South African Centre for Epidemiological Modelling and Analysis (SACEMA)

Systematic review of statistically-derived models of immunological response in HIV-infected adults on antiretroviral therapy in Sub-Saharan Africa

2017-06-06T06:32:01Z

Systematic review of statistically-derived models of immunological response in HIV-infected adults on antiretroviral therapy in Sub-Saharan Africa Sempa, Joseph B.; Ujeneza, Eva L.; Nieuwoudt, Martin Introduction: In Sub-Saharan African (SSA) resource limited settings, Cluster of Differentiation 4 (CD4) counts continue to be used for clinical decision making in antiretroviral therapy (ART). Here, HIV-infected people often remain with CD4 counts <350 cells/μL even after 5 years of viral load suppression. Ongoing immunological monitoring is necessary. Due to varying statistical modeling methods comparing immune response to ART across different cohorts is difficult. We systematically review such models and detail the similarities, differences and problems. Methods: ‘Preferred Reporting Items for Systematic Review and Meta-Analyses’ guidelines were used. Only studies of immune-response after ART initiation from SSA in adults were included. Data was extracted from each study and tabulated. Outcomes were categorized into 3 groups: ‘slope’, ‘survival’, and ‘asymptote’ models. Wordclouds were drawn wherein the frequency of variables occurring in the reviewed models is indicated by their size and color. Results: 69 covariates were identified in the final models of 35 studies. Effect sizes of covariates were not directly quantitatively comparable in view of the combination of differing variables and scale transformation methods across models. Wordclouds enabled the identification of qualitative and semi-quantitative covariate sets for each outcome category. Comparison across categories identified sex, baseline age, baseline log viral load, baseline CD4, ART initiation regimen and ART duration as a minimal consensus set. Conclusion: Most models were different with respect to covariates included, variable transformations and scales, model assumptions, modelling strategies and reporting methods, even for the same outcomes. To enable comparison across cohorts, statistical models would benefit from the application of more uniform modelling techniques. Historic efforts have produced results that are anecdotal to individual cohorts only. This study was able to define ‘prior’ knowledge in the Bayesian sense. Such information has value for prospective modelling efforts. CITATION: Sempa, J. B., Ujeneza, E. L. & Niewoudt, M. 2017. Systematic review of statistically-derived models of immunological response in HIV-infected adults on antiretroviral therapy in Sub-Saharan Africa. PLoS ONE, 12(2):e0171658, doi:10.1371/journal.pone.0171658.; The original publication is available at http://journals.plos.org/plosone

Comparison of cross-sectional HIV incidence assay results from dried blood spots and plasma

2017-06-20T05:47:31Z

Comparison of cross-sectional HIV incidence assay results from dried blood spots and plasma Schlusser, Katherine E.; Pilcher, Christopher; Kallas, Esper G.; Santos, Breno R.; Deeks, Steven G.; Facente, Shelley; Keating, Sheila M.; Busch, Michael P.; Murphy, Gary; Welte, Alex; Quinn, Thomas; Eshleman, Susan H.; Laeyendecker, Oliver Background: Assays have been developed for cross-sectional HIV incidence estimation using plasma samples. Large scale surveillance programs are planned using dried blood spot (DBS) specimens for incidence assessment. However, limited information exists on the performance of HIV cross-sectional incidence assays using DBS. Methods: The assays evaluated were: Maxim HIV-1 Limiting Antigen Avidity EIA (LAg-Avidity), Sedia HIV-1 BED-Capture EIA (BED-CEIA), and CDC modified BioRad HIV-1/2 Plus O Avidity-based Assay (CDC-BioRad Avidity) using pre-determined cutoff values. 100 matched HIV-1 positive plasma and DBS samples, with known duration of infection, from the Consortium for the Evaluation and Performance of HIV Incidence Assays repository were tested. All assays were run in duplicate. To examine the degree of variability within and between results for each sample type, both categorical and continuous results were analyzed. Associations were assessed with Bland Altman, R2 values and Cohen’s kappa coefficient (ĸ). Results: Intra-assay variability using the same sample type was similar for all assays (R2 0.96 to 1.00). The R2 values comparing DBS and plasma results for LAg-Avidity, BED-CEIA, and CDC-BioRad Avidity were 0.96, 0.94, and 0.84, respectively. The concordance and ĸ values between DBS and plasma for all three assays were >87% and >0.64, respectively. The Bland-Altman analysis showed significant differences between plasma and DBS samples. For all three assays, a higher number of samples were classified as recent infections using DBS samples. Conclusions: DBS and plasma sample results were highly correlated. However, when compared to plasma, each assay performed somewhat differently in DBS at the lower and higher ends of the dynamic range. DBS samples were more likely to be classified as recently infected by all three assays, which may lead to overestimation of incidence in surveys using performance criteria derived for plasma samples. CITATION: Schlusser, K. E. et al. 2017. Comparison of cross-sectional HIV incidence assay results from dried blood spots and plasma. PLoS ONE, E 12(2):e0172283, doi:10.1371/journal.pone.0172283.; The original publication is available at http://journals.plos.org/plosone

Is Zimbabwe ready to transition from anonymous unlinked sero-surveillance to using prevention of mother to child transmission of HIV (PMTCT) program data for HIV surveillance? : results of PMTCT utility study, 2012

2017-01-30T12:36:45Z

Is Zimbabwe ready to transition from anonymous unlinked sero-surveillance to using prevention of mother to child transmission of HIV (PMTCT) program data for HIV surveillance? : results of PMTCT utility study, 2012 Gonese, E.; Mushavi, A.; Mungati, M.; Mhangara, M.; Dzangare, J.; Mugurungi, O.; Dee, J.; Kilmarx, P. H.; Shambira, G.; Tshimanga, M. T.; Hargrove, J. Background: Prevention of mother-to-child transmission of HIV (PMTCT) programs collect socio-demographic and HIV testing information similar to that collected by unlinked anonymous testing sero-surveillance (UAT) in antenatal settings. Zimbabwe evaluated the utility of PMTCT data in replacing UAT. Methods: A UAT dataset was created by capturing socio-demographic, testing practices from the woman’s booking-card and testing remnant blood at a laboratory from 1 June to 30 September 2012. PMTCT data were collected retrospectively from ANC registers. UAT and PMTCT data were linked by bar-code labels that were temporarily affixed to the ANC register. A questionnaire was used to obtain facility-level data at 53 sites. Results: Pooled HIV prevalence was 15.8 % (95 % CI 15.3–16.4) among 17,349 women sampled by UAT, and 16.3 % (95 % CI 15.8 %–16.9 %) among 17,150 women in PMTCT datasets for 53 sites. Pooled national percent-positive agreement (PPA) was 91.2 %, and percent-negative agreement (PNA) was 98.7 % for 16,782 women with matched UAT and PMTCT data. Based on UAT methods, overall median prevalence was 12.9 % (Range 4.0 %–19.4 %) among acceptors and refusers of HIV test in PMTCT compared to 12.5 % ((Range 3.4 %–19.5 %) among acceptors in ANC registers. There were variations in prevalence by site. Conclusion: Although, there is no statistical difference between pooled HIV prevalence in UAT compared to PMTCT program, the overall PPA of 91.2 % and PNA of 98.7 % fall below World Health Organisation (WHO) benchmarks of 97.6 % and 99.6 % respectively. Zimbabwe will need to strengthen quality assurance (QA) of rapid HIV testing and data collection practices. Sites with good performance should be prioritised for transitioning. CITATION: Gonese, E., et al. 2016. Is Zimbabwe ready to transition from anonymous unlinked sero-surveillance to using prevention of mother to child transmission of HIV (PMTCT) program data for HIV surveillance? : results of PMTCT utility study, 2012. BMC Infectious Diseases, 16:97, doi:10.1186/s12879-016-1425-2.; The original publication is available at https://bmcinfectdis.biomedcentral.com

Strengthening HIV surveillance in the antiretroviral therapy era : rationale and design of a longitudinal study to monitor HIV prevalence and incidence in the uMgungundlovu District, KwaZulu-Natal, South Africa

2017-01-09T13:19:51Z

Strengthening HIV surveillance in the antiretroviral therapy era : rationale and design of a longitudinal study to monitor HIV prevalence and incidence in the uMgungundlovu District, KwaZulu-Natal, South Africa Kharsany, Ayesha B. M.; Cawood, Cherie; Khanyile, David; Grobler, Anneke; Mckinnon, Lyle R.; Samsunder, Natasha; Frohlich, Janet A.; Karim, Quarraisha Abdool; Puren, Adrian; Welte, Alex; George, Gavin; Govender, Kaymarlin; Toledo, Carlos; Chipeta, Zawadi; Zembe, Lycias; Glenshaw, Mary T.; Madurai, Lorna; Deyde, Varough M.; Bere, Alfred Background: South Africa has over 6,000,000 HIV infected individuals and the province of KwaZulu-Natal (KZN) is the most severely affected. As public health initiatives to better control the HIV epidemic are implemented, timely, detailed and robust surveillance data are needed to monitor, evaluate and inform the programmatic interventions and policies over time. We describe the rationale and design of the HIV Incidence Provincial Surveillance System (HIPSS) to monitor HIV prevalence and incidence. Methods/Design: The household-based survey will include a sample of men and women from two sub-districts of the uMgungundlovu municipality (Vulindlela and the Greater Edendale) of KZN, South Africa. The study is designed as two sequential cross-sectional surveys of 10,000 randomly selected individuals aged 15 – 49 years to be conducted one year apart. From the cross sectional surveys, two sequential cohorts of HIV negative individuals aged 15 – 35 years will be followed-up one year later to measure the primary outcome of HIV incidence. Secondary outcomes include the laboratory measurements for pulmonary tuberculosis, sexually transmitted infections and evaluating tests for estimating population-level HIV incidence. Antiretroviral therapy (ART) access, HIV-1 RNA viral load, and CD4 cell counts in HIV positive individuals will assess the effectiveness of the HIV treatment cascade. Household and individual-level socio-demographic characteristics, exposure to HIV programmatic interventions and risk behaviours will be assessed as predictors of HIV incidence. The incidence rate ratio of the two cohorts will be calculated to quantify the change in HIV incidence between consecutive samples. In anticipation of better availability of population-level HIV prevention and treatment programmes leading to decreases in HIV incidence, the sample size provides 84 % power to detect a reduction of 30 % in the HIV incidence rate between surveys. Discussion: The results from HIPSS will provide critical data regarding HIV prevalence and incidence in this community and will establish whether HIV prevention and treatment efforts in a “ real world ” , non-trial setting have an impact on HIV incidence at a population level. Importantly, the study design and methods will inform future methods for HIV surveillance. CITATION: Kharsany, A. B. M., et al. 2015. Strengthening HIV surveillance in the antiretroviral therapy era : rationale and design of a longitudinal study to monitor HIV prevalence and incidence in the uMgungundlovu District, KwaZulu-Natal, South Africa. BMC Public Health, 15:1149, doi:10.1186/s12889-015-2179-2.; The original publication is available at http://bmcpublichealth.biomedcentral.com

The effect of sexually transmitted co-infections on HIV viral load amongst individuals on antiretroviral therapy : a systematic review and meta-analysis

2016-11-17T09:22:35Z

The effect of sexually transmitted co-infections on HIV viral load amongst individuals on antiretroviral therapy : a systematic review and meta-analysis Champredon, David; Bellan, Steven E.; Delva, Wim; Hunt, Spencer; Shi, Chyun-Fung; Smieja, Marek; Dushoff, Jonathan Background: Antiretroviral therapy (ART) markedly reduces HIV transmission, and testing and treatment programs have been advocated as a method for decreasing transmission at the population level. Little is known, however, about the extent to which sexually transmitted infections (STIs), which increase the HIV infectiousness of untreated individuals, may decrease the effectiveness of treatment as prevention. Methods: We searched major bibliographic databases to August 12th, 2014 and identified studies reporting differences in HIV transmission rate or in viral load between individuals on ART who either were or were not co-infected with another STI. We used hierarchical Bayesian models to estimate viral load differences between individuals with and without STI co-infections. Results: The search strategy retrieved 1630 unique citations of which 14 studies (reporting on 4607 HIV viral load measurements from 2835 unique individuals) met the inclusion criteria. We did not find any suitable studies that estimated transmission rates directly in both groups. Our meta-analysis of HIV viral load measurements among treated individuals did not find a statistically significant effect of STI co-infection; viral loads were, on average, 0.11 log10 (95 % CI −0.62 to 0.83) higher among co-infected versus non-co-infected individuals. Conclusions: Direct evidence about the effects of STI co-infection on transmission from individuals on ART is very limited. Available data suggests that the average effect of STI co-infection on HIV viral load in individuals on ART is less than 1 log10 difference, and thus unlikely to decrease the effectiveness of treatment as prevention. However, there is not enough data to rule out the possibility that particular STIs pose a larger threat. CITATION: Champredon, D. et al. 2015. The effect of sexually transmitted co-infections on HIV viral load amongst individuals on antiretroviral therapy : a systematic review and meta-analysis. BMC Infectious Diseases, 15:249, doi:10.1186/s12879-015-0961-5.; The original publication is available at http://bmcinfectdis.biomedcentral.com

Concurrent partnerships in Cape Town, South Africa : race and sex differences in prevalence and duration of overlap

2016-11-17T09:54:05Z

Concurrent partnerships in Cape Town, South Africa : race and sex differences in prevalence and duration of overlap Beauclair, Roxanne; Hens, Niel; Delva, Wim Introduction: Concurrent partnerships (CPs) have been suggested as a risk factor for transmitting HIV, but their impact on the epidemic depends upon how prevalent they are in populations, the average number of CPs an individual has and the length of time they overlap. However, estimates of prevalence of CPs in Southern Africa vary widely, and the duration of overlap in these relationships is poorly documented. We aim to characterize concurrency in a more accurate and complete manner, using data from three disadvantaged communities of Cape Town, South Africa. Methods: We conducted a sexual behaviour survey (n 878) from June 2011 to February 2012 in Cape Town, using Audio Computer-Assisted Self-Interviewing to collect sexual relationship histories on partners in the past year. Using the beginning and end dates for the partnerships, we calculated the point prevalence, the cumulative prevalence and the incidence rate of CPs, as well as the duration of overlap for relationships begun in the previous year. Linear and binomial regression models were used to quantify race (black vs. coloured) and sex differences in the duration of overlap and relative risk of having CPs in the past year. Results: The overall point prevalence of CPs six months before the survey was 8.4%: 13.4% for black men, 1.9% for coloured men, 7.8% black women and 5.6% for coloured women. The median duration of overlap in CPs was 7.5 weeks.Women had less risk of CPs in the previous year than men (RR 0.43; 95% CI: 0.32 0.57) and black participants were more at risk than coloured participants (RR 1.86; 95% CI: 1.17 2.97). Conclusions: Our results indicate that in this population the prevalence of CPs is relatively high and is characterized by overlaps of long duration, implying there may be opportunities for HIV to be transmitted to concurrent partners. CITATION: Beauclair, R., Hens, N. & Delva, W. 2015. Concurrent partnerships in Cape Town, South Africa : race and sex differences in prevalence and duration of overlap. Journal of the International AIDS Society, 18:19372, doi: 10.7448/IAS.18.1.19372.; The original publication is available at http://www.jiasociety.org

Optimal strategies for controlling riverine Tsetse Flies using targets : a modelling study

2016-09-07T08:02:00Z

Optimal strategies for controlling riverine Tsetse Flies using targets : a modelling study Vale, Glyn A.; Hargrove, John W.; Lehane, Michael J.; Solano, Philippe; Torr, Stephen J. Background: Tsetse flies occur in much of sub-Saharan Africa where they transmit the trypanosomes that cause the diseases of sleeping sickness in humans and nagana in livestock. One of the most economical and effective methods of tsetse control is the use of insecticide-treated screens, called targets, that simulate hosts. Targets have been ~1m2, but recently it was shown that those tsetse that occupy riverine situations, and which are the main vectors of sleeping sickness, respond well to targets only ~0.06m2. The cheapness of these tiny targets suggests the need to reconsider what intensity and duration of target deployments comprise the most cost-effective strategy in various riverine habitats. Methodology/Principal Findings: A deterministic model, written in Excel spreadsheets and managed by Visual Basic for Applications, simulated the births, deaths and movement of tsetse confined to a strip of riverine vegetation composed of segments of habitat in which the tsetse population was either self-sustaining, or not sustainable unless supplemented by immigrants. Results suggested that in many situations the use of tiny targets at high density for just a few months per year would be the most cost-effective strategy for rapidly reducing tsetse densities by the ~90% expected to have a great impact on the incidence of sleeping sickness. Local elimination of tsetse becomes feasible when targets are deployed in isolated situations, or where the only invasion occurs from populations that are not self-sustaining. Conclusion/Significance: Seasonal use of tiny targets deserves field trials. The ability to recognise habitat that contains tsetse populations which are not self-sustaining could improve the planning of all methods of tsetse control, against any species, in riverine, savannah or forest situations. Criteria to assist such recognition are suggested. Author Summary: We employed a deterministic model to simulate the efficacy of various ways of using the tiny, ~0.06m2, insecticide-treated targets recently recommended as replacements for the larger, ~1m2, types previously used to control riverine species of tsetse fly, the main vectors of sleeping sickness in humans. Results suggested that in many situations the use of tiny targets at treble the normal density for a third of the normal time could be the most cost-effective strategy for rapidly reducing or eliminating tsetse populations, so helping with disease control. In deciding whether to aim for local control or elimination, and in planning the operations, it would be highly advantageous to distinguish those parts of the tsetse infestation that support self-sustaining populations, and those containing populations that cannot be sustained unless supplemented by immigrants. Sorts of information that can help to assess the type of sustainability in field habitats are identified. These findings can assist the planning of any method of tsetse control used against any species of tsetse, including those important as vectors of livestock disease. CITATION: Vale, G. A., et al. 2015. Optimal strategies for controlling riverine Tsetse Flies using targets : a modelling study. PLoS Neglected Tropical Diseases, 9(3):e0003615. doi:10.1371/journal.pntd.0003615.; The original publication is available at http://journals.plos.org/plosntds

Tsetse control and Gambian sleeping sickness; implications for control strategy

2016-09-07T08:12:50Z

Tsetse control and Gambian sleeping sickness; implications for control strategy Tirados, Inaki; Esterhuizen, Johan; Mangwiro, T. N. Clement; Vale, Glyn A.; Hastings, Ian; Solano, Philippe; Lehane, Michael J.; Torr, Steve J. Background: Gambian sleeping sickness (human African trypanosomiasis, HAT) outbreaks are brought under control by case detection and treatment although it is recognised that this typically only reaches about 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because it is considered too expensive and difficult to organise in resource-poor settings. We conducted a full scale field trial of a refined vector control technology to determine its utility in control of Gambian HAT. Methods and Findings: The major vector of Gambian HAT is the tsetse fly Glossina fuscipes which lives in the humid zone immediately adjacent to water bodies. From a series of preliminary trials we determined the number of tiny targets required to reduce G. fuscipes populations by more than 90%. Using these data for model calibration we predicted we needed a target density of 20 per linear km of river in riverine savannah to achieve >90% tsetse control. We then carried out a full scale, 500 km2 field trial covering two HAT foci in Northern Uganda to determine the efficacy of tiny targets (overall target density 5.7/km2). In 12 months, tsetse populations declined by more than 90%. As a guide we used a published HAT transmission model and calculated that a 72% reduction in tsetse population is required to stop transmission in those settings. Interpretation: The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within the country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this method of vector control to case detection and treatment is strong. We outline how such a component could be organised. Author Summary: Sleeping sickness is controlled by case detection and treatment but this often only reaches less than 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because of expense. We conducted a full scale field trial of a refined vector control technology. From preliminary trials we determined the number of insecticidal tiny targets required to control tsetse populations by more than 90%. We then carried out a full scale, 500 km2 field trial covering two HAT foci in Northern Uganda (overall target density 5.7/km2). In 12 months tsetse populations declined by more than 90%. A mathematical model suggested that a 72% reduction in tsetse population is required to stop transmission in those settings. The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this new method of vector control to case detection and treatment is strong. We outline how such a component could be organised. CITATION: Tirados, I., et al. 2015. Tsetse control and Gambian sleeping sickness; implications for control strategy. PLoS Neglected Tropical Diseases, 9(8):e0003822, doi:10.1371/journal.pntd.0003822.; The original publication is available at http://journals.plos.org/plosntds

Spatial heterogeneity in projected leprosy trends in India

2016-08-30T12:09:58Z

Spatial heterogeneity in projected leprosy trends in India Brook, Cara E.; Beauclair, Roxanne; Ngwenya, Olina; Worden, Lee; Ndeffo-Mbah, Martial; Lietman, Thomas M.; Satpathy, Sudhir K.; Galvani, Alison P.; Porco, Travis C. Background: Leprosy is caused by infection with Mycobacterium leprae and is characterized by peripheral nerve damage and skin lesions. The disease is classified into paucibacillary (PB) and multibacillary (MB) leprosy. The 2012 London Declaration formulated the following targets for leprosy control: (1) global interruption of transmission or elimination by 2020, and (2) reduction of grade-2 disabilities in newly detected cases to below 1 per million population at a global level by 2020. Leprosy is treatable, but diagnosis, access to treatment and treatment adherence (all necessary to curtail transmission) represent major challenges. Globally, new case detection rates for leprosy have remained fairly stable in the past decade, with India responsible for more than half of cases reported annually. Methods: We analyzed publicly available data from the Indian Ministry of Health and Family Welfare, and fit linear mixed-effects regression models to leprosy case detection trends reported at the district level. We assessed correlation of the new district-level case detection rate for leprosy with several state-level regressors: TB incidence, BCG coverage, fraction of cases exhibiting grade 2 disability at diagnosis, fraction of cases in children, and fraction multibacillary. Results: Our analyses suggest an endemic disease in very slow decline, with substantial spatial heterogeneity at both district and state levels. Enhanced active case finding was associated with a higher case detection rate. Conclusions: Trend analysis of reported new detection rates from India does not support a thesis of rapid progress in leprosy control. CITATION: Brook, C. E. et al. 2015. Spatial heterogeneity in projected leprosy trends in India. Parasites & Vectors, 8:542, doi:10.1186/s13071-015-1124-7.; The original publication is available at http://parasitesandvectors.biomedcentral.com

Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes

2016-09-14T12:43:40Z

Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes Duong, Yen T.; Kassanjee, Reshma; Welte, Alex; Morgan, Meade; De, Anindya; Dobbs, Trudy; Rottinghaus, Erin; Nkengasong, John; Kittinunvorakoon, Chonticha; Raengsakulrach, Boonyos; Martin, Michael; Choopanya, Kachit; Vanichseni, Suphak; Jiang, Yan; Qiu, Maofeng; Yu, Haiying; Hao, Yan; Shah, Neha; Le, Linh-Vi; Kim, Andrea A.; Nguyen, Tuan Anh; Ampofo, William; Parekh, Bharat S.; Curlin, Marcel E. Background: Mean duration of recent infection (MDRI) and misclassification of long-term HIV-1 infections, as proportion false recent (PFR), are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus. Methods: A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs. Results: Using different statistical methods, MDRI values ranged from 88–94 days at cutoff ODn = 1.0 to 177–183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing for misclassification among long-term infections indicated that overall PFRs were 0.6% to 2.5% at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0%) suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D) to 152 days (subtype C). Conclusions: Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118–142). Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use CITATION: Duong, Y. T., et al. 2015. Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes. PLoS ONE, 10(2):1-15, doi:10.1371/journal.pone.0114947.; The original publication is available at http://journals.plos.org/plosone

The risk of tuberculosis reinfection soon after cure of a first disease episode is extremely high in a hyperendemic community

2016-09-14T12:51:41Z

The risk of tuberculosis reinfection soon after cure of a first disease episode is extremely high in a hyperendemic community Uys, Pieter; Brand, Hilmarie; Warren, Robin; Van der Spuy, Gian; Hoal, Eileen G.; Van Helden, Paul D. Elevated rates of reinfection tuberculosis in various hyperendemic regions have been reported and, in particular, it has been shown that in a high-incidence setting near Cape Town, South Africa, the rate of reinfection tuberculosis (TB) disease after cure of a previous TB disease episode is about four times greater than the rate of first-time TB disease. It is not known whether this elevated rate is caused by a high reinfection rate due, for instance, to living circumstances, or a high rate of progress to disease specific to the patients, or both. In order to address that question we analysed an extensive data set from clinics attended by TB patients in the high-incidence setting near Cape Town, South Africa and found that, in fact, the (average) rate of reinfection (as opposed to the rate of reinfection disease) after cure of a previous TB disease episode is initially about 0.85 per annum. This rate diminishes rapidly over time and after about ten years this rate is similar to the rate of infection in the general population. Also, the rate of progress to disease after reinfection is initially high but declines in subsequent years down to the figure typical for the general population. These findings suggest that the first few months after cure of a TB disease episode form a critical period for controlling reinfection disease in a hyperendemic setting and that monitoring such cured patients could pre-empt a reinfection progressing to active disease. CITATION: Uys, P., et al. 2015. The risk of tuberculosis reinfection soon after cure of a first disease episode is extremely high in a hyperendemic community. PLoS ONE, 10(12):1-13, doi:10.1371/journal.pone.0144487.; The original publication is available at http://journals.plos.org/plosone

The association between timing of initiation of antenatal care and stillbirths : a retrospective cohort study of pregnant women in Cape Town, South Africa

2016-07-29T07:59:08Z

The association between timing of initiation of antenatal care and stillbirths : a retrospective cohort study of pregnant women in Cape Town, South Africa Beauclair, Roxanne; Petro, Greg; Myer, Landon Background There is renewed interest in stillbirth prevention for lower-middle income countries. Early initiation of and properly timed antenatal care (ANC) is thought to reduce the risk of many adverse birth outcomes. To this end we examined if timing of the first ANC visit influences the risk of stillbirth. Methods We conducted an analysis of a retrospective cohort of women (n = 34,671) with singleton births in a public perinatal service in Cape Town, South Africa. The main exposure was the gestational age at the first ANC visit. Bivariable analyses examining maternal characteristics by stillbirth status and gestational age at the first ANC visit, were conducted. Logistic regression, adjusting for maternal characteristics, was conducted to determine the risk of stillbirth. Results Of the 34,671 women who initiated ANC, 27,713 women (80%) were retained until delivery. The population stillbirth rate was 4.3 per 1000 births. The adjusted models indicated there was no effect of gestational age at first ANC visit on stillbirth outcomes when analyzed as a continuous variable (aOR 1.01; 95% CI: 0.99-1.04) or in trimesters (2nd Trimester aOR 0.78, 95% CI: 0.39-1.59; 3rd Trimester OR 1.03, 95% CI: 0.50-2.13, both with 1st Trimester as reference category). The findings were unchanged in sensitivity analyses of unobserved outcomes in non-retained women. Conclusion The timing of a woman’s first ANC visit may not be an important determinant of stillbirths in isolation. Further research is required to examine how quality of care, incorporating established, effective biomedical interventions, influences outcomes in this setting. CITATION: Beauclair, R., Petro, G. & Myer, L. 2014. The association between timing of initiation of antenatal care and stillbirths: a retrospective cohort study of pregnant women in Cape Town, South Africa. BMC Pregnancy and Childbirth, 14:204, doi:10.1186/1471-2393-14-204.; The original publication is available at http://bmcpregnancychildbirth.biomedcentral.com

Factors affecting the propensity of tsetse flies to enter houses and attack humans inside : increased risk of sleeping sickness in warmer climates

2016-04-05T07:12:30Z

Factors affecting the propensity of tsetse flies to enter houses and attack humans inside : increased risk of sleeping sickness in warmer climates Vale, Glyn A.; Hargrove, John W.; Chamisa, Andrew; Hall, David R.; Mangwiro, Clement; Torr, Stephen J. Background: Sleeping sickness, or human African trypanosomiasis, is caused by two species of Trypanosoma brucei that are transmitted to humans by tsetse flies (Glossina spp.) when these insects take a bloodmeal. It is commonly assumed that humans must enter the normal woodland habitat of the flies to become infected, but recent studies found that tsetse frequently attack humans inside buildings. Factors affecting human/tsetse contact in buildings need identification. Methodology/Principal Findings: In Zimbabwe, tsetse were allowed access to a house via an open door. Those in the house at sunset, and those alighting on humans in the house during the day, were caught using hand-nets. Total catches were unaffected by: (i) the presence of humans in the house and at the door, (ii) wood smoke from a fire inside the house or just outside, (iii) open windows, and (iv) chemicals simulating the odor of cattle or of humans. Catches increased about 10-fold with rising ambient temperatures, and during the hottest months the proportion of the total catch that was taken from the humans increased from 5% to 13%. Of the tsetse caught from humans, 62% consisted of female G. morsitans morstans and both sexes of G. pallidipes, i.e., the group of tsetse that normally alight little on humans. Some of the tsetse caught were old enough to be effective vectors. Conclusion/Significance: Present results confirm previous suggestions that buildings provide a distinctive and important venue for transmission of sleeping sickness, especially since the normal repellence of humans and smoke seems poorly effective in such places. The importance of the venue would be increased in warmer climates. CITATION: Vale, G.A. et al. 2013. Factors affecting the propensity of tsetse flies to enter houses and attack humans inside: increased risk of sleeping sickness in warmer climates. PLos Neglected Tropical Diseases, 7(4):e2193, doi:10.1371/journal.pntd.0002193.; The original publication is available at http://journals.plos.org/plosntds

Efficacy of electrocuting devices to catch tsetse flies (Glossinidae) and other diptera

2016-08-31T07:43:45Z

Efficacy of electrocuting devices to catch tsetse flies (Glossinidae) and other diptera Vale, Glyn A.; Hargrove, John W.; Cullis, N. Alan; Chamisa, Andrew; Torr, Stephen J. Background: The behaviour of insect vectors has an important bearing on the epidemiology of the diseases they transmit, and on the opportunities for vector control. Two sorts of electrocuting device have been particularly useful for studying the behaviour of tsetse flies (Glossina spp), the vectors of the trypanosomes that cause sleeping sickness in humans and nagana in livestock. Such devices consist of grids on netting (E-net) to catch tsetse in flight, or on cloth (E-cloth) to catch alighting flies. Catches are most meaningful when the devices catch as many as possible of the flies potentially available to them, and when the proportion caught is known. There have been conflicting indications for the catching efficiency, depending on whether the assessments were made by the naked eye or assisted by video recordings. Methodology/Principal Findings: Using grids of 0.5m2 in Zimbabwe, we developed catch methods of studying the efficiency of E-nets and E-cloth for tsetse, using improved transformers to supply the grids with electrical pulses of ~40kV. At energies per pulse of 35–215mJ, the efficiency was enhanced by reducing the pulse interval from 3200 to 1ms. Efficiency was low at 35mJ per pulse, but there seemed no benefit of increasing the energy beyond 70mJ. Catches at E-nets declined when the fine netting normally used became either coarser or much finer, and increased when the grid frame was moved from 2.5cm to 27.5cm from the grid. Data for muscoids and tabanids were roughly comparable to those for tsetse. Conclusion/Significance: The catch method of studying efficiency is useful for supplementing and extending video methods. Specifications are suggested for E-nets and E-cloth that are ~95% efficient and suitable for estimating the absolute numbers of available flies. Grids that are less efficient, but more economical, are recommended for studies of relative numbers available to various baits. CITATION: Vale, G.A., Hargrove, J.W., Cullis, N.A, Chamisa, A. & Torr, S.J. 2015. Efficacy of electrocuting devices to catch tsetse flies (Glossinidae) and other diptera. PLoS Neglected Tropical Diseases, 9(10):e0004169, doi:10.1371/ journal.pntd.0004169.; The original publication is available at http://journals.plos.org/plosntds

Pyrethroid treatment of cattle for tsetse control : reducing its impact on dung fauna

2016-04-19T09:44:35Z

Pyrethroid treatment of cattle for tsetse control : reducing its impact on dung fauna Vale, Glyn A.; Hargrove, John W.; Chamisa, Andrew; Grant, Ian F.; Torr, Stephen J. Background: African trypansomiases of humans and animals can be controlled by attacking the vectors, various species of tsetse fly. Treatment of cattle with pyrethroids to kill tsetse as they feed is the most cost-effective method. However, such treatments can contaminate cattle dung, thereby killing the fauna which disperse the dung and so play an important role in soil fertility. Hence there is a need to identify cost-effective methods of treating cattle with minimal impact on dung fauna. Methodology/Principal Findings: We used dung beetles to field bioassay the levels of dung contamination following the use of spray and pour-on formulations of deltamethrin, applied to various parts of the body of cattle in Zimbabwe. Results suggested that dung was contaminated by contact with insecticide on the body surface as the cattle defecated, and by ingestion of insecticide as the cattle licked themselves. Death of dung beetles was reduced to negligible levels by using only the spray and applying it to the legs and belly or legs alone, i.e., places where most tsetse feed. Conclusion/Significance: The restricted applications suitable for minimising the impact on dung fauna have the collateral benefits of improving the economy and convenience of cattle treatments for tsetse control. The demonstration of collateral benefits is one of the surest ways of promoting environmentally friendly procedures. CITATION: Vale, G.A., Hargrove, J.W., Chamisa, A., Grant, I.F. & Torr, S.J. 2015. Pyrethroid treatment of cattle for tsetse control: Reducing its impact on dung fauna. PLoS Neglected Tropical Diseases, 9(2):e0003560, doi:10.1371/ journal.pntd.0003560.; The original publication is available at http://journals.plos.org/plosntds

Artificial warthog burrows used to sample adult and immature tsetse (Glossina spp) in the Zambezi Valley of Zimbabwe

2016-04-04T06:28:27Z

Artificial warthog burrows used to sample adult and immature tsetse (Glossina spp) in the Zambezi Valley of Zimbabwe Hargrove, John W.; Muzari, M. Odwell Background: The biology of adult tsetse (Glossina spp), vectors of trypanosomiasis in Africa, has been extensively studied – but little is known about larviposition in the field. Methodology/Principal Findings: In September-November 1998, in the hot-dry season in Zimbabwe’s Zambezi Valley, we used artificial warthog burrows to capture adult females as they deposited larvae. Females were subjected to ovarian dissection and were defined as perinatal flies, assumed to have entered burrows to larviposit, if oocyte sizes indicated >95% pregnancy completion. Perinatal flies were defined as full-term pregnant if there was a late third instar larva in utero, or postpartum if the uterus was empty. All other females were defined as pre-full-term pregnant (pre-FT). Of 845 G. m. morsitans captured, 91% (765) were female and 295/724 (41%) of females dissected were perinatal flies. By contrast, of 2805 G. pallidipes captured only 71% (2003) were female and only 33% (596/1825) of females were perinatal. Among all perinatal females 67% (596/891) were G. pallidipes. Conversely, in burrows not fitted with traps – such that flies were free to come and go – 1834 (59%) of pupae deposited were G. m. morsitans and only 1297 (41%) were G. pallidipes. Thus, while more full-term pregnant G. pallidipes enter burrows, greater proportions of G. m. morsitans larviposit in them, reflecting a greater discrimination among G. pallidipes in choosing larviposition sites. Catches of males and pre-FT females increased strongly with temperatures above 32°C, indicating that these flies used burrows as refuges from high ambient temperatures. Conversely, catches of perinatal females changed little with maximum temperature but declined from late September through November: females may anticipate that burrows will be inundated during the forthcoming wet season. Ovarian age distributions of perinatal and pre-FT females were similar, consistent with all ages of females larvipositing in burrows with similar probability. Conclusions/Significance: Artificial warthog burrows provide a novel method for collecting tsetse pupae, studying tsetse behaviour at larviposition, assessing the physiological status of female tsetse and their larvae, and of improving understanding of the physiological dynamics of terminal pregnancy, and population dynamics generally, with a view to improving methods of trypanosomiasis control. CITATION: Hargrove, J.W. & Muzari, M.O. 2015. Artificial warthog burrows used to sample adult and immature tsetse (Glossina spp) in the Zambezi Valley of Zimbabwe. PLoS Neglected Tropical Diseases, 9(3):e0003565, doi:10.1371/journal.pntd.0003565.; The original publication is available at http://journals.plos.org/plosntds

Explaining the host-finding behavior of blood-sucking insects : computerized simulation of the effects of habitat geometry on tsetse fly movement

2016-04-04T06:44:22Z

Explaining the host-finding behavior of blood-sucking insects : computerized simulation of the effects of habitat geometry on tsetse fly movement Vale, Glyn A.; Hargrove, John W.; Solano, Philippe; Courtin, Fabrice; Rayaisse, Jean-Baptiste; Lehane, Michael J.; Esterhuizen, Johan; Tirados, Inaki; Torr, Stephen J. Background: Male and female tsetse flies feed exclusively on vertebrate blood. While doing so they can transmit the diseases of sleeping sickness in humans and nagana in domestic stock. Knowledge of the host-orientated behavior of tsetse is important in designing bait methods of sampling and controlling the flies, and in understanding the epidemiology of the diseases. For this we must explain several puzzling distinctions in the behavior of the different sexes and species of tsetse. For example, why is it that the species occupying savannahs, unlike those of riverine habitats, appear strongly responsive to odor, rely mainly on large hosts, are repelled by humans, and are often shy of alighting on baits? Methodology/Principal Findings: A deterministic model that simulated fly mobility and host-finding success suggested that the behavioral distinctions between riverine, savannah and forest tsetse are due largely to habitat size and shape, and the extent to which dense bushes limit occupiable space within the habitats. These factors seemed effective primarily because they affect the daily displacement of tsetse, reducing it by up to ,70%. Sex differences in behavior are explicable by females being larger and more mobile than males. Conclusion/Significance: Habitat geometry and fly size provide a framework that can unify much of the behavior of all sexes and species of tsetse everywhere. The general expectation is that relatively immobile insects in restricted habitats tend to be less responsive to host odors and more catholic in their diet. This has profound implications for the optimization of bait technology for tsetse, mosquitoes, black flies and tabanids, and for the epidemiology of the diseases they transmit. CITATION: Vale, G.A. et al. 2014. Explaining the host-finding behavior of blood-sucking insects: computerized simulation of the effects of habitat geometry on tsetse fly movement. PLoS Neglected Tropical Diseases, 8(6):e2901, doi:10.1371/journal.pntd.0002901.; The original publication is available at http://journals.plos.org/plosntds

Incidence of TB and HIV in prospectively followed household contacts of TB index patients in South Africa

2016-03-09T09:42:12Z

Incidence of TB and HIV in prospectively followed household contacts of TB index patients in South Africa Van Schalkwyk, Cari; Variava, Ebrahim; Shapiro, Adrienne E.; Rakgokong, Modiehi; Masonoke, Katlego; Lebina, Limakatso; Welte, Alex; Martinson, Neil Objective: To report the incidence rates of TB and HIV in household contacts of index patients diagnosed with TB. Design: A prospective cohort study in the Matlosana sub-district of North West Province, South Africa. Methods: Contacts of index TB patients received TB and HIV testing after counseling at their first household visit and were then followed up a year later, in 2010. TB or HIV diagnoses that occurred during the period were determined. Results: For 2,377 household contacts, the overall observed TB incidence rate was 1.3 per 100 person years (95% CI 0.9–1.9/100py) and TB incidence for individuals who were HIV-infected and HIV seronegative at baseline was 5.4/100py (95% CI 2.9–9.0/100py) and 0.7/100py (95% CI 0.3–1.4/100py), respectively. The overall HIV incidence rate was 2.2/100py (95% CI 1.3–8.4/100py). Conclusions: In the year following a household case finding visit when household contacts were tested for TB and HIV, the incidence rate of both active TB and HIV infection was found to be extremely high. Clearly, implementing proven strategies to prevent HIV acquisition and preventing TB transmission and progression to disease remains a priority in settings such as South Africa. CITATION: Van Schalkwyk, C. et al. 2014. Incidence of TB and HIV in prospectively followed household contacts of TB index patients in South Africa. PLoS ONE, 9(4):e95372, doi:10.1371/journal.pone.0095372.; The original publication is available at http://journals.plos.org/plosone

Effectiveness of a peer-led HIV prevention intervention in secondary schools in Rwanda : results from a non-randomized controlled trial

2015-09-25T09:52:00Z

Effectiveness of a peer-led HIV prevention intervention in secondary schools in Rwanda : results from a non-randomized controlled trial Michielsen, Kristien; Beauclair, Roxanne; Delva, Wim; Roelens, Kristien; Van Rossem, Ronan; Temmerman, Marleen While the HIV epidemic is levelling off in sub-Saharan Africa, it remains at an unacceptably high level. Young people aged 15-24 years remain particularly vulnerable, resulting in a regional HIV prevalence of 1.4% in young men and 3.3% in young women. This study assesses the effectiveness of a peer-led HIV prevention intervention in secondary schools in Rwanda on young people's sexual behavior, HIV knowledge and attitudes. SACEMA (SA Centre for Epidemiological Modelling & Analysis); CITATION: Michielsen et al. 2012. Effectiveness of a peer-led HIV prevention intervention in secondary schools in Rwanda: results from a non-randomized controlled trial. BMC Public Health, 12:729, doi:10.1186/1471-2458-12-729.; The original publication is available at http://www.biomedcentral.com/1471-2458/12/729

A theoretical model for substance abuse in the presence of treatment

2017-03-22T11:01:49Z

A theoretical model for substance abuse in the presence of treatment Kalula, Asha Saidi; Nyabadza, Farai The production and use of addictive stimulants has been a major problem in South Africa. Although research has shown increased demand for drug abuse treatment, the actual size of the drug-abusing population remains unknown. Thus the prevalence of drug abuse requires estimation through available tools. Many questions remain unanswered with regard to interventions, new cases of substance abuse and relapse in recovering persons. A six-state compartmental model including a core and non-core group, with fast and slow progression to addiction, was formulated with the aim of qualitatively investigating the dynamics of substance abuse and predicting drug abuse trends. The analysis of the model was presented in terms of the substance abuse epidemic threshold R0. Numerical simulations were performed to fit the model to available data for methamphetamine use in the Western Cape and to determine the role played by some key parameters. The model was also fitted to data on methamphetamine users who enter rehabilitation using the least squares curve fitting method. It was shown that the model exhibits a backward bifurcation where a stable drug-free equilibrium coexists with a stable drug-persistent equilibrium for a certain defined range of values of R0. The stabilities of the model equilibria were ascertained and persistence conditions established. It was found that it is not sufficient to reduce R0 below unit to control the substance abuse epidemic. The reproduction number should be brought below a determined threshold, R0c. The results also suggested that the substance abuse epidemic can be reduced by intervention programmes targeted at light drug users and by increasing the uptake rate into treatment for those addicted. Projected trends showed a steady decline in the prevalence of methamphetamine abuse until 2015. CITATION: Kalula, A. S. & Nyabadza, F. 2012. A theoretical model for substance abuse in the presence of treatment. South African Journal of Science, 108(3/4), Art. #654, doi:10.4102/sajs.v108i3/4.654.; The original publication is available at http://www.sajs.co.za