Co-prevalent Cases Research Articles

Spatio-temporal analysis of leprosy risks in a municipality in the state of Mato Grosso-Brazilian Amazon: results from the leprosy post-exposure prophylaxis program in Brazil

BackgroundLeprosy post-exposure prophylaxis (LPEP) with single dose rifampicin (SDR) can be integrated into different leprosy control program set-ups once contact tracing has been established. We analyzed the spatio-temporal changes in the distribution of index cases (IC) and co-prevalent cases among contacts of leprosy patients (CP) over the course of the LPEP program in one of the four study areas in Brazil, namely the municipality of Alta Floresta, state of Mato Grosso, in the Brazilian Amazon basin.MethodsLeprosy cases were mapped, and socioeconomic indicators were evaluated to explain the leprosy distribution of all leprosy cases diagnosed in the period 2016–2018. Data were obtained on new leprosy cases [Notifiable diseases information system (Sinan)], contacts traced by the LPEP program, and socioeconomic variables [Brazilian Institute of Geography and Statistics (IBGE)]. Kernel, SCAN, factor analysis and spatial regression were applied to analyze changes.ResultsOverall, the new case detection rate (NCDR) was 20/10 000 inhabitants or 304 new cases, of which 55 were CP cases among the 2076 examined contacts. Changes over time were observed in the geographic distribution of cases. The highest concentration of cases was observed in the northeast of the study area, including one significant cluster (Relative risk = 2.24; population 27 427, P-value < 0.001) in an area characterized by different indicators associated with poverty as identified through spatial regression (Coefficient 3.34, P-value = 0.01).ConclusionsThe disease distribution was partly explained by poverty indicators. LPEP influences the spatial dynamic of the disease and results highlighted the relevance of systematic contact surveillance for leprosy elimination.Graphical

High prevalence of pulmonary tuberculosis among female sex workers, men who have sex with men, and transgender women in Papua New Guinea

BackgroundPapua New Guinea (PNG) has a tuberculosis (TB) case notification rate of 333 cases per 100,000 population in 2016 and is one of the 14 countries classified by the World Health Organization (WHO) as “high-burden” for TB, multi-drug-resistant TB (MDR-TB), and TB/HIV. HIV epidemic is mixed with a higher prevalence among key populations, female sex workers (FSW), men who have sex with men (MSM), and transgender women (TGW).MethodsWe conducted a cross-sectional HIV biobehavioral survey (BBS) using respondent-driven sampling method among FSW, MSM, and TGW in Port Moresby, Lae, and Mt. Hagen (2016–2017). As part of the study, participants were screened for the four symptoms suggestive of TB infection using the WHO TB screening algorithm. Sputum and venous whole blood samples were collected and tested for pulmonary TB and HIV infection, respectively. Pulmonary TB testing was performed using GeneXpert®MTB/RIF molecular point-of-care test, and HIV testing was done following the PNG national HIV testing algorithm. All data discussed are weighted unless otherwise mentioned.ResultsAmong FSW, 72.6%, 52.0%, and 52.9% in Port Moresby, Lae, and Mt. Hagen, respectively, experienced at least one symptom suggestive of TB infection. Among MSM and TGW, 69% and 52.6% in Port Moresby and Lae, respectively, experienced at least one symptom suggestive of TB infection. Based on GeneXpert®MTB/RIF results, the estimated TB prevalence rate among FSW was 1200, 700, and 200 per 100,000 in Port Moresby, Lae, and Mt. Hagen, respectively. Among MSM and TGW, the estimated TB prevalence rate was 1000 and 1200 per 100,000 in Port Moresby and Lae, respectively. Co-prevalence of TB/HIV among FSW was 0.1% in Port Moresby and 0.2% in Lae. There were no co-prevalent cases among FSW in Mt. Hagen or among MSM and TGW in Port Moresby and Lae.ConclusionsKey populations have a higher estimated rate of pulmonary TB than the national rate of pulmonary and extra-pulmonary TB combined. This showed that screening key populations for TB should be integrated into HIV programs regardless of HIV status in PNG’s national TB response.

Overlapping of new leprosy cases in household contact networks in two municipalities in North and Northeast Brazil, 2001-2014

The study aimed to analyze the magnitude and sociodemographic profile of leprosy cases linked to household contact networks with overlapping of the disease in two Brazilian municipalities (counties), one in the North and the other in the Northeast, from 2001 to 2014. This was a cross-sectional, descriptive, analytical study based on primary and secondary data from new leprosy cases in Picos, Piauí State, and Rolim de Moura, Rondônia State. "Overlapping" was defined as new cases with the occurrence of at least one more leprosy case in the individual's household contact network. Each household contact network consisted of the index case (first reported case), co-prevalent cases (contacts that became new cases), and household contacts of the index case. A total of 437 new cases treated by the INTEGRAHANS North-Northeast and Piauí projects were assessed, of which 287 (65.7%) were in Picos and 150 (34.3%) in Rolim de Moura. Of all the cases assessed, 129 (44.9%) in Picos and 98 (65.3%) in Rolim de Moura reported overlapping. There were proportionally more females in Rolim de Moura (n = 95, 63.3%) and males in Picos (n = 147, 51.2%); in the 41-60-year age bracket (Rolim de Moura n = 70, 46.7%; Picos n = 115, 40.1%); with elementary schooling (Rolim de Moura n = 80, 54%; Picos n = 125, 44.5%); and individuals living in the same household with up to 3 persons in Rolim de Moura (n = 105, 70%) and with more than 4 persons in Picos (n = 287, 100%). Overlapping of leprosy cases in household contact networks was considerably high in the contexts analyzed here, displaying aspects of expanded vulnerability. This perspective should be considered and integrated into leprosy surveillance and control activities.

Leprosy among schoolchildren in the Amazon region: A cross-sectional study of active search and possible source of infection by contact tracing.

BackgroundThe high rate of leprosy cases among children under 15 years of age in Brazil indicates ongoing transmission within the community. The identification of the new leprosy cases among contacts can help identify the source of infection and interrupt the transmission chain. This study aims to determine the detection rate of previously undiagnosed cases of leprosy among schoolchildren who are under 15 years of age living in Manaus, Amazonas, Brazil, and their possible source of infection by contact tracing.Methodology/Principal findingsThis was a school-based, cross-sectional study in which the identification of active leprosy cases was conducted in 277 out of 622 randomly selected public schools in Manaus, Amazonas, Brazil. Suspected cases of leprosy were referred to the Alfredo da Matta Foundation, a reference center for leprosy in Manaus. A total of 34,547 schoolchildren were examined, and 40 new leprosy cases were diagnosed. Among new cases, 57.5% were males, and 80.0% demonstrated paucibacillary leprosy. A total of 196 of 206 registered contacts were screened, and 52.5% of the newly diagnosed children’s cases had at least one positive household contact. In these contacts, grandparents (52.4%) were the most common co-prevalent cases, while 14.3% were uncles, 9.5% were parents and 9.5% were granduncles. Seven contacts (5.0%), including four siblings of child patients were newly diagnosed. Our data indicate that the prevalence is 11.58 per 10,000, which is 17 times higher than the registered rate.Conclusions/SignificanceThis study suggests that the detection rate of leprosy among schoolchildren may have remained unchanged over the past thirty years. It also indicates that that active case finding is necessary for reaching the World Health Organization’s goals of zero detection among children, especially in endemic areas where the prevalence of leprosy is obscure. Moreover, we assert that all children must have their household contacts examined in order to identify the possible source of infection and interrupt the disease’s transmission. Novel strategies to reinforce contact tracing associated with large-scale strategies of chemo- and immune-prophylaxis should be expanded to prevent the perpetuation of the disease cycle.

Effectiveness of WHO's pragmatic screening algorithm for child contacts of tuberculosis cases in resource-constrained settings: a prospective cohort study in Uganda

Tuberculosis is a leading cause of global childhood mortality; however, interventions to detect undiagnosed tuberculosis in children are underused. Child contact tracing has been widely recommended but poorly implemented in resource-constrained settings. WHO has proposed a pragmatic screening approach for managing child contacts. We assessed the effectiveness of this screening approach and alternative symptom-based algorithms in identifying secondary tuberculosis in a prospectively followed cohort of Ugandan child contacts. We identified index patients aged at least 18 years with microbiologically confirmed pulmonary tuberculosis at Old Mulago Hospital (Kampala, Uganda) between Oct 1, 1995, and Dec 31, 2008. Households of index patients were visited by fieldworkers within 2 weeks of diagnosis. Coprevalent and incident tuberculosis were assessed in household contacts through clinical, radiographical, and microbiological examinations for 2 years. Disease rates were compared among children younger than 16 years with and without symptoms included in the WHO pragmatic guideline (presence of haemoptysis, fever, chronic cough, weight loss, night sweats, and poor appetite). Symptoms could be of any duration, except cough (>21 days) and fever (>14 days). A modified WHO decision-tree designed to detect high-risk asymptomatic child contacts was also assessed, in which all asymptomatic contacts were classified as high risk (children younger than 3 years or immunocompromised [HIV-infected]) or low risk (aged 3 years or older and immunocompetent [HIV-negative]). We also assessed a more restrictive algorithm (ie, assessing only children with presence of chronic cough and one other tuberculosis-related symptom). Of 1718 household child contacts, 126 (7%) had coprevalent tuberculosis and 24 (1%) developed incident tuberculosis, diagnosed over the 2-year study period. Of these 150 cases of tuberculosis, 95 (63%) were microbiologically confirmed with a positive sputum culture. Using the WHO approach, 364 (21%) of 1718 child contacts had at least one tuberculosis-related symptom and 85 (23%) were identified as having coprevalent tuberculosis, 67% of all coprevalent cases detected (diagnostic odds ratio 9·8, 95% CI 6·8-14·5; p<0·0001). 1354 (79%) of 1718 child contacts had no symptoms, of whom 41 (3%) had coprevalent tuberculosis. The WHO approach was effective in contacts younger than 5 years: 70 (33%) of 211 symptomatic contacts had coprevalent disease compared with 23 (6%) of 367 asymptomatic contacts (p<0·0001). This approach was also effective in contacts aged 5 years and older: 15 (10%) of 153 symptomatic contacts had coprevalent disease compared with 18 (2%) of 987 asymptomatic contacts (p<0·0001). More coprevalent disease was detected in child contacts recommended for screening when the study population was restricted by HIV-serostatus (11 [48%] of 23 symptomatic HIV-seropositive child contacts vs two [7%] of 31 asymptomatic HIV-seropositive child contacts) or to only culture-confirmed cases (47 [13%] culture confirmed cases of 364 symptomatic child contacts vs 29 [2%] culture confirmed cases of 1354 asymptomatic child contacts). In the modified algorithm, high-risk asymptomatic child contacts were at increased risk for coprevalent disease versus low-risk asymptomatic contacts (14 [6%] of 224 vs 27 [2%] of 1130; p=0·0021). The presence of tuberculosis infection did not predict incident disease in either symptomatic or asymptomatic child contacts: in symptomatic contacts, eight (5%) of 169 infected contacts and six (5%) of 111 uninfected contacts developed incident tuberculosis (p=0·80). Among asymptomatic contacts, incident tuberculosis occurred in six (<1%) of 795 contacts infected at baseline versus four (<1%) of 518 contacts uninfected at baseline, respectively (p=1·00). WHO's pragmatic, symptom-based algorithm was an effective case-finding tool, especially in children younger than 5 years. A modified decision-tree identified 6% of asymptomatic child contacts at high risk for subclinical disease. Increasing the feasibility of child-contact tracing using these approaches should be encouraged to decrease tuberculosis-related paediatric mortality in high-burden settings, but this should be partnered with increasing access to microbiological point-of-care testing. National Institutes of Health, Tuberculosis Research Unit, AIDS International Training and Research Program of the Fogarty International Center, and the Center for AIDS Research.

Assessment of tuberculosis contact investigation in Shanghai, China: An 8-year cohort study

BackgroundTuberculosis (TB) contact investigation has been observed as a useful programmatic tool in active case finding. We collected data of contact cases to evaluate the effectiveness of TB contact investigation programme in Shanghai, China. MethodsSince 2009, we screened and followed up the close contacts of bacteria-positive TB cases in Songjiang, Shanghai and calculated the incidence of TB in close contacts and confirmed the transmission by genotyping and sequencing. ResultsA total of 4584 close contacts of 1765 contagious TB index cases were followed up for an average of 4 years. About 62 contacts (333/100 000, 95% CI: 256–428) developed TB excluding 6 co-prevalent cases. The contact cases consisted 1.50% (39/2592) of all the bacteria-positive cases in population. Transmission links were confirmed in 60% (9/15) familial contacts and 22% (2/9) in non-familial contacts. Source cases come from more than close contacts and both index and contact cases created other secondary cases in community. ConclusionsFamilial contacts are more likely to acquire TB from the index, indicating the priority of family members in TB contact investigation in China. However, most non-familial contacts were infected from sources in the community and contact cases attributed little to case finding in the TB-prevalent setting. Thus, active case finding should be strengthened in general population.

Identifying children with tuberculosis among household contacts in The Gambia.

Greater Banjul Area of the Gambia. To identify co-prevalent tuberculosis (TB) among child contacts of adults with smear-positive TB. Child contacts aged <15 years in the immediate household and compound were prospectively enrolled and evaluated for TB disease using screening questionnaires and the tuberculin skin test (TST). Symptomatic and/or TST-positive (10 mm) contacts were further investigated. Of 4042 child contacts who underwent symptom screening and TST, 3339 (82.6%) were diagnosed as TB-exposed but not infected, 639 (15.8%) were latently infected and 64 (1.6%) had co-prevalent TB. Of the 64 TB cases, 50 (78.1%) were from within the immediate household of the index case, and 14 (21.9%) from within the same compound. Of the 27 asymptomatic but TST-positive children diagnosed with TB, 7 were microbiologically confirmed. The median age of the TB cases was 4.4 years (interquartile range 1.9-6.9); 53.1% were aged <5 years. Of the 4042 child contacts, 206 (5%) slept in the same bed as the index case; 28.1% of all TB cases occurred in this group. Symptom screening alone would have detected only 57.8% of the co-prevalent cases. In our community setting, if contact tracing is restricted to symptom screening and immediate households only, nearly half of all co-prevalent TB disease in child contacts would be missed.

Risk-benefit assessment of Bacillus Calmette-Guérin vaccination, anti-phenolic glycolipid I serology, and Mitsuda test response: 10-year follow-up of household contacts of leprosy patients.

Despite multidrug therapy, leprosy remains a public health issue. The intradermal Bacillus Calmette-Guérin (BCG) vaccine, Mitsuda test (lepromin skin test), and anti-phenolic glycolipid I (PGL-I) serology are widely used in leprosy studies and have shown great epidemiological value. This longitudinal study evaluated the relative risks and benefits of these three tools by comparing results observed in household contacts (HHCs) of leprosy patients who developed leprosy with those of HHCs who did not in a population of 2,992 individuals monitored during a 10-year period. Seventy-five (2.5%) new leprosy cases were diagnosed, including 28 (0.9%) co-prevalent cases. Therefore, for the risk-benefit assessment, 47 (1.6%) HHCs were considered as truly diagnosed during follow-up. The comparison between healthy and affected contacts demonstrated that not only did BCG vaccination increase protection, but boosters also increased to 95% relative risk (RR) reduction when results for having two or more scars were compared with having no scars [RR, 0.0459; 95% confidence interval (CI), 0.006-0.338]. Similarly, Mitsuda reactions >7mm in induration presented 7-fold greater protection against disease development compared to reactions of 0-3mm (RR, 0.1446; 95% CI, 0.0566-0.3696). In contrast, anti-PGL-I ELISA seropositivity indicated a 5-fold RR increase for disease outcome (RR, 5.688; 95% CI, 3.2412-9.9824). The combined effect of no BCG scars, Mitsuda reaction of <7mm, and seropositivity to anti-PGL-I increased the risk for leprosy onset 8-fold (RR, 8.109; 95% CI, 5.1167-12.8511). The adoption of these combined assays may impose measures for leprosy control strategies.

High utility of contact investigation for latent and active tuberculosis case detection among the contacts: a retrospective cohort study in Tbilisi, Georgia, 2010-2011.

SettingThe study was conducted at the National Center for Tuberculosis and Lung Diseases (NCTBLD) in Tbilisi, Georgia.ObjectiveTo assess the utility of contact investigation for tuberculosis (TB) case detection. We also assessed the prevalence and risk factors for active TB disease and latent TB infection (LTBI) among contacts of active pulmonary TB cases.DesignA retrospective cohort study was conducted among the contacts of active pulmonary TB cases registered in 2010–2011 at the NCTBLD in Tbilisi, Georgia. Contacts of active TB patients were investigated according to an “invitation model”: they were referred to the NCTBLD by the index case; were queried about clinical symptoms suggestive of active TB disease; tuberculin skin testing and chest radiographs were performed. Demographic, laboratory, and clinical data of TB patients and their contacts were abstracted from existing records up to February 2013.Results869 contacts of 396 index cases were enrolled in the study; a median of 2 contacts were referred per index case. Among the 869 contacts, 47 (5.4%) were found to have or developed active TB disease: 30 (63.8%) were diagnosed with TB during the baseline period (co-prevalent cases) and 17 (36.2%) developed active TB disease during the follow-up period (mean follow up of 21 months) (incident TB cases). The incidence rate of active TB disease among contacts was 1126.0 per 100 000 person years (95% CI 655.7–1802.0 per 100,000 person-years). Among the 402 contacts who had a tuberculin skin test (TST) performed, 52.7% (95% CI 47.7–57.7%) had LTBI.ConclusionsA high prevalence of LTBI and active TB disease was found among the contacts of TB cases in Tbilisi, Georgia. Our findings demonstrated that an “invitation” model of contact investigation was an effective method of case detection. Therefore, contact investigation should be scaled up in Georgia.

Leprosy among patient contacts: a multilevel study of risk factors.

BackgroundThis study aimed to evaluate the risk factors associated with developing leprosy among the contacts of newly-diagnosed leprosy patients.Methodology/Principal FindingsA total of 6,158 contacts and 1,201 leprosy patients of the cohort who were diagnosed and treated at the Leprosy Laboratory of Fiocruz from 1987 to 2007 were included. The contact variables analyzed were sex; age; educational and income levels; blood relationship, if any, to the index case; household or non-household relationship; length of time of close association with the index case; receipt of bacillus Calmette-Guérin (BGG) vaccine and presence of BCG scar. Index cases variables included sex, age, educational level, family size, bacillary load, and disability grade. Multilevel logistic regression with random intercept was applied. Among the co-prevalent cases, the leprosy-related variables that remained associated with leprosy included type of household contact, [odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.02, 1.73] and consanguinity with the index case, (OR = 1.89, 95% CI: 1.42–2.51). With respect to the index case variables, the factors associated with leprosy among contacts included up to 4 years of schooling and 4 to 10 years of schooling (OR = 2.72, 95% CI: 1.54–4.79 and 2.40, 95% CI: 1.30–4.42, respectively) and bacillary load, which increased the chance of leprosy among multibacillary contacts for those with a bacillary index of one to three and greater than three (OR = 1.79, 95% CI: 1.19–2.17 and OR: 4.07–95% CI: 2.73, 6.09), respectively. Among incident cases, household exposure was associated with leprosy (OR = 1.96, 95% CI: 1.29–2.98), compared with non-household exposure. Among the index case risk factors, an elevated bacillary load was the only variable associated with leprosy in the contacts.Conclusions/SignificanceBiological and social factors appear to be associated with leprosy among co-prevalent cases, whereas the factors related to the infectious load and proximity with the index case were associated with leprosy that appeared in the incident cases during follow-up.

Estudo epidemiológico de 107 focos familiares de hanseníase no município de Duque de Caxias - Rio de Janeiro, Brasil

ultibacillary patients are the major source of infection in leprosy. Nevertheless, the risk is higher in household contacts between multibacillary patients than paucibacillary patients and in the general population. Household contacts are in close genetic relationship with the index case-patient. To evaluate epidemiological data of the following variables: age, gender, education level, genetic proximity, and type of contact with the index case-patient (household or not) in 107 families with leprosy. Home visits were conducted to clinically examine family members. The medical charts of index case-patients and co-prevalent cases were reviewed. The controlled analysis of variables such as type of contact and genetic proximity revealed that household contacts and first-degree kinship are independently associated with a higher chance of contracting the disease. Household contacts are often genetically closer to the index case-patient. To investigate the independent relevance of these risks in leprosy surveillance contact studies has been a challenge. Our results confirm literature data that show the influence of genetics in the susceptibility to leprosy per se.

Incidence of Tuberculosis and the Predictive Value of ELISPOT and Mantoux Tests in Gambian Case Contacts

BackgroundStudies of Tuberculosis (TB) case contacts are increasingly being utilised for understanding the relationship between M. tuberculosis and the human host and for assessing new interventions and diagnostic tests. We aimed to identify the incidence rate of new TB cases among TB contacts and to relate this to their initial Mantoux and ELISPOT test results.Methods and FindingsAfter initial Mantoux and ELISPOT tests and exclusion of co-prevalent TB cases, we followed 2348 household contacts of sputum smear positive TB cases. We visited them at 3 months, 6 months, 12 months, 18 months and 24 months, and investigated those with symptoms consistent with TB. Those who were diagnosed separately at a government clinic had a chest x-ray. Twenty six contacts were diagnosed with definite TB over 4312 person years of follow-up (Incidence rate 603/100,000 person years; 95% Confidence Interval, 370–830). Nine index and secondary case pairs had cultured isolates available for genotyping. Of these, 6 pairs were concordant and 3 were discordant. 2.5% of non-progressors were HIV positive compared to 12% of progressors (HR 6.2; 95% CI 1.7–22.5; p = 0.010). 25 secondary cases had initial Mantoux results, 14 (56%) were positive ; 21 had initial ELISPOT results, 11 (52%) were positive; 15 (71%) of 21 tested were positive by one or the other test. Of the 6 contacts who had concordant isolates with their respective index case, 4 (67%) were Mantoux positive at recruitment, 3 (50%) were ELISPOT positive; 5 (83%) were positive by one or other of the two tests. ELISPOT positive contacts, and those with discordant results, had a similar rate of progression to those who were Mantoux positive. Those negative on either or both tests had the lowest rate of progression.ConclusionsThe incidence rate of TB disease in Gambian TB case contacts, after screening for co-prevalent cases, was 603/100,000 person years. Since initial ELISPOT test and Mantoux tests were each positive in only just over half of cases, but 71% were positive by one or other test, positivity by either might be the best indication for preventive treatment. These data do not support the replacement of the Mantoux test by an ELISPOT test in The Gambia or similar settings.