Feasibility of Training Clinical Officers in Point-of-Care Ultrasound for Pediatric Respiratory Diseases in Aweil, South Sudan.

Lower respiratory tract infections (LRTIs) are the leading cause of deaths in children < 5 years old worldwide, particularly affecting low-resource settings such as Aweil, South Sudan. In these settings, diagnosis can be difficult because of either lack of access to radiography or clinical algorithms that overtreat children with antibiotics who only have viral LRTIs. Point-of-care ultrasound (POCUS) has been applied to LRTIs, but not by nonphysician clinicians, and with limited data from low-resource settings. Our goal was to examine the feasibility of training the mid-level provider cadre clinical officers (COs) in a Médecins Sans Frontières project in South Sudan to perform a POCUS algorithm to differentiate among causes of LRTI. Six COs underwent POCUS training, and each subsequently performed 60 lung POCUS studies on hospitalized pediatric patients < 5 years old with criteria for pneumonia. Two blinded experts, with a tiebreaker expert adjudicating discordant results, served as a reference standard to calculate test performance characteristics, assessed image quality and CO interpretation. The COs performed 360 studies. Reviewers rated 99.1% of the images acceptable and 86.0% CO interpretations appropriate. The inter-rater agreement (κ) between COs and experts for lung consolidation with air bronchograms was 0.73 (0.63-0.82) and for viral LRTI/bronchiolitis was 0.81 (0.74-0.87). It is feasible to train COs in South Sudan to use a POCUS algorithm to diagnose pneumonia and other pulmonary diseases in children < 5 years old.

Sub-national variation in measles vaccine coverage and outbreak risk: a case study from a 2010 outbreak in Malawi.

BACKGROUND: Despite progress towards increasing global vaccination coverage, measles continues to be one of the leading, preventable causes of death among children worldwide. Whether and how to target sub-national areas for vaccination campaigns continues to remain a question. We analyzed three metrics for prioritizing target areas: vaccination coverage, susceptible birth cohort, and the effective reproductive ratio (RE) in the context of the 2010 measles epidemic in Malawi. METHODS: Using case-based surveillance data from the 2010 measles outbreak in Malawi, we estimated vaccination coverage from the proportion of cases reporting with a history of prior vaccination at the district and health facility catchment scale. Health facility catchments were defined as the set of locations closer to a given health facility than to any other. We combined these estimates with regional birth rates to estimate the size of the annual susceptible birth cohort. We also estimated the effective reproductive ratio, RE, at the health facility polygon scale based on the observed rate of exponential increase of the epidemic. We combined these estimates to identify spatial regions that would be of high priority for supplemental vaccination activities. RESULTS: The estimated vaccination coverage across all districts was 84%, but ranged from 61 to 99%. We found that 8 districts and 354 health facility catchments had estimated vaccination coverage below 80%. Areas that had highest birth cohort size were frequently large urban centers that had high vaccination coverage. The estimated RE ranged between 1 and 2.56. The ranking of districts and health facility catchments as priority areas varied depending on the measure used. CONCLUSIONS: Each metric for prioritization may result in discrete target areas for vaccination campaigns; thus, there are tradeoffs to choosing one metric over another. However, in some cases, certain areas may be prioritized by all three metrics. These areas should be treated with particular concern. Furthermore, the spatial scale at which each metric is calculated impacts the resulting prioritization and should also be considered when prioritizing areas for vaccination campaigns. These methods may be used to allocate effort for prophylactic campaigns or to prioritize response for outbreak response vaccination.

Four years of case-based surveillance of meningitis following the introduction of MenAfriVac in Moissala, Chad: lessons learned.

OBJECTIVE: Case-based surveillance of bacterial meningitis in sentinel districts has been recommended after the introduction of the conjugated vaccine against Neisseria meningitidis serogroup A (NmA), MenAfriVac, in the African meningitis belt. Here we report data and lessons learnt from four years of surveillance in the district of Moissala, Chad. METHODS: All suspected cases of meningitis were referred free of charge to the district hospital for lumbar puncture and treatment. Cerebrospinal fluid samples were tested with Pastorex latex agglutination in Moissala, and inoculated trans-isolate media were used for culture and PCR at the national reference laboratory and/or at the Norwegian Institute of Public Health. RESULTS: From July 2012 to December 2016, 237 suspected cases of meningitis were notified, and a specimen was collected from 224. Eighty-three samples were positive for a bacterial pathogen by culture, PCR or Pastorex, including 58 cases due to Streptococcus pneumoniae with only 28 of 49 pneumococcal meningitis confirmed by culture or PCR correctly identified by Pastorex. Four cases of NmA were detected by Pastorex, but none were confirmed by PCR. CONCLUSION: Implementation of case-based surveillance for meningitis is feasible in Chad, but has required political and technical engagement. Given the high proportion of S. pneumoniae and its poor detection by Pastorex, continued use of PCR is warranted for surveillance outside of outbreaks, and efforts to accelerate the introduction of pneumococcal conjugate vaccines are needed. Introduction of MenAfriVac in routine immunisation and future availability of a pentavalent meningococcal conjugate vaccine will be key elements for the sustained reduction in meningitis outbreaks in the area.

Nontuberculous Mycobacteria Infections at a Provincial Reference Hospital, Cambodia.

Prevalence of nontuberculous mycobacteria (NTM) disease is poorly documented in countries with high prevalence of tuberculosis (TB). We describe prevalence, risk factors, and TB program implications for NTM isolates and disease in Cambodia. A prospective cohort of 1,183 patients with presumptive TB underwent epidemiologic, clinical, radiologic, and microbiologic evaluation, including >12-months of follow-up for patients with NTM isolates. Prevalence of NTM isolates was 10.8% and of disease was 0.9%; 217 (18.3%) patients had TB. Of 197 smear-positive patients, 171 (86.8%) had TB confirmed (167 by culture and 4 by Xpert MTB/RIF assay only) and 11 (5.6%) had NTM isolates. HIV infection and past TB were independently associated with having NTM isolates. Improved detection of NTM isolates in Cambodia might require more systematic use of mycobacterial culture and the use of Xpert MTB/RIF to confirm smear-positive TB cases, especially in patients with HIV infection or a history of TB.

Improved Neonatal Mortality at a District Hospital in Aweil, South Sudan.

Neonatal deaths comprise a growing proportion of global under-five mortality. However, data from the highest-burden areas is sparse. This descriptive retrospective study analyses the outcomes of all infants exiting the Médecins sans Frontières-managed neonatal unit in Aweil Hospital, rural South Sudan from 2011 to 2014. A total of 4268 patients were treated over 4 years, with annual admissions increasing from 687 to 1494. Overall mortality was 13.5% (n = 576), declining from 18.7% to 11.1% (p for trend <0.001). Newborns weighing <2500 g were at significantly increased mortality risk compared with babies ≥2500 g (odds ratio = 2.27, 95% confidence interval = 1.9-2.71, p < 0.001). Leading causes of death included sepsis (49.7%), tetanus (15.8%), respiratory distress (12.8%) and asphyxia (9.2%). Tetanus had the highest case fatality rate (49.7%), followed by perinatal asphyxia (26.5%), respiratory distress (20.4%) and neonatal sepsis (10.5%). Despite increasing admissions, overall mortality declined, indicating that survival of these especially vulnerable infants can be improved even in a basic-level district hospital programme.

Measles seroprevalence in Chiradzulu district, Malawi: Implications for evaluating vaccine coverage.

INTRODUCTION: Self-reported measles vaccination coverage is frequently used to inform vaccination strategies in resource-poor settings. However, little is known to what extent this is a reliable indicator of underlying seroprotection, information that could provide guidance ensuring the success of measles control and elimination strategies. METHODS: As part of a study exploring HIV infection and measles susceptibility, we conveniently sampled consenting HIV-uninfected patients presenting at the HIV voluntary counselling and testing centre, and HIV-infected patients presenting for regular care, in Chiradzulu district hospital, Malawi, between January and September 2012. RESULTS: A total of 2106 participants were recruited between January and September 2012, three quarters of whom were HIV positive. Vaccination cards were available for just 7 participants (0.36%). 91.9% of participants were measles seropositive. Older age (OR=1.11 per year increase in age; 95%CI: 1.09-1.14) and being female (OR=1.90; 95%CI: 1.26-2.87) were both associated with significantly increased odds for seroprotection. Prior vaccination history was associated with lower odds (Odds Ratio (OR)=0.44; 95% confidence interval (CI): 0.22-0.85) for confirmed seropositivity. Previous measles infection was not significantly associated with seroprotection (OR=1.31; 95%CI: 0.49-3.51). Protection by history and serological status were concordant for 64.3% of participants <35 years old. However, analysis by age group reveals important differences in concordance between the ages, with a greater degree of discordance among younger ages. Vaccination and/or infection history as a predictor of seropositivity was 75.8% sensitive, but just 10.3% specific. CONCLUSION: Reported vaccination and previous infection were poor predictors of seropositivity, suggesting these may be unreliable indicators of seroprotection status. Such serosurveys may be indicated in similar settings in which overestimation of the proportion of seroprotected individuals could have important ramifications if used to guide vaccination strategies.

Drug-resistant tuberculosis in HIV-infected patients in a national referral hospital, Phnom Penh, Cambodia.

BACKGROUND AND OBJECTIVE: There are no recent data on the prevalence of drug-resistant tuberculosis (DR TB) in Cambodia. We aim to describe TB drug resistance amongst adults with pulmonary and extra-pulmonary TB and human immunodeficiency virus (HIV) co-infection in a national referral hospital in Phnom Penh, Cambodia. DESIGN: Between 22 November 2007 and 30 November 2009, clinical specimens from HIV-infected patients suspected of having TB underwent routine microscopy, Mycobacterium tuberculosis culture, and drug susceptibility testing. Laboratory and clinical data were collected for patients with positive M. tuberculosis cultures. RESULTS: M. tuberculosis was cultured from 236 HIV-infected patients. Resistance to any first-line TB drug occurred in 34.7% of patients; 8.1% had multidrug resistant tuberculosis (MDR TB). The proportion of MDR TB amongst new patients and previously treated patients was 3.7 and 28.9%, respectively (p<0.001). The diagnosis of MDR TB was made after death in 15.8% of patients; in total 26.3% of patients with MDR TB died. The diagnosis of TB was established by culture of extra-pulmonary specimens in 23.6% of cases. CONCLUSIONS: There is significant resistance to first-line TB drugs amongst new and previously treated TB-HIV co-infected patients in Phnom Penh. These data suggest that the prevalence of DR TB in Cambodia may be higher than previously recognised, particularly amongst HIV-infected patients. Additional prevalence studies are needed. This study also illustrates the feasibility and utility of analysis of non-respiratory specimens in the diagnosis of TB, even in low-resource settings, and suggests that extra-pulmonary specimens should be included in TB diagnostic algorithms.

Exploring HIV infection and susceptibility to measles among older children and adults in Malawi: a facility-based study.

BACKGROUND: HIV infection increases measles susceptibility in infants, but little is known about this relationship among older children and adults. We conducted a facility-based study to explore whether HIV status and/or CD4 count were associated with either measles seroprotection and/or measles antibody concentration. METHODS: A convenience sample was recruited comprising HIV-infected patients presenting for follow-up care, and HIV-uninfected individuals presenting for HIV testing at Chiradzulu District Hospital, Malawi, from January to September 2012. We recorded age, sex, and reported measles vaccination and infection history. Blood samples were taken to determine the CD4 count and measles antibody concentration. RESULTS: One thousand nine hundred and thirty-five participants were recruited (1434 HIV-infected and 501 HIV-uninfected). The majority of adults and approximately half the children were seroprotected against measles, with lower odds among HIV-infected children (adjusted odds ratio 0.27, 95% confidence interval 0.10-0.69; p=0.006), but not adults. Among HIV-infected participants, neither CD4 count (p=0.16) nor time on antiretroviral therapy (p=0.25) were associated with measles antibody concentration, while older age (p<0.001) and female sex (p<0.001) were independently associated with this measure. CONCLUSIONS: We found no evidence that HIV infection contributes to the risk of measles infection among adults, but HIV-infected children (including at ages older than previously reported), were less likely to be seroprotected in this sample.

Local discrepancies in measles vaccination opportunities: results of population-based surveys in Sub-Saharan Africa.

BACKGROUND: The World Health Organization recommends African children receive two doses of measles containing vaccine (MCV) through routine programs or supplemental immunization activities (SIA). Moreover, children have an additional opportunity to receive MCV through outbreak response immunization (ORI) mass campaigns in certain contexts. Here, we present the results of MCV coverage by dose estimated through surveys conducted after outbreak response in diverse settings in Sub-Saharan Africa. METHODS: We included 24 household-based surveys conducted in six countries after a non-selective mass vaccination campaign. In the majority (22/24), the survey sample was selected using probability proportional to size cluster-based sampling. Others used Lot Quality Assurance Sampling. RESULTS: In total, data were collected on 60,895 children from 2005 to 2011. Routine coverage varied between countries (>95% in Malawi and Kirundo province (Burundi) while <35% in N'Djamena (Chad) in 2005), within a country and over time. SIA coverage was <75% in most settings. ORI coverage ranged from >95% in Malawi to 71.4% [95% CI: 68.9-73.8] in N'Djamena (Chad) in 2005.In five sites, >5% of children remained unvaccinated after several opportunities. Conversely, in Malawi and DRC, over half of the children eligible for the last SIA received a third dose of MCV. CONCLUSIONS: Control pre-elimination targets were still not reached, contributing to the occurrence of repeated measles outbreak in the Sub-Saharan African countries reported here. Although children receiving a dose of MCV through outbreak response benefit from the intervention, ensuring that programs effectively target hard to reach children remains the cornerstone of measles control.

Reaching hard-to-reach individuals: Nonselective versus targeted outbreak response vaccination for measles.

Current mass vaccination campaigns in measles outbreak response are nonselective with respect to the immune status of individuals. However, the heterogeneity in immunity, due to previous vaccination coverage or infection, may lead to potential bias of such campaigns toward those with previous high access to vaccination and may result in a lower-than-expected effective impact. During the 2010 measles outbreak in Malawi, only 3 of the 8 districts where vaccination occurred achieved a measureable effective campaign impact (i.e., a reduction in measles cases in the targeted age groups greater than that observed in nonvaccinated districts). Simulation models suggest that selective campaigns targeting hard-to-reach individuals are of greater benefit, particularly in highly vaccinated populations, even for low target coverage and with late implementation. However, the choice between targeted and nonselective campaigns should be context specific, achieving a reasonable balance of feasibility, cost, and expected impact. In addition, it is critical to develop operational strategies to identify and target hard-to-reach individuals.

Measles outbreak response immunization is context-specific: insight from the recent experience of Médecins Sans Frontières.

Andrea Minetti and colleagues compare measles outbreak responses from the Democratic Republic of the Congo and Malawi and argue that outbreak response strategies should be tailored to local measles epidemiology. Please see later in the article for the Editors' Summary.

Measles in Democratic Republic of Congo: an outbreak description from Katanga, 2010-2011.

BACKGROUND: The Democratic Republic of Congo experiences regular measles outbreaks. From September 2010, the number of suspected measles cases increased, especially in Katanga province, where Medecins sans Frontieres supported the Ministry of Health in responding to the outbreak by providing free treatment, reinforcing surveillance and implementing non-selective mass vaccination campaigns. Here, we describe the measles outbreak in Katanga province in 2010-2011 and the results of vaccine coverage surveys conducted after the mass campaigns. METHODS: The surveillance system was strengthened in 28 of the 67 health zones of the province and we conducted seven vaccination coverage surveys in 2011. RESULTS: The overall cumulative attack rate was 0.71% and the case fatality ratio was 1.40%. CONCLUSIONS: Early investigation of the age distribution of cases is a key to understanding the epidemic, and should guide the vaccination of priority age groups.

Lessons and challenges for measles control from unexpected large outbreak, Malawi.

Despite high reported coverage for routine and supplementary immunization, in 2010 in Malawi, a large measles outbreak occurred that comprised 134,000 cases and 304 deaths. Although the highest attack rates were for young children (2.3%, 7.6%, and 4.5% for children <6, 6-8, and 9-11 months, respectively), persons >15 years of age were highly affected (1.0% and 0.4% for persons 15-19 and >19 years, respectively; 28% of all cases). A survey in 8 districts showed routine coverage of 95.0% for children 12-23 months; 57.9% for children 9-11 months; and 60.7% for children covered during the last supplementary immunization activities in 2008. Vaccine effectiveness was 83.9% for 1 dose and 90.5% for 2 doses. A continuous accumulation of susceptible persons during the past decade probably accounts for this outbreak. Countries en route to measles elimination, such as Malawi, should improve outbreak preparedness. Timeliness and the population chosen are crucial elements for reactive campaigns.

Situación epidemiológica del VIH/SIDA: en Venezuela y el mundo / Epidemiologial situation of the HIV/AIDS: in Venezuela and the world

Se realizó una investigación de tipo descriptivo utilizando la tecnología de la red computarizada de bases de datos INTERNET con el objeto de realizar la revisión de la situación epidemiológica del VIH/sida en el mundo, desde sus orígenes hasta la actualidad, simultáneamente se accedió a diversos organismos nacionales e internacionales con el fín de obtener información actualizada acerca de la epidemia en Venezuela. El VIH/sida se ha convertido en una pandemia de gran magnitud y según las últimas estimaciones de la OMS y la ONUSIDA hubo más de 30 millones de personas infectadas por el VIH al final de 1997, encontrándose que las dos terceras partes de la población afectada se concentra en el continente africano: En Asia la mayor frecuencia de infección ocurre en los niveles socioeconómicos bajos. En América se observa que la subregión con mayor incidencia de casos es Norteamérica en comparación con América Latina y el Caribe, donde la epidemia tiene características muy heterogéneas, en cuanto a modos de transmisión. En Venezuela el número de casos ha ido aumentando progresivamente a lo largo de los años, predominando en las poblaciones de mayor densidad, siendo la vía sexual la forma más importante de transmisión

Efecto hipotensor inducido por metoclopramida en sujetos normotensos e hipertensos / Effect of intravenous metoclopramide on blood pressure in normotensive and hypertensives

En el presente estudio evaluamos el efecto de la metoclopramida intravenosa sobre la presión sanguínea en sujetos normotensos (no entrenados, futbolistas, corredores) y en pacientes hipertensos. Hubo una disminución de la presión arterial sólo observado en sujetos femeninos no entrenados y esta fue más grande en sujetos hipertensos. En futbolistas y corredores, la disminución en la presión arterial fue estadísticamente no significativa. Hubo un efecto no significativo sobre la frecuencia cardíaca. El mecanismo probable de este nuevo efecto farmacológico de la metoclopramida es desconocido; sin embargo, actualmente se están realizando investigaciones para definir su mecanismo de acción

Metoclopramida atenua la hiperreactividad vascular durante la prueba presora por frio en atletas / Metoclopramide attenuant the vascular hyperreactivity during of to cold test by cold in atletics

Veinte (20) sujetos normotensos no entrenados y treinta y dos (32) sujetos normotensos entrenados (futbolistas y corredores) fueron estudiados en la Unidad de Farmacología Clínica de la Escuela de Medicina Vargas en Caracas, Venezuela. Los sujetos recibieron una infisión de solución de glucosa al 5 por ciento antes y despues de una infusión de Metoclopramida intravenosa a una dosis de 7,5 ug/kg/min por un período de 30 minutos. Los sujetos normotensos no entrenados respondieron con un aumento de la presión arterial después de la Prueba por Frío (PPF) (17,2 versus 21,4 mmHg en sistólica y 17,9 versus 24,1 mmHg en diastólica) antes y despues de la administración de Metoclopramida. Los futbolistas respondieron con un aumento de la presión arterial después de la PPF, pero sin embargo, la respuesta de la presión sistólica fue comparativamente menor. Los corredores respondieron con un aumento de la presión arterial después de la PPF (18,7 mmHg en sistólica y 15,8 versus 13,9 mmHd en diastólica) antes y después de la administración de Metoclopramida. La frecuencia cardíaca sólo aumentó en los sujetos entrenados antes de la Metoclopramida. Concluimos lo siguiente: 1. La hiperreactividad vascular inducida por la Metoclopramida está ausente en los sujetos entrenados. 2. La respuesta cardiovascular a la Prueba Presora por Frío está atenuada en los sujetos atletas en comparación con aquellos sujetos no entrenados. Esto podría significar una probable adaptación del sistema dopaminérgico durante el ejercicio

Cardiac workload during exercise under metoclopramide treatment / Presión sanguinea del paciente cardiaco durante el ejercicio y bajo un tratamiento con metoclopramida

Cardiac workload was determined in normotensive and hypertensive subjects during submaximal treadmil exercise under metoclopramide treatment at the José Gregorio Hernández Hospital and at the Vargas Hospital, Caracas, Venezuela. Subjects were submitted to treadmil exercise during a 30 min period of 5 por ciento glucose solution administration (before and after metoclopramide) and during a 30 min period of metoclopramide, 7.5 µg/Kg/min administration. Treadmill exercise induced an increase of cardiac Workload in both normotensive and hypertensive subjects. Metoclopramide induced a decrease of cardiac workload in normotensives and less in hypertensives. We conclude that metoclopramide, a known DA2 dopaminergic blocker, reduces cardiac workload during keadmill exercise in normotensive and hypertensive subjects

Metoclopramide-Induced Vascular Hyperreactivity: A Comparative Study Between Normotensive and Hypertensive Subjects.

In the present study, we have evaluated the cardiovascular responses to the cold pressor test (CPT) under intravenous metoclopramide (MTC) treatment (7.5 &mgr;g kg(minus sign1) min(minus sign1)) during a 30-min period and two additional periods, before and after MTC by using 5% glucose solution. There was a vascular hyperreactivity induced by MTC, Delta mm Hg was 21.4/24/1 mm Hg (systolic/diastolic blood pressure [BP]) during MTC versus Delta 17.2/17.9 mm Hg during 5% glucose infusion. In nine hypertensive subjects, Delta mm Hg was 36.8/25.7 during MTC versus Delta 31/24 mm Hg during 5% glucose. Bromocriptine pretreatment (7.5 mg daily for 7 days) antagonized MTC-BP increase during CPT. We conclude the following: (1) MTC induces a greater BP response during CPT which is blocked by using bromocriptine, a known DA(2) dopaminergic agonist. (2) A dopaminergic influence is present during CPT in normotensive and hypertensive subjects.