Protocol, rationale and design of PEOPLE (Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar): A cluster randomized trial on effectiveness of different modalities of implementation of post-exposure prophylaxis of leprosy contacts

Background: Leprosy is an ancient infectious disease with a global annual incidence that has plateaued above 200,000 new cases since over a decade. New strategies are required to overcome this stalemate. Post-exposure prophylaxis (PEP) with a single dose of Rifampicin (SDR) has conditionally been recommended by the World Health Organization (WHO), based on a randomized-controlled-Trial in Bangladesh. More evidence is required. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial will assess effectiveness of different modalities of PEP on the Comoros and Madagascar. Methods: PEOPLE is a cluster-randomized trial with villages selected on previous leprosy-incidence and randomly allocated to four arms. Four annual door-To-door surveys will be performed in all arms. All consenting permanent residents will be screened for leprosy. Leprosy patients will be treated according to international guidelines and eligible contacts will be provided with SDR-PEP. Arm-1 is the comparator in which no PEP will be provided. In arms 2, 3 and 4, SDR-PEP will be provided at double the regular dose (20 mg/kg) to eligible contacts aged two years and above. In arm 2 all household-members of incident leprosy patients are eligible. In arm 3 not only household-members but also neighbourhood contacts living within 100-m of an incident case are eligible. In arm 4 such neighbourhood contacts are only eligible if they test positive to anti-PGL-I, a serological marker. Incidence rate ratios calculated between the comparator arm 1 and each of the intervention arms will constitute the primary outcome. Discussion: Different trials on PEP have yielded varying results. The pivotal COLEP trial in Bangladesh showed a 57% reduction in incidence over a two-year period post-intervention without any rebound in the following years. A study in a high-incidence setting in Indonesia showed no effect of PEP provided to close contacts but a major effect of PEP provided as a blanket measure to an entire island population. High background incidence could be the reason of the lack of effect of PEP provided to individual contacts. The PEOPLE trial will assess effectiveness of PEP in a high incidence setting and will compare three different approaches, to identify who benefits most from PEP. Trial registration: Clinicaltrials.Gov. NCT03662022. Initial Protocol Version 1.2, 27-Aug-2018

TBHW_FINAL.rec

1. TBHW_FINAL Data base about health-workers during 2014 Ebola outbreak in Guinea. 2. RBPRESUM_FINAL Data about presumptive cases during 2014 Ebola outbreak in Guinea. 3. TBSTOCK_FINAL. Data about stockout during Ebola outbreak in Guinea. 4. TB EVD PATIENTS FINAL. Data on TB patients during Ebola outbreak in Guinea

Effect of Ebola outbreak on tuberculosis care in Conakry, Guinea

<p><b>S1_TBHW_FINAL.rec. </b>This is the database about health workers before and during Ebola Outbreak in Conakry, Guinea, 2014.</p> <p><b>S2_TB_EVD_PATIENTS_FINAL.dta. </b>This is the database about Tuberculosis patients before and during Ebola Outbreak in Conakry, Guinea, 2014..</p> <p><b>S3_TBSTOCK_FINAL.rec. </b>This is the database about stockouts of Tuberculosis drugs before and during Ebola Outbreak in Conakry, Guinea, 2014..</p> <p><b>S4_TBPRESUM_FINAL.rec. </b>This is the database about Tuberculosis presumptive cases before and during Ebola Outbreak in Conakry, Guinea, 2014.. </p

Better programmatic outcome with the shorter regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Guinea: A retrospective cohort study.

SETTING:Since August 2016, after the Ebola outbreak, the Guinean National Tuberculosis Programme and Damien Foundation implemented the shorter treatment regimen (STR) for multidrug-resistant tuberculosis (MDR-TB) in the three MDR-TB sites of Conakry. Previously, the longer regimen was used to treat MDR-TB. OBJECTIVES:In a post-Ebola context, with a weakened health system, we describe the MDR-TB treatment uptake, patients characteristics, treatment outcomes and estimate the effect of using the longer versus STR on having a programmatically adverse outcome. DESIGN:This is a retrospective cohort study in RR-TB patients treated with either the longer regimen or STR. RESULTS:In Conakry, in 2016 and 2017, 131 and 219 patients were diagnosed with rifampicin-resistant tuberculosis (RR-TB); and 108 and 163 started treatment, respectively. Of 271 patients who started treatment, 75 were treated with the longer regimen and 196 with the STR. Patients characteristics were similar regardless of the regimen except that the median age was higher among those treated with a longer regimen (30 years (IQR:24-38) versus 26 years (IQR:21-39) for the STR. Patients treated with a STR were more likely to obtain a programmatically favorable outcome (74.0% vs 58.7%, p = 0.01) as lost to follow up was higher among those treated with a longer regimen (20.0% vs 8.2%, p = 0.006). Patients on a longer regimen were more than 2 times more likely (aOR: 2.5; 95%CI:1.3,4.7) to have a programmatically adverse outcome as well as being 45 years or older (aOR: 2.8; 95%CI:1.3,6.2), HIV positive (aOR:3.3; 95%CI:1.6,6.6) and attendance at a clinic without NGO support (aOR:3.0; 95%:1.6,5.7). CONCLUSION:In Guinea, patients treated with the STR were more likely to have a successful outcome than those treated with the longer MDR-TB treatment regimen. Lost to follow-up was higher in patients on the longer regimen. However, STR treatment outcomes were less good than those reported in the region

Minimally invasive sampling to identify leprosy patients with a high bacterial burden in the Union of the Comoros

The World Health Organization (WHO) endorsed diagnosis of leprosy (also known as Hansen’s disease) entirely based on clinical cardinal signs, without microbiological confirmation, which may lead to late or misdiagnosis. The use of slit skin smears is variable, but lacks sensitivity. In 2017–2018 during the ComLep study, on the island of Anjouan (Union of the Comoros; High priority country according to WHO, 310 patients were diagnosed with leprosy (paucibacillary = 159; multibacillary = 151), of whom 263 were sampled for a skin biopsy and fingerstick blood, and 260 for a minimally-invasive nasal swab. In 74.5% of all skin biopsies and in 15.4% of all nasal swabs, M. leprae DNA was detected. In 63.1% of fingerstick blood samples, M. leprae specific antibodies were detected with the quantitative αPGL-I test. Results show a strong correlation of αPGL-I IgM levels in fingerstick blood and RLEP-qPCR positivity of nasal swabs, with the M. leprae bacterial load measured by RLEP-qPCR of skin biopsies. Patients with a high bacterial load (≥50,000 bacilli in a skin biopsy) can be identified with combination of counting lesions and the αPGL-I test. To our knowledge, this is the first study that compared αPGL-I IgM levels in fingerstick blood with the bacterial load determined by RLEP-qPCR in skin biopsies of leprosy patients. The demonstrated potential of minimally invasive sampling such as fingerstick blood samples to identify high bacterial load persons likely to be accountable for the ongoing transmission, merits further evaluation in follow-up studies. Author summary Leprosy is the oldest infectious disease known to humankind. We still do not succeed in curbing its transmission, with more than 200,000 new patients detected worldwide each year. Identifying persons with a high burden of bacteria is key to curb transmission. To identify these persons, bacteria are counted in invasive and painful samples like slit skin smears and skin biopsies. We evaluated whether we can use less invasive samples, like fingerstick blood or nasal swabs, to determine the bacterial load. We found that the level of antibodies against M. leprae (αPGL-I IgM) in fingerstick blood correlates well with the bacterial load determined in skin biopsies from the same leprosy patient. Therefore, a high level of antibodies against M. leprae in fingerstick blood might identify persons who pose a potential risk for transmission of leprosy and could be prioritized for contact screening, which is essential for control of the disease

Factors associated with ^*unfavorable outcomes among tuberculosis patients placed on treatment in ten health facilities supported by Damien Foundation, before (April to December 2013) and during the Ebola outbreak (April to December 2014), Conakry, Guinea.

<p>Factors associated with ^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157296#t005fn001" target="_blank">*</a>}unfavorable outcomes among tuberculosis patients placed on treatment in ten health facilities supported by Damien Foundation, before (April to December 2013) and during the Ebola outbreak (April to December 2014), Conakry, Guinea.</p

Survival probability of Tuberculosis new (A) and retreatment (B) cases placed on treatment in ten health facilities supported by Damien Foundation, before (April to December 2013) and during the Ebola outbreak (April to December 2014), Conakry, Guinea.

<p>This figure shows the probability of having an unfavourable outcome (lost to follow-up, treatment failure, death or transferred out) during the Ebola outbreak (2014) compared to the periode before (2013).</p

Accomplishment of routine Tuberculosis and Ebola related measures in ten health facilities supported by Damien Foundation and the National Tuberculosis Program before (April to December 2013) and during the Ebola outbreak (April to December 2014), Conakry, Guinea.

<p>Accomplishment of routine Tuberculosis and Ebola related measures in ten health facilities supported by Damien Foundation and the National Tuberculosis Program before (April to December 2013) and during the Ebola outbreak (April to December 2014), Conakry, Guinea.</p