The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, clinical presentation, and corrective interventions

Background Globally, case detection of tuberculosis (TB) has stabilized in recent years. Active case finding (ACF) has regained an increased attention as a complementary strategy to fill the case detection gap. In the Philippines, the DetecTB project implemented an innovative ACF strategy that offered a one-stop diagnostic service with a mobile unit equipped with enhanced diagnostic tools including chest X-ray (CXR) and Xpert®MTB/RIF (Xpert). The project targeted the rural poor, the urban poor, prison inmates, indigenous population and high school students. Methods This is a retrospective review of TB screening data from 25,103 individuals. A descriptive analysis was carried out to compare screening and treatment outcomes across target populations. Univariate and multivariate analyses were performed to identify predictors of TB for each population. The composition of bacteriologically-confirmed cases by smear and symptom status was further investigated. Results The highest yield with lowest number needed to screen (NNS) was found in prison (6.2%, NNS: 16), followed by indigenous population (2.9%, NNS: 34), the rural poor (2.2%, NNS: 45), the urban poor (2.1%, NNS: 48), and high school (0.2%, NNS: 495). The treatment success rate for all populations was high with 89.5% in rifampicin-susceptible patients and 83.3% in rifampicin-resistant patients. A relatively higher loss to follow-up rate was observed in indigenous population (7.5%) and the rural poor (6.4%). Only cough more than two weeks showed a significant association with TB diagnosis in all target populations (Adjusted Odds Ratio ranging from 1.71 to 6.73) while other symptoms and demographic factors varied in their strength of association. The urban poor had the highest proportion of smear-positive patients with cough more than two weeks (72.0%). The proportion of smear-negative (Xpert-positive) patients without cough more than two weeks was the highest in indigenous population (39.3%), followed by prison inmates (27.7%), and the rural poor (22.8%). Conclusions The innovative ACF strategy using mobile unit yielded a substantial number of TB patients and achieved successful treatment outcomes. TB screening in prison, indigenous population, and urban and rural poor communities was found to be effective. The combined use of CXR and Xpert largely contributed to increased case detection.

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Bringing state-of-the-art diagnostics to vulnerable populations: The use of a mobile screening unit in active case finding for tuberculosis in Palawan, the Philippines.

Background. We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial. Methods. We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in 8 countries with high TB burdens. HHCs underwent symptom screenings, chest radiographies, sputum TB bacteriologies, TB infection (TBI) testing (tuberculin skin
test [TST] and interferon gamma release assay [IGRA]), and human immunodeficiency virus (HIV) testing. Results. From October 2015 to April 2016, 1016 HHCs from 284 MDR-TB cases were enrolled. At diagnosis, 69% of MDR-TB cases were positive for acid-fast bacilli sputum smears and 43% had cavitary disease; at study entry, 35% remained smear positive fter a median MDR-TB treatment duration of 8.8 weeks. There were 9 HHCs that were diagnosed with TB prior to entry and excluded. Of the remaining 1007 HHCs, 41% were male and the median age was 25 years. There were 121 (12%) HHCs that had new cases of TB identified: 17 (2%) were confirmed, 33 (3%) probable, and 71 (7%) possible TB cases. The TBI prevalence (defined as either TST or IGRA positivity) was 72% and varied by age, test used, and country. Of 1007 HHCs, 775 (77%) were considered high-risk per these mutually exclusive groups: 102 (10%) were aged <5 years; 63 (6%) were aged ≥5 and were infected with HIV; and 610 (61%) were aged ≥5 years, were negative for HIV or had an unknown HIV status, and were TBI positive. Only 21 (2%) HHCs were on preventive therapy. Conclusions. The majority of HHCs in these high-burden countries were at high risk of TB disease and infection, yet few were receiving routine preventive therapy. Trials of novel, preventive therapies are urgently needed to inform treatment policy and practice.

/pdf/feasibility-of-identifying-household-contacts-of-rifampin-5asvqy9lrv.pdf

Feasibility of Identifying Household Contacts of Rifampin-and Multidrug-resistant Tuberculosis Cases at High Risk of Progression to Tuberculosis Disease.

Two in every five patients with active tuberculosis (TB) remain undiagnosed or unreported. Therefore community-based, active case-finding strategies require urgent implementation. However, whether point-of-care (POC), portable battery-operated, molecular diagnostic tools deployed at a community level, compared with conventionally used POC smear microscopy, can shorten time-to-treatment initiation, thus potentially curtailing transmission, remains unclear. To clarify this issue, we performed an open-label, randomized controlled trial in periurban informal settlements of Cape Town, South Africa, where we TB symptom screened 5,274 individuals using a community-based scalable mobile clinic. Some 584 individuals with HIV infection or symptoms of TB underwent targeted diagnostic screening and were randomized (1:1) to same-day smear microscopy (n = 296) or on-site DNA-based molecular diagnosis (n = 288; GeneXpert). The primary aim was to compare time to TB treatment initiation between the arms. Secondary aims included feasibility and detection of probably infectious people. Of participants who underwent targeted screening, 9.9% (58 of 584) had culture-confirmed TB. Time-to-treatment initiation occurred significantly earlier in the Xpert versus the smear-microscopy arm (8 versus 41 d, P = 0.002). However, overall, Xpert detected only 52% of individuals with culture-positive TB. Notably, Xpert detected almost all of the probably infectious patients compared with smear microscopy (94.1% versus 23.5%, P = <0.001). Xpert was associated with a shorter median time to treatment of probably infectious patients (7 versus 24 d, P = 0.02) and a greater proportion of infectious patients were on treatment at 60 d compared with the probably noninfectious patients (76.5% versus 38.2%, P < 0.01). Overall, a greater proportion of POC Xpert-positive participants were on treatment at 60 d compared with all culture-positive participants (100% versus 46.5%, P < 0.01). These findings challenge the traditional paradigm of a passive case-finding, public health strategy and argues for the implementation of portable DNA-based diagnosis with linkage to care as a community-oriented, transmission-interruption strategy. The study was registered with the South African National Clinical Trials Registry (application ID 4367; DOH-27-0317-5367) and ClinicalTrials.gov (NCT03168945). 

/pdf/comparison-of-two-diagnostic-intervention-packages-for-2uerwmnk.pdf

Comparison of two diagnostic intervention packages for community-based active case finding for tuberculosis: an open-label randomized controlled trial

Setting Haiti has the highest burden of tuberculosis (TB) in the Americas, with an estimated prevalence of 254 per 100 000 population. The Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes, GHESKIO) conducted active case finding (ACF) for TB at the household level in nine slums in Port-au-Prince. Objective We report on the prevalence of undiagnosed TB detected through GHESKIO's ACF campaign. Design From 1 August 2014 to 31 July 2015, we conducted a retrospective cohort analysis using GHESKIO's ACF campaign data. All individuals who reported chronic cough (cough 2 weeks) were tested for TB at GHESKIO, and those aged 10 years were included in the analyses. Results Of 104 097 individuals screened in the community, 5598 (5%) reported chronic cough and satisfied the study inclusion criteria. A total of 1110 (20%) were diagnosed with active TB disease (prevalence of 1066/100 000). Of the 5472 (98%) patients tested for human immunodeficiency virus (HIV), 528 (10%) were HIV-positive; 143 (3%) patients were diagnosed with both diseases. Conclusion Household-level screening for cough with TB and HIV testing for symptomatic patients was a high-yield strategy, leading to the detection of a prevalence of undiagnosed disease exceeding national estimates by more than four-fold for TB, and by five-fold for HIV.

Diagnostic yield of active case finding for tuberculosis and HIV at the household level in slums in Haiti.

Tuberculosis (TB) remains a global public health problem with an estimated 9.6 million new cases in 2014, of which only 6 million (63%) were reported.1 This means that 3.6 million new cases (37%) worldwide went undiagnosed or were not reported. The World Health Organization (WHO) End TB strategy for 2016–2030 emphasises early diagnosis, including universal drug susceptibility testing (DST) and systematic screening of contacts and high-risk groups to reduce the case detection gap.2 The WHO also recommends intensified case finding (ICF) among selected risk groups such as household contacts, people living with the human immunodeficiency virus (PLHIV), prisons and other penitentiary institutions and geographically defined sub-populations with high levels of undetected TB, such as urban slum dwellers.3

ICF has been used extensively in a variety of settings, and has been effective in reducing the prevalence, incidence and mortality of TB.4 With the increased use of the rapid Xpert® MTB/RIF test (Cepheid, Sunnyvale, CA, USA) in low- and middle-income countries and its improved sensitivity in detecting TB, inclusion of Xpert in the screening algorithm has demonstrated improvements in case detection.5 Low TB case detection among poor and marginalised groups is one of the primary strategic challenges faced by the Nepal National Tuberculosis Programme (NTP). The NTP identifies slum dwellers, PLHIV, prisoners, refugees and congregate settings such as factories and hostels as high-risk groups.6 In 2014, of 59 000 estimated prevalent cases, only 37 025 cases were notified to the NTP, with a case notification rate (CNR) of 136 per 100 000 population. There was no substantial improvement in the overall CNR for all forms of TB as well as pulmonary bacteriologically confirmed cases (PBC) during 2010–2013.7

Under the TB REACH project, the non-governmental organisation Health Research and Social Development Forum (HERD, Kathmandu, Nepal), in collaboration with the NTP, has been implementing ICF activities focusing on identified high-risk groups using Xpert and light-emitting diode (LED) microscopy fitted in mobile vans since July 2013.

This study aimed to assess the yield of ICF strategies among different risk groups and their impact on the CNR. The specific objectives were 1) to determine the number and proportion of adults screened, diagnosed and initiated on anti-tuberculosis treatment disaggregated by risk group; 2) to determine the number and proportion diagnosed with multidrug-resistant TB (MDR-TB); and 3) to assess the difference in the CNR in the intervention districts before and after the implementation of ICF strategies compared to the difference in the CNR in control districts where there was no ICF.

/pdf/yield-of-intensified-tuberculosis-case-finding-activities-45jptlcmir.pdf

Yield of intensified tuberculosis case-finding activities using Xpert(®) MTB/RIF among risk groups in Nepal.

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Yield of intensified tuberculosis case-finding activities using Xpert(®) MTB/RIF among risk groups in Nepal.