Programmatic Evaluation of an Algorithm for Intensified Tuberculosis Case Finding and Isoniazid Preventive Therapy for People Living With HIV in Thailand and Vietnam.

BACKGROUND: Tuberculosis (TB) screening affords clinicians the opportunity to diagnose or exclude TB disease and initiate isoniazid preventive therapy (IPT) for people living with HIV (PLHIV). METHODS: We implemented an algorithm to diagnose or rule out TB among PLHIV in 11 HIV clinics in Thailand and Vietnam. We assessed algorithm yield and uptake of IPT and factors associated with TB disease among PLHIV. RESULTS: A total of 1448 PLHIV not yet on antiretroviral therapy (ART) were enrolled and screened for TB. Overall, 634 (44%) screened positive and 119 (8%) were diagnosed with TB; of these, 40% (48/119) were diagnosed by a positive culture following a negative sputum smear microscopy. In total, 55% of those eligible (263/477) started on IPT and of those, 75% (196/263) completed therapy. The prevalence of TB disease we observed in this study was 8.2% (8218 per 100,000 persons): 46 and 25 times the prevalence of TB in the general population in Thailand and Vietnam, respectively. Several factors were independently associated with TB disease including being underweight [aOR (95% CI): 2.3 (1.2 to 2.6)] and using injection drugs [aOR (95% CI): 2.9 (1.3 to 6.3)]. CONCLUSIONS: The high yield of TB disease diagnosed among PLHIV screened with the algorithm, and higher burden among PLHIV who inject drugs, underscores the need for innovative, tailored approaches to TB screening and prevention. As countries adopt test-and-start for antiretroviral therapy, TB screening, sensitive TB diagnostics, and IPT should be included in differentiated-care models for HIV to improve diagnosis and prevention of TB among PLHIV.

Implementing an isoniazid preventive therapy program for people living with HIV in Thailand.

Treatment of people living with HIV (PLHIV) with latent tuberculosis (TB) infection using isoniazid preventive therapy (IPT) can reduce the risk of TB disease, however, the scale-up of IPT among PLHIV in Thailand and worldwide has been slow. To hasten the implementation of IPT in Thailand, we developed IPT implementation training curricula and tools for health care providers and implemented IPT services in seven large government hospitals. Of the 659 PLHIV enrolled, 272 (41.3%) reported symptoms of TB and 39 (14.3% of those with TB symptoms) were diagnosed with TB. A total of 346 (52.4%) participants were eligible for IPT; 318 (91.9%) of these participants opted to have a tuberculin skin test (TST) and 52 (16.3% of those who had a TST) had a positive TST result. Among the 52 participants with a positive TST, 46 (88.5%) initiated and 39 (75.0%) completed 9 months of IPT: physicians instructed three participants to stop IPT, two participants were lost to follow-up, one chose to stop therapy, and one developed TB. IPT can be implemented among PLHIV in Thailand and could reduce the burden of TB in the country.

Self-collected genital swabs compared with cervicovaginal lavage for measuring HIV-1 and HSV-2 and the effect of acyclovir on viral shedding.

HIV-1 and HSV-2 are frequent genital co-infections in women. To determine how self-collected genital swabs compare to provider-collected cervicovaginal lavage, paired self-collected genital swabs and cervicovaginal lavage from women co-infected with HIV-1 and HSV-2 were evaluated. Women were in an acyclovir clinical trial and their samples were tested for HIV-1 RNA (361 samples) and HSV-2 DNA (378 samples). Virus shedding, quantity and acyclovir effect were compared. HIV-1 and HSV-2 were more frequently detected in self-collected genital swabs: 74.5% of self-collected genital swabs and 63.6% of cervicovaginal lavage had detectable HIV-1 (p ≤ 0.001, Fisher's exact test) and 29.7% of self-collected genital swabs and 19.3% of cervicovaginal lavage had detectable HSV-2 (p ≤ 0.001) in the placebo month. Cervicovaginal lavage and self-collected genital swabs virus levels were correlated (Spearman's rho, 0.68 for HIV; 0.61 for HSV-2) and self-collected genital swabs levels were generally higher. In multivariate modeling, self-collected genital swabs and cervicovaginal lavage could equally detect the virus-suppressive effect of acyclovir: for HIV-1, proportional odds ratios were 0.42 and 0.47 and for HSV-2, they were 0.10 and 0.03 for self-collected genital swabs and cervicovaginal lavage, respectively. Self-collected genital swabs should be considered for detection and measurement of HIV-1 and HSV-2 in clinical trials and other studies as they are a sensitive method to detect virus and can be collected in the home with frequent sampling.

Implementation and evaluation of an isoniazid preventive therapy pilot program among HIV-infected patients in Vietnam, 2008-2010.

BACKGROUND: WHO recommends screening for TB and evaluation for isoniazid preventive therapy (IPT) based on evidence that they reduce TB-related morbidity and mortality among HIV-infected persons. In Vietnam, an IPT pilot was implemented in two provinces; TB screening, treatment and outcomes were evaluated to inform the adoption and scale-up of IPT. METHODS: During April 2008 to March 2010, eligible HIV-infected persons aged >15 years, with no previous or current TB treatment, alcohol abuse or liver disease were screened for TB. If TB disease was ruled out based on symptoms, chest x-rays and sputum smears, isoniazid was administered for 9 months. RESULTS: Among 1281 HIV-infected persons who received initial eligibility screening, 520 were referred to and evaluated at district TB clinics for TB disease or IPT eligibility. Active TB was diagnosed in 17 patients and all were started on treatment. Of 520 patients evaluated, 416 (80.0%) initiated IPT: 382 (91.8%) completed IPT, 17 (4.1%) stopped treatment, 8 (1.9%) died, 3 (0.7%) developed TB during IPT and 6 (1.4%) had unknown outcomes. No severe adverse events were reported. CONCLUSIONS: IPT treatment completion was high; no serious complications occurred. Improving and expanding intensified case-finding and IPT should be considered in Vietnam.

Diverse HIV epidemics among people who inject drugs in Thailand: evidence from respondent-driven sampling surveys in Bangkok and Chiang Mai.

BACKGROUND: Thailand's long-standing HIV sero-sentinel surveillance system for people who inject drugs (PWID) is confined to those in methadone-based drug treatment clinics and representative data are scarce, especially outside of Bangkok. METHODS: We conducted probability-based respondent-driven sampling (RDS) surveys in Bangkok (n=738) and Chiang Mai (n=309) to increase understanding of local HIV epidemics and to better inform the planning of evidence-based interventions. RESULTS: PWID had different epidemiological profiles in these two cities. Overall HIV prevalence was higher in Bangkok (23.6% vs. 10.9%, p<0.001) but PWID in Bangkok are older and appear to have long-standing HIV infections. In Chiang Mai, HIV infections appear to be more recently acquired and PWID were younger and had higher levels of recent injecting and sexual risk behaviors with lower levels of intervention exposure. Methamphetamine was the predominant drug injected in both sites and polydrug use was common although levels and patterns of the specific drugs injected varied significantly between the sites. In multivariate analysis, recent midazolam injection was significantly associated with HIV infection in Chiang Mai (adjusted odds ratio=8.1; 95% confidence interval: 1.2-54.5) whereas in Bangkok HIV status was not associated with recent risk behaviors as infections had likely been acquired in the past. CONCLUSION: PWID epidemics in Thailand are heterogeneous and driven by local factors. There is a need to customize intervention strategies for PWID in different settings and to integrate population-based survey methods such as RDS into routine surveillance to monitor the national response.

Use of drug-susceptibility testing for management of drug-resistant tuberculosis, Thailand, 2004-2008.

In 2004, routine use of culture and drug-susceptibility testing (DST) was implemented for persons in 5 Thailand provinces with a diagnosis of tuberculosis (TB). To determine if DST results were being used to guide treatment, we conducted a retrospective chart review for patients with rifampin-resistant or multidrug-resistant (MDR) TB during 2004-2008. A total of 208 patients were identified. Median time from clinical sample collection to physician review of DST results was 114 days. Only 5.8% of patients with MDR TB were empirically prescribed an appropriate regimen; an additional 31.3% received an appropriate regimen after DST results were reviewed. Most patients with rifampin -resistant or MDR TB had successful treatment outcomes. Patients with HIV co-infection and patients who were unmarried or had received category II treatment before DST results were reviewed had less successful outcomes. Overall, review of available DST results was delayed, and results were rarely used to improve treatment.

Effect of mycobacterial drug resistance patterns on patients' survival: a cohort study in Thailand.

BACKGROUND: Drug resistance substantially increases tuberculosis (TB) mortality. This study aimed to describe the prevalence of mycobacterial drug resistance pattern and association of common resistance patterns with TB mortality in Thailand. METHOD: A retrospective cohort study was conducted using TB surveillance data. A total of 9,518 culture-confirmed, pulmonary TB patients registered from 1 October 2004 to 31 December 2008 from the Thailand TB Active Surveillance Network were included in this study. Patients were followed up until TB treatment completion or death. Mycobacterial drug resistance patterns were categorized as pan-susceptible, rifampicin resistance, isoniazid monoresistance, and ethambutol/streptomycin resistance. Drug susceptibility testing (DST) was determined by Mycobacterial Growth Indicator Tube (MGIT) liquid culture systems. Survival analysis was applied. RESULT: Isoniazid monoresistance was the most common pattern, while rifampicin resistance had the largest impact on mortality. Cox regression analysis showed a significantly higher risk of death among patients with rifampicin resistance (adjusted hazard ratio (aHR) 1.9, 95% confident interval (CI), 1.5-2.5) and isoniazid monoresistance (aHR 1.4, 95% CI 1.1-1.7) than those with pan-susceptible group after adjustment for age, nationality, human immunodeficiency virus (HIV) and antiretroviral therapy (ART) status, diabetes mellitus, cavitary disease on chest x-ray, treatment observation, and province. HIV co-infection was associated with higher mortality in patients both on ART (aHR 1.9, 95% CI 1.5-2.5) and not on ART (aHR 8.1, 95% CI 6.8-9.8). CONCLUSION: Rifampicin resistance and isoniazid monoresistance were associated with increased TB mortality. HIV-coinfection was associated with a higher risk of death including among those taking antiretroviral therapy.

Cyclic changes in HIV shedding from the female genital tract during the menstrual cycle.

Factors increasing genital human immunodeficiency virus (HIV) shedding may increase female-to-male HIV transmission risk. We examined HIV shedding in 67 women with HIV type 1 and herpes simplex virus type 2 coinfection, during 2 menstrual cycles. Shedding occurred in 60%, 48%, and 54% of samples during the follicular, periovulatory, and luteal phases, respectively (P = .01). Shedding declined after menses until ovulation, with a slope -0.054 log10 copies/swab/day (P < .001), corresponding to a change of approximately 0.74 log10 copies between peak and nadir levels. Shedding increased during the luteal phase only among women with CD4 counts of <350 cells/µL. In reproductive-aged women, shedding frequency and magnitude are greatest immediately following menses and lowest at ovulation.

Concurrent influenza virus infection and tuberculosis in patients hospitalized with respiratory illness in Thailand.

Thailand, where influenza viruses circulate year-round, is one of 22 WHO-designated high-burden countries for tuberculosis (TB). Surveillance for hospitalized respiratory illness between 2003 and 2011 revealed 23 (<1% of 7180 tested) with concurrent influenza and TB. Only two persons were previously known to have TB suggesting that acute respiratory illness may bring patients to medical attention and lead to TB diagnosis. Influenza/TB was not associated with higher disease severity or mortality.

Health related quality of life among patients with tuberculosis and HIV in Thailand.

INTRODUCTION: Health utilities of tuberculosis (TB) patients may be diminished by side effects from medication, prolonged treatment duration, physical effects of the disease itself, and social stigma attached to the disease. METHODS: We collected health utility data from Thai patients who were on TB treatment or had been successfully treated for TB for the purpose of economic modeling. Structured questionnaire and EuroQol (EQ-5D) and EuroQol visual analog scale (EQ-VAS) instruments were used as data collection tools. We compared utility of patients with two co-morbidities calculated using multiplicative model (U(CAL)) with the direct measures and fitted Tobit regression models to examine factors predictive of health utility and to assess difference in health utilities of patients in various medical conditions. RESULTS: Of 222 patients analyzed, 138 (62%) were male; median age at enrollment was 40 years (interquartile range [IQR], 35-47). Median monthly household income was 6,000 Baht (187 US$; IQR, 4,000-15,000 Baht [125-469 US$]). Concordance correlation coefficient between utilities measured using EQ-5D and EQ-VAS (U(EQ-5D) and U(VAS), respectively) was 0.6. U(CAL) for HIV-infected TB patients was statistically different from the measured U(EQ-5D) (p-value<0.01) and U(VAS) (p-value<0.01). In tobit regression analysis, factors independently predictive of U(EQ-5D) included age and monthly household income. Patients aged ≥40 years old rated U(EQ-5D) significantly lower than younger persons. Higher U(EQ-5D) was significantly associated with higher monthly household income in a dose response fashion. The median U(EQ-5D) was highest among patients who had been successfully treated for TB and lowest among multi-drug resistant TB (MDR-TB) patients who were on treatment. CONCLUSIONS: U(CAL) of patients with two co-morbidities overestimated the measured utilities, warranting further research of how best to estimate utilities of patients with such conditions. TB and MDR-TB treatments impacted on patients' self perceived health status. This effect diminished after successful treatment.

Acceptability of Carraguard vaginal microbicide gel among HIV-infected women in Chiang Rai, Thailand.

BACKGROUND: Few studies of microbicide acceptability among HIV-infected women have been done. We assessed Carraguard® vaginal gel acceptability among participants in a randomized, controlled, crossover safety trial in HIV-infected women in Thailand. METHODOLOGY/PRINCIPAL FINDINGS: Participants used each of 3 treatments (Carraguard gel, methylcellulose placebo gel, and no product) for 7 days, were randomized to one of six treatment sequences, and were blinded to the type of gel they received in the two gel-use periods. After both gel-use periods, acceptability was assessed by face-to-face interview. Responses were compared to those of women participating in two previous Carraguard safety studies at the same study site. Sixty women enrolled with a median age of 34 years; 25% were sexually active. Self-reported adherence (98%) and overall satisfaction rating of the gels (87% liked "somewhat" or "very much") were high, and most (77%) considered the volume of gel "just right." For most characteristics, crossover trial participants evaluated the gels more favorably than women in the other two trials, but there were few differences in the desired characteristics of a hypothetical microbicide. Almost half (48%) of crossover trial participants noticed a difference between Carraguard and placebo gels; 33% preferred Carraguard while 12% preferred placebo (p = 0.01). CONCLUSIONS/SIGNIFICANCE: Daily Carraguard vaginal gel use was highly acceptable in this population of HIV-infected women, who assessed the gels more positively than women in two other trials at the site. This may be attributable to higher perceived need for protection among HIV-infected women, as well as to study design differences. This trial was registered in the U.S. National Institutes of Health clinical trials registry under registration number NCT00213044.

Bridging populations-sexual risk behaviors and HIV prevalence in clients and partners of female sex workers, Bangkok, Thailand 2007.

The aim of this study is to estimate HIV prevalence and assess sexual behaviors in a high-risk and difficult-to-reach population of clients of female sex workers (FSWs). A modified variation of respondent-driven sampling was conducted among FSWs in Bangkok, where FSWs recruited 3 FSW peers, 1 client, and 1 nonpaying partner. After informed consent was obtained, participants completed a questionnaire, were HIV-tested, and were asked to return for results. Analyses were weighted to control for the design of the survey. Among 540 FSWs, 188 (35%) recruited 1 client, and 88 (16%) recruited 1 nonpaying partner. Clients' median age was 38 years. HIV prevalence was 20% and was associated with younger age at first sexual experience [relative risk (RR) = 3.10, 95% confidence interval (CI) 1.16-8.24] and condom use during last sexual encounter with regular partner (RR = 3.97, 95% CI 1.09-14.61). Median age of nonpaying partners was 34 years, and HIV prevalence was 15.1%. There were 56 discordant FSW-client pairs and 14 discordant FSW-nonpaying partner pairs. Condom use was relatively high among discordant FSW-client pairs (90.1%) compared to discordant FSW-nonpaying partner pairs (18.7%). Results suggest that sexual partners of FSWs have a high HIV prevalence and can be a bridge for HIV transmission to other populations. Findings also highlight the importance of initiating surveillance and targeted programs for FSW partners, and demonstrate a recruitment method for hard-to-reach populations.

Formative research to optimize respondent-driven sampling surveys among hard-to-reach populations in HIV behavioral and biological surveillance: lessons learned from four case studies.

Respondent-driven sampling (RDS) is widely adopted as a method to assess HIV and other sexually transmitted infection prevalence and risk factors among hard-to-reach populations. Failures to properly implement RDS in several settings could potentially have been avoided, had formative research been conducted. However, to date there is no published literature addressing the use of formative research in preparing for RDS studies. This paper uses examples from Banja Luka, Bosnia and Herzegovina; Bangkok, Thailand; Podgorica, Montenegro; and St Vincent's and Grenadine Islands, Eastern Caribbean; among populations of men who have sex with men, female sex workers, and injecting drug users to describe how formative research was used to plan, implement, and predict outcomes of RDS surveys and to provide a template of RDS-specific questions for conducting formative research in preparation for RDS surveys. We outline case studies to illustrate how formative research may help researchers to determine whether RDS methodology is appropriate for a particular population and sociocultural context, and to decide on implementation details that lead to successful study outcomes.

HIV genital shedding and safety of Carraguard use by HIV-infected women: a crossover trial in Thailand.

OBJECTIVE: To evaluate the safety, including impact on genital HIV RNA shedding, of Carraguard vaginal gel in HIV-infected women. DESIGN: This is a randomized, controlled, crossover study of Carraguard in HIV-infected women in Thailand. METHODS: Each woman (CD4 cell count 51-500 cells/microl and not on antiretroviral therapy) used each treatment (Carraguard, methylcellulose placebo, and no-product) once daily for 7 days during each 1-month period (3-week wash-out). Women were randomized to one of the six possible treatment sequences. Safety assessments were conducted at baseline (pregel), 15 min postgel, day 7, and day 14, and included HIV RNA measurements in cervicovaginal lavage (CVL) specimens. RESULTS: Sixty women were enrolled, and 99% of scheduled study visits were completed. At baseline, median age (34 years), CD4 lymphocyte count (296 cells/microl), plasma HIV viral load (4.6 log10 copies/ml), CVL HIV viral load (3.1 log10 total copies per CVL), and sexual behaviors were similar among randomization groups. HIV viral load, leukocyte and hemoglobin levels, and epithelial cell counts in CVLs were lower 15 min after application of Carraguard or placebo compared with no product; CVL HIV viral load was still lower at day 7 but returned to baseline by day 14. Carraguard use was not associated with prevalent or incident genital findings or abnormal vaginal flora. CONCLUSION: Carraguard appears to be well tolerated for once-daily vaginal use by HIV-infected women. The observed reduction in CVL HIV viral load in the gel months may be clinically relevant but could have resulted from interference with sample collection by study gels.

Suppressive acyclovir therapy reduces HIV cervicovaginal shedding in HIV- and HSV-2-infected women, Chiang Rai, Thailand.

BACKGROUND: Herpes simplex virus type 2 infection is important in the HIV epidemic and may contribute to increased HIV transmission. We evaluated the effect of suppressive acyclovir therapy on cervicovaginal HIV-1 shedding. METHODS: HIV-1- and herpes simplex virus type 2-coinfected women aged 18-49 years with CD4 counts >200 cells/microL were enrolled in a randomized crossover trial of suppressive acyclovir therapy (NCT00362596, http://www.clinicaltrials.gov). For each woman, monthly plasma and weekly cervicovaginal lavage specimens were collected; the mean of the monthly median cervicovaginal lavage HIV-1 viral load and plasma HIV-1 viral load was compared. RESULTS: Sixty-seven women were enrolled; at baseline, median CD4 count was 366 cells/microL, and median HIV-1 plasma viral load was 4.6 log10 copies/mL. The mean cervicovaginal lavage HIV-1 viral load was 1.9 (SD 0.8) log10 copies/mL during the acyclovir month and 2.2 (SD 0.7) log10 copies/mL during the placebo month (P < 0.0001); the mean decrease in HIV was 0.3 log10 copies/mL. The mean plasma HIV viral load during the acyclovir month (3.78 log10 copies/mL) was reduced compared with the placebo month (4.26 log10 copies/mL, P < 0.001). CONCLUSIONS: Acyclovir reduced HIV genital shedding and plasma viral load among HIV-1- and herpes simplex virus type 2-coinfected women. Further data from clinical trials will examine the effect of suppressive therapy on HIV transmission.

Increase in sexual risk behavior and prevalence of Chlamydia trachomatis among adolescents in Northern Thailand.

BACKGROUND: Monitoring changes in adolescent sexual risk behaviors and sexually transmitted infections is critical for evaluating the effectiveness of human immunodeficiency virus and other prevention programs, but population-based data on adolescents in Thailand are limited. We report findings from 2 cross-sectional surveys conducted in 1999 and 2002 among 15-to 21-year-old vocational students. METHODS: In 1999 and 2002, 1725 and 966 students, respectively, were interviewed using computer-assisted self-interview methods. Urine samples were collected and tested for Chlamydia trachomatis and Neisseria gonorrhoeae by polymerase chain reaction. RESULTS: From 1999 to 2002 C. trachomatis prevalence increased from 3.2% to 7.5% (P <0.001) in women and from 2.5% to 6.0% (P <0.001) in men. There was an increase in the reported mean lifetime number of steady sexual partners among both men (3.4-4.7, P = 0.01) and women (2.5-3.3, P <0.001), and in the mean lifetime number of casual partners among men (1.1-2.1, P <0.001) and women (0.3-1.1, P = 0.04). Reported consistent condom use decreased significantly among women with casual partners (43%-19%, P = 0.03) but not among men (25%-31%, P = 0.31). CONCLUSIONS: Our study identified important increases in the prevalence of chlamydial infection and in sexual risk behaviors among Thai adolescents over a 3-year period. These findings are consistent with other studies suggesting profound social changes are changing norms of adolescent sexual behavior in Thailand, and highlight the need for adolescent sexual health services and prevention programming.

Maternal herpes simplex virus type 2 coinfection increases the risk of perinatal HIV transmission: possibility to further decrease transmission?

OBJECTIVES: To evaluate the association between maternal herpes simplex virus type 2 seropositivity and genital herpes simplex virus type 2 shedding with perinatal HIV transmission. STUDY DESIGN: Evaluation of women who participated in a 1996-1997 perinatal HIV transmission prevention trial in Thailand. METHODS: In this nonbreastfeeding population, women were randomized to zidovudine or placebo from 36 weeks gestation through delivery; maternal plasma and cervicovaginal HIV viral load and infant HIV status were determined for the original study. Stored maternal plasma and cervicovaginal samples were tested for herpes simplex virus type 2 antibodies by enzyme-linked immunoassay and for herpes simplex virus type 2 DNA by real-time PCR, respectively. RESULTS: Among 307 HIV-positive women with available samples, 228 (74.3%) were herpes simplex virus type 2 seropositive and 24 (7.8%) were shedding herpes simplex virus type 2. Herpes simplex virus type 2 seropositivity was associated with overall perinatal HIV transmission [adjusted odds ratio, 2.6; 95% confidence interval, 1.0-6.7)], and herpes simplex virus type 2 shedding was associated with intrapartum transmission (adjusted odds ratio, 2.9; 95% confidence interval, 1.0-8.5) independent of plasma and cervicovaginal HIV viral load, and zidovudine treatment. Median plasma HIV viral load was higher among herpes simplex virus type 2 shedders (4.2 vs. 4.1 log(10)copies/ml; P = 0.05), and more shedders had quantifiable levels of HIV in cervicovaginal samples, compared with women not shedding herpes simplex virus type 2 (62.5 vs. 34.3%; P = 0.005). CONCLUSION: We found an increased risk of perinatal HIV transmission among herpes simplex virus type 2 seropositive women and an increased risk of intrapartum HIV transmission among women shedding herpes simplex virus type 2. These novel findings suggest that interventions to control herpes simplex virus type 2 infection could further reduce perinatal HIV transmission.

Identifying risk factors for underimmunization by using geocoding matched to census tracts: a statewide assessment of children in Hawaii.

OBJECTIVE: Obtaining childhood immunization coverage data for small geographic areas is difficult and resource-intensive, especially in the absence of comprehensive immunization registries. To identify factors that are associated with delayed immunization, we collected school-entry immunization records statewide and used geocoding to link to publicly available census tract sociodemographic data. METHODS: Immunization records were reviewed for children who were enrolled in all public and private school kindergarten programs in Hawaii in the 2002-2003 school year; immunization status at the time of the second birthday was determined. The main outcome variable was up-to-date status for the 4:3:1:3:3 vaccination series (4 doses of diphtheria-tetanus-pertussis, 3 doses of polio, 1 dose of measles-mumps-rubella, 3 doses of Haemophilus influenzae type b, and 3 doses of hepatitis B vaccines). Children's home addresses were geocoded to census tracts; coverage rates by tract were mapped, and sociodemographic data from Census 2000 files were used to identify factors that were associated with delays in immunization. RESULTS: Records were obtained for 15,275 of 15,594 children registered in Hawaii kindergartens. Overall, 78% had completed their 4:3:1:3:3 series by their second birthday. Risk factors for delayed immunization included delayed immunization at 3 months of age, living in Maui County, living in a neighborhood where a low proportion of adults had postsecondary education, and living in a neighborhood where a high proportion of households spoke a language other than English at home. The majority (80%) of underimmunized children would have required only 1 additional visit to bring them up-to-date. CONCLUSIONS: Retrospective review of kindergarten-entry immunization data revealed geographic areas with lower immunization coverage, and geocoding to census tracts identified associated sociodemographic risk factors. This is a practical method for state or city health departments to identify pockets of need and to direct resources appropriately.

Acceptability of Carraguard vaginal gel use among Thai couples.

OBJECTIVES: To evaluate the acceptability of candidate microbicide Carraguard among couples participating in a safety trial. STUDY DESIGN: A 6-month randomized, placebo-controlled trial was conducted in sexually active, low-risk couples in Thailand. METHODS: Couples who were monogamous, HIV uninfected, and not regular condom users were enrolled. Acceptability data were collected through structured questionnaires at repeated intervals. At the closing study visit, participants were asked questions about hypothetical product characteristics and future use. Compliance with gel use was assessed by questionnaires, coital diaries, and tracking of used and unused applicators. RESULTS: Among 55 enrolled couples, follow up and adherence with gel use were high and sustained, with 80% of women using gel in over 95% of vaginal sex acts. Because acceptability results from Carraguard and placebo arms were similar, they were combined for this analysis. Overall, 92% of women and 83% of men liked the gel somewhat or very much; 66% of women and 72% of men reported increased sexual pleasure with gel use; and 55% of women and 62% of men reported increased frequency of intercourse. Only 15% of women but 43% of men thought that gel could be used without the man knowing. Although men and women had similar views overall, concordance within couples was low, with no kappa coefficients above 0.31. CONCLUSION: Carraguard gel use was acceptable to low-risk couples in northern Thailand. Reported associations between gel use and increased sexual pleasure and frequency suggest a potential to market microbicide products for both disease prevention and enhancement of pleasure.

Where giving birth is a forecast of death: maternal mortality in four districts of Afghanistan, 1999-2002.

BACKGROUND: Maternal mortality in Afghanistan is uniformly identified as an issue of primary public-health importance. To guide the implementation of reproductive-health services, we examined the numbers, causes, and preventable factors for maternal deaths among women in four districts. METHODS: We did a retrospective cohort study of women of reproductive age (15-49 years) who died between March 21, 1999, and March 21, 2002, in four selected districts in four provinces: Kabul city, Kabul province (urban); Alisheng district, Laghman province (semirural); Maywand, Kandahar province (rural); and Ragh, Badakshan province (rural, most remote). Deaths among women of reproductive age were identified through a survey of all households in randomly selected villages and investigated through verbal-autopsy interviews of family members. FINDINGS: In a population of 90 816, 357 women of reproductive age died; 154 deaths were related to complications during pregnancy, childbirth, or the puerperal period. Most maternal deaths were caused by ante-partum haemorrhage, except in Ragh, where a greater proportion of women died of obstructed labour. All measures of maternal risk were high, especially in the more remote areas; the maternal mortality ratio (per 100,000 livebirths) was 418 (235-602) in Kabul, 774 (433-1115) in Alisheng, 2182 (1451-2913) in Maywand, and 6507 (5026-7988) in Ragh. In the two rural sites, no woman who died was assisted by a skilled birth attendant. INTERPRETATION: Maternal mortality in Afghanistan is high and becomes significantly greater with increasing remoteness. Deaths could be averted if complications were prevented through optimisation of general health status and if complications that occurred were treated to reduce their severity--efforts that require a multisectoral approach to increase availability and accessibility of health care.