Asymptomatic bacteriuria: effect of screening and treatment on maternal and fetal outcome

INTRODUCTION: Urinary tract infections are the most common bacterial infections during pregnancy and are a common cause of serious maternal and perinatal morbidity. A urinary tract infection may manifest as asymptomatic bacteriuria, acute urethritis or acute cystitis or pyelonephritis. With appropriate screening and treatment this morbidity can be limited. Asymptomatic bacteriuria refers to persistent actively multiplying bacteria within the urinary tract in women who have no symptoms. Worldwide the incidence varies from 5-10% and depends on age, parity, race and socioeconomic status. Urinary tract infections are the most common bacterial infections during pregnancy. They occur in same frequency in pregnancy as in nonpregnant women. However the consequences of infection are far more serious during pregnancy warranting prompt diagnosis and treatment of infection. AIMS OF THE STUDY: 1. To find out the prevalence of asymptomatic bacteriuria in antenatal women at their first antenatal visit. 2. To know the association of bacteriuria with age, parity and socioeconomic status. 3. To know the common causative organism and treatment response to antibiotics 4. To find whether the incidence of symptomatic UTIs, preterm delivery and low birth weight infants decreases by treatment of asymptomatic bacteriuria 5. To find the correlation between asymptomatic bacteriuria and hypertensive disorders of pregnancy and maternal anemia. MATERIALS AND METHODS: During the period from September 2006 to August 2007, 500 antenatal women between 12 to 16 weeks of gestation attending antenatal O.P. at Women and Children Hospital, Egmore were randomly selected. All the women were instructed to wash hands and clean perineum with water and to part the labia with one hand and to collect midstream urine sample without either the initial portion or the after drip. Thus clean voided midstream urine sample was collected and sent to laboratory within 2 hrs. The urine sample of each patient was tested for the presence of nitrite by dipstick and one portion was sent for routine urine analysis and another portion sent for culture and sensitivity and colony count. Occurrence of pink color in the dipstick at the end of 2 minutes indicated positive nitrite test. Colony count of more than one lakh colony forming units of a single uropathogens per ml was taken as diagnostic of asymptomatic bacteriuria. Treatment was given to all patients with significant bacteriuria with oral cephalexin 500mg bd X 7days. Urine culture was repeated one week after completion of treatment. Two patients had persistant bacteriuria were treated with Inj. Gentamicin 80mg bd X 5days and then repeat cultures were negative. Both bacteriurics and non bacteriurics were followed at monthly intervals. They were examined for clinical parameters like weight gain, blood pressure and complete hemogram, rountine urine analysis blood urea, sugar and serum creatinine. For all treated patients urine culture was repeated once in late second trimester and once in third trimester. For other patients, urine culture was repeated once in third trimester. All patients were followed up to delivery and discharge. The occurrence of acute symptomatic urinary tract infections (pyelonephritis and cystitis), preterm labor and delivery, hypertensive disorders and maternal anemia and low birth weight infants were noted. The perinatal outcome was studied. Inclusion criteria - 1. Pregnant women between 12 to 16 weeks of gestation irrespective of parity. 2. The pregnant women randomly selected had no symptoms or signs of UTI. 3. All women had normal BP. 4. Unskilled laborers on unfixed wages were considered to belong to socioeconomic class V. Skilled and semiskilled workers on fixed wages were considered class III and IV respectively. 5. In the absence of symptoms colony count of 105 or more colony forming units per ml of urine was taken as significant bacteriuria. Exclusion criteria - 1. Pregnant women taking antibiotics for any reason were excluded. 2. Antenatal women with symptoms of UTI such as frequency, urgency, dysuria and supra pubic pain were excluded. 3. During the study women who were found to have hydramnios, multiple pregnancy, placenta praevia, congenital anomalies were excluded from the study. 4. Patients with anemia and hypertension at the first prenatal visit were excluded. SUMMARY: 500 antenatal women attending antenatal O.P. at Women and Children Hospital, Egmore, Chennai were screened for ABU at the first prenatal visit between 12-16 weeks of gestation during the period from September 2006 to August 2007 with quantitative urine culture. Five patients who were found to have hydramnios, multiple pregnancy, placenta praevia and congenital anomaly of fetus were excluded from the study. 35 women were lost during followup. 460 women were taken into account for statistical analysis. Both bacteriurics and non bacteriurics were followed upto delivery and the adverse effects of bacteriuria in mother and neonate were observed and analyzed. The results are summarized as follows: The incidence of ABU in the study group was 11.73% attributed to low socioeconomic status of the women. Screening at the first antenatal visit 54 pregnant women were found to be culture positive for bacteria and most were in the age group of 20 – 29 years ( 15.8%) and most were primigravida (13.6%) which may be related to early marriage and peak sexual activity which favors periurethral colonization of bacteria. Among the bacteriurics 70% were primigravidas. This shows that these women might have had bacteriuria even before marriage, which has been unmasked by pregnancy changes in the urinary tract. Among the bacteriurics 80% belonged to socioeconomic class V an important association found in literature. A significant proportion of patients had past history of urinary tract infection and treatment with antibiotics. Nitrite test was positive in only 94% of bacteriurics suggesting that it is not sensitive enough to be used as sole screening test. Pyuria was present in 62% of bacteriurics, which cleared after antimicrobial treatment suggesting infection than mere colonization. Acute cystitis developed in 6 women among bacteriurics and 4 women in non-bacteriuric group. No cases of pyelonephritis occurred in both groups suggesting that early screening and treatment of ABU is essential in preventing this complication. E. coli was the most common causative organism as in various studies world wide. Resistance to ampicillin was present in 30%. The incidence of anemia and preeclampsia in both groups was comparable and this study did not show a cause and effect relationship. The occurrence of low birth weight infants and preterm delivery was reduced similar to that in non-bacteriurics suggesting the importance of screening and treatment of ABU during pregnancy. CONCLUSION: From this study it is concluded that in view of potentially serious sequelae of asymptomatic bacteriuria, routine screening of all pregnant women at their first prenatal visit is recommended and that antibiotic treatment and follow up of cases helps in the reduction in the incidence of symptomatic urinary tract infections, preterm delivery and low birth weight infants

Mutation of the Zebrafish Nucleoporin elys Sensitizes Tissue Progenitors to Replication Stress

The recessive lethal mutation flotte lotte (flo) disrupts development of the zebrafish digestive system and other tissues. We show that flo encodes the ortholog of Mel-28/Elys, a highly conserved gene that has been shown to be required for nuclear integrity in worms and nuclear pore complex (NPC) assembly in amphibian and mammalian cells. Maternal elys expression sustains zebrafish flo mutants to larval stages when cells in proliferative tissues that lack nuclear pores undergo cell cycle arrest and apoptosis. p53 mutation rescues apoptosis in the flo retina and optic tectum, but not in the intestine, where the checkpoint kinase Chk2 is activated. Chk2 inhibition and replication stress induced by DNA synthesis inhibitors were lethal to flo larvae. By contrast, flo mutants were not sensitized to agents that cause DNA double strand breaks, thus showing that loss of Elys disrupts responses to selected replication inhibitors. Elys binds Mcm2-7 complexes derived from Xenopus egg extracts. Mutation of elys reduced chromatin binding of Mcm2, but not binding of Mcm3 or Mcm4 in the flo intestine. These in vivo data indicate a role for Elys in Mcm2-chromatin interactions. Furthermore, they support a recently proposed model in which replication origins licensed by excess Mcm2-7 are required for the survival of human cells exposed to replication stress

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Clinical Evaluation of the effect of Asuvaathi Chooranam for the treatment of Mannun Veluppu Noi

The disease Mannun veluppu noi was taken for the clinical study with Asuvaathi Chooranam as Oral route. For the clinical study, 40 children were selected based on the approved protocol. This study has been approved By GSMC-VI-IEC/2019-Br.IV/15-09.04.2019. Animal studies were carried out after obtaining approval from the Instituitional Animal Ethical Committee (IAEC) Approved and its number RPC/IAEC/004/2021, SARPC/IAEC/04/2021 and the trial was registered in Clinical Trial Registry of India CTRI/2019. Hence the study is safely executed on children and there was no adverse drug reactions noted during the study period. 40 children were treated with trial medicine in OPD, IPD of Department of Kuzhanthai Maruthuvam. Before, treatment, the signs and symptoms for Mannun Veluppu Noi are noticed and confirmed by lab investigation. Findings revealed about the impact of the disease in the body. During treatment, the dose of 500 mg-1gm of Asuvaathi Chooranam, twice a day after meals with buffalo whey, has been given to children affected by Mannun Veluppu Noi depending on their age, body weight and severity of the disease. No adverse effects were reported during or after the course of treatment. The drug selected for the study was found to be easily available drug, easy to administrate and also more effective against Mannun Veluppu Noi without any adverse effects. CONCLUSION: In the study, the patients were selected based on Inclusion and Exclusion criteria. It is clear that Mannun Veluppu Noi is caused due to derangement of pitham followed by derangement of vatham and kabham. The trial drug Asuvaathi Chooranam is easily available and cost effective taken 48 days for study. It raises the haemoglobin level in Iron deficiency anemia patients when given regularly along with other healthy supplementary diets. Symptomatically relieves within 1 week and the children were improved with good appetite. The pre-clinical studies done for the trial drug had been proved effective for Mannun Veluppu Noi and the study proved that the trial drug has given 85% good results in my clinical trial. No adverse effects were noted the entire course of treatment

Mosquito repellent activity of Calotropis gigantea (Apocynaceae) flower extracts against the filarial vector Culex quinquefasciatus

Plan: To assess the repellent efficacy of the flower extracts of Calotropis gigantea against Culex quinquefasciatus mosquito and to screen the bioactive compounds present in the flower extract. Methodology: The flower extracts of Calotropis gigantea were extracted with petroleum ether, chloroform and ethanol and the efficacy of the extracts as repellent were assessed on three day blood starved female Culex quinquefasciatus mosquito. The repellent study was following the method of WHO (1996). Outcome: The results suggested that flower ethanol extract of Calotropis gigantea showed a higher repellency on the adult of female Culex quinquefasciatus mosquito than the other two extracts. The repellent activity was found to be dose dependent and the percentage of protection was found to be directly proportional to the concentration of extract. The results of phytochemical screening showed the presence of bioactive compounds such as alkaloids, tannins, phenol, flavonoids, sterols, anthraquinone, proteins and quinones in the flower extract. It may be concluded from the result that ethanol extract of Calotropis gigantea flower was effective in mosquito vector control and has an excellent potential in controlling the mosquito

Morphometric geometric study of wing shape in <i>Culex quinquefasciatus</i> Say (Diptera: Culicidae) from Tamil Nadu, India

The morphometric geometric study was carried out in 10 males and 10 females of Culex quinquefasciatus. There are 23 landmarks corresponding to points at which wing veins either branch or intersect the margin of the wing. Relative warp analysis has been proved to be very efficient in distinguishing the variation of shape in male and female wings. The multivariate analysis of co-variance (MANCOVA) showed a clear separation of the male and female wings