Comparison of the Effectiveness of Two Scheme Treatments to Treat Plasmodium Vivax Cases in Patients Living in Communities With Persistence of Transmission in Oaxaca and Chiapas, Mexico
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 153
- 主要终点
- Changes in the presence and density of asexual parasites in thick blood smears by microscopy
研究概览
简要总结
In the context of malaria elimination in the Americas, solid evidence is necessary of the effectiveness of anti-malarial control measures delivered to the affected individuals. In the Americas, most P. vivax infections are sensitive to Chloroquine (CQ) and Primaquine (PQ), and the most effective treatment worldwide comprises administration of a total dose of 25 milligrams (mg)/Kilogram (kg) weight of CQ distributed in three days and 3.5 mg/kg body weight of PQ administered during 14 days (T14). In Mexico, CQ and PQ have been administered since the late 50´s to treat malarious patients. In 1999 the National Malaria Control Program implemented an intermittent single doses treatment (ISD) as part of the overall strategy. After the blood sample was obtained for diagnosis of symptomatic patients, a single combined dose of CQ and PQ was administered, and after malaria infection confirmation, additional doses were administered monthly alternating each three months, during 3 years. Although, the number of malaria cases were reduced in most affected regions, in Southern México, many patients under ISD present recurrent blood infections, presumably relapse episodes were observed.
Working hypothesis: the administration of ISD is low effective to eliminate relapse episodes and its effectiveness depends on the coincidence of the relapse episodes and the administration of the medication), while the T14 is highly effective to eliminate P. vivax primary and relapse infections.
Objective: To determine the antimalarial drug effectiveness of the ISD and T14, based on CQ and PQ for the treatment of uncomplicated P. vivax infection (primary and recurrent blood infections) in Southern Mexico.
Methods: The study was carried out in malaria affected communities of Southern Mexico, following the WHO recommendations for clinical studies. Symptomatic patients diagnosed with P. vivax infection that meet the inclusion criteria, were invited to participate. After they accepted by informed consent, patients were semi-randomized and treated with either T14 (14-day treatment) or ISD (18 intermittent single doses of CQ-PQ). Clinical, parasitological, molecular and serological parameters were monitor over a 12-month follow up period to evaluate the treatment outcomes to cure blood infection and relapsing episodes. The study was conducted from February-2007 to October-2010. The results of this study will be used to assist the Ministry of Health of México in assessing the current national treatment guidelines for uncomplicated P. vivax malaria
详细描述
Malaria is in pre-elimination status in Mexico (Rodriguez et al., 2011; WHO, 2012) the local transmission of Plasmodium falciparum was interrupted since 2000, and transmission of P. vivax, the only causative agent in the country, is reduced to very few hot spots (Ministry of Health - Mexico, 1995-2005, Pan American Health Organization (PAHO), 2008, WHO, 2012).
Cloroquine (CQ) and primaquine (PQ) are used since 1940 to treat P. vivax blood and liver infections in most affected areas worldwide (Coatney, 1963). However P. vivax resistant to CQ has been progressively reported in various geographic regions since the late 80´s, (Baird 1995). Chloroquine, no longer recommended as mono-therapy WHO, 2010), administered (25 mg / Kg. body weight) during three consecutive days (10,10 and 5 mg /Kg body weight) in combination with PQ (0.25 - 0.75 mg/Kg body weight) during 14 days, is still used in regions were parasites are susceptible (White, 1998; WHO, 2010). The 14 -day regimen effectively cures primary blood infections and prevents relapses in at least 90% of patients (Galappaththy et al., 2007).
In Mexico, CQ combined with PQ has been used as the standard treatment for P. vivax malaria since the 50´s of the past century. However, PQ treatment is frequently not completed due to undesirable side effects such as stomach upsetting. In locations of difficult access, the extended intervals between blood sampling, parasitological diagnosis and treatment of patients could take as long as 3-4 weeks. Hence, to reduce the risk of transmission, febrile patients in remote areas were blood sampled and immediately treated with a single dose of 10 mg CQ and 0.75 mg PQ/kg body weight, and, only after microscopy confirmation, an intermittent single dose regimen (ISD) was administered (Mendez et al., 1994; Channon et al., 2003; NOM-032-SSA2-2002).
The first single combined CQ-PQ is still administered and it is expected to eliminate blood parasites since PQ may destroy parasites surviving from the effect of CQ [Murphy et al., 1991), and the repeated administration of ISD was intended to suppress parasitemia recurrences (Mendez et al., 1994). However, its effectiveness has not been evaluated.
Assessment and monitoring of the effectiveness of the implemented treatment strategies are necessary to advance towards malaria elimination in the region (malERA, 2011).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recommended by WHO, http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf?ua=1
- •Confirmed P. vivax mono- infection by microscopy
- •Parasitemia, minimum of 500 asexual parasites per µl of blood.
- •Presence of axillary temperature ≥ 37.5 or history of fever during the past 48 hours
- •Ability to swallow oral medication
- •Informed consent from the patient, or from the parent or guardian in the case of children under 7 years old, or both consents by participant and parent for individual´s age ranging within 7 and 18 years old.
- •Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule.
- •Patients living in accessible villages, desirable less than 1 hour far from our facility by car.
排除标准
- •Mixed species infection with another plasmodium species
- •Presence of signs of danger, or severe malaria, according to the definitions of WHO http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf?ua=1
- •if they presented signs of severe malnutrition or anemia
- •had taken an anti-malaria treatment or had a malaria infection within the previous two months.
- •Pregnant woman or positive pregnant test or breast feeding
- •History of hypersensitivity to CQ or PQ
- •Previous malaria attack within one year, identified at the malaria nominal record, sanitary jurisdiction VII of Chiapas, Mexico.
- •had another cause for their fever or other chronic diseases as hypertension, diabetes, liver or kidney disease, etc.
- •if they lived in communities at distances farther than one hour by motor vehicle from the facility.
研究组 & 干预措施
14-day treatment (T14)
The operational treatment-dose was administered by mouth. The number of tablets of Chloroquine phosphate of 150 mg for three days (x-x-x/ number of tablets of Primaquine (15mg or 5 mg)), daily during 14 days. For 1 year old subjects only chloroquine (1-½-½/ ½ of 5 mg); for 2-5 years old (1-¾-1/ 1 of 5 mg); 6-12 years old (2-1-2/ 2 of 5 mg); 13 years old and over with about 60 kg of body weight (3-2-2/ 1 of 15 mg) and above 60 kg of body weight (4-3-3 / 1 of 15 mg).
According to the age group as indicated by the Mexican guidelines for vector borne diseases control (http://www.salud.gob.mx/unidades/cdi/nom/032ssa202.html) (Table 10)
干预措施: Chloroquine phosphate (Drug)
14-day treatment (T14)
The operational treatment-dose was administered by mouth. The number of tablets of Chloroquine phosphate of 150 mg for three days (x-x-x/ number of tablets of Primaquine (15mg or 5 mg)), daily during 14 days. For 1 year old subjects only chloroquine (1-½-½/ ½ of 5 mg); for 2-5 years old (1-¾-1/ 1 of 5 mg); 6-12 years old (2-1-2/ 2 of 5 mg); 13 years old and over with about 60 kg of body weight (3-2-2/ 1 of 15 mg) and above 60 kg of body weight (4-3-3 / 1 of 15 mg).
According to the age group as indicated by the Mexican guidelines for vector borne diseases control (http://www.salud.gob.mx/unidades/cdi/nom/032ssa202.html) (Table 10)
干预措施: primaquine (Drug)
Intermittent single doses (ISD)
The single dose medication was administered orally according to age group as the operational table: (number of tablets of chloroquine phosphate of 150 mg / number of tablets of primaquine (15mg or 5 mg)): for 1 year old (½ / 1 of 5 mg); for 2¬-5 years old (1 / 2 of 5 mg); 6-12 years old (2 / 4 of 5 mg); 13 years old and over of about 60 kg of body weight (3 / 2 of 15 mg), and above 60 kg of body weight (4 / 3 of 15 mg).
It is administered on Days 0 (after the detection of infection by microscopy), and Days 30, 60, 180, 210, 240 and 360 as indicated in the National guidelines for vector borne diseases control (http://www.salud.gob.mx/unidades/cdi/nom/032ssa202.html).
干预措施: Chloroquine phosphate (Drug)
Intermittent single doses (ISD)
The single dose medication was administered orally according to age group as the operational table: (number of tablets of chloroquine phosphate of 150 mg / number of tablets of primaquine (15mg or 5 mg)): for 1 year old (½ / 1 of 5 mg); for 2¬-5 years old (1 / 2 of 5 mg); 6-12 years old (2 / 4 of 5 mg); 13 years old and over of about 60 kg of body weight (3 / 2 of 15 mg), and above 60 kg of body weight (4 / 3 of 15 mg).
It is administered on Days 0 (after the detection of infection by microscopy), and Days 30, 60, 180, 210, 240 and 360 as indicated in the National guidelines for vector borne diseases control (http://www.salud.gob.mx/unidades/cdi/nom/032ssa202.html).
干预措施: primaquine (Drug)
结局指标
主要结局
Changes in the presence and density of asexual parasites in thick blood smears by microscopy
时间窗: at days 2, 3, 7, 14, 21, 28 and monthly from month 2 to month 12, post-treatment administration
Proportion of patients at each time-point by intervention, presenting parasitemia and mean density by examining thick blood films stained with 10% Giemsa. The two thick smears were independently examined under a light microscope using oil immersion 100 × by two trained laboratory technicians. Asexual and sexual parasite densities were determined by counting the number of parasites against 200 white blood cells (WBC) (or 500 WBC, if less than 10 parasites were encountered in 200 WBC fields), assuming 7,000 WBC/μl of blood. At least 500 fields or the whole blood smear were examined before a sample was recorded as negative.
Changes in the presence and severity of clinical symptoms
时间窗: at days 2, 3, 7, 14, 21, 28 and anytime or monitor monthly during 12months, post-treatment administration
The proportion of patients at each time-point by intervension, that present any of the following symptoms; fever, headache, myalgias, arthralgias or paroxysm were indicated by patient reference or detected by field team search; by a clinical revision of the patient, using a calibrated thermometer. Othe signs were search by the clinician as jaundice (yellowish pigmentation of the skin, the conjunctival membranes over the sclerae (whites of the eyes), erythema, herpes-like small blisters on the lips and /or outer edges of the mouth and pruritus or any itching.
Changes in the presence of recurrent infections
时间窗: any time from month 1 to month 12, post T14 or during ISD treatment
Comparing the proportion of patients presenting recurrent infections at any time schedule or unschedule (symptomatic or asymptomatic) detected by any diagnosed method
次要结局
- Changes in the antibodies against blood stages of P. vivax(Monthly; from Day 28 to month 12 post-treatment administration)
- Changes in the detection of parasite DNA in blood samples(at days 2, 3, 7, 14, 21, 28 and when antibody response were increased up to 12 months)
研究者
LILIA GONZALEZ CERON
Researcher in medical Sciences
Instituto Nacional de Salud Publica, Mexico