High level of HIV drug resistance informs dolutegravir roll-out and optimized NRTI backbone strategy in Mozambique.

BACKGROUND: HIV drug resistance (HIV-DR) is rising in sub-Saharan Africa in both ART-naive and ART-experienced patients. OBJECTIVES: To estimate the level of acquired DR (ADR) and pre-treatment DR (PDR) across selected urban and rural sites in Southern Africa, in Mozambique. METHODS: We conducted two cross-sectional surveys among adult HIV patients (October 2017-18) assessing ADR and PDR. In the (ADR) survey, those on NNRTI-based first-line ART for ≥6 months were recruited (three sites). In the PDR survey, those ART-naive or experienced with ≥3 months of treatment interruption prior were enrolled (eight sites). RESULTS: Among 1113 ADR survey participants 83% were receiving tenofovir (TDF)/lamivudine (3TC)/efavirenz (EFV). The median time on ART was 4.5 years (Maputo) and 3.2 years (Tete), 8.3% (95% CI 6.2%-10.6%, Maputo) and 15.5% (Tete) had a VL ≥ 1000 copies/mL, among whom 66% and 76.4% had NNRTI+NRTI resistance, and 52.8% and 66.7% had 3TC+TDF-DR. Among those on TDF regimens, 31.1% (Maputo) and 42.2% (Tete) were still TDF susceptible, whereas 24.4% and 11.5% had TDF+zidovudine (ZDV)-DR. Among those on ZDV regimens, 25% and 54.5% had TDF+ZDV-DR. The PDR survey included 735 participants: NNRTI-PDR was 16.8% (12.0-22.6) (Maputo) and 31.2% (26.2-36.6) (Tete), with a higher proportion (≥50%) among those previously on ART affected by PDR. CONCLUSIONS: In Mozambique, viral failure was driven by NNRTI and NRTI resistance, with NRTI DR affecting backbone options. NNRTI-PDR levels surpassed the WHO 10% 'alert' threshold. Replacing NNRTI first-line drugs is urgent, as is frequent viral load monitoring and resistance surveillance. Changing NRTI backbones when switching to second-line regimens may need reconsideration.

Outcomes of patients on second- and third-line ART enrolled in ART adherence clubs in Maputo, Mozambique.

OBJECTIVES: Adherence clubs (AC) offer patient-centred access to antiretroviral therapy (ART) while reducing the burden on health facilities. AC were implemented in a health centre in Mozambique specialising in patients with a history of HIV treatment failure. We explored the impact of AC on retention in care and VL suppression of these patients. METHODS: We performed a retrospective analysis of patients enrolled in AC receiving second- or third-line ART. The Kaplan-Meier estimates were used to analyse retention in care in health facility, retention in AC and viral load (VL) suppression (VL < 1000 copies/mL). Predictors of attrition and VL rebound (VL ≥ 1000 copies/mL) were assessed using multivariable proportional hazards regression. RESULTS: The analysed cohort contained 699 patients, median age 40 years [IQR: 35-47], 428 (61%) female and 97% second-line ART. Overall, 9 (1.3%) patients died, and 10 (1.4%) were lost to follow-up. Retention in care at months 12 and 24 was 98.9% (95% CI: 98.2-99.7) and 96.4% (95% CI: 94.6-98.2), respectively. Concurrently, 85.8% (95% CI: 83.1-88.2) and 80.9% (95% CI: 77.8-84.1) of patients maintained VL suppression. No association between predictors and all-cause attrition or VL rebound was detected. Among 90 patients attending AC and simultaneously having VL rebound, 64 (71.1%) achieved VL resuppression, 10 (11.1%) did not resuppress, and 14 (15.6%) had no subsequent VL result. CONCLUSION: Implementation of AC in Mozambique was successful and demonstrated that patients with a history of HIV treatment failure can be successfully retained in care and have high VL suppression rate when enrolled in AC. Expansion of the AC model in Mozambique could improve overall retention in care and VL suppression while reducing workload in health facilities.

OBJECTIFS: Les clubs d'adhésion (CA) offrent un accès centré sur le patient à la thérapie antirétrovirale (ART) tout en réduisant la charge des établissements de santé. Les CA ont été mis en œuvre dans un centre de santé au Mozambique spécialisé dans les patients ayant des antécédents d'échec du traitement du VIH. Nous avons exploré l'impact des CA sur la rétention dans les soins et la suppression de la CV chez ces patients. MÉTHODES: Nous avons effectué une analyse rétrospective des patients enrôlés dans les CA sous ART de deuxième ou troisième intention. Les estimations de Kaplan-Meyer ont été utilisées pour analyser la rétention dans les soins dans les établissements de santé, la rétention dans les CA et la suppression de la charge virale (CV) (CV <1000 copies/mL). Les prédicteurs de l'attrition et du rebond de la CV (VL ≥ 1000 copies/mL) ont été évalués à l'aide d'une régression à risques proportionnels multivariés. RÉSULTATS: La cohorte analysée contenait 699 patients, d'âge médian 40 ans [IQR: 35-47], 428 (61%) femmes, 97% de traitement de deuxième intention. Dans l'ensemble, 9 (1,3%) patients sont décédés, 10 (1,4%) ont été perdus de vue. La rétention dans les soins à 12 et 24 mois était de 98,9% (IC95%: 98,2-99,7) et de 96,4% (IC95%: 94,6-98,2), respectivement. De même, 85,8% (IC95%: 83,1-88,2) et 80,9% (IC95%: 77,8-84,1) des patients ont maintenu une suppression de la CV. Aucune association entre les prédicteurs et l'attrition toutes causes ou le rebond de la CV n'a été détectée. Parmi 90 patients enrôlés dans les CA et ayant simultanément un rebond de la CV, 64 (71,1%) ont atteint une re-suppression de la CV, 10 (11,1%) n'ont pas atteint une re-suppression et 14 (15,6%) n'avaient pas de résultats de CV ultérieurs. CONCLUSION: La mise en œuvre des CA au Mozambique a été un succès et a démontré que les patients ayant des antécédents d'échec du traitement anti-VIH peuvent être retenus avec succès dans les soins et ont un taux élevé de suppression de la CV lorsqu'ils sont enrôlés dans les CA. L'expansion du modèle CA au Mozambique pourrait améliorer la rétention globale dans les soins et la suppression de la CV tout en réduisant la charge de travail dans les établissements de santé.

Alternative observational designs to estimate the effectiveness of one dose of oral cholera vaccine in Lusaka, Zambia.

We conducted a matched case-control (MCC), test-negative case-control (TNCC) and case-cohort study in 2016 in Lusaka, Zambia, following a mass vaccination campaign. Confirmed cholera cases served as cases in all three study designs. In the TNCC, control-subjects were cases with negative cholera culture and polymerase chain reaction results. Matched controls by age and sex were selected among neighbours of the confirmed cases in the MCC study. For the case-cohort study, we recruited a cohort of randomly selected individuals living in areas considered at-risk of cholera. We recruited 211 suspected cases (66 confirmed cholera cases and 145 non-cholera diarrhoea cases), 1055 matched controls and a cohort of 921. Adjusted vaccine effectiveness of one dose of oral cholera vaccine (OCV) was 88.9% (95% confidence interval (CI) 42.7-97.8) in the MCC study, 80.2% (95% CI: 16.9-95.3) in the TNCC design and 89.4% (95% CI: 64.6-96.9) in the case-cohort study. Three study designs confirmed the short-term effectiveness of single dose OCV. Major healthcare-seeking behaviour bias did not appear to affect our estimates. Most of the protection among vaccinated individuals could be attributed to the direct effect of the vaccine.

The incubation period of hepatitis E genotype 1: insights from pooled analyses of travellers.

Hepatitis E virus genotype 1 (HEV G1) is an important cause of morbidity and mortality in Africa and Asia. HEV G1's natural history, including the incubation period, remains poorly understood, hindering surveillance efforts and effective control. Using individual-level data from 85 travel-related HEV G1 cases in England and Wales, we estimate the incubation period distribution using survival analysis methods, which allow for appropriate inference when only time ranges, rather than exact times are known for the exposure to HEV and symptom onset. We estimated a 29.8-day (95% confidence interval (CI) 24.1-36.0) median incubation period with 5% of people expected to develop symptoms within 14.3 days (95% CI 10.1-21.7) and 95% within 61.9 days (95% CI 47.4-74.4) of exposure. These estimates can help refine clinical case definitions and inform the design of disease burden and intervention studies.

IPT during HIV treatment in Myanmar: high rates of coverage, completion and drug adherence.

Setting: A southern Myanmar district providing isoniazid preventive therapy (IPT) in one of the last countries to formally recommend it as part of human immunodeficiency virus (HIV) care. Objective: To assess coverage and adherence and the feasibility of IPT scale-up in a routine care setting in Myanmar. Design: A retrospective analysis of people living with HIV (PLHIV) screened for tuberculosis (TB) and enrolled in IPT over a 3-year period (July 2011-June 2014) using clinical databases. Results: Among 3377 patients under HIV care and screened for TB, 2740 (81.1%) initiated IPT, with 2651 (96.8%) completing a 6- or 9-month course of IPT; 83 (3.1%) interrupted treatment for different reasons, including loss to follow-up (n = 41), side effects (n = 15) or drug adherence issues (n = 9); 6 (0.2%) died. Among the IPT patients, 33 (1.2%) were diagnosed with TB, including 9 (0.3%) while on IPT and 24 (0.9%) within 1 year of completion of therapy. Among the PLHIV who completed IPT, one case of isoniazid resistance was detected. Conclusion: Scaling up IPT in Myanmar HIV settings is feasible with high rates of drug adherence and completion, and a low rate of discontinuation due to side effects. IPT scale-up should be prioritised in HIV clinical settings in Myanmar.

Contexte : Un district du sud du Myanmar fournissant le traitement préventif par isoniazide (IPT) dans l'un des derniers pays à le recommander formellement comme élément de la prise en charge de l'infection par le virus de l'immunodéficience humaine (VIH).Objectif : Evaluer la couverture, l'adhérence et la faisabilité d'une accélération de l'IPT dans un contexte de soins de routine au Myanmar.Schéma : Analyse rétrospective de personnes vivant avec le VIH (PVVIH) dépistés pour la tuberculose (TB) et enrôlés dans l'IPT sur une période de 3 ans, de juillet 2011 à juin 2014, grâce à des bases de données cliniques.Résultats : Sur 3377 patients pris en charge pour le VIH et dépistés pour la TB, 2740 (81,1%) ont mis en route le TPI, dont 2651 (96,8%) ont achevé un traitement préventif de 6 ou 9 mois ; 83 (3,1%) ont interrompu leur traitement pour différentes raisons incluant les pertes de vue (n = 41), les effets secondaires (n = 15) ou des problèmes d'adhérence au médicament (n = 9), et six (0,2%) sont décédés. Parmi les patients IPT, 33 (1,2%) ont eu un diagnostic de TB, dont 9 (0,3%) pendant la prophylaxie et 24 (0,9%) dans l'année qui a suivi la fin de l'IPT. Un cas de résistance à l'isoniazide a été détecté parmi les PVVIH qui ont achevé l'IPT.Conclusion: L'accélération de l'IPT dans les structures VIH du Myanmar est faisable, avec un taux élevé d'adhérence au médicament et d'achèvement et un taux faible d'arrêt du traitement dû à des effets secondaires. L'accélération de l'IPT devrait être considérée comme une priorité dans les structures cliniques VIH du Myanmar.

Marco de referencia: Un distrito del sur de Birmania que provee el tratamiento preventivo con isoniazida (IPT). Birmania es uno de los últimos países que incluyó esta profilaxis en las recomendaciones formales de atención de la infección por el virus de la inmunodeficiencia humana (VIH).Objetivo: Evaluar la cobertura, el cumplimiento terapéutico y la factibilidad de ampliar la escala de aplicación del IPT en un entorno de tratamiento corriente en Birmania.Método: Fue este un análisis retrospectivo de personas con infección por el VIH, en quienes se practicó la detección sistemática de la tuberculosis (TB) y se registraron para recibir el IPT. Se obtuvo la información a partir de las bases de datos clínicos durante un período de 3 años, de julio del 2011 hasta junio del 2014.Resultados: De los 3377 pacientes que recibían atención por infección por el VIH, con investigación sistemática de la TB, 2740 iniciaron el TPI (81,1%) y 2651 completaron un esquema de 6 o 9 meses de profilaxis (96,8%). Ochenta y tres pacientes interrumpieron por razones diversas el tratamiento (3,1%), entre ellas, la pérdida durante el seguimiento (n = 41), los efectos secundarios (n = 15) o los problemas de cumplimiento terapéutico (n = 9) y seis pacientes fallecieron (0,2%). De los pacientes que recibieron IPT, en 33 se diagnosticó TB (1,2%), en 9 de ellos durante la profilaxis (0,3%) y en 24 casos durante el primer año después de haber completado el esquema (0,9%). Se detectó un caso de resistencia a isoniazida en las personas infectadas por el VIH que completaron el IPT.Conclusiôn: La ampliación de escala del IPT en los entornos de atención de la infección por el VIH es factible en Birmania y se pueden alcanzar altas tasas de cumplimiento terapéutico y compleción del esquema, con una baja tasa de interrupción debida a efectos colaterales. Es importante dar prioridad a la ampliación de escala del IPT en los medios de atención de la infección por el VIH en el país.

Bacterial diversity across a highly stratified ecosystem: A salt-wedge Mediterranean estuary.

Highly stratified Mediterranean estuaries are unique environments where the tidal range is low and the tidal currents are almost negligible. The main characteristics of these environments are strong salinity gradients and other environmental parameters. In this study, 454 pyrosequencing of the 16S rRNA gene in combination with catalyzed reporter deposition-fluorescence in situ hybridization (CARD-FISH) was used to estimate the bacterial diversity across the Krka estuary in February and July 2013. The comparison of the data derived from these two techniques resulted in a significant but weak positive correlation (R=0.28) indicating a substantial difference in the bacterial community structure, depending on the applied method. The phytoplankton bloom observed in February was identified as one of the main factors shaping the bacterial community structure between the two environmentally contrasting sampling months. Roseobacter, Bacteroidetes and Gammaproteobacteria differed substantially between February and July. Typical freshwater bacterial classes (Actinobacteria and Betaproteobacteria) showed strong vertical distribution patterns depending on the salinity gradient. Cyanobacteria decreased in abundance in February due to competition with phytoplankton, while the SAR11 clade increased its abundance in July as a result of a better adaptation toward more oligotrophic conditions. The results provided the first detailed insight into the bacterial diversity in a highly stratified Mediterranean karstic estuary.

Konzo outbreak among refugees from Central African Republic in Eastern region, Cameroon.

Konzo is a spastic paraparesis of sudden onset, linked to the exclusive consumption of insufficiently processed bitter cassava as staple food combined with low protein intake. Around 60,000 refugees from the Central African Republic sought refuge in villages in eastern Cameroon between 2005 and 2007. Médecins Sans Frontières was providing nutritional and medical assistance in the villages affected by displacement. We describe cases of konzo seen at the mobile clinics organized in these villages. Basic information including demographic data, history and clinical presentation was recorded for each konzo patient. All patients were given nutritional supplements, and selected cases were referred for physiotherapy to a rehabilitation center. A total of 469 patients were diagnosed with konzo. The majority (80%) were refugees. Children and women of reproductive age predominated. Most of the patients developed symptoms after 2007 in a seasonal pattern with most of the cases occurring during the dry winter season. Most of the patients complained about walking difficulties and weight loss and had exaggerated lower limb reflexes and muscle wasting on observation. Eastern Cameroon is an area with konzo. More effort needs to be put into preventive and educational measures. In addition, timely balanced food rations have to be provided to refugees.

Population differences in death rates in HIV-positive patients with tuberculosis.

SETTING: Randomised controlled clinical trial of Mycobacterium vaccae vaccination as an adjunct to anti-tuberculosis treatment in human immunodeficiency virus (HIV) positive patients with smear-positive tuberculosis (TB) in Lusaka, Zambia, and Karonga, Malawi. OBJECTIVE: To explain the difference in mortality between the two trial sites and to identify risk factors for death among HIV-positive patients with TB. DESIGN: Information on demographic, clinical, laboratory and radiographic characteristics was collected. Patients in Lusaka (667) and in Karonga (84) were followed up for an average of 1.56 years. Cox proportional hazard analyses were used to assess differences in survival between the two sites and to determine risk factors associated with mortality during and after anti-tuberculosis treatment. RESULTS: The case fatality rate was 14.7% in Lusaka and 21.4% in Karonga. The hazard ratio for death comparing Karonga to Lusaka was 1.47 (95% confidence interval [CI] 0.9-2.4) during treatment and 1.76 (95%CI 1.0-3.0) after treatment. This difference could be almost entirely explained by age and more advanced HIV disease among patients in Karonga. CONCLUSION: It is important to understand the reasons for population differences in mortality among patients with TB and HIV and to maximise efforts to reduce mortality.