• Efficacy of artesunate-amodiaquine for treating uncomplicated falciparum malaria in sub-Saharan Africa: a multi-centre analysis.

      Zwang, Julien; Olliaro, Piero; Barennes, Hubert; Bonnet, Maryline; Brasseur, Philippe; Bukirwa, Hasifa; Cohuet, Sandra; D'Alessandro, Umberto; Djimdé, Abdulaye; Karema, Corine; et al. (2009-11)
      BACKGROUND: Artesunate and amodiaquine (AS&AQ) is at present the world's second most widely used artemisinin-based combination therapy (ACT). It was necessary to evaluate the efficacy of ACT, recently adopted by the World Health Organization (WHO) and deployed over 80 countries, in order to make an evidence-based drug policy. METHODS: An individual patient data (IPD) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints. RESULTS: A total of 11,700 patients (75% under 5 years old), from 33 different sites in 16 countries were followed for 28 days. Loss to follow-up was 4.9% (575/11,700). AS&AQ was given to 5,897 patients. Of these, 82% (4,826/5,897) were included in randomized comparative trials with polymerase chain reaction (PCR) genotyping results and compared to 5,413 patients (half receiving an ACT). AS&AQ and other ACT comparators resulted in rapid clearance of fever and parasitaemia, superior to non-ACT. Using survival analysis on a modified intent-to-treat population, the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90% (the WHO cut-off) in 11/16 countries. In randomized comparative trials (n = 22), the crude efficacy of AS&AQ was 75.9% (95% CI 74.6-77.1) and the PCR-adjusted efficacy was 93.9% (95% CI 93.2-94.5). The risk (weighted by site) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT, superior to dihydroartemisinin-piperaquine (DP, in one Ugandan site), and not different from AS+SP or AL (artemether-lumefantrine). The risk of gametocyte appearance and the carriage rate of AS&AQ was only greater in one Ugandan site compared to AL and DP, and lower compared to non-ACT (p = 0.001, for all comparisons). Anaemia recovery was not different than comparator groups, except in one site in Rwanda where the patients in the DP group had a slower recovery. CONCLUSION: AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many, but not all, the sub-Saharan African countries where it was studied. Efficacy varies between and within countries. An IPD analysis can inform general and local treatment policies. Ongoing monitoring evaluation is required.
    • Epidemiology and mortality of burns in a general hospital of Eastern Sri Lanka.

      Laloë, V; Médecins Sans Frontières, Paris, France. veronique.laloe@bigfoot.com (Elsevier, 2002-12)
      This 2-year prospective study examined the epidemiology and mortality of 345 patients admitted with burn injuries. Sixty-four percent of all burns were accidental in nature and at least 25% were self-inflicted. The rest were due to assaults or had a doubtful cause. The median age was 22 years. Forty-one percent of the accidents were due to the fall of a homemade kerosene bottle lamp. The main cause was flames, followed by scalds. Females outnumbered males in all categories of burns except cases of assault, and suffered from a higher mortality. Most at risk of accidental burns were children between 1 and 4 years, who suffered primarily from scalds. Self-inflicted burns were most common among women aged 20-29 years. The overall median total body surface area (TBSA) burned was 16%. Self-inflicted and 'doubtful' burns were much more extensive and more often fatal than accidental ones. The overall mortality rate was 27%. Burns involving more than 50% of the body surface area were invariably fatal. Mortality was highest in the elderly and in the 20-29 years age group. Burns were the first single cause of mortality in the surgical wards. The case is made for the establishment of more Burns Units.
    • Foci of Schistosomiasis mekongi, Northern Cambodia: II. Distribution of infection and morbidity.

      Stich, A H; Biays, S; Odermatt, P; Men, C; Saem, C; Sokha, K; Ly, C S; Legros, P; Philips, M; Lormand, J D; et al. (Wiley-Blackwell, 1999-10)
      In the province of Kracheh, in Northern Cambodia, a baseline epidemiological survey on Schistosoma mekongi was conducted along the Mekong River between December 1994 and April 1995. The results of household surveys of highly affected villages of the East and the West bank of the river and of school surveys in 20 primary schools are presented. In household surveys 1396 people were examined. An overall prevalence of infection of 49.3% was detected by a single stool examination with the Kato-Katz technique. The overall intensity of infection was 118.2 eggs per gram of stool (epg). There was no difference between the population of the east and west shore of the Mekong for prevalence (P = 0.3) or intensity (P = 0.9) of infection. Severe morbidity was very frequent. Hepatomegaly of the left lobe was detected in 48.7% of the population. Splenomegaly was seen in 26.8% of the study participants. Visible diverted circulation was found in 7.2% of the population, and ascites in 0.1%. Significantly more hepatomegaly (P = 0.001), splenomegaly (P = 0. 001) and patients with diverted circulation (P = 0.001) were present on the west bank of the Mekong. The age group of 10-14 years was most affected. The prevalence of infection in this group was 71.8% and 71.9% in the population of the West and East of the Mekong, respectively. The intensity of infection was 172.4 and 194.2 epg on the West and the East bank, respectively. In the peak age group hepatomegaly reached a prevalence of 88.1% on the west and 82.8% on the east bank. In the 20 schools 2391 children aged 6-16 years were examined. The overall prevalence of infection was 40.0%, ranging from 7.7% to 72.9% per school. The overalls mean intensity of infection was 110.1 epg (range by school: 26.7-187.5 epg). Both prevalence (P = 0.001) and intensity of infection (P = 0.001) were significantly higher in schools on the east side of the Mekong. Hepatomegaly (55.2%), splenomegaly (23.6%), diverted circulation (4. 1%), ascites (0.5%), reported blood (26.7%) and mucus (24.3%) were very frequent. Hepatomegaly (P = 0.001), splenomegaly (P = 0.001), diverted circulation (P = 0.001) and blood in stool (P = 0.001) were significantly more frequent in schools of the east side of the Mekong. Boys suffered more frequently from splenomegaly (P = 0.05), ascites (P = 0.05) and bloody stools (P = 0.004) than girls. No difference in sex was found for the prevalence and intensity of infection and prevalence of hepatomegaly. On the school level prevalence and intensity of infection were highly associated (r = 0. 93, P = 0.0001). The intensity of infection was significantly associated only with the prevalence of hepatomegaly (r = 0.44, P = 0. 05) and blood in stool (r = 0.40, P = 0.02). This comprehensive epidemiological study documents for the first time the public health importance of schistosomiasis mekongi in the Province of Kracheh, Northern Cambodia and points at key epidemiological features of this schistosome species, in particular the high level of morbidity associated with infection.
    • Illness in Returned Travelers and Immigrants/Refugees: The 6-Year Experience of Two Australian Infectious Diseases Units.

      O'Brien, D P; Leder, K; Matchett, E; Brown, G V; Torresi, J; Victorian Infectious Diseases Service, Centre for Clinical Research Excellence, Royal Melbourne Hospital, Victoria, Australia. obrien@amsterdam.msf.org (2008-02-21)
      BACKGROUND: Data comparing returned travelers and immigrants/refugees managed in a hospital setting is lacking. METHODS: We prospectively collected data on 1,106 patients with an illness likely acquired overseas who presented to two hospital-based Australian infectious diseases units over a 6-year period. RESULTS: Eighty-three percent of patients were travelers and 17% immigrants/refugees. In travelers, malaria (19%), gastroenteritis/diarrhea (15%), and upper respiratory tract infection (URTI) (7%) were the most common diagnoses. When compared with immigrants/refugees, travelers were significantly more likely to be diagnosed with gastroenteritis/diarrhea [odds ratio (OR) 8], malaria (OR 7), pneumonia (OR 6), URTI (OR 3), skin infection, dengue fever, typhoid/paratyphoid fever, influenza, and rickettsial disease. They were significantly less likely to be diagnosed with leprosy (OR 0.03), chronic hepatitis (OR 0.04), tuberculosis (OR 0.05), schistosomiasis (OR 0.3), and helminthic infection (OR 0.3). In addition, travelers were more likely to present within 1 month of entry into Australia (OR 96), and have fever (OR 8), skin (OR 6), gastrointestinal (OR 5), or neurological symptoms (OR 5) but were less likely to be asymptomatic (OR 0.1) or have anaemia (OR 0.4) or eosinophilia (OR 0.3). Diseases in travelers were more likely to have been acquired via a vector (OR 13) or food and water (OR 4), and less likely to have been acquired via the respiratory (OR 0.2) or skin (OR 0.6) routes. We also found that travel destination and classification of traveler can significantly influence the likelihood of a specific diagnosis in travelers. Six percent of travelers developed a potentially vaccine-preventable disease, with failure to vaccinate occurring in 31% of these cases in the pretravel medical consultation. CONCLUSIONS: There are important differences in the spectrum of illness, clinical features, and mode of disease transmission between returned travelers and immigrants/refugees presenting to hospital-based Australian infectious diseases units with an illness acquired overseas.
    • Outcomes for Mycobacterium ulcerans infection with combined surgery and antibiotic therapy: findings from a south-eastern Australian case series.

      O'Brien, D P; Hughes, A; Cheng, A C; Henry, M J; Callan, P; McDonald, A; Holten, I; Birrell, M; Sowerby, J M; Johnson, P D; et al. (Medical Society of Australia, 2007-01-15)
      OBJECTIVE: To describe the effect of antibiotics on outcomes of treatment for Buruli or Bairnsdale ulcer (BU) in patients on the Bellarine Peninsula in south-eastern Australia. DESIGN: Observational, non-randomised study with data collected prospectively or through medical record review. PATIENTS AND SETTING: All 40 patients with BU managed by staff of Barwon Health's Geelong Hospital (a public, secondary-level hospital) between 1 January 1998 and 31 December 2004. MAIN OUTCOME MEASURES: Epidemiology, clinical presentation, diagnosis, treatment and clinical outcomes. RESULTS: There were 59 treatment episodes; 29 involved surgery alone, 26 surgery plus antibiotics, and four antibiotics alone. Of 55 episodes where surgery was performed, minor surgery was required in 22, and major surgery in 33. Failure rates were 28% for surgery alone, and 19% for surgery plus antibiotics. Adjunctive antibiotic therapy was associated with increased treatment success for lesions with positive histological margins (P < 0.01), and lesions requiring major surgery for treatment of a first episode (P < 0.01). The combination of rifampicin and ciprofloxacin resulted in treatment success in eight of eight episodes, and no patients ceased therapy because of side effects with this regimen. CONCLUSIONS: Adjunctive antibiotic therapy may increase the effectiveness of BU surgical treatment, and this should be further assessed by larger randomised controlled trials. The combination of rifampicin and ciprofloxacin appears the most promising.
    • Prevalence and risk factors of Lassa seropositivity in inhabitants of the forest region of Guinea: a cross-sectional study.

      Kernéis, Solen; Koivogui, Lamine; Magassouba, N'Faly; Koulemou, Kekoura; Lewis, Rosamund; Aplogan, Aristide; Grais, Rebecca F; Guerin, Philippe J; Fichet-Calvet, Elisabeth; Epicentre, Paris, France. solen.kerneis@cch.aphp.com (2009-11)
      BACKGROUND: Lassa fever is a viral hemorrhagic fever endemic in West Africa. The reservoir host of the virus is a multimammate rat, Mastomys natalensis. Prevalence estimates of Lassa virus antibodies in humans vary greatly between studies, and the main modes of transmission of the virus from rodents to humans remain unclear. We aimed to (i) estimate the prevalence of Lassa virus-specific IgG antibodies (LV IgG) in the human population of a rural area of Guinea, and (ii) identify risk factors for positive LV IgG. METHODS AND FINDINGS: A population-based cross-sectional study design was used. In April 2000, all individuals one year of age and older living in three prefectures located in the tropical secondary forest area of Guinea (Gueckedou, Lola and Yomou) were sampled using two-stage cluster sampling. For each individual identified by the sampling procedure and who agreed to participate, a standardized questionnaire was completed to collect data on personal exposure to potential risk factors for Lassa fever (mainly contact with rodents), and a blood sample was tested for LV IgG. A multiple logistic regression model was used to determine risk factors for positive LV IgG. A total of 1424 subjects were interviewed and 977 sera were tested. Prevalence of positive LV Ig was of 12.9% [10.8%-15.0%] and 10.0% [8.1%-11.9%] in rural and urban areas, respectively. Two risk factors of positive LV IgG were identified: to have, in the past twelve months, undergone an injection (odds ratio [OR] = 1.8 [1.1-3.1]), or lived with someone displaying a haemorrhage (OR = 1.7 [1.1-2.9]). No factors related to contacts with rats and/or mice remained statistically significant in the multivariate analysis. CONCLUSIONS: Our study underlines the potential importance of person-to-person transmission of Lassa fever, via close contact in the same household or nosocomial exposure.
    • 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.
    • Treating 4,000 diabetic patients in Cambodia, a high-prevalence but resource-limited setting: a 5-year study.

      Raguenaud, Marie-Eve; Isaakidis, Petros; Reid, Tony; Chy, Say; Keuky, Lim; Arellano, Gemma; Van Damme, Wim; Médecins Sans Frontières, Phnom Penh, Cambodia. eve_raguenaud@hotmail.com (2009-08-15)
      BACKGROUND: Despite the worldwide increasing burden of diabetes, there has been no corresponding scale-up of treatment in developing countries and limited evidence of program effectiveness. In 2002, in collaboration with the Ministry of Health of Cambodia, Médecins Sans Frontières initiated an outpatient program of subsidized diabetic care in two hospital-based chronic disease clinics in rural settings. We aimed to describe the outcomes of newly and previously diagnosed diabetic patients enrolled from 2002 to 2008. METHODS: We calculated the mean and proportion of patients who met the recommended treatment targets, and the drop from baseline values for random blood glucose (RBG), hemoglobin A1c (HbA1c), blood pressure (BP), and body mass index (BMI) at regular intervals. Analysis was restricted to patients not lost to follow-up. We used the t test to compare baseline and subsequent paired values. RESULTS: Of 4404 patients enrolled, 2,872 (65%) were still in care at the time of the study, 24 (0.5%) had died, and 1,508 (34%) were lost to follow-up. Median age was 53 years, 2,905 (66%) were female and 4,350 (99%) had type 2 diabetes. Median (interquartile range (IQR)) follow-up was 20 months (5 to 39.5 months). A total of 24% (51/210) of patients had a HbA1c concentration of <7% and 35% (709/1,995) had a RBG <145 mg/dl within 1 year. There was a significant drop of 109 mg/dl (95% confidence interval (CI) 103.1 to 114.3) in mean RBG (P < 0.001) and a drop of 2.7% (95% CI 2.3 to 3.0) in mean HbA1c (P < 0.001) between baseline and month 6. In all, 45% (327/723) and 62% (373/605) of patients with systolic or diastolic hypertension at baseline, respectively, reached = 130/80 mm Hg within 1 year. There was a drop of 13.5 mm Hg (95% CI 12.1 to 14.9) in mean systolic blood pressure (SBP) (P < 0.001), and a drop of 11.7 mm Hg (95% CI 10.8 to 12.6) in mean diastolic blood pressure (DBP) (P < 0.001) between baseline and month 6. Only 22% (90/401) patients with obesity at baseline lowered their BMI <27.5 kg/m2 after 1 year. Factors associated with loss to follow-up were male sex, age >60 years, living outside the province, normal BMI on admission, high RBG on last visit, and coming late for the last consultation. CONCLUSION: Significant and clinically important improvements in glycemia and BP were observed, but a relatively low proportion of diabetic patients reached treatment targets. These results and the high loss to follow-up rate highlight the challenges of delivering diabetic care in rural, resource-limited settings.