Senior Research Officer, Kenya Medical Research Institute
Determining the value of prospective contact investigation of household members of patients with D
In 2016, globally, 10.4 million cases of TB were reported, of these 1.4 million (14%) died. A quarter of these cases and deaths occurred in Africa. One million children developed TB and 14% of them died from the disease. In 2014, there were 89,294 TB cases in Kenya, majority of whom 3355 (3.8%) and 2254 (2.5% ) were from Kisumu and Siaya Counties respectively. The region also had the highest HIV prevalence in the country of 15% against the country’s average of 5.6%. Kenya’s TB Case Detection rate was 80%. TB infection is acquired via inhalation or ingestion of Mycobacteria. Only 5-15% of TB infections will develop into disseminated disease. Children, persons in close contact with TB patients and immune-compromised persons are at risk of disease infection and progression. A person with active TB can infect up to 15 persons a year through close contact. Symptoms of TB can be mild for several months leading to delays in seeking care increasing the risk of TB transmission. TB programs should detect all cases of TB through active tracing and screening of close contacts of TB patients to enable early initiation of treatment. However, in Kenya, contact invitation rather than contact investigation is the norm and demographic information for contacts of TB cases is rarely documented. This study aimed to determine the yield of Contact Investigation in childhood TB control at TB clinics located Kisumu and Siaya Counties of the former Nyanza province, which represent high TB burden regions in urban and rural areas respectively. The specific objectives are to determine, the yield of contact investigation in comparison with contact invitation, identify risk factors for infection after an exposure, the uptake and completion rate of IPT, and to describe challenge of conducting contact investigation among children aged 0-5 years through a prospective cohort study. Contacts of index cases were screened using a symptom screen, Tuberculin Skin test and Chest X rays upon recruitment. Key variables collected included demographic information, relationship to index case, clinical information for index cases and contacts, sleeping arrangements, and housing characteristics.
Abstract: To assess the prevalence of pulmonary tuberculosis among first-degree relative (FDR) contacts not living with tuberculosis (TB) cases.A cross-sectional analysis of household contacts living with an index TB case and FDR contacts living outside of households in Kampala, Uganda, is presented.A total of 177 contacts (52 FDRs and 125 index household contacts) of 31 TB cases were examined. Compared with index household contacts, FDR contacts were older, more likely to be TB symptomatic (50% vs 33%), had a higher percentage of abnormal chest X-rays (19% vs 11%), sputum smear positive (15% vs 5%), and many similar epidemiologic risk factors, including HIV infection (13% vs 10%). Contact groups had similar pulmonary tuberculosis prevalence: 9.6% in FDR vs 10.4% in index household contacts and similar Mycobacterium tuberculosis infection: 62% in FDR vs 61% in index households.TB is common among FDR contacts. High TB prevalence justifies targeting FDRs during household contact investigations. Combining TB active-case finding among FDR contacts with household contact investigation in low-income setting is feasible. This should be part of national TB control program strategies for increasing TB case-detection rates and reducing community TB transmission and death.
Pub.: 29 Oct '15, Pinned: 17 Aug '17
Abstract: To evaluate the effectiveness of social network analysis (SNA) in prioritising contacts in a tuberculosis (TB) contact investigation.We reviewed and analysed patient and contact investigation data from a large outbreak that occurred in Tokyo, Japan, between 2010 and 2012. Relevant data were extracted to create a social matrix, which was then analysed using SNA software to visualise the network and calculate SNA metrics (degree and betweenness) for all patients and contacts. Statistical analyses were conducted to examine whether degree and betweenness centrality scores could prioritise contacts for in-depth investigation by calculating the odds of latent tuberculous infection (LTBI) being diagnosed among contacts with high scores compared to those with low scores.The data on a total of 8 patients and 376 contacts, of whom 56 were diagnosed with LTBI, were analysed. Centrality scores did not show a statistically significant association with the risk of contacts being diagnosed with LTBI. However, contacts with high betweenness scores were more likely to be diagnosed with LTBI than contacts with lower scores (OR 2.88, 95%CI 1.31-5.83, P = 0.007).Our results showed the potential of a betweenness score in prioritising contacts during TB contact investigation.
Pub.: 16 Oct '15, Pinned: 17 Aug '17
Abstract: Although the tuberculin skin test (TST) is frequently used to aid in the diagnosis of tuberculosis (TB) disease and to identify persons with latent TB infection, it is an imperfect test and approximately 10-25% of persons with microbiologically confirmed TB disease have a negative TST. Previous studies have suggested that persons with a negative TST are more likely to present with severe TB disease and have an increased rate of TB-related death.We analyzed culture-confirmed TB cases captured in US TB surveillance data from 1993 to 2008 and performed multivariate logistic regression analysis to determine the association between TST result and death.Of 284,866 cases of TB reported in the US, 58,180 persons were eligible for inclusion in the analysis and 3,270 of those persons died after initiating TB treatment. Persons with a negative TST accounted for only 14% of the eligible cases but accounted for 42% of the deaths. Persons with a TST≥15 mm had 67% lower odds of death than persons with a negative TST (adjusted odds ratio 0.33, 95% confidence interval 0.30-0.36).A negative TST is associated with an increased risk of death among persons with culture-confirmed TB disease, even after adjustment for HIV status, site of TB disease, sputum smear AFB status, drug susceptibility, age, sex, and origin of birth. In addition to indicating risk of developing disease, the TST may also be a marker for increased risk of death.
Pub.: 19 Nov '13, Pinned: 17 Aug '17
Abstract: In Kenya, the comparative incidences of tuberculosis among persons with and without HIV have not been described, and the differential impact of public health interventions on tuberculosis incidence in the two groups is unknown.We estimated annual tuberculosis incidence stratified by HIV status during 2006-2012 based on the numbers of reported tuberculosis patients with and without HIV infection, the prevalence of HIV infection in the general population, and the total population. We also made crude estimates of annual tuberculosis incidence stratified by HIV status during 1998-2012 by assuming a constant ratio of HIV prevalence among tuberculosis patients compared to the general population.Tuberculosis incidence among both adults with HIV and adults without HIV increased during 1998-2004 then remained relatively stable until 2007. During 2007-2012, tuberculosis incidence declined by 28-44% among adults with HIV and by 11-26% among adults without HIV, concurrent with an increase in antiretroviral therapy uptake. In 2012, tuberculosis incidence among adults with HIV (1,839-1,936 cases/100,000 population) was still eight times as high as among adults without HIV (231-238 cases/100,000 population), and approximately one third of tuberculosis cases were attributable to HIV.Although tuberculosis incidence has declined among adults with and without HIV, the persistent high incidence of tuberculosis among those with HIV and the disparity between the two groups are concerning. Early diagnosis of HIV, early initiation of antiretroviral therapy, regular screening for tuberculosis, and isoniazid preventive therapy among persons with HIV, as well as tuberculosis control in the general population, are required to address these issues.
Pub.: 18 Jun '14, Pinned: 17 Aug '17
Abstract: Fifteen human immunodeficiency virus (HIV) clinics in Nyanza Region, Western Kenya.To describe routine tuberculosis (TB) screening and diagnostic practices among newly enrolled people living with HIV (PLHIV) prior to the implementation of World Health Organization recommended TB intensified case finding.Retrospective chart abstraction of PLHIV aged ⩾7 years who were newly enrolled in HIV care in July and August 2009, and who had not received antiretroviral treatment in the preceding 2 years or been diagnosed with TB in the previous year. Factors associated with evidence of TB diagnostic evaluation among symptomatic PLHIV were assessed.Of 1020 patients included in the analysis, 995 (98%) were screened for TB at enrolment and 613 (62%) reported TB symptoms. Ninety-six (16%) patients with symptoms had evidence of referral for TB diagnostic evaluation, including patients at large clinics, those with advanced HIV disease and those reporting multiple TB symptoms. Among the 43 (45%) with documented evaluation results, 26 (60%) were diagnosed with TB.Although most PLHIV were screened for TB, very few underwent an evaluation, and the proportion diagnosed with TB was very low. Efforts to improve TB screening should focus on standardizing the intensified case finding algorithm and linkage to, and adequate infrastructure for, TB diagnostic evaluation.
Pub.: 22 Dec '15, Pinned: 17 Aug '17
Abstract: The World Health Organization recommends direct observation of treatment (DOT) to support patients with tuberculosis (TB) and to ensure treatment completion. As per national programme guidelines in India, a DOT provider can be anyone who is acceptable and accessible to the patient and accountable to the health system, except a family member. This poses challenges among children with TB who may be more comfortable receiving medicines from their parents or family members than from unfamiliar DOT providers. We conducted a non-inferiority trial to assess the effect of family DOT on treatment success rates among children with newly diagnosed TB registered for treatment during June-September 2012.We randomly assigned all districts (n = 30) in Gujarat to the intervention (n = 15) or usual-practice group (n = 15). Adult family members in the intervention districts were given the choice to become their child's DOT provider. DOT was provided by a non-family member in the usual-practice districts. Using routinely collected clinic-based TB treatment cards, we compared treatment success rates (cured and treatment completed) between the two groups and the non-inferiority limit was kept at 5%.Of 624 children with newly diagnosed TB, 359 (58%) were from intervention districts and 265 (42%) were from usual-practice districts. The two groups were similar with respect to baseline characteristics including age, sex, type of TB, and initial body weight. The treatment success rates were 344 (95.8%) and 247 (93.2%) (p = 0.11) among the intervention and usual-practice groups respectively.DOT provided by a family member is not inferior to DOT provided by a non-family member among new TB cases in children and can attain international targets for treatment success.Clinical Trials Registry-India, National Institute of Medical Statistics (Indian Council of Medical Research) CTRI/2015/09/006229.
Pub.: 06 Feb '16, Pinned: 17 Aug '17
Abstract: Diagnosis followed by effective treatment of tuberculosis (TB) reduces transmission and saves lives in persons living with HIV (PLHIV). Sputum smear microscopy is widely used for diagnosis, despite limited sensitivity in PLHIV. Evidence is needed to determine the optimal diagnostic approach for these patients.From May 2011 through June 2012, we recruited PLHIV from 15 HIV treatment centers in western Kenya. We collected up to three sputum specimens for Ziehl-Neelsen (ZN) and fluorescence microscopy (FM), GeneXpert MTB/RIF (Xpert), and culture, regardless of symptoms. We calculated the incremental yield of each test, stratifying results by CD4 cell count and specimen type; data were analyzed to account for complex sampling.From 778 enrolled patients, we identified 88 (11.3%) laboratory-confirmed TB cases. Of the 74 cases who submitted 2 specimens for microscopy and Xpert testing, ZN microscopy identified 25 (33.6%); Xpert identified those plus an additional 18 (incremental yield = 24.4%). Xpert testing of spot specimens identified 48 (57.0%) of 84 cases; whereas Xpert testing of morning specimens identified 50 (66.0%) of 76 cases. Two Xpert tests detected 22/24 (92.0%) TB cases with CD4 counts <100 cells/μL and 30/45 (67.0%) of cases with CD4 counts ≥100 cells/μl.In PLHIV, Xpert substantially increased diagnostic yield compared to smear microscopy and had the highest yield when used to test morning specimens and specimens from PLHIV with CD4 count <100 cells/μL. TB programs unable to replace smear microscopy with Xpert for all symptomatic PLHIV should consider targeted replacement and using morning specimens.
Pub.: 31 Mar '16, Pinned: 17 Aug '17
Abstract: Although an estimated three million tuberculosis (TB) cases worldwide are missed by national TB programs annually, the level of under-reporting of diagnosed cases in high TB burden settings is largely unknown.To quantify and describe under-reporting of sputum smear-positive TB cases in Kenya.A national-level retrospective TB inventory study was conducted. All sputum smear-positive TB cases diagnosed by public or private laboratories during 1 April-30 June 2013 were extracted from laboratory registers in 73 randomly sampled subcounties and matched to TB cases in the national TB surveillance system (TIBU). Bivariate and multivariate analyses were conducted.In the subcounties sampled, 715 of 3409 smear-positive TB cases in laboratory registers were not found in TIBU. The estimated level of under-reporting of smear-positive TB cases in Kenya was 20.7% (95%CI 18.4-23.0). Under-reporting was greatest in subcounties with a high TB burden. Unreported cases were more likely to be patients aged ⩾55 years, have scanty smear results, and be diagnosed at large facilities, private facilities, and facilities in high TB burden regions.In Kenya, one fifth of smear-positive TB cases diagnosed during the study period went unreported, suggesting that the true TB burden is higher than reported. TB surveillance in Kenya should be strengthened to ensure all diagnosed TB cases are reported.
Pub.: 12 Oct '16, Pinned: 17 Aug '17
Abstract: To assess the performance of symptom-based screening for tuberculosis (TB), alone and with chest radiography among people living with HIV (PLHIV), including pregnant women, in Western Kenya.Prospective cohort study.PLHIV from 15 randomly-selected HIV clinics were screened with three clinical algorithms [World Health Organization (WHO), Ministry of Health (MOH), and "Improving Diagnosis of TB in HIV-infected persons" (ID-TB/HIV) study], underwent chest radiography (unless pregnant), and provided two or more sputum specimens for smear microscopy, liquid culture, and Xpert MTB/RIF. Performance of clinical screening was compared to laboratory results, controlling for the complex design of the survey.Overall, 738 (85.6%) of 862 PLHIV enrolled were included in the analysis. Estimated TB prevalence was 11.2% (95% CI, 9.9-12.7). Sensitivity of the three screening algorithms was similar [WHO, 74.1% (95% CI, 64.1-82.2); MOH, 77.5% (95% CI, 68.6-84.5); and ID-TB/HIV, 72.5% (95% CI, 60.9-81.7)]. Sensitivity of the WHO algorithm was significantly lower among HIV-infected pregnant women [28.2% (95% CI, 14.9-46.7)] compared to non-pregnant women [78.3% (95% CI, 67.3-86.4)] and men [77.2% (95% CI, 68.3-84.2)]. Chest radiography increased WHO algorithm sensitivity and negative predictive value to 90.9% (95% CI, 86.4-93.9) and 96.1% (95% CI, 94.4-97.3), respectively, among asymptomatic men and non-pregnant women.Clinical screening missed approximately 25% of laboratory-confirmed TB cases among all PLHIV and more than 70% among HIV-infected pregnant women. National HIV programs should evaluate the feasibility of laboratory-based screening for TB, such as a single Xpert MTB/RIF test for all PLHIV, especially pregnant women, at enrollment in HIV services.
Pub.: 10 Dec '16, Pinned: 17 Aug '17