Tuberculosis caused by Mycobacterium (M.) tuberculosis remains a global public health threat. Over the last few decades, antitubercular research mainly focused on mechanisms of identifying by which activated macrophages can slaughter or the proliferation of M. tuberculosis bacilli prevented in a cell-dependent manner. In this regard, for disease resolution, inflammatory cytokines are very crucial. Here, we demonstrate how macrophages act as the first line of defense against the M. tuberculosis. Studies have revealed a dual role in M. tuberculosis infection played by macrophages. It is worth mentioning that the macrophages are the crucial immune effector and antigen-presenting cells that play the anti-tubercular response, which is the habitat of M. tuberculosis, hence, followed by progressing the disease protecting M. tuberculosis. This dual role can be correlated with the different macrophage polarization statuses, namely, M1 and M2. Herein, we have stated how the several polarization conditions of macrophages are directly linked to the immune responses during host and M. tuberculosis pathogen interactions. We have proposed that macrophage polarization and repolarization are of paramount significance for the anti-tubercular immune response that may involve a sterile cure of the disease. This article summarizes the immune response to M. tuberculosis, the polarization states of macrophages during M. tuberculosis and the repolarization of macrophages by some agents during some diseases including M. tuberculosis, which may be an important factor in the World Health Organization’s target to cure tuberculosis by 2035.

Objective: To determine the current insecticide resistance status of Aedes (Ae.) aegypti and Ae. albopictus to four insecticides, namely 0.05% deltamethrin, 0.75% permethrin, 5% malathion and 0.25% pirimiphos–methyl using the World Health Organisation (WHO) susceptibility test kit.

Methods: Adult bioassays were carried out using the standard protocol of the World Health Organisation. All F1 generation urban and suburban field strains of Ae. aegypti and Ae. albopictus were tested against pyrethroid and organophosphate insecticides, including the presence of piperonyl butoxide (PBO) in four replicates of 25 non-blood-fed female mosquitoes ranging from 3 to 5 days old. The Vector Control Research Unit (VCRU) laboratory strain served as a reference strain.

Results: In this study, 0.05% deltamethrin demonstrated a lower value of knockdown time when 50% of the mosquito population died (KT₅₀) and knockdown time when 95% of the mosquito population died (KT₉₅), which is significantly more effective compared to 0.75% permethrin against adult female Ae. aegypti (urban and suburban) and Ae. albopictus (urban and suburban) (ANOVA, P<0.01). Meanwhile, 5% malathion was a more effective insecticide, amounting to the shorter KT₅₀ and KT₉₅ compared to 0.25% pirimiphos-methyl against Ae. aegypti (urban and suburban) and Ae. albopictus (urban and suburban). Ae. aegypti urban and Ae. aegypti suburban performed a higher resistance ratio (RR) towards both 0.05% deltamethrin and 0.75% permethrin due to the wide use of permethrin in dengue vector control programs in Malaysia. However, Ae. albopictus urban and suburban have lower resistance than Ae. aegypti urban and suburban towards 0.05% deltamethrin and 0.75% permethrin at 24 hours post-treatment. The addition of PBO with these insecticides successfully reduced knockdown time (KT₅₀ and KT₉₅) values of most of the Ae. aegypti and Ae. albopictus field strains except PBO+0.75% permethrin against Ae. aegypti suburban.

Conclusions: The addition of PBO to insecticides has significantly reduced the knockdown time (KT₅₀ and KT₉₅) values on most of Ae. aegypti and Ae. albopictus urban strain except PBO+5% malathion against Ae. albopictus urban strain and PBO+0.75% permethrin against Ae. albopictus suburban strain in comparison to exposure to insecticides without PBO. Ae. aegypti showed a higher resistance ratio of 50 (RR₅₀) when compared with the VCRU laboratory reference strain (susceptible strain) at the exposure to the deltamethrin, including with pre-exposure to PBO. This study found that the addition of PBO with organophosphates (5% malathion and 0.25% pirimiphos–methyl) was significantly more effective than pyrethroids against Ae. aegypti and Ae. albopictus (urban and suburban) due to their high mortality rate at 24 hours. It can be concluded that the usage of PBO can help reduce resistance alteration in Aedes mosquitoes.

Objective: To elucidate the characteristics, management strategies, risk factors, and clinical impacts associated with adverse drug reactions (ADRs) induced by first-line antitubercular drugs to enhance tuberculosis (TB) management.

Methods: A retrospective cohort study was conducted by retrieving drug-susceptible TB records among adult patients who received TB treatment from 2018 to 2021 at 10 public health clinics in Sarawak, Malaysia. Only the initial TB treatment and occurrence of specific ADRs within the study period were considered. Regression analysis was performed to identify the risk factors associated with both overall ADRs and individual types of ADRs.

Results: Among 2 953 cases, 705 (23.9%) developed ADRs. Cutaneous reactions were the most prevalent (47.1%), followed by hepatotoxicity (32.8%) and gastrointestinal disturbances (29.8%). Six out of seven types of ADRs investigated occurred within the intensive phase, mostly manifesting at approximately 2 weeks of initiation. Hepatotoxicity resulted in the majority (85.3%) of treatment discontinuations, while vision problems led to treatment modifications in half of the cases. Risk factors for all ADRs included age ≥60 years, females, illicit drug use, and comorbidities such as HIV-positive, diabetes, and chronic liver disease. Alcohol consumption was independently associated with hepatotoxicity. ADRs caused around one-third of interruptions exceeding 2 weeks (33.0%) and subsequently necessitated treatment restarts (34.5%).

Conclusions: Understanding these various aspects contributes to improving the overall management of ADRs in TB treatment. Close ADR monitoring and reporting are essential to strengthen ADR management.

Objective: To identify the clinical, laboratory, and radiological markers that could predict a positive GeneXpert result in patients suspected of tuberculous meningitis.

Methods: In this prospective, observational study, patients with tuberculous meningitis were systematically evaluated. Various clinical, laboratory [including cerebrospinal fluid (CSF) microscopy, culture, and GeneXpert], and neuroimaging factors were examined. All participants were administered anti-tuberculous treatment and corticosteroids. A six-month follow-up was done to evaluate the outcome.

Results: Of the 116 patients studied, 54 (46.6%) tested positive for GeneXpert, while 62 (53.4%) were negative. Third cranial nerve involvement (OR 3.71, 95% CI 1.052-13.09, P=0.04) and the presence of basal exudates on neuroimaging (OR 5.22, 95% CI 2.03-13.42, P=0.001) emerged as independent predictive factors for a positive GeneXpert result. A positive CSF GeneXpert result (P=0.002) and drug resistance (P=0.004) were significantly linked to adverse outcomes. Additionally, a high score on the Medical Research Council stage III (OR 5.64, 95% CI 1.18-26.87, P=0.03) and elevated CSF cell counts (OR 1.002, 95% CI 1.00-1.001, P=0.03) were identified as independent predictors of poor prognosis.

Conclusions: Third cranial nerve involvement and the presence of basal exudates were significant indicators of a positive GeneXpert result. MRC stage III disability and elevated CSF cell counts predicted poor outcomes.

Rationale: American tegumentary leishmaniasis comprises cutaneous and mucocutaneous manifestations caused by parasitic infections by various Leishmania species. This report details the clinical interventions for a patient with American tegumentary leishmaniasis in Mendoza, Argentina, a non-endemic region.

Patient concerns: A 43-year-old male was admitted to a tertiary care hospital in Mendoza, Argentina Republic with a history of progressive nasal discharge, septal perforation, facial pain, and pruritus. Despite treatment for presumed nasal myiasis and vasculitis with granulomatosis, symptoms persisted.

Diagnosis: American tegumentary leishmaniasis.

Interventions: Intravenous liposomal amphotericin B.

Outcomes: Follow-up at 30 days showed no recurrence of symptoms with a remarkable clinical improvement of the nasal lesion.

Lessons: This case sheds light on the necessity of accurate identification for timely intervention and the need to recognize the diverse manifestations of American tegumentary leishmaniasis to avoid misdiagnosis.