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Introduction: Puerperal sepsis causes 10% of maternal deaths in Africa, but prospective studies on incidence, microbiology and antimicrobial resistance are lacking. Methods: We performed a prospective cohort study of 4,231 Ugandan women presenting to a regional referral hospital for delivery or postpartum care, measured vital signs after delivery, performed structured physical exam, symptom questionnaire, and microbiologic evaluation of febrile and hypothermic women. Malaria rapid diagnostic testing, blood and urine cultures were performed aseptically and processed at Epicentre Mbarara Research Centre. Antimicrobial susceptibility and breakpoints were determined using disk diffusion per EUCAST standards. Hospital diagnoses, treatments and outcomes were abstracted from patient charts. Results: Mean age was 25 years, 12% were HIV-infected, and 50% had cesarean deliveries. Approximately 5% (205/4176) with ≥1 temperature measurement recorded developed postpartum fever or hypothermia; blood and urine samples were collected from 174 (85%), and 17 others were evaluated clinically. Eighty-four (48%) had at least one confirmed source of infection: 39% (76/193) clinical postpartum endometritis, 14% (25/174) urinary tract infection (UTI), 3% (5/174) bloodstream infection. Another 3% (5/174) had malaria. Overall, 30/174 (17%) had positive blood or urine cultures, and Acinetobacter species were the most common bacteria isolated. Of 25 Gram-negatives isolated, 20 (80%) were multidrug-resistant and cefepime non-susceptible. Conclusions: For women in rural Uganda with postpartum fever, we found a high rate of antibiotic resistance among cultured urinary and bloodstream infections, including cephalosporin-resistant Acinetobacter species. Increasing availability of microbiology testing to inform appropriate antibiotic use, development of antimicrobial stewardship programs, and strengthening infection control practices should be high priorities. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is now considered the second leading cause of death among women worldwide, and its incidence has reached alarming levels, especially in developing countries. Similarly, high grade squamous intraepithelial lesion (HSIL), the precursor stage for cervical cancer, represents a growing health problem among younger women as the HSIL management regimes that have been developed are not fully effective. From the etiological point of view, the presence of Human Papillomavirus (HPV) has been demonstrated to play a crucial role for developing cervical malignancies, and viral DNA has been detected in 99.7% of cervical tumors at the later stages. CIGB-300 is a novel cyclic synthetic peptide that induces apoptosis in malignant cells and elicits antitumor activity in cancer animal models. CIGB-300 impairs the Casein Kinase (CK2) phosphorylation, by targeting the substrate's phosphoaceptor domain. Based on the perspectives of CIGB-300 to treat cancer, this "first-in-human" study investigated its safety and tolerability in patients with cervical malignancies. Methods: Thirty-one women with colposcopically and histologically diagnosed microinvasive or pre-invasive cervical cancer were enrolled in a dose escalating study. CIGB-300 was administered sequentially at 14, 70, 245 and 490 mg by intralesional injections during 5 consecutive days to groups of 7 - 10 patients. Toxicity was monitored daily until fifteen days after the end of treatment, when patients underwent conization. Digital colposcopy, histology, and HPV status were also evaluated. Results: No maximum-tolerated dose or dose-limiting toxicity was achieved. The most frequent local events were pain, bleeding, hematoma and erythema at the injection site. The systemic adverse events were rash, facial edema, itching, hot flashes, and localized cramps. 75% of the patients experienced a significant lesion reduction at colposcopy and 19% exhibited full histological regression. HPV DNA was negative in 48% of the previously positive patients. Long term follow-up did not reveal recurrences or adverse events. Conclusion: CIGB 300 was safe and well tolerated. This is the first clinical trial where a drug has been used to target the CK2 phosphoaceptor domain providing an early proof-of-principle of a possible clinical benefit. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of recent prospective data on the incidence of postpartum infections and associated risk factors in sub-Saharan Africa. Retrospective studies estimate that puerperal sepsis causes approximately 10% of maternal deaths in Africa.Methods: We enrolled 4231 women presenting to a Ugandan regional referral hospital for delivery or postpartum care into a prospective cohort and measured vital signs postpartum. Women developing fever (> 38.0 °C) or hypothermia (< 36.0 °C) underwent symptom questionnaire, structured physical exam, malaria testing, blood, and urine cultures. Demographic, treatment, and post-discharge outcomes data were collected from febrile/hypothermic women and a random sample of 1708 normothermic women. The primary outcome was in-hospital postpartum infection. Multivariable logistic regression was used to determine factors independently associated with postpartum fever/hypothermia and with confirmed infection.Results: Overall, 4176/4231 (99%) had ≥1 temperature measured and 205/4231 (5%) were febrile or hypothermic. An additional 1708 normothermic women were randomly selected for additional data collection, for a total sample size of 1913 participants, 1730 (90%) of whom had complete data. The mean age was 25 years, 214 (12%) were HIV-infected, 874 (51%) delivered by cesarean and 662 (38%) were primigravidae. Among febrile/hypothermic participants, 174/205 (85%) underwent full clinical and microbiological evaluation for infection, and an additional 24 (12%) had a partial evaluation. Overall, 84/4231 (2%) of participants met criteria for one or more in-hospital postpartum infections. Endometritis was the most common, identified in 76/193 (39%) of women evaluated clinically. Twenty-five of 175 (14%) participants with urinalysis and urine culture results met criteria for urinary tract infection. Bloodstream infection was diagnosed in 5/185 (3%) participants with blood culture results. Another 5/186 (3%) tested positive for malaria. Cesarean delivery was independently associated with incident, in-hospital postpartum infection (aOR 3.9, 95% CI 1.5-10.3, P = 0.006), while antenatal clinic attendance was associated with reduced odds (aOR 0.4, 95% CI 0.2-0.9, P = 0.02). There was no difference in in-hospital maternal deaths between the febrile/hypothermic (1, 0.5%) and normothermic groups (0, P = 0.11).Conclusions: Among rural Ugandan women, postpartum infection incidence was low overall, and cesarean delivery was independently associated with postpartum infection while antenatal clinic attendance was protective. [ABSTRACT FROM AUTHOR]