Malaria Rapid Diagnostic Tests Research Articles

Cost-Effectiveness of Test-and-Treat Strategies to Reduce the Antibiotic Prescription Rate for Acute Febrile Illness in Primary Healthcare Clinics in Africa.

Inappropriate antibiotic use increases selective pressure, contributing to antimicrobial resistance. Point-of-care rapid diagnostic tests (RDTs) would be instrumental to better target antibiotic prescriptions, but widespread implementation of diagnostics for improved management of febrile illnesses is limited. Our study aims to contribute to evidence-based guidance to inform policymakers on investment decisions regarding interventions that foster more appropriate antibiotic prescriptions, as well as to address the evidence gap on the potential clinical and economic impact of RDTs on antibiotic prescription. A country-based cost-effectiveness model was developed for Burkina Faso, Ghana and Uganda. The decision tree model simulated seven test strategies for patients with febrile illness to assess the effect of different RDT combinations on antibiotic prescription rate (APR), costs and clinical outcomes. The incremental cost-effectiveness ratio (ICER) was expressed as the incremental cost per percentage point (ppt) reduction in APR. For Burkina Faso and Uganda, testing all patients with a malaria RDT was dominant compared to standard-of-care (SoC) (which included malaria testing). Expanding the test panel with a C-reactive protein (CRP) test resulted in an ICER of $0.03 and $0.08 per ppt reduction in APR for Burkina Faso and Uganda, respectively. For Ghana, the pairwise comparison with SoC-including malaria and complete blood count testing-indicates that both testing with malaria RDT only and malaria RDT + CRP are dominant. The use of RDTs for patients with febrile illness could effectively reduce APR at minimal additional costs, provided diagnostic algorithms are adhered to. Complementing SoC with CRP testing may increase clinicians' confidence in prescribing decisions and is a favourable strategy.

Mixed-method evaluation study of a targeted mass drug administration of long-acting anti-malarials among children aged 3 months to 15 years in the Bossangoa sub-prefecture, Ouham, Central African Republic, during the COVID-19 pandemic

BackgroundIn 2020, during the COVID-19 pandemic, Médecins Sans Frontières (MSF) initiated three cycles of dihydroartemisin-piperaquine (DHA-PQ) mass drug administration (MDA) for children aged three months to 15 years within Bossangoa sub-prefecture, Central African Republic. Coverage, clinical impact, and community members perspectives were evaluated to inform the use of MDAs in humanitarian emergencies.MethodsA household survey was undertaken after the MDA focusing on participation, recent illness among eligible children, and household satisfaction. Using routine surveillance data, the reduction during the MDA period compared to the same period of preceding two years in consultations, malaria diagnoses, malaria rapid diagnostic test (RDT) positivity in three MSF community healthcare facilities (HFs), and the reduction in severe malaria admissions at the regional hospital were estimated. Twenty-seven focus groups discussions (FGDs) with community members were conducted.ResultsOverall coverage based on the MDA card or verbal report was 94.3% (95% confidence interval (CI): 86.3–97.8%). Among participants of the household survey, 2.6% (95% CI 1.6–40.3%) of round 3 MDA participants experienced illness in the preceding four weeks compared to 30.6% (95% CI 22.1–40.8%) of MDA non-participants. One community HF experienced a 54.5% (95% CI 50.8–57.9) reduction in consultations, a 73.7% (95% CI 70.5–76.5) reduction in malaria diagnoses, and 42.9% (95% CI 36.0–49.0) reduction in the proportion of positive RDTs among children under five. A second community HF experienced an increase in consultations (+ 15.1% (− 23.3 to 7.5)) and stable malaria diagnoses (4.2% (3.9–11.6)). A third community HF experienced an increase in consultations (+ 41.1% (95% CI 51.2–31.8) and malaria diagnoses (+ 37.3% (95% CI 47.4–27.9)). There were a 25.2% (95% CI 2.0–42.8) reduction in hospital admissions with severe malaria among children under five from the MDA area. FGDs revealed community members perceived less illness among children because of the MDA, as well as fewer hospitalizations. Other indirect benefits such as reduced household expenditure on healthcare were also described.ConclusionThe MDA achieved high coverage and community acceptance. While some positive health impact was observed, it was resource intensive, particularly in this rural context. The priority for malaria control in humanitarian contexts should remain diagnosis and treatment. MDA may be additional tool where the context supports its implementation.

Sub-microscopic Plasmodium falciparum infections and multiple drug resistant single nucleotide polymorphic alleles in pregnant women from southwestern Nigeria

ObjectivesThe study evaluated sub-microscopic malaria infections in pregnancy using two malaria Rapid Diagnostic Tests (mRDTs), microscopy and RT-PCR and characterized Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and Plasmodium falciparum dihydropteroate synthase (Pfdhps) drug resistant markers in positive samples.MethodsThis was a cross sectional survey of 121 pregnant women. Participants were finger pricked, blood drops were collected for rapid diagnosis with P. falciparum histidine-rich protein 11 rapid diagnostic test kit and the ultra-sensitive Alere Pf malaria RDT, Blood smears for microscopy and dried blood spots on Whatman filter paper for molecular analysis were made. Real time PCR targeting the var acidic terminal sequence (varATS) gene of P. falciparum was carried out on a CFX 96 real time system thermocycler (BioRad) in discriminating malaria infections. For each run, laboratory strain of P. falciparum 3D7 and nuclease free water were used as positive and negative controls respectively. Additionally, High resolution melt analyses was employed for genotyping of the different drug resistance markers.ResultsOut of one hundred and twenty-one pregnant women sampled, the SD Bioline™ Malaria Ag P.f HRP2-based malaria rapid diagnostic test (mRDT) detected eight (0.06%) cases, the ultra-sensitive Alere™ malaria Ag P.f rapid diagnostic test mRDT had similar outcome in the same samples as detected by the HRP2-based mRDT. Microscopy and RT-PCR confirmed four out of the eight infections detected by both rapid diagnostic tests as true positive and RT-PCR further detected three false negative samples by the two mRDTs providing a sub-microscopic malaria prevalence of 3.3%. Single nucleotide polymorphism in Pfdhps gene associated with sulphadoxine resistance revealed the presence of S613 mutant genotypes in three of the seven positive isolates and isolates with mixed wild/mutant genotype at codon A613S. Furthermore, four mixed genotypes at the A581G codon were also recorded while the other Pfdhps codons (A436G, A437G and K540E) showed the presence of wild type alleles. In the Pfdhfr gene, there were mutations in 28.6%, 28.6%, and 85.7% at the I51, R59 and N108 codons respectively. Mixed wild and mutant type genotypes were also observed in 28.6% each of the N51I, and C59R codons. For the Pfcrt, two haplotypes CVMNK and CVIET were observed. The SVMNT was altogether absent. Triple mutant CVIET 1(14.3%) and triple mutant + wild genotype CVIET + CVMNK 1(14.3%) were observed. The Pfmdr1 haplotypes were single mutants YYND 1(14.3%); NFND 1(14.3%) and double mutants YFND 4(57.1%); YYDD 1(14.3%).

Comparative evaluation of the diagnostic accuracies of four different malaria rapid diagnostic test kits available in Ghana.

Malaria rapid diagnostic test (mRDT) kit is one of the techniques for diagnosing malaria. Due to its inherent advantages over the microscopy technique, several brands of the kit have flooded malaria endemic countries, without prior in-country evaluation. Two of such mRDT kits are Oscar (India) and Standard Q (Korea Republic). In this study, the performance of Oscar and Standard Q mRDT kits were compared to First Response (India) and CareStart (USA) mRDTs, which have been evaluated and deployed for use approved by the Ministry of Health (MOH). In this comparative study, whole blood samples were collected from patients suspected of malaria. Plasmodium falciparum was detected in each sample using nested polymerase chain reaction (nPCR), microscopy and the four mRDTs. The sensitivities, specificities, accuracies, positive and negative predictive values and accuracies of the mRDTs were determined using nPCR as a reference technique. Kappa statistic was used to determine the level of agreement among the techniques. Two hundred (200) blood samples were analyzed in this study. The overall detection rates of P. falciparum by microscopy, First Response, CareStart, Oscar-PfHRP2, Standard Q mRDT kits and nPCR were 31.5%, 34.5%, 33.5%, 32%, 31% and 43% (x2 = 6.1, p = 0.046), respectively. The accuracies of CareStart and First Response were comparable (90.5% vs. 89.5%). Further, comparing their sensitivities, Oscar-PfHRP2 was 74.4% (95% confidence interval (CI): 63.9-83.2) while that of Standard Q was 72.1% (95% CI: 61.4-81.2), with comparable accuracies (Oscar-PfHRP2-89% and Standard Q -88%). Apart from First Response that was 98.3% specific, the others were 100% specific. Kappa test revealed perfect diagnostic agreement (κ = 0.90-0.98) among the four mRDTs. That notwithstanding, Oscar-PfHRP2 agreed better with CareStart (κ = 0.94) and First Response (κ = 0.92) compared to the agreement between Standard Q and, CareStart (κ = 0.92) and First Response (κ = 0.90). Taken together, the diagnostic performance of the four mRDT kits were statistically similar. That notwithstanding, new mRDT kits should be evaluated prior to deployment for use.

Severe malaria in adolescents in the post-COVID-19 era, at the university hospital of Libreville

Background: Malaria is a parasitic, life-threatening, vector-borne disease that is a significant public health problem in sub-Saharan Africa. The disorganization of health systems characterized the COVID-19 pandemic period. We aimed to assess the impact of these induced changes on adolescent malaria. Methods: We conducted a longitudinal study during the 2021 year in our pediatric ward. We enrolled all patients treated for malaria based on a positive thick smear and rapid diagnostic test for malaria. We noted the age, the delay to consultation, the signs at admission, the haemogram test, the parasites count, and the duration of stay. Results: Of 1734 inpatients, 689 (39.7% (95% CI [37.4%-42%]) were for malaria, including 128 adolescents. We rated 417 (24.3%; 95% CI [22.3%-26.3%]) cases of severe malaria, including 94 (73.4%; 95% IC [65.8-81.1%]) adolescents. The median delay to consultation for adolescents was 2 days vs children 3 days p=0.004. Admission signs were leads by fever (98%), prostration (38%) and pallor (32%). The median length of hospital stay for adolescents was 3 days vs children 4 days (p=0.0263). Adolescent status was associated with more severe forms (OR=2.04 95% CI [1.33-3.13]) and more cerebral forms (OR=3.8 95% CI [2.6-5.6]). Conclusions: The post-COVID-19 era was marked by a higher incidence of malaria and severe forms in adolescents, primarily cerebral malaria. Due to potential sequelae, they need a follow-up to estimate the real aftermaths of the pandemic on the children population.

Evaluation of Malaria Rapid Diagnostic Test Performance and pfhrp2 Deletion in Tanzania School Surveys, 2017.

As part of malaria nationwide monitoring and evaluation initiatives, there is an increasing trend of incorporating malaria rapid diagnostic tests (mRDTs) in surveys conducted within primary schools to detect malaria parasites. However, mRDTs based on the detection of histidine-rich protein 2 (HRP2) are known to yield false-positive results due to persistent antigenemia, and false-negative results may result from low parasitemia or Plasmodium falciparum hrp2/3 gene deletion. We evaluated diagnostic performance of an HRP2 and pan-parasite lactate dehydrogenase (HRP2/pLDH) mRDT against polymerase chain reaction (PCR) for detection of P. falciparum among 17,051 primary school-age children from eight regions of Tanzania in 2017. According to PCR, the prevalence of P. falciparum was 19.2% (95% CI: 18.6-19.8). Using PCR as reference, the sensitivity and specificity of mRDT was 76.2% (95% CI: 74.7-77.7) and 93.9% (95% CI: 93.5-94.3), respectively. Test agreement was lowest in low transmission areas, where true-positive mRDTs were outnumbered by false-negatives due to low parasitemia. Discordant samples (mRDT-negative but PCR-positive) were screened for pfhrp2/3 deletion by real-time PCR. Among those with a parasite density sufficient for analysis, pfhrp2 deletion was confirmed in 60 samples, whereas pfhrp3 deletion was confirmed in two samples; one sample had both pfhrp2 and pfhrp3 deletions. The majority of samples with gene deletions were detected in the high-transmission Kagera region. Compared with mRDTs, PCR and other molecular methods offer increased sensitivity and are not affected by pfhrp2/3 deletions, making them a useful supplement to mRDTs in schools and other epidemiological surveys.

Deletions of Histidine-Rich Protein 2/3 Genes in Natural Plasmodium falciparum Populations from Cameroon and India: Role of Asymptomatic and Submicroscopic Infections.

The bulk of malaria rapid diagnostic tests (RDTs) target histidine-rich protein 2 of Plasmodium falciparum, the deadliest malaria species. The WHO considers pfhrp2/3 deletions as one of the main threats to successful malaria control and/or elimination; as such, parasites that lack part or all of the pfhrp2 gene are missed by pfHRP2-targeting RDTs. Such deletions have been reported in several African and Asian countries, but little is known in Cameroon and India. Blood samples were collected from individuals living in four areas of Cameroon (Douala, Maroua, Mayo-Oulo, Pette) and India (Mewat, Raipur, Ranchi, Rourkela). Deletions in pfhrp2/3 genes were confirmed if samples 1) had ≥100 parasites/µL by quantitative polymerase chain reaction (PCR), 2) PCR negative for pfhrp2/3, and 3) PCR positive for at least two single-copy genes. The overall proportion of pfhrp2 and pfhrp3 deletions in Cameroon was 13.5% and 3.1%. In India, the overall proportion was 8% for pfhrp2 and 4% for pfhrp3. The overall proportions of samples with both gene deletions (pfhrp2-/3-) were 3.1% in Cameroon and 1.3% in India. In Cameroon, pfhrp2-/3+ and pfhrp2-/3- deletions were common in Maroua (P = 0.02), in asymptomatic parasitemia (P = 0.006) and submicroscopic parasitemia (P <0.0001). In both countries, pfhrp2/3 deletions, including pfhrp2-/3- deletions, were mainly seen in monoclonal infections. This study outlines that double deletions that result in false negative RDTs are uncommon in our settings, and highlights the importance of active molecular surveillance for pfhrp2/3 deletions in Cameroon and India.

A qualitative study on determinants of the use of malaria rapid diagnostic test and anti-malarial drug prescription practices by primary healthcare workers in Ebonyi state, Nigeria

BackgroundThe increased availability and use of malaria rapid diagnostic test (RDT) by primary healthcare (PHC) workers has made universal diagnostic testing before malaria treatment more feasible. However, to meaningfully resolve the problem of over-treatment with artemisinin-based combination therapy and the heightened risk of selection pressure and drug resistance, there should be appropriate response (non-prescription of anti-malarial drugs) following a negative RDT result by PHC workers. This study explored the determinants of the use of RDT and anti-malarial drug prescription practices by PHC workers in Ebonyi state, Nigeria.MethodsBetween March 2 and 10, 2020, three focus group discussions were conducted in English with 23 purposively-selected consenting PHC workers involved in the diagnosis and treatment of malaria. Data was analysed thematically as informed by the method by Braun and Clarke.ResultsThe determinants of the use of RDT for malaria diagnosis were systemic (RDT availability and patient load), provider related (confidence in RDT and the desire to make correct diagnosis, PHC worker’s knowledge and training, and fear to prick a patient), client related (fear of needle prick and refusal to receive RDT, and self-diagnosis of malaria, based on symptoms, and insistence on not receiving RDT), and RDT-related (the ease of conducting and interpreting RDT). The determinants of anti-malarial drug prescription practices were systemic (drug availability and cost) and drug related (effectiveness and side-effects of the drugs). The determinants of the prescription of anti-malarial drugs following negative RDT were provider related (the desire to make more money and limited confidence in RDT) and clients’ demand while unnecessary co-prescription of antibiotics with anti-malarial drugs following positive RDT was determined by the desire to make more money.ConclusionsThis evidence highlights many systemic, provider, client, and RDT/drug related determinants of PHC workers’ use of RDT and anti-malarial drug prescription practices that should provide tailored guidance for relevant health policy actions in Ebonyi state, Nigeria, and similar settings.

Prevalence, Associated Factors and Treatment Outcomes of Laboratory-confirmed Pregnancy Malaria at Antenatal Care in Three Healthcare Facilities of Douala, Cameroon

Pregnancy malaria is a life-threatening condition to the mother, the fetus and the newborn. Since the implementation of the World Health Organization’s recommendations of specific malaria control strategies to pregnant women in malaria endemic countries, evaluation studies are needed to assess the prevalence of malaria in pregnancy. This cross-sectional prospective study was therefore set to determine the prevalence and associated factors as well as the treatment outcomes of Plasmodium infection among pregnant women attending antenatal care in three hospitals of Douala in Cameroon.&#x0D; Each volunteered pregnant woman received for antenatal care was questioned according to the study questionnaire to collect sociodemographic data, use of malaria prevention tools and pregnancy history. Then a laboratory test was carried for Plasmodium detection in the peripheral blood using microscopy and a HRP2-based rapid diagnostic test. Plasmodium carrying pregnant women were treated according to the national malaria program scheme followed by post-treatment follow-up. Data were processed and analyzed using SPSS.20 software. Association of Plasmodium infection with risk factors was analyzed as univariate using Pearson Chi-square and Fisher Exact tests considering a P-value &lt; 0.05 as statistically significant.&#x0D; A total of 487 pregnant women aged between 18 years and 42 years were included in the study. The prevalence of Plasmodium infection was 3.5% and 4.3% by malaria rapid diagnostic test and microscopy respectively. Only Plasmodium falciparum asexual stage was detected. Parasite loads were low. Factors associated with Plasmodium falciparum higher prevalence were being less than 21 years old (0.02), not sleeping under mosquitoe net daily (p=0.04) and having fever during the pregnancy (p=0.04). Parenteral treatment with either artesunate, artemether or quinine sulfate showed good efficacy.&#x0D; Conclusion: Pregnant women attending the antenatal cares harbored low Plasmodium infection prevalence and loads. Being of young age, not sleeping under mosquitoe bednet daily and having fever during the pregnancy were predictive Plasmodium falciparum. Plasmodium infected pregnant women were successfully treated with antimalarial medications recommended by the national Ministry of Public Health. The authors recommend increasing efforts by health authorities to strengthen malaria prevention in pregnant women through more adherence to sleeping under ITNs daily and taking IPT-sp as well as systematic detection of Plasmodium infection at each antenatal visit.

Comparison of prevalence estimates of pfhrp2 and pfhrp3 deletions in Plasmodium falciparum determined by conventional PCR and multiplex qPCR and implications for surveillance and monitoring

ObjectivesThe accuracy of malaria rapid diagnostic tests is threatened by Plasmodium falciparum with pfhrp2/3 deletions. This study compares gene deletion prevalence determined by multiplex real time polymerase chain reaction (qPCR) and conventional polymerase chain reaction (cPCR) using existing samples with clonality previously determined by microsatellite genotyping. MethodsMultiplex qPCR was used to estimate prevalence of pfhrp2/3 deletions in three sets of previously collected patient samples from Eritrea and Peru. The qPCR was validated by multiplex digital polymerase chain reaction. Sample classification was compared with cPCR, and receiver operating characteristic curve analysis was used to determine the optimal ΔCq threshold that aligned the results of the two assays. ResultsqPCR classified 75% (637 of 849) of samples as single, and 212 as mixed-pfhrp2/3 genotypes, with a positive association between clonality and proportion of mixed-pfhrp2/3 genotype samples. The sample classification agreement between cPCR and qPCR was 75.1% (95% confidence interval [CI] 68.6-80.7%) and 47.8% (95% CI 38.9-56.9%) for monoclonal and polyclonal infections. The qPCR prevalence estimates of pfhrp2/3 deletions showed almost perfect (κ = 0.804, 95% CI 0.714-0.895) and substantial agreement (κ = 0.717, 95% CI 0.562-0.872) with cPCR for Peru and 2016 Eritrean samples, respectively. For 2019 Eritrean samples, the prevalence of double pfhrp2/3 deletions was approximately two-fold higher using qPCR. The optimal threshold for matching the assay results was ΔCq = 3. ConclusionsMultiplex qPCR and cPCR produce comparable estimates of gene deletion prevalence when monoclonal infections dominate; however, qPCR provides higher estimates where multi-clonal infections are common.

Comparison of SD Bioline Malaria Ag Pf/Pan and Acro Malaria P.f./P.v./Pan with Microscopy and Real Time PCR for the Diagnosis of Human Plasmodium Species.

The early diagnosis of malaria is crucial to controlling morbidity and mortality. The World Health Organization (WHO) recommends diagnosing malaria either using light microscopy or a malaria rapid diagnostic test (RDT). Most RDTs use antibodies to detect two P. falciparum histidine-rich proteins named PfHRP2 and PfHRP3. However, false-negative results are known to occur due to the poor performance of RDTs depending on the species and the deletion of the Pfhrp2 and Pfhrp3 genes. This study evaluated new malaria RDTs for the detection of the human Plasmodium species. The Acro Malaria P.f./P.v./Pan Rapid Test Cassette allows the qualitative detection of parasite antigens, such as PfHRP2 specific to Plasmodium falciparum, PvLDH specific to Plasmodium vivax, and/or panLDH Plasmodium genus lactate dehydrogenase, in the blood of infected individuals. This RDT was assessed against 229 samples collected from imported malaria cases, mainly from Africa. The samples were previously diagnosed using light microscopy and RDT (SD Malaria Ag P.f./Pan, SD Bioline Alere Abbott), then confirmed using real time PCR. The two RDTs were evaluated using a comparison with real time PCR as the reference method, and their performances were compared with each other. Compared to SD RDT, the Acro RDT showed a better sensitivity to P. falciparum (96.8% vs. 89.8%), P. vivax (78.6% vs. 64.3%), P. ovale (73.7% vs. 5.3%), and P. malariae (20.0% vs. 0%). The respective specificities of the Acro RDT and SD RDT are 90.7% vs. 95.3% to P. falciparum, 100% to P. vivax, and 100% vs. 100% to Plasmodium genus. Therefore, Acro RDT showed better performance in the identification of P. ovale and low parasitaemia of P. falciparum. In addition, Acro RDT has the advantage of detecting PvLDH-specific antigens. The Acro Malaria RDT presents the benefits of detecting a P. falciparum antigen (PfHRP2) and a P. vivax antigen (PvLDH) with high sensitivity (96.8% and 73.7%, respectively) and specificity (90.7% and 100%, respectively). Acro Malaria P.f./P.v./Pan rapid diagnostic tests could be effectively used in endemic areas, especially when microscopic examination cannot be performed.

Etiology of febrile illness among patients seeking care at a district hospital in Manyara, Tanzania

Managing febrile illness is complicated due to the increasing involvement of non-malarial pathogens. This hospital-based cross-sectional study was conducted in Kiteto District Hospital in Northern Western, Tanzania, between January and February 2019. Out-patients with a temperature ≥38°C were consecutively enrolled until the sample size was reached. Whole blood samples were collected aseptically and tested for 36 pathogens using a multiplex PCR. Out of the 426 febrile patients, 184 (43.2%) had pathogens detected in their bloodstream. Brucella spp. was isolated in 61 (14.3%) patients, followed by Dengue virus 51 (12.0%), Salmonella Typhi 39 (9.2%), Plasmodium falciparum 37(8.7%), Coxiella burnetii 23 (5.4%) and Leptospira spp., 17 (4.0%). Forty patients (21.7%) had more than one pathogen, whereby co-infection with Brucella spp. and C. burnetii was frequent among study participants. Dengue virus was the most frequent in children aged below 14 years, whereas Brucella spp. was the dominant agent in adults. The cause of fever was not identified in 242 (56.8%) of these patients. Houses surrounded by long grasses were risk factors for febrile illness caused by P. falciparum, consuming untreated milk and consuming sour milk were risk factors for febrile illness caused by bacteria zoonoses while not washing hands after visiting the toilet was a risk factor for febrile illness by S. Typhi. Regarding management, 143 (34.8%) were given anti-malaria despite malaria rapid diagnostic test (MRDT) negative results, while 26.5% were given both anti-malaria and antibiotics for febrile illness. In this study, the majority of febrile illness cases were due to non-malarial pathogens, with P. falciparum accounting for only 8.7% of the cases. We found that about one-third of the cases were wrongly treated for malaria, and more than a quarter were wrongly given antibiotics. A review of the management of febrile illnesses is warranted.

Etiology of febrile illness among patients seeking care at a district hospital in Manyara, Tanzania

Managing febrile illness is complicated due to the increasing involvement of non-malarial pathogens. This hospital-based cross-sectional study was conducted in Kiteto District Hospital in Northern Western, Tanzania, between January and February 2019. Out-patients with a temperature ≥38°C were consecutively enrolled until the sample size was reached. Whole blood samples were collected aseptically and tested for 36 pathogens using a multiplex PCR. Out of the 426 febrile patients, 184 (43.2%) had pathogens detected in their bloodstream. Brucella spp. was isolated in 61 (14.3%) patients, followed by Dengue virus 51 (12.0%), Salmonella Typhi 39 (9.2%), Plasmodium falciparum 37(8.7%), Coxiella burnetii 23 (5.4%) and Leptospira spp., 17 (4.0%). Forty patients (21.7%) had more than one pathogen, whereby co-infection with Brucella spp. and C. burnetii was frequent among study participants. Dengue virus was the most frequent in children aged below 14 years, whereas Brucella spp. was the dominant agent in adults. The cause of fever was not identified in 242 (56.8%) of these patients. Houses surrounded by long grasses were risk factors for febrile illness caused by P. falciparum, consuming untreated milk and consuming sour milk were risk factors for febrile illness caused by bacteria zoonoses while not washing hands after visiting the toilet was a risk factor for febrile illness by S. Typhi. Regarding management, 143 (34.8%) were given anti-malaria despite malaria rapid diagnostic test (MRDT) negative results, while 26.5% were given both anti-malaria and antibiotics for febrile illness. In this study, the majority of febrile illness cases were due to non-malarial pathogens, with P. falciparum accounting for only 8.7% of the cases. We found that about one-third of the cases were wrongly treated for malaria, and more than a quarter were wrongly given antibiotics. A review of the management of febrile illnesses is warranted.

Malaria infection and predictor factors among Chadian nomads’ children

BackgroundIn Chad, malaria remains a significant public health concern, particularly among nomadic populations. Geographical factors and the mobility of human populations have shown to be associated with the diversity of Plasmodium species. The study aims to describe the malaria prevalence among nomadic children and to investigate its associated factors.MethodsA cross-sectional study was conducted in February and October 2021 among nomadic communities in Chad. Blood sample were collected and tested from 187 Arab, Fulani and Dazagada nomadic children aged 3–59 months using malaria rapid diagnostic test (RDT). A structured electronic questionnaire was administered to their parents to collect information about the socio‑economic data. Malaria testing results were categorized according to the SD BIOLINE Malaria Ag Pf/Pan RDT procedures. Logistic regression analysis was used to determine key risk factors explaining the prevalence of malaria. STATA version IC 13 was used for statistical analysis.ResultsThe overall malaria prevalence in nomadic children was 24.60%, with 65.20% being Plasmodium falciparum species and 34.8% mixed species. Boys were twice as likely (COR = 1.83; 95% CI, 0.92–3.62; p = 0.083) to have malaria than girls. Children whose parents used to seek traditional drugs were five times more likely (AOR = 5.59; 95% CI, 1.40–22.30, p = 0.015) to have malaria than children whose parents used to seek health facilities. Children whose parents reported spending the last night under a mosquito net were one-fifth as likely (AOR = 0.17; 95% CI, 0.03–0.90, p = 0.037) to have malaria compared to children whose parents did not used a mosquito net. Furthermore, Daza children were seventeen times (1/0.06) less likely (AOR = 0.06; 95% CI, 0.01–0.70, p = 0.024) to have malaria than Fulani children and children from households piped water as the main source were seven times more likely (AOR = 7.05; 95% CI, 1.69–29.45; p = 0.007) to have malaria than those using surface water.ConclusionsMalaria remains a significant public health issue in the nomadic communities of Chad. Community education and sensitization programs within nomad communities are recommended to raise awareness about malaria transmission and control methods, particularly among those living in remote rural areas. The National Malaria Control Program (NMCP) should increase both the coverage and use of long-lasting insecticidal nets (LLINs) and seasonal malaria chemoprevention (SMC) in addition to promoting treatment-seeking behaviors in nomadic communities.

Use of a health worker-targeted smartphone app to support quality malaria RDT implementation in Busia County, Kenya: A feasibility and acceptability study.

Malaria rapid diagnostic tests (mRDTs) are an essential diagnostic tool in low-resource settings; however, administration and interpretation errors reduce their effectiveness. HealthPulse, a smartphone mRDT reader application, was developed by Audere to aid health workers in mRDT administration and interpretation, with an aim to improve the mRDT testing process and facilitate timely decision making through access to digitized results. Audere partnered with PSI and PS Kenya to conduct a pilot study in Busia County, Kenya between March and September 2021 to assess the feasibility and acceptability of HealthPulse to support malaria parasitological diagnosis by community health volunteers (CHVs) and private clinic health workers (private clinic HWs). Metadata was interpreted to assess adherence to correct use protocols and health worker perceptions of the app. Changes to mRDT implementation knowledge were measured through baseline and endline surveys. The baseline survey identified clear mRDT implementation gaps, such as few health workers correctly knowing the number of diluent drops and minimum and maximum wait times for mRDT interpretation, although health worker knowledge improved after using the app. Endline survey results showed that 99.6% of health workers found the app useful and 90.1% found the app easy to use. Process control data showed that most mRDTs (89.2%) were photographed within the recommended 30-minute time frame and that 91.4% of uploaded photos passed the app filter quality check on the first submission. During 154 encounters (3.5% of all encounters) a health worker dispensed an artemisinin-based combination therapy (ACT) to their patient even with a negative mRDT readout. Overall, study results indicated that HealthPulse holds potential as a mobile tool for use in low-resource settings, with future supportive supervision, diagnostic, and surveillance benefits. Follow-up studies will aim to more deeply understand the utility and acceptance of the HealthPulse app.

Evaluating Malaria Rapid Diagnostic Tests and Microscopy for Detecting Plasmodium Infection and Status of Plasmodium falciparum Histidine-Rich Protein 2/3 Gene Deletions in Southeastern Nigeria.

Delays in malaria diagnosis increase treatment failures and deaths. In endemic regions, standard diagnostic methods are microscopy and malaria rapid diagnostic tests (mRDTs) detecting Plasmodium falciparum histidine-rich protein 2/3 (PFHRP2/PFHRP3), but gene deletions can allow certain parasites to remain undetected. We enlisted a cohort comprising 207 symptomatic individuals, encompassing both children and adults, at a hospital in Nnewi, Nigeria. The prevalence of parasites was determined using a highly sensitive, species-specific quantitative polymerase chain reaction (SS-qPCR). Within a subset of 132 participants, we assessed the sensitivity and specificity of microscopy and HRP2-mRDTs in comparison to SS-qPCR for the detection of P. falciparum. We also investigated the prevalence of pfhrp2/pfhrp3 gene deletions. Greater sensitivity was achieved with mRDTs (95%) compared with microscopy (77%). Also, mRDTs exhibited greater specificity (68%) than microscopy (44%). The positive predictive value of mRDTs (89%) surpassed that of microscopy (80%), suggesting a greater probability of accurately indicating the presence of infection. The negative predictive value of mRDTs (82%) was far greater than microscopy (39%). Of the 165 P. falciparum-positive samples screened for pfhrp2/pfhrp3 gene deletions, one gene deletion was detected in one sample. Regarding infection prevalence, 84% were positive for Plasmodium spp. (by reverse transcription [RT]-qPCR), with P. falciparum responsible for the majority (97%) of positive cases. Thus, exclusive reliance on microscopy in endemic areas may impede control efforts resulting from false negatives, underscoring the necessity for enhanced training and advocating for high-throughput molecular testing such as RT-qPCR or qPCR at referral centers to address limitations.

Meta-analytic review on the impact of factors that affect performance of malaria rapid diagnostic test in Africa

Timely, accurate diagnosis and treatment has improved malaria case management. Malaria Rapid Diagnostic Test (mRDT) kits are largely used in malaria diagnosis. Their performance is compromised by factors related to gene deletions, parasite density, quality of the kit, poor storage conditions and end-user inefficiencies hence diagnosis gives either positive, negative, false negative (FN) or false positive (FP) which defines consequent management strategies. This review assessed reports on prevalence of the Plasmodium falciparum histidine rich protein 2/3 (Pfhrp2/3) gene deletions in malaria infected populations in Africa and the risk of mRDT failure to identify malaria positive cases. Preferred Reporting Items for Systematic Meta-Analysis (PRISMA) statement was used for data collection. Literature search was done using Google and Mendel search for data published in a malaria journal, Journal of infectious diseases, scientific reports, Annals of Ibadan postgraduate medicine, and BMC journals published between 2019 and 2023. Fifty eight reports were identified were screened and tested for eligibility. &#x0D; Majority of studies described the consistent use of Pfhrp2/3 mRDT for malaria diagnosis in rural health facilities in Africa and nine reports met inclusion criteria for review. Five of them certified the world health organization’s sample criteria of ‘more than 350 sample’ to estimate the prevalence of Pfhrp2/3 gene deletions leading to declaration of false negative results of which one study posted FN outcome resulting from these deletions. Four out of nine studies did not meet this WHO criterion. This review affirmed presence of Pfhrp2/3 gene deletions challenges in Africa though other countries recorded the converse. Data was pooled using random effect models with Odds ratio and 95% confidence limit. The prevalence of the gene deletions was heterogeneous, ranging from 0% to 78.1%. The review found that an average prevalence of Pfhrp2/3 deletion as 26.2%. This was above the WHO standard recommended declaration value of 5%.; a factor that demonstrated setback to the use of mRDT in malaria endemic regions. Therefore alternative methods should be used where aspersions are cast on outcome of mRDT for &#x0D; it will help improve malaria treatment, tracking and management.

Evaluation of new haematology analyser, XN-31, for malaria detection in blood donors: A single-centre study from India.

Malaria continues to be a significant public health concern in India, with several regions experiencing endemicity and sporadic outbreaks. The prevalence of malaria in blood donors, in India, varies between 0.02% and 0.07%. Common techniques to screen for malaria, in blood donors and patients, include microscopic smear examination and rapid diagnostic tests (RDTs) based on antigen detection. The aim of this study was to evaluate a new fully automated analyser, XN-31, for malaria detection, as compared with current practice of using RDT. Cross-sectional analytical study was conducted to evaluate clinical sensitivity and specificity of new automated analyser XN-31 among blood donors' samples and clinical samples (patients with suspicion of malaria) from outpatient clinic collected over between July 2021 and October 2022. No additional sample was drawn from blood donor or patient. All blood donors and patients' samples were processed by malaria rapid diagnostic test, thick-smear microscopy (MIC) and the haematology analyser XN-31. Any donor blood unit incriminated for malaria was discarded. Laboratory diagnosis using MIC was considered the 'gold standard' in the present study. Clinical sensitivity and specificity of XN-31 were compared with the gold standard. Fife thousand and five donor samples and 82 diagnostic samples were evaluated. While the clinical sensitivity and specificity for donor samples were 100%, they were 96.3% and 100% for diagnostic samples. Automated haematology analysers represent a promising solution, as they can deliver speedy and sensitive donor malaria screening assessments. This method also has the potential to be used for pre-transfusion malaria screening along with haemoglobin estimation.

Aetiology of non-malaria acute febrile illness fever in children in rural Guinea-Bissau: a prospective cross-sectional investigation.

With growing use of parasitological tests to detect malaria and decreasing incidence of the disease in Africa; it becomes necessary to increase the understanding of causes of non-malaria acute febrile illness (NMAFI) towards providing appropriate case management. This research investigates causes of NMAFI in pediatric out-patients in rural Guinea-Bissau. Children 0-5 years presenting acute fever (≥38°) or history of fever, negative malaria rapid diagnostic test (mRDT) and no signs of specific disease were recruited at the out-patient clinic of 3 health facilities in Bafatá province during 54 consecutive weeks (dry and rainy season). Medical history was recorded and blood, nasopharyngeal, stool and urine samples were collected and tested for the presence of 38 different potential aetiological causes of fever. Samples from 741 children were analysed, the protocol was successful in determining a probable aetiological cause of acute fever in 544 (73.61%) cases. Respiratory viruses were the most frequently identified pathogens, present in the nasopharynx samples of 435 (58.86%) cases, followed by bacteria detected in 167 (22.60%) samples. Despite presenting negative mRDTs, P. falciparum was identified in samples of 24 (3.25%) patients. This research provides a description of the aetiological causes of NMAFI in West African context. Evidence of viral infections were more commonly found than bacteria or parasites.

How Outreach Training and Supportive Supervision (OTSS) Affect Health Facility Readiness and Health-Care Worker Competency to Prevent and Treat Malaria in Niger: A Secondary Analysis of OTSS Data.

The quality of health services is key to the goal of averting morbidity and mortality from malaria. From July 2020 to August 2021, PMI Impact Malaria supported the implementation of four rounds of Outreach Training and Supportive Supervision (OTSS) in 12 health districts in the two regions of Niger: Dosso and Tahoua. Through OTSS, trained supervisors conducted onsite visits to observe an average of 174 healthcare workers (HCWs) per round in 96 public primary health facilities, managing persons with fever or conducting antenatal care (ANC) consultations, and then provided instant and individualized feedback and onsite training. Data from health facility readiness, case management, and malaria in pregnancy (MiP) checklists across the four rounds were analyzed using Wilcoxon's and the χ2 tests. These analyses highlighted improved facility readiness, including an increased likelihood that HCWs had received classroom training, and facilities had increased availability of guidelines and algorithms by round 4 compared with round 1. Median HCW performance scores showed an improvement in the correct performance and interpretation of malaria rapid diagnostic tests, in classification of malaria as uncomplicated or severe, and in the management of uncomplicated malaria across the four rounds. For MiP services, malaria prevention and the management of pregnant women with malaria also improved from round 1 to round 4. These findings provide further evidence that OTSS can achieve rapid improvements in health facility readiness and HCW competency in managing outpatients and ANC clients.