WHO 2010 guidelines for prevention of mother-to-child HIV transmission in Zimbabwe: modeling clinical outcomes in infants and mothers

Background

The Zimbabwean national prevention of mother-to-child HIV transmission (PMTCT) program provided primarily single-dose nevirapine (sdNVP) from 2002–2009 and is currently replacing sdNVP with more effective antiretroviral (ARV) regimens.

Methods

Published HIV and PMTCT models, with local trial and programmatic data, were used to simulate a cohort of HIV-infected, pregnant/breastfeeding women in Zimbabwe (mean age 24.0 years, mean CD4 451 cells/µL). We compared five PMTCT regimens at a fixed level of PMTCT medication uptake: 1) no antenatal ARVs (comparator); 2) sdNVP; 3) WHO 2010 guidelines using “Option A” (zidovudine during pregnancy/infant NVP during breastfeeding for women without advanced HIV disease; lifelong 3-drug antiretroviral therapy (ART) for women with advanced disease); 4) WHO “Option B” (ART during pregnancy/breastfeeding without advanced disease; lifelong ART with advanced disease); and 5) “Option B+:” lifelong ART for all pregnant/breastfeeding, HIV-infected women. Pediatric (4–6 week and 18-month infection risk, 2-year survival) and maternal (2- and 5-year survival, life expectancy from delivery) outcomes were projected.

Results

Eighteen-month pediatric infection risks ranged from 25.8% (no antenatal ARVs) to 10.9% (Options B/B+). Although maternal short-term outcomes (2- and 5-year survival) varied only slightly by regimen, maternal life expectancy was reduced after receipt of sdNVP (13.8 years) or Option B (13.9 years) compared to no antenatal ARVs (14.0 years), Option A (14.0 years), or Option B+ (14.5 years).

Conclusions

Replacement of sdNVP with currently recommended regimens for PMTCT (WHO Options A, B, or B+) is necessary to reduce infant HIV infection risk in Zimbabwe. The planned transition to Option A may also improve both pediatric and maternal outcomes.     

Multi-disciplinary evidence of the Holocene history of a cultivated floodplain area in the wetlands of northern Colombia

An environmental reconstruction of the last 10,000 ¹⁴C years of a frequently flooded wetland ecosystem in the lower Magdalena valley in northern Colombia is presented, on the basis of a multi-disciplinary study of the sediments of the upper 15 m of the core from Boquillas (74°33'E, 9°7'N; 20 m a. s. l.). We used the following studies: pollen, lithology, organic structures, clay mineralogy, soil and sediment geochemistry, and δ¹³C values. The chronology is based on 13 AMS radiocarbon dates; the humic acid fractions were used in the case of seven samples. Pollen from local origin (swamps, open grass-rich vegetation, and gallery forest) show the development of the wetland area. River-transported pollen from a greater distance (dry forest, montane forest, Alnus) show changes in river activity and reflect large-scale changes of climatic conditions in the Momposina basin. From c. 10,010 to 9370 uncal B. P. (zone BQS-Ia) the river system was of high energy, as inferred by the lithological changes. The landscape was dominated by open grass-rich vegetation with gallery forest along the streams. A marked representation of Alnus and montane forest taxa indicate significant water transport and river dynamics. Climatic conditions were dry. From c. 9370-8430 uncal B. P. (zone BQS-Ib) wetlands were isolated from the main river system, and clayey sediments with kaolinite, smectite and illite as the main minerals accumulated in a lower-energy environment. Climatic conditions were dry and changes in the seasonal precipitation favoured the expansion of the gallery forest. From c. 8430 to 8040 uncal B. P. (zone BQS-Ic) low values of river-transported pollen indicate dry climatic conditions and open vegetation became more abundant. The flooding frequency of the Boquillas site diminished. From 8040 to 4900 uncal B. P. (zone BQS-Id) the Boquillas site was dominated by open vegetation with patches of gallery forest along the streams. Supply of river-transported allochthonous pollen (from many sources) was minimal. Clay minerals from the sediments suggest variable temperature and precipitation. From c. 4900 to 1550 uncal B. P. )zone BQS-II) the site was within the reach of the main river system as is the case today. Frequent flooding, coinciding with peaks of river-transported grains of Alnus and high sediment supply, point to high precipitation in the composite catchment area of the Magdalena, Cauca, San Jorge, and Cesár rivers. High values of phosphorous in the upper part of the core point to the presence of a pre-Hispanic civilization, approximately from 2000 uncal B. P. onward. Construction of an extensive drainage system allowed irrigation as well as drainage depending the annual cycle of precipitation. The landscape was significantly modified and allowed an extensive crop production on a system of raised fields. Received May 18, 2001 / Accepted June 15, 2001     

Partial hypoxanthine-guanine phosphoribosyl transferase deficiency with full expression of the Lesch-Nyhan syndrome

Summary A patient with the full clinical expression of the classical Lesch-Nyhan syndrome is presented with a residual hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity of 5–10% in erythrocyte lysate and about 30% in fibroblast lysate. The activities of other erythrocyte enzymes of purine metabolism were typical for a classical Lesch-Nyhan patient. The effects of allopurinol therapy on the excretion of urinary purine metabolites were studied by a newly developed isotachophoretic technique.The unusually high residual activity of HGPRT in erythrodytes and fibroblasts of the patient enabled the enzymologic characterization of the mutant enzyme: in fibroblasts the affinities for the substrates hypoxanthine and guanine were normal. However, there was an increased apparent K _m for phosphoribosylpyrophosphate (PRPP), a complete absence of product inhibition by IMP and GMP, and a decreased heat stability. Addition of PRPP did not stabilize the mutant enzyme. In addition to the altered properties of the fibroblast enzyme, the K _m of the erythrocyte enzyme for hypoxanthine was also increased.Immunoprecipitation experiments revealed the presence of an approximately normal amount of material cross-reacting with anti-human HGPRT antiserum. However, it appeared that this cross-reacting material had a decreased stability. When intact erythrocytes were incubated with radiolabeled purine bases, no formation of IMP or GMP could be detected, despite the relatively high residual activity of HGPRT in the hemolysate. The results fit the following hypothesis: as a consequence of a structural mutation affecting the PRPP-site of the enzyme and a decreased heat stability, the activity of the mutant enzyme under in vivo conditions is virtually zero.In the erythrocytes of the patient's mother a normal HGPRT-activity was found. However, the activity in her fibroblasts was lower than normal, while a decreased heat stability and an intermediate behavior towards IMP could be shown.Hair root analysis of several members of the patient's family confirmed the heterozygosity of the mother, whereas no other heterozygotes could be detected. The family anamnesis did not show other cases of Lesch-Nyhan syndrome. These findings were taken as evidence that the patient described in this paper might represent a mutation orginating from the gametes in either of the maternal grandparents.     

Quenching autofluorescence in the alimentary canal tissues of Bactericera cockerelli (Hemiptera: Triozidae) for immunofluorescence labeling

Immunofluorescence has been widely used to localize microbes or specific molecules in insect tissues or cells. However, significant autofluorescence is frequently observed in tissues which can interfere with the fluorescent identification of target antigens, leading to inaccurate or even false positive fluorescent labeling. The alimentary canal of the potato psyllid, Bactericera cockerelli ?ulc, exhibits intense autofluorescence, hindering the application of immunolocalization for the detection and localization of the economically important pathogen transmitted by this insect, “Candidatus Liberibacter solanacearum” (Lso). In the present study, we tested the use of irradiation, hydrogen peroxide (H₂O₂) and Sudan black B (SBB) treatments to reduce the autofluorescence in the B. cockerelli alimentary canal tissues. Furthermore, we assessed the compatibility of the above‐mentioned treatments with Lso immunolocalization and actin staining using phalloidin. Our results showed that the autofluorescence in the alimentary canal was reduced by irradiation, H₂O₂, or SBB treatments. The compatibility assays indicated that irradiation and H₂O₂ treatment both greatly reduced the fluorescent signal associated with Lso and actin. However, the SBB incubation preserved those target signals, while efficiently eliminating autofluorescence in the psyllid alimentary canal. Therefore, herein we propose a robust method for reducing the autofluorescence in the B. cockerelli alimentary canal with SBB treatment, which may improve the use of immunofluorescence labeling in this organism. This method may also have a wide range of uses by reducing the autofluorescence in other arthropod species.     

Genotypic proportions in hybrid zones

We study a hybrid zone between two populations of a diploid organism. The populations differ at one locus. Homozygotes have equal fitnesses and the heterozygote fitness is reduced by + ( is the birth rate deviation and is the death rate deviation). The populations extend along a one dimensional continuous habitat, and migration occurs by diffusion of individuals. The model is formulated as a set of simple continuous time demographic models without age structure for the three genotypes, and the system is transformed into three new variables, the total population size N, the gene frequency p, and the deviation from Hardy-Weinberg proportions F. The gene frequency in a steady state cline always follows a hyperbolic tangent closely. Analysis of the asymptotic behavior of the cline far from the hybrid zone suggests a qualitative prediction of the shape of N, p and F over the zone. For weak selection the shape is determined by a central steepness of , as observed by Bazykin in 1969, where D is the diffusion coefficient. For strong selection the cline is less steep than the Bazykin cline, and the form is dominated by the migration process. The steepness at the center of the cline is close to where b is the birth rate of homozygotes.Supported in part by grant 11-9639-1 from the Danish Natural Science Research Council and grant 5.18.2023 from the Danish Biotechnological Research and Development Programme     

Incubation of innovative methanogenic communities to seed anaerobic digesters

Applied Microbiology and Biotechnology - The methanogenic communities in alternative inocula and their potential to increase CH4 production in mesophilic and psychrophilic dairy manure-based...     

A two-locus mutation—Selection model and some of its evolutionary implications

The deterministic properties of a two-locus model with mutation and selection have been investigated. The mutation process is unidirectional, and the model is so constructed that the genetic variation at one locus is selectively neutral in the absence of a mutant allele at the other locus. All genotypes with three or four mutant alleles are deleterious, while the double heterozygotes may have the same fitness as the standard genotype. If one of the mutant alleles becomes fixed in the population, then the other locus will show a regular one-locus mutation-selection balance. Such a boundary equilibrium may be unstable or stable in the full two-locus setting. In the symmetric case, which is analyzed in details, the population will either go to one of the two boundary equilibria, or to a fully polymorphic equilibrium at which both the mutant alleles are rare. The origin of reproductive separation between two populations via the fixation of complementary deleterious mutants at different loci, and the fixation of nonfunctional alleles at duplicated loci, are two biological processes which both can be studied with the present model. In the last part of the paper we show how the results from the deterministic analysis can be used to predict how different factors will influence the rates of evolution in these systems.     

Geographical Patterns of Four Polymorphisms in ZOARCES VIVIPARUS as Evidence of Selection

Two unlinked polymorphisms of a marine teleost, one in hemoglobin and one in esterase, show parallel clines through Danish waters, while two unlinked phosphoglucosemutase polymorphisms maintain constant gene frequencies. It is argued that the clinal and the constant polymorphisms cannot be accounted for simultaneously by random genetic drift of selectively neutral genes. It is therefore concluded that selection is responsible for at least one of the two classes of geographical patterns, be it the clinal, the constant, or both.     

Molluscicidal activity of the Puerto Rican Weed,Solatium nodiflorum,against snail hosts ofFasciola hepatica

After screening 200 species of Puerto Rican plants, Solanum nodiflorumwas selected for comprehensive laboratory evaluation as a source of natural molluscicide. All parts of this plant were found toxic to the snails Fossaria (Lymnaea) cubensis, Lymnaea columella, Biomphalaria glabrata,and Physa cubensis.No toxicity was found against Marisa cornuarietisand Tarebia granifera. The toxicant was not affected by pH and dry storage. There was a direct correlation between temperature and molluscicidal activity. The plant is easy to find locally and could be developed into cheap, safe means for controlling both Schistosomaand Fasciolasnail hosts in Puerto Rico.