BACKGROUND: Namibia is a large sparsely populated country with a high prevalence of HIV. People living with HIV who reside in remote areas often travel long distances through tough desert terrain to access HIV care and treatment. To address this barrier, community-based antiretroviral therapy (C-BART) sites were established in Okongo (2007-2008) and Eenhana districts (2016) of northern Namibia with the goal of bringing HIV and other health services closer patients' homes. We conducted a qualitative evaluation of the acceptability and challenges of C-BART to guide program improvement. METHODS: For this qualitative descriptive study, research assistants collected data (August-December 2017) through in-depth interviews with 40 patients, seven health extension workers, and 11 policy/program managers, and through four focus group discussions with healthcare workers. Interviews were audio-recorded, translated, and coded using MAXQDA v.12. Data were analyzed using thematic analysis. RESULTS: The evaluation identified five themes: community ownership, acceptance of the C-BART sites, benefits of the C-BART program for the PLHIV community and their social networks, benefits of the C-BART program to the main health facility, and challenges with the C-BART program. The C-BART program was reported as life-changing by many patients who had previously struggled to afford four-wheel drive vehicles to access care. Patients and healthcare workers perceived that the community as a whole benefited from the C-BART sites not only due to the financial pressure lifted from friends and family members previously asked to help cover expensive transportation, but also due to the perception of diminished stigmatization of people living with HIV and improved health. The C-BART sites became a source of community and social support for those accessing the sites. Healthcare workers reported greater job satisfaction and decongestion of health facilities. The challenges that they reported included delays in authorization of vehicles for transportation to C-BART sites and lack of incentives to provide services in the community. CONCLUSION: The C-BART program can serve as a model of care to expand access to HIV care and treatment and other health services to populations in remote settings, including rural and difficult-to-reach regions. The needs of healthcare workers should also be considered for the optimal delivery of such a model.

Namibia faces a critical shortage of skilled public health workers to perform emergency response operations, preparedness activities and real-time surveillance. The Namibia Field Epidemiology and Laboratory Training Programme (NamFELTP) increases the number of skilled public health professionals and strengthens the public health system in Namibia. We describe the NamFELTP during its first 7 years, assess its impact on the public health workforce and provide recommendations to further strengthen the workforce. We reviewed disease outbreak investigations and response reports, field projects and epidemiological investigations conducted during 2012-2019. The data were analysed using descriptive methods such as frequencies and rates. Maps representing the geographical distribution of NamFELTP workforce were produced using QGIS software V.3.2. There were no formally trained field epidemiologists working in Namibia before the NamFELTP. In its 7 years of operation, the programme graduated 189 field epidemiologists, of which 28 have completed the Advanced FELTP. The graduates increased epidemiological capacity for surveillance and response in Namibia at the national and provincial levels, and enhanced epidemiologist-led outbreak responses on 35 occasions, including responses to outbreaks of human and zoonotic diseases. Trainees analysed data from 51 surveillance systems and completed 31 epidemiological studies. The NamFELTP improved outcomes in the Namibia's public health systems; including functional and robust public health surveillance systems that timely and effectively respond to public health emergencies. However, the current epidemiological capacity is insufficient and there is a need to continue training and mentorship to fill key leadership and strategic roles in the public health system.

BACKGROUND: Namibia introduced the prevention of mother to child HIV transmission (MTCT) program in 2002 and lifelong antiretroviral therapy (ART) for pregnant women (option B-plus) in 2013. We sought to quantify MTCT measured at 4-12 weeks post-delivery. METHODS: During Aug 2014-Feb 2015, we recruited a nationally representative sample of 1040 pairs of mother and infant aged 4-12 weeks at routine immunizations in 60 public health clinics using two stage sampling approach. Of these, 864 HIV exposed infants had DNA-PCR HIV test results available. We defined an HIV exposed infant if born to an HIV-positive mother with documented status or diagnosed at enrollment using rapid HIV tests. Dried Blood Spots samples from HIV exposed infants were tested for HIV. Interview data and laboratory results were collected on smartphones and uploaded to a central database. We measured MTCT prevalence at 4-12 weeks post-delivery and evaluated associations between infant HIV infection and maternal and infant characteristics including maternal treatment and infant prophylaxis. All statistical analyses accounted for the survey design. RESULTS: Based on the 864 HIV exposed infants with test results available, nationally weighted early MTCT measured at 4-12 weeks post-delivery was 1.74% (95% confidence interval (CI): 1.00%-3.01%). Overall, 62% of mothers started ART pre-conception, 33.6% during pregnancy, 1.2% post-delivery and 3.2% never received ART. Mothers who started ART before pregnancy and during pregnancy had low MTCT prevalence, 0.78% (95% CI: 0.31%-1.96%) and 0.98% (95% CI: 0.33%-2.91%), respectively. MTCT rose to 4.13% (95% CI: 0.54%-25.68%) when the mother started ART after delivery and to 11.62% (95% CI: 4.07%-28.96%) when she never received ART. The lowest MTCT of 0.76% (95% CI: 0.36% - 1.61%) was achieved when mother received ART and ARV prophylaxis within 72hrs for infant and highest 22.32% (95%CI: 2.78% -74.25%) when neither mother nor infant received ARVs. After adjusting for mother's age, maternal ART (Prevalence Ratio (PR) = 0.10, 95% CI: 0.03-0.29) and infant ARV prophylaxis (PR = 0.32, 95% CI: 0.10-0.998) remained strong predictors of HIV transmission. CONCLUSION: As of 2015, Namibia achieved MTCT of 1.74%, measured at 4-12 weeks post-delivery. Women already on ART pre-conception had the lowest prevalence of MTCT emphasizing the importance of early HIV diagnosis and treatment initiation before pregnancy. Studies are needed to measure MTCT and maternal HIV seroconversion during breastfeeding.

BACKGROUND: The Namibian Ministry of Health and Social Services (MoHSS) piloted the first HIV Project ECHO (Extension for Community Health Outcomes) in Africa at 10 clinical sites between 2015 and 2016. Goals of Project ECHO implementation included strengthening clinical capacity, improving professional satisfaction, and reducing isolation while addressing HIV service challenges during decentralization of antiretroviral therapy. METHODS: MoHSS conducted a mixed-methods evaluation to assess the pilot. Methods included pre/post program assessments of healthcare worker knowledge, self-efficacy, and professional satisfaction; assessment of continuing professional development (CPD) credit acquisition; and focus group discussions and in-depth interviews. Analysis compared the differences between pre/post scores descriptively. Qualitative transcripts were analyzed to extract themes and representative quotes. RESULTS: Knowledge of clinical HIV improved 17.8% overall (95% confidence interval 12.2-23.5%) and 22.3% (95% confidence interval 13.2-31.5%) for nurses. Professional satisfaction increased 30 percentage points. Most participants experienced reduced professional isolation (66%) and improved CPD credit access (57%). Qualitative findings reinforced quantitative results. Following the pilot, the Namibia MoHSS Project ECHO expanded to over 40 clinical sites by May 2019 serving more than 140 000 people living with HIV. CONCLUSIONS: Similar to other Project ECHO evaluation results in the United States of America, Namibia's Project ECHO led to the development of ongoing virtual communities of practice. The evaluation demonstrated the ability of the Namibia HIV Project ECHO to improve healthcare worker knowledge and satisfaction and decrease professional isolation.

Background: In 2015, Namibia implemented an Acceleration Plan to address the high burden of HIV (13.0% adult prevalence and 216 311 people living with HIV [PLHIV]) and achieve the UNAIDS 90-90-90 targets by 2020. We provide an update on Namibia's overall progress toward achieving these targets and estimate the percent reduction in HIV incidence since 2010. Methods: Data sources include the 2013 Namibia Demographic and Health Survey (2013 NDHS), the national electronic patient monitoring system, and laboratory data from the Namibian Institute of Pathology. These sources were used to estimate (1) the percentage of PLHIV who know their HIV status, (2) the percentage of PLHIV on antiretroviral therapy (ART), (3) the percentage of patients on ART with suppressed viral loads, and (4) the percent reduction in HIV incidence. Results: In the 2013 NDHS, knowledge of HIV status was higher among HIV-positive women 91.8% (95% confidence interval [CI], 89.4%-93.7%) than HIV-positive men 82.5% (95% CI, 78.1%-86.1%). At the end of 2016, an estimated 88.3% (95% CI, 86.3%-90.1%) of PLHIV knew their status, and 165 939 (76.7%) PLHIV were active on ART. The viral load suppression rate among those on ART was 87%, and it was highest among >/=20-year-olds (90%) and lowest among 15-19-year-olds (68%). HIV incidence has declined by 21% since 2010. Conclusions: With 76.7% of PLHIV on ART and 87% of those on ART virally suppressed, Namibia is on track to achieve UNAIDS 90-90-90 targets by 2020. Innovative strategies are needed to improve HIV case identification among men and adherence to ART among youth.

Background: Continued use of standardized, first-line ART containing NNRTIs and NRTIs may contribute to ongoing emergence of HIV drug resistance (HIVDR) in Namibia. Methods: A nationally representative cross-sectional survey was conducted during 2015-16 to estimate the prevalence of significant pretreatment HIV drug resistance (PDR) and viral load (VL) suppression rates 6-12 months after initiating standardized first-line ART. Consenting adult patients (>/=18 years) initiating ART were interviewed about prior antiretroviral drug (ARV) exposure and underwent resistance testing using dried blood spot samples. PDR was defined as mutations causing low-, intermediate- and high-level resistance to ARVs according to the 2014 WHO Surveillance of HIV Drug Resistance in Adults Initiating ART. The prevalence of PDR was described by patient characteristics, ARV exposure and VL results. Results were weighted to be nationally representative. Results: Successful genotyping was performed for 381 specimens; 144 (36.6%) specimens demonstrated HIVDR, of which 54 (12.7%) demonstrated PDR. Resistance to NNRTIs was most prevalent (11.9%). PDR was higher in patients with previous ARV exposure compared with no exposure (30.5% versus 9.6%) (prevalence ratio = 3.17; P < 0.01). Conclusions: This survey demonstrated overall PDR at >10% among adults initiating ART in Namibia. Patients with prior ARV exposure had higher rates of PDR. Introducing a non-NNRTI-based regimen for first-line ART should be considered to maximize benefit of ART and minimize the emergence of HIVDR.

Three hundred sixty-six adult patients in Namibia with second- line virologic failures were evaluated for human immunodeficiency virus drug-resistant (HIVDR) mutations. Less than half (41.5%) harbored =1 HIVDR mutations to standardized second-line antiretroviral therapy (ART) regimen. Optimizing adherence, viral load monitoring, and genotyping are critical to prevent emergence of resistance, as well as unnecessary switching to costly third-line ART regimens.

BACKGROUND: Sex workers in Uganda are at significant risk for HIV infection. We characterized the HIV epidemic among Kampala female sex workers (FSW). METHODS: We used respondent-driven sampling to sample FSW aged 15+ years who reported having sold sex to men in the preceding 30 days; collected data through audio-computer assisted self-interviews, and tested blood, vaginal and rectal swabs for HIV, syphilis, neisseria gonorrhea, chlamydia trachomatis, and trichomonas vaginalis. RESULTS: A total of 942 FSW were enrolled from June 2008 through April 2009. The overall estimated HIV prevalence was 33% (95% confidence intervals [CI] 30%-37%) and among FSW 25 years or older was 44%. HIV infection is associated with low levels of schooling, having no other work, never having tested for HIV, self-reported genital ulcers or sores, and testing positive for neisseria gonorrhea or any sexually transmitted infections (STI). Two thirds (65%) of commercial sex acts reportedly were protected by condoms; one in five (19%) FSW reported having had anal sex. Gender-based violence was frequent; 34% reported having been raped and 24% reported having been beaten by clients in the preceding 30 days. CONCLUSIONS: One in three FSW in Kampala is HIV-infected, suggesting a severe HIV epidemic in this population. Intensified interventions are warranted to increase condom use, HIV testing, STI screening, as well as antiretroviral treatment and pre-exposure prophylaxis along with measures to overcome gender-based violence.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/muL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,dagger, section sign To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence.

BACKGROUND: In the United States, infants have the highest reported pertussis incidence and death rates. Improved understanding of infant risk factors is needed to optimize prevention strategies. METHODS: We prospectively enrolled infants ≤4 months of age with incident-confirmed pertussis from 4 sites during 2002-2005 (preceding pertussis-antigen-containing vaccination recommendations for adolescents/adults); each case-patient was age- and site-matched with 2 control subjects. Caregivers completed structured interviews. Infants and their contacts ≥11 years of age were offered serologic testing for IgG; being seropositive was defined as ≥94 anti-pertussis toxin IgG enzyme-linked immunosorbent assay units/mL. RESULTS: Enrolled subjects (115 case-patients; 230 control subjects) had 4,396 contacts during incubation periods; 83 (72%) case-patients had ≥1 contact with prolonged (≥5 days) new cough in primary or secondary households. In multivariable analysis, the odds for pertussis were higher for infants with primary/secondary household contacts who had a prolonged new cough, compared with infants who did not. These contacts included mother (adjusted matched odds ratio [aMOR] 43.8; 95% confidence interval [CI], 6.45-298.0) and ≥1 nonmother contact (aMOR, 20.1; 95% CI, 6.48-62.7). Infants receiving breast milk with 0-1 formula feedings daily had decreased pertussis odds (aMOR, 0.27; 95% CI, 0.08-0.89), compared with those receiving more formula. Of 41 tested case-patients, 37 (90%) were seropositive. CONCLUSIONS: Pertussis in infants was associated with prolonged new cough (≥5 days) in infants' household contacts. Findings suggest breastfeeding protects against pertussis, and warrants recommendation with pertussis prevention strategies, which currently include pertussis vaccination of pregnant mothers and infants' close contacts.

A 2006 survey of street youth at pre-mapped street youth locations in St. Petersburg, Russia, found extremely high HIV seroprevalence (37.4%) among 313 street youth aged 15-19 years of age, strongly associated with injection drug use, which was reported by 50.6% of participants. In response, multi-sectoral social support and prevention measures were instituted. In 2012, we conducted a follow-up survey of 15- to 19-year-old street youth using the same study procedures as in 2006. Of 311 participants, 45 (14.5%) reported injection drug use; 31 participants (10.0%, 95% confidence interval, 6.0%-16.2%) were HIV-seropositive. Predictors independently associated with HIV seropositivity included injection drug use (adjusted prevalence ratio 53.1) and transactional sex (adjusted prevalence ratio 1.3). None of the 178 participants aged 15-17 years were HIV-positive. Thirty of 31 (96.8%) HIV-seropositive individuals reported injection drug use. Street youth in St Petersburg had a 73% decrease in HIV seroprevalence from 2006 to 2012, primarily due to decreased initiation of injection drug use. This marked reduction in the HIV epidemic among street youth occurred after implementation of extensive support programs and socio-economic improvements.

To improve early enrollment in HIV care, the Swaziland Ministry of Health implemented new linkage procedures for persons HIV diagnosed during the Soka Uncobe male circumcision campaign (SOKA, 2011-2012) and the Swaziland HIV Incidence Measurement Survey (SHIMS, 2011). Abstraction of clinical records and telephone interviews of a retrospective cohort of HIV-diagnosed SOKA and SHIMS clients were conducted in 2013-2014 to evaluate compliance with new linkage procedures and enrollment in HIV care at 92 facilities throughout Swaziland. Of 1,105 clients evaluated, within 3, 12, and 24 months of diagnosis, an estimated 14.0%, 24.3%, and 37.0% enrolled in HIV care, respectively, after adjusting for lost to follow-up and non-response. Kaplan-Meier functions indicated lower enrollment probability among clients 14-24 (P = 0.0001) and 25-29 (P = 0.001) years of age compared with clients >35 years of age. At 69 facilities to which clients were referred for HIV care, compliance with new linkage procedures was low: referral forms were located for less than half (46.8%) of the clients, and few (9.6%) were recorded in the appointment register or called either before (0.3%) or after (4.9%) their appointment. Of over one thousand clients newly HIV diagnosed in Swaziland in 2011 and 2012, few received linkage services in accordance with national procedures and most had not enrolled in HIV care two years after their diagnosis. Our findings are a call to action to improve linkage services and early enrollment in HIV care in Swaziland.

BACKGROUND: In 2007, Swaziland initiated a hub-and-spoke model for decentralizing antiretroviral therapy (ART) access for HIV-infected children (<15 years old). Decentralization was facilitated through: (1) down-referral of stable children on ART from overburdened central facilities (hubs) to primary healthcare clinics (spokes), and (2) pediatric ART initiation at spokes (spoke-initiation). METHODS: We conducted a nationally representative retrospective cohort study among children starting ART during 2004-2010 to assess effect of down-referral and spoke-initiation on rates of loss to follow-up (LTFU), death, and attrition (death or LTFU). Twelve of 28 pediatric ART hubs were randomly selected using probability-proportional-to-size sampling. Seven selected facilities had initiated hub-and-spoke decentralization by study start; at these facilities, 901 of 1,893 hub-initiated and maintained (hub-maintained) children, and 495 of 1,105 down-referred or spoke-initiated children were randomly selected for record abstraction. At the five hub-only facilities, 612 of 1,987 children were randomly selected. Multivariable proportional hazards regression was used to estimate adjusted hazards ratios (AHR) for effect of down-referral (a time-varying covariate) and spoke-initiation on outcomes. RESULTS: Among 2,008 children at ART initiation, median age was 5.0 years, median CD4 percentage 12.0%, median CD4 count 358 cells/microL, and median weight-for-age z-score -1.91. Controlling for known confounders, down-referral was strongly protective against LTFU (AHR 0.40; 95% CI, 0.20-0.79) and attrition (AHR 0.46; 95% CI, 0.26-0.83) but not mortality. Compared with hub-only children or hub-maintained children, spoke-initiated children had similar outcomes. CONCLUSIONS: Decentralization of pediatric ART through down-referral and spoke-initiation within a hub-and-spoke system should be continued and might improve program outcomes.

Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. President's Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(dagger) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage.

HIV testing and counseling (HTC) is an essential component of comprehensive HIV programs. Retrospective HTC program data from 2006 to 2010 were examined to determine patterns of re-testing and seroconversion in Lesotho. Among 104,662 initially negative clients, 6,777 (6.5%) were re-testers. Predictors of re-testing included being male, age ≥ 25 years, divorced/separated, having more than a high school education, being tested as a couple, testing in the year 2006, testing in the capital city, and awareness of partner's recent testing behavior. Among re-testers who seroconverted (N = 259), predictors included being female and having less than a high school education. There is a critical need for more effectively targeting HIV retesting messages to align with WHO (2010) guidelines and identify persons at highest risk for HIV, to increase timely diagnoses and link persons to appropriate HIV prevention, care, and treatment services.

BACKGROUND: American infants are at highest risk of severe pertussis and death. We investigated the role of ≥1 pertussis vaccinations in preventing pertussis-related deaths and risk markers for death among infants aged <42 days. METHODS: We analyzed characteristics of fatal and nonfatal infant pertussis cases reported nationally during 1991-2008. Infants were categorized into 2 age groups on the basis of eligibility to receive a first pertussis vaccine dose at age 6 weeks; dose 1 was considered valid if given ≥14 days before illness onset. Multivariable logistic regression was used to estimate the effect of ≥1 pertussis vaccine doses on outcome and risk markers. RESULTS: Pertussis-related deaths occurred among 258 of 45 404 cases. Fatal and nonfatal cases were confirmed by culture (54% vs 49%) and polymerase chain reaction (31% vs 27%). All deaths occurred before age 34 weeks at illness onset; 64% occurred before age 6 weeks. Among infants aged ≥42 days, receiving ≥1 doses of vaccine protected against death (adjusted odds ratio [aOR]: 0.28; 95% confidence interval [CI]: 0.11-0.74), hospitalization (aOR: 0.69; 95% CI: 0.63-0.77), and pneumonia (aOR: 0.80; 95% CI: 0.68-0.95). Risk was elevated for Hispanic ethnicity (aOR: 2.28; 95% CI: 1.36-3.83) and American Indian/Alaska Native race (aOR: 5.15; 95% CI: 2.37-11.2) and lower for recommended antibiotic treatment (aOR: 0.28; 95% CI: 0.16-0.47). Among infants aged <42 days, risk was elevated for Hispanic ethnicity and lower with recommended antibiotic use. CONCLUSIONS: The first pertussis vaccine dose and antibiotic treatment protect against death, hospitalization, and pneumonia.

BACKGROUND: In 2007, Swaziland initiated a hub-and-spoke model for decentralizing antiretroviral therapy (ART) access. Decentralization was facilitated through (1) down-referral of stable ART patients from overburdened central facilities (hubs) to primary health care clinics (spokes) and (2) ART initiation at spokes (spoke initiation). METHODS: We conducted a nationally representative retrospective cohort study among adult ART enrollees during 2004-2010 to assess the effect of down-referral and spoke-initiation on rates of loss to follow-up (LTFU), death, and attrition (death or LTFU). Sixteen of 31 hubs were randomly selected using probability-proportional-to-size sampling. Seven selected facilities had initiated the hub-and-spoke model by study start. At these facilities, 1149 of 24,782 hub-initiated and maintained and 878 of 7722 down-referred or spoke-initiated patient records were randomly selected and analyzed. At the 9 hub-only facilities, 483 of 6638 records were randomly selected and analyzed. Multivariable proportional hazards regression was used to assess effect of down-referral (a time-varying covariate) and spoke-initiation on outcomes. RESULTS: At ART initiation, median age was 35, 65% were female, and median CD4 count was 147 cells per microliter. Controlling for known confounders, down-referral was strongly protective against LTFU [adjusted hazard ratio (AHR) 0.38; 95% confidence interval (CI): 0.29 to 0.50] and attrition (AHR = 0.50; 95% CI: 0.34 to 0.76) but not mortality. Compared with hub-initiated and maintained patients, spoke-initiated patients had lower LTFU (AHR 0.59; 95% CI: 0.45 to 0.77) and attrition rates (AHR 0.60; 95% CI: 0.47 to 0.77), but not mortality. CONCLUSIONS: Down-referral and spoke-initiation within a hub-and-spoke ART decentralization model were protective against LTFU and overall attrition and could facilitate future ART program expansion.

Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about 30% in the global annual number of human immunodeficiency (HIV)-related deaths and declines in global HIV incidence, estimated annual HIV-related deaths among adolescents have increased by about 50% and estimated adolescent HIV incidence has been relatively stable. In 2012, an estimated 2,500 (40%) of all 6,300 daily new HIV infections occurred among persons aged 15-24 years. Difficulty enrolling adolescents and young adults in ART and high rates of loss to follow-up (LTFU) after ART initiation might be contributing to mortality and HIV incidence in this age group, but data are limited. To evaluate age-related ART retention challenges, data from retrospective cohort studies conducted in seven African countries among 16,421 patients, aged ≥15 years at enrollment, who initiated ART during 2004-2012 were analyzed. ART enrollment and outcome data were compared among three groups defined by age at enrollment: adolescents and young adults (aged 15-24 years), middle-aged adults (aged 25-49 years), and older adults (aged ≥50 years). Enrollees aged 15-24 years were predominantly female (81%-92%), commonly pregnant (3%-32% of females), unmarried (54%-73%), and, in four countries with employment data, unemployed (53%-86%). In comparison, older adults were more likely to be male (p<0.001), employed (p<0.001), and married, (p<0.05 in five countries). Compared with older adults, adolescents and young adults had higher LTFU rates in all seven countries, reaching statistical significance in three countries in crude and multivariable analyses. Evidence-based interventions to reduce LTFU for adolescent and young adult ART enrollees could help reduce mortality and HIV incidence in this age group.

BACKGROUND: Ukraine developed Europe's most severe HIV epidemic due to widespread transmission among persons who inject drugs (PWID). Since 2004, prevention has focused on key populations; antiretroviral therapy (ART) coverage has increased. Recent data show increases in reported HIV cases through 2011, especially attributed to sexual transmission, but also signs of potential epidemic slowing. We conducted a data triangulation exercise to better analyze available data and inform program implementation. METHODS AND FINDINGS: We reviewed data for 2005 to 2012 from multiple sources, primarily national HIV case reporting and integrated biobehavioral surveillance (IBBS) studies among key populations. Annually reported HIV cases increased at a progressively slower rate through 2011 with recent increases only among older, more immunosuppressed individuals; cases decreased 2.7% in 2012. Among women <25 years of age, cases attributed to heterosexual transmission and HIV prevalence in antenatal screening declined after 2008. Reported cases among young PWID declined by three-fourths. In 2011, integrated biobehavioral surveillance demonstrated decreased HIV prevalence among young members of key populations compared with 2009. HIV infection among female sex workers (FSW) remains strongly associated with a personal history of injecting drug use (IDU). CONCLUSIONS: This analysis suggests that Ukraine's HIV epidemic has slowed, with decreasing reported cases and older cases predominating among those diagnosed. Recent decreases in cases and in prevalence support decreased incidence among young PWID and women. Trends among heterosexual men and men who have sex with men (MSM) are less clear; further study and enhanced MSM prevention are needed. FSW appear to have stable prevalence with risk strongly associated with IDU. Current trends suggest the Ukrainian epidemic can be contained with enhanced prevention among key populations and increased treatment access.

Because of widespread distribution of the influenza A (H1N1) 2009 monovalent vaccine (pH1N1 vaccine) and the prior association between Guillain-Barre syndrome (GBS) and the 1976 H1N1 influenza vaccine, enhanced surveillance was implemented to estimate the magnitude of any increased GBS risk following administration of pH1N1 vaccine. The authors conducted active, population-based surveillance for incident cases of GBS among 45 million persons residing at 10 Emerging Infections Program sites during October 2009-May 2010; GBS was defined according to published criteria. The authors determined medical and vaccine history for GBS cases through medical record review and patient interviews. The authors used vaccine coverage data to estimate person-time exposed and unexposed to pH1N1 vaccine and calculated age- and sex-adjusted rate ratios comparing GBS incidence in these groups, as well as age- and sex-adjusted numbers of excess GBS cases. The authors received 411 reports of confirmed or probable GBS. The rate of GBS immediately following pH1N1 vaccination was 57% higher than in person-time unexposed to vaccine (adjusted rate ratio = 1.57, 95% confidence interval: 1.02, 2.21), corresponding to 0.74 excess GBS cases per million pH1N1 vaccine doses (95% confidence interval: 0.04, 1.56). This excess risk was much smaller than that observed during the 1976 vaccine campaign and was comparable to some previous seasonal influenza vaccine risk assessments.

BACKGROUND: An IgG anti-pertussis toxin (PT) enzyme-linked immunosorbent assay (ELISA) was analytically validated for diagnosis of pertussis, using the cut-off of 94 ELISA Units (EU)/mL. Little was known about the performance of this ELISA for diagnosis in adults recently vaccinated with tetanus-diphtheria-acellular pertussis (Tdap), which contains PT. The goal of this study was to determine when the assay can be used following Tdap vaccination. METHODS: A cohort of 102 asymptomatic health care personnel (HCP) vaccinated with Tdap (Adacel, Sanofi Pasteur) were aged 19 to 79 years (median 47 years) at vaccination. For each HCP, specimens were available for evaluation at 2-10 time points (pre-vaccination to 24 months post-vaccination), and geometric mean concentrations (GMC) for the cohort were calculated at each time point. Among 97 HCP who responded to vaccination, a mixed model analysis with prediction and tolerance intervals was performed to estimate the time at which serodiagnosis can be used following vaccination. RESULTS: The GMC was 8, 21, and 9 EU/mL at pre-vaccination, four, and 12 months post-vaccination, respectively. Eight of 102 (8%) HCP reached antibody titers ≥ 94 EU/mL during their peak response but none had these titers by six months post-vaccination. Calculated prediction and tolerance intervals were < 94 EU/mL by 45 and 75 days post-vaccination, respectively. CONCLUSIONS: Tdap vaccination six months prior to testing did not confound result interpretation. This seroassay remains a valuable diagnostic tool for adult pertussis.

Neisseria meningitidis (Nm), Haemophilus influenzae (Hi), and Streptococcus pneumoniae (Sp) are important causes of meningitis and other infections, and rapid, sensitive, and specific laboratory assays are critical for effective public health interventions. Singleplex real-time PCR assays have been developed to detect Nm ctrA, Hi hpd and Sp lytA, and serogroup-specific genes in the cap locus for Nm serogroups A, B, C, W135, X and Y. However, the assay sensitivity for serogroups B, W135 and Y is low. We aimed to improve assay sensitivity and develop multiplex assays to reduce time and cost. New singleplex real-time PCR assays B-synD, W-synG, and Y-synF showed 100% specificity for detecting Nm species, with high sensitivity [B-synD, 99%(75/76); W-synG, 97%(38/39); and Y-synF, 100%(66/66)]. The lower limit of detection (LLD) was 9, 43 and 10 copies/reaction for B-synD, W-synG, and Y-synF assays, respectively, a significant improvement compared to the previous singleplex assays. We developed three multiplex real-time PCR assays for detection of: (i) Nm ctrA, Hi hpd and Sp lytA (NHS); (ii) Nm serogroups A, W135 and X (AWX), and (iii) Nm serogroups B, C and Y (BCY). Each multiplex assay was 100% specific for detecting its target organisms or serogroups, and the LLD was similar to that for singleplex. Pairwise comparison of real-time PCR between multiplex and singleplex showed that cycle threshold values of the multiplex were similar to those for singleplex. There were no substantial differences in the sensitivity and specificity between these multiplex and singleplex real-time PCR assays.

BACKGROUND: In 2006, a mumps outbreak occurred on a university campus despite ≥ 95% coverage of students with 2 doses of measles-mumps-rubella (MMR) vaccine. Using plasma samples from a blood drive held on campus before identification of mumps cases, we compared vaccine-induced preoutbreak mumps antibody levels between individuals who developed mumps (case patients) and those who did not develop mumps (nonpatients). METHODS: Preoutbreak samples were available from 11 case patients, 22 nonpatients who reported mumps exposure but no mumps symptoms, and 103 nonpatients who reported no known exposure and no symptoms. Antibody titers were measured by plaque reduction neutralization assay using Jeryl Lynn vaccine virus and the outbreak virus Iowa-G/USA-06 and by enzyme immunoassay (EIA). RESULTS: Preoutbreak Jeryl Lynn virus neutralization titers were significantly lower among case patients than unexposed nonpatients (P = .023), and EIA results were significantly lower among case patients than exposed nonpatients (P = .007) and unexposed nonpatients (P = .009). Proportionately more case patients than exposed nonpatients had a preoutbreak anti-Jeryl Lynn titer < 31 (64% vs 27%, respectively; P = .065), an anti-Iowa-G/USA-06 titer < 8 (55% vs 14%; P = .033), and EIA index standard ratio < 1.40 (64% vs 9%; P = .002) and < 1.71 (73% vs 14%, P = .001). DISCUSSION: Case patients generally had lower preoutbreak mumps antibody levels than nonpatients. However, titers overlapped and no cutoff points separated all mumps case patients from all nonpatients.

Population incidence of Guillain-Barre syndrome (GBS) is required to assess changes in GBS epidemiology, but published estimates of GBS incidence vary greatly depending on case ascertainment, definitions, and sample size. We performed a meta-analysis of articles on GBS incidence by searching Medline (1966-2009), Embase (1988-2009), Cinahl (1981-2009) and CABI (1973-2009) as well as article bibliographies. We included studies from North America and Europe with at least 20 cases, and used population-based data, subject matter experts to confirm GBS diagnosis, and an accepted GBS case definition. With these data, we fitted a random-effects negative binomial regression model to estimate age-specific GBS incidence. Of 1,683 nonduplicate citations, 16 met the inclusion criteria, which produced 1,643 cases and 152.7 million person-years of follow-up. GBS incidence increased by 20% for every 10-year increase in age; the risk of GBS was higher for males than females. The regression equation for calculating the average GBS rate per 100,000 person-years as a function of age in years was exp[-12.0771 + 0.01813(age in years)] x 100,000. Our findings provide a robust estimate of background GBS incidence in Western countries. Our regression model may be used in comparable populations to estimate the background age-specific rate of GBS incidence for future studies.

BACKGROUND: Tdap is recommended for health care personnel (HCP) aged <65 years who received tetanus diphtheria or tetanus toxoid immunization (Td/TT) ≥2 years earlier. During a medical center Tdap vaccination campaign, we assessed the safety of use of a Td/TT to Tdap interval <2 years in HCP. We also describe reactogenicity in HCP who were aged ≥65 years or pregnant. METHODS: HCP vaccinated with Tdap were surveyed to assess time since last Td/TT (≥2 years vs. <2 years), age, pregnancy status, and injection site adverse events (AEs) during the 2 weeks after Tdap. AE rates were calculated and compared by non-inferiority analysis using a predetermined margin of 10%. We searched clinic logbooks to assess for clinically important adverse events during the 2 months after Tdap. RESULTS: Of the 4524 vaccinated HCP, 2221 (49.1%) completed a safety survey which met criteria for analysis. Non-inferiority analysis found that rates of moderate and/or severe injection site AEs were not significantly greater in those vaccinated <2 years than in those vaccinated ≥2 years after previous Td/TT. Three serious adverse events were reported during the 2 months after vaccination, none in persons who were ≥65 years, pregnant or received Td/TT <2 years before. CONCLUSIONS: Our findings add to the body of evidence that a short interval between Td/TT and a single dose of Tdap is safe.

BACKGROUND: The incidence of varicella disease is declining as a result of vaccination, making clinical diagnosis more challenging, particularly for vaccine-modified cases. We conducted a comprehensive evaluation of laboratory tests and specimen types to assess diagnostic performance and determine what role testing can play after skin lesions have resolved. METHODS: We enrolled patients with suspected varicella disease in 2 communities. Enrollees were visited at the time of rash onset and 2 weeks later. Multiple skin lesion, oral, urine, and blood or serum specimens were requested at each visit and tested for varicella zoster virus (VZV) immunoglobulin (Ig) G, IgM, and IgA antibody by enzyme-linked immunoassay; for VZV antigen by direct fluorescent antibody; and/or for VZV DNA by polymerase chain reaction (PCR). Clinical certainty of the diagnosis of varicella disease was scored. PCR results from first-visit vesicles or scab specimens served as the gold standard in assessing test performance. RESULTS: Of 93 enrollees, 53 were confirmed to have varicella disease. Among 20 unmodified cases, PCR testing was 95%-100% sensitive for macular and/or papular lesions and for oral specimens collected at the first visit; most specimens from the second visit yielded negative results. Among 27 vaccine-modified cases, macular and/or papular lesions collected at the first visit were also 100% sensitive; yields from other specimens were poorer, and few specimens from the second visit tested positive. Clinical diagnosis was 100% and 85% sensitive for diagnosing unmodified and vaccine-modified varicella cases, respectively. CONCLUSIONS: PCR testing of skin lesion specimens remains convenient and accurate for diagnosing varicella disease in vaccinated and unvaccinated persons. PCR of oral specimens can sometimes aid in diagnosis of varicella disease, even after rash resolves.

Adequately sensitive and specific methods to diagnose pertussis in adolescents and adults are not widely available. Currently, no Food and Drug Administration approved diagnostic assays are available for the serodiagnosis of Bordetella pertussis. Since concentrations of B. pertussis-specific antibodies tend to be high during the later-phases of disease, a simple, rapid, easily transferable serodiagnostic test was developed. This paper describes test development, initial evaluation of a prototype kit enzyme-linked immunosorbent assay (ELISA) in an inter-laboratory collaborative study, and the analytical validation. The data presented here demonstrate that the kit met all pre-specified criteria for precision, linearity, and accuracy for samples with anti-pertussis toxin (PT) immunoglobulin G (IgG) antibody concentrations in the range of 50 to 150 ELISA units (EU)/mL, the range believed to be most relevant for serodiagnosis. The assay met the precision and linearity criteria for a wider range, namely from 50 to 200 EU/mL, however, the accuracy criterion was not met at 200 EU/mL. When the newly adopted World Health Organization International Standard for pertussis antiserum (human) reference reagent was used to evaluate accuracy, the accuracy criteria were met from 50 to 200 international units (IU)/mL. In conclusion, the IgG anti-PT ELISA assay met all assay validation parameters within the range considered most relevant for serodiagnosis. This ELISA was developed and analytically validated to be a user-friendly kit that can be used in both qualitative and quantitative formats. The technology for producing the kit is transferrable to public health laboratories.