bluuebunny/crossref_metadata_2025_split huggingface dataset:
ASSESSING THE COMMITMENT, MATURATION AND INFECTIVITY OF SEXUAL STAGES OF MALARIA PARASITES IN SCHOOLCHILDREN LIVING IN A HIGH MALARIA TRANSMISSION AREA OF BURKINA FASO
Authors: Barry Aissata , Tiono Alfred , Sirima Sodiomon , Bousema Teun 
Published: February 2017

BackgroundWith the move towards malaria elimination, it becomes essential to understand the contribution of asymptomatic parasite carriers to disease transmission. However, the dynamics of infection and gametocyte development are poorly understood in asymptomatic versus symptomatic malaria infections. This was addressed in a longitudinal study of school children in Balonghin, district of Saponé, Burkina Faso.MethodsThe study involved healthy schoolchildren (with no malaria parasite at microscopy) age 5–10 years. For the first year survey, children were cleared for subpatent infections using standard malaria therapy. No clearance will occur for the second year survey. Children are followed up for 6 months during which repeated finger prick blood samples for the detection and characterisation of infections are collected. Also at three occasions a venous blood sample is collected for direct membrane feeding assay (DMFA) to assess infectiousness to mosquitoes.ResultsThe first year survey was completed. Fifty (50) children were recruited and followed up. Almost all the children develop infection and symptomatic malaria during the follow-up period post clearance of initial infection. None of the children has infected mosquitoes during the DMFA assays. The second year survey is in process. The full results will be presented during the forum.ConclusionsThese data will be pivotal in understanding human infectious reservoir. This will help designing interventions to tackle the spread of malaria from symptomatic and asymptomatic malaria individuals towards global in eliminating malaria.
MALARIA PREVENTION PRACTICES AMONG PREGNANT MOTHERS IN OSOGBO, NIGERIA
Authors: Tijani Adelani 
Published: February 2017

BackgroundPregnant women are susceptible to symptomatic malaria due to invasion of the placenta byPlasmodium. The study aimed to find out the preventive measures put in place by pregnant mothers against malaria.MethodsIt is a descriptive cross-sectional survey comprising 294 pregnant women selected randomly in three hospitals in Osogbo. The instrument used for data collection was a self-developed, structured questionnaire with reliability of 0.802 using Cronbach's alpha coefficient.ResultsThe results show that 87.8% of the respondents had adequate knowledge about malaria in pregnancy and 75.5% of them were knowledgeable about various available measures in malaria prevention. However, only 34.4% used the insecticide treated nets (ITNs) and 21.4% used intermittent preventive therapy (IPTp). Findings also revealed that the respondents practiced other preventive measures such as clearing of surrounding bushes (12.8%), maintenance of drainages and netting of windows and doors (15.4%). The results of the study revealed that various barriers to the use of ITNs were deficient knowhow (45.9%), spousal disapproval (36.7%), socio-cultural misconceptions about sleeping under ITNs (18.8%) and unaffordability of ITNs (45.5%). The hypotheses were tested using Pearson's chi-square method at 0.05 level of significance. There is no significant relationship between the pregnant mothers' knowledge and their practice of malaria prevention. However, there are respective significant relationships between the age, parity and educational status and practice of malaria prevention.ConclusionsIt was concluded that the practice of malaria prevention was generally low among the respondents. It was therefore recommended that concerted effort be put in place by the nurses, more especially public health nurses to address the barriers to utilisation of the universally accepted effective methods of malaria prevention. This could be done through mass health education to market women at regular interval.
INNOVATIVE CLINICAL TRIAL DESIGNS
Authors: Phillips Patrick 
Published: February 2017

Since the middle of the 20th century, randomised controlled trials have provided the strongest level of evidence to inform the treatment of all diseases. In particular, trials in the 1970s and 1980s in Africa led to a highly efficacious 6-month regimen for the treatment of TB; these were followed by trials in the 1990s and 2000s which resulted in today's HAART regimens that are recommended for all patients living with HIV.These diseases, however, still cause 1.3 million deaths every year in Africa, and further trials are needed to improve treatment and develop control strategies that will ultimately end the epidemics. Furthermore, there are many neglected diseases where few if any trials have been conducted and therefore the evidence base for treatment is extremely weak.The randomised clinical trial is an indispensable tool for defeating poverty-related and neglected diseases in Africa, but it should not be seen as a static instrument that has remained unchanged since its first introduction in the 1940s. Innovations in clinical trial design can overcome many barriers, facilitating more efficient trials where alternatives are prohibitively long or resource-intensive. For example, adding multiple intervention arms or sequential randomisations allows for more questions being answered in a single trial, and adaptive designs permit modifications to ongoing trials in light of internal or external data, thereby making better use of limited resources.This presentation covers the opportunities for innovation in clinical trial design in poverty-related and neglected diseases. Recent developments relate to multi-arm multi-stage and other adaptive trial designs, interpretation of non-inferiority trials, choice of comparator arms, the role of pragmatic trials, and treatment strategy trials. Specific examples will be presented, including recent TB, HIV and Ebola trials, in addition to other areas for possible progress, all with the ultimate goal of faster patient benefit.
PLASMODIUM FALCIPARUMPARASITE DYNAMICS DETERMINED BY QPCR AFTER CONTROLLED HUMAN MALARIA INFECTION IN SEMI-IMMUNES FROM GABON
Authors: Honkpehedji Yabo , Agobe Jean Claude Dejon , Zinsou Frejus , Mengue Juliana , Adegnika Ayola , Richie Thomas , Mordmüller Benjamin , Kremsner Peter , Hoffman Stephen , Lell Bertrand 
Published: February 2017

BackgroundCharacterising the effect of natural acquired immunity and sickle cell anaemia on the pattern ofPlasmodium falciparumparasitaemia may be useful to understand the pathophysiological mechanisms of protection against malaria. Controlled human malaria infection (CHMI) by direct venous inoculation of aseptic, purified, cryopreserved sporozoites (Pf-SPZ challenge) is a new tool which can be used to investigate the pathophysiology of malaria.MethodsThe study was performed in Lambarene, Gabon, one of seven African partners in the EDCTP-funded CHMI platform. Adults aged 18–35 from three groups NI: 5 non-immune (NI), 11 semi-immunes with haemoglobin AA (IA), and 9 semi-immunes with haemoglobin AS (IS) received 3,200 sporozoites after a curative treatment course with clindamycin. Capillary blood samples were taken daily up to Day 28 to determine parasitaemia by real-time quantitative polymerase chain reaction (RT-qPCR). Treatment was administered for a malaria episode or at Day 28, whichever came first.ResultsParasitaemia was detected in 5 (100%) subjects in the NI group, 9 (82%) in the IA group and 7 (78%) in the IS group. All volunteers in the NI group showed similar patterns with parasitaemia starting around Day 8 and rising quickly. Patterns for parasitaemia in the immune groups (IA and IS) were highly heterogeneous. Although time points of initial parasitaemia and duration of parasitaemia varied, all semi-immunes managed to control parasitaemia for at least several days. There were no discernible differences in patterns between the IS and IA group, including the area under curve of parasitaemia over time.ConclusionsNo parasitaemia was detected in 20% of the semi-immunes, likely due to liver stage immunity. The highly variable patterns of parasitaemia did not allow us to discern immune mechanisms against blood stages. Haemoglobin AS had no visible effect on parasite dynamics at the low parasitaemia encountered.
MYCOBACTERIUM TUBERCULOSISRESISTANCE TO ISONIAZID AND RIFAMPICIN IN A HIV-1 ENDEMIC POPULATION IN WESTERN KENYA IN 2014
Authors: Likhovole Clement , Ouma Collins , Vulule John , Musau Susan , Khayumbi Jeremiah , Okumu Albert , Murithi Wilfred 
Published: February 2017

BackgroundThe spread of mono-resistant and multi-drug resistant tuberculosis (MDR-TB) has been enhanced by delays in the identification of resistant strains. However, resistance gene patterns and the extent and distribution of mono-resistant TB and MDR-TB is unknown, particularly for western Kenya where Human Immunodeficiency Virus (HIV) is common. As such, the overall objective of the current study was to identify cases of mono-resistant TB and MDR-TB among enrolled patients in health facilities in western Kenya.MethodsPatients with a suspected TB history were referred by clinicians to the health facilities for TB and HIV diagnosis. HIV testing was done using the Unigold and Abbott Determine kits. Early morning sputum samples were collected and cultured onMycobacteriagrowth indicator tubes (MGIT) and incubated at 37°C. Drug susceptibility testing (DST) using the SIRE® kit was done on ZN smear positive MGIT tubes and line probe assay (LPA) performed to identify specific mutations on therpoB,katG andinhA genes. Mutations on discordant samples were confirmed by the BigDye® Terminator v3.1 Cycle Sequencing Kit.ResultsThe proportion of MDR-TB, RIF mono-resistant (RMR) TB and INH mono-resistant TB as estimated by LPA and DST, was as follows: MDR-TB: 1.38% / 1.26%; RMR-TB: 1.2% / 0.72%; INH mono-resistant TB: 2.1% / 2.4%, respectively. Our study showed that the H526YrpoB and S315T1kat Gmutations were common in HIV-positive patients (8% and 18% respectively) and that the S3I5T1 and S531L was the most common mutation in MDR-TB strains in both HIV-positive and HIV-negative patients (5% and 8% respectively). Binary logistic regression, indicated that RMR-TB significantly predicted HIV status (p=0.025).ConclusionsOur findings show that RIF mono-resistant TB predicts HIV infection.
LOW FALSE RECENT RATE OF LIMITING ANTIGEN AVIDITY ASSAY COMBINED WITH HIV-1 RNA DATA IN BOTSWANA
Authors: Moyo Sikhulile , Kotokwe Kenanao , Mohammed Terence , Boleo Coretah , Mupfumi Lucy , Chishala Samuel , Gaseitsiwe Simani , Tsalaile Lesedi , Bussmann Herman , Makhema Joseph , Baum Marianna , Marlink Richard , Engelbretch Susan , Essex Max , Novitsky Vladimir 
Published: February 2017

BackgroundCross-sectional tests for recency of HIV infection are increasing in utility for estimating HIV incidence and evaluating impact of interventions. However, they have been shown to misclassify individuals with long standing infection as recent. Local performance characteristics are essential for their application. We estimated the false recency rate (FRR) among long term HIV-1 infected individuals from Botswana.MethodsA total of 1036 specimens from treatment naïve individuals known to be HIV-infected 1.5 to 2 years from baseline were tested using the limiting antigen-avidity assay (LAg) using a cut-off of 1.5 normalised optical density units (OD-n). Study participants were enrolled in HIV disease progression and did not qualify for treatment according to national guidelines at the time of enrolment. Baseline HIV status was determined using double ELISA. Viral and CD4 measures were done every 3 months.ResultsMost participants were females (74.8%) and median age was 35 years (IQR 30–42). The median CD4 cell count and viral load were 394 cells/µL (IQR 303–524) and 4.25 copies/mL (IQR 3.51–4.87), respectively. Overall the FRR was 0.97% (10/1036; 95% CI: 0.46–1.77). Four samples had viral loads >1000 copies/mL, giving an adjusted FRR of 0.39% (4/1036; 95% CI 0.11–0.99).ConclusionsLAg had a very low FRR in this Botswana population using the algorithm involving viral load. We found viral load to be a complementary marker for improving the specificity of the LAg-avidity assay. To our knowledge, this is the first report of LAg-avidity FRR for the Botswana population, which is much lower than the 2% recommended by the WHO Incidence Assays Working Group.
NEED FOR REANALYSIS OF CURRENT TESTING OF HIV-EXPOSED INFANTS
Authors: Saka Emmanuel , Kalipalire Zex , Bhairavabhotla Ravikiran , Midiani Dalitso , Sherman Judith 
Published: February 2017

BackgroundIn 2015, 12% of HIV-exposed infants in Malawi received an early infant diagnostic test (EID) in the first two months of life. Provider-initiated testing and counselling (PITC) is recommended as a standard component of comprehensive clinical management for inpatients and outpatients in entry points, including at mother-infant pair (MIP) clinics, nutrition rehabilitation units (NRU) and paediatric wards.MethodsAn analysis of the 2015 databases of Community Management of Acute Malnutrition (CMAM), Laboratory Information Management System (LMIS) and EID at point-of-care (EID POC) was conducted to identify optimal entry points for identifying HIV-infected children. A chi-square test was used to determine differences between groups.ResultsA total of 7629 children below 5 years of age were admitted in NRUs; 60% were tested for HIV and 17% were HIV-infected. The EID POC database showed that most (50%) of the children identified from the inpatient paediatric ward were HIV-infected as compared to 2.5% in MIP clinics and 11% in outpatient paediatric wards. A chi-square test of significance shows that the HIV positivity varies between entry points (chi-square value=182.34, with 2 degrees of freedom and p-value <0.001). The LMIS database showed that 45% of children identified in the paediatric ward were HIV-infected compared to 30% of children identified via NRUs and 4% in MIP clinics. A chi-square test of significance shows that HIV positivity varies between entry points (chi-square value=597.83, with 6 degrees of freedom and p-value <0.001).ConclusionsHigh yield of HIV positivity in children was found in the paediatric wards and NRUs as opposed to MIP and outpatient wards. Targeting EID POC testing to these settings can reduce infant mortality and morbidity as HIV-infected children will be identified and initiated on treatment more quickly.
ENHANCING TUBERCULOSIS DETECTION BY TRAINED RATS AND TRACKING OF MISSED PATIENTS THROUGH COMMUNITY-BASED STRATEGY IN TB HIGH-BURDEN COUNTRIES
Authors: Mgode Georgies , Cox Christophe , Bwana Dickens , Mtui Leah , Magesa Daniel , Kahwa Amos , Mfinanga Godfrey , Mulder Christiaan 
Published: February 2017

BackgroundTuberculosis (TB) diagnosis in most sub-Saharan African countries with high TB burden is by direct smear microscopy that has low sensitivity. More sensitive tests like GeneXpert are expensive and not yet available in most African settings. Therefore, a need for cheap and rapid tests is inevitable. Trained rats (Cricetomysspp.) detect TB by targeting theMycobacterium tuberculosisspecific volatile compounds. Accredited rats evaluated 150 sputa in 20 minutes. We report on intervention involving TB detection by rats and additional patient tracking by community healthcare workers from MUKIKUTE and PASADA for treatment.MethodsSputum was collected in hospitals in Dar es Salaam, Coast and Morogoro, Tanzania after microscopy. Sputa were heat inactivated at 100oC×30 minutes to kill pathogens and thereafter presented to rats in random computer generated positions for evaluation. Samples indicated as TB-positive by rats were confirmed by concentrated smear microscopy whether they contained TB bacilli. Confirmed TB cases were reported to community healthcare workers and hospitals for tracking and treatment. Healthcare workers recorded contact details of presumptive TB patients for subsequent tracking when detected by rats.ResultsFrom 2011 to 2015 detection rats evaluated 306,346 sputum samples from 152,118 presumptive TB patients, which were also tested by microscopy in hospitals. DOTS smear-positive TB patients were 21,911 and rats detected an additional 7961 patients missed in hospitals. Community healthcare workers tracking the additional patients brought 2715 additional TB patients to treatment whereas treatment initiation increased from 56% (1020/1812) in 2013 to 73% (870/1,198) in 2015. This prevented TB transmission to 27,150 to 40,725 people since one untreated TB patient can spread the disease to 10–15 persons annually.ConclusionsTB detection using rats and involvement of community healthcare workers to track the additional TB patients for treatment can increase TB detection and treatment initiation rate of missed TB cases.
MOLECULAR TYPING AND DRUG RESISTANCE INMYCOBACTERIUM TUBERCULOSISCOMPLEX ISOLATES FROM JAMOT AND MBALMAYO DISTRICT HOSPITALS, CAMEROON
Authors: Tekwu Emmanuel Mouafo , Sidze Larissa Kamgue , Assam Jean Paul Assam , Eyangoh Sarah , Niemann Stefan , Ntoumi Francine , Beng Veronique Penlap , Frank Matthias 
Published: February 2017

BackgroundCameroon is a country where tuberculosis still remains a major public health problem. The aim of the present research was to evaluate the potential of molecular markers in predicting first-line drug resistance and to investigate the predominant genotypes representative ofMycobacterium tuberculosisstrains in the Centre region of Cameroon.MethodsA total of 169 strains ofM. tuberculosisisolate from the Centre Region of Cameroon were screened for mutations associated with first-line drug resistance by DNA sequence analysis. Spoligotyping and MIRU-VNTR (24 loci; mycobacterial interspersed repetitive units typing – variable number tandem repeat) were combined to identify clustered isolates.ResultsRifampicin-resistant strains had therpoBmutations D516V, H526D or S531L; isoniazid-resistant strains had the mutationskatGS315T or inhA promoter C15T; streptomycin-resistant strains had the mutationsrpsLK43R,gidBV36G, H48N, P75S, L79W, or A138P; ethambutol-resistant strains had the mutationembBM306V. Among thoseM. tuberculosisisolates, 52.5% isolates were Cameroon genotypes followed by Haarlem genotype (22.1%). The frequencies of isoniazid, rifampin, streptomycin and multidrug-resistant isolates were equally distributed in Cameroon genotype strains and non-Cameroon strains. Furthermore, the analysis also shows the very low frequency ofM. africanumsince only 2.6% of isolates belong to this species.ConclusionsMutations of common genes known to be involved in resistance had high specificities in detecting resistance. This study reveals the highly diverseM.tuberculosispopulation structure, It confirms a predominance of the Cameroon lineage in the Centre Region of Cameroon and the disappearance ofM. africanumin Cameroon.
COMBINED SPECIFIC IGG – AND IGA-BASED DIAGNOSIS OF TUBERCULOSIS IN AFRICAN PRIMARY HEALTHCARE CLINIC ATTENDEES WITH SIGNS AND SYMPTOMS SUGGESTIVE OF TUBERCULOSIS
Authors: Awoniyi Dolapo , Baumann Ralf , Chegou Novel , Kriel Belinda , Jacobs Ruschca , Kidd Martin , Loxton Andre , Kaempfer Susanne , Singh Mahavir , Walzl Gerhard 
Published: February 2017

BackgroundIgG-based tests for the diagnosis of active tuberculosis disease (TB) often show a lack of specificity in TB endemic regions, which is mainly due to a high background prevalence of latent TB infection (LTBI). Here, we investigate the combined performance of the responses of different Ig classes to selected mycobacterial antigens in primary healthcare clinic attendees with signs and symptoms suggestive of TB.MethodsWe evaluated the sensitivity and specificity of serologic IgA, IgG and/or IgM to LAM, 7 mycobacterial protein antigens (ESAT-6, Tpx, PstS1, AlaDH, MPT64, 16 kDa and 19 kDa) and 2 antigen combinations (TUB, TB-LTBI) in the plasma of 42 individuals with other respiratory diseases (separated into 21 LTBI controls and 21 uninfected healthy controls), and 21 active TB patients at baseline, of whom 19 were followed up at month 6 at the end of TB treatment.ResultsThe leading single serodiagnostic markers were anti-16 kDa IgA, anti-MPT64 IgA, anti-LAM IgG and anti-TB-LTBI IgG. IgA responses to MPT64 and 16 kDa had the highest sensitivity/specificity of 95%/95% and 95%/90% in differentiating active TB from other respiratory diseases and active TB from LTBI controls, respectively. The combined use of 3 or 4 antibodies further improved this performance to accuracies above 95%. After successful completion of anti-TB treatment at month 6, only particularly anti-TUB IgG showed distinctively decreased levels.ConclusionsThese results show the potential of combining IgG and IgA responses against selected protein and non-protein antigens in differentiating active TB from other respiratory diseases in TB endemic settings, and may provide a benchmark for vaccines.
DISCORDANT RESULTS BETWEEN GENOTYPIC ASSAYS (XPERT MTB/RIF AND HAIN MTBDRPLUS) AND BACTEC MGIT 960 SYSTEM FOR DETECTION OF RIFAMPICIN-RESISTANTMYCOBACTERIUM TUBERCULOSISISOLATES IN ZAMBIA
Authors: Mwanza Winnie , Milimo Deborah , Moyo Maureen , Kasese Nkatya , Cheeba-Lengwe Maina , Munkondya Stembiso , Ayles Helen , Haas Petra De , Muyoyeta Monde 
Published: February 2017

BackgroundCombination of genotypic assays (Xpert MTB/ RIF and MTBDRplus (LiPA) would be a powerful tool to shorten the time for diagnosis of MDR tuberculosis (TB). However, the algorithm used for these assays in Zambia has not yet been implemented and the most widely used drug susceptibility testing (DST) method remains MGIT DST. Missed rifampicin resistance on the MGIT 960 system has been reported by several studies due to silent rpoB gene mutations. We report comparative observations made on the performance of Xpert, LiPA and MGIT DST methods for detection of rifampicin resistance (RR) at the ZAMBART Central Laboratory (ZCL).MethodsSpecimens were collected from consecutive patients with Xpert rifampicin resistance positive (RR+) or rifampicin resistance indeterminate (RRI) results at peripheral site laboratories for further testing at the ZCL. Each sample was tested using Xpert, LiPA and MGIT culture/DST.Results30 patient samples were received and 17 were RR+, 8 were rifampicin-sensitive (RR-) and 5 were TB-negative by Xpert. All 17 RR+ on Xpert were RR+ on LiPA and all 8 Xpert RR – were sensitive on LiPA giving a 100% concordance for diagnosis of RR. Three isolates that were rifampicin sensitive by the MGIT system (Gold standard) were RR+ by both genotypic tests. Genotypic tests showed evidence of mutation in the codon 526 region of the rpoB gene for all the three isolates with discordant RR MGIT DST results. Xpert positive predictive value for Multidrug Resistance (MDR) TB was 62.5% and 81.2% compared to MGIT DST and LiPA, respectively.ConclusionsThere is need for Zambia to perform a full classification of rpoB mutations to determine the prevalence of silent mutations. This will optimise national guidelines for diagnosis of RR – and MDR-TB.