Mirjam I. Bakker

Epidemiology of leprosy on five isolated islands in the Flores Sea, Indonesia.

We conducted a population‐based survey on five small islands in South Sulawesi Province (Indonesia) to collect baseline data previous to a chemoprophylactic intervention study aiming at interrupting the transmission of Mycobacterium leprae. Here we describe the present leprosy epidemiology on these geographically isolated islands. Of the 4774 inhabitants living in the study area 4140 were screened for leprosy (coverage: 87%). We identified 96 leprosy patients (85 new and 11 old patients), representing a new case detection rate (CDR) of 205/10 000 and a prevalence rate of 195/10 000. CDRs were similar for males and females. Male patients were more often classified as multibacillary (MB) than women. Of the new patients, 33 (39%) were classified as MB, 16 (19%) as paucibacillary (PB) 2–5 lesions and 36 (42%) as PB single lesion. In this area of high leprosy endemicity leprosy patients were extensively clustered, i.e. not equally distributed among the islands and within the islands among the houses.

Genetic, household and spatial clustering of leprosy on an island in Indonesia: a population-based study

BackgroundIt is generally accepted that genetic factors play a role in susceptibility to both leprosy per se and leprosy type, but only few studies have tempted to quantify this. Estimating the contribution of genetic factors to clustering of leprosy within families is difficult since these persons often share the same environment. The first aim of this study was to test which correlation structure (genetic, household or spatial) gives the best explanation for the distribution of leprosy patients and seropositive persons and second to quantify the role of genetic factors in the occurrence of leprosy and seropositivity.MethodsThe three correlation structures were proposed for population data (n = 560), collected on a geographically isolated island highly endemic for leprosy, to explain the distribution of leprosy per se, leprosy type and persons harbouring Mycobacterium leprae-specific antibodies. Heritability estimates and risk ratios for siblings were calculated to quantify the genetic effect. Leprosy was clinically diagnosed and specific anti-M. leprae antibodies were measured using ELISA.ResultsFor leprosy per se in the total population the genetic correlation structure fitted best. In the population with relative stable household status (persons under 21 years and above 39 years) all structures were significant. For multibacillary leprosy (MB) genetic factors seemed more important than for paucibacillary leprosy. Seropositivity could be explained best by the spatial model, but the genetic model was also significant. Heritability was 57% for leprosy per se and 31% for seropositivity.ConclusionGenetic factors seem to play an important role in the clustering of patients with a more advanced form of leprosy, and they could explain more than half of the total phenotypic variance.

Patient enrolment into HIV care and treatment within 90 days of HIV diagnosis in eight Rwandan health facilities: a review of facility-based registers.

Introduction Access to antiretroviral therapy (ART) has increased greatly in sub-Saharan Africa. However many patients do not enrol timely into HIV care and treatment after HIV diagnosis. We studied enrolment into care and treatment and determinants of non-enrolment in Rwanda. Methods Data were obtained from routine clinic registers from eight health facilities in Rwanda on patients who were diagnosed with HIV at the antenatal care, voluntary counselling-and-testing, outpatient or tuberculosis departments between March and May 2009. The proportion of patients enrolled into HIV care and treatment was calculated as the number of HIV infected patients registered in ART clinics for follow-up care and treatment within 90 days of HIV diagnosis divided by the total number of persons diagnosed with HIV in the study period. Results Out of 482 patients diagnosed with HIV in the study period, 339 (70%) were females, and the median age was 29 years (interquartile range [IQR] 24–37). 201 (42%) enrolled into care and treatment within 90 days of HIV diagnosis. The median time between testing and enrolment was six days (IQR 2–14). Enrolment in care and treatment was not significantly associated with age, sex, or department of testing, but was associated with study site. None of those enrolled were in WHO stage 4. The median CD4 cell count among adult patients was 387 cells/mm3 (IQR: 242–533 cells/mm3); 81 of 170 adult patients (48%) were eligible to start ART (CD4 count<350 cells/mm3 or WHO stage 4). Among those eligible, 45 (56%) started treatment within 90 days of HIV diagnosis. Conclusion Less than 50% of diagnosed HIV patients from eight Rwandan health facilities had enrolled into care and treatment within 90 days of diagnosis. Improving linkage to care and treatment after HIV diagnosis is needed to harness the full potential of ART.

Comparative meta-analysis of tuberculosis contact investigation interventions in eleven high burden countries.

Background Screening of household contacts of tuberculosis (TB) patients is a recommended strategy to improve early case detection. While it has been widely implemented in low prevalence countries, the most optimal protocols for contact investigation in high prevalence, low resource settings is yet to be determined. This study evaluated contact investigation interventions in eleven lower and middle income countries and reviewed the association between context or program-related factors and the yield of cases among contacts. Methods We reviewed data from nineteen first wave TB REACH funded projects piloting innovations to improve case detection. These nineteen had fulfilled the eligibility criteria: contact investigation implementation and complete data reporting. We performed a cross-sectional analysis of the percentage yield and case notifications for each project. Implementation strategies were delineated and the association between independent variables and yield was analyzed by fitting a random effects logistic regression. Findings Overall, the nineteen interventions screened 139,052 household contacts, showing great heterogeneity in the percentage yield of microscopy confirmed cases (SS+), ranging from 0.1% to 6.2%). Compared to the most restrictive testing criteria (at least two weeks of cough) the aOR’s for lesser (any TB related symptom) and least (all contacts) restrictive testing criteria were 1.71 (95%CI 0.94−3.13) and 6.90 (95% CI 3.42−13.93) respectively. The aOR for inclusion of SS- and extra-pulmonary TB was 0.31 (95% CI 0.15−0.62) compared to restricting index cases to SS+ TB. Contact investigation contributed between <1% and 14% to all SS+ cases diagnosed in the intervention areas. Conclusions This study confirms that high numbers of active TB cases can be identified through contact investigation in a variety of contexts. However, design and program implementation factors appear to influence the yield of contact investigation and its concomitant contribution to TB case detection.

A pragmatic approach to measuring, monitoring and evaluating interventions for improved tuberculosis case detection

The inability to detect all individuals with active tuberculosis has led to a growing interest in new approaches to improve case detection. Policy makers and program staff face important challenges measuring effectiveness of newly introduced interventions and reviewing feasibility of scaling-up successful approaches. While robust research will continue to be needed to document impact and influence policy, it may not always be feasible for all interventions and programmatic evidence is also critical to understand what can be expected in routine settings. The effects of interventions on early and improved tuberculosis detection can be documented through well-designed program evaluations. We present a pragmatic framework for evaluating and measuring the effect of improved case detection strategies using systematically collected intervention data in combination with routine tuberculosis notification data applying historical and contemporary controls. Standardized process evaluation and systematic documentation of program implementation design, cost and context will contribute to explaining observed levels of success and may help to identify conditions needed for success. Findings can then guide decisions on scale-up and replication in different target populations and settings.

Provider-Initiated HIV Testing and Counselling in Rwanda: Acceptability among Clinic Attendees and Workers, Reasons for Testing and Predictors of Testing

Introduction Routine provider-initiated HIV testing and counselling (PITC) may increase HIV testing rates, but whether PITC is acceptable to health facility (HF) attendees is unclear. In the course of a PITC intervention study in Rwanda, we assessed the acceptability of PITC, reasons for being or not being tested and factors associated with HIV testing. Methods Attendees were systematically interviewed in March 2009 as they left the HF, regarding knowledge and acceptability of PITC, history of testing and reasons for being tested or not. Subsequently, PITC was introduced in 6 of the 8 HFs and a second round of interviews was conducted. Independent factors associated with testing were analysed using logistic regression. Randomly selected health care workers (HCWs) were also interviewed. Results 1772 attendees were interviewed. Over 95% agreed with the PITC policy, both prior to and after implementation of PITC policy. The most common reasons for testing were the desire to know one’s HIV status and having been offered an HIV test by an HCW. The most frequent reasons for not being tested were known HIV status and test not being offered. In multivariable analysis, PITC, age ≥15 years, and not having been previously tested were factors significantly associated with testing. Although workload was increased by PITC, HIV testing rates increased and HCWs overwhelmingly supported the policy. Conclusion Among attendees and HCWs in Rwandan clinics, the acceptability of PITC was very high. PITC appeared to increase testing rates and may be helpful in prevention and early access to treatment.

Adherence to tuberculosis treatment, sputum smear conversion and mortality: a retrospective cohort study in 48 Rwandan clinics.

Background Adherence to treatment and sputum smear conversion after 2 months of treatment are thought to be important for successful outcome of tuberculosis (TB) treatment. Methods Retrospective cohort study of new adult TB patients diagnosed in the first quarter of 2007 at 48 clinics in Rwanda. Data were abstracted from TB registers and individual treatment charts. Logistic regression analysis was done to examine associations between baseline demographic and clinical factors and three outcomes adherence, sputum smear conversion at two months, and death. Results Out of 725 eligible patients the treatment chart was retrieved for 581 (80%). Fifty-six (10%) of these patients took <90% of doses (defined as poor adherence). Baseline demographic characteristics were not associated with adherence to TB treatment, but adherence was lower among HIV patients not taking antiretroviral therapy (ART); p = 0.03). Sputum smear results around 2 months after start of treatment were available for 220 of 311 initially sputum-smear-positive pulmonary TB (PTB+) patients (71%); 175 (80%) had achieved sputum smear conversion. In multivariable analysis, baseline sputum smear grade (odds ratio [OR] = 2.7, 95% Confidence interval [CI] 1.1–6.6 comparing smear 3+ against 1+) and HIV infection (OR 3.0, 95%CI 1.3–6.7) were independent predictors for non-conversion at 2 months. Sixty-nine of 574 patients (12%) with known TB treatment outcomes had died. Besides other known determinants, poor adherence had an independent, strong effect on mortality (OR 3.4, 95%CI 1.4–7.8). Conclusion HIV infection is an important independent predictor of failure of sputum smear conversion at 2 months among PTB+ patients. Poor adherence to TB treatment is an important independent determinant of mortality.

Sputum completion and conversion rates after intensive phase of tuberculosis treatment: an assessment of the Rwandan control program

BackgroundIn Rwanda tuberculosis (TB) is one of the major health problems. To contribute to an improved performance of the Rwandan National TB Control Program, we conducted a study with the following objectives: (1) to assess the completion rate of sputum smear examinations at the end of the intensive phase of TB treatment; (2) to assess the sputum conversion rate (SCR); (3) to assess associations between smear completion rate or SCR with key health facility characteristics.MethodsTB registers in 89 health facilities in five provinces were reviewed. Data of new and retreatment smear-positive pulmonary TB (PTB+) cases registered between January and June 2006 were included in the study. Data on key characteristics of the selected health facilities were also collected.ResultsAmong 1509 new PTB + cases, 32 (2.1%) had died by 2 months, and 178 (11.8%) had been transferred-out. Among the remaining 1299 patients, a smear examination at month 2 was done in 1039 (smear completion rate 80.0%). Among these 1039, 852 (82.0%) had become smear-negative. The smear completion rate and SCR varied considerably between health facilities. A high number of new PTB cases at a health facility was the only significant predictor of a low completion rate, while the only independent factor associated with low sputum conversion rates was rural (vs. urban) location of the health facility.ConclusionsIn Rwanda, too few patients get a smear examination after 2 months of TB treatment; the SCR among those with smear results was adequate at 82%. A high number of new TB patients at a health facility was a significant predictor of a low completion rate. The national TB control program should design strategies to improve completion rates.

Linkage to HIV care before and after the introduction of provider-initiated testing and counselling in six Rwandan health facilities.

ABSTRACT HIV testing and counselling forms the gateway to the HIV care and treatment continuum. Therefore, the World Health Organization recommends provider-initiated testing and counselling (PITC) in countries with a generalized HIV epidemic. Few studies have investigated linkage-to-HIV-care among out-patients after PITC. Our objective was to study timely linkage-to-HIV-care in six Rwandan health facilities (HFs) before and after the introduction of PITC in the out-patient departments (OPDs). Information from patients diagnosed with HIV was abstracted from voluntary counselling and testing, OPD and laboratory registers of six Rwandan HFs during three-month periods before (March–May 2009) and after (December 2009–February 2010) the introduction of PITC in the OPDs of these facilities. Information on patients’ subsequent linkage-to-pre-antiretroviral therapy (ART) care and ART was abstracted from ART clinic registers of each HF. To triangulate the findings from HF routine, a survey was held among patients to assess reasons for non-enrolment. Of 635 patients with an HIV diagnosis, 232 (36.5%) enrolled at the ART clinic within 90 days of diagnosis. Enrolment among out-patients decreased after the introduction of PITC (adjusted odds ratio, 2.0; 95% confidence interval, 1.0–4.2; p = .051). Survey findings showed that retesting for HIV among patients already diagnosed and enrolled into care was not uncommon. Patients reported non-acceptance of disease status, stigma and problems with healthcare services as main barriers for enrolment. Timely linkage-to-HIV-care was suboptimal in this Rwandan study before and after the introduction of PITC; the introduction of PITC in the OPD may have had a negative impact on linkage-to-HIV-care. Healthier patients tested through PITC might be less ready to engage in HIV care. Fear of HIV stigma and mistrust of test results appear to be at the root of these problems.

Risk Factors of Typhoid Infection in the Indonesian Archipelago

Background Knowledge of risk factors and their relative importance in different settings is essential to develop effective health education material for the prevention of typhoid. In this study, we examine the effect of household level and individual behavioural risk factors on the risk of typhoid in three Indonesian islands (Sulawesi, Kalimantan and Papua) in the Eastern Indonesian archipelago encompassing rural, peri-urban and urban areas. Methods We enrolled 933 patients above 10 years of age in a health facility-based case-control study between June 2010 and June 2011. Individuals suspected of typhoid were tested using the typhoid IgM lateral flow assay for the serodiagnosis of typhoid fever followed by blood culture testing. Cases and controls were defined post-recruitment: cases were individuals with a culture or serology positive result (n = 449); controls were individuals negative to both serology and culture, with or without a diagnosis other than typhoid (n = 484). Logistic regression was used to examine the effect of household level and individual level behavioural risk factors and we calculated the population attributable fraction (PAF) of removing each risk significant independent behavioural risk factor. Results Washing hands at critical moments of the day and washing hands with soap were strong independent protective factors for typhoid (OR = 0.38 95% CI 0.25 to 0.58 for each unit increase in hand washing frequency score with values between 0 = Never and 3 = Always; OR = 3.16 95% CI = 2.09 to 4.79 comparing washing hands with soap sometimes/never vs. often). These effects were independent of levels of access to water and sanitation. Up to two thirds of cases could be prevented by compliance to these practices (hand washing PAF = 66.8 95% CI 61.4 to 71.5; use of soap PAF = 61.9 95%CI 56.7 to 66.5). Eating food out in food stalls or restaurant was an important risk factor (OR = 6.9 95%CI 4.41 to 10.8 for every unit increase in frequency score). Conclusions Major gains could potentially be achieved in reducing the incidence of typhoid by ensuring adherence to adequate hand-washing practices alone. This confirms that there is a pivotal role for ‘software’ related interventions to encourage behavior change and create demand for goods and services, alongside development of water and sanitation infrastructure.