Treatment administered to newborns with congenital syphilis during a penicillin shortage in 2015, Fortaleza, Brazil.

BACKGROUND: Between 2014 and 2016, Brazil experienced a severe shortage in penicillin supply, resulting in a lack of treatment among some pregnant women and newborns with syphilis and the use of non-evidence-based regimens. This study evaluated all live births in Fortaleza reported with CS in 2015 in order to identify the different therapeutic regimens used in newborns during this period of penicillin shortage. METHODS: A retrospective cross-sectional study design was conducted using manually extracted data from medical chart review of maternal and infant cases delivered in 2015 from all public maternity hospitals in the city of Fortaleza. Data collection occurred from June 2017 to July 2018. RESULTS: A total of 575 congenital syphilis cases were reported to the municipality of Fortaleza during 2015 and 469 (81.5%) were analyzed. Of these, only 210 (44.8%) were treated with a nationally-recommended treatment. As alternative therapeutic options, ceftriaxone was used in 65 (13.8%), Cefazolin in 15 (3.2%) and the combination of more than one drug in 179 (38.2%). Newborns with serum VDRL titers ≥1:16 (p = 0.021), who had some clinical manifestation at birth (p = 0.003), who were born premature (p <  0.001), with low birth weight (p = 0.010), with jaundice indicative of the need for phototherapy (p = 0.019) and with hepatomegaly (p = 0.045) were more likely to be treated with penicillin according to national treatment guidelines compared to newborns treated with other regimens. CONCLUSION: During the period of shortage of penicillin in Fortaleza, less than half of the infants reported with CS were treated with a nationally-recommended regimen, the remaining received treatment with medications available in the hospital of birth including drugs that are not part of nationally or internationally-recommended treatment recommendations.

Inclusion of pregnant women in COVID-19 treatment trials: a review and global call to action.

Inclusion of pregnant women in COVID-19 clinical trials would allow evaluation of effective therapies that might improve maternal health, pregnancy, and birth outcomes, and avoid the delay of developing treatment recommendations for pregnant women. We explored the inclusion of pregnant women in treatment trials of COVID-19 by reviewing ten international clinical trial registries at two timepoints in 2020. We identified 155 COVID-19 treatment studies of non-biological drugs for the April 7-10, 2020 timepoint, of which 124 (80%) specifically excluded pregnant women. The same registry search for the July 10-15, 2020 timepoint, yielded 722 treatment studies, of which 538 (75%) specifically excluded pregnant women. We then focused on studies that included at least one of six drugs (remdesivir, lopinavir-ritonavir, interferon beta, corticosteroids, chloroquine and hydroxychloroquine, and ivermectin) under evaluation for COVID-19. Of 176 such studies, 130 (74%) listed pregnancy as an exclusion criterion. Of 35 studies that evaluated high-dose vitamin treatment for COVID-19, 27 (77%) excluded pregnant women. Despite the surge in treatment studies for COVID-19, the proportion excluding pregnant women remains consistent. Exclusion was not well justified as many of the treatments being evaluated have no or low safety concerns during pregnancy. Inclusion of pregnant women in clinical treatment trials is urgently needed to identify effective COVID-19 treatment for this population.

Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra).

BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

Trials and projects on cervical cancer and human papillomavirus prevention in sub-Saharan Africa.

Cervical cancer is the leading cause of cancer morbidity and mortality in women in sub-Saharan Africa (SSA), accounting for about 50,000 deaths annually. Until recently, cytology was the gold standard for screening and prevention of cervical cancer. This method of screening has not been successful in SSA due to a lack of human, financial and material resources and poor health care infrastructure. It is estimated that less than 5% of at risk women have ever being screened. In the past two decades alternative approaches to cytology for cervical cancer screening have been evaluated in low- and medium-income countries. Visual inspection with acetic acid (VIA) and/or Lugol's iodine (VILI) have been shown to have adequate sensitivity, although low specificity, in a number of cross-sectional research and demonstration projects. Visual inspection methods require minimal resources, are technologically accessible, and are feasible for screening for precancerous lesions. Linking screening with VIA/VILI to treatment with cryotherapy may enable screening and treatment to take place in one visit, but this is likely to result in large numbers of women being subjected to unnecessary treatment. A number of studies have shown that cryotherapy is not associated with significant side effects or complications and is well tolerated. Creating the infrastructure for screening of older women is considered desirable, despite the limitations of visual inspection methods as screening tests. Understanding the role of human papillomavirus (HPV) infection in the etiology of cervical cancer and the discovery of HPV rapid test kits, as well as the development of vaccines against the HPV oncogenic types, have created new opportunities for prevention of cervical cancer. Trials and projects have established (and are still ongoing) the feasibility of using these molecular tests for screening. The ultimate in prevention method is primary prevention, offered by the advent of prophylactic vaccines against the most important oncogenic types, namely HPV16 and 18. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Sub-Saharan Africa Region" Vaccine Volume 31, Supplement 5, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

Effective health interventions for adolescents that could be integrated with human papillomavirus vaccination programs.

PURPOSE: We reviewed published data to identify health interventions for 9-15-year-old girls and boys that could to be usefully integrated with programs of human papillomavirus (HPV) vaccination in low- and middle-income countries (LMICs). METHODS: Relevant literature reviews, bibliographic databases, and journals were searched to identify health-related interventions, other than immunizations, that had been found to have beneficial outcomes among adolescent girls and/or boys. An intervention was excluded if there was no evidence of its effective delivery in LMICs or no demonstrated potential for its adaptation for delivery in such countries, and/or if there was, apparently, no feasible way in which it could be delivered during a course of HPV vaccinations. RESULTS: Overall, 33 different interventions were found to have had beneficial outcomes among adolescents living in LMICs. Of these, 19 were excluded because they were deemed too expensive or too difficult to deliver within the calendar of a HPV vaccination program. The remaining 14 health-related interventions, in the fields of screening (for schistosomiasis and defects in vision), health education (on mosquito-borne diseases, the benefits of exercise, accessing health care, and sexual and reproductive health), skills building (improving condom usage) and delivery of commodities (anthelminthic drugs, vitamin A supplements, soap and/or bed nets) were deemed potential candidates for delivery in conjunction with the HPV vaccine. CONCLUSIONS: The potential benefits and selection of other health-related interventions that are delivered in conjunction with HPV vaccine will be influenced by a range of factors, including the ease of delivery, the epidemiology of the priority health problems affecting adolescents, the vaccine delivery schedule, and various environmental, economic, and social factors. However, there appear to be several interventions that could usefully be integrated in many, if not all, HPV vaccination programs. The ability to deliver multiple interventions along with HPV vaccine could not only offer important efficiencies but also serve as an entry point to increase adolescents' access to health care and services.

Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data.

BACKGROUND: The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥ 90% of pregnant women to be tested for syphilis and ≥ 90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. METHODS AND FINDINGS: Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was "probable active," and for testing and treatment coverage. CONCLUSIONS: Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment. In this analysis, most adverse outcomes occurred among women who attended ANC but were not tested or treated for syphilis, highlighting the need to improve the quality of ANC as well as ANC coverage. In addition, improved ANC data on syphilis testing coverage, positivity, and treatment are needed. Please see later in the article for the Editors' Summary.