Malaria symptoms should raise suspicion of HIV in sub-Saharan Africa

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Screening for HIV in people who present with suspected malarial fever could identify large numbers of very recent HIV infections in countries with a high HIV burden, and could represent an effective way of integrating HIV and malaria control activities at the primary care level, especially if better point-of- care tests for diagnosing acute HIV infection can be developed, researchers report.

Between December 2006 to January 2007, one to three percent of all adults presenting at seven government rural health clinics in Uganda with suspected malaria were identified as having acute or early HIV infection, reported Lisa M. Bebell and colleagues in a cross-sectional study published in the advance online June edition of AIDS.

Settings that offer routine primary care and focus on the diagnosis and treatment of malaria in sub-Saharan African provide a unique opportunity to identify large numbers of people with acute HIV infection by offering point-of-care HIV testing and counselling, note the authors.


acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).


A serious disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans. People who get malaria are typically very sick with high fevers, shaking chills, and flu-like illness. 

ribonucleic acid (RNA)

The chemical structure that carries genetic instructions for protein synthesis. Although DNA is the primary genetic material of cells, RNA is the genetic material for some viruses like HIV.



The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

window period

In HIV testing, the period of time after infection and before seroconversion during which markers of infection are still absent or too scarce to be detectable. All tests have a window period, the length of which depends on the marker of infection (HIV RNA, p24 antigen or HIV antibodies) and the specific test used. During the window period, a person can have a negative result on an HIV test despite having HIV.

Acute HIV infection means high levels of the virus are circulating in blood and genital secretions. Transmission risks are higher during this time. Individuals in the acute phase of HIV infection, which lasts one to three months, are highly infectious and probably account for 30% or more of new infections, note the authors. Identification of individuals at this stage is challenging and thus infrequent. People may not seek care, and even when they do HIV may not be considered.

The symptoms of acute HIV infection can mimic those of malaria. Over 300 million cases of malaria are diagnosed each year in sub-Saharan Africa where the burden of HIV is the greatest. Flu-like symptoms consistent with malaria are the most common reason for health clinic visits in sub-Saharan Africa accounting for 30 to 50% of all outpatient visits.

So identification of those with acute HIV infection presents a critical missed opportunity to help prevent HIV transmission, note the authors.

The authors used a cross-sectional design to see what the prevalence of acute, early and established HIV infection was among patients suspected of having malaria.

Following accepted methodology, adapted for use on dried blood, the authors identified acute, early and established HIV infection.

Acute HIV infection was defined as a period of approximately three weeks in which patients show detectable HIV-1 RNA but have negative or indeterminate results on antibody immunoassay and Western blot tests. Early HIV infection was defined as HIV-1 RNA positive with a positive Western blot pattern but a poor antibody response.

Seven thousand patients of all ages referred by health care providers for malaria blood smears (but not for consideration of HIV infection) were prospectively (and consecutively) recruited at seven rural government health clinics representative of the diversity of malaria and HIV prevalence across Uganda. Services were provided free of charge.

Of the 7000, those aged 13 and over (2893 or 41%) were included in the study.

Of these, 17% (494) had blood smears positive for malaria, varying from 3.4 to 30% by site; 324 (11.2%) were HIV-infected, with site prevalence ranging from 1.4 to 16.9%.

In total, 26.5% of all HIV-positive adults were identified as having acute (30 or 9.3%) or early (56 or 17.3%) HIV infection. Of the total population, patients with acute, early and established infection represented 1.0%, 1.8% and 8% respectively.

Site prevalence for acute and early HIV infection varied ranging from 0.5 to 6% of all adult patients.

Site-level predictors for acute HIV infection, among all patients, included high HIV prevalence (greater than 10 percent) (OR 4.5, P=0.006) and low levels of endemic malaria (OR 2.8, P=0.015).

Four to six per cent of all adults suspected of having malaria and who met the criteria for acute HIV infection were from the three study sites with the highest HIV prevalence, ranging from 10.6 to 16.9%.

The authors believe by evaluating patients who present with flu-like symptoms at general health clinics across sub-Saharan Africa, large numbers with acute or early infection can be identified.

The authors cite a study that showed patients with acute HIV infection reduced their HIV transmission risk behaviour by 98% in the eight weeks following diagnosis compared to the eight weeks before diagnosis. This would further provide an impetus for finding HIV sero-discordant couples, that is before transmission has occurred to the negative partner.

Limitations, according to the authors, include cross-sectional analysis that could have led to misclassification. In additional, methods used involving dried blood spots and pooling estimates may have underestimated those with acute infection. Improved methods are needed to identify the true proportion of those with early HIV infection, note the authors.

The authors highlighted the fact that the resource-intensive nature of the testing used in this study is not practical in most resource-poor settings. The unique method of using RNA in pooled dried blood spots is easily used in such a setting, while the nucleic acid amplification testing used requires a central laboratory and specialised equipment. This is not practical for real-time detection of infection, they note, but it could be used in further research to confirm clinical cases where refrigeration and transportation are lacking.

However, fourth-generation antibody/antigen tests, which narrow the period in which HIV infection cannot be diagnosed down to a window of around three weeks after exposure, could be used in primary health care settings. Further innovation in detecting acute infection could further shrink this window period.

Their findings, the authors believe, suggest the potential for identifying large numbers of Africans with acute or early HIV infection by co-ordinating HIV and malaria control strategies.

The authors conclude, “With the arrival of reliable diagnostics capable of identifying acute HIV infections at the point-of-care, screening of populations suspected to have malaria could identify significant numbers of acutely HIV-infected persons [in conjunction with the appropriate counselling and continuum of treatment and care]. Institution of such a strategy in areas that are endemic for malaria could represent a major opportunity for global HIV prevention.”


Bebell, LM et al. Acute HIV-1 infection is highly prevalent in Ugandan adults with suspected malaria. AIDS, advance online publication, June 2010.