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Long-lasting insecticidal nets (LLINs) were first introduced in 2010 as a vector control intervention, to complement indoor residual spraying, to reduce malaria transmission in Zimbabwe. The objective of this study was to investigate factors that were associated with LLIN ownership and utilization among households in malaria transmission regions of Zimbabwe.
A secondary analysis of cross sectional data from the Zimbabwe demographic and health survey (ZDHS) conducted in 2010 and 2015 surveys round was conducted. The analysis used household-level datasets from across the country to generate evidence for the study. Univariate analysis was used to yield descriptive statistics. Principal component analysis (PCA) was used to calculate wealth quintiles. Binary logistic regression approach was used to identify determinants of LLIN ownership and utilization after controlling for other factors. Data analyses were conducted using STATA version 14 software.
There were no major changes in demographic characteristics of households sampled between 2010 and 2015 survey cycles. LLIN ownership increased significantly by 42 percentage points from 2010 to 2015. There was a tremendous increase in universal coverage of LLINs between 2010 and 2015. The overall utilization levels of LLINs among children under-5 years decreased by 11 percentage points between 2010 and 2015. LLIN usage amongst households followed the same trend with that of the under-fives. Using logistic regression model for 2015 data, region/province, type of place of residence, availability of electricity, radio, roof type, gender of head of household, having telephone, type of cooking fuel, presence of mobile phone, owning a bank account, IRS spraying in the previous 12 months, wealth index, and satellite television decorder were independently associated with net ownership among households. Type of place of residence, age of household head, type of cooking fuel, IRS in previous 12 months, and pregnancy were associated with LLIN utilization.
This study revealed increasing LLIN coverage and low usage in malaria-transmission regions of Zimbabwe. Strengthening of LLIN campaigns, social behaviour change communication (SBCC) interventions and programme routine monitoring are recommended.
HIV-infected individuals on antiretroviral therapy (ART) require treatment with artemisinin-based combination therapy (ACT) when infected with malaria. Dihydroartemisinin–piperaquine (DPQ) is recommended for treatment of Plasmodium falciparum malaria, but its efficacy and safety has not been evaluated in HIV-infected individuals on ART, among whom drug–drug interactions are expected. Day-42 adequate clinical and parasitological response (ACPR) and incidence of adverse events were assessed in HIV-infected individuals on non-nucleoside reverse transcriptase inhibitor-based ART (efavirenz and nevirapine) with uncomplicated P. falciparum malaria treated with dihydroartemisinin–piperaquine.
An open label single arm clinical trial was conducted in Malawi (Blantyre and Chikhwawa districts) and Mozambique (Manhiça district) involving patients aged 15–65 years with uncomplicated P. falciparum malaria who were on efavirenz-based or nevirapine-based ART. They received a directly-observed 3-day standard treatment of DPQ and were followed up until day 63 for malaria infection and adverse events. Day-42 PCR-corrected-ACPRs (95% confidence interval [CI]) were calculated for the intention-to-treat (ITT) population.
The study enrolled 160 and 61 patients on efavirenz and nevirapine-based ART, with a baseline geometric mean (95% CI) parasite density of 2681 (1964–3661) and 9819 (6606–14,593) parasites/µL, respectively. The day-42 PCR-corrected ACPR (95% CI) was 99.4% (95.6–99.9%) in the efavirenz group and 100% in the nevirapine group. Serious adverse events occurred in 5.0% (8/160) and 3.3% (2/61) of the participants in the efavirenz and nevirapine group, respectively, but none were definitively attributable to DPQ. Cases of prolonged QT interval (> 60 ms from baseline) occurred in 31.2% (48/154) and 13.3% (8/60) of the patients on the efavirenz and nevirapine ART groups, respectively. These were not clinically significant and resolved spontaneously over time. As this study was not designed to compare the efficacy and safety of DPQ in the two ART groups, no formal statistical comparisons were made between the two ART groups.
DPQ was highly efficacious and safe for the treatment of malaria in HIV-infected patients concurrently taking efavirenz- or nevirapine-based ART, despite known pharmacokinetic interactions between dihydroartemisinin–piperaquine and efavirenz- or nevirapine-based ART regimens.
Trial registration Pan African Clinical Trials Registry (PACTR): PACTR201311000659400. Registered on 4 October 2013, https://pactr.samrc.ac.za/Search.aspx
Finkelstein J, Colt S, Layden A, et al.
AbstractBackgroundMicronutrients are known to modulate host immunity and there is limited literature on this association in the context of dengue virus infection (DENV).MethodsUsing a nested case-control design in a surveillance program, we measured anthropometry; nutritional biomarkers including serum ferritin, soluble transferrin receptor, retinol-binding protein (RBP), 25-hydroxy vitamin D, folate, and vitamin B12; and a panel of immune response markers and compared these measures across four illness categories: healthy control, non-febrile DENV, other febrile illness (OFI), and apparent DENV using multivariate polytomous logistic regression models.ResultsAmong 142 participants, serum ferritin (ng/mL) was associated with apparent DENV compared to healthy controls (OR 2.66; CI 1.53, 4.62; p=0.001), and RBP concentrations (µmol/L) were associated with apparent DENV (OR 0.03; CI 0.00, 0.30; p=0.003) and OFI (OR 0.02; CI 0.00, 0.24; p=0.003). In a subset of 71 participants, IL-15 levels (MFI) were positively associated with apparent DENV (OR 1.09; CI 1.03, 1.14; p=0.001) and negatively associated with non-febrile DENV (OR 0.89; CI 0.80, 0.99; p=0.03) compared to healthy controls.ConclusionsAfter adjusting for the acute phase response, serum ferritin and RBP concentrations were associated with apparent DENV and may represent biomarkers of clinical importance in the context of dengue illness.
Tan X, Ramond E, Jamet A, et al.
AbstractStaphylococcus aureus is a leading cause of both acute and chronic infections in humans. The importance of the pentose phosphate pathway (PPP) during S. aureus infection is currently largely unexplored. Here, we focused on one key PPP enzyme, transketolase. We showed that inactivation of the unique gene encoding transketolase activity in S. aureus USA300 (∆tkt) led to drastic metabolomic changes. Using time-lapse video imaging and mice infection, we observed a major defect of the ∆tkt strain compared to wild-type strain in early intracellular proliferation and in the ability to colonise kidneys. Transcriptional activity of the two master regulators Sigma B and RpiRc was drastically reduced in the ∆tkt mutant during host cells invasion. The concomitant increased RNAIII transcription, suggests that TKT -or a functional PPP- strongly influences the ability of S. aureus to proliferate within host cells by modulating key transcriptional regulators.
Cacciotto C, Dessì D, Cubeddu T, et al.
AbstractMycoplasma lipoproteins play a relevant role in pathogenicity and directly interact with the host immune system. Among human mycoplasmas, Mycoplasma hominis is described as a commensal bacterium that can be associated with a number of genital and extra-genital conditions.Mechanisms of M. hominis pathogenicity are still largely obscure, and only a limited number of proteins have been associated to virulence. This work focuses on investigating the role of MHO_0730 as a virulence factor. We demonstrate that MHO_0730 is a surface lipoprotein, potentially expressed in vivo during natural infection both acting as nuclease with its amino acidic portion and as a potent inducer of NETosis with its N-terminal lipid moiety. Also, evidence for M. hominis NETs escape is presented. Results highlight the relevance of MHO_0730 in promoting infection and modulation and evasion of innate immunity, and provide additional knowledge to M. hominis virulence and survival in the host.
No comparison data have been reported on viral and epidemiological profiles of hospitalized children with severe acute respiratory infection (SARI) in Beijing or Shanghai, China.
We collected 700 nasopharyngeal aspirates (NPA) from hospitalized children with SARI in Beijing (northern China) and Shanghai (southern China). Multiple respiratory viruses (including 15 common viruses) were screened by validated polymerase chain reaction (PCR) or real-time reverse transcription-PCR assays and confirmed by sequencing. Demographic data and the distribution of viral infections were also examined.
Of 700 samples, 547 (78.1%) tested positive for viral infections. The picornaviruses (PIC), which included rhinovirus (RV) and enterovirus (EV), were the most common (34.0%), followed by respiratory syncytial virus (RSV) (28.3%), human bocavirus (HBoV) (19.1%), adenovirus (ADV) (13.7%), human coronaviruses (HCoV) (10.7%), influenza A and B (8.9%), parainfluenza virus (PIV 1–3) (7.9%), and human metapneumovirus (HMPV) (5.0%). PIC (RV/EV) and RSV were the most prevalent etiological agents of SARI in both cities. The total and age-matched prevalence of RSV, HCoV, and hMPV among SARI children under 5 years old were significantly higher in Beijing than in Shanghai. Different age and seasonal distribution patterns of the viral infections were found between Beijing and Shanghai.
Viral infection was tested and shown to be the most prevalent etiological agent among children with SARI in either the Beijing or the Shanghai area, while showing different patterns of viral and epidemiological profiles. Our findings provide a better understanding of the roles of geographic location and climate in respiratory viral infections in hospitalized children with SARI.
Isoniazid resistant tuberculosis is the most prevalent type of resistance in Swaziland and over two-thirds of the isoniazid resistant tuberculosis patients are tuberculosis and human immunodeficiency virus co-infected. The study aimed to determine risk factors associated with isoniazid resistant tuberculosis among human immunodeficiency virus positive patients in Swaziland.
This was a case-control study conducted in nine healthcare facilities across Swaziland. Cases were patients with isoniazid resistant tuberculosis (including 78 patients with isoniazid mono-resistant tuberculosis, 42 with polydrug-resistant tuberculosis, and 77 with multidrug-resistant tuberculosis). Controls were presumed drug-susceptible tuberculosis patients (n = 203). Multinomial logistic regression was used to determine related factors.
The median time lag from diagnosis to tuberculosis treatment initiation was 50 days for isoniazid mono or poly drug-resistant tuberculosis, 17 days for multidrug-resistant tuberculosis compared to 1 day for drug-susceptible tuberculosis patients. History of previous tuberculosis treatment was positively associated with either isoniazid mono or poly drug-resistant tuberculosis (OR = 7.91, 95% CI: 4.14–15.11) and multidrug-resistant tuberculosis (OR = 12.20, 95% CI: 6.07–24.54). Isoniazid mono or poly resistant tuberculosis patients were more likely to be from rural areas (OR = 2.05, 95% CI: 1.23–3.32) and current heavy alcohol drinkers compared to the drug-susceptible tuberculosis group. Multi drug-resistant tuberculosis patients were more likely to be non-adherent to tuberculosis treatment compared to drug-susceptible tuberculosis group (OR = 3.01, 95% CI: 1.56–5.82).
To prevent and control isoniazid resistant tuberculosis among HIV-positive patients in Swaziland, the tuberculosis program should strengthen the use of rapid diagnostic tests, detect resistance early, promptly initiate supervised tuberculosis treatment and decentralize quality tuberculosis services to the rural areas. Adherence to tuberculosis treatment should be improved.
Solobacterium moorei, the only species in the genus Solobacterium, is a Gram-positive, non-spore-forming, strict anaerobic, short to long bacillus. It has rarely been documented to cause blood stream infections. Here we report the first case of bacteremia caused by S.moorei in China.
A 61-year-old male presented to Peking Union Medical College Hospital (Beijing) with thrombotic thrombocytopenic purpura (TTP) and several other underlying diseases. He also had persistent coma accompanied by intermittent convulsions, halitosis, and intermittent fever. Blood cultures taken when the patient had a high fever were positive, with the anaerobic bottle yielding an organism identified as S.moorei by 16S rRNA gene sequencing, whilst the aerobic bottle grew Streptococcus mitis. After replacement of venous pipeline, and empirical use of vancomycin and meropenem, the patient’s body temperature and white blood cell count returned to normal. Unfortunately, the patient died of severe TTP.
This is the first case report of S. moorei isolation from blood stream in China. 16S rRNA gene sequencing is the only method that can identify S. moorei. Blood cultures must be taken before administration of antibiotics, and anaerobic culture should be considered for such rare pathogens in patients with oral diseases and immune deficiency.
Lyme borreliosis (LB) is a tick-borne disease caused by spirochetes belonging to the Borrelia burgdorferi sensu lato species. Due to a variety of clinical manifestations, diagnosing LB can be challenging, and laboratory work-up is usually required in case of disseminated LB. However, the current standard of diagnostics is serology, which comes with several shortcomings. Antibody formation may be absent in the early phase of the disease, and once IgG-seroconversion has occurred, it can be difficult to distinguish between a past (cured or self-cleared) LB and an active infection. It has been postulated that novel cellular tests for LB may have both higher sensitivity earlier in the course of the disease, and may be able to discriminate between a past and active infection.
VICTORY is a prospective two-gate case-control study. We strive to include 150 patients who meet the European case definitions for either localized or disseminated LB. In addition, we aim to include 225 healthy controls without current LB and 60 controls with potentially cross-reactive conditions. We will perform four different cellular tests in all of these participants, which will allow us to determine sensitivity and specificity. In LB patients, we will repeat cellular tests at 6 weeks and 12 weeks after start of antibiotic treatment to assess the usefulness as ‘test-of-cure’. Furthermore, we will investigate the performance of the different cellular tests in a cohort of patients with persistent symptoms attributed to LB.
This article describes the background and design of the VICTORY study protocol. The findings of our study will help to better appreciate the utility of cellular tests in the diagnosis of Lyme borreliosis.
NL7732 (Netherlands Trial Register, trialregister.nl).
At a time when programs were struggling to design effective regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB), the marketing authorization of bedaquiline and delamanid was a critical development in the MDR-TB treatment landscape. However, despite their availability for routine programmatic use, the uptake of these drugs has remained slow; concerns included a lack of evidence on safety and efficacy and the need to protect the new drugs from the development of acquired resistance. As part of the endTB Project, we aimed to address these barriers by generating evidence on safety and efficacy of bedaquiline or delamanid based MDR-TB regimens.
This is a protocol for a multi-center prospective cohort study to enroll 2600 patients from April 2015 through September 2018 in 17 countries. The protocol describes inclusion of patients started on treatment with bedaquiline- or delamanid- containing regimens under routine care, who consented to participate in the endTB observational study. Patient follow-up was according to routine monitoring schedules recommended for patients receiving bedaquiline or delamanid as implemented at each endTB site. Therefore, no additional tests were performed as a part of the study. Data were to be collected in a customized, open-source electronic medical record (EMR) system developed as a part of the endTB Project across all 17 countries.
The endTB observational study will generate evidence on safety and efficacy of bedaquiline- and delamanid-containing regimens in a large, extremely heterogeneous group of MDR-TB patients, from 17 epidemiologically diverse countries. The systematic, prospective data collection of repeated effectiveness and safety measures, and analyses performed on these data, will improve the quality of evidence available to inform MDR-TB treatment and policy decisions. Further, the resources available to countries through implementation of the endTB project will have permitted countries to: gain experience with the use of these drugs in MDR-TB regimens, improve local capacity to record and report adverse events (pharmacovigilance), and enhance significantly the body of data available for safety evaluation of these drugs and other novel treatments.
This study was registered on 24 August 2017 at clincaltrials.gov (Registration number: NCT03259269).
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