Trimethoprim-Sulfamethoxazole Plus Azithromycin to Prevent Malaria and Sexually Transmitted Infections in Pregnant Women With HIV (PREMISE): A Randomized, Double-Masked, Placebo-Controlled, Phase IIB Clinical Trial.

Background: This trial tested the effectiveness of a novel regimen to prevent malaria and sexually transmitted infections (STIs) among pregnant women with HIV in Cameroon. Our hypothesis was that the addition of azithromycin (AZ) to standard daily trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis would reduce malaria and STI infection rates at delivery. Methods: Pregnant women with HIV at gestational age <28 weeks were randomized to adjunctive monthly oral AZ 1 g daily or placebo for 3 days and both groups received daily standard oral TMP-SMX through delivery. Primary outcomes were (1) positive peripheral malaria infection by microscopy or polymerase chain reaction and (2) composite bacterial genital STI (Chlamydia trachomatis, Neisseria gonorrhoeae, or syphilis) at delivery. Relative risk and 95% confidence intervals were estimated using 2 × 2 tables with significance as P < .05. Results: Pregnant women with HIV (n = 308) were enrolled between March 2018 and August 2020: 155 women were randomized to TMP-SMX-AZ and 153 women to TMP-SMX-placebo. Groups were similar at baseline and loss to follow up was 3.2%. There was no difference in the proportion with malaria (16.3% in TMP-SMX-AZ vs 13.2% in TMP-SMX; relative risk, 1.24 [95% confidence interval, .71-2.16]) or STI at delivery (4.2% in TMP-SMX-AZ vs 5.8% in TMP-SMX; relative risk, 0.72 [95% confidence interval, .26-2.03]). Adverse birth outcomes were not significantly different, albeit lower in the TMP-SMX-AZ arm (preterm delivery 6.7% vs 10.7% [P = .3]; low birthweight 3.4% vs 5.4% [P = .6]). Conclusions: The addition of monthly azithromycin to daily TMP-SMX prophylaxis in pregnant women living with HIV in Cameroon did not reduce the risk of malaria or bacterial STI at delivery.

Predicting peripartum infection in laboring patients at high risk in Cameroon, Africa.

OBJECTIVE: To develop a predictive model for peripartum infection among high risk laboring patients in Cameroon, Africa. STUDY DESIGN: We conducted a secondary analysis of the Cameroon Antibiotic Prophylaxis Trial (NCT03248297), a multicenter 3-arm double-blind randomized controlled trial of oral azithromycin ± amoxicillin among term pregnancies with prolonged labor or rupture of membranes in Cameroon 1/2018-5/2020. Patients with chorioamnionitis prior to randomization, study drug contraindications, or planned cesarean were excluded. The outcome of interest was a composite of maternal peripartum infection (chorioamnionitis, endometritis, sepsis by World Health Organization criteria, wound infection/abscess) diagnosed up to 6 weeks postpartum. Potential predictors were compared between patients with and without the composite outcome, and evaluated at a 0.05 alpha level. Statistically significant exposures were analyzed using multivariable regression (to generate adjusted odds ratios and 95 % confidence intervals) with backwards selection to generate a parsimonious model. Receiver operating characteristic curves with associated area under the curve assessed the model's predictive ability. A nomogram based on the final best fit multivariable model was constructed. RESULTS: Of 756 patients in the parent trial, 652 were analyzed: 45 (7 %) had peripartum infection. Those with infection were more likely to be nulliparous, lower education level, higher gestational age, receive antibiotics per hospital protocols, and undergo cesarean. In our best-fit multivariable model, none/primary education (vs university), cesarean birth, and antibiotic receipt per physician discretion (vs for cesarean prophylaxis) were significantly associated with increased infection risk. This model was moderately predictive (AUC = 0.75, 95 % CI 0.67-0.82). When using this 3 factor model, for a patient with a cesarean birth, receipt of antibiotics per physician discretion, and university education, the probability of peripartum infection was 35 % (95 % CI 0.11-0.73). CONCLUSIONS: While several variables such as parity are associated with infectious morbidity within 6 weeks among high risk laboring patients in Cameroon, only education level, antibiotic indication, and cesarean birth were independently associated, and a model including these 3 factors was moderately predictive. Validation of our findings in a larger population is warranted.

COVID-19 vaccine acceptance and perceived risk among pregnant and non-pregnant adults in Cameroon, Africa.

BACKGROUND: The public health response to the global COVID-19 pandemic has varied widely by region. In Africa, uptake of effective COVID-19 vaccines has been limited by accessibility and vaccine hesitancy. The aim of this study was to compare perceptions of COVID-19 infection and vaccination between pregnant women and non-pregnant adults in four regions of Cameroon, located in Central Africa. METHODS: A cross-sectional survey study was conducted at urban and suburban hospital facilities in Cameroon. Participants were randomly selected from a convenience sample of adult pregnant and non-pregnant adults in outpatient clinical settings between June 1st and July 14th, 2021. A confidential survey was administered in person by trained research nurses after obtaining written informed consent. Participants were asked about self-reported sociodemographics, medical comorbidities, perceptions of COVID-19 infection, and vaccination. Descriptive statistics were used for survey responses and univariate and multivariable logistic regression models were created to explore factors associated with COVID-19 vaccine acceptability. RESULTS: Fewer than one-third of participants were interested in receiving the COVID-19 vaccine (31%, 257/835) and rates did not differ by pregnancy status. Overall, 43% of participants doubted vaccine efficacy, and 85% stated that the vaccine available in Africa was less effective than vaccine available in Europe. Factors independently associated with vaccine acceptability included having children (aOR = 1.5; p = 0.04) and higher education (aOR = 1.6 for secondary school vs primary/none; p = 0.03). Perceived risks of vaccination ranged from death (33%) to fetal harm (31%) to genetic changes (1%). Health care professionals were cited as the most trusted source for health information (82%, n = 681). CONCLUSION: COVID-19 vaccine hesitancy and misinformation in Cameroon was highly prevalent among pregnant and non-pregnant adults in 2021 while vaccine was available but not recommended for use in pregnancy. Based on study findings, consistent public health messaging from medical professionals about vaccine safety and efficacy and local production of vaccine are likely to improve acceptability.

Single Dose of Oral Azithromycin With or Without Amoxicillin to Prevent Peripartum Infection in Laboring, High-Risk Women in Cameroon: A Randomized Controlled Trial.

OBJECTIVE: To compare the effectiveness of single-dose azithromycin, with or without amoxicillin, with placebo to prevent peripartum infection in laboring women. METHODS: We conducted a multicenter, three-group, double-blind randomized controlled trial of women with viable term nonanomalous pregnancies with either prolonged labor of 18 hours or longer or rupture of membranes for 8 hours or longer in Cameroon. Women with chorioamnionitis before randomization, study drug contraindications, or planned cesarean births were excluded. Women were randomized to oral azithromycin 1 g-placebo (group 1), oral azithromycin 1 g-oral amoxicillin 2 g (group 2), or placebo-placebo (group 3). All groups received usual care, including antibiotics given at the health care professional's discretion. The primary outcome was a composite of maternal peripartum infection or death from any cause up to 6 weeks postpartum. Two primary comparisons (group 1 vs group 3 and group 2 vs group 3) were planned. We estimated that 241 women per group (planning for 750 total) would provide 80% power at two-sided α=0.05 (0.025 per comparison) to detect a 50% effect size assuming 20% baseline composite infection rate. RESULTS: From January 6, 2018, to May 15, 2020, 6,531 women were screened, and 756 (253 in group 1, 253 in group 2, and 250 in group 3) were randomized. Baseline characteristics (including body mass index, duration of rupture of membranes or labor, and parity) were balanced across groups, except for maternal age. More than 60% of women in each group received usual-care antibiotics: more than 90% penicillin and approximately 50% for prolonged rupture of membranes across all study groups. Composite outcome incidences were similar in antibiotic groups 1 (6%) and 2 (7%) compared with placebo group 3 (10%) (RR 0.6, 95% CI 0.3-1.2; 0.7, 95% CI 0.4-1.3, respectively). Chorioamnionitis and wound infection were significantly lower in group 2 (3.2% vs 0.4% and 4% vs 0.8% respectively, both P=.02) compared with group 3. There were no differences in other maternal or neonatal outcomes including neonatal infection. CONCLUSION: A single dose of oral azithromycin with or without amoxicillin for prolonged labor or rupture of membranes at term did not reduce maternal peripartum or neonatal infection. Observed lower than expected infection rates and frequent usual-care antibiotic use may have contributed to these findings. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03248297. FUNDING SOURCE: Merck for Mothers Investigator Studies Program grant.

Prevalence of group B streptococcus anogenital colonization and feasibility of an intrapartum screening and antibiotic prophylaxis protocol in Cameroon, Africa.

OBJECTIVE: To evaluate group B streptococcus (GBS) colonization prevalence and feasibility of intrapartum GBS screening/antibiotic prophylaxis (IAP) in Cameroon, Africa. METHODS: Prospective cohort in the Cameroon Baptist Convention Health Services network. Maternity providers collected anogenital swabs from consenting term women in labor for testing by a rapid GBS-polymerase chain reaction (PCR) system. Positive tests (GBS+) resulted in initiation of intravenous ampicillin until delivery. Primary outcomes were GBS prevalence and proportion of GBS+ women receiving ampicillin before delivery and more than 4 hours before delivery. RESULTS: A total of 219 women were enrolled from January 10 to April 27, 2017. GBS prevalence was 12.3% (95% confidence interval [CI] 7.9-16.7) with GBS+ women more likely to reside in urban areas (19.6% vs 9.7%, P=0.004). Of 27 GBS+ women, 19 (70.4%) received ampicillin before delivery and 14 (51.9%) 4 hours or longer before delivery. A median two doses of ampicillin (interquartile range [IQR] 1-5) were given and started at a median of 105 minutes (IQR 90-155) after swab collection and 20 minutes (IQR 10-45) after GBS result. Of the 8 women who did not receive ampicillin, 7 (87.5%) delivered before test results. CONCLUSION: A GBS IAP protocol is feasible in Cameroon and should be evaluated for widespread implementation in Cameroon and other low-income countries to decrease GBS-related morbidity.

Hepatitis B, HIV, and Syphilis Seroprevalence in Pregnant Women and Blood Donors in Cameroon.

Objectives. We estimated seroprevalence and correlates of selected infections in pregnant women and blood donors in a resource-limited setting. Methods. We performed a cross-sectional analysis of laboratory seroprevalence data from pregnant women and voluntary blood donors from facilities in Cameroon in 2014. Rapid tests were performed to detect hepatitis B surface antigen, syphilis treponemal antibodies, and HIV-1/2 antibodies. Blood donations were also tested for hepatitis C and malaria. Results. The seroprevalence rates and ranges among 7069 pregnant women were hepatitis B 4.4% (1.1-9.6%), HIV 6% (3.0-10.2%), and syphilis 1.7% (1.3-3.8%) with significant variability among the sites. Correlates of infection in pregnancy in adjusted regression models included urban residence for hepatitis B (aOR 2.9, CI 1.6-5.4) and HIV (aOR 3.5, CI 1.9-6.7). Blood donor seroprevalence rates and ranges were hepatitis B 6.8% (5.0-8.8%), HIV 2.2% (1.4-2.8%), syphilis 4% (3.3-4.5%), malaria 1.9%, and hepatitis C 1.7% (0.5-2.5%). Conclusions. Hepatitis B, HIV, and syphilis infections are common among pregnant women and blood donors in Cameroon with higher rates in urban areas. Future interventions to reduce vertical transmission should include universal screening for these infections early in pregnancy and provision of effective prevention tools including the birth dose of univalent hepatitis B vaccine.