Antibiotics for Leptospirosis

BACKGROUND: Leptospirosis has a wide-ranging clinical and public health impact. Leptospira are globally distributed. Case attack rates are as high as 1:4 to 2:5 persons in exposed populations. In some settings mortality has exceeded 10% of infected people. The benefit of antibiotic therapy in the disease has been unclear. OBJECTIVES: We sought to characterise the risks and benefits associated with use of antibiotic therapy in the management of leptospirosis. SEARCH METHODS: We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded regardless of study language. This was augmented by a manual search. The last date of search was November, 2011. SELECTION CRITERIA: To be included in assessment of benefits, trials had to specifically assess the use of antibiotics in a randomised clinical trial. A broad range of study types were incorporated to seek potential harms. DATA COLLECTION AND ANALYSIS: Included trials were systematically abstracted, as were excluded studies for the purposes of assessing harms. Analyses were conducted in accordance with The Cochrane Handbook and practices of The Cochrane Hepato-Biliary Group. MAIN RESULTS: Seven randomised trials were included. Four trials with 403 patients compared an antibiotic with placebo or no intervention. Three trials compared at least one antibiotic regimen with another antibiotic regimen. The trials all had high risk of bias. The trials varied in the severity of leptospirosis among trial patients. The ability to group data for meta-analysis was limited. While all four trials that compared antibiotics with placebo reported mortality and used parenteral penicillin, there were no deaths in two of them. Since odds ratio calculations cannot employ zero-event trials, only two trials contributed to this estimate. The number of deaths were 16/200 (8.0%) in the antibiotic arm versus 11/203 (5.4%) in the placebo arm giving a fixed-effect OR 1.56 (95% CI 0.70 to 3.46). The random-effects OR is 1.16 (95% CI 0.23 to 5.95). The heterogeneity among these four trials for the mortality outcome was moderate (I(2)= 50%). Only one trial (253 patients) reported days of hospitalisation. It compared parenteral penicillin to placebo without significant effect of therapy (8.9 versus 8.8 days; mean difference (MD) 0.10 days, 95% CI -0.83 to 1.03). The difference in days of clinical illness was reported in two of these trials (71 patients). While parenteral penicillin therapy conferred 4.7 to 5.6 days of clinical illness in contrast to 7.7 to 11.6 days in the placebo arm, the size of the estimate of effect increased but statistical significance was lost under the random-effect model (fixed-effect: MD -2.13 days, 95% CI -2.46 to -1.80; random-effects: MD -4.04, 95% CI -8.66 to 0.58). I(2) for this outcome was high (81%). When duration of fever alone was assessed between antibiotics and placebo in a single trial (79 patients), no significant difference existed (6.9 versus 6.6 days; MD 0.30, 95% CI -1.26 to 1.86). Two trials with 332 patients in relatively severe and possibly late leptospirosis, resulted in trends towards increased dialysis when penicillin was used rather than placebo, but the estimate of effect was small and did not reach statistical significance (42/163 (25.8%) versus 31/169 (18.4%); OR 1.54, 95% CI 0.91 to 2.60). When one antibiotic was assessed against another antibiotic, there were no statistically significant results. For mortality in particular, these comparisons included cephalosporin versus penicillin (2 trials, 6/176 (3.4%) versus 9/175 (5.2%); fixed-effect: OR 0.65, 95% CI 0.23 to 1.87, I(2)= 16%), doxycycline versus penicillin (1 trial, 2/81 (2.5%) versus 4/89 (4.5); OR 0.54, 95% CI 0.10 to 3.02), cephalosporin versus doxycycline (1 trial, 1/88 (1.1%) versus 2/81 (2.5%); OR 0.45, 95% CI 0.04 to 5.10). There were no adverse events of therapy which reached statistical significance. AUTHORS\u27 CONCLUSIONS: Insufficient evidence is available to advocate for or against the use of antibiotics in the therapy for leptospirosis. Among survivors who were hospitalised for leptospirosis, use of antibiotics for leptospirosis may have decreased the duration of clinical illness by two to four days, though this result was not statistically significant. When electing to treat with an antibiotic, selection of penicillin, doxycycline, or cephalosporin does not seem to impact mortality nor duration of fever. The benefit of antibiotic therapy in the treatment of leptospirosis remains unclear, particularly for severe disease. Further clinical research is needed to include broader panels of therapy tested against placebo

Literacy and recent history of diarrhoea are predictive of plasmodium falciparum parasitaemia in Kenyan adults

Background - Malaria is one of the most serious health problems in Kenya. In 2004, the Kenya Medical Research Institute and the US Army Medical Research Unit – Kenya surveyed adults in Samburu, Malindi, and Busia districts to determine socioeconomic risk factors for infection. Methods - Sociodemographic, health, and antimalarial data were collected along with blood for malaria testing. A smear was considered negative only if no Plasmodium falciparum parasites were observed in 100 high-powered fields. Univariate analysis was performed with Pearson\u27s Chi-square test and univariate logistic regression. A multivariate logistic regression model was then created which included only variables found to be at least marginally significant in univariate analysis. Results - A total of 1,141 subjects were recruited: 238 from Samburu, 442 from Malindi, and 461 from Busia. Smear positivities for P. falciparum were 1.7% in Samburu, 7.2% in Malindi and 22.3% in Busia. Interdistrict differences were statistically significant (p \u3c 0.001) in univariate analysis and in a multivariate logistic regression model which included district, literacy, occupation, and recent illness as independent variables. In the model, literacy and recent diarrhoeal illness were positively and at least marginally significantly associated with parasitaemia (p = 0.023 and p = 0.067, respectively). Neither age, sex, occupation, history of malaria in the previous three months, nor use of antimalarials in the previous four weeks were significantly associated with parasitaemia. Conclusion - While district of residence was the variable most highly predictive for parasitaemia among Kenyan adults surveyed, both a recent history of diarrhoeal illness and literacy were at least marginally statistically significant predictors

Serotype Diversity of Respiratory Human Adenoviruses amongst Pediatric Patients from Western Kenya, 2010-2012

Background: Respiratory illnesses are common among pediatric patients in Kenya, and many are attributed to viral causes. However, there is limited knowledge of the diversity of viral etiologies associated with these illnesses. Objective: To characterize respiratory adenoviruses isolates using serological and molecular approaches. Methods: A total of 1,879 samples were collected from symptomatic pediatric patients seeking medical care at New Nyanza Provincial General Hospital during the period of June 2010 to June 2012 and screened for adenoviruses as well as other respiratory viruses. Sixteen respiratory human adenoviruses (HAdVs) were isolated in Hep2 cell culture and characterized them using Immunofluorescence Assay, viral DNA amplification, sequencing and phylogenomics. Results: Phylogenetic characterization of the HAdVs using the hyper variable region 7 of the hexon gene identified HAdV B and C as the major species associated with respiratory infections during the study period. Amongst these, a single B-type and four C-type serotypes were identified.  The serotype distribution consisted of 31% HAdV B7, 25% HAdV C1, 25% HAdV C2, 6% HAdV C5, and 13% HAdV C6. Positive selection was observed in the nucleotide sequences from HAdV B7 and HAdV C5 signaling evolution of these two serotypes. Conclusion: These finding may be useful to policy makers regarding appropriate strain selection for vaccination in Kenya. Keywords: Respiratory Human adenovirus, Kenya, Pediatric, Serotype, Hexon, HVR-

Molecular Surveillance of Adamantane Resistance among Human Influenza A Viruses Isolated in Four Epidemic Seasons in Kenya

Background: Adamantanes impede influenza A virus replication and are important in the treatment and prophylaxis of disease caused by these viruses. Genotypic characterization of influenza A viruses for mutations associated with resistance to adamantanes has not been fully investigated in Kenya. Objective: To characterize susceptibility of influenza A virus subtypes that circulated in Kenya from 2008-2011 to adamantanes. Methods: Archived influenza A virus strains obtained from 2008 to 2011 were propagated in MDCK cells prior to sequencing of the matrix and hemagglutinin gene segments, followed by bioinformatics analyses. Results: Ninety two virus strains consisting of 21 A/H3N2, 18 A/H1N1 and 53 A/H1N1pdm09 were analyzed.  All A/H3N2 and A/H1N1pdm09 viruses displayed resistance to adamantanes due to the S31N/S31D amino acid substitution. All A/H1N1pdm09 virus strains belonged to the N-lineage characterized by S203T amino acid substitution in the HA1. All A/H1N1 viruses were sensitive to adamantane and were characterized by K140E amino acid substitution in the HA1. Conclusion: All Kenyan influenza A/H3N2 and A/H1N1pdm09 virus strains were resistant to adamantanes while seasonal A/H1N1 strains were sensitive to these drugs. During the study period, Amantadine and Rimantadine were inappropriate for prophylaxis and treatment of influenza disease caused by A/H3N2 and A/H1N1pdm09 virus subtypes in Kenya. Key words: Kenya, influenza A/H3N2, A/H1N1pdm09, A/H1N1, adamantane

Increased prevalence of the pfdhfr/phdhps quintuple mutant and rapid emergence of pfdhps resistance mutations at codons 581 and 613 in Kisumu, Kenya

<p>Abstract</p> <p>Background</p> <p>Anti-malarial drug resistance in Kenya prompted two drug policy changes within a decade: sulphadoxine-pyrimethamine (SP) replaced chloroquine (CQ) as the first-line anti-malarial in 1998 and artemether-lumefantrine (AL) replaced SP in 2004. Two cross-sectional studies were conducted to monitor changes in the prevalence of molecular markers of drug resistance over the period in which SP was used as the first-line anti-malarial. The baseline study was carried out from 1999-2000, shortly after implementation of SP, and the follow-up study occurred from 2003-2005, during the transition to AL.</p> <p>Materials and methods</p> <p>Blood was collected from malaria smear-positive, symptomatic patients presenting to outpatient centers in Kisumu, Kenya, during the baseline and follow-up studies. Isolates were genotyped at codons associated with SP and CQ resistance. <it>In vitro </it>IC₅₀values for antifolates and quinolones were determined for isolates from the follow-up study.</p> <p>Results</p> <p>The prevalence of isolates containing the <it>pfdhfr </it>N51I/C59R/S108N/<it>pfdhps </it>A437G/K540E quintuple mutant associated with SP-resistance rose from 21% in the baseline study to 53% in the follow-up study (p < 0.001). Isolates containing the <it>pfdhfr </it>I164L mutation were absent from both studies. The <it>pfdhps </it>mutations A581G and A613S/T were absent from the baseline study but were present in 85% and 61%, respectively, of isolates from the follow-up study. At follow-up, parasites with mutations at five <it>pfdhps </it>codons, 436, 437, 540, 581, and 613, accounted for 39% of isolates. The CQ resistance-associated mutations <it>pfcrt </it>K76T and <it>pfmdr1 </it>N86Y rose from 82% to 97% (p = 0.001) and 44% to 76% (p < 0.001), respectively, from baseline to follow-up.</p> <p>Conclusions</p> <p>During the period in which SP was the first-line anti-malarial in Kenya, highly SP-resistant parasites emerged, including isolates harboring <it>pfdhps </it>mutations not previously observed there. SP continues to be widely used in Kenya; however, given the highly resistant genotypes observed in this study, its use as a first-line anti-malarial should be discouraged, particularly for populations without acquired immunity to malaria. The increase in the <it>pfcrt </it>K76T prevalence, despite efforts to reduce CQ use, suggests that either these efforts are not adequate to alleviate CQ pressure in Kisumu, or that drug pressure is derived from another source, such as the second-line anti-malarial amodiaquine.</p

Tickborne Arbovirus Surveillance in Market Livestock, Nairobi, Kenya

Numerous tickborne viruses, including Dhori virus and foot-and-mouth disease virus, were isolated

Yellow Fever Outbreak, Imatong, Southern Sudan

In May 2003, the World Health Organization received reports about a possible outbreak of a hemorrhagic disease of unknown cause in the Imatong Mountains of southern Sudan. Laboratory investigations were conducted on 28 serum samples collected from patients in the Imatong region. Serum samples from 13 patients were positive for immunoglobulin M antibody to flavivirus, and serum samples from 5 patients were positive by reverse transcription–polymerase chain reaction with both the genus Flavivirus–reactive primers and yellow fever virus–specific primers. Nucleotide sequencing of the amplicons obtained with the genus Flavivirus oligonucleotide primers confirmed yellow fever virus as the etiologic agent. Isolation attempts in newborn mice and Vero cells from the samples yielded virus isolates from five patients. Rapid and accurate laboratory diagnosis enabled an interagency emergency task force to initiate a targeted vaccination campaign to control the outbreak

Seroprevalence and distribution of arboviral infections among rural Kenyan adults: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Arthorpod-borne viruses (arboviruses) cause wide-spread morbidity in sub-Saharan Africa, but little research has documented the burden and distribution of these pathogens.</p> <p>Methods</p> <p>Using a population-based, cross-sectional study design, we administered a detailed questionnaire and used ELISA to test the blood of 1,141 healthy Kenyan adults from three districts for the presence of anti-viral Immunoglobulin G (IgG) antibodies to the following viruses: dengue (DENV), West Nile (WNV), yellow fever (YFV), Chikungunya (CHIKV), and Rift Valley fever (RVFV).</p> <p>Results</p> <p>Of these, 14.4% were positive for DENV, 9.5% were WNV positive, 9.2% were YFV positive, 34.0% were positive for CHIKV and 0.7% were RVFV positive. In total, 46.6% had antibodies to at least one of these arboviruses.</p> <p>Conclusions</p> <p>For all arboviruses, district of residence was strongly associated with seropositivity. Seroprevalence to YFV, DENV and WNV increased with age, while there was no correlation between age and seropositivity for CHIKV, suggesting that much of the seropositivity to CHIKV is due to sporadic epidemics. Paradoxically, literacy was associated with increased seropositivity of CHIKV and DENV.</p