Feasibility and Coverage of Implementing Intermittent Preventive Treatment of Malaria in Pregnant women Contacting Private or Public Clinics in Tanzania: Experience-based Viewpoints of Health Managers in Mkuranga and Mufindi districts.

Evidence on healthcare managers' experience on operational feasibility of malaria intermittent preventive treatment for malaria during pregnancy (IPTp) using sulphadoxine-pyrimethamine (SP) in Africa is systematically inadequate. This paper elucidates the perspectives of District Council Health Management Team (CHMT)s regarding the feasibility of IPTp with SP strategy, including its acceptability and ability of district health care systems to cope with the contemporary and potential challenges. The study was conducted in Mkuranga and Mufindi districts. Data were collected between November 2005 and December 2007, involving focus group discussion (FGD) with Mufindi CHMT and in-depth interviews were conducted with few CHMT members in Mkuranga where it was difficult to summon all members for FGD. Participants in both districts acknowledged the IPTp strategy, considering the seriousness of malaria in pregnancy problem; government allocation of funds to support healthcare staff training programmes in focused antenatal care (fANC) issues, procuring essential drugs distributed to districts, staff remuneration, distribution of fANC guidelines, and administrative activities performed by CHMTs. The identified weaknesses include late arrival of funds from central level weakening CHMT's performance in health supervision, organising outreach clinics, distributing essential supplies, and delivery of IPTp services. Participants anticipated the public losing confidence in SP for IPTp after government announced artemither-lumefantrine (ALu) as the new first-line drug for uncomplicated malaria replacing SP. Role of private healthcare staff in IPTp services was acknowledged cautiously because CHMTs rarely supplied private clinics with SP for free delivery in fear that clients would be required to pay for the SP contrary to government policy. In Mufindi, the District Council showed a strong political support by supplementing ANC clinics with bottled water; in Mkuranga such support was not experienced. A combination of health facility understaffing, water scarcity and staff non-adherence to directly observed therapy instructions forced healthcare staff to allow clients to take SP at home. Need for investigating in improving adherence to IPTp administration was emphasised. High acceptability of the IPTp strategy at district level is meaningless unless necessary support is assured in terms of number, skills and motivation of caregivers and availability of essential supplies

Epidemiology of Subpatent Plasmodium Falciparum Infection: Implications for Detection of Hotspots with Imperfect Diagnostics.

At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings

Effect of malaria transmission reduction by insecticide-treated bed nets (ITNs) on the genetic diversity of Plasmodium falciparum merozoite surface protein (MSP-1) and circumsporozoite (CSP) in western Kenya

Background Although several studies have investigated the impact of reduced malaria transmission due to insecticide-treated bed nets (ITNs) on the patterns of morbidity and mortality, there is limited information on their effect on parasite diversity. Methods Sequencing was used to investigate the effect of ITNs on polymorphisms in two genes encoding leading Plasmodium falciparum vaccine candidate antigens, the 19 kilodalton blood stage merozoite surface protein-1 (MSP-119kDa) and the Th2R and Th3R T-cell epitopes of the pre-erythrocytic stage circumsporozoite protein (CSP) in a large community-based ITN trial site in western Kenya. The number and frequency of haplotypes as well as nucleotide and haplotype diversity were compared among parasites obtained from children <5 years old prior to the introduction of ITNs (1996) and after 5 years of high coverage ITN use (2001). Results A total of 12 MSP-119kDa haplotypes were detected in 1996 and 2001. The Q-KSNG-L and E-KSNG-L haplotypes corresponding to the FVO and FUP strains of P. falciparum were the most prevalent (range 32–37%), with an overall haplotype diversity of > 0.7. No MSP-119kDa 3D7 sequence-types were detected in 1996 and the frequency was less than 4% in 2001. The CSP Th2R and Th3R domains were highly polymorphic with a total of 26 and 14 haplotypes, respectively detected in 1996 and 34 and 13 haplotypes in 2001, with an overall haplotype diversity of > 0.9 and 0.75 respectively. The frequency of the most predominant Th2R and Th3R haplotypes was 14 and 36%, respectively. The frequency of Th2R and Th3R haplotypes corresponding to the 3D7 parasite strain was less than 4% at both time points. There was no significant difference in nucleotide and haplotype diversity in parasite isolates collected at both time points. Conclusion High diversity in these two genes has been maintained overtime despite marked reductions in malaria transmission due to ITNs use. The frequency of 3D7 sequence-types was very low in this area. These findings provide information that could be useful in the design of future malaria vaccines for deployment in endemic areas with high ITN coverage and in interpretation of efficacy data for malaria vaccines based on 3D7 parasite strains

Genetic decomposition of the heritable component of reported childhood maltreatment

BackgroundDecades of research have shown that environmental exposures, including self-reports of trauma, are partly heritable. Heritable characteristics may influence exposure to and interpretations of environmental factors. Identifying heritable factors associated with self-reported trauma could improve our understanding of vulnerability to exposure and the interpretation of life events.MethodsWe used genome-wide association study summary statistics of childhood maltreatment, defined as reporting of abuse (emotional, sexual, and physical) and neglect (emotional and physical) (N = 185,414 participants). We calculated genetic correlations (rg) between reported childhood maltreatment and 576 traits to identify phenotypes that might explain the heritability of reported childhood maltreatment, retaining those with |rg| &gt; 0.25. We specified multiple regression models using genomic structural equation modeling to detect residual genetic variance in childhood maltreatment after accounting for genetically correlated traits.ResultsIn 2 separate models, the shared genetic component of 12 health and behavioral traits and 7 psychiatric disorders accounted for 59% and 56% of heritability due to common genetic variants (single nucleotide polymorphism–based heritability [h2SNP]) of childhood maltreatment, respectively. Genetic influences on h2SNP of childhood maltreatment were generally accounted for by a shared genetic component across traits. The exceptions to this were general risk tolerance, subjective well-being, posttraumatic stress disorder, and autism spectrum disorder, identified as independent contributors to h2SNP of childhood maltreatment. These 4 traits alone were sufficient to explain 58% of h2SNP of childhood maltreatment.ConclusionsWe identified putative traits that reflect h2SNP of childhood maltreatment. Elucidating the mechanisms underlying these associations may improve trauma prevention and posttraumatic intervention strategies.</p

Genetic Decomposition of the Heritable Component of Reported Childhood Maltreatment

BACKGROUND: Decades of research have shown that environmental exposures, including self-reports of trauma, are partly heritable. Heritable characteristics may influence exposure to and interpretations of environmental factors. Identifying heritable factors associated with self-reported trauma could improve our understanding of vulnerability to exposure and the interpretation of life events. METHODS: We used genome-wide association study summary statistics of childhood maltreatment, defined as reporting of abuse (emotional, sexual, and physical) and neglect (emotional and physical) (N = 185,414 participants). We calculated genetic correlations (rg) between reported childhood maltreatment and 576 traits to identify phenotypes that might explain the heritability of reported childhood maltreatment, retaining those with |rg| > 0.25. We specified multiple regression models using genomic structural equation modeling to detect residual genetic variance in childhood maltreatment after accounting for genetically correlated traits. RESULTS: In 2 separate models, the shared genetic component of 12 health and behavioral traits and 7 psychiatric disorders accounted for 59% and 56% of heritability due to common genetic variants (single nucleotide polymorphism–based heritability [h2SNP]) of childhood maltreatment, respectively. Genetic influences on h2SNP of childhood maltreatment were generally accounted for by a shared genetic component across traits. The exceptions to this were general risk tolerance, subjective well-being, posttraumatic stress disorder, and autism spectrum disorder, identified as independent contributors to h2SNP of childhood maltreatment. These 4 traits alone were sufficient to explain 58% of h2SNP of childhood maltreatment. CONCLUSIONS: We identified putative traits that reflect h2SNP of childhood maltreatment. Elucidating the mechanisms underlying these associations may improve trauma prevention and posttraumatic intervention strategies

A Randomized Placebo-Controlled Trial of Intermittent Preventive Treatment in Pregnant Women in the Context of Insecticide Treated Nets Delivered through the Antenatal Clinic

Background:Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets(ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of theircombined use.Methods:1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC)visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess thesafety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight.Findings:Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence atdelivery (RR, 0.92 [95% CI, 0.79-1.08]), low birth weight (RR, 0.99 [95% CI, 0.70-1.39]), or overall placental infection(p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40-61.20]; p = 0.020) in the incidence of clinicalmalaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p,0.001), and ofactively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderlinestatistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITN's use was morethan 90% in both groups.Conclusions:Two-dose SP was associated with a reduction in some indicators, but these were not translated to significantimprovement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administerIPTp. ITNs should be part of the ANC package in sub-Saharan Afric

Maternal Malaria and Perinatal HIV Transmission, Western Kenya1,2

To determine whether maternal placental malaria is associated with an increased risk for perinatal mother-to-child HIV transmission (MTCT), we studied HIV-positive women in western Kenya. We enrolled 512 mother-infant pairs; 128 (25.0%) women had malaria, and 102 (19.9%) infants acquired HIV perinatally. Log10 HIV viral load and episiotomy or perineal tear were associated with increased perinatal HIV transmission, whereas low-density malaria (<10,000 parasites/μL) was associated with reduced risk (adjusted relative risk [ARR] 0.4). Among women dually infected with malaria and HIV, high-density malaria (>10,000 parasites/μL) was associated with increased risk for perinatal MTCT (ARR 2.0), compared to low-density malaria. The interaction between placental malaria and MTCT appears to be variable and complex: placental malaria that is controlled at low density may cause an increase in broad-based immune responses that protect against MTCT; uncontrolled, high-density malaria may simultaneously disrupt placental architecture and generate substantial antigen stimulus to HIV replication and increase risk for MTCT

Putting It Together: AIDS and the Millennium Development Goals

Failure to halt and reverse the HIV/AIDS epidemic, say the authors, will continue to jeopardize progress on achieving a wide range of the MDGs

Efficacy of a nurse-led sexual rehabilitation intervention for women with gynaecological cancers receiving radiotherapy:results of a randomised trial

Background: The multicentre randomised SPARC trial evaluated the efficacy of a nurse-led sexual rehabilitation intervention on sexual functioning, distress, dilator use, and vaginal symptoms after radiotherapy for gynaecological cancers. Methods: Eligible women were randomised to the rehabilitation intervention or care-as-usual. Four intervention sessions were scheduled over 12 months, with concurrent validated questionnaires and clinical assessments. Primary outcome was the Female Sexual Function Index (FSFI). A generalised-mixed-effects model compared groups over time. Results: In total, 229 women were included (n = 112 intervention; n = 117 care-as-usual). No differences in FSFI total scores were found between groups at any timepoint (P = 0.37), with 12-month scores of 22.57 (intervention) versus 21.76 (care-as-usual). The intervention did not significantly improve dilator use, reduce sexual distress or vaginal symptoms compared to care-as-usual. At 12 months, both groups had minimal physician-reported vaginal stenosis; 70% of women were sexually active and reported no or mild vaginal symptoms. After radiotherapy and brachytherapy, 85% (intervention) versus 75% (care-as-usual) of participants reported dilation twice weekly. Discussion: Sexual rehabilitation for women treated with combined (chemo)radiotherapy and brachytherapy improved before and during the SPARC trial, which likely contributed to comparable study groups. Best practice involves a sexual rehabilitation appointment 1 month post-radiotherapy, including patient information, with dilator guidance, preferably by a trained nurse, and follow-up during the first year after treatment. Clinical trial registration: NCT03611517.</p