Variations in helminth faecal egg counts in Kato-Katz thick smears and their implications in assessing infection status with Schistosoma mansoni

Examination of stool specimens by Kato-Katz (K-K) thick smears is the standard method recommended by the WHO for field diagnosis of intestinal schistosomiasis. However, there is increasing concern that this technique has low diagnostic sensitivity. In 326 study subjects, we compared the diagnostic yield of examining one, three or five Kato-Katz thick smears prepared from one stool specimen using 41.7 mg templates. In a subset of 169 subjects who had no demonstrable Schistosoma mansoni eggs in their first three Kato-Katz thick smears, we assessed the comparative advantage of examining an additional three Kato-Katz thick smears from another stool specimen, taken four weeks later, to that of cumulative yield obtained by examining all five Kato-Katz thick smears derived from the first stool specimen. For all helminth infections, single Kato-Katz thick smear-based prevalence estimates were significantly lower than those obtained from triplet or quintet Kato-Katz thick smears. Prevalence of S. mansoni infection based on single, triplet and quintet Kato-Katz thick smears from one stool specimen were 31.3%, 45.7% and 52.1%, respectively. Prevalence estimate of S. mansoni based on quintet Kato-Katz thick smears from the first day stool specimens was not different from cumulative estimate obtained with two triplet Kato-Katz thick smears from two stool specimens, 52.1% and 52.8%, respectively. In conclusion, either examination of quintet Kato-Katz thick smears from one stool specimen using 41.7 mg template or initial triplet Kato-Katz thick smears from one stool specimen, and if these are negative, followed by examination of additional triplet Kato-Katz thick smears from subsequent day stool specimen can adequately assess individuals for infection status with S. mansoni.     

Congenital Anomalies in Neonates Admitted to a Tertiary Hospital in Southwest Ethiopia: A Cross Sectional Study

BackgroundCongenital anomalies affect 2–3% of all live births. Anomalies of the central nervous system account for the highest incidence followed by that of the cardiovascular and renal systems. There is scarcity of data in developing countries like Ethiopia. The aim of the study was determining the magnitude and type of congenital anomalies and associated factors in neonates admitted to the neonatology ward of Jimma Medical Center, Southwest Ethiopia.MethodsInstitution based cross sectional study was done from March 1 to July 30, 2020. A total of 422 mother-infant pairs were enrolled into the study. Structured questionnaires were used to capture the socio-demographic, obstetric and medical characteristics of the mothers, demographic characteristics of the infants and type of congenital anomalies. Univariate and multivariate logistic regression analyses were done and results are presented as narratives and using figures and tables.ResultsCloser to one in five neonates admitted to the neonatology ward (78, 18.5%, 95%CI 14.7–22.3) had congenital anomalies; the majority (59, 13.98%) having only one type of anomaly. Anomalies of the nervous system (29, 6.87%) and gastrointestinal system (24, 5.68%) accounted for the majority of the cases. Inadequate antenatal care follow-up (p=0.018, AOR=1.9, 95%CI1.115, 3.257) and lack of folate supplementation during pregnancy (p=0.027, AOR=2.35, 95%CI 1.101, 5.015) were associated with congenital anomalies in the neonates.ConclusionCongenital anomalies account for significant number of admissions. Significant association was seen between neonatal congenital anomalies and poor antenatal attendance and lack of folic acid supplementation during pregnancy.     

Doubly robust and multiple-imputation-based generalized estimating equations

Generalized estimating equations (GEE), proposed by Liang and Zeger (1986), provide a popular method to analyze correlated non-Gaussian data. When data are incomplete, the GEE method suffers from its frequentist nature and inferences under this method are valid only under the strong assumption that the missing data are missing completely at random. When response data are missing at random, two modifications of GEE can be considered, based on inverse-probability weighting or on multiple imputation. The weighted GEE (WGEE) method involves weighting observations by the inverse of their probability of being observed. Imputation methods involve filling in missing observations with values predicted by an assumed imputation model, multiple times. The so-called doubly robust (DR) methods involve both a model for the weights and a predictive model for the missing observations given the observed ones. To yield consistent estimates, WGEE needs correct specification of the dropout model while imputation-based methodology needs a correctly specified imputation model. DR methods need correct specification of either the weight or the predictive model, but not necessarily both. Focusing on incomplete binary repeated measures, we study the relative performance of the singly robust and doubly robust versions of GEE in a variety of correctly and incorrectly specified models using simulation studies. Data from a clinical trial in onychomycosis further illustrate the method.     

Combination echinocandin-polyene treatment of murine mucormycosis

We previously found that caspofungin synergized with amphotericin B lipid complex in treating murine mucormycosis. We now report a similarly enhanced activity of liposomal amphotericin combined with micafungin or anidulafungin in mice with disseminated mucormycosis. The efficacy of combination echinocandin-polyene therapy for mucormycosis is a class effect.     

Assessment of the implementation of HIV-rapid test kits at different levels of health institutions in Ethiopia

OBJECTIVE: Evaluation and monitoring of Human Immunodeficiency Virus (HIV) testing reagents at the point of service is helpful to prevent the occurrence of problems related to testing and interpretation. To evaluate the implementation of HIV rapid test kits at the point of services in voluntarily counseling and testing (VCT) and diagnostic centers in Ethiopia. METHODS: The assessment was the third phase of evaluation of HIV rapid test kits in Ethiopia followed from phase-I and phase-II. Known proficiency testing panels, well-structured questionnaire (addressing type of tests, human resource and problems related to tests), onsite supervision and retesting of samples collected from sites were used to evaluate the performances of reagents and laboratories. RESULTS: Forty-four health institutions were included. Thirty-six (90.0%) health institutions had trained human resource on HIV testing. In 27 (61.4%) three types of HIV rapid test kits (Determine, Capillus and Unigold) were available. Serial-algorithm was used in all the laboratories. In 31 (70.4%) of them external quality control specimens were not used. Twenty two (50.0%) of the laboratories reported frequent shortage of reagents. All (100%) were able to identify negative specimens distributed. Positive proficiency panel samples were identified in 37 (94.8%) of the 39 laboratories. There was 98.3% agreement at a screening level between the sites and the central laboratory. Rate of discrepancy between screening and confirmatory assays was found to be 3.0% and 2.1% at the sites and at central laboratory, respectively. CONCLUSION: The test kits showed a good performance at the point of services in the field sites. However, continuous assessment of HIV test kits at the point of service and training of professionals on newly arrived techniques are recommended to have effective testing performance with acceptable sensitive and specific testing algorithm. Effective quality assurance program should be in place to support programs such as VCT, prevention of mother-to-child-transmission and antiretroviral therapy.     

Activation of caspase-8 and caspase-12 pathways by 7-ketocholesterol in human retinal pigment epithelial cells

PURPOSE: To determine whether caspase or cathepsin pathways are activated in human retinal pigment epithelial cells (ARPE-19) after exposure to 7-ketocholesterol (7kCh). METHODS: ARPE-19 cells were exposed to 7kCh with or without z-VAD-fmk, a pan-caspase inhibitor. Caspase-3, -8, and -9 activities were measured by a fluorochrome inhibitor of caspase (FLICA) assay. Caspase-12 activity was detected by Western blotting. RT-PCR was performed for 18s, mortalin-2, cathepsins B, D, and L/V2. RESULTS: At 24 hours, 7kCh-treated cultures had increased caspase-8 (P < 0.001) and caspase-3 (P < 0.001) activities compared with vehicle-treated cultures. 7kCh-induced caspase-3 activation was blocked by z-VAD-fmk (P < 0.001). Caspase-9 was not activated by 7kCh treatment (P > 0.05). Procaspase-12 was cleaved into its active form after treatment with 7kCh for 24 hours. At 6 hours, the RNA level for mortalin-2, a pro-survival gene, was upregulated. ARPE-19 cells did not express RNA for cathepsins B, D, or L/V2 under any conditions. CONCLUSIONS: In ARPE-19 cells, 7kCh-induced apoptosis uses the receptor-mediated caspase-8 pathway and the endoplasmic reticulum stress-induced caspase-12 pathway but not the mitochondrial caspase-9 pathway. The cathepsin pathways are not involved in 7kCh-induced cell death. These data demonstrate that 7kCh causes a loss of cell viability through caspase-dependent apoptosis and can act as an oxidative stressor leading to retinal pigment epithelial cell atrophy. Elucidating the specific apoptotic pathways involved may have therapeutic potential for AMD and other retinal diseases.