Evaluation of the 2007 WHO guideline to improve the diagnosis of tuberculosis in ambulatory HIV-positive adults.

BACKGROUND: In 2007 WHO issued a guideline to improve the diagnosis of smear-negative and extrapulmonary tuberculosis (EPTB) in HIV-positive patients. This guideline relies heavily on the acceptance of HIV-testing and availability of chest X-rays. METHODS AND FINDINGS: Cohort study of TB suspects in four tuberculosis (TB) clinics in Phnom Penh, Cambodia. We assessed the operational performance of the guideline, the incremental yield of investigations, and the diagnostic accuracy for smear-negative tuberculosis in HIV-positive patients using culture positivity as reference standard. 1,147 (68.9%) of 1,665 TB suspects presented with unknown HIV status, 1,124 (98.0%) agreed to be tested, 79 (7.0%) were HIV-positive. Compliance with the guideline for chest X-rays and sputum culture requests was 97.1% and 98.3% respectively. Only 35 of 79 HIV-positive patients (44.3%) with a chest X-ray suggestive of TB started TB treatment within 10 days. 105 of 442 HIV-positive TB suspects started TB treatment (56.2% smear-negative pulmonary TB (PTB), 28.6% smear-positive PTB, 15.2% EPTB). The median time to TB treatment initiation was 5 days (IQR: 2-13 days), ranging from 2 days (IQR: 1-11.5 days) for EPTB, over 2.5 days (IQR: 1-4 days) for smear-positive PTB to 9 days (IQR: 3-17 days) for smear-negative PTB. Among the 34 smear-negative TB patients with a confirmed diagnosis, the incremental yield of chest X-ray, clinical suspicion or abdominal ultrasound, and culture was 41.2%, 17.6% and 41.2% respectively. The sensitivity and specificity of the algorithm to diagnose smear-negative TB in HIV-positive TB suspects was 58.8% (95%CI: 42.2%-73.6%) and 79.4% (95%CI: 74.8%-82.4%) respectively. CONCLUSIONS: Pending point-of-care rapid diagnostic tests for TB disease, diagnostic algorithms are needed. The diagnostic accuracy of the 2007 WHO guideline to diagnose smear-negative TB is acceptable. There is, however, reluctance to comply with the guideline in terms of immediate treatment initiation

Advanced HIV Disease at Enrolment in HIV Care: Trends and Associated Factors over a Ten Year Period in Cambodia.

Early HIV diagnosis and enrolment in care is needed to achieve early antiretroviral treatment (ART) initiation. Studies on HIV disease stage at enrolment in care from Asian countries are limited. We evaluated trends in and factors associated with late HIV disease presentation over a ten-year period in the largest ART center in Cambodia.We conducted a retrospective analysis of program data including all ARV-naïve adults (> 18 years old) enrolling into HIV care from March 2003-December 2013 in a non-governmental hospital in Phnom Penh, Cambodia. We calculated the proportion presenting with advanced stage HIV disease (WHO clinical stage IV or CD4 cell count <100 cells/μL) and the probability of ART initiation by six months after enrolment. Factors associated with late presentation were determined using multivariate logistic regression.From 2003-2013, a total of 5642 HIV-infected patients enrolled in HIV care. The proportion of late presenters decreased from 67% in 2003 to 44% in 2009 and 41% in 2013; a temporary increase to 52% occurred in 2011 coinciding with logistical/budgetary constraints at the national program level. Median CD4 counts increased from 32 cells/μL (IQR 11-127) in 2003 to 239 cells/μL (IQR 63-291) in 2013. Older age and male sex were associated with late presentation across the ten-year period. The probability of ART initiation by six months after enrolment increased from 22.6% in 2003-2006 to 79.9% in 2011-2013.Although a gradual improvement was observed over time, a large proportion of patients still enroll late, particularly older or male patients. Interventions to achieve early HIV testing and efficient linkage to care are warranted

Evolution in the median CD4 count at enrolment into HIV care, Phnom Penh, Cambodia (2003–2013).

<p>Evolution in the median CD4 count at enrolment into HIV care, Phnom Penh, Cambodia (2003–2013).</p

Characteristics of adults enrolling into HIV care stratified by period, Phnom Penh, Cambodia (2003–2013; N = 5642).

<p>IQR: interquartile range; VCT: voluntary counselling and testing; WHO: World Health Organization</p><p>Characteristics of adults enrolling into HIV care stratified by period, Phnom Penh, Cambodia (2003–2013; N = 5642).</p

Factors associated with advanced HIV at enrolment in HIV care, Phnom Penh, Cambodia (2003–2013).

<p>CI: confidence interval; OR: adjusted odds ratio (adjusted for all variables in the table); VCT: voluntary counselling and testing</p><p>^aData are shown stratified per period since there were statistically significant interactions between period and age group, and between period and enrolment referral source.</p><p>Associations with a <i>P</i>-value < 0.05 are written in bold</p><p>^bOverall P value for age: (2003–2006); <0.001 (2007–2010); <0.001 (2011–2013)</p><p>^cP value for trend for age: 0.231 (2003–2006); <0.001 (2007–2010); <0.001 (2011–2013)</p><p>^dOverall P value for enrolment referral source: <0.001 (2003–2006); 0.0043 (2007–2010); 0.032 (2011–2013)</p><p>Factors associated with advanced HIV at enrolment in HIV care, Phnom Penh, Cambodia (2003–2013).</p

Evolution in the proportion of individuals enrolling with WHO clinical stage IV, Phnom Penh, Cambodia (2003–2013).

<p>Evolution in the proportion of individuals enrolling with WHO clinical stage IV, Phnom Penh, Cambodia (2003–2013).</p

Evolution in the proportion of individuals enrolling with advanced HIV disease (CD4 cell count < 100 cells/μL or WHO clinical stage IV), Phnom Penh, Cambodia (2003–2013).

<p>Evolution in the proportion of individuals enrolling with advanced HIV disease (CD4 cell count < 100 cells/μL or WHO clinical stage IV), Phnom Penh, Cambodia (2003–2013).</p

Community-based active tuberculosis case finding in poor urban settlements of Phnom Penh, Cambodia: a feasible and effective strategy.

In light of the limitations of the current case finding strategies and the global urgency to improve tuberculosis (TB) case-detection, a renewed interest in active case finding (ACF) has risen. The WHO calls for more evidence on innovative ways of TB screening, especially from low-income countries, to inform global guideline development. We aimed to assess the feasibility of community-based ACF for TB among the urban poor in Cambodia and determine its impact on case detection, treatment uptake and outcome.Between 9/2/2012-31/3/2013 the Sihanouk Hospital Center of HOPE conducted a door-to-door survey for TB in deprived communities of Phnom Penh. TB workers and community health volunteers performed symptom screening, collected sputum and facilitated specimen transport to the laboratories. Fluorescence microscopy was introduced at three referral hospitals. The GeneXpert MTB/RIF assay (Xpert) was performed at tertiary level for individuals at increased risk of HIV-associated, drug-resistant or smear-negative TB. Mobile phone/short message system (SMS) was used for same-day issuing of positive results. TB workers contacted diagnosed patients and referred them for care at their local health centre.In 14 months, we screened 315.874 individuals; we identified 12.201 aged ≥ 15 years with symptoms suggestive of TB; 84% provided sputum. We diagnosed 783, including 737 bacteriologically confirmed, TB cases. Xpert testing yielded 41% and 48% additional diagnoses among presumptive HIV-associated and multidrug-resistant TB cases, respectively. The median time from sputum collection to notification (by SMS) of the first positive (microscopy or Xpert) result was 3 days (IQR 2-6). Over 94% commenced TB treatment and 81% successfully completed it.Our findings suggest that among the urban poor ACF for TB, using a sensitive symptom screen followed by smear-microscopy and targeted Xpert, contributed to improved case detection of drug-susceptible and drug-resistant TB, shortening the diagnostic delay, and successfully bringing patients into care