Global Sickle Cell Disease Network
Small Study Group B Report from Benin Workshop
Infectious Diseases in Sickle Cell Disease Including Malaria and Bacterial Infections
Co-Chairs: Chifumbe Chintu (Zambia) and Jacques Elion (France)
The discussions focused on:
- Clinical diagnosis of malaria in patients with SCD
- Laboratory diagnosis of malaria
- Pneumococcal infections in patients with SCD
- Causes of febrile illnesses in patients with SCD
- Data on malaria infections in patients with SCD is needed to establish the role of malaria as a cause of febrile illness in children. As malaria is a significant cause of infant and under-five mortality, incidence studies have to include infants and younger children, so that the natural history of SCD can be more accurately charted from birth to adulthood.
- With the implementation of the Integrated Management of Childhood Illness (IMCI) in many parts of sub-Saharan Africa, every child with fever is treated as clinical malaria. This, inevitably, results in over-diagnosis of malaria infection. The introduction of the antigen-based Rapid Diagnostic Test (RDT) for the diagnosis of malaria provides opportunities to minimize this problem.
- As children with severe forms of malaria infections may die before they reach hospital, studies to ascertain the incidence of infections have to be performed in community settings.
- The study of malaria infections is complicated by the fact that transmission rates vary with each season (e.g. rainy or dry season). Community-based surveys will be necessary to document and measure malaria transmission rates especially in children.
- Since many children and adults have asymptomatic malarial parasitemia, is there a threshold level of parasitemia on which anti-malarial therapy should be based?
- Studies in Senegal, for example, have reported average malarial parasitemia of approximately 10% in children during the months of high transmission. These studies recommend malarial chemoprophylaxis, especially during the months of high transmission.
- There is considerable evidence that the protective effect of Hb S against malaria infections in heterozygous carriers may be limited only to infancy. The situation is even less clear with patients with homozygous S or other compound heterozygous SCD syndromes (SC, S β-thalassemia). Further research is needed to clarify the protective effect of SCD, if any, against severe forms of malaria infections.
While pneumococcal infections are important causes of morbidity and mortality in Africa, more evidence-based incidence studies are needed. In designing these studies, it is important to note that SCD patients with fulminant pneumococcal bacteremia may die before they reach hospital for confirmation.
Questions to be answered include:
- In Africa, are the strains of Streptococcus pneumoniae penicillin-sensitive?
- Do the available vaccines cover the spectrum of Streptococcus pneumoniae serotypes present in the communities?
- How can the limited availability of laboratory facilities for confirmatory diagnosis of invasive pneumococcal infections be overcome to enable the conduct of incidence/prevalence studies?
- What is the role of pneumococcal and other vaccines (e.g. Haemophilus influenza and hepatitis B) in tackling the problems of infections in patients with SCD?
- Thick smear microscopy is the gold standard for the laboratory diagnosis of malaria infection. However, this methodology does not lend itself for use in field or community-based studies.
- Antigen-based RDT kits in the form of dipsticks for malaria diagnosis have been used (e.g. in Tanzania and Zambia) and have been found to be cost-effective with low labor and maintenance costs. However, their reliability in these settings has not yet been fully tested. Dipsticks do not quantify parasitemia but are highly sensitive (can detect parasitemia of 500/mm3) and specific. Many public health programs (e.g. in India and Africa) employ dipsticks as a rapid diagnostic test for malaria in field studies.
- Quality control measures will be necessary to allow for comparison of diagnostic data in the context of future multi-centre international studies.
In Africa, laboratory facilities for the diagnosis of invasive pneumococcal infections are limited to a few major tertiary hospitals. This poses a major barrier in establishing the true incidence of invasive pneumococcal infections.
- The question was raised as to whether malarial chemoprophylaxis influences the course of SCD, and if so which drugs are effective?
- The protective role of G6PD deficiency against malaria infection was also discussed.
- Studies in Senegal report the use of intermittent malarial chemoprophylaxis for short spells of three months (during periods of high transmission), together with insecticide-treated bed nets. However, the impact of these interventions on the sub-group of individuals with SCD was not the focus of these studies
- In light of the dearth of strong evidence for its effectiveness, each region should determine if there is any need for malarial chemoprophylaxis in children with SC
- Regions that have demonstrated evidence of benefit (e.g. Nigeria, Cameroon and Senegal) should continue the use of chemoprophylactic agents such as proguanil and pyrimethamine. Chloroquine resistance in certain regions of Africa would make chloroquine unsuitable for chemoprophylaxis in those areas.
- Educational programs relating to prompt recognition of signs of infection and timely medical intervention are best executed in the context of neonatal screening programs
- The benefits of pneumococcal immunization and penicillin prophylaxis need to be explored. The fact that other bacterial infections may be more prevalent that pneumococcal, is no reason not to adopt these approaches as the goal is to minimize preventable infective morbidity and mortality.
- Mobilizing resources for more widespread use of insecticide-treated bed nets, as well as malarial chemoprophylaxis, would be beneficial especially during periods of high malaria transmission rates.