[Effectiveness of three biological larvicides and of an insect growth regulator against Anopheles arabiensis in Senegal]. / Efficacité de trois larvicides d'origine biologique et d'un régulateur de croissance contre Anopheles arabiensis au Sénégal.

Urban malaria is a major public health problem in Africa. In Senegal, the environmental changes seem to favor the persistence of malaria transmission in Dakar suburbs by creating, throughout the year, potential breeding sites of malaria vectors. In such a situation and in a context of a growing threat of insecticide resistance in anopheline vectors, the larval control making use of products from biological origin or growth regulators could represent an additional tool to the current strategies developed against anophelines. In this study conducted in 2012, the efficiency and residual effect of three biological larvicides (VectoBac® WG, Vecto-Max® CG, and VectoBac® GR) and an insect growth regulator (MetaLarv™) were evaluated on Anopheles gambiae s.l. larvae in seminatural conditions (experimental station) and natural breeding sites in the suburbs of Dakar. The formulations were tested according to the manufacturer recommendations, namely 0.03 g/m2 for VectoBac® WG, 0.5 g/m2 for VectoBac® GR, 0.75 g/m2 for VectoMax® CG, and 0.5 g/m2 for MetaLarv™. In experimental station, the treatment with larvicides was effective over a period of 14 days with a mortality ranging between 92% and 100%. The insect growth regulator remained effective up to 55 days with a single emergence recorded in the 27th day after treatment. In natural conditions, a total effectiveness (100% mortality) of larvicides was obtained 48 hours after treatment, then a gradual recolonization of breeding sites was noted. However, the insect growth regulator has reduced adult emergence higher than 80% until the end of follow-up (J28). This study showed a good efficiency of the larvicides and of the growth regulator tested. These works provide current data on potential candidates for the implementation of larval control interventions in addition to that of chemical adulticide for control of urban malaria.

Review of policy and status of implementation of collaborative HIV-TB activities in 23 high-burden countries.

Issuance of national policy guidance is a critical step to ensure quality HIV-TB (human immunodeficiency virus-tuberculosis) coordination and programme implementation. From the database of the Joint United Nations Programme on HIV/AIDS (UNAIDS), we reviewed 62 national HIV and TB guidelines from 23 high-burden countries for recommendations on HIV testing for TB patients, criteria for initiating antiretroviral therapy (ART) and the Three I's for HIV/TB (isoniazid preventive treatment [IPT], intensified TB case finding and TB infection control). We used UNAIDS country-level programme data to determine the status of implementation of existing guidance. Of the 23 countries representing 89% of the global HIV-TB burden, Brazil recommends ART irrespective of CD4 count for all people living with HIV, and four (17%) countries recommend ART at the World Health Organization (WHO) 2013 guidelines level of CD4 count â©¿500 cells/mm(3) for asymptomatic persons. Nineteen (83%) countries are consistent with WHO 2013 guidelines and recommend ART for HIV-positive TB patients irrespective of CD4 count. IPT is recommended by 16 (70%) countries, representing 67% of the HIV-TB burden; 12 recommend symptom-based screening alone for IPT initiation. Guidelines from 15 (65%) countries with 79% of the world's HIV-TB burden include recommendations on HIV testing and counselling for TB patients. Although uptake of ART, HIV testing for TB patients, TB screening for people living with HIV and IPT have increased significantly, progress is still limited in many countries. There is considerable variance in the timing and content of national policies compared with WHO guidelines. Missed opportunities to implement new scientific evidence and delayed adaptation of existing WHO guidance remains a key challenge for many countries.

Clinical predictors for death in HIV-positive and HIV-negative tuberculosis patients in Guinea-Bissau.

OBJECT: To assess easily monitored predictors for tuberculosis mortality. DESIGN: Risk factors for tuberculosis mortality were assessed during the 8-month treatment in 440 men and 269 women diagnosed with confirmed or presumed intrathoracic tuberculosis included prospectively in Guinea-Bissau from May 1996 to April 2001. A civil war occurred in the study area from June 1998 to May 1999. RESULTS: 12% were HIV-1 positive, 16% HIV-2 positive and 7% were HIV dually infected. Case fatality rates for HIV positive were higher during (35% [22/63]) and after the war (29% [27/92]) compared to before the war (17% [15/88]). The war did not have an effect on the case fatality rate in HIV negative (10% [13/135] before the war). HIV-1-infected patients had higher mortality than HIV-2 infected, mortality rate ratio (MRR) = 2.28 (95% confidence interval 1.17-4.46). Men had higher mortality than women but only among the HIV negative (MRR = 2.09 [0.95-4.59]). Hence, the negative impact of HIV infection on mortality was stronger in women (MRR = 6.51 [2.98-14.2]) than in men (MRR = 2.64 [1.67-4.17]) (test of homogeneity, p = 0.051). Anergy to tuberculin was associated with death in HIV positive (MRR = 2.77 [1.38-5.54]) but not in HIV negative (MRR = 1.14 [0.52-2.53]). Signs of immune deficiency, such as oral candida infection or leukoplakia (MRR = 4.25 [1.92-9.44]) and diarrhea (MRR = 2.15 [1.29-3.58] was associated with mortality in HIV positive. Tendencies were similar among HIV negative. HIV-positive relapse cases were at increased risk of dying (MRR = 2.42 [1.10-5.34]). Malnutrition, measured through mid-upper arm circumference (MUAC), increased the risk of death. CONCLUSION: Easily monitored predictors for mortality in tuberculosis patients include clinical signs of immune deficiency and low MUAC.

The frailty hypothesis revisited: mainly weak children die of measles.

It has been suggested that measles infection mainly kills frail children who are likely to die anyhow of other infections. If that were true, the proportion of frail children should increase after the introduction of measles vaccination and post-measles mortality compared with mortality in uninfected children should increase when the case fatality declines and frail children are no longer dying of measles. The latter deduction was investigated in Niakhar, Senegal, where the measles case fatality has declined markedly. Measles has been studied in Niakhar during 12 years from 1983 to 1994. We compared long-term mortality after measles infection in periods with both high and low case fatality. The acute measles case fatality rate (CFR) declined from 6.5% in 1983-1986 to 1.5% in 1987-1994, an age-adjusted decline of 66% (RR=0.34 (0.19-0.58)). Between 1983-1986 and 1987-1994, mortality in the first year after measles infection declined by 35% (RR=0.65 (0.37-1.16)), the pattern being the same in the second and third year after infection (RR=0.63 (0.33-1.21)). This reduction could not be related to introduction of immunization, treatment of measles with Vitamin A, or prophylactic use of antibiotics. Controlling for age, immunization, and season, the decline in post-measles mortality was similar to the fall in non-measles-related mortality between the two periods (mortality rate ratio=0.72 (0.64-0.80)). Since the mortality decline in survivors of measles was as large as the decline in mortality among uninfected children, reduction in acute measles mortality did not lead to accumulation of frail children. We doubt measles infection ever eliminated mainly weak children; it always killed a broad spectrum of children, most of whom were "fit to survive". Hence, it seems unlikely that measles vaccination has contributed to the survival of more frail children.

Tuberculosis mortality during a civil war in Guinea-Bissau.

CONTEXT: Tuberculosis (TB) is an increasing global problem, despite effective drug therapies. Access to TB therapy during conflict situations has not been studied. OBJECTIVE: To determine the effect of irregular TB treatment due to an armed conflict in Guinea-Bissau, West Africa. DESIGN, SETTING, AND PATIENTS: Ongoing retrospective cohort study conducted in the capital city of Bissau among 101 patients with TB who received irregular or no treatment during the civil war (war cohort; June 7-December 6, 1998) and 108 patients with TB who received treatment 12 months earlier (peace cohort; June 7-December 6, 1997) and comparison of an additional 42 patients who had completed treatment before June 6, 1998, and 69 patients who had completed treatment before June 6, 1997. MAIN OUTCOME MEASURE: Mortality rates, compared by irregular (war cohort) vs regular (peace cohort) access to treatment, by intensive vs continuation phase of treatment, and by those who had previously completed treatment for TB. RESULTS: Irregular treatment was associated with an increased mortality rate among patients with TB. The mortality rate ratio (MR) was 3.12 (95% confidence interval [CI], 1.20-8.12) in the war cohort, adjusting for age, sex, human immunodeficiency virus (HIV) infection, residence, and length of treatment. Each additional week of treatment before the war started increased probability of survival by 5% (95% CI, 0%-10%). In the intensive phase of treatment, the adjusted MR was 3.30 (95% CI, 1.04-10.50) and in the continuation phase it was 2.26 (95% CI, 0.33-15.34). Increased mortality among the war cohort was most marked in HIV-positive patients, who had an adjusted MR of 8.19 (95% CI, 1.62-41.25). Mortality was not increased in HIV-positive or HIV-negative patients who had completed TB treatment when the war started. CONCLUSIONS: Interruption of treatment had a profound impact on mortality among patients with TB during the war in Guinea-Bissau. Regular treatment for TB was associated with significantly improved survival for HIV-infected individuals. In emergencies, it is crucial to ensure availability of TB drugs.

Ordinary and opportunistic enteropathogens associated with diarrhea in Senegalese adults in relation to human immunodeficiency virus serostatus.

OBJECTIVES: A survey was conducted in Dakar, Senegal, to identify major types and prevalences of bacteria, parasites, fungi, and Rotaviruses associated with diarrhea in relation to human immunodeficiency virus (HIV) serostatus with the goal to provide guidance to physicians for case management. METHODS: Etiologic agents were identified in a case control study: cases were HIV-infected patients with diarrhea (HIV+ D+) and HIV seronegative patients with diarrhea (HIV D+); controls were HIV-infected patients without diarrhea (HIV+ D ) and seronegative controls without diarrhea (HID D ). Ordinary enteric pathogens were identified by conventional methods. Different Escherichia coli pathotypes were characterized by polymerase chain reaction (PCR), identification of HEp-2 cell adherence pattern, Sereny test, GM1-ELISA, and the suckling mouse assay. Opportunistic parasites, such as Cryptosporidium and Microsporidium, were identified by the Kinyoun method and trichromic stain of Weber, respectively. Rotaviruses were identified with a commercial latex agglutination kit. Antimicrobial susceptibility testing was carried out by the disk diffusion method. RESULTS: Among the 594 patients examined, 158 were HIV+ D+, 121 were HIV2 D+, 160 were HIV+ D , and 155 were HIV D . The main etiologies of diarrhea were different according to HIV serostatus of patients. In immunocompetent adults the main causes of diarrhea were Shigella sp (12.4%), Entamoeba histolytica(10.7%), Salmonella enterica (6.6%), and Giardia (4.9%). In the immunocompromised host the more frequent pathogens were enteroaggregative E. coli (19.6%), Microsporidium (9.4%), Cryptosporidium sp (8.2%), Rotavirus (8.2%), Shigella sp (7.6%), Candida albicans (7.6%), E. histolytica (5.1%), S. enterica (4.4%), and Isospora belli (4.4%). Also, Blastocystis hominis has to be considered as an opportunistic parasite, because it was identified only in HIV-infected patients, with higher prevalence in adults with diarrhea (2.5% in HIV+ D+ patients; 0.6% in HIV+ D patients). High level of asymptomatic carriage of Ascaris lumbricoides and Trichuris trichiura and some cases of multiple infections were observed. Fungi, Cryptosporidium sp and Microsporidium sp, were often identified in patients with low CD4 counts (range, 79 250 cells/mL). Independently from HIV-serostatus, CD4 count was lower in diarrheic persons, suggesting that diarrhea is a debilitating illness and that effective management of diarrhea can prevent immunosuppression. Isolated enteropathogenic strains displayed high resistance to most antibiotics used in Senegal for treating diarrhea (ampicillin, tetracycline, cotrimoxazole); they were susceptible to amikacin, gentamicin, and norfloxacin. CONCLUSION: These epidemiologic data suggest that guidelines for the management of diarrhea during HIV infection in Dakar should be updated.

Tuberculosis, human immunodeficiency virus infection, and malnutrition in Burundi.

In order to compare the nutritional status of tuberculosis (TB) patients who were human immunodeficiency virus (HIV)-seropositive with those who were seronegative, we carried out a cross-sectional anthropometric and biochemical assessment, together with bioelectrical impedance analysis (BIA) of the nutritional status of TB patients hospitalized in the Department of Internal Medicine, Bujumbura University Hospital, Burundi, East Africa. Of the 65 TB patients (33 pulmonary, 6 extrapulmonary, and 26 disseminated TB), 50 (76.9%) were HIV-seropositive (HIV+). When assessed according to anthropometric, BIA, and biochemical variables, HIV+ TB patients had more pronounced malnutrition than HIV- patients. Similar results were obtained when the comparison was restricted to patients with only pulmonary TB: HIV+ patients were more malnourished than HIV- patients. The results according to anthropometric measurements were: weight loss (13.5% of HIV- patients versus 26.4% of HIV+ patients, P = 0.005), body mass index (18.6 versus 15.1, P = 0.003), fat free mass (FFM) (13.9 versus 11.9, P < 0.01), and body fat (BF) (4.55 versus 3.71, P = 0.03) expressed per unit height2. BIA showed that the difference in FFM between HIV- and HIV+ TB pulmonary patients was mostly due to a decrease in body cellular mass. Measurements of albumin, prealbumin, and transferrin showed a marked decrease in all three markers in HIV+ TB pulmonary patients. The nutritional status of HIV+ patients with disseminated versus pulmonary TB was similar. The nutritional status of HIV+ TB patients is far worse than that of HIV- TB patients. In such patients, anthropometry underestimates the degree of malnutrition because it does not account for the water component of FFM. Nutritional status should be assessed and nutritional intervention should be provided in an attempt to improve the prognosis of TB patients, especially those who are infected by HIV.

Risk factors for negative sputum acid-fast bacilli smears in pulmonary tuberculosis: results from Dakar, Senegal, a city with low HIV seroprevalence.

SETTING: Two teaching hospitals in Dakar, Senegal, a West African country with a low prevalence of human immunodeficiency virus (HIV) infection. OBJECTIVE: To determine whether patients with HIV-associated pulmonary tuberculosis have fewer acid-fast bacilli (AFB) in their sputum as assessed by routine microscopy, and to correlate the findings with systematically obtained clinical, radiographic and laboratory variables. DESIGN: Prospective study from November 1995 to October 1996 of 450 consecutive patients diagnosed with pulmonary tuberculosis. RESULTS: Tuberculosis was diagnosed in 380 patients (84.4%) by positive bacteriology, in 61 (13.6%) by a favorable response to anti-tuberculosis chemotherapy, and in nine (2.0%) by the presence of a miliary radiographic pattern. Forty (8.9%) patients were HIV-seropositive. AFB-negative smears were found in 14/40 (35.0%) of the HIV-seropositive patients with pulmonary tuberculosis compared with 71/410 (17.3%) of the seronegative patients (risk ratio [RR] = 2.02, 95% confidence interval [CI] 1.26-3.24, P = 0.01). Multivariate analysis revealed that AFB smear negativity was associated with absence of cavitation (P = 0.002), lack of cough (P = 0.005), the presence of HIV seropositivity (P = 0.02), a CD4+ cell count above 200/mm3 (P = 0.02), and age over 40 years (P = 0.03). CONCLUSIONS: Compared with HIV-seronegative patients with pulmonary tuberculosis, seropositive patients in Dakar, Senegal, are more likely to have negative sputum-AFB smears. This phenomenon has now been observed in seven of eight sub-Saharan African countries with varying HIV seroprevalence from which reports are available.

Seroconversions in unvaccinated infants: further evidence for subclinical measles from vaccine trials in Niakhar, Senegal.

BACKGROUND: Increases in measles antibodies without rash-illnesses have been documented in previously vaccinated children exposed to measles cases. The phenomenon has been incompletely evaluated in young unvaccinated infants with immunity of maternal origin. METHODS: Monthly cohorts of newborns were prospectively randomized to vaccine and placebo control groups during a trial of high-titre vaccines in Niakhar, Senegal. Measles antibodies were assayed in blood samples of enrolled children collected at 5 months old, when controls received a placebo injection, and at 10 months, when the placebo group was given measles vaccine. Intensive prospective surveillance for measles was conducted throughout the trial. RESULTS: One-fifth (n = 53) of the placebo controls seroconverted, with known exposure to a measles case in only three of them. None of the seroconverters developed a measles-like rash. Sixteen-fold or greater increases in titres were noted in about one-quarter of them. Compared with placebo controls who did not seroconvert, seroconverters were more likely to have had exposure to a measles case and to travel, more likely to be boys than girls, and had significantly lower baseline antibody titres. Measles was endemic in the study area throughout the trial. Seroconversions did not adversely effect subsequent nutritional indices or mortality. CONCLUSIONS: Although laboratory errors and inadvertent injection of vaccine rather than placebo may have played some role, they do not fully explain the above observations, which are consistent with subclinical measles in the seroconverters. The possible role of subclinical measles in occult transmission, its potential effect on the type and duration of subsequent immunity, and its impact on response to primary vaccination need to be determined.

Role of schools in the transmission of measles in rural Senegal: implications for measles control in developing countries.

Patterns of measles transmission at school and at home were studied in 1995 in a rural area of Senegal with a high level of vaccination coverage. Among 209 case children with a median age of 8 years, there were no deaths, although the case fatality ratio has previously been 6-7% in this area. Forty percent of the case children had been vaccinated against measles; the proportion of vaccinated children was higher among secondary cases (47%) than among index cases (33%) (prevalence ratio = 1.36, 95% confidence interval (CI) 1.04-1.76). Vaccinated index cases may have been less infectious than unvaccinated index cases, since they produced fewer clinical cases among exposed children (relative risk = 0.55, 95% CI 0.29-1.04). The secondary attack rate was lower in the schools than in the homes (relative risk = 0.31, 95% CI 0.20-0.49). The school outbreaks were protracted, with 4-5 generations of cases being seen in the two larger schools. Vaccine efficacy was found to be 57% (95% CI -23 to 85) in the schools and 74% (95% CI 62-82) in the residential compounds. Measles infection resulted in a mean of 3.8 days of absenteeism per case, though this did not appear to have an impact on the children's grades. Among the index cases, 56% of children were probably infected by neighbors in the community, and 7% were probably infected at health centers, 13% outside the community, and 24% in one of the three schools which had outbreaks during the epidemic. However, most of the school-related cases occurred at the beginning and therefore contributed to the general propagation of the epidemic. To prevent school outbreaks, it may be necessary to require vaccination prior to school entry and to revaccinate children in individual schools upon detection of cases of measles. Multidose measles vaccination schedules will be necessary to control measles in developing countries.

Waning of vaccine-induced immunity: is it a problem in Africa?

PIP: Strebel et al. misinterpreted the authors' paper on the role of schools in measles transmission. As Strebel et al. noted, the main reason for the outbreak was low vaccine coverage among children aged 5-14 years, together with a marked reduction in the incidence of measles over the past 10 years. Because of the high measles vaccine coverage in younger age groups, many children in Niakhar have gone through their first 5 years of life without being infected with the measles virus. The waning of vaccine-induced immunity has played a role. Strebel et al. believe that there is no indication of waning immunity in the authors' paper and that there is a downward bias in vaccine efficacy due to faulty methodology. Their argument, however, misses the point. The children's ages at vaccination with standard vaccine were completely different in those age groups, with the median age being 295 days for those under age 5 years and 1017 days for those aged 10-14 years. Whether waning immunity will translate into declining vaccine efficacy with age depends upon whether misclassification of vaccination status and measles history is the same in all age groups. Other observations support the existence of waning immunity. The phenomenon of waning vaccine-induced immunity needs to be examined for measles and other vaccine-preventable diseases.^ieng

Effect of subclinical infection on maintaining immunity against measles in vaccinated children in West Africa.

BACKGROUND: Despite a high coverage with measles vaccines in parts of west Africa, epidemics of measles occur with reduced severity in an increasing proportion of older children who have been vaccinated. We examined the effect of exposure to natural measles on immunity in vaccinated children. METHODS: Our study was carried out in 1992 during an epidemic of measles in Niakhar, a rural area of Senegal with about 27,000 inhabitants who mostly live in compounds that include several households; within each household people live in different huts. Vaccine coverage in Niakhar was 81% at the time of our study. We measured haemagglutinin-inhibiting antibody at exposure and twice thereafter (after 4-5 weeks and at 6 months) in 36 vaccinated and 87 unvaccinated children. The frequency of measles and subclinical measles--defined as a four-fold or greater rise in antibody titre without clinical signs or symptoms--was related to intensity of exposure according to whether the index case was in the same hut, household, or compound. FINDINGS: Clinical measles occurred in 20 (56%) of 36 unvaccinated children and in one (1%) of 87 vaccinated children. Subclinical measles occurred in 39 (45%) of 86 vaccinated children who were exposed to measles and in four (25%) of 16 unvaccinated children. The frequency was inversely related to pre-exposure antibody concentration (p<0.001 for trend) and directly related to intensity of exposure (p=0.002 for trend). Antibody concentrations in subclinical cases increased on average by 45-fold and remained raised for at least 6 months. INTERPRETATION: Increased antibody titre after subclinical measles may be common in vaccinated children in West Africa where the intensity of exposure is high. As measles vaccination coverage increases, the circulation of wild measles will decrease, and vaccine-induced antibody is less likely to be boosted. Thus, new epidemics, albeit milder in form, may occur in vaccinated areas which should be recognised in campaigns to eradicate measles.

Increased long term mortality associated with rash after early measles vaccination in rural Senegal.

OBJECTIVES: To examine whether clinical symptoms, including rash, were more common after measles immunization compared with placebo and to study the association between postvaccination symptoms and later mortality. DESIGN: Examination of side effects in the 3 weeks after immunization in a trial of high titer and standard titer measles vaccines. PATIENTS: Two hundred twenty-four children randomly selected to be included in the surveillance for diarrhea, fever and rash. RESULTS: There was no difference in fever and diarrhea between recipients of high titer vaccines and recipients of placebo. However, high titer recipients tended to have more measles-like rashes than placebo recipients [relative risk, 2.12 (range, 0.90 to 5.03)]. Among recipients of high titer vaccines, children who presented a rash had higher mortality in the following 5 to 7 years than those who did not develop rash [mortality rate ratio, 3.85 (range, 1.52 to 9.79)]. High titer recipients without a rash had the same mortality as children in the placebo group who were given standard doses of measles vaccine at 10 months of age [mortality rate, 0.76 (range, 0.35 to 1.62)]. CONCLUSIONS: These observations suggest that in this particular study, rash after high titer measles vaccine may identify children who received a particularly high dose of vaccine or children with more severe and persistent postvaccination immunosuppression. Whether high titer vaccine is more likely than standard titer measles vaccine to provoke such reaction is not known, given that we did not compare side effects after different titers of measles vaccine. Future trials of live measles vaccine should monitor the development of rash.

Poor serologic responses five to seven years after immunization with high and standard titer measles vaccines.

BACKGROUND: Few data exist on the persistence of measles antibodies after vaccination of West African infants. Therefore we examined measles antibody titers 5 to 7 years after children in rural Senegal had received high titer Edmonston-Zagreb (EZ-HT), high titer Schwarz (SW-HT) or standard titer Schwarz (SW-STD) measles vaccines in infancy. METHODS: Children had received either high titer vaccines at 5 months of age or standard titer at 10 months of age. Finger prick blood samples were tested for measles antibody 5 to 7 years later by the hemagglutinin inhibition test. RESULTS: Persistence of antibody after high titer vaccines was poor with the result that 39 and 50% of the EZ-HT and the SW-HT groups had low titers of hemagglutinin inhibition measles antibodies (< or =125 mIU/ml). Nineteen percent of the children in the SW-STD group had low titers which is a lower prevalence than in the high titer groups [relative risk (95% confidence intervals), 0.05 (0.28 to 0.88) vs. EZ-HT; relative risk, 0.38 (0.22 to 0.66) vs. SW-HT]. Geometric mean (95% confidence interval) antibody titers in children with detectable values were 616 (435 to 871) in the EZ-HT, 1106 (616 to 1866) in the SW-HT and 1271 (871 to 1741) mIU/ml in the SW-STD groups, respectively. Multivariant regression analysis showed that mean titers were 2.00 (1.03 to 3.89) times higher for children with low prevaccination antibody titers (< or =125 mIU/ml) and 3.06 (1.90 to 4.94) times higher if blood was collected in the rainy season. INTERPRETATION: Given the rapid decline in antibody titers over a 5- to 6-year period in an area where measles vaccine coverage was high, it seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody concentrations (>125 mIU/ml) in West Africa. The role of subclinical boosting by exposure to natural measles and the possible role of malaria, which increases immunoglobulin turnover, in influencing long term antibody persistence after vaccination deserve further investigation.

Impact of chloroquine resistance on malaria mortality.

Over 12 years, from 1984 to 1995, we conducted a prospective study of overall and malaria specific mortality among three rural populations in the Sahel, savanna and forest areas of Senegal. The emergence of chloroquine resistance has been associated with a dramatic increase in malaria mortality in each of the studied populations. After the emergence of chloroquine resistance, the risk of malaria death among children 0-9 years old in the three populations was multiplied by 2.1, 2.5 and 5.5, respectively. This is the first study to document malaria mortality at the community level in Africa before and after the emergence of chloroquine resistance. Findings suggest that the spread of chloroquine resistance has had a dramatic impact on the level of malaria mortality in most epidemiological contexts in tropical Africa.

Acute and long-term changes in T-lymphocyte subsets in response to clinical and subclinical measles. A community study from rural Senegal.

To investigate the possibility of long-term suppression of T-lymphocyte subsets, we examined children exposed to measles at home during an epidemic in rural Senegal, at time of exposure and 1 and 6 months later. The measles case fatality ratio was 1%. Subclinical measles was common among vaccinated children exposed to measles (45%). Both clinical and subclinical cases of measles showed a significant rise in absolute CD4 count in the incubation period. In the prodromal phase and the first week after the rash, the lymphocyte percentage, the white blood cell count and the absolute CD4 cell numbers were significantly reduced. There was no persistent decrease of absolute CD4 or CD8 numbers at 1 or 6 months after exposure. Measles infection was followed by significant changes in the subset composition, both CD4 and CD8 percentages being significantly higher in the second month after measles than among non-seroresponders. These changes were more marked among girls, since they had significantly higher CD4 percentages and CD4/CD8 ratios than boys in the convalescence phase. In conclusion, measles infection is not associated with a long-term suppression of CD4+ or CD8+ T-lymphocytes.

[Prevention of viral hepatitis in travelers and expatriots in a tropical and subtropical environment]. / Prévention des hépatites virales chez les voyageurs et les expatriés en milieu tropical et subtropical.

Hepatitis A and B are hyperendemic in tropical and, to a lesser extent, subtropical countries. This high level of endemicity is in sharp contrast with the low frequency of these infections in the industrialized world. As a consequence, the incidences of hepatitis A and B are high among travellers to or foreigners living in tropical or subtropical countries. Therefore, these subjects should be vaccinated against hepatitis A and B. Furthermore, the usual preventive measures should be maintained. Risk of infection with the hepatitis C and E virus are much lower. Given the increasing number of travellers to tropical and subtropical countries, imported hepatitis is a public health problem for industrialized countries. Preventive measures must, then, be reinforced.

Nutritional status of HIV-seropositive subjects in an AIDS clinic in Paris.

OBJECTIVE: To measure the prevalence and analyse the characteristics of malnutrition among subjects attending an AIDS outpatient clinic and a day care center, to improve the nutritional management of HIV-infected subjects. DESIGN: Prospective cross-sectional study. SETTING: AIDS clinic in a University Hospital in Paris. SUBJECTS: 124 HIV-seropositive adults attending the clinic. MAIN OUTCOME MEASURES: Evaluation of nutritional status using anthropometry, impedancemetry, plasma albumin and pre-albumin assays. Degree of malnutrition, defined by the percentage of body weight loss (BWL), calculated by reference to the usual body weight. RESULTS: Among the 124 subjects recruited (M:F sex ratio: 3.3, mean age: 36.3 +/- 7.2 y), 77 (62.1%, 95%CI: 53.9-70.3) had normal nutrition status (BWL < or = 5%), 16 (12.9%, 95%CI: 7.0-18.2) moderate malnutrition (5% < BWL < or = 10%), 21 (16.9% 95%CI: 10.3-23.5) intermediate malnutrition (10% < BWL < or = 20%), and 10 (8.1%, 95%CI: 3.3-12.9) severe malnutrition (BWL > 20%). BWL was related to the CDC class (variance analysis, P < 9 x 10(-5)) and CD4 cell count (P < 3 x 10(-5)). Malnutrition was observed even among CDC class A subjects (14.9%). BWL was also related to the body mass index (P < 3 x 10(-6)), lean body mass (P < 3 x 10(-5)), body fat (P < 7 x 10(-6)), and as assessed by impedancemetry, body cell mass (P < 10(-5)) an the extra/intra cellular water ratio (P < 2 x 10(-4)). The decrease in lean body mass was related to the decrease in body cell mass. CONCLUSIONS: Given its high frequency, malnutrition should be prevented, detected, monitored and treated from the early stages of HIV infection among patients attending AIDS clinics in order to improve survival and quality of life.

Methods for diagnosing tuberculosis among in-patients in eastern Africa whose sputum smears are negative.

SETTING: Two University hospitals in Eastern African capital cities where large prospective studies had been carried out on hospitalized patients to determine the cause of their respiratory diseases. OBJECTIVE: To identify features that differentiated between tuberculosis (TB) and non-tuberculous respiratory disease (non-TB) in hospitalized patients from Bujumbura, Burundi (n = 111) and Dar es Salaam, Tanzania (n = 71) whose sputum smears were negative on microscopic examination for acid-fast bacilli (AFB). DESIGN: Review of clinical findings, radiologic abnormalities, and laboratory test results from 182 patients, first by univariate and then by multivariate (stepwise logistic regression) analysis to assess the contribution of each factor to the final diagnosis. RESULTS: Of the 182 patients with two or more negative AFB smears, 41 had TB and 141 had non-TB. Stepwise regression analysis revealed four easily ascertained symptoms were associated with TB: 1) cough > 21 days; 2) chest pain > 15 days; 3) absence of expectoration; and 4) absence of shortness of breath. Any two of the four diagnosed TB with 85% sensitivity and 67% specificity; any three of the four with 49% sensitivity and 86% specificity. Multivariate analysis showed that adding lymphadenopathy and hematocrit < 30% improved discrimination. CONCLUSION: This methodological approach provides a means for diagnosing TB among all AFB smear-negative hospitalized patients. In this setting, simple clinical symptoms alone are helpful. Similar studies are needed to develop a system for out-patient TB suspects.