Wasif A Khan

Tufts Medical Center, Boston, MA, USA

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Publications (17)172.44 Total impact

  • Article: Mobile phones improve case detection and management of malaria in rural Bangladesh.
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    ABSTRACT: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
    Malaria Journal 02/2013; 12(1):48. · 3.19 Impact Factor
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    Article: Evaluation of the OnSite (Pf/Pan) rapid diagnostic test for diagnosis of clinical malaria
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    ABSTRACT: Background Accurate diagnosis of malaria is an essential prerequisite for proper treatment and drug resistance monitoring. Microscopy is considered the gold standard for malaria diagnosis but has limitations. ELISA, PCR, and Real Time PCR are also used to diagnose malaria in reference laboratories, although their application at the field level is currently not feasible. Rapid diagnostic tests (RDTs) however, have been brought into field operation and widely adopted in recent days. This study evaluates OnSite (Pf/Pan) antigen test, a new RDT introduced by CTK Biotech Inc, USA for malaria diagnosis in a reference setting. Methods Blood samples were collected from febrile patients referred for malaria diagnosis by clinicians. Subjects were included in this study from two different Upazila Health Complexes (UHCs) situated in two malaria endemic districts of Bangladesh. Microscopy and nested PCR were considered the gold standard in this study. OnSite (Pf/Pan) RDT was performed on preserved whole blood samples. Results In total, 372 febrile subjects were included in this study. Of these subjects, 229 (61.6%) tested positive for Plasmodium infection detected by microscopy and nested PCR. OnSite (Pf/Pan) RDT was 94.2% sensitive (95% CI, 89.3-97.3) and 99.5% specific (95% CI, 97.4-00.0) for Plasmodium falciparum diagnosis and 97.3% sensitive (95% CI, 90.5-99.7) and 98.7% specific (95% CI, 96.6-99.6) for Plasmodium vivax diagnosis. Sensitivity varied with differential parasite count for both P. falciparum and P. vivax. The highest sensitivity was observed in febrile patients with parasitaemia that ranged from 501--1,000 parasites/muL regardless of the Plasmodium species. Conclusion The new OnSite (Pf/Pan) RDT is both sensitive and specific for symptomatic malaria diagnosis in standard laboratory conditions.
    Malaria Journal 12/2012; 11(415). · 3.19 Impact Factor
  • Article: Genotyping of Plasmodium falciparum using antigenic polymorphic markers and to study anti-malarial drug resistance markers in malaria endemic areas of Bangladesh.
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    ABSTRACT: BACKGROUND: In the past many regions of Bangladesh were hyperendemic for malaria. Malaria control in the 1960s to 1970s eliminated malaria from the plains but in the Chittagong Hill Tracts remained a difficult to control reservoir.. The Chittagong Hill Tracts have areas with between 1 and 10% annual malaria rates, predominately 90-95% Plasmodium falciparum. In Southeast Asia, multiplicity of infection for hypo-endemic regions has been approximately 1.5. Few studies on the genetic diversity of P. falciparum have been performed in Bangladesh. Anderson et al. performed a study in Khagrachari, northern Chittagong Hill Tracts in 2002 on 203 patients and found that parasites had a multiplicity of infection of 1.3 by MSP-1, MSP-2 and GLURP genotyping. A total of 94% of the isolates had the K76T Pfcrt chloroquine resistant genotype, and 70% showed the N86Y Pfmdr1 genotype. Antifolate drug resistant genotypes were high with 99% and 73% of parasites having two or more mutations at the dhfr or dhps loci. METHODS: Nested and real-time polymerase chain reaction (PCR) methods were used to genotype P. falciparum using antigenic polymorphic markers and to study anti-malarial drug resistance markers in malaria endemic areas of Bangladesh. RESULTS: The analysis of polymorphic and drug resistant genotype on 33 paired recrudescent infections after drug treatment in the period 2004 to 2008 in the Chittagong Hill Tracts, which is just prior to countrywide provision of artemisinin combination therapy. Overall the multiplicity of infection for MSP-1 was 2.7 with a slightly smaller parasite diversity post-treatment. The 13 monoclonal infections by both GLURP and MSP-1 were evenly divided between pre- and post-treatment. The MSP-1 MAD block was most frequent in 66 of the samples. The prevalence of the K76T PfCRT chloroquine resistant allele was approximately 82% of the samples, while the resistant Pfmdr1 N86Y was present in 33% of the samples. Interestingly, the post-treatment samples had a small but significantly higher frequency of the sensitive PfCRT alleles by RT-PCR. CONCLUSION: The parasite population retains high population diversity despite hypo-endemic transmission with retention, but decrease in the chloroquine-resistant allele and Pfmdr1 resistant alleles in the Chittagong Hill Tracts of Bangladesh.
    Malaria Journal 11/2012; 11(1):386. · 3.19 Impact Factor
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    Article: Diversity of anopheline species and their Plasmodium infection status in rural Bandarban, Bangladesh.
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    ABSTRACT: Historically, the Chittagong Hill Tracts (CHT) of Bangladesh was considered hyperendemic for malaria. To better understand the contemporary malaria epidemiology and to develop new and innovative control strategies, comprehensive epidemiologic studies are ongoing in two endemic unions of Bandarban district of CHT. Within these studies entomological surveillance has been undertaken to study the role of the existing anopheline species involved in the malaria transmission cycle throughout the year. CDC miniature light traps were deployed to collect anopheline mosquitoes from the sleeping room of the selected houses each month in a single union (Kuhalong). Molecular identification was carried out for available Anopheles species complexes. Circumsporozoite proteins (CSP) for Plasmodium falciparum, Plasmodium vivax-210 (Pv-210) and Plasmodium vivax-247(Pv-247) were detected by Enzyme-linked immunosorbent assay (ELISA) from the female anopheline mosquitoes. To confirm CSP-ELISA results, polymerase chain reaction (PCR) was also performed. A total of 2,837 anopheline mosquitoes, of which 2,576 were female, belonging to 20 species were collected from July 2009-June 2010. Anopheles jeyporiensis was the most abundant species (18.9%), followed by An. vagus (16.8%) and An. kochi (14.4%). ELISA was performed on 2,467 female mosquitoes of 19 species. 15 (0.6%) female anophelines belonging to eight species were found to be positive for Plasmodium infection by CSP-ELISA. Of those, 11 (0.4%) mosquitoes were positive for P. falciparum and four (0.2%) for Pv-210. No mosquito was found positive for Pv-247. An. maculatus (2.1%, 2/97) had the highest infection rate followed by An. umbrosus (1.7%, 2/115) and An. barbirostris (1.1%, 2/186). Other infected species were An. nigerrimus, An. nivipes, An. jeyporiensis, An. kochi, and An. vagus. Out of 11 P. falciparum CSP positive samples, seven turned out to be positive by PCR. None of the samples positive for Pv-210 was positive by PCR. In terms of abundance and incrimination, the results suggest that An. maculatus, An. jeyporiensis and An. nivipes play important roles in malaria transmission in Kuhalong. The findings of this study suggest that even in the presence of an insecticide impregnated bed-net intervention, a number of Anopheles species still play a role in the transmission of malaria. Further investigations are required to reveal the detailed biology and insecticide resistance patterns of the vector mosquito species in endemic areas in Bangladesh in order to assist with the planning and implementation of improved malaria control strategies.
    Parasites & Vectors 07/2012; 5:150. · 2.94 Impact Factor
  • Article: Systemic antibody responses to the immunodominant p23 antigen and p23 polymorphisms in children with cryptosporidiosis in Bangladesh.
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    ABSTRACT: Cryptosporidium is a major cause of diarrhea in children in developing countries. However, there is no vaccine available and little is known about immune responses to protective antigens. We investigated antibody responses to p23, a putative vaccine candidate, in children in Bangladesh with cryptosporidiosis and diarrhea (cases) and uninfected children with diarrhea (controls), and p23 gene polymorphisms in infecting species. Serum IgM, IgG, and IgA responses to p23 were significantly greater in cases than controls after three weeks of follow-up. Cases with acute diarrhea had significantly greater serum IgA and IgM responses than those with persistent diarrhea, which suggested an association with protection from prolonged disease. The p23 sequences were relatively conserved among infecting species and subtype families. Although most children were infected with Cryptosporidium hominis, there was a cross-reactive antibody response to C. parvum antigen. These results support further development of p23 as a vaccine candidate.
    The American journal of tropical medicine and hygiene 02/2012; 86(2):214-22. · 2.59 Impact Factor
  • Article: Antibody responses to the immunodominant Cryptosporidium gp15 antigen and gp15 polymorphisms in a case-control study of cryptosporidiosis in children in Bangladesh.
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    ABSTRACT: Although Cryptospridium hominis is the dominant Cryptosporidium species infecting humans, immune responses to cognate antigens in C. hominis-infected persons have not been reported. We investigated antibody responses to the immunodominant gp15 antigen from C. hominis and C. parvum, in C. hominis-infected Bangladeshi children less than five years of age with diarrhea (cases) and uninfected children with diarrhea (controls). We also investigated polymorphisms in the C. hominis gp15 sequence from cases. Serum IgG responses to gp15 from both species were significantly greater in cases than controls. In spite of polymorphisms in the gp15 sequence, there was a significant correlation between antibody levels to gp15 from both species, indicating cross-reactivity to conserved epitopes. Cases with acute diarrhea had a significantly greater serum IgA response to gp15 compared with those with persistent diarrhea, suggesting that this response may be associated with protection from prolonged disease. These findings support further investigation of gp15 as a vaccine candidate.
    The American journal of tropical medicine and hygiene 07/2011; 85(1):97-104. · 2.59 Impact Factor
  • Article: Genetic diversity of Cryptosporidium spp. from Bangladeshi children.
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    ABSTRACT: The genetic diversity of Cryptosporidium spp. from infected children was characterized for the first time in Bangladesh. Seven C. hominis and C. parvum subtype families (including a new family, IIm) and 15 subtypes (including 2 new subtypes) were identified. The dominance of specific families and subtypes was different from that in other countries.
    Journal of clinical microbiology 04/2011; 49(6):2307-10. · 4.16 Impact Factor
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    Article: Mapping hypoendemic, seasonal malaria in rural Bandarban, Bangladesh: a prospective surveillance.
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    ABSTRACT: Until recently the Chittagong Hill tracts have been hyperendemic for malaria. A past cross-sectional RDT based survey in 2007 recorded rates of approximately 15%. This study was designed to understand the present epidemiology of malaria in this region, to monitor and facilitate the uptake of malaria intervention activities of the national malaria programme and to serve as an area for developing new and innovative control strategies for malaria. This research field area was established in two rural unions of Bandarban District of Bangladesh north of Bandarban city, which are known to be endemic for malaria due to Plasmodium falciparum. The project included the following elements: a) a demographic surveillance system including an initial census with updates every four months, b) periodic surveys of knowledge attitude and practice, c) a geographic information system, d) weekly active and continuous passive surveillance for malaria infections using smears, rapid tests and PCR, f) monthly mosquito surveillance, and e) daily weather measures. The programme included both traditional and molecular methods for detecting malaria as well as lab methods for speciating mosquitoes and detecting mosquitoes infected with sporozoites. The demographic surveillance enumerated and mapped 20,563 people, 75% of which were tribal non-Bengali. The monthly mosquito surveys identified 22 Anopheles species, eight of which were positive by circumsporozoite ELISA. The annual rate of malaria was close to 1% with 85% of cases in the rainy months of May-October. Definitive clustering identified in the low transmission season persisted during the high transmission season. This demographically and geographically defined area, near to the Myanmar border, which is also hypoendemic for malaria, will be useful for future studies of the epidemiology of malaria and for evaluation of strategies for malaria control including new drugs and vaccines.
    Malaria Journal 01/2011; 10:124. · 3.19 Impact Factor
  • Article: Transferable quinolone resistance in Vibrio cholerae.
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    ABSTRACT: Ciprofloxacin was introduced for treatment of patients with cholera in Bangladesh because of resistance to other agents, but its utility has been compromised by the decreasing ciprofloxacin susceptibility of Vibrio cholerae over time. We correlated levels of susceptibility and temporal patterns with the occurrence of mutation in gyrA, which encodes a subunit of DNA gyrase, followed by mutation in parC, which encodes a subunit of DNA topoisomerase IV. We found that ciprofloxacin activity was more recently further compromised in strains containing qnrVC3, which encodes a pentapeptide repeat protein of the Qnr subfamily, members of which protect topoisomerases from quinolone action. We show that qnrVC3 confers transferable low-level quinolone resistance and is present within a member of the SXT integrating conjugative element family found commonly on the chromosomes of multidrug-resistant strains of V. cholerae and on the chromosomes of Escherichia coli transconjugants constructed in the laboratory. Thus, progressive increases in quinolone resistance in V. cholerae are linked to cumulative mutations in quinolone targets and most recently to a qnr gene on a mobile multidrug resistance element, resulting in further challenges for the antimicrobial therapy of cholera.
    Antimicrobial Agents and Chemotherapy 11/2009; 54(2):799-803. · 4.84 Impact Factor
  • Chapter: Antimicrobial Resistance in Vibrios
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    ABSTRACT: This chapter addresses antimicrobial resistance in a genus – Vibrio – that results in two distinct clinical syndromes. One is profound diarrheal disease – cholera – caused by Vibrio cholerae O1 or O139. The other is often the fatal wound infection and sepsis caused by a variety of halophilic (saltloving) vibrios (1) – with V. vulnificus and V. parahaemolyticus perhaps being the most commonly occurring species (2–4) but including infections with V. alginolyticus (5), V. harveyi, V. fl uvialis, and others (6).
    12/2008: pages 833-845;
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    Article: Emergence of multidrug-resistant strain of Vibrio cholerae O1 in Bangladesh and reversal of their susceptibility to tetracycline after two years.
    Journal of Health Population and Nutrition 07/2007; 25(2):241-3. · 0.95 Impact Factor
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    Article: Single-dose azithromycin for the treatment of cholera in adults.
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    ABSTRACT: 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.).
    New England Journal of Medicine 06/2006; 354(23):2452-62. · 53.30 Impact Factor
  • Article: Low risk of hemolytic uremic syndrome after early effective antimicrobial therapy for Shigella dysenteriae type 1 infection in Bangladesh.
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    ABSTRACT: Hemolytic uremic syndrome (HUS) may complicate up to 15% of cases of Shiga toxin (Stx)-expressing enterohemorrhagic Escherichia coli (STEC) O157:H7 infections in children. Administration of antimicrobials has been reported to increase the risk of STEC-associated HUS by >10-fold, presumably by increasing the expression and release of Stx by dying STEC bacteria. Shigella dysenteriae type 1 also expresses Stx. However, the effect of antimicrobial therapy on Stx release and the risk of HUS in humans is unknown. We measured serial stool Stx concentrations before and after administration of antimicrobials in 20 children infected with S. dysenteriae type 1 who had frank dysentery of <72 h duration. We also reviewed the results of 7 shigellosis drug trials performed in Bangladesh during 1988-2000 to estimate the risk of HUS. In these studies, antimicrobials were administered within 96 h after the onset of dysentery. Stx levels decreased in stool samples obtained from 17 of 20 children after administration of antimicrobial agents; none of the 20 children developed HUS. Of 378 individuals infected with S. dysenteriae type 1 who were enrolled in drug trials (128 adult men [age, 18-60 years] and 250 children [age, 6 months to 15 years]), 351 (93%) received an antimicrobial agent to which the S. dysenteriae organism was susceptible <or=96 h after the onset of symptoms; HUS developed in 1 child. The risk of developing HUS was 0.0026 for all participants (95% confidence interval, <0.001 to 0.015) and was 0.004 for children (95% confidence interval, 0.001-0.022). In persons infected with S. dysenteriae type 1, early administration of effective antibiotics is associated with decreased Stx concentrations in stool and a low risk of developing HUS.
    Clinical Infectious Diseases 02/2006; 42(3):356-62. · 9.15 Impact Factor
  • Article: Cryptosporidiosis among Bangladeshi children with diarrhea: a prospective, matched, case-control study of clinical features, epidemiology and systemic antibody responses.
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    ABSTRACT: We conducted a prospective case-control study to investigate the epidemiology, clinical features, and systemic antibody responses of cryptosporidiosis in Bangladeshi children. Forty-six children presenting to the International Center for Diarrheal Disease Research, Bangladesh in Dhaka, Bangladesh with diarrhea and Cryptosporidium spp. oocysts in the stool were enrolled as cases. Forty-six age-matched children with diarrhea, but without cryptosporidial infection, were enrolled as controls. Thirty cases and 23 controls returned for follow-up three weeks after discharge. Infection with Cryptosporidium spp. occurred most commonly in those less than two years of age, was accompanied by watery diarrhea and vomiting, and was more likely to be associated with persistent diarrhea. Other than duration of diarrhea, there were no significant differences in clinical or epidemiologic features between cases and controls. Cryptosporidium-specific serum IgM levels were significantly higher in cases compared with controls at presentation. In addition, there was a significant increase in serum Cryptosporidium-specific serum IgG levels over the three-week follow-up period in cases compared with controls. Within the case group, there was no difference between children with acute and persistent diarrhea in the change in IgG levels over the follow-up period. However, there was a significant difference between children with acute and persistent diarrhea in changes in both IgA and IgM levels, with persistent diarrhea being associated with a decrease in levels of both antibodies.
    The American journal of tropical medicine and hygiene 11/2004; 71(4):412-9. · 2.59 Impact Factor
  • Article: Comparison of single-dose azithromycin and 12-dose, 3-day erythromycin for childhood cholera: a randomised, double-blind trial.
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    ABSTRACT: Cholera is a major public-health problem, with children most affected. However, effective single-dose antimicrobial regimens have been identified only for adults. Our aim was to compare the efficacy of azithromycin and erythromycin regimens in the treatment of children. We did a double-blind, randomised study of 128 severely dehydrated children (age 1-15 years) with cholera, treated at one of two treatment centres in Bangladesh in 1999. Children were assigned single-dose azithromycin (20 mg/kg bodyweight, maximum individual dose 1 g; n=65) or 12.5 mg/kg erythromycin (maximum dose 500 mg; n=63) every 6 h for 3 days. Patients stayed in hospital for 5 days. We measured fluid balance every 6 h, and obtained a rectal swab or stool sample for culture daily. Our primary outcome measures were clinical success of treatment-ie, cessation of watery diarrhoea within 48 h-and bacteriological success-ie, absence of Vibrio cholerae O1 or O139 from cultures of stool or rectal swab samples after study day 2. Analysis was per protocol. Two children in both groups withdrew from the study, and we excluded one child in the erythromycin group. Treatment was clinically successful in 48 (76%) patients who received azithromycin and 39 (65%) who received erythromycin (difference 11%, 95% CI -5 to 27, p=0.244); and bacteriologically successful in 45 (71%) and 49 (82%) patients, respectively (10%, -5 to 25, p=0.261). Patients treated with azithromycin had a shorter duration of diarrhoea (median 24 h vs 42 h; difference 12 h, 0-18 h, p=0.019) and fewer episodes of vomiting (1 vs 4; difference 1 episode, 0-3 episodes, p=0.023). Single-dose azithromycin is as effective for treatment of cholera in children as standard erythromycin therapy, but is associated with less vomiting.
    The Lancet 12/2002; 360(9347):1722-7. · 38.28 Impact Factor
  • Article: Single-dose ciprofloxacin versus 12-dose erythromycin for childhood cholera: a randomised controlled trial.
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    ABSTRACT: Single-dose ciprofloxacin is effective for the treatment of severe cholera in adults. We assessed whether single-dose ciprofloxacin would be as effective as 3-day, 12-dose erythromycin in achieving clinical cure in children with severe cholera. We did a randomised, open label, controlled trial in children age 2-15 years with V cholerae O1 or O139 present in stool on dark-field microscopy. Children received either a single 20 mg/kg dose of ciprofloxacin (n=90) or 12.5 mg/kg of erythromycin (n=90) every 6 h for 3 days, and remained in hospital for 5 days. The primary outcome was clinical success of treatment, defined as cessation of watery stools within 48 h of start of drug treatment. Analysis was per protocol. This study is registered with the ClinicalTrials.gov Protocol Registration System at http://www.clinicaltrials.gov (registration number NCT 00142272) [corrected] Of 180 children randomised 162 completed the study. Treatment was clinically successful in 60% (47/78) of children treated with ciprofloxacin and in 55% (46/84) of those treated with erythromycin (difference 5% [95% CI -10 to 21]). Children receiving ciprofloxacin vomited less often (58%vs 74%; difference 16% [2 to 30]), had fewer stools (15 vs 21; 6 [0 to 9]), and less stool volume (152 vs 196 mL/kg; 43 mL/kg [13 to 87]) than those receiving erythromycin. Bacteriological failure was more common in ciprofloxacin-treated patients (58%vs 30%; 28% [13 to 43]) than erythromycin-treated patients. Single-dose ciprofloxacin achieves clinical outcomes similar to, or better than, those achieved with 12-dose erythromycin treatment in childhood cholera, but is less effective in eradicating V cholerae from stool.
    The Lancet 366(9491):1085-93. · 38.28 Impact Factor
  • Article: LETTER-TO-THE-EDITOR - Emergence of Multidrug-resistant Strain of Vibrio cholerae O1 in Bangladesh and Reversal of Their Susceptibility to Tetracycline after Two Years
    The Journal of Health, Population and Nutrition (ISSN: 1606-0997) Vol 25 Num 2.