PREDICTORS AND THE EFFECTS ON MATERNAL AND BIRTH OUTCOMES OF PLASMODIUM FALCIPARUM INFECTION IN THE FIRST TRIMESTER AMONG NULLIPAROUS WOMEN FROM THE DEMOCRATIC REPUBLIC OF THE CONGO, KENYA, AND ZAMBIA

Protective measures against malaria during pregnancy are rarely initiated until the second trimester, leaving at-risk pregnancies unprotected from malaria infection in the critical first trimester. This dissertation details the first large-scale multi-site study of malaria in the first trimester, and is nested within the NICHD Global Network’s trial of low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (the ASPIRIN Trial). This dissertation aimed to (1) characterize the factors which increase the likelihood of malaria in the first trimester and (2) estimate the causal effects of malaria in the first trimester on adverse maternal and birth outcomes.Aim 1 first calculated the parasite prevalence in the first trimester and found that among 485 Congolese women it was 62.9%, among 677 Kenyan women it was 37.8%, and among 351 Zambian women it was 6.3%. Kenyan women younger than 20 years old were more likely to have malaria in the first trimester (prevalence difference (PD) = 0.17 [99% confidence interval (CI): 0.07, 0.26]), and across all three study countries, lower (no secondary education) vs. higher overall educational attainment was associated with higher prevalence of malaria in the first trimester (summary PD = 0.09 [99% CI: 0.01, 0.17]) Aim 2 found higher prevalences of preterm delivery (adjusted PD (aPD) = 0.06 [99% CI: -0.04, 0.16]) and low birth weight (aPD = 0.07 [99% CI: -0.03, 0.16]) among Congolese women with malaria in the first trimester, and higher prevalence of anemia in late pregnancy among Kenyan (aPD = 0.05 [99% CI: -0.06, 0.17]), Zambian (aPD = 0.07 [99% CI: -0.12, 0.36]), and Congolese (aPD = 0.04 [99% CI: -0.09, 0.16]) women who had malaria in the first trimester. These findings suggest that malaria in the first trimester is very common in areas of high transmission, and is associated with higher prevalences of preterm delivery and low birth weight in an area of high transmission, and with higher prevalence of anemia in late pregnancy at all three sites. These results suggest a need to improve strategies to prevent and treat malaria infections in the first trimester.Doctor of Public Healt

Recalling, Sharing and Participating in a Social Media Intervention Promoting HIV Testing: A Longitudinal Analysis of HIV Testing Among MSM in China.

Social media interventions may enhance HIV services among key populations, including men who have sex with men (MSM). This longitudinal analysis examined the effect of recalling, sharing, and participating in different components of a social media intervention on HIV testing among MSM. The social media intervention included six images/texts and information about an online local community contest to promote testing. Of the 1033 men, they recalled a mean of 2.7 out of six images and shared an average of one image online. 34.5% of men recalled information on the online local community contest and engaged in a mean of 1.3 contest. Recalling images/texts (aOR = 1.13, 95% CI 1.02-1.25) and recalling a local contest (aOR = 1.59, 95% CI 1.13-1.24) were associated with facility-based HIV testing. This study has implications for the development and evaluation of social media interventions to promote HIV testing

Medication Non-adherence and Condomless Anal Intercourse Increased Substantially During the COVID-19 Pandemic Among MSM PrEP Users: A Retrospective Cohort Study in Four Chinese Metropolises

BackgroundThe coronavirus disease (COVID-19) pandemic has impacted HIV prevention strategies globally. However, changes in pre-exposure prophylaxis (PrEP) adherence and HIV-related behaviors, and their associations with medication adherence among men who have sex with men (MSM) PrEP users remain unclear since the onset of the COVID-19 pandemic.MethodsA Retrospective Cohort Study of HIV-negative MSM PrEP users was conducted in four Chinese metropolises from December 2018 to March 2020, assessing the changes in PrEP adherence and HIV-related behaviors before and during the COVID-19. The primary outcome was poor PrEP adherence determined from self-reported missing at least one PrEP dose in the previous month. We used multivariable logistic regression to determine factors correlated with poor adherence during COVID-19.ResultsWe enrolled 791 eligible participants (418 [52.8%] in daily PrEP and 373 [47.2%] in event-driven PrEP). Compared with the data conducted before the COVID-19, the proportion of PrEP users decreased from 97.9 to 64.3%, and the proportion of poor PrEP adherence increased from 23.6 to 50.1% during the COVID-19 [odds ratio (OR) 3.24, 95% confidence interval (CI) 2.62–4.02]. While the percentage of condomless anal intercourse (CAI) with regular partners (11.8 vs. 25.7%) and with casual partners (4.4 vs. 9.0%) both significantly increased. The proportion of those who were tested for HIV decreased from 50.1 to 25.9%. Factors correlated with poor PrEP adherence during the COVID-19 included not being tested for HIV (adjusted odds ratio [aOR] = 1.38 [95% CI: 1.00, 1.91]), using condoms consistently with regular partners (vs. never, aOR = 2.19 [95% CI: 1.16, 4.13]), and being married or cohabitating with a woman (vs. not married, aOR = 3.08 [95% CI: 1.60, 5.95]).ConclusionsIncreased poor PrEP adherence and CAI along with the decrease in HIV testing can lead to an increase in HIV acquisition and drug resistance to PrEP. Targeted interventions are needed to improve PrEP adherence and HIV prevention strategies

The efficacy of low-dose aspirin in pregnancy among women in malaria-endemic countries

Background: Low dose aspirin (LDA) is an effective strategy to reduce preterm birth. However, LDA might have differential effects globally, based on the etiology of preterm birth. In some regions, malaria in pregnancy could be an important modifier of LDA on birth outcomes and anemia. Methods: This is a sub-study of the ASPIRIN trial, a multi-national, randomized, placebo controlled trial evaluating LDA effect on preterm birth. We enrolled a convenience sample of women in the ASPIRIN trial from the Democratic Republic of Congo (DRC), Kenya and Zambia. We used quantitative polymerase chain reaction to detect malaria. We calculated crude prevalence proportion ratios (PRs) for LDA by malaria for outcomes, and regression modelling to evaluate effect measure modification. We evaluated hemoglobin in late pregnancy based on malaria infection in early pregnancy. Results: One thousand four hundred forty-six women were analyzed, with a malaria prevalence of 63% in the DRC site, 38% in the Kenya site, and 6% in the Zambia site. Preterm birth occurred in 83 (LDA) and 90 (placebo) women, (PR 0.92, 95% CI 0.70, 1.22), without interaction between LDA and malaria (p = 0.75). Perinatal mortality occurred in 41 (LDA) and 43 (placebo) pregnancies, (PR 0.95, 95% CI 0.63, 1.44), with an interaction between malaria and LDA (p = 0.014). Hemoglobin was similar by malaria and LDA status. Conclusions: Malaria in early pregnancy did not modify the effects of LDA on preterm birth, but modified the effect of LDA on perinatal mortality. This effect measure modification deserves continued study as LDA is used in malaria endemic regions

Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

The efficacy of low-dose aspirin in pregnancy among women in malaria-endemic countries

Background: Low dose aspirin (LDA) is an effective strategy to reduce preterm birth. However, LDA might have differential effects globally, based on the etiology of preterm birth. In some regions, malaria in pregnancy could be an important modifier of LDA on birth outcomes and anemia.Methods: This is a sub-study of the ASPIRIN trial, a multi-national, randomized, placebo controlled trial evaluating LDA effect on preterm birth. We enrolled a convenience sample of women in the ASPIRIN trial from the Democratic Republic of Congo (DRC), Kenya and Zambia. We used quantitative polymerase chain reaction to detect malaria. We calculated crude prevalence proportion ratios (PRs) for LDA by malaria for outcomes, and regression modelling to evaluate effect measure modification. We evaluated hemoglobin in late pregnancy based on malaria infection in early pregnancy.Results: One thousand four hundred forty-six women were analyzed, with a malaria prevalence of 63% in the DRC site, 38% in the Kenya site, and 6% in the Zambia site. Preterm birth occurred in 83 (LDA) and 90 (placebo) women, (PR 0.92, 95% CI 0.70, 1.22), without interaction between LDA and malaria (p = 0.75). Perinatal mortality occurred in 41 (LDA) and 43 (placebo) pregnancies, (PR 0.95, 95% CI 0.63, 1.44), with an interaction between malaria and LDA (p = 0.014). Hemoglobin was similar by malaria and LDA status.Conclusions: Malaria in early pregnancy did not modify the effects of LDA on preterm birth, but modified the effect of LDA on perinatal mortality. This effect measure modification deserves continued study as LDA is used in malaria endemic regions

The efficacy of low-dose aspirin in pregnancy among women in malaria-endemic countries

Background Low dose aspirin (LDA) is an effective strategy to reduce preterm birth. However, LDA might have differential effects globally, based on the etiology of preterm birth. In some regions, malaria in pregnancy could be an important modifier of LDA on birth outcomes and anemia. Methods This is a sub-study of the ASPIRIN trial, a multi-national, randomized, placebo controlled trial evaluating LDA effect on preterm birth. We enrolled a convenience sample of women in the ASPIRIN trial from the Democratic Republic of Congo (DRC), Kenya and Zambia. We used quantitative polymerase chain reaction to detect malaria. We calculated crude prevalence proportion ratios (PRs) for LDA by malaria for outcomes, and regression modelling to evaluate effect measure modification. We evaluated hemoglobin in late pregnancy based on malaria infection in early pregnancy. Results One thousand four hundred forty-six women were analyzed, with a malaria prevalence of 63% in the DRC site, 38% in the Kenya site, and 6% in the Zambia site. Preterm birth occurred in 83 (LDA) and 90 (placebo) women, (PR 0.92, 95% CI 0.70, 1.22), without interaction between LDA and malaria (p = 0.75). Perinatal mortality occurred in 41 (LDA) and 43 (placebo) pregnancies, (PR 0.95, 95% CI 0.63, 1.44), with an interaction between malaria and LDA (p = 0.014). Hemoglobin was similar by malaria and LDA status. Conclusions Malaria in early pregnancy did not modify the effects of LDA on preterm birth, but modified the effect of LDA on perinatal mortality. This effect measure modification deserves continued study as LDA is used in malaria endemic regions