An Augmented SMS Intervention to Improve Access to Antenatal CD4 Testing and ART Initiation in HIV-Infected Pregnant Women: A Cluster Randomized Trial

BackgroundLess than one-third of HIV-infected pregnant women eligible for combination antiretroviral therapy (ART) globally initiate treatment prior to delivery, with lack of access to timely CD₄ results being a principal barrier. We evaluated the effectiveness of an SMS-based intervention to improve access to timely antenatal ART.MethodsWe conducted a stepped-wedge cluster randomized trial of a low-cost programmatic intervention in 20 antenatal clinics in Gaborone, Botswana. From July 2011-April 2012, 2 clinics were randomly selected every 4 weeks to receive an ongoing clinic-based educational intervention to improve CD₄ collection and to receive CD₄ results via an automated SMS platform with active patient tracing. CD₄ testing before 26 weeks gestation and ART initiation before 30 weeks gestation were assessed.ResultsThree-hundred-sixty-six ART-naïve women were included, 189 registering for antenatal care under Intervention and 177 under Usual Care periods. Of CD₄-eligible women, 100 (59.2%) women under Intervention and 79 (50.6%) women under Usual Care completed CD₄ phlebotomy before 26 weeks gestation, adjusted odds ratio (aOR, adjusted for time that a clinic initiated Intervention) 0.87 (95% confidence interval [CI]0.47–1.63, P = 0.67). The SMS-based platform reduced time to clinic receipt of CD₄ test result from median of 16 to 6 days (P<0.001), was appreciated by clinic staff, and was associated with reduced operational cost. However, rates of ART initiation remained low, with 56 (36.4%) women registering under Intervention versus 37 (24.2%) women under Usual Care initiating ART prior to 30 weeks gestation, aOR 1.06 (95%CI 0.53–2.13, P = 0.87).ConclusionsThe augmented SMS-based intervention delivered CD₄ results more rapidly and efficiently, and this type of SMS-based results delivery platform may be useful for a variety of tests and settings. However, the intervention did not appear to improve access to timely antenatal CD₄ testing or ART initiation, as obstacles other than CD₄ impeded ART initiation during pregnancy.     

Loss from Treatment for Drug Resistant Tuberculosis: Risk Factors and Patient Outcomes in a Community-Based Program in Khayelitsha,South Africa

Background

A community based drug resistant tuberculosis (DR-TB) program has been incrementally implemented in Khayelitsha, a high HIV and TB burden community in South Africa. We investigated loss from treatment (LFT), and post treatment outcomes of DR-TB patients in this setting.

Methodology

LFT, defined as interruption of treatment for ≥2 consecutive months was assessed among patients initiating DR-TB treatment for the first time between January 2009 and July 2011. Patients were traced through routine data sources to identify those who subsequently restarted treatment and those who died. Additional information on patient status and survival after LTF was obtained from community DR-TB counselors and from the national death registry. Post treatment outcomes were observed until July 2013.

Results

Among 452 patients initiating treatment for the first time within the given period, 30% (136) were LFT, with 67% retention at 18 months. Treatment was restarted in 27 (20%) patients, with additional resistance recorded in 2/25 (8%), excluding two with presumed DR-TB. Overall, 34 (25%) patients died, including 11 who restarted treatment. Males and those in the age category 15-25 years had a greater hazard of LFT; HR 1.93 (95% CI 1.35-2.75), and 2.43 (95% CI 1.52-3.88) respectively. Older age (>35 years) was associated with a greater hazard of death; HR 3.74 (1.13- 12.37) post treatment. Overall two-year survival was 62%. It was lower (45%) in older patients, and was 92% among those who received >12 months treatment.

Conclusion

LFT was high, occurred throughout the treatment period and was particularly high among males and those aged 15-25 years. Overall long term survival was poor. High rates of LFT should however not preclude scale up of community based care given its impact in increasing access to treatment. Further research is needed to support retention of DR-TB patients on treatment, even within community based treatment programs.     

Transmission of single and multiple viral variants in primary HIV-1 subtype C infection

To address whether sequences of viral gag and env quasispecies collected during the early post-acute period can be utilized to determine multiplicity of transmitted HIV's, recently developed approaches for analysis of viral evolution in acute HIV-1 infection [1,2] were applied. Specifically, phylogenetic reconstruction, inter- and intra-patient distribution of maximum and mean genetic distances, analysis of Poisson fitness, shape of highlighter plots, recombination analysis, and estimation of time to the most recent common ancestor (tMRCA) were utilized for resolving multiplicity of HIV-1 transmission in a set of viral quasispecies collected within 50 days post-seroconversion (p/s) in 25 HIV-infected individuals with estimated time of seroconversion. The decision on multiplicity of HIV infection was made based on the model's fit with, or failure to explain, the observed extent of viral sequence heterogeneity. The initial analysis was based on phylogeny, inter-patient distribution of maximum and mean distances, and Poisson fitness, and was able to resolve multiplicity of HIV transmission in 20 of 25 (80%) cases. Additional analysis involved distribution of individual viral distances, highlighter plots, recombination analysis, and estimation of tMRCA, and resolved 4 of the 5 remaining cases. Overall, transmission of a single viral variant was identified in 16 of 25 (64%) cases, and transmission of multiple variants was evident in 8 of 25 (32%) cases. In one case multiplicity of HIV-1 transmission could not be determined. In primary HIV-1 subtype C infection, samples collected within 50 days p/s and analyzed by a single-genome amplification/sequencing technique can provide reliable identification of transmission multiplicity in 24 of 25 (96%) cases. Observed transmission frequency of a single viral variant and multiple viral variants were within the ranges of 64% to 68%, and 32% to 36%, respectively.     

In vitro morphogenesis of organogenic nodules derived from <Emphasis Type="Italic">Sclerocarya birrea</Emphasis> subsp. <Emphasis Type="Italic">caffra</Emphasis> leaf explants

Sclerocarya birrea (marula) is an indigenous South African tree with highly valued medicinal and nutritional properties. Induction of nodular meristemoids from leaf explants was achieved on Murashige and Skoog (MS) and woody plant medium (WPM) supplemented with 6-benzyladenine (BA) in combination with naphthalene acetic acid (NAA), indole-3-butryric acid (IBA) and indole-3-acetic acid (IAA). Induction of nodular meristemoids from 86% of the leaf cultures was achieved on MS medium with 4.0 μM BA and 1.0 μM NAA. High levels (78–100%) of induction were also achieved on WPM with different concentrations of BA (1.0–4.0 μM) and IBA (1.0–4.0 μM). The highest conversion of meristemoids into shoots was only 22% for 4.0 μM BA and 1.0 μM NAA on MS initiation medium. This was improved to 62% when nodular clusters were cultured in a MS liquid medium. Histological studies revealed the globular stage of the nodular meristemoids. This protocol has potential for application in mass micropropagation and plant breeding of S. birrea.     

Physiological effects of a novel aromatic cytokinin analogue in micropropagated Aloe arborescens and Harpagophytum procumbens

Globally, there is a continuous effort geared toward improving micropropagation protocols with much emphasis on the type of cytokinins (CKs). We investigated the effect of meta-topolin tetrahydropyran-2-yl [mTTHP—a novel derivative of the aromatic cytokinin meta-topolin (mT)] on shoot proliferation, photosynthetic pigment content, phytochemicals and antioxidant activity of two widely used medicinal plants, Aloe arborescens and Harpagophytum procumbens. In terms of shoot proliferation, besides mTTHP and mT (at equimolar level) showing comparable effects, both topolins were significantly better than the control and benzyladenine riboside (BAR) in micropropagated A. arborescens. In H. procumbens, mT-treated cultures were the most responsive treatment at 2.5 μM when compared to the control. At 5.0 μM concentration, mTTHP and meta-topolin riboside (mTR) demonstrated a comparable effect on shoot proliferation. To a certain extent (particularly at low concentrations), mTTHP had a better rooting stimulatory effect when compared to the other CKs in both investigated species. In micropropagated A. arborescens, 2.5 μM mTTHP showed the best antioxidant activity (ferric reducing power) which was significantly higher than the control and all BAR-treated plants. Although 2.5 μM mTTHP exhibited a significant antioxidant activity (in β-carotene based assay) when compared to mTR at equimolar level in H. procumbens, it was not significantly different from the treatment with 2.5 μM mT and the control. As evidenced in the current study, the efficacy of the novel cytokinin may be species-specific and beneficial for few physiological parameters. It is conceivable that mTTHP is another viable alternative topolin with the extra advantage of inducing rooting at a low concentration.     

Photoperiod and plant growth regulator combinations influence growth and physiological responses in Pelargonium sidoides DC.

The aim of the present study was to evaluate the influence of photoperiod and meta-methoxytopolin riboside (MemTR)-auxin combinations on in vitro growth and physiological responses of Pelargonium sidoides DC. Shoot proliferation was highest under the conventional 16-h photoperiod. Based on the superiority of MemTR among other cytokinins from our previous study, it was selected for evaluating the cytokinin-auxin combination effect under long-day conditions. MemTR-auxin combinations had a significant effect on shoot proliferation compared to the control. The highest shoot proliferation rate (4.5 shoots/explant) was obtained on Murashige and Skoog medium supplemented with a combination of MemTR (1.0 μM) and α-naphthaleneacetic acid (NAA; 0.5 μM). Furthermore, combinations of MemTR and auxins had a synergistic effect on the concentration of photosynthetic pigments. On the other hand, photoperiod had no significant effect on the concentration of photosynthetic pigments. Formation of leaf glandular trichomes was influenced by photoperiod. Both 12- and 16-h photoperiods led to higher glandular trichome densities on the abaxial leaf surfaces of P. sidoides compared to plants grown under the 24-h photoperiod. MemTR-auxin combinations had a significant effect on the concentration of total phenolic compounds and flavonoids.     

Growth,mortality and reproduction of Sargochromis codringtonii in Lake Kariba,Zimbabwe

Age determination of Sargochromis codringtonii was undertaken using scalimetry. Marginal scale analysis, used for age validation, indicated that annulus formation occurred in October and November. The possible reasons for this are discussed. S. codringtonii is relatively long-lived, surviving up to 8 years. It is sexually dimorphic with males growing at a faster rate and attaining a larger size than females. It is suggested that the mouth brooding habits of the female fish is one possible reason for sexual dimorphism. A higher total mortality rate (Z) was recorded for females as compared to males. S. codringtonii reproduces throughout the year, but with a peak during the hot wet months. The right ovary is atrophied and the possible significance of this is discussed.     

Design,synthesis and antibacterial properties of pyrimido[4,5-b]indol-8-amine inhibitors of DNA gyrase

According to the World Health Organization (WHO), approximately 1.7 million deaths per year are caused by tuberculosis infections. Furthermore, it has been predicted that, by 2050, antibacterial resistance will be the cause of approximately 10 million deaths annually if the issue is not tackled. As a result, novel approaches to treating broad-spectrum bacterial infections are of vital importance. During the course of our wider efforts to discover unique methods of targeting multidrug-resistant (MDR) pathogens, we identified a novel series of amide-linked pyrimido[4,5-b]indol-8-amine inhibitors of bacterial type II topoisomerases. Compounds from the series were highly potent against gram-positive bacteria and mycobacteria, with excellent potency being retained against a panel of relevant Mycobacterium tuberculosis drug-resistant clinical isolates.     

Ixodid ticks of African buffalo (<Emphasis Type="Italic">Syncerus caffer</Emphasis>), impala (<Emphasis Type="Italic">Aepyceros melampus</Emphasis>) and elephant (<Emphasis Type="Italic">Loxodonta africana</Emphasis>) in five protected park estates in the Zambezi valley,Zimbabwe

Wildlife hosts many pathogens of economic importance and is considered as a reservoir of important tick-borne diseases of livestock in southern Africa. The species composition of ticks parasitizing buffalo (Syncerus caffer), impala (Aepyceros melampus) and elephant (Loxodonta africana) was investigated in five protected parks in the Zambezi valley, Zimbabwe. A total of 1104 adult ticks was collected from 75 adult animals comprising five buffaloes, five elephants and five impalas drawn from five protected wildlife parks. Five tick species belonging to two genera were recovered, with Rhipicephalus decoloratus being the most prevalent species in all the three animal groups. Amblyomma hebraeum was only recovered from buffaloes whereas Rhipicephalus zambeziensis was recovered from buffalos and elephants. Significant differences in mean tick species distribution and concentration were observed amongst the wildlife parks and these appeared to be influenced by the number of hosts in each park. The study revealed that buffaloes are the major host of R. decoloratus in the Zambezi valley. The presence of these ixodid ticks within the Zambezi valley may have significant ecological and economic impacts on wildlife conservation, domestic animals and human health.     

Preterm Birth and Low Birth Weight after In Utero Exposure to Antiretrovirals Initiated during Pregnancy in Yaoundé, Cameroon

Background

Effects of antiretroviral therapy (ART) on birth outcomes remain controversial.

Objective

To assess the impact of antenatal exposure to ART on the occurrence of preterm birth (PTB) and low birth weight (LBW).

Methods

A cross-sectional study conducted at the Essos Hospital Center in Yaounde from 2008 to 2011 among HIV vertically exposed infants with two distinct maternal antiretroviral experiences: monotherapy group (Zidovudine, ZDV) and the combination ART group (cART). Mothers already receiving cART before pregnancy were ineligible. In both groups, events of PTB (<37 weeks) and LBW (<2,500g) were analyzed using univariate and multivariate logistic regression; with p<0.05 considered statistically significant.

Results

Of the 760 infants, 481 were born from cART-exposed mothers against 279 from maternal-ZDV. Median maternal CD4 count was 378 [interquartile range (IQR): 253–535] cells/mm³. Median duration of ART at onset of delivery was 13 [IQR: 10–17] weeks. In the cART-group, 64.9% (312/481) of mothers were exposed to Zidovudine/Lamuvidine/Nevirapine and only 2% (9/481) were on protease inhibitor-based regimens. Events of PTB were not significantly higher in the cART-group compared to the ZDV-group (10.2% vs. 6.4% respectively, p = 0.08), while onsets of LBW were significantly found in the cART-group compared to ZDV-group (11.6% vs. 7.2% respectively, p = 0.05). Other factors (parity, maternal age at delivery or CD4 cell count) were not associated with PTB.

Conclusion

cART, initiated during pregnancy, would be an independent factor of LBW. In the era of option B+ (lifelong ART to all HIV-pregnant women), further studies would guide towards measures limiting onsets of LBW.