Serign J. Ceesay

Changes in malaria indices between 1999 and 2007 in The Gambia: a retrospective analysis

Summary Background Malaria is a major cause of morbidity and mortality in Africa. International effort and funding for control has been stepped up, with substantial increases from 2003 in the delivery of malaria interventions to pregnant women and children younger than 5 years in The Gambia. We investigated the changes in malaria indices in this country, and the causes and public-health significance of these changes. Methods We undertook a retrospective analysis of original records to establish numbers and proportions of malaria inpatients, deaths, and blood-slide examinations at one hospital over 9 years (January, 1999–December, 2007), and at four health facilities in three different administrative regions over 7 years (January, 2001–December, 2007). We obtained additional data from single sites for haemoglobin concentrations in paediatric admissions and for age distribution of malaria admissions. Findings From 2003 to 2007, at four sites with complete slide examination records, the proportions of malaria-positive slides decreased by 82% (3397/10861 in 2003 to 337/6142 in 2007), 85% (137/1259 to 6/368), 73% (3664/16932 to 666/11333), and 50% (1206/3304 to 336/1853). At three sites with complete admission records, the proportions of malaria admissions fell by 74% (435/2530 to 69/1531), 69% (797/2824 to 89/1032), and 27% (2204/4056 to 496/1251). Proportions of deaths attributed to malaria in two hospitals decreased by 100% (seven of 115 in 2003 to none of 117 in 2007) and 90% (22/122 in 2003 to one of 58 in 2007). Since 2004, mean haemoglobin concentrations for all-cause admissions increased by 12 g/L (85 g/L in 2000–04 to 97 g/L in 2005–07), and mean age of paediatric malaria admissions increased from 3·9 years (95% CI 3·7–4·0) to 5·6 years (5·0–6·2). Interpretation A large proportion of the malaria burden has been alleviated in The Gambia. Our results encourage consideration of a policy to eliminate malaria as a public-health problem, while emphasising the importance of accurate and continuous surveillance. Funding UK Medical Research Council.

Continued decline of malaria in The Gambia with implications for elimination.

Background A substantial decline in malaria was reported to have occurred over several years until 2007 in the western part of The Gambia, encouraging consideration of future elimination in this previously highly endemic region. Scale up of interventions has since increased with support from the Global Fund and other donors. Methodology/Principal Findings We continued to examine laboratory records at four health facilities previously studied and investigated six additional facilities for a 7 year period, adding data from 243,707 slide examinations, to determine trends throughout the country until the end of 2009. We actively detected infections in a community cohort of 800 children living in rural villages throughout the 2008 malaria season, and assayed serological changes in another rural population between 2006 and 2009. Proportions of malaria positive slides declined significantly at all of the 10 health facilities between 2003 (annual mean across all sites, 38.7%) and 2009 (annual mean, 7.9%). Statistical modelling of trends confirmed significant seasonality and decline over time at each facility. Slide positivity was lowest in 2009 at all sites, except two where lowest levels were observed in 2006. Mapping households of cases presenting at the latter sites in 2007–2009 indicated that these were not restricted to a few residual foci. Only 2.8% (22/800) of a rural cohort of children had a malaria episode in the 2008 season, and there was substantial serological decline between 2006 and 2009 in a separate rural area. Conclusions Malaria has continued to decline in The Gambia, as indicated by a downward trend in slide positivity at health facilities, and unprecedented low incidence and seroprevalence in community surveys. We recommend intensification of control interventions for several years to further reduce incidence, prior to considering an elimination programme.

Pilot trial of a pentavalent pneumococcal polysaccharide/protein conjugate vaccine in Gambian infants

BACKGROUND Invasive pneumococcal disease is a major cause of mortality and morbidity in young children in developing countries. Pneumococcal polysaccharide/protein conjugate vaccines, which are likely to be immunogenic in the very young, offer a potential way for preventing these infections. Therefore a pilot safety and immunogenicity study of a five-valent conjugate vaccine has been undertaken in an area of rural Africa where invasive pneumococcal disease is prevalent. METHODS Thirty Gambian infants were vaccinated with 3 doses of a five-valent pneumococcal conjugate vaccine containing 5 micrograms of type 6B, 14, 18, 19F and 23F polysaccharides conjugated to the diphtheria toxin mutant protein CRM197 at the ages of 2, 3 and 4 months; 30 infants received 2 doses at the ages of 2 and 4 months and 30 infants who received three doses of a Haemophilus influenzae type b vaccine acted as controls. Local and systemic reactions were recorded after vaccination and antibody titers were measured by an enzyme-linked immunosorbent assay. RESULTS No serious local or systemic reactions to vaccination were recorded. Antibody responses to each component of the vaccine were demonstrated. One month after immunization with three doses of vaccine, antibody titers were 3 to 11 times higher than before vaccination (postvaccination titers ranged from 2.49 micrograms/ml for type 19 polysaccharide to 7.59 micrograms/ml for type 14). Elevated titers were well-maintained during the subsequent 4 months. Three doses of vaccine induced higher titers than did two doses. Antibody titers increased 2- to 3-fold over the period of immunization in children who received H. influenzae type b vaccine. CONCLUSIONS A five-valent pneumococcal conjugate vaccine proved safe and immunogenic in Gambian infants. However, a vaccine containing a larger number of serotypes will be necessary to achieve a maximal clinical impact.

A Decline in the Incidence of Invasive Non-Typhoidal Salmonella Infection in the Gambia Temporally Associated with a Decline in Malaria Infection

Background Malaria is a risk factor for invasive non-typhoidal Salmonella (NTS) infection in children. In the last 10 years, indices of malaria infection in The Gambia have fallen substantially. Methods We compared temporal trends of childhood malaria and NTS infection in two Gambian locations. In Fajara, on the coast, the incidence of NTS infection at three time points between 1979 and 2005 was compared to the percentage of malaria positive outpatient thick blood films and the percentage of admissions associated with malaria over time. In Basse, in the eastern part of the country, the incidence of NTS infection at three time points between 1989 and 2008 was compared to the prevalence of malaria parasitaemia at four time points between 1992 and 2008. Results The estimated incidence of NTS infection in Fajara fell from 60 (1979–1984) to 10 (2003–05) cases per 100,000 person years. The proportion of outpatients in Fajara with suspected malaria who were parasitaemic fell from 33% (1999) to 6% (2007) while the proportion of admissions associated with malaria fell from 14.5% (1999) to 5% (2007). In Basse, the estimated incidence of NTS infection fell from 105 (1989–1991) to 29 (2008) cases per 100,000 person years while the prevalence of malaria parasitaemia fell from 45% (1992) to 10% (2008). The incidence of pneumococcal bacteraemia in Fajara and Basse did not fall over the study period. Conclusions These data support an association between malaria and NTS infection. Reductions in malaria infection may be associated with reduced rates of invasive childhood NTS infection.

Malaria in infants aged less than six months - is it an area of unmet medical need?

Despite the protection provided by several factors, including maternal antibodies, the burden of malaria in young infants may be higher than previously thought. Infants with congenital or neonatal malaria may have a different clinical presentation than older children, and diagnosis may be confused with other neonatal diseases due to an overlap of clinical manifestations. In addition, there is little information on the use of artemisinin-based combination therapy in young infants. There is the need for a more accurate estimate of the parasite prevalence and the incidence of clinical malaria in infants under 6 months old, as well as a better characterization of risk factors, pharmacokinetic profiles, safety and efficacy of currently available anti-malarial treatments, in order to develop evidence-based treatment guidelines for this population.

A qualitative study to assess community barriers to malaria mass drug administration trials in the Gambia

BackgroundMass drug administration (MDA) is a strategy widely used in the control of human parasitic diseases but has been rarely attempted with malaria, the most common and dangerous parasitic disease in humans. MDA is an intervention strategy that involves simultaneously dispensing treatment to an entire population in a given geographic area. With some areas in sub-Saharan Africa documenting a decline in malaria transmission, the feasibility of MDA to further reduce malaria transmission is being considered. Understanding community perceptions of such an activity is vitally important for the design of the study and gaining the support of participants in order to maximize compliance and adherence.MethodsA qualitative study to assess factors likely to influence community acceptance of MDA in the seasonal and low malaria transmission setting of The Gambia was conducted. Using in-depth interviews, the perceptions, knowledge and attitudes of medical personnel and community members who have undergone MDA trials in The Gambia were investigated.ResultsSeveral major themes emerged, namely: 1) the importance of timing of rounds of MDA doses for maximum participation; 2) the need to educate the target population with accurate information on the procedures, drug regimen, and possible side effects to enhance adherence; 3) the need for continuous sensitization meetings to maintain and increase uptake of MDA; and, 4) the importance for defining roles in the delivery and assessment of MDA, including existing healthcare structures.DiscussionTo increase the likelihood of participation in MDA trials in this setting, activities should be undertaken just before and during the rainy season when community members are less mobile. Importantly, fears regarding blood sampling and side effects of the drug regimen need to be addressed prior to the start of the trial and repeated throughout the study period. Accurate and frequent communication is essential, and village leaders should consistently be included in sensitization meetings to enhance community participation. Additionally, village healthcare workers should be included in training and implementation, with supervision by a fieldworker permanently posted in every few villages during the trial. Future collaboration with Senegal may prove important for enhanced elimination efforts in The Gambia.

Sahel, Savana, Riverine and Urban Malaria in West Africa: Similar Control Policies with Different Outcomes

The study sites for the West African ICEMR are in three countries (The Gambia, Senegal, Mali) and are located within 750 km of each other. In addition, the National Malaria Control Programmes of these countries have virtually identical policies: (1) Artemisinin Combination Therapies (ACTs) for the treatment of symptomatic Plasmodium falciparum infection, (2) Long-Lasting Insecticide-treated bed Nets (LLINs) to reduce the Entomololgic Inoculation Rate (EIR), and (3) sulfadoxine-pyrimethamine for the Intermittent Preventive Treatment of malaria during pregnancy (IPTp). However, the prevalence of P. falciparum malaria and the status of malaria control vary markedly across the four sites with differences in the duration of the transmission season (from 4-5 to 10-11 months), the intensity of transmission (with EIRs from unmeasurably low to 4-5 per person per month), multiplicity of infection (from a mean of 1.0 to means of 2-5) and the status of malaria control (from areas which have virtually no control to areas that are at the threshold of malaria elimination). The most important priority is the need to obtain comparable data on the population-based prevalence, incidence and transmission of malaria before new candidate interventions or combinations of interventions are introduced for malaria control.

Detecting Foci of Malaria Transmission with School Surveys: A Pilot Study in the Gambia

Background In areas of declining malaria transmission such as in The Gambia, the identification of malaria infected individuals becomes increasingly harder. School surveys may be used to identify foci of malaria transmission in the community. Methods The survey was carried out in May–June 2011, before the beginning of the malaria transmission season. Thirty two schools in the Upper River Region of The Gambia were selected with probability proportional to size; in each school approximately 100 children were randomly chosen for inclusion in the study. Each child had a finger prick blood sample collected for the determination of antimalarial antibodies by ELISA, malaria infection by microscopy and PCR, and for haemoglobin measurement. In addition, a simple questionnaire on socio-demographic variables and the use of insecticide-treated bed nets was completed. The cut-off for positivity for antimalarial antibodies was obtained using finite mixture models. The clustered nature of the data was taken into account in the analyses. Results A total of 3,277 children were included in the survey. The mean age was 10 years (SD = 2.7) [range 4–21], with males and females evenly distributed. The prevalence of malaria infection as determined by PCR was 13.6% (426/3124) [95% CI = 12.2–16.3] with marked variation between schools (range 3–25%, p<0.001), while the seroprevalence was 7.8% (234/2994) [95%CI = 6.4–9.8] for MSP119, 11.6% (364/2997) [95%CI = 9.4–14.5] for MSP2, and 20.0% (593/2973) [95% CI = 16.5–23.2) for AMA1. The prevalence of all the three antimalarial antibodies positive was 2.7% (79/2920). Conclusions This survey shows that malaria prevalence and seroprevalence before the transmission season were highly heterogeneous.

Improving malaria control in West Africa: interruption of transmission as a paradigm shift.

With the paradigm shift from the reduction of morbidity and mortality to the interruption of transmission, the focus of malaria control broadens from symptomatic infections in children ≤5 years of age to include asymptomatic infections in older children and adults. In addition, as control efforts intensify and the number of interventions increases, there will be decreases in prevalence, incidence and transmission with additional decreases in morbidity and mortality. Expected secondary consequences of these changes include upward shifts in the peak ages for infection (parasitemia) and disease, increases in the ages for acquisition of antiparasite humoral and cellular immune responses and increases in false-negative blood smears and rapid diagnostic tests. Strategies to monitor these changes must include: (1) studies of the entire population (that are not restricted to children ≤5 or ≤10 years of age), (2) study sites in both cities and rural areas (because of increasing urbanization across sub-Saharan Africa) and (3) innovative strategies for surveillance as the prevalence of infection decreases and the frequency of false-negative smears and rapid diagnostic tests increases.

Malaria Prevalence among Young Infants in Different Transmission Settings, Africa.

Preventive measures and treatment guidelines are needed to address the sizeable prevalence of disease in this population.