Badara Samb

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.

Non-specific beneficial effect of measles immunisation: analysis of mortality studies from developing countries

Abstract Objective: To examine whether the reduction in mortality after standard titre measles immunisation in developing countries can be explained simply by the prevention of acute measles and its long term consequences. Design: An analysis of all studies comparing mortality of unimmunised children and children immunised with standard titre measles vaccine in developing countries. Studies: 10 cohort and two case-control studies from Bangladesh, Benin, Burundi, Guinea-Bissau, Haiti, Senegal, and Zaire. Main outcome measures: Protective efficacy of standard titre measles immunisation against all cause mortality. Extent to which difference in mortality between immunised and unimmunised children could be explained by prevention of measles disease. Results: Protective efficacy against death after measles immunisation ranged from 30% to 86%. Efficacy was highest in the studies with short follow up and when children were immunised in infancy (range 44-100%). Vaccine efficacy against death was much greater than the proportion of deaths attributed to acute measles disease. In four studies from Guinea-Bissau, Senegal, and Burundi vaccine efficacy against death remained almost unchanged when cases of measles were excluded from the analysis. Diphtheria-tetanus-pertussis and polio vaccinations were not associated with reduction in mortality. Conclusion: These observations suggest that standard titre measles vaccine may confer a beneficial effect which is unrelated to the specific protection against measles disease.

Morbidity and Mortality in South African Gold Miners: Impact of Untreated Disease Due to Human Immunodeficiency Virus

A cohort of 1792 human immunodeficiency virus (HIV)-positive and 2970 HIV-negative South African miners was observed for 12 months starting in February 1998. All-cause hospitalizations and deaths were significantly associated with HIV infection (respective unadjusted incidence rate ratios, 2.9 and 9.2; respective 95% confidence intervals, 2.5-3.4 and 5.5-16.0). Tuberculosis (TB), bacterial pneumonia, cryptococcosis, and trauma were the major causes of admission for HIV-positive patients, whereas Pneumocystis carinii pneumonia was an uncommon cause (respective admission rates, 8.5, 6.9, 2.2, 6.0, and 0.53 admissions per 100 person-years). Enteritis, bronchitis, urinary tract infections, and soft-tissue infections were also significantly associated with HIV infection. Cryptococcosis caused 44% of deaths among HIV-positive patients. Trauma was the main hazard for HIV-negative men, causing 42% of admissions and 60% of deaths. A broad range of infectious conditions is significantly associated with HIV infection in South African miners. Identification and implementation of effective prophylactic regimens are urgently needed.

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.

Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: reanalysis of West African studies

BACKGROUND Females given high-titre measles vaccine (HTMV) have high mortality; diphtheria-tetanus-pertussis (DTP) vaccination might be associated with increased female mortality. We aimed to assess whether DTP or inactivated poliovirus (IPV) administered after HTMV was associated with increased female-male mortality ratio. METHODS In three trials from West Africa, 2000 children were randomised to HTMV or control vaccine at 4-5 months of age; a second vaccination was given at age 9-10 months (standard measles vaccine). Children in high-titre groups were given IPV or DTP-IPV. Another 944 children received HTMV as routine vaccination in Senegal. FINDINGS When we compared high-titre and control groups, no difference in mortality between the first and the second vaccination was noted. After the second vaccination, the female-male mortality ratio was 1.84 (95% CI 1.19-2.84) in children in the high-titre groups who received DTP-IPV or IPV, and 0.59 (0.34-1.04) in controls who received standard measles vaccine (p=0.007). Children who received HTMV but no additional DTP-IPV or IPV had a female-male mortality ratio of 0.83 (0.41-1.67). This ratio was 2.22 (1.04-4.71) for children who received DTP-IPV after routine HTMV and 1.00 (0.68-1.47) for those who did not. When we combined the results from all trials, the female-male mortality ratio was 1.93 (1.33-2.81) for those who received DTP or IPV after HTMV, and 0.96 (0.69-1.34) for those who did not (p=0.006). INTERPRETATION A change in sequence of vaccinations, rather than HTMV itself, may have been the cause of increased female mortality in these trials.

Serologic status and measles attack rates among vaccinated and unvaccinated children in rural Senegal

During a measles vaccine trial in a rural area of Senegal, antibody status was examined within 10 days of exposure for 228 previously vaccinated and 313 unvaccinated children more than 12 months old who were exposed to measles at home. Thirty-six percent of the children developed clinical measles, the clinical diagnosis being confirmed for 135 of the 137 children from whom 2 blood samples were collected. Vaccine efficacy was 90% (95% confidence interval, 83 to 94%). The hemagglutinin-inhibiting antibodies (HI) or plaque neutralizing antibodies (PN) assays were equally efficient in predicting susceptibility and protection against measles. Vaccinated children who had no detectable HI or PN antibodies at exposure had significant protection against measles compared with seronegative unvaccinated children (HI vaccine efficacy, 49% (95% confidence interval, 21 to 68%); PN vaccine efficacy, 43% (95% confidence interval, 12 to 62%)). The attack rate was high for children with a titer of 40 to 125 mIU) 67% (4 of 6) of those with a positive hemagglutinin-inhibiting antibody test and 36% (13 of 36) of those with a positive PN test developed measles. Attack rates among children with HI or PN titers above 125 mIU were 2% (6 of 295) and 3% (7 of 258), respectively. Because titers of ≥120 mIU have been found to offer little protection in another study, this antibody level may be the best screening value for assessing susceptibility and protection against measles. However, it should be noted that many seronegative vaccinated children are protected against measles infection.

Can the deployment of community health workers for the delivery of HIV services represent an effective and sustainable response to health workforce shortages? Results of a multicountry study.

In countries severely affected by HIV/AIDS, shortages of health workers present a major obstacle to scaling up HIV services. Adopting a task shifting approach for the deployment of community health workers (CHWs) represents one strategy for rapid expansion of the health workforce. This study aimed to evaluate the contribution of CHWs with a focus on identifying the critical elements of an enabling environment that can ensure they provide quality services in a manner that is sustainable.The method of work included a collection of primary data in five countries: Brazil, Ethiopia, Malawi, Namibia, and Uganda.The findings show that delegation of specific tasks to cadres of CHWs with limited training can increase access to HIV services, particularly in rural areas and among underserved communities, and can improve the quality of care for HIV. There is also evidence that CHWs can make a significant contribution to the delivery of a wide range of other health services.The findings also show that certain conditions must be observed if CHWs are to contribute to well-functioning and sustainable service delivery. These conditions involve adequate systems integration with significant attention to: political will and commitment; collaborative planning; definition of scope of practice; selection and educational requirements; registration, licensure and certification; recruitment and deployment; adequate and sustainable remuneration; mentoring and supervision including referral system; career path and continuous education; performance evaluation; supply of equipment and commodities.The study concludes that, where there is the necessary support, the potential contribution of CHWs can be optimized and represents a valuable addition to the urgent expansion of human resources for health, and to universal coverage of HIV services.

Ordinary and Opportunistic Enteropathogens Associated with Diarrhea in Senegalese Adults in Relation to Human Immunodeficiency Virus Serostatus

Abstract 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 immunodeficieny 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, GIvl1-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 HIV− 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.

Use of antiretroviral therapy in resource-limited countries in 2006: distribution and uptake of first- and second-line regimens

Objective: To address the information gap on current use of antiretroviral drugs (ARTs) in developing countries. Methods: The AIDS Medicines and Diagnostics Service of the World Health Organization (WHO) carried out a multi-country survey in early 2006. Questionnaires covered the use of first- and second-line regimens in adults and children, and the rates of switching from first-line to second-line regimen. Weighted percentages of use of ARTs across the cohort of adults and children were calculated and correlated with 2006 WHO guidelines. A second analysis compared demand for ARTs with rates of production of active pharmaceutical ingredients. Results: Twenty-three countries (96%) returned the questionnaires, representing 53% of relevant patients in developing countries as of June 2006, and comprising 92% adults and 8% children receiving ARTs. Response rates were highest for questions regarding first-line use and lowest for those regarding pediatric regimens. The distribution of first-line: second-line use was 96%: 4% among adults and 99%: 1% among children. For adults, 95% of those receiving first-line treatment, but only 25% of those receiving second-line treatment, were on regimens consistent with those preferred by the WHO. Among first-line users, the most common regimen (61%) was stavudine+lamivudine+nevirapine. Among second-line users, abacavir+didanosine+lopinavir/ritonavir was the most common regimen (24%). Among children, compliance with WHO guidelines was high among the respondents, with zidovudine+lamivudine+nevirapine reported as the main option. Estimates of first-year switching rate were highly variable, ranging from 1% to 15%, with only ten responses. Comparison of supply and demand showed that the stated production capacity for active pharmaceutical ingredients is sufficient to meet current demands for ARTs. Conclusion: This survey has provided valuable information on the uptake of ARTs in developing countries and will help forecast future demand. Reporting for second-line and pediatric antiretroviral therapy should improve as national programs gain more experience. The current availability of active pharmaceutical ingredients appears to be sufficient to meet current demand. Further work is needed for an understanding of switching rates.

Epidemiological and molecular characteristics of HIV infection in Gabon, 1986-1994.

OBJECTIVE To describe trends in the prevalence of HIV-1 infection in different populations in Gabon, and the molecular characteristics of circulating HIV strains. METHODS Data were collected on HIV prevalence through sentinel surveillance surveys in different populations in Libreville (the capital) and in Franceville. In Libreville, a total of 7082 individuals (hospitalized patients, tuberculosis patients, pregnant women, asymptomatic adults, prisoners) were recruited between 1986 and 1994. In Franceville, we tested 771 pregnant women and 886 healthy asymptomatic adults (1986-1988). Sera were screened for HIV antibodies by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot or line immunoassay (LIA). Reactive samples in ELISA were tested for the presence of antibodies to HIV-1 group O viruses by ELISA using V3 peptides from HIV-1 ANT-70 and HIV-1 MVP-5180 followed by confirmation by LIA and a specific Western blot. Seventeen HIV-1 strains were isolated (1988-1993) and a 900 base-pair fragment encoding the env region containing V3, V4, V5 and beginning of gp41 was sequenced and a phylogenetic tree was constructed. RESULTS HIV prevalence was relatively low and remained stable (0.7-1.6% in pregnant women, 2.1-2.2% in the general population). The prevalence was also stable among prisoners (2.1-2.6%). Among hospitalized and tuberculosis patients prevalence was higher and increased (1.8-12.7% and 1.5-16.2%, respectively). Only three sera had antibodies to HIV-1 group O. The 17 HIV-1 strains represent six different genetic subtypes including type O. CONCLUSION Our data from 1986 to 1994 show a stable and low HIV prevalence in Gabon, and a high genetic diversity of HIV-1 strains. This, also observed in Cameroon, is in contrast to that found elsewhere in Africa. Differences in rate of spread of HIV infection are probably explained by interplay between numerous factors. The role of different HIV subtypes in the dynamics of the HIV epidemic should be examined further.