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.

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.

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.

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.

Preventing opportunistic infections among human immunodeficiency virus-infected adults in African countries.

The burden of human immunodeficiency virus (HIV)-related disease in sub-Saharan Africa continues to increase; providing adequate care for the huge number of people affected is a daunting task, especially given the limited resources available. Recent studies have shown that low-cost regimens can prevent some of the most important causes of HIV-related disease in African countries. Isoniazid preventive therapy can reduce the incidence of tuberculosis; priorities are to seek opportunities for implementation, to assess effectiveness under operational conditions, and to monitor its effect on resistance patterns. Cotrimoxazole was shown to be highly effective in reducing morbidity and mortality among individuals with symptomatic HIV disease in Côte d'Ivoire, and should be implemented where it is likely to be of benefit. Pneumococcal polysaccharide vaccine was disappointingly ineffective among HIV-infected Ugandan adults, but newer conjugate vaccines are becoming available that should be investigated. The benefit of these preventive regimens to the individual may be modest when compared with the effect of antiretroviral therapy. However, simple preventive therapies could reach a much wider population than is immediately feasible for expensive and complex antiretroviral regimens, and thus have the potential for substantial benefit at the population level. The availability of effective and affordable regimens to prevent HIV-related disease may also encourage people to seek HIV testing, combat denial, and help overcome the sense of powerlessness in countries where the HIV epidemic has hit hardest.

HIV infection and silicosis: the impact of two potent risk factors on the incidence of mycobacterial disease in South African miners.

OBJECTIVE: To investigate the combined effects of HIV infection and silicosis on mycobacterial disease. DESIGN AND SETTING: A retrospective cohort of 1374 HIV-positive and 2648 HIV-negative miners who attended a South African gold mining hospital and primary health clinics. PARTICIPANTS: Miners who had been tested for HIV, with consent, at primary health clinics during 1991-1996, predominantly because of a symptomatic sexually transmitted disease. RESULTS: Tuberculosis (TB) incidence was 4.9 and 1.1 per 100 person-years in HIV-positive and HIV-negative miners respectively. The incidence of Mycobacterium kansasii disease was also high (0.32 and 0.10 per 100 person-years, respectively). Silicosis was highly prevalent, implying inadequate dust control, and was a significant TB risk factor among both HIV-positive and HIV-negative men (adjusted incidence rate ratios 1.4-2.5 according to radiological severity). The data were consistent with the risks of silicosis and HIV combining multiplicatively, but did not fit an additive model. The incidence of HIV-associated TB increased significantly during the study, with no corresponding change in HIV-negative rates, to reach 16.1 per 100 person-years among HIV-positive silicotics. CONCLUSIONS: The risks of silicosis and HIV infection combine multiplicatively, so that TB remains as much a silica-related occupational disease in HIV-positive as in HIV-negative miners, and HIV-positive silicotics have considerably higher TB incidence rates than those reported from other HIV-positive Africans. The increasing impact of HIV over time may indicate epidemic TB transmission with rapid disease development in HIV-infected miners. Similar but currently unrecognized interactions may be contributing to TB control problems in other industrializing countries affected by the HIV epidemic.

Factors associated with an increased case-fatality rate in HIV-infected and non-infected South African gold miners with pulmonary tuberculosis.

SETTING: A gold mining company in the Free State Province, South Africa. AIM AND DESIGN: A retrospective cohort study to investigate factors associated with an increased case-fatality rate (CFR) at 6 months in human immunodeficiency virus (HIV) positive and negative tuberculosis (TB) patients. RESULTS: Between April 1993 and March 1997, there were 2236 men with culture-confirmed pulmonary TB in whom HIV status and treatment outcome were known. The overall CFR within the first 6 months of therapy was low (3.6%). After adjusting for confounding factors, HIV infection (OR 15.0, 95%CI 7.4-30.6), self-presentation compared to detection by the active radiological screening programme (OR 5.6, 95%CI 2.6-12.2) and presence of silicosis (OR 3.0, 95%CI 1.4-6.3) were significantly associated with an increased CFR. Opportunistic infections accounted for 56.2% (36/64) of deaths in HIV-positive men. Cryptococcal disease accounted for 75% (27/36) of deaths from opportunistic infections. CONCLUSION: HIV infection and silicosis are both powerful risk factors for TB and are associated with an increased risk of death. Strategies aimed at reducing these two risk factors within the workforce could reduce TB incidence and mortality. In settings with functional DOTS programmes and sufficient resources, expanding the DOTS programme to include active case detection should be explored as a means of reducing TB prevalence and mortality.

HIV/AIDS among African Americans: progress or progression?

OBJECTIVES: To review data on the extent of HIV infection and associated risk behaviors, the occurrence of AIDS, and HIV-related mortality in African Americans and to suggest what can be done to reduce HIV exposure and infection in this population. DESIGN/METHODS: Review of epidemiologic, published, multisite data on HIV infection in, and related behaviors of, African Americans. RESULTS: On every epidemiologic measure in common use, African Americans, compared with the four other federally recognized racial/ethnic groups, have the most severe epidemic. The trend data show continuing growth in the African American epidemic despite the availability of effective behavioral interventions and biomedical treatments. Few published intervention studies with African American populations have been adequately evaluated; nor have they focused proportionately on men who have sex with men, a group in the African American community with continuing high rates of infection. CONCLUSIONS: Rates of HIV transmission and disease among African Americans are high, disproportionate, and are not declining as significantly in response to effective interventions as they are among whites. Attention is urgently needed to increase our understanding of risk behaviors, social networks, and specific factors in the African American community that can be altered to reduce HIV infection. Macroenvironmental factors--poverty, social class, racism--need to be studied to suggest possible intervention components to reduce rates of HIV transmission and to increase the use of therapies that are more effectively slowing disease progression and lowering death rates among whites.

Drug-resistant tuberculosis in South African gold miners: incidence and associated factors.

SETTING: A gold mining company in the Free State Province of South Africa. OBJECTIVE: To document the incidence of and factors associated with drug-resistant tuberculosis (TB) in South African gold miners. DESIGN: Review of Mycobacterium tuberculosis drug susceptibility records for the period from 1 July 1993 to 30 June 1997. RESULTS: Over the study period, 2241 miners had culture-positive M. tuberculosis pulmonary disease where isolates were tested for drug susceptibility to the four primary anti-tuberculosis drugs. The proportions of primary and acquired drug resistance were respectively 7.3% and 14.3% for isoniazid and 1.0% and 2.8% for resistance to at least isoniazid and rifampicin (multidrug resistance). Resistance to streptomycin and ethambutol was uncommon, and rifampicin monoresistance was rare. No significant factors for primary drug resistance were identified. Patients with retreatment pulmonary TB who failed primary TB treatment (versus cure) were significantly more likely to have TB with resistance to any TB drug or MDR (odds ratios respectively 9.82, 95%CI 2.97-33.5, and 18.74, 95%CI 1.76-475). Human immunodeficiency virus (HIV) infection was not significantly associated with primary or acquired drug resistance, and there was no trend of increasing resistance over time. CONCLUSION: Anti-tuberculosis drug resistance has remained stable despite the HIV epidemic and increasing TB rates. Directly observed therapy may have contributed to containing the level of drug resistance. Adherence to and completion of treatment are essential to prevent drug resistance and treatment failure, including in situations with high HIV prevalence.

The impact of HIV infection on recurrence of tuberculosis in South African gold miners.

UNLABELLED: DESIGN AND OBJECTIVES: Potential risk factors for recurrence of tuberculosis (TB) were investigated in a retrospective cohort study of 305 human immunodeficiency virus (HIV) positive and 984 HIV-negative South African gold miners treated for TB with directly-observed, rifampicin-based regimens. Standard treatment changed from rifampicin, isoniazid and pyrazinamide (RHZ) to RHZ plus ethambutol (RHZE) during the study period. RESULTS: Recurrence occurred in 37 HIV-positive and 46 HIV-negative men. HIV infection was associated with a significantly higher recurrence rate (8.2 vs 2.2 per 100 person-years; multivariate-adjusted incidence rate ratio [IRR] 4.9, 95% confidence interval [CI] 3.0-8.1), as were post-tuberculous scarring (multivariate-adjusted IRR 1.6 for one or two scarred lung zones, 4.0 for three or more zones; test for trend P < 0.001) and drug resistance (multivariate-adjusted IRR 2.7, 95%CI 1.01-7.4). The recurrence rate was significantly higher following treatment with RHZ than RHZE (multivariate-adjusted IRR 2.1, 95%CI 1.1-4.0). The difference between regimens needs to be interpreted with caution, however, as allocation was not randomised. CONCLUSION: The high recurrence rate among HIV-positive men requires further investigation to distinguish relapse from re-infection as the predominant cause, leading to consideration of further intensification of the initial regimen or use of secondary prophylaxis.

Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice.

Each year, an estimated 590,000 infants acquire human immunodeficiency virus type 1 (HIV) infection from their mothers, mostly in developing countries that are unable to implement interventions now standard in the industrialized world. In resource-poor settings, the HIV pandemic has eroded hard-won gains in infant and child survival. Recent clinical trial results from international settings suggest that short-course antiretroviral regimens could significantly reduce perinatal HIV transmission worldwide if research findings could be translated into practice. This article reviews current knowledge of mother-to-child HIV transmission in developing countries, summarizes key findings from the trials, outlines future research requirements, and describes public health challenges of implementing perinatal HIV prevention interventions in resource-poor settings. Public health efforts must also emphasize primary prevention strategies to reduce incident HIV infections among adolescents and women of childbearing age. Successful implementation of available perinatal HIV interventions could substantially improve global child survival.