A cost-benefit algorithm for rapid diagnosis of tuberculosis and rifampicin resistance detection during mass screening campaigns.

BACKGROUND: Active tuberculosis (TB) case finding is important as it helps detect pulmonary TB cases missed by the other active screening methods. It requires periodic mass screening in risk population groups such as prisoners and refugees. Unfortunately, in these risk population groups periodic mass screening can be challenging due to lengthy turnaround time (TAT), cost and implementation constraints. The aim of this study was to evaluate a diagnostic algorithm that can reduce the TAT and cost for TB and Rifampicin resistance (RR) detection. The algorithm involves testing with TB-LAMP followed by Xpert MTB/RIF for positive TB-LAMP cases to diagnose TB during mass campaigns in prisons and refugee camps. METHODS: The National Tuberculosis Control Program (NTCP) organized routine TB mass-screening campaigns in 34 prisons and 3 villages with refugees camps in Cameroon in 2019. TB LAMP was used for initial TB diagnosis and all TB-LAMP positive cases tested with the Xpert MTB/RIF assay to determine RR. TAT and cost benefits analysis of the combined use of TB-LAMP and Xpert MTB/RIF assays was determined and compared to the Xpert MTB/RIF assay when used only. RESULTS: A total of 4075 sputum samples were collected from TB presumptive, 3672 cases in 34 prisons and 403 samples in 3 villages. Of the 4,075 samples screened with TB-LAMP, 135 were TB positive (3.31%) and run on the Xpert MTB/RIF. Of the 135 positives cases, Xpert MTB/RIF revealed 3 were RR (2.22%). The use of TB-LAMP followed by testing with Xpert MTB/RIF for TB and RR detection reduced the TAT by 73.23% in prisons and 74.92% in villages. In addition to a reduced TAT, the two molecular tests used in synergy is cost benefit from year 2 onwards. CONCLUSION: This study demonstrates the advantages of a diagnostic algorithm based on an initial testing with TB-LAMP followed by testing with Xpert MTB/RIF for TB diagnosis. This approach improved early and rapid TB detection with an added advantage of providing RR status. The proposed algorithm is effective and less costly from the second year of implementation and should be used by TB control programs.

Hot-spots of HIV infection in Cameroon: a spatial analysis based on Demographic and Health Surveys data.

BACKGROUND: The Human Immunodeficiency Virus(HIV) infection prevalence in Cameroon has decreased from [Formula: see text] in 2004 to [Formula: see text] in 2018. However, this decrease in prevalence does not show disparities especially in terms of spatial or geographical pattern. Efficient control and fight against HIV infection may require targeting hotspot areas. This study aims at presenting a cartography of HIV infection situation in Cameroon using the 2004, 2011 and 2018 Demographic and Health Survey data, and investigating whether there exist spatial patterns of the disease, may help to detect hot-spots. METHODS: HIV biomarkers data and Global Positioning System (GPS) location data were obtained from the Cameroon 2004, 2011, and 2018 Demographic and Health Survey (DHS) after an approved request from the MEASURES Demographic and Health Survey Program. HIV prevalence was estimated for each sampled area. The Moran's I (MI) test was used to assess spatial autocorrelation. Spatial interpolation was further performed to estimate the prevalence in all surface points. Hot-spots were identified based on Getis-Ord (Gi*) spatial statistics. Data analyses were done in the R software(version 4.1.2), while Arcgis Pro software tools' were used for all spatial analyses. RESULTS: Generally, spatial autocorrelation of HIV infection in Cameroon was observed across the three time periods of 2004 ([Formula: see text], [Formula: see text]), 2011 ([Formula: see text], [Formula: see text]) and 2018 ([Formula: see text], [Formula: see text]). Subdivisions in which one could find persistent hot-spots for at least two periods including the last period 2018 included: Mbéré, Lom et Djerem, Kadey, Boumba et Ngoko, Haute Sanaga, Nyong et Mfoumou, Nyong et So'o Haut Nyong, Dja et Lobo, Mvila, Vallée du Ntem, Océan, Nyong et Kellé, Sanaga Maritime, Menchum, Dounga Mantung, Boyo, Mezam and Momo. However, Faro et Déo emerged only in 2018 as a subdivision with HIV infection hot-spots. CONCLUSION: Despite the decrease in HIV epidemiology in Cameroon, this study has shown that there are spatial patterns for HIV infection in Cameroon and possible hot-spots have been identified. In its effort to eliminate HIV infection by 2030 in Cameroon, the public health policies may consider these detected HIV hot-spots, while maintaining effective control in other parts of the country.

High seroprevalence of severe acute respiratory syndrome coronavirus 2 among healthcare workers in Yaoundé, Cameroon after the first wave of Covid-19 pandemic and associated factors.

BACKGROUND: Healthcare workers (HWs) are at a high risk of exposure to emerging health threats. Following the first wave of the coronavirus disease 2019 pandemic in Cameroon, we explored the presence and persistence of naturally acquired antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the factors associated with seropositivity in HWs. METHODS: Staff at two referral hospitals in Yaoundé or two Health District Hospitals in Obala and Mbalmayo were included in a 6-month prospective cohort analysis or cross-sectional survey, respectively. Seroprevalence and associated factors were determined, and Kaplan-Meier curves and Cox proportional hazards models were used to assess antibody persistence or positive seroconversion over time. RESULTS: From August 2020 to March 2021, 426 HWs (median age: 31 years, interquartile range: 27-37 years; 66.4% female) were enrolled. The overall seroprevalence of anti-SARS-CoV-2 antibodies was 54.0% (95% confidence interval [CI]: 49.1-58.8) and was significantly different between study sites (p = 0.04). Of the 216 HWs included in the 6-month cohort, 109 (50.5%) HWs were seropositive at inclusion; the probability of persistent antibodies or of becoming seropositive was 93.8% (95% CI: 84.2-100) and 78.9% (95% CI: 61.7-88.4), respectively. Seroconversion was associated with study site and occupation but not with infection prevention and control (IPC) practices. CONCLUSIONS: We observed high seroprevalence of SARS-CoV-2 antibody and seroconversion among HWs associated with occupational risk. This suggests low compliance to the COVID-19 control measures. Continued training and implementation of IPC measures and accelerated preparedness are needed to better tackle future threats.

Observed versus estimated actual trend of COVID-19 case numbers in Cameroon: A data-driven modelling.

Controlling the COVID-19 outbreak remains a challenge for Cameroon, as it is for many other countries worldwide. The number of confirmed cases reported by health authorities in Cameroon is based on observational data, which is not nationally representative. The actual extent of the outbreak from the time when the first case was reported in the country to now remains unclear. This study aimed to estimate and model the actual trend in the number of COVID -19 new infections in Cameroon from March 05, 2020 to May 31, 2021 based on an observed disaggregated dataset. We used a large disaggregated dataset, and multilevel regression and poststratification model was applied prospectively for COVID-19 cases trend estimation in Cameroon from March 05, 2020 to May 31, 2021. Subsequently, seasonal autoregressive integrated moving average (SARIMA) modeling was used for forecasting purposes. Based on the prospective MRP modeling findings, a total of about 7450935 (30%) of COVID-19 cases was estimated from March 05, 2020 to May 31, 2021 in Cameroon. Generally, the reported number of COVID-19 infection cases in Cameroon during this period underestimated the estimated actual number by about 94 times. The forecasting indicated a succession of two waves of the outbreak in the next two years following May 31, 2021. If no action is taken, there could be many waves of the outbreak in the future. To avoid such situations which could be a threat to global health, public health authorities should effectively monitor compliance with preventive measures in the population and implement strategies to increase vaccination coverage in the population.

Non-inferiority test for a continuous variable with a flexible margin in an active controlled trial: an application to the "Stratall ANRS 12110 / ESTHER" trial.

BACKGROUND: Non-inferiority trials are becoming increasingly popular in public health and clinical research. The choice of the non-inferiority margin is the cornerstone of such trials. Most of the time, the non-inferiority margin is fixed and constant, determined from historical trials as a fraction of the effect of the reference intervention. But in some circumstances, there may some uncertainty around the reference treatment that one would like to account for when performing the hypothesis testing. In this case, the non-inferiority margin is not fixed in advance and depends on the reference intervention estimate. Hence, the uncertainty surrounding the non-inferiority margin should be accounted for in statistical tests. In this work, we explore how to perform the non-inferiority test for a continuous variable with a flexible margin. METHODS: We have proposed in this study, two procedures for the non-inferiority test with a flexible margin for continuous endpoints. The proposed test procedures are based on a test statistic and confidence interval approaches respectively. Simulations have been used to assess the performances and properties of the proposed test procedures. An application was done on a real-world clinical data, to assess the efficacy of clinical monitoring alone versus laboratory and clinical monitoring in HIV-infected adult patients. RESULTS: Basically, for both proposed methods, the type I error estimate was not dependent on the values of the reference treatment. In the test statistic approach, the type 1 error rate estimate was approximatively equal to the nominal value. It has been found that the confidence interval level determined approximatively the level of significance. For a given nominal type I error α, the appropriate one- and two-sided confidence intervals should be with levels 1-α and 1-2α, respectively. CONCLUSIONS: Based on the type I error rate and power estimates, the proposed non-inferiority hypothesis test procedures had good performances and were applicable in practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT00301561. Registered on March 13, 2006, url: https://clinicaltrials.gov/ct2/show/NCT00301561 .

Improving the management and security of COVID 19 diagnostic test data with a digital platform in resource-limited settings: The case of PlaCARD in Cameroon.

During the COVID 19 pandemic, round-the-clock demand for COVID -19 laboratory tests exceeded capacity, placing a significant burden on laboratory staff and infrastructure. The use of laboratory information management systems (LIMS) to streamline all phases of laboratory testing (preanalytical, analytical, and postanalytical) has become inevitable. The objective of this study is to describe the architecture, implementation, and requirements of PlaCARD, a software platform for managing patient registration, medical specimens, and diagnostic data flow, as well as reporting and authentication of diagnostic results during the 2019 coronavirus pandemic (COVID -19) in Cameroon. Building on its experience with biosurveillance, CPC developed an open-source, real-time digital health platform with web and mobile applications called PlaCARD to improve the efficiency and timing of disease-related interventions. PlaCARD was quickly adapted to the decentralization strategy of the COVID 19 testing in Cameroon and, after specific user training, was deployed in all COVID 19 diagnostic laboratories and the regional emergency operations center. Overall, 71% of samples tested for COVID 19 by molecular diagnostics in Cameroon from 05 March 2020 to 31 October 2021 were entered into PlaCARD. The median turnaround time for providing results was 2 days [0-2.3] before April 2021 and decreased to 1 day [1- 1] after the introduction of SMS result notification in PlaCARD. The integration of LIMS and workflow management into a single comprehensive software platform (PlaCARD) has strengthened COVID 19 surveillance capabilities in Cameroon. PlaCARD has demonstrated that it can be used as a LIMS for managing and securing test data during an outbreak.

Long-term effectiveness and safety of didanosine combined with lamivudine and efavirenz or nevirapine in antiretroviral-naive patients: a 9-year cohort study in Senegal.

OBJECTIVE: The use of didanosine (ddI) in first-line antiretroviral therapy has been recently promoted for resource-limited settings. We therefore compared the long-term effectiveness and safety of the regimen combining ddI, lamivudine, and efavirenz or nevirapine with that of the WHO-recommended regimen of zidovudine (ZDV), lamivudine, and efavirenz or nevirapine in antiretroviral-naïve patients in Senegal. METHODS: Observational cohort study of patients enrolled between January 2000 and April 2002 in the Senegalese antiretroviral drug access initiative. Multivariate analyses were performed to compare, between the ddI and ZDV groups, the proportion of patients with a viral load <500 copies/ml during follow-up; the increase in the CD4 cell count; survival; treatment changes and severe adverse events. RESULTS: Of 151 patients, 71 received the ddI-based treatment and 80 received the ZDV-based treatment. Throughout follow-up, 80-95% of patients had a viral load below 500 copies/ml in both the ddI and ZDV groups (P = 0.5). The CD4 cell count increased after treatment initiation from 176 to 497 cells/mm(3) in the ddI group and from 176 to 567 cells/mm(3) in the ZDV group (P > 0.3). The rate of death tended to be higher in the ddI group (P = 0.06). ddI was less commonly discontinued than ZDV (P = 0.03). CONCLUSION: The combination of ddI, lamivudine, and efavirenz or nevirapine resulted in sustained viral suppression and immunological recovery.

Virological failure and antiretroviral resistance among HIV-infected children after five years follow-up in the ANRS 12225-PEDIACAM cohort in Cameroon.

OBJECTIVE: In the present study, we aimed to evaluate the virological failure (VF) and drug resistance among treated HIV-infected children after five years follow-up in the ANRS-Pediacam cohort in Cameroon. METHODS: From November 2007 to October 2011, HIV-infected children born to HIV-infected mothers were included in the ANRS-PEDIACAM study and followed-up for more than 5 years. Plasma viral load (VL) was measured at each visit (every three months until month 24 and every 6 months thereafter). VF was the main outcome and HIV drug resistance test was performed using the ANRS procedures and algorithm. RESULTS: Data from 155 children were analyzed. The median age at combination antiretroviral therapy (cART) initiation was 4.2 months (interquartile range (IQR): 3.2-5.8), with 103 (66.5%) children taking LPV/r-containing regimen and 51 (32.9%) children taking NVP. After five years follow-up, 63 (40.6%; CI: 32.9-48.8) children experienced VF. The median duration between cART initiation and VF was 22.1 months (IQR: 11.9-37.1) with a median VL of 4.8 log10 (IQR: 4.0-5.5). Among the 57 children with HIV drug resistance results, 40 (70.2%) had at least one drug resistance mutation. The highest resistance rates (30.4-66.1%) were obtained with Lamivudine; Efavirenz; Nevirapine and Rilpivirine. CONCLUSIONS: These results show high resistance to NNRTI and emphasize the need of VL and resistance tests for optimal follow-up of HIV-infected people especially children.

Effect of a Single Standard Dose (150-200 µg/kg) of Ivermectin on Loa loa Microfilaremia: Systematic Review and Meta-analysis.

BACKGROUND: In central Africa, millions of individuals infected with Loa loa have received the anthelminthic drug ivermectin (IVM) as part of mass drug administration (MDA) campaigns targeting onchocerciasis control or elimination. Nonetheless, the parasitological surveys that are occasionally conducted to evaluate the impact of IVM treatments on Onchocerca volvulus do not include an assessment of the extra benefits of those MDA campaigns on L. loa. METHODS: We conducted a systematic review of trials on the effect of a single standard (150-200 µg/kg) dose of IVM on L. loa microfilarial density (MFD). The dynamics of MFD over 365 days of treatment were described using multilevel regression and latent class modeling. RESULTS: IVM brings about a rapid, dramatic, and sustained decrease, with reduction rates of 60%, 75%, 85%, and 90% on day 1 (D1), D2, D7, and D365, respectively. At D365, no participants (0/238) with an initial MFD of <20 000 microfilariae (mf)/mL were at risk of postivermectin severe adverse events, and only 1/57 individuals with an initial MFD of ≥20 000 mf/mL presented with an MFD above this value. The main predictor of post-treatment MFD was the pretreatment value, but this post-treatment value varied little between D8 and D365 regardless of the pretreatment level. CONCLUSIONS: A single dose of IVM is very effective at substantially reducing L. loa MFD for at least a year, irrespective of the initial level of parasitemia. Individuals treated with IVM are probably not any more at risk of severe adverse events when retreated 1 year later.