In 2019, the WHO released guidelines on HIV testing service (HTS). We aim to assess the adoption of six of these recommendations on HIV testing strategies among African countries.
Policy review.
47 countries within the WHO African region.
National HTS policies from the WHO African region as of December 2021.
Uptake of WHO recommendations across national HTS policies including the standard three-test strategy; discontinuation of a tiebreaker test to rule in HIV infection; discontinuation of western blotting (WB) for HIV diagnosis; retesting prior to antiretroviral treatment (ART) initiation and the use of dual HIV/syphilis rapid diagnostic tests (RDTs) in antenatal care. Country policy adoption was assessed on a continuum, based on varying levels of complete adoption.
National policies were reviewed for 96% (n=45/47) of countries in the WHO African region, 38% (n=18) were published before 2019 and 60% (n=28) adopted WHO guidance. Among countries that had not fully adopted WHO guidance, not yet adopting a three-test strategy was the most common reason for misalignment (45%, 21/47); of which 31% and 22% were in low-prevalence (<5%) and high-prevalence (≥5%) countries, respectively. Ten policies (21%) recommended the use of WB and 49% (n=23) recommended retesting before ART initiation. Dual HIV/syphilis RDTs were recommended in 45% (n=21/47) of policies.
Many countries in the African region have adopted WHO-recommended HIV testing strategies; however, efforts are still needed to fully adopt WHO guidance. Countries should accelerate their efforts to adopt and implement a three-test strategy, retesting prior to ART initiation and the use of dual HIV/syphilis RDTs.

Central nervous system tuberculosis (CNSTB) is a severe condition, sometimes associated with a poor prognosis. Early diagnosis of CNSTB remains challenging, considering that conventional methods lack sensitivity or might lead to certain side effects. Herein, we presented a protocol for a systematic review and meta-analysis to assess the diagnostic efficacy of MRI for CNSTB.
SinoMed, Wanfang database, China National Knowledge Infrastructure, Embase, the Cochrane Library and PubMed will be searched to identify studies reporting on the use of MRI in the diagnosis of CNSTB from database inception to December 2023. The following keywords will be applied: \'Intracranial tuberculosis\', \'Cerebral tuberculosis\', \'Central nervous system tuberculosis\', \'Spinal tuberculous arachnoiditis\' and \'Magnetic Resonance Imaging\'. Studies that evaluate the diagnostic accuracy of MRI for the diagnosis of CNSTB and report clear reference criteria will be included. Studies from which full true positive, false positive, false negative and true negative values cannot be extracted, those published in languages other than English or Chinese, abstracts not reporting the full text, and case reports will be excluded. Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) will be used to evaluate the methodological quality of each included study. Stata V.15.0 and RevMan V.5.3 will be used to perform a meta-analysis and generate forest plots and summary receiver operating characteristic curves. In case of significant heterogeneity between studies, possible sources of heterogeneity will be explored through subgroup and meta-regression analyses.
This research is based on public databases and does not require ethical approval. Results will be submitted for publication in a peer-reviewed journal.
CRD42023415690.

With the rising resistance to artemisinin-based combination treatments, there is a need to hasten the discovery and development of newer antimalarial agents. Herbal medicines are key for the development of novel drugs. Currently, herbal medicine usage in communities for treatment of malaria symptoms is common as an alternative to conventional (modern) antimalarial agents. However, the efficacy and safety of most of the herbal medicines has not yet been established. Therefore, this systematic review and evidence gap map (EGM) is intended to collate and map the available evidence, identify the gaps and synthesise the efficacy of herbal antimalarial medicines used in malaria affected regions globally.
The systematic review and EGM will be done following PRISMA and Campbell Collaboration guidelines respectively. This protocol has been registered in PROSPERO. Data sources will include PubMed, MEDLINE Ovid, EMBASE, Web of Science, Google Scholar and grey literature search. Data extraction will be done in duplicate using a data extraction tool tailored in Microsoft Office excel for herbal antimalarials discovery research questions following the PICOST framework. The Risk of Bias and overall quality of evidence will be assessed using Cochrane risk of bias tool (clinical trials), QUIN tool (in vitro studies), Newcastle-Ottawa tool (observational studies) and SYRCLE\'s risk of bias tool for animal studies (in vivo studies). Data analysis will be done using both structured narrative and quantitative synthesis. The primary review outcomes will be clinically important efficacy and adverse drug reactions. Laboratory parameters will include Inhibitory Concentration killing 50% of parasites, IC50; Ring Stage Assay, RSA0-3 hou; Trophozoite Survival Assay, TSA50. ETHICS AND DISSEMINATION: The review protocol was approved by the School of Biomedical Science Research Ethics Committee, Makerere University College of Health Sciences (SBS-2022-213).
CRD42022367073.

Worldwide, COVID-19 pandemic lead to a large fall in the number of newly reported TB cases. In sub-Saharan Africa, microbiological diagnosis of TB is generally based on smear microscopy and Xpert MTB/RIF on sputum samples, but good quality sputum samples are often difficult to obtain, leading clinicians to rely on more invasive procedures for diagnosis. Aim of this study was to investigate pooled sensitivity and specificity of Xpert MTB/RIF on stool samples compared to respiratory microbiological reference standards in African countries.
Four investigators independently searched PubMed, SCOPUS, and Web of Science until 12th October 2022, then screened titles and abstracts of all potentially eligible articles. The authors applied the eligibility criteria, considered the full texts. All the studies reported the data regarding true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Risk of bias and applicability concerns were assessed with the Quadas-2 tool.
overall, among 130 papers initially screened, we evaluated 47 works, finally including 13 papers for a total of 2,352 participants, mainly children. The mean percentage of females was 49.6%, whilst the mean percentage of patients reporting HIV was 27.7%. Pooled sensitivity for Xpert MTB/RIF assay for detecting pulmonary tuberculosis was 68.2% (95%CI: 61.1-74.7%) even if characterized by a high heterogeneity (I2=53.7%). Specificity was almost 100% (99%, 95%CI: 97-100%; I2 = 45.7%). When divided for reference standard, in the six studies using sputum and nasogastric aspirate the accuracy was optimal (AUC = 0.99, SE = 0.02), whilst in the studies using only sputum for tuberculosis detection the AUC was 0.85 (with a SE = 0.16). The most common source of bias was exclusion of enrolled patients in the analysis.
Our study confirms that, in Africa, stool Xpert MTB/RIF may be a useful rule-in test for children above and below 5 years of age under evaluation for pulmonary tuberculosis. Sensitivity increased substantially when using both sputum and nasogastric aspirate as reference samples.

Diagnosis of childhood tuberculosis (TB) poses several challenges. Therefore, clinical signs and symptoms, radiological studies, laboratory examinations, point-based scoring systems or diagnostic algorithms have been developed to improve diagnostic yields in this population. However, there are limited data on the diagnostic test accuracy of paediatric TB scoring systems. Therefore, this systematic review and meta-analysis aims to synthesise the available evidence on the diagnostic accuracy of childhood TB diagnostic scoring systems.
This protocol describes a systematic review, developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Diagnostic Test Accuracy. We will conduct a comprehensive literature search for relevant articles in the following databases: PubMed, CINAHL, Embase, Scopus and Cochrane Databases. The eligibility criteria for studies will be formulated based on the Participants (Population), Index Test, Comparator Test and Target Condition criteria for the review question. The index test will be defined as any attempt to diagnose childhood TB using either a scoring system or a diagnostic algorithm, whereas a composite reference standard will be used as a reference standard. This will include any attempt to confirm diagnosis of TB. Where bacteriological confirmation is not obtained and there are at least two of the following features: chest radiograph consistent with TB, immunological evidence of Mycobacterium tuberculosis infection and/or positive response to TB treatment will also be considered. The QUADAS-2 Tool will be used to assess the quality of the studies. The diagnostic accuracy measures (ie, sensitivity, specificity, negative predictive and positive predictive values) will be pooled with the random-effects or fixed-effects models, as appropriate. All statistical analyses will be performed using the Review Manager V.5.4.
This research is exempt from ethics approval given that this is a protocol for a systematic review, which uses published data. The findings from this review will be disseminated through peer-reviewed publications and scientific conferences.
CRD42022367049.

In 2014, the WHO published high-priority target product profiles (TPPs) for new tuberculosis (TB) diagnostics to align end-user needs with test targets and specifications; nevertheless, no TB test meets these targets to date. The COVID-19-driven momentum in the diagnostics world offers an opportunity to address the long-standing lack of innovation in the field of TB diagnostics. This scoping review aims to summarise point-of-care (POC) molecular and antigen tests for COVID-19 diagnosis that, when applied to TB, potentially meet WHO TPPs. This summary of currently available innovative diagnostic tools will guide the development of novel TB diagnostics toward the WHO-set targets.
We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension Scoping Reviews recommendations. MEDLINE (via PubMed), bioRxiv, MedRxiv and other publicly available in vitro diagnostic test databases were searched on 23 November 2022. POC antigen or molecular tests developed for SARS-CoV-2 detection that meet the eligibility criteria will be included in the review. Developer description, test description, operation characteristics, pricing information, performance and commercialisation status of diagnostic tests identified will be extracted using a predefined standardised data extraction form. Two reviewers will independently perform the screening and data extraction. A narrative synthesis of the final data will be provided.
No ethical approval is required because individual patient data will not be included. The findings will be published in open-access scientific journals.

Leptospirosis is a zoonotic disease with high prevalence in low-income and middle-income countries and tropical and subtropical regions. The clinical symptoms of the disease are similar to symptoms presented by other endemic infectious diseases that could be present simultaneously. Thus, leptospirosis could be masked by similar infections like dengue, malaria, hantavirus, melioidosis and borreliosis, among others. Therefore, leptospirosis could present itself as an under-reported infection or as a coinfection with another pathogen, as has been reported in the literature. However, there is a lack of documented evidence about the specific risk factors of leptospirosis infection, the symptoms, the coinfection\'s mortality and the frequency of coinfection. Additionally, leptospirosis coinfections have not been considered a neglected public health concern. Therefore, this systematic review aims to evaluate published articles that show the risk factors associated with leptospirosis infection and coinfection with other pathogens.
The search process to identify eligible studies will be conducted including the LILACS, ProQuest, PubMed and Scopus databases with no restriction in terms of publication date. Also, grey literature will be included in the research. Authors will independently screen the title and abstracts of the articles identified from the search using Rayyan free software. Eligibility criteria include peer-reviewed research articles written in English or Spanish, including observational studies, cohorts, case-control, cross-sectional, ecological studies and report cases. The systematic review will include studies that report descriptions of leptospirosis cases with coinfection or co-occurrence. The search will be accomplished by articles from 1950 to May 2022. The data will be extracted in a standard extraction form using an Excel format.
Results will be published in a peer-reviewed journal. Also, findings will be disseminated through scientific meetings. Ethical approval will not be required as this is a systematic review and primary data will be not collected or included.
CRD42021234754.

The purpose of this study was systematically and quantitatively to assess the value of the neutrophil-to-lymphocyte ratio (NLR) for the diagnosis of neonatal sepsis by systematic review and meta-analysis.
Systematic review and meta-analysis.
Eight major databases, including The Cochrane, PubMed, Embase, Web of Science, CNKI, Wanfang, China Biomedical Literature Database and VIP Database, were systematically searched for NLR diagnoses of neonatal sepsis from inception to June 2022. Two investigators independently conducted the literature search, screening, data extraction and quality evaluation with the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. Statistical analysis was performed using Review Manager V.5.3, Stata V.16.0, R (V.3.6.0) and Meta-DISC V.1.4.
A total of 14 studies comprising 1499 newborns were included in this meta-analysis. With a cut-off value ranging from 0.1 to 9.4, the pooled sensitivity of the NLR in the diagnosis of neonatal sepsis was 0.74 (95% CI: 0.61 to 0.83), the pooled specificity was 0.88 (95% CI: 0.73 to 0.95), the positive likelihood ratio (LR+) was 6.35 (95% CI: 2.6 to 15.47), the negative likelihood ratio (LR-) was 0.30 (95% CI: 0.19 to 0.46), the diagnostic OR (DOR) was 12.88 (95% CI: 4.47 to 37.08), area under the curve (AUC) was 0.87 (95% CI: 0.84 to 0.89). In the subgroup analysis of early-onset neonatal sepsis, the pooled sensitivity was 0.75 (95% CI: 0.47 to 0.91), the pooled specificity was 0.99 (95% CI: 0.88 to 1.00), the LR+ was 63.3 (95% CI: 5.7 to 696.8), the LR- was 0.26 (95% CI: 0.10 to 0.63), the DOR was 247 (95% CI: 16 to 3785) and the AUC was 0.97 (95% CI: 0.95 to 0.98).
Our findings suggest that the NLR is a helpful indicator for the diagnosis of early neonatal sepsis, but it still needs to be combined with other laboratory tests and specific clinical manifestations.

Increasing numbers of patients with non-haematological diseases are infected with invasive pulmonary aspergillosis (IPA), with a high mortality reported which is mainly due to delayed diagnosis. The diagnostic capability of mycological tests for IPA including galactomannan test, (1,3)-β-D-glucan test, lateral flow assay, lateral flow device and PCR for the non-haematological patients remains unknown. This protocol aims to conduct a systematic review and meta-analysis of the diagnostic performance of mycological tests to facilitate the early diagnosis and treatments of IPA in non-haematological diseases.
Database including PubMed, CENTRAL and EMBASE will be searched from 2002 until the publication of results. Cohort or cross-sectional studies that assessing the diagnostic capability of mycological tests for IPA in patients with non-haematological diseases will be included. The true-positive, false-positive, true-negative and false-negative of each test will be extracted and pooled in bivariate random-effects model, by which the sensitivity and specificity will be calculated with 95% CI. The second outcomes will include positive (negative) likelihood ratio, area under the receiver operating characteristic curve and diagnostic OR will also be computed in the bivariate model. When applicable, subgroup analysis will be performed with several prespecified covariates to explore potential sources of heterogeneity. Factors that may impact the diagnostic effects of mycological tests will be examined by sensitivity analysis. The risk of bias will be appraised by the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2).
This protocol is not involved with ethics approval, and the results will be peer-reviewed and disseminated on a recognised journal.
CRD42021241820.

Urinary antigen tests have been used for the rapid identification of Streptococcus pneumoniae infection in patients with pneumonia, thereby leading to earlier targeted therapy than when using conventional diagnostic culture methods. This study aimed to update the knowledge on the diagnostic accuracy of urinary antigen tests for S. pneumoniae among patients with acute respiratory failure suspected of pneumonia based on a systematic review and meta-analysis.
A systematic search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials for studies published up to 3 June 2020. Prospective and retrospective cohort studies (in English) that reported on the diagnostic performance of urinary antigen tests versus culture or smear diagnostic methods in adult patients with clinically diagnosed pneumonia were selected and analysed. The QUADAS-2 tool was used to assess the risk of bias, and a bivariate random effects model was applied to perform a meta-analysis of the selected studies.
A total of 2179 studies were screened, of which 30 met the eligibility criteria for quality assessment and meta-analysis. Overall, data from 12 366 patients, including 1548 patients (12.5%) with the target condition and suspected pneumococcal pneumonia, were included in the analysis. The overall quality of the included studies was determined to be serious. The calculated pooled sensitivity and specificity were of 0.66 (95% CI 0.62 to 0.69) and 0.90 (95% CI 0.85 to 0.93), respectively.
The urinary antigen test is useful for achieving a definitive diagnosis of S. pneumoniae infection in patients with pneumonia.