Trends in TB and HIV care and treatment cascade, Kenya, 2008-2018.

BACKGROUND: HIV infection is associated with high mortality among people with TB. Antiretroviral therapy (ART) reduces TB incidence and mortality among people living with HIV (PLHIV). Since 2005, Kenya has scaled up TB and HIV prevention, diagnosis and treatment. We evaluated the impact of these services on trends and TB treatment outcomes.METHODS: Using Microsoft Excel (2016) and Epi-Info 7, we analysed Kenya Ministry of Health TB surveillance data from 2008 to 2018 to determine trends in TB notifications, TB classification, HIV and ART status, and TB treatment outcomes.RESULTS: Among the 1,047,406 people reported with TB, 93% knew their HIV status, and 37% of these were HIV-positive. Among persons with TB and HIV, 69% received ART. Between 2008 and 2018, annual TB notifications declined from 110,252 to 96,562, and HIV-coinfection declined from 45% to 27%. HIV testing and ART uptake increased from 83% to 98% and from 30% to 97%, respectively. TB case fatality rose from 3.5% to 3.9% (P <0.018) among HIV-negative people and from 5.1% to 11.2% (P <0.001) among PLHIV on ART.CONCLUSION: TB notifications decreased in settings with suboptimal case detection. Although HIV-TB services were scaled-up, HIV-TB case fatality rose significantly. Concerted efforts are needed to address case detection and gaps in quality of TB care.

Can isoniazid preventive therapy be scaled up rapidly? Lessons learned in Kenya, 2014-2018.

BACKGROUND: TB is the leading cause of mortality among people living with HIV (PLHIV), for whom isoniazid preventive therapy (IPT) has a proven mortality benefit. Despite WHO recommendations, countries have been slow in scaling up IPT. This study describes processes, challenges, solutions, outcomes and lessons learned during IPT scale-up in Kenya.METHODS: We conducted a desk review and analyzed aggregated Ministry of Health (MOH) IPT enrollment data from 2014 to 2018 to determine trends and impact of program activities. We further analyzed IPT completion reports for patients initiated from 2015 to 2017 in 745 MOH sites in Nairobi, Central, Eastern and Western Kenya.RESULTS: IPT was scaled up 75-fold from 2014 to 2018: the number of PLHIV covered increased from 9,981 to 749,890. The highest percentage increases in the cumulative number of PLHIV on IPT were seen in the quarters following IPT pilot projects in 2014 (49%), national launch in 2015 (54%), and HIV treatment acceleration in 2016 (158%). Among 250,069 patients initiating IPT from 2015 to 2017, 97.5% completed treatment, 0.2% died, 0.8% were lost to follow-up, 1.0% were not evaluated, and 0.6% discontinued treatment.CONCLUSIONS: IPT can be scaled up rapidly and effectively among PLHIV. Deliberate MOH efforts, strong leadership, service delivery integration, continuous mentorship, stakeholder involvement, and accountability are critical to program success.

Musculoskeletal ultrasound for interventional physiatry.

More and more physiatrists are interested in learning how to use musculoskeletal ultrasonography in their clinical practice. The possibility of high resolution, dynamic, comparative and repeatable imaging makes it an important diagnostic tool for soft tissue pathology. There is also growing interest to use sonography for guiding interventions such as aspirations and infiltrations. In daily practice these are often done blindly or palpation-guided. To improve the accuracy of interventions, fluoroscopy or computed tomography were traditionally used for guidance. Since sonography is non-ionizing, readily available and relatively low cost, it has become the first choice to guide many musculoskeletal interventions. Ultrasound allows real-time imaging of target and needle as well as surrounding vulnerable structures such as vessels and nerves. Many different techniques are proposed in the literature. Interventions under ultrasound guidance have been proven to be more accurate than unguided ones. Further studies are required to prove better clinical results and fewer complications. Infection is the most dreaded complication. This review wants to highlight technical aspects of ultrasound guidance of interventions and give a survey of different interventions that have been introduced, with emphasis on applications in Physical Medicine and Rehabilitation. Results and complications are discussed. Finally training requirements and modalities are presented.

Antiretroviral therapy and the control of HIV-associated tuberculosis. Will ART do it?

The human immunodeficiency virus (HIV) associated tuberculosis (TB) epidemic remains an enormous challenge to TB control in countries with a high prevalence of HIV. In their 1999 article entitled 'Will DOTS do it?', De Cock and Chaisson questioned whether the World Health Organization's DOTS Strategy could control this epidemic. Data over the past 10 years have clearly shown that DOTS is insufficient as a single TB control intervention in such settings because it does not address the fundamental epidemiological interactions between TB and HIV. Immunodeficiency is a principal driver of this epidemic, and the solution must therefore include immune recovery using antiretroviral therapy (ART). Thus, in the era of global ART scale-up, we now ask the question, 'Will ART do it?' ART reduces the risk of TB by 67% (95%CI 61-73), halves TB recurrence rates, reduces mortality risk by 64-95% in cohorts and prolongs survival in patients with HIV-associated drug-resistant TB. However, the cumulative lifetime risk of TB in HIV-infected individuals is a function of time spent at various CD4-defined levels of risk, both before and during ART. Current initiation of ART at low CD4 cell counts (by which time much HIV-associated TB has already occurred) and low effective coverage greatly undermine the potential impact of ART at a population level. Thus, while ART has proven a critical intervention for case management of HIV-associated TB, much of its preventive potential for TB control is currently being squandered. Much earlier ART initiation with high coverage is required if ART is to substantially influence the incidence of TB.

Flow cytometric immunobead assay for the detection of BCR-ABL fusion proteins in leukemia patients.

BCR-ABL fusion proteins show increased signaling through their ABL tyrosine kinase domain, which can be blocked by specific inhibitors, thereby providing effective treatment. This makes detection of BCR-ABL aberrations of utmost importance for diagnosis, classification and treatment of leukemia patients. BCR-ABL aberrations are currently detected by karyotyping, fluorescence in situ hybridization (FISH) or PCR techniques, which are time consuming and require specialized facilities. We developed a simple flow cytometric immunobead assay for detection of BCR-ABL fusion proteins in cell lysates, using a bead-bound anti-BCR catching antibody and a fluorochrome-conjugated anti-ABL detection antibody. We noticed protein stability problems in lysates caused by proteases from mature myeloid cells. This problem could largely be solved by adding protease inhibitors in several steps of the immunobead assay. Testing of 145 patient samples showed fully concordant results between the BCR-ABL immunobead assay and reverse transcriptase PCR of fusion gene transcripts. Dilution experiments with BCR-ABL positive cell lines revealed sensitivities of at least 1%. We conclude that the BCR-ABL immunobead assay detects all types of BCR-ABL proteins in leukemic cells with high specificity and sensitivity. The assay does not need specialized laboratory facilities other than a flow cytometer, provides results within approximately 4 h, and can be run in parallel to routine immunophenotyping.

Free radical scavengers have a preventive effect on heterotopic bone formation following manipulation of immobilized rabbit legs.

AIM: The pathogenesis of heterotopic ossification (HO) is still unclear and the preventive measures and therapies are usually insufficient. The authors compared free radical scavengers with placebo in order to assess the magnitude of their inhibitory effect on the development of HO. METHODS: A standard immobilization-manipulation model was used to induce HO in the hind legs of twenty female New Zealand albino rabbits. The animals were divided into two groups and received daily either placebo or a free radical scavenger (A/A) cocktail in a randomized double-blind fashion. Every four days an X-ray was taken and the thickness and length of new bone formation were measured at the thigh by two investigators independently. RESULTS: Fisher's exact test revealed a significant difference in the development of heterotopic ossification between the placebo group and the A/A group (70% versus none, respectively ; P=0.0031). CONCLUSION: The ischemia/reperfusion syndrome could be an important precipitating factor in the pathogenesis of heterotopic ossification and free radical scavengers were found to have a significant inhibitory effect on its development in a rabbit model. The results of this experimental model can be an impetus for further research into the prevention of heterotopic bone formation in humans.

Contribution of reinfection to recurrent tuberculosis in South African gold miners.

SETTING: A gold mine in South Africa. OBJECTIVE: To investigate incidence and risk factors for tuberculosis (TB) recurrence and the relative contribution of reinfection and relapse to recurrence. DESIGN: Prospective cohort study. METHODS: Employees cured of a first episode of culture-positive TB were followed up for recurrence, which was classified as reinfection or relapse by restriction fragment length polymorphism using an insertion sequence (IS) 6110 probe. RESULTS: Among 609 patients, 57 experienced recurrence during a median follow-up period of 1.02 years, corresponding to a recurrence rate of 7.89 per 100 person-years (py). The culture positive recurrence rate was 5.79/100 py, and was higher in human immunodeficiency virus (HIV) infected patients (8.86/100 py in HIV-infected vs. 3.35/100 py in non-HIV-infected). Among HIV-infected patients, the risk of culture-positive recurrence was higher with decreasing CD4 count (compared with CD4 < 200, hazard ratios for recurrence among individuals with CD4 200-500 and CD4 > 500 were 0.40 [95%CI 0.14-1.09] and 0.14 [95%CI 0.02-1.10], respectively, Ptrend = 0.01). IS6110 genotyping was available on both the initial and subsequent isolate for 16/42 (38%, 14 HIV-infected) patients with culture-positive recurrence, and showed reinfection in 11 (69%). CONCLUSION: HIV-infected gold miners, particularly those who are more immunosuppressed, are at higher risk of TB recurrence. TB control strategies need to take into account reinfection as an important cause of recurrent TB.

Tuberculosis risk among staff of a large public hospital in Kenya.

SETTING: In sub-Saharan Africa, high rates of tuberculosis (TB) and human immunodeficiency virus (HIV) infection pose a serious threat for occupationally acquired TB among health care workers. OBJECTIVE: To identify factors associated with TB disease among staff of an 1800-bed hospital in Kenya. DESIGN: We calculated TB incidence among staff and conducted a case-control study where cases (n = 65) were staff diagnosed with TB and controls (n = 316) were randomly selected staff without recent TB. RESULTS: The annual incidence of TB from 2001 to 2005 ranged from 645 to 1115 per 100000 population. Factors associated with TB disease were additional daily hours spent in rooms with patients (adjusted odds ratio [aOR] 1.3, 95%CI 1.2-1.5), working in areas where TB patients received care (aOR 2.1, 95%CI 1.1-4.2), HIV infection (aOR 29.1, 95%CI 5.1-167) and living in a slum (aOR 4.7, 95%CI 1.8-12.5) or hospital-provided low-income housing (aOR 2.6, 95%CI 1.2-5.6). CONCLUSION: Hospital exposures were associated with TB disease among staff at this hospital regardless of their job designation, even after controlling for living conditions, suggesting transmission from patients. Health care facilities should improve infection control practices, provide quality occupational health services and encourage staff testing for HIV infection to address the TB burden in hospital staff.

Provider-initiated HIV testing and counselling for TB patients and suspects in Nairobi, Kenya.

SETTING: Integrated tuberculosis (TB) and human immunodeficiency virus (HIV) services in a resource-constrained setting. OBJECTIVE: Pilot provider-initiated HIV testing and counselling (PITC) for TB patients and suspects. DESIGN: Through partnerships, resources were mobilised to establish and support services. After community sensitisation and staff training, PITC was introduced to TB patients and then to TB suspects from December 2003 to December 2005. RESULTS: Of 5457 TB suspects who received PITC, 89% underwent HIV testing. Although not statistically significant, TB suspects with TB disease had an HIV prevalence of 61% compared to 63% for those without. Of the 614 suspects who declined HIV testing, 402 (65%) had TB disease. Of 2283 patients referred for cotrimoxazole prophylaxis, 1951 (86%) were enrolled, and of 1727 patients assessed for antiretroviral treatment (ART), 1618 (94%) were eligible and 1441 (83%) started treatment. CONCLUSIONS: PITC represents a paradigm shift and is feasible and acceptable to TB patients and TB suspects. Clear directives are nevertheless required to change practice. When offered to TB suspects, PITC identifies large numbers of persons requiring HIV care. Community sensitisation, staff training, multitasking and access to HIV care contributed to a high acceptance of HIV testing. Kenya is using this experience to inform national response and advocate wide PITC implementation in settings faced with the TB-HIV epidemic.

The relation of arterial stiffness to endothelial function in healthy subjects.

Local wall stiffness affects endothelial responsiveness but how global measures affect responsiveness is unanswered. We assessed this by comparing reactive hyperaemic responses of brachial diameter (RHRBD) with central (heart-to-brachial artery pulse wave velocity (PWV); large (C1)) and peripheral (C2) arterial stiffness. Twelve healthy subjects were investigated. RHRBD was induced via an upper- or forearm occluding cuff. Arterial diameter changes were measured using echo ultrasound. Arterial stiffness and RHRBD were compared using a Pearson correlation coefficient (r) and Bland-Altman analysis of Z-scores (indicated as 95% confidence intervals (CI) and expressed in units of standard deviation (SD) from the mean). Weak relations were found between upper-arm RHRBD responses and C2 (r = 0.56, P = 0.06; 95% CI +/- 1.84 SDs) and C1 (r = 0.55, P = 0.06; 95% CI +/- 1.86 SDs). An inverse relation was found between upper-arm RHRBD responses and PWV (r = -0.55, P = 0.06), but Bland-Altman plots revealed no agreement between these parameters (P > 0.05; 95% CI +/- 3.46 SDs). Forearm RHRBD were not related to PWV, C1 or C2 (P > 0.05; 95% CI > 2 SDs). The weak relation between upper-arm endothelial responses and C2 and C1 seems to suggest that C2, and also C1, is not a good and reliable method for assessments of endothelial health. Furthermore, if anything, upper-arm mediated RHRBD responses are more affected by arterial stiffness than forearm responses.

Free radical scavengers are more effective than indomethacin in the prevention of experimentally induced heterotopic ossification.

The pathogenesis of heterotopic ossification is still unclear and the preventive therapies are usually insufficient. The present study was designed to investigate the possible preventive effect of free radical scavengers on the development of experimentally induced heterotopic ossification in a rabbit model and to compare free radical scavengers with indomethacin to determine whether they act synergistically. A standard immobilization-manipulation model was used to induce heterotopic ossification in the hind legs of 40 1-year-old female New Zealand albino rabbits. The animals were divided into four groups and received daily either placebo, a free radical scavenger cocktail [allopurinol and N-acetylcysteine (A/A)], indomethacin or the combination of A/A and indomethacin in a randomized double-blind fashion. Every 4 days an X-ray was taken and the thickness and length of new bone formation was measured at the thigh. A marked statistically significant difference was found between the four groups. In the groups that received A/A, either alone or combined with indomethacin, an inhibition of bone growth, both in thickness and in length was demonstrated. In this experimental model free radical scavengers had a superior inhibitory effect on heterotopic ossification than indomethacin. Free radicals could play an important role in the pathogenesis of heterotopic ossification.

Comparison of the nutrient analysis and caloric density of 30 commercial seed mixtures (in toto and dehulled) with 27 commercial diets for parrots.

In this paper, an overview is given of the composition of 30 commercially available parrot seed mixtures. As parrots dehull the seeds, the analysis of the total seed mixture tends to differ from that of the ingested feed. Statistical evaluation and comparison of the dehulled seeds vs. the whole seeds indicates that most parrot species are fed a diet rich in fat (31.7 +/- 13.1% crude fat) and energy (22.4 +/- 2.9 MJ ME/kg). As the analysis of the total seed mixtures underestimates fat and energy content of the ingested feed, it is suggested that researchers, bird nutritionists and bird food producers should calculate diets based on the analysis of the dehulled seeds. Finally, the calculated data were compared with the composition of formulated pelleted/extruded diets on the market. These data indicate that the energy density of most diets (15.6 +/- 1.4 MJ ME/kg) is far below the energy density of common seed mixtures.

Quantitation of 11 -nor-delta9-tetrahydrocannabinol-9-carboxylic acid with GC-MS in urine collected for doping analysis.

An accurate, reproducible, and validated gas chromatography-mass spectrometry (GC-MS) method for the quantitation of 11 -nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), the major metabolite of delta9-tetrahydrocannabinol, in urine is described. Extraction was performed with n-hexane/ethyl acetate. Deuterated THC-COOH was used as the internal standard. The GC-MS analysis was done by selected ion monitoring. No interferences were detected in 20 blank urine samples of different origin. The calibration curve was found to be linear over the range of 10-100 ng/mL. The calculated limits of detection and quantitation were 1.0 ng/mL and 1.7 ng/mL, respectively. Results of positive findings for cannabis use in doping control in Flanders and Portugal in the period of 1997-2000 are commented.

Persistent radiological changes following miliary tuberculosis in miners exposed to silica dust.

SETTING: Silicosis leads to increased susceptibility to tuberculosis, but it has also been suggested that tuberculosis may interact with intra-pulmonary silica to exacerbate fibrotic lung disease. OBJECTIVES: To investigate the possibility that silicosis developed due to or was exacerbated by tuberculosis. METHODS: In a case series of 15 miners presenting with culture-positive miliary tuberculosis, serial radiographs taken premorbidly, at presentation, and after 2 and 6 months of standard anti-tuberculosis treatment were graded for nodularity using the International Labour Organization system. RESULTS: Increased nodule profusion (compared to premorbid film) remained in 13 (87%) and eight (53%) patients after 2 and 6 months of treatment, respectively, despite clinical improvement in all and documented bacteriological cure in eight (53%). These phenomena, observed irrespective of human immunodeficiency virus (HIV) status, were most pronounced in men with minor premorbid changes. Abnormal pulmonary collagenisation related to silica particles was apparent at post-mortem in two men who died of HIV-associated cryptococcosis after completing TB treatment. CONCLUSIONS: Previous silica exposure appears to result in delayed and potentially incomplete radiological resolution of miliary TB. We postulate that the immune response in tubercles may evoke a 'bystander' fibrotic response, as cytokines play a central role in the pathogenesis of both TB and silicosis.

The Serostatus Approach to Fighting the HIV Epidemic: prevention strategies for infected individuals.

In the United States, HIV prevention programs have historically tailored activities for specific groups primarily on the basis of behavioral risk factors and demographic characteristics. Through the Serostatus Approach to Fighting the Epidemic (SAFE), the Centers for Disease Control and Prevention is now expanding prevention programs, especially for individuals with HIV, to reduce the risk of transmission as a supplement to current programs that primarily focus on reducing the risk of acquisition of the virus. For individuals with HIV, SAFE comprises action steps that focus on diagnosing all HIV-infected persons, linking them to appropriate high-quality care and prevention services, helping them adhere to treatment regimens, and supporting them in adopting and sustaining HIV risk reduction behavior. SAFE couple a traditional infectious disease control focus on the infected person with behavioral interventions that have been standard for HIV prevention programs.

HIV in the United States at the turn of the century: an epidemic in transition.

OBJECTIVES: The current status of and changes in the HIV epidemic in the United States are described. METHODS: Surveillance data were used to evaluate time trends in AIDS diagnoses and deaths. Estimates of HIV incidence were derived from studies done during the 1990s; time trends in recent HIV incidence were inferred from HIV diagnoses and seroprevalence rates among young persons. RESULTS: Numbers of deaths and AIDS diagnoses decreased dramatically during 1996 and 1997 but stabilized or declined only slightly during 1998 and 1999. Proportional decreases were smallest among African American women, women in the South, and persons infected through heterosexual contact, HIV incidence has been roughly constant since 1992 in most populations with time trend data, remains highest among men who have sex with men and injection drug users, and typically is higher among African Americans than other racial/ethnic groups. CONCLUSIONS: The epidemic increasingly affects women minorities, persons infected through heterosexual contact, and the poor. Renewed interest and investment in HIV and AIDS surveillance and surveillance of behaviors associated with HIV transmission are essential to direct resources for prevention to populations with greatest need and to evaluate intervention programs.

Epidemiology and the emergence of human immunodeficiency virus and acquired immune deficiency syndrome.

Although acquired immune deficiency syndrome (AIDS) was first described in the USA in 1981, there is evidence that individual cases occurred considerably earlier in Central Africa, and serological and virological data show human immunodeficiency virus (HIV) was present in the Democratic Republic of Congo (DRC) as far back as 1959. It is likely that HIV-1 infection in humans was established from cross-species transmission of simian immunodeficiency virus of chimpanzees, but the circumstances surrounding this zoonotic transfer are uncertain. This presentation will review how causality is established in epidemiology, and review the evidence (a putative ecological association) surrounding the hypothesis that early HIV-1 infections were associated with trials of oral polio vaccine (OPV) in the DRC. From an epidemiological standpoint, the OPV hypothesis is not supported by data and the ecological association proposed between OPV use and early HIV/AIDS cases is unconvincing. It is likely that Africa will continue to dominate global HIV and AIDS epidemiology in the near to medium-term future, and that the epidemic will evolve over many decades unless a preventive vaccine becomes widely available.