Spatial distribution and determinants of tuberculosis incidence in Mozambique: A nationwide Bayesian disease mapping study.

INTRODUCTION: Mozambique is a high-burden country for tuberculosis (TB). International studies show that TB is a disease that tends to cluster in specific regions, and different risk factors (HIV prevalence, migration, overcrowding, poverty, house condition, temperature, altitude, undernutrition, urbanization, and inadequate access to TB diagnosis and treatment) are reported in the literature to be associated with TB incidence. Although Mozambique has a higher burden of TB, the spatial distribution, and determinants of TB incidence at the sub-national level have not been studied yet for the whole country. Therefore, we aimed to analyze the spatial distribution and determinants of tuberculosis incidence across all 154 districts of Mozambique and identify the hotspot areas. METHOD: We conducted an ecological study with the district as our unit of analysis, where we included all cases of tuberculosis diagnosed in Mozambique between 2016 and 2020. We obtained the data from the Mozambique Ministry of Health and other publicly available open sources. The predictor variables were selected based on the literature review and data availability at the district level in Mozambique. The parameters were estimated through Bayesian hierarchical Poisson regression models using Markov Chain Monte Carlo simulation. RESULTS: A total of 512 877 people were diagnosed with tuberculosis in Mozambique during our five-year study period. We found high variability in the spatial distribution of tuberculosis incidence across the country. Sixty-two districts out of 154 were identified as hotspot areas. The districts with the highest incidence rate were concentrated in the south and the country's central regions. In contrast, those with lower incidence rates were mainly in the north. In the multivariate analysis, we found that TB incidence was positively associated with the prevalence of HIV (RR: 1.23; 95 % CrI 1.13 to 1.34) and negatively associated with the annual average temperature (RR: 0.83; 95 % CrI 0.74 to 0.94). CONCLUSION: The incidence of tuberculosis is unevenly distributed across the country. Lower average temperature and high HIV prevalence seem to increase TB incidence. Targeting interventions in higher-risk areas and strengthening collaboration between HIV and TB programs is paramount to ending tuberculosis in Mozambique, as established by the WHO's End TB strategy and the Sustainable Development Goals.

Extrapulmonary tuberculosis mortality according to clinical and point of care ultrasound features in Mozambique.

In resource-limited settings, point-of-care ultrasound (POCUS) has great potential to support the timely diagnosis of extrapulmonary tuberculosis (EPTB). We aim to determine the in-hospital mortality due to EPTB according to clinical and POCUS features and risk factors in newly diagnosed patients hospitalized for EPTB in Chókwè district, Mozambique. We analyzed routinely collected data from paper medical files and electronic POCUS records of EPTB in infected patients aged 15 years or older and admitted to Carmelo Hospital of Chókwè from 2016 to 2020. Kaplan-Meier survival curves and adjusted Cox regression analyses were used to model predictors of mortality and time to death. The 390 included in-patients with EPTB and POCUS data contributed a total of 6240 in-hospital person-days of observation. The overall mortality rate was 2.16 per 100 person-days. Adjusted Cox regression showed a higher risk of death in those with abdominal tenderness (adjusted hazard ratio [aHR] 1.61, 95% confidence interval [CI] 1.00-2.82, p = 0.050), antiretroviral treatment (ART) for more than 90 days (aHR 4.03, 95% CI 1.50-10.78, p = 0.006), and mixed patterns on kidney POCUS (aHR 2.91, 95% CI 1.38-6.10, p = 0.005). An optimal immunovirological response to ART was a protective factor against death [aHR] 0.12, 95% CI 0.04-0.35, p < 0.001). Variables associated with an increased risk of death were male gender, abdominal pain, ART for more than three months (with immunovirological failure or non-response to ART) and having a mixed pattern of kidney POCUS characteristics. Early detection of these risk factors may have a direct impact on reducing TB mortality, and the POCUS approach as a complementary diagnostic method for EPTB provides a simple, feasible and affordable intervention in resource-limited settings like Mozambique.

Manual de manejo Clínico e programático da tuberculose multirresistente / Clinical and programmatic management manual for multidrug-resistant tuberculosis

O surgimento de resistência aos fármacos usados para tratar a tuberculose (TB), particularmente a Tuberculose Multirresistente (TB-MR), tornou-se um problema de saúde pública em vários países e, um sério obstáculo na luta contra Tuberculose, razão pela qual a OMS recomenda desde o ano 2000 uma abordagem clínica e programática da TB-MR . Naquela época, o Green Light Commitee (GLC) foi estabelecido para promover o acesso a serviços de medicamentos da segunda linha de alta qualidade para uso adequado em programas de TB. Em 2002, o Fundo Global de Combate à SIDA, TB e Malária começou a financiar programas de controlo de TB, incluindo TB Multirresistente, reduzindo assim a barreira económica para a implementação dos serviços de TB Multirresistente. Desde então, os serviços Gestão Programática da Tuberculose Multirresistente (PMDT) expandiram-se rapidamente. Com base nos dados e na experiência desses projectos e práticas, a evidência científica continua a evoluir no que diz respeito aos serviços de TB-R.

Tuberculosis infection risk, preventive therapy care cascade and incidence of tuberculosis disease in healthcare workers at Maputo Central Hospital.

BACKGROUND: Mozambican healthcare workers have high rates of latent and active tuberculosis, but occupational screening for tuberculosis is not routine in this setting. Furthermore, the specificity of tuberculin skin testing in this population compared with interferon gamma release assay testing has not been established. METHODS: This study was conducted among healthcare workers at Maputo Central Hospital, a public teaching quaternary care hospital in Mozambique. With a cross sectional study design, risk factors for tuberculosis were assessed using multivariable logistic regression. The care cascade is reported for participants who were prescribed six months of isoniazid preventive therapy for HIV or highly reactive testing for latent tuberculosis infection. The agreement of interferon-gamma release assay results with positive tuberculin skin testing was calculated. RESULTS: Of 690 screened healthcare workers, three (0.4%) had active tuberculosis and 426 (61.7%) had latent tuberculosis infection. Less education, age 35-49, longer hospital service, and work in the surgery department were associated with increased likelihood of being tuberculosis infected at baseline (p < 0.05). Sex, Bacillus Calmette-Guerin vaccination, HIV, outside tuberculosis contacts, and professional category were not. Three new cases of active tuberculosis developed during the follow-up period, two while on preventive therapy. Among 333 participants offered isoniazid preventive therapy, five stopped due to gastrointestinal side effects and 181 completed treatment. For HIV seropositive individuals, the agreement of interferon gamma release assay positivity with positive tuberculin skin testing was 50% among those with a quantitative skin test result of 5-10 mm, and among those with a skin test result ≥10 mm it was 87.5%. For HIV seronegative individuals, the agreement of interferon gamma release assay positivity with a tuberculin skin test result of 10-14 mm was 63.6%, and for those with a quantitative skin test result ≥15 mm it was 82.2%. CONCLUSIONS: There is a high prevalence of tuberculosis infected healthcare workers at Maputo Central Hospital. The surgery department was most heavily affected, suggesting occupational risk. Isoniazid preventive therapy initiation was high and just over half completed therapy. An interferon gamma release assay was useful to discern LTBI from false positives among those with lower quantitative tuberculin skin test results.

Treatment Outcomes of Patients Switching From an Injectable Drug to Bedaquiline During Short Standardized Treatment for Multidrug-resistant Tuberculosis in Mozambique.

Bedaquiline was recommended by the World Health Organization as the preferred option in treatment of multidrug-resistant tuberculosis (MDR-TB) with long regimens. However, no recommendation was given for the short MDR-TB regimen. Data from our small cohort of patients who switched from injectable drug to bedaquiline suggest that a bedaquiline-based short regimen is effective and safe.

Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique.

BACKGROUND: Single-dose nevirapine (sd-NVP) has been the main option for prevention of mother-to-child transmission (PMTCT) of HIV-1 in low-resource settings. However, sd-NVP can induce the selection of HIV-1 resistant mutations in mothers and infants. In Mozambique, there are limited data regarding the profile of NVP resistance associated mutations (RAM) in the context of PMTCT. OBJECTIVES: To assess the prevalence and the factors associated with NVP RAM among children born to HIV-1 infected mothers enrolled in the PMTCT programme adopted in Mozambique. METHODS: One hundred and fifty seven children aged 6 to 48 weeks were sequentially included (July 2011 to March 2012) at four centres in Maputo. Genotyping of RAM was performed in samples with HIV-1 RNA≥ 100 copies/µL (Viroseq). Sequencing was performed with ABI 3100 (Applied Biosystems). Logistic regression modelling was undertaken to identify the factors associated with NVP RAM. RESULTS: Seventy-nine children had their samples genotyped. Their median age was 7.0 (3-12) months and 92.4% received prophylaxis with sd-NVP at birth plus daily NVP. 35.4% of mothers received antiretrovirals (ARVs) for PMTCT. ARV RAM were detected in 43 (54.4%) of the children. 45.6% of these children had at least one NVP RAM. The most common mutations associated with NVP resistance were K103N (n = 16) and Y181C (n = 15). NVP RAM was significantly associated with mother exposure to PMTCT (crude odds ratio [OR] 30.3, 95% CI 4.93-186.34) and with mother's CD4 count < 350 cells/mm3 (crude OR 3.08, 95% CI 1.02-9.32). In the multivariable analysis the mother's exposure to PMTCT was the only variable significantly associated with NVP RAM (adjusted OR 48.65, 95% CI 9.33-253.66). CONCLUSIONS: We found a high prevalence of NVP RAM among children who were exposed to the drug regimen for PMTCT in Mozambique. The mothers' exposure to PMTCT significantly increased the risk of NVP RAM.