Does cotrimoxazole prophylaxis in HIV patients increase the drug resistance of pneumococci? A comparative cross-sectional study in southern Ethiopia.

BACKGROUND: Infections caused by antibiotic-resistant bacteria results in high rates of morbidity and mortality. Although the prolonged cotrimoxazole (CTX) prophylaxis is arguably associated with the risk of increasing drug resistance in the common pathogens, information regarding its impact on Streptococci pneumoniae / pneumococcus is very limited. OBJECTIVE: This study was conducted to investigate the effect of cotrimoxazole prophylaxis on nasopharyngeal colonization rate and antimicrobial resistance using Streptococci pneumoniae (pneumococcus) as an indicator organism among HIV patients in Arba Minch, Ethiopia. MATERIALS AND METHODS: A comparative cross-sectional study was designed and conducted among HIV patients attending the Anti-Retroviral Treatment (ART) clinic of Arba Minch General Hospital (AMGH) from April 01 to August 31, 2018. A total of 252 participants were systematically selected and clustered into two study groups based on their CTX prophylaxis status, one taking CTX prophylaxis, and the second one, the control group (without prophylaxis). A structured questionnaire was used to collect socio-demographic and clinical data from patients. A nasopharyngeal swab was collected and cultured for pneumococcal isolation and identification in accordance with standard microbiological techniques. An antibiotics sensitivity test was performed according to the CLSI guidelines. Data were analyzed using the Statistical package for social science (SPSS) version 20. The primary outcome was determined using logistic regression analysis. RESULTS: Of the 252 enrolled HIV patients (mean age (37.38± 9.03 years), 144 (57.14%) were males. The overall, nasopharyngeal colonization rate of S. pneumoniae was 13.5% (95% CI: 8.4-15.6). Asymptomatic pneumococcal carriage rates among patients on CTX prophylaxis and the control group were 16.3%, and 10.3% respectively (p-value = 0.03). Regarding the risk factors analyzed, CTX prophylaxis (AOR: 2.2; 95% CI: 1.05-4.9) and gender (AOR: 2.5; 95% CI: 1.09-5.93) were significantly associated with pneumococcal colonization, showing a male preponderance. Cotrimoxazole-resistant pneumococci were 85.7% vs. 47.4% in the prophylaxis group and the control group respectively and it was statistically significant (AOR: 6.7; 95% CI: 1.3-36). Percentages of multi-drug resistant isolates in these two groups were 38.09 and 15.38 respectively (p-value = 0.04). Among the CTX resistant pneumococci isolates, 85% were also found to be co-resistant towards penicillin and was statistically significant. CONCLUSION: The percentage prevalence of nasopharyngeal pneumococci colonization was higher in patients taking CTX prophylaxis. It was noted that CTX prophylaxis eventually results in the selection of cotrimoxazole resistance and multi-drug resistance in pneumococci. There is evidence of existing cross-resistance between cotrimoxazole and penicillin antibiotics. Therefore, CTX prophylaxis must be administered judiciously. Surveillance for antimicrobial susceptibility is warranted where the prophylaxis is common.

The Effects of Physicochemical Properties of Nanomaterials on Their Cellular Uptake In Vitro and In Vivo.

Understanding the cellular uptake of nanomaterials (NMs) is a fundamental and critical issue for uncovering biomedical effects of NMs and facilitating their practical applications in the clinic. In this Review, by highlighting the differences of NMs cellular uptake between in vitro and in vivo, a focus on reviewing recent works about the effects of four physicochemical parameters of NMs (size, rigidity, shape, surface modification) on regulating NMs cellular uptake in vitro and in vivo is undertaken. This review can provide readers some useful clues and new thinking for understanding NMs cellular uptake in depth.

Whole genome sequencing reveals within-host genetic changes in paired meningococcal carriage isolates from Ethiopia.

BACKGROUND: Meningococcal colonization is a prerequisite for transmission and disease, but the bacterium only very infrequently causes disease while asymptomatic carriage is common. Carriage is highly dynamic, showing a great variety across time and space within and across populations, but also within individuals. The understanding of genetic changes in the meningococcus during carriage, when the bacteria resides in its natural niche, is important for understanding not only the carriage state, but the dynamics of the entire meningococcal population. RESULTS: Paired meningococcal isolates, obtained from 50 asymptomatic carriers about 2 months apart were analyzed with whole genome sequencing (WGS). Phylogenetic analysis revealed that most paired isolates from the same individual were closely related, and the average and median number of allelic differences between paired isolates defined as the same strain was 35. About twice as many differences were seen between isolates from different individuals within the same sequence type (ST). In 8%, different strains were detected at different time points. A difference in ST was observed in 6%, including an individual who was found to carry three different STs over the course of 9 weeks. One individual carried different strains from the same ST. In total, 566 of 1605 cgMLST genes had undergone within-host genetic changes in one or more pairs. The most frequently changed cgMLST gene was relA that was changed in 47% of pairs. Across the whole genome, pilE, differed mostly, in 85% of the pairs. The most frequent mechanisms of genetic difference between paired isolates were phase variation and recombination, including gene conversion. Different STs showed variation with regard to which genes that were most frequently changed, mostly due to absence/presence of phase variation. CONCLUSIONS: This study revealed within-host genetic differences in meningococcal isolates during short-term asymptomatic carriage. The most frequently changed genes were genes belonging to the pilin family, the restriction/modification system, opacity proteins and genes involved in glycosylation. Higher resolution genome-wide sequence typing is necessary to resolve the diversity of isolates and reveals genetic differences not discovered by traditional typing schemes, and would be the preferred choice of technology.

Seroepidemiology of Human Brucellosis Among Blood Donors in Southern Ethiopia: Calling Attention to a Neglected Zoonotic Disease.

Human brucellosis is neglected in southern Ethiopia. Although traditional food processing practices and animal husbandry which increase the risk of brucellosis are common, it has not been properly studied yet. This study was conducted to determine the seroepidemiology of brucellosis among apparently healthy individuals in southern Ethiopia. In the study, blood samples were collected to screen for serum agglutinins reactive to stained antigen of Brucella abortus Standard tube titration was performed for reactive serum to determine the titer of the agglutinin. A structured questionnaire was used to collect data on possible risk factors for brucellosis. The seroprevalence of human brucellosis in this study was found to be 10.6% (95% confidence interval = 7.0, 14.0). Possession of domestic ruminant animals, contact with ruminant animals, and husbandry practices at home were associated with seropositivity. The higher seroprevalence of human brucellosis in the study area needs attention and additional confirmatory investigation.

Prevalence and epidemiology of meningococcal carriage in Southern Ethiopia prior to implementation of MenAfriVac, a conjugate vaccine.

BACKGROUND: Neisseria meningitidis colonizes humans and transmits mainly by asymptomatic carriage. We sought to determine the prevalence and epidemiology of meningococcal carriage in Ethiopia prior to the introduction of MenAfriVac, a serogroup A meningococcal conjugate vaccine. METHODS: A cross-sectional meningococcal carriage study was conducted in Arba Minch, southern Ethiopia. A total of 7479 oropharyngeal samples were collected from 1 to 29 year old volunteers, between March and October, 2014. The swabs were cultured for N. meningitidis and Neisseria lactamica in Ethiopia. N. meningitidis isolates were confirmed and characterized by their serogroup, sequence type (ST) and PorA:FetA profile in Norway. RESULTS: Overall carriage prevalence was 6.6 %. There was no significant difference in overall carriage between male (6.7 %) and female (6.4 %) participants. Highest carriage prevalence (10.9 %) for females was found in the 15-19 years of age, while prevalence among males was highest (11.3 %) in the 20-24 age group. Non-groupable isolates dominated (76.4 %), followed by serogroups X (14.0 %) and W (5.9 %) isolates. No serogroup A was found. Most non-groupable isolates were ST-192. Serogroup W isolates were assigned to the ST-11 clonal complex, and serogroup X isolates to the ST-181 and ST-41/44 clonal complexes. Overall carriage prevalence of N. lactamica was 28.1 %. Carriage of N. meningitidis and N. lactamica varied depending on age and geographic area, but there was no association between carriage of the two species. CONCLUSIONS: Epidemic strains of serogroups W and X were circulating in this area of Ethiopia. As no serogroup A was found among the carriage isolates the immediate impact of mass-vaccination with MenAfriVac on transmission of N. meningitidis in this population is expected to be marginal.

DIAGNOSTIC PERFORMANCE EVALUATION OF THE SD BIOLINE MALARIA ANTIGEN AG PF/PAN TEST (05FK60) IN A MALARIA ENDEMIC AREA OF SOUTHERN ETHIOPIA.

Rapid diagnostic tests (RDTs) capable of detecting and differentiating Plasmodium species are needed in areas in which microscopy is unsuitable. This study was conducted to assess the diagnostic performance of the rapid test kit - SD BIOLINE Malaria Ag Pf/Pan(r) (05FK60) in an endemic area. Microscopy of Giemsa-stained blood films were performed to detect and estimate the Plasmodium density in malaria suspected patients. The performance of the SD BIOLINE Malaria Ag Pf/Pan test was evaluated using 272 Plasmodium-positive and 102 negative blood samples. The overall sensitivity of the SD BIOLINE Malaria Ag Pf/Pan test was 99.5% for P. falciparum and 92.6% for non-P. falciparum malaria infections. The respective specificity, PPV, and NPV of the test were 98.0, 98.4, and 99.0% for the diagnosis of P. falciparum, and 100.0 %, 100.0%, and 94.4% for non-P. falciparum species. The SD BIOLINE Malaria Ag Pf/Pan test showed an excellent performance in diagnosing Plasmodium infections in an endemic setting. Therefore, this point-of-care test could be used as an alternative to microscopy in places where P. falciparum is endemic and microscopy is unsuitable.

Genotype diversity of Mycobacterium isolates from children in Jimma, Ethiopia.

BACKGROUND: Paediatric tuberculosis (TB) is poorly addressed in Ethiopia and information about its magnitude and the genotype distribution of the causative Mycobacterium tuberculosis strains responsible for its spread are scanty. METHODS: Gastric lavage or sputum samples were collected from consecutively enrolled TB suspect children visiting Jimma University Hospital in 2011 and cultured on Middlebrook 7H11 and Löwenstein-Jensen media. Acid fast bacterial (AFB) isolates were subjected to molecular typing targeting regions of difference (RDs), 16S rDNA gene and the direct repeat (DR) region using multiplex polymerase chain reaction (mPCR), gene sequencing and spoligotyping, respectively. Molecular drug susceptibility testing of M. tuberculosis isolates was performed by Genotype®MTBDRplus line probe assay (LPA) (Hain Life Sciences, Germany). RESULTS: Gastric lavage (n = 43) or sputum (n = 58) samples were collected from 101 children and 31.7% (32/101) of the samples were positive for AFB by microscopy, culture and/or PCR. Out of 25 AFB isolates, 60% (15/25) were identified as M. tuberculosis by PCR, and 40% isolates (10/25) were confirmed to be non-tuberculous mycobacteria (NTM) by genus typing and 16S rDNA gene sequencing. Lineage classification assigned the M. tuberculosis strains into Euro-American (EUA, 66.7%; 10/15), East-African-Indian (EAI; 2/15), East-Asian (EA; 1/15) and Indio-Oceanic (IO; 1/15) lineages. Seven M. tuberculosis strains were new to the SpolDB4 database. All of the M. tuberculosis isolates were susceptible to isoniazid (INH) and rifampicin (RIF), except for one strain (of spoligotype SIT-149 or T3_ETH family) which had a mutation at the inhA locus which often confers resistance to INH (low level) and ethionamide. CONCLUSIONS: Analysis of the genetic population structure of paediatric M. tuberculosis strains suggested similarity with that of adults, indicating an on-going and active transmission of M. tuberculosis from adults to children in Ethiopia. There were no multidrug-resistant TB (MDR-TB) strains among the isolates.