemics (~ 56% TB/HIV co-infected). While individual- and system-level factors influencing progression along the TB cascade have been identified, the impact of stigma is underexplored and underappreciated. We conducted an exploratory study to 1) describe differences in perceived community-level TB stigma among community members, TB presumptives, and TB patients, and 2) identify factors associated with TB stigma levels among these groups.MethodsA cross sectional study was conducted in November 2017 at public health care facilities in Buffalo City Metro (BCM) and Zululand health districts, South Africa. Community members, TB presumptives, and TB patients were recruited. Data were collected on sociodemographic characteristics, TB knowledge, health and clinical history, social support, and both HIV and TB stigma. A validated scale assessing perceived community TB stigma was used. Univariate and multivariate linear regression models were used to describe differences in perceived community TB stigma by participant type and to identify factors associated with TB stigma.ResultsWe enrolled 397 participants. On a scale of zero to 24, the mean stigma score for TB presumptives (14.7 ± 4.4) was statistically higher than community members (13.6 ± 4.8) and TB patients (13.3 ± 5.1). Community members from Zululand (β = 5.73; 95% CI 2.19, 9.72) had higher TB stigma compared to those from BCM. Previously having TB (β = − 2.19; 95% CI − 4.37, 0.0064) was associated with reduced TB stigma among community members. Understanding the relationship between HIV and TB disease (β = 2.48; 95% CI 0.020, 4.94), and having low social support (β = − 0.077; 95% CI − 0.14, 0.010) were associated with increased TB stigma among TB presumptives. Among TB Patients, identifying as Black African (β = − 2.90; 95% CI − 4.74, − 1.04) and knowing the correct causes of TB (β = − 2.93; 95% CI − 4.92, − 0.94) were associated with decreased TB stigma, while understanding the relationship between HIV and TB disease (β = 2.48; 95% CI 1.05, 3.90) and higher HIV stigma (β = 0.32; 95% CI 0.21, 0.42) were associated with increased TB stigma.ConclusionsTB stigma interventions should be developed for TB presumptives, as stigma may increase initial-loss-to-follow up. Given that stigma may be driven by numerous factors throughout the TB cascade, adaptive stigma reduction interventions may be required.

A prospective cohort study of outcomes for isoniazid prevention therapy: a nested study from a national QI collaborative in Uganda

BackgroundTuberculosis (TB) and human immunodeficiency virus (HIV) co-infection constitute a deadly infectious disease synergy disease and major public health problem throughout the world. The risk of developing active TB in people living with HIV (PLHIV) is 21 times higher than the rest of the world population. The overlap of latent TB infection and HIV infection has resulted in marked increases in TB incidence in countries with dual epidemics. Although antiretroviral therapy (ART) is the single most significant way to reduce incident TB in PLHIV, besides early ART initiation, isoniazid preventive therapy (IPT) is the key intervention to prevent TB among PLHIV. This prospective cohort and longitudinal study aimed to document; retention, adherence, development of active TB disease, possible adverse drug reactions and completion among patients initiated on IPT in Jan 2019.MethodsThis was both a prospective cohort and longitudinal study nested within a national quality improvement collaborative in which multiple quality improvement teams tested changes in care delivery to improve the delivery of IPT. The prospective cohort were HIV patients without TB disease initiated on a dosage of Isoniazid 300 mg/day for adults and 150 mg/day for children for a period of 6 months. Association statistics were used to describe patient characteristics and outcomes. Variables with p-value < 0.05 were used to determine linear by linear associations between patient characteristics assumed to influence both primary and secondary outcomes. Variables with a p-value < 0.05 were included in the logistical regression model. The final model included those factors that retained statistical significance. The odds ratios (OR) and adjusted OR (AOR) along with its 95% confidence interval were used to determine the power of relationship in determining the outcomes of interest. The model was tested for fitness using goodness-of-fit Hosmer–Lemeshow tests.ResultsThe completion of IPT was at 89%. A significant proportion of patients adhered to treatment (89%) and kept their appointment schedules-retention (89%). All patients (100%) received IPT at each appointment visit. Only 4% of patients experienced side effects of isoniazid (INH) but none of them developed active TB at the end of the 6 month INH dose. Multivariate logistic regression analysis of covariates of IPT completion revealed a strong and statistical association between IPT completion and age, gender, retention and side effects of INH. Our multivariate model found that children below 15 years were less likely to complete INH than patients ≥ 15 years (AOR = 0.416, p = 0.230, df = 1). Female patients were 2 times more likely to complete INH dose than male patients (AOR = 1.598, p = 0.018). Patients who kept all their appointment schedules were 10 times more likely to complete IPT than those who missed one or more schedules (AOR = 10.726, p = 0.000, df = 1). We also found that patients who did not report any side effects associated with INH were 2 times more likely to complete INH (AOR = 1.958, p = 0.016, df = 1) than patients who reported one or more side effects.ConclusionTreatment completion is the end-point of the IPT initiation strategy in Uganda. With a completion rate of 89%, our results seem re-assuring and suggest that improvement collaborative is an effective approach to achieving results through combined efforts. The high rates of completion are encouraging indicators of progress in the implementation of collaborative activities in the study setting. However, such collaboratives would require periodic evaluation to prevent possible relapses in progress attained.

Multidrug-Resistant Tuberculosis in Patients with Human Immunodeficiency Virus. Management Considerations within High-resourced Settings.

The management of multidrug-resistant tuberculosis (MDR TB) is notably complex among patients with human immunodeficiency virus (HIV). TB treatment recommendations typically include very little information specific to HIV and MDR TB, which often is derived from clinical trials conducted in low-resource settings. Mortality rates among patients with HIV and MDR TB remain high. We reviewed the published literature and recommendations to synthesize possible patient management approaches demonstrated to improve treatment outcomes in high-resourced countries for patients with MDR TB and HIV. Approaches to diagnostic testing, impact and timing of antiretroviral therapy on mortality, anti-MDR TB and antiretroviral drug interactions, and the potential role for short-course MDR TB therapy are examined. The combination of antiretroviral therapy with expanded TB drug therapy, along with the management of immune reconstitution inflammatory syndrome, other potential HIV-associated opportunistic diseases, and drug toxicities, necessitate an integrated multidisciplinary patient care approach using public health case management and provider expertise in drug-resistant TB and HIV management.

HIV–TB co-infection treatment control using multi-objective optimized sliding mode

Abstract Mycobacterium tuberculosis (MTB) and Human immunodeficiency virus (HIV) are two causes of infection which threaten human health over recent decades. There is abundant evidence indicating that these diseases are related to each other. People living with HIV have a 30-fold increase in tuberculosis infection compared to healthy people. In recent years, medical researchers and other specialists including engineers and basic scientists have tried to propose treatments for dangerous diseases by means of mathematical simulation. In this paper, a mathematical model of the HIV-TB co-infection individuals is regarded in order to represent different characteristics of such people. In the next step, a sliding mode controller is implemented on first and second HIV treatment rates to minimize the Total Burden resulted from the co-infection. Moreover, the multi-objective genetic algorithm (MOGA) is used to optimize the sliding mode controller coefficients. The MOGA is accurate and resilient and its Pareto front has a reasonable variety. In this method, designers acceptably use defeated points with more than one objective function and are also able to choose appropriate solutions according to their preferences. The results suggest that disease deaths, new infections, and immune reconstitution inflammatory syndrome cases play an important role in the problem.

A mortality review of adult inpatients with tuberculosis in Mendi, Papua New Guinea.

Mendi Provincial Hospital, Southern Highlands Province, Papua New Guinea (PNG). PNG is a high burden country for tuberculosis (TB) and TB-human immunodeficiency virus (HIV). TB is the second most common cause of death in PNG. To identify the number of adult inpatients with TB who died between 1 January 2015 and 30 August 2017; describe these patients' characteristics and identify contributing factors that could be modified. This was a retrospective case series review. Among 905 inpatients with TB during the study period, there were 90 deaths. The patients who died were older than those who survived (median age 40 years vs. 32 years, P = 0.011). The majority of patients who died lived less than 3 hours from the hospital (71%), were diagnosed after admission (79%) and were clinically diagnosed (77%). HIV status was not known in 50% of the deaths. Of patients with a known status, 27% (12/45) were HIV-positive. The median symptom duration prior to presentation was 28 days, with females presenting later than males (84 vs. 28 days, P = 0.008). This study highlights areas where community and hospital-based management of TB could be improved to potentially reduce TB mortality, including earlier detection and treatment, improved bacteriological diagnosis and increased HIV testing.

CHARACTERISTICS OF LYMPHADENITIS IN HOSPITALISED PATIENTS BANDAR LAMPUNG-INDONESIA

Background: Lymphadenitis is an inflammation of the lymph nodes caused by a variety of microorganisms such as Mycobacterium tuberculosis, human immunodeficiency virus (HIV), and other microorganisms. Patient characteristics lymphadenitis diverse views on the etiology, age, gender, and lymph nodes affected.Purpose: The purpose of this study was to describe the characteristics of patients with lymphadenitis.Methods: The design of this study is descriptive cross sectional method is done by looking at medical records of patients in Dr. H. Abdul Moeloek hospital Bandar Lampung 2015. The samples were taken using stratified random sampling technique so that 161 samples used in this study.Results: The results showed the frequency distribution of patients with tuberculous lymphadenitis is the highest (57.14%), lymphadenitis other microorganisms (21.74%), and HIV lymphadenitis (21.12%). The frequency distribution of TB lymphadenitis patient age was 15-24 years (45.7%), patients with HIV lymphadenitis most at the age of 45-64 (29.4%), while the age of the patient lymphadenitis other microorganisms highest in the 15-24 age (28 , 6%). The frequency distribution of TB lymphadenitis gender, HIV and most were female (58.7% and 52.9%), while the frequency distribution of the sexes in most other microorganisms lymphadenitis patients were male (54.3%).Conclusion: The frequency distribution locations lymphadenitis TB, HIV and other microorganisms most was the neck (regio colli) (96%, 55.9% and 57.1%).

Effect of HIV infection on TB treatment outcomes and time to mortality in two urban hospitals in Ghana-a retrospective cohort study.

IntroductionTuberculosis (TB) is currently causing more deaths than Human Immunodeficiency Virus (HIV) globally. Ghana as one of the 30 high burden TB/HIV countries has a high annual TB case-fatality rate of 10%. The study sought to assess the effect of HIV infection on TB treatment outcomes and assess the time to mortality after treatment onset.MethodsWe conducted a review of treatment files of TB patients who were treated from January 2013 to December 2015 in two urban hospitals in the Accra Metropolis. Modified Poisson regression analysis was used to measure the association between HIV infection and TB treatment outcomes. Kaplan-Meier survival estimates were used to plot survival curves.ResultsSeventy-seven percent (83/107) of HIV infected individuals had successful treatment, compared to 91.2% (382/419) treatment success among HIV non-infected individuals. The proportion of HIV-positive individuals who died was 21.5% (23/107) whilst that of HIV-negative individuals was 5.5% (23/419). Being HIV-positive increased the risk of adverse outcome relative to successful outcome by a factor of 2.89(95% CI 1.76-4.74). The total number of deaths recorded within the treatment period was 46; of which 29(63%) occurred within the first two months of TB treatment. The highest mortality rate observed was among HIV infected persons (38.6/1000 person months). Of the 107 TB/HIV co-infected patients, 4(3.7%) initiated ART during TB treatment.ConclusionThe uptake of ART in co-infected individuals in this study was very low. Measures should be put in place to improve ART coverage among persons with TB/HIV co-infection to help reduce mortality.

Delay before drug susceptibility testing among patients with presumptive multidrug-resistant tuberculosis in Gujarat, India.

Reducing delay in the diagnosis of multidrug-resistant tuberculosis (MDR-TB) by performing genotypic drug susceptibility testing (DST) among eligible patients as early as possible can improve clinical presentation and treatment outcomes and reduce transmission. We aimed to determine the delay from being eligible for DST to performing DST and factors associated with the delay. This was a retrospective cohort study involving record review among presumptive MDR-TB patients who underwent genotypic DST from five selected districts in the state of Gujarat, India (2014). Specimens were couriered from the designated microscopy centres (DMCs) to two designated genotypic DST facilities located outside the districts. Of 2212 patients, the median duration from eligibility to the specimen being sent, from the specimen being sent to DST and from eligibility to DST was 3, 5 and 8 d, respectively. Patients from DMCs in teaching hospitals and with presumptive MDR-TB criteria 'follow-up smear positive' and 'TB-human immunodeficiency virus co-infection' had a significantly higher risk of delay between eligibility and testing (≥8 d). The delay in the specimen being sent after eligibility contributed to high delays in these subgroups. The districts were doing well in implementing timely DST among presumptive MDR-TB patients. However, there is room for improvement in reducing the delays in the sending of specimens among certain patient subgroups.

Spectrum of tuberculosis in children at Federal Medical Centre, Gusau, Zamfara State, Northwestern Nigeria

Background: Children contribute a significant proportion of tuberculosis (TB) burden and suffer severe morbidity and mortality, particularly in endemic areas. The diagnosis of TB in children can be challenging because TB can mimic many common childhood diseases, and therefore, high index of suspicion is required to improve detection of cases. Aims: To determine the prevalence and pattern of TB in children at Federal Medical Centre, Gusau. Subjects and Methods: A retrospective study in children aged 4 months to 13 years admitted to the pediatrics medical ward with TB (over a 1 year period) in the year 2008. Results: Of the 1392 children admitted over this period, 67 were suspected cases of TB, giving a prevalence of 4.8%. Six (9%) patients had TB-human immunodeficiency virus co-infection. Only 6 (9%) children received Bacille-Calmette–Guerin (BCG) vaccine. Disseminated TB (DTB) accounted for 34 (50.7%) of the 67 cases, pulmonary TB was present in 26.9% while 9 (13.4%) had spinal TB. Forty (59.7%) patients successfully completed treatment, 15 (22.4%) were lost to follow-up, and 7 (10.4%) died in the course of treatment. Three (4.5%) defaulted and were retreated while 2 (3%) were referred. Conclusion: The prevalence of childhood TB was 4.8% with low BCG vaccine uptake. DTB was the predominant form, followed by pulmonary and spinal TB. Significant proportion of children successfully completed their treatment regimen while case fatality rate was 10.4%.

Drug-resistant tuberculosis in HIV-infected patients in a national referral hospital, Phnom Penh, Cambodia

Background and objectiveThere are no recent data on the prevalence of drug-resistant tuberculosis (DR TB) in Cambodia. We aim to describe TB drug resistance amongst adults with pulmonary and extra-pulmonary TB and human immunodeficiency virus (HIV) co-infection in a national referral hospital in Phnom Penh, Cambodia.DesignBetween 22 November 2007 and 30 November 2009, clinical specimens from HIV-infected patients suspected of having TB underwent routine microscopy, Mycobacterium tuberculosis culture, and drug susceptibility testing. Laboratory and clinical data were collected for patients with positive M. tuberculosis cultures.ResultsM. tuberculosis was cultured from 236 HIV-infected patients. Resistance to any first-line TB drug occurred in 34.7% of patients; 8.1% had multidrug resistant tuberculosis (MDR TB). The proportion of MDR TB amongst new patients and previously treated patients was 3.7 and 28.9%, respectively (p<0.001). The diagnosis of MDR TB was made after death in 15.8% of patients; in total 26.3% of patients with MDR TB died. The diagnosis of TB was established by culture of extra-pulmonary specimens in 23.6% of cases.ConclusionsThere is significant resistance to first-line TB drugs amongst new and previously treated TB–HIV co-infected patients in Phnom Penh. These data suggest that the prevalence of DR TB in Cambodia may be higher than previously recognised, particularly amongst HIV-infected patients. Additional prevalence studies are needed. This study also illustrates the feasibility and utility of analysis of non-respiratory specimens in the diagnosis of TB, even in low-resource settings, and suggests that extra-pulmonary specimens should be included in TB diagnostic algorithms.

Acquired rifampicin resistance in thrice-weekly antituberculosis therapy: impact of HIV and antiretroviral therapy.

Risk factors for acquired rifampicin resistance (ARR) in human immunodeficiency virus (HIV)/tuberculosis coinfection, in the highly active antiretroviral therapy (HAART) era, needs evaluation. We studied the impact of HIV and HAART on ARR among patients taking thrice-weekly antituberculosis therapy. This cross-protocol analysis included patients with newly diagnosed, rifampicin-susceptible pulmonary tuberculosis, with and without HIV, enrolled in clinical trials (who took >80% of medication) at the National Institute for Research in Tuberculosis between 1999 and 2013. All patients received rifampicin and isoniazid for 6 months reinforced with pyrazinamide and ethambutol in the first 2 months, given thrice-weekly throughout the study along with HAART in one of the groups. Outcomes were categorized and multivariate logistic regression analysis performed to identify risk factors for ARR. The per-protocol results included patients with tuberculosis: 246 HIV-uninfected patients (HIV(-)TB(+)), 212 HIV patients not on HAART (non-HAART), and 116 HIV-infected patients on HAART. Median CD4 counts of the latter 2 groups were 150 and 93 cells/µL, respectively, and the median viral loads were 147 000 and 266 000 copies/mL, respectively. Compared with HIV(-)TB(+), the relative risks (RRs) for an unfavorable response in the coinfected, non-HAART and HAART groups were 2.1 (95% confidence interval [CI], 1.7-14.8; P<.0001) and 2.1 (95% CI, .9-5.2; P=.3), whereas for ARR, the RRs were 21.1 (95% CI, 2.6-184; P<.001) and 8.2 (95% CI, .6-104; P=.07), respectively. HIV-infected patients with tuberculosis treated with a thrice-weekly antituberculosis regimen are at a higher risk of ARR, compared with HIV-uninfected patients, in the presence of baseline isoniazid resistance. HAART reduces but does not eliminate the risk of ARR.

Incidence and Risk Factors of Serious Adverse Events during Antituberculous Treatment in Rwanda: A Prospective Cohort Study

BackgroundTuberculosis (TB) and TB-human immunodeficiency virus infection (HIV) coinfection is a major public health concern in resource-limited settings. Although TB treatment is challenging in HIV-infected patients because of treatment interactions, immunopathological reactions, and concurrent infections, few prospective studies have addressed this in sub-Saharan Africa.In this study we aimed to determine incidence, causes of, and risk factors for serious adverse events among patients on first-line antituberculous treatment, as well as its impact on antituberculous treatment outcome.Methods and findingsProspective observational cohort study of adults treated for TB at the Internal Medicine department of the Kigali University Hospital from May 2008 through August 2009.Of 263 patients enrolled, 253 were retained for analysis: median age 35 (Interquartile range, IQR 28–40), 55% male, 66% HIV-positive with a median CD4 count 104 cells/mm3 (IQR 44–248 cells/mm3). Forty percent had pulmonary TB, 43% extrapulmonary TB and 17% a mixed form. Sixty-four (26%) developed a serious adverse event; 58/167 (35%) HIV-infected vs. 6/86 (7%) HIV-uninfected individuals. Commonest events were concurrent infection (n = 32), drug-induced hepatitis (n = 24) and paradoxical reactions/TB-IRIS (n = 23).HIV-infection (adjusted Hazard Ratio, aHR 3.4, 95% Confidence Interval, CI 1.4–8.7) and extrapulmonary TB (aHR 2, 95%CI 1.1–3.7) were associated with an increased risk of serious adverse events. For TB/HIV co-infected patients, extrapulmonary TB (aHR 2.0, 95%CI 1.1–3.9) and CD4 count <100 cells/mm3 at TB diagnosis (aHR 1.7, 95%CI 1.0–2.9) were independent predictors. Adverse events were associated with an almost two-fold higher risk of unsuccessful treatment outcome at 6 months (HR 1.89, 95%CI 1.3–3.0).ConclusionAdverse events frequently complicate the course of antituberculous treatment and worsen treatment outcome, particularly in patients with extrapulmonary TB and advanced immunodeficiency. Concurrent infection accounts for most events. Our data suggest that deterioration in a patient already receiving antituberculous treatment should prompt an aggressive search for additional infections.

Usefulness of the Polymerase Chain Reaction Dot-Blot Assay, Used with Ziehl-Neelsen Staining, for the Rapid and Conveni­ent Diagnosis of Pulmonary Tuberculosis in Human Immuno­deficiency Virus-Seropositive and -Seronegative Individuals

There are scarce data regarding the value of molecular tests, when used in parallel with classical tools, for the diagnosis of tuberculosis (TB) under field conditions, especially in regions with a high burden of TB-human immunodeficiency virus (HIV) co-infection. We evaluated the usefulness of the polymerase chain reaction dot-blot assay (PCR) used in parallel with Ziehl-Neelsen staining (ZN) for pulmonary tuberculosis (PTB) diagnosis, in a TB-HIV reference hospital. All sputum samples from 277 patients were tested by ZN, culture, and PCR. Performances were assessed individually, in parallel, for HIV status, history of anti-TB treatment, and in different simulated TB prevalence rates. Overall, the PTB prevalence was 46% (128/277); in HIV-seropositive (HIV+) individuals, PTB prevalence was 54% (40/74); the ZN technique had a lower sensitivity (SE) in the HIV+ group than in the HIV-seronegative (HIV−) group (43% vs. 68%; Fisher test, P<0.05); and the SE of PCR was not affected by HIV status (Fisher test; P=0.46). ZN, in parallel with PCR, presented the following results: i) among all PTB suspects, SE of 90%, specificity (SP) of 84%, likelihood ratio (LR)+ of 5.65 and LR− of 0.12; ii) in HIV− subjects: SE of 92%, LR− of 0.10; iii) in not previously treated cases: SE of 90%, LR− of 0.11; iv) in TB, prevalence rates of 5–20%; negative predictive values (NPV) of 98–99%. ZN used in parallel with PCR showed an improvement in SE, LR−, and NPV, and may offer a novel approach in ruling out PTB cases, especially in not previously treated HIV− individuals, attended in hospitals in developing nations.