Beyond effectiveness. The adversities of implementing a fortification program : a case study on the quality of iron fortification of fish and soy sauce in Cambodia

Fortification of fish and soy sauces is a cost-effective strategy to deliver and increase iron intake in the Cambodian diet, as both are widely consumed by the entire population. In order to qualify as fortified sauces recognized by international regulations, iron content must be between 230 and 460 mg/L, whilst nitrogen and salt should contain no less than 10 g/L and 200 g/L respectively. This survey aims to analyze the progress of the fortification program. Through a better understanding of its obstacles and successes, the paper will then consider approaches to strengthen the program. Two hundred and fifty two samples were collected from 186 plants and 66 markets in various provinces. They were then analyzed for iron, nitrogen and salt content. The study demonstrates that 74% of fortified fish and soy sauces comply with Cambodian regulations on iron content. 87% and 53.6% of the collected samples do not have adequate level of nitrogen and salt content, respectively. The paper will discuss additional efforts that need to be implemented to ensure the sustainability of the project, including the need to: (i) comply with International Codex; (ii) adopt mandatory legislation; and (iii) ensure enforcement

Invisible medicine sellers and their use of antibiotics: a qualitative study in Cambodia.

BACKGROUND: Global attention to antimicrobial resistance has increased interest in tackling the widespread inappropriate dispensing of antibiotics by informal, for-profit healthcare providers (HCPs). We provide new evidence on an understudied group of informal HCPs: invisible medicine sellers (IMS) who operate without any marked facility. We investigated factors that influence community decisions on which HCPs to purchase medicines from, focusing on reasons for using IMS, and compared different HCPs' knowledge of antibiotic use. METHODS: We conducted community focus group discussions (FGDs) in seven purposively selected villages representing high and low informal HCPs use in two peri-urban districts in Phnom Penh, Cambodia. Using information from the FGDs to identify HCPs that sell medicines, we interviewed 35 participants: 21 HCPs (including five IMS) and 14 key informants, including government HCPs and village leaders. We adopted an interpretative approach and conducted a thematic analysis. RESULTS: Community members typically knew of several formal and informal HCPs selling medicines nearby, and IMS were common, as were doctors that sell medicines covertly. Two factors were most salient in influencing the choice of HCP for medicine purchasing. The first was trust in the effectiveness of medicines provided, judged by the speed of symptomatic relief. This pushed HCPs to provide several medicines, including antibiotics, at the first consultation. The second was the convenience offered by IMS and other informal HCPs: supplying medicines when other facilities are closed, accepting delayed payments, providing incomplete courses of medication and selling human antibiotics for animal use. CONCLUSION: This first study focusing on IMS indicates that it is important, but challenging, for public health agencies to engage with them to reduce inappropriate use of antibiotics. Although public health facilities must fill some gaps that informal HCPs are currently addressing, such as access to medicines at night, reducing demand for unnecessary antibiotics is also critical

Risk and prognostic significance of tuberculosis in patients from The TREAT Asia HIV Observational Database

10.1186/1471-2334-9-46BMC Infectious Diseases94

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation

Prevalence of MDR organism (MDRO) carriage in children and their household members in Siem Reap Province, Cambodia

Background The rising incidence of infections caused by MDR organisms (MDROs) poses a significant public health threat. However, little has been reported regarding community MDRO carriage in low- and middle-income countries. Methods We conducted a cross-sectional study in Siem Reap, Cambodia comparing hospital-associated households, in which an index child (age: 2–14 years) had been hospitalized for at least 48 h in the preceding 2–4 weeks, with matched community households on the same street, in which no other child had a recent history of hospitalization. Participants were interviewed using a survey questionnaire and tested for carriage of MRSA, ESBL-producing Enterobacterales (ESBL-E) and carbapenemase-producing Enterobacterales (CPE) by culture followed by antibiotic susceptibility testing. We used logistic regression analysis to analyse associations between collected variables and MDRO carriage. Results Forty-two pairs of households including 376 participants with 376 nasal swabs and 290 stool specimens were included in final analysis. MRSA was isolated from 26 specimens (6.9%). ESBL-producing Escherichia coli was detected in 269 specimens (92.8%) whereas ESBL-producing Klebsiella pneumoniae was isolated from 128 specimens (44.1%), of which 123 (42.4%) were co-colonized with ESBL-producing E. coli. Six (2.1%) specimens tested positive for CPE (4 E. coli and 2 K. pneumoniae). The prevalence ratios for MRSA, ESBL-producing E. coli and ESBL-producing K. pneumoniae carriage did not differ significantly in hospital-associated households and hospitalized children compared with their counterparts. Conclusions The high prevalence of ESBL-E across both household types suggests that MDRO reservoirs are common in the community. Ongoing genomic analyses will help to understand the epidemiology and course of MDRO spread

Mycobacterial antibody levels and immune restoration disease in HIV patients treated in South East Asia

Aim: Immune restoration disease (IRD) associated with Mycobacterium tuberculosis parallels the reconstitution of a pathogen-specific Th1 response. However, it is not clear whether humoral responses to M. tuberculosis antigens also rise, or whether antibody levels predict IRD. Here, humoral immunity to M. tuberculosis antigens was investigated in four Asian cohorts. Methods: Plasma samples were obtained from longitudinal prospective studies of HIV patients beginning antiretroviral therapy (ART) in New Delhi (India), Kuala Lumpur (Malaysia), Jakarta (Indonesia) and Phnom Penh (Cambodia). IgG antibodies to purified protein derivative, lipoarabinomannan and 38-kDa antigens of M. tuberculosis were quantitated using in-house ELISAs. IRD was defined as exacerbated symptoms of tuberculosis in patients on anti-tuberculosis therapy or a novel presentation of tuberculosis on ART. Results: Pre-ART IgG levels to purified protein derivative, lipoarabinomannan and 38-kDa antigen were similar in the IRD and control groups from each site. Compared with non-IRD controls, a higher proportion of IRD patients had elevated IgG levels to lipoarabinomannan (defined as a greater than twofold increase) over 12 weeks of ART. However, this trend was not significant for the other antigens and longitudinal analyses did not reveal clear rises in antibody levels at the time of IRD. Conclusion: Levels of antibody to mycobacterial antigens do not predict IRD, but levels of antibody reactive with lipoarabinomannan rise during an IRD in some patients. © 2011 Future Medicine Ltd

Is enhancing the professionalism of healthcare providers critical to tackling antimicrobial resistance in low- and middle-income countries?

BACKGROUND: Healthcare providers' (HCPs) professionalism refers to their commitment and ability to respond to the health needs of the communities they serve and to act in the best interest of patients. Despite attention to increasing the number of HCPs in low- and middle-income countries (LMIC), the quality of professional education delivered to HCPs and their resulting professionalism has been neglected. The Global Action Plan on Antimicrobial Resistance (AMR) seeks to reduce inappropriate use of antibiotics by urging patients to access antibiotics only through qualified HCPs, on the premise that qualified HCPs will act as more responsible and competent gatekeepers of access to antibiotics than unqualified HCPs. METHODS: We investigate whether weaknesses in HCP professionalism result in boundaries between qualified HCPs and unqualified providers being blurred, and how these weaknesses impact inappropriate provision of antibiotics by HCPs in two LMIC with increasing AMR-Pakistan and Cambodia. We conducted 85 in-depth interviews with HCPs, policymakers, and pharmaceutical industry representatives. Our thematic analysis was based on a conceptual framework of four components of professionalism and focused on identifying recurring findings in both countries. RESULTS: Despite many cultural and sociodemographic differences between Cambodia and Pakistan, there was a consistent finding that the behaviour of many qualified HCPs did not reflect their professional education. Our analysis identified five areas in which strengthening HCP education could enhance professionalism and reduce the inappropriate use of antibiotics: updating curricula to better cover the need for appropriate use of antibiotics; imparting stronger communication skills to manage patient demand for medications; inculcating essential professional ethics; building skills required for effective collaboration between doctors, pharmacists, and lay HCPs; and ensuring access to (unbiased) continuing medical education. CONCLUSIONS: In light of the weaknesses in HCP professionalism identified, we conclude that global guidelines urging patients to only seek care at qualified HCPs should consider whether HCP professional education is equipping them to act in the best interest of the patient and society. Our findings suggest that improvements to HCP professional education are needed urgently and that these should focus not only on the curriculum content and learning methods, but also on the social purpose of graduates