Uptake and usage of proguanil as malaria chemoprophylaxis and the socio-economic determinants of proguanil usage in children with sickle cell anemia in Benin City.

Background: Proguanil is currently the recommended drug used for malaria chemoprophylaxis in children with Sickle cell anaemia (SCA). Aims: This study aims to determine the uptake and usage of proguanil as malaria chemoprophylaxis and the socioeconomic determinants of its usage in children aged 6-59 months. This was a descriptive cross-sectional study carried out in two major sickle cell clinics in Benin City, Edo state, Nigeria. A total of 420 participants were interviewed using semistructured questionnaires. Patients and Methods: Descriptive, bivariate, and multivariate analysis of quantitative data were done using SPSS version 21. Results: The uptake of proguanil among study participants was 67.4%; of these number, 268 (94.7%) reported daily use of proguanil. Only 3 (0.7%) used pyrimethamine as chemoprophylaxis, while 134 (31.9%) used no form of malaria chemoprophylaxis. Having mothers with higher level of education (LOE) (P = 0.013, odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.15-3.17), attending clinic at the University of Benin Teaching Hospital (UBTH) (P = 0.044, OR = 2.15, 95% CI = 1.02-4.54), older age group (36-59 months) (P = 0.015, OR = 1.67, 95% CI = 1.11-2.51), and owning insecticide-treated net (ITN) (P = 0.000, OR = 3.11, 95% CI = 1.98-4.88) were significant positive predictors for the usage of proguanil. Conclusion: Proguanil uptake was low. Attending sickle-cell clinic at UBTH, having mothers with tertiary LOE, and owning ITN were social factors associated with high usage of proguanil amongst children with SCA. Continuous monitoring and evaluation of the uptake and usage of proguanil in children is important, so as to aid policy implementation and review.

Prevalence of Molecular Markers of Plasmodium Falciparum Resistance to Proguanil and Pyrimethamine in Children with Haemoglobin Phenotypes SS and AA in Benin City, Nigeria.

BACKGROUND: Chemoprophylaxis against Plasmodium falciparum (Pf) is advocated in children with sickle cell anaemia (SCA). Among them, antifolates: proguanil and pyrimethamine had replaced initial chemoprophylactic drugs because of widespread resistance. In recent past, efficacy of these antifolates has also come under scrutiny due to increasing level of drug resistance. Specific point mutations on Plasmodium falciparum dihydrofolate reductase gene (pfdhfr) have been linked with resistance to proguanil and pyrimethamine and they can be used as markers in monitoring prevalence and level of resistance to the drugs. OBJECTIVES: To determine the prevalence of molecular markers of Plasmodium falciparum resistance to proguanil and pyrimethamine in children with SCA. METHODS: A total of 146 Plasmodium falciparum isolates (71 from children with SCA and 75 from those with Haemoglobin AA: HbAA) were evaluated for point mutations and mutant haplotypes on the pfdhfr gene using nested polymerase chain reaction amplification followed by direct sequencing. RESULTS: The triple (S108N+N51I+C59N) mutant haplotype was present in 100.0% and 96.0% of samples from children with SCA and HbAA respectively. S108T, A16V and 1164L mutationswere not present in both groups. CONCLUSION: High prevalence of triple mutant haplotype mediates significant resistance to pyrimethamine and implies that pyrimethamine resistance is fixed in the study locale. However, the absence of pfdhfr S108T and A16V mutations, which indicate specific resistance to proguanil but not to pyrimethamine, suggests that proguanil is still useful even in the face of pyrimethamine resistance. The threat of proguanil resistance is however real due to high prevalence of the triple mutant pfdhfr haplotype.

CONTEXTE: La chimioprophylaxie contre Plasmodium falciparum (Pf) est préconisée chez les enfants atteints de drépanocytose. (DCA). Parmi eux, les antifoliques : proguanil et pyriméthamine ont remplacé les médicaments chimioprophylactiques initiaux en raison d'une résistance généralisée. Ces derniers temps, l'efficacité de ces antifoliques a également été remise en question en raison de l'augmentation de la résistance aux médicaments. Des mutations ponctuelles spécifiques sur le dihydrofolate de Plasmodium falciparum dihydrofolate réductase (pfdhfr) ont été associées à la résistance au proguanil et à l'antifongiqueet elles peuvent être comme marqueurs pour surveiller la prévalence et le niveau de la résistance à ces médicaments. OBJECTIFS: Déterminer la prévalence des marqueurs moléculaires de la résistance de Plasmodium falciparum au proguanil et à la pyriméthamine chez les enfants atteints d'ACS. MÉTHODES: Un total de 146 isolats de Plasmodium falciparum (71 falciparum (71 provenant d'enfants atteints d'ACS et 75 d'enfants présentant une hémoglobine AA : HbAA) ont été évalués pour détecter des mutations ponctuelles et des haplotypes mutants sur le gène pfdhfr en utilisant une amplification en chaîne par réaction en chaîne par polymérase nichée suivie d'un séquençage direct. RÉSULTATS: L'haplotype mutant triple (S108N+N51I+C59N) était présent chez 100,0 % et 96 % des patients.était présent dans 100,0 % et 96,0 % des échantillons provenant d'enfants atteints de SCA et HbAA respectivement. Les mutations S108T, A16V et 1164L n'étaient pas présentes dans les deux groupes. CONCLUSION: La prévalence élevée de l'haplotype triple mutant est à l'origine d'une résistance significative à la pyriméthamine et à l'HbA une résistance significative à la pyriméthamine et implique que la résistance à la pyriméthamine est fixe dans le groupe pyriméthamine et implique que la résistance à la pyriméthamine est fixe dans la région étudiée. Cependant, l'absence des mutations S108T et A16V de pfdhfr, qui indiquent une résistance une résistance spécifique au proguanil mais pas à la pyriméthamine, suggère que le proguanil reste utile même en cas de résistance à la pyriméthamine résistance à la pyriméthamine. La menace de la résistance au proguanil est cependant réelle en raison de la prévalence élevée de l'haplotype triple mutant pfdhfr haplotype.

Implementing Comprehensive Health Care Management for Sickle Cell Disease in an African Setting

Sickle cell disease is the commonest single gene disease in Africa. Morbidity and mortality from this disease has remained unacceptably high in Africa whereas there has been a marked reduction in the burden of this disease in the developed countries. This reduction was not achieved through the use of sophisticated care such as bone marrow transplant; but through the adoption of a Comprehensive Health Care Management protocol for sickle cell disease. This protocol of care emphasizes prevention of crises through effective management of the disease. In Africa; where sickle cell disease is prevalent; this strategy of care is yet to be globally adopted. In 2003; this protocol of care was adopted at the University of Benin Teaching Hospital; Nigeria and this has contributed to the improved clinical status of children with sickle cell disease in the hospital. The mortality rate among children with sickle cell disease has reduced to 1.3%; requirement for recurrent blood transfusion has reduced to about 2%; and their nutritional status has improved: 75.9% have normal nutritional status while 7% are actually overweight. The frequency of bone pain crisis has reduced to about one in every two years and some of the patients have been crisisfree for as long as five years. Hydroxyurea is not routinely used for our patients so this cannot explain the marked improvement recorded. In conclusion; comprehensive health care; adapted to our setting is a very cheap and effective way of managing sickle cell disease. It can be utilized in all health facilities for the care of children with sickle cell disease and is capable of reducing the morbidity and mortality associated with the disease as well as improving their quality of life

Newborn screening for sickle cell disease in a Nigerian hospital.

UNLABELLED: Sickle cell disease (SCD) is the most common genetic disorder to affect Blacks. The mortality rate associated with SCD has remained high despite the use of appropriate interventions to manage the various forms of crisis. In developed countries, newborn screening programmes are conducted routinely, which has resulted in a reduction in the SCD mortality rate from 16% to <1%. In developing countries where the disease is prevalent, newborn screening programmes are yet to be established, and the acceptability of such programmes by the parents of newly delivered infants is unknown. OBJECTIVES: This study was carried out to determine the acceptability of newborn screening for SCD on mothers of newly delivered infants, and to establish disease prevalence amongst a newborn population in Nigeria. STUDY DESIGN: This prospective cross-sectional study was conducted at St. Philomena's Hospital, Benin City with mothers of newly delivered infants and their newborn babies. METHODS: Newly delivered mothers were recruited consecutively into the study. Knowledge of their own haemoglobin phenotype status was assessed, and their wishes regarding SCD screening of their babies were determined. Babies were screened using isofocusing electrophoresis. RESULTS: Six hundred and thirty mothers, delivered of 649 babies, were recruited into this study. Nineteen sets of babies were twins. Two mothers refused screening for their babies and 628 mothers or caregivers accepted screening; hence the acceptance rate was 99.7%. Four hundred and fifty-seven (71%) mothers did not know their own haemoglobin phenotype. Six hundred and forty-seven babies were screened for SCD. Of these, two samples were lost to testing and one baby had an indeterminate result; these three cases were not included in the analysis. Of the 644 babies whose results were analysed, 332 (51.6%) were male, 312 (48.4%) were female, 485 (75.3%) were AA, 133 (20.6%) were AS, seven (1.1%) were AC, 18 (2.8%) were SS, and one (0.2%) was SC. CONCLUSION: The majority of mothers in this study did not know their haemoglobin phenotype. Newborn screening for SCD was acceptable to 99.7% of the mothers. The prevalence of SCD in the newborn population was 3% (2.8% SS and 0.2% SC).