Risk Factors for Pre-Treatment Mortality among HIV-Infected Children in Rural Zambia: A Cohort Study

Many HIV-infected children in sub-Saharan Africa enter care at a late stage of disease. As preparation of the child and family for antiretroviral therapy (ART) can take several clinic visits, some children die prior to ART initiation. This study was undertaken to determine mortality rates and clinical predictors of mortality during the period prior to ART initiation.A prospective cohort study of HIV-infected treatment-naïve children was conducted between September 2007 and September 2010 at the HIV clinic at Macha Hospital in rural Southern Province, Zambia. HIV-infected children younger than 16 years of age who were treatment-naïve at study enrollment were eligible for analysis. Mortality rates prior to ART initiation were calculated and risk factors for mortality were evaluated.351 children were included in the study, of whom 210 (59.8%) were eligible for ART at study enrollment. Among children ineligible for ART at enrollment, 6 children died (mortality rate: 0.33; 95% CI:0.15, 0.74). Among children eligible at enrollment, 21 children died before initiation of ART and their mortality rate (2.73 per 100 person-years; 95% CI:1.78, 4.18) was significantly higher than among children ineligible for ART (incidence rate ratio: 8.20; 95% CI:3.20, 24.83). In both groups, mortality was highest in the first three months of follow-up. Factors associated with mortality included younger age, anemia and lower weight-for-age z-score at study enrollment.These results underscore the need to increase efforts to identify HIV-infected children at an earlier age and stage of disease progression so they can enroll in HIV care and treatment programs prior to becoming eligible for ART and these deaths can be prevented

Weight and height z-scores improve after initiating ART among HIV-infected children in rural Zambia: a cohort study

<p>Abstract</p> <p>Background</p> <p>Deficits in growth observed in HIV-infected children in resource-poor settings can be reversed with antiretroviral treatment (ART). However, many of the studies have been conducted in urban areas with older pediatric populations. This study was undertaken to evaluate growth patterns after ART initiation in a young pediatric population in rural Zambia with a high prevalence of undernutrition.</p> <p>Methods</p> <p>Between 2007 and 2009, 193 HIV-infected children were enrolled in a cohort study in Macha, Zambia. Children were evaluated every 3 months, at which time a questionnaire was administered, height and weight were measured, and blood specimens were collected. Weight- and height-for-age z-scores were constructed from WHO growth standards. All children receiving ART at enrollment or initiating ART during the study were included in this analysis. Linear mixed effects models were used to model trajectories of weight and height-for-age z-scores.</p> <p>Results</p> <p>A high proportion of study children were underweight (59%) and stunted (72%) at treatment initiation. Improvements in both weight- and height-for-age z-scores were observed, with weight-for-age z-scores increasing during the first 6 months of treatment and then stabilizing, and height-for-age z-scores increasing consistently over time. Trajectories of weight-for-age z-scores differed by underweight status at treatment initiation, with children who were underweight experiencing greater increases in z-scores in the first 6 months of treatment. Trajectories of height-for-age z-scores differed by age, with children older than 5 years of age experiencing smaller increases over time.</p> <p>Conclusions</p> <p>Some of the effects of HIV on growth were reversed with ART initiation, although a high proportion of children remained underweight and stunted after two years of treatment. Partnerships between treatment and nutrition programs should be explored so that HIV-infected children can receive optimal nutritional support.</p

Excellent outcomes among HIV+ children on ART, but unacceptably high pre-ART mortality and losses to follow-up: a cohort study from Cambodia

BACKGROUND: Although HIV program evaluations focusing on mortality on ART provide important evidence on treatment effectiveness, they do not asses overall HIV program performance because they exclude patients who are eligible but not started on ART for whatever reason. The objective of this study was to measure mortality that occurs both pre-ART and during ART among HIV-positive children enrolled in two HIV-programs in Cambodia. METHODS: Retrospective cohort study on 1168 HIV-positive children <15 years old registered in two HIV-programs over a four-year period. Mortality rates were calculated for both children on treatment and children not started on ART. RESULTS: Over half (53%) of children were 5 years or above and only 69(6%) were <18 months. Overall, 9% (105/1168) of children died since the set-up of the programs. By the end of the observation period, 66(14.5%) patients not on ART had died compared to 39(5.5%) of those under treatment, and 100(22%) who did not start ART were lost-to-follow-up compared to 13(2%) on ART. 66/105 (62.8%) of all in-program deaths occurred before starting ART, of which 56% (37/66) and 79% (52/66) occurred within 3 and 6 months of enrollment respectively. Mortality rate ratio between children not on ART and children on ART was 4.1 (95%CI: 2.7-6.2) (P < 0.001). The most common contributing cause of death in first 3 months of treatment and in first 3 months of program enrollment was tuberculosis. 41/52 (79%) children who died within 6 months of enrollment had met the ART eligibility criteria before death. CONCLUSION: HIV-positive children experienced a high mortality and loss-to-follow-up rates before starting ART. These program outcomes may be improved by a more timely ART initiation. Measuring overall in-program mortality as opposed to only mortality on ART is recommended in order to more accurately evaluate pediatric HIV-programs performance

On the Expressivity and Applicability of Model Representation Formalisms

A number of first-order calculi employ an explicit model representation formalism for automated reasoning and for detecting satisfiability. Many of these formalisms can represent infinite Herbrand models. The first-order fragment of monadic, shallow, linear, Horn (MSLH) clauses, is such a formalism used in the approximation refinement calculus. Our first result is a finite model property for MSLH clause sets. Therefore, MSLH clause sets cannot represent models of clause sets with inherently infinite models. Through a translation to tree automata, we further show that this limitation also applies to the linear fragments of implicit generalizations, which is the formalism used in the model-evolution calculus, to atoms with disequality constraints, the formalisms used in the non-redundant clause learning calculus (NRCL), and to atoms with membership constraints, a formalism used for example in decision procedures for algebraic data types. Although these formalisms cannot represent models of clause sets with inherently infinite models, through an additional approximation step they can. This is our second main result. For clause sets including the definition of an equivalence relation with the help of an additional, novel approximation, called reflexive relation splitting, the approximation refinement calculus can automatically show satisfiability through the MSLH clause set formalism.Comment: 15 page

Secular trends in pediatric antiretroviral treatment programs in rural and urban Zambia: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Since 2003 pediatric antiretroviral treatment (ART) programs have scaled-up in sub-Saharan Africa and should be evaluated to assess progress and identify areas for improvement. We evaluated secular trends in the characteristics and treatment outcomes of children in three pediatric ART clinics in urban and rural areas in Zambia.</p> <p>Methods</p> <p>Routinely collected data were analyzed from three ART programs in rural (Macha and Mukinge) and urban (Lusaka) Zambia between program implementation and July 2008. Data were obtained from electronic medical record systems and medical record abstraction, and were categorized by year of program implementation. Characteristics of all HIV-infected and exposed children enrolled in the programs and all children initiating treatment were compared by year of implementation.</p> <p>Results</p> <p>Age decreased and immunologic characteristics improved in all groups over time in both urban and rural clinics, with greater improvement observed in the rural clinics. Among children both eligible and ineligible for ART at clinic enrollment, the majority started treatment within a year. A high proportion of children, particularly those ineligible for ART at clinic enrollment, were lost to follow-up prior to initiating ART. Among children initiating ART, clinical and immunologic outcomes after six months of treatment improved in both urban and rural clinics. In the urban clinics, mortality after six months of treatment declined with program duration, and in the rural clinics, the proportion of children defaulting by six months increased with program duration.</p> <p>Conclusions</p> <p>Treatment programs are showing signs of progress in the care of HIV-infected children, particularly in the rural clinics where scale-up increased rapidly over the first three years of program implementation. However, continued efforts to optimize care are needed as many children continue to enroll in ART programs at a late stage of disease and thus are not receiving the full benefits of treatment.</p

Barriers to the care of HIV-infected children in rural Zambia: a cross-sectional analysis

<p>Abstract</p> <p>Background</p> <p>Successful antiretroviral treatment programs in rural sub-Saharan Africa may face different challenges than programs in urban areas. The objective of this study was to identify patient characteristics, barriers to care, and treatment responses of HIV-infected children seeking care in rural Zambia.</p> <p>Methods</p> <p>Cross-sectional analysis of HIV-infected children seeking care at Macha Hospital in rural southern Zambia. Information was collected from caretakers and medical records.</p> <p>Results</p> <p>192 HIV-infected children were enrolled from September 2007 through September 2008, 28% of whom were receiving antiretroviral therapy (ART) at enrollment. The median age was 3.3 years for children not receiving ART (IQR 1.8, 6.7) and 4.5 years for children receiving ART (IQR 2.7, 8.6). 91% travelled more than one hour to the clinic and 26% travelled more than 5 hours. Most participants (73%) reported difficulties accessing the clinic, including insufficient money (60%), lack of transportation (54%) and roads in poor condition (32%). The 54 children who were receiving ART at study enrollment had been on ART a median of 8.6 months (IQR: 2.7, 19.5). The median percentage of CD4⁺T cells was 12.4 (IQR: 9.2, 18.6) at the start of ART, and increased to 28.6 (IQR: 23.5, 36.1) at the initial study visit. However, the proportion of children who were underweight decreased only slightly, from 70% at initiation of ART to 61% at the initial study visit.</p> <p>Conclusion</p> <p>HIV-infected children in rural southern Zambia have long travel times to access care and may have poorer weight gain on ART than children in urban areas. Despite these barriers, these children had a substantial rise in CD4⁺T cell counts in the first year of ART although longer follow-up may indicate these gains are not sustained.</p

Magnetothermodynamics of BPS baby skyrmions

The magnetothermodynamics of skyrmion type matter described by the gauged BPS baby Skyrme model at zero temperature is investigated. We prove that the BPS property of the model is preserved also for boundary conditions corresponding to an asymptotically constant magnetic field. The BPS bound and the corresponding BPS equations saturating the bound are found. Further, we show that one may introduce pressure in the gauged model by a redefinition of the superpotential. Interestingly, this is related to non-extremal type solutions in the so-called fake supersymmetry method. Finally, we compute the equation of state of magnetized BSP baby skyrmions inserted into an external constant magnetic field $H$ and under external pressure $P$, i.e., $V=V(P,H)$, where $V$ is the "volume" (area) occupied by the skyrmions. We show that the BPS baby skyrmions form a ferromagnetic medium.Comment: Latex, 39 pages, 14 figures. v2: New results and references added, physical interpretation partly change

Growth, immune and viral responses in HIV infected African children receiving highly active antiretroviral therapy: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Scale up of paediatric antiretroviral therapy in resource limited settings continues despite limited access to routine laboratory monitoring. We documented the weight and height responses in HIV infected Ugandan children on highly active antiretroviral therapy and determined clinical factors associated with successful treatment outcomes.</p> <p>Methods</p> <p>A prospective cohort of HIV infected children were initiated on HAART and followed for 48 weeks. Body mass index for age z scores(BAZ), weight and height-for-age z scores (WAZ & HAZ) were calculated: CD4 cell % and HIV-1 RNA were measured at baseline and every 12 weeks. Treatment outcomes were classified according to; both virological and immunological success (VS/IS), virological failure and immunological success (VF/IS). virological success and immunological failure (VS/IF) and both virological and immunological failure (VF/IF).</p> <p>Results</p> <p>From March 2004 until May 2006, 124 HIV infected children were initiated on HAART. The median age (IQR) was 5.0 years (2.1 - 7.0) and 49% (61/124) were female. The median [95% confidence interval (CI)] BAZ, WAZ and HAZ at baseline were 0.29 (-2.9, -1.2), -1.2 (-2.1, -0.5) and -2.06 (-2.9, -1.2) respectively. Baseline median CD4 cell % and log10 HIV-1 RNA were; 11.8% (7.5-18.0) and 5.6 (5.2-5.8) copies/ml. By 48 weeks, mean WAZ and HAZ in the VF/IS group, which was younger, increased from - 0.98 (SD 1.7) to + 1.22 (SD 1.2) and from -1.99 (1.7) to + 0.76 (2.4) respectively. Mean increase in WAZ and HAZ in the VS/IF group, an older group was modest, from -1.84 (1.3) to - 0.41 (1.2) and -2.25 (1.2) to -1.16 (1.3) respectively. Baseline CD4 cell % [OR 6.97 95% CI (2.6 -18.6)], age [OR 4.6 95% CI (1.14 -19.1)] and WHO clinical stage [OR 3.5 95%CI (1.05 -12.7)] were associated with successful treatment outcome.</p> <p>Conclusions</p> <p>HIV infected Ugandan children demonstrated a robust increase in height and weight z scores during the first 48 weeks of HAART, including those who failed to completely suppress virus. Older children initiating HAART with severe immune suppression were less likely to achieve a successful treatment outcome. These data emphasize the importance of initiating HAART early to ensure adequate immune and growth responses.</p

Baryonic Popcorn

In the large N limit cold dense nuclear matter must be in a lattice phase. This applies also to holographic models of hadron physics. In a class of such models, like the generalized Sakai-Sugimoto model, baryons take the form of instantons of the effective flavor gauge theory that resides on probe flavor branes. In this paper we study the phase structure of baryonic crystals by analyzing discrete periodic configurations of such instantons. We find that instanton configurations exhibit a series of "popcorn" transitions upon increasing the density. Through these transitions normal (3D) lattices expand into the transverse dimension, eventually becoming a higher dimensional (4D) multi-layer lattice at large densities. We consider 3D lattices of zero size instantons as well as 1D periodic chains of finite size instantons, which serve as toy models of the full holographic systems. In particular, for the finite-size case we determine solutions of the corresponding ADHM equations for both a straight chain and for a 2D zigzag configuration where instantons pop up into the holographic dimension. At low density the system takes the form of an "abelian anti-ferromagnetic" straight periodic chain. Above a critical density there is a second order phase transition into a zigzag structure. An even higher density yields a rich phase space characterized by the formation of multi-layer zigzag structures. The finite size of the lattices in the transverse dimension is a signal of an emerging Fermi sea of quarks. We thus propose that the popcorn transitions indicate the onset of the "quarkyonic" phase of the cold dense nuclear matter.Comment: v3, 80 pages, 18 figures, footnotes 5 and 7 added, version to appear in the JHE

Reduced Risk of Malaria Parasitemia Following Household Screening and Treatment: A Cross-Sectional and Longitudinal Cohort Study

BACKGROUND: In regions of declining malaria transmission, new strategies for control are needed to reduce transmission and achieve elimination. Artemisinin-combination therapy (ACT) is active against immature gametocytes and can reduce the risk of transmission. We sought to determine whether household screening and treatment of infected individuals provides protection against infection for household members. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted in two areas in Southern Province, Zambia in 2007 and 2008/2009. To determine the impact of proactive case detection, households were randomly selected either to join a longitudinal cohort, in which participants were repeatedly screened throughout the year and those infected treated with artemether-lumefantrine, or a cross-sectional survey, in which participants were visited only once. Cross-sectional surveys were conducted throughout the year. The prevalence of RDT positivity was compared between the longitudinal and cross-sectional households at baseline and during follow-up using multilevel logistic regression. In the 2007 study area, 174 and 156 participants enrolled in the cross-sectional and longitudinal groups, respectively. In the 2008/2009 study area, 917 and 234 participants enrolled in the cross-sectional and longitudinal groups, respectively. In both study areas, participants and households in the longitudinal and cross-sectional groups were similar on demographic characteristics and prevalence of RDT positivity at baseline (2007: OR = 0.97; 95% CI:0.46, 2.03 | 2008/2009: OR = 1.28; 95% CI:0.44, 3.79). After baseline, the prevalence of RDT positivity was significantly lower in longitudinal compared to cross-sectional households in both study areas (2007: OR = 0.44; 95% CI:0.20, 0.96 | 2008/2009: OR = 0.16; 95% CI:0.05, 0.55). CONCLUSIONS/SIGNIFICANCE: Proactive case detection, consisting of screening household members with an RDT and treating those positive with ACT, can reduce transmission and provide indirect protection to household members. A targeted test and treat strategy could contribute to the elimination of malaria in regions of low transmission