The Philippines has a high incidence of tuberculosis disease (TB), with an increasing prevalence of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) strains making its control difficult. Although the M . tuberculosis “Manila” ancient lineage 1 strain-type is thought to be prevalent in the country, with evidence of export to others, little is known about the genetic diversity of circulating strains. By whole genome sequencing (WGS) 178 isolates from the Philippines National Drug Resistance Survey, we found the majority (143/178; 80.3%) belonged to the lineage 1 Manila clade, with the minority belonging to lineages 4 (European-American; n = 33) and 2 (East Asian; n = 2). A high proportion were found to be multidrug-resistant (34/178; 19.1%), established through highly concordant laboratory drug susceptibility testing and in silico prediction methods. Some MDR-TB isolates had near identical genomic variation, providing potential evidence of transmission. By placing the Philippine isolates within a phylogeny of global M . tuberculosis (n > 17,000), we established that they are genetically similar to those observed outside the country, including a clade of Manila-like strain-types in Thailand. An analysis of the phylogeny revealed a set of ~200 SNPs that are specific for the Manila strain-type, and a subset can be used within a molecular barcode. Sixty-eight mutations known to be associated with 10 anti-TB drug resistance were identified in the Philippine strains, and all have been observed in other populations. Whilst nine putative streptomycin resistance conferring markers in gid (8) and rrs (1) genes appear to be novel and with functional consequences. Overall, this study provides an important baseline characterisation of M . tuberculosis genetic diversity for the Philippines, and will fill a gap in global datasets and aid the development of a nation-wide database for epidemiological studies and clinical decision making. Further, by establishing a molecular barcode for detecting Manila strains it will assist with the design of diagnostic tools for disease control activities.

BackgroundThis phase III clinical trial compared the immunogenicity and safety of a purified chick-embryo cell rabies vaccine (PCECV) administered according to a shortened post-exposure prophylaxis (PEP) 4-site/1-week intradermal regimen, compared with the currently recommended 2-site/Thai Red Cross (TRC) regimen.Methodology/Principal findingsThis controlled, open-label, multi-center study (NCT02177032) enrolled healthy individuals ≥1 year of age, randomized into 4 groups to receive intradermal PCECV according to one of the 2 regimens, with or without human rabies immunoglobulin (HRIG) administration at first visit (in adults only). Rabies virus neutralizing antibody (RVNA) concentrations and percentages of participants with RVNA concentrations ≥0.5 IU/mL (considered as adequate concentrations following PEP) were assessed up to day (D) 365 post-first vaccination. Non-inferiority of the 4-site/1-week regimen to the 2-site/TRC regimen was demonstrated if at D49, the lower limit of the 95% confidence interval (CI) for the difference between groups in the percentage of participants with adequate RVNA concentrations was >-5%. Of the 443 participants receiving the 4-site/1-week regimen, 88 adults received HRIG; 442 participants received the 2-site/TRC regimen (88 with HRIG). All participants achieved adequate RVNA concentrations by D14. At D49, the difference in percentage of participants with adequate RVNA concentrations between the 4-site/1-week and the 2-site/TRC groups was -1 (95%CI: -2.4–0.0); thus, non-inferiority was concluded. RVNA geometric mean concentrations were 18 IU/mL in 4-site/1-week groups and 12 IU/mL in 2-site/TRC groups at D14, and subsequently declined in all groups. RVNA concentrations were consistently lower in adults with HRIG administration than in those without. The 2 regimens had similar safety profiles. Of the 15 serious adverse events reported in 4-site/1-week groups and 19 in 2-site/TRC groups, none were vaccination-related.SignificanceThe data suggest that the 4-site/1-week regimen might be an alternative to current recommendations, with potential benefits in terms of improved cost-efficiency and compliance to vaccination.

Introduction: Xpert MTB/RIF is recommended for the simultaneous detection of tuberculosis (TB) and rifampicin resistance directly from sputum specimens. Since young children cannot always expectorate, we assessed urine as a possible specimen source to diagnose TB in children using Xpert MTB/RIF. Methods: During a field study to enhance childhood TB identification, spot urine samples were prospectively collected from consecutive ambulatory children aged 0 to 14 years presenting with presumptive pulmonary TB in community health centers. Urine Xpert MTB/RIF was performed by blinded technicians in 182 samples using 2 ml of unprocessed urine. Results: The mean age of presumptive TB cases was 5.9 years (median 5.4, range 0.1 to 14.7) with more males (113, 62%) compared to females. All urine samples tested negative for Xpert MTB/RIF, regardless of whether concentration was performed or not. Out of these 182 presumptive TB cases, 50 (28%) were clinically diagnosed and 5 (3%) were bacteriologically diagnosed to have TB disease using either sputum or nasopharyngeal aspirate specimens. Conclusions: In this community-based study, urine Xpert MTB/RIF does not appear to contribute to the diagnosis of childhood TB.

The Pediatric Infectious Disease Society of the Philippines (PIDSP) has a mandate to promote and conduct relevant infectious disease-related research by its members, fellows in training institutions, and resident physicians in training hospitals. Part of such a mandate is the creation of a priority list of research topics, which directs the researcher to what information is deemed important by the PIDSP, if the research is to receive funding from the Society, should such be requested. This list was first created in 2016. In April 2021, the PIDSP Research Committee met and agreed to update the list, by conducting a series of three internal surveys to determine if the items in the existing list were still relevant, and if new topics should be included. Twenty three PIDSP members, which included board members, known researchers, and university faculty, were surveyed using an online Google form, over three surveys between May 31, 2021 and October 3, 2021. New items were elicited from the respondents, and the old and new items were asked to be prioritized into the headings: high, medium, low, and not a priority. Only the high and medium priority items were included in the final updated list.

Background. Childhood tuberculosis (TB) remains a significant health problem worldwide despite the increase on its emphasis in national health programs. Objective. This study aimed to describe how TB in children is identified and managed in a routine TB program in a rural setting in a high-burden country. Methods. This is a prospective, community-based surveillance study in public rural clinics in the Philippines. Observations on case finding and management of TB in children as well as contact tracing in an existing TB program are described. Results. Out of 266 children with presumptive TB, 41 (15.4%) were cases of TB, 15 (5.6%) had latent TB infection (LTBI), 81 (30.5%) had TB exposure, and 129 (48.5%) had no TB. There were 37 (90%) TB cases who were clinically diagnosed. Ninety-three per cent (93%) of children with TB disease were cured or completed treatment. Among 25 children targeted for isoniazid preventive therapy (IPT) for LTBI and TB exposure, only 12 (52%) completed the recommended 6 months of IPT. Only 40 (43%) children aged 0 to 4 years exposed to smear-positive TB cases were screened. Conclusion. Barriers in the diagnosis, low IPT completion and problems in contact tracing may hinder successful implementation of TB programs for children.