A prospective longitudinal study of tuberculosis among household contacts of smear-positive tuberculosis cases in Lima, Peru

Household contacts (HHCs) of tuberculosis (TB) patients are at higher risk for TB infection and disease. In recent studies, 4.5 to 7.8 % of HHCs have been found to have active disease [1–3]. Investigating HHCs may facilitate timely diagnosis and treatment of active TB as well as of latent TB infection. However, contact tracing in general and HHC investigation in particular are resource-intensive activities, and their consistent implementation is a challenge in both high- and low-income countries. TB control programs in low-income high-incidence settings face competing priorities [4–6] but limited data suggest that screening HHCs of TB cases for active disease may be cost-effective in low- and middle-income countries [7]. The World Health Organization recently extended its recommendations for HHC tracing to these countries [8].

TB risk in HHCs may vary by individual and household as well as by background community incidence, and investigating all HHCs in high-burden, low-resource countries may be inefficient or unfeasible. Estimates of risk should consider the correlation of risk factors of HHCs within a single household [9] to avoid overestimating effects when ignoring that correlation. To better inform TB programs on the precise burden of TB over time in HHCs, studies with sufficiently long follow-up and with comparable methods need to be conducted [1, 2, 10]. A better understanding of TB risk over time and risk factors would provide evidence to increase efficiency of HHC investigation guidelines in high TB burden settings [6] by strategies and timing following epidemiological data.

Studies have shown a high burden of TB among HHC of multidrug resistant (MDR) TB and drug susceptible cases in Peru [10–13]. We conducted a prospective study to determine the TB incidence over 2 years among HHC of all new TB cases in eastern Lima, and to identify individual and household level risk factors that determine this incidence.

The incidence of TB in HHC of new smear-positive TB cases in this district was 1918 per 100,000 person-years, ten times higher than that for the general population in the district. Among incident TB cases, 59 % occurred beyond six months of the index case’s diagnosis and would not have been identified as by current HHC investigation contracting procedures. TB burden in households was high, with 34 % of households having a HHC with past, recent or incident TB in addition to the index case. Being a sibling or a partner of the index case, and more than 30 days between symptoms treatment initiation or a high bacillary load in the index cases were associated with incident TB.

Index cases included in the study were representative of the new TB cases in the district, but this study has some limitations. Incident TB in HHC could have been diagnosed outside the district or in facilities not managed by the Ministry of Health and not appear in the TB register. We conducted household visits to ascertain these cases. However, households of index cases who defaulted treatment or died were not visited. This could lead to underestimating TB incidence in HHC. Furthermore, our definition of incidence was based on diagnosis and case notification. Since only individuals with symptoms are likely to present for diagnosis, true incidence may be underestimated. Past and recent TB episodes might also be underestimated as these were reported by the index case. Strengths of this study include its prospective design, the use of two complementary follow up approaches to ascertain incident TB in HHC and accounting for the correlation of data at household level in the analysis.

In a systematic review of 25 studies in low- and middle-income countries, the weighted estimated average of incident TB in HHC in the first year of follow-up was 478 (95%CI 897–2427) per 100,000 person-years and 831 (95%CI 624–1106) per 100,000 person-years in the second year [1]. We found rates approximately two and five times higher, respectively. Some studies conducted in Lima have determined incident TB among HHCs of selected TB cases. In the first and in the second year, 2360 incident TB episodes per 100,000 person-years occurred among HHC of 80 MDR-TB index cases in southern Lima [10], while a more recent study found 2456 incident TB episodes per 100,000 person-years occurred among HHC of 213 multidrug resistant TB cases and 4351 incident TB episodes per 100,000 person-years among HHC of 487 drug susceptible index cases [13]. A retrospective study that included 693 MDR and extensively drug resistant TB index cases found 3165 and 1092 incident TB cases in HHC per 100,000 person-years in the first and second year, respectively [12]. Our data demonstrate similar high rates of incident TB among HHCs of a large sample of unselected new pulmonary TB patients.

Our findings confirm that siblings and partners [15, 16], male HHC [10, 16], and HHC exposed to index cases with higher sputum bacillary loads [13] or that are infectious for a longer period [17] are more likely to develop incident TB. Contrary to what is expected, HHC under six years old were not found to be at higher risk for incident TB than older age groups. However, it is possible that TB in children is under diagnosed in Peru. One explanation consistent with our findings is that there are important effects at the household/index case level on the incidence of TB in HHCs. This was also found in a multilevel study in Pakistan that looked into household and HHC determinants of TB infection [9]. Characteristics at household level that may have influence should be considered in future studies, such as ventilation, sleeping arrangements, frequent exposure to non-household members as well as genetic predisposition of families. Measuring these potential risk factors might strengthen of the index case/household association on incidence rate ratio of TB among HHCs. Prioritizing individuals at highest risk for HHC investigation could reduce the number of HHC to be screened, but such selection may be logistically cumbersome. In addition, staff, patients and HHC themselves may not find it acceptable. However, it could be an option to use index case characteristics that put households at higher risk in order to select complete households in which to screen all contacts.

While HHCs of active TB patients may have a much higher risk of TB than the general population, TB cases in HHCs still account for only a small proportion of the total TB burden in a medium and high incidence area [18]. For example, the 205 incident cases found in our study corresponded to approximately 5 % of the district’s TB notifications during the same period. Furthermore, in some high incidence areas, community transmission can be higher than household transmission [19, 20]. The background TB incidence at which full HHC contact investigation becomes cost-effective as compared to investigating only selected high-risk HHC or index cases/households would provide valuable information for National TB Programs decision-making.

Finally, National TB Programs typically attempt to evaluate HHC at the start of the index case’s TB treatment, at the change of their treatment phase and at the end of their treatment. However, this approach does not take into consideration the time that may elapse occur between TB infection and disease [1, 18, 20]. For that reason, even full compliance to Peruvian guidelines for HHC investigation of drug sensitive cases would have failed to identify 59 % of incident TB episodes as HHCs.

This study demonstrated that HHC of TB cases in Lima, Peru are at very high risk for incident TB. Studies comparing the feasibility and cost effectiveness of all-inclusive versus risk based HHC investigation strategies within National TB Programs are needed to inform policy formulation.

CI, confidence interval; GLMM, generalized linear mixed models; HHC, household contact; IRR, incidence rate ratio; TB, tuberculosis