Favipiravir in SARS-CoV-2 Infection: Is it Worth it?

Favipiravir is a potential antiviral drug undergoing clinical trials to manage various viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Favipiravir possesses antiviral properties against RNA viruses, including SARS-CoV-2. Unfortunately, these viruses do not have authorized antiviral drugs for the management of diseases resulting from their infection, hence the dire need to accentuate the discovery of antiviral drugs that are efficacious and have a broad spectrum. Favipiravir acts primarily by blocking inward and outward movements of the virus from cells. Favipiravir is a prodrug undergoing intracellular phosphorylation and ribosylation to form an active form, favipiravir-RTP, which binds viral RNA-dependent RNA polymerase (RdRp). Considering the novel mechanism of favipiravir action, especially in managing viral infections, it is vital to pay more attention to the promised favipiravir hold in the management of SARS-CoV-2, its efficacy, and dosage regimen, and interactions with other drugs. In conclusion, favipiravir possesses antiviral properties against RNA viruses, including COVID- 19. Favipiravir is effective against SARS-CoV-2 infection through inhibition of RdRp. Pre-clinical and large-scalp prospective studies are recommended for efficacy and long-term safety of favipiravir in COVID-19.

Annona muricata Linn and Khaya grandifoliola C.DC. Reduce Oxidative Stress In Vitro and Ameliorate Plasmodium berghei-Induced Parasitemia and Cytokines in BALB/c Mice.

BACKGROUND: Annona muricata and Khaya grandifoliola are ethnomedicinally used for the treatment of malaria and have been experimentally shown to have an anti-plasmodial effect, but the mechanisms involved are not fully understood. This study investigated the effect of the ethanol extracts of their leaves on parasitemia, radical scavenging and cytokines in Plasmodium berghei ANKA-infected BALB/c mice. METHODS: BALB/c mice were infected with P. berghei and treated with chloroquine, A. muricata or K. grandifoliola extract for 4 days. The percentage of parasitemia and the level of cytokine expression were determined after treatment. Trace element, phytochemical and nitric oxide (NO) scavenging activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging properties assays were done to study the antioxidant effects of AN and KG in vitro. RESULTS: P. berghei consistently increased parasitemia in BALB/c mice. The tested doses (100-, 200-, and 400 mg/kg) of A. muricata and K. grandifoliola attenuated the P. berghei-induced elevation of parasitemia and cytokines (TNF-α, IL-5, and IL-6) in vivo during the experimental period, though not as much as chloroquine. Moreover, both extracts scavenged the DPPH and NO radicals, though A. muricata had more anti-oxidant effect than K. grandifoliola in-vitro. CONCLUSION: The ethanol extracts of A. muricata and K. grandifoliola reduce parasitemia in P. berghei-treated mice BALB/c by scavenging free radicals and reducing cytokines, though the extracts were not as effective as chloroquine.

Substance Use, Highly Active Antiretroviral Therapy, and Liver Enzymes: Evidence From a Cross-Sectional Study of HIV-Infected Adult Patients Without Comorbidities on HAART in the University of Port Harcourt Teaching Hospital.

This study applied a structural equation modeling (SEM) to evaluate the role of substance use (alcohol, smoking, and trado-medicine use) to changes in the liver enzymes (AST, ALT, and ALP) levels in HIV-infected adult patients on a highly active antiretroviral treatment (HAART) for not <1 year. The study was a cross-sectional, part of a randomized comparative trial (Ref: UPH/CEREMAD/REC/19), involving 129 (46 males and 83 females) HIV-infected adult patients. Liver enzyme levels were determined from analyzed blood samples using the Clinical Chemistry Analyser (VS10) manufactured by Vitro Scient, while the study determined substance use using a reliable (Cronbach alpha = 0.805) rapid-exploratory survey questionnaire. Liver enzyme values were further categorized into: normal or abnormal using normal reference ranges (ALT = 7-55 U/L, AST = 8-48 U/L, and ALP = 40-129 U/L). STATGRAPHICS V16.1.11 (StatPoint Tech., Inc.) and SPSS (IBM® Amos V21.0.0, USA) were used to analyze the data. Among the HIV-HAART patients, 27.9% were alcohol users, 20.9% smokers, and 20.1% trado-medicine users. In addition, ALP (71.3%) abnormality was higher than ALT (34.9%) and AST (28.7%). The result from the SEM provided only a partial support for our hypotheses of direct substance use effects on the liver enzyme levels and abnormalities; with a direct association of alcohol with an elevated AST (b = 0.170, p = 0.05) and smoking with a higher AST (b = 0.484, p < 0.01) and ALT (b = 0.423, p < 0.01) values. Trado-medicine use was not directly associated with enzyme elevation and abnormality. In conclusion, ALP abnormality was the most common, and there is a close association between an elevated ALT and AST, with or without an elevated ALP. The study found that HIV-HAART patients who drink or smoke will have at least one or more abnormal transaminases. The possible explanation to the increased risk among HIV-HAART patients could be associated with the metabolic pressures and supra-additive effects on the livers.

Alginate-coated chitosan microparticles encapsulating an oral plasmid-cured live Salmonella enterica serovar Gallinarum vaccine cause a higher expression of interferon-gamma in chickens compared to the parenteral live vaccine.

Salmonella enterica serovar Gallinarum causes a disease in chickens known as fowl typhoid. Interferon-gamma (IFN-γ) has been shown to be crucial in eliminating salmonellosis infection because of its strong association with T-cell responses. This study was undertaken to compare the expression of IFN-γ in chickens generated by different vaccine formulations. Eighty one-day-old Lohmann layer chicks were divided into four groups of 20 birds each for the experiment. This comprised an unvaccinated negative control group (NEG), a group vaccinated with the live 9R vaccine by the injection route (SC), a group vaccinated with alginate-coated chitosan microparticles encapsulating live plasmid-cured S. Gallinarum strain 9 (PC) by the oral route, and a group vaccinated with a weak attenuated live S. Gallinarum strain 9 encapsulated in alginate-coated chitosan microparticles (VM) given orally. Vaccinations were done at 10 and 14 weeks of age followed by challenge at 16 weeks of age. IgG was measured using ELISA. qRT-PCR was used to compare the mRNA fold expression of IFN-γ in the PC, VM and SC groups using the unvaccinated/unchallenged group as the control. There were significant differences in the IgG levels between each vaccinated group and the unvaccinated group (P < 0.05) after booster vaccination and post-challenge. There was 100% protection of the birds in SC and VM groups, 80% protection in PC group and 0% protection in the NEG group. Using 2-ΔΔCT calculation, IFN-γ was more highly expressed in the PC group than in the SC group or VM group. In conclusion, the IFN-γ was more highly expressed in the PC group (though not significantly higher) compared to the SC and VM groups and this could be attributed to the alginate-coated chitosan microparticles which acted as an adjuvant.

Spontaneous subgaleal aerocele.

Apart from reporting about a case of spontaneous subgaleal aerocele this paper looks at the possible causes and management also. A 35-year-old Igbo-Nigerian female, about 4 weeks post-natal, with a 10-month old steadily and gradually enlarging mass around the back of her head, including both temporal regions was referred to us. Plain skull radiographs showed air in this mass. Needle puncture produced air leading to immediate and complete flattening of the lesion. A few hours after this procedure while still in the hospital premises, she had generalized convulsions, for which she was hospitalized and treated. With no further attacks, her request for discharge the following day was granted. At the next visit, 7 days later, there was a re-accumulation, which was treated the same way as previously and with the same result. She has not reported back since then, though she was advised to visit us again in 7 day-time. This lesion should be considered when masses on the head are presented. Our health institutions should have adequate investigative facilities.

Surgically treated symptomatic prolapsed lumbar and sacral intervertebral discs in females: a comparative study of incidence and causative factors and treatment.

BACKGROUND AND OBJECTIVE: There are various postulated possible causes of surgically symptomatic prolapsed intervertebral discs in the lumbar and sacral regions. They may be acting singularly or collectively. Yet, these factors, which could vary in different environments, have not been satisfactorily confirmed. The intention of this study is to share the experience of the author in the occurrence, possible causative factors, and treatment of surgically symptomatic prolapsed lumbar and sacral intervertebral discs in females, and to compare this experience in Switzerland, Nigeria, and Jamaica using surgery records for a period of over 39 years. MATERIALS AND METHODS: Records of these cases were examined and analyzed with the intent of comparing the frequency of occurrence and possible causative factors of this lesion in some countries. RESULTS: There were 60 locations in 51 patients in Basel (Caucasian population only), 4 locations in 1 patient in Imo and Ebonyi States (African population only), and none in Jamaica (mixed population). The patients' ages ranged from 19 to 71 years in Switzerland, and the only patient in Nigeria was 49 years old. CONCLUSION: The study revealed that surgically treated symptomatic prolapsed lumbar and sacral intervertebral discs in females occurred more in Basel, Switzerland, than in Imo and Ebonyi States of Nigeria and none occurred in Jamaica, West Indies. Racial differences, certain sporting/recreational activities, smoking, and type of profession could have contributed to the development of this disease.

Physicochemical Analysis of the Aqueous Extracts of Six Nigerian Medicinal Plants

Purpose: Extracts of Picralima nitida seeds; Detarium microcarpum stem bark; Aframomum melagueta seeds; Terminalia catappa leaves; Acacia nilotica pods; and Morinda lucida stem bark; are under consideration for development into suitable dosage forms for treating diabetes mellitus; sickle cell anemia and malaria. This study aimed at evaluating the extracts for features that would influence decisions on them in the course of the project. Methods: Physicochemical determinations; including proximate analysis; were done by sensory examination; and gravimetric and electrochemical techniques. Thin layer chromatography was carried out with normal silica plates using various solvent systems. Metallic content analyses were carried out by atomic absorption spectroscopy. Results: The extracts were dry but hygroscopic; with a loss on drying range of 0.26 - 12.00w/w. The pH of the 5 - 10solutions ranged 5 - 7. No harsh sensory effects; such as lacrimation; were detected in any of the extracts. Total ash ranged from 3.79 - 20.68w/w; while acid insoluble ash values were below detection. The extracts yielded reproducible chromatograms on normal silica plates developed with various solvent systems. Copper; present at 0.16 - 0.58 mg/100g; was the lowest occurring microelement while calcium content was highest; at 41 - 216 mg/100g. The level of lead; a heavy metal; was 0.05 - 0.22 mg/100g. Conclusion: The results confirm that the extracts require no special handling; possess characteristics that would allow their possible development into solid dosage forms; and that their lead contents complied with official limits

Analysis of Ig subclass deficiency: First reported case of IgG2, IgG4, and IgA deficiency caused by deletion of C alpha 1, psi C gamma, C gamma 2, C gamma 4, and C epsilon in a Mongoloid patient.

BACKGROUND: The cause of Ig class or subclass deficiencies has been unclear except for IgH gene deletions and a homozygous 1-base insertion (1793insG) in C gamma 2 exon 4 of IgG2 deficiency. In addition, there are no reports that IgH gene deletions are found in patients who are Mongoloid (a category that includes most of the people of Asia, such as the Japanese, Chinese, Indonesians and Malaysians). OBJECTIVE: To investigate the cause of Ig subclass deficiency, we extensively investigated 4 Japanese patients with low serum IgG2 levels. Patient 1 was a 23-month-old girl whose serum IgG2, IgG4, and IgA levels were under the detection limits; she also had idiopathic thrombocytopenic purpura. Patient 2 was a 5-year-old boy whose serum IgG2 level was under the detection limit. Patient 3 was a 14-month-old boy whose serum IgG2 and IgG4 levels were under the detection limits. Patient 4 was 3-year-old girl whose IgG2 level was low and whose IgA level was under the detection limit. METHODS: DNA was extracted from neutrophils, and Southern blot analysis was performed. RESULTS: Southern blot analysis revealed that patient 1 had lost the C alpha 1, psi C gamma, C gamma 2, C gamma 4, and C epsilon genes and was a homozygous carrier of the deletion described above. Her mother was of the heterozygous genotype. DNA from patients 2, 3, and 4 revealed no deletions in comparison with control DNA. CONCLUSION: This is a report of the first case of a Mongoloid in whom IgG2, IgG4, and IgA deficiency was caused by deletion of C alpha 1, psi C gamma, C gamma 2, C gamma 4, and C epsilon. Our finding contributes to investigations of Ig subclass deficiency.

Diplazium sammatii: Athyraceae ('Nyama idim'): age-related nutritional and antinutritional analysis.

Tender and mature leaflets and leaves of Diplazium sammatii ('Nyama idim'), were separately investigated for their nutritional and antinutritional properties. Results showed little difference in proximate nutritional contents between tender and mature leaves, except for crude fat, which was present in levels 1.5 times higher in younger than in older leaves. Crude fiber levels were low. Zinc (Zn) and copper (Cu) were higher in younger leaves (6.8 and 3.5 mg/100 g dry matter, respectively, compared to 4.5 and 2.5 mg/100 g dry matter, respectively in older leaves). Older leaves contained higher levels of iron (Fe): 6.7 mg/100 g dry matter, in comparison to 4.3 mg/100 g dry matter, in young leaves. Oxalate levels were slightly higher in younger than older leaves. However, the reverse was true for tannin content. Both antinutritional compounds were present in levels which should be safe.

[Clinical study of 33 children with systemic pneumococcal infections].

We retrospectively analyzed 33 cases of children with systemic pneumococcal infections, 22 bacteremia and 11 meningitis, diagnosed and treated in Asahi General Hospital between 1985 and 1999. The median age at diagnosis was 15 months old and the incidence peaked in infants between 7 and 24 months of age (57.6%). Two cases showed low serum IgG2 levels. Fever was a common symptom in all cases and 13 (39.4%) presented convulsions. Meningitis [median age: 10 months] tended to occur, if not significant, in younger children than bacteremia [16 months]. All cases of meningitis were diagnosed 12 hours or later after the onset of fever, though 54.5% of the cases of bacteremia were diagnosed within 12 hours. The cases of meningitis showed statistically lower white blood cell counts [median: 9,700/mm3] and higher CRP levels [median: 25.6 mg/dl] than those of bacteremia [23,900/mm3 and 4.2 mg/dl, respectively] at diagnosis. Although all cases of bacteremia were cured without any sequelae by antibiotic treatment, 3 cases (27.3%) of meningitis died and 4 (36.4%) developed severe neurological sequelae. Our findings suggest that the putative pathogenesis by which pneumococcal meningitis results from bacteremia and, taking in the account of the poor outcome of meningitis, may justify the early antibiotic intervention against pneumococcal bacteremia.

[Two children with suspected primary vasculitis of mesenteric vessels--a case report].

We reported 2 children with suspected primary vasculitis of mesenteric vessels. Both children were admitted to our hospital with the complaints of abdominal pain, bloody stool or diarrhea. Laboratory examination simultaneously revealed leukocytosis with dominant neutrophils, positive CRP, and hypoalbuminemia. Although prothrombin time and activated partial thromboplastin time were within normal limits, the increased levels of FDP-E, D-dimer, and von Willebrand factor activity were observed, which suggested the endothelial cell activation and the coagulation/fibrinolysis system activation. Abdominal echography and CT scanning demonstrated the edematous thickening of intestinal or colon walls probably due to the vasculitic permeability changes of mesenteric artery. During the disease courses, skin rash, bleeding tendency, arthritis and proteinuria were not observed, and no autoantibodies including anti-nuclear antibody, anti-DNA antibody, and myeloperoxidase-antineutrophil cytoplasmic antibody, were detected. Taken together, we suspected these children as restricted vasculitis of mesenteric vessels. Intravenous prednisolone was administrated, and the clinical and laboratory abnormalities recovered completely within 2 weeks. Thus, we suggested that the leukocyte counts, CRP, and the determination of von Willebrand factor and coagulation/fibrinolysis study accompanied with X-ray, echography, and CT scanning will be useful for the early diagnosis of vasculitis before the pathologic and irreversible vascular damage are demonstrated.

Pleomorphic angioleiomyoma.

We describe two cases of pleomorphic angioleiomyoma. In one case, a 46-year-old man presented with a single nodule on his scrotum of 1 year's duration, and in another, a 38-year-old woman presented with a single nodule on her right knee of 1 year's duration. In both cases, histopathologic examination showed a well-circumscribed nodule composed of smooth muscle and numerous veins and capillaries. Contrary to the ordinary angioleiomyoma, marked nuclear pleomorphism was noted. Although mitoses were rare, immunohistochemistry revealed many tumor cells that were positive for proliferating cell nuclear antigen, Ki-67, and p53, indicating that the pleomorphic appearance does not simply represent a degenerative change of some tumor cells.

[Why there were few isolations of tubercle bacilli in young children with pulmonary tuberculosis?].

We retrospectively evaluated the factors influencing the isolation of tubercle bacilli in 51 children under 14 years of age with pulmonary tuberculosis who were admitted to Yokohama City University Hospital from 1975 to 1998. Young children (0-6 years of age) with pulmonary tuberculosis were significantly less positive by smear and culture than elder children (7-14 years of age) with pulmonary tuberculosis. According to the Japanese Society for Tuberculosis classification of finding on chest X-ray film for pulmonary tuberculosis, the culture-positive patients with type II (cavitary lesions) were found in all, the culture-positive patients with type III (non-cavitary lesions) in 39.3%, and the culture-positive patients with type H (hilar and mediastinal lymphadenopathys) in 35.3%. Patients with cavitary lesions (type II) were significantly more positive by smear and culture than patients with non-cavitary lesions (type III + type H). Only 15.8% of the young children with pulmonary tuberculosis had received BCG vaccine and all had non-cavitary lesions (type III and type H). But, 84.6% out of the older children had received BCG vaccine and half had cavitary lesions. Taken together, the result was that there were few isolation of tubercle bacilli in young children with pulmonary tuberculosis because they had non-cavitary tuberculosis without delayed-type hypersensitivity to tubercle bacilli.

[Two infants with classical polyarteritis nodosa but not Kawasaki disease].

We experienced two infants with polyarteritis nodosa (PN). The symptoms started with high fever and skin rash, which were similar to those of Kawasaki disease (KD). However, the involvement of central nervous system and lung, such as distension of large fontanel, stridor and mild disturbance of consciousness, occurred and the systemic vasculitis resulted in hypoalbuminemia and severe generalized edema. They flared up twice or three times during the long clinical courses. Finally, both had multiple giant coronary aneurysms and lung fibrosis. The clinical courses of these patients were different from those of KD in that: (1) the severity of vasculitis, (2) the wide-spread nature of the vasculitis, and (3) the chronic and recurrent clinical course. It is very difficult to distinguish PN from severe KD in the early stage of the diseases especially in infancy. But in the cases intractable to high-dose gamma-globulin therapy and plasma exchange, it is needed to suspect PN and to induce more aggressive immunosuppressive therapy, such as methylprednisolone pulses and cyclophosphamide pulse therapy as soon as possible.

[Analysis of tuberculin reaction of tuberculous children below 4 years of age].

To clarify whether the size of tuberculin reaction could be used as an useful index of the severity of tuberculosis, we analyzed the sizes of tuberculin reaction (TR) of 60 children below 4 years of age with active tuberculosis at the time of diagnosis. Of 60 patients, 53 (88.9%) had positive reactions to tuberculin. The mean size of TR of 60 patients was 24.0 +/- 13.9 mm and maximum size was 60 mm. Seven patients who had no reaction to the tuberculin skin test consisted of three primary complex and four serious tuberculosis (two miliary tuberculosis and two tuberculous meningitis). The patients without BCG vaccination showed significantly smaller TR than the patients with BCG vaccination (p < 0.05). The patients less than 1 year of age showed significantly smaller TR than the patients of 4 years of age (p < 0.05). The patients with serious tuberculosis showed significantly smaller TR than the patients with primary complex (p < 0.05). Of patients with primary complex, there were no difference of the size of TR between the patients with pulmonary tuberculosis (III) and hilar lymphadenopathy (H). Together with, it did not necessarily mean that negative TR showed no infection with tuberculosis and the sizes of TR depended on the severity of tuberculosis in infantis and young children.

[Effective combination therapy of plasma exchange and subsequent cyclophosphamide pulses for catastrophic antiphospholipid antibody syndrome: a case report].

A 7-year-old girl with catastrophic antiphospholipid antibody syndrome was described. She firstly admitted to the local hospital with the complaints of persistent fever and abdominal pain, and was diagnosed as systemic lupus erythematosus with the laboratory findings as follows; positive for antinuclear antibody, anti-DNA antibody, and platelet-associated IgG, thrombocytopenia, and hypocomplementemia. 10 days after the initiation of oral prednisolone, she suddenly manifested tonic convulsion and unconsciousness accompanied by high fever. Because of the unresponsiveness to the methylprednisolone pulse therapy for supposed CNS lupus, she was transferred to our hospital. Her unconsciousness persisted, and pulsation on dorsalis pedis was not palpable on admission. Laboratory investigation revealed the falsely positive VDRL, a prolonged aPTT, positive for lupus-anticoagulant and antiphospholipid antibody. The magnetic resonance image demonstrated multiple spotty hyperintensity (T2) in the brain consistent with multiple hemorrhagic infarcts. Arteriogram demonstrated the infarct of dorsalis pedis, and coronary aneurysms. These findings were compatible with the criteria of catastrophic antiphospholipid antibody syndrome, she was diagnosed as catastrophic antiphospholipid antibody syndrome. The plasma exchange and subsequent cyclophosphamide-pulse therapy, which was given once a month for first 6 months, and later, at 3 months intervals, was effectively administered. This combination and oral anti-thrombotic therapy revealed effective for this kind of fatal disorder.

The influence of methicillin-resistant Staphylococcus aureus (MRSA) carriers in a nursery and transmission of MRSA to their households.

We examined two persistent MRSA-carrier nurses in a maternity hospital to elucidate the transmission of methicillin-resistant Staphylococcus aureus (MRSA) from healthcare providers to newborn infants and to the nurses' own families. Genotyping of the MRSA strains was performed by analyzing genomic DNA restriction length polymorphisms from pulsed-field gel electrophoresis (PFGE-RFLPs). The children of these nurses were carrying genotypically identical MRSA strains as their mother. Both MRSA carrier families remained asymptomatic over a two-year follow-up period. Eradication of nasal MRSA carriage from the two nurses resulted in declining MRSA carriage rates among infants in the nursery. Healthcare providers may become transient or persistent MRSA carriers whilst working in hospitals in which MRSA is endemic. They may then become a source of infection for patients as well as their own families. We recommend that healthcare providers should be examined for MRSA if an MRSA epidemic occurs in a hospital. The families of any such carriers should also be examined for MRSA.

[Computed tomography with normal chest radiography in childhood tuberculosis].

During the recent 2 years we experienced 5 children (2 months-5 years old) with lung tuberculosis, all of whom had positive tuberculin skin-tests, and were in close contact with their family members who had active tuberculosis. However, no abnormal findings on chest X-ray films were pointed out by 2 independent roentogenologists, and no increased levels of inflammatory markers including WBC numbers, CRP, and ESR were detected in all but one child. Moreover, mycobacterial examination of sputa and/or gastric aspirates by microscope, culture technique, and PCR amplification revealed no causative bacilli in 4 children. To clarify whether these children were affected by Mycobacterium tuberculosis, chest CT scan was applied. Surprisingly, all 5 children were revealed to have abnormal changes including primary complexes in the lung field. Taken together, it is important to pursuit the apparent lung tuberculosis in children with a positive family history and positive tuberculin skin-test.