Acute undifferentiated febrile illness (AFI) is the most common reason for clinical presentation to health care services in developing countries. It can range from mild, self-limiting to progressive, life-threatening disease. AFI patients present with non-specific symptoms such as fever, headache and malaise, which can be caused by a wide range of pathogens [1].In the past decade, there has been a shift in importance of pathogens causing AFI. Studies on malaria showed that 80% of febrile illness, even in malaria-endemic regions, are caused by other pathogens, like Rickettsia, Borrelia, Leishmania and arboviruses [2][3][4][5]. Moreover, the decline of

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), an emerging virus in late 2019 causing coronavirus disease 2019 (COVID‐19), has caused a catastrophic effect, resulting in an unprecedented global crisis. The immunopathology of COVID‐19 appears to be clearly associated with a dysregulated immune response leading to organ failure and death. Similarly, over two billion people worldwide are infected with helminth, with those living in low‐middle‐income countries disproportionately affected. Helminth infections have been shown to possess immunomodulatory effects in several conditions. Helminth co‐infection in COVID‐19 patients is one of the potential reasons for global attention to answer why COVID‐19 severity is still lower in helminth endemic countries. Recent studies have shown that helminth endemic countries showed fewer cases and deaths so far and helminth co‐infection might reduce the severity of COVID‐19. Moreover, lessons from other diseases with helminth co‐infection have been shown to substantially reduce vaccine efficacy that could also be implicated for COVID‐19. This immunomodulatory effect of helminth has intended and unintended consequences, both advantageous and disadvantageous which could decrease the severity of COVID‐19 and COVID‐19 vaccine efficacy respectively. Herewith, we discuss the overview of COVID‐19 immune response, immunomodulatory effects of helminth co‐infections in COVID‐19, lessons from other diseases, and perspectives on the efficacy of COVID‐19 vaccines.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has rapidly spread across the world since its first emergence in China in late 2019. It is a major public health concern with no effective treatct 3ments. The immunopathology of SARS-CoV-2 is associated with an excessive inflammatory response. Macrophage activation syndrome (MAS) is also associated with the severity of the disease in SARS-CoV-2-infected patients. Neopterin is a macrophage activation marker produced by monocytes and macrophages upon activation by interferon-gamma (IFN-γ). Neopterin is a well-established marker in a variety of diseases, and recent evidence indicates that it could be helpful in early prediction of the severity of COVID-19 disease and serve as a prognostic marker. Here, we outline the role of macrophage activation syndrome in the pathogenesis of SARS-CoV-2 and suggest that neopterin could be used as a biomarker for progression of COVID-19.

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In low-resource settings, treatment is often given empirically without knowledge of the aetiology due to a lack of diagnostics. In the search for reliable rapid tests to guide treatment work-up, this study was performed to determine whether two biomarkers could differentiate bacterial from nonbacterial infections in acute febrile patients. Methods: Adults with acute fever were recruited at a referral hospital in Ethiopia. The QuikRead Go test was used to quantify C-reactive protein (qCRP) and the FebriDx test was used for combined qualitative detection of the bacterial CRP marker with myxovirus resistance protein A (MxA), a viral biomarker. Results: Of the 200 patients included in this study, most presented with 2-3 days of fever, headache, and joint pain. Antibiotics were prescribed for 83.5% and antimalarials for 36.5%, while a bacterial infection was only confirmed in 5% and malaria in 11%. The median qCRP level for confirmed bacterial infections was 128 mg/l. The FebriDx and QuikRead Go test had an overall agreement of 72.0%. Conclusions: An over-prescription of antibiotics for febrile patients was observed, even for those with low CRP levels and without a confirmed bacterial infection. The added value of the FebriDx was limited, while the combined use of rapid tests for qCRP and malaria should be considered for the management of acute febrile illness and antibiotic stewardship.

Phage therapy is one of the alternatives to treat infections caused by both antibiotic-sensitive and antibiotic-resistant bacteria, with no or low toxicity to patients. It was started a century ago, although rapidly growing bacterial antimicrobial resistance, resulting in high levels of morbidity, mortality, and financial cost, has initiated the revival of phage therapy. It involves the use of live lytic, bioengineered, phage-encoded biological products, in combination with chemical antibiotics to treat bacterial infections. Importantly, phages will be removed from the body within seven days of clearing an infection. They target specific bacterial strains and cause minimal disruption to the microbial balance in humans. Phages for medication must be screened for the absence of resistant genes, virulent genes, cytotoxicity, and their interaction with the host tissue and organs. Since they are immunogenic, applying a high phage titer for therapy exposes them and activates the host immune system. To date, no serious side effects have been reported with human phage therapy. In this review, we describe phage–phagocyte interaction, bacterial resistance to phages, how phages conquer bacterial resistance, the role of genetic engineering and other technologies in phage therapy, and the therapeutic application of modified phages and phage-encoded products. We also highlight the comparison of antibiotics and lytic phage therapy, the pros and cons of phage therapy, determinants of human phage therapy trials, phage quality and safety requirements, phage storage and handling, and current challenges in phage therapy.

Background: T1DM is a chronic organ-specific T-cell-mediated autoimmune disease characterized by the selective destruction of βcells in the islets of Langerhans, resulting in insulin deficiency and hyperglycemia. Genes for cytotoxic T lymphocyte-associated antigen 4 have been hypothesized as possible contender genes for T1DM vulnerability. However, it has not been studied in the Ethiopian population yet. Objective: The aim of the study was to investigate CTLA-4 exon 1 was linked to A49G polymorphism with T1DM and its biological features of CTLA-4 among T1DM patients, in Ethiopia. Methods: A case-control study was done from December 2019 to March 2020 on 210 study participants (105 T1DM patients and 105 healthy controls). Polymerase Chain Reaction amplification with forward and reverse primers was followed by restriction fragment length polymorphism and gel electrophoresis to determine gene polymorphism. Bioinformatics data of SNP was retrieved from National Centers for Biotechnology Information databases. The chi-square test and logistic regression were used. Statistical significance was defined as a P-value of less than 0.05. Results:The CTLA-4 (+A49G) gene polymorphism was observed on 56 (26.7%) study participants, 39 (18.57%) of T1DM patients, and 17 (0.08%) were controls. In T1DM and controls, the frequency of the A allele was 73.3% and 89.5%, while the G allele was 26.7% and 10.5%, respectively. The G allele was found to be associated with T1DM (OR=3.1; 95% CI, 1.82 −5.32; P=0.001). Statistical analysis revealed an association between the likelihood of T1DM and GG genotype of the CTLA-4 (+A49G) gene polymorphism (OR=3.11; 95% CI, 1.37-10.90; P=0.01). Further in silico analyzed the SNP to assess its biological features. Conclusion:The study showed as CTLA-4 (+A49G) gene polymorphism is linked with T1DM in the Ethiopian population.

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