Automated Detection of Healthcare Associated Infections: External Validation and Updating of a Model for Surveillance of Drain-Related Meningitis

Objective

Automated surveillance of healthcare-associated infections can improve efficiency and reliability of surveillance. The aim was to validate and update a previously developed multivariable prediction model for the detection of drain-related meningitis (DRM).

Design

Retrospective cohort study using traditional surveillance by infection control professionals as reference standard.

Patients

Patients receiving an external cerebrospinal fluid drain, either ventricular (EVD) or lumbar (ELD) in a tertiary medical care center. Children, patients with simultaneous drains, <1 day of follow-up or pre-existing meningitis were excluded leaving 105 patients in validation set (2010–2011) and 653 in updating set (2004–2011).

Methods

For validation, the original model was applied. Discrimination, classification and calibration were assessed. For updating, data from all available years was used to optimally re-estimate coefficients and determine whether extension with new predictors is necessary. The updated model was validated and adjusted for optimism (overfitting) using bootstrapping techniques.

Results

In model validation, the rate of DRM was 17.4/1000 days at risk. All cases were detected by the model. The area under the ROC curve was 0.951. The positive predictive value was 58.8% (95% CI 40.7–75.4) and calibration was good. The revised model also includes Gram stain results. Area under the ROC curve after correction for optimism was 0.963 (95% CI 0.953– 0.974). Group-level prediction was adequate.

Conclusions

The previously developed multivariable prediction model maintains discriminatory power and calibration in an independent patient population. The updated model incorporates all available data and performs well, also after elaborate adjustment for optimism.     

Evaluation of two new commercial tests for the diagnosis of acute dengue virus infection using NS1 antigen detection in human serum

Background

We compared the performance of two new commercial tests for the detection of dengue NS1 protein during the clinical phase of dengue virus (DENV) infection—an immunochromatographic test allowing rapid detection of the NS1 antigen, Dengue NS1 Ag STRIP (Bio-Rad Laboratories - Marnes La Coquette, France), and a two-step sandwich-format microplate enzyme-linked immunosorbent assay (ELISA), pan-E Dengue Early ELISA (Panbio - Brisbane, Australia)—with a one-step sandwich-format microplate ELISA, the Platelia Dengue NS1 Ag test (Bio-Rad).

Methods

We tested 272 serum samples from patients with dengue disease. Of these, 222 were from patients with acute infection of one of the four dengue serotypes, detected by RT-PCR and/or virus isolation. Forty-eight acute-phase serum samples from patients not infected with dengue virus were also included.

Results

The sensitivity of the Platelia Dengue NS1 Ag test on acute serum samples (n = 222) was 87.4% (95% confidence interval: 82.3% to 91.5%); that of Dengue NS1 Ag STRIP was 81.5% (95% CI: 75.8% to 86.4%) after 15 minutes and 82.4% (95% CI: 76.8% to 87.2%) after 30 minutes. Both tests had a specificity of 100% (97.5% CI, one-sided test: 92.6% to 100.0%). The pan-E Dengue Early ELISA had a sensitivity of 60.4% (95% CI: 53.4% to 66.8%) and a specificity of 97.9% (95% CI: 88.9% to 99.9%).

Conclusion

Our findings support the use of diagnostic tools based on the NS1 antigen detection for the diagnosis of acute DENV infection. The immunochromatographic test, Dengue NS1 Ag STRIP—the first rapid diagnostic test for DENV infection—was highly sensitive and specific, and would therefore be a suitable first-line test in the field. The pan-E Dengue Early ELISA was less sensitive than the Platelia test; this two-step ELISA should be combined with DENV IgM antibody detection for the diagnosis of DENV infection.     

Congenital cytomegalovirus mortality in the United States, 1990-2006

Background

Congenital cytomegalovirus (CMV) infection is the most common intrauterine infection in the United States disproportionately affecting minority races and those of lower socio-economic class. Despite its importance there is little information on the burden of congenital CMV-related mortality in the US. To measure congenital CMV-associated mortality in the US and assess possible racial/ethnic disparities, we reviewed national death certificate data for a 17-year period.

Methods

Congenital CMV-associated deaths from 1990 through 2006 were identified from multiple-cause-coded death records and were combined with US census data to calculate mortality rates.

Results

A total of 777 congenital CMV-associated deaths occurred over the 17-year study period resulting in 56,355 years of age-adjusted years of potential life lost. 71.7% (557) of congenital CMV-associated deaths occurred in infants (age less than 1 year). Age-adjusted mortality rates stratified by race/ethnicity revealed mortality disparities. Age-adjusted rate ratios were calculated for each racial/ethnic group using whites as the reference. Native Americans and African Americans were 2.34 (95% CI, 2.11–2.59) and 1.89 (95% CI, 1.70–2.11) times respectively, more likely to die from congenital CMV than whites. Asians and Hispanics were 0.54 (95% CI, 0.44–0.66) and 0.96 (95% CI, 0.83–1.10) times respectively, less likely to die from congenital CMV than whites.

Conclusions/Significance

Congenital CMV infection causes appreciable mortality in the US exacting a particular burden among African Americans and Native Americans. Enhanced surveillance and increased screening are necessary to better understand the epidemiology of congenital CMV infection in addition to acceleration of vaccine development efforts.     

National prevalence and trends of HIV transmitted drug resistance in Mexico

Background

Transmitted drug resistance (TDR) remains an important concern for the management of HIV infection, especially in countries that have recently scaled-up antiretroviral treatment (ART) access.

Methodology/Principal Findings

We designed a study to assess HIV diversity and transmitted drug resistance (TDR) prevalence and trends in Mexico. 1655 ART-naïve patients from 12 Mexican states were enrolled from 2005 to 2010. TDR was assessed from plasma HIV pol sequences using Stanford scores and the WHO TDR surveillance mutation list. TDR prevalence fluctuations over back-projected dates of infection were tested. HIV subtype B was highly prevalent in Mexico (99.9%). TDR prevalence (Stanford score>15) in the country for the study period was 7.4% (95% CI, 6.2∶8.8) and 6.8% (95% CI, 5.7∶8.2) based on the WHO TDR surveillance mutation list. NRTI TDR was the highest (4.2%), followed by NNRTI (2.5%) and PI (1.7%) TDR. Increasing trends for NNRTI (p = 0.0456) and PI (p = 0.0061) major TDR mutations were observed at the national level. Clustering of viruses containing minor TDR mutations was observed with some apparent transmission pairs and geographical effects.

Conclusions

TDR prevalence in Mexico remains at the intermediate level and is slightly lower than that observed in industrialized countries. Whether regional variations in TDR trends are associated with differences in antiretroviral drug usage/ART efficacy or with local features of viral evolution remains to be further addressed.     

Brain drain and health workforce distortions in Mozambique

Introduction

Trained human resources are fundamental for well-functioning health systems, and the lack of health workers undermines public sector capacity to meet population health needs. While external brain drain from low and middle-income countries is well described, there is little understanding of the degree of internal brain drain, and how increases in health sector funding through global health initiatives may contribute to the outflow of health workers from the public sector to donor agencies, non-governmental organisations (NGOs), and the private sector.

Methods

An observational study was conducted to estimate the degree of internal and external brain drain among Mozambican nationals qualifying from domestic and foreign medical schools between 1980–2006. Data were collected 26-months apart in 2008 and 2010, and included current employment status, employer, geographic location of employment, and main work duties.

Results

Of 723 qualifying physicians between 1980–2006, 95.9% (693) were working full-time, including 71.1% (493) as clinicians, 20.5% (142) as health system managers, and 6.9% (48) as researchers/professors. 25.5% (181) of the sample had left the public sector, of which 62.4% (113) continued working in-country and 37.6% (68) emigrated from Mozambique. Of those cases of internal migration, 66.4% (75) worked for NGOs, 21.2% (24) for donor agencies, and 12.4% (14) in the private sector. Annual incidence of physician migration was estimated to be 3.7%, predominately to work in the growing NGO sector. An estimated 36.3% (41/113) of internal migration cases had previously held senior-level management positions in the public sector.

Discussion

Internal migration is an important contributor to capital flight from the public sector, accounting for more cases of physician loss than external migration in Mozambique. Given the urgent need to strengthen public sector health systems, frank reflection by donors and NGOs is needed to assess how hiring practices may undermine the very systems they seek to strengthen.     

Efficacy and safety of nitazoxanide, albendazole, and nitazoxanide-albendazole against Trichuris trichiura infection: a randomized controlled trial

Background

The currently used anthelmintic drugs, in single oral application, have low efficacy against Trichuris trichiura infection, and hence novel anthelmintic drugs are needed. Nitazoxanide has been suggested as potential drug candidate.

Methodology

The efficacy and safety of a single oral dose of nitazoxanide (1,000 mg), or albendazole (400 mg), and a nitazoxanide-albendazole combination (1,000 mg–400 mg), with each drug administered separately on two consecutive days, were assessed in a double-blind, randomized, placebo-controlled trial in two schools on Pemba, Tanzania. Cure and egg reduction rates were calculated by per-protocol analysis and by available case analysis. Adverse events were assessed and graded before treatment and four times after treatment.

Principal Findings

Complete data for the per-protocol analysis were available from 533 T. trichiura-positive children. Cure rates against T. trichiura were low regardless of the treatment (nitazoxanide-albendazole, 16.0%; albendazole, 14.5%; and nitazoxanide, 6.6%). Egg reduction rates were 54.9% for the nitazoxanide-albendazole combination, 45.6% for single albendazole, and 13.4% for single nitazoxanide. Similar cure and egg reduction rates were calculated using the available case analysis. Children receiving nitazoxanide had significantly more adverse events compared to placebo recipients. Most of the adverse events were mild and had resolved within 24 hours posttreatment.

Conclusions/Significance

Nitazoxanide shows no effect on T. trichiura infection. The low efficacy of albendazole against T. trichiura in the current setting characterized by high anthelmintic drug pressure is confirmed. There is a pressing need to develop new anthelmintics against trichuriasis.

Trial Registration

Controlled-Trials.com ISRCTN08336605     

Analysing the large decline in coronary heart disease mortality in the Icelandic population aged 25-74 between the years 1981 and 2006

Background

Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s. We examined how much of the decrease between 1981 and 2006 could be attributed to medical and surgical treatments and how much to changes in cardiovascular risk factors.

Methodology

The previously validated IMPACT CHD mortality model was applied to the Icelandic population. The data sources were official statistics, national quality registers, published trials and meta-analyses, clinical audits and a series of national population surveys.

Principal Findings

Between 1981 and 2006, CHD mortality rates in Iceland decreased by 80% in men and women aged 25 to 74 years, which resulted in 295 fewer deaths in 2006 than if the 1981 rates had persisted. Incidence of myocardial infarction (MI) decreased by 66% and resulted in some 500 fewer incident MI cases per year, which is a major determinant of possible deaths from MI. Based on the IMPACT model approximately 73% (lower and upper bound estimates: 54%–93%) of the mortality decrease was attributable to risk factor reductions: cholesterol 32%; smoking 22%; systolic blood pressure 22%, and physical inactivity 5% with adverse trends for diabetes (−5%), and obesity (−4%). Approximately 25% (lower and upper bound estimates: 8%–40%) of the mortality decrease was attributable to treatments in individuals: secondary prevention 8%; heart failure treatments 6%; acute coronary syndrome treatments 5%; revascularisation 3%; hypertension treatments 2%, and statins 0.5%.

Conclusions

Almost three quarters of the large CHD mortality decrease in Iceland between 1981 and 2006 was attributable to reductions in major cardiovascular risk factors in the population. These findings emphasize the value of a comprehensive prevention strategy that promotes tobacco control and a healthier diet to reduce incidence of MI and highlights the potential importance of effective, evidence based medical treatments.     

Risk factors associated with positive QuantiFERON-TB Gold In-Tube and tuberculin skin tests results in Zambia and South Africa

Introduction

The utility of T-cell based interferon-gamma release assays for the diagnosis of latent tuberculosis infection remains unclear in settings with a high burden of tuberculosis.

Objectives

To determine risk factors associated with positive QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) results and the level of agreement between the tests; to explore the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST.

Methods

Adult household contacts of tuberculosis patients were invited to participate in a cross-sectional study across 24 communities in Zambia and South Africa. HIV, QFT-GIT and TST tests were done. A questionnaire was used to assess risk factors.

Results

A total of 2,220 contacts were seen. 1,803 individuals had interpretable results for both tests, 1,147 (63.6%) were QFT-GIT positive while 725 (40.2%) were TST positive. Agreement between the tests was low (kappa = 0.24). QFT-GIT and TST results were associated with increasing age (adjusted OR [aOR] for each 10 year increase for QFT-GIT 1.15; 95% CI: 1.06–1.25, and for TST aOR: 1.10; 95% CI 1.01–1.20). HIV positivity was less common among those with positive results on QFT-GIT (aOR: 0.51; 95% CI: 0.39–0.67) and TST (aOR: 0.61; 95% CI: 0.46–0.82). Smear positivity of the index case was associated with QFT-GIT (aOR: 1.25; 95% CI: 0.90–1.74) and TST (aOR: 1.39; 95% CI: 0.98–1.98) results. We found little evidence in our data to support our hypotheses.

Conclusion

QFT-GIT may not be more sensitive than the TST to detect risk factors associated with tuberculous infection. We found little evidence to support the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST.     

The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach

Background

Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1) has been identified as an early marker for acute dengue, and is typically present between days 1–9 post-onset of illness but following seroconversion it can be difficult to detect in serum.

Aims

To evaluate the performance of a newly developed Panbio® Dengue Early Rapid test for NS1 and determine if it can improve diagnostic sensitivity when used in combination with a commercial IgM/IgG rapid test.

Methodology

The clinical performance of the Dengue Early Rapid was evaluated in a retrospective study in Vietnam with 198 acute laboratory-confirmed positive and 100 negative samples. The performance of the Dengue Early Rapid in combination with the IgM/IgG Rapid test was also evaluated in Malaysia with 263 laboratory-confirmed positive and 30 negative samples.

Key Results

In Vietnam the sensitivity and specificity of the test was 69.2% (95% CI: 62.8% to 75.6%) and 96% (95% CI: 92.2% to 99.8) respectively. In Malaysia the performance was similar with 68.9% sensitivity (95% CI: 61.8% to 76.1%) and 96.7% specificity (95% CI: 82.8% to 99.9%) compared to RT-PCR. Importantly, when the Dengue Early Rapid test was used in combination with the IgM/IgG test the sensitivity increased to 93.0%. When the two tests were compared at each day post-onset of illness there was clear differentiation between the antigen and antibody markers.

Conclusions

This study highlights that using dengue NS1 antigen detection in combination with anti-glycoprotein E IgM and IgG serology can significantly increase the sensitivity of acute dengue diagnosis and extends the possible window of detection to include very early acute samples and enhances the clinical utility of rapid immunochromatographic testing for dengue.     

Rates of anti-tuberculosis drug resistance in Kampala-Uganda are low and not associated with HIV infection

Background

Drug resistance among tuberculosis patients in sub-Saharan Africa is increasing, possibly due to association with HIV infection. We studied drug resistance and HIV infection in a representative sample of 533 smear-positive tuberculosis patients diagnosed in Kampala, Uganda.

Methods/Principal Findings

Among 473 new patients, multidrug resistance was found in 5 (1.1%, 95% CI 0.3–2.5) and resistance to any drug in 57 (12.1%, 9.3–15.3). Among 60 previously treated patients this was 7 (11.7%, 4.8–22.6) and 17 (28.3%; 17.5–41.4), respectively. Of 517 patients with HIV results, 165 (31.9%, 27.9–36.1) tested positive. Neither multidrug (adjusted odds ratio (OR^adj) 0.7; 95% CI 0.19–2.6) nor any resistance (OR^adj 0.7; 0.43–1.3) was associated with HIV status. Primary resistance to any drug was more common among patients who had worked in health care (OR^adj 3.5; 1.0–12.0).

Conclusion/Significance

Anti-tuberculosis drug resistance rates in Kampala are low and not associated with HIV infection, but may be associated with exposure during health care.     

Anal HPV infection in HIV-positive men who have sex with men from China

Background

Anal HPV infection, which contributes to the development of anal warts and anal cancer, is well known to be common among men who have sex with men (MSM), especially among those HIV positives. However, HIV and anal HPV co-infection among MSM has not been addressed in China.

Methods

A cross-sectional study was conducted in Beijing and Tianjin, China. Study participants were recruited using multiple methods with the collaboration of local volunteer organizations. Blood and anal swabs were collected for HIV-1 serological test and HPV genotyping.

Results

A total of 602 MSM were recruited and laboratory data were available for 578 of them (96.0%). HIV and anal HPV prevalence were 8.5% and 62.1%, respectively. And 48 MSM (8.3%) were found to be co-infected. The HPV genotypes identified most frequently were HPV06 (19.6%), HPV16 (13.0%), HPV52 (8.5%) and HPV11 (7.6%). Different modes of HPV genotypes distribution were observed with respect to HIV status. A strong dose-response relationship was found between HIV seropositivity and multiplicity of HPV genotypes (p<0.001), which is consistent with the observation that anal HPV infection was an independent predictor for HIV infection.

Conclusions

A high prevalence of HIV and anal HPV co-infection was observed in the MSM community in Beijing and Tianjin, China. Anal HPV infection was found to be independently associated with increased HIV seropositivity, which suggests the application of HPV vaccine might be a potential strategy to reduce the acquisition of HIV infection though controlling the prevalence of HPV.     

Comparison of HIV prevalence estimates for Zimbabwe from antenatal clinic surveillance (2006) and the 2005-06 Zimbabwe Demographic and Health Survey

Objective

To assess whether HIV surveillance data from pregnant women attending antenatal care (ANC) clinics in Zimbabwe represent infection levels in the general population.

Methods

HIV prevalence estimates from ANC surveillance sites in 2006 were compared with estimates from the corresponding Zimbabwe Demographic and Health Survey 2005–06 (ZDHS) clusters using geographic information systems.

Results

The ANC HIV prevalence estimate (17.9%, 95% CI 17.0%–18.8%) was similar to the ZDHS estimates for all men and women aged 15–49 years (18.1%, 16.9%–18.8%), for pregnant women (17.5%, 13.9%–21.9%), and for ANC attendees living within 30 km of ANC surveillance sites (19.9%, 17.1%–22.8%). However, the ANC surveillance estimate (17.9%) was lower than the ZDHS estimates for all women (21.1%, 19.7%–22.6%) and for women living within 30 km catchment areas of ANC surveillance sites (20.9%, 19.4%–22.3%). HIV prevalence in ANC sites classified as urban and rural was significantly lower than in sites classified as “other”.

Conclusions

Periodic population surveys can be used to validate ANC surveillance estimates. In Zimbabwe, ANC surveillance provides reliable estimates of HIV prevalence among men and women aged 15–49 years in the general population. Three classifications of ANC sites (rural/urban/other) should be used when generating national HIV estimates.     

HIV incidence, risk factors, and motivation for biomedical intervention among gay, bisexual men, and transgender persons in Northern Thailand

Background

HIV prevalence among men who have sex with men (MSM) and transgender (TG) persons is high and increasing in Chiang Mai, northern Thailand.

Objectives

To describe demographic, socioeconomic, sexual behavior and interest in future HIV prevention trials among gay and bisexual MSM and TG presenting for HIV testing (VCT) and pre-screening for the iPrEx pre-exposure chemoprophylaxis trail.

Methods

In 2008–09, MSM/TG participants attending VCT were interviewed and tested for HIV and STI. Univariate and multivariate regression analyses were done to assess associations with HIV infection.

Results

A total of 551 MSM clients (56.1% gay, 25.4% TG, and 18.5% bisexual (BS)) were enrolled. The mean age was 23.9 years. HIV prevalence among MSM overall was 12.9% (71/551); 16.5% among gay men, 9.3% among TG, and 6.9% among BS. Consistent use of condom was low, 33.3% in insertive anal sex and 31.9% in receptive anal sex. Interest in participation was high, 86.3% for PrEP, 69.7% for HIV vaccine trials, but 29.9% for circumcision. HIV was independently associated with being gay identified, aOR 2.8, p = 0.037 and with being aged 25–29, aOR 2.7, p = 0.027. Among repeat testers, HIV incidence was 8.2/100 PY, 95% CI, 3.7/100PY to 18.3/100PY.

Conclusion

HIV risks and rates varied by self-reported sexual orientation and gender identity. HIV was associated with sexual practices, age, and being gay-identified. These are populations are in need of novel prevention strategies and willing to participate in prevention research.     

Incidence of influenza in healthy adults and healthcare workers: a systematic review and meta-analysis

Background

Working in healthcare is often considered a risk factor for influenza; however, this risk has not been quantified. We aimed to systematically review evidence describing the annual incidence of influenza among healthy adults and healthcare workers (HCWs).

Methods and Findings

We searched OVID MEDLINE (1950 to 2010), EMBASE (1947 to 2010) and reference lists of identified articles. Observational studies or randomized trials reporting full season or annual influenza infection rates for healthy, working age adult subjects and HCWs were included. Influenza infection was defined as a four-fold rise in antibody titer, or positive viral culture or polymerase chain reaction.From 24,707 citations, 29 studies covering 97 influenza seasons with 58,245 study participants were included. Pooled influenza incidence rates (IR) (95% confidence intervals (CI)) per 100 HCWs per season and corresponding incidence rate ratios (IRR) (95% CI) as compared to healthy adults were as follows. All infections: IR 18.7 (95% CI, 15.8 to 22.1), IRR 3.4 (95% CI, 1.2 to 5.7) in unvaccinated HCWs; IR 6.5 (95% CI, 4.6 to 9.1), IRR 5.4 (95% CI, 2.8 to 8.0) in vaccinated HCWs. Symptomatic infections: IR 7.5 (95% CI, 4.9 to 11.7), IRR 1.5 (95% CI, 0.4 to 2.5) in unvaccinated HCWs, IR 4.8 (95% CI, 3.2 to 7.2), IRR 1.6 (95% CI, 0.5 to 2.7) in vaccinated HCWs.

Conclusions

Compared to adults working in non-healthcare settings, HCWs are at significantly higher risk of influenza.     

Risk factors for ocular infection with Chlamydia trachomatis in children 6 months following mass treatment in Tanzania

Background

Trachoma is the leading infectious cause of blindness in the world, and for endemic communities, mass treatment with azithromycin reduces the pool of infection. High coverage is essential, especially in children as they are the infectious reservoir. However, infection remains post-mass treatment. We sought to determine risk factors for infection in children post-mass treatment.

Methodology

All children under 9 years in 4 villages in Tanzania were followed from baseline pre-mass treatment to six months post treatment. 1,991 children under nine years were enrolled in the longitudinal study and data on individual and household characteristics was collected at baseline. Clinical trachoma was determined by an ocular exam and infection detected by PCR of an eyelid swab. Azithromycin was offered and infection was reassessed at 6 months. A multilevel logistic regression model was used, accounting for household clustering of children for analysis.

Principal Findings

Baseline infection was 23.7% and at 6 months was 10.4%, despite 95% coverage. Infection at baseline was positively associated with infection at 6 months (OR = 3.31, 95%CI 2.40–4.56) and treatment had a protective effect (OR = 0.45, 95%CI 0.25–0.80). The age group 2–4 years had an increased risk of infection at 6 months. The household characteristics predictive of infection at 6 months were increasing number of children infected in the household at baseline and increasing number of untreated children in the household.

Conclusions

While one round of mass treatment with high coverage did decrease infection by over 50%, it appears that it is not sufficient to eliminate infection. Findings that young children (ages 2–4 years) and households with increasing numbers of infected and untreated children have a positive association with infection at 6 months suggest that such households could be targeted for more intensive follow up.     

Comparison of methods to correct survival estimates and survival regression analysis on a large HIV African cohort

Objective

The evaluation of HIV treatment programs is generally based on an estimation of survival among patients receiving antiretroviral treatment (ART). In large HIV programs, loss to follow-up (LFU) rates remain high despite active patient tracing, which is likely to bias survival estimates and survival regression analyses.

Methods

We compared uncorrected survival estimates derived from routine program data with estimates obtained by applying six correction methods that use updated outcome data by a field survey targeting LFU patients in a rural HIV program in Malawi. These methods were based on double-sampling and differed according to the weights given to survival estimates in LFU and non-LFU subpopulations. We then proposed a correction of the survival regression analysis.

Results

Among 6,727 HIV-infected adults receiving ART, 9% were LFU after one year. The uncorrected survival estimates from routine data were 91% in women and 84% in men. According to increasing sophistication of the correction methods, the corrected survival estimates ranged from 89% to 85% in women and 82% to 77% in men. The estimates derived from uncorrected regression analyses were highly biased for initial tuberculosis mortality ratios (RR; 95% CI: 1.07; 0.76–1.50 vs. 2.06 to 2.28 with different correction weights), Kaposi sarcoma diagnosis (2.11; 1.61–2.76 vs. 2.64 to 3.9), and year of ART initiation (1.40; 1.17–1.66 vs. 1.29 to 1.34).

Conclusions

In HIV programs with high LFU rates, the use of correction methods based on non-exhaustive double-sampling data are necessary to minimise the bias in survival estimates and survival regressions.     

Establishing a cohort at high risk of HIV infection in South Africa: challenges and experiences of the CAPRISA 002 acute infection study

Objectives

To describe the baseline demographic data, clinical characteristics and HIV-incidence rates of a cohort at high risk for HIV infection in South Africa as well as the challenges experienced in establishing and maintaining the cohort.

Methodology/Principle Findings

Between August 2004 and May 2005 a cohort of HIV-uninfected women was established for the CAPRISA 002 Acute Infection Study, a natural history study of HIV-1 subtype C infection. Volunteers were identified through peer-outreach. The cohort was followed monthly to determine HIV infection rates and clinical presentation of early HIV infection. Risk reduction counselling and male and female condoms were provided. After screening 775 individuals, a cohort of 245 uninfected high-risk women was established. HIV-prevalence at screening was 59.6% (95% CI: 55.9% to 62.8%) posing a challenge in accruing HIV-uninfected women. The majority of women (78.8%) were self-identified as sex-workers with a median of 2 clients per day. Most women (95%) reported more than one casual sexual partner in the previous 3 months (excluding clients) and 58.8% reported condom use in their last sexual encounter. Based on laboratory testing, 62.0% had a sexually transmitted infection at baseline. During 390 person-years of follow-up, 28 infections occurred yielding seroincidence rate of 7.2 (95% CI: 4.5 to 9.8) per 100 person-years. Despite the high mobility of this sex worker cohort retention rate after 2 years was 86.1%. High co-morbidity created challenges for ancillary care provision, both in terms of human and financial resources.

Conclusions/Significance

Challenges experienced were high baseline HIV-prevalence, lower than anticipated HIV-incidence and difficulties retaining participants. Despite challenges, we have successfully accrued this cohort of HIV-uninfected women with favourable retention, enabling us to study the natural history of HIV-1 during acute HIV-infection. Our experiences provide lessons for others establishing similar cohorts, which will be key for advancing the vaccine and prevention research agenda in resource-constrained settings.     

Influenza-related mortality trends in Japanese and American seniors: evidence for the indirect mortality benefits of vaccinating schoolchildren

Background

The historical Japanese influenza vaccination program targeted at schoolchildren provides a unique opportunity to evaluate the indirect benefits of vaccinating high-transmitter groups to mitigate disease burden among seniors. Here we characterize the indirect mortality benefits of vaccinating schoolchildren based on data from Japan and the US.

Methods

We compared age-specific influenza-related excess mortality rates in Japanese seniors aged ≥65 years during the schoolchildren vaccination program (1978–1994) and after the program was discontinued (1995–2006). Indirect vaccine benefits were adjusted for demographic changes, socioeconomics and dominant influenza subtype; US mortality data were used as a control.

Results

We estimate that the schoolchildren vaccination program conferred a 36% adjusted mortality reduction among Japanese seniors (95%CI: 17–51%), corresponding to ∼1,000 senior deaths averted by vaccination annually (95%CI: 400–1,800). In contrast, influenza-related mortality did not change among US seniors, despite increasing vaccine coverage in this population.

Conclusions

The Japanese schoolchildren vaccination program was associated with substantial indirect mortality benefits in seniors.     

Long-term weekly iron-folic acid and de-worming is associated with stabilised haemoglobin and increasing iron stores in non-pregnant women in Vietnam

Background

The prevalence of anaemia and iron deficiency in women remains high worldwide. WHO recommends weekly iron-folic acid supplementation where anaemia rates in non-pregnant women of reproductive age are higher than 20%. In 2006, a demonstration project consisting of weekly iron-folic acid supplementation and regular de-worming was set up in two districts in a northern province in Vietnam where anaemia and hookworm rates were 38% and 76% respectively. In 2008 the project was expanded to all districts in the province, targeting some 250,000 women. The objectives of this study were to: 1) examine changes in haemoglobin, iron stores and soil transmitted helminth infection prevalence over three years and 2) assess women''s access to and compliance with the intervention.

Methods and Findings

The study was a semi-cross-sectional, semi-longitudinal panel design with a baseline survey, three impact surveys at three-, twelve- and thirty months after commencement of the intervention, and three compliance surveys after ten weeks, eighteen and thirty six months.

Results

After thirty months, mean haemoglobin stabilised at 130.3 g/L, an increase of 8.2 g/L from baseline, and mean serum ferritin rose from 23.9 µg/L to 52 µg/L. Hookworm prevalence fell from 76% to 22% over the same period. After thirty six months, 81% of the target population were receiving supplements and 87% were taking 75% or more of the supplements they received.

Conclusions

Weekly iron-folic acid supplementation and regular de-worming was effective in significantly and sustainably reducing the prevalence of anaemia and soil transmitted helminth infections and high compliance rates were maintained over three years.