Historical and contemporary views on cholera transmission: are we repeating past discussions? Can lessons learned from cholera be applied to COVID-19?

Cholera, a devastating diarrheal disease that caused several global pandemics in the last centuries, may share some similarities with the new COVID-19. Cholera has affected many populations in history and still remains a significant burden in developing countries. The main transmission route was thought to be predominantly through contaminated drinking water. However, revisiting the historical data collected during the Copenhagen 1853 cholera outbreak allowed us to re-evaluate the role of drinking-water transmission in a city-wide outbreak and reconsider some critical transmission routes, which have been neglected since the time of John Snow. Recent empirical and cohort data from Bangladesh also strengthened the dynamic potentiality of other transmission routes (food, fomite, fish, flies) for transmitting cholera. Analyzing this particular nature of the cholera disease transmission, this paper will describe how the pattern of transmission routes are similar to COVID-19 and how the method of revisiting old data can be used for further exploration of new and known diseases.

Effect of Moderate Aerobic Exercise on Complement Activation Pathways in Polycystic Ovary Syndrome Women.

BACKGROUND: The complement system is pivotal in host defense mechanisms, protecting against pathogenic infection by regulating inflammation and cell immunity. Complement-related protein activation occurs through three distinct pathways: classical, alternative, and lectin-dependent pathways, which are regulated by cascades of multiple proteins. Complement activation is recognized in polycystic ovary syndrome (PCOS) to be associated with obesity and insulin sensitivity. Exercise reduces insulin resistance and may help reduce obesity, and therefore, this study was undertaken to determine the effect of exercise on the activation of complement-related proteins in PCOS and control women. SUBJECTS AND MEASUREMENTS: In this study, 10 controls and 11 PCOS subjects who were age- and weight-matched underwent an 8-week supervised exercise program at 60% maximal oxygen consumption. Weight was unchanged though insulin sensitivity was increased in PCOS subjects and controls. Fasting baseline and post-exercise samples were collected and 14 complement-related proteins belonging to classical, alternative, and lectin-dependent pathways were measured. RESULTS: Baseline levels of complement C4b and complement C3b/iC3b were higher in PCOS (P < 0.05) compared with controls. Exercise reduced complement C1q (P < 0.05), C3 (P < 0.001), C4 (P < 0.01), factor B (P < 0.01), factor H (P < 0.01), and properdin (P < 0.05) in controls, but not in PCOS women. CONCLUSION: Exercise induced complement changes in controls that were not seen in PCOS subjects, suggesting that these pathways remain dysregulated even in the presence of improved insulin sensitivity and not improved by moderate aerobic exercise. CLINICAL TRIAL REGISTRATION: ISRCTN registry, ISRCTN42448814.

Dynamic Changes in Circulating Endocrine FGF19 Subfamily and Fetuin-A in Response to Intralipid and Insulin Infusions in Healthy and PCOS Women.

Background: The fibroblast growth factors (FGF) 19 subfamily, also referred to as endocrine FGFs, includes FGF19, FGF21, and FGF23 are metabolic hormones involved in the regulation of glucose and lipid metabolism. Fetuin-A is a hepatokine involved in the regulation of beta-cell function and insulin resistance. Endocrine FGFs and fetuin-A are dysregulated in metabolic disorders including obesity, type 2 diabetes, non-alcoholic fatty liver disease and polycystic ovary syndrome (PCOS). Our study was designed to examine the response of endocrine FGFs and fetuin-A to an acute intralipid, insulin infusion and exercise in PCOS and healthy women. Subjects and Measurements: Ten healthy and 11 PCOS subjects underwent 5-h saline infusions with a hyperinsulinemic-euglycemic clamp (HIEC) performed during the final 2 h. One week later, intralipid infusions were undertaken with a HIEC performed during the final 2 h. After an 8 week of exercise intervention the saline, intralipid, and HIEC were repeated. Plasma levels of endocrine FGFs and fetuin-A were measured. Results: Baseline fetuin-A was higher in PCOS women but FGF19, FGF21, and FGF23 did not differ and were unaffected by exercise. Insulin administration elevated FGF21 in control and PCOS, suppressed FGF19 in controls, and had no effects on FGF23 and fetuin-A. Intralipid infusion suppressed FGF19 and increased FGF21. Insulin with intralipid synergistically increased FGF21 and did not have effects on lipid-mediated suppression of FGF19 in both groups. Conclusion: Our study provides evidence for insulin and lipid regulation of endocrine FGFs in healthy and PCOS women, suggesting that FGF family members play a role in lipid and glucose metabolism. Clinical Trial Registration: www.isrctn.org, Identifier: ISRCTN42448814.

Salivary creatinine as a diagnostic tool for evaluating patients with chronic kidney disease.

BACKGROUND: Preliminary studies have shown the potential use of salivary creatinine concentration in the diagnosis of chronic kidney disease (CKD). For saliva to replace serum as a diagnostic tool, studies must be done to determine its effectiveness in the diagnosis and staging of CKD. The aim of the present study was to evaluate the use of salivary creatinine as a safe and non-invasive alternative for identifying patients with CKD. METHODS: A cross-sectional study was conducted at Tygerberg Hospital in Cape Town, on 230 patients, across all stages of CKD. Ethical approval to conduct the study was obtained from the University of the Western Cape Biomedical Research Ethics Committee, and written informed consent was provided by each participant. Saliva and serum samples were collected for creatinine analysis and the correlation determined using Spearman's correlation. Receiver operating characteristics (ROC) analysis was used to determine the diagnostic ability of salivary creatinine. A cut-off value for optimal sensitivity and specificity of salivary creatinine to diagnose CKD with glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 was obtained. RESULTS: Serum creatinine values ranged from 46 µmol/L to 1581 µmol/L, with a median value of 134 µmol/L. Salivary creatinine values ranged from 3 µmol/L to 400 µmol/L, with a median of 11 µmol/L. There was a strong positive correlation (r = 0.82) between serum and salivary creatinine values. Linear regression analysis of serum and salivary creatinine for CKD patients was significant in all CKD stages, except for stage 1. Area under the curve for salivary creatinine was 0.839. A cut-off value of 8.5 µmol/L yielded a sensitivity of 78.3% and specificity of 74.0% for classifying patients as having CKD based on estimated GFR < 60 mL/min/1.73 m2. CONCLUSIONS: The results support the potential of salivary creatinine as a non-invasive diagnostic tool for estimating GFR and identifying patients with CKD.

Mitochondrial-Derived Peptides Are Down Regulated in Diabetes Subjects.

Background: Mitochondrial dysfunction is implicated in the pathogenesis of Type 2 diabetes (T2D) and the development of diabetes related complications such as cardiovascular disease and stroke. Mitochondria produce several small polypeptides that may influence mitochondrial function and may impact on insulin sensitivity, such as humanin (HN) and the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) that are mitochondrial derived proteins (MDP). The aim of this study was to determine MDP in normal, prediabetes and diabetes subjects. Subjects and Measurements: In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects. The relationship of serum MDP and ADP concentrations with biochemical and anthropometric measurements were performed and assessed by multilinear regression. Results: Serum HN concentrations were lower in T2D (p < 0.0001) and negatively correlated with age (p < 0.0001), HbA1c (p < 0.0001), glucose (p < 0.0001), triglycerides (p < 0.003), ALT (p < 0.004), and TG/HDL ratio (p < 0.001). Circulating HN levels were positively correlated to cholesterol (p < 0.017), LDL (p < 0.001), and HDL (p < 0.001). Linear regression analysis showed that HbA1c and ALT were two independent predictors of circulating HN. Similarly, serum MOTS-c was significantly lower in T2D subjects compared to controls (p < 0.007). Circulating MOTS-c positively correlated with BMI (p < 0.035), total cholesterol (p < 0.0001), and LDL (p < 0.001) and negatively correlated with age (p < 0.002), HbA1c (p < 0.001), and glucose (p < 0.002). Serum ADP concentrations were lower in T2D (p < 0.002) and negatively correlated with HbA1c (p < 0.001), weight (p < 0.032) TG (p < 0.0001), and ALT (p < 0.0001); and positively correlated with HDL (p < 0.0001) and HN (p < 0.003). Linear regression analysis showed that HbA1c and weight were two independent predictors of circulating ADP. Multilinear regression showed that HN and MOT-c correlated with each other, and only HN correlated with HbA1c. Conclusion: The MDPs HN and MOT-c, similar to ADP, are decreased in T2D and correlate with HbA1c. The data provide an additional evidence that mitochondrial dysfunction contributes to glycemic dysregulation and metabolic defects in T2D.

Craniofacial manifestations in osteogenesis imperfecta type III in South Africa.

OBJECTIVES: Osteogenesis imperfecta type III (OMIM 259420) is a severe autosomal recessive disorder. Affected individuals have multiple fractures, develop limb deformities with spinal malalignment and stunted stature. MATERIALS AND METHODS: The frequency of Osteogenesis imperfecta type III (OI III) is relatively high in the indigenous Black African population of South Africa. A review of the literature revealed a paucity of information regarding the craniofacial manifestations of the disorder in this ethnic group. The findings in 64 affected persons are documented. RESULTS: These abnormalities are related to the abnormal bone matrix which results in a deformed skull and dental malocclusion. The physiological process of swallowing may be an aetiological factor in the progressive development of a flattened palate. Mild changes in the shape of the head of the mandibular condyle and a lack of cortical bone on the joint surfaces were observed on cone beam computed tomography (CBCT) images. Affected persons had marked variations in the paranasal sinuses, including sinus hypoplasia and partial opacification. Cranial base anomalies were diagnosed from cephalometric radiographs and lateral skull radiographs. Platybasia and a 'J' shaped sella turcica were observed. CONCLUSION: The craniofacial abnormalities emphasize the importance of a raised level of awareness in terms of dental management and the challenges.

Drinking cholera: salinity levels and palatability of drinking water in coastal Bangladesh.

OBJECTIVES: To measure the salinity levels of common water sources in coastal Bangladesh and explore perceptions of water palatability among the local population to investigate the plausibility of linking cholera outbreaks in Bangladesh with ingestion of saline-rich cholera-infected river water. METHODS: Hundred participants took part in a taste-testing experiment of water with varying levels of salinity. Salinity measurements were taken of both drinking and non-drinking water sources. Informal group discussions were conducted to gain an in-depth understanding of water sources and water uses. RESULTS: Salinity levels of non-drinking water sources suggest that the conditions for Vibrio cholerae survival exist 7-8 days within the local aquatic environment. However, 96% of participants in the taste-testing experiment reported that they would never drink water with salinity levels that would be conducive to V. cholerae survival. Furthermore, salinity levels of participant's drinking water sources were all well below the levels required for optimal survival of V. cholerae. Respondents explained that they preferred less salty and more aesthetically pleasing drinking water. CONCLUSION: Theoretically, V. cholerae can survive in the river systems in Bangladesh; however, water sources which have been contaminated with river water are avoided as potential drinking water sources. Furthermore, there are no physical connecting points between the river system and drinking water sources among the study population, indicating that the primary driver for cholera cases in Bangladesh is likely not through the contamination of saline-rich river water into drinking water sources.

Is human immunodeficiency virus (HIV) stage an independent risk factor for altering the periodontal status of HIV-positive patients? A South African study.

BACKGROUND: The immunosuppresion in HIV patients makes them highly susceptible to microbial infections. The aim of the study was to establish whether HIV stage (as depicted by CD4+ T lymphocyte counts) could independently be associated with periodontal status (as revealed by the measurement of clinical indices). METHODS: One hundred and twenty HIV-infected patients attending an infectious diseases clinic in the Western Cape, South Africa were included in the study. The periodontal clinical indices such as plaque index, gingival index, pocket probing depth and clinical attachment levels were measured on the mesial aspect of the six Ramfjord teeth. The CD4 + T cell counts were taken from the patients' medical records and patients' HIV stage determined and grouped according to their CD4+ T cell counts into A (<200 cells /mm3), B (200-500 cells /mm3) and C (>500 cells /mm3). RESULTS: The mean age of 120 HIV-positive patients was 33.25 years and the mean CD4 + T cell count was 293.43 cells/mm3. The probing depth and clinical attachment loss were found to be significantly associated with the total CD4 + T cell counts but not with HIV stage. Significant correlations were found between age and all clinical indices except for clinical attachment loss. No correlation was found between age and HIV stage of the patients. The use of antiretroviral therapy was significantly associated with probing depth and clinical attachment loss, but not with plaque nor gingival index. Significant associations were observed between smoking and all of the clinical indices except for the gingival index. A significant association was observed between the use of interdental aids and all the clinical indices except for probing depth, while brushing was significantly associated with plaque index only. CD4 + T cell counts were significantly associated with brushing frequency (p = 0.0190) and the use of interdental aids (p = 0.0170). CONCLUSION: The findings of this study conclude that HIV stage, ART and age are not independent risk factors for changes in the periodontal status of HIV-positive subjects but rather that smoking and oral hygiene habits determine their susceptibility to disease.

The imaging characteristics of odontogenic myxoma and a comparison of three different imaging modalities.

OBJECTIVE: To report the imaging characteristics of odontogenic myxoma (OM) and compare the different imaging modalities used. STUDY DESIGN: The radiological images of 33 OM cases were retrospectively analyzed. The radiographs were severally examined to describe the features of OM as seen on conventional radiographs (CRs), computed tomography (CT) scans, and magnetic resonance images (MRIs). RESULTS: MRI was effective in displaying the true extension and contents of OMs. CT scans demonstrated the extensions of OMs, expansion, growth pattern, and rendered it possible to compare density of OM with that of surrounding muscles. Assessment of CRs revealed great limitations about the diagnostic values and failed to display important features. CONCLUSIONS: All 3 radiographic techniques, conventional radiography, CT, and magnetic resonance imaging (MRI), have inherent advantages and disadvantages; however, all 3 should be routinely used in the diagnosis of OM. The results of CT and MRI can accurately reveal margins of tumors and greatly aid in diagnosis.

Cleidocranial dysplasia: a review of the dental, historical, and practical implications with an overview of the South African experience.

Cleidocranial dysplasia (CCD) is an uncommon but well-known genetic skeletal condition. Several hundred affected persons are members of a large extended family in the Cape Town Mixed Ancestry community of South Africa. The clinical manifestations are often innocuous, but hyperdontia and other developmental abnormalities of the teeth are a major feature and may require special dental management. Over the past 40 years, the authors have encountered more than 100 affected persons in Cape Town. Emphasis has been on dental management, but medical, genetic, and social problems have also been addressed. In this article, we have reviewed the manifestations of the disorder in the light of our own experience, and performed a literature search with emphasis on the various approaches to dental management and treatment options in CCD. Advances in the understanding of the biomolecular pathogenesis of CCD are outlined and the international and local history of the disorder is documented.

BANA-Positive Plaque Samples Are Associated with Oral Hygiene Practices and Not CD4+ T Cell Counts in HIV-Positive Patients.

Background. The "red complex" microorganisms, namely, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia are considered as potential pathogens causing HIV-associated periodontal diseases. Moreover, it has been recognized that an association exists between CD4+ T cell counts and periodontal disease progression. Objective. To establish whether CD4+ T cell counts or oral hygiene plays a greater role in producing BANA-positive results in HIV-associated periodontal disease. Materials and Methods. One hundred and twenty HIV-positive patients participated in the study, and their CD4+ T cell counts were obtained from their medical records. The six Ramfjord teeth were used for evaluating periodontal clinical indices and subgingival plaque sampling. BANA test was used for the detection and prevalence of the "red complex" bacteria in plaque samples. Results. A majority of 69.17% HIV-positive patients were BANA-positive. No significant associations were found between BANA and CD4+ T cell counts. A highly significant association was found between BANA with probing depth and clinical attachment level (P ≤ 0.0001) and between BANA and the use of interdental aids (P = 0.0168). Conclusion. HIV-associated periodontal diseases are strongly related to oral hygiene practices rather than the effect of CD4+ T cell counts, and the use of interdental aids was marked as a significant predictor of BANA-negative plaque samples.

Palatal ulceration as the first sign of pulmonary tuberculosis: a case report.

Tuberculosis (TB) is one of the leading casues of morbidity and death in a number of countries worldwide. A healthy 42-year-old patient presented with a chronic palatal ulcer that was not responsive to routine antibiotic treatment. A biopsy and further systemic investigation revealed a diagnosis of TB. An eight-month extended course of oral rifampin and isoniazid was instituted successfully resulting in complete resolution of symptoms. It is important that clinicians be aware that chronic oral ulcerations may be the first sign of systemic disease. A biopsy should therefore be mandatory for any chronic oral ulcer not responsive to conventional treatment.

Fibrodysplasia ossificans progressiva (FOP) in South Africa: dental implications in 5 cases.

Fibrodysplasia ossificans progressiva (FOP) is a severe genetic disorder in which progressive ossification of subcutaneous tissues leads to immobility and profound physical handicap. Dental management of affected persons may be constrained by impaired mobility of the temporomandibular joints. Equally, the traumatic aspects of dental intervention can exacerbate the ossification process. In the later stages of the disorder, thoracic immobility impairs pulmonary ventilation and compromises dental anesthesia. We have undertaken dental appraisal and treatment of 5 South Africans with FOP, with ages ranging from 2 to 52 years. The age relationship of the manifestations of FOP was apparent in these persons, as were the dental problems that emerged. These dental observations illustrate the importance of accurate diagnosis and the awareness of potential complications that may be encountered in dental management. Our observations are presented and discussed in this article.

Alveolar ridge preservation using leukocyte and platelet-rich fibrin: a report of a case.

In order for a dental implant to be restored optimally, it must be placed in an ideal anatomic position. However, this is not always possible, since physiological wound healing after tooth removal, often results in hard and soft tissue changes which ultimately compromises ideal implant placement. With the aim of minimising the need for tissue augmentation, several alveolar ridge preservation (ARP) techniques have been developed. These often require the use of grafting material and therefore increase the risk of disease transmission. Leukocyte and platelet-rich fibrin (L-PRF) is a newly developed platelet concentrate that is prepared from the patient's own blood. Clinical research has indicated that it improves wound healing and stimulates bone formation. We present a case where L-PRF was successfully used in an ARP procedure to facilitate implant placement in a compromised extraction socket.

Klippel-Trenaunay-Weber syndrome: orodental manifestations and management considerations.

Klippel-Trenaunay-Weber syndrome is characterized by a triad of features, namely, vascular nevi, venous varicosities, and hyperplasia of hard and soft tissues in the affected area. Involvement of the orofacial region is uncommon, but nevertheless, a wide range of orofacial abnormalities may necessitate specialized dental and anesthesia management. We have documented the manifestations in 2 affected persons, outlined the nosology, reviewed the literature, and tabulated craniofacial anomalies and orodental complications. Special emphasis is given to the hematologic factors (bleeding tendencies) and vascular involvement (hemangiomata) which may significantly influence orodental management and anesthesia.

Lennox gastaut syndrome, review of the literature and a case report.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe form of childhood epilepsy that is defined by generalized multiple type seizures, slowness of intellectual growth, and a specific EEG disturbance. Children affected might previously have infantile spasms or underlying brain disorder but etiology can be idiopathic. In South Africa, the incidence of secondary epilepsy is higher than what is found in developed countries resulting in higher incidence of the disease. LGS seizures are often treatment resistant and the long term prognosis is poor. REPORT: A twenty six year old female, presented with anterior open bite, macroglossia, supragingival as well as subgingival calculus. The gingiva was red, swollen and friable and there was generalized bleeding and localized suppuration. The patient had gingival recession. After periodontal therapy a remarkable improvement in oral health status was noted. CONCLUSION: The clinical findings in LGS included facial deformities, periodontitis and gingival swellings. Interdisciplinary treatment of these patients is fundamental and oral attention is of outstanding importance. Non-surgical periodontal therapy was effective in controlling periodontal disease in the reported case, but prevention of periodontal and dental diseases is preferable for this high-risk group of patients.

Dilated cardiomyopathy and left bundle branch block associated with ingestion of colloidal gold and silver is reversed by British antiLewisite and vitamin E: the potential toxicity of metals used as health supplements.

A case of left bundle branch block and a dilated, nonhypertrophic cardiomyopathy associated with ingestion of colloidal gold and silver as an 'energy tonic' is described. The cardiac disease was reversed within two months by a course of dimercaprol (Akorn Inc, USA) (British antiLewisite) and vitamin E. This is the first case of gold and silver cardiomyopathy in humans, and highlights the risks of these colloidal metal 'health supplements'.

More men than women make mucosal IgA antibodies to Human papillomavirus type 16 (HPV-16) and HPV-18: a study of oral HPV and oral HPV antibodies in a normal healthy population.

BACKGROUND: We have previously shown the high prevalence of oral anti-human papillomavirus type 16 (HPV-16) antibodies in women with HPV-associated cervical neoplasia. It was postulated that the HPV antibodies were initiated after HPV antigenic stimulation at the cervix via the common mucosal immune system. The present study aimed to further evaluate the effectiveness of oral fluid testing for detecting the mucosal humoral response to HPV infection and to advance our limited understanding of the immune response to HPV. METHODS: The prevalence of oral HPV infection and oral antibodies to HPV types 16, 18 and 11 was determined in a normal, healthy population of children, adolescents and adults, both male and female, attending a dental clinic. HPV types in buccal cells were determined by DNA sequencing. Oral fluid was collected from the gingival crevice of the mouth by the OraSure method. HPV-16, HPV-18 and HPV-11 antibodies in oral fluid were detected by virus-like particle-based enzyme-linked immunosorbent assay. As a reference group 44 women with cervical neoplasia were included in the study. RESULTS: Oral HPV infection was highest in children (9/114, 7.9%), followed by adolescents (4/78, 5.1%), and lowest in normal adults (4/116, 3.5%). The predominant HPV type found was HPV-13 (7/22, 31.8%) followed by HPV-32 (5/22, 22.7%). The prevalence of oral antibodies to HPV-16, HPV-18 and HPV-11 was low in children and increased substantially in adolescents and normal adults. Oral HPV-16 IgA was significantly more prevalent in women with cervical neoplasia (30/44, 68.2%) than the women from the dental clinic (18/69, 26.1% P = 0.0001). Significantly more adult men than women displayed oral HPV-16 IgA (30/47 compared with 18/69, OR 5.0, 95% CI 2.09-12.1, P < 0.001) and HPV-18 IgA (17/47 compared with 13/69, OR 2.4, 95% CI 0.97-6.2, P = 0.04). CONCLUSION: The increased prevalence of oral HPV antibodies in adolescent individuals compared with children was attributed to the onset of sexual activity. The increased prevalence of oral anti-HPV IgA in men compared with women was noteworthy considering reportedly fewer men than women make serum antibodies, and warrants further investigation.