Evaluation of a Rapid Diagnostic Test, Boson Biotech SARS CoV-2 Ag, for the Detection of SARS-CoV-2 in Gabon

1) Background: Rapid and acurate diagnostic testing for case identification, quarantine, and contact tracing is essential for managing the COVID 19 pandemic. Rapid antigen detection tests are available, however, it is important to evaluate their performances before use. We tested a rapid antigen detection of SARS-CoV-2, based on the immunochromatography (Boson Biotech SARS-CoV-2 Ag Test (Xiamen Boson Biotech Co., Ltd., China)) and the results were compared with the real time reverse transcriptase-Polymerase chain reaction (RT-PCR) (Gold standard) results;2) Methods: From November 2021 to December 2021, samples were collected from symptomatic patients and asymptomatic individuals referred for testing in a hospital during the second pandemic wave in Gabon. All these participants attending “CTA Angondjé”, a field hospital set up as part of the management of COVID-19 in Gabon. Two nasopharyngeal swabs were collected in all the patients, one for Ag test and the other for RT-PCR;3) Results: A total of 300 samples were collected from 189 symptomatic and 111 asymptomatic individuals. The sensitivity and specificity of the antigen test were 82.5% [95%CI 73.8 - 89.3] and 97.9 % [95%CI 92.2 - 98.2] respectively, and the diagnostic accuracy was 84.4% (95% CI: 79.8 - 88.3%). The antigen test was more likely to be positive for samples with RT-PCR Ct values ≤ 32, with a sensitivity of 89.8%;4) Conclusions: The Boson Biotech SARS-CoV-2 Ag Test has good sensitivity and can detect SARS-CoV-2 infection, especially among symptomatic individuals with low viral load. This test could be incorporated into efficient testing algorithms as an alternative to PCR to decrease diagnostic delays and curb viral transmission.

Secondary analysis of malaria rapid diagnostic tests from rounds 5–8 of WHO product testing with a focus on false-negative results

Despite the widespread use of malaria rapid diagnostic test(RDT)in clinical practice,there are a lot of challenges.We conducted a secondary analysis of 129 malaria RDT data from rounds 5–8 of the World Health Organization(WHO)product testing summary and discuss the causes of false-negative(FN)results with a focus on low parasite density,improper RDT storage,operation and interpretation,and Plasmodium falciparum with a pfhrp2/3 gene deletion.The results demonstrated that the malaria RDTs currently commercially available might cause FN results in practice.

Assessment of Rapid Diagnostic Tests Algorithms in Transfusion Medicine Setting

Background: The rapid diagnostic tests play a pivotal role in the screening of viral markers in blood qualification for transfusion in limited resource setting. Therefore, it is important to assess their analytical performances to ensure their proper functioning. Material and Methods: We performed a cross- sectional study by successive recruitment to assess the diagnostic value of rapid diagnostic tests algorithms using ELISA as a reference test. A total of 661 blood from donors were enrolled for this study. Rapid Diagnostic Tests (RDTs) and ELISA tests were performed for each sample by a couple of double-blinded biotechnologists. Data were collected on case report form and captured in Microsoft Excel then the file was imported and analyzed using R software version 4.0.3. Results: The diagnostic accuracy for the algorithms are summarized in Table 1. For HIV-algorithm, the internal validity parameters were as follow: sensitivity (sens) 99.0% (95% CI = 97.8, 99.5);specificity (spec) 98.3% (95% CI = 90.9, 99.7);positive likelihood ratio (PLR) 57.4 (95% CI = 8.2, 401.0);negative likelihood ratio (NLR) 0.01 (95% CI = 0.0005, 0.02);diagnostic odd ratio (DOR) 4710. HBV-Ag/Ab RDTs achieve the following diagnostic accuracy: sens 99.7% (95% CI = 98.3, 99.9);spec 98.8% (95% CI = 96.9, 95.5);PLR 81.8 (95% CI = 30.9, 217.0);NLR 0.003 (95% CI = 0.0004, 0.02);DOR 14,110. The analytical performances of HCV-Ab RDTs were as follow: sens 98.7% (95% CI = 97.5, 99.4);spec 93.1% (95% CI = 78.0, 98.1);PLR 14.3 (95% CI = 3.8, 54.5);NLR 1.5 (95% CI = 0.8, 2.8);DOR 962.6. The parameters evaluating the external validity of RDTs screening for the three viral markers when the theorical prevalence was < 5% are summarized in Figure 3. At the prevalence < 5%, the NPV of the three RDTs were 99.96%, 99.99% and 99.94%. At the same prevalence, we found the following Positive Predictive Values (PPV) 70.82%, 77.59% and 37.35% for HIV-Ag/Ab RDTs, HBV-Ag RDTs and HCV-Ab RDTs algorithms, respectively. The overall areas under the received operating characteristic (ROC) curves were 98.6%, 99.2% and 99.2%;95.9% for HIV-Ag/Ab RDTs, HBV-Ag RDTs and HCV-Ab RDTs algorithms, respectively. Conclusion: RDTs algorithms can play a pivotal role in the screening of HIV-Ab/Ag, HBs-Ag in the setting of resources limited-countries where financial and technical expertise shortages are a standard fare. However, their use for diagnostic purposes must be done with great caution and the result must necessarily be confirmed with an ELISA or molecular technique particularly for HCV-RDTs algorithm which achieved an NLR value > 0.1.

Cost-effectiveness analysis of malaria rapid diagnostic tests:a systematic review

Background:Rapid diagnostic tests(RDT)can effectively manage malaria cases and reduce excess costs brought by misdiagnosis.However,few studies have evaluated the economic value of this technology.The purpose of this study is to systematically review the economic value of RDT in malaria diagnosis.Main text:A detailed search strategy was developed to identify published economic evaluations that provide evidence regarding the cost-effectiveness of malaria RDT.Electronic databases including MEDLINE,EMBASE,Biosis Previews,Web of Science and Cochrane Library were searched from Jan 2007 to July 2018.Two researchers screened studies independently based on pre-specified inclusion and exclusion criteria.The Consolidated Health Economic Evaluation Reporting Standards(CHEERS)checklist was applied to evaluate the quality of the studies.Then cost and effectiveness data were extracted and summarized in a narrative way.Fifteen economic evaluations of RDT compared to other diagnostic methods were identified.The overall quality of studies varied greatly but most of them were scored to be of high or moderate quality.Ten of the fifteen studies reported that RDT was likely to be a cost-effective approach compared to its comparisons,but the results could be influenced by the alternatives,study perspectives,malaria prevalence,and the types of RDT.Conclusions:Based on available evidence,RDT had the potential to be more cost-effective than either microscopy or presumptive diagnosis.Further research is also required to draw a more robust conclusion.

Cost-effectiveness analysis of malaria rapid diagnostic test in the elimination setting

Background:As more and more countries approaching the goal of malaria elimination,malaria rapid diagnostic tests(RDT)was recomendated to be a diagnostic strategy to achieve and maintain the statute of malaria free,as it’s less requirments on equipment and experitise than microscopic examination.But there are very few economic evaluations to confirm whether RDT was cost-effective in the setting of malaria elimination.This research aimed to offer evidence for helping decision making on malaria diagnosis strategy.Methods:A cost-effectiveness analysis was conducted to compare RDT with microscopy examination for malaria diagnosis,by using a decision tree model.There were three strategies of malaria diagnostic testing evaluated in the model,1)microscopy,2)RDT,3)RDT followed by microscopy.The effect indicator was defined as the number of malaria cases treated appropriately.Based on the joint perspective of health sector and patient,costs data were collected from hospital information systems,key informant interviews,and patient surveys.Data collection was conducted in Jiangsu from September 2018 to January 2019.Epidemiological data were obtained from local malaria surveillance reports.A hypothetical cohort of 300000 febrile patients were simulated to calculate the total cost and effect of each strategy.One-way,two-way,and probabilistic sensitivity analysis were performed to test the robustness of the result.Results:The results showed that RDT strategy was the most effective(245 cases)but also the most costly(United States Dollar[USD]4.47 million)compared to using microscopy alone(238 cases,USD 3.63 million),and RDT followed by microscopy(221 cases,USD 2.75 million).There was no strategy dominated.One-way sensitivity analysis reflected that the result was sensitive to the change in labor cost and two-way sensitivity analysis indicated that the result was not sensitive to the proportion of falciparum malaria.The result of Monte Carlo simulation showed that RDT strategy had higher effects and higher cost than other strategies with a high probability.Conclusions:Compared to microscopy and RDT followed by microscopy,RDT strategy had higher effects and higher cost in the setting of malaria elimination.

Evaluating the implementation of rapid diagnostic tests in a malaria elimination setting

Background It was recommended that malaria rapid diagnostic tests(RDTs)should be available in all epidemiological situations.But evidence was limited on the implementation of RDTs and its effectiveness in malaria elimination settings.This study examined the implementation of RDTs and how it affected the diagnosis of imported malaria patients in Jiangsu Province,China.Methods To scale up RDTs,this study developed an intervention package with four major elements covering the supply of RDT test,the training on RDTs,the monitoring and management of RDT use,and the advocacy of RDTs.By using a pretest-posttest control group design,we implemented the interventions in 4 cities in Jiangsu Province with the rest nine cities as controlled areas,from January 2017 to January 2018.Difference-in-Difference approach was used to evaluate the impact of the scale-up of RDTs on the identification of malaria cases.Three binary outcome measures were included to indicate delayed malaria diagnosis,malaria cases with confirmed malaria diagnosis at township-level institutions,and severe malaria cases,respectively.Linear probability regression was performed with time and group fixed effects and the interaction term between time and group.Results Intervention areas received sufficient RDT test supply,regular professional training programs,monthly tracking and management of RDT supply and use,and health education to targeted population.The implementation of interventions was associated with 10.8%(P=0.021)fewer patients with delayed diagnosis.But intervention areas did not see a higher likelihood of having confirmed diagnosis from township-level institutions(coefficient=-0.038,P=0.185)or reduced severe malaria cases(coef.=0.040,P=0.592).Conclusions The comprehensive package of RDT implementation in this study is promising in scaling up RDT use and improving access to care among malaria patients,especially in malaria elimination settings.

Ultrabright NIR AIEgen nanoparticles-enhanced lateral flow immunoassay platform for accurate diagnostics of complex samples

Accurate and sensitive near-infrared(NIR)luminescent lateralflow immunoassay(LFIA)has attracted considerable attention in thefield of point-of-care testing(POCT).However,the detection accuracy and sensitivity are often compromised by the lowfluorescence quantum efficiency of the NIRfluorescent probe.(<10%)Herein,ultrabright NIR AIEgen nanoparticles(PS@AIE830NPs)composed of polystyrene(PS)nanoparticles and NIR aggregation-induced emission luminogen(AIEgen)with the maximum emission at 830 nm(AIE830)is reported,and its poten-tial to promote an accurate and sensitive detection of complex samples by LFIA is described.The relative quantum yield(QY)of the PS@AIE830NPs was 14.76%,which was superior to that of the polymer embedding method and indocyanine green(ICG)-based NIR nanoparticles.The PS@AIE830NPs immunolabeled-LFIA com-bined with laboratory-built NIR-LFIA portable quantitative instruments(detected light range 800 nm)completely eliminated background interference and allowed>highly accurate and sensitive detection without any pre-treatment steps.The limits of detection(LODs)for aflatoxin B1(AFB1)in soy sauce,alpha hemolysin(Hla)of Staphylococcus aureus biomarker in jointfluid,and C-reactive protein(CRP)in human haemolysed samples were 0.01 ng mL-1,0.02µg mL-1,and 0.156 mg L-1,respectively,commensurating with those of the corresponding gold standard assays and covering the detection range of interests.It is anticipated that the ultrabright NIR AIEgen nanoparticles will serve as a universally applicable signal probe for NIR-LFIA diagnostics,promising to expand the range of applications for quantitative detection of complex samples.

Integrating innovations:a qualitative analysis of referral non-completion among rapid diagnostic test-positive patients in Uganda’s human African trypanosomiasis elimination programme

Background:The recent development of rapid diagnostic tests(RDTs)for human African trypanosomiasis(HAT)enables elimination programmes to decentralise serological screening services to frontline health facilities.However,patients must still undertake multiple onwards referral steps to either be confirmed or discounted as cases.Accurate surveillance thus relies not only on the performance of diagnostic technologies but also on referral support structures and patient decisions.This study explored why some RDT-positive suspects failed to complete the diagnostic referral process in West Nile,Uganda.Methods:Between August 2013 and June 2015,85%(295/346)people who screened RDT-positive were examined by microscopy at least once;10 cases were detected.We interviewed 20 RDT-positive suspects who had not completed referral(16 who had not presented for their first microscopy examination,and 4 who had not returned for a second to dismiss them as cases after receiving discordant[RDT-positive,but microscopy-negative results]).Interviews were analysed thematically to examine experiences of each step of the referral process.Results:Poor provider communication about HAT RDT results helped explain non-completion of referrals in our sample.Most patients were unaware they were tested for HAT until receiving results,and some did not know they had screened positive.While HAT testing and treatment is free,anticipated costs for transportation and ancillary health services fees deterred many.Most expected a positive RDT result would lead to HAT treatment.RDT results that failed to provide a definitive diagnosis without further testing led some to question the expertise of health workers.For the four individuals who missed their second examination,complying with repeat referral requests was less attractive when no alternative diagnostic advice or treatment was given.Conclusions:An RDT-based surveillance strategy that relies on referral through all levels of the health system is inevitably subject to its limitations.In Uganda,a key structural weakness was poor provider communication about the possibility of discordant HAT test results,which is the most common outcome for serological RDT suspects in a HAT elimination programme.Patient misunderstanding of referral rationale risks harming trust in the whole system and should be addressed in elimination programmes.

Performance of three rapid diagnostic tests for the detection of Cryptosporidium spp.and Giardia duodenalis in children with severe acute malnutrition and diarrhoea

Background:There is significant need for accurate diagnostic tools for Cryptosporidium spp.and Qiordia duodenalis infections in resource limited countries where diarrhoeal disease caused by these parasites is often prevalent.The present study assessed the diagnostic performance of three commercially available rapid diagnostic tests(RDTs)based on faecal-antigen detection for Cryptosporidium spp.and/or G.duodenalis infections in stool samples of children admitted with severe acute malnutrition(SAM)and diarrhoea.An established multiplex PCR was used as reference test.Methods:Stool samples from children with SAM and diarrhoea enrolled in a randomized controlled trial(registered at clinicaltrials.gov/ct2/show/NCT02246296)in Malawi(n=175)and Kenya(n=120)between December 2014 and December 2015 were analysed by a multiplex PCR for the presence of Cryptosporidium sppv G.duodenalis or Entomoebo histolytica parasite DNA.Cryptosporidium-positive samples were species typed using restriction fragment length polymorphism analysis.A sub-sample of the stool specimens(n=236)was used for testing with three different RDTs.Diagnostic accuracy of the tests under evaluation was assessed using the results of PCR as reference standard using MedCalc software.Pearson Chi-square test and Fisher's exact test were used to determine(significant)difference between the number of cryptosporidiosis or giardiasis cases found by PCR in Malawi and Kenya.The overall diagnostic accuracy of each RDT was calculated by plotting a receiver operating characteristic(ROC)curve for each test and to determine the area under the curve(AUC)using SPSS8 software.Results:Prevalence of Cryptosporidium spp.by PCR was 20.0 and 21.7%in Malawi and Kenya respectively,mostly C.hominis.G.duodenalis prevalence was 23.4 and 5.8%in Malawi and Kenya respectively.E histolytica was not detected by PCR.RDT testing followed the same pattern of prevalence.RDT sensitivities ranged for cryptosporidiosis from 42.9 to 76.9%and for G.duodenalis from 48.2 to 85.7%.RDT specificities ranged from 88.4 to 100%for Cryptosporidium spp.and from 91.2 to 99.2%for G.duodenalis infections.Based on the estimated area under the curve(AUC)values,all tests under evaluation had an acceptable overall diagnostic accuracy(>0.7),with the exception of one RDT for Cryptosporidium spp.in Malawi.Conclusions:All three RDTs for Cryptosporidium spp.and Giardia duodenalis evaluated in this study have a moderate sensitivity,but sufficient specificity.The main value of the RDTs is within their rapidness and their usefulness as screening assays in surveys for diarrhoea.

Performance of clinical signs and symptoms,rapid and reference laboratory diagnostic tests for diagnosis of human African trypanosomiasis by passive screening in Guinea:a prospective diagnostic accuracy study

Background Passive diagnosis of human African trypanosomiasis(HAT)at the health facility level is a major component of HAT control in Guinea.We examined which clinical signs and symptoms are associated with HAT,and assessed the performance of selected clinical presentations,of rapid diagnostic tests(RDT),and of reference laboratory tests on dried blood spots(DBS)for diagnosing HAT in Guinea.Method The study took place in 14 health facilities in Guinea,where 2345 clinical suspects were tested with RDTs(HAT Sero-K-Set,rHAT Sero-Strip,and SD Bioline HAT).Seropositives underwent parasitological examination(reference test)to confirm HAT and their DBS were tested in indirect enzyme-linked immunoassay(ELISA)/Trypanosoma brucei gambiense,trypanolysis,Loopamp Trypanosoma brucei Detection kit(LAMP)and m18S quantitative PCR(qPCR).Multivariable regression analysis assessed association of clinical presentation with HAT.Sensitivity,specificity,positive and negative predictive values of key clinical presentations,of the RDTs and of the DBS tests for HAT diagnosis were determined.Results The HAT prevalence,as confirmed parasitologically,was 2.0%(48/2345,95%CI:1.5–2.7%).Odds ratios(OR)for HAT were increased for participants with swollen lymph nodes(OR=96.7,95%CI:20.7–452.0),important weight loss(OR=20.4,95%CI:7.05–58.9),severe itching(OR=45.9,95%CI:7.3–288.7)or motor disorders(OR=4.5,95%CI:0.89–22.5).Presence of at least one of these clinical presentations was 75.6%(95%CI:73.8–77.4%)specific and 97.9%(95%CI:88.9–99.9%)sensitive for HAT.HAT Sero-K-Set,rHAT Sero-Strip,and SD Bioline HAT were respectively 97.5%(95%CI:96.8–98.1%),99.4%(95%CI:99.0–99.7%)and 97.9%(95%CI:97.2–98.4%)specific,and 100%(95%CI:92.5–100.0%),59.6%(95%CI:44.3–73.3%)and 93.8%(95%CI:82.8–98.7%)sensitive for HAT.The RDT’s positive and negative predictive values ranged from 45.2–66.7%and 99.2–100%respectively.All DBS tests had specificities≥92.9%.While LAMP and m18S qPCR sensitivities were below 50%,trypanolysis and ELISA/T.b.gambiense had sensitivities of 85.3%(95%CI:68.9–95.0%)and 67.6%(95%CI:49.5–82.6%).Conclusions Presence of swollen lymph nodes,important weight loss,severe itching or motor disorders are simple but accurate clinical criteria for HAT referral in HAT endemic areas in Guinea.Diagnostic performances of HAT Sero-K-Set and SD Bioline HAT are sufficient for referring positives to microscopy.Trypanolysis on DBS may discriminate HAT patients from false RDT positives.

Study of Malaria in Patients Operated on at the Reference Health Center of Commune I Bamako

Malaria is a febrile and hemolyzing erythrocytopathy due to the development and multiplication of one or more of the five plasmodial species dependent on humans: Plasmodium falciparum, P. malariae, P. ovale, P. vivax and P. knowlesi. These parasites are inoculated into humans by the infective bite of a female mosquito, female anopheles of the genus Anopheles, during a blood meal. The study aimed to: determine the frequency of fever due to malaria after surgery;describe malaria symptomatology and clinical evolution after surgical intervention;determine the average length of hospital stay for operated patients with malaria;evaluate the average cost of malaria treatment. This was a prospective study which involved 110 operated patients, which took place over a period of 12 months from March 2017 to February 2018 in the general surgery department at the Reference Health Center of commune I of the Bamako district. The frequency of malaria was 11.82% before the intervention and 3.64% after the intervention, with an average age of 29.80 years;extremes of 2 years and 76 years and a sex ratio of 1.5 in favor of the male sex. The main clinical signs were fever (38.18%), headache (20.91%) and vomiting (36.36%) and physical asthenia (18.18%). Diagnosed and treated early, malaria progressed favorably. The outcome was simple for all our patients and we did not record any deaths. The cost of treatment was borne by the patients and/or their families. The average cost of treatment was 7915 CFA francs, significantly below the Malian minimum wage which is around 30,000 FCFA. The implementation of preventive measures is necessary to reduce the importance of malaria in hospitals: staff awareness, indoor spraying, use of impregnated mosquito nets.

Predominance of Plasmodium malariae-falciparum Co-Infection by Molecular Speciation in Bangolan, North West Region of Cameroon

Although microscopy still remains the gold standard for the diagnosis of malaria, rapid diagnostic tests （RDTs） and PCR assays have been shown to be sensitive and specific. Very few comparative studies have been reported of the three diagnostic methods on the same samples in vulnerable groups. Microscopy, RDTs and PCR assays were used for detection and speciation of Plasmodium falciparum （P）＇）, Plasmodium malariae （Pm） and Plasmodium ovale （Po） in patients in a rice culture savanna ecotype. Fifty four children and 16 pregnant women presenting with a fever were recruited. Bloods collected was used for thin and thick smears, perform RDTs and spotted blood on filter paper for DNA extraction and performance of a PCR. Mean parasitaemia was 37,619.06 （＋ 33,599.04） p/pL and 7,512.5 （＋ 12,446.11） p/μL for children and pregnant women, respectively. A total of 87.14% were positive by microscopy, 85.71% by RDTs and 90% by PCR. Distribution of Plasmodium species as identified by PCR was 72.86% Pf/Pm, 11.43% Pf/Pm/Po and 5.43% Pm while 10% were negative. Cohen＇s Kappa value for PCR and RDTs was K = 0.75 （CI = 0.28-1.22） while PCR and microscopy was K = 0.64 （CI = 0.18-1.10）. Malaria infection in Bangolan was mostly due to mix infection predominantly P. falciparum/P, malariae.

Assessment of HRP2-Based RDT in Diagnosing Malaria Cases

Background： HRP2-based Rapid Diagnostic Tests （RDTs） for malaria ensure a rational use of artemisinin-based combination therapy （ACT）. The HRP2 antigen can go through the cerebrospinal fluid （CSF）. Purpose： To assess the HRP2-based RDT in malaria and detect the HRP2 in CSF. Methods： From November 2006 to May 2007, all patients under 15 years showing clinical symptoms of malaria were included. RDT was performed on the CSF and peripheral blood. Results： Out of the 951 patients included, 131 （13.7%） were confirmed through RDT and 130 （13.6%） through thick blood smear. Sensitivity and specificity stood at 96.96% and 99.71% respectively, for uncomplicated cases and at 100% and 99.13% for severe cases. Tests to detect HRP2 in the CSF of 52 cases were negative. Conclusion： Tests to detect HRP2 in the CSF could make it possible to diagnose severe malaria cases when peripheral parasitemia would be below the detection threshold.

Performance of the procedure for ultra-rapid extraction and loop-mediated isothermal amplifcation (PURE-LAMP) method to detect malaria in Haiti

Background Malaria continues to cause burden in various parts of the world.Haiti,a Caribbean country,is among those aiming to eliminate malaria within a few years.Two surveys were conducted in Haiti during which we aimed to evaluate the performance of the simple and rapid procedure for ultra-rapid extraction-loop-mediated isothermal amplifcation(PURE-LAMP)method with dried blood spots as an alternative diagnostic method for malaria in the context of low to very low rates of transmission.Methods Febrile and afebrile people were recruited from three administrative divisions within Haiti:Nippes,Sud and Grand’Anse,during the summers of 2017(early August to early September)and 2018(late July to late August).Their blood samples were tested by microscopy,rapid diagnostic tests(RDT),PURE-LAMP and nested PCR to detect Plasmodium infection.Sensitivity,specifcity,positive and negative predictive values and kappa statistics were estimated with the nested PCR results as the gold standard.Results Among 1074 samples analyzed,a positive rate of 8.3%was calculated based on the nested PCR results.Among febrile participants,the rates in 2017 and 2018 were 14.6%and 1.4%,respectively.Three positives were detected among 172 afebrile participants in 2018 by PURE-LAMP and nested PCR,and all three were from the same locality.There was no afebrile participants recruited in 2017.The PURE-LAMP,RDT and microscopy had respective sensitivities of 100%,85.4%and 49.4%.All of the testing methods had specifcities over 99%.Conclusions This study confrmed the high performance of the PURE-LAMP method to detect Plasmodium infection with dried blood spots and recommends its use in targeted mass screening and treatment activities in low endemic areas of malaria.

Comparison of conventional and non-invasive diagnostic tools for detecting Plasmodium falciparum infection in southwestern Cameroon:a cross-sectional study

Background:Malaria remains a significant health challenge in sub-Saharan Africa,with early diagnosis critical to reducing its morbidity and mortality.Despite the increasing Plasmodium spp.diagnostic capabilities,access to testing is limited in some cases by the almost absolute requirement for blood from potentially infected subjects as the only sample source for all conventional methods.A rapid test on non-invasive specimen with comparable performance to microscopy for the screening or diagnosis of all participants is invaluable.This study sought to compare conventional and non-invasive diagnostic tools for detecting Plasmodium falciparum.

Epidemiology of onchocerciasis-associated epilepsy in the Mbam and Sanaga river valleys of Cameroon:impact of more than 13 years of ivermectin

Background:A high epilepsy prevalence has been reported in several onchocerciasis-endemic villages along the Mbam and Sanaga river valleys in Cameroon,including Bilomo and Kelleng.We sought to determine the prevalence of epilepsy in these two villages following more than 13 years of community-directed treatment with ivermectin(CDTI).Methods:Door-to-door surveys were performed on the entire resident population in the villages in August 2017 and January 2018.Epilepsy was diagnosed using a 2-step approach:administration of a standardized 5-item questionnaire followed by confirmation by a neurologist.Previously published diagnostic criteria for onchocerciasis-associated epilepsy(OAE)were used.Ov16 serology was done for children aged 7-10 years to assess onchocerciasis transmission.Findings were compared with previous data from these two villages.Results:A total of 1525 individuals(1321 in Bilomo and 204 in Kelleng)in 233 households were surveyed in both villages.The crude prevalence of epilepsy was 4.6%in Bilomo(2017)and 7.8%in Kelleng(2018),including 12(15.6%of cases)persons with epilepsy(PWE)with nodding seizures.The age and sex-standardized prevalence in Kelleng decreased from 13.5%in 2004 to 9.3%in 2018(P<0.001).The median age of PWE shifted from 17(IQR:12-22)years to 24(IQR:20-30)years in Bilomo(P<0.001);and slightly from 24(IQR:14-34)years to 28(IQR:21.25-36.75)years in Kelleng(P=0.112).Furthermore,47.6%of all tested children between 7 and 10 years had Ov16 antibodies.Conclusions:There is a decrease in epilepsy prevalence after 13 years and more of CDTI in both villages.The age-shift observed in PWE suggests that ivermectin may prevent OAE in younger residents.Ov16 seropositivity in children indicates ongoing onchocerciasis transmission possibly due to suboptimal control measures.Our findings support the existence of OAE in Cameroon and highlight the need to strengthen onchocerciasis elimination programs.

Impact of five annual rounds of mass drug administration with ivermectin on onchocerciasis in Sierra Leone

Background:Onchocerciasis is endemic in 12 of the 14 health districts of Sierra Leone.Good treatment coverage of community-directed treatment with ivermectin was achieved between 2005 and 2009 after the 11-year civil conflict.Sentinel site surveys were conducted in 2010 to evaluate the impact of five annual rounds of ivermectin distribution.Methods:In total,39 sentinel villages from hyper-and meso-endemic areas across the 12 endemic districts were surveyed using skin snips in 2010.Results were analyzed and compared with the baseline data from the same 39 villages.Results:The average microfilaridermia(MF)prevalence across 39 sentinel villages was 53.10%at baseline.The MF prevalence was higher in older age groups,with the lowest in the age group of 1-9 years(11.00%)and the highest in the age group of 40-49 years(82.31%).Overall mean MF density among the positives was 28.87 microfilariae(mf)/snip,increasing with age with the lowest in the age group of 1-9 years and the highest in the age group of 40-49 years.Males had higher MF prevalence and density than females.In 2010 after five rounds of mass drug administration,the overall MF prevalence decreased by 60.26%from 53.10%to 21.10%;the overall mean MF density among the positives decreased by 71.29%from 28.87 mf/snip to 8.29 mf/snip;and the overall mean MF density among all persons examined decreased by 88.58%from 15.33 mf/snip to 1.75 mf/snip.Ten of 12 endemic districts had>50%reduction in MF prevalence.Eleven of 12 districts had≥50%reduction in mean MF density among the positives.Conclusions:A significant reduction of onchocerciasis MF prevalence and mean density was recorded in all 12 districts of Sierra Leone after five annual MDAs with effective treatment coverage.The results suggested that the onchocerciasis elimination programme in Sierra Leone was on course to reach the objective of eliminating onchocerciasis in the country by the year 2025.Annual MDA with ivermectin should continue in all 12 districts and further evaluations are needed across the country to assist the NTDP with programme decision making.

Distribution of Plasmodium spp.infection in asymptomatic carriers in perennial and low seasonal malaria transmission settings in West Africa

countries in West Africa remain a hotspot for malaria with all age groups at risk.Asymptomatic carriers of Plasmodium spp.are important sources of infections for malaria vectors and thus contribute to the anchoring of the disease in favourable eco-epidemiological settings.The objective of this study was to assess the asymptomatic malaria case rates in Korhogo and Kaedi,two urban areas in northern Côte d’Ivoire and southern Mauritania,respectively.Methods:Cross-sectional surveys were carried out during the rainy season in 2014 and the dry season in 2015 in both settings.During each season,728 households were randomly selected and a household-based questionnaire was implemented to collect demographic and epidemiological data,including of malaria preventive methods used in communities.Finger-prick blood samples were obtained for biological examination using microscopy and rapid diagnostic tests(RDTs).Results:Overall,2672 households and 15858 consenting participants were surveyed.Plasmodium spp.infection was confirmed in 12.4%(n=832)and 0.3%(n=22)of the assessed individuals in Korhogo and Kaedi,respectively.In Korhogo,the prevalence of asymptomatic malaria was 10.5%(95%CI:9.7-11.2)as determined by microscopy and 9.3%(95%CI:8.6-10.0%)when assessed by RDT.In Kaedi,asymptomatic malaria prevalence was 0.2%(95%CI:0.1-0.4%)according to microscopy,while all RDTs performed were negative(n=8372).In Korhogo,asymptomatic malaria infection was significantly associated with age and season,with higher risk within the 5-14 years-old,and during the rainy season.In Kaedi,the risk of asymptomatic malaria infection was associated with season only(higher during the dry season;crude OR(cOR):6.37,95%CI:1.87-21.63).P.falciparum was the predominant species identified in both study sites representing 99.2%(n=825)in Korhogo and 59.1%(n=13)in Kaedi.Gametocytes were observed only in Korhogo and only during the rainy season at 1.3%(95%CI:0.7-2.4%).Conclusions:Our findings show a low prevalence of clinical malaria episodes with a significant proportion of asymptomatic carriers in both urban areas.National policies for malaria infections are focused on treatment of symptomatic cases.Malaria control strategies should be designed for monitoring and managing malaria infections in asymptomatic carriers.Additional measures,including indoor residual spraying,effective use of long-lasting insecticidal nets is strongly needed to reduce the number of Plasmodium spp.infections in Korhogo and Kaedi.

Burden and factors associated with schistosomiasis and soil-transmitted helminth infections among school-age children in Huambo,Uige and Zaire provinces,Angola

Background:Schistosomiasis and soil-transmitted helminths(STHs)contribute high disease burdens amongst the neglected tropical diseases(NTDs)and are public health problems in Angola.This study reports the prevalence,intensity and risk factors for schistosomiasis and STH infection in Huambo,Uige and Zaire provinces,Angola,to inform a school-based preventive chemotherapy program.Methods:A two-stage cluster design was used to select schools and schoolchildren to participate in parasitological and water,sanitation and hygiene(WASH)surveys across Huambo,Uige,and Zaire provinces.Point-of-care circulating cathodic antigen and urinalysis rapid diagnostic tests(RDTs)were used to determine the prevalence of Schistosoma mansoni and S.haematobium,respectively.Kato-Katz was used to identify and quantify STH species and quantify and compare with RDTs for S.mansoni.Urine filtration was used to quantify and compare with RDTs for S.haematobium.Descriptive statistics were used for prevalence and infection intensity of schistosomiasis and STH infection.Performance of RDTs was assessed through specificity and Cohen’s Kappa agreement with microscopy.A multivariate regression analysis was used to determine demographic and WASH factors associated with schistosomiasis and STH infection.Results:A total 575 schools and 17,093 schoolchildren participated in the schistosomiasis survey,of which 121 schools and 3649 schoolchildren participated in the STH survey.Overall prevalence of S.mansoni was 21.2%(municipality range 0.9–74.8%)and S.haematobium 13.6%(range 0–31.2%),with an overall prevalence of schistosomiasis of 31.4%(range 5.9–77.3%).Overall prevalence of Ascaris lumbricoides was 25.1%(range 0–89.7%),hookworm 5.2%(range 0–42.6%),and Trichuris trichiura 3.6%(range 0–24.2%),with an overall prevalence of STH infection of 29.5%(range 0.8–89.7%).Ecological zone and ethnicity were factors associated with schistosomiasis and STH infection,with older age and female sex additional risk factors for S.haematobium.Conclusions:Most municipalities met World Health Organization defined prevalence thresholds for a schistosomiasis preventive chemotherapy program.A STH preventive chemotherapy program is indicated for nearly all municipalities in Uige and select municipalities in Huambo and Zaire.The association between ecological zone and ethnicity with schistosomiasis and STH infection necessitates further evaluation of home and school environmental,sociodemographic and behavioural factors to inform targeted control strategies to complement preventive chemotherapy programs.

Prevalence of Plasmodium falciparum isolates lacking the histidine rich protein 2 gene among symptomatic malaria patients in Kwilu Provinee of the Democratic Republic of Congo

Background:Malaria rapid diagnostic tests have become a primary and critical tool for malaria diagnosis in malariaendemic countries where Plasmodium falciparum Histidine Rich Protein 2-based rapid diagnostic tests(PflHRP2-based RDTs)are widely used.However,in the last decade,the accuracy of PflHRP2-based RDTs has been challenged by the emerge nee of P.falciparum strains harbouring deletions of the P.falciparum histidine rich protein 2(pflnrp2)gene,resulting in false-negative results.In the Democratic Republic of Congo(D.R.Congo),little is known about the prevalence of the pfhrp2 gene deletion among P.falciparum isolates infecting symptomatic patients,especially in low to moderate transmission areas where pfhrp2 deletion parasites are assumed to emerge and spread.Here we determine the local prevalence and factors associated with pfhrp2 gene deletions among symptomatic malaria patients in the Kwilu Province of the D.R.Congo.