Last data update: May 13, 2024. (Total: 46773 publications since 2009)
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Query Trace: Smit M[original query] |
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Post-discharge risk of mortality in children under 5 years of age in western Kenya: A retrospective cohort study
Kwambai TK , Kariuki S , Smit MR , Nevitt S , Onyango E , Oneko M , Khagayi S , Samuels AM , Hamel MJ , Laserson K , Desai M , Ter Kuile FO . Am J Trop Med Hyg 2023 109 (3) 704-712 Limited evidence suggests that children in sub-Saharan Africa hospitalized with all-cause severe anemia or severe acute malnutrition (SAM) are at high risk of dying in the first few months after discharge. We aimed to compare the risks of post-discharge mortality by health condition among hospitalized children in an area with high malaria transmission in western Kenya. We conducted a retrospective cohort study among recently discharged children aged < 5 years using mortality data from a health and demographic surveillance system that included household and pediatric in-hospital surveillance. Cox regression was used to compare post-discharge mortality. Between 2008 and 2013, overall in-hospital mortality was 2.8% (101/3,639). The mortality by 6 months after discharge (primary outcome) was 6.2% (159/2,556) and was highest in children with SAM (21.6%), followed by severe anemia (15.5%), severe pneumonia (5.6%), "other conditions" (5.6%), and severe malaria (0.7%). Overall, the 6-month post-discharge mortality in children hospitalized with SAM (hazard ratio [HR] = 3.95, 2.60-6.00, P < 0.001) or severe anemia (HR = 2.55, 1.74-3.71, P < 0.001) was significantly higher than that in children without these conditions. Severe malaria was associated with lower 6-month post-discharge mortality than children without severe malaria (HR = 0.33, 0.21-0.53, P < 0.001). The odds of dying by 6 months after discharge tended to be higher than during the in-hospital period for all children, except for those admitted with severe malaria. The first 6 months after discharge is a high-risk period for mortality among children admitted with severe anemia and SAM in western Kenya. Strategies to address this risk period are urgently needed. |
Addressing Personal Protective Equipment (PPE) Decontamination: Methylene Blue and Light Inactivates SARS-CoV-2 on N95 Respirators and Masks with Maintenance of Integrity and Fit (preprint)
Lendvay TS , Chen J , Harcourt BH , Scholte FE , Lin YL , Kilinc-Balci FS , Lamb MM , Homdayjanakul K , Cui Y , Price A , Heyne B , Sahni J , Kabra KB , Lin YC , Evans D , Mores CN , Page K , Chu LF , Haubruge E , Thiry E , Ludwig-Begall LF , Wielick C , Clark T , Wagner T , Timm E , Gallagher T , Faris P , Macia N , Mackie CJ , Simmons SM , Reader S , Malott R , Hope K , Davies JM , Tritsch SR , Dams L , Nauwynck H , Willaert JF , De Jaeger S , Liao L , Zhao M , Laperre J , Jolois O , Smit SJ , Patel AN , Mayo M , Parker R , Molloy-Simard V , Lemyre JL , Chu S , Conly JM , Chu MC . medRxiv 2020 2020.12.11.20236919 Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in severe shortages of personal protective equipment (PPE) necessary to protect front-line healthcare personnel. These shortages underscore the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed PPE enabling safe reuse of masks and respirators. Efficient decontamination must be available not only in low-resourced settings, but also in well-resourced settings affected by PPE shortages. Methylene blue (MB) photochemical treatment, hitherto with many clinical applications including those used to inactivate virus in plasma, presents a novel approach for widely applicable PPE decontamination. Dry heat (DH) treatment is another potential low-cost decontamination method.Methods MB and light (MBL) and DH treatments were used to inactivate coronavirus on respirator and mask material. We tested three N95 filtering facepiece respirators (FFRs), two medical masks (MMs), and one cloth community mask (CM). FFR/MM/CM materials were inoculated with SARS-CoV-2 (a Betacoronavirus), murine hepatitis virus (MHV) (a Betacoronavirus), or porcine respiratory coronavirus (PRCV) (an Alphacoronavirus), and treated with 10 µM MB followed by 50,000 lux of broad-spectrum light or 12,500 lux of red light for 30 minutes, or with 75°C DH for 60 minutes. In parallel, we tested respirator and mask integrity using several standard methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method. Intact FFRs/MMs/CM were subjected to five cycles of decontamination (5CD) to assess integrity using International Standardization Organization (ISO), American Society for Testing and Materials (ASTM) International, National Institute for Occupational Safety and Health (NIOSH), and Occupational Safety and Health Administration (OSHA) test methods.Findings Overall, MBL robustly and consistently inactivated all three coronaviruses with at least a 4-log reduction. DH yielded similar results, with the exception of MHV, which was only reduced by 2-log after treatment. FFR/MM integrity was maintained for 5 cycles of MBL or DH treatment, whereas one FFR failed after 5 cycles of VHP+O3. Baseline performance for the CM was variable, but reduction of integrity was minimal.Interpretation Methylene blue with light and DH treatment decontaminated masks and respirators by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination of masks is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings. These attractive features support the utilization and continued development of this novel PPE decontamination method.Competing Interest StatementAuthors Thomas S. Lendvay, James Chen are Co-Founders and equity owners of Singletto, Inc. (Seattle, WA, USA) Authors Yi Cui and Steven Chu are Co-Founders and equity owners of 4C Air, Inc. (Sunnyvale, CA)Funding StatementThis study was funded by Open Philanthropy; Amazon Inc./University of Washington Catalyst Award; University of Liege (Belgium) and the Walloon Region, Belgium; Li Ka Shing Institute; Alberta Health Services; and an Anonymous donor to the University of Washington, Department of Urology.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Stanford University and Alberta Health Services/University of Calgary were exempt from IRB as the human fit testing was considered Quality Improvement. ERB for clinical specimen use: A clinical saliva specimen with a SARS-CoV-2 was provided by Dr. John Conly from Calgary, Alberta with Calgary ERB approval (ID# Pro00099761).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective inte ventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData will be freely shared post publication on reasonable request by contacting the corresponding author of the study. |
Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data
Stepniewska K , Allen EN , Humphreys GS , Poirot E , Craig E , Kennon K , Yilma D , Bousema T , Guerin PJ , White NJ , Price RN , Raman J , Martensson A , Mwaiswelo RO , Bancone G , Bastiaens GJH , Bjorkman A , Brown JM , D'Alessandro U , Dicko AA , El-Sayed B , Elzaki SE , Eziefula AC , Gonçalves BP , Hamid MMA , Kaneko A , Kariuki S , Khan W , Kwambai TK , Ley B , Ngasala BE , Nosten F , Okebe J , Samuels AM , Smit MR , Stone WJR , Sutanto I , Ter Kuile F , Tine RC , Tiono AB , Drakeley CJ , Gosling R , Stergachis A , Barnes KI , Chen I . BMC Med 2022 20 (1) 350 BACKGROUND: In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns. METHODS: A systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models. RESULTS: Data comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms. CONCLUSIONS: Our results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients. TRIAL REGISTRATION: PROSPERO, CRD42019128185. |
Addressing personal protective equipment (PPE) decontamination: Methylene blue and light inactivates severe acute respiratory coronavirus virus 2 (SARS-CoV-2) on N95 respirators and medical masks with maintenance of integrity and fit.
Lendvay TS , Chen J , Harcourt BH , Scholte FE , Lin YL , Kilinc-Balci FS , Lamb MM , Homdayjanakul K , Cui Y , Price A , Heyne B , Sahni J , Kabra KB , Lin YC , Evans D , Mores CN , Page K , Chu LF , Haubruge E , Thiry E , Ludwig-Begall LF , Wielick C , Clark T , Wagner T , Timm E , Gallagher T , Faris P , Macia N , Mackie CJ , Simmons SM , Reader S , Malott R , Hope K , Davies JM , Tritsch SR , Dams L , Nauwynck H , Willaert JF , De Jaeger S , Liao L , Zhao M , Laperre J , Jolois O , Smit SJ , Patel AN , Mayo M , Parker R , Molloy-Simard V , Lemyre JL , Chu S , Conly JM , Chu MC . Infect Control Hosp Epidemiol 2021 43 (7) 1-83 OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE) underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed masks and respirators. We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus. DESIGN: The two arms of the study included: 1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment, and 2) PPE treatment with MBL for 5 cycles of decontamination (5CD) to determine maintenance of PPE performance. METHODS: MBL treatment was used to inactivate coronaviruses on three N95 filtering facepiece respirator (FFR) and two medical mask (MM) models. We inoculated FFR and MM materials with three coronaviruses, including SARS-CoV-2, and treated with 10 µM MB and exposed to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5CD using multiple US and international test methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method. RESULTS: Overall, MBL robustly and consistently inactivated all three coronaviruses with 99.8 - to >99.9% virus inactivation across all FFRs and MMs tested. FFR and MM integrity was maintained after 5 cycles of MBL treatment, whereas one FFR model failed after 5 cycles of VHP+O3. CONCLUSIONS: MBL treatment decontaminated respirators and masks by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings. |
Efficacy of single dose primaquine with artemisinin combination therapy on P. falciparum gametocytes and transmission: A WWARN individual patient meta-analysis
Stepniewska K , Humphreys GS , Gonçalves BP , Craig E , Gosling R , Guerin PJ , Price RN , Barnes KI , Raman J , Smit MR , D'Alessandro U , Stone WJR , Bjorkman A , Samuels AM , Arroyo-Arroyo MI , Bastiaens GJH , Brown JM , Dicko A , El-Sayed BB , Elzaki SG , Eziefula AC , Kariuki S , Kwambai TK , Maestre AE , Martensson A , Mosha D , Mwaiswelo RO , Ngasala BE , Okebe J , Roh ME , Sawa P , Tiono AB , Chen I , Drakeley CJ , Bousema T . J Infect Dis 2020 225 (7) 1215-1226 BACKGROUND: Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy. METHODS: An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected. RESULTS: In 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08-0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. CONCLUSION: Primaquine's transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP. |
Causes of fever in primary care in Southeast Asia and the performance of C-reactive protein in discriminating bacterial from viral pathogens
Althaus T , Thaipadungpanit J , Greer RC , Swe MMM , Dittrich S , Peerawaranun P , Smit PW , Wangrangsimakul T , Blacksell S , Winchell JM , Diaz MH , Day NPJ , Smithuis F , Turner P , Lubell Y . Int J Infect Dis 2020 96 334-342 OBJECTIVES: We investigated causes of fever in the primary levels of care in Southeast Asia, and evaluated whether C-reactive protein (CRP) could distinguish bacterial from viral pathogens. METHODS: Blood and nasopharyngeal swab specimens were taken from children and adults with fever (>37.5 C) or history of fever (<14 days) in Thailand and Myanmar. RESULTS: Of 773 patients with at least one blood or nasopharyngeal swab specimen collected, 227 (29.4%) had a target organism detected. Influenza virus type A was detected in 85/227 cases (37.5%), followed by dengue virus (30 cases, 13.2%), respiratory syncytial virus (24 cases, 10.6%) and Leptospira spp. (9 cases, 4.0%). Clinical outcome was similar between patients with a bacterial or a viral organism, regardless of antibiotic prescription. CRP was higher among patients with a bacterial organism compared to those with a viral organism (median 18mg/L, interquartile range [10-49] versus 10mg/L [</=8-22], p-value 0.003), with an area under the curve of 0.65, 95% confidence interval (0.55-0.75). CONCLUSIONS: Serious bacterial infections requiring antibiotics are exceptions rather than the rule in the first lines of care. CRP-testing could assist in ruling out such cases in settings where diagnostic uncertainty is high and routine antibiotic prescription is common. The original CRP randomised-controlled trial (RCT) was registered with ClinicalTrials.gov, number NCT02758821. |
A ten-year retrospective evaluation of acute flaccid myelitis at 5 pediatric centers in the United States, 2005-2014
Cortese MM , Kambhampati AK , Schuster JE , Alhinai Z , Nelson GR , Guzman Perez-Carrillo GJ , Vossough A , Smit MA , McKinstry RC , Zinkus T , Moore KR , Rogg JM , Candee MS , Sejvar JJ , Hopkins SE . PLoS One 2020 15 (2) e0228671 BACKGROUND: Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics. METHODS: We conducted a retrospective study covering 2005-2014 at 5 pediatric centers in 3 U.S. regions. Possible AFM cases aged </=18 years were identified by searching discharge ICD-9 codes and spinal cord MRI reports (>37,000). Neuroradiologists assessed MR images, and medical charts were reviewed; possible cases were classified as AFM, not AFM, or indeterminate. RESULTS: At 5 sites combined, 26 AFM cases were identified from 2005-2013 (average annual number, 3 [2.4 cases/100,000 pediatric hospitalizations]) and 18 from 2014 (12.6 cases/100,000 hospitalizations; Poisson exact p<0.0001). A cluster of 13 cases was identified in September-October 2014 (temporal scan p = 0.0001). No other temporal or seasonal trend was observed. Compared with cases from January 2005-July 2014 (n = 29), cases from August-December 2014 (n = 15) were younger (p = 0.002), more frequently had a preceding respiratory/febrile illness (p = 0.03), had only upper extremities involved (p = 0.008), and had upper extremity monoplegia (p = 0.03). The cases had higher WBC counts in cerebrospinal fluid (p = 0.013). CONCLUSION: Our data support emergence of AFM in 2014 in the United States, and those cases demonstrated distinctive features compared with preceding sporadic cases. |
Human direct skin feeding versus membrane feeding to assess the mosquitocidal efficacy of high-dose ivermectin (IVERMAL Trial)
Smit MR , Ochomo EO , Aljayyoussi G , Kwambai TK , Abong'o BO , Bousema T , Waterhouse D , Bayoh NM , Gimnig JE , Samuels AM , Desai MR , Phillips-Howard PA , Kariuki SK , Wang D , Ward SA , Ter Kuile FO . Clin Infect Dis 2018 69 (7) 1112-1119 Background: Ivermectin is being considered for mass-drug-administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals. In a recent trial, 3-day courses of 300 and 600 mcg/kg/day were shown to kill Anopheles mosquitoes for at least 28 days post-treatment when fed patients' venous blood using membrane-feeding-assays. Direct-skin-feeding on humans may lead to higher mosquito-mortality as ivermectin capillary-concentrations are higher. We compared mosquito-mortality following direct-skin- and membrane-feeding. Methods: We conducted a mosquito feeding study nested within a randomized, double-blind, placebo-controlled trial of 141 adults with uncomplicated malaria in Kenya comparing 3-day ivermectin 0 (n=46), 300 (n=48), or 600 mcg/kg/day (n=47), co-administered with dihydroartemisinin-piperaquine. On post-treatment day-7, direct-skin and membrane-feeding assays were conducted using laboratory-reared Anopheles gambiae s.s.. Mosquito survival was assessed daily for 28-days-post-feeding. Results: Between July-20-2015 and May-7-2016, 69 of 141 patients participated in both direct-skin- and membrane-feeding (placebo n=23, 300mcg/kg/day n=24, 600mcg/kg/day n=22). The 14-day-post-feeding mortality for mosquitoes fed on blood 7-days post-treatment from patients in both ivermectin arms pooled was similar with direct-skin-feeding (n=2,941 mosquitoes) versus membrane-feeding (n=7,380 mosquitoes): cumulative-mortality (RR=0.99, 0.95-1.03, p=0.69) and survival-time (HR=0.96, 0.91-1.02, p=0.19). Results were consistent by sex, body-mass-index, and across the range of ivermectin capillary concentrations studied (0.72-73.9 ng/mL). Conclusions: Direct-skin-feeding and membrane-feeding on day 7 resulted in similar mosquitocidal-effects of ivermectin across a wide range of drug-concentrations, suggesting that the mosquitocidal-effects seen with membrane-feeding accurately reflect those of natural-biting. Membrane-feeding, which is more patient-friendly and ethically acceptable, can likely reliably be used to assess ivermectin's mosquitocidal-efficacy. |
Pharmacokinetics-pharmacodynamics of high-dose ivermectin with dihydroartemisinin-piperaquine on mosquitocidal activity and QT-prolongation (IVERMAL)
Smit MR , Ochomo EO , Waterhouse D , Kwambai TK , Abong'o BO , Bousema T , Bayoh NM , Gimnig JE , Samuels AM , Desai MR , Phillips-Howard PA , Kariuki SK , Wang D , Ter Kuile FO , Ward SA , Aljayyoussi G . Clin Pharmacol Ther 2018 105 (2) 388-401 High-dose ivermectin, co-administered for 3-days with dihydroartemisinin-piperaquine (DP), killed mosquitoes feeding on individuals for at least 28-days post-treatment in a recent trial (IVERMAL), while 7-days was predicted pre-trial. The current study assessed the relationship between ivermectin blood concentrations and the observed mosquitocidal effects against Anopheles gambiae. 3-days ivermectin 0, 300, or 600 mcg/kg/day plus DP was randomly assigned to 141 adults with uncomplicated malaria in Kenya. During 28-days follow-up, 1,393 venous and 335 paired capillary plasma samples, 850 mosquito-cluster mortality rates, and 524 QTcF-intervals were collected. Using pharmacokinetic-pharmacodynamic (PK-PD) modeling, we show a consistent correlation between predicted ivermectin concentrations and observed mosquitocidal-effects throughout the 28-day study duration, without invoking an unidentified mosquitocidal metabolite or drug-drug-interaction. Ivermectin had no effect on piperaquine's pharmacokinetics or QTcF-prolongation. The PK-PD model can be used to design new treatment regimens with predicted mosquitocidal effect. This methodology could be used to evaluate effectiveness of other endectocides. This article is protected by copyright. All rights reserved. |
Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine in Kenyan adults with uncomplicated malaria (IVERMAL): a randomised, double-blind, placebo-controlled trial
Smit MR , Ochomo EO , Aljayyoussi G , Kwambai TK , Abong'o BO , Chen T , Bousema T , Slater HC , Waterhouse D , Bayoh NM , Gimnig JE , Samuels AM , Desai MR , Phillips-Howard PA , Kariuki SK , Wang D , Ward SA , Ter Kuile FO . Lancet Infect Dis 2018 18 (6) 615-626 BACKGROUND: Ivermectin is being considered for mass drug administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals. However, standard, single doses of 150-200 mug/kg used for onchocerciasis and lymphatic filariasis have a short-lived mosquitocidal effect (<7 days). Because ivermectin is well tolerated up to 2000 mug/kg, we aimed to establish the safety, tolerability, and mosquitocidal efficacy of 3 day courses of high-dose ivermectin, co-administered with a standard malaria treatment. METHODS: We did a randomised, double-blind, placebo-controlled, superiority trial at the Jaramogi Oginga Odinga Teaching and Referral Hospital (Kisumu, Kenya). Adults (aged 18-50 years) were eligible if they had confirmed symptomatic uncomplicated Plasmodium falciparum malaria and agreed to the follow-up schedule. Participants were randomly assigned (1:1:1) using sealed envelopes, stratified by sex and body-mass index (men: <21 vs >/=21 kg/m(2); women: <23 vs >/=23 kg/m(2)), with permuted blocks of three, to receive 3 days of ivermectin 300 mug/kg per day, ivermectin 600 mug/kg per day, or placebo, all co-administered with 3 days of dihydroartemisinin-piperaquine. Blood of patients taken on post-treatment days 0, 2 + 4 h, 7, 10, 14, 21, and 28 was fed to laboratory-reared Anopheles gambiae sensu stricto mosquitoes, and mosquito survival was assessed daily for 28 days after feeding. The primary outcome was 14-day cumulative mortality of mosquitoes fed 7 days after ivermectin treatment (from participants who received at least one dose of study medication). The study is registered with ClinicalTrials.gov, number NCT02511353. FINDINGS: Between July 20, 2015, and May 7, 2016, 741 adults with malaria were assessed for eligibility, of whom 141 were randomly assigned to receive ivermectin 600 mug/kg per day (n=47), ivermectin 300 mug/kg per day (n=48), or placebo (n=46). 128 patients (91%) attended the primary outcome visit 7 days post treatment. Compared with placebo, ivermectin was associated with higher 14 day post-feeding mosquito mortality when fed on blood taken 7 days post treatment (ivermectin 600 mug/kg per day risk ratio [RR] 2.26, 95% CI 1.93-2.65, p<0.0001; hazard ratio [HR] 6.32, 4.61-8.67, p<0.0001; ivermectin 300 mug/kg per day RR 2.18, 1.86-2.57, p<0.0001; HR 4.21, 3.06-5.79, p<0.0001). Mosquito mortality remained significantly increased 28 days post treatment (ivermectin 600 mug/kg per day RR 1.23, 1.01-1.50, p=0.0374; and ivermectin 300 mug/kg per day 1.21, 1.01-1.44, p=0.0337). Five (11%) of 45 patients receiving ivermectin 600 mug/kg per day, two (4%) of 48 patients receiving ivermectin 300 mug/kg per day, and none of 46 patients receiving placebo had one or more treatment-related adverse events. INTERPRETATION: Ivermectin at both doses assessed was well tolerated and reduced mosquito survival for at least 28 days after treatment. Ivermectin 300 mug/kg per day for 3 days provided a good balance between efficacy and tolerability, and this drug shows promise as a potential new tool for malaria elimination. FUNDING: Malaria Eradication Scientific Alliance (MESA) and US Centers for Disease Control and Prevention (CDC). |
Evaluating the electronic tuberculosis register surveillance system in Eden District, Western Cape, South Africa, 2015
Mlotshwa M , Smit S , Williams S , Reddy C , Medina-Marino A . Glob Health Action 2017 10 (1) 1360560 BACKGROUND: Tuberculosis (TB) surveillance data are crucial to the effectiveness of National TB Control Programs. In South Africa, few surveillance system evaluations have been undertaken to provide a rigorous assessment of the platform from which the national and district health systems draws data to inform programs and policies. OBJECTIVE: Evaluate the attributes of Eden District's TB surveillance system, Western Cape Province, South Africa. METHODS: Data quality, sensitivity and positive predictive value were assessed using secondary data from 40,033 TB cases entered in Eden District's ETR.Net from 2007 to 2013, and 79 purposively selected TB Blue Cards (TBCs), a medical patient file and source document for data entered into ETR.Net. Simplicity, flexibility, acceptability, stability and usefulness of the ETR.Net were assessed qualitatively through interviews with TB nurses, information health officers, sub-district and district coordinators involved in the TB surveillance. RESULTS: TB surveillance system stakeholders report that Eden District's ETR.Net system was simple, acceptable, flexible and stable, and achieves its objective of informing TB control program, policies and activities. Data were less complete in the ETR.Net (66-100%) than in the TBCs (76-100%), and concordant for most variables except pre-treatment smear results, antiretroviral therapy (ART) and treatment outcome. The sensitivity of recorded variables in ETR.Net was 98% for gender, 97% for patient category, 93% for ART, 92% for treatment outcome and 90% for pre-treatment smear grading. CONCLUSIONS: Our results reveal that the system provides useful information to guide TB control program activities in Eden District. However, urgent attention is needed to address gaps in clinical recording on the TBC and data capturing into the ETR.Net system. We recommend continuous training and support of TB personnel involved with TB care, management and surveillance on TB data recording into the TBCs and ETR.Net as well as the implementation of a well-structured quality control and assurance system. |
Efficacy and Safety of High-Dose Ivermectin for Reducing Malaria Transmission (IVERMAL): Protocol for a Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Trial in Western Kenya.
Smit MR , Ochomo E , Aljayyoussi G , Kwambai T , Abong'o B , Bayoh N , Gimnig J , Samuels A , Desai M , Phillips-Howard PA , Kariuki S , Wang D , Ward S , Ter Kuile FO . JMIR Res Protoc 2016 5 (4) e213 BACKGROUND: Innovative approaches are needed to complement existing tools for malaria elimination. Ivermectin is a broad spectrum antiparasitic endectocide clinically used for onchocerciasis and lymphatic filariasis control at single doses of 150 to 200 mcg/kg. It also shortens the lifespan of mosquitoes that feed on individuals recently treated with ivermectin. However, the effect after a 150 to 200 mcg/kg oral dose is short-lived (6 to 11 days). Modeling suggests higher doses, which prolong the mosquitocidal effects, are needed to make a significant contribution to malaria elimination. Ivermectin has a wide therapeutic index and previous studies have shown doses up to 2000 mcg/kg (ie, 10 times the US Food and Drug Administration approved dose) are well tolerated and safe; the highest dose used for onchocerciasis is a single dose of 800 mcg/kg. OBJECTIVE: The aim of this study is to determine the safety, tolerability, and efficacy of ivermectin doses of 0, 300, and 600 mcg/kg/day for 3 days, when provided with a standard 3-day course of the antimalarial dihydroartemisinin-piperaquine (DP), on mosquito survival. METHODS: This is a double-blind, randomized, placebo-controlled, parallel-group, 3-arm, dose-finding trial in adults with uncomplicated malaria. Monte Carlo simulations based on pharmacokinetic modeling were performed to determine the optimum dosing regimens to be tested. Modeling showed that a 3-day regimen of 600 mcg/kg/day achieved similar median (5 to 95 percentiles) maximum drug concentrations (Cmax) of ivermectin to a single of dose of 800 mcg/kg, while increasing the median time above the lethal concentration 50% (LC50, 16 ng/mL) from 1.9 days (1.0 to 5.7) to 6.8 (3.8 to 13.4) days. The 300 mcg/kg/day dose was chosen at 50% of the higher dose to allow evaluation of the dose response. Mosquito survival will be assessed daily up to 28 days in laboratory-reared Anopheles gambiae s.s. populations fed on patients' blood taken at days 0, 2 (Cmax), 7 (primary outcome), 10, 14, 21, and 28 after the start of treatment. Safety outcomes include QT-prolongation and mydriasis. The trial will be conducted in 6 health facilities in western Kenya and requires a sample size of 141 participants (47 per arm). Sub-studies include (1) rich pharmacokinetics and (2) direct skin versus membrane feeding assays. RESULTS: Recruitment started July 20, 2015. Data collection was completed July 2, 2016. Unblinding and analysis will commence once the database has been completed, cleaned, and locked. CONCLUSIONS: High-dose ivermectin, if found to be safe and well tolerated, might offer a promising new tool for malaria elimination. |
A comparison of facemask and respirator filtration test methods
Rengasamy S , Shaffer R , Williams B , Smit S . J Occup Environ Hyg 2016 14 (2) 0 NIOSH published a Federal Register Notice to explore the possibility of incorporating FDA required filtration tests for surgical masks (SMs) in the 42 CFR Part 84 respirator certification process. There have been no published studies comparing the filtration efficiency test methods used for NIOSH certification of N95 filtering facepiece respirators (N95 FFRs) with those used by the FDA for clearance of SMs. To address this issue, filtration efficiencies of "N95 FFRs" including six N95 FFR models and three surgical N95 FFR models, and three SM models were measured using the NIOSH NaCl aerosol test method, and FDA required particulate filtration efficiency (PFE) and bacterial filtration efficiency (BFE) methods, and viral filtration efficiency (VFE) method. Five samples of each model were tested using each method. Both PFE and BFE tests were done using unneutralized particles as per FDA guidance document. PFE was measured using 0.1 microm size polystyrene latex particles and BFE with approximately 3.0 microm size particles containing Staphylococcus aureus bacteria. VFE was obtained using approximately 3.0 microm size particles containing phiX 174 as the challenge virus and Escherichia coli as the host. Results showed that the efficiencies measured by the NIOSH NaCl method for "N95 FFRs" were from 98.15 to 99.68% compared to 99.74 to 99.99% for PFE, 99.62 to 99.9% for BFE and 99.8 to 99.9% for VFE methods. Efficiencies by the NIOSH NaCl method were significantly (p = <0.05) lower than the other methods. SMs showed lower efficiencies (54.72 to 88.40%) than "N95 FFRs" measured by the NIOSH NaCl method, while PFE, BFE and VFE methods produced no significant difference. The above results show that the NIOSH NaCl method is relatively conservative and is able to identify poorly performing filtration devices. The higher efficiencies obtained using PFE, BFE and VFE methods show that adding these supplemental particle penetration methods will not improve respirator certification. |
Measles outbreak reveals measles susceptibility among adults in Namibia, 2009 - 2011
Ogbuanu IU , Muroua C , Allies M , Chitala K , Gerber S , Shilunga P , Mhata P , Kriss JL , Caparos L , Smit SB , De Wee RJ , Goodson JL . S Afr Med J 2016 106 (7) 715-720 BACKGROUND: The World Health Organization, African Region, set the goal of achieving measles elimination by 2020. Namibia was one of seven African countries to implement an accelerated measles control strategy beginning in 1996. Following implementation of this strategy, measles incidence decreased; however, between 2009 and 2011 a major outbreak occurred in Namibia. METHODS: Measles vaccination coverage data were analysed and a descriptive epidemiological analysis of the measles outbreak was conducted using measles case-based surveillance and laboratory data. RESULTS: During 1989 - 2008, MCV1 (the first routine dose of measles vaccine) coverage increased from 56% to 73% and five supplementary immunisation activities were implemented. During the outbreak (August 2009 - February 2011), 4 605 suspected measles cases were reported; of these, 3 256 were confirmed by laboratory testing or epidemiological linkage. Opuwo, a largely rural district in north-western Namibia with nomadic populations, had the highest confirmed measles incidence (16 427 cases per million). Infants aged ≤11 months had the highest cumulative age-specific incidence (9 252 cases per million) and comprised 22% of all confirmed cases; however, cases occurred across a wide age range, including adults aged ≥30 years. Among confirmed cases, 85% were unvaccinated or had unknown vaccination history. The predominantly detected measles virus genotype was B3, circulating in concurrent outbreaks in southern Africa, and B2, previously detected in Angola. CONCLUSION: A large-scale measles outbreak with sustained transmission over 18 months occurred in Namibia, probably caused by importation. The wide age distribution of cases indicated measles-susceptible individuals accumulated over several decades prior to the start of the outbreak. |
Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study
null , Carlo DD , Bester PA , Reyes-Teran G , Romero K , Avila-Rios S , Gregson J , Tang M , Rhee SY , Shafer RW , Ndembi N , Hamers RL , de Wit TFR , Marconi VC , Diero L , Brooks K , Theys K , Camacho R , Kantor R , Arruda M , Garcia F , Monge S , Gunthard HF , Hoffmann CJ , Kanki PJ , Kumarasamy N , Kerschberger B , Mor O , Charpentier C , Todesco E , Rokx C , Gras L , Halvas EK , Sunpath H , Di Carlo D , Santoro MM , Antinori A , Andreoni M , Latini A , Mussini C , Aghokeng A , Sonnerborg A , Neogi U , Fessel WJ , Agolory S , Raizes E , Yang C , Blanco JL , Juma JM , Smit E , Schmidt D , Watera C , Asio J , Kirungi W , Tostevin A , Dunn D , El-Hay T , Clumeck N , Goedhals D , van Vuuren C , Sabin C , Mukui I , Perno CF , Hunt G , Morris L , de Oliveira T , Pillay D , Gupta RK , Schulter E , Murakami-Ogasawara A , Sirivichayakul S , Ruxrungtham K , Mekprasan S , Kaleebu P . Lancet Infect Dis 2016 16 (5) 565-575 BACKGROUND: Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. METHODS: The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. FINDINGS: We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1.50, 95% CI 1.27-1.77 for CD4 cell count <100 cells per muL). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1.48, 95% CI 1.20-1.82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0.626]). INTERPRETATION: We recorded drug resistance in a high proportion of patients after virological failure on a tenofovir-containing first-line regimen across low-income and middle-income regions. Effective surveillance for transmission of drug resistance is crucial. FUNDING: The Wellcome Trust. |
Antecedent causes of a measles resurgence in the Democratic Republic of the Congo
Scobie HM , Ilunga BK , Mulumba A , Shidi C , Coulibaly T , Obama R , Tamfum JJM , Simbu EP , Smit SB , Masresha B , Perry RT , Alleman MM , Kretsinger K , Goodson J . Pan Afr Med J 2015 21 (30) 30 INTRODUCTION: Despite accelerated measles control efforts, a massive measles resurgence occurred in the Democratic Republic of the Congo (DRC) starting in mid-2010, prompting an investigation into likely causes. METHODS: We conducted a descriptive epidemiological analysis using measles immunization and surveillance data to understand the causes of the measles resurgence and to develop recommendations for elimination efforts in DRC. RESULTS: During 2004-2012, performance indicator targets for case-based surveillance and routine measles vaccination were not met. Estimated coverage with the routine first dose of measles-containing vaccine (MCV1) increased from 57% to 73%. Phased supplementary immunization activities (SIAs) were conducted starting in 2002, in some cases with sub-optimal coverage (≤95%). In 2010, SIAs in five of 11 provinces were not implemented as planned, resulting in a prolonged interval between SIAs, and a missed birth cohort in one province. During July 1, 2010-December 30, 2012, high measles attack rates (>100 cases per 100,000 population) occurred in provinces that had estimated MCV1 coverage lower than the national estimate and did not implement planned 2010 SIAs. The majority of confirmed case-patients were aged <10 years (87%) and unvaccinated or with unknown vaccination status (75%). Surveillance detected two genotype B3 and one genotype B2 measles virus strains that were previously identified in the region. CONCLUSION: The resurgence was likely caused by an accumulation of unvaccinated, measles-susceptible children due to low MCV1 coverage and suboptimal SIA implementation. To achieve the regional goal of measles elimination by 2020, efforts are needed in DRC to improve case-based surveillance and increase two-dose measles vaccination coverage through routine services and SIAs. |
Namibia's transition from whole blood-derived pooled platelets to single-donor apheresis platelet collections
Pitman JP , Basavaraju SV , Shiraishi RW , Wilkinson R , von Finckenstein B , Lowrance DW , Marfin AA , Postma M , Mataranyika M , Smit Sibinga CT . Transfusion 2015 55 (7) 1685-92 BACKGROUND: Few African countries separate blood donations into components; however, demand for platelets (PLTs) is increasing as regional capacity to treat causes of thrombocytopenia, including chemotherapy, increases. Namibia introduced single-donor apheresis PLT collections in 2007 to increase PLT availability while reducing exposure to multiple donors via pooling. This study describes the impact this transition had on PLT availability and safety in Namibia. STUDY DESIGN AND METHODS: Annual national blood collections and PLT units issued data were extracted from a database maintained by the Blood Transfusion Service of Namibia (NAMBTS). Production costs and unit prices were analyzed. RESULTS: In 2006, NAMBTS issued 771 single and pooled PLT doses from 3054 whole blood (WB) donations (drawn from 18,422 WB donations). In 2007, NAMBTS issued 486 single and pooled PLT doses from 1477 WB donations (drawn from 18,309 WB donations) and 131 single-donor PLT doses. By 2011, NAMBTS issued 837 single-donor PLT doses per year, 99.1% of all PLT units. Of 5761 WB donations from which PLTs were made in 2006 to 2011, a total of 20 (0.35%) were from donors with confirmed test results for human immunodeficiency virus or other transfusion-transmissible infections (TTIs). Of 2315 single-donor apheresis donations between 2007 and 2011, none of the 663 donors had a confirmed positive result for any pathogen. As apheresis replaced WB-derived PLTs, apheresis production costs dropped by a mean of 8.2% per year, while pooled PLT costs increased by an annual mean of 21.5%. Unit prices paid for apheresis- and WB-derived PLTs increased by 9 and 7.4% per year on average, respectively. CONCLUSION: Namibia's PLT transition shows that collections from repeat apheresis donors can reduce TTI risk and production costs. |
Blood component use in a sub-Saharan African country: results of a 4-year evaluation of diagnoses associated with transfusion orders in Namibia
Pitman JP , Wilkinson R , Liu Y , von Finckenstein B , Smit Sibinga CT , Lowrance DW , Marfin AA , Postma MJ , Mataranyika M , Basavaraju SV . Transfus Med Rev 2014 29 (1) 45-51 National blood use patterns in sub-Saharan Africa are poorly described. Although malaria and maternal hemorrhage remain important drivers of blood demand across Africa, economic growth and changes in malaria, HIV/AIDS, and noncommunicable disease epidemiology may contribute to changes in blood demand. We evaluated indications for blood use in Namibia, a country in southern Africa, using a nationally representative sample and discuss implications for the region. Clinical and demographic data related to the issuance of blood component units in Namibia were reviewed for a 4-year period (August 1, 2007-July 31, 2011). Variables included blood component type, recipient age and sex, and diagnosis. Diagnoses reported by clinicians were reclassified into International Statistical Classification of Diseases, 10th Revision categories. Multiple imputation methods were used to complete a data set missing age, sex or diagnosis data. Descriptive analyses were conducted to describe indications for transfusions and use of red blood cells (RBCs), platelets, and plasma. A total of 39 313 records accounting for 91 207 blood component units were analyzed. The median age of Namibian transfusion recipients was 45 years (SD, +/-19). A total of 78 660 RBC units were issued in Namibia during the study period. Red blood cells transfused for "unspecified anemia" accounted for the single largest category of blood issued (24 798 units). Of the overall total, 38.9% were for diseases of the blood and blood-forming organs (D50-D89). Infectious disease (A00-B99), pregnancy (O00-O99), and gastrointestinal (K20-K93) accounted for 14.8%, 11.1%, and 6.1% of RBC units issued, respectively. Although a specific diagnosis of malaria accounted for only 2.7% of pediatric transfusions, an unknown number of additional transfusions for malaria may have been categorized by requesting physicians as unspecified anemia and counted under diseases of blood forming organs. During the study period, 9751 units of fresh-frozen plasma were issued. Nearly one-quarter of these units (23.1%) were issued for gastrointestinal (K20-K93) diagnoses. Malignant neoplasms (C00-C97) accounted for 38.1% of 2978 platelet units issued. Blood use in Namibia reflects changes in the health care system due to economic development, improvement in HIV/AIDS and malaria epidemiology, high rates of health care facility-based childbirth, and access to noncommunicable disease treatment. However, better documentation of the indications for transfusion is needed to confirm these observations. Changing patterns of health care will result in changing demands for blood components. Improved methods to evaluate blood use patterns in sub-Saharan Africa may help set realistic national blood collection goals. |
Measles resurgence in southern Africa: challenges to measles elimination
Shibeshi ME , Masresha BG , Smit SB , Biellik RJ , Nicholson JL , Muitherero C , Shivute N , Walker O , Reggis K , Goodson JL . Vaccine 2014 32 (16) 1798-807 INTRODUCTION: In seven southern African countries (Botswana, Lesotho, Malawi, Namibia, South Africa, Swaziland and Zimbabwe), following implementation of a measles mortality reduction strategy starting in 1996, the number of annually reported measles cases decreased sharply to less than one per million population during 2006-2008. However, during 2009-2010, large outbreaks occurred in these countries. In 2011, a goal for measles elimination by 2020 was set in the World Health Organization (WHO) African Region (AFR). We reviewed the implementation of the measles control strategy and measles epidemiology during the resurgence in the seven southern African countries. METHODS: Estimated coverage with routine measles vaccination, supplemental immunization activities (SIA), annually reported measles cases by country, and measles surveillance and laboratory data were analyzed using descriptive analysis. RESULTS: In the seven countries, coverage with the routine first dose of measles-containing vaccine (MCV1) decreased from 80% to 65% during 1996-2004, then increased to 84% in 2011; during 1996-2011, 79,696,523 people were reached with measles vaccination during 45 SIAs. Annually reported measles cases decreased from 61,160 cases to 60 cases and measles incidence decreased to <1 case per million during 1996-2008. During 2009-2010, large outbreaks that included cases among older children and adults were reported in all seven countries, starting in South Africa and Namibia in mid-2009 and in the other five countries by early 2010. The measles virus genotype detected was predominantly genotype B3. CONCLUSION: The measles resurgence highlighted challenges to achieving measles elimination in AFR by 2020. To achieve this goal, high two-dose measles vaccine coverage by strengthening routine immunization systems and conducting timely SIAs targeting expanded age groups, potentially including young adults, and maintaining outbreak preparedness to rapidly respond to outbreaks will be needed. |
Measles outbreak in South Africa: epidemiology of laboratory-confirmed measles cases and assessment of intervention, 2009-2011
Ntshoe GM , McAnerney JM , Archer BN , Smit SB , Harris BN , Tempia S , Mashele M , Singh B , Thomas J , Cengimbo A , Blumberg LH , Puren A , Moyes J , van den Heever J , Schoub BD , Cohen C . PLoS One 2013 8 (2) e55682 BACKGROUND: Since 1995, measles vaccination at nine and 18 months has been routine in South Africa; however, coverage seldom reached >95%. We describe the epidemiology of laboratory-confirmed measles case-patients and assess the impact of the nationwide mass vaccination campaign during the 2009 to 2011 measles outbreak in South Africa. METHODS: Serum specimens collected from patients with suspected-measles were tested for measles-specific IgM antibodies using an enzyme-linked immunosorbent assay and genotypes of a subset were determined. To estimate the impact of the nationwide mass vaccination campaign, we compared incidence in the seven months pre- (1 September 2009-11 April 2010) and seven months post-vaccination campaign (24 May 2010-31 December 2010) periods in seven provinces of South Africa. RESULTS: A total of 18,431 laboratory-confirmed measles case-patients were reported from all nine provinces of South Africa (cumulative incidence 37 per 100,000 population). The highest cumulative incidence per 100,000 population was in children aged <1 year (603), distributed as follows: <6 months (302/100,000), 6 to 8 months (1083/100,000) and 9 to 11 months (724/100,000). Forty eight percent of case-patients were ≥5 years (cumulative incidence 54/100,000). Cumulative incidence decreased with increasing age to 2/100,000 in persons ≥40 years. A single strain of measles virus (genotype B3) circulated throughout the outbreak. Prior to the vaccination campaign, cumulative incidence in the targeted vs. non-targeted age group was 5.9-fold higher, decreasing to 1.7 fold following the campaign (P<0.001) and an estimated 1,380 laboratory-confirmed measles case-patients were prevented. CONCLUSION: We observed a reduction in measles incidence following the nationwide mass vaccination campaign even though it was conducted approximately one year after the outbreak started. A booster dose at school entry may be of value given the high incidence in persons >5 years. |
Lessons learned during tuberculosis screening in public medical clinics in Francistown, Botswana
Bloss E , Makombe R , Kip E , Smit M , Chirenda J , Gammino VM , Creek T , Oeltmann JE . Int J Tuberc Lung Dis 2012 16 (8) 1030-2 In Botswana, where one quarter of the adult population is infected with the human immunodeficiency virus and the annual tuberculosis (TB) incidence is among the highest globally, intensified TB case finding is needed in health care facilities to detect and treat TB cases early and prevent transmission. During August-December 2009, TB screening was implemented among adults at patient intake in five clinics in Francistown. Among 11,779 TB screenings at intake, 926 were positive. Nineteen patients were diagnosed with TB. Routine TB screening at intake was operationally feasible, but had low yield. Innovative case-finding strategies are needed in Botswana. |
Status of global virologic surveillance for rubella viruses
Abernathy ES , Hubschen JM , Muller CP , Jin L , Brown D , Komase K , Mori Y , Xu W , Zhu Z , Siqueira MM , Shulga S , Tikhonova N , Pattamadilok S , Incomserb P , Smit SB , Akoua-Koffi C , Bwogi J , Lim WW , Woo GK , Triki H , Jee Y , Mulders MN , de Filippis AM , Ahmed H , Ramamurty N , Featherstone D , Icenogle JP . J Infect Dis 2011 204 Suppl 1 S524-32 The suspected measles case definition captures rubella cases. Therefore, measles surveillance will be improved in the course of the control and eventual elimination of rubella transmission. One aspect of rubella control, virologic surveillance, is reviewed here. A systematic nomenclature for rubella viruses (RVs) based on 13 genotypes has been established and is updated when warranted by increases in information about RVs. From 2005 through 2010, the genotypes of RVs most frequently reported were 1E, 1G, and 2B, and genotypes 1a, 1B, 1C, 1h, 1j, and 2C were less frequently reported. Virologic surveillance can support rubella control and elimination. Synopses of rubella virologic surveillance in various countries, regions, and globally are given, including characterization of viruses from imported cases in a country that has eliminated rubella and studies of endemic viruses circulating in countries without rubella control objectives. Current challenges are discussed. |
Global distribution of measles genotypes and measles molecular epidemiology
Rota PA , Brown K , Mankertz A , Santibanez S , Shulga S , Muller CP , Hubschen JM , Siqueira M , Beirnes J , Ahmed H , Triki H , Al-Busaidy S , Dosseh A , Byabamazima C , Smit S , Akoua-Koffi C , Bwogi J , Bukenya H , Wairagkar N , Ramamurty N , Incomserb P , Pattamadilok S , Jee Y , Lim W , Xu W , Komase K , Takeda M , Tran T , Castillo-Solorzano C , Chenoweth P , Brown D , Mulders MN , Bellini WJ , Featherstone D . J Infect Dis 2011 204 Suppl 1 S514-23 A critical component of laboratory surveillance for measles is the genetic characterization of circulating wild-type viruses. The World Health Organization (WHO) Measles and Rubella Laboratory Network (LabNet), provides for standardized testing in 183 countries and supports genetic characterization of currently circulating strains of measles viruses. The goal of this report is to describe the lessons learned from nearly 20 years of virologic surveillance for measles, to describe the global databases for measles sequences, and to provide regional updates about measles genotypes detected by recent surveillance activities. Virologic surveillance for measles is now well established in all of the WHO regions, and most countries have conducted at least some baseline surveillance. The WHO Global Genotype Database contains >7000 genotype reports, and the Measles Nucleotide Surveillance (MeaNS) contains >4000 entries. This sequence information has proven to be extremely useful for tracking global transmission patterns and for documenting the interruption of transmission in some countries. The future challenges will be to develop quality control programs for molecular methods and to continue to expand virologic surveillance activities in all regions. |
Hospitalization and mortality among primarily non-breastfed children during a large outbreak of diarrhea and malnutrition in Botswana, 2006
Creek TL , Kim A , Lu L , Bowen A , Masunge J , Arvelo W , Smit M , Mach O , Legwaila K , Motswere C , Zaks L , Finkbeiner T , Povinelli L , Maruping M , Ngwaru G , Tebele G , Bopp C , Puhr N , Johnston SP , Dasilva AJ , Bern C , Beard RS , Davis MK . J Acquir Immune Defic Syndr 2009 53 (1) 14-9 BACKGROUND: In 2006, a pediatric diarrhea outbreak occurred in Botswana, coinciding with heavy rains. Surveillance recorded a 3 times increase in cases and a 25 fold increase in deaths between January and March. Botswana has high HIV prevalence among pregnant women (33.4% in 2005), and an estimated 35% of all infants under the age of 6 months are not breastfed. METHODS: We followed all children <5 years old with diarrhea in the country's second largest referral hospital at the peak of the outbreak by chart review, interviewed mothers, and conducted laboratory testing for HIV and enteric pathogens. RESULTS: Of 153 hospitalized children with diarrhea, 97% were <2 years old; 88% of these were not breastfeeding. HIV was diagnosed in 18% of children and 64% of mothers. Cryptosporidium and enteropathogenic Escherichia coli were common; many children had multiple pathogens. Severe acute malnutrition (kwashiorkor or marasmus) developed in 38 (25%) patients, and 33 (22%) died. Kwashiorkor increased risk for death (relative risk 2.0; P = 0.05); only one breastfeeding child died. Many children who died had been undersupplied with formula. CONCLUSIONS: Most of the severe morbidity and mortality in this outbreak occurred in children who were HIV negative and not breastfed. Feeding and nutritional factors were the most important determinants of severe illness and death. Breastfeeding is critical to infant survival in the developing world, and support for breastfeeding among HIV-negative women, and HIV-positive women who cannot formula feed safely, may prevent further high-mortality outbreaks. |
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