The role of implementation science training in global health: from the perspective of graduates of the field's first dedicated doctoral program.

Bridging the 'know-do gap' is an enormous challenge for global health practitioners. They must be able to understand local health dynamics within the operational and social contexts that engender them, test and adjust approaches to implementation in collaboration with communities and stakeholders, interpret data to inform policy decisions, and design adaptive and resilient health systems at scale. These skills and methods have been formalized within the nascent field of Implementation Science (IS). As graduates of the world's first PhD program dedicated explicitly to IS, we have a unique perspective on the value of IS and the training, knowledge, and skills essential to bridging the 'know-do gap'. In this article, we describe the philosophy and curricula at the core of our program, outline the methods vital to IS in a global health context, and detail the role that we believe IS will increasingly play in global health practice. At this junction of enormous challenges and opportunities, we believe that IS offers the necessary tools for global health professionals to address complex problems in context and raises the bar of success for the global health programs of the future.

Assessment of linkages from HIV testing to enrolment and retention in HIV care in Central Mozambique.

INTRODUCTION: Effectiveness of the rapid expansion of antiretroviral therapy (ART) throughout sub-Saharan Africa is highly dependent on adequate enrolment and retention in HIV care. However, the measurement of both has been challenging in these settings. This study aimed to assess enrolment and retention in HIV care (pre-ART and ART) among HIV-positive adults in Central Mozambique, including identification of barriers and facilitators. METHODS: We assessed linkages to and retention in HIV care using a mixed quantitative and qualitative approach in six districts of Manica and Sofala provinces. We analyzed routine district and health facility monthly reports and HIV care registries from April 2012 to March 2013 and used single imputation and trimmed means to adjust for missing values. In eight health facilities in the same districts and period, we assessed retention in HIV care among 795 randomly selected adult patient charts (15 years and older). We also conducted 25 focus group discussions and 53 in-depth interviews with HIV-positive adults, healthcare providers and community members to identify facilitators and barriers to enrolment and retention in HIV care. RESULTS: Overall, 46% of the monthly HIV testing reports expected at the district level were missing, compared to 6.4% of the pre-ART registry reports. After adjustment for missing values, we estimated that the aggregate numbers of adults registered in pre-ART was 75% of the number of persons tested HIV-positive in the six districts. In the eight health facilities, 40% of the patient charts for adults enrolled in pre-ART and 44% in ART were missing. Of those on ART for whom charts were found, retention in treatment within 90 and 60 days prior to the study team visit was 34 and 25%, respectively. Combining these multiple data sources, the overall estimated retention was 18% in our sample. Individual-level factors were perceived to be key influences to enrolment in HIV care, while health facility and structural-level factors were perceived to be key influences of retention. CONCLUSIONS: Efforts to increase linkages to and retention in HIV care should address individual, health facility, and structural-level factors in Central Mozambique. However, their outcomes cannot be reliably assessed without improving the quality of routine health information systems.

Prospective study of vaginal bacterial flora and other risk factors for vulvovaginal candidiasis.

BACKGROUND: It has been suggested that vaginal colonization with lactobacilli may reduce the risk of vulvovaginal candidiasis (VVC), but supporting data are limited. Our objective was to determine the relationship between vaginal bacterial flora and VVC. METHODS: We conducted a prospective cohort analysis that involved 151 Kenyan sex workers. At monthly follow-up visits, VVC was defined as the presence of yeast buds, pseudohyphae, or both on a wet preparation (including potassium hydroxide preparation) of vaginal secretions. Generalized estimating equations were used to identify correlates of VVC. RESULTS: Participants returned for a median of 12 visits (interquartile range, 11-12 visits). VVC was identified at 162 visits, including 26 involving symptomatic VVC. Bacterial vaginosis was associated with fewer episodes of VVC (adjusted odds ratio [aOR], 0.29 [95% confidence interval {CI}, 0.16-0.50]). After excluding women with concurrent bacterial vaginosis, another possible cause of vaginal symptoms, the likelihood of symptomatic VVC was higher among those who had had yeast identified on wet preparation of vaginal secretions during the past 60 days (aOR, 4.06 [95% CI, 1.12-14.74]) and those with concurrent vaginal Lactobacillus colonization (aOR, 3.75 [95% CI, 1.30-10.83]). CONCLUSIONS: Contrary to the commonly posited hypothesis that vaginal Lactobacillus colonization has a protective effect, we found that such colonization was associated with a nearly 4-fold increase in the likelihood of symptomatic VVC.

Improvement of vaginal health for Kenyan women at risk for acquisition of human immunodeficiency virus type 1: results of a randomized trial.

BACKGROUND: Vaginal infections are common and have been associated with increased risk for acquisition of human immunodeficiency virus type 1 (HIV-1). METHODS: We conducted a randomized trial of directly observed oral treatment administered monthly to reduce vaginal infections among Kenyan women at risk for HIV-1 acquisition. A trial intervention of 2 g of metronidazole plus 150 mg of fluconazole was compared with metronidazole placebo plus fluconazole placebo. The primary end points were bacterial vaginosis (BV), vaginal candidiasis, trichomoniasis vaginalis (hereafter, "trichomoniasis"), and colonization with Lactobacillus organisms. RESULTS: Of 310 HIV-1-seronegative female sex workers enrolled (155 per arm), 303 were included in the primary end points analysis. A median of 12 follow-up visits per subject were recorded in both study arms (P = .8). Compared with control subjects, women receiving the intervention had fewer episodes of BV (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.49-0.63) and more frequent vaginal colonization with any Lactobacillus species (HR, 1.47; 95% CI, 1.19-1.80) and H(2)O(2)-producing Lactobacillus species (HR, 1.63; 95% CI, 1.16-2.27). The incidences of vaginal candidiasis (HR, 0.84; 95% CI, 0.67-1.04) and trichomoniasis (HR, 0.55; 95% CI, 0.27-1.12) among treated women were less than those among control subjects, but the differences were not statistically significant. CONCLUSIONS: Periodic presumptive treatment reduced the incidence of BV and promoted colonization with normal vaginal flora. Vaginal health interventions have the potential to provide simple, female-controlled approaches for reducing the risk of HIV-1 acquisition.

Infection with Trichomonas vaginalis increases the risk of HIV-1 acquisition.

We conducted a prospective study among women in Mombasa, Kenya, to determine whether Trichomonas vaginalis infection was associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) infection. At monthly follow-up visits, laboratory screening for HIV-1 and genital tract infections was conducted. Among 1335 HIV-1-seronegative women monitored for a median of 566 days, there were 806 incident T. vaginalis infections (23.6/100 person-years), and 265 women seroconverted to HIV-1 (7.7/100 person-years). Trichomoniasis was associated with a 1.52-fold (95% confidence interval, 1.04-2.24-fold) increased risk of HIV-1 acquisition after adjustment for potential confounding factors. Treatment and prevention of T. vaginalis infection could reduce HIV-1 risk in women.

Associations between intravaginal practices and bacterial vaginosis in Kenyan female sex workers without symptoms of vaginal infections.

BACKGROUND: Bacterial vaginosis (BV) is highly prevalent among African women and has been associated with adverse pregnancy outcomes, sexually transmitted diseases, and HIV-1. GOAL: The goal of this study was to analyze the relationship among intravaginal practices, bathing, and BV. STUDY DESIGN: The authors conducted a cross-sectional study of HIV-1-seronegative Kenyan female sex workers without symptoms of vaginal infections. RESULTS: Of 237 women enrolled, 206 (87%) reported vaginal washing using either a finger or cloth. Increasing frequency of vaginal washing was associated with a higher likelihood of BV (chi(2) test for trend, P = 0.05). In multivariate analysis, vaginal lubrication with petroleum jelly (odds ratio [OR] = 2.8, 95% confidence interval [CI] = 1.4-5.6), lubrication with saliva (OR = 2.3, 95% CI = 1.1-4.8), and bathing less than the median for the cohort (14 times/week; OR = 4.6, 95% CI = 1.2-17.5) were associated with a significantly higher likelihood of BV. CONCLUSIONS: Modification of intravaginal and general hygiene practices should be evaluated as potential strategies for reducing the risk of BV.

HIV-1 acquisition and disease progression are associated with decreased high-risk sexual behaviour among Kenyan female sex workers.

BACKGROUND: Changes in sexual risk behaviour may occur following HIV-1 infection. OBJECTIVE: To test the hypothesis that HIV-1 seroconversion and disease progression are associated with changes in risk behaviours, using data from a cohort of Kenyan female sex workers (FSWs). METHODS: HIV-1-seronegative FSWs were enrolled in a prospective cohort study of risk factors for HIV-1 acquisition. At monthly visits, standardized interviews were conducted to assess sexual risk behaviour and HIV-1 serologic testing was performed. Seroconverters were invited to continue with follow-up. Between 1993 and 2004 (when antiretroviral therapy was introduced in the cohort), 265 women seroconverted for HIV-1 (incidence 7.7/100 person-years) and were included in this analysis. RESULTS: Unprotected intercourse was reported at 546/2037 (27%) pre-seroconversion visits versus 557/3732 (15%) post-seroconversion visits (P < 0.001). These findings remained significant after adjustment for potential confounding factors [adjusted odds ratio (AOR) 0.69; 95% confidence interval (CI), 0.55-0.86]. Compared with HIV-1-seronegative women, there was a progressive stepwise decrease in unprotected intercourse among HIV-1-seropositive women with CD4 cell counts > or = 500 (AOR, 0.93; 95% CI, 0.62-1.39), 200-499 (AOR, 0.58; 95% CI, 0.41-0.82) and < 200 cells/microl (AOR, 0.45; 95% CI, 0.25-0.82). Decreases in unprotected intercourse reflected increases in both abstinence and 100% condom use. Women also reported fewer partners and fewer episodes of intercourse after HIV-1 seroconversion. CONCLUSIONS: HIV-1 seroconversion and disease progression were associated with decreases in sexual risk behaviour among Kenyan FSWs.

Higher set point plasma viral load and more-severe acute HIV type 1 (HIV-1) illness predict mortality among high-risk HIV-1-infected African women.

BACKGROUND: There is limited information on the natural history of human immunodeficiency virus type 1 (HIV-1) infection in Africa, especially from individuals with well-defined dates of infection. We used data from a prospective cohort study of female sex workers in Mombasa, Kenya, who were followed up monthly from before the date of HIV-1 infection. METHODS: Antiretroviral-naive women who had a well-defined date of HIV-1 infection were included in this analysis. The effects of set point plasma viral load (measured 4-24 months after infection), early CD4+ cell count, and symptoms of acute HIV-1 infection on mortality were assessed using Cox proportional hazards analysis. RESULTS: Among 218 women, the median duration of follow-up after HIV-1 infection was 4.6 years. Forty women died, and at 8.7 years (the time of the last death), the cumulative survival rate was 51% by Kaplan-Meier analysis. Higher set point viral load, lower early CD4+ cell count, and more-symptomatic acute HIV-1 illness each predicted death. In multivariate analysis, set point viral load (hazard ratio [HR], 2.28 per 1 log10 copies/mL increase; P=.001) and acute HIV-1 illness (HR, 1.14 per each additional symptom; P=.05) were independently associated with higher mortality. CONCLUSION: Among this group of African women, the survival rate was similar to that for HIV-1-infected individuals in industrialized nations before the introduction of combination antiretroviral therapy. Higher set point viral load and more-severe acute HIV-1 illness predicted faster progression to death. Early identification of individuals at risk for rapid disease progression may allow closer clinical monitoring, including timely initiation of antiretroviral treatment.

Vaginal washing and increased risk of HIV-1 acquisition among African women: a 10-year prospective study.

BACKGROUND: No prospective study has examined the risk of HIV-1 acquisition associated with vaginal washing, although intravaginal practices have been identified as potentially important contributors to HIV-1 susceptibility. OBJECTIVE: To evaluate the contribution of vaginal washing to incident HIV-1 infection. DESIGN: Prospective cohort study. METHODS: Data were derived from a 10-year study of risk factors for HIV-1 acquisition among 1270 Kenyan female sex workers. Intravaginal practices were ascertained at study enrollment. At monthly follow-up visits, women completed a standardized interview and specimens were collected for diagnosis of HIV-1 and genital tract infections. RESULTS: : Compared with women who did not perform vaginal washing, there was an increased risk for acquiring HIV-1 among women who used water [adjusted hazard ratio (HR), 2.64; 95% confidence interval (CI), 1.00-6.97] or soap (adjusted HR 3.84; 95% CI, 1.51-9.77) to clean inside the vagina, after adjustment for demographic factors, sexual behavior, and sexually transmitted infections. Furthermore, women who performed vaginal washing with soap or other substances were at higher risk for HIV-1 compared with those who used water alone (adjusted HR, 1.47; 95% CI, 1.02-2.13). CONCLUSIONS: In populations where vaginal washing is common, this practice may be an important factor promoting the spread of HIV-1. Intervention strategies aimed at modifying intravaginal practices should be evaluated as a possible female-controlled HIV-1 prevention strategy.

Hormonal contraception and risk of cervical infections among HIV-1-seropositive Kenyan women.

OBJECTIVE: To evaluate the relationship between hormonal contraceptive use and the acquisition of cervical sexually transmitted infections (STI) among HIV-1-infected women. DESIGN: A prospective cohort study of 242 commercial sex workers in Mombasa, Kenya, followed from the time of HIV-1 infection. METHODS: At monthly follow-up visits, sexual behavior and contraceptive use were recorded, and laboratory screening for STI was performed. Multivariate Andersen-Gill proportional hazards models were constructed to examine the association between the use of hormonal contraception and the occurrence of cervical STI. RESULTS: The median duration of follow-up after HIV-1 acquisition was 35 months, and 799 person-years of follow-up were accrued. After adjustment for demographic factors and sexual behavior, women using the injectable contraceptive depot medroxyprogesterone acetate were at increased risk of Chlamydia trachomatis infection [hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.0-9.4, P = 0.05] and cervicitis (HR 1.6, 95% CI 1.0-2.3, P = 0.03) compared with women using no contraception. The use of oral contraceptive pills was associated with an increased risk of cervicitis (HR 2.3, 95% CI 1.4-3.8, P = 0.001). Hormonal contraception was not associated with an increased risk of infection with Neisseria gonorrhoeae. CONCLUSION: The use of hormonal contraception by HIV-1-infected women was associated with an increased risk of cervicitis and cervical chlamydia infection. HIV-1-seropositive women using hormonal contraception should be counseled about the importance of consistent condom use to prevent both STI and HIV-1 transmission.

Shedding of human herpesvirus 8 in oral and genital secretions from HIV-1-seropositive and -seronegative Kenyan women.

Polymerase chain reaction was used to determine the prevalence and correlates of human herpesvirus 8 (HHV8) in saliva, mouth, cervical, vaginal, plasma, and peripheral-blood mononuclear cell (PBMC) samples from 174 HHV8-seropositive female prostitutes in Mombasa, Kenya. The prevalence of detection of HHV8 was 32% in saliva samples, 28% in mouth swabs, 4% in cervical swabs, 2.3% in vaginal swabs, 9% in plasma samples, and 18% in PBMC samples. Human immunodeficiency virus type 1 (HIV-1) seropositivity was associated with detection of HHV8 from any mucosal surface (odds ratio, 2.1 [95% confidence interval, 1.1-4.0]). In HIV-1-seropositive women, there was no association between detection of HHV8 and either CD4 count or HIV-1 viral load.

Injectable contraceptive use and genital ulcer disease during the early phase of HIV-1 infection increase plasma virus load in women.

We examined the association between host factors present near the time of human immunodeficiency virus type 1 (HIV-1) acquisition and subsequent virus loads, in a prospective cohort study of women in Mombasa, Kenya. Women were prospectively followed monthly before HIV-1 infection. One hundred sixty-one commercial sex workers who became infected with HIV-1 were followed for a median of 34 months, and 991 plasma samples collected > or =4 months after infection were tested for HIV-1 RNA. The median virus set point at 4 months after infection was 4.46 log10 copies/mL, and the average virus load increase during subsequent follow-up was 0.0094 log10 copies/mL/month. In a multivariate analysis that controlled for sexual behavior, the use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) at the time of HIV-1 infection was associated with a higher virus set point, and the presence of genital ulcer disease (GUD) during the early phase of HIV-1 infection was associated with greater change in virus load during follow-up. These findings suggest that, in women, the use of DMPA and the presence of GUD during the early phase of HIV-1 infection may influence the natural course of infection.