Using interviewer random effects to remove selection bias from HIV prevalence estimates

Background: Selection bias in HIV prevalence estimates occurs if non-participation in testing is correlated with HIV status. Longitudinal data suggests that individuals who know or suspect they are HIV positive are less likely to participate in testing in HIV surveys, in which case methods to correct for missing data which are based on imputation and observed characteristics will produce biased results. Methods: The identity of the HIV survey interviewer is typically associated with HIV testing participation, but is unlikely to be correlated with HIV status. Interviewer identity can thus be used as a selection variable allowing estimation of Heckman-type selection models. These models produce asymptotically unbiased HIV prevalence estimates, even when non-participation is correlated with unobserved characteristics, such as knowledge of HIV status. We introduce a new random effects method to these selection models which overcomes non-convergence caused by collinearity, small sample bias, and incorrect inference in existing approaches. Our method is easy to implement in standard statistical software, and allows the construction of bootstrapped standard errors which adjust for the fact that the relationship between testing and HIV status is uncertain and needs to be estimated. Results: Using nationally representative data from the Demographic and Health Surveys, we illustrate our approach with new point estimates and confidence intervals (CI) for HIV prevalence among men in Ghana (2003) and Zambia (2007). In Ghana, we find little evidence of selection bias as our selection model gives an HIV prevalence estimate of 1.4% (95% CI 1.2% – 1.6%), compared to 1.6% among those with a valid HIV test. In Zambia, our selection model gives an HIV prevalence estimate of 16.3% (95% CI 11.0% - 18.4%), compared to 12.1% among those with a valid HIV test. Therefore, those who decline to test in Zambia are found to be more likely to be HIV positive. Conclusions: Our approach corrects for selection bias in HIV prevalence estimates, is possible to implement even when HIV prevalence or non-participation is very high or very low, and provides a practical solution to account for both sampling and parameter uncertainty in the estimation of confidence intervals. The wide confidence intervals estimated in an example with high HIV prevalence indicate that it is difficult to correct statistically for the bias that may occur when a large proportion of people refuse to test.

On the Assumption of Bivariate Normality in Selection Models: A Copula Approach Applied to Estimating HIV Prevalence

Background: Heckman-type selection models have been used to control HIV prevalence estimates for selection bias when participation in HIV testing and HIV status are associated after controlling for observed variables. These models typically rely on the strong assumption that the error terms in the participation and the outcome equations that comprise the model are distributed as bivariate normal.
Methods: We introduce a novel approach for relaxing the bivariate normality assumption in selection models using copula functions. We apply this method to estimating HIV prevalence and new confidence intervals (CI) in the 2007 Zambia Demographic and Health Survey (DHS) by using interviewer identity as the selection variable that predicts participation (consent to test) but not the outcome (HIV status).
Results: We show in a simulation study that selection models can generate biased results when the bivariate normality assumption is violated. In the 2007 Zambia DHS, HIV prevalence estimates are similar irrespective of the structure of the association assumed between participation and outcome. For men, we estimate a population HIV prevalence of 21% (95% CI = 16%–25%) compared with 12% (11%–13%) among those who consented to be tested; for women, the corresponding figures are 19% (13%–24%) and 16% (15%–17%).
Conclusions: Copula approaches to Heckman-type selection models are a useful addition to the methodological toolkit of HIV epidemiology and of epidemiology in general. We develop the use of this approach to systematically evaluate the robustness of HIV prevalence estimates based on selection models, both empirically and in a simulation study.

Adjusting HIV Prevalence Estimates for Non-participation: an Application to Demographic Surveillance

Introduction: HIV testing is a cornerstone of efforts to combat the HIV epidemic, and testing conducted as part of surveillance provides invaluable data on the spread of infection and the effectiveness of campaigns to reduce the transmission of HIV. However, participation in HIV testing can be low, and if respondents systematically select not to be tested because they know or suspect they are HIV positive (and fear disclosure), standard approaches to deal with missing data will fail to remove selection bias. We implemented Heckman-type selection models, which can be used to adjust for missing data that are not missing at random, and established the extent of selection bias in a population-based HIV survey in an HIV hyperendemic community in rural South Africa.

Methods: We used data from a population-based HIV survey carried out in 2009 in rural KwaZulu-Natal, South Africa. In this survey, 5565 women (35%) and 2567 men (27%) provided blood for an HIV test. We accounted for missing data using interviewer identity as a selection variable which predicted consent to HIV testing but was unlikely to be independently associated with HIV status. Our approach involved using this selection variable to examine the HIV status of residents who would ordinarily refuse to test, except that they were allocated a persuasive interviewer. Our copula model allows for flexibility when modelling the dependence structure between HIV survey participation and HIV status.

Results: For women, our selection model generated an HIV prevalence estimate of 33% (95% CI 27–40) for all people eligible to consent to HIV testing in the survey. This estimate is higher than the estimate of 24% generated when only information from respondents who participated in testing is used in the analysis, and the estimate of 27% when imputation analysis is used to predict missing data on HIV status. For men, we found an HIV prevalence of 25% (95% CI 15–35) using the selection model, compared to 16% among those who participated in testing, and 18% estimated with imputation. We provide new confidence intervals that correct for the fact that the relationship between testing and HIV status is unknown and requires estimation.

Conclusions: We confirm the feasibility and value of adopting selection models to account for missing data in population-based HIV surveys and surveillance systems. Elements of survey design, such as interviewer identity, present the opportunity to adopt this approach in routine applications. Where non-participation is high, true confidence intervals are much wider than those generated by standard approaches to dealing with missing data suggest.

Supra-treatment threshold neonatal jaundice: Incidence in HIV-exposed compared to non-exposed neonates at Queen Elizabeth Central Hospital in Blantyre, Malawi

INTRODUCTION: Jaundice is the yellowish pigmentation of the skin, sclera, and mucous membranes resulting from bilirubin deposition. Children born to mothers with HIV are more likely to be born premature, with low birth weight, and to become septic-all risk factors for neonatal jaundice. Further, there has been a change in the prevention of mother-to-child transmission (PMTCT) of HIV guidelines from single-dose nevirapine to a six-week course, all of which theoretically put HIV-exposed newborns at greater risk of developing neonatal jaundice.

AIM: We carried out a study to determine the incidence of severe and clinical neonatal jaundice in HIV-exposed neonates admitted to the Chatinkha Nursery (CN) neonatal unit at Queen Elizabeth Central Hospital (QECH) in Blantyre.

METHODS: Over a period of four weeks, the incidence among non-exposed neonates was also determined for comparison between the two groups of infants. Clinical jaundice was defined as transcutaneous bilirubin levels greater than 5 mg/dL and severe jaundice as bilirubin levels above the age-specific treatment threshold according the QECH guidelines. Case notes of babies admitted were retrieved and information on birth date, gestational age, birth weight, HIV status of mother, type of feeding, mode of delivery, VDRL status of mother, serum bilirubin, duration of stay in CN, and outcome were extracted.

RESULTS: Of the 149 neonates who were recruited, 17 (11.4%) were HIV-exposed. One (5.88%) of the 17 HIV-exposed and 19 (14.4%) of 132 HIV-non-exposed infants developed severe jaundice requiring therapeutic intervention (p = 0.378). Eight (47%) of the HIV-exposed and 107 (81%) of the non-exposed neonates had clinical jaundice of bilirubin levels greater than 5 mg/dL (p < 0.001).

CONCLUSIONS: The study showed a significant difference in the incidence of clinical jaundice between the HIV-exposed and HIV-non-exposed neonates. Contrary to our hypothesis, however, the incidence was greater in HIV-non-exposed than in HIV-exposed infants.

Explanations for child sexual abuse given by convicted offenders in Malawi:no evidence for "HIV cleansing"

OBJECTIVE: A commonly cited, but unproven reason given for the rise in reported cases of child sexual abuse in Sub-Saharan Africa is the "HIV cleansing myth"-the belief that an HIV infected individual can be cured by having sex with a child virgin. The purpose of this study was to explore in Malawi the reasons given by convicted sex offenders for child sexual abuse and to determine if a desire to cure HIV infection motivated their offence.

METHODS: Offenders convicted of sexual crimes against victims under the age of 18 were interviewed in confidence in Malawi's two largest prisons. During the interview the circumstances of the crime were explored and the offenders were asked what had influenced them to commit it. Each participant was asked the closed question "Did you think that having sex with your victim would cure or cleanse you from HIV?"

RESULTS: 58 offenders agreed to participate. The median (range) age of offenders and victims was 30 (16-66) years and 14 (2-17) years, respectively. Twenty one respondents (36.2%) denied that an offence had occurred. Twenty seven (46.6%) admitted that they were motivated by a desire to satisfy their sexual desires. Six (10.3%) stated they committed the crime only because they were under the influence of drugs or alcohol. None of the participants said that a desire to cure or avoid HIV infection motivated the abuse.

CONCLUSION: This study suggests that offenders convicted of a sexual crime against children in Malawi were not motivated by a desire to be cured or "cleansed" from HIV infection. A need to fulfil their sexual urges or the disinhibiting effect of drugs or alcohol was offered by the majority of participants as excuses for their behaviour.

Do Gifts Increase Consent to Home-based HIV Testing? A Difference-in-differences Study in Rural KwaZulu-Natal, South Africa

Background Despite the importance of HIV testing for controlling the HIV epidemic, testing rates remain low. Efforts to scale-up testing coverage and frequency in hard-to-reach and at-risk populations commonly focus on home-based HIV testing. This study evaluates the effect of a gift (a food voucher for families, worth US$ 5) on consent rates for home-based HIV testing.
Methods We use data on 18,478 men and women who participated in the 2009 and 2010 population-based HIV surveillance carried out by the Wellcome Trust Africa Centre for Health and Population Studies in rural KwaZulu-Natal, South Africa. Our quasi-experimental difference-in-differences approach controls for unobserved confounding in estimating the causal effect of the intervention on HIV testing consent rates.
Results Allocation of the gift to a family in 2010 increased the probability of family members consenting to test in 2010 by 25 percentage points (95% CI 21-30; p<0.001). The intervention effect persisted, slightly attenuated, in the year following the intervention (2011), further increasing intervention value for money.
Conclusions In HIV hyperendemic settings a gift can be highly effective at increasing consent rates for home-based HIV testing. Given the importance of HIV testing for treatment uptake and individual health, as well as for HIV treatment-and-prevention strategies and for monitoring the population impact of the HIV response, gifts should be considered as a supportive intervention for HIV testing initiatives where consent rates have been low.

Base de dados e chaves electrónicas ("e-keys"): ferramentas úteis no diagnóstico e identificação de nemátodes fitoparasitas

O objectivo do estudo centrou-se na avaliação da dinâmica de nemátodes fitoparasitas, e relação com alguns parâmetros físico-químicos, num terreno utilizado para produção de beterraba sacarina, na zona de Coruche. Com o intuito de acompanhar o processo de crescimento da cultura, o estudo foi efectuado de Janeiro a Junho de 2003. Recorreu-se a métodos standard para a amostragem, extracção e observação dos nemátodes. Empregaram-se comparações estatísticas entre a sua presença e distribuição. As relações entre fitoparasitas e vários parâmetros físico-químicos do seu habitat foram verificadas por análise de componentes principais (PCA), análise canónica de correspondência (CCA) e correlações. Em virtude das acções causadas pelas práticas agrícolas, a comunidade decresceu de Janeiro a Abril, aumentando até Junho com o início do processo de rega. O número de nemátodes do género Meloidogyne foi significativamente superior, secundado por Helicotylenchus e Tylenchus. As correlações entre indivíduos e parâmetros ambientais indicam que, aparte a influência directa do hospedeiro, o cálcio, o potássio e o azoto influenciaram as relações de abundância entre os géneros.

Base de dados e chaves electrónicas (ekeys): ferramentas úteis no diagnóstico e identificação de nemátodes fitoparasitas

Com o desenvolvimento das tecnologias de computação, o acesso à informação digital nos diversos domínios científicos tem revolucionado e facilitado a obtenção e utilização rápida de dados biológicos. Nos últimos anos, várias bases de dados (catálogos electrónicos) têm sido desenvolvidas, servindo de portal à biodiversidade existente em diversas áreas do globo (ex. Fauna Europaea, Tree of Life). Este tipo de informação permite a manutenção e a catalogação da biodiversidade existente a nível global; particularmente a biodiversidade de florestas, áreas cultivadas, ecossistemas aquáticos, bem como de espécies exóticas/invasivas encontradas nos diversos ecossistemas. Em 1999, foi detectada pela primeira vez, em Portugal e na Europa, o nemátode da madeira do pinheiro (Bursaphelenchus xylophilus, espécie de quarentena e classificada como A1 pela EPPO), associado ao pinheiro bravo (Pinus pinaster). Na sequência deste trabalho foram desenvolvidas diversas bases de dados, nomeadamente para as espécies do género Bursaphelenchus e outros géneros com espécies de elevado interesse económico (Aphelenchoides, Dolichodorus); bem como para outros grupos de espécies com especial interesse biológico (Laimaphelenchus, Parasitaphelenchus). A reunião deste tipo de informação possibilita a construção de matrizes, e a determinação dos caracteres diagnósticos mais importantes para a identificação das espécies, posteriormente utilizados na elaboração de chaves electrónicas politómicas (com base no sistema PICKEY, Dianov & Lobanov). A utilização e versatilidade deste sistema, nomeadamente para o diagnóstico e a identificação de nemátodes fitoparasitas de elevado interesse económico, é demonstrada como exemplo

Levantamiento de una base de datos para el diagnóstico de fallas en motores de combustión interna ciclo Otto con sistema MPFI mediante el análisis del sensor MAP

En el presente documento se presenta el desarrollo de la creación de una base de datos para el diagnóstico de fallas en los motores de combustión interna MPFI mediante el análisis del sensor MAP (Manifold Absolute Pressure), a través del cual se puede determinar y diagnosticar fallas en sensores, actuadores y sistemas auxiliares.

Infecção de mycobacterium bovis em células fagocíticas: estratégia aplicada ao diagnóstico da tuberculose bovina

Neste trabalho foram estudadas as interacções entre Mycobacterium bovis e células hospedeiras, na perspectiva de aplicar os conhecimentos resultantes desse estudo ao melhoramento do diagnóstico da tuberculose bovina. Foi estudada a dinâmica da infecção de células fagocíticas com estirpes de M. bovis, com ênfase para a invasão e multiplicação intracelular das micobactérias. Avaliações efectuadas por citometria de fluxo, microscopia de fluorescência e contagem de colónias demonstraram que as micobactérias invadiram e replicaram em todos os modelos celulares, sendo que as células epiteliais de pulmão de bovino foram as mais permissivas ao seu crescimento. Foi nas células macrofágicas J774 e THP-1 que se verificaram as maiores concentrações micobacterianas, pelo que foram utilizadas para a detecção e identificação de M. bovis por um método molecular. A optimização da extracção de DNA, por um processo mecânico, e o desenvolvimento do método de PCR-RFLP baseado no gene gyrB, com controlo interno, permitiram a identificação de M. bovis. A sensibilidade deste método foi de 100% quando aplicado a estirpes isoladas e apenas de 40% quando utilizado directamente em amostras de macerados de tecidos de bovinos com tuberculose. Uma pré-incubação (3 dias) das amostras nas culturas celulares contribuiu para melhorar significativamente a sensibilidade (77%) do PCR-RFLP gyrB. A cultura celular, como matriz a ser utilizada para aumentar a quantidade de M. bovis presente em amostras biológicas, revela-se um método promissor para o diagnóstico laboratorial rápido, específico e sensível da tuberculose bovina. ### - Summary - Interactions between Mycobacterium bovis and host cells were studied with the purpose to apply the outcome knowledge in the improvement of bovine tuberculosis diagnosis. The dynamic of infection of four cell models with three strains of M. bovis was evaluated, with emphasis given to the invasion and intracellular multiplication of mycobacteria. Assessments by flow cytometry, fluorescence microscopy and colony counting showed that every cell models permitted the replication of mycobacteria, although bovine lung epithelial cells had been the most permissive one. The highest mycobacteria) load was found, however, in J774 and THP-1 macrophages, and hence these cells were used for the optimization of a molecular method for detection and identification of M. bovis. The optimisation of a DNA extraction step, by a mechanical process, and the development of PCR-RFLP based on gyrB gene, with an internal control, allowed the identification of M. bovis. The sensitivity of this method was 100% when applied to isolated strains and only 40% when directly used on samples of macerated of tissues from cattle with tuberculosis. Assays in which a pre-incubation step (three days) of biological samples in cell cultures was introduced significantly improved the sensitivity (77%) of the gyrB PCR-RFLP. Cell cultures as a support for growth and rapid isolation of M. bovis is a promising method for the specific, sensitive and rapid laboratorial diagnosis of bovine tuberculosis.