Cotrimoxazole Prophylaxis and Risk of Severe Anemia or Severe Neutropenia in HAART-Exposed, HIV-Uninfected Infants

Background: Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia. Methods: We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana. Results: A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure–risk difference, −0.69% (95% confidence interval [CI] −2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI −1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93). Conclusions: Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1–6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. ClinicalTrials.gov Registration Numbers NCT01086878 (http://clinicaltrials.gov/show/NCT01086878), NCT00197587 (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296 (http://clinicaltrials.gov/show/NCT00270296)

Closed-form equation for subsidence due to fluid production from a cylindrical confined aquifer

Ground surface subsidence due to groundwater production is a significant problem. Many attempts have been made to develop analytical models to forecast subsidence rates as a consequence of groundwater production. Previous analytical solutions either make limiting assumptions about the stress regime (e.g., radially symmetric with uniaxial strain or radially symmetric with zero incremental vertical total stress) or assume that the pressure distribution within the aquifer is uniform. Imposing assumptions about the stress regime lead to an overestimate of subsidence. Imposing a uniform pressure assumption often leads to an underestimate of subsidence. In this article, the principle of superposition is applied to extend a previous analytical solution, for a cylindrical uniform pressure change, to allow for a non-uniform pressure distribution resulting from constant rate production of a viscous fluid from a cylindrical confined aquifer of finite permeability. Results from the analytical solution are verified by comparison with a set of fully coupled hydro-mechanical finite element simulations. The analytical solution for subsidence directly above the production well (or uplift above an injection well) can be written in closed-form and is straightforward to evaluate. The equation also shows that, for many practical purposes, ground surface subsidence is insensitive to production fluid viscosity and aquifer permeability when the aquifer radius is less than the aquifer depth below the ground surface

Severe infant anemia and severe neutropenia by prophylactic cotrimoxazole exposure.

<p>Analysis restricted to severe anemia or neutropenia (grade 3 or 4) detected at scheduled measurements at 3 and/or 6 months of age in HIV-exposed uninfected infants in the CTX, Mashi, and Mma Bana cohorts.</p><p>Note: 95% CI, 95% confidence interval.</p>a<p>Mantel-Haenszel methodology.</p>b<p>Exact Cochran-Mantel-Haenszel.</p

Factors associated with severe anemia and severe neutropenia among HIV-exposed, uninfected infants.

<p>Prophylactic cotrimoxazole, maternal antenatal HAART use, and infant feeding method are included in the multivariable model, as are other significant factors from the univariate analysis.</p><p>OR, odds ratio; aOR, adjusted odds ratio; CI, confidence interval; HAART, highly-active antiretroviral therapy.</p>a<p>Wald chi-square.</p>b<p>To avoid confounding effect of infant feeding method, univariate estimate for effect of cotrimoxazole is restricted to formula-fed infants. Multivariable analysis includes both formula-fed and breastfed infants.</p>c<p>A modest but significant interaction was noted between feeding method and maternal HAART with increased risk of severe neutropenia associated with breastfeeding from a mother receiving HAART. However, in multivariable analysis this interaction was no longer significant.</p

Schematic of infant exposures in study cohorts.

<p>ZDV, zidovudine; supp., supplementation; CTX, cotrimoxazole; HAART, highly-active antiretroviral therapy; mo., month. ^aHAART became available through a national program in October 2002, subsequently women in Mashi trial with CD4≤200 cells/ µL were offered HAART.^bInfants in the Mma Bana trial received 1 month of ZDV and breastfed infants in the Mashi trial received 6 months of ZDV.^cNineteen mothers (9.1%) in CTX cohort received non-ZDV-containing HAART.</p

Harmonization service and global library of models to support country-driven global information on salt-affected soils

Abstract Global distribution of salt-affected soils (SAS) has remained at about 1 billion hectares in the literature over the years despite changes in climate, sea levels, and land use patterns which influence the distribution. Lack of periodic update of input soil data, data gaps, and inconsistency are part of the reasons for constant SAS distribution in the literature. This paper proposes harmonization as a suitable alternative for managing inconsistent data and minimizing data gaps. It developed a new harmonization service for supporting country-driven global SAS information update. The service contains a global library of harmonization models for harmonizing inconsistent soil data. It also contains models for identifying gaps in SAS database and for showing global distribution where harmonization of available data is needed. The service can be used by countries to develop national SAS information and update global SAS distribution. Its data availability index is useful in identifying countries without SAS data in the global database, which is a convenient way to identify countries to mobilize when updating global SAS information. Its application in 27 countries showed that the countries have more SAS data than they currently share with the global databases and that most of their data require SAS harmonization

Cohort characteristics of HIV-exposed uninfected infants alive through 30 days of age.

<p>Note: CTX, cotrimoxazole; IQR, interquartile range.</p

Enrollment and follow-up of study infants.

<p>HIV-uninfected infants in the Mashi and Mma Bana trials did not receive cotrimoxazole prophylaxis and serve as a comparison group to the new cohort (CTX) that received cotrimoxazole prophylaxis. CTX, cotrimoxazole; 1 mo., one month; FF, formula-fed; BF, breastfed.</p