• Adherence to a Six-Dose Regimen of Artemether-Lumefantrine for Treatment of Uncomplicated Plasmodium Falciparum Malaria in Uganda.

      Fogg, C; Bajunirwe, F; Piola, P; Biraro, S; Checchi, F; Kiguli, J; Namiiro, P; Musabe, J; Kyomugisha, A; Guthmann, J P; et al. (Published by: American Society of Tropical Medicine and Hygiene, 2004-11)
      Measuring baseline levels of adherence and identifying risk factors for non-adherence are important steps before the introduction of new antimalarials. In Mbarara in southwestern Uganda, we assessed adherence to artemether-lumefantrine (Coartem) in its latest World Health Organization blister formulation. Patients with uncomplicated Plasmodium falciparum malaria were prescribed artemether-lumefantrine and received an explanation of how to take the following five doses at home. A tablet count was made and a questionnaire was completed during a home visit. Among 210 analyzable patients, 21 (10.0%) were definitely or probably non-adherent, whereas 189 (90.0%) were probably adherent. Age group was not associated with adherence. Lack of formal education was the only factor associated with non-adherence after controlling for confounders (odds ratio = 3.1, 95% confidence interval [CI] = 1.1-9.7). Mean lumefantrine blood levels were lower among non-adherent (n = 16) (2.76 microg/mL, 95% CI = 1.06-4.45) than among adherent (n = 171) (3.19 microg/mL, 95% CI = 2.84-3.54) patients, but this difference was not statistically significant. The high adherence to artemether-lumefantrine found in our study suggest that this drug is likely to be very effective in Mbarara provided that patients receive clear dosage explanations.
    • Card Agglutination Test for Trypanosomiasis (CATT) End-Dilution Titer and Cerebrospinal Fluid Cell Count as Predictors of Human African Trypanosomiasis (Trypanosoma brucei gambiense) Among Serologically Suspected Individuals in Southern Sudan.

      Chappuis, F; Stivanello, E; Adams, K; Kidane, S; Pittet, A; Bovier, P A; Médecins Sans Frontières, Swiss Section, Geneva, Switzerland. francois.chappuis@hcuge.ch (Published by: American Society of Tropical Medicine and Hygiene, 2004-09)
      The diagnosis of human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense relies on an initial serologic screening with the card agglutination test for trypanosomiasis (CATT) for T. b. gambiense, followed by parasitologic confirmation in most endemic areas. Unfortunately, field parasitologic methods lack sensitivity and the management of serologically suspected individuals (i.e., individuals with a positive CATT result but negative parasitology) remains controversial. In Kajo-Keji County in southern Sudan, we prospectively collected sociodemographic and laboratory data of a cohort of 2,274 serologically suspected individuals. Thirty-three percent (n = 749) attended at least one follow-up visit and HAT was confirmed in 64 (9%) cases. Individuals with lower initial CATT-plasma (CATT-P) end-dilution titers had lowest risks (10.4 and 13.8/100 person-years for 1:4 and 1:8 titers, respectively) that significantly increased for higher dilutions: relative risks = 5.1 (95% confidence interval [CI] = 2.6-9.5) and 4.6 (95% CI = 2.8-9.8) for 1:16 and 1:32 titers, respectively. The cumulative yearly risk was also high (76%) in individuals found with 11-20 cells in the cerebrospinal fluid, but this involved only eight patients. Adjustment for potential confounders did not affect the results. In conclusion, treatment with pentamidine should be considered for all serologically suspected individuals with a CATT-P end-dilution titer >/= 1:16 in areas of a moderate to high prevalence of HAT.
    • Evaluation of a New Recombinant K39 Rapid Diagnostic Test for Sudanese Visceral Leishmaniasis.

      Ritmeijer, K; Melaku, Y; Mueller, M; Kipngetich, S; O'keeffe, C; Davidson, R N; Médecins sans Frontières-Holland, Amsterdam, The Netherlands. koert.ritmeijer@amsterdam.msf.org (Published by: American Society of Tropical Medicine and Hygiene, 2006-01)
      A new rK39 rapid diagnostic dipstick test (DiaMed-IT-Leish) was compared with aspiration and a direct agglutination test (DAT) for diagnosis of visceral leishmaniasis (VL) in 201 parasitologically confirmed cases, 133 endemic controls, and in 356 clinical suspects in disease-endemic and -epidemic areas in Sudan. The sensitivity of the rK39 test in parasitologically confirmed VL cases was 90%, whereas the specificity in disease-endemic controls was 99%. The sensitivity of the DAT was 98%. In clinically suspected cases, the sensitivity of the rK39 test was 81% and the specificity was 97%. When compared with the diagnostic protocol based on the DAT and aspiration used by Médecins sans Frontières in epidemic situations, the positive predictive value was 98%, and the negative predictive value was 71%. This rK39 rapid diagnostic test is suitable for screening as well as diagnosis of VL. Further diagnostic work-up of dipstick-negative patients with clinically suspected VL is important. The ease and convenience of the dipstick test will allow decentralization and improved access to care in disease-endemic areas in Sudan.
    • Falciparum Malaria and Climate Change in the Northwest Frontier Province of Pakistan.

      Bouma, M J; Dye, C; van der Kaay, H J; Medecins Sans Frontieres-Holland, Amsterdam, The Netherlands. (Published by: American Society of Tropical Medicine and Hygiene, 1996-08)
      Following a striking increase in the severity of autumnal outbreaks of Plasmodium falciparum during the last decade in the Northwest Frontier Province (NWFP) of Pakistan, the role of climatologic variables was investigated. A multivariate analysis showed that during the transmission season of P. falciparum, the amount of rainfall in September and October, the temperature in November and December, and the humidity in December were all correlated (r2 = 0.82) with two measures of P. falciparum, the falciparum rate (percent of slides examined positive for P. falciparum) since 1981 and the annual P. falciparum proportion (percent of all malaria infections diagnosed as P. falciparum) since 1978. Climatologic records since 1876 show an increase in mean November and December temperatures by 2 degrees C and 1.5 degrees C, respectively, and in October rainfall. Mean humidity in December has also been increasing since 1950. These climatologic changes in the area appear to have made conditions for transmission of P. falciparum more favorable, and may account for the increase in incidence observed in the NWFP in recent years.
    • High Efficacy of Two Artemisinin-Based Combinations (Artesunate + Amodiaquine and Artemether + Lumefantrine) in Caala, Central Angola.

      Guthmann, J P; Cohuet, S; Rigutto, C; Fortes, F; Saraiva, N; Kiguli, J; Kyomuhendo, J; Francis, M; Noël, F; Mulemba, M; et al. (Published by: American Society of Tropical Medicine and Hygiene, 2006-07)
      In April 2004, 137 children 6-59 months of age with uncomplicated Plasmodium falciparum (Pf) malaria (Caala, Central Angola) were randomized to receive either artemether-lumefantrine (Coartem) or artesunate + amodiaquine (ASAQ). After 28 days of follow-up, there were 2/61 (3.2%) recurrent parasitemias in the Coartem group and 4/64 (6.2%) in the ASAQ group (P = 0.72), all classified as re-infections after PCR genotyping (cure rate = 100% [95%CI: 94-100] in both groups). Only one patient (ASAQ group) had gametocytes on day 28 versus five (Coartem) and three (ASAQ) at baseline. Compared with baseline, anemia was significantly improved after 28 days of follow-up in both groups (Coartem: from 54.1% to 13.4%; ASAQ: from 53.1% to 15.9%). Our findings are in favor of a high efficacy of both combinations in Caala. Now that Coartem has been chosen as the new first-line anti-malarial, the challenge is to insure that this drug is available and adequately used.
    • Identifying Health Centers in Honduras Infested with Rhodnius Prolixus Using the Seroprevalence of Chagas Disease in Children Younger than 13 Years.

      Spurling, G; Lucas, R; Doust, J; University of Queensland, Brisbane, Australia; Médecins Sans Frontières, Paris, France. g.spurling@uq.edu.au (Published by: American Society of Tropical Medicine and Hygiene, 2005-08)
      The objective of this study is to determine if a Chagas disease protocol starting with a serological survey is as reliable at identifying insect-infested areas as one using the gold standard entomological survey. The study found that health center areas infested with Rhodnius prolixus were identified using a threshold seroprevalence of 0.1%. The serological survey took half the time and was 30% less expensive than the entomological survey. Developing countries with limited resources may find this strategy useful in combating Chagas disease. This strategy also identifies seropositive children, which facilitates their treatment.
    • Incidence, Management, and Outcome of Childhood Empyema: A Prospective Study of Children in Cambodian Refugee Camps.

      Fontanet, A L; McCauley, R G; Coyette, Y; Larchiver, F; Bennish, M L; Medecins Sans Frontieres, Paris, France. (Published by: American Society of Tropical Medicine and Hygiene, 1993-12)
      To determine the incidence, outcome, and optimal management of empyema, all children less than 15 years of age admitted to Khao-I-Dang Hospital with a diagnosis of empyema during a 23-month period were prospectively studied. Khao-I-Dang Hospital provides care to 137,000 Cambodian children residing in eight refugee camps along the Thai-Cambodian border. Ninety-eight children with empyema were identified, for an annual incidence of 0.37 cases per 1,000 children. All patients had chest tubes inserted on admission, and all were treated with parenteral antibiotics, which included chloramphenicol in 92% of the patients and cloxacillin in 72%. Patients were hospitalized a mean of 30 days, and chest tubes were in place for a mean of 12 days. Surgery was performed on four patients who had bronchopleural fistulas that persisted for more than 14 days. Only one (1%) of the 70 patients treated with cloxacillin required thoracotomy, compared with three (11%) of the 28 patients who did not receive cloxacillin (P = 0.07). In a multiple regression analysis, the presence of pneumatoceles or mediastinal shift on admission chest radiograph, a history of tuberculosis in the family, and an age of more than five years were predictive of a longer duration of chest tube drainage. No patient died in the hospital, and only one patient died in the six months following discharge from the hospital. Chest radiographs that were obtained six months after discharge in 25 patients were all essentially normal, despite marked abnormalities on chest radiographs obtained at discharge. In summary, conservative medical management with the use of chest tubes for these 98 children with empyema resulted in a mortality rate of 1.0%, and should be considered as an effective alternative to the surgical management of patients presenting with this complication.
    • A Killing Disease Epidemic Among Displaced Sudanese Population Identified as Visceral Leishmaniasis.

      de Beer, P; el Harith, A; Deng, L; Semiao-Santos, S J; Chantal, B; van Grootheest, M; Medecins Sans-Frontieres-Holland, Amersterdam, The Netherlands. (Published by: American Society of Tropical Medicine and Hygiene, 1991-03)
      A fatal disease epidemic affected the Bentiu area in southern Sudan and led to a mass migration of the Nuer tribe searching for treatment. The initially available information revealed a high mortality rate due to a possible occurrence of tuberculosis, malaria, enteric fever or visceral leishmaniasis (VL). Serological screening of 53 of the most severely affected patients in an enzyme-linked immunosorbent assay (ELISA) or an improved direct agglutination test (DAT) revealed positivity for VL. In 39 of those patients, diagnosis was confirmed by identification of Leishmania donovani amastigotes in lymph node or bone-marrow aspirates. In a total of 2714 patients observed, 1195 (44.0%) had clinical symptoms suggesting VL: DAT positive titers (1:3200-greater than or equal to 1:12800) were obtained in 654 (24.1%), of whom 325 were confirmed parasitologically. Forty-two VL cases died before or during treatment, giving a mortality rate of 6.4%. Among the intercurrent infections diagnosed in the VL population (654), respiratory involvements (31.7%) and malaria (10.7%) were most prevalent. With the exception of four (0.6%), all other VL patients (509) responded readily to sodium stibogluconate. The factors initiating the outbreak are discussed. Malnutrition and nomadic movements to potential VL endemic areas appeared to be the most important. HIV infection as a possible predisposition seemed remote considering the clinical and epidemiological similarity to VL occurring in East Africa, adequate humoral response in DAT, and immediate positive response to specific anti-Leishmania chemotherapy.
    • Short Report: Association Between Chloroquine and Amodiaquine Resistance and Allelic Variation in the Plasmodium Falciparum Multiple Drug Resistance 1 Gene and the Chloroquine Resistance Transporter Gene in Isolates from the Upper Nile in Southern Sudan.

      Ochong, E; van den Broek, I; Keus, K; Nzila, A; Kenya Medical Research Institute, Wellcome Trust Collaborative Program, Médecins sans Frontières-Holland, South Sudan Section, Nairobi, Kenya. (Published by: American Society of Tropical Medicine and Hygiene, 2003-08)
      Amodiaquine, a 4-aminoquinoline compound, is being considered as an alternative to chloroquine and pyrimethamine/sulfadoxine where resistance in Plasmodium falciparum to both drugs has been selected. Although amodiaquine is more potent than chloroquine, its effectiveness is reduced in areas where chloroquine resistance is high. We report an association of the P. falciparum chloroquine resistance transporter (pfcrt) gene and the P. falciparum multiple drug resistance 1 (pfmdr1) gene, two chloroquine resistance markers, with chloroquine and amodiaquine efficacy in vivo in southern Sudan. The data show that the allele of the pfcrt gene with a lysine to threonine change at codon 76 is strongly associated with both chloroquine and amodiaquine resistance. No such association was observed with the pfmdr1 gene.
    • Trypanosoma Brucei Gambiense Trypanosomiasis in Terego County, Northern Uganda, 1996: A Lot Quality Assurance Sampling Survey.

      Hutin, Y; Legros, D; Owini, V; Brown, V; Lee, E; Mbulamberi, D; Paquet, C; Epicentre Office in Uganda, Kampala, Uganda. (Published by: American Society of Tropical Medicine and Hygiene, 2004-04)
      We estimated the pre-intervention prevalence of Trypanosoma brucei gambiense (Tbg) trypanosomiasis using the lot quality assurance sampling (LQAS) methods in 14 parishes of Terego County in northern Uganda. A total of 826 participants were included in the survey sample in 1996. The prevalence of laboratory confirmed Tbg trypanosomiasis adjusted for parish population sizes was 2.2% (95% confidence interval =1.1-3.2). This estimate was consistent with the 1.1% period prevalence calculated on the basis of cases identified through passive and active screening in 1996-1999. Ranking of parishes in four categories according to LQAS analysis of the 1996 survey predicted the prevalences observed during the first round of active screening in the population in 1997-1998 (P < 0.0001, by chi-square test). Overall prevalence and ranking of parishes obtained with LQAS were validated by the results of the population screening, suggesting that these survey methods may be useful in the pre-intervention phase of sleeping sickness control programs.
    • Utility of Lymph Node Aspiration in the Diagnosis of Visceral Leishmaniasis in Sudan.

      Babiker, Z O E; Davidson, R N N; Mazinda, C; Kipngetich, S; Ritmeijer, K; Médecins Sans Frontières-Holland, Amsterdam, The Netherlands. zahir_babiker@yahoo.co.uk (Published by: American Society of Tropical Medicine and Hygiene, 2007-04)
      We evaluated lymph node aspiration (LNA) as a simple diagnostic procedure for visceral leishmaniasis (VL). Lymph node aspiration was compared with the direct agglutination test (DAT) using a diagnostic titer > or = 1:6,400 in 7,880 suspected VL patients in eastern Sudan. Compared with DAT, LNA had a sensitivity of 65.1% (95% confidence interval = 63.5-66.6%). Parasite density in LNA correlated strongly with DAT titers (P < 0.0001), and low parasite density accounted for 78.1% of positive LNA results with DAT titers < 1:6,400 (n = 782). Risk factors predictive of a positive LNA result were an age of 1-29 years, male sex, a hemoglobin level < 10.0 g/dL, a DAT titer > or = 1:800, and a location with a higher prevalence of VL. Lymph node and splenic aspirations were similarly accurate as tests of cure after treatment of 50 VL patients in southern Sudan. Pre-treatment LNA results were negative in 20 cases of severe post kala-azar dermal leishmaniasis.