Antimalarial drugs resistance genes of Plasmodium falciparum: a review.

Malaria remains the most common parasitic disease on the planet, with 229 million cases and 409,000 deaths worldwide in 2019, including 274,030 children under the age of 5. It is one of the most important infectious diseases in the world and its control is compromised by the spread of the parasite's resistance to antimalarial drugs. This study aims to review the literature of resistant Plasmodium falciparum genes over the past twenty years. One hundred and five (105) articles were collected and read while the resistance of P. falciparum was being studied. Several P. falciparum gene resistances antimalarial drugs were discovered over the past twenty years. The most recent one is the Kelch13 gene of P. falciparum (Pfkelch13) which has showed resistance to artemisinin in Asia. In Africa, this gene represents a potential candidate for resistance to artemisinin, although no resistance was reported.

Mastomys natalensis, Cricetomys gambianus and Taterillus sp. were found PCR positive for Leishmania major in Burkina Faso, West Africa.

Ouagadougou, the capital city of Burkina Faso, was recognized as a focus of zoonotic cutaneous leishmaniosis in April 2000. Leishmania major was the only strain isolated in this focus. We conducted a prospective study to detect L. major in rodents, animals which are described as reservoir of the parasite. Rodents were caught in five city areas from November 2005 to October 2006. Giemsa stained smears were realized from the cutaneous lesions when present after macroscopic examination of external lesions. The spleen of each rodent was sterilely removed and split into 3 parts for microscopic examination of smears, culture on NNN media and PCR, respectively. A total of 101 rodents belonging to 9 genera were trapped. All the direct examinations and cultures were negative. By using PCR of lesions and spleen samples, three animals were found infected by L. major: one out of 24 (4.2%) Mastomys natalensis; one out of 8 (12.5%) Taterillus sp. and one out of three Cricetomys gambianus. This is the first detection of L. major in rodent species in Burkina Faso. Further studies are needed to confirm their role as reservoirs of L. major.

High concordance of Pfdhfr and Pfdhps genotypes between matched peripheral and placental isolates of delivered women in Bobo-Dioulasso, Burkina Faso

Whether maternal peripheral parasites constitute a representative sample of the overall population infecting the individual, remains unknown in Burkina Faso. We therefore compared Pfdhfr and Pfdhps genotypes between matched peripheral and placental isolates. PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of polymorphic codons of the Pfdhfr gene (51, 59, 108 and 164) and the Pfdhps gene (437 and 540) was performed in 18 matched peripheral and placental dried blood spots of delivered women in Bobo-Dioulasso. Both Pfdhfr and Pfdhps genes were successfully genotyped in 94.4% (17/18) of the matched samples. Only 8.8% (3/34) of genotypes were of the wild type, while 20.6% (7/34), 20.6% (7/34), 23.5% (8/34) and 26.5% (9/34) comprised one, two, three and four mutations, respectively. None of the samples carried both Pfdhfr I164L and Pfdhps K540E mutations. A concordance of 82.4% was observed in matched samples for both the Pfdhfr and Pfdhps genes. Setting placental alleles as the reference, a concordance of 100% was obtained with Pfdhfr mutation S108N, Pfdhfr mutation C59R+S108N, and Pfdhfr mutation N51I+C59R +S108N, respectively. Likewise, a concordance of 85.7% was observed with the Pfdhps mutation A437G. For epidemiological purposes, peripheral blood Pfdhfr and Pfdhps genotyping is sufficient for monitoring SP resistant molecular markers in pregnant women.

Seroprevalence and risk factors of Toxoplasma gondii infection in pregnant women from Bobo Dioulasso, Burkina Faso.

BACKGROUND: Toxoplasmosis is one of the common worldwide parasitic zoonosis due to Toxoplasma gondii (T. gondii). Toxoplasmosis during pregnancy can result in fetal and neonatal death or various congenital defects. The aim of this study was to assess the seroprevalence and risk factors of T. gondii infection in pregnant women following antenatal care (ANC) services at Bobo Dioulasso. METHODS: A cross-sectional study was conducted enrolling a sample of 316 pregnant women attending ANC at centers for maternal and child health of Bobo-Dioulasso town from March 2013 to February 2014. Data on socio-demographic and potential risk factors were collected from each study participant using structured questionnaire through face-to-face interview. Moreover, venous blood specimens were collected and tested for IgM and IgG anti-T. gondii antibodies by enzyme-linked immunosorbent assay and enzyme linked fluorescent assay, respectively. Multivariable logistic regression modeling was used to identify the potential predictor variables for T. gondii infection. RESULTS: The overall seroprevalence for T. gondii infection was 31.1% (98/316). All the pregnant women were positive for IgG anti-bodies exclusively. Multivariable logistic regression analysis showed that having at least a secondary education level (AOR = 2.23; 95% CI: [1.04-4.63]); being urban resident (AOR = 2.81; 95% CI: [1.24-6.86]) and the consumption of meat combination (pork + beef + mutton + wild meat + poultry) (AOR = 4.00; 95% CI: [1.06-15.24]) were potential risk factors of T. gondii infection. CONCLUSION: Toxoplasmosis is frequent in pregnant women and studies that show incidence of T. gondii among the neonates have to be done to introduce routine antenatal screening program to control congenital toxoplasmosis. There is the need for preventive measures such as education of pregnant women about the transmission routes and prevention methods of toxoplasmosis at ANC clinics.

Recent uptake of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine is associated with increased prevalence of Pfdhfr mutations in Bobo-Dioulasso, Burkina Faso.

BACKGROUND: The impact of sulfadoxine-pyrimethamine (SP) used as intermittent preventive treatment during pregnancy (IPTp-SP) on mutant parasite selection has been poorly documented in Burkina Faso. This study sought first to explore the relationship between IPTp-SP and the presence of mutant parasites. Second, to assess the relationship between the mutant parasites and adverse pregnancy outcomes. METHODS: From September to December 2010, dried blood spots (DBS) were collected during antenatal care visits and at delivery from 109 pregnant women with microscopically confirmed falciparum malaria infection. DBS were analysed by PCR-restriction fragment length polymorphism (PCR-RFLP) for the polymorphisms at codons 51, 59, 108, and 164 of the Pfdhfr gene and codons 437 and 540 in the Pfdhps gene. RESULTS: Both the Pfdhfr and Pfdhps genes were successfully genotyped in 92.7% (101/109) of the samples. The prevalence of Pfdhfr mutations N51I, C59R and S108N was 71.3, 42.6 and 64.4%, respectively. Overall, 80.2% (81/101) of samples carried the Pfdhps A437G mutation. None of the samples had the Pfdhfr I164L and the Pfdhps K540E mutations. The prevalence of the triple mutation N51I + C59R + S108N was 25.7% (26/101). The use of IPTp-SP was associated with a threefold increased odds of Pfdhfr C59R mutation [crude OR 3.29; 95% CI (1.44-7.50)]. Pregnant women with recent uptake of IPTp-SP were at higher odds of both the Pfdhfr C59R mutation [adjusted OR 4.26; 95% CI (1.64-11.07)] and the Pfdhfr intermediate-to-high resistance, i.e., ≥ 2 Pfdhfr mutations [adjusted OR 3.45; 95% CI (1.18-10.07)]. There was no statistically significant association between the presence of the Pfdhfr intermediate-to-high resistance and parasite densities or both maternal haemoglobin level and anaemia. CONCLUSION: The data indicate that despite the possibility that IPTp-SP contributes to the selection of resistant parasites, it did not potentiate pregnancy-associated malaria morbidity, suggesting the continuation of SP use as IPTp in Burkina Faso.

Epidemiological and clinical aspects of urogenital schistosomiasis in women, in Burkina Faso, West Africa.

BACKGROUND: Because infections with Schistosoma Haematobium usually peak in childhood, the majority of studies on schistosomiasis have focused on school-aged children. This study aimed to assess the epidemiological and clinical aspects of urogenital schistosomiasis in women in Burkina Faso, West Africa. METHODS: A cross-sectional study was conducted in a mesoendemic region (Kombissiri) and a hyperendemic region (Dori) for schistosomiasis in Burkina Faso. A total of 287 females aged 5 to 50 years were included in the study. S. haematobium infection was assessed using the urine filtration method and dipsticks were used for the detection of hematuria. Interviews were conducted to identify clinical aspects and risk factors related to urogenital schistosomiasis. RESULTS: The overall prevalence of S. haematobium infection in Dori was 21.3 %, where as Kombissiri was less affected with a prevalence of 4.6 %. The most affected age group was the 10- to 14-year-olds (41.2 %), followed by the 15- to 19-year-olds (26.3 %). Risk factors significantly associated with schistosomiasis (P <0.05) were place of residence, age, contact with open water in the past year, and distance of home to open water. The percentage of participants who had contact with open water was significantly higher among the women living in Dori compared to Kombissiri. Females over 15 years of age showed a significant higher rate of water contact compared to the 5- to 15-year-olds. A significant correlation between schistosomiasis and hematuria was established. Microhematuria showed a sensitivity of 80.6 %, a specificity of 92.7 %, and a positive predictive value of 61.7 %, whereas macrohematuria had a sensitivity of 47.2 %, a specificity of 99.2 %, and a positive predictive value of 89.5 %. The mass distribution of praziquantel in Burkina Faso is well established. However, over half of the participants with schistosomiasis in this study said they took praziquantel in the past 6 months, which indicates a high reinfection rate. This may be associated with a lack of knowledge about the transmission of schistosomiasis. Only 6 % of the participants in Kombissiri and 1.5 % in Dori knew about the correct mode of transmission. CONCLUSIONS: The results of our study indicate that distribution campaigns should be extended from school-aged children to young women. Our data also demonstrate the necessity of combining already established mass distribution campaigns with information campaigns, so that long-term elimination, or at least reduction, of schistosomiasis can be achieved.

Seroprevalence of Toxoplasma gondii and direct genotyping using minisequencing in free-range pigs in Burkina Faso.

BACKGROUND: Swine are a major source of meat for humans. As such, they can play an important role in the epidemiology of human toxoplasmosis. Therefore, we performed an epidemiological study to determine the prevalence and genotypes of Toxoplasma gondii in Burkina Fasan swine. METHODS: The prevalence of T. gondii infection was evaluated in a 3-month prospective study at the slaughterhouse of Bobo-Dioulasso, Burkina Faso. Anti-Toxoplasma IgG titers were determined on meat juices from pig diaphragms using a commercially available ELISA assay. The DNA was extracted from 25mg of heart biopsies of seropositive animals (IgG ≥50% of the control) and the presence of T. gondii DNA was detected using a quantitative PCR assay. Genotyping was performed directly on DNA from PCR-positive biopsies using high-resolution melting and minisequencing analyses of the repeated B1 gene. RESULTS: The prevalence of carcasses positive for anti-Toxoplasma IgG was 29% (87/300) with no difference according to sex and age in contrast to the village of origin (p=0.018). Of the 87 seropositive animals, two were PCR positive (parasitic load at 64 and 128 parasites/mg of heart biopsy). Two new genotypes belonging to Type II and Type III and different from the genotypes previously described using minisequencing were identified. CONCLUSION: Our study provides the first T. gondii seroprevalence data in Burkina Fasan swine. In addition, this direct typing method suggests diversity of the T. gondii genotypes circulating in domestic animals in Burkina Faso. This needs to be confirmed on a wider sampling of subjects.

Prevalence of the dhfr and dhps Mutations among Pregnant Women in Rural Burkina Faso Five Years after the Introduction of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine.

BACKGROUND: The emergence and spread of drug resistance represents one of the biggest challenges for malaria control in endemic regions. Sulfadoxine-pyrimethamine (SP) is currently deployed as intermittent preventive treatment in pregnancy (IPTp) to prevent the adverse effects of malaria on the mother and her offspring. Nevertheless, its efficacy is threatened by SP resistance which can be estimated by the prevalence of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) mutations. This was measured among pregnant women in the health district of Nanoro, Burkina Faso. METHODS: From June to December 2010, two hundred and fifty six pregnant women in the second and third trimester, attending antenatal care with microscopically confirmed malaria infection were invited to participate, regardless of malaria symptoms. A blood sample was collected on filter paper and analyzed by PCR-RFLP for the alleles 51, 59, 108, 164 in the pfdhfr gene and 437, 540 in the pfdhps gene. RESULTS: The genes were successfully genotyped in all but one sample (99.6%; 255/256) for dhfr and in 90.2% (231/256) for dhps. The dhfr C59R and S108N mutations were the most common, with a prevalence of 61.2% (156/255) and 55.7% (142/255), respectively; 12.2% (31/255) samples had also the dhfr N51I mutation while the I164L mutation was absent. The dhps A437G mutation was found in 34.2% (79/231) isolates, but none of them carried the codon K540E. The prevalence of the dhfr double mutations NRNI and the triple mutations IRNI was 35.7% (91/255) and 11.4% (29/255), respectively. CONCLUSION: Though the mutations in the pfdhfr and pfdhps genes were relatively common, the prevalence of the triple pfdhfr mutation was very low, indicating that SP as IPTp is still efficacious in Burkina Faso.

Prevalence of intestinal opportunistic parasites infections in the University hospital of Bobo-Dioulasso, Burkina Faso.

BACKGROUND: Gastrointestinal parasites infections are widespread in Africa and their prevalence infections vary from country to country. This study aimed at assessing the prevalence of opportunistic intestinal parasites infection and other gastrointestinal parasites infection among patients attending the laboratory of Parasitology and Mycology of the University Hospital Souro Sanou of Bobo-Dioulasso. METHODS: A hospital cross-sectional based study was conducted from April to August, 2012. Participants were persons whom parasitological examination of stools has been prescribed by a clinician. The stools examination methods included direct wet saline examination, lugol's iodine staining technique, formol-ether concentration and modified Ziehl-Neelsen staining. We recorded age and sex information for each patient. RESULTS: The overall prevalence of intestinal parasite infections was 65.3 % (190/291). Majority of the parasitic infections was waterborne (64.3 %) consisting of high prevalence of Cryptosporidium sp. (26.5 %) and Entamoeba histolytica/dispar (23.4 %). The prevalence of opportunistic parasites was 28.9 % and Cryptosporidium sp. was the most prevalent species followed by Blastocystis sp. (1.0 %), Cyclospora sp. (0.7 %) and Isospora belli (0.7 %). The prevalence of intestinal helminthes was 1.7 %. CONCLUSIONS: The prevalence of intestinal parasitism in general remains high in Bobo-Dioulasso requiring the establishment of adequate diagnostic techniques, treatment and prevention.

Ex vivo anti-malarial drug susceptibility of Plasmodium falciparum isolates from pregnant women in an area of highly seasonal transmission in Burkina Faso.

BACKGROUND: Ex vivo assays are usually carried out on parasite isolates collected from patients with uncomplicated Plasmodium falciparum malaria, from which pregnant women are usually excluded as they are often asymptomatic and with relatively low parasite densities. Nevertheless, P. falciparum parasites infecting pregnant women selectively sequester in the placenta and may have a different drug sensitivity profile compared to those infecting other patients. The drug sensitivity profile of P. falciparum isolates from infected pregnant women recruited in a treatment efficacy trial conducted in Burkina Faso was determined in an ex vivo study. METHODS: The study was conducted between October 2010 and December 2012. Plasmodium falciparum isolates were collected before treatment and at the time of any recurrent infection whose parasite density was at least 100/µl. A histidine-rich protein-2 assay was used to assess their susceptibility to a panel of seven anti-malarial drugs. The concentration of anti-malarial drug inhibiting 50% of the parasite maturation to schizonts (IC(50)) for each drug was determined with the IC Estimator version 1.2. RESULTS: The prevalence of resistant isolates was 23.5% for chloroquine, 9.2% for mefloquine, 8.0% for monodesethylamodiaquine, and 4.4% for quinine. Dihydroartemisinin, mefloquine, lumefantrine, and monodesethylamodiaquine had the lowest mean IC(50) ranging between 1.1 and 1.5 nM respectively. The geometric mean IC(50) of the tested drugs did not differ between chloroquine-sensitive and resistant parasites, with the exception of quinine, for which the IC(50) was higher for chloroquine-resistant isolates. The pairwise comparison between the IC(50) of the tested drugs showed a positive and significant correlation between dihydroartemisinin and both mefloquine and chloroquine, between chloroquine and lumefantrine and between monodesethylamodiaquine and mefloquine. CONCLUSION: These ex vivo results suggest that treatment with the currently available artemisinin-based combinations is efficacious for the treatment of malaria in pregnancy in Burkina Faso. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00852423.

Prevalence and risk factors for Plasmodium falciparum malaria in pregnant women attending antenatal clinic in Bobo-Dioulasso (Burkina Faso).

BACKGROUND: Malaria during pregnancy remains a serious public health problem. The aim of this study was to determine the prevalence and possible risk factors for malaria in pregnant women attending antenatal clinic at two primary health facilities in Bobo-Dioulasso. METHODS: We conducted a cross sectional study from September to December 2010 in two primary health facilities located in the periurban area of Bobo-Dioulasso. Pregnant women attending antenatal clinic (ANC) were included in the study after signing informed consent. For each participant, the social-demographic profile, malaria and obstetric histories were investigated through a questionnaire. Peripheral blood was collected and thick and thin blood smears were prepared to check Plasmodium falciparum parasitaemia. Hemoglobin concentration was measured. The associations between age, parity, gestational age, schooling, number of ANC visits, use of IPTp-SP, use of insecticide-treated nets (ITN) and anemia with the occurrence of P. falciparum malaria infection during pregnancy were analyzed through logistic regression. RESULTS: During the period of study, 105 (18.1%) out of 579 pregnant women were infected by P. falciparum. The hemoglobin concentration mean was 10.5 ± 1.7/dL and was significantly lower in pregnant women with malaria infection (9.8 g/dL ±1.6) than in those who had no malaria infection (10.6 g/dL ±1.7) (P < 0.001). Multivariate analysis indicated that, education (AOR 1.9, 95% CI = [1.2-3.2]), parity [primigravidae (AOR 5.0, 95% CI = [2.5-9.8]) and secundigravidae (AOR 2.1, 95% CI = [1.2-3.8])], and anaemia (AOR 2.1, 95% CI = [1.3-3.5]) were significantly associated with P. falciparum malaria infection. The use of IPTp-SP was not associated with P. falciparum malaria infection. CONCLUSIONS: P. falciparum malaria infection is common in pregnant women attending antenatal clinic and anaemia is an important complication. The results show that the use of IPTp-SP does not reduce the risk of malaria incidence during pregnancy.

Guinea worm (Dracunculiasis) eradication: update on progress and endgame challenges.

The International Commission for the Certification of Dracunculiasis Eradication (ICCDE) met in December to review progress towards eradication. The status of the programme was presented by WHO and The Carter Center, Atlanta. The Commission received reports from international certification teams that Cote d'Ivoire, Niger and Nigeria were free of transmission and should be certified, while four countries, namely Chad, Ethiopia, Mali and South Sudan, remained endemic. The Commission certified that Somalia and South Africa were free of transmission. During 2013, there was a decline of about 78% in the numbers of cases reported in South Sudan. A report of the perplexing dracunculiasis epidemiology in Chad was also discussed, where dogs have been found to be infected with Dracunculus medinensis.

The impact of clinical research activities on communities in rural Africa: the development of the Clinical Research Unit of Nanoro (CRUN) in Burkina Faso.

BACKGROUND: The opportunities for developing new drugs and vaccines for malaria control look brighter now than ten years ago. However, there are few places in sub-Saharan Africa with the necessary infrastructure and expertise to support such research in compliance to international standards of clinical research (ICH-GCP). The Clinical Research Unit of Nanoro (CRUN) was founded in 2008 to provide a much-needed GCP-compliant clinical trial platform for an imminent large-scale Phase 3 malaria vaccine trial. A dynamic approach was used that entailed developing the required infrastructure and human resources, while engaging local communities in the process as key stakeholders. This provided a better understanding and ownership of the research activities by the local population. CASE DESCRIPTION: Within five years (2008-2013), the CRUN set up a fully and well-equipped GCP-compliant clinical trial research facility, which enabled to attract 25 grants. The research team grew from ten health workers prior to 2008 to 254 in 2013. A Health and Demographic Surveillance System (HDSS), which covers a total population of about 60,000 people in 24 villages was set up in the district. The local community contributed to the development of the facility through the leadership of the king and the mayor of Nanoro. As a result of their active advocacy, the government extended the national electrical grid to the new research center, and later to the entire village. This produced a positive impact on the community's quality of life. The quality of health care improved substantially, due to the creation of more elaborate clinical laboratory services and the acquisition of state-of-the-art equipment. CONCLUSION: Involving the community in the key steps of establishing the centre provided the foundation for what was to become the CRUN success story. This experience demonstrates that when clinical trials research sites are carefully developed and implemented, they can have a positive and powerful impact on local communities in resource-poor settings, well beyond the task of generating expected study data.

Clinical signs and symptoms cannot reliably predict Plasmodium falciparum malaria infection in pregnant women living in an area of high seasonal transmission.

BACKGROUND: Malaria in pregnancy is a major public health problem in endemic countries. Though the signs and symptoms of malaria among pregnant women have been already described, clinical presentation may vary according to intensity of transmission and local perceptions. Therefore, determining common signs and symptoms among pregnant women with a malaria infection may be extremely useful to identify those in need of further investigation by rapid diagnostic test or microscopy. METHODS: Six hundred pregnant women attending the maternity clinic of Nanoro District Hospital, Burkina Faso were recruited, 200 with suspected clinical malaria and 400 as controls. Cases were matched with controls by gestational age and parity. Signs and symptoms were collected and a blood sample taken for rapid diagnostic test, microscopy and haemoglobin measurement. A multivariate model was used to assess the predictive value of signs and symptoms for malaria infection. RESULTS: The overall prevalence of malaria was 42.6% (256/600) while anaemia was found in 60.8% (365/600) of the women. Nearly half (49%) of the cases and 39.5% of the controls had a malaria infection (p = 0.03). The most common signs and symptoms among the cases were fever (36%,72/200), history of fever (29%,58/200) and headache (52%,104/200). The positive predictive value for fever was 53% (95% CI:41-64), history of fever 58% (95% CI:37-63) and headache 51% (95% CI:41-61). CONCLUSION: Signs and symptoms suggestive of malaria are frequent among pregnant women living in areas of intense transmission. Common malaria symptoms are not strong predictors of infection. For a better management of malaria in pregnancy, active screening to detect and treat malaria infection early should be performed on all pregnant women attending a health facility.

A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants.

BACKGROUND: The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial. METHODS: We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed. RESULTS: The incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222). CONCLUSIONS: The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.).

Decreasing incidence of cryptococcal meningitis in West Africa in the era of highly active antiretroviral therapy.

Cryptococcosis remains a major opportunistic infection in AIDS in sub-Saharan Africa, but few data exist from its western part. We report data from Bobo Dioulasso University Hospital, Bobo-Dioulasso, Burkina Faso, with a steady decline from 14 to two cases per year from 2002 to 2010 which contrasts with the increase (from 147 to 3940) of patients on antiretroviral therapy (ART). Better ART availability decreases the incidence of cryptococcosis in Burkina Faso.

An analysis of timing and frequency of malaria infection during pregnancy in relation to the risk of low birth weight, anaemia and perinatal mortality in Burkina Faso.

BACKGROUND: A prospective study aiming at assessing the effect of adding a third dose sulphadoxine-pyrimethamine (SP) to the standard two-dose intermittent preventive treatment for pregnant women was carried out in Hounde, Burkina Faso, between March 2006 and July 2008. Pregnant women were identified as earlier as possible during pregnancy through a network of home visitors, referred to the health facilities for inclusion and followed up until delivery. METHODS: Study participants were enrolled at antenatal care (ANC) visits and randomized to receive either two or three doses of SP at the appropriate time. Women were visited daily and a blood slide was collected when there was fever (body temperature > 37.5°C) or history of fever. Women were encouraged to attend ANC and deliver in the health centre, where the new-born was examined and weighed. The timing and frequency of malaria infection was analysed in relation to the risk of low birth weight, maternal anaemia and perinatal mortality. RESULTS: Data on birth weight and haemoglobin were available for 1,034 women. The incidence of malaria infections was significantly lower in women having received three instead of two doses of SP. Occurrence of first malaria infection during the first or second trimester was associated with a higher risk of low birth weight: incidence rate ratios of 3.56 (p < 0.001) and 1.72 (p = 0.034), respectively. After adjusting for possible confounding factors, the risk remained significantly higher for the infection in the first trimester of pregnancy (adjusted incidence rate ratio = 2.07, p = 0.002). The risk of maternal anaemia and perinatal mortality was not associated with the timing of first malaria infection. CONCLUSION: Malaria infection during first trimester of pregnancy is associated to a higher risk of low birth weight. Women should be encouraged to use long-lasting insecticidal nets before and throughout their pregnancy.

First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children.

BACKGROUND: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries. METHODS: From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories. RESULTS: In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64). CONCLUSIONS: The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).