The Bacteriology and Its Virulence Factors in Neonatal Infections: Threats to Child Survival Strategies

Background. Neonatal infection refers to the infection of the newborn during the first twenty-eight days of life. It is one of the causes of infant morbidity and mortality worldwide. The aim of the study is to determine the relative contribution of the different pathogens to the overall disease burden. It will also determine the mechanisms of virulence of these pathogens that cause neonatal infections at Chukwuemeka Odumegwu Ojukwu University Teaching Hospital (COOUTH), Awka. Methods. Biological samples were collected from 30 neonates admitted at the special care baby unit (SCBU) of COOUTH and cultured using selective media and nutrient agar. The isolates were identified using microbiological and biochemical tests. The antibiogram study was determined using Kirby-Bauer disc diffusion method on Mueller Hinton Agar. Several methods previously reported in literature were used for the characterization of the virulence factors. Results. From the 30 blood samples collected, Pseudomonas spp. (19.7%), Escherichia coli (23%), Salmonella spp. (24.6%), and Staphylococcus aureus (32.8%) were isolated. Male to female ratio of study population was 1.5: 1. The isolates were 100 % resistant to ticarcillin, cephalothin, ceftazidime, and cefuroxime but appreciably susceptible to only levofloxacin (88.85%). They were moderately susceptible to ceftriaxone/sulbactam (39.05%) and azithromycin (26.46%). Common virulence factors identified among the isolates (up to 90 %) were hemolysin, biofilm formation, and acid resistance. Less common virulence factors were proteases (50 %), deoxyribonucleases (50 %), enterotoxins (63%), and lipopolysaccharide (70%). The virulence factors were found mostly among the S. aureus isolates. Conclusions. Pseudomonas spp., Escherichia coli, Salmonella spp., and Staphylococcus aureus were implicated in neonatal infections in the center and most of them were resistant to conventional antibiotics. The organisms showed marked virulence and multidrug resistance properties. Levofloxacin, a fluoroquinolone, had superior activity on the isolates compared to other antibiotics used in the study

Carbapenem-Resistant Enterobacteriaceae Posing a Dilemma in Effective Healthcare Delivery

The emergence and spread of Carbapenem-resistant Enterobacteriaceae (CRE) is seriously posing threats in effective healthcare delivery. The aim of this study was to ascertain the emergence of CRE at Chukwuemeka Odumegwu Ojukwu University Teaching Hospital (COOUTH) Awka. Biological samples were collected from 153 consenting patient from 5 clinics in the hospital. The isolates were identified using standard microbiological protocols. Susceptibility to meropenem was done using Kirby-Bauer disc diffusion method on Mueller Hinton Agar. A total of 153 patients were recruited in this study. About one half of those from rural, 63.64% from Sub-urban and 42.27% from urban areas had significant E. coli and Klebsiella spp infections. The male: female ratio of the Enterobacteriaceae infection was 1:1. Almost as much inpatient as outpatient study participants had the infections. The infections were observed mostly on participants with lower educational status. The unmarried individuals were most infected compared to their married counterparts. Enterobacteriaceae infection rate was 50.98%. Of this, 28.21% had CRE infection while the overall prevalence of the CRE in the studied population was 14.38% (22/153). This study shows that CRE is quickly emerging in both community and hospital environments. Klebsiella spp was the most common CRE in this hospital especially Klebsiella oxytoca. Hospitalization was a strong risk factor in the CRE infections. Rapid and accurate detection is critical for their effective management and control

Clinical illness and outcomes in Nigerian children with persistent early-appearing anaemia following initiation of artemisinin-based combination treatments of uncomplicated falciparum malaria

In non-anaemic children with malaria, early-appearing anaemia (EAA) is common following artemisinin-based combination treatments (ACTs) and it may become persistent (PEAA). The factors contributing to and kinetics of resolution of the deficit in haematocrit from baseline (DIHFB) characteristic of ACTs-related PEAA were evaluated in 540 consecutive children with malaria treated with artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine. Asymptomatic PEAA occurred in 62 children. In a multiple logistic regression model, a duration of illness ≤3 days before presentation, haematocrit <35% before and <25% one day after treatment initiation, drug attributable fall in haematocrit ≥6%, and treatment with dihydroartemisinin-piperaquine independently predicted PEAA. Overall, mean DIHFB was 5.7% (95% CI 4.8–6.6) 7 days after treatment initiation and was similar for all treatments. Time to 90% reduction in DIHFB was significantly longer in artemether-lumefantrine-treated children compared with other treatments. In a one compartment model, declines in DIHFB were monoexponential with overall mean estimated half-time of 3.9 days (95% CI 2.6–5.1), Cmax of 7.6% (95% CI 6.7–8.4), and Vd of 0.17 L/kg (95% CI 0.04–0.95). In Bland-Altman analyses, overall mean anaemia recovery time (AnRT) of 17.4 days (95% CI 15.5–19.4) showed insignificant bias with 4, 5 or 6 multiples of half-time of DIHFB. Ten children after recovery from PEAA progressed to late-appearing anaemia (LAA). Progression was associated with female gender and artesunate-amodiaquine treatment. Asymptomatic PEAA is common following ACTs. PEAA or its progression to LAA may have implications for case and community management of anaemia and for anaemia control efforts in sub-Saharan Africa where ACTs have become first-line antimalarials. Trial registration: Pan Africa Clinical Trial Registration PACTR201709002064150, 1 March 2017 http://www.pactr.or

Parasite reduction ratio one day after initiation of artemisinin-based combination therapies and its relationship with parasite clearance time in acutely malarious children

Abstract Background In acute falciparum malaria, asexual parasite reduction ratio two days post-treatment initiation (PRRD2) ≥ 10 000 per cycle has been used as a measure of the rapid clearance of parasitaemia and efficacy of artemisinin derivatives. However, there is little evaluation of alternative measures; for example, parasite reduction ratio one day after treatment initiation (PRRD1) and its relationship with parasite clearance time (PCT) or PRRD2. This study evaluated the use of PRRD1 as a measure of responsiveness to antimalarial drugs. Methods In acutely malarious children treated with artesunate-amodiaquine (AA), artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHP), the relationships between PRRD1 or PRRD2 and PCT, and between PRRD1 and PRRD2 were evaluated using linear regression. Agreement between estimates of PCT using PRRD1 and PRRD2 linear regression equations was evaluated using the Bland-Altman analysis. Predictors of PRRD1 > 5000 per half cycle and PRRD2 ≥ 10 000 per cycle were evaluated using stepwise multiple logistic regression models. Using the linear regression equation of the relationship between PRRD1 and PCT previously generated in half of the DHP-treated children during the early study phase, PCT estimates were compared in a prospective blinded manner with PCTs determined by microscopy during the later study phase in the remaining half. Results In 919 malarious children, PRRD1 was significantly higher in DHP- and AA-treated compared with AL-treated children (P  15 months, parasitaemia > 10 000/μl and DHP treatment independently predicted PRRD1 > 5000 per half cycle, while age > 30 months, haematocrit ≥31%, body temperature > 37.4 °C, parasitaemia > 100 000/μl, PRRD1 value > 1000 and no gametocytaemia independently predicted PRRD2 ≥ 10 000 per cycle. Using the linear regression equation generated during the early phase in 166 DHP-treated children, PCT estimates and PCTs determined by microscopy in the 155 children in the later phase were similar in the same patients. Conclusions PRRD1 and estimates of PCT using PRRD1 linear regression equation of PRRD1 and PCT can be used in therapeutic efficacy studies. Trial registration Pan African Clinical Trial Registration PACTR201709002064150, 1 March 2017, http://www.pactr.or

Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials

Abstract Background Artemisinin-based combination therapies (ACTs) have remained efficacious treatments of acute falciparum malaria in many endemic areas but there is little evaluation of factors contributing to the anaemia of acute falciparum malaria following long term adoption of ACTs as first-line antimalarials in African children. Methods Malarious 4% were evaluated by stepwise multiple logistic regression models. Survival analysis and kinetics of DAFH were evaluated by Kaplan-Meier estimator and non-compartment model, respectively. Results Pre-treatment, 355 of 959 children were anaemic. Duration of illness >2 days and parasitaemia ≤10,000 μL−1 were independent predictors of anaemia pre-treatment. EAA occurred in 301 of 604 children. Predictors of EAA were age ≤ 15 months, history of fever pre-treatment and enrolment haematocrit ≤35%. The probabilities of progression from normal haematocrit to EAA were similar for all treatments. MAFH >4% occurred in 446 of 694 children; its predictors were anaemia pre-treatment, enrolment parasitaemia ≤50,000 μL−1, parasitaemia one day post-treatment initiation and gametocytaemia. DAFH >4% occurred in 334 of 719 children; its predictors were history of fever pre-and fever 1 day post-treatment initiation, haematocrit ≥37%, and parasitaemia >100,000 μL−1. In 432 children, declines in DAFH deficits were monoexponential with overall estimated half-time of 2.2d (95% CI 1.9–2.6). Area under curve of deficits in DAFH versus time and estimated half-time were significantly higher in non-anaemic children indicating greater loss of haematocrit in these children. Conclusion After ten years of adoption of ACTs, anaemia is common pre-and early post-treatment, falls in haematocrit attributable to a single infection is high, and DAFH >4% is common and significantly lower in anaemic compared to non-anaemic Nigerian children. Trial registration Pan African Clinical Trial Registry (PACTR) [ PACTR201709002064150, 1 March 2017 ]