• Quantifying the incidence of severe-febrile-illness hospital admissions in sub-Saharan Africa.

      Roddy, P; Dalrymple, U; Jensen, TO; Dittrich, S; Rao, VB; Pfeffer, DA; Twohig, KA; Roberts, T; Bernal, O; Guillen, E (Public Library of Science, 2019-07-25)
      Severe-febrile-illness (SFI) is a common cause of morbidity and mortality across sub-Saharan Africa (SSA). The burden of SFI in SSA is currently unknown and its estimation is fraught with challenges. This is due to a lack of diagnostic capacity for SFI in SSA, and thus a dearth of baseline data on the underlying etiology of SFI cases and scant SFI-specific causative-agent prevalence data. To highlight the public health significance of SFI in SSA, we developed a Bayesian model to quantify the incidence of SFI hospital admissions in SSA. Our estimates indicate a mean population-weighted SFI-inpatient-admission incidence rate of 18.4 (6.8-31.1, 68% CrI) per 1000 people for the year 2014, across all ages within areas of SSA with stable Plasmodium falciparum transmission. We further estimated a total of 16,200,337 (5,993,249-27,321,779, 68% CrI) SFI hospital admissions. This analysis reveals the significant burden of SFI in hospitals in SSA, but also highlights the paucity of pathogen-specific prevalence and incidence data for SFI in SSA. Future improvements in pathogen-specific diagnostics for causative agents of SFI will increase the abundance of SFI-specific prevalence and incidence data, aid future estimations of SFI burden, and enable clinicians to identify SFI-specific pathogens, administer appropriate treatment and management, and facilitate appropriate antibiotic use.
    • Rates and Causes of Death in Chiradzulu District, Malawi, 2008: A Key Informant Study

      Checchi, Francesco; Nyasulu, Peter; Chandramohan, Daniel; Roberts, Bayard; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK; Médecins Sans Frontières, Blantyre, Malawi; Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, UK (2010-12-03)
      In September 2008, we measured all-cause mortality in Chiradzulu District, Malawi (population 291 000) over a 60-day retrospective period, using capture-recapture analysis of three lists of deaths provided by (i) key community informants, (ii) graveyard officials and (iii) health system sources. Estimated crude and under-5-year mortality rates were 18.6 (95% CI 13.9-24.5) and 30.6 (95% CI 17.5-59.9) deaths per 1000 person-years. We also classified causes of death through verbal autopsy interviews on 50 deaths over the previous 40 days. Half of deaths were attributable to infection, and half of deaths among children aged under 5 were attributable to neonatal causes. HIV/AIDS was the leading cause of death (16.6%), with a cause-attributable mortality rate of 1.8 (0.4-3.6) deaths per 1000 person-years.
    • Real-time analysis of the diphtheria outbreak in forcibly displaced Myanmar nationals in Bangladesh

      Finger, F; Funk, S; White, K; Siddiqui, MR; Edmunds, WJ; Kucharski, AJ (2019-03-12)
      Between August and December 2017, more than 625,000 Rohingya from Myanmar fled into Bangladesh, settling in informal makeshift camps in Cox’s Bazar district and joining 212,000 Rohingya already present. In early November, a diphtheria outbreak hit the camps, with 440 reported cases during the first month. A rise in cases during early December led to a collaboration between teams from Médecins sans Frontières—who were running a provisional diphtheria treatment centre—and the London School of Hygiene and Tropical Medicine with the goal to use transmission dynamic models to forecast the potential scale of the outbreak and the resulting resource needs. Methods We first adjusted for delays between symptom onset and case presentation using the observed distribution of reporting delays from previously reported cases. We then fit a compartmental transmission model to the adjusted incidence stratified by age group and location. Model forecasts with a lead time of 2 weeks were issued on 12, 20, 26 and 30 December and communicated to decision-makers. Results The first forecast estimated that the outbreak would peak on 19 December in Balukhali camp with 303 (95% posterior predictive interval 122–599) cases and would continue to grow in Kutupalong camp, requiring a bed capacity of 316 (95% posterior predictive interval (PPI) 197–499). On 19 December, a total of 54 cases were reported, lower than forecasted. Subsequent forecasts were more accurate: on 20 December, we predicted a total of 912 cases (95% PPI 367–2183) and 136 (95% PPI 55–327) hospitalizations until the end of the year, with 616 cases actually reported during this period. Conclusions Real-time modelling enabled feedback of key information about the potential scale of the epidemic, resource needs and mechanisms of transmission to decision-makers at a time when this information was largely unknown. By 20 December, the model generated reliable forecasts and helped support decision-making on operational aspects of the outbreak response, such as hospital bed and staff needs, and with advocacy for control measures. Although modelling is only one component of the evidence base for decision-making in outbreak situations, suitable analysis and forecasting techniques can be used to gain insights into an ongoing outbreak.
    • Real-Time PCR for the Evaluation of Treatment Response in Clinical Trials of Adult Chronic Chagas Disease: Usefulness of Serial Blood Sampling and qPCR Replicates

      Parrado, R; Ramirez, JC; de la Barra, A; Alonso-Vega, C; Juiz, N; Ortiz, L; Illanes, D; Torrico, F; Gascon, J; Alves, F; et al. (American Society for Microbiology, 2018-12-03)
      This work evaluated a serial blood sampling procedure to enhance the sensitivity of duplex real-time PCR (qPCR) for baseline detection and quantification of parasitic loads and post-treatment identification of failure in the context of clinical trials for treatment of chronic Chagas disease, namely DNDi-CH-E1224-001 (NCT01489228) and MSF-DNDi PCR sampling optimization study (NCT01678599). Patients from Cochabamba (N= 294), Tarija (N= 257), and Aiquile (N= 220) were enrolled. Three serial blood samples were collected at each time-point and qPCR triplicates were tested per sample. The first two samples were collected during the same day and the third one seven days later.A patient was considered PCR positive if at least one qPCR replicate was detectable. Cumulative results of multiple samples and qPCR replicates enhanced the proportion of pre-treatment sample positivity from 54.8 to 76.2%, 59.5 to 77.8%, and 73.5 to 90.2% in Cochabamba, Tarija, and Aiquile cohorts, respectively. This strategy increased the detection of treatment failure from 72.9 to 91.7%, 77.8 to 88.9%, and 42.9 to 69.1% for E1224 low, short, and high dosage regimens, respectively; and from 4.6 to 15.9% and 9.5 to 32.1% for the benznidazole arm in the DNDi-CH-E1224-001 and MSF-DNDi studies, respectively. The addition of the third blood sample and third qPCR replicate in patients with non-detectable PCR results in the first two samples, gave a small, non-statistically significant improvement in qPCR positivity. No change in clinical sensitivity was seen with a blood volume increase from 5 to 10 ml. The monitoring of patients treated with placebo in the DNDi-CH-E1224-001 trial revealed fluctuations in parasitic loads and occasional non-detectable results. In conclusion, serial sampling strategy enhanced PCR sensitivity to detecting treatment failure during follow-up and has the potential for improving recruitment capacity in Chagas disease trials, which require an initial positive qPCR result for patient admission.
    • Recommendations for Dealing with Waste Contaminated with Ebola Virus: a Hazard Analysis of Critical Control Points Approach

      Edmunds, KL; Elrahman, SA; Bell, DJ; Brainard, J; Dervisevic, S; Fedha, TP; Few, R; Howard, G; Lake, I; Maes, P; et al. (World Health Organization, 2016-06-15)
      To assess, within communities experiencing Ebola virus outbreaks, the risks associated with the disposal of human waste and to generate recommendations for mitigating such risks.
    • Reducing harm caused by substance use in adolescents.

      Souza, R; de Leon, M (Elsevier, 2007-06-30)
    • Reply to Colebunders

      Rosenke, K; Adjemian, J; Munster, VJ; Strong, JE; Sprecher, A; Feldmann, H; de Wit, E (Oxford University Press, 2016-12-15)
    • Research Priorities to Achieve Universal Access to Hepatitis C Prevention, Management and Direct-Acting Antiviral Treatment Among People Who Inject Drugs

      Grebely, J; Bruneau, J; Lazarus, J; Dalgard, O; Bruggmann, P; Treloar, C; Hickman, M; Hellard, M; Roberts, T; Crooks, L; et al. (Elsevier, 2017-07-03)
      Globally, it is estimated that 71.1 million people have chronic hepatitis C virus (HCV) infection, including an estimated 7.5 million people who have recently injected drugs (PWID). There is an additional large, but unquantified, burden among those PWID who have ceased injecting. The incidence of HCV infection among current PWID also remains high in many settings. Morbidity and mortality due to liver disease among PWID with HCV infection continues to increase, despite the advent of well-tolerated, simple interferon-free direct-acting antiviral (DAA) HCV regimens with cure rates >95%. As a result of this important clinical breakthrough, there is potential to reverse the rising burden of advanced liver disease with increased treatment and strive for HCV elimination among PWID. Unfortunately, there are many gaps in knowledge that represent barriers to effective prevention and management of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network on Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the prevention and management of HCV among PWID. This round table consisted of a one-day workshop held on 6 September, 2016, in Oslo, Norway, prior to the International Symposium on Hepatitis in Substance Users (INHSU 2016). International experts in drug and alcohol, infectious diseases, and hepatology were brought together to discuss the available scientific evidence, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment. This paper highlights the outcomes of the roundtable discussion focused on future research priorities for enhancing HCV prevention, testing, linkage to care and DAA treatment for PWID as we strive for global elimination of HCV infection.
    • A Review of Antimicrobial Resistance in East Africa

      Ampaire, L; Muhindo, A; Orikiriza, P; Mwanga-Amumpaire, J; Bebell, L; Boum, Y II (African Society for Laboratory Medicine, 2016-09-15)
    • Reviewing evidence of the clinical effectiveness of commercially available antivenoms in sub-Saharan Africa identifies the need for a multi-centre, multi-antivenom clinical trial

      Potet, J; Smith, J; McIver, L (Public Library of Science, 2019-06-24)
      BACKGROUND: Snakebite envenoming kills more than more than 20,000 people in Sub-Saharan Africa every year. Poorly regulated markets have been inundated with low-price, low-quality antivenoms. This review aimed to systematically collect and analyse the clinical data on all antivenom products now available in markets of sub-Saharan Africa. METHODOLOGY/PRINCIPAL FINDINGS: Our market analysis identified 12 polyspecific and 4 monospecific antivenom products in African markets. Our search strategy was first based on a systematic search of publication databases, followed by manual searches and discussions with experts. All types of data, including programmatic data, were eligible. All types of publications were eligible, including grey literature. Cohorts of less than 10 patients were excluded. 26 publications met the inclusion criteria. Many publications had to be excluded because clinical outcomes were not clearly linked to a specific product. Our narrative summaries present product-specific clinical data in terms of safety and effectiveness against the different species and envenoming syndromes. Three products (EchiTabPlus, EchiTabG, SAIMR-Echis-monovalent) were found to have been tested in robust clinical studies and found effective against envenoming caused by the West African carpet viper (Echis ocellatus). Four products (Inoserp-Panafricain, Fav-Afrique, SAIMR-Polyvalent, Antivipmyn-Africa) were found to have been evaluated only in observational single-arm studies, with varying results. For nine other products, there are either no data in the public domain, or only negative data suggesting a lack of effectiveness. CONCLUSIONS/SIGNIFICANCE: Clinical data vary among the different antivenom products currently in African markets. Some products are available commercially although they have been found to lack effectiveness. The World Health Organization should strengthen its capacity to assess antivenom products, support antivenom manufacturers, and assist African countries and international aid organizations in selecting appropriate quality antivenoms.
    • Rift Valley fever outbreak--Kenya, November 2006-January 2007.

      Centers for Disease Control and Prevention (CDC) (2007-02-02)
      In mid-December 2006, several unexplained fatalities associated with fever and generalized bleeding were reported to the Kenya Ministry of Health (KMOH) from Garissa District in North Eastern Province (NEP). By December 20, a total of 11 deaths had been reported. Of serum samples collected from the first 19 patients, Rift Valley fever (RVF) virus RNA or immunoglobulin M (IgM) antibodies against RVF virus were found in samples from 10 patients; all serum specimens were negative for yellow fever, Ebola, Crimean-Congo hemorrhagic fever, and dengue viruses. The outbreak was confirmed by isolation of RVF virus from six of the specimens. Humans can be infected with RVF virus from bites of mosquitoes or other arthropod vectors that have fed on animals infected with RVF virus, or through contact with viremic animals, particularly livestock. Reports of livestock deaths and unexplained animal abortions in NEP provided further evidence of an RVF outbreak. On December 20, an investigation was launched by KMOH, the Kenya Field Epidemiology and Laboratory Training Program (FELTP), the Kenya Medical Research Institute (KEMRI), the Walter Reed Project of the U.S. Army Medical Research Unit, CDC-Kenya's Global Disease Detection Center, and other partners, including the World Health Organization (WHO) and Médecins Sans Frontières (MSF). This report describes the findings from that initial investigation and the control measures taken in response to the RVF outbreak, which spread to multiple additional provinces and districts, resulting in 404 cases with 118 deaths as of January 25, 2007.
    • Risk factors for buruli ulcer: a case control study in Cameroon

      Pouillot, Régis; Matias, Gonçalo; Wondje, Christelle Mbondji; Portaels, Françoise; Valin, Nadia; Ngos, François; Njikap, Adelaïde; Marsollier, Laurent; Fontanet, Arnaud; Eyangoh, Sara; et al. (2007-12-19)
      BACKGROUND: Buruli ulcer is an infectious disease involving the skin, caused by Mycobacterium ulcerans. This disease is associated with areas where the water is slow-flowing or stagnant. However, the exact mechanism of transmission of the bacillus and the development of the disease through human activities is unknown. METHODOLOGY/PRINCIPAL FINDINGS: A case-control study to identify Buruli ulcer risk factors in Cameroon compared case-patients with community-matched controls on one hand and family-matched controls on the other hand. Risk factors identified by the community-matched study (including 163 pairs) were: having a low level of education, swamp wading, wearing short, lower-body clothing while farming, living near a cocoa plantation or woods, using adhesive bandages when hurt, and using mosquito coils. Protective factors were: using bed nets, washing clothes, and using leaves as traditional treatment or rubbing alcohol when hurt. The family-matched study (including 118 pairs) corroborated the significance of education level, use of bed nets, and treatment with leaves. CONCLUSIONS/SIGNIFICANCE: Covering limbs during farming activities is confirmed as a protective factor guarding against Buruli ulcer disease, but newly identified factors including wound treatment and use of bed nets may provide new insight into the unknown mode of transmission of M. ulcerans or the development of the disease.
    • Risk factors for diagnosed noma in northwest Nigeria: A case-control study, 2017

      Farley, E; Lenglet, A; Ariti, C; Jiya, N M; Adetunji, A S; van der Kam, S; Bil, K (Public Library of Science, 2018-08-23)
      Noma (cancrum oris), a neglected tropical disease, rapidly disintegrates the hard and soft tissue of the face and leads to severe disfiguration and high mortality. The disease is poorly understood. We aimed to estimate risk factors for diagnosed noma to better guide existing prevention and treatment strategies using a case-control study design.
    • Risk factors for measles mortality and the importance of decentralized case management during an unusually large measles epidemic in eastern Democratic Republic of Congo in 2013

      Gignoux, E; Polonsky, J; Ciglenecki, I; Bichet, M; Coldiron, M; Thuambe Lwiyo, E; Akonda, I; Serafini, M; Porten, K (Public Library of Science, 2018-03-14)
      In 2013, a large measles epidemic occurred in the Aketi Health Zone of the Democratic Republic of Congo. We conducted a two-stage, retrospective cluster survey to estimate the attack rate, the case fatality rate, and the measles-specific mortality rate during the epidemic. 1424 households containing 7880 individuals were included. The estimated attack rate was 14.0%, (35.0% among children aged <5 years). The estimated case fatality rate was 4.2% (6.1% among children aged <5 years). Spatial analysis and linear regression showed that younger children, those who did not receive care, and those living farther away from Aketi Hospital early in the epidemic had a higher risk of measles related death. Vaccination coverage prior to the outbreak was low (76%), and a delayed reactive vaccination campaign contributed to the high attack rate. We provide evidences suggesting that a comprehensive case management approach reduced measles fatality during this epidemic in rural, inaccessible resource-poor setting.
    • Rotavirus Surveillance in Urban and Rural Areas of Niger, April 2010–March 2012

      Page, Anne-Laure; Jusot, Viviane; Mamaty, Abdoul-Aziz; Adamou, Lagare; Kaplon, Jérôme; Pothier, Pierre; Djibo, Ali; Manzo, Mahamane L.; Toure, Brahima; Langendorf, Céline; et al. (Centers for Disease Control and Prevention, 2014-03)
      Knowledge of rotavirus epidemiology is necessary to make informed decisions about vaccine introduction and to evaluate vaccine impact. During April 2010–March 2012, rotavirus surveillance was conducted among 9,745 children <5 years of age in 14 hospitals/health centers in Niger, where rotavirus vaccine has not been introduced. Study participants had acute watery diarrhea and moderate to severe dehydration, and 20% of the children were enrolled in a nutrition program. Of the 9,745 children, 30.6% were rotavirus positive. Genotyping of a subset of positive samples showed a variety of genotypes during the first year, although G2P[4] predominated. G12 genotypes, including G12P[8], which has emerged as a predominant strain in western Africa, represented >80% of isolates during the second year. Hospitalization and death rates and severe dehydration among rotavirus case-patients did not differ during the 2 years. The emergence of G12P[8] warrants close attention to the characteristics of associated epidemics and possible prevention measures.
    • Rural-urban gradient in seasonal forcing of measles transmission in Niger

      Ferrari, Matthew J; Djibo, Ali; Grais, Rebecca F; Bharti, Nita; Grenfell, Bryan T; Bjornstad, Ottar N; The Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, PA, USA; The Center for Infectious Disease Dynamics, Department of Entomology, The Pennsylvania State University, University Park, PA, USA; Ministry of Health, Niamey, Niger; Epicentre, Paris, France; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA; Fogerty Center for International Health, National Institutes of Health, Bethesda, MD, USA (2010-04-28)
      Seasonally driven cycles of incidence have been consistently observed for a range of directly transmitted pathogens. Though frequently observed, the mechanism of seasonality for directly transmitted human pathogens is rarely well understood. Despite significant annual variation in magnitude, measles outbreaks in Niger consistently begin in the dry season and decline at the onset of the seasonal rains. We estimate the seasonal fluctuation in measles transmission rates for the 38 districts and urban centres of Niger, from 11 years of weekly incidence reports. We show that transmission rates are consistently in anti-phase to the rainfall patterns across the country. The strength of the seasonal forcing of transmission is not correlated with the latitudinal rainfall gradient, as would be expected if transmission rates were determined purely by environmental conditions. Rather, seasonal forcing is correlated with the population size, with larger seasonal fluctuation in more populous, urban areas. This pattern is consistent with seasonal variation in human density and contact rates due to agricultural cycles. The stronger seasonality in large cities drives deep inter-epidemic troughs and results in frequent local extinction of measles, which contrasts starkly to the conventional observation that large cities, by virtue of their size, act as reservoirs of measles.
    • SARS and Carlo Urbani.

      Reilley, B; Van Herp, M; Sermand, D; Dentico, N; Médecins sans Frontières, USA. (Massachusetts Medical Society, 2003-05-15)
    • The Scenario Approach for Countries Considering the Addition of Oral Cholera Vaccination in Cholera Preparedness and Control Plans

      Deen, J; von Seidlein, L; Luquero, FJ; Troeger, C; Reyburn, R; Lopez, AL; Debes, A; Sack, DA (Elsevier, 2016-01-01)
      Oral cholera vaccination could be deployed in a diverse range of situations from cholera-endemic areas and locations of humanitarian crises, but no clear consensus exists. The supply of licensed, WHO-prequalified cholera vaccines is not sufficient to meet endemic and epidemic needs worldwide and so prioritisation is needed. We have developed a scenario approach to systematically classify situations in which oral cholera vaccination might be useful. Our scenario approach distinguishes between five types of cholera epidemiology based on experiences from around the world and provides evidence that we hope will spur the development of detailed guidelines on how and where oral cholera vaccines could, and should, be most rationally deployed.
    • Screening for Glucose-6-Phosphate Dehydrogenase Deficiency Using Three Detection Methods: A Cross-Sectional Survey in Southwestern Uganda

      Roh, ME; Oyet, C; Orikiriza, P; Wade, M; Mwanga-Amumpaire, J; Boum, Y; Kiwanuka, GN; Parikh, S (American Society of Tropical Medicine and Hygiene, 2016-09-26)
      Despite the potential benefit of primaquine in reducing Plasmodium falciparum transmission and radical cure of Plasmodium vivax and Plasmodium ovale infections, concerns over risk of hemolytic toxicity in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd) have hampered its deployment. A cross-sectional survey was conducted in 2014 to assess the G6PDd prevalence among 631 children between 6 and 59 months of age in southwestern Uganda, an area where primaquine may be a promising control measure. G6PDd prevalence was determined using three detection methods: a quantitative G6PD enzyme activity assay (Trinity Biotech(®) G-6-PDH kit), a qualitative point-of-care test (CareStart(™) G6PD rapid diagnostic test [RDT]), and molecular detection of the G6PD A- G202A allele. Qualitative tests were compared with the gold standard quantitative assay. G6PDd prevalence was higher by RDT (8.6%) than by quantitative assay (6.8%), using a < 60% activity threshold. The RDT performed optimally at a < 60% threshold and demonstrated high sensitivity (≥ 90%) and negative predictive values (100%) across three activity thresholds (below 60%, 30%, and 40%). G202A allele frequency was 6.4%, 7.9%, and 6.8% among females, males, and overall, respectively. Notably, over half of the G202A homo-/hemizygous children expressed ≥ 60% enzyme activity. Overall, the CareStart(™) G6PD RDT appears to be a viable screening test to accurately identify individuals with enzyme activities below 60%. The low prevalence of G6PDd across all three diagnostic modalities and absence of severe deficiency in our study suggests that there is little barrier to the use of single-dose primaquine in this region.