•Ivermectin, an FDA-approved anti-parasitic agent, was found to be an inhibitor of SARS-CoV-2 replication in the laboratory.•Ivermectin may be effective for the treatment of early-onset mild COVID-19 ...in adult patients.•Early viral clearance of SARS-CoV-2 was observed in ivermectin treated patients.•Remission of fever, cough and sore throat did not differ among treatment groups. No severe adverse event was observed.•Larger trials will be needed to confirm these preliminary findings.
Ivermectin, a US Food and Drug Administration-approved anti-parasitic agent, was found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. A randomized, double-blind, placebo-controlled trial was conducted to determine the rapidity of viral clearance and safety of ivermectin among adult SARS-CoV-2 patients. The trial included 72 hospitalized patients in Dhaka, Bangladesh, who were assigned to one of three groups: oral ivermectin alone (12 mg once daily for 5 days), oral ivermectin in combination with doxycycline (12 mg ivermectin single dose and 200 mg doxycycline on day 1, followed by 100 mg every 12 h for the next 4 days), and a placebo control group. Clinical symptoms of fever, cough, and sore throat were comparable among the three groups. Virological clearance was earlier in the 5-day ivermectin treatment arm when compared to the placebo group (9.7 days vs 12.7 days; p = 0.02), but this was not the case for the ivermectin + doxycycline arm (11.5 days; p = 0.27). There were no severe adverse drug events recorded in the study. A 5-day course of ivermectin was found to be safe and effective in treating adult patients with mild COVID-19. Larger trials will be needed to confirm these preliminary findings.
We identified a poor clinical response to treatment of cholera with a single 1 g dose of ciprofloxacin, a standard treatment for cholera.
To determine reasons for the poor response and better ...therapeutic approaches we examined the minimal inhibitor concentration (MIC, n = 275) and disc-diffusion zone sizes (n = 205) for ciprofloxacin and nalidixic acid of V. cholerae O1 strains isolated in Bangladesh from 1994 to 2012, and reexamined data from 161 patients infected with Vibrio cholerae O1 recruited in four clinical trials who received single- or multiple-dose ciprofloxacin for treatment of cholera and compared their clinical response to the V. cholerae O1 susceptibility.
Although all 275 isolates of V. cholerae O1 remained susceptible to ciprofloxacin using standard MIC and disc-diffusion thresholds, the MIC90 to ciprofloxacin increased from 0.010 in 1994 to 0.475 μgm/ml in 2012. Isolates became frankly resistant to nalidixic with the MIC90 increasing from 21 μgm/ml in 1994 to >256 μgm/ml and 166 of 205 isolates from 1994 to 2005 being frankly resistant using disc-diffusion testing. Isolates resistant to nalidixic acid by disc-diffusion testing had a median ciprofloxacin MIC of 0.190 μgm/ml (10th-90th centiles 0.022 to 0.380); nalidixic acid-susceptible isolates had a median ciprofloxacin MIC of 0.002 (0.002 to 0.012).The rate of clinical success with single-dose ciprofloxacin treatment for nalidixic acid-susceptible strains was 94% (61 of 65 patients) and bacteriologic success 97% (63/65) compared to 18% (12/67) and 8% (5/67) respectively with nalidixic acid-resistant strains (P<0.001 for both comparisons). Multiple-dose treatment with ciprofloxacin had 86% and 100% clinical and bacteriologic success rates respectively in patients infected with nalidixic acid-susceptible strains of V. cholerae O1 compared to clinical success 67% and bacteriologic success 60% with nalidixic acid-resistant strains.
Single-dose ciprofloxacin is not effective for treating cholera caused by V. cholerae O1 with diminished susceptibility to ciprofloxacin, and nalidixic acid disc-diffusion testing effectively screens for such isolates.
Antibiotic resistance poses a great threat to global health, especially in low- and middle-income countries with a high infectious disease burden and limited resources. In spite of regulations, ...antibiotics are sold in many settings as non-prescription medicines, resulting in inappropriate use and resistance.
This study aimed to investigate the current status of access and use of antibiotics in rural Bangladesh, by exploring the perspectives and sales practices of antibiotic drug dispensers.
We used a mixed methods approach (qualitative and quantitative). We mapped and characterized antibiotic purchasing and dispensing sites in the Matlab Health and Demographic Surveillance System catchment area. Furthermore, we investigated the volume of provision of systemic antibiotics in 10 drug outlets. We held 16 in-depth interviews with randomly selected antibiotics dispensers. Interviews explored factors associated with antibiotic selling. Responses were transcribed, coded for themes, and summarized. We used ATLAS.ti 5.2 for conducting a thematic analysis.
A total of 301 antibiotic dispensers were identified, of whom 92% (
= 278) were private and 8% (
= 23) public. 52% (
= 155) operated informally (i.e. without legal authorization). In order to promote and survive in their business, dispensers sell antibiotics for a range of conditions without a qualified physician's prescription. Factors that facilitate these inappropriate sales include lack of access to healthcare in the rural community, inadequate doctor: population ratio, limited dispenser knowledge, poor pharmacovigilance concerning safety of self medication, lack of enforcement of policies, financial benefits for both customers and dispensers, and high dependency on pharmaceutical companies' information.
Dispensers in rural Bangladesh sell antibiotics inappropriately by ignoring existing national regulations. They operate the antibiotic sales without facing any legal barriers and primarily with a view to sustain their business, resulting in inappropriate sales of antibiotics to the rural community. The influence of the drug industry needs to be replaced with evidence-based, not commercially driven information. Awareness programs for antibiotic providers that promote understanding of antibiotics and antibiotic resistance through tailored interventions may be helpful in changing current antibiotic sales practices.
Single-dose azithromycin is effective in the treatment of severe cholera in children, but its effectiveness in adults has not been evaluated.
We conducted a double-blind, randomized trial comparing ...the equivalence of azithromycin and ciprofloxacin (each given in a single 1-g dose of two 500-mg tablets) among 195 men with severe cholera caused by Vibrio cholerae O1 or O139. Patients were hospitalized for five days. A stool culture was performed daily. Primary outcome measures were clinical success (the cessation of watery stools within 48 hours after drug administration) and bacteriologic success (the inability to isolate V. cholerae after 48 hours).
Therapy was clinically successful in 71 of 97 patients receiving azithromycin (73 percent) and in 26 of 98 patients receiving ciprofloxacin (27 percent) (P<0.001) and bacteriologically successful in 76 of 97 patients receiving azithromycin (78 percent) and in 10 of 98 patients receiving ciprofloxacin (10 percent) (P<0.001). Patients who were treated with azithromycin had a shorter duration of diarrhea than did patients treated with ciprofloxacin (median, 30 vs. 78 hours); a lower frequency of vomiting (43 percent vs. 67 percent); fewer stools (median, 36 vs. 52); and a lower stool volume (median, 114 vs. 322 ml per kilogram of body weight). The median minimal inhibitory concentration of ciprofloxacin for the 177 isolates of V. cholerae O1 was 0.25 mug per milliliter, which was 11 to 83 times as high as that in previous studies at this site.
Single-dose azithromycin was effective in the treatment of severe cholera in adults. The lack of efficacy of ciprofloxacin may result from its diminished activity against V. cholerae O1 strains currently circulating in Bangladesh. (ClinicalTrials.gov number, NCT00229944.).
Malaria is endemic in 13 of 64 districts of Bangladesh, representing a population at risk of about 27 million people. The highest rates of malaria in Bangladesh occur in the Chittagong Hill ...Districts, and Plasmodium falciparum (predominately chloroquine resistant) is the most prevalent species.
The objective of this research was to describe the epidemiology of symptomatic P. falciparum malaria in an area of Bangladesh following the introduction of a national malaria control program. We carried out surveillance for symptomatic malaria due to P. falciparum in two demographically defined unions of the Chittagong Hill Districts in Bangladesh, bordering western Myanmar, between October 2009 and May 2012. The association between sociodemographics and temporal and climate factors with symptomatic P. falciparum infection over two years of surveillance data was assessed. Risk factors for infection were determined using a multivariate regression model.
472 cases of symptomatic P. falciparum malaria cases were identified among 23,372 residents during the study period. Greater than 85% of cases occurred during the rainy season from May to October, and cases were highly clustered geographically within these two unions with more than 80% of infections occurring in areas that contain approximately one-third of the total population. Risk factors statistically associated with infection in a multivariate logistic regression model were living in the areas of high incidence, young age, and having an occupation including jhum cultivation and/or daily labor. Use of long lasting insecticide-treated bed nets was high (89.3%), but its use was not associated with decreased incidence of infection.
Here we show that P. falciparum malaria continues to be hypoendemic in the Chittagong Hill Districts of Bangladesh, is highly seasonal, and is much more common in certain geographically limited hot spots and among certain occupations.
Pregnancy is a known risk factor for malaria which is associated with increased maternal and infant mortality and morbidity in areas of moderate-high malaria transmission intensity where Plasmodium ...falciparum predominates. The nature and impact of malaria, however, is not well understood in pregnant women residing in areas of low, unstable malaria transmission where P. falciparum and P. vivax co-exist.
A large longitudinal active surveillance study of malaria was conducted in the Chittagong Hill Districts of Bangladesh. Over 32 months in 2010-2013, the period prevalence of asymptomatic P. falciparum infections was assessed by rapid diagnostic test and blood smear and compared among men, non-pregnant women and pregnant women. A subset of samples was tested for infection by PCR. Hemoglobin was assessed. Independent risk factors for malaria infection were determined using a multivariate logistic regression model.
Total of 34 asymptomatic P. falciparum infections were detected by RDT/smear from 3,110 tests. The period prevalence of asymptomatic P. falciparum infection in pregnant women was 2.3%, compared to 0.5% in non-pregnant women and 0.9% in men. All RDT/smear positive samples that were tested by PCR were PCR-positive, and PCR detected additional 35 infections that were RDT/smear negative. In a multivariate logistic regression analysis, pregnant women had 5.4-fold higher odds of infection as compared to non-pregnant women. Malaria-positive pregnant women, though asymptomatic, had statistically lower hemoglobin than those without malaria or pregnancy. Asymptomatic malaria was found to be evenly distributed across space and time, in contrast to symptomatic infections which tend to cluster.
Pregnancy is a risk factor for asymptomatic P. falciparum infection in the Chittagong Hill Districts of Bangladesh, and pregnancy and malaria interact to heighten the effect of each on hemoglobin. The even distribution of asymptomatic malaria, without temporal and spatial clustering, may have critical implications for malaria elimination strategies.
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•Evidence before this study: Most active screens for subclinical malaria in hypoendemic regions reveal a pattern of 20% Plasmodium prevalence by PCR only in asymptomatic individuals, ...with 1–4% RDT or microscopy positive prevalence. Few studies have looked at the risk factors and seasonal and spatial distribution of the subclinical individuals.•Added value of this study: Subclinical malaria is not seasonal, nor confined to the same geographic hotspots as clinical malaria, but does have similar risk factors as clinical malaria. Subclinical malaria individuals were not asymptomatic.•Implications of all the available evidence: Detection of the hidden subclinical reservoir is important to eliminate ongoing malaria transmission and will require novel approaches distinct from strategies for the control of clinical malaria.
An analysis of the risk factors and seasonal and spatial distribution of individuals with subclinical malaria in hypoendemic Bangladesh was performed.
From 2009 to 2012, active malaria surveillance without regard to symptoms was conducted on a random sample (n=3971) and pregnant women (n=589) during a cohort malaria study in a population of 24000.
The overall subclinical Plasmodium falciparum malaria point prevalence was 1.0% (n=35), but was 3.2% (n=18) for pregnant women. The estimated incidence was 39.9 per 1000 person-years for the overall population. Unlike symptomatic malaria, with a marked seasonal pattern, subclinical infections did not show a seasonal increase during the rainy season. Sixty-nine percent of those with subclinical P. falciparum infections reported symptoms commonly associated with malaria compared to 18% without infection. Males, pregnant women, jhum cultivators, and those living closer to forests and at higher elevations had a higher prevalence of subclinical infection.
Hypoendemic subclinical malaria infections were associated with a number of household and demographic factors, similar to symptomatic cases. Unlike clinical symptomatic malaria, which is highly seasonal, these actively detected infections were present year-round, made up the vast majority of infections at any given time, and likely acted as reservoirs for continued transmission.
The recent introduction of mobile phones into the rural Bandarban district of Bangladesh provided a resource to improve case detection and treatment of patients with malaria.
During studies to define ...the epidemiology of malaria in villages in south-eastern Bangladesh, an area with hypoendemic malaria, the project recorded 986 mobile phone calls from families because of illness suspected to be malaria between June 2010 and June 2012.
Based on phone calls, field workers visited the homes with ill persons, and collected blood samples for malaria on 1,046 people. 265 (25%) of the patients tested were positive for malaria. Of the 509 symptomatic malaria cases diagnosed during this study period, 265 (52%) were detected because of an initial mobile phone call.
Mobile phone technology was found to be an efficient and effective method for rapidly detecting and treating patients with malaria in this remote area. This technology, when combined with local knowledge and field support, may be applicable to other hard-to-reach areas to improve malaria control.
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