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Implementation and Operational Research: Implementation of the WHO 2011 Recommendations for Isoniazid Preventive Therapy (IPT) in Children Living With HIV/AIDS: A Ugandan Experience.
Journal of Acquired Immune Deficiency Syndromes. 2016 Jan 1; 71(1):e1-8.BACKGROUND: Intensified tuberculosis (TB) case finding and isoniazid preventive therapy (IPT) are strongly recommended for children who are HIV infected. Data are needed to assess the feasibility of the WHO 2011 intensified tuberculosis case finding/IPT clinical algorithm. METHODS: Children who are HIV infected and attending Nsambya Home Care at Nsambya Hospital, Uganda, were screened for TB following WHO recommendations. IPT was given for 6 months after excluding TB. Factors associated with time to IPT initiation were investigated by multivariate Cox proportional hazard regression. Health care workers were interviewed on reasons for delay in IPT initiation. RESULTS: Among the 899 (49% male) children with HIV, 529 (58.8%) were screened for TB from January 2011 to February 2013. Children with active TB were 36/529 (6.8%), 24 (4.5%) were lost to follow-ups and 280 (52.9%) started IPT, 86/280 (30.7%) within 3 months of TB screening and 194/280 (69.3%) thereafter. Among the 529 children screened for TB, longer time to IPT initiation was independently associated with cough at TB screening (hazard ratio 0.62, P = 0.02, 95% confidence interval: 0.41 to 0.94). Four children (1% of those starting treatments) interrupted IPT because of a 5-fold increase in liver function measurements. In the survey, Health care workers reported poor adherence to antiretroviral therapy, poor attendance to periodic HIV follow-ups, and pill burden as the 3 main reasons to delay IPT. CONCLUSION: In resource-constrained settings, considerable delays in IPT initiation may occur, particularly in children with HIV who are presenting with cough at TB screening. The good safety profile of isoniazid in antiretroviral-therapy-experienced children provides further support to IPT implementation in this population.
Improving tuberculosis screening and isoniazid preventive therapy in an HIV clinic in Addis Ababa, Ethiopia.
International Journal of Tuberculosis and Lung Disease. 2013 Nov; 17(11):1396-401.BACKGROUND: The World Health Organization (WHO) recommends active tuberculosis (TB) case finding among people living with human immunodeficiency virus (HIV) in resource-limited settings using a symptom-based algorithm; those without active TB disease should be offered isoniazid preventive therapy (IPT). OBJECTIVE: To evaluate rates of adherence to WHO recommendations and the impact of a quality improvement intervention in an HIV clinic in Addis Ababa, Ethiopia. DESIGN: A prospective study design was utilized to compare TB symptom screening and IPT administration rates before and after a quality improvement intervention consisting of 1) educational sessions, 2) visual reminders, and 3) use of a screening checklist. RESULTS: A total of 751 HIV-infected patient visits were evaluated. The proportion of patients screened for TB symptoms increased from 22% at baseline to 94% following the intervention (P < 0.001). Screening rates improved from 51% to 81% (P < 0.001) for physicians and from 3% to 100% (P < 0.001) for nurses. Of the 281 patients with negative TB symptom screens and eligible for IPT, 4% were prescribed IPT before the intervention compared to 81% after (P < 0.001). CONCLUSIONS: We found that a quality improvement intervention significantly increased WHO-recommended TB screening rates and IPT administration. Utilizing nurses can help increase TB screening and IPT provision in resource-limited settings.
Performance of the new WHO diagnostic algorithm for smear-negative pulmonary tuberculosis in HIV prevalent settings: a multisite study in Uganda.
Tropical Medicine and International Health. 2012 Jul; 17(7):884-95.OBJECTIVE: To compare the performance of the new WHO (2007) diagnostic algorithm for pulmonary tuberculosis (PTB) in high HIV prevalent settings (WHO07) to the WHO 2003 guidelines used by the Ugandan National Tuberculosis Program (UgWHO03). METHODS: A prospective observational cohort design was used at Reach Out Mbuya Parish HIV/AIDS Initiative, an urban slum community-based AIDS Service Organisation (ASO) and Kayunga Rural District Government Hospital. Newly diagnosed and enrolled HIV-infected patients were assessed for PTB. Research staff interviewed patients and staff and observed operational constraints. RESULTS: WHO07 reduced the time to diagnosis of smear-negative PTB with increased sensitivity compared with the UgWHO03 at both sites. Time to diagnosis of smear-negative PTB was significantly shorter at the urban ASO than at the rural ASO (12.4 vs. 28.5 days, P = 0.003). Diagnostic specificity and sensitivity [95% confidence intervals (CIs)] for smear-negative PTB were higher at the rural hospital compared with the urban ASO: [98% (93-100%) vs. 86% (77-92%), P = 0.001] and [95% (72-100%) vs. 90% (54-99%), P > 0.05], respectively. Common barriers to implementation of algorithms included failure by patients to attend follow-up appointments and poor adherence by healthcare workers to algorithms. CONCLUSION: At both sites, WHO07 expedited diagnosis of smear-negative PTB with increased diagnostic accuracy compared with the UgWHO03. The WHO07 expedited diagnosis more at the urban ASO but with more diagnostic accuracy at the rural hospital. Barriers to implementation should be taken into account when operationalising these guidelines for TB diagnosis in resource-limited settings. (c) 2012 Blackwell Publishing Ltd.
Lancet. 2010 May 22; 375(9728):1757-8.This article describes several urgent actions that are needed to promote rapid scale-up of effective and integrated services for tuberculosis and HIV and to tackle the factors that increase vulnerability and put people at risk of HIV-related tuberculosis. These include: bold national leadership, health system restructuring to foster greater integration of tuberculosis and HIV services that provide routine tuberculosis screening, treatment, and prevention to people living with HIV; and to offer HIV counseling and testing to all patients with signs and symptoms of tuberculosis, decentralized care to ensure improved access, investment in new tools and better use of existing tools, and global leadership from donors, countries of the global south, and key health agencies.
Two vs. three sputum samples for microscopic detection of tuberculosis in a high HIV prevalence population.
International Journal of Tuberculosis and Lung Disease. 2009 Jul; 13(7):842-7.SETTING: A busy urban hospital in Cameroon. OBJECTIVES: To compare the yield in bacteriologically proven tuberculosis (TB) cases examining two morning vs. three spot-morning-spot sputum specimens (MM vs. SMS) by direct microscopy for acid-fast bacilli (AFB). DESIGN: Repeated temporal cross-over between MM and SMS sampling for successive TB suspects, using culture as gold standard. RESULTS: A total of 799 suspects were screened using the MM strategy, identifying 223 smear-positives, and 808 suspects with the SMS strategy, yielding 236 smear-positives. Of the MM, 256 were culture-positive, of whom 195 (76%) were smear-positive. For SMS, these figures were respectively 281 and 206 (73%), a non-significant difference. The MM and SMS strategies also detected respectively 28 and 30 smear-positive cases not confirmed by culture. No cases were lost to treatment with either strategy. CONCLUSIONS: In this population with a high prevalence of human immunodeficiency virus (HIV) with late case presentation, smear microscopy of two morning specimens detected at least as many positive cases as the classical strategy, and no cases were lost before treatment. Two specimens for initial TB suspect screening can thus be recommended, also without excessive workload. Comparative studies in populations presenting with paucibacillary sputum are needed to determine the equivalent quality and yield of an alternative strategy with two spot specimens at consultation.
Symptom-based screening of child tuberculosis contacts: improved feasibility in resource-limited settings.
Pediatrics. 2008 Jun; 121(6):e1646-52.OBJECTIVE: National tuberculosis programs in tuberculosis-endemic countries rarely implement active tracing and screening of child tuberculosis contacts, mainly because of resource constraints. We aimed to evaluate the safety and feasibility of applying a simple symptom-based approach to screen child tuberculosis contacts for active disease. METHODS: We conducted a prospective observational study from January through December 2004 at 3 clinics in Cape Town, South Africa. All of the children <5 years old in household contact with an adult tuberculosis source case were assessed by documenting current symptoms and tuberculin skin test and chest radiograph results. RESULTS: During the study period, 357 adult tuberculosis cases were identified; 195 cases (54.6%) had sputum smear and/or culture positive results and were in household contact with children aged <5 years. Complete information was available for 252 of 278 children; 176 (69.8%) were asymptomatic at the time of screening. Tuberculosis treatment was administered to 33 (13.1%) of 252; 27 were categorized as radiologically "certain tuberculosis," the majority (n = 22) of which had uncomplicated hilar adenopathy. The negative predictive value of symptom-based screening varied according to the case definition used, with 95.5% including all of the children treated for tuberculosis and 97.1% including only those with radiologically "certain tuberculosis." CONCLUSIONS: Our findings support current World Health Organization recommendations, demonstrating that symptom-based screening of child tuberculosis contacts should improve feasibility in resource-limited settings and seems to be safe.
Journal of the Pakistan Medical Association. 2006 Sep; 56(9):390-391.Tuberculosis, one of the oldest and deadliest infectious diseases had a dramatic comeback in the last quarter of the century. WHO declared Tuberculosis (TB) as a global emergency in 1993. Though no nation was immune from the disease, the main brunt of the disease was found in the developing countries. The escalating incidence of tuberculosis in Pakistan is due to persistence of poor socio-political conditions, inadequate health care infrastructure, undernutrition, overcrowded living conditions, influx of refugees, rising incidence of HIV/AIDS, and a general apathy towards health and related problems. Pakistan is identified as sixth among the 22 countries of the EMRO region with the highest burden of TB. In 2001, the Government of Pakistan declared Tuberculosis as a National Emergency. In 2002 the National Tuberculosis Control Programme (NTP) a project of Ministry of Health (MoH), Government of Pakistan, adopted and initiated the implementation of DOTS programme. The objective of the NTP was to provide 100 percent DOTS coverage by 2005, detecting 70% of all cases and successfully treating 85% of them by 2005 and reducing the prevalence and deaths due to tuberculosis by 50% by 2010. (excerpt)
Bulletin of the World Health Organization. 2006 Apr; 84(4):265-266.Nearly a decade after starting work with the Russian Federation to stem a tuberculosis (TB) epidemic, WHO is reporting slow but steady progress. The WHO-recommended DOTS treatment strategy is gradually taking hold across world's largest country, but its vast network of prisons and labour camps remains a hotbed of the disease. (excerpt)
UN Chronicle. 2005 Jun-Aug; 42(2): p..The battle against tuberculosis (TB) is being successfully fought in most areas of the world, but in Africa the disease has reached alarming proportions with an increasing number of cases and deaths linked to HIV, said the World Health Organization in its WHO Report 2005, Global Tuberculosis Control: Surveillance, Planning, Financing, released on 24 March to coincide with World TB Day. The WHO Report focuses on five principal indicators: incidence, prevalence, deaths, case detection and treatment success. It finds that its prevalence has declined worldwide by more than 20 per cent since 1990 and that incidence rates are falling or stable in all regions except in Africa, where TB rates have tripled since 1990 in countries with high HIV prevalence and continue to rise at 3 to 4 per cent annually. (excerpt)
Impact of the 1994 expanded World Health Organization AIDS case definition on AIDS surveillance in university hospitals and tuberculosis centers in Cote d'Ivoire.
AIDS. 1997 Dec; 11(15):1867-72.To assess the impact of the 1994 expanded World Health Organization (WHO) AIDS case definition upon AIDS surveillance in Cote d'Ivoire, passive AIDS case surveillance was conducted from March 1994 through December 1996 at the 3 university hospitals in Abidjan, while active AIDS case surveillance was conducted at the 8 large tuberculosis (TB) centers throughout Cote d'Ivoire. Standardized questionnaires were administered and blood samples for HIV testing were collected from patients evaluated. 3658 of the 8648 hospital patients met the clinical and/or expanded case definition: 744 HIV-seropositive individuals met only the expanded definition, 44 HIV-seropositive individuals met only the clinical definition, 2334 HIV-seropositive individuals met both definitions, and 536 HIV-seronegative persons met only the clinical definition. Of 18,661 TB center patients, 9664 met the clinical and/or expanded case definition: 5685 HIV-seropositive individuals met only the expanded definition, none of the HIV-seropositive individuals met only the clinical definition, 2625 HIV-seropositive individuals met both definitions, and 1354 HIV-seronegative persons met only the clinical definition. The use of the 1994 expanded definition for surveillance purposes should be encouraged in areas of the developing world where HIV serologic testing is available.
NEW ENGLAND JOURNAL OF MEDICINE. 1991 Mar 21; 324(12):848.Dr. Goodgame pleads for more openness in discussing the diagnosis of AIDS with the patient. On the other hand, he believes testing for HIV antibodies is largely unnecessary for diagnosis in Uganda, which has 1 of the highest prevalences in the world. Given, however, that the WHO clinical AIDS definition has a positive predictive value of 73% in Ugandan patients (or 83% if cough due to tuberculosis is excluded), 27% of patients in whom there is a clinical suspicion will be erroneously told they have AIDS--"dreadful and at times almost unbearable" news. In other parts of Africa with a lower prevalence this may be even less acceptable. In Gemena, northern Zaire, we evaluated the WHO clinical Aids definition, as modified by Colebunders et al., in 166 patients in 1988-1989. The positive predictive value was 61% (67% if patients with tuberculosis were excluded). This means a wrong diagnosis of AIDS in 1 of every 3 patients. The HIV seroprevalence in this population was 7.9%, as measured in a group of 340 healthy pregnant women. Another problem is the lack of sensitivity of the clinical case definition of AIDS, leading to the possible exclusion of 30-46% of African patients with HIV-related disease in the absence of testing for HIV antibodies. Many patients with AIDS would thus escape detection until they were ill enough to meet the diagnostic criteria. If a standard of care for patients with AIDS is to be achieved in Africa, as Dr. Goodgame proposes, correctly identifying the patients early in the course of the disease is necessary, and we do not believe this is possible without laboratory confirmation. We are aware of the problems that may arise when anti-HIV testing is introduced, and the questions raised (e.g. Who will be tested? What will be done when a positive result is found?) should be thoroughly discussed with the local health team before the test is introduced. In addition, screening of blood donors should have absolute priority over diagnostic testing if a choice has to be made because of the dearth of reagents. (full text)
Evaluation of the World Health Organization clinical case definition of AIDS among tuberculosis patients in Kinshasa, Zaire [letter]
JOURNAL OF INFECTIOUS DISEASES. 1989 Nov; 160(5):902-3.Although the World Health Organization (WHO) clinical case definition for AIDS has been confirmed to have fair sensitivity, specificity, and positive prediction value in sub-Saharan Africa, its application among tuberculosis patients at the Makala Sanatorium in Kinshasa, Zaire, were evaluated in terms of this case definition by physicians who were not aware of their human immunodeficiency virus (HIV) serostatus. Screening for HIV-1 enzyme-liked immunosorbent assay (ELISA) and Western blot indicated that 85 (36%) of these patients were HIV-positive. In this population, the WHO clinical case definition had a sensitivity of 33%, a specificity of 86%, and a positive predictive value of 58% for HIV infection. When the case definition was modified to exclude chronic cough in tuberculosis patients as a minor criterion, the sensitivity decreased to 18% and the specificity and positive predictive value increased to 97% and 77%, respectively. A possible explanation for the low sensitivity of the WHO clinical case definition of HIV infection among tuberculosis patients is that tuberculosis may be an early manifestation of immunosuppression that precedes other signs and symptoms of AIDS. It is also possible that the chemotherapy administered to tuberculosis patients eliminates symptoms contained in the WHO case definition such as fever, cough, weight loss, and lymphadenopathy. These findings suggest that periodic serosurveys of tuberculosis patients may be more effective than use of the WHO clinical case definition in detecting HIV infection.
An assessment of the lower limit of specificity of the clinical definition of AIDS in Africa [letter]
AIDS. 1989 May; 3(5):323-4.Clinical data from 104 adult tuberculosis patients from Bangladesh, a country where AIDS has not been reported, were used to apply the original WHO clinical definition of AIDS, 2 variants, and a new definition that omits persistent cough, to eliminate false positive diagnosis of AIDS in TB patients. The patients had either acid-fast bacilli (61) or positive radiology. All had negative ELISA screens for HIV-1. WHO definitions 1, 2 and 3 gave false-positive rates of 66,80 and 47% respectively. Modification of the definitions to exclude persistent cough reduced this rate to 2%. Only 3 cases remained positive by at least 1 definition: 2 by lymphadenopathy and 1 by neurological signs (meningitis). This study confirms the substantial risk run by patients with unrecognized TB of being misdiagnosed as AIDS patients. For the health worker with little laboratory support, the clinical definition of AIDS in Africa would be a valuable tool provided that patients with chronic cough are tested for TB, and the modified definition applied.
JAMA. 1988 Dec 9; 260(22):3286-9.In Africa, as in many developing countries where AIDS has been documented, the specific serologic test for antibody to the human immunodeficiency virus is not feasible, and the case definition of the Centers for Disease Control is impracticable because facilities for diagnosing the opportunistic infections are inadequate and the clinical spectrum of AIDS is different in tropical countries. The World Health Organization developed a clinical case definition at a 1985 AIDS workshop in the Central African Republic. It was tested to determine its generalizability in Zaire, and the present paper is a report on experience using the definition to identify AIDS in Uganda. A clinical case of AIDS is defined by the presence of at least 2 major signs and 1 minor sign. The major signs are fever for more than 1 month, weight loss greater than 10%, and chronic diarrhea for more than 1 month. The minor signs are persistent cough for more than 1 month, pruritic dermatitis, herpes zoster, oropharyngeal candidiasis, ulcerated herpes simplex, and general lymphadenopathy. The presence of disseminated Kaposi's sarcoma or disseminated cryptococcosis is sufficient by itself to diagnose AIDS. The Uganda study included 1328 patients at 15 hospitals. 562 patients (42%) tested positive by enzyme-linked immunosorbent assay, and 776 (58%) tested negative. 424 patients (32%) met the world Health Organization clinical case definition for AIDS. The World Health Organization definition had a sensitivity of 55%, a specificity of 85%, and a positive predictive value of 73%. However, so many of the patients in this sample had active tuberculosis that it was decided to substitute "persistent cough for more than 1 month without concurrent tuberculosis" as a minor sign in place of "cough for longer than 1 month." With this modification 350 patients met the clinical case definition for AIDS. Sensitivity dropped to 52%, but specificity rose to 92%, and positive predictive value rose to 83%. Moreover, 26% of the seropositive females indicated amenorrhea as a symptom. Addition of amenorrhea to the modified case definition gave it a sensitivity of 56%, a specificity of 93%, and a positive predictive value of 86%. However, this is the 1st report of amenorrhea as a symptom of AIDS, and it may only be a symptom of severe weight loss in women of childbearing age. The findings in the Ugandan experience support the generalizability of the modified World Health Organization clinical case definition of AIDS and its use for surveillance purposes in Africa.