Timely intervention and control of a novel coronavirus (COVID-19) outbreak at a large skilled nursing facility-San Francisco, California, 2020.

OBJECTIVE: To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled-nursing facility (SNF), and the strategies that controlled transmission. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted during March 22-May 4, 2020, among all staff and residents at a 780-bed SNF in San Francisco, California. METHODS: Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPSs) in units with confirmed cases. Cases were confirmed by real-time reverse transcription-polymerase chain reaction testing for SARS-CoV-2, and whole-genome sequencing (WGS) was used to characterize viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact with a confirmed case; restricting movement between units; implementing surgical face masking facility-wide; and the use of recommended PPE (ie, isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases. RESULTS: Of 725 staff and residents tested through targeted testing and serial PPSs, 21 (3%) were SARS-CoV-2 positive: 16 (76%) staff and 5 (24%) residents. Fifteen cases (71%) were linked to a single unit. Targeted testing identified 17 cases (81%), and PPSs identified 4 cases (19%). Most cases (71%) were identified before IPC interventions could be implemented. WGS was performed on SARS-CoV-2 isolates from 4 staff and 4 residents: 5 were of Santa Clara County lineage and the 3 others were distinct lineages. CONCLUSIONS: Early implementation of targeted testing, serial PPSs, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.

Molecular Epidemiology and Transmission Dynamics of Recent and Long-Term HIV-1 Infections in Rural Western Kenya.

OBJECTIVE: To identify unique characteristics of recent versus established HIV infections and describe sexual transmission networks, we characterized circulating HIV-1 strains from two randomly selected populations of ART-naïve participants in rural western Kenya. METHODS: Recent HIV infections were identified by the HIV-1 subtype B, E and D, immunoglobulin G capture immunoassay (IgG BED-CEIA) and BioRad avidity assays. Genotypic and phylogenetic analyses were performed on the pol gene to identify transmitted drug resistance (TDR) mutations, characterize HIV subtypes and potential transmission clusters. Factors associated with recent infection and clustering were assessed by logistic regression. RESULTS: Of the 320 specimens, 40 (12.5%) were concordantly identified by the two assays as recent infections. Factors independently associated with being recently infected were age ≤19 years (P = 0.001) and history of sexually transmitted infections (STIs) in the past six months (P = 0.004). HIV subtype distribution differed in recently versus chronically infected participants, with subtype A observed among 53% recent vs. 68% chronic infections (p = 0.04) and subtype D among 26% recent vs. 12% chronic infections (p = 0.012). Overall, the prevalence of primary drug resistance was 1.16%. Of the 258 sequences, 11.2% were in monophyletic clusters of between 2-4 individuals. In multivariate analysis factors associated with clustering included having recent HIV infection P = 0.043 and being from Gem region P = 0.002. CONCLUSIONS: Recent HIV-1 infection was more frequent among 13-19 year olds compared with older age groups, underscoring the ongoing risk and susceptibility of younger persons for acquiring HIV infection. Our findings also provide evidence of sexual networks. The association of recent infections with clustering suggests that early infections may be contributing significant proportions of onward transmission highlighting the need for early diagnosis and treatment as prevention for ongoing prevention. Larger studies are needed to better understand the structure of these networks and subsequently implement and evaluate targeted interventions.

Creating an African HIV clinical research and prevention trials network: HIV prevalence, incidence and transmission.

HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner.

Host genetics and viral load in primary HIV-1 infection: clear evidence for gene by sex interactions.

Research in the past two decades has generated unequivocal evidence that host genetic variations substantially account for the heterogeneous outcomes following human immunodeficiency virus type 1 (HIV-1) infection. In particular, genes encoding human leukocyte antigens (HLA) have various alleles, haplotypes, or specific motifs that can dictate the set-point (a relatively steady state) of plasma viral load (VL), although rapid viral evolution driven by innate and acquired immune responses can obscure the long-term relationships between HLA genotypes and HIV-1-related outcomes. In our analyses of VL data from 521 recent HIV-1 seroconverters enrolled from eastern and southern Africa, HLA-A*03:01 was strongly and persistently associated with low VL in women (frequency = 11.3 %, P < 0.0001) but not in men (frequency = 7.7 %, P = 0.66). This novel sex by HLA interaction (P = 0.003, q = 0.090) did not extend to other frequent HLA class I alleles (n = 34), although HLA-C*18:01 also showed a weak association with low VL in women only (frequency = 9.3 %, P = 0.042, q > 0.50). In a reduced multivariable model, age, sex, geography (clinical sites), previously identified HLA factors (HLA-B*18, B*45, B*53, and B*57), and the interaction term for female sex and HLA-A*03:01 collectively explained 17.0 % of the overall variance in geometric mean VL over a 3-year follow-up period (P < 0.0001). Multiple sensitivity analyses of longitudinal and cross-sectional VL data yielded consistent results. These findings can serve as a proof of principle that the gap of "missing heritability" in quantitative genetics can be partially bridged by a systematic evaluation of sex-specific associations.

Dynamics of viremia in primary HIV-1 infection in Africans: insights from analyses of host and viral correlates.

In HIV-1 infection, plasma viral load (VL) has dual implications for pathogenesis and public health. Based on well-known patterns of HIV-1 evolution and immune escape, we hypothesized that VL is an evolving quantitative trait that depends heavily on duration of infection (DOI), demographic features, human leukocyte antigen (HLA) genotypes and viral characteristics. Prospective data from 421 African seroconverters with at least four eligible visits did show relatively steady VL beyond 3 months of untreated infection, but host and viral factors independently associated with cross-sectional and longitudinal VL often varied by analytical approaches and sliding time windows. Specifically, the effects of age, HLA-B(⁎)53 and infecting HIV-1 subtypes (A1, C and others) on VL were either sporadic or highly sensitive to time windows. These observations were strengthened by the addition of 111 seroconverters with 2-3 eligible VL results, suggesting that DOI should be a critical parameter in epidemiological and clinical studies.

Disease progression by infecting HIV-1 subtype in a seroconverter cohort in sub-Saharan Africa.

OBJECTIVE: To describe immunologic, virologic, and clinical HIV disease progression by HIV-1 subtype among Africans with well documented estimated dates of HIV infection (EDIs). DESIGN: Prospective cohort. METHODS: Adults and youth with documented HIV-1 infection in the past 12 months were recruited from seroincidence cohorts in East and Southern Africa and followed at 3-6 month intervals. Blood for lymphocyte subset and viral load determination was collected at each visit. Pol was sequenced from the first positive specimen to ascertain subtype. Preantiretroviral therapy disease progression was measured by three time-to-event endpoints: CD4 cell count 350 cells/µl or less, viral load measurement at least 1 × 10 copies/ml, and clinical AIDS. RESULTS: From 2006 to 2011, 615 participants were enrolled at nine research centers in Kenya, Rwanda, South Africa, Uganda, and Zambia; 579 (94.1%) had viral subtyping completed. Predominant subtypes were C (256, 44.2%), A (209, 36.1%), and D (84, 14.5%). After adjustment for age, sex, and human leukocyte antigen alleles in Cox regression analyses, subtype C-infected participants progressed faster than subtype A to all three endpoints [CD4 hazard ratio 1.60, 95% (confidence interval) CI 1.16, 2.20; viral load hazard ratio 1.59, 95% CI 1.12, 2.25; and AIDS hazard ratio 1.60, 95% CI 1.11, 2.31). Subtype D-infected participants reached high viral load more rapidly (hazard ratio 1.61, 95% CI 1.01, 2.57) and progressed nearly twice as fast to AIDS compared to subtype A (hazard ratio 1.93, 95% CI 1.21, 3.09). CONCLUSION: Subtype-specific differences in HIV disease progression suggest that the local subtype distribution be considered when planning HIV programs and designing and defining clinical endpoints for HIV prevention trials.

HLA-B*57 versus HLA-B*81 in HIV-1 infection: slow and steady wins the race?

Two human leukocyte antigen (HLA) variants, HLA-B*57 and -B*81, are consistently known as favorable host factors in human immunodeficiency virus type 1 (HIV-1)-infected Africans and African-Americans. In our analyses of prospective data from 538 recent HIV-1 seroconverters and cross-sectional data from 292 subjects with unknown duration of infection, HLA-B*57 (mostly B*57:03) and -B*81 (exclusively B*81:01) had mostly discordant associations with virologic and immunologic manifestations before antiretroviral therapy. Specifically, relatively low viral load (VL) in HLA-B*57-positive subjects (P ≤ 0.03 in various models) did not translate to early advantage in CD4(+) T-cell (CD4) counts (P ≥ 0.37). In contrast, individuals with HLA-B*81 showed little deviation from the normal set point VL (P > 0.18) while maintaining high CD4 count during early and chronic infection (P = 0.01). These observations suggest that discordance between VL and CD4 count can occur in the presence of certain HLA alleles and that effective control of HIV-1 viremia is not always a prerequisite for favorable prognosis (delayed immunodeficiency). Of note, steady CD4 count associated with HLA-B*81 in HIV-1-infected Africans may depend on the country of origin, as observations differed slightly between subgroups enrolled in southern Africa (Zambia) and eastern Africa (Kenya, Rwanda, and Uganda).

Molecular identification, cloning and characterization of transmitted/founder HIV-1 subtype A, D and A/D infectious molecular clones.

We report the molecular identification, cloning and initial biological characterization of 12 full-length HIV-1 subtype A, D and A/D recombinant transmitted/founder (T/F) genomes. T/F genomes contained intact canonical open reading frames and all T/F viruses were replication competent in primary human T-cells, although subtype D virus replication was more efficient (p<0.05). All 12 viruses utilized CCR5 but not CXCR4 as a co-receptor for entry and exhibited a neutralization profile typical of tier 2 primary virus strains, with significant differences observed between subtype A and D viruses with respect to sensitivity to monoclonal antibodies VRC01, PG9 and PG16 and polyclonal subtype C anti-HIV IgG (p<0.05 for each). The present report doubles the number of T/F HIV-1 clones available for pathogenesis and vaccine research and extends their representation to include subtypes A, B, C and D.

Differences in HIV natural history among African and non-African seroconverters in Europe and seroconverters in sub-Saharan Africa.

INTRODUCTION: It is unknown whether HIV treatment guidelines, based on resource-rich country cohorts, are applicable to African populations. METHODS: We estimated CD4 cell loss in ART-naïve, AIDS-free individuals using mixed models allowing for random intercept and slope, and time from seroconversion to clinical AIDS, death and antiretroviral therapy (ART) initiation by survival methods. Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of heterosexually-infected individuals, aged ≥15 years, infected ≥2000, we compared estimates between non-African Europeans, Africans in Europe, and Africans in SSA. RESULTS: Of 1,959 (913 non-Africans, 302 Europeans-African origin, 744 SSA), two-thirds were female; median age at seroconversion was 31 years. Individuals in SSA progressed faster to clinical AIDS but not to death or non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell counts. In adjusted models, Africans (especially from Europe) had lower CD4 counts at seroconversion and slower CD4 decline than non-African Europeans. Median (95% CI) CD4 count at seroconversion for a 15-29 year old woman was 607 (588-627) (non-African European), 469 (442-497) (European-African origin) and 570 (551-589) (SSA) cells/µL with respective CD4 decline during the first 4 years of 259 (228-289), 155 (110-200), and 199 (174-224) cells/µL (p<0.01). DISCUSSION: Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were similar across study groups. It is therefore prudent to apply current ART guidelines from resource-rich countries to African populations.

Identifying at-risk populations in Kenya and South Africa: HIV incidence in cohorts of men who report sex with men, sex workers, and youth.

OBJECTIVE: To identify and describe populations at risk for HIV in 3 clinical research centers in Kenya and South Africa. DESIGN: Prospective cohort study. METHODS: Volunteers reporting recent sexual activity, multiple partners, transactional sex, sex with an HIV-positive partner, or, if male, sex with men (MSM; in Kenya only) were enrolled. Sexually active minors were enrolled in South Africa only. Risk behavior, HIV testing, and clinical data were obtained at follow-up visits. RESULTS: From 2005 to 2008, 3023 volunteers were screened, 2113 enrolled, and 1834 contributed data on HIV incidence. MSM had the highest HIV incidence rate of 6.8 cases per 100 person-years [95% confidence interval (CI): 4.9 to 9.2] followed by women in Kilifi and Cape Town (2.7 cases per 100 person-years, 95% CI: 1.7 to 4.2). No seroconversions were observed in Nairobi women or men in Nairobi or Cape Town who were not MSM. In 327 MSM, predictors of HIV acquisition included report of genital ulcer (Hazard Ratio: 4.5, 95% CI: 1.7 to 11.6), not completing secondary school education (HR: 3.4, 95% CI: 1.6 to 7.2) and reporting receptive anal intercourse (HR: 8.2, 95% CI: 2.7 to 25.0). Paying for sex was inversely associated with HIV infection (HR: 0.2, 95% CI: 0.04 to 0.8). 279 (13.0%) volunteers did not return after the first visit; subsequent attrition rates ranged from 10.4 to 21.8 volunteers per 100 person-years across clinical research centers. CONCLUSIONS: Finding, enrolling, and retaining risk populations for HIV prevention trials is challenging in Africa. African MSM are not frequently engaged for research, have high HIV incidence, need urgent risk reduction counseling, and may represent a suitable population for future HIV prevention trials.

Human leukocyte antigen variants B*44 and B*57 are consistently favorable during two distinct phases of primary HIV-1 infection in sub-Saharan Africans with several viral subtypes.

As part of an ongoing study of early human immunodeficiency virus type 1 (HIV-1) infection in sub-Saharan African countries, we have identified 134 seroconverters (SCs) with distinct acute-phase (peak) and early chronic-phase (set-point) viremias. SCs with class I human leukocyte antigen (HLA) variants B*44 and B*57 had much lower peak viral loads (VLs) than SCs without these variants (adjusted linear regression beta values of -1.08 ± 0.26 log(10) [mean ± standard error] and -0.83 ± 0.27 log(10), respectively; P < 0.005 for both), after accounting for several nongenetic factors, including gender, age at estimated date of infection, duration of infection, and country of origin. These findings were confirmed by alternative models in which major viral subtypes (A1, C, and others) in the same SCs replaced country of origin as a covariate (P ≤ 0.03). Both B*44 and B*57 were also highly favorable (P ≤ 0.03) in analyses of set-point VLs. Moreover, B*44 was associated with relatively high CD4(+) T-cell counts during early chronic infection (P = 0.02). Thus, at least two common HLA-B variants showed strong influences on acute-phase as well as early chronic-phase VL, regardless of the infecting viral subtype. If confirmed, the identification of B*44 as another favorable marker in primary HIV-1 infection should help dissect mechanisms of early immune protection against HIV-1 infection.

Population-based biochemistry, immunologic and hematological reference values for adolescents and young adults in a rural population in Western Kenya.

BACKGROUND: There is need for locally-derived age-specific clinical laboratory reference ranges of healthy Africans in sub-Saharan Africa. Reference values from North American and European populations are being used for African subjects despite previous studies showing significant differences. Our aim was to establish clinical laboratory reference values for African adolescents and young adults that can be used in clinical trials and for patient management. METHODS AND FINDINGS: A panel of 298, HIV-seronegative individuals aged 13-34 years was randomly selected from participants in two population-based cross-sectional surveys assessing HIV prevalence and other sexually transmitted infections in western Kenya. The adolescent (<18 years)-to-adults (≥ 18 years) ratio and the male-to-female ratio was 1∶1. Median and 95% reference ranges were calculated for immunohematological and biochemistry values. Compared with U.S-derived reference ranges, we detected lower hemoglobin (HB), hematocrit (HCT), red blood cells (RBC), mean corpuscular volume (MCV), neutrophil, glucose, and blood urea nitrogen values but elevated eosinophil and total bilirubin values. Significant gender variation was observed in hematological parameters in addition to T-bilirubin and creatinine indices in all age groups, AST in the younger and neutrophil, platelet and CD4 indices among the older age group. Age variation was also observed, mainly in hematological parameters among males. Applying U.S. NIH Division of AIDS (DAIDS) toxicity grading to our results, 40% of otherwise healthy study participants were classified as having an abnormal laboratory parameter (grade 1-4) which would exclude them from participating in clinical trials. CONCLUSION: Hematological and biochemistry reference values from African population differ from those derived from a North American population, showing the need to develop region-specific reference values. Our data also show variations in hematological indices between adolescent and adult males which should be considered when developing reference ranges. This study provides the first locally-derived clinical laboratory reference ranges for adolescents and young adults in western Kenya.

Seroprevalence, predictors and estimated incidence of maternal and neonatal Herpes Simplex Virus type 2 infection in semi-urban women in Kilifi, Kenya.

BACKGROUND: Herpes Simplex Virus type 2 (HSV-2) has public health importance as a leading cause of genital ulcers, a co-factor in HIV-1 acquisition and transmission and as a cause of neonatal herpes infections. Little is known of its epidemiology and burden in Coastal Kenya. METHODS: We screened plasma samples for HSV-2 infection from 826 women aged 15-34 years who participated in an HIV-1 survey in Kilifi in 2004. The sample comprised 563 women selected randomly from a demographic surveillance system (DSS) and 263 women who presented for voluntary counseling and testing (VCT). Predictors for HSV-2 seropositivity were determined using multivariate logistic regression. The incidence of HSV-2 infection and risk of neonatal herpes were estimated by a simple catalytic model fitted to age-seroprevalence data. RESULTS: HSV-2 prevalence was 32% in the DSS recruits vs. 44% in the VCT recruits (P < 0.001), while, HIV-1 prevalence was 8% in the DSS recruits vs. 12% in the VCT recruits (P = 0.12). Independent risk factors for HSV-2 infection in all women were: older age (30-34 years; odds ratio (OR) 10.5, 95% confidence interval (CI): 5.2 - 21.0), recruitment from VCT (OR 1.5, 95% CI: 1.1 - 2.1), history of genital ulcers (OR 1.7, 95% CI: 1.2 - 2.3) and HIV infection (OR 2.7, 95% CI: 1.6-4.6). Education beyond primary (OR 0.7, 95% CI: 0.5 - 0.9) was inversely associated with HSV-2 infection. In the DSS sample, HSV-2 incidence was estimated at 4 cases (95% CI: 3.3 - 4.4) per 100 women per year, 17 cases (95% CI: 16-18) per 1,000 pregnancies per year and 33 neonatal cases (95% CI: 31-36) per 100,000 births per year. CONCLUSIONS: HSV-2 transmission is rapid following the onset of sexual activity and likely to result in a significant burden of genital ulcer disease. Nevertheless, the burden of neonatal HSV-2 can be predicted to be low. Educating young women about HSV-2 infection may help in reducing its burden in this semi-urban population.

International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations.

Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for HIV-1 and other pathogens have been shown to be limited by high titers of Ad5 neutralizing antibodies (NAbs) in the developing world. Alternative serotype rAd vectors have therefore been constructed. Here we report Ad5, Ad26, Ad35, and Ad48 NAb titers in 4381 individuals from North America, South America, sub-Saharan Africa, and Southeast Asia. As expected, Ad5 NAb titers were both frequent and high magnitude in sub-Saharan Africa and Southeast Asia. In contrast, Ad35 NAb titers proved infrequent and low in all regions studied, and Ad48 NAbs were rare in all regions except East Africa. Ad26 NAbs were moderately common in adults in sub-Saharan Africa and Southeast Asia, but Ad26 NAb titers proved markedly lower than Ad5 NAb titers in all regions, and these relatively low Ad26 NAb titers did not detectably suppress the immunogenicity of 4×10(10)vp of a rAd26-Gag/Pol/Env/Nef vaccine in rhesus monkeys. These data inform the clinical development of alternative serotype rAd vaccine vectors in the developing world.

Triple-antiretroviral prophylaxis to prevent mother-to-child HIV transmission through breastfeeding--the Kisumu Breastfeeding Study, Kenya: a clinical trial.

BACKGROUND: Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT) in resource-limited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretroviral regimen that was designed to maximally suppress viral load in late pregnancy and the first 6 mo of lactation was a safe, well-tolerated, and effective PMTCT intervention. METHODS AND FINDINGS: HIV-infected pregnant women took zidovudine, lamivudine, and either nevirapine or nelfinavir from 34-36 weeks' gestation to 6 mo post partum. Infants received single-dose nevirapine at birth. Women were advised to breastfeed exclusively and wean rapidly just before 6 mo. Using Kaplan-Meier methods we estimated HIV-transmission and death rates from delivery to 24 mo. We compared HIV-transmission rates among subgroups defined by maternal risk factors, including baseline CD4 cell count and viral load. Among 487 live-born, singleton, or first-born infants, cumulative HIV-transmission rates at birth, 6 weeks, and 6, 12, and 24 mo were 2.5%, 4.2%, 5.0%, 5.7%, and 7.0%, respectively. The 24-mo HIV-transmission rates stratified by baseline maternal CD4 cell count <500 and ≥500 cells/mm(3) were 8.4% (95% confidence interval [CI] 5.8%-12.0%) and 4.1% (1.8%-8.8%), respectively (p = 0.06); the corresponding rates stratified by baseline maternal viral load <10,000 and ≥10,000 copies/ml were 3.0% (1.1%-7.8%) and 8.7% (6.1%-12.3%), respectively (p = 0.01). None of the 12 maternal and 51 infant deaths (including two second-born infants) were attributed to antiretrovirals. The cumulative HIV-transmission or death rate at 24 mo was 15.7% (95% CI 12.7%-19.4%). CONCLUSIONS: This trial shows that a maternal triple-antiretroviral regimen from late pregnancy through 6 months of breastfeeding for PMTCT is safe and feasible in a resource-limited setting. These findings are consistent with those from other trials using maternal triple-antiretroviral regimens during breastfeeding in comparable settings.

Transmitted HIV type 1 drug resistance among individuals with recent HIV infection in East and Southern Africa.

To characterize WHO-defined transmitted HIV drug resistance mutation (TDRM) data from recently HIV-infected African volunteers, we sequenced HIV (pol) and evaluated for TDRM the earliest available specimens from ARV-naive volunteers diagnosed within 1 year of their estimated date of infection at eight research centers in sub-Saharan Africa. TDRMs were detected in 19/408 (5%) volunteers. The prevalence of TDRMs varied by research center, from 5/26 (19%) in Entebbe, 6/78 (8%) in Kigali, 2/49 (4%) in Kilifi, to 3/106 (3%) in Lusaka. One of five volunteers from Cape Town (20%) had TDRMs. Despite small numbers, our data suggest an increase in DRMs by year of infection in Zambia (p = 0.004). The prevalence observed in Entebbe was high across the entire study. ARV history data from 12 (63%) HIV-infected sexual partners were available; 3 reported ARV use prior to transmission. Among four partners with sequence data available, transmission linkage was confirmed and two had the same TDRMs as the newly infected volunteer (both K103N). As ARV therapy continues to increase in availability throughout Africa, monitoring incident virus strains for the presence of TDRMs should be a priority. Early HIV infection cohorts provide an excellent and important platform to monitor the development of TDRMs to inform treatment guidelines, drug choices, and strategies for secondary prevention of TDRM transmission.

Haematological and biochemistry laboratory abnormalities associated with splenomegaly in asymptomatic adults in Masaka, Uganda: implications for HIV biomedical prevention trials.

OBJECTIVES: To assess the degree of haematological and biochemistry abnormalities associated with splenomegaly in asymptomatic adults in order to determine whether they may be eligible for inclusion in HIV biomedical prevention trials. METHODS: Asymptomatic adults (50% women) aged 18-60 with splenomegaly (>or=grade II by Hackett's classification) who agreed to provide blood and urine specimens for laboratory testing were invited to participate in a cross-sectional study. Volunteers who were menstruating, pregnant, infected with HIV, syphilis or Hepatitis B and C, or had significant clinical findings were excluded. Haematological and biochemistry laboratory evaluations were performed for enrolled volunteers, and the results were compared to local reference ranges. The proportion of volunteers with out-of-range (OOR) values was estimated for each parameter. Linear regression models were fitted to investigate the association between grade of splenomegaly and laboratory values. RESULTS: The proportion of volunteers with OOR haematology values ranged from 4.5% (mean corpuscular volume) and 15% (CD4 cells) to 31% (basophils). Increasing spleen size was significantly associated with anaemia, thrombocytopenia and low CD4 count. OOR biochemistry values were found in about 10% of volunteers. Increasing spleen size was associated with reduced creatinine phosphokinase and creatinine (in men) and raised lactate dehydrogenase. CONCLUSIONS: In areas with a high prevalence of splenomegaly, most asymptomatic individuals with this condition have haematology and biochemistry values that fall within the local reference ranges, and they could therefore be eligible for inclusion in HIV biomedical prevention trials. However, the effect of splenomegaly on certain parameters should be taken into account during interpretation of laboratory-based adverse events.

HIV prevalence and associated risk factors among individuals aged 13-34 years in Rural Western Kenya.

OBJECTIVES: To estimate HIV prevalence and characterize risk factors among young adults in Asembo, rural western Kenya. DESIGN: Community-based cross-sectional survey. METHODS: From a demographic surveillance system, we selected a random sample of residents aged 13-34 years, who were contacted at home and invited to a nearby mobile study site. Consent procedures for non-emancipated minors required assent and parental consent. From October 2003 - April 2004, consenting participants were interviewed on risk behavior and tested for HIV and HSV-2. HIV voluntary counseling and testing was offered. RESULTS: Of 2606 eligible residents, 1822 (70%) enrolled. Primary reasons for refusal included not wanting blood taken, not wanting to learn HIV status, and partner/parental objection. Females comprised 53% of 1762 participants providing blood. Adjusted HIV prevalence was 15.4% overall: 20.5% among females and 10.2% among males. HIV prevalence was highest in women aged 25-29 years (36.5%) and men aged 30-34 years (41.1%). HSV-2 prevalence was 40.0% overall: 53% among females, 25.8% among males. In multivariate models stratified by gender and marital status, HIV infection was strongly associated with age, higher number of sex partners, widowhood, and HSV-2 seropositivity. CONCLUSIONS: Asembo has extremely high HIV and HSV-2 prevalence, and probable high incidence, among young adults. Further research on circumstances around HIV acquisition in young women and novel prevention strategies (vaccines, microbicides, pre-exposure prophylaxis, HSV-2 prevention, etc.) are urgently needed.

Contacting passengers after exposure to measles on an international flight: Implications for responding to new disease threats and bioterrorism.

On May 21, 2000, a passenger with measles traveled from Japan to Hawai'i on a seven-hour flight. When the flight landed, the U.S. Public Health Service (USPHS) Quarantine Station in Honolulu alerted passengers that a suspected case of measles had been identified, but they were not detained. The next day, to offer appropriate post-exposure prophylaxis, the Hawai'i Department of Health (HDOH) attempted to contact all passengers from the flight using information from the airline, U.S. Customs declaration forms, and tour agencies. Of 335 total passengers, 270 (81%) were successfully reached and provided complete information. The mean time from exposure to contact for all respondents was 61 hours (95% confidence interval 57, 66). A total of 202 (75%) of the responding passengers were contacted within 72 hours after exposure, the time period during which administration of measles vaccine would have provided protection for susceptible individuals. The time-to-contact was significantly longer for passengers who did not stay in hotels than for hotel guests. Customs forms proved to be of limited utility in contacting international travelers. This experience highlights the need for more complete and timely methods of contacting passengers potentially exposed to infectious agents aboard flights.

Low risk of measles transmission after exposure on an international airline flight.

In May 2000, a passenger with measles traveled aboard a 7-hour flight from Japan to Hawaii. A follow-up survey was sent to 307 (91%) of the 336 exposed passengers to identify susceptible passengers and subsequent occurrences of measles. The median age of the 276 respondents (90%) was 34 years; 268 (97%) were residents of Japan. Self-reports determined that 173 (63%) were immune through prior measles or vaccination; 6 (2%) denied a history of prior measles or immunization, and 97 (35%) were unaware of their status. Only 1 nonimmune respondent received immunoprophylaxis. None of the respondents developed a febrile rash illness 7-21 days after exposure. The risk of in-flight measles transmission among passenger populations with similar susceptibility profiles appears to be low. An aggressive response by health departments may not be warranted after airborne exposure to measles. Each health department should make such determinations on the basis of specific circumstances and availability of resources.