Beyond the 95s: What happens when uniform program targets are applied across a heterogenous HIV epidemic in Eastern and Southern Africa?

The UNAIDS 95-95-95 targets are an important metric for guiding national HIV programs and measuring progress towards ending the HIV epidemic as a public health threat by 2030. Nevertheless, as proportional targets, the outcome of reaching the 95-95-95 targets will vary greatly across, and within, countries owing to the geographic diversity of the HIV epidemic. Countries and subnational units with a higher initial prevalence and number of people living with HIV (PLHIV) will remain with a larger number and higher prevalence of virally unsuppressed PLHIV-persons who may experience excess morbidity and mortality and can transmit the virus to others. Reliance on achievement of uniform proportional targets as a measure of program success can potentially mislead resource allocation and progress towards equitable epidemic control. More granular surveillance information on the HIV epidemic is required to effectively calibrate strategies and intensity of HIV programs across geographies and address current and projected health disparities that may undermine efforts to reach and sustain HIV epidemic control even after the 95 targets are achieved.

Retrospective longitudinal analysis of low-level viremia among HIV-1 infected adults on antiretroviral therapy in Kenya.

Background: HIV low-level viremia (LLV) (51-999 copies/mL) can progress to treatment failure and increase potential for drug resistance. We analyzed retrospective longitudinal data from people living with HIV (PLHIV) on antiretroviral therapy (ART) in Kenya to understand LLV prevalence and virologic outcomes. Methods: We calculated rates of virologic suppression (≤50 copies/mL), LLV (51-999 copies/mL), virologic non-suppression (≥1000 copies/mL), and virologic failure (≥2 consecutive virologic non-suppression results) among PLHIV aged 15 years and older who received at least 24 weeks of ART during 2015-2021. We analyzed risk for virologic non-suppression and virologic failure using time-dependent models (each viral load (VL) <1000 copies/mL used to predict the next VL). Findings: Of 793,902 patients with at least one VL, 18.5% had LLV (51-199 cp/mL 11.1%; 200-399 cp/mL 4.0%; and 400-999 cp/mL 3.4%) and 9.2% had virologic non-suppression at initial result. Among all VLs performed, 26.4% were LLV. Among patients with initial LLV, 13.3% and 2.4% progressed to virologic non-suppression and virologic failure, respectively. Compared to virologic suppression (≤50 copies/mL), LLV was associated with increased risk of virologic non-suppression (adjusted relative risk [aRR] 2.43) and virologic failure (aRR 3.86). Risk of virologic failure increased with LLV range (aRR 2.17 with 51-199 copies/mL, aRR 3.98 with 200-399 copies/mL and aRR 7.99 with 400-999 copies/mL). Compared to patients who never received dolutegravir (DTG), patients who initiated DTG had lower risk of virologic non-suppression (aRR 0.60) and virologic failure (aRR 0.51); similarly, patients who transitioned to DTG had lower risk of virologic non-suppression (aRR 0.58) and virologic failure (aRR 0.35) for the same LLV range. Interpretation: Approximately a quarter of patients experienced LLV and had increased risk of virologic non-suppression and failure. Lowering the threshold to define virologic suppression from <1000 to <50 copies/mL to allow for earlier interventions along with universal uptake of DTG may improve individual and program outcomes and progress towards achieving HIV epidemic control. Funding: No specific funding was received for the analysis. HIV program support was provided by the President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Centers for Disease Control and Prevention (CDC).

A national household survey on HIV prevalence and clinical cascade among children aged ≤15 years in Kenya (2018).

We analyzed data from the 2018 Kenya Population-Based HIV Impact Assessment (KENPHIA), a cross-sectional, nationally representative survey, to estimate the burden and prevalence of pediatric HIV infection, identify associated factors, and describe the clinical cascade among children aged < 15 years in Kenya. Interviewers collected information from caregivers or guardians on child's demographics, HIV testing, and treatment history. Blood specimens were collected for HIV serology and if HIV-positive, the samples were tested for viral load and antiretrovirals (ARV). For participants <18 months TNA PCR is performed. We computed weighted proportions with 95% confidence intervals (CI), accounting for the complex survey design. We used bivariable and multivariable logistic regression to assess factors associated with HIV prevalence. Separate survey weights were developed for interview responses and for biomarker testing to account for the survey design and non-response. HIV burden was estimated by multiplying HIV prevalence by the national population projection by age for 2018. Of 9072 survey participants (< 15 years), 87% (7865) had blood drawn with valid HIV test results. KENPHIA identified 57 HIV-positive children, translating to an HIV prevalence of 0.7%, (95% CI: 0.4%-1.0%) and an estimated 138,900 (95% CI: 84,000-193,800) of HIV among children in Kenya. Specifically, children who were orphaned had about 2 times higher odds of HIV-infection compared to those not orphaned, adjusted Odds Ratio (aOR) 2.2 (95% CI:1.0-4.8). Additionally, children whose caregivers had no knowledge of their HIV status also had 2 times higher odds of HIV-infection compared to whose caregivers had knowledge of their HIV status, aOR 2.4 (95% CI: 1.1-5.4)". From the unconditional analysis; population level estimates, 78.9% of HIV-positive children had known HIV status (95% CI: 67.1%-90.2%), 73.6% (95% CI: 60.9%-86.2%) were receiving ART, and 49% (95% CI: 32.1%-66.7%) were virally suppressed. However, in the clinical cascade for HIV infected children, 92% (95% CI: 84.4%-100%) were receiving ART, and of these, 67.1% (95% CI: 45.1%-89.2%) were virally suppressed. The KENPHIA survey confirms a substantial HIV burden among children in Kenya, especially among orphans.

HIV Risk Factors and Risk Perception Among Adolescent Girls and Young Women: Results From a Population-Based Survey in Western Kenya, 2018.

BACKGROUND: In sub-Saharan Africa, HIV prevalence in adolescent girls and young women (AGYW) is 2-fold to 3-fold higher than that in adolescent boys and young men. Understanding AGYW's perception of HIV risk is essential for HIV prevention efforts. METHODS: We analyzed data from a HIV biobehavioral survey conducted in western Kenya in 2018. Data from AGYW aged 15-24 years who had a documented HIV status were included. We calculated weighted prevalence and evaluated factors associated with outcomes of interest (HIV infection and high risk perception) using generalized linear models to calculate prevalence ratios. RESULTS: A total of 3828 AGYW were included; 63% were aged 15-19 years. HIV prevalence was 4.5% and 14.5% of sexually active AGYW had high risk perception. Over 70% of participants had accessed HIV testing and counseling in the past 12 months. Factors associated with both HIV infection and high risk perception included having an HIV-positive partner or partner with unknown status and having a sexually transmitted infection in the past 12 months. Having an older (by ≥10 years) partner was associated with HIV infection, but not high risk perception. Less than 30% of sexually active AGYW with 3 or more HIV risk factors had high perception of HIV risk. CONCLUSION: Gaps in perceived HIV risk persist among AGYW in Kenya. High access to HIV testing and prevention services in this population highlights platforms through which AGYW may be reached with improved risk counseling, and to increase uptake of HIV prevention strategies.

Development and Validation of a Sociodemographic and Behavioral Characteristics-Based Risk-Score Algorithm for Targeting HIV Testing Among Adults in Kenya.

To inform targeted HIV testing, we developed and externally validated a risk-score algorithm that incorporated behavioral characteristics. Outpatient data from five health facilities in western Kenya, comprising 19,458 adults ≥ 15 years tested for HIV from September 2017 to May 2018, were included in univariable and multivariable analyses used for algorithm development. Data for 11,330 adults attending one high-volume facility were used for validation. Using the final algorithm, patients were grouped into four risk-score categories: ≤ 9, 10-15, 16-29 and ≥ 30, with increasing HIV prevalence of 0.6% [95% confidence interval (CI) 0.46-0.75], 1.35% (95% CI 0.85-1.84), 2.65% (95% CI 1.8-3.51), and 15.15% (95% CI 9.03-21.27), respectively. The algorithm's discrimination performance was modest, with an area under the receiver-operating-curve of 0.69 (95% CI 0.53-0.84). In settings where universal testing is not feasible, a risk-score algorithm can identify sub-populations with higher HIV-risk to be prioritized for HIV testing.

Expanded eligibility for HIV testing increases HIV diagnoses-A cross-sectional study in seven health facilities in western Kenya.

Homa Bay, Siaya, and Kisumu counties in western Kenya have the highest estimated HIV prevalence (16.3-21.0%) in the country, and struggle to meet program targets for HIV testing services (HTS). The Kenya Ministry of Health (MOH) recommends annual HIV testing for the general population. We assessed the degree to which reducing the interval for retesting to less than 12 months increased diagnosis of HIV in outpatient departments (OPD) in western Kenya. We conducted a retrospective analysis of routinely collected program data from seven high-volume (>800 monthlyOPD visits) health facilities in March-December, 2017. Data from persons ≥15 years of age seeking medical care (patients) in the OPD and non-care-seekers (non-patients) accompanying patients to the OPD were included. Outcomes were meeting MOH (routine) criteria versus criteria for a reduced retesting interval (RRI) of <12 months, and HIV test result. STATA version 14.2 was used to calculate frequencies and proportions, and to test for differences using bivariate analysis. During the 9-month period, 119,950 clients were screened for HIV testing eligibility, of whom 79% (94,766) were eligible and 97% (92,153) received a test. Among 92,153 clients tested, the median age was 28 years, 57% were female and 40% (36,728) were non-patients. Overall, 20% (18,120) of clients tested met routine eligibility criteria: 4% (3,972) had never been tested, 10% (9,316) reported a negative HIV test in the past >12 months, and 5% (4,832) met other criteria. The remaining 80% (74,033) met criteria for a RRI of < 12 months. In total 1.3% (1,185) of clients had a positive test. Although the percent yield was over 2-fold higher among those meeting routine criteria (2.4% vs. 1.0%; p<0.001), 63% (750) of all HIV infections were found among clients tested less than 12 months ago, the majority (81%) of whom reported having a negative test in the past 3-12 months. Non-patients accounted for 45% (539) of all HIV-positive persons identified. Percent yield was higher among non-patients as compared to patients (1.5% vs. 1.2%; p-value = <0.001) overall and across eligibility criteria and age categories. The majority of HIV diagnoses in the OPD occurred among clients reporting a negative HIV test in the past 12 months, clients ineligible for testing under the current MOH guidelines. Nearly half of all HIV-positive individuals identified in the OPD were non-patients. Our findings suggest that in the setting of a generalized HIV epidemic, retesting persons reporting an HIV-negative test in the past 3-12 months, and routine testing of non-patients accessing the OPD are key strategies for timely diagnosis of persons living with HIV.

Disclosure and Clinical Outcomes Among Young Adolescents Living With HIV in Kenya.

PURPOSE: Informing adolescents of their own HIV infection is critical as the number of adolescents living with HIV increases. We assessed the association between HIV disclosure and retention in care and mortality among adolescents aged 10-14 years in Kenya's national program. METHODS: We abstracted routinely collected patient-level data for adolescents enrolled into HIV care in 50 health facilities from November 1, 2004, through March 31, 2010. We defined disclosure as any documentation that the adolescent had been fully or partially made aware of his or her HIV status. We compared weighted proportions for categorical variables using χ2 and weighted logistic regression to identify predictors of HIV disclosure; we estimated the probability of LTFU using Kaplan-Meier methods and dying using Cox regression-based test for equality of survival curves. RESULTS: Of the 710 adolescents aged 10-14 years analyzed; 51.3% had severe immunosuppression, 60.3% were in WHO stage 3 or 4, and 36.6% were aware of their HIV status. Adolescents with HIV-infected parents, histories of opportunistic infections (OIs), and enrolled in support groups were more likely to be disclosed to. At 36 months, disclosure was associated with lower mortality [1.5% (95% CI .6%-4.1%) versus 5.4% (95% CI 3.6.6%-8.0%, p < .001)] and lower LTFU [6.2% (95% CI 3.0%-12.6%) versus 33.9% (95% CI 27.3%-41.1%) p < .001]. CONCLUSIONS: Only one third of HIV-infected Kenyan adolescents in treatment programs had been told they were infected, and knowing their HIV status was associated with reduced LTFU and mortality. The disclosure process should be systematically encouraged and organized for HIV-infected adolescents.

Preexposure Prophylaxis for Human Immunodeficiency Virus (HIV) Prevention Among HIV-uninfected Pregnant Women: Estimated Coverage Using Risk-based Versus Regional Prevalence Approaches.

Antenatal register data from 62 clinics in 5 regions of Kenya were used to estimate women with human immunodeficiency virus (HIV) risk (partner HIV status, syphilis). With individual risk-guided preexposure prophylaxis (PrEP) offer in all regions, 39% of pregnant women would be offered PrEP nationally. Offering PrEP to all women in high-prevalence regions reached 26% of the pregnant women.

Trends, treatment outcomes, and determinants for attrition among adult patients in care at a large tertiary HIV clinic in Nairobi, Kenya: a 2004-2015 retrospective cohort study.

BACKGROUND: Understanding trends in patient profiles and identifying predictors for adverse outcomes are key to improving the effectiveness of HIV care and treatment programs. Previous work in Kenya has documented findings from a rural setting. This paper describes trends in demographic and clinical characteristics of antiretroviral therapy (ART) treatment cohorts at a large urban, referral HIV clinic and explores treatment outcomes and factors associated with attrition during 12 years of follow-up. METHODS: This was a retrospective cohort analysis of HIV-infected adults who started ART between January 1, 2004, and September 30, 2015. ART-experienced patients and those with missing data were excluded. The Cochran-Armitage test was used to determine trends in baseline characteristics over time. Cox proportional hazards models were used to determine the effect of baseline characteristics on attrition. RESULTS: ART uptake among older adolescents (15-19 years), youth, and young adults increased over time (p=0.0001). Independent predictors for attrition included (adjusted hazard ratio [95% CI]) male sex: 1.30 (1.16-1.45), p=0.0001; age: 15-19 years: 1.83 (1.26-2.66), p=0.0014; 20-24 years: 1.93 (1.52-2.44), p=0.0001; and 25-29 years: 1.31 (1.11-1.54), p=0.0012; marital status - single: 1.27 (1.11-1.44), p=0.0005; and divorced/separated: 1.56 (1.30-1.87), p=0.0001; urban residence: 1.40 (1.20-1.64), p=0.0001; entry into HIV care following hospitalization: 1.31 (1.10-1.57), p=0.0026, or transfer from another facility: 1.60 (1.26-2.04), p=0.0001; initiation of ART more than 12 months after the date of HIV diagnosis: 1.36 (1.19-1.55), p=0.0001, and history of a current or past opportunistic infection (OI): 1.15 (1.02-1.30), p=0.0284. CONCLUSION: Although ART uptake among adolescents and young people increased over time, this group was at increased risk for attrition. Single marital status, urban residence, history of hospitalization or OI, and delayed initiation of ART also predicted attrition. This calls for focused evidence-informed strategies to address attrition and improve outcomes.

Factors Associated with Outcomes of Pre-ART HIV Care.

The World Health Organization recommended removing all CD4 requirements for initiation of antiretroviral therapy (ART) in resource-limited settings. We examined the pre-ART period to identify and assess factors associated with outcomes of pre-ART care. Four modes of transition out of pre-ART care were considered. Beta estimates from the competing risks Cox models were used to investigate whether the effects of covariates differed by mode of transition. Median CD4 counts at entry showed no meaningful change over time. Advanced disease progression and presence of opportunistic infections were significant predictors of pre-ART mortality. Men were more likely to die before initiating ART, transfer to another facility, or be lost to follow-up than were women. Removing CD4 thresholds is not likely to substantially reduce program mortality prior to ART initiation unless and until patients enroll earlier in disease progression. Care programs should focus on diagnosis and treatment of opportunistic infections to reduce pre-ART mortality.

High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy.

A survey of 461 HIV-infected Kenyan children receiving antiretroviral therapy found 143 (31%) failing virologically. Drug resistance mutations were found in 121; 37 had L74V/I mutations, with 95% receiving abacavir (ABC)-containing regimens. L74V/I was associated with current ABC usage (P = 0.0001). L74V/I may be more prevalent than previously realized in children failing ABC-containing regimens, even when time on treatment has been short. Ongoing rigorous pediatric drug resistance surveillance is needed.

Trends in clinical characteristics and outcomes of Pre-ART care at a large HIV clinic in Nairobi, Kenya: a retrospective cohort study.

BACKGROUND: The success of antiretroviral therapy in resource-scarce settings is an illustration that complex healthcare interventions can be successfully delivered even in fragile health systems. Documenting the success factors in the scale-up of HIV care and treatment in resource constrained settings will enable health systems to prepare for changing population health needs. This study describes changing demographic and clinical characteristics of adult pre-ART cohorts, and identifies predictors of pre-ART attrition at a large urban HIV clinic in Nairobi, Kenya. METHODS: We conducted a retrospective cohort analysis of data on HIV infected adults (≥15 years) enrolling in pre-ART care between January 2004 and September 2015. Attrition (loss to program) was defined as those who died or were lost to follow-up (having no contact with the facility for at least 6 months). We used Kaplan-Meier survival analysis to determine time to event for the different modes of transition, and Cox proportional hazards models to determine predictors of pre-ART attrition. RESULTS: Over the 12 years of observation, there were increases in the proportions of young people (age 15 to 24 years); and patients presenting with early disease (by WHO clinical stage and higher median CD4 cell counts), p = 0.0001 for trend. Independent predictors of attrition included: aHR (95% CI): male gender 1.98 (1.69-2.33), p = 0.0001; age 20-24 years 1.80 (1.37-2.37), p = 0.0001), or 25-34 years 1.22 (1.01-1.47), p = 0.0364; marital status single 1.55 (1.29-1.86), p = 0.0001) or divorced 1.41(1.02-1.95), p = 0.0370; urban residency 1.83 (1.40-2.38), p = 0.0001; CD4 count of 0-100 cells/µl 1.63 (1.003-2.658), p = 0.0486 or CD4 count >500 cells/µl 2.14(1.46-3.14), p = 0.0001. CONCLUSIONS: In order to optimize the impact of HIV prevention, care and treatment in resource scarce settings, there is an urgent need to implement prevention and treatment interventions targeting young people and patients entering care with severe immunosuppression (CD4 cell counts <100 cells/µl). Additionally, care and treatment programmes should strengthen inter-facility referrals and linkages to improve care coordination and prevent leakages in the HIV care continuum.

Enhancing Maternal and Child Health using a Combined Mother & Child Health Booklet in Kenya.

Under Kenyan guidelines, HIV-exposed infants should be tested for HIV DNA at 6 weeks or at first clinical contact thereafter, as infants come for immunization. Following the introduction of early infant diagnoses programmes, however, many infants were not being tested and linked to care and treatment. We developed the Mother & Child Health Booklet to help relate mothers' obstetrical history to infants' healthcare providers to facilitate follow-up and timely management. The booklet contains information on the mother's pregnancy, delivery and postpartum course and her child's growth and development, immunization, nutrition and other data need to monitor the child to 5 years of age. It replaced three separate record clinical cards. In a 1 year pilot evaluation of the booklet in Nyanza province in 2007-08, the number of HIV DNA tests on infants increased by 34% from 9966 to 13 379. The booklet was subsequently distributed nationwide in 2009. Overall, the numbers of infants tested for HIV DNA rose from 27 000 in 2007 to 60 000 in 2012, which represents approximately 60% of the estimated HIV-exposed infants in Kenya. We believe that the booklet is an important strategy for identifying and treating infected infants and, thus, in progress toward Millennium Development Goal 4.

Maternal Tenofovir Disoproxil Fumarate Use in Pregnancy and Growth Outcomes among HIV-Exposed Uninfected Infants in Kenya.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and preexposure prophylaxis regimens. We evaluated the relationship of prenatal TDF use and growth outcomes among Kenyan HIV-exposed uninfected (HEU) infants. MATERIALS AND METHODS: We included PCR-confirmed HEU infants enrolled in a cross-sectional survey of mother-infant pairs conducted between July and December 2013 in Kenya. Maternal ART regimen during pregnancy was determined by self-report and clinic records. Six-week and 9-month z-scores for weight-for-age (WAZ), weight-for-length (WLZ), length-for-age (LAZ), and head circumference-for-age (HCAZ) were compared among HEU infants with and without TDF exposure using t-tests and multivariate linear regression models. RESULTS: Among 277 mothers who received ART during pregnancy, 63% initiated ART before pregnancy, of which 89 (32%) used TDF. No differences in birth weight (3.0 kg versus 3.1 kg, p = 0.21) or gestational age (38 weeks versus 38 weeks, p = 0.16) were detected between TDF-exposed and TDF-unexposed infants. At 6 weeks, unadjusted mean WAZ was lower among TDF-exposed infants (-0.8 versus -0.4, p = 0.03), with a trend towards association in adjusted analyses (p = 0.06). There were no associations between prenatal TDF use and WLZ, LAZ, and HCAZ in 6-week or 9-month infant cohorts. CONCLUSION: Maternal TDF use did not adversely affect infant growth compared to other regimens.

Comparison of trends in tuberculosis incidence among adults living with HIV and adults without HIV--Kenya, 1998-2012.

BACKGROUND: In Kenya, the comparative incidences of tuberculosis among persons with and without HIV have not been described, and the differential impact of public health interventions on tuberculosis incidence in the two groups is unknown. METHODS: We estimated annual tuberculosis incidence stratified by HIV status during 2006-2012 based on the numbers of reported tuberculosis patients with and without HIV infection, the prevalence of HIV infection in the general population, and the total population. We also made crude estimates of annual tuberculosis incidence stratified by HIV status during 1998-2012 by assuming a constant ratio of HIV prevalence among tuberculosis patients compared to the general population. RESULTS: Tuberculosis incidence among both adults with HIV and adults without HIV increased during 1998-2004 then remained relatively stable until 2007. During 2007-2012, tuberculosis incidence declined by 28-44% among adults with HIV and by 11-26% among adults without HIV, concurrent with an increase in antiretroviral therapy uptake. In 2012, tuberculosis incidence among adults with HIV (1,839-1,936 cases/100,000 population) was still eight times as high as among adults without HIV (231-238 cases/100,000 population), and approximately one third of tuberculosis cases were attributable to HIV. CONCLUSIONS: Although tuberculosis incidence has declined among adults with and without HIV, the persistent high incidence of tuberculosis among those with HIV and the disparity between the two groups are concerning. Early diagnosis of HIV, early initiation of antiretroviral therapy, regular screening for tuberculosis, and isoniazid preventive therapy among persons with HIV, as well as tuberculosis control in the general population, are required to address these issues.

Galactose-α-1,3-galactose-specific IgE is associated with anaphylaxis but not asthma.

RATIONALE: IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract. OBJECTIVES: To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens. METHODS: Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131). MEASUREMENTS AND MAIN RESULTS: Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001). CONCLUSIONS: These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled.

The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose.

BACKGROUND: In 2009, we reported a novel form of delayed anaphylaxis to red meat that is related to serum IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. OBJECTIVES: We sought to investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. METHODS: Serum assays were carried out with biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. RESULTS: Prospective studies on IgE antibodies in 3 subjects after tick bites showed an increase in levels of IgE to alpha-gal of 20-fold or greater. Other evidence included (1) a strong correlation between histories of tick bites and levels of IgE to alpha-gal (χ(2) = 26.8, P < .001), (2) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and (3) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A americanum (r(s) = 0.75, P < .001). CONCLUSION: The results presented here provide evidence that tick bites are a cause, possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.

Preventing mother-to-child transmission of HIV in Western Kenya: operational issues.

OBJECTIVES: To improve uptake in a program to prevent mother-to-child HIV transmission and describe lessons relevant for prevention of mother-to-child transmission programs in resource-poor settings. METHODS: Implementation of a pilot project that evaluates approaches to increase program uptake at health facility level at New Nyanza Provincial General Hospital, a public hospital in western Kenya, an area with high HIV prevalence. Client flow was revised to integrate counseling, HIV testing, and dispensing of single-dose nevirapine into routine antenatal services. The number of facilities providing PMCT services was expanded to increase district-wide coverage. Main outcome measures were uptake of counseling, HIV testing, nevirapine, and estimated program impact. RESULTS: Uptake of counseling and testing improved from 55 to 68% (P < 0.001), nevirapine uptake from 57% to 70% (P < 0.001), and estimated program impact from 15% to 23% (P = 0.03). Aggregate reports compare well with computer-entered data. CONCLUSION: Addressing institutional factors can improve uptake, but expected program impact remains low for several reasons, including relatively low efficacy of the intervention and missed opportunities in the labor room.

Comparison of PCR with the routine procedure for diagnosis of tuberculosis in a population with high prevalences of tuberculosis and human immunodeficiency virus.

Direct smear examination with Ziehl-Neelsen (ZN) staining for the diagnosis of tuberculosis (TB) as employed in most low-income countries is cheap and easy to use, but its low sensitivity is a major drawback. The low specificity of chest X-rays, used for the diagnosis of smear-negative TB, risks high levels of overdiagnosis. Major advances in molecular techniques, which rapidly identify mycobacterial DNA in sputa, may overcome these obstacles. In this study, the AMPLICOR PCR system was used to diagnose pulmonary TB in a developing country with high prevalences of both TB and human immunodeficiency virus (HIV). The sensitivity and specificity of this technique were compared to those of the usual diagnostic techniques. Sputum specimens were collected from 1,396 TB suspects attending the Rhodes Chest Clinic, Nairobi, Kenya. The specimens were analyzed for the presence of Mycobacterium tuberculosis by PCR; culture on Löwenstein-Jensen medium was used as the "gold standard." All culture-positive samples were genotyped to identify the mycobacterial species. The sensitivity and specificity of PCR were 93 and 84%, respectively. HIV status did not affect the sensitivity of PCR. A total of 99.7% of the true smear-positive and 82.1% of the true smear-negative TB patients were correctly identified by PCR. PCR detected M. tuberculosis in 11.7% of the culture-negative suspects, 60% of which had one or two PCR-positive sputum specimens. Of the 490 positive cultures, 486 were identified as M. tuberculosis. The high sensitivity of Amplicor PCR merits usage in a clinical setting with high TB and HIV burdens. Thus, PCR can be considered as an alternative to ZN staining in combination with chest X-ray for diagnosis of TB; however, cost-effectiveness studies and operational studies are required to support an evidence-based decision of introducing PCR for TB control in high-burden environments.