Positive Rapid Diagnostic Test Research Articles

BCG vaccination is associated with reduced malaria prevalence in children under the age of 5 years in sub-Saharan Africa

IntroductionMalaria continues to be a major cause of morbidity and mortality in sub-Saharan Africa (SSA) without effective interventions. Bacillus Calmette-Guérin (BCG) vaccine possesses protective non-specific effects, which extend beyond protection...

Impact of Malaria in Pregnancy on Risk of Malaria in Young Children: Systematic Review and Meta-Analyses

Background: The impact of prenatal exposure to Plasmodium falciparum on young children’s susceptibility to malaria has not been well characterized. Our aim was to quantify the risk of acquiring malaria among progeny of women with malaria during pregnancy. Methods: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for eligible prospective studies published through August 28, 2017. Thesaurus search terms included “malaria AND pregnancy AND (child OR infant)”. The primary predictor was malaria during pregnancy defined as placental malaria, maternal parasitemia, maternal clinical malaria, or pregnancy-associated malaria. Primary outcomes were parasitemia or clinically defined malaria of young children. Infection with P. falciparum was confirmed with a positive blood smear or rapid diagnostic test. We performed meta-analyses to pool adjusted risk estimates (odds ratio [aOR] or hazard ratio [aHR]) using a random effects model. Findings: Nineteen of 2053 eligible studies met inclusion criteria for the systemic review. Eleven of these studies were quantitative and were included in the meta-analyses. The pooled aOR or aHR of malaria during pregnancy for detection of parasitemia in young children were 1·94 [95% confidence interval (CI), 0·93-4·07; p=0·08] and 1·46 (95% CI, 1·07-2·00; p<0·001), respectively. The pooled aOR or aHR for clinically defined malaria in young children were 2·82 (95% CI, 1·82-4·38; p<0·001) and 1·31 (95% CI, 0·96-1·79; p=0·09), respectively. Interpretation: Our results confirmed that malaria during pregnancy significantly increases the overall risk of malaria in young children, and emphasize the urgent need to implement safe and highly effective strategies to prevent malaria during pregnancy. Funding Statement: This work was supported by the COBRE for Reproductive Health at Women & Infants Hospital of Rhode Island/NIGMS P20GM121298-01. An NIH/NIAID award to ICM (K08AI100997) supported this work. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The authors performed a systematic review according to the guidelines of PRISMA and MOOSE.

Lineage-specific rapid diagnostic tests can resolve Trypanosoma cruzi TcII/V/VI ecological and epidemiological associations in the Argentine Chaco

BackgroundTrypanosoma cruzi, the protozoan agent of Chagas disease, is comprised of at least 6 genetic lineages (TcI-TcVI). Their geographical distribution, clinical associations and reservoir hosts are not fully elucidated, as genotyping is hampered due to the difficulty in isolating representative populations of organisms. Lineage-specific serological techniques may address these issues.MethodsTrypanosoma cruzi lineage-specific serological assays were performed on human, canine, feline and armadillo sera from the Gran Chaco in northern Argentina, a region of ongoing transmission. Synthetic peptides representing lineage-specific epitopes of the trypomastigote small surface antigen (TSSA) were used in ELISA, and the TcII/V/VI shared epitope peptide (TSSApep-II/V/VI) was used in the Chagas Sero K-SeT rapid diagnostic test (RDT).ResultsChagas Sero K-SeT RDT, using Protein G to detect human and canine IgG, was at least as sensitive as TSSApep-II/V/VI ELISA using specific secondary antibodies. For sera from humans TSSApep-II/V/VI seroprevalence by Chagas Sero K-SeT was 273/393 (69.5%), for dogs 48/73 (65.8%) and for armadillos 1/7 (14.3%); by ELISA for cats 5/19 (26.3%). The seroprevalence for humans was similar to that for Bolivian patients, amongst whom we previously observed an association of TSSApep-II/V/VI seropositivity with severity of cardiomyopathy. In humans, prevalence of TSSApep-II/V/VI recognition was associated with locality, and with increasing and decreasing age within the Qom and Creole populations, respectively. For dogs TSSApep-II/V/VI recognition was associated with being born before community-wide insecticide spraying (P = 0.05) and with Qom household (P < 0.001).ConclusionsWe show here that Chagas Sero K-SeT RDT can replace ELISA for TSSApep-II/V/VI serology of humans and dogs; for humans there were statistically significant associations between a positive Chagas Sero K-SeT RDT and being resident in Area IV, and for dogs association with Qom household or with being born before the mass spraying campaign; we also show that with cats the TcII/V/VI epitope can be detected by ELISA. We assessed the lineage distribution in an unprecedented 83% of the human T. cruzi-seropositive population. These results form the basis for more detailed studies, enabling rapid in-the-field surveillance of the distribution and clustering of these lineages among humans and mammalian reservoirs of T. cruzi infection.

Asymptomatic Plasmodium infection and glycemic control in adults: Results from a population-based survey in south-central Côte d’Ivoire

AIMSWe investigated the cross-sectional associations of Plasmodium infection (PI) with fasting glucose (FG) and glycated hemoglobin (HbA1c) in malaria-endemic south-central Côte d’Ivoire. MethodsWe studied 979 participants (non-pregnant; no treated diabetes; 51% males; 18–87 years) of the Côte d’Ivoire Dual Burden of Disease study. Fasting venous blood was obtained for PI, FG, and HbA1c assessment. We defined PI as a positive malaria rapid diagnostic test (RDT) or microscopic identification of Plasmodium species. We applied multivariable linear regressions to assess beta coefficients (β) and 95% confidence intervals (CIs) of PI positivity for FG and HbA1c independent of diabetes risk factors. ResultsPrevalence of PI was 10.1% (5.5% microscopy; 9.7% RDT) without clinical fever. Prevalence of FG-based prediabetes (45.8%) and diabetes (3.6%) were considerably higher than HbA1c-based values (2.7% and 0.7%, respectively). PI was independently associated with FG among participants with higher body temperature (β 0.34, 95% CI 0.06–0.63, pheterogeneity = 0.028), or family history of diabetes (β 0.88, 95% CI 0.28–1.47, pheterogeneity = 0.009). Similar patterns observed with HbA1c were obliterated on accounting for FG. We also observed consistent associations with parasite density. ConclusionsFG-based diabetes diagnosis in the presence of asymptomatic PI may misclassify or overestimate diabetes burden in malaria-endemic settings. Longitudinal studies are needed to confirm these findings and determine the risk for diabetes.

The impact on malaria of biannual treatment with azithromycin in children age less than 5\xa0years: a prospective study

BackgroundThe MORDOR study, a cluster randomized clinical trial, showed that single-dose azithromycin (20 mg/kg) administered biannually for 2 years to preschool children reduced mortality; a study was conducted to determine its effect on clinical symptomatic episodes of malaria as a potential mechanism for mortality benefit.MethodsA randomized control trial (RCT) was conducted, whereby 30 randomly selected communities in Kilosa District, Tanzania were randomized to receive 6-monthly treatment of children ages 1–59 months with single-dose azithromycin (20 mg/kg) vs. placebo. A prospective cohort study was nested within the RCT: children, aged 1 to 35 months at baseline, were randomly selected in each community and evaluated at 6-monthly intervals for 2 years. At each visit, the children were assessed for recent or ongoing fever and anti-malarial treatment; a rapid diagnostic test (RDT) for malaria was performed. The two major outcomes of interest were prevalence of RDT positivity and clinical malaria. The latter was defined as RDT-positivity with fever at time of evaluation and/or reported fever in the 3 days prior to evaluation. Methods that account for correlations at community level and within individuals over time were used to evaluate associations.ResultsAt baseline, the prevalence rates in the children in the azithromycin and placebo arms were 17.6% vs. 15.5% for RDT positivity (p = 0.76) and 6.1% vs. 4.3% (p = 0.56) for clinical malaria. There was a decline in both RDT-positivity and clinical malaria over time in both arms. The difference by treatment assignment was not significant for clinical malaria; it was significant for RDT-positivity with greater odds of decline in the placebo arm (p = 0.01).ConclusionsLack of evidence for a significant difference in the prevalence of clinical malaria in children at any visit following treatment suggests that the effect of single-dose azithromycin on malaria is at best transient and limited in scope. Chance overrepresentation of non-seasonal transmission in the communities in the azithromycin arm may account for higher rates of RDT-positivity and less decline over time.Trial registration Clinicaltrials.gov NCT02047981

Proof of concept: used malaria rapid diagnostic tests applied for parallel sequencing for surveillance of molecular markers of anti-malarial resistance in Bissau, Guinea-Bissau during 2014\u20132017

BackgroundLarge-scale surveillance of molecular markers of anti-malarial drug resistance is an attractive method of resistance monitoring, to complement therapeutic efficacy studies in settings where the latter are logistically challenging.MethodsBetween 2014 and 2017, this study sampled malaria rapid diagnostic tests (RDTs), used in routine clinical care, from two health centres in Bissau, Guinea-Bissau. In order to obtain epidemiological insights, RDTs were collected together with patient data on age and sex. A subset of positive RDTs from one of the two sites (n = 2184) were tested for Plasmodium DNA content. Those testing positive for Plasmodium DNA by PCR (n = 1390) were used for library preparation, custom designed dual indexing and next generation Miseq targeted sequencing of Plasmodium falciparum genes pfcrt, pfmdr1, pfdhfr, pfdhps and pfk13.ResultsThe study found a high frequency of the pfmdr1 codon 86N at 88–97%, a significant decrease of the pfcrt wildtype CVMNK haplotype and elevated levels of the pfdhfr/pfdhps quadruple mutant ranging from 33 to 51% between 2014 and 2017. No polymorphisms indicating artemisinin tolerance were discovered. The demographic data indicate a large proportion of young adults (66%, interquartile range 11–28 years) presenting with P. falciparum infections. While a total of 5532 gene fragments were successfully analysed on a single Illumina Miseq flow cell, PCR-positivity from the library preparation varied considerably from 13 to 87% for different amplicons. Furthermore, pre-screening of samples for Plasmodium DNA content proved necessary prior to library preparation.ConclusionsThis study serves as a proof of concept for using leftover clinical material (used RDTs) for large-scale molecular surveillance, encompassing the inherent complications regarding to methodology and analysis when doing so. Factors such as RDT storage prior to DNA extraction and parasitaemia of the infection are likely to have an effect on whether or not parasite DNA can be successfully analysed, and are considered part of the reason the data yield is suboptimal. However, given the necessity of molecular surveillance of anti-malarial resistance in settings where poor infrastructure, poor economy, lack of educated staff and even surges of political instability remain major obstacles to performing clinical studies, obtaining the necessary data from used RDTs, despite suboptimal output, becomes a feasible, affordable and hence a justifiable method.

Seasonal malaria chemoprevention combined with community case management of malaria in children under 10 years of age, over 5 months, in south-east Senegal: A cluster-randomised trial.

BackgroundSeasonal malaria chemoprevention (SMC) is recommended in the Sahel region of Africa for children under 5 years of age, for up to 4 months of the year. It may be appropriate to include older children, and to provide protection for more than 4 months. We evaluated the effectiveness of SMC using sulfadoxine-pyrimethamine plus amodiaquine given over 5 months to children under 10 years of age in Saraya district in south-east Senegal in 2011.Methods and findingsTwenty-four villages, including 2,301 children aged 3–59 months and 2,245 aged 5–9 years, were randomised to receive SMC with community case management (CCM) (SMC villages) or CCM alone (control villages). In all villages, community health workers (CHWs) were trained to treat malaria cases with artemisinin combination therapy after testing with a rapid diagnostic test (RDT). In SMC villages, CHWs administered SMC to children aged 3 months to 9 years once a month for 5 months. The study was conducted from 27 July to 31 December 2011. The primary outcome was malaria (fever or history of fever with a positive RDT). The prevalence of anaemia and parasitaemia was measured in a survey at the end of the transmission season. Molecular markers associated with resistance to SMC drugs were analysed in samples from incident malaria cases and from children with parasitaemia in the survey. SMC was well tolerated with no serious adverse reactions. There were 1,472 RDT-confirmed malaria cases in the control villages and 270 in the SMC villages. Among children under 5 years of age, the rate difference was 110.8/1,000/month (95% CI 64.7, 156.8; p < 0.001) and among children 5–9 years of age, 101.3/1,000/month (95% CI 66.7, 136.0; p < 0.001). The mean haemoglobin concentration at the end of the transmission season was higher in SMC than control villages, by 6.5 g/l (95% CI 2.0, 11; p = 0.007) among children under 5 years of age, and by 5.2 g/l (95% CI 0.4, 9.9; p = 0.035) among children 5–9 years of age. The prevalence of parasitaemia was 18% in children under 5 years of age and 25% in children 5–9 years of age in the control villages, and 5.7% and 5.8%, respectively, in these 2 age groups in the SMC villages, with prevalence differences of 12.5% (95% CI 6.8%, 18.2%; p < 0.001) in children under 5 years of age and 19.3% (95% CI 8.3%, 30.2%; p < 0.001) in children 5–9 years of age. The pfdhps-540E mutation associated with clinical resistance to sulfadoxine-pyrimethamine was found in 0.8% of samples from malaria cases but not in the final survey. Twelve children died in the control group and 14 in the SMC group, a rate difference of 0.096/1,000 child-months (95% CI 0.99, 1.18; p = 0.895). Limitations of this study include that we were not able to obtain blood smears for microscopy for all suspected malaria cases, such that we had to rely on RDTs for confirmation, which may have included false positives.ConclusionsIn this study SMC for children under 10 years of age given over 5 months was feasible, well tolerated, and effective in preventing malaria episodes, and reduced the prevalence of parasitaemia and anaemia. SMC with CCM achieved high coverage and ensured children with malaria were promptly treated with artemether-lumefantrine.Trial registrationwww.clinicaltrials.gov NCT01449045.

Clinical Characteristics and Outcome of Children Hospitalized With Scrub Typhus in an Area of Endemicity.

BackgroundScrub typhus, caused by Orientia tsutsugamushi, is a major cause of acute febrile illness in children in the rural tropics.MethodsWe recruited 60 febrile pediatric patients with a positive scrub typhus rapid diagnostic test result and 40 healthy controls from Chiang Rai Province in northern Thailand. Diagnosis was confirmed by the detection of (1) O. tsutsugamushi–specific DNA in blood or eschar samples with a polymerase chain reaction assay, (2) a fourfold rise in immunoglobulin M (IgM) titer to ≥1:3200 in paired plasma samples with an indirect immunofluorescence assay (IFA), or (3) a single IgM titer of ≥1:3200 in an acute plasma sample with an IFA. Demographic, clinical, and laboratory data were collected, and patients were followed up for 1 year.ResultsDiagnosis was confirmed in 35 (58%) of 60 patients, and all controls tested negative for scrub typhus. Patients with confirmed scrub typhus had clinical symptoms, including fever (35 of 35 [100%]), eschar (21 of 35 [60%]), cough (21 of 35 [60%]), tachypnea (16 of 35 [46%]), lymphadenopathy (15 of 35 [43%]), and headache (14 of 35 [40%]). Only 4 (11%) of 35 patients received appropriate antibiotic treatment for scrub typhus before admission. The median fever-clearance time was 36 hours (interquartile range, 24–53 hours). Complications observed include hepatitis (9 of 35 [26%]), severe thrombocytopenia (7 of 35 [20%]), pneumonitis (5 of 35 [14%]), circulatory shock (4 of 35 [11%]), and acute respiratory distress syndrome (3 of 35 [9%]). Treatment failure, defined by failure to defervesce within 72 hours of antibiotic treatment initiation, was noted in 8 (23%) of 35 patients, and 1 (3%) of the 35 patients died. No evidence of relapse or reinfection was found.ConclusionPediatric scrub typhus in northern Thailand is often severe and potentially fatal with delays in treatment a likely contributing factor. Additional studies to investigate the bacterial, pharmacologic, and immunologic factors related to treatment outcome along with measures to improve public awareness should be prioritized.

In vivo compartmental kinetics of Plasmodium falciparum histidine-rich protein II in the blood of humans and in BALB/c mice infected with a transgenic Plasmodium berghei parasite expressing histidine-rich protein II

BackgroundThe Plasmodium falciparum histidine-rich protein II (PfHRP2) is a common biomarker used in malaria rapid diagnostic tests (RDTs), but can persist in the blood for up to 40 days following curative treatment. The persistence of PfHRP2 presents a false positive limitation to diagnostic interpretation. However, the in vivo dynamics and compartmentalization underlying PfHRP2 persistence have not been fully characterized in the plasma and erythrocyte (RBC) fraction of the whole blood.MethodsThe kinetics and persistence of PfHRP2 in the plasma and RBC fractions of the whole blood were investigated post-treatment in human clinical samples and samples isolated from BALB/c mice infected with a novel transgenic Plasmodium berghei parasite engineered to express PfHRP2 (PbPfHRP2).ResultsPfHRP2 levels in human RBCs were consistently 20–40 times greater than plasma levels, even post-parasite clearance. PfHRP2 positive, DNA negative, once-infected RBCs were identified in patients that comprised 0.1–1% of total RBCs for 6 and 12 days post-treatment, even post-atovaquone–proguanil regimens. Transgenic PbPfHRP2 parasites in BALB/c mice produced and exported tgPfHRP2 to the RBC cytosol similar to P. falciparum. As in humans, tgPfHRP2 levels were found to be approximately 20-fold higher within the RBC fraction than the plasma post-treatment. RBC localized tgPfHRP2 persisted longer than tgPfHRP2 in the plasma after curative treatment. tgPfHRP2 positive, but DNA negative once-infected RBCs were also detected in mouse peripheral blood for 7–9 days after curative treatment.ConclusionsThe data suggest that persistence of PfHRP2 is due to slower clearance of protein from the RBC fraction of the whole blood. This appears to be a result of the presence PfHRP2 in previously infected, pitted cells, as opposed to PfHRP2 binding naïve RBCs in circulation post-treatment. The results thus confirm that the extended duration of RDT positivity after parasite clearance is likely due to pitted, once-infected RBCs that remain positive for PfHRP2.

Concurrence of CareStart\u2122 Malaria HRP2 RDT with microscopy in population screening for Plasmodium falciparum infection in the Mount Cameroon area: predictors for RDT positivity

BackgroundMalaria remains a diagnostic challenge in many endemic communities. Although rapid diagnostic tests (RDTs) are presently widely used for malaria diagnosis, there is a dearth of information on post-marketing surveillance on its efficacy in Cameroon. The present study evaluated the performance characteristics of CareStart™ Malaria HRP2 (histidine-rich protein 2) antigen (Ag) RDT in diagnosing Plasmodium falciparum infection in the Mount Cameroon area and predictors associated with RDT positivity.MethodsThe CareStart™ Malaria HRP2 Plasmodium falciparum (G0141) Ag RDT was evaluated in a cross-sectional community-based survey involving 491 children of both sexes aged 6 months to 14 years between April and May 2018. Malaria parasitaemia was confirmed by light microscopy. Sensitivity (Se), specificity (Sp), positive (PPV) and negative (NPV) predictive values of the RDT, and the corresponding accuracy and Kappa value (κ) were determined using microscopy as the gold standard. Haemoglobin (Hb) concentration was obtained using an auto-haematology analyser. Results were compared using the chi-square test and associations between predictor variables, and RDT results were assessed using logistic regression analysis.ResultsMicroscopically confirmed malaria parasite prevalence was 27.7%, and geometric mean density was 187 parasites/μL of blood (range 70–1162). Se, Sp, PPV, NPV and accuracy were 82.4, 76.6, 57.4, 91.9 and 78.2%, respectively. Sensitivity depended on parasitaemia and reached 96.1% at densities ≥ 200 parasites/μL of blood. The accuracy of malaria parasitaemia (as assessed by the area under the receiver operating characteristic curve) to predict malaria by RDT was 75.4% (95% CI 70.6–80.1). The agreement between microscopy and RDT was moderate (κ = 0.52). RDT positivity was significantly associated with fever (P < 0.001), children less than 5 years (P = 0.02), history of fever within a month (P < 0.001) and anaemia (P = 0.002).ConclusionThe overall concurrence of CareStart™ Malaria HRP2 pf Ag RDT with microscopy in the detection of P. falciparum infection is moderate and is most useful at parasitaemia ≥ 200 parasites/μL of blood and presentation with fever. While RDT is effective as a diagnostic test for confirmation of clinical cases of malaria, its applications in population screening with a higher proportion of asymptomatic cases are limited.

Epidemiological links between malaria parasitaemia and hypertension: findings from a population-based survey in rural Côte d'Ivoire.

Background:Although potential links between malaria parasitaemia and hypertension have been hypothesized, there is paucity of epidemiologic evidence on this link. We investigated in a population-based survey, the association between malaria parasitaemia and hypertension in Ivorian adults.Methods:We estimated the adjusted odds ratios (OR) and 95% confidence intervals (CI) of hypertension in relation to malaria parasitaemia using multinomial regression, in 997 randomly selected adults in the ‘Côte d’Ivoire Dual Burden of Disease Study’ (CoDuBu), in south-central Côte d’Ivoire. We defined malaria parasitaemia as a positive rapid diagnostic test or identification of Plasmodium spp. on microscopy. Using the mean of the last two of three blood pressure (BP) measurements and questionnaire data, we defined hypertension as SBP at least 140 mmHg or DBP at least 90 mmHg or clinician-diagnosed hypertension.Results:Prevalence of malaria parasitaemia and hypertension were 10 and 22%, respectively. Malaria parasitaemia was negatively associated with hypertension in participants with body temperature 36.5 °C or less [OR 0.23 (95% CI 0.06–0.84)]. Contrastingly, microscopic malaria parasitaemia showed positive associations with hypertension in participants with elevated body temperature [>36.5 °C; OR: 2.93 (95% CI 0.94–9.14)]. Participants having microscopic malaria parasitaemia with elevated body temperature had three-fold higher odds of hypertension [OR: 3.37 (95% CI 1.12–10.0)] than malaria parasitaemia-negatives with lower body temperature.Conclusion:Malaria parasitaemia and hypertension are prevalent and seemingly linked comorbidities in African settings. This link may depend on malaria parasitaemia symptomaticity/latency where individuals with more latent/asymptomatic malaria parasitaemia have lower risk of hypertension and those with more acute/symptomatic malaria parasitaemia have a tendency toward higher BP. The cross-sectional nature of the study limited the distinction of short-term BP elevation (interim pathophysiological stress) from hypertension development. Future longitudinal studies considering malaria/hypertension phenotypes and host molecular variations are needed to clarify involved biological mechanisms, toward comorbidity management.

Investigation of the public health event in the Cafunfu town, Lunda-Norte, December 2017

Purpose: On November 22th, 2017, the people from Cafunfu municipality in Lunda-Norte Province, alerted through the media, “the occurrence of unidentified disease, manifested mainly by high fevers, among other symptoms”. After verification of the alert, a multidisciplinary outbreak investigation team was sent to the town in December to investigate this public health event. Methods & Materials: In order to investigate the etiology of this public health event, 370 febrile children were randomly selected for testing with rapid diagnostic tests (RDT) for malaria. Further, 25 RDT for dengue and chikunguya were performed. In order to evaluate the factors associated with the disease, a 1:2 age-matched case-control study was conducted in the neighborhoods of Elevação and Bala bala. The target population were children under 15 years old. The sample size was calculated using the EPI Info Calculator: 60 cases and 120 controls were recruited. Significance level was set at p < 0.05 for all hypothesis tests. Results: The RDT positivity rate was 70% for malaria. Of the 60 cases analyzed, 39 (65%) were male; 34 (57%)> 5 years, 36 (60%) lived in Bala bala. The epidemic curve was typical of vector-borne disease and revealed the occurrence of underreporting with the arrival of the external teams and the beginning of the outbreak investigation. Logistic regression identified the following associated factors for contracting malaria: having an open dump close to home, OR of 11.3 [4.54–28.32] (p < 0.001); not sleeping under mosquito net, OR = 16.3 [6.23–42.49] (p < 0.001). Conclusion: The upsurge in malaria cases was the trigger for the rumor that circulated through the media by the population of Cafunfo. Control measures taken included: distribution of LLITNs; vector control strategies, improved case management. It was further recommended that local health authorities strengthen the epidemiological surveillance system, improve basic sanitation, maintain vector control strategies and develop risk communication strategies.

The effect of malaria rapid diagnostic tests results on antimicrobial prescription practices of health care workers in Burkina Faso

BackgroundMalaria rapid diagnostic tests (RDT) are widely used in endemic areas in order to comply with the recommendation that malaria treatment should only be given after the clinical diagnosis has been confirmed by RDT or microscopy. However, the overestimation of malaria infection with the use of PfHRP2 based RDT, makes the management of febrile illnesses more challenging. This study aimed to assess the effect of the use of malaria RDT on antimicrobial prescription practices.MethodsA prospective study was conducted among febrile children under-5 years of age attending four health facilities and the referral hospital in the Nanoro Health District (Burkina Faso). To assess the effect of malaria RDT testing on the prescriptions of antimicrobials in febrile children, the initial diagnosis and antimicrobial prescriptions following a malaria RDT testing were recorded. The necessity of these prescriptions was subsequently checked by assessing the actual cause of fever by expert malaria microscopy and a microbiology analysis of blood, urine, stool and nasopharynx swabs that were collected from febrile cases to determine the actual cause of the fever episode.ResultsMalaria was diagnosed by nurses, who are the primary health care providers, with a malaria RDT in 72.7% (798/1098) of febrile children, but only 53.7% (589/1097) cases could be confirmed by expert microscopy. Health care workers were likely to prescribe antimalarials to malaria positive RDT compared to malaria negative RDT (RR = 7.74, p = 0.00001). Malaria negative RDT result had a significant influence on the antibiotic prescriptions (RR = 3.57, p = 0.0001). The risk of prescribing antimicrobials was higher in health facility level compared to referral hospital. By cross-checking of laboratory findings to antimicrobial prescriptions, an important part of children with positive bacterial infection have received antibiotic prescriptions although the majority without any infection have also received antibiotics.ConclusionDespite the good attitude of health care workers to adhere to diagnostic test results, antimalarials and antibiotics remain inappropriate prescribed to febrile children. The low specificity of malaria RDT used could be an important cause of these practices.

Epidemiological description of a protracted cholera outbreak in Tonj East and Tonj North counties, former Warrap State, South Sudan, May-Oct 2017

BackgroundOn 18th May 2017, State Ministry of Health of former Warrap State received a report from Tonj East County of an outbreak of acute watery diarrhoea and vomiting in Makuac payam. We conducted this investigation to confirm the causative organism and describe the epidemiology of the outbreak in order to support evidence-based control measures.MethodsWe defined a suspected case as a resident of Tonj East or Tonj North County with sudden onset of acute watery diarrhoea and vomiting between May 1 and October 15, 2017. A probable case was defined as a suspected case with a positive rapid test for Vibrio cholerae; a confirmed case was a probable case with a positive stool culture for V. cholerae. We conducted systematic case finding by visiting health facilities and villages in the affected payams. We reviewed patient records from 1 May 2017 to 15 October 2017, to identify suspected cholera case-patients. We conducted a descriptive epidemiologic study, examining the distribution of the cases. We computed the attack rates by age, sex, and payam of residence. Case fatality rate was calculated as the ratio of the total number of suspected cholera death to the total number of cholera case-patients. We conducted an oral cholera vaccination campaign after the peak of the outbreak to control and prevent the spread to other payams.ResultsWe identified 1451 suspected cholera cases between May and October 2017. Of these, 81% (21/26) had a positive rapid diagnostic test for V. cholerae; out of the 16 rectal swabs transported to the National Public Laboratory, 88% (14/16) were confirmed to be V. cholerae O1 serotype Inaba. The epidemic curve shows continuous common source outbreak with several peaks. The mean age of the case-patients was 24 years (Range: 0.2-75y). The clinical presentations of the case-patients were consistent with cholera. Males had an attack rate of 9.9/10000. The highest attack rate was in ≥30y (14 per 10,000). Among the six payams affected, Makuac had the highest attack rate of 3/100. The case fatality rate (CFR) was 3.0% (44/1451). Paliang and Wunlit had an oral cholera vaccination coverage of ≥100%, while 4 payams had a vaccination coverage of < 90%.ConclusionThis was a continuous common source cholera outbreak caused by V. cholerae 01 sero type Inaba. We recommended strengthening of the surveillance system to improve early detection and effective response.

Adherence of private sector providers to uncomplicated malaria management policy in Madagascar

IntroductionCette étude se propose d’évaluer l’adhérence des professionnels de santé du secteur privé à l'utilisation du TDR-palu (Test de Diagnostic Rapide-palu) et à la prescription de l’ACT (Artemisinin-based combination therapy) en cas de paludisme simple.MéthodesUne approche évaluative rétrospective et transversale a été menée en septembre et octobre 2015 auprès de 11 districts sanitaires repartis dans les quatre faciès épidémiologiques existant à Madagascar. Au total, 43 prestataires de soins issus de 39 formations sanitaires privées (FSP) ont été interviewés et visités.RésultatsLes prestataires déclarent avoir lu le manuel de prise en charge du paludisme dans 16,3% des cas (4/43). Seul le quart (25,6%) des prestataires dispose de TDR dans leur bureau. L’ACT a été cité par 83,7% des prestataires comme médicament de première intention pour traiter le paludisme simple. Dans la pratique, 55,6% des prestataires émettent des doutes sur les résultats des TDR. L’utilisation des antipaludéens malgré les résultats négatifs des TDR (38,2%) est plus fréquente chez ceux ayant émis des doutes (p = 0,03). Inversement, malgré un TDR positif, la moitié des prestataires ne prescrit pas d’ACT (50%). La non-participation aux revues périodiques du District sanitaire (p = 0,05) influence négativement l’adhérence aux politiques.ConclusionLa faible adhérence des prestataires de soin du secteur privé aux directives nationales sur la prise en charge des cas de paludisme simple interpelle sur l’intérêt d’encadrer davantage ce secteur.

Effect of malaria on the outcomes of sickle cell phenotypes in a semi-nomadic population

Studies have shown that malaria contribute significantly to mortality among infants and children with Sickle Cell Anemia (SCA). The nomadic lifestyle of the Fulanis make access to health care difficult and exposure to malaria high. We conducted a cross sectional study among consenting members of a semi-nomadic Fulani population in Nigeria to determine the impact of malaria on the outcome of SCA. On-the-spot malaria rapid diagnostic test (RDT) and hemoglobin electrophoresis were done. A total of 229 subjects participated, 100 (43.7%) females. Median age was 35 years (yrs) with range of 15-80 yrs. Hemoglobin AS phenotype was found among 53 (23.1%) subjects; none had hemoglobin SS. A positive malaria RDT was found among 24 (10.5%) individuals. The FGD revealed that majority of the respondents considered malaria as an important cause of ill-health but were not aware of SCA as an important disease. The high prevalences of malaria, hemoglobin AS phenotype, and absent of hemoglobin SS in the community implies the potentially fatal effect of malaria on individuals with hemoglobin SS. A comprehensive intervention to reach this vulnerable population is thus recommended.

Molecular Surveillance of Plasmodium falciparum Drug Resistance Markers in Clinical Samples from Botswana.

Drug-resistant Plasmodium falciparum is a major threat to global malaria control and elimination efforts. In Botswana, a southern African country approaching malaria elimination, P. falciparum molecular data are not available. Parasites were assessed through pollymerase chain reaction (PCR) for confirmation of positive rapid diagnostic tests, multiplicity of infection (MOI), and drug resistance markers among isolates from clinical uncomplicated malaria cases collected at health facilities. Of 211 dried blood spot samples selected for the study, 186 (88.2%) were PCR positive for P. falciparum. The mean MOI based on MSP1 genotyping was 2.3 and was not associated with age. A high prevalence of wild-type parasites for pfcrt and pfmdr1 was found, with a haplotype frequency (K76/N86) of 88.8% and 17.7% of the isolates having two copies of the pfmdr1 gene. For pfATPase6, all the parasites carried the wild-type S769 allele. Sequencing showed no evidence of non-synonymous mutations associated with reduced artemisinin derivative sensitivity in the P. falciparum k13 gene. In conclusion, we found that P. falciparum parasites in Botswana were mostly wild type for the drug resistance markers evaluated. Yet, there was a high rate of a molecular marker associated to reduced sensitivity to lumefantrine. Our results indicate the need for systematic drug efficacy surveillance to complement malaria elimination efforts.

2054. Physician Responses to Positive Rapid Diagnostic Tests for Candida Fungemia in the Absence of Concomitant Positive Blood Cultures

Background Candida species are the fourth leading cause of nosocomial bloodstream infections in the United States. Unfortunately, detection, identification and susceptibility testing using standard instrumented blood culture systems and routine microbiological techniques may take 4–10 days. Moreover, sensitivity of routine blood cultures for candidemia is only ~50 to 75%. The T2 Candida Panel (T2CP) is an FDA-approved assay that rapidly detects the presence of five Candida species directly from whole blood in 3–5 hours. We examined mortality and antifungal therapy (AFT) decisions based on positive (pos) results of a T2CP in patients with negative (neg) blood cultures.MethodsWe performed a case series of all patients who had a pos T2CP with concomitant neg blood cultures at our institution from March 1, 2016 to March 1, 2018. If a patient had multiple valid T2CP, only the first pos result was used for analysis. Medical records were reviewed for demographics, comorbidities, risk factors for candida infection, length of stay, use and duration of AFT, and 14-day and in-hospital mortality from the time of the T2CP.ResultsFifteen patients were identified who met inclusion criteria. Eight patients were immunocompromised: four (26.7%) solid cancer malignancy, three (20%) hematologic malignancy, and one kidney transplant recipient. Pos T2CP results by species were as follows: 53.3% C. albicans/C. tropicalis, 40% C. parapsilosis, and 6.7% C. glabrata/C. krusei. Median SOFA, Charlson comorbidity index, and Candida scores were 6, 6, and 9, respectively. Fourteen-day mortality was 40% and in-hospital mortality was 53.3%. Only two patients were on prophylactic AFT due to an underlying hematologic malignancy at the time of T2CP; in both cases, azole AFT was replaced with an echinocandin in response to the pos T2CP. Of the remaining 13 patients who were not on prophylactic AFT, all were started on AFT after pos T2CP result.ConclusionPhysicians escalated or initiated AFT therapy based on pos T2CP in severely ill patients who had negative blood cultures. Unfortunately, the population had high severity index scores and high mortality despite initiation or escalation of AFT. We hypothesize that earlier testing and detection of Candida fungemia may lead to faster initiation of AFT and better outcomes.Disclosures All authors: No reported disclosures.

Identification and characterization of Loa loa antigens responsible for cross-reactivity with rapid diagnostic tests for lymphatic filariasis.

The Global Program to Eliminate Lymphatic Filariasis (LF) relies on rapid diagnostic tests (RDTs) to determine where annual mass drug administration for LF is required and when it can be stopped. These tests detect a Wuchereria bancrofti glycoprotein in the blood of infected persons via a carbohydrate moiety recognized by the monoclonal antibodies AD12 and DH6.5. Loiasis cross-reactivity with LF RDTs has recently been recognized as a serious obstacle to LF elimination in loiasis-endemic areas. To better understand the nature of this cross-reactivity, we used the DH6.5 antibody to immunoaffinity purify Loa loa antigens from the sera of individuals with a positive RDT due to loiasis. Immunoblot analysis revealed many circulating AD12/DH6.5-reactive antigens, and proteomic analysis identified multiple L. loa proteins in LF RDT-positive loiasis sera. These included both secreted and somatic proteins, suggesting that they may be released by dying L. loa adult worms and/or microfilariae. Unlike the single high molecular weight W. bancrofti circulating filarial antigen that is reliably present in the blood of persons with bancroftian filariasis, reactive L. loa antigens appeared to be only transiently present in the blood of a subset of persons with loiasis. These key differences between the circulating antigens of W. bancrofti and L. loa can be used to differentiate positive results generated by both species and may lead to improved diagnostic tests for LF and loiasis.

Malaria elimination in remote communities requires integration of malaria control activities into general health care: an observational study and interrupted time series analysis in Myanmar

BackgroundCommunity health workers (CHWs) can provide diagnosis and treatment of malaria in remote rural areas and are therefore key to the elimination of malaria. However, as incidence declines, uptake of their services could be compromised if they only treat malaria.MethodsWe conducted a retrospective analysis of 571,286 malaria rapid diagnostic tests conducted between 2011 and 2016 by 1335 CHWs supported by Medical Action Myanmar. We assessed rates of decline in Plasmodium falciparum and Plasmodium vivax incidence and rapid diagnostic test (RDT) positivity rates using negative binomial mixed effects models. We investigated whether broadening the CHW remit to provide a basic health care (BHC) package was associated with a change in malaria blood examination rates.ResultsCommunities with CHWs providing malaria diagnosis and treatment experienced declines in P. falciparum and P. vivax malaria incidence of 70% (95% CI 66–73%) and 64% (59–68%) respectively each year of operation. RDT positivity rates declined similarly with declines of 70% (95% CI 66–73%) for P. falciparum and 65% (95% CI 61–69%) for P. vivax with each year of CHW operation. In four cohorts studied, adding a BHC package was associated with an immediate and sustained increase in blood examination rates (step-change rate ratios 2.3 (95% CI 2.0–2.6), 5.4 (95% CI 4.0–7.3), 1.7 (95% CI 1.4–2.1), and 1.1 (95% CI 1.0.1.3)).ConclusionsCHWs have overseen dramatic declines in P. falciparum and P. vivax malaria in rural Myanmar. Expanding their remit to general health care has sustained community uptake of malaria services. In similar settings, expanding health services offered by CHWs beyond malaria testing and treatment can improve rural health care while ensuring continued progress towards the elimination of malaria.