Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial

Background

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs).

Methods and Findings

A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27–0.82]; p = 0.008), placental malaria (RR, 0.52 [95% CI 0.29–0.90]; p = 0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37–0.95]; p = 0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p = 0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14–3.33]; p = 0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis.

Conclusions

An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT 00811421","term_id":"NCT00811421"}}NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors'' Summary     

The role of farm structure on bird assemblages around a Kenyan tropical rainforest

Although it is clear that the farmlands neighbouring fragmented forests are utilized by some forest birds, it is not clear how birds in general respond to farmland habitat mosaic. An effort was made to determine how bird density and foraging assemblages were influenced by farm structural characteristics and distance from forest edge. Thirty farms up to a distance of 12 km around Kakamega forest in western Kenya were studied. Farm structure entailed size, hedge volume, habitat heterogeneity, woody plant density, plant diversity and crop cover. Birds were surveyed using line transects and DISTANCE analyses and classified into six feeding guilds and three habitat associations. Size of farms increased away from the forest, as woody plant density, plant diversity, indigenous trees and subsistence crop cover declined. The most important farm structure variable was hedge volume, which enhanced bird species richness, richness of shrub‐land bird species and insectivorous bird density (R = 0.58, P < 0.01). Bird density increased with tree density while indigenous trees were suitable for insectivores and nectarivores. There were very few forest bird encounters. Agricultural practices incorporating maintenance of hedges and sound selection of agroforestry trees can enhance conservation of birds on farmland, though, not significantly for forest species.     

Prevalence of enlarged salivary glands in wild populations of Glossina pallidipes in Kenya,with a note on the ultrastructure of the affected organ

Enlarged salivary gland was found to be widespread among wild populations of Glossina pallidipes in Kenya. The incidence of this abnormality varied from 0.9% in Meru National Park in Central Kenya to 5.4% in the Shimba hills area on the Kenya coast. Ultrastructurally, the enlarged glands were multinucleated with lumen reduced substantially in size. A large number of viruses filled both the lumen and the broken pieces of epithelial cytoplasm. In some cases Trypanosoma brucei trypanosomes were seen in the lumen of the enlarged glands. The epithelial cytoplasm was heavily vacuolated. Comment is made on the suitability of the diseased flies as transmitters of T. brucei.     

The combined effect of soil‐applied azadirachtin with entomopathogens for integrated management of western flower thrips

Performance of soil application of azadirachtin products with entomopathogens was evaluated as single treatments, in multiple combinations and in different concentrations against the soil stages of western flower thrips, Frankliniella occidentalis (Pergande), in French beans Phaseolus vulgaris L. Treatments consisted of NeemAzal‐T solution, neem pellets, Steinernema carpocapsae (Weiser) Nemastar^®, isolates of Metarhizium anisopliae (Metschnikoff) Sorokin (IPP 2539 and ICIPE‐69) and Beauveria bassiana (Balsamo) – Naturalis^®. All treatments were analysed for the number of emerging adults, while emerged adults in fungi‐based treatments were analysed additionally for the retarded development of mycosis as a possible cause of secondary mortality. Possible interactive effects in combined treatments were analysed using a generalized linear model (GLM) approach, and three levels of dose–response combinations of the selected treatments were further tested. Bioassay results of the single treatments indicated between 43% and 60% reduction in adult emergence with NeemAzal‐T solution thus proving to be the most efficient. However, most cadavers with entomopathogenic fungi (EPF) treatments showed the development of mycosis. Therefore, the reduction in adult emergence attributed to the EPF was altogether >87%. Combined treatments with Steinernema, Metarhizium (ICIPE‐69), NeemAzal‐T and neem pellets resulted in total reduction in adult emergence of 95–97% when late mortality by mycosis was considered. Of the treatment combinations, two showed synergistic, four additive and one an antagonistic response. Combining low concentration of entomopathogenic nematode (EPN) (100 IJ/cm²) with NeemAzal‐T resulted in satisfactory control compared to the operational dose of EPN, while the highest concentration of M. anisopliae (10⁸ conidia) combined with Steinernema showed the best performance with 74% reduction in adult emergence.     

Molecular Epidemiology and Transmission Dynamics of Recent and Long-Term HIV-1 Infections in Rural Western Kenya

Objective

To identify unique characteristics of recent versus established HIV infections and describe sexual transmission networks, we characterized circulating HIV-1 strains from two randomly selected populations of ART-naïve participants in rural western Kenya.

Methods

Recent HIV infections were identified by the HIV-1 subtype B, E and D, immunoglobulin G capture immunoassay (IgG BED-CEIA) and BioRad avidity assays. Genotypic and phylogenetic analyses were performed on the pol gene to identify transmitted drug resistance (TDR) mutations, characterize HIV subtypes and potential transmission clusters. Factors associated with recent infection and clustering were assessed by logistic regression.

Results

Of the 320 specimens, 40 (12.5%) were concordantly identified by the two assays as recent infections. Factors independently associated with being recently infected were age ≤19 years (P = 0.001) and history of sexually transmitted infections (STIs) in the past six months (P = 0.004). HIV subtype distribution differed in recently versus chronically infected participants, with subtype A observed among 53% recent vs. 68% chronic infections (p = 0.04) and subtype D among 26% recent vs. 12% chronic infections (p = 0.012). Overall, the prevalence of primary drug resistance was 1.16%. Of the 258 sequences, 11.2% were in monophyletic clusters of between 2–4 individuals. In multivariate analysis factors associated with clustering included having recent HIV infection P = 0.043 and being from Gem region P = 0.002.

Conclusions

Recent HIV-1 infection was more frequent among 13–19 year olds compared with older age groups, underscoring the ongoing risk and susceptibility of younger persons for acquiring HIV infection. Our findings also provide evidence of sexual networks. The association of recent infections with clustering suggests that early infections may be contributing significant proportions of onward transmission highlighting the need for early diagnosis and treatment as prevention for ongoing prevention. Larger studies are needed to better understand the structure of these networks and subsequently implement and evaluate targeted interventions.     

Patterns of CO<Subscript>2</Subscript> exchange and productivity of the herbaceous vegetation and trees in a humid savanna in western Kenya

Factors governing the dynamics between woody and herbaceous vegetation in the savanna are of ecological interest since they determine ecosystem productivity and stability. Field measurements were conducted in a humid savanna in the Lambwe valley, western Kenya, to compare CO2 exchange of the herbaceous vegetation and trees and its regulation. Soil characteristics and root distribution patterns under tree canopies and in the open locations dominated by the herbaceous vegetation were profiled in 1-m-deep soil layers. Soil water content (SWC) was measured at 30 cm depth both in the herbaceous vegetation and also under the tree canopies. The mean maximum monthly gross primary production (GPPmax) in the herbaceous vegetation was determined from chamber measurements, while daily GPP (GPPday) in both the grass and tree canopies was simulated using the PIXGRO model. The highest mean GPPmax in the herbaceous vegetation was 26.2 ± 3.7 μmol m-2 s-1 during April. Seasonal fluctuations of GPP in the herbaceous vegetation were explained by soil water availability (R ² = 0.78) within the upper 30-cm soil profile. Seasonal GPPday fluctuations were larger (between 1 gC m-2 d-1 and 10 gC m-2 d-1) in the herbaceous vegetation compared to the trees, which fluctuated around 4.3 ± 0.3 gC m-2 d-1 throughout most of the measurement period. Daily tree canopy transpiration (Ec), canopy conductance (Gc), and GPPday were decoupled from SWC in the top 30-cm soil profile. On average, ecosystem GPPday (mean of tree and herbaceous vegetation) was 14.3 ± 1.2 gC m-2 d-1 during the wet period and 6.1 ± 0.9 gC m-2 d-1 during drought. Differences between the herbaceous and tree canopy responses were attributed to soil moisture availability.     

The Role of Obesity‐associated Loci Identified in Genome‐wide Association Studies in the Determination of Pediatric BMI

The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Besides environmental factors, genetic factors are known to play an important role in the pathogenesis of obesity. A number of genetic determinants of adult BMI have already been established through genome‐wide association (GWA) studies. In this study, we examined 25 single‐nucleotide polymorphisms (SNPs) corresponding to 13 previously reported genomic loci in 6,078 children with measures of BMI. Fifteen of these SNPs yielded at least nominally significant association to BMI, representing nine different loci including INSIG2, FTO, MC4R, TMEM18, GNPDA2, NEGR1, BDNF, KCTD15, and 1q25. Other loci revealed no evidence for association, namely at MTCH2, SH2B1, 12q13, and 3q27. For the 15 associated variants, the genotype score explained 1.12% of the total variation for BMI z‐score. We conclude that among 13 loci that have been reported to associate with adult BMI, at least nine also contribute to the determination of BMI in childhood as demonstrated by their associations in our pediatric cohort.     

Ethnomedicine of the Kagera Region, north western Tanzania. Part 2: The medicinal plants used in Katoro Ward, Bukoba District

Background

The Kagera region of north western Tanzania has a rich culture of traditional medicine use and practices. The dynamic inter-ethnic interactions of different people from the surrounding countries constitute a rich reservoir of herbal based healing practices. This study, the second on an ongoing series, reports on the medicinal plant species used in Katoro ward, Bukoba District, and tries to use the literature to establish proof of the therapeutic claims.

Methodology

Ethnomedical information was collected using Semi-structured interviews in Kyamlaile and Kashaba villages of Katoro, and in roadside bushes on the way from Katoro to Bukoba through Kyaka. Data collected included the common/local names of the plants, parts used, the diseases treated, methods of preparation, dosage, frequency and duration of treatments. Information on toxicity and antidote were also collected. Literature was consulted to get corroborative information on similar ethnomedical claims and proven biological activities of the plants.

Results

Thirty three (33) plant species for treatement of 13 different disease categories were documented. The most frequently treated diseases were those categorized as specific diseases/conditions (23.8% of all remedies) while eye diseases were the least treated using medicinal plants (1.5% of all remedies). Literature reports support 47% of the claims including proven anti-malarial, anti-microbial and anti-inflammatory activity or similar ethnomedical uses. Leaves were the most frequently used plant part (20 species) followed by roots (13 species) while making of decoctions, pounding, squeezing, making infusions, burning and grinding to powder were the most common methods used to prepare a majority of the therapies.

Conclusion

Therapeutic claims made on plants used in traditional medicine in Katoro ward of Bukoba district are well supported by literature, with 47% of the claims having already been reported. This study further enhances the validity of plants used in traditional medicine in this region as resources that can be relied on to provide effective, accessible and affordable basic healthcare to the local communities. The plants documented also have the potential of being used in drug development and on farm domestication initiatives.     

Risk mapping of Rinderpest sero-prevalence in Central and Southern Somalia based on spatial and network risk factors

Background  

In contrast to most pastoral systems, the Somali livestock production system is oriented towards domestic trade and export with seasonal movement patterns of herds/flocks in search of water and pasture and towards export points. Data from a rinderpest survey and other data sources have been integrated to explore the topology of a contact network of cattle herds based on a spatial proximity criterion and other attributes related to cattle herd dynamics. The objective of the study is to integrate spatial mobility and other attributes with GIS and network approaches in order to develop a predictive spatial model of presence of rinderpest.