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ABSTRACT: BACKGROUND: The role of HIV-1 RNA in the emergence of resistance to antiretroviral therapies (ARTs) is well documented while less is known about the role of historical viruses stored in the proviral DNA. The primary focus of this work was to characterize the genetic diversity and evolution of HIV drug resistant variants in an individual's provirus during antiretroviral therapy using next generation sequencing. METHODS: Blood samples were collected prior to antiretroviral therapy exposure and during the course of treatment from five patients in whom drug resistance mutations had previously been identified using consensus sequencing. The spectrum of viral variants present in the provirus at each sampling time-point were characterized using 454 pyrosequencing from multiple combined PCR products. The prevalence of viral variants containing drug resistant mutations (DRMs) was characterized at each time-point. RESULTS: Low abundance drug resistant viruses were identified in 14 of 15 sampling time-points from the five patients. In all individuals DRMs against current therapy were identified at one or more of the sampling time-points. In two of the five individuals studied these DRMs were present prior to treatment exposure and were present at high prevalence within the amplified and sequenced viral population. DRMs to drugs other than those being currently used were identified in four of the five individuals. CONCLUSION: The presence of DRMs in the provirus, regardless of their observed prevalence did not appear to have an effect on clinical outcomes in the short term suggesting that the drug resistant viral variants present in the proviral DNA do not appear to play a role in the short term in facilitating the emergence of drug resistance.
BMC Infectious Diseases 01/2013; 13(1):52. · 3.12 Impact Factor
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ABSTRACT: The rise in tuberculosis (TB) incidence following generalized HIV epidemics can overwhelm TB control programmes in resource-limited settings, sometimes accompanied by rising rates of drug resistance. This has led to claims that DOTS-based TB control has failed in such settings. However, few studies have described the effect of a sustained and well-supported DOTS programme on TB incidence and drug resistance over a long period. We present long-term trends in incidence and drug resistance in rural Malawi.
Karonga District in northern Malawi has an adult HIV prevalence of ∼10%. A research group, the Karonga Prevention Study, collaborates with the National Tuberculosis Programme to support core TB control activities. Bacteriological, demographic and clinical (including HIV status) information from all patients starting TB treatment in the District have been recorded since 1988. During that period isolates from each culture-positive TB patient were exported for drug sensitivity testing. Antiretroviral therapy (ART) has been widely available since 2005.
Incidence of new smear-positive adult TB peaked at 124/100,000/year in the mid-90s, but has since fallen to 87/100,000/year. Drug sensitivity information was available for 95% (3132/3307) of all culture-positive cases. Initial resistance to isoniazid was around 6% with no evidence of an increase. Fewer than 1% of episodes involved a multi-drug resistant strain.
In this setting with a generalised HIV epidemic and medium TB burden, a well-supported DOTS programme enhanced by routine culture and drug sensitivity testing may well have reduced TB incidence and maintained drug resistance at low levels.
PLoS ONE 01/2013; 8(3):e58192. · 4.09 Impact Factor
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ABSTRACT: BACKGROUND: Decentralised health services form a key part of chronic care strategies in resource-limited settings by reducing the distance between patient and clinic and thereby the time and costs involved in travelling. However, few tools exist to evaluate the impact of decentralisation on patient travel time or what proportion of patients attend their nearest clinic. Here we develop methods to monitor changes in travel time, using data from the antiretroviral therapy (ART) roll-out in a rural district in North Malawi. METHODS: Clinic position was combined with GPS information on the home village of patients accessing ART services in Karonga District (North Malawi) between July 2005 and July 2009. Potential travel time was estimated as the travel time for an individual attending their nearest clinic, and estimated actual travel time as the time to the clinic attended. This allowed us to calculate changes in potential and actual travel time as new clinics opened and track the proportion and origin of patients not accessing their nearest clinic. RESULTS: The model showed how the opening of further ART clinics in Karonga District reduced median potential travel time from 83 to 43 minutes, and median actual travel time fell from 83 to 47 minutes. The proportion of patients not attending their nearest clinic increased from 6% when two clinics were open, to 12% with four open. DISCUSSION: Integrating GPS information with patient data shows the impact of decentralisation on travel time and clinic choice to inform policy and research questions. In our case study, travel time decreased, accompanied by an increased uptake of services. However, the model also identified an increasing proportion of ART patients did not attend their nearest clinic.
International Journal of Health Geographics 11/2012; 11(1):49. · 2.62 Impact Factor
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The Lancet 09/2012; 380(9844):802; author reply 802-3. · 38.28 Impact Factor
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ABSTRACT: OBJECTIVE:: To estimate the impact of antiretroviral therapy (ART) on the incidence of recurrent tuberculosis in an African population. DESIGN:: A long-term population cohort in Karonga District, northern Malawi. METHODS:: Patients who had completed treatment for laboratory-confirmed TB diagnosed since 1996 were visited annually to record vital status, ART use, and screen for TB. Survival analysis estimated the effect of HIV/ART status at completion of treatment on mortality and recurrence. Analyses were stratified by time since treatment completion to estimate the effects on relapse (predominates during first year) and reinfection disease (predominates later). RESULTS:: Among 1133 index TB cases contributing 4353 person-years of follow-up, there were 307 deaths and 103 laboratory-confirmed recurrences (recurrence rate 4.6/100py). Half the recurrences occurred in the first year since completing treatment. HIV infection increased the recurrence rate (rate ratio [RR] adjusted for age, sex, time period and TB type 2.69, 95%CI 1.69-4.26), but with less effect in the first year (adjusted RR 1.71, 0.87-3.35) than subsequently (adjusted RR 4.2, 2.16-8.15). Recurrence rates on ART were intermediate between those of HIV-negative individuals and HIV-positive individuals without ART. Compared to HIV-positive individuals without ART the adjusted RR was 0.74 (0.27-2.06) in the first year, and 0.43 (0.11-1.73) later. CONCLUSION:: The increased incidence of TB recurrence observed in HIV positive patients appeared to be reduced by ART. The effects are mostly on later (likely reinfection) disease so the impact of ART on reducing recurrence will be highest in high TB incidence settings.
AIDS (London, England) 08/2012; · 4.91 Impact Factor
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Menard Chihana,
Sian Floyd,
Anna Molesworth,
Amelia C Crampin,
Ndoliwe Kayuni,
Alison Price,
Basia Zaba,
Andreas Jahn,
Hazzie Mvula,
Albert Dube,
Bagrey Ngwira, Judith R Glynn,
Neil French
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ABSTRACT: Developing countries are undergoing demographic transition with a shift from high mortality caused by communicable diseases (CD) to lower mortality rates caused by non-communicable diseases (NCD). HIV/AIDS has disrupted this trend in sub-Saharan Africa. However, in recent years, HIV-associated mortality has been reduced with the introduction of widely available antiretroviral therapy (ART). Side effects of ART may lead to increased risk of cardiovascular diseases, raising the prospects of an accelerated transition towards NCD as the primary cause of death. We report population-based data to investigate changes in cause of death owing to NCD during the first 4 years after introduction of HIV treatment.
We analysed data from a demographic surveillance system in Karonga district, Malawi, from September 2004 to August 2009. ART was introduced in mid-2005. Clinician review of verbal autopsies conducted 2-6 weeks after a death was used to establish a single principal cause of death.
Over the entire period, there were 905 deaths, AIDS death rate fell from 505 to 160/100,000 person-years, and there was no evidence of an increase in NCD rates. The proportion of total deaths attributable to AIDS fell from 42% to 17% and from NCD increased from 37% to 49%.
Our findings show that 4 years after the introduction of ART into HIV care in Karonga district, all-cause mortality has fallen dramatically, with no evidence of an increase in deaths owing to NCD.
Tropical Medicine & International Health 08/2012; 17(8):e74-83. · 2.80 Impact Factor
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Sian Floyd,
Anna Molesworth,
Albert Dube,
Amelia C Crampin,
Rein Houben,
Menard Chihana,
Alison Price,
Ndoliwe Kayuni,
Jacqueline Saul,
Neil French, Judith R Glynn
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ABSTRACT: OBJECTIVE:: To quantify refusal bias due to prior HIV-testing, and its effect on HIV prevalence estimates, in general-population surveys. DESIGN:: Four annual, cross-sectional, house-to-house HIV sero-surveys conducted during 2006-2010 within a demographic surveillance population of 33,000 in northern Malawi. METHODS:: The effect of prior knowledge of HIV status on test acceptance in subsequent surveys was analysed. HIV prevalence was then estimated using ten adjustment methods, including age-standardisation; multiple imputation of missing data; a conditional probability equations approach incorporating refusal bias; using longitudinal data on previous and subsequent HIV results; including self-reported HIV status; and including linked antiretroviral therapy clinic data. RESULTS:: HIV test acceptance was 55-65% in each sero-survey. By 2009/10 79% of men and 85% of women had tested at least once. Known HIV-positive individuals were more likely to be absent, and refuse interviewing and testing. Using longitudinal data, and adjusting for refusal bias, the best estimate of HIV prevalence was 7% in men and 9% in women in 2008/9. Estimates using multiple imputation were 4.8% and 6.4% respectively. Using the conditional probability approach gave good estimates using the refusal risk ratio of HIV-positive to HIV-negative individuals observed in this study, but not when using the only previously published estimate of this ratio, even though this was also from Malawi. CONCLUSION:: As the proportion of the population who know their HIV-status increases, survey-based prevalence estimates become increasingly biased. Since an adjustment method for cross-sectional data remains elusive, sources of data with high coverage, such as ANC surveillance, remain important.
AIDS (London, England) 07/2012; · 4.91 Impact Factor
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Amelia C Crampin,
Albert Dube,
Sebastian Mboma,
Alison Price,
Menard Chihana,
Andreas Jahn,
Angela Baschieri,
Anna Molesworth,
Elnaeus Mwaiyeghele,
Keith Branson,
Sian Floyd,
Nuala McGrath,
Paul E M Fine,
Neil French, Judith R Glynn,
Basia Zaba
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ABSTRACT: The Karonga Health and Demographic Surveillance System (Karonga HDSS) in northern Malawi currently has a population of more than 35 000 individuals under continuous demographic surveillance since completion of a baseline census (2002-2004). The surveillance system collects data on vital events and migration for individuals and for households. It also provides data on cause-specific mortality obtained by verbal autopsy for all age groups, and estimates rates of disease for specific presentations via linkage to clinical facility data. The Karonga HDSS provides a structure for surveys of socio-economic status, HIV sero-prevalence and incidence, sexual behaviour, fertility intentions and a sampling frame for other studies, as well as evaluating the impact of interventions, such as antiretroviral therapy and vaccination programmes. Uniquely, it relies on a network of village informants to report vital events and household moves, and furthermore is linked to an archive of biological samples and data from population surveys and other studies dating back three decades.
International Journal of Epidemiology 06/2012; 41(3):676-85. · 6.41 Impact Factor
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ABSTRACT: Recent UNAIDS guidelines recommend measuring concurrency 6 months before the interview date, based on overlapping partnership dates. This has theoretical advantages, but little is known about how well it can be measured in practice.
The assumptions underlying the UNAIDS measure were tested using data from a sexual behaviour survey conducted in rural northern Malawi. All resident adults aged 15-59 were eligible. Questions included self-reported concurrency and dates for all marital and nonmarital partnerships in the past 12 months.
A total of 6796 women and 5253 men were interviewed, 83 and 72% of those eligible, respectively. Since few women reported multiple partners, detailed analysis was restricted to men. Overall 19.2% [95% confidence interval (CI) 18.1-20.2] of men self-reported concurrent relationships in the past year (almost all of those with more than one partner). Using overlapping dates the estimate was 16.7% (15.7-17.7). Excluding partnerships which tied on dates (making overlap uncertain) or restricting the analysis to the three most recent partners gave similar results. The UNAIDS 6-month measure was 12.0% (11.1-12.9), and current concurrency was 11.5% (10.6-12.4). The difference between dates-based and self-reported 12-month measures was much larger for unmarried men: 11.1% (9.7-12.4) self-reported; 7.1% (6.9-8.2) on dates. Polygyny (15% of married men) and the longer duration of relationships stabilized the estimates for married men. Nonmarital partnerships were under-reported, particularly those starting longer ago.
The difficulties of recall of dates for relationships, and under-reporting of partners lead to underestimation of concurrency using date-based measures. Self-reported concurrency is much easier to measure and appears more complete.
AIDS (London, England) 05/2012; 26(8):977-85. · 4.91 Impact Factor
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ABSTRACT: To identify clinical predictors of mortality in HIV-2-infected individuals that may be used in place of CD4 count or plasma viral load (PVL) to guide treatment management in resource-limited settings.
A prospective community cohort study of HIV-infected and HIV-negative individuals in a rural area of Guinea-Bissau has been ongoing since 1989. In 2003 participants were invited for a clinical examination and blood tests. They were followed-up for vital status until 2010. Antiretroviral treatment (ART) became available in 2007. Cox regression was used to examine the association of clinical measures (World Health Organization (WHO) stage, body mass index (BMI), mid-upper arm circumference (MUAC), and WHO performance scale) measured in 2003 with subsequent mortality.
In 2003, 146 HIV-2-infected individuals (68% women; mean age 56 years) were examined. Over the next 7 years, 44 (30%) died. BMI<18.5kg/m(2) was associated with a crude mortality hazard ratio (HR) of 1.9 (95% confidence interval (CI) 1.0-3.9, p=0.08); adjusted for age and sex, HR 1.8 (95% CI 0.9-3.8, p=0.1). MUAC <230mm in women and <240mm in men was also associated with an elevated mortality HR, though statistical evidence was weak (crude HR 2.2, 95% CI 0.9-5.3, p=0.1). WHO clinical stage and WHO performance scale were not associated with mortality (p=0.6 and p=0.2, respectively, for crude associations).
Baseline BMI, MUAC, WHO stage, and WHO performance scale were not strong or statistically significant predictors of mortality among HIV-2-infected individuals. CD4 count and PVL are more reliable tools, when available, for the management of HIV-2-infected patients in the community setting.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 03/2012; 16(5):e337-43. · 2.17 Impact Factor
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ABSTRACT: HIV and tuberculosis (TB) are the most common causes of death in South Africa. Antiretroviral therapy (ART) programmes should have had an impact on mortality rates. This study describes the impact of HIV, a Wellness (HIV/ART) programme and TB on population-wide trends in mortality and causes of death among South African platinum miners, from before the HIV epidemic into the ART era.
Retrospective analysis was conducted using routinely-collected data from an open cohort. Mortality and causes of death were determined from multiple sources, including cardiorespiratory autopsy records. All-cause and cause-specific mortality rates were calculated by calendar year. 41,665 male miners were observed for 311,938 person years (py) with 3863 deaths. The all-cause age-standardised mortality rate increased from 5.9/1000 py in 1992 to 20.2/1000 py in 2002. Following ART rollout in 2003, annual mortality rates fluctuated between 12.4/1000 py and 19.3/1000 py in the subsequent 7 years. Half of all deaths were HIV-related and 21% were caused by TB. Half (50%) of miners who died of HIV after ART rollout had never been registered on the Wellness programme. TB was the most common cause of death in HIV positive miners, increasing from 28% of deaths in the pre-ART period to 41% in the post-ART period.
This population-based cohort experienced a rapid increase in mortality from 1996 to 2003 due to increases in HIV and TB mortality. Following ART rollout there was a decrease in mortality, but a steady decrease has not been sustained. Possible explanations for these trends include the changing composition of the workforce, maturation of the HIV epidemic, insufficient uptake of ART and an increase in the proportion of deaths due to TB. In order to make a significant and sustained reduction in mortality in this population, expanding and integrating HIV and TB care and treatment is essential.
PLoS ONE 01/2012; 7(6):e38598. · 4.09 Impact Factor
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David Maman, Judith R Glynn,
Amelia C Crampin,
Katharina Kranzer,
Jacqueline Saul,
Andreas Jahn,
Venance Mwinuka,
Msenga Hc Ngwira,
Hazzie Mvula,
Fipson Munthali,
Nuala McGrath
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ABSTRACT: Antiretroviral (ART) scale-up in Malawi has been achieved on a large scale based mainly on clinical criteria. Simple markers of prognosis are useful, and we investigated the value of very early anthropometric changes in predicting mortality.
Adult patients who initiated ART in Karonga District, northern Malawi, between September 2005 and August 2006 were included in a prospective cohort study, and followed for up to one year. We used Cox regression to examine the association between anthropometric changes at 2 and 6 weeks and deaths within the first year. 573 patients were included, of whom 59% were women; the median age at initiation was 37 and 64% were in WHO stage 4. Both body mass index (BMI) and mid-upper arm circumference (MUAC) increased linearly with increased time on ART, and were closely correlated with each other. There were 118 deaths. After 2 weeks on ART, a BMI increase of <0.5 kg/m(2) (HR 2.47, 95%CI 1.24-4.94, p=0.005) or a MUAC increase of <0.5cm (HR 2.79, 95%CI 1.19-6.55, p=0.008) were strong predictors of death, and these associations were stronger after adjusting for baseline charactertistics. Similar results were found after 6 weeks on ART.
Very early anthropometric changes, after 2 and 6 weeks on ART, are strong predictors of survival, independent of baseline characteristics. This should help identify patients requiring more detailed assessment where facilities are limited. MUAC is particularly valuable, requiring the simplest equipment and being appropriate for patients who have problems standing.
The Open AIDS Journal 01/2012; 6:36-44.
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ABSTRACT: Knowledge of HIV status may influence fertility desires of married men and women. There is little knowledge about the importance of this influence among monogamously married couples and how knowledge of HIV status influences use of contraception among these couples.
We carried out a cross-sectional analysis of interview data collected between October 2008 and September 2009 on men aged 15-59 years and women aged 15-49 years who formed 1766 monogamously married couples within the Karonga Prevention Study demographic surveillance study in northern Malawi.
5% of men and 4% of women knew that they were HIV positive at the time of interview and 81% of men and 89% of women knew that they were HIV negative. 73% of men and 83% of women who knew that they were HIV positive stated that they did not want more children, compared to 35% of men and 38% of women who knew they were HIV negative. Concordant HIV positive couples were more likely than concordant negative couples to desire to stop child bearing (odds ratio 11.5, 95%CI 4.3-30.7, after adjusting for other factors) but only slightly more likely to use contraceptives (adjusted odds ratio 1.5 (95%CI 0.8-3.3).
Knowledge of HIV positive status is associated with an increase in the reported desire to cease childbearing but there was limited evidence that this desire led to higher use of contraception. More efforts directed towards assisting HIV positive couples to access and use reproductive health services and limit HIV transmission among couples are recommended.
PLoS ONE 01/2012; 7(12):e51861. · 4.09 Impact Factor
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ABSTRACT: Evidence of a link between sexual violence and HIV is growing; however, studies among children are scarce. The authors sought to characterise child sexual abuse in Harare, Zimbabwe, and explore its links with HIV and orphanhood.
Records for new clients attending a child sexual abuse clinic from July 2004 to June 2005 were computerised and reviewed. Information on characteristics, medical examinations, laboratory tests and perpetrators were summarised. Orphan prevalence was compared with Demographic and Health Survey (DHS) 2005/2006 data for Harare, and a household-based survey in a neighbouring community.
Over 1 year, 1194 new clients (90% female) aged 7 weeks to 16 years were assessed, with 93% of boys and 59% of girls classified clinically as prepubertal. 94% of clients reported penetrative sexual abuse, occurring most often in the child's home. Most perpetrators were identified as relatives or neighbours by children under 12 years, and 'boyfriends' by adolescent girls. At presentation, 31/520 (6%) clients tested were HIV-positive. Where recorded, 39 (6%) clients presented within 3 days of abuse, and 36 were given postexposure prophylaxis for HIV (PEP). Among female clients, orphan prevalence was higher than in the DHS (OR=1.7; 1.4 to 2.2) and neighbouring community (OR=1.7; 0.7 to 4.3).
High numbers of children in Harare experience penetrative sexual abuse, and most present too late for PEP. More immediate presentation of sexual abuse can help to prevent HIV and recurrent abuse, and assist in examination and prosecution. Orphanhood emerged as a possible risk factor for sexual abuse and an important area for further research.
Journal of epidemiology and community health 12/2011; 65(12):1075-82. · 3.04 Impact Factor
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ABSTRACT: A key conclusion of the Four Cities Study, carried out to explore reasons for heterogeneity in the HIV epidemic between two cities in sub-Saharan Africa with relatively low prevalence (Cotonou and Yaoundé) and two with high prevalence (Kisumu and Ndola), was that differences in biological cofactors outweighed differences in sexual risk behaviours. The authors explore an alternative hypothesis, that risk behaviours were historically higher in the high-prevalence cities. They also investigate the effects of different prevalence of male circumcision on the HIV epidemics in the four cities.
A transmission model was fitted to data from the Four Cities Study. Default scenarios included biological cofactor effects on HIV transmission. Counter-factual scenarios were simulated without biological cofactors, with and without higher historical sexual behaviours, and with various rates of male circumcision.
Simulated adult HIV prevalence in 1997 for the default scenarios was 3.1%, 7.8%, 28.9% and 27.1% in Cotonou, Yaoundé, Kisumu and Ndola, respectively, in line with data. Without biological cofactors, even implausibly high historical levels of risk behaviour in East Africa could not reproduce the observed heterogeneity in the late 1990s. Increasing the proportion of men circumcised in Ndola from 10% to 100% reduced HIV prevalence in 1997 to 7%. Decreasing the proportion circumcised in Yaoundé from 100% to 10% increased HIV prevalence to 26%.
Differences in male circumcision rates are likely to have played a key role in the heterogeneous spread of HIV across Africa. The effect of circumcision interventions can vary depending on the epidemic setting, with a larger effect in more generalised epidemics.
Sexually transmitted infections 09/2011; 87(7):640-5. · 2.18 Impact Factor
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The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 09/2011; 15(9):1271-2. · 2.73 Impact Factor
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ABSTRACT: Traditional tuberculosis (TB) treatment outcome measures, such as cure rate, do not provide insight into the underlying reasons for missing clinical targets. We evaluated a TB Process-Based Performance Review (TB-PBPR) tool, developed to identify "missed opportunities" for timely and accurate diagnosis of TB. The tool enables performance assessment at the level of process and quality of care.
The TB-PBPR tool is a single-page structured flow-sheet that identifies 14 clinical actions (grouped into elicited symptoms, clinical examination and investigations). Medical records from selected deceased patients were reviewed at two South African mine hospitals (A = 56 cases; B = 26 cases), a South African teaching hospital (C = 20 cases) and a UK teaching hospital (D = 13 cases).
In hospital A, where autopsy was routine, TB was missed in life in 52% (23/44) of cases and was wrongly attributed as the cause of death in 16% (18/110). Clinical omissions were identified at each hospital and at every stage of clinical management. For example, recording of chest symptoms was omitted in up to 39% of cases, sputum smear examination in up to 85% and chest radiograph in up to 38% of cases respectively.
This study introduces the TB-PBPR tool as a novel method to review and evaluate clinical performance in TB management. We found that simple clinical actions were omitted in many cases. The tool, in conjunction with a manual describing best practice, is adaptable to a range of settings, is educational and enables detailed feedback within a TB programme. The TB-PBPR tool and manual are both freely available for general use.
BMC Public Health 02/2011; 11:127. · 2.00 Impact Factor
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Judith R Glynn,
Ndoliwe Kayuni,
Emmanuel Banda,
Fiona Parrott,
Sian Floyd,
Monica Francis-Chizororo,
Misheck Nkhata,
Clare Tanton,
Joanne Hemmings,
Anna Molesworth,
Amelia C Crampin,
Neil French
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ABSTRACT: Sexual behaviour surveys are widely used, but under-reporting of particular risk behaviours is common, especially by women. Surveys in whole populations provide an unusual opportunity to understand the extent and nature of such under-reporting.
All consenting individuals aged between 15 and 59 within a demographic surveillance site in northern Malawi were interviewed about their sexual behaviour. Validity of responses was assessed by analysis of probing questions; by comparison of results with in-depth interviews and with Herpes simplex type-2 (HSV-2) seropositivity; by comparing reports to same sex and opposite sex interviewers; and by quantifying the partnerships within the local community reported by men and by women, adjusted for response rates.
6,796 women and 5,253 men (83% and 72% of those eligible) consented and took part in sexual behaviour interviews. Probing questions and HSV-2 antibody tests in those who denied sexual activity identified under-reporting for both men and women. Reports varied little by sex or age of the interviewer. The number of marital partnerships reported was comparable for men and women, but men reported about 4 times as many non-marital partnerships. The discrepancy in reporting of non-marital partnerships was most marked for married women (men reported about 7 times as many non-marital partnerships with married women as were reported by married women themselves), but was only apparent in younger married women.
We have shown that the under-reporting of non-marital partnerships by women was strongly age-dependent. The extent of under-reporting of sexual activity by young men was surprisingly high. The results emphasise the importance of triangulation, including biomarkers, and the advantages of considering a whole population.
PLoS ONE 01/2011; 6(7):e22840. · 4.09 Impact Factor
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ABSTRACT: Treatment seeking delays among people living with HIV have adverse consequences for outcome. Gender differences in treatment outcomes have been observed in sub-Saharan Africa.
To better understand antiretroviral treatment (ART) seeking behaviour in HIV-infected adults in rural Malawi.
Qualitative interviews with male and female participants in an ART cohort study at a treatment site in rural northern Malawi triangulated with analysis of baseline clinical and demographic data for 365 individuals attending sequentially for ART screening between January 2008 and September 2009.
43% of the cohort presented with late stage HIV disease classified as WHO stage 3/4. Respondents reported that women's frequency of testing, health awareness and commitment to children led to earlier ART uptake and that men's commitment to wider social networks of influence, masculine ideals of strength, and success with sexual and marital partners led them to refuse treatment until they were sick. Quantitative analysis of the screening cohort provided supporting evidence for these expressed views. Overall, male gender (adjusted OR 2.3, 95% CI1.3-3.9) and never being married (adjusted OR 4.1, 95% CI1.5-11.5) were risk factors for late presentation, whereas having ≥3 dependent children was associated with earlier presentation (adjusted OR 0.31, 95% CI0.15-0.63), compared to those with no dependent children.
Gender-specific barriers and facilitators operate throughout the whole process of seeking care. Further efforts to enrol men into care earlier should focus on the masculine characteristics that they value, and the risks to these of severe health decline. Our results emphasise the value of exploring as well as identifying behavioural correlates of late presentation.
PLoS ONE 01/2011; 6(11):e27917. · 4.09 Impact Factor
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ABSTRACT: Survival analysis using time-updated CD4+ counts during antiretroviral therapy is frequently employed to determine risk of clinical events. The time-point when the CD4+ count is assumed to change potentially biases effect estimates but methods used to estimate this are infrequently reported.
This study examined the effect of three different estimation methods: assuming i) a constant CD4+ count from date of measurement until the date of next measurement, ii) a constant CD4+ count from the midpoint of the preceding interval until the midpoint of the subsequent interval and iii) a linear interpolation between consecutive CD4+ measurements to provide additional midpoint measurements. Person-time, tuberculosis rates and hazard ratios by CD4+ stratum were compared using all available CD4+ counts (measurement frequency 1-3 months) and 6 monthly measurements from a clinical cohort. Simulated data were used to compare the extent of bias introduced by these methods.
The midpoint method gave the closest fit to person-time spent with low CD4+ counts and for hazard ratios for outcomes both in the clinical dataset and the simulated data.
The midpoint method presents a simple option to reduce bias in time-updated CD4+ analysis, particularly at low CD4 cell counts and rapidly increasing counts after ART initiation.
PLoS ONE 01/2011; 6(11):e27763. · 4.09 Impact Factor
