Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique

Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p < 0.001), with a lower expected heterozygosity and higher relatedness of microhaplotypes surrounding pfdhps mutants than wild-type parasites suggestive of recent selection. pfdhfr/pfdhps quintuple mutants also increased from 72% in the north to 95% in the south (2018; p < 0.001). This resistance gradient was accompanied by a concentration of mutations at pfdhps-436 (17%) in the north, a south-to-north increase in the genetic complexity of P. falciparum infections (p = 0.001) and a microhaplotype signature of regional differentiation. The parasite population structure identified here offers insights to guide antimalarial interventions and epidemiological surveys.

Success in controlling a major outbreak of malaria because of Plasmodium falciparum in Jamaica.

In 2006, after 44 years of eradication of malaria, Jamaica had an outbreak of Plasmodium falciparum: 406 confirmed cases between September 2006 and December 2009 with a peak of the epidemic in December 2006. In response to the outbreak, the Ministry of Health launched an emergency response through early detection and prompt treatment of cases, vector control, public education and intersectoral collaboration. Ninety percent (361) of cases were residents of Kingston, and 63.6% were identified through house to house surveillance visits. For 56% of the confirmed cases, treatment with chloroquine was initiated within a week of onset of symptoms. Only one (0.3%) of 358 cases who had a post-treatment smear on day 7 had a persistent asexual parasitaemia, while none of the 149 persons who had a follow-up smear on day 28 was positive. The outbreak highlighted the need for increased institutional capacity for surveillance, confirmation and treatment of malaria as well as effective prevention and control of outbreaks which can occur after elimination. Jamaica appears to have successfully eliminated malaria after its reintroduction.

Malária grave em gestantes / Severe malaria in pregnant women

OBJETIVO: analisar a evolução clínica de três pacientes grávidas com malária grave internadas em unidade de terapia intensiva de um hospital localizado em Porto Velho (RO). MÉTODOS: foi realizado estudo descritivo em três gestantes, portadoras de malária por Plasmodium falciparum, internadas em unidade de terapia intensiva em Porto Velho, no período de 2005 a 2006. As variáveis categóricas utilizadas foram os critérios de classificação da Organização Mundial de Saúde para classificação de malária grave e os índices Acute Physiology and Chronic Health disease Classification System II (APACHE II) e Sepsis Related Organ Failure Assessment (SOFA) preditores de morbidade e gravidade das doenças em unidade de terapia intensiva. RESULTADOS: a malária adquirida pelas gestantes, caracterizada pela infecção por Plasmodium falciparum na forma grave da doença, resultou em óbito para as três pacientes e seus conceptos. CONCLUSÕES: embora a casuística seja pequena, a importância deste estudo reflete a repercussão da malária grave em gestantes, bem como a necessidade de um acompanhamento pré-natal mais criterioso e atento à identificação precoce do início das complicações da malária em gestantes.

PURPOSE: to analyze the clinical course of three pregnant patients with severe malaria admitted to the intensive care unit of a hospital in Porto Velho (RO), Brazil. METHODS: a descriptive study was conducted on three pregnant women infected with Plasmodium falciparum malaria, admitted to the intensive care unit of a hospital in Porto Velho from 2005 to 2006. Categorical variables used were the classification criteria of the World Health Organization which ranks severe malaria and the Acute Physiology and Chronic Health Disease Classification System II (APACHE II) and Sepsis Related Organ Failure Assessment (SOFA) predictors of morbidity and severity of intensive care unit diseases. RESULTS: the malaria acquired by the pregnant subjects characterized by infection with Plasmodium falciparum in its most serious form resulted in death for all three patients and their fetuses. CONCLUSIONS: although the sample of this study was small it reflects the important impact of severe malaria on pregnant women as well as the need for a more judicious and attentive prenatal care to identify the disease in its early stages and its first complications in pregnant women.

[Severe malaria in pregnant women]. / Malária grave em gestantes.

PURPOSE: to analyze the clinical course of three pregnant patients with severe malaria admitted to the intensive care unit of a hospital in Porto Velho (RO), Brazil. METHODS: a descriptive study was conducted on three pregnant women infected with Plasmodium falciparum malaria, admitted to the intensive care unit of a hospital in Porto Velho from 2005 to 2006. Categorical variables used were the classification criteria of the World Health Organization which ranks severe malaria and the Acute Physiology and Chronic Health Disease Classification System II (APACHE II) and Sepsis Related Organ Failure Assessment (SOFA) predictors of morbidity and severity of intensive care unit diseases. RESULTS: the malaria acquired by the pregnant subjects characterized by infection with Plasmodium falciparum in its most serious form resulted in death for all three patients and their fetuses. CONCLUSIONS: although the sample of this study was small it reflects the important impact of severe malaria on pregnant women as well as the need for a more judicious and attentive prenatal care to identify the disease in its early stages and its first complications in pregnant women.

Imported cases of malaria admitted to two hospitals of Margarita Island, Venezuela, 1998-2005.

BACKGROUND: Imported cases of malaria constitute an important public health problem in many countries, even in those with autochthonous cases, where disease could be acquired in these areas and then seen in non-endemic regions. Non-immune populations are susceptible to complications due to malaria infection, particularly in malaria caused by Plasmodium falciparum. However, Plasmodium vivax the predominant Plasmodium spp. in Venezuela can also lead to severe malaria. METHODS: We reviewed retrospectively cases of malaria to identify the clinical features of those imported cases diagnosed at two institutions in Margarita Island (a non-endemic area), Venezuela, in an 8-year period. We conducted a retrospective observational study to identify the clinical and epidemiological features among hospitalized patients at Hospital Central and Hospital Agustin Hernández with malaria acquired at malaria-endemic locations. RESULTS: We identified eighteen imported cases of malaria confirmed by thin and thick peripheral blood smears at these two institutions over an 8-year period. The mean age of diagnosis was 27 years. P. vivax was responsible for the majority of cases. All patients presented with fever, 89% with malaise, 78% with chills, and 67% with myalgia, among others symptoms. Mean haemoglobin levels on admission were 8.1g/dL (100% <12g/dL); platelets: 79,283cells/mm(3) (89% had platelets below 150,000); and a mean total leukocyte count: 3.4x10(3)cells/mm(3) (78% had leukopenia). Thirty nine percent of patients required blood transfusions. Two fatalities were identified (CFR=11%), one associated to severe malaria due to P. falciparum and the other due to a complicated case of P. vivax malaria. DISCUSSION: Imported cases of malaria due to P. vivax and P. falciparum in the studied population are associated with significant hematological complications. These findings illustrate the importance of educating non-immune populations about the malaria risk and prevention strategies; and from a pubic health perspective, the need to develop further malaria prevention strategies at a national level.

[Characterization of malaria mortality in Valle del Cauca, 2005-2006]. / Caracterización de la mortalidad por malaria en el Valle del Cauca, 2005-2006.

INTRODUCTION: Valle del Cauca is one of the states in Colombia that reports a high number of deaths due to malaria. Understanding the basis of malarial deaths is useful for assessing the efficacy of the health system and to identify areas where improvements are necessary to decrease malaria mortality. OBJECTIVE: Potential determinants of mortality in malaria cases are characterized in a demographic study centered in Valle del Cauca. MATERIALS AND METHODS: A descriptive analysis was directed to 25 cases of malaria death occurring in Valle del Cauca during 2005 and 2006. RESULTS: The mean age was 31.3 years (range, 2 to 71 yr), 11 were women (1 pregnant), 11 were from the malaria-endemic port of Buenaventura, and 5 from other Pacific coastal states. After entering the health system facility, the standard malaria diagnostic, the thick smear, was not ordered for 7 cases at any time during the treatment period. In cases where a thick smear was taken at first contact, 11 had a positive and 5 had a negative initial report. Cerebral malaria (7/18 cases) and renal failure (6/18 cases) were the most frequent complications. During hospitalization, 13/18 cases developed other complications, mainly acute lung edema (8/18 cases) and shock (5/18 cases). CONCLUSIONS: Failures in primary health care of patients with malaria were recognized. This information has been used to implement actions aimed at improving initial care of malaria subjects in the health services of Valle del Cauca. The study recommends that other states in Colombia increase their efforts to decrease malaria mortality.

Plasmodium falciparum malaria in splenectomized patients: two case reports in French Guiana and a literature review.

Some of the immunologic mechanisms involved in malaria physiopathology remain unclear. In animals, the spleen seems to play a key role in protecting the host against malaria. However, little is known about the effect of spleen dysfunction on human malaria. We report two severe cases of Plasmodium falciparum infection with unusual clinical and parasitologic features in two splenectomized men living in French Guiana. The peripheral blood of these cases showed hyperparasitemia, with a high proportion of mature parasites and leukocytes with malaria pigment. Despite appropriate treatment and adequate absorption, hyperparasitemia persisted. Parasite clearance was delayed and one patient died. Only the patient who died had the merozoite surface protein 1 allele B-K1 and the varD gene genotype, which is considered to be a probable parasite virulence factor. These uncommon cases differ from most of those described in the literature, illustrating the complexity of the mechanisms underlying the protective function of the spleen in human malaria.

Eficacia terapéutica del uso de la quinina + clindamicina por 5 y 7 días en el tratamiento de la malaria por plasmodium falciparum no complicada / Therapeutic effectiveness of the use of quinine + clindamicina by 5 and 7 days in the treatment of the malaria by noncomplicated plasmodium falciparum

Considerando la aparición de la resistencia del P falciparum a los antimaláricos, y teniendo como una alternativa terapéutica la asociación quinina clindamicina, se evaluó la eficacia de estos medicamentos utilizando esquemas de 5 y 7 días. Se incluyeron 102 pacientes con diagnóstico de malaria por P falciparum registrados en el Hospital de EsSalud, 51 recibieron el esquema de 5 días y 52 el de 7 días. Ambos grupos no tuvieron diferencias significativas en cuanto a edad, sexo y lugar de procedencia, tampoco hubieron diferencias respecto a la carga parasitaria. El 64.5 por ciento de pacientes del primer esquema y el 54.9 por ciento del segundo esquema presentaron reacciones adversas. No hubo diferencias en cuanto a la eficacia de los esquemas utilizados. }

A rapid assessment approach for public health decision-making related to the prevention of malaria during pregnancy

Objective: To develop a rapid field assessment methodology to address the burden of malaria during pregnancy and the options for intervening within the existing antenatal care system in Kenya. Methods: Surveys consisting of questionnaires, sampling of blood for parasitaemia and anaemia, and birth outcome assessment were conducted in antenatal clinics, delivery units, and in the community in Ksumu and Mombasa, Kenya. Findings: T he ratges of maternal anaemia and severe anaemia, were, resctively, 79 cent and 8 cent in Kisumu, and 95 cent and 24 cent in Mombasa. The rates of placental parasitaemia were 27 cent and 24 cent and the ratges of low birth weight were 18 cent and 24 cent in Kisumu and Mombasa, respectively. Women with placental parasitaemia had a higher incidence of low birth wight compared with women without placental parasitaemai in both Kisumu (28 cent vs 16 cent,P=0.0004) and Mombasa (42 cent vs 20 cent, P=0.004). A total of 95 cent and 98 cent for women in Kisumu and Mombasa, respectively, reported attending an antenatal clinic during their previous pregnancy. Conclusion: This metodology can be used by ministries of health to collect data for decision-making regarding malaria control during pregnancy: it can also privide a baseline measurement on which to evaluate subsequent interventions

Manejo en UCI de la malaria falciparum severa y complicada / I manage in UCI of the malaria severe and complicated falciparum

Se realizó el estudio descriptivo, prospectivo y transversal de 186 pacientes que presentaron malaria grave y complicada por P. falciparum en la Unidad de Cuidados Intensivos del Hospital Regional de Loreto (Iquitos). Se hospitalizaron casos de malaria grave y complicaciones desde junio de 1996 hasta mayo de 1999. Procediendo el mayor número de casos del Río Nanay y de la zona urbana marginal de Iquitos, la edad más afectada fue la comprendida entre los 15 a 39 años de edad, predominando el sexo femenino en el 58.1 por ciento, las estancias hospitalarias en la Unidad de Cuidados Intensivos fue de 3 a 5 días en la mayoría de los casos. El cuadro clínico predominante fue malestar, cefalea, fiebre, escalofríos. La Gota Gruesa fue positiva a P. falciparum en el 93.01 por ciento de los casos. Se utilizó quinina endovenoso de inicio en el 97.3 por ciento de los casos, continuándose con la combinación quinina tetracilina. Las complicaciones más frecuentes encontradas fueron: anemia severa (41.9 por ciento), malaria cerebral (25.3 por ciento) e hipoglicemia y RAM (22.6 por ciento c/u). La mortalidad encontrada fue de 8.1 por ciento, siendo la causa más frecuente, la insuficiencia renal aguda.

Enfermedades parasitarias como emergencias médicas / Parasite diseases how medical emergencies

Las enfermedades parasitarias se pueden presentar como emergencias médicas, en los países tropicales y subdesarrollados. La actualización permanente de su manejo clínico-terapéutico se puede realizar mediante la descripción de casos representativos. Se describen seis pacientes atendidos como emergencias: un electricista con absceso hepático amibiano que drenó a pleura, una hiperinfección por Strongyloides stercoralis, una recaida por leishmaniasis visceral, una niña con leishmaniasis de la mucosa nasal, un minero con insuficiencia renal que adquirió un paludismo por P.facilparum resistente a la cloroquina y un transportista con paludismo por P.vivax resistente a primaquina. Se discuten las complicaciones clínico-terapéuticas de los pacientes y se revisa la literatura médica disponible para actualizar estas parasitosis

Malária grave por P.falciparum. Avaliaçäo das falhas no diagnóstico e na conduta terapêutica em pacientes antes de sua internaçäo em Hospital de Referência / Severe P. falciparum Malaria. Assessment of the failures in diagnosis and therapeutic conducts in patients, before being hospitalized

Falhas no diagónstico e na conduta terapêutica antes da internaçäo foram analisadas em relaçäo a letalidade em 102 pacientes portadores da forma grave da Malária por P. falciparum, segundo critérios da OMS (1990). Diagnóstico coreto foi observado em 62 (60.8) (pôr cento) pacientes, com letalidade de 17.7 (pôr cento) e incorreto em 40 (39.3) (pôr cento), com letalidade de 40(pôr cento) (p=0.01). Conduta terapêutica apropriada foi observada em 21/62 pacientes (33.9) (pôr cento), com letalidade de 9.5 (pôr cento) e inapropriada em 41/62 (66.1) (pôr cento), com letalidade de 21.9(pôr cento) e inapropriada (p> 0.05). Nos pacientes com até 4 dias de doença a letalidade foi de 5.0(pôr cento), nos com 5 a 7 dias, 25.8(pôr cento)e com mais de 7 dias 35.3(pôr cento) (p< 0.05). Os diagnóstico incorretos mais freqüentes foram: Hepatite 30(pôr cento), Infeçäo do trato urinário 25(pôr cento), Malària por P. vivax e febre amarela 15(pôr cento) e Septicemia 7.5(pôr cento). A letalidade foi significativamente maior (p=0.01) naqueles com diagnóstico incorreto e com mais de 4 dias de doença. Os dados mostram um elevado índice de erro no diagnóstico e na conduta terapêutica especíifica na Malária Grave, bem como suas consequências deletérias para os pacientes