Foodborne Toxicity in the Pediatric Population: Etiology, Diagnosis, and Prevention Strategies

BackgroundHIV disease progresses more rapidly in children than adults with mortality rates exceeding 50% by 2 years of age without antiretroviral therapy (ART) in sub-Saharan Africa. Recent World Health Organization (WHO) guidelines recommend universal treatment for all living persons with HIV, yet there is limited supporting evidence in pediatric populations. The objective of this study was to determine whether CD4 cell counts reflect immunological markers associated with disease progression in ART naïve perinatally-infected HIV+ children and adolescents and their response to ART.MethodsPBMC and plasma samples were collected from 71 HIV negative and 132 HIV+ children (65 ART naïve and 67 on ART) between ages 1–19 years from Mombasa, Kenya. Untreated HIV+ subjects were sub-categorized by high or low CD4 T cell counts. Immune activation markers CD38, HLA-DR and Ki67 were analyzed by flow cytometry. Plasma soluble CD14 (sCD14) was quantified by ELISA.ResultsHIV-infected children and adolescents with preserved CD4 cell counts had depleted CD4 percentages and CD4:CD8 ratios, and high immune activation levels. ART initiation rapidly and persistently reversed T cell activation, but failed to normalize CD4:CD8 ratios and plasma sCD14 levels.ConclusionsDiminished CD4 percentages and CD4:CD8 ratios along with profound immune activation occur independent of CD4 cell count thresholds in ART naïve HIV+ children and adolescents. Immediate ART initiation, as recommended in the most recent WHO guidelines may protect them from pathologic sequelae associated with persistent inflammation.

Background Approximately 1.2 million children are estimated to be infected with tuberculosis (TB) worldwide. The World Health Organization (WHO) routinely updates guidelines for the treatment to lateen tuberculosis infection (LTBI) in children with the last update provided in 2020. The objective of our study was to assess the impact of these updates on national LTBI guidelines devised by 30 high burden countries. Method We collected National LTBI guidelines from health ministries of high burden countries. Eleven countries had guidelines that were in English and published in the last 6 years out of the 30 high burden countries. The guidelines from the respective countries were compared for concordance with the most recent WHO guidelines on LTBI management in the pediatric population. Results We identified four subsections of the WHO guidelines: at-risk groups for LTBI testing, algorithms to rule out active TB disease, testing for LTBI, and TB preventive treatment options. Guidelines from Nigeria and Pakistan had the highest concordance in identifying at-risk groups for LTBI at 83.3% each, whereas Namibia had the lowest concordance for this subcategory at 16.67% . Nigeria had 100% concordance in defining an algorithm to rule out active TB disease. Pakistan and Uganda had 80% concordance for algorithms to rule out disease. Philippines, Nigeria and Pakistan had 100% concordance with testing for LTBI, with Ethiopia, Kenya and Myanmar having the lowest concordance with 0%. Namibia and Myanmar had the highest concordance in regards to TB preventive treatment options, with 64% and 50% concordance respectively; all other included guidelines had low concordance for TB preventive treatment options. Conclusion Our study examined general concordance of national LTBI guidelines with the WHO guidelines and in the domains of identification, testing, algorithms, treatment, and prevention. Most guidelines among the high burden countries had high concordance in identifying at-risk groups for LTBI testing and algorithms to rule out active TB disease. Further research is needed to assess factors that lead to discordance between national and WHO guidelines.

Improving the Radical Cure of Plasmodium vivax Malaria

In disasters and emergency situations, a lot of drug and medical supplies comes to the affected area from local or international donors. But, those donations often generate more problems for the recipients. The WHO and major humanitarian organisations developed WHO Guidelines for Drug Donations in 1996. The guidelines based on four core principles which are all donation should benefit the recipient, respect for wishes and authority of the recipient, there should not be a double standard in quality, and effective communication between donor and recipient. The guidelines influenced positively to drug donation practices for several years until 2004. The drug donation practices during 2004 tsunami relief in Sri Lanka and Aceh (Indonesia) showed that the compliance with WHO Guidelines for Drug Donations was low. This study aim was to strengthen the effectiveness of WHO Guidelines for Drug Donations in disaster and emergency situations. While the objectives are to explore the strength and weakness of the WHO Guidelines for Drug Donations and to recommend how to improve the effectiveness of drug donations. In this study, the WHO Guidelines for Drug Donations were analysed using the model of health policy analysis from Walt and Gilson, which is specifically used for analysing health policies. The framework is viewed as a tool to describe the interactions and interconnections systems between content, context, process and groups of actors. The author concludes that presence of donation operator team for drug donations is needed during the emergency situations and it should be stated in the WHO Guidelines for Drug Donations. The WHO needs to encourage donors and recipients to refer to WHO Guidelines for Drug Donations when they are making their own guidelines. The guidelines can be strengthened at country level and adjusted to regulations in the countries. The WHO Guidelines for Drug Donations should state that donations are preferred in form of New Emergency Health Kit (NEHK) or cash donations, and the necessity of information and communication centre in the WHO Guidelines for Drug Donations.

The World Health Organization (WHO) guidelines on evaluation of similar biotherapeutic products (SBPs; also called biosimilars) were adopted by the WHO Expert Committee on Biological Standardization (ECBS) in 2009. In 2019, the ECBS considered that a more tailored and potentially reduced clinical data package may be acceptable in cases where this was clearly supported by the available scientific evidence. The goal of this publication is to review the current clinical experience and scientific evidence and to provide an expert perspective for updating the WHO guidelines to provide more flexibility and clarity. As the first step, the relevant guidelines by other regulatory bodies were reviewed in order to identify issues that might help with updating the WHO guidelines. Next, a literature search was conducted for information on the long-term efficacy, safety, and immunogenicity of biosimilars to identify possible long-term problems. Finally, a search for articles concerning the role of clinical studies in the benefit–risk evaluation of biosimilars was conducted. The analysis of other guidelines suggested that the WHO guidelines may need more emphasis on the importance of the state-of-the-art physicochemical and structural comparability exercise and in vitro functional testing. The use of “foreign” reference product will also need clarifications. The value of in vivo toxicological tests in the development of biosimilars is questionable, and the non-clinical part needs revisions accordingly. The concepts of “totality of evidence,” “stepwise development,” and “residual uncertainty” were applied in the evaluation of the clinical sections of the guideline. The review of long-term safety and efficacy demonstrated the robustness of the current biosimilar development concept. The analysis of the roles of different development phases suggested that the large efficacy, safety, and immunogenicity studies are, in most cases, redundant. The residual uncertainty of safety, immunogenicity, and efficacy of biosimilars that has shaped the current regulatory guidelines is now substantially reduced. This will allow the re-evaluation of the non-clinical and clinical requirements of the current WHO main guideline. The shift of the relative impact of the development phases towards physico-chemical and in vitro functional testing will provide a relief to the manufacturers and new challenges to the regulators.

Mathematical modeling studies are frequently conducted to guide policy in global health. However, the contribution of mathematical modeling studies to World Health Organization (WHO) guideline recommendations, and the quality of evidence contributed by these studies remains unknown. We conducted a systematic review of the WHO Guidelines Review Committee database to identify guideline recommendations that included evidence from mathematical modeling studies since inception of the Guidelines Review Committee on 1 December, 2007. We included WHO guideline recommendations citing a mathematical modeling study in the primary evidence base. We defined a mathematical model as a framework that predicted epidemiologic, health or economic impact of an intervention or decision in the clinical or public health context. The primary outcome was inclusion of evidence from mathematical modeling studies in a guideline recommendation. We evaluated each unique modeling study across multiple domains of quality. Between 1 December 2007 and 1 April 2019, the WHO Guidelines Review Committee approved 154 guidelines providing 1619 guideline recommendations. Mathematical modeling studies informed 46 WHO guidelines (29.9%) and 101 unique guideline recommendations (6.2%). Modeling evidence addressed topics related to infectious diseases in 38 guidelines (82.6%) and 81 recommendations (80.2%), most commonly for HIV and tuberculosis. Evidence from modeling studies was assessed in the GRADE evidence profile for 12 recommendations (12.9%) and GRADE evidence-to-decision framework for 45 recommendations (44.6%). Modeling-informed recommendations were more likely than other recommendations within the same guidelines to be issued with a “conditional” rather than “strong” strength of recommendation (53.5% versus 37.8%), and the evidence underlying modeling-informed recommendations was more likely to be assessed as very low quality (41.6% versus 24.1%). Upon review of individual modeling studies, we estimated that 33.8% of models performed a calibration, 29.4% of models performed a validation of results, and 20.6% of models reported a change in the study conclusion in the sensitivity analysis. While policy recommendations in WHO guidelines are informed by evidence from modeling studies, the validity of modeling studies included in guidelines development is heterogeneous. Quality assessment is needed to support the evaluation and incorporation of evidence from mathematical modeling studies in guidelines development.

BackgroundCoronavirus disease 2019 (COVID‐19) began in 2019 with several unknown factors. The World Health Organization (WHO) subsequently developed COVID‐19 occupational safety and health (OSH) guidelines to reduce occupational COVID‐19 transmission. Many countries also developed their own COVID‐19 OSH guidelines, but whether these guidelines included WHO's guidelines and whether including WHO's guidelines in countries' COVID‐19 OSH guidelines reduced COVID‐19 transmission is unknown.ObjectivesThe objectives of our study were to (1) compare the COVID‐19 OSH guidelines of several countries to WHO's OSH guidelines, (2) estimate associations between characteristics of countries and their OSH guidelines and the number of WHO's OSH guidelines included in countries' OSH guidelines, and (3) estimate associations between WHO's OSH guidelines included in countries' OSH guidelines and COVID‐19 risk, death risk, and case‐fatality proportion.MethodsThis study represents international, ecological research of 36 countries from all six world health regions. Countries' COVID‐19 OSH guidelines were compared with WHO's OSH guidelines. Linear regression models adjusted for potential confounders were used to estimate associations of interest.ResultsThe median number of WHO's 15 COVID‐19 OSH guidelines included in countries' COVID‐19 OSH guidelines was eight. Countries' COVID‐19 OSH guidelines focused on workers included significantly more of WHO's COVID‐19 OSH guidelines than countries' COVID‐19 OSH guidelines focused on general populations. Including “provide personal protective equipment for workers” and “create workplace policy for wearing personal protective equipment” in countries' COVID‐19 OSH guidelines were significantly related to decreased COVID‐19 risk, death risk, and/or case‐fatality proportion.ConclusionsCountries' COVID‐19 OSH guidelines should include WHO's guidelines, focus on workers, and include “provide personal protective equipment for workers” and “create workplace policy for wearing personal protective equipment.”

In Brazil, increasing air pollution in urban areas has led to a rise in respiratory diseases among children and the elderly and has also been the main cause of hospital admissions. This study aims to evaluate the air pollution levels in Vitória, capital of Espírito Santo State, Brazil, in comparison to Brazilian legislation and recent World Health Organization (WHO) guidelines, analyzing the spatial distribution of asthma cases treated at local outpatient services. A descriptive epidemiological study was performed with daily records on air pollution and outpatient treatment for respiratory diseases from 2001 to 2003, for children under 6 years of age. A geographic information system (GIS) was used to identify asthma distribution in the municipality. Air pollution levels were relatively low when compared to the Brazilian legislation and WHO guidelines. Only mean PM10 and NO2 exceeded the annual quality standard. The three highest asthma outpatient treatment rates were observed in the districts of São José, Jabou, and Morro do Quadro.

Recent World Health Organization (WHO) guidelines recommend antiretroviral therapy (ART) for all HIV-infected people; previously CD4+ T lymphocyte quantification (CD4 count) or clinical staging determined eligibility for children ≥ 5 years old in low- and middle-income countries. We examined positive predictive value (PPV) of a rapid diagnostic test (RDT) algorithm and ART eligibility for hospitalized children with newly diagnosed HIV infection. We enrolled 363 hospitalized Malawian children age 2 months to 16 years with two serial positive HIV RDT from 2013 to 2015. Children aged ≤ 18 months whose nucleic acid testing was negative or unavailable were later excluded from the analysis (N = 16). If RNA PCR was undetectable, human immunodeficiency virus (HIV) enzyme immunoassay (EIA) and western blot (WB) were performed. Those with negative or discordant EIA and WB were considered HIV negative and excluded from further analysis (N = 6). ART eligibility was assessed using age, CD4 count, and clinical HIV stage. Among 150 patients with HIV RNA PCR results, 15 had undetectable HIV RNA. Of those, EIA and WB were positive in nine patients and negative or discordant in six patients. PPV of serial RDT was 90% versus RNA PCR alone and 96% versus combined RNA PCR, EIA, and WB. Of all patients aged ≥ 5 years, 8.9% were ineligible for ART under previous WHO guidelines. Improved HIV testing algorithms are needed for accurate diagnosis of HIV infection in children as prevalence of pediatric HIV declines. Universal treatment will significantly increase the numbers of older children who qualify for ART.

To assess the cost-effectiveness of cotrimoxazole prophylaxis in HIV-infected children in Zambia, as implementation at the local health centre level has yet to be undertaken in many resource-limited countries despite recommendations in recent updated World Health Organization (WHO) guidelines. A probabilistic decision analytical model of HIV/AIDS progression in children based on the CD4 cell percentage (CD4%) was populated with data from the placebo-controlled Children with HIV Antibiotic Prophylaxis trial that had reported a 43% reduction in mortality with cotrimoxazole prophylaxis in HIV-infected children aged 1-14 years. Unit costs (US$ in 2006) were measured at University Teaching Hospital, Lusaka. Cost-effectiveness expressed as cost per life-year saved, cost per quality adjusted life-year (QALY) saved, cost per disability adjusted life-year (DALY) averted was calculated across a number of different scenarios at tertiary and primary healthcare centres. : Cotrimoxazole prophylaxis was associated with incremental cost-effectiveness ratios (ICERs) of US$72 per life-year saved, US$94 per QALY saved and US$53 per DALY averted, i.e. substantially less than a cost-effectiveness threshold of US$1019 per outcome (gross domestic product per capita, Zambia 2006). ICERs of US$5 or less per outcome demonstrate that cotrimoxazole prophylaxis is even more cost-effective at the local healthcare level. The intervention remained cost-effective in all sensitivity analyses including routine haematological and CD4% monitoring, varying starting age, AIDS status, cotrimoxazole formulation, efficacy duration and discount rates. Cotrimoxazole prophylaxis in HIV-infected children is an inexpensive low technology intervention that is highly cost-effective in Zambia, strongly supporting the adoption of WHO guidelines into essential healthcare packages in low-income countries.

Background: Animal bites are one of the leading causes of visits to an emergency room (ER) in Thailand. Rabies is an almost invariably fatal disease. Objectives: We evaluated the appropriateness of rabies vaccination in clinical practice following the World Health Organization (WHO) guidelines. Methods: All patients who visited the ER at Ramathibodi Hospital of Mahidol University because of mammal bites and received rabies vaccination by the WHO rabies postexposure regimen were enrolled. Data were retrievedfrom medical records. Wound categories were classified by WHO guidelines both in real practice and by the investigators on subsequent investigation. Results: The agreement between clinical practice and the WHO guidelines was calculated and reported as kappa statistics. There were 372 eligible patients. The mean age was 36 years and 172 patients were male.The agreement between clinical practice and the WHO guidelines was a disturbing 26.9% with a kappa statistic of -0.02, P = 0.56. Conclusion: Even in a referral and teaching hospital, rabies postexposure vaccination in Thailand was not appropriate according to WHO guidelines. Keywords: Postexposure, pragmatic study, rabies, vaccination, WHO guideline

Antiretroviral Therapy and Tuberculosis: What's the Connection and What's the Way Forward?

Poor adherence to guidelines during empirical antibiotic prescription in low-income countries could increase antimicrobial resistance without improving outcomes. Revised World Health Organization (WHO) guidelines published in 2014 on childhood (2-59 months) pneumonia re-defined the classification of severe pneumonia and changed the first-line treatment. The adherence to WHO guidelines in southern Ethiopia at the hospital level is unknown. We sought to determine the adherence to WHO guidelines on severe pneumonia first-line treatment in children in an Ethiopian referral hospital and assess the impact of non-adherence on patient outcomes. An observational study was conducted on all children (2-59 months) clinically diagnosed with severe pneumonia and admitted to the Pediatric Ward of Jinka Hospital from 1 June 2021 to 31 May 2022. Exclusion criteria included a known HIV infection, ongoing antibiotic treatment before the event not related to acute pneumonia, or any other severe bacterial infection, confirmed or suspected. Adherence to guidelines was defined as first-line treatment with ampicillin or benzylpenicillin and gentamicin at the recommended dose. We compared the patients treated adherently vs. non-adherently. For categorical variables, the chi-square or Fisher's exact test was used, while for continuous variables, the Mann-Whitney U-test was used. Multivariate logistic regression was used to evaluate the association between adherence and demographic and clinical characteristics. During the observational period, 266 patients were registered as having severe pneumonia with an age between 2 and 59 months. After excluding 114 patients due to missing charts or other exclusion criteria, a total of 152 patients were included in the analysis. Of these, 78 (51%) were girls with a median age of 10 months (IQR 7-14). Overall, 75 (49%) patients received therapy according to the WHO guidelines. Compared to patients treated adherently to the guidelines, patients not treated adherently had similar outcomes [median length of stay of 3 (IQR 3-5) and 4 (IQR 3-6) days], median duration of oxygen therapy of 2 (IQR 1-3) for both the groups, and self-discharge rates of 5% and 6.5%, respectively). Adherence to the revised WHO guideline was limited and not associated with outcomes. Efforts should focus on reducing the gap between theory and practice.

Background: Cotrimoxazole prophylactic therapy (CPT) is a feasible, cost-effective, and safe way of using cotrimoxazole intervention to reduce HIV/AIDS related morbidities and mortalities associated with opportunistic infections. Despite its effectiveness in reducing the incidence of opportunistic infections, the actual drug utilization process has been shown to deviate from World Health Organization (WHO) guideline in Ethiopia. This study, therefore, aims to evaluate CPT among HIV/AIDS patients in Jugel Hospital (JH), Harar and Dilchora Referral Hospital (DRH), Dire Dawa, Eastern Ethiopia.Methods: A cross sectional study was conducted to evaluate the use of cotrimoxazole as prophylactic therapy. In this study, 556 medical records (305 in JH and 251 in DRH) of HIV/AIDS patients who had been taking CPT within September 2015–August 2016 were reviewed. Systematic random sampling was employed to obtain medical records from the sampling frame. Data were abstracted from the patient medical records using structured checklist customized from the WHO guideline. The data were entered into Epi-data 3.1 and exported to and analyzed with statistical Package for Social Sciences (SPSS) version 20. The finding was evaluated against the WHO guideline on the use of cotrimoxazole prophylaxis in HIV/AIDS patients. Descriptive statistics was used to present the data in tables, figures and pie chart.Results: Majority of the HIV/AIDS patients who had been taking CPT were adults (95.9%), female (61.2%), married (43.7%), Orthodox Christian (54.3%), and attended primary school (40.1%). At the initiation of CPT, most of the patients were at WHO clinical stage III (40.8%). The major comorbid illnesses identified were tuberculosis and pneumocystis-jiroveci pneumonia. Initially, majority of the patients were at CD4 count of less than 350 cells/mm3 (n = 504, 90.6%). Greater proportion of patients started CPT prior to initiating antiretroviral therapy (ART). Most of the patients took CPT for greater than 6 months. The primary reasons for premature discontinuation of CPT were CD4 greater than 350 cells/mm3, severe sulfa allergy and first trimester of pregnancy. Generally, the use of cotrimoxazole prophylaxis was consistent with the WHO guideline for indication to start (n = 519, 93.3%) and dose (n = 552, 99.28%), despite the presence of contraindication in 6.65% patients.Conclusion: In reference to the WHO guideline, the use of CPT was found to be fully appropriate in nearly two-thirds of HIV/AIDS patients. For the rest patients, inappropriate use of cotrimoxazole was observed based on the WHO criteria for initiation, discontinuation, continuation and dose with rate of discontinuation being the dominant one. Such practice may lead to adverse health outcomes including adverse drug reactions and negative treatment outcome.

Could we have better occupational health guidelines, please?