Artemisinin derivatives are the mainstay of antimalarial treatment, both for uncomplicated malaria and for severe disease. Artemisinins are known for their rapid onset of action, good tolerability, and safety. However, besides the sporadic but worrying reports of delayed parasite clearance after treatment with artemisinins, there have been an increasing number of reports of acute haemolytic anaemia following their use and the safety of this class of antimalarials is being questioned. In this systematic review, all reports of patients experiencing haemolysis following the use of artemisinins for the treatment of malaria were identified and collated into an electronic database. Summary statistics were calculated to characterize the epidemiology and clinical features of this safety concern related to artemisinin derivatives. A total of 37 patients were identified suffering from haemolysis following the treatment of severe malaria with artemisinin derivatives. Thirty-one cases had received intravenous artesunate, while the remaining cases were attributed to other parenteral or oral regimens of artemisinin derivatives. The majority of patients were returning travellers (n=30), and six clinical cases had been reported in paediatric patients. The median onset of haemolysis was 15 (interquartile range (IQR) 13-15) days after the initiation of treatment for the 'delayed-onset' pattern and 17 (IQR 13-22) days for the 'persistent' haemolysis pattern. The median reduction in haemoglobin due to haemolysis was 6 g/dl (IQR 4-8 g/dl). The estimated proportion of patients suffering from severe malaria experiencing haemolysis after treatment with artemisinin derivatives was 13% (95% confidence interval 9-18%), and 73% of these (i.e., 9% of the total population) required blood transfusions. No fatal outcome has been reported in the literature to date. Haemolysis is commonly associated with the class of artemisinin drugs when used for the treatment of severe malaria. Potential causes of this safety issue are discussed. Although no deaths attributed to haemolysis have been reported so far, this safety issue may lead to life-threatening anaemia and is particularly worrying for regions where safe blood products are not readily available.

To determine the vaccination refusal rate, associated factors and perceptions of parents who refused routine immunization for their children using the World Health Organization (WHO) SAGE Working Group on Vaccine Hesitancy Survey Tool. A cross-sectional survey was conducted using multi-stage cluster sampling in Bannu District, Khyber Pakhtunkhwa Province, Pakistan from March 2019 to July 2019. A WHO validated questionaire was used. The outcome variable was parental refusal of routine immunization of their children. Logistic regression was performed for associations, and multi-regression was applied to identify any confounders. Of 610 parents, 170 (27.9%) refused vaccination of their children. Of these, the majority of mothers had no education [n = 145 (85.3%); p = 0.03], and mothers were less likely to own a mobile phone than fathers [24 (14.1%) vs 152 (89.4%); p ≤ 0.001]. The vaccination refusal rate was higher in parents with food security [n = 88 (51.8%)] compared with parents with minimal food insecurity [n = 62 (36.5%)] and high food insecurity [20 (11.8%); p ≤ 0.05)]. On multi-variate logistic regression, fathers who were employed [adjusted odds ratio (OR) 0.59, 95% confidence interval (CI) 0.37-0.94; p = 0.02] and had a high level of education (adjusted OR 0.21, 95% CI 0.08-0.50; p ≤ 0.001) were less likely to refuse vaccination of their children. Parents with high food insecurity were more likely to refuse vaccination of their children (adjusted OR 2.2, 95% CI 1.0-0.50; p = 0.04) compared with parents with minimal food insecurity (adjusted OR 1.6, 95% CI 1.0-2.5; p = 0.02). The vaccination refusal rate was very high among parents, and this was associated with inability to read or write, no education, owning a mobile phone, unemployment and food security.

Since the onset of the ongoing civil war in Syria, the governmental surveillance system for leishmaniasis has lost access to provinces of northern Syria. The MENTOR Initiative, an international not-for-profit organization, was commissioned to implement an integrated leishmaniasis control program, providing an opportunity to reassess the epidemiology of leishmaniasis in northern Syria. Epidemiologic data and biologic samples for molecular species diagnostics were collected from collaborating local health centers. Incidence peaked in March 2015 at 7,743 estimated monthly cases. High levels of transmission were observed in traditional endemic regions but extended to previously hypoendemic regions, such as Al-Raqqa and Al-Hasakah. Incidence decreased to 3,209 in July 2015. Data indicate that the prewar trend of increasing incidence of cutaneous leishmaniasis accelerated during the beginning of armed conflict but declined after implementation of the comprehensive control program by the MENTOR Initiative. Molecular analysis revealed a spectrum of Leishmania species and sporadic cases of visceral leishmaniasis.

Proper oral hygiene and absence of periodontal inflammation is pre-requisite for orthodontic treatment. Chlorhexidine (CHX) is an established oral antiseptic used in the treatment of periodontal disease, but its role in orthodontic therapy is unclear. To assess the efficacy of adjunct use of CHX-containing products in maintaining gingival health among orthodontic patients with fixed appliances. Five databases were searched without limitations up to August 2021. Randomized clinical trials (RCTs) assessing Gingival Index (GI) (primary outcome), Plaque Index (PI), Bleeding Index (BI), or Pocket Probing Depth (PPD). Study selection, data extraction, and risk of bias assessment were done independently in duplicate. Random-effects meta-analyses of mean differences (MDs) or standardized mean differences (SMDs) with their 95% confidence intervals (CIs) were conducted, followed by sensitivity and Grades of Recommendations, Assessment, Development and Evaluation analysis. Twenty RCTs (1001 patients) were included assessing CHX-containing mouthwashes (n = 11), toothpastes (n = 2), gels (n = 3), or varnishes (n = 4) compared to placebo/control (n = 19) or sodium fluoride-products (n = 4). In the short-term, CHX-containing mouthwash was associated with lower GI (n = 9; MD = −0.68; 95% CI = −0.97 to −0.38; P < 0.001; high quality), lower PI (n = 9; MD = −0.65; 95% CI = −0.86 to −0.43; P < 0.001; high quality), lower BI (n = 2; SMD = −1.61; 95% CI = −2.99 to −0.22; P = 0.02; low quality), and lower PPD (n = 2; MD = −0.60 mm; 95% CI = −1.06 to −0.14 mm; P = 0.01; low quality). No considerable benefits were found from the use of CHX-gel or CHX-varnish in terms of GI, PI, or PPD (P > 0.05/low quality in all instances). Use of a CHX-containing toothpaste was more effective in lowering PI (Heintze-index) than adjunct use of fluoride-containing mouthwash (n = 2; MD = −5.24; 95% CI = −10.46 to −0.02; P = 0.04), but not GI (P = 0.68) or BI (P = 0.27), while sensitivity analyses indicated robustness. Adjunct use of CHX mouthwash during fixed-appliance treatment is associated with improved gingival inflammation, plaque control, and pocket depths, but caution is warranted and recommendations about CHX use during orthodontic treatment of children/adults should consider the heterogeneous patient response, cost-effectiveness, and potential adverse effects. PROSPERO registration (CRD42021228759).

Crimean-Congo haemorrhagic fever (CCHF) is a potentially fatal disease endemic in Pakistan. The causative virus is transmitted by the bite of Hyalomma ticks or by contact with infected blood or tissue. First cases of the disease were reported in Pakistan in 1976 but regular outbreaks have been observed since the year 2000. A huge agricultural base with more than 175 million livestock, the concomitant presence of Hyalomma ticks and a lack of precautionary measures to prevent transmission lead to a considerable risk for exposed populations to contract CCHF in Pakistan. At the same time, secondary cases contracted by nosocomial transmission are reported from hospitals. Here we present an outbreak of CCHF with four of six patients succumbing to the disease before the suspicion for CCHF was raised. Importantly, the main clinical features of these cases were gastrointestinal symptoms without any clinical signs of bleeding. Only the last two patients in this outbreak presented with typical signs of bleeding disorder and were then confirmed being infected by CCHF. Confirmation of diagnosis was done at the National Institute of Health by real-time RT-PCR. This case series highlights the importance of early clinical suspicion for CCHF in exposed individuals and the need for improved precautionary measures against the spread of CCHF within the Pakistani population and hospitals.

Solid organ transplant recipients are particularly vulnerable for infectious diseases due to prolonged immunosuppressive treatment. Residents of endemic regions and travellers may be exposed to malaria and may, therefore, require prolonged antimalarial chemoprophylaxis. The hypothesis of this study was that certain immunosuppressive drugs may exert clinically relevant anti-malarial activity. It was therefore designed to assess the intrinsic anti-malarial activity of everolimus, mycophenolic acid, and rapamycin against Plasmodium falciparum in an in vitro model.