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Background: Case reports have hypothesised that proteinuria, sometimes with glomerulopathy or nephrotic syndromes, might be associated with loiasis. To our knowledge, no study has been done to assess this association. We aimed to investigate the association between Loa loa microfilariae burden and proteinuria., Methods: We did a cross-sectional study between May 16, 2022, and June 11, 2022, to assess the relationship between Loa loa microfilaraemia densities and proteinuria in a rural area of the Republic of Congo. We included all consenting adults living in the target area at study commencement who had L loa microfilarial densities greater than 500 microfilariae per mL during previous screening for a clinical trial in 2019. This study is part of the MorLo project, and used the project's study population of individuals aged 18 years or older who were living near Sibiti. For each microfilaraemic individual, two individuals without L loa microfilarial densities matched on age, sex, and place of residence were included. The association between proteinuria (assessed by dipstick) and L loa microfilarial densities, age, and sex was assessed using an unconstrained ordinal regression model since the parallel-lines assumption was violated for microfilarial densities., Findings: 991 participants were included, of whom 342 (35%) were L loa microfilaraemic. The prevalence of microfilaraemia was 38% (122 of 325) among individuals with trace proteinuria (<300 mg/24 h), 51% (45 of 89) among individuals with light proteinuria (300 mg to 1 g/24 h), and 71% (15 of 21) among individuals with high proteinuria (>1 g/24 h). Individuals with high proteinuria had significantly higher L loa microfilarial densities (p<0·0001): mean microfilariae per mL were 1595 (SD 4960) among individuals with no proteinuria, 2691 (7982) for those with trace proteinuria, 3833 (9878) for those with light proteinuria, and 13 541 (20 118) for those with high proteinuria. Individuals with 5000-14 999 microfilariae per mL and individuals with 15 000 microfilariae per mL or greater were, respectively, 5·39 and 20·49 times more likely to have a high proteinuria than individuals with no microfilaraemia., Interpretation: The risk of proteinuria increases with L loa microfilaraemia. Further studies are needed to identify renal disorders (eg, tubulopathies, glomerulopathies, or nephrotic syndromes) responsible for loiasis-related proteinuria., Funding: European Research Council, MorLo project., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests CB is the recipient of a grant from the Bettencourt-Schueller Foundation (CCU-AH-INSERM-Bettencourt). All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The elimination of onchocerciasis requires increasing ivermectin treatment coverage in communities hypoendemic for onchocerciasis. In areas where loiasis is co-endemic, this approach is complicated by the risk of serious adverse events following treatment with ivermectin in individuals with a high Loa loa microfilarial density (MFD). We aimed to evaluate the extent to which the pre-treatment MFD can be inferred from post-treatment MFDs., Methods: For this retrospective analysis, we used data from seven clinical or community trials (six were used for the main analysis and one for the secondary analysis) conducted in Cameroon, in which MFDs were measured both before and after (within 14 days) receiving a single dose of ivermectin (150-200 μg/kg bodyweight). The primary objective was to establish the receiver operating characteristic curves and the corresponding area under the curve statistics of MFD measured after treatment to classify pre-treatment MFD (MFD D0 ) according to common risk thresholds of serious adverse events. We assessed the performance of post-treatment MFD to accurately classify MFD D0 according to commonly used thresholds using bootstrap procedures., Findings: 281 individuals with MFD measurements available before and 3-10 days after ivermectin treatment were enrolled. Our results show that an MFD of more than 3500 L loa microfilariae per mL of blood (mf per mL) 3 or 4 days after treatment indicates a 68·6% chance (positive predictive value) of an MFD D0 of more than 20 000 mf per mL. An MFD of more than 3500 mf per mL at day 5-10 corresponds to a 72·2% chance of having an MFD D0 of more than 20 000 mf per mL. Conversely, an MFD of less than 2500 microfilariae per mL at day 3-4 or day 5-10 corresponds to a probability of 92·3% or 92·8% (negative predictive value) of having MFD D0 of less than 20 000 mf per mL. An MFD less than 1500 mf per mL on days 3-4 after treatment was associated with a 78·3% probability of having an MFD D0 less than 8000 mf per mL; this probability increased to 89·6% on days 5-10 after treatment., Interpretation: The MFD threshold of 1000 mf per mL within 1 month of treatment, which is commonly used to attribute the occurrence of a serious adverse event to ivermectin, should be revised. In this study, we present tables that can help to assess this attributability as part of mass or individual treatments., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Implementation of onchocerciasis elimination programmes has been delayed in Central Africa because of the risk of ivermectin-related serious adverse events (SAEs) in individuals with high Loa loa microfilarial densities (MFD). We developed the first statistical models enabling prediction of SAE risk in individuals with a given MFD., Methods: We used individual participant data from two trials conducted in loiasis-onchocerciasis co-endemic areas in Cameroon. among the 10 506 ivermectin-treated subjects included in the analysis, 38 (0·36%) developed an ivermectin-related SAE. To predict individual-level risk of SAE, we developed mixed multivariate logistic models including subjects' sex, age, pre-treatment L loa and Mansonella perstans MFDs, and study region., Findings: The models predicted that regardless of sex, about 1% of people with 20 000 L loa microfilariae per millilitre of blood (mf/mL), 10% of people with 50 000 mf/mL and about one third of those with 100 000 mf/mL will develop an SAE. For a given MFD, males have a three-fold higher risk of developing an SAE than females., Interpretation: By enabling the prediction of post-ivermectin SAE risk in communities with known distribution of L loa MFDs, our results can guide decisions on the choice of ivermectin-based treatment strategies. They also predict that 37 SAEs were prevented in 2015 by using a Test-and-Treat strategy in the Okola District of Cameroon., Funding: UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases; Institut de Recherche pour le Développement; Mectizan Donation Program; Bill & Melinda Gates Foundation ., Competing Interests: We declare no competing interests., (© 2020 The Authors.)

Background: Surveys conducted in 1991-1992 in the Mbam Valley (Cameroon) revealed that onchocerciasis was highly endemic, with community microfilarial loads (CMFL) > 100 microfilariae/snip in some villages. Also in 1991-1992, a survey of suspected cases of epilepsy (SCE) found 746 SCE using a questionnaire administered to individuals identified by key informants, with prevalences reaching 13.6% in some communities. From 1998, annual community-directed treatment with ivermectin (CDTI) was implemented to control onchocerciasis. In 2017, a door-to-door household survey was conducted in three of the villages visited in 1991-1992, using a standardized 5-item epilepsy screening questionnaire., Results: In 2017, a total of 2286 individuals living in 324 households were screened (582 in Bayomen, 553 in Ngongol and 1151 in Nyamongo) and 112 SCE were identified (4.9%). Neurologists examined 92 of these SCE and confirmed the diagnosis of epilepsy for 81 of them (3.5%). Between the surveys in 1991-1992 and 2017, the prevalence of SCE decreased from 13.6% to 2.5% in Bayomen (P = 0.001), from 8.7% to 6.6% in Ngongol (P = 0.205) and from 6.4% to 5.4% in Nyamongo (P = 0.282). The median age of SCE shifted from 20 (IQR: 12-23) to 29 years (IQR: 18-33; P = 0.018) in Bayomen, from 16 (IQR: 12-21) to 26 years (IQR: 21-39; P < 0.001) in Ngongol and from 16 (IQR: 13-19) to 24 years (IQR: 19-32; P < 0.001) in Nyamongo. The proportions of SCE aged < 10, 10-19, 20-29 and ≥ 30 years shifted from 9.5, 58.3, 25.0 and 7.1% in 1991-1992 to 2.7, 20.5, 39.3 and 37.5% in 2017, respectively., Conclusions: SCE prevalence decreased overall between 1991-1992 and 2017. The age shift observed is probably due to a decrease in the number of new cases of epilepsy resulting from the dramatic reduction of Onchocerca volvulus transmission after 19 years of CDTI.

Background: A high prevalence of epilepsy has been observed in several onchocerciasis-endemic countries, including Cameroon. However, little is known on the clinical presentations of the affected persons with epilepsy (PWE). A community-based study was conducted with the aim of describing the spectrum of seizures in selected onchocerciasis-endemic villages in Cameroon and documenting relevant medical history in patients with onchocerciasis-associated epilepsy (OAE)., Methods: We carried out door-to-door surveys in 5 onchocerciasis-endemic villages in Cameroon and recruited all consenting PWE. Epilepsy was diagnosed using a 2-step approach consisting of the administration of a standardized 5-item questionnaire followed by confirmation of the suspected cases by a neurologist. Onchocerciasis-associated epilepsy was defined as ≥2 seizures without an obvious cause, starting between the ages of 3-18 years in previously healthy persons having resided for at least 3 years in an onchocerciasis-endemic area. Ivermectin use by PWE was verified. Seizure history, relevant past medical, and family history, as well as neurological findings, were noted., Results: In all, 156 PWE were recruited in the 5 villages. The modal age group for epilepsy onset was 10-14 years. The diagnostic criteria for OAE were met by 93.2% of the PWE. Participants had one or more of the following seizure types: generalized tonic-clonic seizures (89.1%), absences (38.5%), nodding (21.8%), focal nonmotor (7.7%), and focal motor seizures (1.9%). One case (0.6%) with the "Nakalanga syndrome" was identified. More than half (56.4%) of PWE had at least one seizure per month. In one village, 56.2% of PWE had onchocercal skin lesions., Conclusion: People with epilepsy in onchocerciasis-endemic villages in Cameroon present with a wide clinical spectrum including nodding seizures and Nakalanga features. A great majority of participants met the diagnostic criteria for OAE, suggesting that better onchocerciasis control could prevent new cases. Epilepsy management algorithms in these areas must be adjusted to reflect the varied seizure types., (Copyright © 2018. Published by Elsevier Inc.)

Background: Many studies have suggested that onchocerciasis might be associated with epilepsy. Therefore, we did a cohort study to assess the incidence of epilepsy relative to Onchocerca volvulus skin microfilarial density (MFD) measured during childhood and to assess the possibility of a temporal relationship., Methods: During onchocerciasis surveys undertaken in 25 villages in Cameroon during 1991-93, we measured MFD in individuals aged 5 years or older. In 2017, we revisited seven of these villages. With a standardised five-item questionnaire, we collected information on the occurrence of epilepsy in 856 individuals who were aged 5-10 years in 1991-93, and had MFD determined during the original surveys. We did multivariable analyses to assess the overall incidence and incidence ratios taking into account age, sex, individual MFD in 1991-93, and onchocerciasis endemicity level in the village., Findings: In 2017, we obtained data on the history of epilepsy for 85% (729 of 856) of individuals. Among these individuals, we classified 60 as being suspected cases of epilepsy. The overall incidence of epilepsy was 350 per 100 000 person-years (95% CI 270-450). The adjusted incidence ratio for developing epilepsy was 7·07 (95% CI 0·98-51·26; p=0·0530) in individuals with initial MFD of one to five microfilariae per skin snip (mf per snip), 11·26 (2·73-46·43) in individuals with six to 20 mf per snip, 12·90 (4·40-37·83) in individuals with 21-50 mf per snip, 20·00 (3·71-108·00) in individuals with 51-100 mf per snip, 22·58 (3·21-158·56) in individuals with 101-200 mf per snip, and 28·50 (95% CI 3·84-211·27; p=0·0010) in individuals with more than 200 mf per snip, compared with that of individuals without detectable densities of skin microfilariae., Interpretation: Individual O volvulus MFD in childhood was associated with the risk of either seizures or epilepsy in an onchocerciasis focus in Cameroon. This temporal relationship suggests a potential causal link between onchocerciasis and epilepsy., Funding: European Research Council, NSETHIO Project., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: In rural Africa, data on virologic effectiveness of antiretroviral treatment (ART) are not sufficient to assess the gap with the UNAIDS 90-90-90 treatment targets. We investigated the prevalences of unsuppressed viral load and antiretroviral drug resistance and the profile of genotypic resistance mutations among patients routinely treated in rural Cameroon., Methods: A cross-sectional study was performed in 2013-2014 among patients ≥15 years and on first-line ART for ≥6 months in a district hospital. Patients were offered free access to human immunodeficiency virus viral load testing. Genotypic drug resistance testing was done when the viral load was >1000 copies/mL. Multivariate logistic regression models were used to assess the relationship of unsuppressed viral load or antiretroviral drug resistance with sociodemographic and medical characteristics., Results: Of 407 patients (women 74.9%, median age 41.8 years, median time on ART 29.2 months), 96 (23.6%; 95% confidence interval [CI], 19.5-28.0) had unsuppressed viral load and 74 (18.2%; 95% CI, 14.6-22.3) had antiretroviral drug resistance. The prevalences of unsuppressed viral load and resistance increased with time on ART, from 12.0% and 8.0% in the 6- to 12-month group to 31.3% and 27.1% in the >72-month group, respectively. All 74 patients with antiretroviral drug resistance were resistant to nonnucleoside reverse-transcriptase inhibitors, and 57 of them were also resistant to nucleoside reverse-transcriptase inhibitors., Conclusions: Our estimations were among the highest observed in the west and central African region. The proportion of patients with virologic failure should be divided at least by 2 to reach the UNAIDS 90-90-90 treatment targets., (© The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: Evidence of gender differences in antiretroviral treatment (ART) outcomes in sub-Saharan Africa is conflicting. Our objective was to assess gender differences in (1) adherence to ART and (2) virologic failure, immune reconstitution, mortality, and disease progression adjusting for adherence., Methods: Cohort study among 459 ART-naive patients followed up 24 months after initiation in 2006-2010 in 9 rural district hospitals. Adherence to ART was assessed using (1) a validated tool based on multiple patient self-reports and (2) antiretroviral plasma concentrations. The associations between gender and the outcomes were assessed using multivariate mixed models or accelerated time failure models., Results: One hundred thirty-five patients (29.4%) were men. At baseline, men were older, had higher body mass index and hemoglobin level, and received more frequently efavirenz than women. Gender was not associated with self-reported adherence (P = 0.872, 0.169, and 0.867 for moderate adherence, low adherence, and treatment interruption, respectively) or with antiretroviral plasma concentrations (P = 0.549 for nevirapine/efavirenz). In contrast, male gender was associated with virologic failure [odds ratio: 2.18, 95% confidence interval (CI): 1.31 to 3.62, P = 0.003], lower immunologic reconstitution (coefficient: -58.7 at month 24, 95% CI: -100.8 to -16.6, P = 0.006), and faster progression to death (time ratio: 0.30, 95% CI: 0.12 to 0.78, P = 0.014) and/or to World Health Organization stage 4 event (time ratio: 0.27, 95% CI: 0.09 to 0.79, P = 0.017)., Conclusions: Our study provides important evidence that African men are more vulnerable to ART failure than women and that the male vulnerability extends beyond adherence issues. Additional studies are needed to determine the causes for this vulnerability to optimize HIV care. However, personalized adherence support remains crucial.

Objectives: The objectives of this study were to describe the pretreatment HIV-1 DNA concentrations in children infected with HIV and to evaluate the impact of antiretroviral therapy (ART) on HIV-DNA concentrations., Methods: This was a retrospective analysis of all children followed up in the 'Programme Enfant Yopougon' cohort, Abidjan, Côte d'Ivoire, from 2000 to 2004, who had cryopreserved peripheral blood mononuclear cells (PBMCs) and plasma samples. HIV-DNA was measured using a real-time PCR assay. Mixed-model analysis was used to analyse the factors associated with change in HIV-DNA concentration., Results: The study included 121 children infected with HIV-1. The median age at inclusion was 6 years (IQR: 3.5-9) and children were at an advanced stage of HIV disease (46.6% and 20.3% presenting CDC stage B and CDC stage C, respectively). At baseline, the median HIV-DNA concentration was 3.4 log₁₀ copies/10(6) PBMCs (IQR: 3.1-3.6). Fifty-four children were initiated on ART during follow-up. After 24 months of ART, HIV-DNA load decreased by 0.32 (IQR: 0.08-0.57) log₁₀ copies/10(6) PBMCs. The only factor associated with the HIV-DNA decrease was a concomitant low HIV-RNA viral load result. Children with efficient ART had a 0.51 log₁₀ copies (IQR: 0.40-0.86) HIV-DNA decrease per million PBMCs., Conclusions: HIV-DNA concentrations decreased following ART initiation in a large African paediatric cohort. This decline was exclusively associated with the decrease in ongoing replication level achieved. Our study points out that a strong adherence is needed for ART to be efficient on the viral reservoirs, and further reinforces that adherence support is also essential to diminish the reservoir., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Dengue and malaria are two major public health concerns in tropical settings. Although the pathogeneses of these two arthropod-borne diseases differ, their clinical and biological presentations are unspecific. During dengue epidemics, several hundred patients with fever and diffuse pain are weekly admitted at the emergency room. It is difficult to discriminate them from patients presenting malaria attacks. Furthermore, it may be impossible to provide a parasitological microscopic examination for all patients. This study aimed to establish a diagnostic algorithm for communities where dengue fever and malaria occur at some frequency in adults., Methodology/principal Findings: A sub-study using the control groups of a case-control study in French Guiana--originally designed to compare dengue and malaria co-infected cases to single infected cases--was performed between 2004 and 2010. In brief, 208 patients with malaria matched to 208 patients with dengue fever were compared in the present study. A predictive score of malaria versus dengue was established using .632 bootstrap procedures. Multivariate analysis showed that male gender, age, tachycardia, anemia, thrombocytopenia, and CRP>5 mg/l were independently associated with malaria. The predictive score using those variables had an AUC of 0.86 (95%CI: 0.82-0.89), and the CRP was the preponderant predictive factor. The sensitivity and specificity of CRP>5 mg/L to discriminate malaria from dengue were of 0.995 (95%CI: 0.991-1) and 0.35 (95%CI 0.32-0.39), respectively., Conclusions/significance: The clinical and biological score performed relatively well for discriminating cases of dengue versus malaria. Moreover, using only the CRP level turned to be a useful biomarker to discriminate feverish patients at low risk of malaria in an area where both infections exist. It would avoid more than 33% of unnecessary parasitological examinations with a very low risk of missing a malaria attack.

Our study in Cameroonian rural district hospitals showed that the immunologic and clinical failure criteria had poor performance to identify human immunodeficiency virus drug resistance in a timely manner. Switching to second-line antiretroviral therapy after 2 consecutive viral loads ≥5000 copies/mL, as recommended by the World Health Organization, appeared to be the most appropriate strategy.

Background: Task shifting to nurses for antiretroviral therapy (ART) is promoted by the World Health Organization to compensate for the severe shortage of physicians in Africa. We assessed the effectiveness of task shifting from physicians to nurses in rural district hospitals in Cameroon., Methods: We performed a cohort study using data from the Stratall trial, designed to assess monitoring strategies in 2006-2010. ART-naive patients were followed up for 24 months after treatment initiation. Clinical visits were performed by nurses or physicians. We assessed the associations between the consultant ratio (ie, the ratio of the number of nurse-led visits to the number of physician-led visits) and HIV virological success, CD4 recovery, mortality, and disease progression to death or to the World Health Organization clinical stage 4 in multivariate analyses., Results: Of the 4141 clinical visits performed in 459 patients (70.6% female, median age 37 years), a quarter was task shifted to nurses. The consultant ratio was not significantly associated with virological success [odds ratio 1.00, 95% confidence interval (CI): 0.59 to 1.72, P = 0.990], CD4 recovery (coefficient -3.6, 95% CI: -35.6; 28.5, P = 0.827), mortality (time ratio 1.39, 95% CI: 0.27 to 7.06, P = 0.693), or disease progression (time ratio 1.60, 95% CI: 0.35 to 7.37, P = 0.543)., Conclusions: This study brings important evidence about the comparability of ART-related outcomes between HIV models of care based on physicians or nurses in resource-limited settings. Investing in nursing resources for the management of noncomplex patients should help reduce costs and patient waiting lists while freeing up physician time for the management of complex cases, for mentoring and supervision activities, and for other health interventions.

Background: Although 90% of HIV-1-infected children live in sub-Saharan Africa, morbidity data after highly active antiretroviral therapy (HAART) initiation in these settings are limited. The objective of this study was to document the incidence of AIDS-defining events and non-AIDS-defining diseases in African children receiving HAART., Methods: Incidences rates (IRs) of AIDS-defining events and 10 other common diseases were estimated overall and by current CD4-strata (<15%, 15 - <25% and ≥25%) from 2 prospective cohorts of African children., Results: One hundred eighty-eight children contributing to 355 children-years were included. The documented morbidity IRs per 100 children-years were upper respiratory infections, 100 (87-114); infectious diarrhea, 37 (31-44); World Health Organization (WHO) stage 2 events, 22.9 (18.2-28.1); and WHO stage 3/4 events, 12.3 (9.1-16.7). IRs of WHO stage 2 events, severe bacterial infections, infectious diarrhea and pneumonia decreased linearly across all CD4%-strata, whereas WHO stage 3/4 events and viral infections occurred mostly when CD4% <15%. Overall, IRs decreased during the first 2 years on HAART except for upper respiratory infection, mycosis and oral candidiasis., Conclusion: This incidence of AIDS- and non-AIDS-defining diseases declined substantially after HAART in 2 African cohorts, although estimates remained high compared with high-resource settings. Without renewed efforts to increase antiretroviral scale-up, children in developing countries will continue to have a high burden of infections.

Background: Community-acquired pneumonia (CAP) is the major manifestation of Q fever, an emerging disease in French Guiana. Consequently, the empirical antibiotherapy used for the treatment of CAP combines doxycycline and the recommended amoxicillin. Our objectives were to estimate the prevalence of Q fever pneumonia and to build a prediction rule to identify patients with Q fever pneumonia for empirical antibiotic guidance., Methods: A retrospective case-control study was conducted on inpatients admitted with CAP in the Department of Infectious Diseases of Cayenne Hospital from 2004 to 2007. Serodiagnosis for Coxiella burnetii was performed for all patients. Risk factor analysis was performed using multivariate logistic regression, and a prognostic score was computed using bootstrap procedures. The score performance characteristics were used to choose the best prediction rule to identify patients with Q fever pneumonia., Results: One hundred thirty-one patients with CAP were included and the Q fever pneumonia prevalence was 24.4% (95% confidence interval [CI], 17.1-31.9). In multivariate analysis, male sex, middle age (age, 30-60 years), headache, leukocyte count <10 × 10(9)/L and C-reactive protein level >185 mg/L were independently associated with Q fever pneumonia. Patients with a predictive score ≤3 had a low risk of Q fever pneumonia with a negative predictive value of 0.97 (95% CI, .90-1) and a sensitivity of 0.97 (95% CI, .89-1)., Conclusions: The prediction rule described here accurately identifies patients with low risk of Q fever pneumonia and may help physicians to make more rational decisions about the empirical use of antibiotherapy. Further prospective studies should be performed to validate this score.

Multiple electrolytic lesions were placed in the raphe area of pigeons. Basal plasma corticosterone level (B) was found not to be altered. Stress-induced adrenocortical activation was markedly reduced in raphe lesioned pigeons as compared to controls. Electrical stimulation of the nucleus raphes in permanently implanted, unrestrained and unanesthetized birds induced a significant rise in B. However the magnitude of the response to raphe stimulating was lower (1/2 approximately) and especially later than after hypothalamic stimulation since it paralleled exactly the pattern of stress induced activation.