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

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.     

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.     

Molecular characteristics and susceptibility to antibiotics of serogroup A Neisseria meningitidis strains isolated in Senegal in 1999

A total of 22 strains of Neisseria meningitidis isolated from cerebrospinal fluid samples of patients in Dakar, Senegal, in the course of an epidemic of meningococcal meningitis in 1999 were studied. All the strains were serogroup A, serotype 21:P1.9 and belonged to clonal subgroup III-1. The strains were resistant to sulphonamide, but were susceptible to ampicillin, ceftriaxone and chloramphenicol, which are used in the treatment of cerebrospinal meningitis in Senegal.     

Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon

BACKGROUND: The development of novel artemisinin-combination therapies suitable for the treatment of pediatric patients suffering from malaria is a research priority. The aim of this study was to investigate a novel fixed-dose pyronaridine-artesunate combination for the treatment of uncomplicated falciparum malaria in Gabonese patients 2-14 years old. METHODS: The study was designed as an open-label dose-escalation study recruiting 60 pediatric patients sequentially in 4 treatment cohorts: study drugs were administered once daily for 3 days, as tablet coformulations (pyronaridine:artesunate ratios of 6:2, 9:3, and 12:4 mg/kg) and as a granule coformulation (pyronaridine:artesunate ratio of 9:3 mg/kg). The primary end points were tolerability, safety, and pharmacokinetics of pyronaridine-artesunate treatment. Efficacy was treated as a secondary outcome measure. RESULTS: The drugs had a good tolerability and safety profile, at all dose levels. Pharmacokinetic analysis revealed a dose-dependent increase in the maximum plasma/blood concentration and the area under the curve, as well as comparable relative bioavailability for the granule coformulation. Polymerase chain reaction-corrected cure rates at day 28 were 100% in per-protocol analysis, at all dose levels. CONCLUSIONS: Pyronaridine-artesunate is a promising novel artemisinin-combination therapy for pediatric patients with uncomplicated Plasmodium falciparum malaria, and the development of both the tablet and the granule coformulations is warranted.     

Impact of intermittent preventive anti-malarial treatment on the growth and nutritional status of preschool children in rural Senegal (west Africa)

Negative consequences of malaria might account for seasonality in nutritional status in children in the Sahel. We report the impact of a randomized, double-blind, placebo-controlled trial of seasonal intermittent preventive anti-malarial treatment on growth and nutritional status in 1,063 Senegalese preschool children. A combination of artesunate and sulfadoxine-pyrimethamine was given monthly from September to November. In the intervention arm, mean weight gain was significantly greater (122.9 +/- 340 versus 42.9 +/- 344 [SD] g/mo, P < 0.0001) and losses in triceps and subscapular skinfold measurements were less (-0.39 +/- 1.01 versus -0.66 +/- 1.01 mm/mo, and -0.15 +/- 0.64 versus -0.36 +/- 0.62 mm/mo, respectively, P < 0.0001 for both). There was no difference in height increments. The prevalence of wasting increased significantly in the control arm (4.6% before versus 9.5% after, P < 0.0001), but remained constant in intervention children: 5.6% versus 7.0% (P = 0.62). The prevention of malaria would improve child nutritional status in areas with seasonal transmission.     

Tuberculosis-associated severe CD4+ T-lymphocytopenia in HIV-seronegative patients from Dakar. SIDAK Research Group

OBJECTIVES: To determine the frequency and associated features of severe CD4+ T-lymphocytopenia (<300 cells/mm(3)) in HIV-seronegative patients with tuberculosis. METHODS: Statistical analysis of 430 consecutively enrolled HIV-seronegative inpatients with tuberculosis in two teaching hospitals in Dakar, Senegal. RESULTS: The mean CD4 + cell count was 602+/-318.3 cells/mm(3). CD4 + cell counts were below 300 cells/mm(3)in 62 patients (14.4%). Patients with fewer than 300 CD4+ cells/mm(3)differed from those with higher counts in being less likely to have a positive smear for acid-fast bacilli; in having a higher frequency of extrapulmonary involvement (pleural effusion, adenopathy and miliary disease) and oral candidiasis; and in having smaller tuberculin reactions, lower haemoglobin levels, less cavitation and less patchy infiltration. After adjustment for gender and age, all differences remained except miliary disease. CONCLUSIONS: A substantial percentage (14.4%) of HIV-seronegative hospitalized patients for tuberculosis in a West African country presented with severe CD4 + T-lymphocyte depletion and had clinical and radiographic features indicative of more advanced disease and accompanying immunodepression. These results and those already published suggest that tuberculosis should be regarded as one of the diseases associated with a subgroup of patients with "idiopathic CD4 + T-lymphocytopenia".