Chloroquine Chemoprophylaxis Research Articles

Machine learning prediction of malaria vaccine efficacy based on antibody profiles.

Immunization through repeated direct venous inoculation of Plasmodium falciparum (Pf) sporozoites (PfSPZ) under chloroquine chemoprophylaxis, using the PfSPZ Chemoprophylaxis Vaccine (PfSPZ-CVac), induces high-level protection against controlled human malaria infection (CHMI). Humoral and cellular immunity contribute to vaccine efficacy but only limited information about the implicated Pf-specific antigens is available. Here, we examined Pf-specific antibody profiles, measured by protein arrays representing the full Pf proteome, of 40 placebo- and PfSPZ-immunized malaria-naïve volunteers from an earlier published PfSPZ-CVac dose-escalation trial. For this purpose, we both utilized and adapted supervised machine learning methods to identify predictive antibody profiles at two different time points: after immunization and before CHMI. We developed an adapted multitask support vector machine (SVM) approach and compared it to standard methods, i.e. single-task SVM, regularized logistic regression and random forests. Our results show, that the multitask SVM approach improved the classification performance to discriminate the protection status based on the underlying antibody-profiles while combining time- and dose-dependent data in the prediction model. Additionally, we developed the new fEature diStance exPlainabilitY (ESPY) method to quantify the impact of single antigens on the non-linear multitask SVM model and make it more interpretable. In conclusion, our multitask SVM model outperforms the studied standard approaches in regard of classification performance. Moreover, with our new explanation method ESPY, we were able to interpret the impact of Pf-specific antigen antibody responses that predict sterile protective immunity against CHMI after immunization. The identified Pf-specific antigens may contribute to a better understanding of immunity against human malaria and may foster vaccine development.

COVID-19 Contamination in Hospital Staff: Determinism, Epidemiological Features

The first cases of SARS-CoV-2 were diagnosed in BENIN in early March 2020. Measures have been instituted to control its spread, including barrier measures. The objective of this study is to determine the effectiveness of self-application of these measures among hospital staff at CNHU-HKM. Methods: This is a case-control study conducted from July 1, 2020 to January 1, 2021 on the risk factors of COVID-19 contamination. Included were any CNHU-HKM staff who underwent PCR testing for COVID-19 at the CNHU-HKM triage center during the study period. Data were collected using a survey form administered to respondents. Data analysis was performed with R 4.1.0 software. Results: A total of 141 patients were included in the study. The mean age was 35.5 (±11.1) years. The sex ratio (M/F) was 1.87. Fon and Mina ethnic groups were the most represented (74.5%). Workers older than 50 years were more likely to be exposed to COVID-19 (OR=4.83). Nurses in contact with patients (87.2% of the study population) had a higher risk of contamination (OR=3.6), compared to administrative staff. The FFP2 mask was a protective factor (OR=0.35) as well as long-term chemoprophylaxis with chloroquine (OR=0.44). Conclusion: Health care workers are at high risk of contamination by COVID-19. Barrier measures and chloroquine chemoprophylaxis are indeed mandatory in controlling the spread of the pandemic.

COVID-19 Contamination in Hospital Staff: Determinism, Epidemiological Features

The first cases of SARS-CoV-2 were diagnosed in BENIN in early March 2020. Measures have been instituted to control its spread, including barrier measures. The objective of this study is to determine the effectiveness of self-application of these measures among hospital staff at CNHU-HKM. Methods: This is a case-control study conducted from July 1, 2020 to January 1, 2021 on the risk factors of COVID-19 contamination. Included were any CNHU-HKM staff who underwent PCR testing for COVID-19 at the CNHU-HKM triage center during the study period. Data were collected using a survey form administered to respondents. Data analysis was performed with R 4.1.0 software. Results: A total of 141 patients were included in the study. The mean age was 35.5 (±11.1) years. The sex ratio (M/F) was 1.87. Fon and Mina ethnic groups were the most represented (74.5%). Workers older than 50 years were more likely to be exposed to COVID-19 (OR=4.83). Nurses in contact with patients (87.2% of the study population) had a higher risk of contamination (OR=3.6), compared to administrative staff. The FFP2 mask was a protective factor (OR=0.35) as well as long-term chemoprophylaxis with chloroquine (OR=0.44). Conclusion: Health care workers are at high risk of contamination by COVID-19. Barrier measures and chloroquine chemoprophylaxis are indeed mandatory in controlling the spread of the pandemic.

Chloroquine as weekly chemoprophylaxis or intermittent treatment to prevent malaria in pregnancy in Malawi: a randomised controlled trial

Sulfadoxine-pyrimethamine resistance threatens efficacy of intermittent preventive treatment of malaria during pregnancy, and alternative regimens need to be identified. With the return of chloroquine efficacy in southern Africa, we postulated that chloroquine either as an intermittent therapy or as weekly chemoprophylaxis would be more efficacious than intermittent sulfadoxine-pyrimethamine for prevention of malaria in pregnancy and associated maternal and newborn adverse outcomes. We did an open-label, single-centre, randomised controlled trial at Ndirande Health Centre, Blantyre, in southern Malawi. We enrolled pregnant women (first or second pregnancy) at 20-28 weeks' gestation who were HIV negative. Participants were randomly assigned in a 1:1:1 ratio using a computer-generated list to either intermittent sulfadoxine-pyrimethamine (two doses of 1500 mg sulfadoxine and 75 mg pyrimethamine, 4 weeks apart), intermittent chloroquine (two doses of 600 mg on day 1, 600 mg on day 2, and 300 mg on day 3), or chloroquine prophylaxis (600 mg on day 1 then 300 mg every week). The primary endpoint was placental malaria in the modified intent-to-treat population, which consisted of participants who contributed placental histopathology data at birth. Secondary outcomes included clinical malaria, maternal anaemia, low birthweight, and safety. This trial is registered with ClinicalTrials.gov, number NCT01443130. Between February, 2012, and May, 2014, we enrolled and randomly allocated 900 women, of whom 765 contributed histopathological data and were included in the primary analysis. 108 (14%) women had placental malaria, which was lower than the anticipated prevalence of placental malaria infection. Protection from placental malaria was not improved by chloroquine as either prophylaxis (30 [12%] of 259 had positive histopathology; relative risk [RR] 0·75, 95% CI 0·48-1·17) or intermittent therapy (39 [15%] of 253; RR 1·00, 0·67-1·50) compared with intermittent sulfadoxine-pyrimethamine (39 [15%] of 253). In protocol-specified analyses adjusted for maternal age, gestational age at enrolment, bednet use the night before enrolment, anaemia at enrolment, and malaria infection at enrolment, women taking chloroquine as prophylaxis had 34% lower placental infections than did those allocated intermittent sulfadoxine-pyrimethamine (RR 0·66, 95% CI 0·46-0·95). Clinical malaria was reported in nine women assigned intermittent sulfadoxine-pyrimethamine, four allocated intermittent chloroquine (p=0·26), and two allocated chloroquine prophylaxis (p=0·063). Maternal anaemia was noted in five women assigned intermittent sulfadoxine-pyrimethamine, 15 allocated intermittent chloroquine (p=0·038), and six assigned chloroquine prophylaxis (p>0·99). Low birthweight was recorded for 31 babies born to women allocated intermittent sulfadoxine-pyrimethamine, 29 assigned intermittent chloroquine (p=0·78), and 41 allocated chloroquine prophylaxis (p=0·28). Four women assigned intermittent sulfadoxine-pyrimethamine had adverse events possibly related to study product compared with 94 women allocated intermittent chloroquine (p<0·0001) and 26 allocated chloroquine prophylaxis (p<0·0001). Three women had severe or life-threatening adverse events related to study product, of whom all were assigned intermittent chloroquine (p=0·25). Chloroquine administered as intermittent therapy did not provide better protection from malaria and related adverse effects compared with intermittent sulfadoxine-pyrimethamine in a setting of high resistance to sulfadoxine-pyrimethamine. Chloroquine chemoprophylaxis might provide benefit in protecting against malaria during pregnancy, but studies with larger sample sizes are needed to confirm these results. US National Institutes of Health.

Humanized DRAGA mice immunized with Plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity

BackgroundHuman-immune-system humanized mouse models can bridge the gap between humans and conventional mice for testing human vaccines. The HLA-expressing humanized DRAGA (HLA-A2.HLA-DR4.Rag1KO.IL2RγcKO.NOD) mice reconstitute a functional human-immune-system and sustain the complete life cycle of Plasmodium falciparum. Herein, the DRAGA mice were investigated for immune responses following immunization with live P. falciparum sporozoites under chloroquine chemoprophylaxis (CPS-CQ), an immunization approach that showed in human trials to confer pre-erythrocytic immunity.ResultsThe CPS-CQ immunized DRAGA mice (i) elicited human CD4 and CD8 T cell responses to antigens expressed by P. falciparum sporozoites (Pfspz) and by the infected-red blood cells (iRBC). The Pfspz-specific human T cell responses were found to be systemic (spleen and liver), whereas the iRBCs-specific human T cell responses were more localized to the liver, (ii) elicited stronger antibody responses to the Pfspz than to the iRBCs, and (iii) they were protected against challenge with infectious Pfspz but not against challenge with iRBCs.ConclusionsThe DRAGA mice represent a new pre-clinical model to investigate the immunogenicity and protective efficacy of P. falciparum malaria vaccine candidates.

Protection against malaria by immunization with non-attenuated sporozoites under single-dose piperaquine-tetraphosphate chemoprophylaxis

Experimental whole-parasite immunization through concurrent administration of infectious Plasmodium sporozoites with drugs that prevent pathogenic blood-stage infection represents the current benchmark in malaria vaccine development. Key questions concerning translation remain, including the requirement for single-dose drug regimens that can reliably prevent breakthrough infections. We assessed the feasibility and efficacy of immunization with single-dose piperaquine chemoprophylaxis and concurrent sporozoite administration (PPQ-CPS) in the murine P. berghei ANKA/C57BL/6 infection model. We demonstrate that PPQ-CPS is protective with an efficacy comparable to previous findings using whole-parasite immunization under chloroquine chemoprophylaxis. PPQ-CPS immunization resulted in an expansion of intrahepatic and intrasplenic effector memory CD8+ T cells. In summary, PPQ-CPS appears to be a safe and efficacious immunization regimen in the rodent malaria model and may thus become an important improvement regarding the translation of whole-parasite immunization toward a human malaria vaccine.

Cytotoxic markers associate with protection against malaria in human volunteers immunized with Plasmodium falciparum sporozoites.

Background. Immunization of healthy volunteers by bites from Plasmodium falciparum–infected mosquitoes during chloroquine chemoprophylaxis (hereafter, chemoprophylaxis and sporozoites [CPS] immunization) induces sterile protection against malaria. CPS-induced protection is mediated by immunity against pre-erythrocytic stages, presumably at least partially by cytotoxic cellular responses. We therefore aimed to investigate the association of CPS-induced cytotoxic T-cell markers with protection.Methods. In a double-blind randomized controlled trial, we performed dose titration of CPS immunization followed by homologous challenge infection in 29 subjects. Immune responses were assessed by in vitro restimulation of peripheral blood mononuclear cells and flow cytometry.Results. Dose-dependent complete protection was obtained in 4 of 5 volunteers after immunization with bites from 45 P. falciparum–infected mosquitoes, in 8 of 9 volunteers with bites from 30, and in 5 of 10 volunteers with bites from 15 (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.5–17). Completely protected subjects had significantly higher proportions of CD4 T cells expressing the degranulation marker CD107a (OR, 8.4; 95% CI, 1.5–123; P = .011) and CD8 cells producing granzyme B (OR, 11; 95% CI, 1.9–212; P = .004) after P. falciparum restimulation.Conclusions. These data underline the efficiency of CPS immunization to induce sterile protection and support a possible role for cytotoxic CD4 and CD8 T-cell responses in pre-erythrocytic immunity.Clinical Trials Registration. NCT01218893.

Idiopathic acute myocarditis during treatment for controlled human malaria infection: a case report

A 23-year-old healthy male volunteer took part in a clinical trial in which the volunteer took chloroquine chemoprophylaxis and received three intradermal doses at four-week intervals of aseptic, purified Plasmodium falciparum sporozoites to induce protective immunity against malaria. Fifty-nine days after the last administration of sporozoites and 32 days after the last dose of chloroquine the volunteer underwent controlled human malaria infection (CHMI) by the bites of five P. falciparum-infected mosquitoes. Eleven days post-CHMI a thick blood smear was positive (6 P. falciparum/μL blood) and treatment was initiated with atovaquone/proguanil (Malarone®). On the second day of treatment, day 12 post-CHMI, troponin T, a marker for cardiac tissue damage, began to rise above normal, and reached a maximum of 1,115 ng/L (upper range of normal = 14 ng/L) on day 16 post-CHMI. The volunteer had one ~20 minute episode of retrosternal chest pain and heavy feeling in his left arm on day 14 post-CHMI. ECG at the time revealed minor repolarization disturbances, and cardiac MRI demonstrated focal areas of subepicardial and midwall delayed enhancement of the left ventricle with some oedema and hypokinesia. A diagnosis of myocarditis was made. Troponin T levels were normal within 16 days and the volunteer recovered without clinical sequelae. Follow-up cardiac MRI at almost five months showed normal function of both ventricles and disappearance of oedema. Delayed enhancement of subepicardial and midwall regions decreased, but was still present. With the exception of a throat swab that was positive for rhinovirus on day 14 post-CHMI, no other tests for potential aetiologies of the myocarditis were positive. A number of possible aetiological factors may explain or have contributed to this case of myocarditis including, i) P. falciparum infection, ii) rhinovirus infection, iii) unidentified pathogens, iv) hyper-immunization (the volunteer received six travel vaccines between the last immunization and the CHMI), v) atovaquone/proguanil treatment, or vi) a combination of these factors. Definitive aetiology and pathophysiological mechanism for the myocarditis have not been established.

English

Malaria in pregnancy is a significant contributor to adverse pregnancy outcome. In low resource setting of India to contain malaria in the vast chloroquine resistant endemic zone LLIN (Long lasting insecticide treated Nets) has been introduced as an intervention to prevent malarial morbidity and mortality in the population among anemic pregnant women in malarias zone is quite high, oral ferrous ascorbate has an edge over commonly available ferrous sulfate to rectify Anemia with least side effect in those pregnant women. INTRODUCTION: Malaria in pregnancy is an important public health problem that affects 25 million pregnant women in endemic zones of world and contributes heavily on maternal and infant morbidity and mortality. Acquired immunity in endemic zones is compromised in pregnant state. Maternal Anemia (70%) still birth, premature birth and LBW are adverse outcome in pregnant women in endemic zones of Malaria, especially in chloroquine resistant areas. Although in 2004 WHO recommended prophylactic two doses of sulfadoxine pyrimethamine (Ref-5) in 2nd trimester of pregnancy in endemic zones, sub optimal drug adherence and increasing sulfadoxine pyrimethamine resistance has stood as an obstacle for Malaria containment. Now effect of long lasting insecticide net (LLIN) insecticide treated net (ITN) is being promoted through UNICEF and Govt. in endemic zones resistant to chloroquine chemoprophylaxis. Here is a camp based study in one heavily affected Malarias zone of Odisha on effect of LLIN in pregnant women and effect of Oral ferrous Ascorbate in improving the anaemic status of pregnant women in malarious zone. MATERIALS & METHODS: Ramagiri PHC was selected for study as it comes under Intensive Falciparum zone of Koraput district, API-32 in 2012. A pre-camp advertisement in the area was performed. A three member doctor team along with four paramedical assistants, one lab technician and two Divine Life Society volunteers were employed for the camp and 100 nos. of Antenatal cases were registered out of which only 50 cases were randomly studied whose socio economic status was noted to be poor. Antenatal check up Height of Uterus, Abdominal girth/ Wt, BP, HB, urine ALB, splenic examination and Cervical smear and peripheral blood smear were studied. In all cases MP was studied by thick blood sample. Hemoglobin was instantly estimated by hemocue instrument (HB301) after finger prick. Only 10 cases gave their consent for vaginal cytology inspite of maintenance of privacy in presence of a female attendant. Ferrous sulfate 45 tab and Ferrous Ascorbate (Elferri xt supplied by Svizera Health Care - Constituent Per tab Ferrous Ascorbate 100 mg, Folic Acid-1.5 mg, Zinc -22.5 mg ) 45 tabs were given on alternate making them Group 'A' and Group 'B' respectively. HB was reestimated after 45 days in both groups by same

Evaluation of the efficacy of chloroquine chemoprophylaxis for vivax malaria among Republic of Korea military personnel

Chloroquine has been used massively for vivax malaria prophylaxis and treatment in the Republic of Korea (ROK) military personnel from 1997. Although prophylaxis is generally regarded as successful among ROK military, prophylaxis failure has been repeatedly reported. Before the prophylaxis program was started on July 4th 2011, which was completed on October 16th 2011, by the ROK military, more than 60% of malaria cases were attributed to new infection or long-latency relapse. During the prophylaxis program, the authors re-examined the efficiency of chloroquine chemoprophylaxis in ROK military during the last 6months of 2011 by measuring compliance and whole blood chloroquine levels in 41 malaria patients immediately before instituting antimalarial therapy between July and December. Three patients (7.3%) showed good compliance, and had whole blood total chloroquine levels above the minimally inhibitory concentration (100ng/mL). However, 28 (69.3%) of these 41 patients when admitted to hospital showed poor or no compliance with prophylaxis; 4 of the 28 (14.3%) were stationed outside the mass prophylaxis region, and 5 (17.9%) subjects were infected after the prophylaxis program had finished. These findings indicate that the current malaria control program should be carefully reconsidered, in terms of, individual instruction, current chemoprophylaxis program regimens, and schedules to improve the efficacy of prophylaxis in the ROK military.

Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity

Volunteers immunized under chloroquine chemoprophylaxis with Plasmodium falciparum sporozoites (CPS) develop complete, long-lasting protection against homologous sporozoite challenge. Chloroquine affects neither sporozoites nor liver-stages, but kills only asexual forms in erythrocytes once released from the liver into the circulation. Consequently, CPS immunization exposes the host to antigens from both preerythrocytic and blood stages, and induced immunity might target either of these stages. We therefore explored the life cycle stage specificity of CPS-induced protection. Twenty-five malaria-naïve volunteers were enrolled in a clinical trial, 15 of whom received CPS immunization. Five immunized subjects and five controls received a sporozoite challenge by mosquito bites, whereas nine immunized and five control subjects received an i.v. challenge with P. falciparum-infected erythrocytes. The latter approach completely bypasses preerythrocytic stages, enabling a direct comparison of protection against either life cycle stage. CPS-immunized subjects (13 of 14) developed anticircumsporozoite antibodies, whereas only one volunteer generated minimal titers against typical blood-stage antigens. IgG from CPS-immunized volunteers did not inhibit asexual blood-stage growth in vitro. All CPS-immunized subjects (5 of 5) were protected against sporozoite challenge. In contrast, nine of nine CPS-immunized subjects developed parasitemia after blood-stage challenge, with identical prepatent periods and blood-stage multiplication rates compared with controls. Intravenously challenged CPS-immunized subjects showed earlier fever and increased plasma concentrations of inflammatory markers D-dimer, IFN-γ, and monokine induced by IFN-γ than i.v. challenged controls. The complete lack of protection against blood-stage challenge indicates that CPS-induced protection is mediated by immunity against preerythrocytic stages. However, evidence is presented for immune recognition of P. falciparum-infected erythrocytes, suggesting memory responses unable to generate functional immunity.

Taking a Bite out of Malaria: Controlled Human Malaria Infection by Needle and Syringe

Taking a Bite out of Malaria: Controlled Human Malaria Infection by Needle and Syringe

Adaptive clinical trials of three PfSPZ products for development of a whole sporozoite vaccine that prevents Plasmodium falciparum infection, disease and transmission

An ideal, single stage vaccine useful for elimination of Plasmodium falciparum (Pf) would prevent infection at the pre-erythrocytic stage of the parasite life cycle, thereby preventing all Pf-caused disease and transmission from humans to mosquitoes. The only approach to immunization shown to consistently induce greater than 90% protection against infection and protection sustained for at least 10-28 months has been immunization by mosquito bite with whole Pf sporozoites (SPZ) of two types. The first type, radiation-attenuated PfSPZ, invade hepatoctyes and expresses new proteins, but cannot replicate. The second type fully develop in hepatocytes, producing tens of thousands of merozoites that invade erythrocytes, but are unable to fully develop within erythrocytes because they are killed by an antimalarial drug. This approach called chemoprophylaxis with sporozoites (CPS) harnesses the infectious agent’s inherent replicative properties to amplify production of protective immunogens spanning multiple developmental stages, and then eliminates the infectious agent with an anti-infective drug before the onset of disease. Sanaria was founded to develop PfSPZ vaccines. The first vaccine developed and tested was the PfSPZ Vaccine. The PfSPZ Vaccine is comprised of aseptic, purified, radiation attenuated, cryopreserved PfSPZ. It was shown to be safe and well-tolerated when administered ID or SC to 80 volunteers in the U.S., but sub-optimally immunogenic. It is now being tested in the U.S. and soon in Tanzania when administered by IV injection, since it induced high levels of PfSPZ-specific CD8+ T cells in the livers of immunized non-human primates when administered IV. A second product, PfSPZ Challenge, is comprised of non-irradiated, fully infectious PfSPZ. PfSPZ Challenge has been shown to infect 100% of volunteers after ID or IM administration by needle and syringe. It has been or will be tested for optimization of adminstration by the ID, IM, and IV routes in 2012 or early 2013 in the Netherlands, UK, Tanzania, U.S., Germany, Spain, and Kenya. A third product, PfSPZ-CVac, is comprised of PfSPZ Challenge administered to volunteers receiving chloroquine chemoprophylaxis. It will be assessed in 2012-2013 in the Netherlands, Mali, Germany and Tanzania. Assessment of these three products in synergistic, interactive and adaptive clinical trials will facilitate progress toward optimizing administration and dosage regimen of all three whole PfSPZ products, as well as those developed in the future from genetically altered parasites, thereby facilitating licensure of one or more PfSPZ-based vaccines. Progress and plans for development will be discussed.

Long Term Protection after Immunization with P. berghei Sporozoites Correlates with Sustained IFNγ Responses of Hepatic CD8+ Memory T Cells

Protection against P. berghei malaria can successfully be induced in mice by immunization with both radiation attenuated sporozoites (RAS) arresting early during liver stage development, or sporozoites combined with chloroquine chemoprophylaxis (CPS), resulting in complete intra-hepatic parasite development before killing of blood-stages by chloroquine takes place. We assessed the longevity of protective cellular immune responses by RAS and CPS P. berghei immunization of C57BL/6j mice. Strong effector and memory (TEM) CD8+ T cell responses were induced predominantly in the liver of both RAS and CPS immunized mice while CD4+ T cells with memory phenotype remained at base line levels. Compared to unprotected naïve mice, we found high sporozoite-specific IFNγ ex vivo responses that associated with induced levels of in vivo CD8+ TEM cells in the liver but not spleen. Long term evaluation over a period of 9 months showed a decline of malaria-specific IFNγ responses in RAS and CPS mice that significantly correlated with loss of protection (r2 = 0.60, p<0.0001). The reducing IFNγ response by hepatic memory CD8+ T cells could be boosted by re-exposure to wild-type sporozoites. Our data show that sustainable protection against malaria associates with distinct intra-hepatic immune responses characterized by strong IFNγ producing CD8+ memory T cells.

Different approaches for delivery of Intermittent Preventive Treatment (IPT) to pregnant women in Burkina Faso

Background In Africa the burden of malaria in pregnancy is highest in rural areas. In many Sub-Saharan African countries, IPTp/SP is being adopted to replace chloroquine (CQ) chemoprophylaxis shown to be inefficacious. Many publications showed a very poor compliance with CQ chemoprophylaxis among pregnant women and might explain the failure of this preventive strategy rather than increased levels of CQ resistance. In this study, we compare three approaches of IPTp/SP delivery to pregnant women in term of improving coverage and compliance. These three approaches are: i) Passive health centre services, ii) Extended delivery outreach services, iii) Community based distribution delivery approach.

Malaria Burden Among Pregnant Women Living in the Rural District of Boromo, Burkina Faso

In two cross-sectional surveys carried out in the rural health district of Boromo, Burkina Faso, malaria infection was evaluated in 295 pregnant women in May 2003 and 288 pregnant women in December 2003. Malaria prevalence, all P. falciparum infection, was higher in December (32.2%) than in May (11.9%) (P < 0.0001). In both surveys primigravidae had a significantly higher risk of infection than multigravidae (P < 0.0001). Such risk decreased significantly and progressively with gestational age, the highest risk being during the first trimester. Women who had not attended the antenatal clinic had also a significantly higher risk of malaria infection. Despite the high antenatal clinic attendance and the use (or misuse) of chloroquine chemoprophylaxis, malaria remains an important problem for pregnant women living in the rural district of Boromo. This requires a major effort by the health authorities to guarantee all pregnant women have access to and use preventive measures.

Is chloroquine chemoprophylaxis still effective to prevent low birth weight? Results of a study in Benin

BackgroundIn areas of stable transmission, malaria during pregnancy is associated with severe maternal and foetal outcomes, especially low birth weight (LBW). To prevent these complications, weekly chloroquine (CQ) chemoprophylaxis is now being replaced by intermittent preventive treatment with sulfadoxine-pyrimethamine in West Africa. The prevalence of placental malaria and its burden on LBW were assessed in Benin to evaluate the efficacy of weekly CQ chemoprophylaxis, prior to its replacement by intermittent preventive treatment.MethodsIn two maternity clinics in Ouidah, an observational study was conducted between April 2004 and April 2005. At each delivery, placental blood smears were examined for malaria infection and women were interviewed on their pregnancy history including CQ intake and dosage. CQ was measured in the urine of a sub-sample (n = 166). Multiple logistic and linear regression were used to assess factors associated with LBW and placental malaria.ResultsAmong 1090 singleton live births, prevalence of placental malaria and LBW were 16% and 17% respectively. After adjustment, there was a non-significant association between placental malaria and LBW (adjusted OR = 1.43; P = 0.10). Multiple linear regression showed a positive association between placental malaria and decreased birth weight in primigravidae. More than 98% of the women reported regular chemoprophylaxis and CQ was detectable in 99% of urine samples. Protection from LBW was high in women reporting regular CQ prophylaxis, with a strong duration-effect relationship (test for linear trend: P < 0,001).ConclusionDespite high parasite resistance and limited effect on placental malaria, a CQ chemoprophylaxis taken at adequate doses showed to be still effective in reducing LBW in Benin.

MALARIA PREVENTION DURING PREGNANCY: ASSESSING THE DISEASE BURDEN ONE YEAR AFTER IMPLEMENTING A PROGRAM OF INTERMITTENT PREVENTIVE TREATMENT IN KOUPÉLA DISTRICT, BURKINA FASO

The World Health Organization recommends that pregnant women in malaria-endemic areas receive >or= 2 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp/SP) in the second and third trimesters of pregnancy to prevent maternal anemia, placental parasitemia, and low birth weight (LBW). In 2001, a program evaluation in Koupéla District, Burkina Faso demonstrated that despite widespread use of chloroquine chemoprophylaxis, the burden of malaria during pregnancy remained high. In 2003, the Burkina Faso Ministry of Health piloted a program of IPTp/SP (three doses) and accelerated distribution of insecticide-treated nets (ITN) to pregnant women in Koupéla District. In 2004, a follow-up program evaluation was conducted. Coverage with >or= 1 doses of IPTp/SP was high among women attending antenatal clinics (ANCs) (96.2%) and delivery units (DUs) (93.5%); ITN ownership was moderately high (ANC = 53.9%, DU = 61.6%). In multivariate analysis, >or= 1 dose of IPTp/SP was associated with a significant reduction in the prevalence of peripheral parasitemia at ANCs (risk ratio [RR] = 0.49, P = 0.008), >or= 2 doses of IPTp/SP were associated with a reduction in the prevalence of placental parasitemia (RR = 0.56, P = 0.02), and three doses of IPTp/SP were associated with a reduced risk of LBW (RR = 0.51, P = 0.04). The proportions of women at ANCs with peripheral parasitemia and anemia were significantly lower in 2004 than in 2001 (RR = 0.53, P = 0.001 and RR = 0.78, P = 0.003, respectively). The proportions of women at DUs with peripheral and placental parasitemia were also significantly lower in 2004 than in 2001 (RR = 0.66, P < 0.0001 and RR = 0.71, P = 0.0002, respectively). These data suggest that a package of IPTp/SP and ITNs is effective in reducing the burden of malaria during pregnancy in Burkina Faso.

Prevention of malaria during pregnancy in West Africa: policy change and the power of subregional action

Despite a broadening consensus about the effectiveness of intermittent preventive treatment (IPTp) in preventing the adverse outcomes of malaria during pregnancy, policy change to IPTp was initially limited to East Africa. In West Africa, where the policy change process for the prevention of malaria during pregnancy started much later, IPTp has been taken up swiftly. To describe the factors that contributed to the rapid adoption of policies to prevent malaria during pregnancy in West Africa. Several factors appear to have accelerated the process: (1) recognition of the extent of the problem of malaria during pregnancy and its adverse consequences; (2) a clear, evidence-based program strategy strongly articulated by an important multilateral organization (World Health Organization); (3) subregionally generated evidence to support the proposed strategy; (4) a subregional forum for dissemination of data and discussion regarding the proposed policy changes; (5) widespread availability of the proposed intervention drug (sulfadoxine-pyrimethamine); (6) technical support from reputable and respected institutions in drafting new policies and planning for implementation; (7) donor support for pilot experiences in integrating proposed policy change into a package of preventive services; and (8) financial support for scaling up the proposed interventions.

Comparison of Intermittent Preventive Treatment with Chemoprophylaxis for the Prevention of Malaria during Pregnancy in Mali

Malaria during pregnancy contributes to maternal anemia and low birth weight. In East Africa, several studies have demonstrated that intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) is more efficacious than weekly chloroquine (CQ) chemoprophylaxis in preventing these adverse consequences. To our knowledge, there are no published trials evaluating IPT in West Africa. We undertook a randomized controlled trial of weekly CQ chemoprophylaxis, 2-dose IPT with CQ, and 2-dose IPT with SP; 1163 women were enrolled. In multivariate analyses, when compared with weekly CQ, IPT/SP was associated with a reduction in third-trimester anemia (adjusted odds ratio [AOR], 0.49; P<.001), placental parasitemia (AOR, 0.69; P=.04), and low birth weight (<2500 g) (AOR, 0.69; P=.04). The prevalence of placental infection remained unexpectedly high, even in the IPT/SP group (24.5%), possibly because of the intensity of seasonal transmission. There were no significant differences in stillbirths, spontaneous abortions, or neonatal deaths among the 3 groups. In Mali, IPT with SP appears more efficacious than weekly chloroquine chemoprophylaxis in preventing malaria during pregnancy. These data support World Health Organization recommendations to administer at least 2 doses of IPT during pregnancy. In intensely seasonal transmission settings in Mali, >2 doses may be required to prevent placental reinfection prior to delivery.