Is the Differentiated Service Delivery Model Suited to the Needs of People Living with HIV in Rwanda?

The primary goal of antiretroviral treatment is to improve the health of individuals with HIV, and a secondary goal is to prevent further transmission. In 2016, Rwanda adopted the World Health Organization's "treat-all" approach in combination with the differentiated service delivery (DSD) model. The model's goal was to shorten the time from HIV diagnosis to treatment initiation, regardless of the CD4 T-cell count. This study sought to identify perceptions, enablers, and challenges associated with DSD model adoption among PLHIV.This study included selected health centers in Kigali city, Rwanda, between August and September 2022. The patients included were those exposed to the new HIV care model (DSD) model and those exposed to the previous model who transitioned to the current model. Interviews and focus group discussions were also held to obtain views and opinions on the DSD model. The data were collected via questionnaires and audio-recorded focus group discussions and were subsequently analyzed.The study identified several themes, including participants' initial emotions about a new HIV diagnosis, disclosure, experiences with transitioning to the DSD model, the effect of peer education, and barriers to and facilitators of the DSD model. Participants appreciated reduced clinic visits under the DSD model but faced transition and peer educator mobility challenges.The DSD model reduces waiting times, educates patients, and aligns with national goals. Identified barriers call for training and improved peer educator retention. Recommendations include enhancing the DSD model and future research to evaluate its long-term impact and cost-effectiveness.

Effects of Multi-Month Dispensing on Clinical Outcomes: Retrospective Cohort Analysis Conducted in Kenya.

Multi-month dispensing (MMD) has been widely adopted by national HIV programs as a key strategy for improving the quality of HIV care and treatment services while meeting the unique needs of diverse client populations. We assessed the clinical outcomes of clients receiving MMD in Kenya by conducting a retrospective cohort study using routine programmatic data in 32 government health facilities in Kenya. We included clients who were eligible for multi-month antiretroviral therapy (ART) dispensing for ≥ 3 months (≥ 3MMD) according to national guidelines. The primary exposure was enrollment into ≥ 3MMD. The outcomes were lost to follow-up (LTFU) and viral rebound. Multilevel modified-Poisson regression models with robust standard errors were used to compare clinical outcomes between clients enrolled in ≥ 3MMD and those receiving ART dispensing for less than 3 months (< 3MMD). A total of 3,501 clients eligible for ≥ 3MMD were included in the analysis, of whom 65% were enrolled in ≥ 3MMD at entry into the cohort. There was no difference in LTFU of ≥ 180 days between the two types of care (aRR 1.1, 95% CI 0.7-1.6), while ≥ 3MMD was protective for viral rebound (aRR 0.1 95% CI 0.0-0.2). As more diverse client-focused service delivery models are being implemented, robust evaluations are essential to guide the implementation, monitor progress, and assess acceptability and effectiveness to deliver optimal people-centered care.

A simple model for the total number of SARS-CoV-2 infections on a national level.

This study aimed to identify an appropriate simple mathematical model to fit the number of coronavirus disease 2019 (COVID-19) cases at the national level for the early portion of the pandemic, before significant public health interventions could be enacted. The total number of cases for the COVID-19 epidemic over time in 28 countries was analysed and fit to several simple rate models. The resulting model parameters were used to extrapolate projections for more recent data. While the Gompertz growth model (mean R2 = 0.998) best fit the current data, uncertainties in the eventual case limit introduced significant model errors. However, the quadratic rate model (mean R2 = 0.992) fit the current data best for 25 (89%) countries as determined by R2 values of the remaining models. Projection to the future using the simple quadratic model accurately forecast the number of future total number of cases 50% of the time up to 10 days in advance. Extrapolation to the future with the simple exponential model significantly overpredicted the total number of future cases. These results demonstrate that accurate future predictions of the case load in a given country can be made using this very simple model.

Comparative antimicrobial activity of two new mutacins.

OBJECTIVES: To compare the in vitro activity of mutacins D-123.1 and F-59.1 against different bacteria including antibiotic-resistant strains, in order to evaluate their application potential. DESIGN AND METHODS: The antibacterial activity spectrum of purified F-59.1 and the MIC and MBC of F-59.1 and D-123.1 against target bacteria were determined. RESULTS: Most bacteria were inhibited by the purified mutacins. Mutacin F-59.1 shows a relatively wide activity spectrum. Mutacin D-123.1 has low Minimum Inhibitory Concentrations [MICs] (0.25-4 microg/ml) against human pathogens while F-59.1 has higher MICs (3.2-12.8 microg/ml) mainly against food-borne pathogens. CONCLUSION: The effectiveness of mutacins D-123.1 and F-59.1 against human and food-borne pathogens is demonstrated. Mutacin D-123.1 shows potential as a new antibiotic while F-59.1 shows promising application in food products.

Oral microbial ecology and the role of salivary immunoglobulin A.

In the oral cavity, indigenous bacteria are often associated with two major oral diseases, caries and periodontal diseases. These diseases seem to appear following an imbalance in the oral resident microbiota, leading to the emergence of potentially pathogenic bacteria. To define the process involved in caries and periodontal diseases, it is necessary to understand the ecology of the oral cavity and to identify the factors responsible for the transition of the oral microbiota from a commensal to a pathogenic relationship with the host. The regulatory forces influencing the oral ecosystem can be divided into three major categories: host related, microbe related, and external factors. Among host factors, secretory immunoglobulin A (SIgA) constitutes the main specific immune defense mechanism in saliva and may play an important role in the homeostasis of the oral microbiota. Naturally occurring SIgA antibodies that are reactive against a variety of indigenous bacteria are detectable in saliva. These antibodies may control the oral microbiota by reducing the adherence of bacteria to the oral mucosa and teeth. It is thought that protection against bacterial etiologic agents of caries and periodontal diseases could be conferred by the induction of SIgA antibodies via the stimulation of the mucosal immune system. However, elucidation of the role of the SIgA immune system in controlling the oral indigenous microbiota is a prerequisite for the development of effective vaccines against these diseases. The role of SIgA antibodies in the acquisition and the regulation of the indigenous microbiota is still controversial. Our review discusses the importance of SIgA among the multiple factors that control the oral microbiota. It describes the oral ecosystems, the principal factors that may control the oral microbiota, a basic knowledge of the secretory immune system, the biological functions of SIgA, and, finally, experiments related to the role of SIgA in oral microbial ecology.

A quantitative risk assessment of West Nile virus introduction into Barbados.

OBJECTIVE: To present a quantitative risk assessment of West Nile (WNV) virus introduction into Barbados, West Indies. DESIGN AND METHODS: Three possible modes were considered: a) WNV infected mosquitoes via air transport, by city of departure, b) WNV infected mosquitoes via marine transport and c) viraemic migratory, birds. We estimated the number of WNV infected migratory birds as the product of the proportion of migratory birds infected and the number of migratory birds entering Barbados in three taxonomic groups. We further estimated the number of days these birds would be infectious as: [formula: see text]. We then estimated the number (#) of infectious mosquito-days for mosquitoes entering Barbados via air transport as: # infected mosquitoes = (total flights per week/city) x (duration of WNV season) x (number of Culex mosquitoes aboard each flight) x (Culex mosquito WNV infection prevalence) x (vector competence index) x (days infectious). The number of infected mosquitoes entering Barbados via marine transport was estimated using a similar expression as for air transport, except that the number of airplanes and mosquitoes/airplane were substituted with the # of sea containers during a 22-week mosquito season and # of mosquitoes/container. RESULTS: Migratory birds (approximately 69-101 infected birds/year) were associated with the highest introductory risk followed by mode (a) (approximately 2 infected mosquitoes/year) and mode (b) (0. 004 infected mosquitoes/year). CONCLUSIONS: Migratory birds and mosquitoes via air are imminent threats for virus introduction. Impending co-circulation of West Nile virus and four strains of dengue virus may present new challenges for public health.

Purification and structure of mutacin B-Ny266: a new lantibiotic produced by Streptococcus mutans.

Mutacins are bactericidal substances of proteinaceous nature produced by Streptococcus mutans. Lantibiotics are antibacterial substances containing post-translationally modified amino acids such as lanthionine. Mutacin B-Ny266 was purified from the cell pellet of S. mutans strain Ny266 by ethanol extraction at pH 2.0 followed by reversed-phase chromatography (Sep-Pak cartridge) and by HPLC on a C18 column. The mean purification factor was 3240 +/- 81 and the mean yield was 1.0 +/- 0.1%. Molecular mass of mutacin B-Ny266 as determined by mass spectroscopy is 2270.29 +/- 0.21 Da. The amino acid sequence of the purified active fraction was obtained by Edman degradation after treatment with alkaline ethanethiol. Twenty-one amino acids were detected in this analysis. Mutacin B-Ny266 belongs to the type A lantibiotics. The proposed sequence is: F-K-A-W-U-F-A-Abu-P-G-A-A-K-O-G-A-F-N-U-Y-A. The molecule differs from that of epidermin/staphylococcin 1580 and gallidermin at positions 1, 2, 4, 5 and 6.

Effect of dietary components on the indigenous oral bacterial flora of BALB/c mice.

Diet is recognized as one of the most important factors affecting the equilibrium of the oral bacterial flora. Studies related to dental caries development have focused mainly on the effect of carbohydrates. In the present work, using swabbing coupled with an immuno-colony-blot assay, we followed the indigenous oral bacterial populations of BALB/c mice fed diets with different concentrations of sucrose, starch, proteins, lipids, vitamins, and minerals for a period of 14 days. The results indicate that although high-sucrose diet favored an increase of the proportion of S. faecalis, only variations in the protein and the starch concentrations significantly influenced the composition of the indigenous oral bacterial populations of BALB/c mice. With low-protein diets, the proportion of Lactobacillus murinus decreased, that of Streptococcus faecalis increased, while that of Staphylococcus aureus was relatively stable. A diet containing a high proportion of starch (65%) resulted in a significant increase in the population of S. faecalis, while that of S. aureus decreased proportionally. With the same diets used as in vitro culture media, growth of L. murinus was the fastest at high protein concentrations, while that of S. faecalis was not affected by the protein concentrations. These results indicate a direct effect of dietary protein content on the indigenous oral bacterial populations of BALB/c mice.

Antibiotic resistance and production of inhibitory substances among bacterial strains isolated from the oral cavities of BALB/c mice.

In the oral cavities of BALB/c mice, microbial population levels are regulated by multifactorial processes. Factors include the production of inhibitory substances and the exchange of genetic material. In this work, 371 isolates from different sites (saliva, tongue, teeth, and mucosa) of the oral cavities of BALB/c mice were screened for resistance to antibiotics and antimicrobial activity. Antibiotic-resistant strains represented 25% of the total flora. Among the predominant species, all the S. faecalis isolates showed multiresistance, and 23% of the Lactobacillus murinus isolates and 15% of the Staphylococcus aureus were resistant to at least one antibiotic. Resistance to aminoglycosides (neomycin, streptomycin, kanamycin, and gentamicin) was most frequently encountered. In S. faecalis, high levels of resistance were recorded to neomycin and streptomycin but not to gentamicin or kanamycin. Macrolides (M), lincosamides (L), streptogramin B (S), tetracycline (Tc), and chloramphenicol (Cm) resistance was also present in multiresistance patterns, especially among S. faecalis isolates. Hemolytic (Hly+) streptococci were less resistant to MLS, Tc, and Cm than were non-hemolytic (Hly-) isolates. Resistance to beta-lactam antibiotics was detected only among staphylococci and with a low prevalence (4%). The frequencies of strains producing antimicrobial substances against the indicator strains (S. mutans LG-1, S. sanguis Ny 101, and A. viscosus Ny 1) were high for L. murinus (76%) and S. faecalis (57% for Hly- and 90% for Hly+), but low for S. aureus (7%). These results indicate that the indigenous oral flora could interfere with colonization by allochthonous micro-organisms and that resistance patterns should be taken into account for the elimination of the oral indigenous flora by antibiotic treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Proteolytic activity of bacteria isolated from the oral cavities of BALB/c mice toward salivary proteins.

The proteolytic activities of 350 bacterial isolates from different sites (saliva, tongue, teeth, and mucosa) of the oral cavities of BALB/c mice were tested against different proteins found in saliva (immunoglobulins A, M, G, albumin, lysozyme, mucin, lactoferrin, and lactoperoxidase), some of which are considered to possess antibacterial activity. The results indicate that: (1) lysozyme, lactoferrin, and lactoperoxidase are hydrolyzed by from 46 to 70% of the indigenous flora of the oral cavities of BALB/c mice; (2) IgA and IgM appeared less sensitive to the proteolytic activities of these strains than did the other proteins tested; (3) the colonization of the oral cavity does not seem to be correlated with the proteolytic activity; and (4) the presence of specific Ig proteases is relatively scarce within this population.

Comparison of the proportions of oral bacterial species in BALB/c mice from different suppliers.

In order to assess the influence of the origin of mice on their oral bacteria, the proportions of bacterial species found in the oral cavity of BALB/c mice from 5 suppliers were determined. The results indicated that mice from different origins harboured different oral bacterial populations upon arrival at our animal facilities and the differences persisted for at least one week after arrival. Except in one case, the oral bacteria did not differ from one shipment to another from each supplier and remained similar after one week at our animal facilities. The results thus indicate that the composition of the oral bacterial population is influenced by the origin of the mice.

Identification of strains isolated as total and fecal coliforms and comparison of both groups as indicators of fecal pollution in tropical climates.

This study was undertaken to better characterize the groups of total coliforms (TC) and fecal coliforms (FC) and to evaluate both groups as indicators of fecal contamination of drinking well water in a tropical climate (The Ivory Coast, West Africa). Isolated colonies obtained as TC or FC on membrane filters were identified using the API-20E system. From the well water samples, 58 golden-green colonies with a metallic sheen isolated on Endo medium (TC) were identified as Escherichia coli (55%), Enterobacter (26%), Klebsiella (14%), Proteus (3%), and Citrobacter (2%). Among 132 colonies isolated on Endo medium as non-TC (not showing the characteristic golden metallic sheen), 10% were identified as E. coli. The 196 blue colonies isolated on M-FC medium at 44.5 degrees C (FC) were identified as E. coli (66%), Klebsiella (12%), Enterobacter (10%), Citrobacter (5%), Salmonella (3%), Serratia (3%), Proteus (2%), and Yersinia (0.5%). Among 24 nonblue colonies on M-FC medium, none were identified as E. coli. Of the colonies isolated from human feces, E. coli represents 92% of the TC and 89% of the FC. Although these results are limited, they tend to confirm the greater specificity of the fecal coliform technique over that of total coliform for the detection of fecal contamination of untreated well water. From the results presented here and the observations of other workers, it is suggested that the use of FC instead of TC should be considered as the method of choice for determining drinking water pollution of untreated groundwater supplies.

Effects of dietary carbohydrates on mutacin production and activity.

Although mutacins (bacteriocins produced by Streptococcus mutans) were shown to be active in vivo, their ecological role in the oral cavity is still controversial. In the present paper, the effect of dietary carbohydrates, one of the ecological parameters which influences oral bacterial populations, on the activity and the production of mutacins from four S. mutans strains (C67-1, Ny257, Ny266 and T8) is described. Results obtained by the deferred antagonism test in solid media and by the mixed cultivation of the mutacinogenic strains with a sensitive indicator strain in liquid batch cultures, indicate that a minimal fermentable sugar concentration is needed for mutacin production. Among all the fermentable carbohydrates tested (fructose, glucose, lactose, mannitol and sucrose), none significantly affected the production and the activity of the four mutacinogenic strains used, in concentrations up to 5%. Although the results do not discount the possibility of mutacin inactivation in vivo, they indicate that they are not affected by dietary carbohydrates.

Comparison of the indigenous oral microbiota and immunoglobulin responses of athymic (nu/nu) and euthymic (nu/+) mice.

The role of the immune system in the homeostasis of indigenous oral bacterial populations is poorly understood. In this study, we compared the evolution of the indigenous oral microbiota of specific pathogen-free athymic nude (nu/nu) BALB/c mice with that of their corresponding phenotypically normal (nu/-) littermates. We also evaluated corresponding salivary and serum antibody activities (IgA and IgG) against the predominant indigenous oral bacteria. The bacterial species recovered from the two mouse strains were Lactobacillus murinus, Enterococcus faecalis, Streptococcus oralis and Staphylococcus epidermidis. From 27 days of age, nu/+ and nu/nu mice had significantly different proportions of oral bacterial populations. When the microbiota stabilized (at 40 days of age), the total cultivable microbiota of nu/+ mice was dominated by L. murinus (65-85%), while that of nu/nu mice was dominated by E. faecalis (40-60%). The precise factors that alter the oral resident microbiota in nu/nu mice are unknown. We found that total salivary IgA levels were significantly lower in nu/nu mice, but no association were observed between the level of salivary IgA antibody against indigenous bacteria and the proportion of these indigenous bacteria in the oral microbiota. The change in the microbiota of nude mice may have been caused by other factors such as defects in other immune functions or cold stress.

Comparison of different membranes for use in the colony-immunoblot technique.

We compared five different supports (Whatman paper filters Nos. 1, 5, and 40, nitrocellulose, and Nylon 66) for their suitability in the colony-immunoblot (CIB) technique. Results indicate that Whatman No. 5 filter paper recovered 94-98% of the bacterial colonies tested, were more resistant to tearing than the other Whatman papers tested, and showed reduced cross-reactions as compared with nitrocellulose membranes. Whatman No. 5 filters are 20 times less expensive than the nitrocellulose membranes usually used in the CIB technique. We thus adopted the former for our ecological studies of the murine oral cavity.

Evaluation of mouse salivary IgA directed against indigenous oral bacteria.

We are developing an ELISA to follow the evolution of specific salivary IgA directed against the indigenous oral bacteria of the BALB/c mouse. To reduce the variability of the IgA levels detected between different mice, we standardized the method used for sampling saliva and the method used for bacterial cell fixation. Incubation of whole bacteria for one hour at 4 degrees C in poly-L-lysine-treated plates followed by glutaraldehyde fixation increased ELISA reactivities by improving cell fixation. Our results also indicate that salivary IgA concentrations in BALB/c mice peak at the age of three months and that biweekly carbachol-stimulated saliva sampling does not significantly affect the amount of salivary IgA detected.

Evolution of resident oral bacterial biota in BALB/c mice during pregnancy and lactation.

To assess the influence of pregnancy and lactation on the oral microbial ecology of BALB/c mice, we followed the distribution of the predominant oral bacteria of four groups of these mice during these two periods. Compared with nonpregnant control female mice of the same age maintained under the same conditions, the distribution of the resident oral bacterial species differed significantly only during the lactation period (8-16 days after parturition). This difference could possibly be attributed to hormonal influences and/or grooming habits.